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Articles by Callie L. Janik in JoVE

 JoVE Clinical and Translational Medicine

Identification of Sleeping Beauty Transposon Insertions in Solid Tumors using Linker-mediated PCR

1Department of Obstetrics, Gynecology & Women's Health, Masonic Cancer Center, University of Minnesota, Minneapolis, 2Department of Genetics, Cell Biology & Development, Center for Genome Engineering, University of Minnesota, Minneapolis


JoVE 50156

A method of identifying unknown drivers of carcinogenesis using an unbiased approach is described. The method uses the Sleeping Beauty transposon as a random mutagen directed to specific tissues. Genomic mapping of transposon insertions that drive tumor formation identifies novel oncogenes and tumor suppressor genes

Other articles by Callie L. Janik on PubMed

Whistle Rates of Wild Bottlenose Dolphins (Tursiops Truncatus): Influences of Group Size and Behavior

In large social groups acoustic communication signals are prone to signal masking by conspecific sounds. Bottlenose dolphins (Tursiops truncatus) use highly distinctive signature whistles that counter masking effects. However, they can be found in very large groups where masking by conspecific sounds may become unavoidable. In this study we used passive acoustic localization to investigate how whistle rates of wild bottlenose dolphins change in relation to group size and behavioral context. We found that individual whistle rates decreased when group sizes got larger. Dolphins displayed higher whistle rates in contexts when group members were more dispersed as in socializing and in nonpolarized movement than during coordinated surface travel. Using acoustic localization showed that many whistles were produced by groups nearby and not by our focal group. Thus, previous studies based on single hydrophone recordings may have been overestimating whistle rates. Our results show that although bottlenose dolphins whistle more in social situations they also decrease vocal output in large groups where the potential for signal masking by other dolphin whistles increases.

Multimodality Monitoring of the Central Nervous System Using Motor-evoked Potentials

This review was conducted to examine the role of motor-evoked potential monitoring in spine and central nervous system surgery to determine whether other monitoring modalities such as the wake-up test or somatosensory-evoked potentials can be eliminated.

Interactions of T Helper Cells with Fibroblast-like Synoviocytes: Up-regulation of Matrix Metalloproteinases by Macrophage Migration Inhibitory Factor from Both Th1 and Th2 Cells

Interactions of immune cells, such as activated T helper cells, with fibroblast-like synoviocytes (FLS) play a crucial role in the joint destruction during human rheumatoid arthritis (RA). This study was undertaken to investigate the expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) by T helper cells, and to assess the role of MIF in overexpression of matrix metalloproteinases (MMPs) in cocultures of FLS from arthritic mice with either Th1 or Th2 cells.

Zn(1-x)MnxTe Diluted Magnetic Semiconductor Nanowires Grown by Molecular Beam Epitaxy

It is shown that the growth of II-VI diluted magnetic semiconductor nanowires is possible by the catalytically enhanced molecular beam epitaxy (MBE). Zn(1-x)MnxTe NWs with manganese content up to x=0.60 were produced by this method. X-ray diffraction, Raman spectroscopy, and temperature dependent photoluminescence measurements confirm the incorporation of Mn(2+) ions in the cation substitutional sites of the ZnTe matrix of the NWs.

Anti-HTLV Antibody Profiling Reveals an Antibody Signature for HTLV-I-associated Myelopathy/tropical Spastic Paraparesis (HAM/TSP)

HTLV-I is the causal agent of adult T cell leukemia (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Biomarkers are needed to diagnose and/or predict patients who are at risk for HAM/TSP or ATLL. Therefore, we investigated using luciferase immunoprecipitation technology (LIPS) antibody responses to seven HTLV-I proteins in non-infected controls, asymptomatic HTLV-I-carriers, ATLL and HAM/TSP sera samples. Antibody profiles were correlated with viral load and examined in longitudinal samples.

[Polymorphism of Gene P53 and Apoptosis in Patients with Malignant Lung Disease--our Observation]

Many proved alterations in genoms of cells are said to be related to tumorigenesis. Apoptosis--a "programmed" death of cell, which has different morphology from necrosis, is one of the control mechanisms of cell division and participates in tumorigenesis.

Dynamic Spin Ice: Pr2Sn2O7

In this Letter, we report a new spin ice--Pr2Sn2O7--which appears to have enhanced residual entropy due to the dynamic nature of the spins. Neutron scattering experiments show that at 200 mK, there is a significant amount of magnetic diffuse scattering which can be fit to the dipolar spin-ice model. However, these short-ranged ordered spins have a quasielastic response that is atypical of the canonical spin ices, and suggests that the ground state is dynamic (i.e., composed of locally ordered two-in-two-out spin configurations that can tunnel between energetically equivalent orientations). We report this as an example of a dynamic spin ice down to 200 mK.

[Analysis of Treatment Results of Boys Referred to Outpatient Paediatric Surgery Centre with Recognition of Phimosis]

The problem with prepuce retraction is caused not only by its narrowing, called phimosis, but also frequently by the inner prepuce adhesion to glans. The spontaneous prepuce retraction is received in 80% cases of boys up to the age of two, whereas in remaining cases, after the age of two it is necessary to take up the medical treatment. The purpose of the research was to estimate the effectiveness of conservative therapy using steroid ointments which was undertaken in boys referred to Outpatient Paediatric Surgery Centre with recognition of phimosis.

[Treatment of Hemosuccus Pancreaticus by Bilateral Embolization of Gastric Arteries]

Arosion of peripancreatic arteries in acute or chronic pancreatitis is a rare cause of bleeding into gastrointestinal tract--hemosuccus pancreaticus. Aim of the paper is to show the diagnostic and therapeutic options in this serious clinical stage.

A First Principles Comparison of the Mechanism and Site Requirements for the Electrocatalytic Oxidation of Methanol and Formic Acid over Pt

First principles density functional theoretical calculations were carried out to examine and compare the reaction paths and ensembles for the electrocatalytic oxidation of methanol and formic acid in the presence of solution and applied electrochemical potential. Methanol proceeds via both direct and indirect pathways which are governed by the initial C-H and O-H bond activation, respectively. The primary path requires an ensemble size of between 3-4 Pt atoms, whereas the secondary path is much less structure sensitive, requiring only 1-2 metal atoms. The CO that forms inhibits the surface at potentials below 0.66 V NHE. The addition of Ru results in bifunctional as well as electronic effects that lower the onset potential for CO oxidation. In comparison, formic acid proceeds via direct, indirect and formate pathways. The direct path, which involves the activation of the C-H bond followed by the rapid activation of the O-H bond, was calculated to be the predominant path especially at potentials greater than 0.6 V. The activation of the O-H bond of formic acid has a very low barrier and readily proceeds to form surface formate intermediates as the first step of the indirect formate path. Adsorbed formate, however, was calculated to be very stable, and thus acts as a spectator species. At potentials below 0.6 V NHE, CO, which forms via the non-Faradaic hydrolytic splitting of the C-O bond over stepped or defect sites in the indirect path, can build up and poison the surface. The results indicate that the direct path only requires a single Pt atom whereas the indirect path requires a larger surface ensemble and stepped sites. This suggests that alloys will not have the same influence on formic acid oxidation as they do for methanol oxidation.

Zn(1-x)Mg(x)Te Nanowires Grown by Solid Source Molecular Beam Epitaxy

This paper reports on the epitaxial growth of single-crystalline ternary Zn(1-x)Mg(x)Te nanowires covering a broad compositional range of molar fraction 0≤x≤0.75. The nanowires were grown on (100), (110), and (111) GaAs substrates using a vapor-liquid-solid mechanism. Solid source molecular beam epitaxy and an Au-based nanocatalyst were used for these purposes. The composition of nanowires can be adjusted by changing the ratio of Mg to Zn molecular beam fluxes. Electron microscopy images show that the nanowires are smooth and slightly tapered. The diameters of the obtained nanowires are from 30 to 70 nm and their length is around 1 µm. X-ray diffraction analysis and transmission electron microscopy reveal that the nanowires have a zinc-blende structure throughout the whole range of obtained compositions, and have a [Formula: see text] growth axis. The Raman measurements reveal both the expected splitting and shift of phonon lines with increasing Mg content, thus proving the substitutional incorporation of Mg into metallic sites of the ZnTe lattice.

Definition, Prognostic Factors, Treatment, and Response Criteria of Adult T-cell Leukemia-lymphoma: a Proposal from an International Consensus Meeting

Adult T-cell leukemia-lymphoma (ATL) is a distinct peripheral T-lymphocytic malignancy associated with a retrovirus designated human T-cell lymphotropic virus type I (HTLV-1). The diversity in clinical features and prognosis of patients with this disease has led to its subclassification into the following four categories: acute, lymphoma, chronic, and smoldering types. The chronic and smoldering subtypes are considered indolent and are usually managed with watchful waiting until disease progression, analogous to the management of some patients with chronic lymphoid leukemia (CLL) or other indolent histology lymphomas. Patients with aggressive ATL generally have a poor prognosis because of multidrug resistance of malignant cells, a large tumor burden with multiorgan failure, hypercalcemia, and/or frequent infectious complications as a result of a profound T-cell immunodeficiency. Under the sponsorship of the 13th International Conference on Human Retrovirology: HTLV, a group of ATL researchers joined to form a consensus statement based on established data to define prognostic factors, clinical subclassifications, and treatment strategies. A set of response criteria specific for ATL reflecting a combination of those for lymphoma and CLL was proposed. Clinical subclassification is useful but is limited because of the diverse prognosis among each subtype. Molecular abnormalities within the host genome, such as tumor suppressor genes, may account for these diversities. A treatment strategy based on the clinical subclassification and prognostic factors is suggested, including watchful waiting approach, chemotherapy, antiviral therapy, allogeneic hematopoietic stem-cell transplantation (alloHSCT), and targeted therapies.

Gene Expression Profiling of ATL Patients: Compilation of Disease-related Genes and Evidence for TCF4 Involvement in BIRC5 Gene Expression and Cell Viability

Adult T-cell leukemia/lymphoma (ATL) is an aggressive and fatal disease. We have examined 32 patients with smoldering, chronic, lymphoma and acute leukemia using Affymetrix HG-U133A2.0 arrays. Using the BRB array program, we identified genes differentially expressed in leukemia cells compared with normal lymphocytes. Several unique genes were identified that were overexpressed in leukemic cells, including TNFSF11, RGS13, MAFb, CSPG2, C/EBP-alpha, and TCF4; 200 of the most highly overexpressed ATL genes were analyzed by the Pathway Studio, version 4.0 program. ATL leukemia cells were characterized by an increase in genes linked to "central" genes CDC2/cyclin B1, SYK/LYN, proliferating cell nuclear antigen, and BIRC5. Because of its potential therapeutic importance, we focused our studies on the regulation and function of BIRC5, whose expression was increased in 13 of 14 leukemia samples. TCF4 reporter assays and transfection of DN-TCF4 demonstrated that TCF4 regulates BIRC5 gene expression. Functionally, transfection of ATL cells with BIRC5 shRNA decreased BIRC5 expression and cell viability 80%. Clinical treatment of ATL patients with Zenapax or bortezomib decreased BIRC5 expression and cell viability. These experiments represent the first direct experimental evidence that BIRC5 plays an important role in ATL cell viability and provides important insight into ATL genesis and potential targeted therapies.

Binding of Indanocine to the Colchicine Site on Tubulin Promotes Fluorescence, and Its Binding Parameters Resemble Those of the Colchicine Analogue AC

Indanocine, a synthetic indanone, has shown potential antiproliferative activity against several tumor types. It is different from many other microtubule-disrupting drugs, because it displays toxicity toward multidrug resistance cells. We have examined the interaction of indanocine with tubulin and determined their binding and thermodynamic parameters using isothermal titration calorimetry (ITC). Indanocine is weakly fluorescent in aqueous solution, and the binding to tubulin enhances fluorescence with a large blue shift in the emission maxima. Indanocine binds to the colchicine site of tubulin, although it bears no structural similarity with colchicine. Nevertheless, like colchicine analogue AC, indanocine is a flexible molecule in which two halves of the molecule are connected through a single bond. Also, like AC, indanocine binds to the colchicine binding site of tubulin in a reversible manner and the association reaction occurs at a faster rate compared to that of colchicine-tubulin binding. The binding kinetics was studied using stopped-flow fluorescence. The association process follows biphasic kinetics similar to that of the colchicine-tubulin interaction. The activation energy of the reaction was 10.5 +/- 0.81 kcal/mol. Further investigation using ITC revealed that the enthalpy of association of indanocine with tubulin is negative and occurs with a negative heat capacity change (DeltaC(p) = -175.1 cal mol(-1) K(-1)). The binding is unique with a simultaneous participation of both hydrophobic and hydrogen bonding forces. Finally, we conclude that even though indanocine possesses no structural similarity with colchicine, it recognizes the colchicine binding site of tubulin and its binding properties resemble those of the colchicine analogue AC.

Coprophenomena in Tourette Syndrome

The aims of this descriptive study were to examine the prevalence and associations of coprophenomena (involuntary expression of socially unacceptable words or gestures) in individuals with Tourette syndrome. Participant data were obtained from the Tourette Syndrome International Database Consortium. A specialized data collection form was completed for each of a subset of 597 consecutive new patients with Tourette syndrome from 15 sites in seven countries. Coprolalia occurred at some point in the lifetime of 19.3% of males and 14.6% of females, and copropraxia in 5.9% of males and 4.9% of females. Coprolalia was three times as frequent as copropraxia, with a mean onset of each at about 11 years, 5 years after the onset of tics. In 11% of those with coprolalia and 12% of those with copropraxia these coprophenomena were one of the initial symptoms of Tourette syndrome. The onsets of tics, coprophenomena, smelling of non-food objects, and spitting were strongly intercorrelated. Early onset of coprophenomena was not associated with its longer persistence. The most robust associations of coprophenomena were with the number of non-tic repetitive behaviors, spitting, and inappropriate sexual behavior. Although coprophenomena are a frequently feared possibility in the course of Tourette syndrome, their emergence occurs in only about one in five referred patients. Because the course and actual impact of coprophenomena are variable, additional prospective research is needed to provide better counseling and prognostic information.

The Influence of Sulfur Substituents on the Molecular Geometry and Packing of Thio Derivatives of N-methylphenobarbital

The room-temperature crystal structures of four new thio derivatives of N-methylphenobarbital [systematic name: 5-ethyl-1-methyl-5-phenylpyrimidine-2,4,6(1H,3H,5H)-trione], C(13)H(14)N(2)O(3), are compared with the structure of the parent compound. The sulfur substituents in N-methyl-2-thiophenobarbital [5-ethyl-1-methyl-5-phenyl-2-thioxo-1,2-dihydropyrimidine-4,6(3H,5H)-dione], C(13)H(14)N(2)O(2)S, N-methyl-4-thiophenobarbital [5-ethyl-1-methyl-5-phenyl-4-thioxo-3,4-dihydropyrimidine-2,6(1H,5H)-dione], C(13)H(14)N(2)O(2)S, and N-methyl-2,4,6-trithiophenobarbital [5-ethyl-1-methyl-5-phenylpyrimidine-2,4,6(1H,3H,5H)-trithione], C(13)H(14)N(2)S(3), preserve the heterocyclic ring puckering observed for N-methylphenobarbital (a half-chair conformation), whereas in N-methyl-2,4-dithiophenobarbital [5-ethyl-1-methyl-5-phenyl-2,4-dithioxo-1,2,3,4-tetrahydropyrimidine-6(5H)-one], C(13)H(14)N(2)OS(2), significant flattening of the ring was detected. The number and positions of the sulfur substituents influence the packing and hydrogen-bonding patterns of the derivatives. In the cases of the 2-thio, 4-thio and 2,4,6-trithio derivatives, there is a preference for the formation of a ring motif of the R(2)(2)(8) type, which is also a characteristic of N-methylphenobarbital, whereas a C(6) chain forms in the 2,4-dithio derivative. The preferences for hydrogen-bond formation, which follow the sequence of acceptor position 4 > 2 > 6, confirm the differences in the nucleophilic properties of the C atoms of the heterocyclic ring and are consistent with the course of N-methylphenobarbital thionation reactions.

Experimental System to Evaluate the Effective Diffusion Coefficient of Radon

The effective diffusion coefficient of radon is a very important factor in estimating the rate of radon exhalation from the ground surface. In this study, we developed an experimental system that overcomes technical problems in previous studies to accurately evaluate the effective diffusion coefficient. The radon source used for this system was the National Institute of Radiological Sciences radon chamber. This chamber is a calibrated international standard facility that can produce stable radon concentrations for long periods of time. Our tests showed that leakage of radon from the system was negligible. After the leakage test, we evaluated the effective diffusion coefficient in free-space and in dry porous materials at porosities of 35% and 45%. To ensure that the porous material in the column was as homogeneous as possible, we filled the column with an artificial soil with controlled grain size and grain composition. The measured values and theoretical calculations agreed well, which indicate that the proposed system can be used to accurately and quickly evaluate the effective diffusion coefficient.

Whale Song

Variable CD52 Expression in Mature T Cell and NK Cell Malignancies: Implications for Alemtuzumab Therapy

The anti-CD52 antibody alemtuzumab has been explored as a novel targeted therapy in T cell malignancies. To assess the suitability of alemtuzumab therapy, we carried out a comprehensive study of CD52 expression using flow cytometry (FC) in 78 untreated patients diagnosed with mature T/natural killer (NK) cell neoplasms, including 34 adult T cell leukaemia/lymphomas (ATLL), two anaplastic large cell lymphomas (ALCL), three angioimmunoblastic T cell lymphomas (AITL), 16 cutaneous T cell lymphomas (CTCL), four extra-nodal T/NK cell lymphomas (ENT/NKCL), four hepatosplenic T cell lymphomas (HSTCL), 13 peripheral T cell lymphomas, not otherwise specified (PTCL-NOS) and two T-prolymphocytic leukaemia (T-PLL). The level of CD52 expression was quantified using QuantiBRITE standard beads. The level of CD52 expression varied widely within each diagnostic category. All AITL, HSTCL and T-PLL cases were CD52-positive and the frequency of CD52 expression was high in PTCL-NOS (92.3%), ATLL (94.1%) and CTCL (87.5%), implying a rational role for alemtuzumab in the treatment of these diseases; however, CD52 expression was low in ALCL (50%) and ENT/NKCL (25%). FC testing for cell surface expression of CD52 is indicated in patients with T/NK cell malignancies being considered for alemtuzumab therapy. Further studies are necessary to determine if the level of CD52 expression correlates with response to therapy.

Pulsed Electron Beam Water Radiolysis for Submicrosecond Hydroxyl Radical Protein Footprinting

Hydroxyl radical footprinting is a valuable technique for studying protein structure, but care must be taken to ensure that the protein does not unfold during the labeling process due to oxidative damage. Footprinting methods based on submicrosecond laser photolysis of peroxide that complete the labeling process faster than the protein can unfold have been recently described; however, the mere presence of large amounts of hydrogen peroxide can also cause uncontrolled oxidation and minor conformational changes. We have developed a novel method for submicrosecond hydroxyl radical protein footprinting using a pulsed electron beam from a 2 MeV Van de Graaff electron accelerator to generate a high concentration of hydroxyl radicals by radiolysis of water. The amount of oxidation can be controlled by buffer composition, pulsewidth, dose, and dissolved nitrous oxide gas in the sample. Our results with ubiquitin and beta-lactoglobulin A demonstrate that one submicrosecond electron beam pulse produces extensive protein surface modifications. Highly reactive residues that are buried within the protein structure are not oxidized, indicating that the protein retains its folded structure during the labeling process. Time-resolved spectroscopy indicates that the major part of protein oxidation is complete in a time scale shorter than that of large scale protein motions.

EBV-related Lymphoproliferative Disease Complicating Therapy with the Anti-CD2 Monoclonal Antibody, Siplizumab, in Patients with T-cell Malignancies

We report an increased incidence of EBV-induced B-cell lymphoproliferative disease (LPD) in patients treated with siplizumab, an anti-CD2 antibody. The development of EBV-LPD has been associated with the use of immunosuppressive agents used in solid organ, bone marrow, and stem cell transplantation and in certain congenital immunodeficiencies.

Mitigation of the Effective Dose of Radon Decay Products Through the Use of an Air Cleaner in a Dwelling in Okinawa, Japan

Field measurements were conducted to assess the effects of an air cleaner on radon mitigation in a dwelling with a high radon concentration in Okinawa, Japan. The measurements included indoor radon concentration, individual radon progeny concentration, equilibrium equivalent concentration of radon (EECRn), unattached fraction, and size distribution of aerosol-attached radon progeny. These measurements were conducted in a 74 m(3) room with/without the use of an air cleaner. The results showed that the mean radon concentration during the measurement was quite high (301 Bq m(-3)). The operation of air cleaner decreased the radon progeny activity concentration, EECRn and equilibrium factor by 33%, 57% and 71%, respectively, whereas the unattached fraction increased by 174%. In addition, the activity concentration of attached radon progeny in the accumulation mode (50-2000 nm) was obviously deceased by 42%, when the air cleaner was operated. According to dosimetric calculations, the operation of air cleaner reduced the effective dose due to radon progeny by about 50%.

International Intercomparisons of Integrating Radon Detectors in the NIRS Radon Chamber

An international intercomparison of integrating detectors was conducted at NIRS (National Institute of Radiological Science, Japan) with a 24.4 m(3) inner volume walk-in radon chamber that has systems to control radon concentration, temperature and humidity. During the first intercomparison (05.2007) four groups participated from four countries and for the second intercomparison (10.2007) 17 participants were involved from 11 countries. Most of detectors are in good agreement with each other when compared to the radon level provided by the radon chamber. It appeared that the 70% of detectors are unified within the 20% margin of uncertainty.

Differential Efficacy of Bortezomib Plus Chemotherapy Within Molecular Subtypes of Diffuse Large B-cell Lymphoma

Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed distinct molecular subtypes that include germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL. ABC DLBCL has a worse survival after upfront chemotherapy and is characterized by constitutive activation of the antiapoptotic nuclear factor-kappa B (NF-kappaB) pathway, which can inhibit chemotherapy. We hypothesized that inhibition of NF-kappaB might sensitize ABC but not GCB DLBCL to chemotherapy and improve outcome. As the proteasome inhibitor bortezomib can inhibit NF-kappaB through blocking IkappaBalpha degradation, we investigated bortezomib alone followed by bortezomib and doxorubicin-based chemotherapy in recurrent DLBCL. Tumor tissue was analyzed by gene expression profiling and/or immunohistochemistry to identify molecular DLBCL subtypes. As a control, we showed that relapsed/refractory ABC and GCB DLBCL have equally poor survivals after upfront chemotherapy. Bortezomib alone had no activity in DLBCL, but when combined with chemotherapy, it demonstrated a significantly higher response (83% vs 13%; P < .001) and median overall survival (10.8 vs 3.4 months; P = .003) in ABC compared with GCB DLBCL, respectively. These results suggest bortezomib enhances the activity of chemotherapy in ABC but not GCB DLBCL, and provide a rational therapeutic approach based on genetically distinct DLBCL subtypes. This trial is registered with http://www.ClinicalTrials.gov under identifier NCT00057902.

Supramolecular Organization of the Main Photosynthetic Antenna Complex LHCII: a Monomolecular Layer Study

The light-harvesting pigment-protein complex LHCII is a main antenna complex of the photosynthetic apparatus of plants, responsible for collecting light energy and also for photoprotection against overexcitation-induced damage. Realization of both functions depends on molecular organization of the complex. Monolayer technique has been applied to address the problem of supramolecular organization of LHCII. Analysis of the isotherms of compression of monomolecular films formed at the argon-water interface shows that LHCII appears in two phases: one characterized by the specific molecular area characteristic of trimeric and one of monomeric organization of LHCII. Monolayers of LHCII were deposited by means of the Langmuir-Blodgett technique to solid supports and examined by means of AFM, FTIR, fluorescence spectroscopy, and fluorescence lifetime imaging microscopy (FLIM). FTIR analysis shows that organization of the trimers of LHCII within a monolayer is associated with formation of intermolecular hydrogen bonds between neighboring polypeptides. The linear-dichroism FTIR analysis reveals that polypeptide fragments involved in intermolecular interactions are oriented at an angle of 67 degrees with respect to the normal axis to the plane of the layer. Fluorescence and fluorescence lifetime analysis reveal that the organization of LHCII within monolayers is associated with formation of the low-lying excitonic energy levels that can be potentially responsible for excess excitation quenching. FLIM and AFM reveal heterogeneous organization of LHCII monolayers, in particular, formation of ring-like structures. The potential of LHCII to form molecular structures characterized by pigment excitonic interactions is discussed in terms of regulation of the photosynthetic accessory function and photoprotection against overexcitation-induced damage.

Role of Chemotherapy in Hodgkin's Lymphoma

The development of curative chemotherapy regimens for the treatment of Hodgkin's lymphoma (HL) is one of the true success stories in oncology. Most patients diagnosed with HL today can be cured. The major task remaining before us is curing as many patients as possible with their initial therapeutic approach while minimizing the acute toxicities and limiting the lifetime risks of important secondary events such as cardiovascular complications and secondary malignancies. In the 40 years since DeVita et al. developed the mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy regimen, we have learned a great deal about risk stratification to minimize treatment-related toxicity. Positron emission tomography may further assist us in reducing radiation treatment without compromising cures. This review will discuss the development of the chemotherapy regimens used in the management of early and advanced stage HL and the advantages and disadvantages of their use in combination with radiation therapy.

Nonhematopoietic Cells Control the Outcome of Infection with Listeria Monocytogenes in a Nucleotide Oligomerization Domain 1-dependent Manner

We analyzed the defensive role of the cytosolic innate recognition receptor nucleotide oligomerization domain 1 (NOD1) during infection with Listeria monocytogenes. Mice lacking NOD1 showed increased susceptibility to systemic intraperitoneal and intravenous infection with high or low doses of L. monocytogenes, as measured by the bacterial load and survival. NOD1 also controlled dissemination of L. monocytogenes into the brain. The increased susceptibility to reinfection of NOD1(-/-) mice was not associated with impaired triggering of listeria-specific T cells, and similar levels of costimulatory molecules or activation of dendritic cells was observed. Higher numbers of F480(+) Gr1(+) inflammatory monocytes and lower numbers of F480(-) Gr1(+) neutrophils were recruited into the peritoneum of infected WT mice than into the peritoneum of infected NOD1(-/-) mice. We determined that nonhematopoietic cells accounted for NOD1-mediated resistance to L. monocytogenes in bone marrow radiation chimeras. The levels of NOD1 mRNA in fibroblasts and bone marrow-derived macrophages (BMM) were upregulated after infection with L. monocytogenes or stimulation with different Toll-like receptor ligands. NOD1(-/-) BMM, astrocytes, and fibroblasts all showed enhanced intracellular growth of L monocytogenes compared to WT controls. Gamma interferon-mediated nitric oxide production and inhibition of L. monocytogenes growth were hampered in NOD1(-/-) BMM. Thus, NOD1 confers nonhematopoietic cell-mediated resistance to infection with L. monocytogenes and controls intracellular bacterial growth in different cell populations in vitro.

Granulomatous Pneumonia Caused by Mycobacterium Genavense in a Dwarf Rabbit (Oryctolagus Cuniculus)

A juvenile dwarf rabbit (Oryctolagus cuniculus) with clinical signs of dyspnea and suspected ascites was submitted for necropsy. The main macroscopic findings were a watery red pleural effusion and some whitish striated foci in the lungs. In addition, there were multifocal scars in the cortex of the kidneys. The histologic examination of the lungs showed a severe granulomatous pneumonia with detection of acid-fast bacilli, in the kidneys, an interstitial chronic lymphoplasmacellular nephritis with interstitial fibrosis, and in the brain, a multifocal granulomatous and partly necrotizing encephalitis with detection of spores, suggestive of encephalitozoonosis. In the lungs, Mycobacterium genavense was verified by polymerase chain reaction and 16S ribosomal RNA gene sequencing. To our knowledge, this is the first report of an M. genavense infection in a rabbit, with the lungs being the only affected organ. Therefore, an aerogen infection seems to be the most contemplable way of infection.

Two Coincident Coronary Anomalies: Absent Left Main Coronary Artery and Origin of the Right Coronary Artery from the Middle Left Anterior Descending Artery

Effect of Nociceptin/Orphanin FQ (N/OFQ) and Isoflurane on the Corticosterone Secretory Response in Mice Lacking the N/OFQ Prepropeptide (ppN/OFQ-/-)

The effects of subcutaneous Nociceptin/Orphanin FQ (N/OFQ) administration on corticosterone (CORT) secretion were determined in male and female wild-type mice and mice lacking the N/OFQ prepropeptide. Additionally the effect of pretreating animals with isoflurane anesthesia to minimize the potential stress of injection was examined. Although N/OFQ itself did not specifically increase CORT levels in males or females of either genotype, injection alone (either vehicle or N/OFQ) or isoflurane exposure both increased CORT levels in all groups. These results demonstrate that N/OFQ does not elevate circulating CORT levels; however the injection process itself results in increased CORT secretion. Pretreatment with isoflurane did not significantly diminish the CORT response to injection, except in wild-type males. In fact, isoflurane exposure alone increased CORT levels above basal values. Additionally, a gender difference was evident; females displayed a greater change of plasma CORT levels than males. Finally, because even saline injection increased CORT levels, we closely investigated another possible non-specific stress effect, i.e. the effect of transporting animals from their home environment in the animal facility to the laboratory on the day of the experiment. Although basal CORT levels were similar to values reported in other studies, circulating CORT levels were elevated in animals transported to the laboratory, even after a 30 min acclimation period. These results indicate that the experimental protocol that is followed when conducting stress experiments needs to be carefully considered.

Analysis of Pax6 Contiguous Gene Deletions in the Mouse, Mus Musculus, Identifies Regions Distinct from Pax6 Responsible for Extreme Small-eye and Belly-spotting Phenotypes

In the mouse Pax6 function is critical in a dose-dependent manner for proper eye development. Pax6 contiguous gene deletions were shown to be homozygous lethal at an early embryonic stage. Heterozygotes express belly spotting and extreme microphthalmia. The eye phenotype is more severe than in heterozygous Pax6 intragenic null mutants, raising the possibility that deletions are functionally different from intragenic null mutations or that a region distinct from Pax6 included in the deletions affects eye phenotype. We recovered and identified the exact regions deleted in three new Pax6 deletions. All are homozygous lethal at an early embryonic stage. None express belly spotting. One expresses extreme microphthalmia and two express the milder eye phenotype similar to Pax6 intragenic null mutants. Analysis of Pax6 expression levels and the major isoforms excluded the hypothesis that the deletions expressing extreme microphthalmia are directly due to the action of Pax6 and functionally different from intragenic null mutations. A region distinct from Pax6 containing eight genes was identified for belly spotting. A second region containing one gene (Rcn1) was identified for the extreme microphthalmia phenotype. Rcn1 is a Ca(+2)-binding protein, resident in the endoplasmic reticulum, participates in the secretory pathway and expressed in the eye. Our results suggest that deletion of Rcn1 directly or indirectly contributes to the eye phenotype in Pax6 contiguous gene deletions.

Field Experience with Soil Gas Mapping Using Japanese Passive Radon/thoron Discriminative Detectors for Comparing High and Low Radiation Areas in Serbia (Balkan Region)

Based on results of fieldwork in the Balkan Region of Serbia from 2005 to 2007, soil gas radon and thoron concentrations as well as gamma dose rates were measured. Campaigns were conducted in two different geological regions: Niska Banja, considered a high natural radiation area, and Obrenovac around the TentB Thermal Power Plant (TPP), a low natural radiation area. Radon and thoron gas measurements were made by using two types of Japanese passive radon/thoron detectors, which included GPS data and gamma dose rates. The concentrations of soil radon gas in Niska Banja ranged from 1.8 to 161.1 kBq m(-3), whereas the concentrations for soil thoron gas ranged from 0.9 to 23.5 kBq m(-3). The gamma dose rates varied from 70 to 320 nGy h(-1). In the TentB area, radon concentration was found to range from 0.8 to 24.9 kBq m(-3) and thoron from 0.6 to 1.9 kBq m(-3). The gamma dose rate ranged from 90 to 130 nGy h(-1). In addition, the natural radioactivity of the soil was investigated at the low background area. The radium and thorium contents in collected soil samples ranged from 23 to 58 and 33 to 67 Bq kg(-1), respectively. As a result of correlation analyses between the measured values, the highest correlation coefficient (R > 0.95) was found for thorium in the soil and the thoron gas concentration.

One-neutron Removal Measurement Reveals 24O As a New Doubly Magic Nucleus

The first measurement of the momentum distribution for one-neutron removal from (24)O at 920A MeV performed at GSI, Darmstadt is reported. The observed distribution has a width (FWHM) of 99 +/- 4 MeV/c in the projectile rest frame and a one-neutron removal cross section of 63 +/- 7 mb. The results are well explained with a nearly pure 2s_{1/2} neutron spectroscopic factor of 1.74 +/- 0.19 within the eikonal model. This large s-wave probability shows a spherical shell closure thereby confirming earlier suggestions that (24)O is a new doubly magic nucleus.

Intraoperative Autologous Transfusion of Hemolyzed Blood

During two cases of lumbar spine surgery with instrumentation, we used intraoperative autologous transfusion (IAT), resulting in hemolysis during collection and hemoglobinuria and coagulation abnormalities after transfusion. Hemolysis during IAT collection can lead to hemoglobinuria and binding of nitric oxide, leading to vasoconstriction. The literature suggests that stroma from damaged cells and contact of the blood with the IAT device can lead to coagulation abnormalities and other morbidities, including adult respiratory distress syndrome.

Reactivation of DNA Viruses in Association with Histone Deacetylase Inhibitor Therapy: a Case Series Report

Histone deacetylase inhibitors are a class of anti-neoplastic agents that induce growth arrest, differentiation, and/or apoptotic cell death of transformed cells in vitro and in vivo. A phase II study exploring the efficacy of romidepsin, an histone deacetylase inhibitor, in patients with cutaneous or peripheral T-cell lymphomas was initiated at the National Cancer Institute. To date, over 120 patients with T-cell lymphoma have been treated on a multi-institutional phase II trial of romidepsin. Reactivation of latent DNA viruses including EBV, HBV, and VZV is well described as a consequence of the immune suppression associated with systemic chemotherapy. The incidence of viral reactivation in patients treated with histone deacetylase inhibitors is not yet known. We report the observation of EBV-associated illnesses in 2 patients and the reactivation of HBV in an additional patient treated with romidepsin. These cases may represent reactivation of DNA viruses due to histone deacetylase inhibitor induced immunosuppression, or direct promotion of viral replication via histone deacetylase inhibitor induced chromatin remodeling, or, alternatively, may be related to the underlying disease process. These observations suggest that vigilance for DNA virus reactivation is needed to quantify the risk in patients treated with histone deacetylase inhibitors.

[Endoscopic Diagnostics and Treatment of Flat Intestinal Lesions]

The aim of the article is to provide information on current options for endoscopic diagnostics and treatment of flat tumor intestinal lesions. These neoplasms are frequently and inaccurately described as sessile polyps, which have different genetic and diagnostic features, different prognosis and therapy. Although until recently, the lesions have been managed using surgery, the current approach is predominantly endoscopic.

Experimental and Density Functional Theory Study of the Tribochemical Wear Behavior of SiO2 in Humid and Alcohol Vapor Environments

This paper investigates the reaction steps involved in tribochemical wear of SiO(2) surfaces in humid ambient conditions and the mechanism of wear prevention due to alcohol adsorption. The friction and wear behaviors of SiO(2) were tested in three distinct gaseous environments at room temperature: dry argon, argon with 50% relative humidity (RH), and argon with n-pentanol vapor pressure 50% relative to the saturation pressure (P/P(sat)). Adsorbed gas molecules have significant chemical influences on the wear of the surface. The SiO(2) surface wears more readily in humid ambient compared to the dry case; however, it does not show any measurable wear in 50% P/P(sat) n-pentanol vapor at the same nominal contact load tested in the dry and humid environments. The tribochemical wear of the SiO(2) surface can be considered the Si-O-Si bond cleavage upon reactions with the impinging vapor molecules under tribological stress. DFT calculations were used to estimate the apparent activation energy needed to cleave the Si-O-Si bond at beta-cristobalite (111) and alpha-quartz (001) surfaces by reactions with impinging water and alcohol vapor molecules. The alkoxide termination of the SiO(2) surfaces increases the energy barrier required to cleave the Si-O-Si bonds when compared to hydroxyl-terminated SiO(2) surfaces.

Ab Initio Thermodynamic Evaluation of Pd Atom Interaction with CeO(2) Surfaces

Palladium supported on ceria is an effective catalytic material for three-way automotive catalysis, catalytic combustion, and solid-oxide fuel cell (SOFC) anodes. The morphology, oxidation state, and particle size of Pd on ceria affect catalytic activity and are a function of experimental conditions. This work utilizes ab initio thermodynamics using density functional theory (DFT) (DFT+U) methods to evaluate the stability of Pd atoms, PdO(x) species, and small Pd particles in varying configurations on CeO(2) (111), (110), and (100) single crystal surfaces. Over specific oxygen partial pressure and temperature ranges, palladium incorporation to form a mixed surface oxide is thermodynamically favorable versus other single Pd atom states on each ceria surface. For example, Pd atoms may incorporate into Ce fluorite lattice positions in a Pd(4+) oxidation state on the CeO(2) (111) surface. The ceria support shifts the transition between formal Pd oxidation states (Pd(0), Pd(2+), Pd(4+)) relative to bulk palladium and stabilizes certain oxidized palladium species on each surface. We show that temperature, oxygen pressure, and cell potential in a SOFC can influence the stable states of palladium supported on ceria surfaces, providing insight into structural stability during catalytic operation.

Urgent Segmental Resection As the Primary Strategy in Management of Benign Tracheal Stenosis. A Single Center Experience in 164 Consecutive Cases

The report is a retrospective review of 238 benign tracheal stenoses of various etiologies treated between 1995 and 2008. To show that urgent segmental resection has complication rates similar to elective resection and, therefore, preoperative dilation is not necessary, we analysed records of patients who underwent either standard segmental resections with anterolateral mediastinal tracheal mobilization, single-suture anastomosis and neck flexion; or insertion of T-tube with oval-shaped horizontal arm. Primary segmental resection was performed in 164 patients (68.9%), including 14 cases with concomitant tracheo-esophageal fistula (TEF). T-tube as an initial treatment suited 74 (31.1%) patients. We encountered two partial and one complete anastomotic disruptions following subglottic resections treated by T-tube insertion and costal cartilage tracheoplasty or permanent tracheostomy. Restenosis rate in segmental resection was 3.1%. No difference in complication rate between urgent and elective segmental resections was experienced. We treated a small number of patients by endotracheal stent insertion but the results were discouraging. Urgent segmental resection without prior rigid bronchoscopy dilation is our strategy of choice whenever possible. As an alternative to dilation we prefer temporary insertion of modified T-tube. Stand-alone endoluminal dilation and stenting has yet to prove its safety and long-term efficacy.

Prognostic Value of Adenosine Stress Cardiovascular Magnetic Resonance in Patients with Low-risk Chest Pain

Approximately 5% of patients with an acute coronary syndrome are discharged from the emergency room with an erroneous diagnosis of non-cardiac chest pain. Highly accurate non-invasive stress imaging is valuable for assessment of low-risk chest pain patients to prevent these errors. Adenosine stress cardiovascular magnetic resonance (AS-CMR) is an imaging modality with increasing application. The goal of this study was to evaluate the negative prognostic value of AS-CMR among low-risk acute chest pain patients.

Consideration of Endoscopic Retrograde Cholangiopancreatography in Cases of Acute Biliary Pancreatitis

The important question to be answered in all cases of ABP is whether or not a calculous biliary obstruction is still present. Answering this question conditions subsequent management, including the need for endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to determine the relationship between persistent common bile duct stone (CBDS) and laboratory values, and dilation of bile duct in order to find possible significant associations in patients with acute biliary pancreatitis (ABP).

Preliminary in Vivo Studies of a New Lecithin-based Formulation of Paclitaxel

Amorphous paclitaxel dissolves rapidly (1 mg mL(-1)) in an isotonic aqueous dispersion of egg lecithin (5% w/w), a new biocompatible submicron drug carrier consisting of structured aggregates with average size 0.5 microm. The solution is physically stable for at least 24 h and can be administered as an intravenous infusion. After a 5 h infusion in rabbits (0.66 mg kg(-1) h(-1)), changes in blood morphology were comparable to those observed in rabbits that received the commercial product Taxol. No changes in the enzyme profiles (alanine/aspartate aminotransferase or alkaline phosphatase) were observed. However, during infusion of the new formulation plasma concentration of paclitaxel (292 +/- 182 ng mL(-1)) was lower than observed after Cremophor-containing Taxol (540 +/- 262 ng mL(-1)). This result may indicate that the tissue distribution is different for the two drug formulations. Daily intraperitoneal administrations (3 doses/day) in mice demonstrated that the new carrier solution was non-toxic and, relative to Taxol, the new formulation exhibited similar or less toxicity.

Electronic Structure Models of Oxygen Adsorption at the Solvated, Electrified Pt(111) Interface

The adsorption of molecular oxygen is the first step in the oxygen reduction reaction. Influences of interfacial water structure and electrode potential on oxygen adsorption to the Pt(111) surface were evaluated using density functional theory. Two approaches were used to model the electrification of the interface, an applied homogeneous electric field and the double-reference method of Filhol, Taylor, and Neurock. The free energy change for molecular oxygen replacement of water at the surface shows qualitatively different trends between the two models. The inclusion of solvation effects and direct control of the electrode potential offered by the double-reference method lead to the conclusion that O(2) replacement of water is favorable at all potentials studied, and O(2) binding becomes more favorable with increasing potential. This trend is contrary to that observed using an external electric field model to represent the electrochemical double layer, and arises due to the compounded effect of potential on water-surface, oxygen-surface, and water-molecular oxygen interactions. These results indicate that oxygen replacement of adsorbed water does not limit the overall oxygen reduction reaction rate at a proton-exchange membrane fuel cell cathode. The impacts of aspects of model construction (number of water layers, water density) and variation of electrode potential on the O(2)-Pt(111) interaction are described.

Survivin(g) Adult T-cell Leukemia/lymphoma

Evaluation of Matrix Metalloproteinases in Serum of Patients with Amyotrophic Lateral Sclerosis with Pattern Recognition Methods

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases, which are present in central and peripheral nervous system. They are considered to be involved in the pathogenesis of several neurological diseases, as multiple sclerosis, Alzheimer disease, and amyotrophic lateral sclerosis (ALS). The aim of the present study was to evaluate the application of the pattern recognition methods for the assessment of MMPs in serum of patients with ALS. Thirty patients with amyotrophic lateral sclerosis (ALS), in two subgroups: (i) with mild and (ii) severe progressing ALS, and 15 control healthy subjects were studied. The metalloproteinases MT-MMP-1, MMP-2, MMP-9 were examined. Additional variables (age of subjects and disease duration) were also analyzed by using a standard, parallel and hierarchical classifiers. Our results indicate that: (i) MMP-2 in serum may be an important marker for the evaluation of ALS progress; (ii) the set of two features {MT-MMP-1, MMP-9} may be helpful in differentiation between ALS and healthy subjects; (iii) the error rates obtained for the pair-wise linear classifier were similar to those received for the classifiers (standard, parallel, and hierarchical) based on k-NN rule. We conclude that the pattern recognition methods may be useful for the evaluation of significance MMPs as markers in neurodegenerative diseases, such as ALS.

Itinerant Spin Excitations Near the Hidden Order Transition in URu(2)Si(2)

By means of neutron scattering we show that the high temperature precursor to the hidden order state of the heavy fermion superconductor URu(2)Si(2) exhibits heavily damped incommensurate paramagnons whose strong energy dispersion is very similar to that of the long-lived longitudinal f spin excitations that appear below T(0). This suggests that there is a strongly hybridized character to the itinerant excitations observed previously above the hidden order transition. Here we present evidence that the itinerant excitations, like those in chromium, are due to Fermi surface nesting of hole and electron pockets; hence the hidden order phase probably originates from a Fermi surface instability. We identify wavevectors that span nested regions of a f-d hybridized band calculation and that match the neutron spin crossover from incommensurate to commensurate on approach to the hidden order phase.

Low Frequency of the PARK2 Gene Mutations in Polish Patients with the Early-onset Form of Parkinson Disease

Mutations in the PARK2 (Parkin) gene result in an early-onset autosomal recessive form of Parkinson Disease (EO-PD). Although the frequency of the PARK2 mutations in EO-PD patients according to several studies is high and has been reported in up to 50% in familial and 19% in sporadic cases, these data remain controversial.

Influence of the Nature of Soil Organic Matter on the Sorption Behaviour of Pentadecane As Determined by PLS Analysis of Mid-infrared DRIFT and Solid-state 13C NMR Spectra

The nature of soil organic matter (SOM) functional groups associated with sorption processes was determined by correlating partitioning coefficients with solid-state (13)C nuclear magnetic resonance (NMR) and diffuse reflectance mid-infrared (DRIFT) spectral features using partial least squares (PLS) regression analysis. Partitioning sorption coefficients for n-pentadecane (n-C(15)) were determined for three alternative models: the Langmuir model, the dual distributed reactive domain model (DRDM) and the Freundlich model, where the latter was found to be the most appropriate. NMR-derived constitutional descriptors did not correlate with Freundlich model parameters. By contrast, PLS analysis revealed the most likely nature of the functional groups in SOM associated with n-C(15) sorption coefficients (K(F)) to be aromatic, possibly porous soil char, rather than aliphatic organic components for the presently investigated soils. High PLS cross-validation correlation suggested that the model was robust for the purpose of characterising the functional group chemistry important for n-C(15) sorption.

Blue-light-controlled Photoprotection in Plants at the Level of the Photosynthetic Antenna Complex LHCII

Plants have developed several adaptive regulatory mechanisms, operating at all the organization levels, to optimize utilization of light energy and to protect themselves against over-excitation-related damage. We report activity of a previously unknown possible regulatory mechanism that operates at the molecular level of the major photosynthetic pigment-protein complexes of plants, LHCII. This mechanism is driven exclusively by blue light, operates in the trimeric but not in the monomeric complex, and results in singlet excitation quenching leading to thermal energy dissipation. The conclusions are based on single molecule fluorescence lifetime analysis, direct measurements of thermal energy dissipation by photo-thermal spectroscopy, and on fluorescence spectroscopy. Possible molecular mechanisms involved in the blue-light-induced photoprotective effect are discussed, including xanthophyll photo-isomerization and the thermo-optic effect.

Matrix Metalloproteinases and Their Tissue Inhibitors in Serum and Cerebrospinal Fluid of Patients with Amyotrophic Lateral Sclerosis

Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). We investigated the expression of MMPs and tissue inhibitors of matrix metalloproteinases (TIMPs) in serum and cerebrospinal fluid (CSF) correlating the results with age, disease duration and the clinical course.

ZnTe-ZnO Core-shell Radial Heterostructures Grown by the Combination of Molecular Beam Epitaxy and Atomic Layer Deposition

ZnTe-ZnO core-shell radial heterostructures were grown using a new method of combining molecular beam epitaxy (MBE) and atomic layer deposition (ALD). Zinc telluride nanowires (core) were grown on a GaAs substrate using gold catalyzed vapor-liquid-solid mechanism. An atomic layer deposition technique using diethyl zinc and deionized water as precursors was applied for zinc oxide shell formation. The core-shell ZnTe-ZnO heterostructures thus obtained were characterized by scanning electron microscopy, transmission electron microscopy, x-ray diffraction and photoluminescence measurements.

Erythropoietin Concentration in Serum and Cerebrospinal Fluid of Patients with Amyotrophic Lateral Sclerosis

Erythropoietin (EPO) acts as a neuroprotective factor and is upregulated after neuronal injury. It has been reported that in cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients, the EPO concentration is decreased. In this study, EPO levels in serum and CSF of 30 patients with ALS and in 15 controls, using an ELISA technique, were estimated. EPO level in serum was decreased, especially in patients with bulbar onset ALS. A trend toward a progressive EPO decline with the duration of the disease in the mild + moderate ALS cases was observed. In severe cases, a tendency towards a positive correlation of EPO and duration of the disease was present. Serum EPO values were age related only in mild + moderate ALS in patients below 40 years of age. In CSF, the EPO levels were significantly decreased. Lower EPO values in the bulbar onset ALS when compared with the spinal onset ALS were present. The EPO decrease did not correlate with the severity and duration of the disease. Age relation of the EPO level only in the mild + moderate ALS cases more than 40 years was present. Lack of differences in EPO levels between patients with ALS of rapid and slow progression indicates that EPO concentration cannot be used as a prognostic factor. Nevertheless, the decreased serum and CSF EPO concentration and the known EPO neuroprotective action may indicate that EPO administration can be a new promising therapeutic approach in ALS.

Visual Inspection Versus Quantitative Flow Cytometry to Detect Aberrant CD2 Expression in Malignant T Cells

Abnormal levels of T-cell antigen expression occur in T-cell neoplasia. We examined CD2 expression in malignant and normal T cells to determine if the level of CD2 expression differed significantly and if quantitation assisted in detecting this difference.

Epicardial Adipose Tissue and Coronary Artery Plaque Characteristics

Epicardial adipose tissue (EAT) has been implicated in the pathogenesis of coronary atherosclerosis. The association of EAT volume with type of coronary artery plaque on computed tomography angiography (CTA) is not known.

Adenosine Stress Magnetic Resonance Imaging in Women with Low Risk Chest Pain: the Emory University Experience

The purpose of this study was to evaluate the accuracy of adenosine stress magnetic resonance imaging (ASMRI) for the evaluation of women with low-risk chest pain (CP).

Solvated Electron Extinction Coefficient and Oscillator Strength in High Temperature Water

The decadic extinction coefficient of the hydrated electron is reported for the absorption maximum from room temperature to 380 degrees C. The extinction coefficient is established by relating the transient absorption of the hydrated electrons in the presence of a scavenger to the concentration of stable product produced in the same experiment. Scavengers used in this report are SF(6,) N(2)O, and methyl viologen. The room temperature value is established as 22,500 M(-1) cm(-1), higher by 10-20% than values used over the last several decades. We demonstrate how previous workers arrived at a low value by incorrect choice of a radiolysis yield value. With this revision, the integrated oscillator strength, corrected by refractive index, is definitely (ca. 10%) larger than unity. This result is fully consistent with EPR and resonance Raman results which indicate mixing of the hydrated electron wave function with solvent electronic orbitals. Oscillator strength appears to be conserved vs temperature.

Interresidue Carbonyl-carbonyl Polarization Transfer Experiments in Uniformly 13C,15N-labeled Peptides and Proteins

In this work, we demonstrate that Homonuclear Rotary Resonance Recoupling (HORROR) can be used to reintroduce carbonyl-carbonyl interresidue dipolar interactions and to achieve efficient polarization transfer between carbonyl atoms in uniformly (13)C,(15)N-labeled peptides and proteins. We show that the HORROR condition is anisotropically broadened and overall shifted to higher radio frequency intensities because of the CSA effects. These effects are analyzed theoretically using Average Hamiltonian Theory. At spinning frequencies used in this study, 22kHz, this broadening is experimentally found to be on the order of a kilohertz at a proton field of 600MHz. To match HORROR condition over all powder orientations, variable amplitude radio frequency (RF) fields are required, and efficient direct transfers on the order of 20-30% can be straightforwardly established. Two- and three-dimensional chemical shift correlation experiments establishing long-range interresidue connectivities (e.g., (N[i]-CO[i-2])) are demonstrated on the model peptide N-acetyl-valine-leucine, and on the third immunoglobulin binding domain of protein G. Possible future developments are discussed.

Effect of Alpha3beta1 and Alphavbeta3 Integrin Glycosylation on Interaction of Melanoma Cells with Vitronectin

The metastatic transformation of melanocytes is associated with altered expression of adhesion molecules, including alpha(v)beta(3) and alpha(3)beta(1) integrins. Integrin alpha(v)beta(3) is a primary vitronectin (VN) receptor, while both integrin types take part in adhesion to VN when they are in complex with uPAR. Although their role in melanoma cell interaction with VN is of great interest, the influence of N-oligosaccharides attached to these glycoproteins is still unappreciated. The present study assesses the role of alpha(v)beta(3) and alpha(3)beta(1) integrins and the influence of their glycosylation status on WM9 and WM239 metastatic melanoma cell interactions with VN. Cell adhesion to and migration on VN were selected as the studied cell behaviour parameters. Function-blocking antibodies and swainsonine (SW) treatment were used in these tests. Both cell lines interacted with VN in an integrin-mediated but cell-line-specific manner. In WM9 cells, migration was not completely inhibited by antibodies against alpha(3)beta(1) or alpha(v)beta(3) integrins, suggesting the participation of other VN receptors. In both cell lines in coprecipitation test the formation of an integrins/uPAR complex was shown. In the presence of SW formation of the complex did not occur, suggesting the participation of glycosylation in this process. Additionally, the adhesion properties of WM9 cells were changed after SW treatment. Our results suggest that in these two metastatic cell lines integrin-linked N-oligosaccharides influence the VN adhesion receptor activity and function.

Carbonate Radical Formation in Radiolysis of Sodium Carbonate and Bicarbonate Solutions Up to 250 Degrees C and the Mechanism of Its Second Order Decay

Pulse radiolysis experiments published several years ago (J. Phys. Chem. A, 2002, 106, 2430) raised the possibility that the carbonate radical formed from reaction of *OH radicals with either HCO(3)(-) or CO(3)(2-) might actually exist predominantly as a dimer form, for example, *(CO(3))(2)(3-). In this work we re-examine the data upon which this suggestion was based and find that the original data analysis is flawed. A major omission of the original analysis is the recombination reaction *OH + *CO(3)(-) --> HOOCO(2)(-). Upon reanalysis of the published data for sodium bicarbonate solutions and analysis of new transient absorption data we are able to establish the rate constant for this reaction up to 250 degrees C. The mechanism for the second-order self-recombination of the carbonate radical has never been convincingly demonstrated. From a combination of literature data and new transient absorption experiments in the 1-400 ms regime, we are able to show that the mechanism involves pre-equilibrium formation of a C(2)O(6)(2-) dimer, which dissociates to CO(2) and peroxymonocarbonate anion: *CO3(-)+*CO3(-)<-->C2O6(2-)-->CO2+O2COO(2-) *CO3(-) reacts with the product peroxymonocarbonate anion, producing a peroxymonocarbonate radical *O2COO(-), which can also recombine with the carbonate radical: *CO3(-)+CO4(2-)-->*CO4(-)+CO3(2-) *CO3(-)+CO4(-)-->C2O7(2-).

Minimal Residual Disease Detection by Flow Cytometry in Adult T-cell Leukemia/lymphoma

Little information exists regarding the detection of minimal residual disease (MRD) in adult T-cell leukemia/lymphoma (ATLL). We evaluated 75 peripheral blood samples from 17 ATLL cases using flow cytometry (FC); 50 of the samples were concurrently evaluated by polymerase chain reaction (PCR) for clonal T-cell receptor gamma chain (TRG) gene rearrangement and the presence of human T-cell lymphotropic virus-1 proviral sequences. Residual ATLL cells were identified using a multiparametric approach to identify aberrant T-cell immunophenotypes. Malignant T cells were CD4+, CD3 dim+, CD26-, CD25 bright, CD7+, and CD27+, with occasional dim expression of CD2 or CD5. FC exhibited a high sensitivity, detecting as few as 0.29% ATLL cells/WBC (4.9 cells/microL) in the peripheral blood. PCR for TRG gene rearrangement was slightly more sensitive, and FC and PCR complemented each other in detecting MRD. In 2 patients, there was complete remission; 4 patients had disease refractory to therapy, and 3 died; 11 others had persistent disease with variable numbers of ATLL cells in the peripheral blood. Higher levels of ATLL cells appeared to correlate with disease severity. FC detection of aberrant T cells permits sensitive and quantitative monitoring of MRD in ATLL.

Cell Migration-the Role of Integrin Glycosylation

Cell migration is an essential process in organ homeostasis, in inflammation, and also in metastasis, the main cause of death from cancer. The extracellular matrix (ECM) serves as the molecular scaffold for cell adhesion and migration; in the first phase of migration, adhesion of cells to the ECM is critical. Engagement of integrin receptors with ECM ligands gives rise to the formation of complex multiprotein structures which link the ECM to the cytoplasmic actin skeleton. Both ECM proteins and the adhesion receptors are glycoproteins, and it is well accepted that N-glycans modulate their conformation and activity, thereby affecting cell-ECM interactions. Likely targets for glycosylation are the integrins, whose ability to form functional dimers depends upon the presence of N-linked oligosaccharides. Cell migratory behavior may depend on the level of expression of adhesion proteins, and their N-glycosylation that affect receptor-ligand binding.

Actin Re-organization Induced by Chlamydia Trachomatis Serovar D--evidence for a Critical Role of the Effector Protein CT166 Targeting Rac

The intracellular bacterium Chlamydia trachomatis causes infections of urogenital tract, eyes or lungs. Alignment reveals homology of CT166, a putative effector protein of urogenital C. trachomatis serovars, with the N-terminal glucosyltransferase domain of clostridial glucosylating toxins (CGTs). CGTs contain an essential DXD-motif and mono-glucosylate GTP-binding proteins of the Rho/Ras families, the master regulators of the actin cytoskeleton. CT166 is preformed in elementary bodies of C. trachomatis D and is detected in the host-cell shortly after infection. Infection with high MOI of C. trachomatis serovar D containing the CT166 ORF induces actin re-organization resulting in cell rounding and a decreased cell diameter. A comparable phenotype was observed in HeLa cells treated with the Rho-GTPase-glucosylating Toxin B from Clostridium difficile (TcdB) or HeLa cells ectopically expressing CT166. CT166 with a mutated DXD-motif (CT166-mut) exhibited almost unchanged actin dynamics, suggesting that CT166-induced actin re-organization depends on the glucosyltransferase motif of CT166. The cytotoxic necrotizing factor 1 (CNF1) from E. coli deamidates and thereby activates Rho-GTPases and transiently protects them against TcdB-induced glucosylation. CNF1-treated cells were found to be protected from TcdB- and CT166-induced actin re-organization. CNF1 treatment as well as ectopic expression of non-glucosylable Rac1-G12V, but not RhoA-G14A, reverted CT166-induced actin re-organization, suggesting that CT166-induced actin re-organization depends on the glucosylation of Rac1. In accordance, over-expression of CT166-mut diminished TcdB induced cell rounding, suggesting shared substrates. Cell rounding induced by high MOI infection with C. trachomatis D was reduced in cells expressing CT166-mut or Rac1-G12V, and in CNF1 treated cells. These observations indicate that the cytopathic effect of C. trachomatis D is mediated by CT166 induced Rac1 glucosylation. Finally, chlamydial uptake was impaired in CT166 over-expressing cells. Our data strongly suggest CT166's participation as an effector protein during host-cell entry, ensuring a balanced uptake into host-cells by interfering with Rac-dependent cytoskeletal changes.

Aversiveness of Sounds in Phocid Seals: Psycho-physiological Factors, Learning Processes and Motivation

Aversiveness of sounds and its underlying physiological mechanisms in mammals are poorly understood. In this study we tested the influence of psychophysical parameters, motivation and learning processes on the aversiveness of anthropogenic underwater noise in phocid seals (Halichoerus grypus and Phoca vitulina). We compared behavioural responses of seals to playbacks of sounds based on a model of sensory unpleasantness for humans, sounds from acoustic deterrent devices and sounds with assumed neutral properties in different contexts of food motivation. In a captive experiment with food presentation, seals habituated quickly to all sound types presented at normalised received levels of 146 dB re. 1 microPa (r.m.s., root mean square). However, the fast habituation of avoidance behaviour was also accompanied by a weak sensitisation process affecting dive times and place preference in the pool. Experiments in the wild testing animals without food presentation revealed differential responses of seals to different sound types. We observed avoidance behaviour at received levels of 135-144 dB re. 1 microPa (sensation levels of 59-79 dB). In this experiment, sounds maximised for 'roughness' perceived as unpleasant by humans also caused the strongest avoidance responses in seals, suggesting that sensory pleasantness may be the result of auditory processing that is not restricted to humans. Our results highlight the importance of considering the effects of acoustic parameters other than the received level as well as animal motivation and previous experience when assessing the impacts of anthropogenic noise on animals.

Safety, Tolerability, and Mechanisms of Antiretroviral Activity of Pegylated Interferon Alfa-2a in HIV-1-monoinfected Participants: a Phase II Clinical Trial

To our knowledge, the antiviral activity of pegylated interferon alfa-2a has not been studied in participants with untreated human immunodeficiency virus type 1 (HIV-1) infection but without chronic hepatitis C virus (HCV) infection.

Epicardial Adipose Tissue Volume and Coronary Artery Calcium to Predict Myocardial Ischemia on Positron Emission Tomography-computed Tomography Studies

There appears to be an association of epicardial adipose tissue (EAT) with coronary artery disease (CAD) and its risk factors. EAT is assumed to influence CAD development by altering vasomotor tone and via toxic paracrine effects. The relationship of EAT to myocardial perfusion has not been studied.

Spectrum of the Product of Independent Random Gaussian Matrices

We show that the eigenvalue density of a product X=X1X2...XM of M independent NxN Gaussian random matrices in the limit N-->infinity is rotationally symmetric in the complex plane and is given by a simple expression rho(z,z)=1/Mpisigma(-2/M)|z|(-2+(2/M)) for |z|sigma. The parameter sigma corresponds to the radius of the circular support and is related to the amplitude of the Gaussian fluctuations. This form of the eigenvalue density is highly universal. It is identical for products of Gaussian Hermitian, non-Hermitian, and real or complex random matrices. It does not change even if the matrices in the product are taken from different Gaussian ensembles. We present a self-contained derivation of this result using a planar diagrammatic technique. Additionally, we conjecture that this distribution also holds for any matrices whose elements are independent centered random variables with a finite variance or even more generally for matrices which fulfill Pastur-Lindeberg's condition. We provide a numerical evidence supporting this conjecture.

A Rare Coincidence of Two Coronary Anomalies in an Adult

Anomalous right-sided left main coronary arteries and dual type IV left anterior descending arteries are rare coronary anomalies. In this case report, we present a 59 year old man with atypical chest pain and a combination of the above coronary anomalies as identified by selective coronary angiography and computed tomography angiography. To the best of our knowledge, the coincidence of these coronary anomalies has not been previously described.

DMP1 C-terminal Mutant Mice Recapture the Human ARHR Tooth Phenotype

DMP1 mutations in autosomal recessive hypophosphatemic rickets (ARHR) patients and mice lacking Dmp1 display an overlapping pathophysiology, such as hypophosphatemia. However, subtle differences exist between the mouse model and human ARHR patients. These differences could be due to a species specificity of human versus mouse, or it may be that the mutant DMP1 in humans maintains partial function of DMP1. In this study we report a deformed tooth phenotype in a human DMP1 deletion mutation case. Unexpectedly, the deletion of nucleotides 1484 to 1490 (c.1484_1490delCTATCAC, delMut, resulting in replacement of the last 18 residues with 33 random amino acids) showed a severe dentin and enamel defect similar to a dentinogenesis imperfecta (DI) III-like phenotype. To address the molecular mechanism behind this phenotype, we generated delMut transgenic mice with the endogenous Dmp1 gene removed. These mutant mice did not recapture the abnormal phenotype observed in the human patient but displayed a mild rachitic tooth phenotype in comparison with that in the Dmp1-null mice, suggesting that the DI III-like phenotype may be due to an as-yet-undetermined acquired gene modifier. The mechanism studies showed that the mutant fragment maintains partial function of DMP1 such as stimulating MAP kinase signaling in vitro. Last, the in vitro and in vivo data support a role of odontoblasts in the control of fibroblast growth factor 23 (FGF-23) regulation during early postnatal development, although this regulation on Pi homeostasis is likely limited.

TEM Characterization of MBE Grown CdTe/ZnTe Axial Nanowires

CdTe/ZnTe axial nanowires were successfully fabricated by molecular beam epitaxy with the use of Au nano-catalysts and vapour-liquid-solid growth mechanism. Nanowires had zinc-blende structure with numerous stacking faults in the bottom ZnTe part and near perfect crystalline structure in the top CdTe part. Energy dispersive X-ray spectroscopy (EDXS) and lattice fringe spacing analysis revealed nonabrupt nature of hetero-interface, whose width was estimated to be 50-70 nm for the nanowires having a diameter in the range from 40 to 50 nm.

Vaginal Birth After Cesarean: New Insights on Maternal and Neonatal Outcomes

To systematically review the evidence about maternal and neonatal outcomes relating to vaginal birth after cesarean (VBAC).

Oxidative Stress and 8-oxoguanine Repair Are Enhanced in Colon Adenoma and Carcinoma Patients

Oxidative stress is involved in the pathogenesis of colon cancer. We wanted to elucidate at which stage of the disease this phenomenon occurs. In the examined groups of patients with colorectal cancer (CRC, n = 89), benign adenoma (AD, n = 77) and healthy volunteers (controls, n = 99), we measured: vitamins A, C and E in blood plasma, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) in leukocytes and urine, leukocyte 8-oxoGua excision activity, mRNA levels of APE1, OGG1, 8-oxo-7,8-dihydrodeoxyguanosine 5'-triphosphate pyrophosphohydrolase (MTH1) and OGG1 polymorphism. The vitamin levels decreased gradually in AD and CRC patients. 8-OxodG increased in leukocytes and urine of CRC and AD patients. 8-OxoGua was higher only in the urine of CRC patients. 8-OxoGua excision was higher in CRC patients than in controls, in spite of higher frequency of the OGG1 Cys326Cys genotype, encoding a glycosylase with decreased activity. mRNA levels of OGG1 and APE1 increased in CRC and AD patients, which could explain increased 8-oxoGua excision rate in CRC patients. MTH1 mRNA was also higher in CRC patients. The results suggest that oxidative stress occurs in CRC and AD individuals. This is accompanied by increased transcription of DNA repair genes, and increased 8-oxoGua excision rate in CRC patients, which is, however, insufficient to counteract the increased DNA damage.

Mouse Sarcoma L1 Cell Line Holoclones Have a Stemness Signature

Accumulating data suggest that cancers contain a fraction of cells called cancer stem cells (CSCs), that may be responsible for upkeep and relapses of disease. In experimental settings, CSCs are regarded as most effective at tumour initiation in in vivo assays. Since the first isolation of cancer stem cells from acute myeloid leukaemia in 1994, cancer stem cells have been identified in human solid tumours and they have also been found in the established cell lines, based on ability of CSCs to form in vitro colonies of a specific morphology, called holoclones. Our study examined the ability of a mouse sarcoma cell line, derived from a lung metastasis of a BALB/c mouse and established as a stably growing line (L1), to produce holoclones in vitro. We aimed to verify a stemness signature of the holoclone cells. The L1 cell line was found to form holoclone colonies in vitro, which were shown to contain a percentage of CSC-like cells. A fraction of the L1 cells was able to repopulate the original cell line, and presented an increased clonogenic and metastatic potential (18th passage). In addition, MTT assay and flow cytometry of the side population fraction revealed that these cells were more resistant to chemotherapeutic drugs than the original cell line, and over-expressed the anti-apoptotic genes, GRP78 and GADD153. We conclude that mouse L1 sarcoma cell line contains CSC-like cells.

Involvement of Oxidatively Damaged DNA and Repair in Cancer Development and Aging

DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important factors in the development and pathology of an organism, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen species (RNS) directly and also by products of lipid peroxidation (LPO), which form exocyclic adducts to DNA bases. A wide variety of oxidatively-generated DNA lesions are present in living cells. 8-oxoguanine (8-oxoGua) is one of the best known DNA lesions due to its mutagenic properties. Among LPO-derived DNA base modifications the most intensively studied are ethenoadenine and ethenocytosine, highly miscoding DNA lesions considered as markers of oxidative stress and promutagenic DNA damage. Although at present it is impossible to directly answer the question concerning involvement of oxidatively damaged DNA in cancer etiology, it is likely that oxidatively modified DNA bases may serve as a source of mutations that initiate carcinogenesis and are involved in aging (i.e. they may be causal factors responsible for these processes). To counteract the deleterious effect of oxidatively damaged DNA, all organisms have developed several DNA repair mechanisms. The efficiency of oxidatively damaged DNA repair was frequently found to be decreased in cancer patients. The present work reviews the basis for the biological significance of DNA damage, particularly effects of 8-oxoGua and ethenoadduct occurrence in DNA in the aspect of cancer development, drawing attention to the multiplicity of proteins with repair activities.

Pt Promotion and Spill-over Processes During Deposition and Desorption of Upd-H(ad) and OH(ad) on Pt(x)Ru(1-x)/Ru(0001) Surface Alloys

The electrochemical adsorption of underpotential deposited hydrogen (upd-H(ad)) and OH(ad) on structurally well-defined Pt(x)Ru(1-x)/Ru(0001) surface alloys was investigated by cyclic voltammetry and density functional theory (DFT) calculations. The adsorption energies of both upd-H(ad) and OH(ad) decrease with increasing Pt content in the adsorption ensemble, shifting the onset of upd-H(ad) and OH(ad) formation to increasingly cathodic and anodic potentials, respectively. For bare Ru(0001) and for Ru(3) sites in the surface alloy, the stability regions of these two species overlap or almost overlap, respectively. Similar to previous findings for upd-H(ad) adsorption/desorption on partly Pt monolayer island covered Ru(0001) surfaces (J. Phys. Chem. B 2004, 108, 14780), we find a sharp peak at approximately 100 mV vs. RHE in each scan direction, which is attributed to a Pt catalyzed OH(ad)<--> upd-H(ad) replacement on Ru(3) sites, via adsorption on Pt rich sites and spill-over to Ru(3) sites. The decrease of the integrated charge in these peaks with the third power of the Ru surface concentration, which for a random distribution of surface atoms reflects the availability of Ru(3) sites, supports the above assignment.

Aberrant Repair of Etheno-DNA Adducts in Leukocytes and Colon Tissue of Colon Cancer Patients

To assess the role of lipid peroxidation-induced DNA damage and repair in colon carcinogenesis, the excision rates and levels of 1,N(6)-etheno-2'-deoxyadenosine (epsilondA), 3,N(4)-etheno-2'-deoxycytidine (epsilondC), and 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-epsilondG) were analyzed in polymorphic blood leukocytes (PBL) and resected colon tissues of 54 colorectal carcinoma (CRC) patients and PBL of 56 healthy individuals. In PBL the excision rates of 1,N(6)-ethenoadenine (epsilonAde) and 3,N(4)-ethenocytosine (epsilonCyt), measured by the nicking of oligodeoxynucleotide duplexes with single lesions, and unexpectedly also the levels of epsilondA and 1,N(2)-epsilondG, measured by LC/MS/MS, were lower in CRC patients than in controls. In contrast the mRNA levels of repair enzymes, alkylpurine- and thymine-DNA glycosylases and abasic site endonuclease (APE1), were higher in PBL of CRC patients than in those of controls, as measured by QPCR. In the target colon tissues epsilonAde and epsilonCyt excision rates were higher, whereas the epsilondA and epsilondC levels in DNA, measured by (32)P-postlabeling, were lower in tumor than in adjacent colon tissue, although a higher mRNA level was observed only for APE1. This suggests that during the onset of carcinogenesis, etheno adduct repair in the colon seems to be under a complex transcriptional and posttranscriptional control, whereby deregulation may act as a driving force for malignancy.

The Analysis of Selected Neurotransmitter Concentrations in Serum of Patients with Tourette Syndrome

Metabolic disturbances of excitatory and inhibitory neurotransmitters are implicated in pathogenesis of Tourette syndrome (TS). The aim of the study was to measure serum concentrations of glutamic acid, g-aminobutyric acid (GABA) and glycine in TS patients and evaluate any correlation between neurotransmitter levels and age at onset, actual age, gender, tic severity, duration of the disease and concomitant psychiatric disorders.

Structural and Functional Modifications of the Major Light-harvesting Complex II in Cadmium- or Copper-treated Secale Cereale

The effects of 50 microM cadmium (Cd) or copper (Cu) ions on the supramolecular conformation of the light-harvesting pigment-protein complex of PSII (LHCII) isolated from rye seedlings were studied. It was found that the action of these two metal ions on the LHCII structure and organization is dissimilar. The Fourier transform infrared (FTIR) measurements indicated inhibition or stimulation of formation of parallel beta-structures and aggregates in the presence of Cd or Cu ions, respectively. The Chl a fluorescence excitation spectra of LHCII extracted from Cd-treated plants showed that the decreased aggregation of complexes was correlated with a decline in efficiency of quenching of excitation energy. From the results of mass spectrometry, changes in LHCII aggregation in the presence of Cd ions might be based on decreases in the molecular mass of Lhcb1 and Lhcb2 proteins. An increase in the content of LHCII aggregates under Cu ion excess was associated with changes in the LHCII xanthophyll pigment pool. In the complexes isolated from Cu-treated plants, all-trans violaxanthin and 9'-cis neoxanthin content declined and the simultaneous appearance of the fraction of 9-cis violaxanthin was observed. 9-cis violaxanthin formation under Cu ion excess might facilitate LHCII inter-trimer interaction and, therefore, aggregation of complexes. RLS (resonance light scattering) spectra indicated that the excitonic interaction between Chl molecules and between Chls and xanthophylls was responsible for the effective dissipation of excitation energy in LHCII isolated from Cu-treated plants. Also, changes in singlet excitation energy transfer between carotenoids and Chls under the action of heavy metals were observed.

Vaginal Birth After Cesarean: New Insights

To synthesize the published literature on vaginal birth after cesarean (VBAC). Specifically, to review the trends and incidence of VBAC, maternal benefits and harms, infant benefits and harms, relevant factors influencing each, and the directions for future research.

The Photoprotective Mechanisms in Secale Cereale Leaves Under Cu and High Light Stress Condition

The influence of excess Cu ions and high light treatment on the function of photosystem II was investigated in order to examine how this heavy metal modifies the photoprotective mechanisms operating at the molecular level in Secale cereale plants. Thus, non-treated plants and those treated with 5 or 50 microM Cu, simultaneously illuminated with 150 micromol m(-2) s(-1) or 1200 micromol m(-2) s(-1) light intensity, were studied. To analyze the PSII reaction to the stress conditions, Chl a fluorescence induction was applied. An increase in the value of Phi(PSII) and R(fd) parameters indicated that the photosynthetic apparatus adapted to the high light condition by effective utilization of excitation energy in the light and dark phases of photosynthesis. This phenomenon was accompanied by dissipation of excitation energy within the antenna complexes. The xanthophyll cycle pigments in Secale cereale leaves were separated and quantified by the HPLC technique. The results showed that, under high light irradiance, both 5 and 50 microM Cu induced the process of violaxanthin de-epoxidation and zeaxanthin accumulation. The significant zeaxanthin accumulation was found to be involved in photoprotective energy dissipation as heat, which was supported by correlation between the rate of violaxanthin de-epoxidation and the value of SV parameters. Interestingly, Cu treatment caused violaxanthin isomerization from its trans to 15-, 13- and 9-cis forms in proportional correlation to the metal concentration. This phenomenon was confirmed by a study of Cu-induced violaxanthin isomerization in vitro, which suggests a direct metal-pigment molecule interaction. We also observed that the violaxanthin trans-cis isomerization increased simultaneously with anteraxanthin content. On the basis of these findings, it can be speculated that violaxanthin isomerization is the basic process responsible for the xanthophyll cycle operation.

A Multiplex Immunoassay Using the Guthrie Specimen to Detect T-cell Deficiencies Including Severe Combined Immunodeficiency Disease

Severe combined immunodeficiency (SCID) fulfills many of the requirements for addition to a newborn screening panel. Two newborn screening SCID pilot studies are now underway using the T-cell receptor excision circle (TREC) assay, a molecular technique. Here we describe an immunoassay with CD3 as a marker for T cells and CD45 as a marker for total leukocytes that can be used with the Guthrie specimen.

[Computed Tomography Laser Mammography]

Computed tomography laser mammography (CTLM) is a new examination method, which is used for visualization of vascular structures, not only physiological blood vessels, but also neovascularization. Neovascularization can accompany growing malignant tumour. CTLM uses laser beam of the wavelength equal to 808 nanometres, which is absorbed in blood pigments of physiological and pathological blood-vessels and is able to display their distribution. CTLM offers new possibilities of breast disease diagnostic with demonstration of neovascularisation. CTLM is able to recognize malignant tumour from benign lesion. At present, CTLM is used only as a supplementary method of the basic examination.

Eradication of B-lineage Cells and Regression of Lymphoma in a Patient Treated with Autologous T Cells Genetically Engineered to Recognize CD19

Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) that recognized the B-cell antigen CD19. The patient's lymphoma underwent a dramatic regression, and B-cell precursors were selectively eliminated from the patient's bone marrow after infusion of anti-CD19-CAR-transduced T cells. Blood B cells were absent for at least 39 weeks after anti-CD19-CAR-transduced T-cell infusion despite prompt recovery of other blood cell counts. Consistent with eradication of B-lineage cells, serum immunoglobulins decreased to very low levels after treatment. The prolonged and selective elimination of B-lineage cells could not be attributed to the chemotherapy that the patient received and indicated antigen-specific eradication of B-lineage cells. Adoptive transfer of anti-CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies. This study is registered at www.clinicaltrials.gov as #NCT00924326.

Multiple Papules and Nodules of the Scalp. Angiolymphoid Hyperplasia with Eosinophilia (ALHE)

Long-term Determination of Airborne Radon Progeny Concentrations Using LR 115 Detectors and the Effects of Thoron

The 'proxy equilibrium factor' (F(p)) method has been developed for long-term determination of airborne radon progeny concentrations using LR 115 solid-state nuclear track detectors. In this paper, the effects of (220)Rn on the F(p) method have been studied. The correction to the track density was related to a parameter α which was the ratio of the sum of activity concentrations of alpha-particle emitting radionuclides in the (220)Rn decay chain to the activity concentration of (220)Rn alone. Under commonly encountered circumstances, α could not be smaller than 2. An attempt was made to verify this using the exposure chamber at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. A most interesting observation of α < 2 for very high (220)Rn concentrations and very low equilibrium factors for (220)Rn in the exposure chambers was made. A possible explanation was the substantial deposition of (216)Po under the extreme conditions inside the exposure chambers.

Preliminary Indoor Thoron Measurements in High Radiation Background Area of Southeastern Coastal Orissa, India

This paper presents the preliminary results of radon and thoron measurements in the houses of Chhatrapur area of southeastern coast of Orissa, India. This area is one of the high radiation background radiation areas in India, which consists of monazite sand as the source of thoron. Both active and passive methods were employed for the measurements. Radon and thoron concentrations were measured in the houses of Chhatrapur area using twin cup radon dosemeters, RAD7 and radon-thoron discriminative detector (Raduet). Thoron progeny concentration was also measured in the houses using deposition rate measurements. Radon and thoron concentrations in the houses of study area were found to vary from 8 to 47 Bq m(-3) and the below detection level to 77 Bq m(-3), respectively. While thoron progeny concentration in these houses ranges between 0.17 and 4.24 Bq m(-3), preliminary investigation shows that the thoron concentration is higher than radon concentration in the houses of the study area. The thoron progeny concentration was found to be comparatively higher, which forms a base for further study in the area. The comparison between the results of various techniques is presented in this paper.

Quality Assurance and Quality Control for Thoron Measurement at NIRS

The National Institute of Radiological Sciences (NIRS) has developed passive radon ((222)Rn)-thoron ((220)Rn) discriminative detectors for a large-scale survey and has established a thoron chamber to calibrate such detectors. In order to establish quality assurance and quality control for the (220)Rn measurement at NIRS, intercomparison studies have been carried out. The intercomparisons using a scintillation cell method, which has been used as a standard for (220)Rn measurement at NIRS, were conducted at New York University (NYU, USA) and Physikalisch-Technische Bundesanstalt (PTB, Germany). As a result, it was found that the result from the NIRS was in good agreement with that from the NYU. On the other hand, it was observed that the relative discrepancy between the (220)Rn concentrations from the NIRS and PTB monitors was, on average, >50 %. Using the NIRS (220)Rn chamber, the international intercomparison experiment for passive (220)Rn detectors started in 2008.

Separately Measuring Radon and Thoron Concentrations Exhaled from Soil Using AlphaGUARD and Liquid Scintillation Counter Methods

It was shown that radon and thoron concentrations exhaled from soil were separately measured using the AlphaGUARD and liquid scintillation counter (LSC) methods. The thoron concentrations from the RAD 7 were used to create the conversion equation to calculate thoron levels with the AlphaGUARD. However, the conversion factor was found to depend on the air flow rate. When air containing thoron of ∼60 kBq m(-3) was fed to the scintillation cocktail, thoron and thoron progeny could not be measured with the LSC method. The radon concentration of about 10 kBq m(-3) was measured with three methods, first with the LSC method and then with two AlphaGUARDs (one in the diffusion mode and the other in the flow mode (0.5 l min(-1))). There were no significant differences between these results. Finally, it was shown that the radon and thoron concentrations in air could be measured with the AlphaGUARD and LSC methods.

A Comparative Study of Thorium Activity in NORM and High Background Radiation Area

Several industrial processes are known to enrich naturally occurring radioactive materials (NORM). To assess such processes with respect to their radiological relevance, characteristic parameters describing this enrichment will lead to interesting information useful to UNSCEAR. In case of mineral treatment plants, the high temperatures used in smelting and refining processes lead to high concentrations of (238)U and (232)Th. Also due to thermal power combustion, concentration of U and Th in the fly ash increases manifold. NORM samples were collected from a Thailand mineral treatment plant and Philippine coal-fired thermal power plants for investigation. Some studies are initiated from a high background radiation area near Gopalpur of Orissa state in India. These NORM samples were analysed by gamma-ray spectrometry as well as inductively coupled plasma mass spectrometry. The radioactivity in case of Orissa soil samples is found to be mainly contributed from thorium. This study attempts to evaluate levels of thorium activity in NORM samples.

Influence of Soil Environmental Parameters on Thoron Exhalation Rate

Field measurements of thoron exhalation rates have been carried out using a ZnS(Ag) scintillation detector with an accumulation chamber. The influence of soil surface temperature and moisture saturation on the thoron exhalation rate was observed. When the variation of moisture saturation was small, the soil surface temperature appeared to induce a strong effect on the thoron exhalation rate. On the other hand, when the variation of moisture saturation was large, the influence of moisture saturation appeared to be larger than the soil surface temperature. The number of data ranged over 405, and the median was estimated to be 0.79 Bq m(-2) s(-1). Dependence of geology on the thoron exhalation rate from the soil surface was obviously found, and a nationwide distribution map of the thoron exhalation rate from the soil surface was drawn by using these data. It was generally high in the southwest region than in the northeast region.

International Intercomparisons of Integrating Radon/thoron Detectors with the NIRS Radon/thoron Chambers

Intercomparisons of radon/thoron detectors play an important role not only for domestic radon/thoron survey but also for international or interregional discussion about radon/thoron mapping in dwellings as well as that in the soil. For these purposes, it is necessary to improve and standardise technical methods of measurement and to verify quality assurance by intercomparisons between laboratories. Therefore, the first thoron international intercomparison was provided at the NIRS (National Institute of Radiological Sciences, Japan) thoron chamber with a 150 dm(3) inner volume. In addition, a second intercomparison of radon detectors was conducted at NIRS with a 24.4 m(3) inner volume walk-in radon chamber. Only etched-track detectors were used during thoron intercomparison as well as three types for the radon intercomparison: etched-track, charcoal and electret. In general, 45 % results for thoron experiment do not differ more than 20 % from the reference value of thoron concentration and 69 % for radon.

Autocrine/paracrine Cytokine Stimulation of Leukemic Cell Proliferation in Smoldering and Chronic Adult T-cell Leukemia

Adult T-cell leukemia (ATL), a heterogeneous disease, can be divided into smoldering, chronic, lymphoma, and acute types clinically. In addition to different clinical manifestations, different stages of ATL have different molecular signatures. Here, we demonstrated that smoldering/chronic ATL peripheral blood mononuclear cells spontaneously proliferated ex vivo in a cytokine (interleukin-12 [IL-12]/IL-9/IL-15)-dependent manner, while acute-type ATL peripheral blood mononuclear cells did not proliferate or proliferated independent of cytokines. Smoldering/chronic ATL cells produced IL-2 and IL-9 in 6-day ex vivo cultures. Interestingly, the addition of an anti-IL-2R-α monoclonal antibody profoundly inhibited IL-9 expression, suggesting optimal expression of IL-9 was dependent on IL-2 signaling in these patients. To determine whether there would be autonomous proliferation of ATL leukemic cells, we purified leukemic cells from patients with smoldering/chronic ATL. Purified leukemic cells cultured alone produced IL-2/IL-9, and the downstream Janus kinase/signal transducer and activator of transcription pathway was activated. However, the leukemic cells did not proliferate independently, but required coculture with autologous monocytes to induce proliferation. Moreover, interaction between leukemic cells and monocytes was contact dependent, and major histocompatibility complex class II expression may have contributed to this interaction. In conclusion, our data provide evidence that there is autocrine/paracrine cytokine stimulation of leukemic cell proliferation in patients with smoldering/chronic ATL that could be targeted for treatment.

New Insights on Vaginal Birth After Cesarean: Can It Be Predicted?

To evaluate existing vaginal birth after cesarean (VBAC) screening tools and to identify additional factors that may predict VBAC or failed trial of labor.

Midrapidity Antiproton-to-proton Ratio in Pp Collisons at Sqrt[s]=0.9 and 7 TeV Measured by the ALICE Experiment

The ratio of the yields of antiprotons to protons in pp collisions has been measured by the ALICE experiment at sqrt[s]=0.9 and 7 TeV during the initial running periods of the Large Hadron Collider. The measurement covers the transverse momentum interval 0.45

Clear Cell Acanthoma: a Rare Clinical Diagnosis Prior to Biopsy

Clear cell acanthoma is a rare, benign epidermal tumor with a clinical hybrid appearance and a distinct histological one. It is frequently mistaken for other clinical lesions.

Elemental Composition of Physarum Compressum Alb. Et Schw. Sporocarps and Their Structures Cultivated on Rabbit Dung and Agar Substrates

The elemental composition of spores, peridium walls, and lime nodes of Physarum compressum sporocarps, cultivated on rabbit dung as a natural growing environment for the slime mold and on artificial agar medium, was compared to evaluate differences that may be dependent on substrates. Whole fruiting bodies and samples of both experimental media were extracted with nitric acid or Parr digest bomb, respectively, and analyzed by means of total X-ray reflection fluorescence (TXRF). Electron probe microanalysis (EPMA) of spores, peridium walls, and lime nodes structure was carried out with the scanning electron microscope equipped with energy-dispersive spectrometer. Because of minute sizes and roughness of investigated structures, Monte Carlo simulations were utilized to establish analytical conditions of EPMA. Biological and geological standards were used in the quantification of element concentrations. According to TXRF, the fruiting bodies from agar medium revealed lower concentrations of K, Ca, Cr, Mn, and Fe in relation to fruiting bodies from the dung, reflecting elemental relationships in the experimental media. According to EPMA, the highest Ca concentration was found in the lime nodes followed by the peridium and the spores. Culturing of the slime molds on the rabbit dung indicated higher concentration of Ca in the lime nodes and peridium walls when compared with those obtained from the sporocarps grown on agar media. The opposite relation was found for the spores. The concentration of Na, Mg, P, S, and Cl was generally lower in all structures of the sporocarps harvested from the dung than from the agar medium. K was in higher concentration in analyzed structures from dung than from agar. Different element uptake (except for Ca and K) was revealed by the two methods: TXRF and EPMA.

[Possibilities and Results of Surgical Treatment of Benign Tracheoesophageal Fistula]

Review of literature and a single-institution retrospective analysis of possibilities and results of various surgical techniques in treatment of benign tracheoesophageal fistula (TEF).

[The Management of Restenosis Following Segmental Resection for Postintubation Tracheal Injury]

In dealing with benign tracheal stenosis, segmental tracheal resection yields superior results in experienced hands when properly indicated, timed end executed. Several factors may contribute to early or delayed failure of resectional treatment. In our retrospective study we analyze the potential causes of tracheal restenosis in patients who underwent segmental tracheal resection for benign tracheal stenosis between 1995-2009 and propose an algorithm for prevention and treatment of such complication.

New Strategies in Peripheral T-cell Lymphoma: Understanding Tumor Biology and Developing Novel Therapies

Peripheral T-cell lymphomas (PTCL) constitute a group of heterogeneous diseases that are uncommon, representing, in Western countries, only approximately 10% of all non-Hodgkin lymphomas. They are typically associated with a poor prognosis compared with their B-cell counterparts and are much less well understood with respect to tumor biology, owing to their rarity and biologic heterogeneity, and to the fact that characteristic cytogenetic abnormalities are few compared with B-cell lymphomas. Although the outcome for patients with anaplastic large cell lymphoma (ALCL), particularly anaplastic lymphoma kinase (ALK)-positive ALCL, is good, other types of PTCLs are associated with a poor prognosis, even with aggressive anthracycline-based chemotherapy. In this respect, there is a need for new approaches in these diseases, and this review focuses on and explores recent experience with novel therapies in PTCL.

Neuroimaging Diagnosis in Neurodegenerative Diseases

Dementia affects about 8% of people age 65 years and older. Identification of dementia is particularly difficult in its early phases when family members and physicians often incorrectly attribute the patient's symptoms to normal aging. The most frequently occurring ailments that are connected with neurodegeneration are: Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. A variety of powerful techniques that have allowed visualization of organ structure and function with exact detail have been introduced in the last twenty-five years. One such neuroimaging technique is positron emission tomography (PET), which measures in detail the functioning of distinct areas of the human brain and as a result plays a critical role in clinical and research applications. Radiotracer-based functional imaging provides a sensitive means of recognizing and characterizing the regional changes in brain metabolism and receptor binding associated with cognitive disorders. The next functional imaging technique widely used in the diagnosis of cognitive disorders is single photon emission computed tomography (SPECT). New radiotracers are being developed and promise to expand further the list of indications for PET. Prospects for developing new tracers for imaging other organ diseases also appear to be very promising. In this review, we present current opportunities of neuroimaging techniques in the diagnosis and differentiation of neurodegenerative disorders.

Clinical Microbiology of Neonatal Candidiasis in Hungary

The occurrence of Candida spp. was investigated during a three-year period in two neonatal intensive care units, Budapest, Hungary. The species distribution among the 41 analysed cases was the following: C. albicans (30/41, 73%), C. parapsilosis (10/41, 24%) and C. glabrata (1/41, 3%). All of the isolates were susceptible to the tested drugs. There was a significant difference in the birth weight, the gestational age <30 weeks and the occurrence of caesarean section between the C. albicans and the C. parapsilosis groups of the cases. Respiratory tract colonization was the same (76-77%) in the extremely low birth weight (ELBW) and the very low birth weight (VLBW) groups. Comparing the ELBW, VLBW, and >1500 g birth weight groups, significant difference was found in the parenteral nutrition, the gestation weeks <36 or <30, the polymicrobial infection and the transfusion. The ratio of C. albicans, C. parapsilosis and C. glabrata was 9:7:1 in ELBW group; 6:3:0 in VLBW group and 15:1:0 in >1500 g group. The mortality rate for C. parapsilosis was higher than for C. albicans.

Charged-particle Multiplicity Density at Midrapidity in Central Pb-Pb Collisions at Sqrt[S(NN)] = 2.76 TeV

The first measurement of the charged-particle multiplicity density at midrapidity in Pb-Pb collisions at a center-of-mass energy per nucleon pair √ S NN = 2.76 TeV is presented. For an event sample corresponding to the most central 5% of the hadronic cross section, the pseudorapidity density of primary charged particles at midrapidity is 1584 ± 4(stat) ± 76(syst), which corresponds to 8.3 ± 0.4(syst) per participating nucleon pair. This represents an increase of about a factor 1.9 relative to pp collisions at similar collision energies, and about a factor 2.2 to central Au-Au collisions at √ S NN = 2.76 TeV. This measurement provides the first experimental constraint for models of nucleus-nucleus collisions at LHC energies.

Elliptic Flow of Charged Particles in Pb-Pb Collisions at Sqrt[S(NN)] = 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at sqrt[S(NN)] =2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|η|<0.8) and transverse momentum range 0.2

[Intrathoracic Goitre--undiagnosed--nevertheless Operated]

A case review of a female patient, who was indicated for surgery for a goitre with minor bilateral retrosternal spread. The procedure included bilateral thyroidectomy during which the surgeon noticed unusual intrathoracic pathology in the left hemithorax, under the removed lobe. Postoperative chest x-ray and CT examinations revealed intrathoracic goitre, which was then removed during a following procedure. In the article, the authors discuss this uncommon pathology. Because of its uncommon location, the pathology was not detected on standard preoperative endocrinological examination. It was the follow up, postoperative examination, based on which the correct treatment was initiated.

Emergence of Canine Distemper in Bavarian Wildlife Associated with a Specific Amino Acid Exchange in the Haemagglutinin Protein

A widespread, severe outbreak of canine distemper encephalitis was observed in wildlife in Southern Bavaria in the spring and summer of 2008. The haemagglutinin (HA) genes of six representative canine distemper virus (CDV) samples originating from five red foxes and one badger during this outbreak had a Y549H amino acid substitution in the HA protein compared to sequences from two captive domesticated ferrets which succumbed to CDV in the same area 2 years earlier. As this specific substitution at the receptor-binding site has been hypothesised to contribute to the emergence of CDV and its spread to novel hosts, the outbreak in wildlife in Southern Bavaria might, directly or indirectly, be associated with a Y549H amino acid exchange.

CP-690,550, a Therapeutic Agent, Inhibits Cytokine-mediated Jak3 Activation and Proliferation of T Cells from Patients with ATL and HAM/TSP

The retrovirus, human T-cell-lymphotrophic virus-1 (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL) and the neurological disorder HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-I-encoded protein tax constitutively activates interleukin-2 (IL-2), IL-9, and IL-15 autocrine/paracrine systems that in turn activate the Jak3 (Janus kinase 3)/STAT5 (signal transducers and activators of transcription 5) pathway, suggesting a therapeutic strategy that involves targeting Jak3. We evaluated the action of the Jak3 inhibitor CP-690,550 on cytokine dependent ex vivo proliferation that is characteristic of peripheral blood mononuclear cells (PBMCs) from select patients with smoldering or chronic subtypes of ATL, or from those with HAM/TSP whose PBMCs are associated with autocrine/paracrine pathways that involve the production of IL-2, IL-9, IL-15, and their receptors. CP-690,550 at 50 nM inhibited the 6-day ex vivo spontaneous proliferation of PBMCs from ATL and HAM/TSP patients by 67.1% and 86.4%, respectively. Furthermore, CP-690,550 inhibited STAT5 phosphorylation in isolated ATL T cells ex vivo. Finally, in an in vivo test of biological activity, CP-690,550 treatment of mice with a CD8 T-cell IL-15-transgenic leukemia that manifests an autocrine IL-15/IL-15Rα pathway prolonged the survival duration of these tumor-bearing mice. These studies support further evaluation of the Jak3 inhibitor CP-690,550 in the treatment of select patients with HTLV-I-associated ATL and HAM/TSP.

Oil Refinery Dusts: Morphological and Size Analysis by TEM

The objectives of this work were to develop a means of sampling atmospheric dusts on the premises of an oil refinery for electron microscopic study to carry out preliminary morphological analyses and to compare these dusts with those collected at sites beyond the refinery limits. Carbon and collodion membranes were used as a support for collection of dust particles straight on transmission electron microscopy (TEM) grids. Micrographs of the dust particles were taken at magnifications from ×4,000 to ×80,000 with a Tesla BS500 transmission electron microscope. Four parameters were defined on the basis of the micrographs: surface area, Feret diameter, circumference, and shape coefficient. The micrographs and literature data were used to classify the atmospheric dusts into six groups: particles with an irregular shape and rounded edges; particles with an irregular shape and sharp edges; soot and its aggregates; spherical particles; singly occurring, ultrafine dust particles; and particles not allocated to any of the previous five groups. The types of dusts found in all the samples were similar, although differences did exist between the various morphological parameters. Dust particles with the largest Feret diameter were present in sample 3 (mean, 0.739 μm)-these were collected near the refinery's effluent treatment plant. The particles with the smallest diameter were found in the sample that had been intended to be a reference sample for the remaining results (mean, 0.326 μm). The dust particles collected in the refinery had larger mean Feret diameters, even 100% larger, than those collected beyond it. Particles with diameters from 0.1 to 0.2 μm made up the most numerous group in all the samples collected in the refinery.

An Update on Thoron Exposure in Canada with Simultaneous ²²²Rn and ²²⁰Rn Measurements in Fredericton and Halifax

Naturally occurring isotopes of radon in indoor air are identified as the second leading cause of lung cancer after tobacco smoking. Radon-222 (radon gas) and radon-220 (thoron gas) are the most common isotopes of radon. While extensive radon surveys have been conducted, indoor thoron data are very limited. To better assess thoron exposure in Canada, radon/thoron discriminating detectors were deployed in 45 homes in Fredericton and 65 homes in Halifax for a period of 3 months. In this study, radon concentrations ranged from 16 to 1374 Bq m(-3) with a geometric mean (GM) of 82 Bq m(-3) and a geometric standard deviation (GSD) of 2.56 in Fredericton, and from 4 to 2341 Bq m(-3) with a GM of 107 Bq m(-3) and a GSD of 3.67 in Halifax. It is estimated that 18 % of Fredericton homes and 32 % of Halifax homes could have radon concentrations above the Canadian indoor radon guideline of 200 Bq m(-3). This conclusion is significantly higher than the previous estimates made 30 y ago with short-term radon measurements. Thoron concentrations were below the detection limit in 62 % of homes in both cities. Among the homes with detectable thoron concentrations, the values varied from 12 to 1977 Bq m(-3) in Fredericton and from 6 to 206 Bq m(-3) in Halifax. The GM and GSD were 86 Bq m(-3) and 3.19 for Fredericton, and 35 Bq m(-3) and 2.35 for Halifax, respectively. On the basis of these results, together with previous measurements in Ottawa, Winnipeg and the Mont-Laurier region of Quebec, it is estimated that thoron contributes ∼8 % of the radiation dose due to indoor radon exposure in Canada.

Adult T-cell Leukemia/lymphoma with Epstein-Barr Virus-positive Hodgkin-like Cells

Hodgkin-like cells have been described in a variety of non-Hodgkin lymphomas including chronic lymphocytic leukemia and peripheral T-cell lymphoma. There have been rare reports in the Japanese population of human T-cell lymphotrophic virus-1-associated adult T-cell leukemia/lymphoma harboring Hodgkin-like cells; however, no similar cases have been described in Western patients. We report a 53-year-old African American man who presented with progressive weakness and lethargy, and was found to have generalized lymphadenopathy and hypercalcemia. A lymph node biopsy showed involvement by adult T-cell leukemia/lymphoma with scattered Epstein-Barr virus-positive cells, some of which resembled Hodgkin cells that had a B-cell phenotype, consistent with an Epstein-Barr virus-lymphoproliferative disorder. The patient had stage 4 disease with bone marrow involvement. In light of the associated B-cell lymphoproliferative process, the patient was treated with 6 cycles of intensive chemotherapy that targeted both the adult T-cell leukemia/lymphoma and the Epstein-Barr virus-lymphoproliferative disorder that resulted in a complete response. An awareness of the association of Epstein-Barr virus-lymphoproliferative disorder with Hodgkin-like cells in the context of adult T-cell leukemia/lymphoma is necessary to avoid potential misdiagnosis and to aid in therapeutic decisions.

8-Oxoguanine Incision Activity is Impaired in Lung Tissues of NSCLC Patients with the Polymorphism of OGG1 and XRCC1 Genes

Decreased repair of oxidative DNA damage is a risk factor for developing certain human malignancies. We have previously found that the capacity of 8-oxo-7,8-dihydroguanine repair was lower in leukocytes of NSCLC patients than in controls. To explain these observations, we searched for mutations and polymorphisms in the OGG1 gene among 88 NSCLC patients and 79 controls. One patient exhibited a heterozygous mutation in exon 1, which resulted in Arg46Gln substitution. Normal lung and tumor tissue carrying this mutation showed markedly lower 8-oxoG incision activity than the mean for all patients. The predominant polymorphism of OGG1 was Ser326Cys. A significant difference was observed in the frequencies of the OGG1 variants between populations of NSCLC patients and controls. The frequency of the Cys326 allele and the number of Cys326Cys homozygotes was higher among patients than controls. In individuals with either Ser326Cys or Cys326Cys genotype 8-oxoG incision rate was lower than in those with both Ser326 alleles, either in lung or leukocytes. Moreover, 8-oxodG level was higher in lung tissue and leukocytes of patients carrying two Cys326 alleles and in leukocytes of patients with the Ser326Cys genotype. We also screened for polymorphisms of the XRCC1 gene. Only heterozygotes of the XRCC1 variants Arg194Trp, Arg280His and Arg399Gln were found among patients and controls, with the frequency of Arg280His being significantly higher among patients. NSCLC patients with Arg280His or Arg399Gln polymorphism revealed lower 8-oxoG incision activity in their lung tissues, but not in leukocytes. We can conclude that the OGG1 Ser326Cys polymorphisms may have an impact on the efficiency of 8-oxoG incision in humans and the XRCC1 His280 and Gln399 may influence the OGG1 activity in tissues exposed to chronic oxidative/inflammatory stress. Higher frequency of the OGG1 Cys326 allele among NSCLC patients may partially explain the impairment of the 8-oxoG repair observed in their leukocytes.

Risk for Mycobacterium Celatum Infection from Ferret

Intramyocardial Plasmid-encoding Human Vascular Endothelial Growth Factor A165/basic Fibroblast Growth Factor Therapy Using Percutaneous Transcatheter Approach in Patients with Refractory Coronary Artery Disease (VIF-CAD)

VIF-CAD randomized, placebo-controlled, double-blind trial was an attempt to induce therapeutic angiogenesis by percutaneous intramyocardial transfer of bicistronic (vascular endothelial growth factor/fibroblast growth factor [VEGF/FGF]) plasmid (pVIF) in patients with refractory heart ischemia. Myocardial perfusion, clinical symptoms, exercise tolerance, left ventricular function, and safety were assessed.

Centrality Dependence of the Charged-particle Multiplicity Density at Midrapidity in Pb-Pb Collisions at Sqrt[s(NN)] = 2.76 TeV

The centrality dependence of the charged-particle multiplicity density at midrapidity in Pb-Pb collisions at sqrt[s_{NN}]=2.76  TeV is presented. The charged-particle density normalized per participating nucleon pair increases by about a factor of 2 from peripheral (70%-80%) to central (0%-5%) collisions. The centrality dependence is found to be similar to that observed at lower collision energies. The data are compared with models based on different mechanisms for particle production in nuclear collisions.

Expression of the OmpATb Operon Accelerates Ammonia Secretion and Adaptation of Mycobacterium Tuberculosis to Acidic Environments

Homeostasis of intracellular pH is a trait critical for survival of Mycobacterium tuberculosis in macrophages. However, mechanisms by which M. tuberculosis adapts to acidic environments are poorly understood. In this study, we analysed the physiological functions of OmpATb, a surface-accessible protein of M. tuberculosis. OmpATb did not complement the permeability defects of a Mycobacterium smegmatis porin mutant to glucose, serine and glycerol, in contrast to the porin MspA. Uptake rates of these solutes were unchanged in an ompATb operon mutant of M. tuberculosis indicating that OmpATb is not a general porin. Chemical analysis of low-pH culture filtrates showed that the proteins encoded by the ompATb operon are involved in generating a rapid ammonia burst, which neutralized medium pH and preceded exponential growth of M. tuberculosis. Addition of ammonia accelerated growth of the ompATb operon mutant demonstrating that ammonia secretion is indeed a mechanism by which M. tuberculosis neutralizes acidic environments. Infection experiments revealed that the ompATb operon was not required for full virulence in mice suggesting that M. tuberculosis has multiple mechanisms of resisting phagosomal acidification. Taken together, these results show that the ompATb operon is necessary for rapid ammonia secretion and adaptation of M. tuberculosis to acidic environments in vitro but not in mice.

Tumor Markers in Hairy Cell Leukemia

Despite the availability of highly effective therapies for hairy cell leukemia, including cladrabine, deoxycoformycin, and interferon α, a significant fraction of patients relapse. The use of flow cytometry, bone marrow examination for minimal residual disease, and peripheral blood counts provides details about the level of disease activity, but the optimal method for following patient response and risk for relapse has not been established. Flow cytometry provides accurate assessments of circulating malignant cell counts even at very low levels, but does not provide details on the extent of bone marrow involvement. Bone marrow involvement can be assessed by biopsy, but is a painful procedure, and the extent of involvement by hairy cell leukemia is not always uniform. Thus, a single biopsy may not identify active disease when it is present. Magnetic resonance imaging is being evaluated as a means for assessing total body burden of disease in the marrow and shows great promise. Tumor markers that can be measured in the serum provide a method for assessing total body disease burden. Cell surface proteins can be shed by tumor cells through proteolytic cleavage to release portions of their extracellular domains. These proteolytic degradation products can be measured in the serum and provide a tool to monitor disease burden and response to therapy. Three cell surface molecules expressed by the malignant hairy cells, CD25, CD22, and CD307, have been used to monitor disease activity and follow patients at risk for relapse. Serum tumor markers provide a reliable, inexpensive, and non-invasive means of following patients with hairy cell leukemia for response to treatment and relapse.

Impacting Tumor Cell-fate by Targeting the Inhibitor of Apoptosis Protein Survivin

Survivin (BIRC5), a member of the inhibitor of apoptosis protein (IAP) family that inhibits caspases and blocks cell death is highly expressed in cancer and is associated with a poorer clinical outcome. Functioning simultaneously during cell division and apoptosis inhibition, survivin plays a pivotal role in determining cell survival. Survivin has consistently been identified by molecular profiling analysis to be associated with higher tumor grade, more advanced disease, abbreviated survival, accelerated rates of recurrence, and chemotherapy and radiation resistance. Survivin's differential expression in cancer compared to normal tissue and its role as a nodal protein in a number of cellular pathways make it a highly flexible therapeutic target, suitable for small-molecule inhibitiors, molecular antagonists, and vaccination-based therapies. By targeting survivin it is hoped that multiple tumor signaling circuitries may be simultaneously disabled. This effect may be applicable to many tumor histologies irrespective of specific genetic makeup. To date, survivin inhibitors have shown modest activity as single agents, but it is anticipated that when given in combination with cytotoxic chemotherapy or monoclonal antibodies they may exhibit enhanced efficacy. This review discusses the complex circuitry of survivin in human cancers and highlights clinical trials involving novel agents that target this important protein.

Disseminated Strongyloides Stercoralis Infection in HTLV-1-associated Adult T-cell Leukemia/lymphoma

A 55-year-old woman with human T-cell lymphotropic virus type-1 (HTLV-1)-associated adult T-cell leukemia (ATL) and a history of previously treated Strongyloides stercoralis infection received anti-CD52 monoclonal antibody therapy with alemtuzumab on a clinical trial. After an initial response, she developed ocular involvement by ATL. Alemtuzumab was stopped and high-dose corticosteroid therapy was started to palliate her ocular symptoms. Ten days later, the patient developed diarrhea, vomiting, fever, cough, skin rash, and a deteriorating mental status. She was diagnosed with disseminated S. stercoralis. Corticosteroids were discontinued and the patient received anthelmintic therapy with ivermectin and albendazole with complete clinical recovery.

Repeated Elicitation of the Acoustic Startle Reflex Leads to Sensitisation in Subsequent Avoidance Behaviour and Induces Fear Conditioning

Autonomous reflexes enable animals to respond quickly to potential threats, prevent injury and mediate fight or flight responses. Intense acoustic stimuli with sudden onsets elicit a startle reflex while stimuli of similar intensity but with longer rise times only cause a cardiac defence response. In laboratory settings, habituation appears to affect all of these reflexes so that the response amplitude generally decreases with repeated exposure to the stimulus. The startle reflex has become a model system for the study of the neural basis of simple learning processes and emotional processing and is often used as a diagnostic tool in medical applications. However, previous studies did not allow animals to avoid the stimulus and the evolutionary function and long-term behavioural consequences of repeated startling remain speculative. In this study we investigate the follow-up behaviour associated with the startle reflex in wild-captured animals using an experimental setup that allows individuals to exhibit avoidance behaviour.

Long-term Measurements of Thoron, Its Airborne Progeny and Radon in 205 Dwellings in Ireland

Long-term (circa 3 months) simultaneous measurements of indoor concentrations of thoron gas, airborne thoron progeny and radon were made using passive alpha track detectors in 205 dwellings in Ireland during the period 2007-09. Thoron progeny concentrations were measured using passive deposition monitors designed at the National Institute of Radiological Sciences (NIRS), Japan, whereas thoron gas concentrations were measured using Raduet detectors (Radosys, Budapest). Radon concentrations were measured in these dwellings by means of NRPB/SSI type alpha track radon detectors as normally used by the Radiological Protection Institute of Ireland (RPII). The concentration of thoron gas ranged from <1 to 174 Bq m(-3) with an arithmetic mean (AM) of 22 Bq m(-3). The concentration of radon gas ranged from 4 to 767 Bq m(-3) with an AM of 75 Bq m(-3). For radon, the estimated annual doses were 0.1 (min), 19.2 (max) and 1.9 (AM) mSv y(-1). The concentration of thoron progeny ranged from <0.1 to 3.8 Bq m(-3) [equilibrium equivalent thoron concentration (EETC)] with an AM of 0.47 Bq m(-3) (EETC). The corresponding estimated annual doses were 2.9 (max) and 0.35 (mean) mSv y(-1). In 14 or 7% of the dwellings, the estimated doses from thoron progeny exceeded those from radon.

Singular DYT6 Phenotypes in Association with New THAP1 Frameshift Mutations

Biodegradable Polydioxanone Stents: a New Option for Therapy-resistant Anastomotic Strictures of the Colon

To assess the outcome of self-expandable, biodegradable stent insertion for anastomotic strictures following treatment for rectosigmoid carcinoma.

Improved Immunoassay for the Detection of Severe Combined Immunodeficiency

Flow Cytometric Immunophenotypic Assessment of T-cell Clonality by Vβ Repertoire Analysis: Detection of T-cell Clonality at Diagnosis and Monitoring of Minimal Residual Disease Following Therapy

Flow cytometric T-cell receptor (TCR)-V(β) repertoire analysis (TCR-V(β)-R) is a sensitive method for detection of T-cell clonality; however, no uniform approach exists to define clonality in neoplastic T cells. TCR-V(β)-R was evaluated in patients with a diagnosis of T-cell neoplasia in initial diagnostic specimens from 41 patients and for minimal residual disease (MRD) monitoring in 61 sequential samples from 14 patients with mature T-cell neoplasia. Gating strategies and criteria for detection of T-cell clonality were determined. In all 41 initial specimens, T-cell clonality was demonstrated via TCR-V(β)-R. The frequency of V(β) usage was consistent with random neoplastic transformation of TCR-V(β) subsets. MRD was successfully detected in follow-up samples from all 14 patients evaluated, Furthermore, MRD after therapy was quantitated in 48 peripheral blood specimens. TCR-V(β)-R analysis is a sensitive method for detection of T-cell clonality and is useful for diagnosis and MRD detection in multiple specimen types.

Vaccination with Patient-specific Tumor-derived Antigen in First Remission Improves Disease-free Survival in Follicular Lymphoma

Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) -specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial.

DETERMINATION OF THORON EQUILIBRIUM FACTOR FROM SIMULTANEOUS LONG-TERM THORON AND ITS PROGENY MEASUREMENTS

With 3-month simultaneous measurements of thoron and its progeny concentrations in the lowest floors of 109 homes, the geometric mean (GM) of thoron equilibrium factor was determined to be 0.019 with a geometric standard deviation (GSD) of 3.63. Combined with the analysis from results obtained from a previous study in 138 homes, the GM of thoron equilibrium factor was determined to be 0.022 with a GSD of 3.02. The results indicate that the F value of 0.02 for thoron recommended by UNSCEAR is a reasonable value for those Canadian homes tested.

Treatment Results of Non-varicose Bleeding from Upper Gastrointestinal Tract

Treatment results of non-varicose bleeding from upper gastrointestinal tract are changing by improved endoscopic methods and introduction of new drugs in treatment.

Design, Synthesis and Biological Evaluation of New 2-benzoxazolinone Derivatives As Potential Cholinesterase Inhibitors for Therapy of Alzheimer's Disease

Currently acetylcholinesterase inhibitor (AChEI) therapy is one of the most frequently used methods in the treatment of Alzheimer's disease; tacrine, donepezil, rivastygmine and galantamine are applied in different stages of AD. In the present study, we propose a new series of 2-benzoxazolinone derivatives as potential cholinesterase inhibitors. These compounds were synthesized by condensation of 6-chloro acetyl-2-benzoxa zolinone with the corresponding amine and evaluated as acetylcholinesterase inhibitors using the colorimetric Ellman's method. Selectivity and the IC50 values were determined for the received derivatives. All tested compounds exhibited the inhibitory activity towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compound 3e showed stronger activity than the standard tacrine, and compound 3a showed activity similar to that of tacrine for AChE. Compounds 3a, 3b, 3c, and 3e showed stronger activity than the standard donepezil towards the inhibition of BChE, and the compound 3e showed stronger activity than donepezil towards AChE.

Phase I Trial of 7-hydroxystaurosporine and Fludararbine Phosphate: in Vivo Evidence of 7-hydroxystaurosporine Induced Apoptosis in Chronic Lymphocytic Leukemia

This is a phase I study of 7-hydroxystaurosporine (UCN-01) and fludararbine monophosphate (FAMP) in relapsed lymphoma. UCN-01 alone was administered in cycle 1 and with FAMP in cycles 2-6. FAMP was escalated in cohorts from 1 to 5 days. UCN-01 and FAMP pharmacokinetics and apoptosis of malignant lymphocytes was evaluated. Eighteen patients were enrolled. Standard FAMP with UCN-01 was tolerated without dose-limiting toxicity (DLT) and those seen were common to either agent alone. One patient died due to Stevens-Johnson syndrome. Seven of 18 patients responded. No pharmacological effect of UCN-01 by FAMP was noted. Lymphocytosis occurred in 15 of 18 patients following UCN-01 to paradoxically increase circulating tumor cells. UCN-01 induced apoptosis in six of eight patients with chronic lymphocytic leukemia (CLL). UCN-01 does not increase FAMP toxicity. Transient lymphocytosis followed by apoptosis occurs with UCN-01. Mobilization from tissue reservoirs may play a role in the induction of cell death in malignant lymphocytes.

Photo-responsive Polymer with Erasable and Reconfigurable Micro- and Nano-patterns: an in Vitro Study for Neuron Guidance

The interaction of cells with nanoscale topography has proven to be an important modality in controlling cell responses. Topographic parameters on material surfaces play a role in cell growth. We have synthesized a new bio compatible polymer containing photoswitching molecules. Stripepatterned (groove/ridge pattern) were patterned and erased with ease on this bio azopolymer with two different set-ups: one with the projection of an optical interference pattern and the other one by molecular self-organization with one single laser beam. These two set-ups allow the re-writing of pattern after erasing and its inscription in vitro. PC12 cells were cultured on the bio-photoswitching patterned polymer and compared with PC12 cells growing on a well know substrate: poly-L-lysine. This result is of interest for facilitating contact guidance and designing reconfigurable scaffold for neural network formation in vitro.

FERM Domain Mutations Induce Gain of Function in JAK3 in Adult T-cell Leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATLL) is an incurable disease where most patients succumb within the first year of diagnosis. Both standard chemotherapy regimens and mAbs directed against ATLL tumor markers do not alter this aggressive clinical course. Therapeutic development would be facilitated by the discovery of genes and pathways that drive or initiate ATLL, but so far amenable drug targets have not been forthcoming. Because the IL-2 signaling pathway plays a prominent role in ATLL pathogenesis, mutational analysis of pathway components should yield interesting results. In this study, we focused on JAK3, the nonreceptor tyrosine kinase that signals from the IL-2R, where activating mutations have been found in diverse neoplasms. We screened 36 ATLL patients and 24 ethnically matched controls and found 4 patients with mutations in JAK3. These somatic, missense mutations occurred in the N-terminal FERM (founding members: band 4.1, ezrin, radixin, and moesin) domain and induced gain of function in JAK3. Importantly, we show that these mutant JAK3s are inhibited with a specific kinase inhibitor already in human clinical testing. Our findings underscore the importance of this pathway in ATLL development and offer a therapeutic handle for this incurable cancer.

Curcumin Recognizes a Unique Binding Site of Tubulin

Although curcumin is known for its anticarcinogenic properties, the exact mechanism of its action or the identity of the target receptor is not completely understood. Studies on a series of curcumin analogues, synthesized to investigate their tubulin binding affinities and tubulin self-assembly inhibition, showed that: (i) curcumin acts as a bifunctional ligand, (ii) analogues with substitution at the diketone and acetylation of the terminal phenolic groups of curcumin are less effective, (iii) a benzylidiene derivative, compound 7, is more effective than curcumin in inhibiting tubulin self-assembly. Cell-based studies also showed compound 7 to be more effective than curcumin. Using fluorescence spectroscopy we show that curcumin binds tubulin 32 Ã… away from the colchicine-binding site. Docking studies also suggests that the curcumin-binding site to be close to the vinblastine-binding site. Structure-activity studies suggest that the tridented nature of compound 7 is responsible for its higher affinity for tubulin compared to curcumin.

Higher Harmonic Anisotropic Flow Measurements of Charged Particles in Pb-Pb Collisions at Sqrt(s(NN)) = 2.76  TeV

We report on the first measurement of the triangular v3, quadrangular v4, and pentagonal v5 charged particle flow in Pb-Pb collisions at sqrt(s(NN)) = 2.76  TeV measured with the ALICE detector at the CERN Large Hadron Collider. We show that the triangular flow can be described in terms of the initial spatial anisotropy and its fluctuations, which provides strong constraints on its origin. In the most central events, where the elliptic flow v2 and v3 have similar magnitude, a double peaked structure in the two-particle azimuthal correlations is observed, which is often interpreted as a Mach cone response to fast partons. We show that this structure can be naturally explained from the measured anisotropic flow Fourier coefficients.

Density Functional Theory-based Electrochemical Models for the Oxygen Reduction Reaction: Comparison of Modeling Approaches for Electric Field and Solvent Effects

A series of density functional theory (DFT) based electrochemical models are applied to systematically examine the effect of solvent, local electric field, and electrode potential on oxygen reduction reaction (ORR) kinetics. Specifically, the key elementary reaction steps of molecular oxygen dissociation, molecular oxygen protonation, and reduction of a hydroxyl adsorbate to water over the Pt(111) surface were considered. The local electric field has slight influence on reaction energetics at the vacuum interface. Solvent molecules stabilize surface adsorbates, assisting oxygen reduction. A collective solvation-potential coupled effect is identified by including long range solvent-solvent interactions in the DFT model. The dominant path of the ORR reaction varies with electrode potential and among the modeling approaches considered. The potential dependent reaction path determined from the solvated model qualitatively agrees with experiment ORR kinetics.

Human Aortic Endothelial Cell Labeling with Positive Contrast Gadolinium Oxide Nanoparticles for Cellular Magnetic Resonance Imaging at 7 Tesla

Positive T(1) contrast using gadolinium (Gd) contrast agents can potentially improve detection of labeled cells on magnetic resonance imaging (MRI). Recently, gadolinium oxide (Gd(2)O(3)) nanoparticles have shown promise as a sensitive T(1) agent for cell labeling at clinical field strengths compared to conventional Gd chelates. The objective of this study was to investigate Gado CELLTrack, a commercially available Gd(2O3) nanoparticle, for cell labeling and MRI at 7 T. Relaxivity measurements yielded r(1)  =  4.7 s(-1) mM(-1) and r(2)/r(1)  =  6.2. Human aortic endothelial cells were labeled with Gd(2)O(3) at various concentrations and underwent MRI from 1 to 7 days postlabeling. The magnetic resonance relaxation times T(1) and T(2) of labeled cell pellets were measured. Cellular contrast agent uptake was quantified by inductively coupled plasma-atomic emission spectroscopy, which showed very high uptake compared to conventional Gd compounds. MRI demonstrated significant positive T(1) contrast and stable labeling on cells. Enhancement was optimal at low Gd concentrations, attained in the 0.02 to 0.1 mM incubation concentration range (corresponding cell uptake was 7.26 to 34.1 pg Gd/cell). Cell viability and proliferation were unaffected at the concentrations tested and up to at least 3 days postlabeling. Gd(2O3) is a promising sensitive and stable positive contrast agent for cellular MRI at 7 T.

Brentuximab Vedotin (SGN-35)

Brentuximab vedotin (SGN-35) is an antibody-drug conjugate (ADC) directed against the CD30 antigen expressed on Hodgkin lymphoma and anaplastic large cell lymphoma. SGN-35 consists of the cAC10 chimerized IgG1 monoclonal antibody SGN30, modified by the addition of a valine-citrulline dipeptide linker to permit attachment of the potent inhibitor of microtubule polymerization monomethylauristatin E (MMAE). In phase II trials, SGN-35 produced response rates of 75% in patients with Hodgkin lymphoma (n = 102) and 87% in patients with anaplastic large cell lymphoma (n = 30). Responses to SGN-35 might be related not only to the cytotoxic effect due to release of MMAE within the malignant cell but also to other effects. First, SGN-35 may signal malignant cells through CD30 ligation to deliver an apoptotic or proliferative response. The former would amplify the cytotoxicity of MMAE. A proliferative signal delivered in the context of MMAE intoxication could enhance cell death. Second, the efficacy of SGN-35, particularly in Hodgkin lymphoma, might be attributed to its effect on the tumor microenvironment. Diffusion of free MMAE from the targeted tumor cells could result in a bystander effect that kills the normal supporting cells in close proximity to the malignant cells. The elimination of T regulatory cells that inhibit cytotoxic effector cells and elimination of cells that provide growth factor support for Hodgkin/Reed-Sternberg cells could further enhance the cytotoxic activity of SGN-35. Here we review the biology of SGN-35 and the clinical effects of SGN-35 administration.

Dissociative Electron Attachment to Triflates

Gas phase studies of dissociative electron attachment to simple alkyl (CF(3)SO(3)CH(3)) and aryl (C(6)H(5)SO(3)CF(3) and CF(3)SO(3)C(6)H(4)CH(3)) triflates, model molecules of nonionic photoacid generators for modern lithographic applications, were performed. The fragmentation pathways under electron impact below 10 eV were identified by means of crossed electron-molecular beam mass spectrometry. Major dissociation channels involved C-O, S-O, or C-S bond scissions in the triflate moiety leading to the formation of triflate (OTf(-)), triflyl (Tf(-)), or sulfonate (RSO(3)(-)) anions, respectively. A resonance leading to C-O bond breakage and OTf(-) formation in alkyl triflates occurred at electron energies about 0.5 eV lower than the corresponding resonance in aryl triflates. A resonance leading to S-O bond breakage and Tf(-) formation in aryl triflates occurred surprisingly at the same electron energies as C-O bond breakage. In case of alkyl triflates S-O bond breakage required 1.4 eV higher electron energies to occur and proceeded with substantially lower yields than in aryl triflates. C-S bond scission occurred for all presently studied triflates at energies close to 3 eV.

[Neuroendocrine Tumours of the Upper Gastrointestinal Tract, Characteristics and Comparison of Localization Diagnostics]

In daily clinical practice it's important to think of neuroendocrine tumors, since their prevalence for the past 5 years exceeded even the common occurrences of stomach, esophageal and pancreatic cancers. Patients diagnosed early and accurately with NET, have a greater chance for complete cure. The diagnostic tools over the past century were significantly inefficient in diagnosing NET i.e. (40% of tumors were not localized after USG, CT, MRI, AG investigations). Until the past 2 decades that major turnover in diagnostic methods has been achieved. In particular, the introduction of the somatostatine receptor scintigrafy (SRS) and endoscopic ultrasonography (EUS) have increased sensitivity of localization diagnostics up to 90%. Our work is to test the success of the localization diagnostics in 22 patients with surgically and histologically confirmed NET ofthe pancreas and duodenum. These patients fulfilled jointly SRS, CT and/or MRI, but also classic USG and EUS. From our comparison, clearly endoscopic USG is the most efficient tool with 90% sensitivity.

Multiplication Law and S Transform for Non-Hermitian Random Matrices

We derive a multiplication law for free non-Hermitian random matrices allowing for an easy reconstruction of the two-dimensional eigenvalue distribution of the product ensemble from the characteristics of the individual ensembles. We define the corresponding non-Hermitian S transform being a natural generalization of the Voiculescu S transform. In addition, we extend the classical Hermitian S transform approach to deal with the situation when the random matrix ensemble factors have vanishing mean including the case when both of them are centered. We use planar diagrammatic techniques to derive these results.

Prognostic Value of Adenosine Stress Cardiovascular Magnetic Resonance and Dobutamine Stress Echocardiography in Patients with Low-risk Chest Pain

Excluding obstructive coronary artery disease (CAD) as the etiology of acute chest pain in patients without diagnostic electrocardiographic changes or elevated serum cardiac biomarkers is challenging. Stress testing is a valuable risk-stratifying technique reserved for the subset of these patients with low-risk chest pain who have an intermediate clinical probability of obstructive CAD. Given the risks of radiation inherent to nuclear and computed tomography imaging, both adenosine stress cardiovascular magnetic resonance (AS-CMR) imaging and dobutamine stress echocardiography (DSE) are attractive alternative stress modalities. An essential characteristic of stress modalities is their negative prognostic value; as one must exclude clinically-relevant CAD such that patients can be discharged safely. Therefore, the aim of this study was to validate a favorable negative prognostic value for both AS-CMR and DSE in patients presenting with low-risk acute chest pain. This retrospective study included 255 patients with low-risk acute chest pain and no prior history of CAD presenting to the emergency department at our institution, with 89 patients evaluated by AS-CMR and 166 by DSE. Median follow-up was 292 days, and consisted of medical record review. The primary end-point was the composite of cardiac death, nonfatal acute myocardial infarction, obstructive CAD on invasive coronary angiography (ICA) or recurrent chest pain requiring hospital admission. Test characteristics such as sensitivity and specificity could not be evaluated as patients were not routinely evaluated with ICA. All patients completed the stress protocol without adverse events during testing. 82/89 patients (92.1%) and 164/166 patients (98.8%) had negative AS-CMR and DSE studies, respectively. Both AS-CMR and DSE had excellent negative prognostic values for the primary endpoint, 100 and 99%, respectively. Both AS-CMR and DSE are effective stress modalities for excluding clinically significant coronary artery disease in patients presenting acute low-risk chest pain. Patients without findings to suggest ischemia have an excellent intermediate-term prognosis.

Olfactory Neuroblastoma in Dogs and Cats--a Histological and Immunohistochemical Analysis

Olfactory neuroblastoma (ONB) was identified in 13 dogs and nine cats. The tumours were subjected to microscopical examination and were graded using a human pathological grading system. In the canine and feline tumours there was more necrosis and higher mitotic activity (mitotic index and Ki67 labelling index) than reported in human ONB. Rosettes were a common feature of feline ONBs. A significant correlation was observed between the histological grade and the Ki67 labelling index. The histopathological diagnosis of ONB was confirmed immunohistochemically by demonstration of the neuronal marker neuron-specific enolase (NSE). Two other neuron-specific antibodies specific for microtubule-associated protein-2 (MAP-2) and neuronal nuclei antigen (NeuN) were evaluated. MAP-2 expression proved to have higher specificity than labelling for NSE. NeuN expression was less sensitive and of limited practical value.

Increased Serum Soluble IL-15Rα Levels in T-cell Large Granular Lymphocyte Leukemia

Large granular lymphocyte (LGL) leukemia is a clonal lymphoproliferative disease of mature T and natural killer cells. The etiology of LGL leukemia is unknown. IL-15 is an inflammatory cytokine that stimulates T and natural killer cells and is critical for their survival and proliferation. IL-15 signals through a heterotrimeric receptor that is composed of a private receptor, IL-15Rα and IL-2/IL-15Rβ and γ(c) shared with IL-2. Using a newly developed assay, we demonstrated increased levels of soluble IL-15Rα in the serum of patients with T-LGL leukemia. Furthermore, IL-15Rα mRNA levels were also up-regulated in the PBMCs of these patients. FACS analysis indicated that IL-15Rα was expressed both on monocytes as well as on some CD8+ leukemic cells of the patients. Interestingly, the mRNA levels of IFN-γ, a known inducer of IL-15Rα, were also up-regulated in patients' PBMCs. Moreover, PBMCs of some T-LGL patients proliferated at higher levels in response to exogenously added IL-15 compared with those of normal donors. In summary, our study demonstrated increased expression of IL-15Rα in T-LGL leukemia. It is conceivable that higher IL-15Rα expression may lower IL-15 response threshold in vivo and, therefore, may contribute to the pathogenesis of the disease.

Strong Light-induced Reorganization of Pigment-protein Complexes of Thylakoid Membranes in Rye (spectroscopic Study)

The supramolecular reorganization of LHCII complexes within the thylakoid membrane in Secale cereale leaves under low and high light condition was examined. Rye seedlings were germinated hydroponically in a climate chamber with a 16 h daylight photoperiod, photosynthetic photon flux density (PPFD) of 150 μmo lm(-2)s(-1) and 24/16°C day/night temperature. The influence of pre-illumination of the plants with high light intensity on the PSII antenna complexes was studied by comparison of the structure and function of the LHCII complexes and organization of thylakoid membranes isolated from 10-day-old plants illuminated with low (150 μmo lm(-2)s(-1)) or high (1200 μmo lm(-2)s(-1)) light intensity. Aggregated and trimeric with monomeric forms of LHCII complexes were separated from the whole thylakoid membranes using non-denaturing electrophoresis. Analyses of fluorescence emission spectra of these different LHCII forms showed that the monomer was the most effective aggregating antenna form. Moreover, photoprotection connected with LHCII aggregation was more effective upon LHCII monomers in comparison to trimer aggregation. Light stress induced specific organization of neighboring LHCII complexes, causing an increase in fluorescence yield of the long-wavelength bands (centered at 701 and 734 nm). The changes in the organization of the thylakoid membrane under light stress, observed by analysis of absorbance spectra obtained by Fourier transform infrared spectroscopy, also indicated light-induced LHCII aggregation.

Adaptive Kalman Filtering for Real-time Mapping of the Visual Field

This paper demonstrates the feasibility of real-time mapping of the visual field for clinical applications. Specifically, three aspects of this problem were considered: (1) experimental design, (2) statistical analysis, and (3) display of results. Proper experimental design is essential to achieving a successful outcome, particularly for real-time applications. A random-block experimental design was shown to have less sensitivity to measurement noise, as well as greater robustness to error in modeling of the hemodynamic impulse response function (IRF) and greater flexibility than common alternatives. In addition, random encoding of the visual field allows for the detection of voxels that are responsive to multiple, not necessarily contiguous, regions of the visual field. Due to its recursive nature, the Kalman filter is ideally suited for real-time statistical analysis of visual field mapping data. An important feature of the Kalman filter is that it can be used for nonstationary time series analysis. The capability of the Kalman filter to adapt, in real time, to abrupt changes in the baseline arising from subject motion inside the scanner and other external system disturbances is important for the success of clinical applications. The clinician needs real-time information to evaluate the success or failure of the imaging run and to decide whether to extend, modify, or terminate the run. Accordingly, the analytical software provides real-time displays of (1) brain activation maps for each stimulus segment, (2) voxel-wise spatial tuning profiles, (3) time plots of the variability of response parameters, and (4) time plots of activated volume.

MicroRNA Profiling of Follicular Lymphoma Identifies MicroRNAs Related to Cell Proliferation and Tumor Response

MicroRNAs can play an important role in tumorigenesis through post-transcriptional regulation of gene expression, and are not well characterized in follicular lymphoma.

Efficient Sampling of Early Signal Arrival for Estimation of Perfusion and Transit Time in Whole-brain Arterial Spin Labeling

Arterial spin labeling can be used to measure both cerebral perfusion and arterial transit time. However, accurate estimation of these parameters requires adequate temporal sampling of the arterial spin labeling difference signal. In whole-brain multislice acquisitions, two factors reduce the accuracy of the parameter estimates: saturation of labeled blood in transit and inadequate sampling of early difference signal in superior slices. Label saturation arises when slices are acquired inferior-to-superior such that slice selection in proximal slices spoils the label for a distal slice. Inadequate sampling arises when the time spent acquiring inferior slices is too long to allow early sampling of the difference signal in superior slices. A novel approach to multislice imaging is proposed to address these two issues. In round-robin arterial spin labeling, slices are acquired in a different order after every pair of control-label acquisitions. Round-robin arterial spin labeling enables the acquisitions of all slices across the same range of postlabel delays in a descending superior-to-inferior order. This eliminates the temporal sampling problem and greatly reduces label saturation. Arterial transit time estimates obtained for the whole brain with round-robin arterial spin labeling show better agreement with a single-slice acquisition than do conventional multislice acquisitions.

Airway Management of Recovered Pediatric Patients with Severe Head and Neck Burns: a Review

There are approximately 10,000 pediatric burn survivors in the United States each year, many of whom will present for reconstructive surgery after severe burns in the head and neck (1). These recovered burn victims, who are beyond the acute phase of injury, often have significant scarring and contractures in the face, mouth, nares, neck, and chest, which can make airway management challenging and potentially lead to a 'cannot intubate, cannot ventilate' scenario (2). Although numerous cases have been presented in the literature on this topic (3-17), there are no comprehensive review articles on the unique challenges of airway management in the recovered pediatric burn patient with distorted airway anatomy. This article aims to provide a comprehensive review of airway management in such patients, focusing on challenges encountered during mask ventilation and tracheal intubation, as well as the role of surgical release of neck contractures to facilitate tracheal intubation. Lessons learned from all reported cases identified in a thorough literature search are incorporated into this review.

Flow Cytometric Immunophenotypic Assessment of T-cell Clonality by Vβ Repertoire Analysis in Fine-needle Aspirates and Cerebrospinal Fluid

Flow cytometric T-cell receptor V(β) repertoire analysis (TCR-V(β)-R) is a sensitive method to detect T-cell clonality; however, its implementation in low-cellularity specimens has not been established. We developed a strategy to use TCR-V(β)-R in cerebrospinal fluid (CSF) and fine-needle aspirate (FNA) specimens. Initially, full TCR-V(β)-R was evaluated in diagnostic/screening specimens from 8 patients with T-cell neoplasia to determine tumor-specific TCR-V(β) protein expression. Subsequently, an abbreviated, patient-specific TCR-V(β)-R evaluation was performed in 17 paucicellular specimens from the patients (8 CSF, 9 FNA) for staging and monitoring of minimal residual disease (MRD). A single cocktail containing 3 anti-V(β) antibodies (1 tumor-specific and 2 negative controls) in combination with other antibodies chosen to help gate on atypical T cells is highly sensitive and specific for detecting low-level neoplastic T-cell involvement in paucicellular specimens. This TCR-V(β)-R strategy is valuable in staging and evaluating MRD in patients with T-cell non-Hodgkin lymphoma.

Kyphoplasty and Intra-operative Radiotheray, Combination of Kyphoplasty and Intra-operative Radiation for Spinal Metastases: Technical Feasibility of a Novel Approach

To evaluate whether this new method is clinically applicable after theoretical and cadaver testing.

Acoustic Ecology and Behavior of Minke Whales in the Hawaiian and Marianas Islands: Localization, Abundance Estimation, and Characterization of Minke Whale "boings"

[Searching for Tourette's Syndrome Gene. Part 1. Heterogeneity of Clinical Phenotypes]

The French neuropsychiatrist Georges Gilles de la Tourette described in 1885 the "Maladie des Tics" which later was named after him, as Gilles de la Tourette syndrome (GTS). Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by simple and complex motor and vocal tics with multiple neuropsychiatric comorbidities. GTS is often concurrent with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). There are several clinical GTS subtypes: GTS only, GTS+OCD, and GTS+OCD+ADHD. Additional clinical aspects of the disorder include occurrence of anger episodes, anxiety and mood disorders, and learning and sleeping disturbances. The genetics of GTS is complex and remains unclear. So far, no causative candidate genes have been identified. However, segregation studies in families and twins with GTS provide strong evidence for the existence of a genetic background associated with a multifactorial mode of inheritance. Progress in studies on genome variability among patients with GTS is necessary to improve pharmacotherapeutic strategies of the disorder.

[Searching for Tourette's Syndrome Gene. Part 2. Patient's Genome Variability]

Gilles de la Tourette syndrome (GTS) is a complex, heterozygous genetic disorder. Twenty chromosomal rearrangements (7q22-q31, 8q13-q22, and 18q22) indicating genomic regions which may be involved in the etiology of the disorder have been reported in families with GTS. Moreover, pathogenic mutations responsible for GTS were found in the SLITRK1 and the L-histidine decarboxylase (HDC) genes. The W317X mutation in the HDC gene points to a possible role for histaminergic neurotransmission in the mechanism and modulation of tic disorder. The distribution of single nucleotide polymorphisms (SNPs) was examined in at least 14 candidate genes (DRD1, DRD2, DRD3, DRD4, DAT1, MAOA, 5HTR2A, 5HTR3A, TDO2, CNR1, HLA-DRB, IL1RA, MOG, and SGCE) using a case-control genetic association analysis. Still, a lack of replicated and consistent results was observed. Recently, rare structural variants of different genes involved in neurodevelopment determined by recurrent exonic copy number variations (CNVs) have been found in a subset of patients suffering from GTS.

Bottlenose Dolphins Exchange Signature Whistles when Meeting at Sea

The bottlenose dolphin, Tursiops truncatus, is one of very few animals that, through vocal learning, can invent novel acoustic signals and copy whistles of conspecifics. Furthermore, receivers can extract identity information from the invented part of whistles. In captivity, dolphins use such signature whistles while separated from the rest of their group. However, little is known about how they use them at sea. If signature whistles are the main vehicle to transmit identity information, then dolphins should exchange these whistles in contexts where groups or individuals join. We used passive acoustic localization during focal boat follows to observe signature whistle use in the wild. We found that stereotypic whistle exchanges occurred primarily when groups of dolphins met and joined at sea. A sequence analysis verified that most of the whistles used during joins were signature whistles. Whistle matching or copying was not observed in any of the joins. The data show that signature whistle exchanges are a significant part of a greeting sequence that allows dolphins to identify conspecifics when encountering them in the wild.

Ab Initio Thermodynamics Examination of Sulfur Species Present on Rh, Ni, and Binary Rh-Ni Surfaces Under Steam Reforming Reaction Conditions

The stable form of adsorbed sulfur species and their coverage were investigated on Rh, Ni, and Rh-Ni binary metal surfaces using density functional theory calculations and the ab initio thermodynamics framework. S adsorption, SO(x) (x = 1-4) adsorption, and metal sulfide formation were examined on Rh(111) and Ni(111) pure metals. Both Rh and Ni metals showed a preference for S surface adsorption rather than SO(x) adsorption under steam reforming conditions. The transition temperature from a clean surface (<(1)/(9) ML) to S adsorption was identified on Rh(111), Ni(111), Rh(1)Ni(2)(111), and Rh(2)Ni(1)(111) metals at various P(H(2))/P(H(2)S) ratios. Bimetallic Rh-Ni metals transition to a clean surface at lower temperatures than does the pure Rh metal. Whereas Rh is covered with (1)/(3) ML of sulfur under the reforming conditions of 4-100 ppm S and 800 °C, Rh(1)Ni(2) is covered with (1)/(9) ML of sulfur at the lower end of this range (4-33 ppm S). The possibility of sulfate formation on Rh catalysts was examined by considering higher oxygen pressures, a Rh(221) stepped surface, and the interface between a Rh(4) cluster and CeO(2)(111) surface. SO(x) surface species are stable only at high oxygen pressure or low temperatures outside those relevant to the steam reforming of hydrocarbons.

Superantigen-induced CD4 Memory T Cell Anergy. I. Staphylococcal Enterotoxin B Induces Fyn-mediated Negative Signaling

Memory CD4 T cells must provide robust protection for an organism while still maintaining self-tolerance. Superantigens reveal a memory cell-specific regulatory pathway, by which signaling through the TCR can lead to clonal tolerance (anergy). Here we show that the src kinase Fyn is a critical regulator of anergy in murine memory CD4 T cells induced by the bacterial superantigen staphylococcal enterotoxin B (SEB). Exposure to SEB results in impaired TCR signaling due to failed CD3/ZAP-70 complex formation. Further, signal transduction through the TCR remains similarly blocked when anergic memory cells are subsequently exposed to agonist peptide antigen. Pharmacological inhibition or genetic elimination of Fyn kinase reverses memory cell anergy, resulting in SEB-induced cell proliferation. The mechanism underlying impaired TCR signaling and subsequent memory cell anergy must involve a Fyn signaling pathway given that the suppression of Fyn activity restores CD3/ZAP-70 complex formation and TCR proximal signaling.

J/ψ Polarization in Pp Collisions at √s=7 TeV

The ALICE Collaboration has studied J/ψ production in pp collisions at √s=7 TeV at the LHC through its muon pair decay. The polar and azimuthal angle distributions of the decay muons were measured, and results on the J/ψ polarization parameters λ(θ) and λ(φ) were obtained. The study was performed in the kinematic region 2.5

Particle-yield Modification in Jetlike Azimuthal Dihadron Correlations in Pb-Pb Collisions at √s(NN)=2.76 TeV

The yield of charged particles associated with high-p(t) trigger particles (83 GeV/c on the away side drops to about 60% of that observed in pp collisions, while on the near side a moderate enhancement of 20%-30% is found.

Human Aortic Endothelial Cell Labeling with Positive Contrast Gadolinium Oxide Nanoparticles for Cellular Magnetic Resonance Imaging at 7 Tesla

Positive T₁ contrast using gadolinium (Gd) contrast agents can potentially improve detection of labeled cells on magnetic resonance imaging (MRI). Recently, gadolinium oxide (Gd₂O₃) nanoparticles have shown promise as a sensitive T₁ agent for cell labeling at clinical field strengths compared to conventional Gd chelates. The objective of this study was to investigate Gado CELLTrack, a commercially available Gd₂O₃ nanoparticle, for cell labeling and MRI at 7 T. Relaxivity measurements yielded r1  =  4.7 s⁻¹ mM⁻¹ and r₂/r₁  =  6.2. Human aortic endothelial cells were labeled with Gd₂O₃ at various concentrations and underwent MRI from 1 to 7 days postlabeling. The magnetic resonance relaxation times T₁ and T₂ of labeled cell pellets were measured. Cellular contrast agent uptake was quantified by inductively coupled plasma-atomic emission spectroscopy, which showed very high uptake compared to conventional Gd compounds. MRI demonstrated significant positive T₁ contrast and stable labeling on cells. Enhancement was optimal at low Gd concentrations, attained in the 0.02 to 0.1 mM incubation concentration range (corresponding cell uptake was 7.26 to 34.1 pg Gd/cell). Cell viability and proliferation were unaffected at the concentrations tested and up to at least 3 days postlabeling. Gd₂O₃ is a promising sensitive and stable positive contrast agent for cellular MRI at 7 T.

Comparison of Acid Generation in EUV Lithography Films of Poly(4-hydroxystyrene) (PHS) and Noria Adamantyl Ester (Noria-AD(50))

The mechanism for acid production in phenolic extreme ultraviolet (EUV) lithography films containing triphenylsulfonium triflate (Ph(3)S(+)TfO(-)) acid generator has been investigated by electron paramagnetic resonance (EPR) spectroscopy and by use of the acid indicator coumarin 6 (C6). Gamma radiolysis was substituted for the EUV radiation with the assumption that the chemistry generated by ionization of the matrix does not depend on the ionization source. Poly(4-hydroxystyrene) (PHS) was first investigated as a well-studied standard, after which the water-wheel-like cyclic oligomer derivative containing pendant adamantyl ester groups, noria-AD(50), was investigated. EPR measurements confirm that the dominant free radical product is a phenoxyl derivative (PHS-O(•) or noria-O(•)) that exhibits quite slow stretched exponential recombination kinetics at room temperature. Also observed at 77 K was the presence of a significant hydrogen atom product of radiolysis. The G value or yield of acid production in thin lithography films was measured with the C6 indicator on a fused silica substrate. It was found that a significant amount of acid is generated via energy transfer from the irradiated fused-silica substrate to the Ph(3)S(+)TfO(-) in the films. By varying the film thickness on the substrates, the substrate effect on the acid yield was quantitatively determined. After subtraction of the contribution from the substrates, the acid yield G value in the PHS film with 10 wt % Ph(3)S(+)TfO(-) and 5 wt % C6 was determined to be 2.5 ± 0.3 protons per 100 eV of radiation. The acid yield of noria-AD(50) films was found to be 3.2 ± 0.3 protons per 100 eV.

The Combined Algorithm of Venous Ulcer Therapy

This prospective study was undertaken to find a new combined algorithm to help patients suffering from long-term chronic non-healing venous ulcers.

Interleukin-2 Receptor Targeted Therapy of Ocular Disease of HTLV-1-associated Adult T-cell Leukemia

To report two cases of patients with ocular manifestations of human T-cell lymphotropic virus type-1 (HTLV-1) associated adult T-cell leukemia/lymphoma (ATL) who were successfully treated with interleukin-2 receptor targeted therapies.

Progress in Used Tyres Management in the European Union: a Review

The dynamic increase in the manufacture of rubber products, particularly those used in the automobile industry, is responsible for a vast amount of wastes, mostly in the form of used tyres, of which more than 17 million tonnes are produced globally each year. The widely differing chemical compositions and the cross-linked structures of rubber in tyres are the prime reason why they are highly resistant to biodegradation, photochemical decomposition, chemical reagents and high temperatures. The increasing numbers of used tyres therefore constitute a serious threat to the natural environment. The progress made in recent years in the management of polymer wastes has meant that used tyres are starting to be perceived as a potential source of valuable raw materials. The development of studies into their more efficient recovery and recycling, and the European Union's restrictive legal regulations regarding the management of used tyres, have led to solutions enabling this substantial stream of rubber wastes to be converted into energy or new polymer materials. In this article we present the relevant literature describing innovative organizational approaches in the management of used tyres in the European Union member countries and the possible uses of waste tyres as a source of raw materials or alternative fossil fuels.

Superallowed Gamow-Teller Decay of the Doubly Magic Nucleus 100Sn

The shell structure of atomic nuclei is associated with 'magic numbers' and originates in the nearly independent motion of neutrons and protons in a mean potential generated by all nucleons. During β(+)-decay, a proton transforms into a neutron in a previously not fully occupied orbital, emitting a positron-neutrino pair with either parallel or antiparallel spins, in a Gamow-Teller or Fermi transition, respectively. The transition probability, or strength, of a Gamow-Teller transition depends sensitively on the underlying shell structure and is usually distributed among many states in the neighbouring nucleus. Here we report measurements of the half-life and decay energy for the decay of (100)Sn, the heaviest doubly magic nucleus with equal numbers of protons and neutrons. In the β-decay of (100)Sn, a large fraction of the strength is observable because of the large decay energy. We determine the largest Gamow-Teller strength so far measured in allowed nuclear β-decay, establishing the 'superallowed' nature of this Gamow-Teller transition. The large strength and the low-energy states in the daughter nucleus, (100)In, are well reproduced by modern, large-scale shell model calculations.

Radiation Therapy for the Management of Patients with HTLV-1-associated Adult T-cell Leukemia/lymphoma

Human T-cell leukemia virus type 1-associated adult T-cell leukemia/lymphoma (ATL) typically has survivals measured in months with chemotherapy. One prior published series (1983-1991) assessed local radiotherapy for ATL. Ten consecutive patients with pathologically confirmed ATL treated with radiotherapy were reviewed. Subtypes included acute (n = 7), smoldering (n = 2), and lymphomatous (n = 1). Patients received an average of 2.5 systemic therapy regimens before radiotherapy. Twenty lesions (cutaneous = 10, nodal = 8, extranodal = 2) were treated to a mean of 35.4 Gy/2-3 Gy (range, 12-60 Gy). At 9.0-month mean follow-up (range, 0.1-42.0 months), all lesions symptomatically and radiographically responded, with in-field complete responses in 40.0% (nodal 37.5% vs. cutaneous 50.0%; P = .62). No patient experienced in-field progression. Nine patients developed new/progressive out-of-field disease. Median survival was 17.0 months (3-year survival, 30.0%). No Radiation Therapy Oncology Group acute grade ≥ 3 or any late toxicity was noted. This report is the first to use modern radiotherapy techniques and finds effective local control across ATL subtypes. Radiotherapy should be considered for symptomatic local progression of ATL.

Giant Spin Splitting in Optically Active ZnMnTe/ZnMgTe Core/shell Nanowires

An enhancement of the Zeeman splitting as a result of the incorporation of paramagnetic Mn ions in ZnMnTe/ZnMgTe core/shell nanowires is reported. The studied structures are grown by gold-catalyst assisted molecular beam epitaxy. The near band edge emission of these structures, conspicuously absent in the case of uncoated ZnMnTe nanowires, is activated by the presence of ZnMgTe coating. Giant Zeeman splitting of this emission is studied in ensembles of nanowires with various average Mn concentrations of the order of a few percent, as well as in individual nanowires. Thus, we show convincingly that a strong spin sp-d coupling is indeed present in these structures.

Trial of Labor and Vaginal Delivery Rates in Women with a Prior Cesarean

OBJECTIVE: To evaluate evidence on trial of labor (TOL) and vaginal delivery rates in women with a prior cesarean and to understand the characteristics of women offered a trial of labor. DATA SOURCES: MEDLINE, DARE, and Cochrane databases were searched for articles evaluating mode of delivery for women with a prior cesarean delivery published between 1980 and September 2009. STUDY SELECTION: Studies were included if they involved human participants, were in English, conducted in the United States or in developed countries, and if they were rated fair or good base on U.S. Preventive Services Task Force (USPSTF) criteria. DATA EXTRACTION AND SYNTHESIS: The search yielded 3,134 abstracts: 69 full-text papers on TOL and vaginal birth after cesarean (VBAC) rates and 10 on predictors of TOL. The TOL rate in U.S. studies was 58% (95% CI [52, 65]) compared with 64% (95% CI [59, 70]) in non U.S. studies. The TOL rate in the U.S. was 62% (95% CI [57, 66]) for studies completed prior to 1996 and dropped to 44% (95% CI [34, 53]) in studies launched after 1996, p = .016. In U.S. studies, 74% (95% CI [72, 76]) of women who had a TOL delivered vaginally. Women who had a prior vaginal birth or delivered at a large teaching hospital were more likely to be offered a TOL. CONCLUSIONS: Although the TOL rate has dropped since 1996, the rate of vaginal delivery after a TOL has remained constant. Efforts to increase rates of TOL will depend on patients understanding the risks and benefits of both options. Maternity providers are well positioned to provide key education and counseling when patients are not informed of their options.

Levels of Thoron and Progeny in High Background Radiation Area of Southeastern Coast of Odisha, India

Exposure to radon, (222)Rn, is assumed to be the most significant source of natural radiation to human beings in most cases. It is thought that radon and its progeny are major factors that cause cancer. The presence of thoron, (220)Rn, was often neglected because it was considered that the quantity of thoron in the environment is less than that of radon. However, recent studies have shown that a high thoron concentration was found in some regions and the exposure to (220)Rn and its progeny can equal or several time exceed that of (220)Rn and its progeny. The results of thoron and its progeny measurements in the houses of high background radiation area (HBRA) of the southeastern coast of Odisha, India presented here. This area is one of the high background radiation areas in India with a large deposit of monazite sand which is the probable source of thoron. Both active and passive methods were employed for the measurement of thoron and its progeny in cement, brick and mud houses in the study area. Thoron concentration was measured using RAD-7 and Raduet. A CR-39 track detector was employed for the measurement of environmental thoron progeny, both in active and passive modes. Thoron and its progeny concentrations were found to be comparatively high in the area. A comparison between the results obtained with various techniques is presented in this paper.

Bleeding in Acute Pancreatitis Treated by Transcatheter Arterial Embolization with Ethylene-vinyl Alcohol Copolymer (Onyx)

Hemorrhagic complications are usually manifestations of the progress of severe pancreatitis. In major arterial hemorrhage resulting from pancreatic inflammatory disease, visceral angiography is valuable in localizing the site of bleeding, and hemostasis can be achieved by transcatheter arterial embolization. Successful transcatheter embolization of bleeding in the anterior superior pancreaticoduodenal artery using ethylene-vinyl alcohol copolymer (Onyx) was performed in a 38-year-old woman with acute biliary necrotic-hemorrhagic pancreatitis.

Determination of the Minimum Measurement Time for Estimating Long-term Mean Radon Concentration

Radon measurements, as do any measurements, include errors in their readings. The relative values of such errors depend principally on the measurement methods used, the radon concentration to be measured and the duration of the measurements. Typical exposure times for radon surveys using passive detectors [nuclear track detectors, activated charcoal, electrostatic (E-perm), etc.)] may extend from a few days to months, whereas, in the case of screening methods utilising active radon monitors (AlphaGUARD, RAD7, EQF, etc.), the measurements may be completed quickly within a few hours to a few days. Thus, the latter may have relatively large error values, which affect the measurement accuracy significantly compared with the former measurements made over long time periods. The method presented in this paper examines the uncertainty of a short-term radon measurement as an estimate of the long-term mean and suggests a minimum measurement time to achieve a given margin of uncertainty of that estimate.

Effects of Air Exchange Property of Passive-type Radon-thoron Discriminative Detectors on Performance of Radon and Thoron Measurements

Pairs of diffusion chambers with different air exchange rates are used in a large-scale survey to determine radon and thoron, separately. When they are enclosed in radon-proof bags for keeping after the exposure, since radon does not escape out immediately from the low-diffusion chamber, it leads to further exposure in the bags and disturbs the estimation of radon and thoron concentrations. In this study, the effects of the different air exchange properties of the radon-thoron discriminative detectors with CR-39 chips on the estimations of radon and thoron concentrations were investigated. The commercially available and frequently used detectors, Raduet, are examined in this study. The result shows that radon escapes out in 10 h. When degassing is not enough after the exposure in a calibration experiment or high-background radiation area, the residual radon causes the overestimation of the radon concentration and increase in the uncertainty in the thoron concentration, i.e. a low-performance quality of radon and thoron measurements.

Innovations in Phenotyping of Mouse Models in the German Mouse Clinic

Under the label of the German Mouse Clinic (GMC), a concept has been developed and implemented that allows the better understanding of human diseases on the pathophysiological and molecular level. This includes better understanding of the crosstalk between different organs, pleiotropy of genes, and the systemic impact of envirotypes and drugs. In the GMC, experts from various fields of mouse genetics and physiology, in close collaboration with clinicians, work side by side under one roof. The GMC is an open-access platform for the scientific community by providing phenotypic analysis in bilateral collaborations ("bottom-up projects") and as a partner and driver in international large-scale biology projects ("top-down projects"). Furthermore, technology development is a major topic in the GMC. Innovative techniques for primary and secondary screens are developed and implemented into the phenotyping pipelines (e.g., detection of volatile organic compounds, VOCs).

Thoron Experimental Room at the National Institute of Radiological Sciences (NIRS), Japan

A new thoron ((220)Rn) experimental room (TER) was established at National Institute of Radiological Sciences in 2011 to respond to the appearance of new passive devices for (220)Rn and its progeny ((212)Pb, (212)Bi) measurement. The room volume is 21.7 m(3) with a low air exchange rate, 0.016 h(-1). Environmental parameters, such as temperature, relative and absolute humidities, wind speed, aerosol distribution and concentration, are monitored, but not controlled. Commercially available lantern mantles (500 pcs), which can generate maximum concentrations of 6000 Bq m(-3) of (220)Rn and 2000 Bq m(-3) of its progeny, are used as a (220)Rn source. Based on preliminary results from the TER, stable and homogenised concentrations of (220)Rn and its progeny can be ensured; therefore, in the near future the room will be used for testing measuring instruments.

The Ascension Health Experience: Maximizing the Chief Nursing Officer Role in a Large, Multihospital System to Advance Patient Care Quality and Safety

Ascension Health is the largest Catholic and nonprofit health system in the United States, encompassing 70 acute care hospitals organized into 34 health ministries. Consistent with its distributed leadership model, Ascension Health has created a Chief Nursing Officer (CNO) Advisory Council to provide strategic direction and thought leadership on major system-level initiatives that impact quality, safety, operational performance, nursing leadership, and patient care delivery. The council fosters systemwide CNO engagement and dialogue through a unique structure of regional CNO work teams called "pods," each of which is chaired by a member of the council. This communication structure has facilitated consensus on major system initiatives at Ascension Health related to clinical goals, patient safety, nursing leadership, and systemwide capital investments. This article describes the history, structure, goals, processes, and successes of the CNO Advisory Council shared governance model.

Modulation of Murine Alzheimer Pathogenesis and Behavior by Surgery

OBJECTIVE:: Previous research suggests that a link between anesthetic exposure and Alzheimer disease exists. Because anesthetics are rarely given alone, we ask whether addition of surgery further modulates Alzheimer disease. BACKGROUND:: Cognitive dysfunction occurs after surgery in humans. Anesthesia alone produces cognitive decline in both older wild-type (WT) mice and rats, and the addition of surgery produces transient decline in young, adult WT mice. Because neuroinflammation has been implicated and occurs early in Alzheimer disease, we hypothesized that the neuroinflammatory stress associated with surgery would accelerate the progression of Alzheimer disease. METHODS:: Cecal ligation and excision were performed on presymptomatic 5- to 11-month-old triple-transgenic Alzheimer disease (3×TgAD) and C57BL/6 WT mice under desflurane anesthesia. Surgery animals were compared with aged-matched 3×TgAD and WT mice exposed to air or desflurane alone. Cognitive function was assessed via Morris water maze at 2 and 13 weeks postoperatively. Amyloid and tau pathology and inflammation and synaptic markers were quantified with immunohistochemistry, Luminex assay, enzyme-linked immunosorbent assay, or Western blot assays. RESULTS:: A significant cognitive impairment in 3×TgAD mice that underwent surgery compared with air or desflurane controls persisted to at least 14 weeks after surgery. Microglial activation, amyloidopathy, and tauopathy were enhanced by surgery as compared with desflurane alone. No differences between surgery, anesthetic, or air controls were detected in WT mice CONCLUSIONS:: Surgery causes a durable increment in Alzheimer pathogenesis, primarily through a transient activation of neuroinflammation.

Grain Type and Size of Particulate Matter from Diesel Vehicle Exhausts Analysed by Transmission Electron Microscopy

The aim of this research was to apply a simple and quick method of size and shape characterization by TEM to diesel exhaust particles from large-capacity, high-performance trucks. Particulate matter (PM) samples were collected while the engines were idling. Investigation of this type of emission is essential because vehicles are idling at stop lights, in traffic, or during slow movement, goods loading and unloading. In these conditions, PM emission cumulates in a small area. It was found that PM from vehicle exhaust emissions can be divided into three groups: soot, irregular-shaped particles and circular particles. Irregular-shaped particles and soot aggregates were present in the exhausts of the three types of vehicle tested. Circular particles were identified only in the samples collected from exhaust emissions from the MAN vehicle, and were present in small amounts. The average surface area was in the range of 0.06 microm2 to 0.24 microm2. Mean perimeter fluctuated from 2.09 microm to 4.14 microm, and Feret diameter from 0.21 microm to 0.31 microm. Circularity was in the range of 0.12 to 0.30. Aspect ratio was around 0.30 to 0.45. Feret diameter seems to be a good parameter to define the mean size of particles, but does not take into account the influence of the shape. Therefore, this measurement seems to be useful just in the case of spherical or very rounded particles, not for all diesel PM. Thus, it is necessary to consider circularity or aspect ratio for DPM characterization.

Characteristics of Thermalization of Boost-invariant Plasma from Holography

We report on the approach toward the hydrodynamic regime of boost-invariant N=4 super Yang-Mills plasma at strong coupling starting from various far-from-equilibrium states at τ=0. The results are obtained through a numerical solution of Einstein's equations for the dual geometries, as described in detail in the companion article [M. P. Heller, R. A. Janik, and P. Witaszczyk, arXiv:1203.0755]. Despite the very rich far-from-equilibrium evolution, we find surprising regularities in the form of clear correlations between initial entropy and total produced entropy, as well as between initial entropy and the temperature at thermalization, understood as the transition to a hydrodynamic description. For 29 different initial conditions that we consider, hydrodynamics turns out to be definitely applicable for proper times larger than 0.7 in units of inverse temperature at thermalization. We observe a sizable anisotropy in the energy-momentum tensor at thermalization, which is nevertheless entirely due to hydrodynamic effects. This suggests that effective thermalization in heavy-ion collisions may occur significantly earlier than true thermalization.

Production of Muons from Heavy Flavor Decays at Forward Rapidity in Pp and Pb-Pb Collisions at Sqrt[s_{NN}]=2.76  TeV

The ALICE Collaboration has measured the inclusive production of muons from heavy-flavor decays at forward rapidity, 2.5

J/ψ Suppression at Forward Rapidity in Pb-Pb Collisions at √s(NN) = 2.76 TeV

The ALICE experiment has measured the inclusive J/ψ production in Pb-Pb collisions at √s(NN) = 2.76 TeV down to zero transverse momentum in the rapidity range 2.5 < y < 4. A suppression of the inclusive J/ψ yield in Pb-Pb is observed with respect to the one measured in pp collisions scaled by the number of binary nucleon-nucleon collisions. The nuclear modification factor, integrated over the 0%-80% most central collisions, is 0.545 ± 0.032(stat) ± 0.083(syst) and does not exhibit a significant dependence on the collision centrality. These features appear significantly different from measurements at lower collision energies. Models including J/ψ production from charm quarks in a deconfined partonic phase can describe our data.

Successful Recanalization of Acute Superior Mesenteric Artery Thromboembolic Occlusion by a Combination of Intraarterial Thrombolysis and Mechanical Thrombectomy with a Carotid Filter

Acute superior mesenteric artery (SMA) occlusion is a life-threatening disease, and acute intestinal ischemia develops from the sudden decrease in perfusion to the intestines. The key to saving the patient's life is early diagnosis, and prompt revascularization of the SMA can prevent intestinal infarction and decrease the risk of bowel segment necrosis. Computed tomographic angiography may be useful for rapid diagnosis. We report recanalization of an SMA occlusion in an 80-year-old man with a combination of intraarterial thrombolysis and mechanical thrombectomy with a carotid filter.

A Computational Investigation of Ring-shift Isomerization of Sym-octahydrophenanthrene to Sym-octahydroanthracene Catalyzed by Acidic Zeolites

The ring-shift isomerization of sym-octahydrophenanthrene (sym-OHP) to sym-octahydroanthracene (sym-OHA) catalyzed by acidic zeolites (Mordenite (MOR) and Faujasite (FAU)) was investigated by the ONIOM(DFT:UFF) and DFT approaches. A "five-membered ring" mechanism through carbocation rearrangement via 1-2 migration was proved to be kinetically favored over a "six-membered ring" mechanism through Friedel-Crafts reactions. Computational studies based on the "five-membered ring" mechanism demonstrate that a decreasing Brønsted acid site strength from Al-H-MOR to Ga-H-MOR to B-H-MOR reduces the catalytic activity. The catalyst acid site strength would thereby impact the yield of sym-OHA. The isomerization barrier increases when using an Al-H-FAU catalyst that has a similar Brønsted acid site strength as Al-H-MOR but considerably bigger cages, indicating that apart from the desired density and strength of acid sites, optimal zeolite catalysts should have a pore size that better fits the intermediates and transition states. DFT calculations on Gibbs free energy were performed to evaluate the equilibrium ratios of sym-OHA to sym-OHP at specific reaction temperatures from 175 to 325 °C. The results indicate that reaction temperature has a moderate impact on the equilibrium yield of sym-OHA, whose formation is relatively favorable at a lower temperature under experimental conditions.

Estimation of Radon Diffusion Coefficients in Soil Using an Updated Experimental System

Radon diffusion through soil is strongly affected by the degree of water saturation of the soil pores. Methods have been developed by many researchers to measure radon diffusion coefficient. We developed an updated experimental system to estimate radon diffusion coefficients for typical types of soil in Japan and applied it to a typical loam with different water saturation levels (0-0.82). The system consists of a passive-type scintillation cell, soil column, accumulation tank, and radon source. The radon concentration in the accumulation tank is kept stable, and radon diffused through the soil column is continuously measured with the passive-type scintillation cell. We found the radon diffusion coefficients vary from 9.60 × 10(-6) m(2) s(-1) to 1.27 × 10(-7) m(2) s(-1) for the loam samples. Generally, the diffusion coefficients are almost constant for a water saturation range of 0-0.4 and decrease with increasing water saturation from 0.4 to 0.82.

Brain Structure Links Loneliness to Social Perception

Loneliness is the distressing feeling associated with the perceived absence of satisfying social relationships. Loneliness is increasingly prevalent in modern societies and has detrimental effects on health and happiness. Although situational threats to social relationships can transiently induce the emotion of loneliness, susceptibility to loneliness is a stable trait that varies across individuals [6-8] and is to some extent heritable. However, little is known about the neural processes associated with loneliness (but see [12-14]). Here, we hypothesized that individual differences in loneliness might be reflected in the structure of the brain regions associated with social processes. To test this hypothesis, we used voxel-based morphometry and showed that lonely individuals have less gray matter in the left posterior superior temporal sulcus (pSTS)--an area implicated in basic social perception. As this finding predicted, we further confirmed that loneliness was associated with difficulty in processing social cues. Although other sociopsychological factors such as social network size, anxiety, and empathy independently contributed to loneliness, only basic social perception skills mediated the association between the pSTS volume and loneliness. Taken together, our results suggest that basic social perceptual abilities play an important role in shaping an individual's loneliness.

Serum Ghrelin Level and TNF-α/ghrelin Ratio in Patients with Previous Myocardial Infarction

Studies investigating serum ghrelin level in atherosclerosis yielded contradictory results. Interaction of ghrelin with adipocytokines is obscure in cardiovascular diseases. We undertook this study to determine which molecules influence ghrelin level and to see whether post-myocardial infarction (MI) patients have decreased ghrelin levels.

[Importance of Expression of DNA Repair Proteins in Non-small-cell Lung Cancer]

Proteins XRCC1 and ERCC1 are involved in DNA repair. XRCC1 plays a role in DNA base excision repair and ERCC1 in nucleotide excision repair pathway. Higher expression profile of both proteins in cancer cells may contribute to development of drug resistance. ERCC1 is involved in removal of platinum adducts and might be a potential predictive and prognostic marker in NSCLC (non-small-cell lung cancer) treated with a cisplatin-based regimen. The purpose of study was determination of XRCC1 and ERCC1 levels and their correlation with basic clini-copathological parameters in NSCLC.

Determination of Soil Pore Water Salinity Using an FDR Sensor Working at Various Frequencies Up to 500 MHz

This paper presents the application of a frequency-domain reflectometry (FDR) sensor designed for soil salinity assessment of sandy mineral soils in a wide range of soil moisture and bulk electrical conductivity, through the determination of soil complex dielectric permittivity spectra in the frequency range 10-500 MHz. The real part of dielectric permittivity was assessed from the 380-440 MHz, while the bulk electrical conductivity was calculated from the 165-325 MHz range. The FDR technique allows determination of bulk electrical conductivity from the imaginary part of the complex dielectric permittivity, without disregarding the dielectric losses. The soil salinity status was determined using the salinity index, defined as a partial derivative of the soil bulk electrical conductivity with respect to the real part of the soil complex dielectric permittivity. The salinity index method enables determining the soil water electrical conductivity value. For the five sandy mineral soils that have been tested, the relationship between bulk electrical conductivity and the real part of dielectric permittivity is essentially linear. As a result, the salinity index method applied for FDR measurements may be adapted to field use after examination of loam and clayey soils.

Fatal and Survived Motorcycle Accidents: A selected Topics for Medicolegal Evaluation

Motorcyclists are extremely vulnerable road participants who are exposed to severe, often fatal injuries. Relative to four - wheeled vehicles, motorcycle pose a greater hazard of death or serious injury to operators and passengers. In fatal crashes, the motorcyclist typically collides with moving or stationary objects in the riding environment. The most common mechanism of crashes is hitting a moving vehicle followed by hitting a stationary object. The mechanism of injury resulting in death usually comes from severe blunt force trauma, creating internal and external injuries to the motorcyclist, especially craniocerebral, spinal, and sometimes with very characteristic injury patterns. The paper also identified effects of alcohol, which represent a significant risk factor for motorcycle operators. Presented concise review of selected risk factors and typical motorcycle-related injuries may be useful for both forensic pathologists, clinicians and law enforcement in preventive and repressive steps. Keywords: motorcycle fatalities - risk factors - injury patterns - alcohol impairment - medicolegal study.

Effects of Alcohol on the Brain Biomembranes: A review

Alcohol consumption is a worldwide spread phenomenon influence of which on a human organism may even be fatal. Consequences of alcoholism are not only medical but also social and economical. The basic principles of alcohol dependence development remain still unclear. Submitted article offers a short review of alcohols effects mechanisms and its interaction with neurotransmitters. Keywords: alcohol - biomembranes fluidity - GABA - dopamine - serotonine - neurotransmitters.

International Symposium on the Natural Radiation Exposures and Low-Dose Radiation Epidemiological Studies

A New Role of the Complement System: C3 Provides Protection in a Mouse Model of Lung Infection with Intracellular Chlamydia Psittaci

The complement system modulates the intensity of innate and specific immunity. While it protects against infections by extracellular bacteria its role in infection with obligate intracellular bacteria, such as the avian and human pathogen Chlamydia (C.) psittaci, is still unknown. In the present study, knockout mice lacking C3 and thus all main complement effector functions were intranasally infected with C. psittaci strain DC15. Clinical parameters, lung histology, and cytokine levels were determined. A subset of infections was additionally performed with mice lacking C5 or C5a receptors. Complement activation occurred before symptoms of pneumonia appeared. Mice lacking C3 were ∼100 times more susceptible to the intracellular bacteria compared to wild-type mice, with all C3(-/-) mice succumbing to infection after day 9. At a low infective dose, C3(-/-) mice became severely ill after an even longer delay, the kinetics suggesting a so far unknown link of complement to the adaptive, protective immune response against chlamydiae. The lethal phenotype of C3(-/-) mice is not based on differences in the anti-chlamydial IgG response (which is slightly delayed) as demonstrated by serum transfer experiments. In addition, during the first week of infection, the absence of C3 was associated with partial protection characterized by reduced weight loss, better clinical score and lower bacterial burden, which might be explained by a different mechanism. Lack of complement functions downstream of C5 had little effect. This study demonstrates for the first time a strong and complex influence of complement effector functions, downstream of C3 and upstream of C5, on the outcome of an infection with intracellular bacteria, such as C. psittaci.

New Isomers in the Full Seniority Scheme of Neutron-rich Lead Isotopes: the Role of Effective Three-body Forces

The neutron-rich lead isotopes, up to (216)Pb, have been studied for the first time, exploiting the fragmentation of a primary uranium beam at the FRS-RISING setup at GSI. The observed isomeric states exhibit electromagnetic transition strengths which deviate from state-of-the-art shell-model calculations. It is shown that their complete description demands the introduction of effective three-body interactions and two-body transition operators in the conventional neutron valence space beyond (208)Pb.

The Negative Feedback Molecular Mechanism Which Regulates Excitation Level in the Plant Photosynthetic Complex LHCII: Towards Identification of the Energy Dissipative State

Overexcitation of the photosynthetic apparatus is potentially dangerous because it can cause oxidative damage. Photoprotection realized via the feedback de-excitation in the pigment-protein light-harvesting complex LHCII, embedded in the chloroplast lipid environment, was studied with use of the steady-state and time-resolved fluorescence spectroscopy techniques. Illumination of LHCII results in the pronounced singlet excitation quenching, demonstrated by decreased quantum yield of the chlorophyll a fluorescence and shortening of the fluorescence lifetimes. Analysis of the 77K chlorophyll a fluorescence emission spectra reveals that the light-driven excitation quenching in LHCII is associated with the intensity increase of the spectral band in the region of 700nm, relative to the principal band at 680nm. The average chlorophyll a fluorescence lifetime at 700nm changes drastically upon temperature decrease: from 1.04ns at 300K to 3.63ns at 77K. The results of the experiments lead us to conclude that: (i) the 700nm band is associated with the inter-trimer interactions which result in the formation of the chlorophyll low-energy states acting as energy traps and non-radiative dissipation centers; (ii) the Arrhenius analysis, supported by the results of the FTIR measurements, suggests that the photo-reaction can be associated with breaking of hydrogen bonds. Possible involvement of photo-isomerization of neoxanthin, reported previously (Biochim. Biophys. Acta 1807 (2011) 1237-1243) in generation of the low-energy traps in LHCII is discussed.

Whistle Vocalizations of Indo-Pacific Bottlenose Dolphins (Tursiops Aduncus) Inhabiting the South-west Indian Ocean

Populations of Indo-Pacific bottlenose dolphin (Tursiops aduncus) are distributed along coastal regions of the south-west Indian Ocean (SWIO), from South Africa to Kenya. An account of whistles from wild T. aduncus inhabiting the SWIO is provided here. Recordings were made at Plettenberg Bay (South Africa) and Zanzibar Island (Tanzania) and the frequency trace of whistle contours (n = 1677) was extracted. Multiple parameters were measured from each whistle and compared between regions and encounters. Regional variation was significant in all parameters assessed except for start and middle frequency (frequency at half the duration). Whistles from Zanzibar Island ended on average 4 kHz higher than those from Plettenberg Bay, and had a steeper frequency gradient. However, mean frequencies differed by <1 kHz and population averages for the adopted frequency distribution showed similar patterns, with a peak between 5 and 7 kHz. Whistle parameters were strongly influenced by recording encounter, likely reflecting the presence of different individuals, group compositions and behavioral contexts during recording occasions. Comparisons within the genus showed that T. aduncus from the SWIO have amongst the lowest start and minimum frequency of whistles within Tursiops.

Hemodynamic Effects of Cholinesterase Inhibition in Mild Alzheimer's Disease

PURPOSE: To evaluate the spatiotemporal progression of perfusion changes in early stages of Alzheimer's disease (AD), we imaged the perfusion response to pharmacological treatment in a group of mild AD patients and contrasted it to the perfusion of age-, sex-, and education-matched healthy volunteers over the same time interval. MATERIALS AND METHODS: We used pseudo continuous arterial spin labeling (PCASL) MRI for quantitative three-dimensional mapping of perfusion immediately before and 6 months after cholinesterase inhibitor treatment. RESULTS: Before treatment, patients were found hypoperfused relative to their healthy counterparts in the gray matter of lateral temporal lobe, posterior cingulate, and anterior cingulate as well as in the white matter of the posterior cingulate. Most of the cortical regions investigated and the white matter of posterior cingulate and prefrontal regions showed treatment-elicited increases in perfusion, which were not secondary to changes in regional tissue volume nor were they associated with improvement in either MMSE or ADAS-Cog scores, although lack of deterioration suggested a cognitive benefit. CONCLUSION: This study provides a hemodynamic profile of mild AD and sheds light on the perfusion changes related to prolonged cholinesterase inhibition in this early disease stage. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.

Optimizing T1-weighted Imaging of Cortical Myelin Content at 3.0 T

With increases in the sensitivity and resolution of anatomical MRI for the brain, methods for mapping the organization of the cerebral cortex by imaging its myelin content have emerged. This identifies major sensory and motor regions and could be used in studies of cortical organization, particularly if patterns of myelination can be visualized over the cortical surface robustly in individual subjects. The imaging problem is difficult, however, because of the relative thinness of the cerebral cortex and the low intracortical tissue contrast. In this paper, we optimize the contrast of T(1)-weighted MRI to help better visualize patterns of myelination. We measure a small but statistically significant difference in T(1) of 171 ± 40 ms between cortical regions with low and high myelin contents in the human cortex at 3T, and then perform simulations to choose parameters for an inversion-recovery pulse sequence that utilizes this T(1) difference to increase contrast within the cortex. We show that lengthening the delay between signal acquisition and the next inversion pulse in the sequence increases intracortical contrast more effectively than does image averaging. Using the optimized sequence, we show that major myelinated regions that are relatively thick, such as the primary motor and auditory regions, can be visualized well in individuals at 3T using whole-cortex 3D images made at 1mm isotropic resolution, while thinner regions, such as the primary visual cortex, can be visualized using targeted 3D images made at 0.5mm isotropic resolution. Our findings demonstrate that patterns of myelination can be better visualized in individual subjects when the imaging is optimized to highlight intracortical contrast and can help to pave the way for the creation of matched maps of microanatomy and function in the cortex of living individual humans.

Value of Histopathology, Immunohistochemistry, and Real-time Polymerase Chain Reaction in the Confirmatory Diagnosis of Encephalitozoon Cuniculi Infection in Rabbits

Morphological lesions in kidneys and brain are all too often considered diagnostic for confirmation of encephalitozoonosis in rabbits. The current study evaluated the diagnostic value of histology versus other etiological tests, including immunohistochemistry and real-time polymerase chain reaction (PCR) for Encephalitozoon cuniculi infection diagnosis. Samples of brain, heart, lungs, intestine, liver, and kidneys from 81 rabbits were examined for morphological lesions attributed to E. cuniculi infection as well as for the presence of spores and E. cuniculi antigen. Of these, 55 rabbits were tested for E. cuniculi DNA. Histological changes consistent with E. cuniculi infection were seen in 33 rabbits (41%, 33/81) representing 87% (33/38) of all rabbits with confirmed E. cuniculi infection. Brains of these rabbits displayed 6 different types of focal lesions corresponding to the stage of infection and specific tissue response. In 5 rabbits that were tested positive, histology was either inconclusive or inconspicuous. Etiological diagnosis was based on histological spore detection in 16% (6/38) of infected rabbits. Immunohistochemistry was more sensitive (42%, 16/38) than histological spore detection, and real-time PCR proved to be the most sensitive of all investigated methods (30/35, 86% of the examined rabbits with E. cuniculi infection). Encephalitozoon cuniculi infection rarely occurs without characteristic kidney and brain lesions. However, the spectrum of brain changes is wider than previously reported. Based on these findings, confirmation of pathogenic E. cuniculi infection should include standard histology of the predilection sites and a specific etiological assay, preferably real-time PCR.

Phase 1 Trial of IL-15 Trans Presentation Blockade Using Humanized Mik-Beta-1 MAb in Patients with T-cell Large Granular Lymphocytic Leukemia

In the present study, Hu-Mikβ1, a humanized mAb directed at the shared IL-2/IL-15Rβ subunit (CD122) was evaluated in patients with T-cell large granular lymphocytic (T-LGL) leukemia. Hu-Mikβ1 blocked the trans presentation of IL-15 to T cells expressing IL-2/IL-15Rβ and the common γ-chain (CD132), but did not block IL-15 action in cells that expressed the heterotrimeric IL-15 receptor in cis. There was no significant toxicity associated with Hu-Mikβ1 administration in patients with T-LGL leukemia, but no major clinical responses were observed. One patient who had previously received murine Mikβ1 developed a measurable Ab response to the infused Ab. Nevertheless, the safety profile of this first in-human study of the humanized mAb to IL-2/IL-15Rβ (CD122) supports its evaluation in disorders such as refractory celiac disease, in which IL-15 and its receptor have been proposed to play a critical role in the pathogenesis and maintenance of disease activity. The protocol is registered with www.clinicaltrials.gov as number NCT 00076180.

Comparative Analysis of Radon, Thoron and Thoron Progeny Concentration Measurements

This study examined correlations between radon, thoron and thoron progeny concentrations based on surveys conducted in several different countries. For this purpose, passive detectors developed or modified by the National Institute of Radiological Sciences (NIRS) were used. Radon and thoron concentrations were measured using passive discriminative radon-thoron detectors. Thoron progeny measurements were conducted using the NIRS-modified detector, originally developed by Zhuo and Iida. Weak correlations were found between radon and thoron as well as between thoron and thoron progeny. The statistical evaluation showed that attention should be paid to the thoron equilibrium factor for calculation of thoron progeny concentrations based on thoron measurements. In addition, this evaluation indicated that radon, thoron and thoron progeny were independent parameters, so it would be difficult to estimate the concentration of one from those of the others.

Age-related Differences in Everyday Prospective Memory Tasks: The Role of Planning and Personal Importance

The aim of the present studies was to investigate whether age-related improvement found in naturalistic but experimenter-given prospective memory (PM) tasks can be generalized to real-life intentions. In Study 1, younger, middle-aged, and older adults generated a list of intended activities for the following week; one week later they marked the tasks that they had performed. The participants were also asked to rate the importance of each listed intention and to describe the circumstances of completion that were already known to them. We found that, compared with younger adults, older adults attributed a higher degree of importance to their intentions and had the circumstances of their completion better planned. However, the age-related benefit in the PM performance for all listed intentions was not present for the very important and well-planned tasks. In Study 2 we manipulated whether younger adults engaged or not in the detailed planning of when their intentions could be completed. It was demonstrated that younger adults who had to perform detailed planning completed their intended activities more often than those who did not plan for their intentions. The results support explanations of the age-related benefit in everyday PM that highlight the role of importance and planning.

Markedly Additive Anti-tumor Activity with the Combination of a Selective Survivin Suppressant YM155 and Alemtuzumab in Adult T Cell Leukemia

Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4(+)CD25(+) lymphocytes caused by human T-cell lymphotropic virus I (HTLV-1). Currently, there is no accepted curative therapy for ATL. In gene expression profiling the anti-apoptotic protein survivin (BIRC5) demonstrated a striking increase in ATL and its expression was increased in patient ATL cells resistant to the anti-CD52 monoclonal antibody alemtuzumab (Campath-1H). YM155, a selective small-molecule survivin suppressant, is currently in phase 2 trials in solid tumors and B-cell malignancies. In this study, we investigated the anti-tumor activity of YM155 alone and in combination with alemtuzumab in a murine model of human ATL (MET-1). Both YM155 alone and its combination with alemtuzumab demonstrated therapeutic efficacy by lowering serum soluble IL-2Rα (sIL-2Rα) levels (P<0.001) and prolonged the survival of tumor-bearing mice (P<0.0001). Moreover, the combination of YM155 with alemtuzumab demonstrated markedly additive anti-tumor activity by significantly lowering serum sIL-2Rα levels and improving the survival of leukemia-bearing mice compared to monotherapy with either YM155 (P<0.001) or alemtuzumab (P<0.05). More significantly, all mice that received the combination therapy survived and were tumor-free more than 6 months after treatment. Our data supports a clinical trial of the combination of YM155 with alemtuzumab in patients with ATL. Clinicaltrials.gov NCT00061048.

Giant Cell Myocarditis and Endomyocardial Calcification in a 2.5-Month-Old Infant Triggered by Excessive Maternal Alcohol Abuse: Case Study of an Unusual Association

This report describes an unusual case of a 2.5-month-old infant's sudden death secondary to giant cell myocarditis and endomyocardial calcification, both unusual entities in pediatric patients. The mother had a history of excessive alcohol consumption during pregnancy and the postnatal period. No infectious etiologies, hypersensivity, or autoimmune disorders were identified. Therefore, the authors assume that alcohol exposure might be responsible for the inflammatory giant cell process complicated with endomyocardial calcification in susceptible infants. This report is the first to describe the rare form of noninfectious myocarditis complicated with endomyocardial calcification possibly triggered by a toxic agent. The authors discuss the possible interaction between these processes that led to the infant's sudden death.

Selectivity of CO(2) Reduction on Copper Electrodes: The Role of the Kinetics of Elementary Steps

On the right path: Based on DFT calculations (incorporating the role of water solvation) of the activation barriers of elementary steps, a new path that leads to methane and ethylene for CO(2) electroreduction on Cu(111) was identified. Methane formation proceeds through reduction of CO to COH (path II), which leads to CH(x) species that can produce both methane and ethylene, as observed experimentally.

Cerebral Microvascular Network Geometry Changes in Response to Functional Stimulation

The cortical microvessels are organized in an intricate, hierarchical, three-dimensional network. Superimposed on this anatomical complexity is the highly complicated signaling that drives the focal blood flow adjustments following a rise in the activity of surrounding neurons. The microvascular response to neuronal activation remains incompletely understood. We developed a custom two photon fluorescence microscopy acquisition and analysis to obtain 3D maps of neuronal activation-induced changes in the geometry of the microvascular network of the primary somatosensory cortex of anesthetized rats. An automated, model-based tracking algorithm was employed to reconstruct the 3D microvascular topology and represent it as a graph. The changes in the geometry of this network were then tracked, over time, in the course of electrical stimulation of the contralateral forepaw. Both dilatory and constrictory responses were observed across the network. Early dilatory and late constrictory responses propagated from deeper to more superficial cortical layers while the response of the vertices that showed initial constriction followed by later dilation spread from cortical surface toward increasing cortical depths. Overall, larger caliber adjustments were observed deeper inside the cortex. This work yields the first characterization of the spatiotemporal pattern of geometric changes on the level of the cortical microvascular network as a whole and provides the basis for bottom-up modeling of the hemodynamically-weighted neuroimaging signals.

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