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Articles by L. Cornelissen in JoVE

 JoVE Neuroscience

Electrophysiological माप और Nociception के मानव शिशुओं में विश्लेषण


JoVE 3118 12/20/2011

1Neuroscience, Physiology and Pharmacology, University College London, 2Department of Clinical Neurophysiology, Great Ormond Street Hospital, 3Elizabeth Garrett Anderson Obstetric Hospital, University College Hospital, 4Nuffield Department of Anaesthetics, University of Oxford

और शिशुओं में दर्द का आकलन के उपचार के लिए मुश्किल है क्योंकि शिशुओं को मौखिक रूप से उनके अनुभव की रिपोर्ट नहीं कर सकते हैं. इस वीडियो में हम मात्रात्मक electrophysiological तरीकों और विश्लेषण तकनीकों है कि शिशु तंत्रिका तंत्र से हानिकारक घटनाओं के लिए प्रतिक्रिया को मापने के लिए इस्तेमाल किया जा सकता है का वर्णन.

Other articles by L. Cornelissen on PubMed

The Use of the Saccade Target As a Visual Reference when Localizing Flashes During Saccades

Flashes presented around the time of a saccade are often mislocalized. Such mislocalization is influenced by various factors. Here, we evaluate the role of the saccade target as a landmark when localizing flashes. The experiment was performed in a normally illuminated room to provide ample other visual references. Subjects were instructed to follow a randomly jumping target with their eyes. We flashed a black dot on the screen around the time of saccade onset. The subjects were asked to localize the black dot by touching the appropriate location on the screen. In a first experiment, the saccade target was displaced during the saccade. In a second experiment, it disappeared at different moments. Both manipulations affected the mislocalization. We conclude that our subjects' judgments are partly based on the flashed dot's position relative to the saccade target.

Virus-like Particles Templated by DNA Micelles: a General Method for Loading Virus Nanocarriers

DNA amphiphile particles template formation of virus capsids and enable their loading.

Experimental Studies and Modeling on Concentration Polarization in Forward Osmosis

Concentration polarization (CP) is an important issue in forward osmosis (FO) processes and it is believed that the coupled effect of dilutive internal CP (DICP) and concentrative external CP (CECP) limits FO flux. The objective of this study was to distinguish individual contribution of different types of DICP and CECP via modeling and to validate it by pilot studies. The influence of DICP/CECP on FO flux has been investigated in this study. The CP model presented in this work was derived from a previous study and evaluated by bench-scale FO experiments. Experiments were conducted with drinking water as the feed and NaCl/MgSO(4) as draw solutions at different concentrations and velocities. Modeling results indicated that DICP contributed to a flux reduction by 99.9% for 0.5 M NaCl as a draw solution although the flow pattern of both feed and draw solutions was turbulent. DICP could be improved via selection of the draw solution. The modeling results were well fit with the experimental data. It was concluded that the model could be used for selection of the draw solution and prediction of water flux under similar situation. A draw solution with greater diffusion coefficient or a thinner substrate of an asymmetric FO membrane resulted in a higher flux.

Complex Assembly Behavior During the Encapsulation of Green Fluorescent Protein Analogs in Virus Derived Protein Capsules

Enzymes encapsulated in nanocontainers are a better model of the conditions inside a living cell than free enzymes in solution. In a first step toward the encapsulation of multiple enzymes inside the cowpea chlorotic mottle virus (CCMV) capsid, enhanced green fluorescent protein (EGFP) was attached to CCMV capsid proteins. The capsid protein-EGFP complex was then co-assembled with wild-type capsid protein (wt CP) in various ratios. At higher complex to wt CP ratios, the number of EGFP per capsid decreased instead of leveling off. We propose that this unexpected behavior is caused by pH-induced disassembly of the capsid protein-EGFP complex as well as by concentration and ratio dependent dimerization of the complex, making it partially unavailable for incorporation into the capsid.

The Small Heat Shock Protein 20 RSI2 Interacts with and is Required for Stability and Function of Tomato Resistance Protein I-2

Race-specific disease resistance in plants depends on the presence of resistance (R) genes. Most R genes encode NB-ARC-LRR proteins that carry a C-terminal leucine-rich repeat (LRR). Of the few proteins found to interact with the LRR domain, most have proposed (co)chaperone activity. Here, we report the identification of RSI2 (Required for Stability of I-2) as a protein that interacts with the LRR domain of the tomato R protein I-2. RSI2 belongs to the family of small heat shock proteins (sHSPs or HSP20s). HSP20s are ATP-independent chaperones that form oligomeric complexes with client proteins to prevent unfolding and subsequent aggregation. Silencing of RSI2-related HSP20s in Nicotiana benthamiana compromised the hypersensitive response that is normally induced by auto-active variants of I-2 and Mi-1, a second tomato R protein. As many HSP20s have chaperone properties, the involvement of RSI2 and other R protein (co)chaperones in I-2 and Mi-1 protein stability was examined. RSI2 silencing compromised the accumulation of full-length I-2 in planta, but did not affect Mi-1 levels. Silencing of heat shock protein 90 (HSP90) and SGT1 led to an almost complete loss of full-length I-2 accumulation and a reduction in Mi-1 protein levels. In contrast to SGT1 and HSP90, RSI2 silencing led to accumulation of I-2 breakdown products. This difference suggests that RSI2 and HSP90/SGT1 chaperone the I-2 protein using different molecular mechanisms. We conclude that I-2 protein function requires RSI2, either through direct interaction with, and stabilization of I-2 protein or by affecting signalling components involved in initiation of the hypersensitive response.

A Single Immunization with Soluble Recombinant Trimeric Hemagglutinin Protects Chickens Against Highly Pathogenic Avian Influenza Virus H5N1

The highly pathogenic avian influenza (HPAI) virus H5N1 causes multi-organ disease and death in poultry, resulting in significant economic losses in the poultry industry. In addition, it poses a major public health threat as it can be transmitted directly from infected poultry to humans with very high (60%) mortality rate. Effective vaccination against HPAI H5N1 would protect commercial poultry and would thus provide an important control measure by reducing the likelihood of bird-to-bird and bird-to-human transmission.

Immune Monitoring with ITAg MHC Tetramers for Prediction of Recurrent or Persistent Cytomegalovirus Infection or Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients: a Prospective Multicenter Study

Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant recipients despite the introduction of posttransplantation viral monitoring and preemptive antiviral therapy. We evaluated the use of HLA class I tetramers in monitoring CMV-specific T-cell recovery to predict patients at risk for CMV-related complications. This prospective multicenter clinical trial obtained nearly 1400 tetramer/allele results in more than 800 biweekly blood samples from 83 patients monitored for 1 year after transplantation. Major HLA types were included (A*0101, A*0201, B*0702, B*0801, B*3501). iTAg MHC Tetramers (Beckman Coulter) were used to enumerate CMV-specific CD8(+) T cells by flow cytometry using a single-platform absolute counting method. Assay variability was 8% or less and results were available within 3 hours. Delayed recovery of CMV-specific T cells (< 7 cells/μL in all blood samples during the first 65 days after transplantation) was found to be a significant risk factor for CMV-related complications; these patients were more likely to develop recurrent or persistent CMV infection (relative risk 2.6, CI 1.2-5.8, P = .01) than patients showing rapid recovery, which was associated with protection from CMV-related complications (P = .004). CMV tetramer-based immune monitoring, in conjunction with virologic monitoring, can be an important new tool to assess risk of CMV-related complications and to guide preemptive therapeutic choices.

Effect of Gabapentin on Pain After Cardiac Surgery: a Randomised, Double-blind, Placebo-controlled Trial

This study evaluated whether perioperative administration of gabapentin in cardiac surgery patients could reduce postoperative opioid consumption, postoperative sleep or perceived quality of recovery. This randomised controlled trial assigned 60 patients undergoing cardiac surgery to receive 1200 mg of gabapentin or placebo two hours preoperatively, and then 600 mg of gabapentin or placebo twice a day for the next two postoperative days. Postoperative opioid use was measured by the amount of fentanyl used in the first 48 hours postoperatively. Pain at rest and with movement at 12, 24, 48 and 72 hours after surgery, sleep scores on postoperative days two and three and patient-perceived quality of recovery were also assessed. Fentanyl use, visual analog pain scores, sleep scores, adjunctive pain medication use and number of anti-emetics given were not significantly different between the gabapentin and placebo groups. The incidence of side-effects was similar between the gabapentin and placebo groups, and no difference was found between groups in relation to quality of recovery. These findings indicate that preoperative use of gabapentin followed by postoperative dosing for two days did not significantly affect the postoperative pain, sleep, opioid consumption or patient-perceived quality of recovery for patients undergoing cardiac surgery.

Models As Instruments for Optimizing Hospital Processes: a Systematic Review

The purpose of this article is to find decision-making models for the design and control of processes regarding patient flows, considering various problem types, and to find out how usable these models are for managerial decision making.

HIV RNA Levels in Transmission Sources Only Weakly Predict Plasma Viral Load in Recipients

Insect Herbivores of Coccoloba Cereifera Do Not Select Asymmetric Plants

Fluctuating asymmetry (FA) represents small, random variations from the symmetric bilateral pattern, and it is a frequently used measurement of plant and animal stresses. Some studies have shown a relationship between FA and herbivory, suggesting that FA might be a reliable indicator of plant quality and plant susceptibility to herbivore attack. In this study, we investigated the relationship between leaf FA of Coccoloba cereifera Schwacke (Polygonaceae) and the pattern of attack by the scale insect Abgrallaspis cyanophylly Signoret (Hemiptera: Diaspididae). Thirty individuals of C. cereifera were marked and followed during 2007 in southeastern Brazil, and all leaves of three shoots per plant were sampled, numbered, and categorized as young, mature, or senescent. We measured right and left widths of all leaves after digitizing the images to determine levels of FA for each leaf sampled per plant. Individuals of A. cyanophylli were counted using a stereoscope in the laboratory to determine infestation levels. Leaves of C. cereifera exhibited true patterns of FA, as shown by the normal distribution of asymmetry values. We observed high variation in attack rates by A. cyanophylly among C. cereifera individuals, with 43.3% of plants with no insects, whereas others exhibited up to 23,000 insects. No statistically significant relationship was observed between variation in FA and variation in A. cyanophylli among plants. These results suggest that FA cannot be used as an indicator of plant quality and susceptibility to herbivore attack but suggest that herbivores themselves might act as plant stressors.

Bioaccumulation of Polychlorinated Dibenzo-p-dioxins/dibenzofurans in E. Fetida from Floodplain Soils and the Effect of Activated Carbon Amendment

Laboratory studies were conducted to evaluate the bioaccumulation of aged polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in soil near the base of the terrestrial food chain using earthworms (E. fetida) as a model organism. This research also assessed the effect of activated carbon (AC) addition to soil on PCDD/F bioaccumulation in earthworms and passive uptake in polyoxymethylene (POM) samplers. Two soils taken from a wetland and a levee along the Tittabawassee River floodplain downstream of Midland, MI were used in this study. In the untreated soils, biota sediment accumulation factors (BSAFs) ranged from 0.17 for 2,3,7,8-TCDD to 0.02 for some of the higher chlorinated congeners, which were substantially lower than would be predicted using a conventional equilibrium partitioning model. The addition of AC to the floodplain soils generally reduced the BSAF values to lower than 0.02. Amendment of the wetland soil (having a high organic content) with 2% and 5% AC resulted in a 78 and 91% reduction of toxicity equivalent (TEQ) in earthworms, respectively. More strikingly, amendment of the natural levee soil (having a low organic content) with 2% and 5% AC showed >99% reduction of TEQ in earthworms. Also, freely dissolved aqueous concentrations of PCDD/Fs in soil slurries, as measured by equilibrium passive samplers, decreased up to 99% with AC treatment. Results of this study indicate that bioaccumulation of PCDD/Fs in earthworms from historically impacted floodplain soils is low and can be further reduced by amending with a strong sorbent.

Effect of Creatine Supplementation As a Potential Adjuvant Therapy to Exercise Training in Cardiac Patients: a Randomized Controlled Trial

To investigate the effect of oral creatine supplementation in conjunction with an exercise programme on physical fitness in patients with coronary artery disease or chronic heart failure.

Neonatal and Maternal Concentrations of Hydroxil Radical and Total Antioxidant System: Protective Role of Placenta Against Fetal Oxidative Stress

Reactive oxygen species (ROS) may cause peroxydation of lipids, proteins and deoxyribonucleic acids with subsequent cell damage. The hydroxyl radical (OH*) represents a measure of global oxidative stress. Hydroxyl radicals are short-lived; they form an important part of radical chemistry nonetheless. The measure of total antioxidant system (TAS) can give useful information about the extent of defence capable of counteracting the oxidative damage. Pregnancy is an important condition that favors oxidative stress in the fetus. Clinical studies indicate a protective mechanism against O2 toxicity in the human feto-placental unit.

Non-pharmacological Care for Patients with Generalized Osteoarthritis: Design of a Randomized Clinical Trial

Non-pharmacological treatment (NPT) is a useful treatment option in the management of hip or knee osteoarthritis. To our knowledge however, no studies have investigated the effect of NPT in patients with generalized osteoarthritis (GOA). The primary aim of this study is to compare the effectiveness of two currently existing health care programs with different intensity and mode of delivery on daily functioning in patients with GOA. The secondary objective is to compare the cost-effectiveness of both interventions.

Virtual Electron Microscopy in Cell Biology

Virtual microscopy of histological glass slides can emulate conventional light microscopy. Up till now, such a digital simulation does not exist for ultrathin electron microscopic slides. Because of the relative inaccessibility of electron microscopy, evaluation of subcellular structures by (bio)medical students is performed with the aid of photographic prints. In this article, the generation and evaluation of virtual electron microscopic slides is discussed. A T-lymphoblastic cell was used as an example. Electron microscopic pictures were taken at two magnifications (25,000 and 50,000), processed in an analogue or digital way and stitched to reconstruct the image of the total cell. This image is viewed with a webviewer equipped with pan and zoom functions. The possibility of distinguishing the trilaminar structure of cellular membranes was the requisite. Virtual images obtained at an original magnification of 25,000, scanned at a resolution of 800 ppi could compete with pictures developed directly from negatives obtained by electron microscopy. It is possible to navigate and zoom into details in a way emulating electron microscopy. Virtual electron microscopy is innovative and offers new perspectives to interpret cytological pictures and to teach cell biology in an interactive and unique way. Microsc. Res. Tech., 2010. (c) 2010 Wiley-Liss, Inc.

Detection of Occult Endoleaks After Endovascular Treatment of Abdominal Aortic Aneurysm Using Magnetic Resonance Imaging with a Blood Pool Contrast Agent: Preliminary Observations

To determine whether blood pool contrast agent-enhanced magnetic resonance imaging (MRI) can visualize endoleaks that are occult on computed tomography (CT) in patients with nonshrinking aneurysms after endovascular aneurysm repair.

Analysis of Infectious Virus Clones from Two HIV-1 Superinfection Cases Suggests That the Primary Strains Have Lower Fitness

Two HIV-1 positive patients, L and P, participating in the Amsterdam Cohort studies acquired an HIV-1 superinfection within half a year from their primary HIV-1 infection (Jurriaans et al., JAIDS 2008, 47:69-73). The aim of this study was to compare the replicative fitness of the primary and superinfecting HIV-1 strains of both patients. The use of isolate-specific primer sets indicated that the primary and secondary strains co-exist in plasma at all time points after the moment of superinfection.

A Hydrogel-based Enzyme-loaded Polymersome Reactor

In this study we report the immobilization of enzyme-containing polymersomes into a macromolecular hydrogel. Whereas free enzyme shows progressive leakage from the hydrogel in a period of days, leakage of the polymersome-protected enzyme is virtually absent. The preparation of the hydrogel occurs under mild conditions and does not inhibit the activity of the encapsulated enzymes nor does it affect the structure of the polymersomes. The stability of the polymersome hydrogel architecture is demonstrated by the facile recycling of the polymersomes and their use in repeated reaction cycles. A 'continuous-flow polymersome reactor' is constructed in which substrate is added to the top of the reactor and product is collected at the bottom. This set-up allows the use of different enzymes and the processing of multiple substrates, as is demonstrated by the conversion of 2-methoxyphenyl acetate to tetraguaiacol in a reactor loaded with polymersome hydrogels containing the enzymes Candida antarctica lipase B (CALB) and glucose oxidase (GOx).

Coordinated Variation in Leaf and Root Traits Across Multiple Spatial Scales in Chinese Semi-arid and Arid Ecosystems

• Variation in plant functional traits is the product of evolutionary and environmental drivers operating at different scales. Little is known about whether, or how, this variation is coordinated between aboveground and belowground organs across and within spatial scales. • We address these questions using a hierarchically designed dataset of pairwise leaf and root traits related to carbon and nutrient economy of 64 species belonging to 14 plant communities in northern Chinese semi-arid and arid regions. • While both root and leaf traits showed most of their variance among (individuals and) species within communities, leaf trait variance tended to be relatively higher at coarser spatial scales than root trait variance. While leaf nitrogen (N) per area to root N per length ratio increased and specific leaf area to specific root length and leaf [N] to root [N] ratios decreased from semi-arid to arid environments owing to climatic/edaphic shifts, the matching pairs showed a strong pattern of positive correlation that was upheld across spatial scales and geographic areas. • Thus, trade-offs in plant resource investment across organs within individual vascular plants are constrained within a rather narrow range of variation. A new challenge will be to test whether and how such trait coordination is also seen within and across other biomes of the world.

Field Measurement of Diffusional Mass Transfer of HOCs at the Sediment-water Interface

The sediment to water diffusive flux of PAHs and PCBs was measured under field conditions with a novel infinite-sink benthic flux chamber that deployed semipermeable membrane devices (SPMD) as a sorbing material. Fluxes were measured before and after in situ capping of sediments in Oslo Harbour with clean clay. The fluxes of native pyrene and PCB 52 from uncapped contaminated sediment measured with the flux chamber were 0.3-1.6 microg m(-2) d(-1) and 2-8 ng m(-2) d(-1), respectively. Fluxes from the capped sediment were reduced by 93-97%. The in situ measured fluxes were compared to fluxes independently calculated from freely dissolved concentrations in pore water and overlying water, measured using equilibrium passive samplers, diffusive boundary layer (DBL) thickness, measured by an alabaster dissolution method and literature values of diffusion coefficients. Measured fluxes from the uncapped sediment agreed well with calculated fluxes, the median of the ratio of the measured flux over the calculated flux was 0.9 with an inter quartile range of 0.5-1.6.

Introducing the Scanning Air Puff Tonometer for Biological Studies

It is getting increasingly evident that physical properties such as elastoviscoplastic properties of living materials are quite important for the process of tissue development, including regulation of genetic pathways. Measuring such properties in vivo is a complicated and challenging task. In this paper, we present an instrument, a scanning air puff tonometer, which is able to map point by point the viscoelastic properties of flat or gently curved soft materials. This instrument is an improved version of the air puff tonometer used by optometrists, with important modifications. The instrument allows one to obtain a direct insight into gradients of material properties in vivo. The instrument capabilities are demonstrated on substances with known elastoviscoplastic properties and several biological objects. On the basis of the results obtained, the role of the gradients of elastoviscoplastic properties is outlined for the process of angiogenesis, limb development, bacterial colonies expansion, etc. which is important for bridging the gaps in the theory of the tissue development and highlighting new possibilities for tissue engineering, based on a clarification of the role of physical features in developing biological material.

Stomatal Vs. Genome Size in Angiosperms: the Somatic Tail Wagging the Genomic Dog?

Genome size is a function, and the product, of cell volume. As such it is contingent on ecological circumstance. The nature of 'this ecological circumstance' is, however, hotly debated. Here, we investigate for angiosperms whether stomatal size may be this 'missing link': the primary determinant of genome size. Stomata are crucial for photosynthesis and their size affects functional efficiency.

Effect of Anionic Fluidized Ion Exchange (FIX) Pre-treatment on Nanofiltration (NF) Membrane Fouling

Anionic Fluidized Ion Exchange (FIX) is used to improve the performance of downstream Nanofiltration (NF). The research is divided in three parts: (i) NOM removal by FIX, (ii) the effect of FIX treatment on NF fouling and (iii) FIX treatment in relation to biological stability. Pre-treated anaerobic groundwater was (i) fed directly to a 4-inch membrane element and (ii) fed to another 4-inch membrane element after anionic FIX treatment. The operational parameters of the membrane set-up were monitored during 42 days, followed by a membrane autopsy study in which accumulated biological, organic and inorganic fouling was determined. Parallel to this experiment, two small ion exchange (IEX) resin and glass beads filled columns were operated to study the effect of FIX on the biomass concentration of the feed water. FIX operated satisfactory and selectively removed humic substances (>90%) and hydrophobic organic carbon (HOC) (>80%) from the feed water. Furthermore, iron was substantially removed (71%) which was explained by complexation with humic substances. Removal of NOM by FIX did not reduce membrane fouling problems; the Membrane Transport Coefficient (MTC) decreased and the Normalized Pressure Drop (NPD) increased more rapidly for the NF membrane after FIX compared to the membrane without FIX pre-treatment. NOM removal by FIX did not reduce adsorption of organic matter onto the downstream membrane element, since predominantly humic substances were removed which did not adsorb to the membrane surface. FIX treatment resulted in higher biomass densities (400%) and slightly less iron deposition (20%) onto the membrane surface. Fouling of the membrane element after FIX treatment was dominated by biofouling and fouling of the reference membrane element experienced more colloidal iron fouling compared to the membrane element after FIX, both resulting in an increase in NPD. The microbiological water quality deteriorated after anionic FIX treatment, as was observed by an increase in ATP content. Growth of biomass onto the IEX resins was observed which was caused by both IEX materials and feed water components, such as NOM fractions.

During Visual Word Recognition, Phonology is Accessed Within 100 Ms and May Be Mediated by a Speech Production Code: Evidence from Magnetoencephalography

Debate surrounds the precise cortical location and timing of access to phonological information during visual word recognition. Therefore, using whole-head magnetoencephalography (MEG), we investigated the spatiotemporal pattern of brain responses induced by a masked pseudohomophone priming task. Twenty healthy adults read target words that were preceded by one of three kinds of nonword prime: pseudohomophones (e.g., brein-BRAIN), where four of five letters are shared between prime and target, and the pronunciation is the same; matched orthographic controls (e.g., broin-BRAIN), where the same four of five letters are shared between prime and target but pronunciation differs; and unrelated controls (e.g., lopus-BRAIN), where neither letters nor pronunciation are shared between prime and target. All three priming conditions induced activation in the pars opercularis of the left inferior frontal gyrus (IFGpo) and the left precentral gyrus (PCG) within 100 ms of target word onset. However, for the critical comparison that reveals a processing difference specific to phonology, we found that the induced pseudohomophone priming response was significantly stronger than the orthographic priming response in left IFG/PCG at approximately 100 ms. This spatiotemporal concurrence demonstrates early phonological influences during visual word recognition and is consistent with phonological access being mediated by a speech production code.

Slow Cooling Cryopreservation of Cell-microcarrier Constructs

Ideally, tissue engineered constructs should be readily available to meet the need for fast intervention in complex bone defects. To circumvent the long culture period of these constructs before implantation, we investigated the possibility of cryopreserving cell-loaded constructs. Goat bone marrow-derived mesenchymal stem cells (BMSC) and mouse osteoblast-like cells from the MC3T3-E1 cell line were cultured on gelatin CultiSpher-S(R) microcarriers. These constructs were cryopreserved using the slow cooling technique, i.e. cooling to -80 degrees C at a rate of -1.5 degrees C/min, and were then stored in liquid nitrogen for 1 week. Four different cryomedia were tested, i.e. 90 vol% serum with 10 vol% dimethylsulphoxide (Me(2)SO) with or without ascorbic acid (AA) and 90 vol% serum supplemented with 5 vol% Me(2)SO and 5 vol% hydroxyethyl starch or 5 vol% sucrose (60 mM). Cell viability on the constructs was assessed with fluorescent live/dead staining and the colorimetric MTS assay. Cell viability was compared before freezing and at fixed time points after thawing. Immediately after thawing, the viability percentages in all groups were significantly lower than before cryopreservation (p = 0.0369). No significant differences were observed between the viability percentages on the cell constructs cryopreserved in the different media; however, there was a general tendency for higher cell survival and faster recolonization of constructs cryopreserved in Me(2)SO with or without AA than of the constructs cryopreserved in the other media. For constructs cryopreserved in 10 vol% Me(2)SO with or without AA, the recolonization period was 3 days for the BMSC constructs and 3.6 and 3.8 days, respectively, for the MC3T3-E1 constructs.

Self-assembly and Optically Triggered Disassembly of Hierarchical Dendron-virus Complexes

Nature offers a vast array of biological building blocks that can be combined with synthetic materials to generate a variety of hierarchical architectures. Viruses are particularly interesting in this respect because of their structure and the possibility of them functioning as scaffolds for the preparation of new biohybrid materials. We report here that cowpea chlorotic mottle virus particles can be assembled into well-defined micrometre-sized objects and then reconverted into individual viruses by application of a short optical stimulus. Assembly is achieved using photosensitive dendrons that bind on the virus surface through multivalent interactions and then act as a molecular glue between the virus particles. Optical triggering induces the controlled decomposition and charge switching of dendrons, which results in the loss of multivalent interactions and the release of virus particles. We demonstrate that the method is not limited to the virus particles alone, but can also be applied to other functional protein cages such as magnetoferritin.

Macromolecular Multi-chromophoric Scaffolding

This critical review describes recent efforts in the field of chromophoric scaffolding. The advances in this research area, with an emphasis on rigid scaffolds, for example, synthetic polymers, carbon nanotubes (CNTs), nucleic acids, and viruses, are presented (166 references).

Methylation Patterns in CD34 Positive Chronic Myeloid Leukemia Blast Crisis Cells

Enhancing Bone Healing and Regeneration: Present and Future Perspectives in Veterinary Orthopaedics

Methods currently used to restore bone defects in human and veterinary orthopaedics are often not satisfactory. This is especially the case in the healing of large, irregular defects which result in the formation of tissues with inferior qualities compared to the original structures. For these reasons, several new approaches are currently being explored to improve bone healing capacities in different situations. This review will examine the different techniques used to enhance bone regeneration, highlighting both experimental and clinically applicable methods with regard to veterinary orthopaedics.

Cysteine-containing Polyisocyanides As Versatile Nanoplatforms for Chromophoric and Bioscaffolding

The straightforward syntheses of polyisocyanides containing the alanine-cysteine motif in their side chains have been achieved. Detailed characterization of the polymers revealed a well-defined and highly stable helical conformation of the polyimine backbone responsible for the formation of rodlike structures of over one hundred nanometers. The 4(1) helix is further stabilized by beta-sheet-like interactions between the peptide arms. As a result, the cysteine sulfur atoms are regularly aligned along the polymer axis, which provides a unique platform for the scaffolding of various entities by using versatile click-chemistry postmodification approaches. For instance, pyrene derivatives were introduced through thio-specific reactions involving either maleimide, iodoacetamide, or thioester groups, leading to arrays of stacked chromophores with excimer-like emission. A water-soluble cysteine-rich polyisocyanide was successfully biotinylated and coupled to streptavidin.

Lack of Detection of XMRV in Seminal Plasma from HIV-1 Infected Men in The Netherlands

Xenotropic murine leukaemia virus-related virus (XMRV) is a recently discovered human gammaretrovirus with yet unknown prevalence and transmission route(s). Its presence in prostate stromal fibroblasts and prostatic secretions suggests that XMRV might be sexually transmitted. We chose to study a compartment closely connected to the prostate, a location where XMRV was detected in independent studies. Seminal plasma samples from HIV-1 infected men were examined as they have an increased probability of acquiring sexually transmitted pathogens.

Which Anatomical Region Determines a Positive Flexion Test of the Distal Aspect of a Forelimb in a Nonlame Horse?

The flexion test is used routinely as part of lameness and prepurchase examinations. However, little is known about the mechanisms that cause a positive response to a flexion test.

Polymersome Stomatocytes: Controlled Shape Transformation in Polymer Vesicles

We report here a controllable shape transformation of polymer vesicles (polymersomes) constructed from block copolymers of which the hydrophobic part is a high-molecular-weight glassy segment. Control over the shape transformation is obtained by kinetic manipulation of the phase behavior of this glassy hydrophobic segment. Kinetic manipulation of the phase behavior of polymer membranes allows for different shapes of polymersomes to be captured at specific times, which directly translates into physically robust nanostructures that are otherwise unobtainable. Combining the morphological diversity of giant liposomes and the physical robustness of polymersomes, our finding can be a general way to realize unusual nanostructures in a predictable manner.

Economic Assessment of Flash Co-pyrolysis of Short Rotation Coppice and Biopolymer Waste Streams

The disposal problem associated with phytoextraction of farmland polluted with heavy metals by means of willow requires a biomass conversion technique which meets both ecological and economical needs. Combustion and gasification of willow require special and costly flue gas treatment to avoid re-emission of the metals in the atmosphere, whereas flash pyrolysis mainly results in the production of (almost) metal free bio-oil with a relatively high water content. Flash co-pyrolysis of biomass and waste of biopolymers synergistically improves the characteristics of the pyrolysis process: e.g. reduction of the water content of the bio-oil, more bio-oil and less char production and an increase of the HHV of the oil. This research paper investigates the economic consequences of the synergistic effects of flash co-pyrolysis of 1:1 w/w ratio blends of willow and different biopolymer waste streams via cost-benefit analysis and Monte Carlo simulations taking into account uncertainties. In all cases economic opportunities of flash co-pyrolysis of biomass with biopolymer waste are improved compared to flash pyrolysis of pure willow. Of all the biopolymers under investigation, polyhydroxybutyrate (PHB) is the most promising, followed by Eastar, Biopearls, potato starch, polylactic acid (PLA), corn starch and Solanyl in order of decreasing profits. Taking into account uncertainties, flash co-pyrolysis is expected to be cheaper than composting biopolymer waste streams, except for corn starch. If uncertainty increases, composting also becomes more interesting than flash co-pyrolysis for waste of Solanyl. If the investment expenditure is 15% higher in practice than estimated, the preference for flash co-pyrolysis compared to composting biopolymer waste becomes less clear. Only when the system of green current certificates is dismissed, composting clearly is a much cheaper processing technique for disposing of biopolymer waste.

[Pulmonary Necrotizing Sarcoid Granulomatosis in a Patient with Primary Biliary Cirrhosis]

A 53-year-old woman presented with recurrent episodes of cough and non-specific pulmonary symptoms. For many years she had been known to have primary biliary cirrhosis.

Neurocognitive Functioning in School-aged Cystinosis Patients

Cystinosis is an autosomal recessive disorder leading to intralysosomal cystine accumulation in various tissues. It causes renal Fanconi syndrome and end stage renal failure around the age of 10 years if not treated with cysteamine. Children with cystinosis seem to have a normal intelligence but frequently show learning difficulties. These problems may be due to specific neurocognitive deficits rather than impaired renal function. Whether cysteamine treatment can improve cognitive functioning of cystinosis patients is thus far unknown. We aim to analyze neurocognitive functioning of school-aged cystinosis patients treated with cysteamine in order to identify specific deficits that can lead to learning difficulties.

Oral Sucrose As an Analgesic Drug for Procedural Pain in Newborn Infants: a Randomised Controlled Trial

Many infants admitted to hospital undergo repeated invasive procedures. Oral sucrose is frequently given to relieve procedural pain in neonates on the basis of its effect on behavioural and physiological pain scores. We assessed whether sucrose administration reduces pain-specific brain and spinal cord activity after an acute noxious procedure in newborn infants.

Post-plasma Grafting of AEMA As a Versatile Tool to Biofunctionalise Polyesters for Tissue Engineering

In the last decade, substantial research in the field of post-plasma grafting surface modification has focussed on the introduction of carboxylic acids on surfaces by grafting acrylic acid (AAc). In the present work, we report on an alternative approach for biomaterial surface functionalisation. Thin poly-ε-caprolactone (PCL) films were subjected to a dielectric barrier discharge Ar-plasma followed by the grafting of 2-aminoethyl methacrylate (AEMA) under UV-irradiation. X-ray photoelectron spectroscopy (XPS) confirmed the presence of nitrogen. The ninhydrin assay demonstrated, both quantitatively and qualitatively, the presence of free amines on the surface. Confocal fluorescence microscopy (CFM), atomic force microscopy (AFM) and scanning electron microscopy (SEM) were used to visualise the grafted surfaces, indicating the presence of pAEMA. Static contact angle (SCA) measurements indicated a permanent increase in hydrophilicity. Furthermore, the AEMA grafted surfaces were applied for comparing the physisorption and covalent immobilisation of gelatin. CFM demonstrated that only the covalent immobilisation lead to a complete coverage of the surface. Those gelatin-coated surfaces obtained were further coated using fibronectin. Osteosarcoma cells demonstrated better cell-adhesion and cell-viability on the modified surfaces, compared to the pure PCL films.

Preliminary Study of Osmotic Membrane Bioreactor: Effects of Draw Solution on Water Flux and Air Scouring on Fouling

Preliminary study on a novel osmotic membrane bioreactor (OMBR) was explored. Objective of this study was to investigate the effects of draw solution on membrane flux and air scouring at the feed side on fouling tendency in a pilot OMBR system composing the anoxic/aerobic and forward osmosis (FO) processes. Domestic sewage was the raw feed, FO membrane from HTI and NaCl/MgSO4 draw solutions were used in the experiments. Fluxes of 3 l/m2/h (LMH) and 7.2 LMH were achieved at osmotic pressure of 5 and 22.4 atm, respectively. No significant flux decline was observed at 3 LMH over 190 h and at 7.2 LMH over 150 h when air scouring was provided at the feed side of the membrane. However, without air scouring, the flux at 22.4 atm osmotic pressure declined by 30% after 195 h and then levelled off. The potential advantages of the fouling reversibility with air scouring under the operating conditions of the pilot OMBR and better water quality in OMBR over the conventional MBR were preliminarily demonstrated.

Generation of Representative Primary Virus Isolates from Blood Plasma After Isolation of HIV-1 with CD44 MicroBeads

Infection of cell cultures with cell-free virus isolated from HIV-infected patients is notoriously difficult and results in a loss of viral variation. Here, we describe viral sequences from PBMC, U87.CD4.CCR5 and U87.CD4.CXCR4 cell cultures and compare them to those from blood plasma from 12 patients from whom virus particles were isolated using CD44 MicroBeads. In both PBMC and U87.CD4.CCR5 cultures, 66% of the plasma viral strains were retrieved after culturing. In addition, coreceptor use was predicted based on the env-V3 sequence and tested in U87.CD4 cells expressing either CCR5 or CXCR4. Recovery was lower for the CXCR4-using viruses. Only 50% of the virus clusters predicted to use CXCR4 could be retrieved from cell cultures, while 71% of CCR5-using strains were found in U87.CCR5 cultures. Therefore, isolation of primary viruses with CD44 MicroBeads results in a good representation in cell culture of the in vivo divergence.

A New Ultrafast and High-throughput Mass Spectrometric Approach for the Therapeutic Drug Monitoring of the Multi-targeted Anti-folate Pemetrexed in Plasma from Lung Cancer Patients

An analytical assay has been developed and validated for ultrafast and high-throughput mass spectrometric determination of pemetrexed concentrations in plasma using matrix assisted laser desorption/ionization-triple quadrupole-tandem mass spectrometry. Patient plasma samples spiked with the internal standard methotrexate were measured by multiple reaction monitoring. The detection limit was 0.4 fmol/μL, lower limit of quantification was 0.9 fmol/μL, and upper limit of quantification was 60 fmol/μL, respectively. Overall observed pemetrexed concentrations in patient samples ranged between 8.7 (1.4) and 142.7 (20.3) pmol/μL (SD). The newly developed mass spectrometric assay is applicable for (routine) therapeutic drug monitoring of pemetrexed concentrations in plasma from non-small cell lung cancer patients.

Abnormalities in Circadian Blood Pressure Variability and Endothelial Function: Pragmatic Markers for Adverse Cardiometabolic Profiles in Asymptomatic Obese Adults

Cardiovascular disease (CVD) risk, although perceived to be high, is often difficult to demonstrate in disease free (healthy) obese adults.

The Impact of CD4+Foxp3+ Treg on Immunity to Murine Cytomegalovirus After Bone Marrow Transplantation Depends on the Peripheral or Thymic Source of T Cell Regeneration

The adoptive transfer of regulatory T cells (Treg) in murine models has been shown to ameliorate graft-versus-host disease while it may preserve the graft-versus-leukemia effect. However, the impact of Treg on infectious immunity after bone marrow transplantation (BMT) is still unclear. Immunocompetence against opportunistic viral infections depends on the kinetics of T cell recovery after BMT through two distinctive processes, i.e. lymphopenia-induced proliferation (LIP) of mature T cells and generation of T cells through thymopoiesis.

Encapsulation of DNA-templated Chromophore Assemblies Within Virus Protein Nanotubes

Differences in Eye-movement Patterns Between Anorexic and Control Observers when Judging Body Size and Attractiveness

Attentional biases may influence the eye-movements made when judging bodies and so alter the visual information sampled when making a judgment. This may lead to an overestimation of body size. We measured the eye-movements made by 16 anorexic observers and 16 age-matched controls when judging body size and attractiveness. We combined behavioural data with a novel eye-movement analysis technique that allowed us to apply spatial statistical techniques to make fine spatial discriminations in the pattern of eye-movements between our observer groups. Our behavioural results show that anorexic observers overestimate body size relative to controls and find bodies with lower body mass indexes more attractive. For both judgments, the controls' fixations centre on the stomach, but the anorexic observers show a much wider fixation pattern extending to encompass additional features such as the prominence of the hip and collar bones. This additional visual information may serve to alter their behavioural judgments towards an overestimation of body size and shift their ideal body size towards a significantly lower value.

Allogeneic Stem-cell Transplantation in Patients with Waldenström Macroglobulinemia: Report from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation

Allogeneic stem-cell transplantation (alloSCT) is a curative therapeutic option for patients with low-grade lymphoid malignancies. Information regarding alloSCT in Waldenström macroglobulinemia (WM) is limited. This study presents the long-term outcome of a large series of patients with WM treated with alloSCT.

Similar Cation Exchange Capacities Among Bryophyte Species Refute a Presumed Mechanism of Peatland Acidification

Fen-bog succession is accompanied by strong increases of carbon accumulation rates. We tested the prevailing hypothesis that living Sphagna have extraordinarily high cation exchange capacity (CEC) and therefore acidify their environment by exchanging tissue-bound protons for basic cations in soil water. As Sphagnum invasion in a peatland usually coincides with succession from a brown moss-dominated alkaline fen to an acidic bog, the CEC of Sphagna is widely believed to play an important role in this acidification process. However, Sphagnum CEC has never been compared explicitly to that of a wide range of other bryophyte taxa. Whether high CEC directly leads to the ability to acidify the environment in situ also remains to be tested. We screened 20 predominant subarctic bryophyte species, including fen brown mosses and bog Sphagna for CEC, in situ soil water acidification capacity (AC), and peat acid neutralizing capacity (ANC). All these bryophyte species possessed substantial CEC, which was remarkably similar for brown mosses and Sphagna. This refutes the commonly accepted idea of living Sphagnum CEC being responsible for peatland acidification, as Sphagnum's ecological predecessors, brown mosses, can do the same job. Sphagnum AC was several times higher than that of other bryophytes, suggesting that CE (cation exchange) sites of Sphagna in situ are not saturated with basic cations, probably due to the virtual absence of these cations in the bog water. Together, these results suggest that Sphagna can not realize their CEC in bogs, while fen mosses can do so in fens. The fen peat ANC was 65% higher than bog ANC, indicating that acidity released by brown mosses in the CE process was neutralized, maintaining an alkaline environment. We propose two successional pathways indicating boundaries for a fen-bog shift with respect to bryophyte CEC. In neither of them is Sphagnum CE an important factor. We conclude that living Sphagnum CEC does not play any considerable role in the fen-bog shift. Alternatively, we propose that exclusively indirect effects of Sphagnum expansion such as peat accumulation and subsequent blocking of upward alkaline soil water transport are keys to the fen-bog succession and therefore for bog-associated carbon accumulation.

Targeting the Nucleus: an Overview of Auger-electron Radionuclide Therapy

The review presented here lays out the present state of the art in the field of radionuclide therapies specifically targeted against the nucleus of cancer cells, focussing on the use of Auger-electron-emitters. Nuclear localisation of radionuclides increases DNA damage and cell kill, and, in the case of Auger-electron therapy, is deemed necessary for therapeutic effect. Several strategies will be discussed to direct radionuclides to the nucleoplasm, even to specific protein targets within the nucleus. An overview is given of the applications of Auger-electron-emitting radionuclide therapy targeting the nucleus. Finally, a few suggestions are made as how radioimmunotherapy with nuclear targets can be improved, and the challenges that might be met, such as how to perform accurate dosimetry measurements, are examined.

Roles and Interactions Among Protease-activated Receptors and P2ry12 in Hemostasis and Thrombosis

Toward understanding their redundancies and interactions in hemostasis and thrombosis, we examined the roles of thrombin receptors (protease-activated receptors, PARs) and the ADP receptor P2RY12 (purinergic receptor P2Y G protein-coupled 12) in human and mouse platelets ex vivo and in mouse models. Par3(-/-) and Par4(+/-) mouse platelets showed partially decreased responses to thrombin, resembling those in PAR1 antagonist-treated human platelets. P2ry12(+/-) mouse platelets showed partially decreased responses to ADP, resembling those in clopidogrel-treated human platelets. Par3(-/-) mice showed nearly complete protection against carotid artery thrombosis caused by low FeCl(3) injury. Par4(+/-) and P2ry12(+/-) mice showed partial protection. Increasing FeCl(3) injury abolished such protection; combining partial attenuation of thrombin and ADP signaling, as in Par3(-/-):P2ry12(+/-) mice, restored it. Par4(-/-) mice, which lack platelet thrombin responses, showed still better protection. Our data suggest that (i) the level of thrombin driving platelet activation and carotid thrombosis was low at low levels of arterial injury and increased along with the contribution of thrombin-independent pathways of platelet activation with increasing levels of injury; (ii) although P2ry12 acts downstream of PARs to amplify platelet responses to thrombin ex vivo, P2ry12 functioned in thrombin/PAR-independent pathways in our in vivo models; and (iii) P2ry12 signaling was more important than PAR signaling in hemostasis models; the converse was noted for arterial thrombosis models. These results make predictions being tested by ongoing human trials and suggest hypotheses for new antithrombotic strategies.

Cause of Heart Murmurs in 57 Apparently Healthy Cats

Heart murmurs are caused by turbulent blood flow or by vibration of cardiac structures. Turbulent blood flow may originate from structural heart disease or from physiological phenomena. The aims of this study were to establish the cause of heart murmurs in apparently healthy adult cats and to determine whether a heart murmur is a reliable indicator of heart disease. In this retrospective study, we reviewed the medical records of cats in which a heart murmur was detected during physical examination by one of the authors in the period January 2008 to December 2009. Cats younger than 6 months and those with systemic disease were excluded. Timing, grade, and point of maximum intensity of the murmur were determined by one observer (MD) before 2D-, M-mode and Doppler echocardiography. Fifty-seven cats (median age 76 months, range 6-194) were included, 30 neutered females and 27 neutered males. All murmurs were systolic and varied in intensity from 2/6 to 5/6. The point of maximum intensity was the left or right parasternal region in 34/57 (61%) of murmurs. Murmurs were caused by dynamic left ventricular outflow tract obstruction in 25/57 (44%) cats, dynamic right ventricular outflow tract obstruction in 9/57 (16%) cats, and combined dynamic left and right outflow tract obstruction in 11/57 (19%) cats. In 5 (9%) cats the cause of the murmur could not be identified. Heart disease was present in 50 (88%) cats, namely, left ventricular hypertrophy in 44 (77%) and congenital defects in 6 (11%) cats. In conclusion, most heart murmurs in apparently healthy cats are detected in the left or right parasternal region and are caused by dynamic left and right ventricular outflow tract obstruction. Because most cats (88%) with a heart murmur had heart disease in this study, if a heart murmur is detected in an apparently healthy cat, echocardiography is recommended to determine the cause of the heart murmur and the presence of heart disease.

The Trait Contribution to Wood Decomposition Rates of 15 Neotropical Tree Species

The decomposition of dead wood is a critical uncertainty in models of the global carbon cycle. Despite this, relatively few studies have focused on dead wood decomposition, with a strong bias to higher latitudes. Especially the effect of interspecific variation in species traits on differences in wood decomposition rates remains unknown. In order to fill these gaps, we applied a novel method to study long-term wood decomposition of 15 tree species in a Bolivian semi-evergreen tropical moist forest. We hypothesized that interspecific differences in species traits are important drivers of variation in wood decomposition rates. Wood decomposition rates (fractional mass loss) varied between 0.01 and 0.31 yr(-1). We measured 10 different chemical, anatomical, and morphological traits for all species. The species' average traits were useful predictors of wood decomposition rates, particularly the average diameter (dbh) of the tree species (R2 = 0.41). Lignin concentration further increased the proportion of explained inter-specific variation in wood decomposition (both negative relations, cumulative R2 = 0.55), although it did not significantly explain variation in wood decomposition rates if considered alone. When dbh values of the actual dead trees sampled for decomposition rate determination were used as a predictor variable, the final model (including dead tree dbh and lignin concentration) explained even more variation in wood decomposition rates (R2 = 0.71), underlining the importance of dbh in wood decomposition. Other traits, including wood density, wood anatomical traits, macronutrient concentrations, and the amount of phenolic extractives could not significantly explain the variation in wood decomposition rates. The surprising results of this multi-species study, in which for the first time a large set of traits is explicitly linked to wood decomposition rates, merits further testing in other forest ecosystems.

Egeson's (George's) Transtridecadal Weather Cycling and Sunspots

In the late 19th century, Charles Egeson, a map compiler at the Sydney Observatory, carried out some of the earliest research on climatic cycles, linking them to about 33-year cycles in solar activity, and predicted that a devastating drought would strike Australia at the turn of the 20th century. Eduard Brückner and William J. S. Lockyer, who, like Egeson, found similar cycles, with notable exceptions, are also, like the map compiler, mostly forgotten. But the transtridecadal cycles are important in human physiology, economics and other affairs and are particularly pertinent to ongoing discusions of climate change. Egeson's publication of daily weather reports preceded those officially recorded. Their publication led to clashes with his superiors and his personal life was marked by run-ins with the law and, possibly, an implied, but not proven, confinement in an insane asylum and premature death. We here track what little is known of Egeson's life and of his bucking of the conventional scientific wisdom of his time with tragic results.

Polymorphisms in the Multidrug Resistance Gene MDR1 (ABCB1) Predict for Molecular Resistance in Patients with Newly Diagnosed Chronic Myeloid Leukemia Receiving High-dose Imatinib

Evidence for Acute Neurotoxicity After Chemotherapy

Chronic neurotoxicity is a recognized long-term complication following chemotherapy in a range of diseases. Neurotoxicity adversely affects patients' quality of life. The objective of this study is to examine whether there is evidence of acute neurotoxicity.

Search for New Particles in Two-jet Final States in 7 TeV Proton-proton Collisions with the ATLAS Detector at the LHC

A search for new heavy particles manifested as resonances in two-jet final states is presented. The data were produced in 7 TeV proton-proton collisions by the LHC and correspond to an integrated luminosity of 315  nb⁻¹ collected by the ATLAS detector. No resonances were observed. Upper limits were set on the product of cross section and signal acceptance for excited-quark (q*) production as a function of q* mass. These exclude at the 95% C.L. the q* mass interval 0.30

Observation of a Centrality-dependent Dijet Asymmetry in Lead-lead Collisions at Sqrt[S(NN)] =2.76 TeV with the ATLAS Detector at the LHC

By using the ATLAS detector, observations have been made of a centrality-dependent dijet asymmetry in the collisions of lead ions at the Large Hadron Collider. In a sample of lead-lead events with a per-nucleon center of mass energy of 2.76 TeV, selected with a minimum bias trigger, jets are reconstructed in fine-grained, longitudinally segmented electromagnetic and hadronic calorimeters. The transverse energies of dijets in opposite hemispheres are observed to become systematically more unbalanced with increasing event centrality leading to a large number of events which contain highly asymmetric dijets. This is the first observation of an enhancement of events with such large dijet asymmetries, not observed in proton-proton collisions, which may point to an interpretation in terms of strong jet energy loss in a hot, dense medium.

Moral Distress Among Healthcare Managers: Conditions, Consequences and Potential Responses

Moral distress - the physical and emotional response to feeling prevented from carrying out ethically proper action - can have serious consequences for health professionals and healthcare organizations. We investigated perceived moral distress qualitatively with managers in two BC health authorities.RESPONDENTS DESCRIBED CONDITIONS UNDER WHICH THEY EXPERIENCED DISTRESS: when they set priorities within highly resource-constrained environments, when they observed inequities between budget allocations and management responsibilities, and when organizational priorities did not align with their personal values. When coping proved insufficient, managers would respond by leaving positions, organizations or the healthcare field altogether.Respondents asked for leadership development and the creation of spaces in which moral distress could be openly discussed. However, formal training in priority setting did not appear to be helpful on its own. Rather, it increased managers' awareness of the ethical dimensions of resource allocation without (in this instance) entrenching supports that would help them resolve these concerns.

Residual Normal Stem Cells Can Be Detected in Newly Diagnosed Chronic Myeloid Leukemia Patients by a New Flow Cytometric Approach and Predict for Optimal Response to Imatinib

Insensitivity of chronic myeloid leukemia (CML) hematopoietic stem cells to tyrosine kinase inhibitors (TKIs) prevents eradication of the disease and may be involved in clinical resistance. For improved treatment results more knowledge about CML stem cells is needed. We here present a new flow cytometric approach enabling prospective discrimination of CML stem cells from their normal counterparts within single-patient samples. In 24 of 40 newly diagnosed CML patients residual normal CD34(+)CD38(-) stem cells could be identified by lower CD34 and CD45 expression, lower forward/sideward light scatter and by differences of lineage marker expression (CD7, CD11b and CD56) and of CD90. fluorescent in situ hybridization (FISH) analysis on Fluorescence-activated cell sorting sorted cells proved that populations were BCR-ABL positive or negative and long-term liquid culture assays with subsequent colony forming unit assays and FISH analysis proved their stem cell character. Patients with residual non-leukemic stem cells had lower clinical risk scores (Sokal, Euro), lower hematological toxicity of imatinib (IM) and better molecular responses to IM than patients without. This new approach will expand our possibilities to separate CML and normal stem cells, present in a single bone marrow or peripheral blood sample, thereby offering opportunities to better identify new CML stem-cell-specific targets. Moreover, it may guide optimal clinical CML management.Leukemia advance online publication, 9 December 2011; doi:10.1038/leu.2011.347.

Effects of Chemical, Biological, and Physical Aging As Well As Soil Addition on the Sorption of Pyrene to Activated Carbon and Biochar

In this study, the suitability of biochar and activated carbon (AC) for contaminated soil remediation is investigated by determining the sorption of pyrene to both materials in the presence and absence of soil and before as well as after aging. Biochar and AC were aged either alone or mixed with soil via exposure to (a) nutrients and microorganisms (biological), (b) 60 and 110 °C (chemical), and (c) freeze-thaw cycles (physical). Before and after aging, the pH, elemental composition, cation exchange capacity (CEC), microporous SA, and sorption isotherms of pyrene were quantified. Aging at 110 °C altered the physicochemical properties of all materials to the greatest extent (for example, pH increased by up to three units and CEC by up to 50% for biochar). Logarithmic K(Fr) values ranged from 7.80 to 8.21 (ng kg(-1))(ng L(-1))(-nF) for AC and 5.22 to 6.21 (ng kg(-1))(ng L(-1))(-nF) for biochar after the various aging regimes. Grinding biochar to a smaller particle size did not significantly affect the sorption of d(10) pyrene, implying that sorption processes operate on the subparticle scale. Chemical aging decreased the sorption of pyrene to the greatest extent (up to 1.8 log unit for the biochar+soil). The sorption to AC was affected more by the presence of soil than the sorption to biochar was. Our results suggest that AC and biochar have a high sorption capacity for pyrene that is maintained both in the presence of soil and during harsh aging. Both materials could therefore be considered in contaminated land remediation.

[Differential Diagnosis and Therapy of Pulmonary Diseases with Angiitis and Granulomatosis]

Cell Survival and Proliferation After Encapsulation in a Chemically Modified Pluronic(R) F127 Hydrogel

Pluronic® F127 is a biocompatible, injectable, and thermoresponsive polymer with promising biomedical applications. In this study, a chemically modified form, i.e., Pluronic ALA-L with tailored degradation rate, was tested as an encapsulation vehicle for osteoblastic cells. UV cross-linking of the modified polymer results in a stable hydrogel with a slower degradation rate. Toxicological screening showed no adverse effects of the modified Pluronic ALA-L on the cell viability. Moreover, high viability of embedded cells in the cross-linked Pluronic ALA-L was observed with life/death fluorescent staining during a 7-day-culture period. Cells were also cultured on macroporous, cross-linked gelatin microbeads, called CultiSpher-S® carriers, and encapsulated into the modified cross-linked hydrogel. Also, in this situation, good cell proliferation and migration could be observed in vitro. Preliminary in vivo tests have shown the formation of new bone starting from the injected pre-loaded CultiSpher-S® carriers.

Water Recovery from Sewage Using Forward Osmosis

This research is part of the Sewer Mining project aimed at developing a new technological concept by extracting water from sewage by means of forward osmosis (FO). FO, in combination with a reconcentration system, e.g. reverse osmosis (RO) is used to recover high-quality water. Furthermore, the subsequent concentrated sewage (containing an inherent energy content) can be converted into a renewable energy (RE) source (i.e. biogas). The effectiveness of FO membranes in the recovery of water from sewage has been evaluated. Stable FO water flux values (>4.3 LMH) were obtained with primary effluent (screened, not treated) used as the feed solution. Fouling of the membrane was also induced and further investigated. Accumulated fouling was found to be apparent, but not irreversible. Sewer Mining could lead to a more economical and sustainable treatment of wastewater, facilitating the extraction of water and energy from sewage and changing the way it is perceived: not as waste, but as a resource.

Search for a Standard Model Higgs Boson in the H→ZZ→ℓ(+)ℓ(-)νν Decay Channel with the ATLAS Detector

A search for a heavy standard model Higgs boson decaying via H→ZZ→→ℓ(+)ℓ(-)νν, where ℓ=e, μ, is presented. It is based on proton-proton collision data at √s=7 TeV, collected by the ATLAS experiment at the LHC in the first half of 2011 and corresponding to an integrated luminosity of 1.04 fb(-1). The data are compared to the expected standard model backgrounds. The data and the background expectations are found to be in agreement and upper limits are placed on the Higgs boson production cross section over the entire mass window considered; in particular, the production of a standard model Higgs boson is excluded in the region 340

Search for the Higgs Boson in the H→WW→lνjj Decay Channel in Pp Collisions at ˆs=7 TeV with the ATLAS Detector

A search for a Higgs boson has been performed in the H→WW→ℓνjj channel in 1.04 fb(-1) of pp collision data at √s=7 TeV recorded with the ATLAS detector at the Large Hadron Collider. No significant excess of events is observed over the expected background and limits on the Higgs boson production cross section are derived for a Higgs boson mass in the range 240 GeV

A Genetic Predisposition Score for Muscular Endophenotypes Predicts the Increase in Aerobic Power After Training: the CAREGENE Study

It is widely accepted that genetic variability might explain a large part of the observed heterogeneity in aerobic capacity and its response to training. Significant associations between polymorphisms of different genes with muscular strength, anaerobic phenotypes and body composition have been reported. Muscular endophenotypes are positively correlated with aerobic capacity, therefore, we tested the association of polymorphisms in twelve muscular related genes on aerobic capacity and its response to endurance training.

Effects of Visual Priming on Taste-odor Interaction

Little is known about the influence of visual characteristics other than colour on flavor perception, and the complex interactions between more than two sensory modalities. This study focused on the effects of recognizability of visual (texture) information on flavor perception of odorized sweet beverages. Participants rated the perceived sweetness of odorized sucrose solutions in the presence or absence of either a congruent or incongruent visual context. Odors were qualitatively reminiscent of sweet foods (strawberry and caramel) or not (savoury). Visual context was either an image of the same sweet foods (figurative context) or a visual texture derived from this product (non-figurative context). Textures were created using a texture synthesis method that preserved perceived food qualities while removing object information. Odor-taste combinations were rated sweeter within a figurative than a non-figurative context. This behaviour was exhibited for all odor-taste combinations, even in trials without images, indicating sustained priming by figurative visual context. A non-figurative context showed a transient sweetening effect. Sweetness was generally enhanced most by the strawberry odor. We conclude that the degree of recognizability of visual information (figurative versus non-figurative), influences flavor perception differently. Our results suggest that this visual context priming is mediated by separate sustained and transient processes that are differently evoked by figurative and non-figurative visual contexts. These components operate independent of the congruency of the image-odor-taste combinations.

Signaling by IL-31 and Functional Consequences

Cytokines are key to control cellular communication. Interleukin-31 (IL-31) was recently discovered as a new member of the IL-6 family of cytokines. IL-31 signals through a heterodimeric receptor composed of OSMR and IL-31RA, a complex that stimulates the JAK-STAT, the RAS/ERK and the PI3K/AKT signal transduction pathways. The available data suggests that IL-31 is important for both innate and adaptive immunity in tissues that are in close contact with the environment, i.e. the skin, the airways and the lung, and the lining of the intestine. Enhanced expression of IL-31 is associated with a number of diseases, including pruritic diseases such as atopic dermatitis, but also in allergy and inflammatory bowel disease. In these tissues IL-31 coordinates the interaction of different immune cells, including T-cells, mast cells, and eosinophils, with epithelial cells. In this review we have summarized the available data on IL-31 and its receptor, their expression pattern and how they are regulated. We describe the current state of knowledge of the involvement of IL-31 in diseases, both in humans and in mouse models. From these studies it is becoming clear that IL-31 plays an important role in the proper functioning of the skin and of airway and intestinal epithelia. The findings available suggest that IL-31 might be an interesting target for directed drug therapy.

Micro-CT for Anatomic Referencing in PET and SPECT: Radiation Dose, Biologic Damage, and Image Quality

CT is widely used for anatomic referencing of PET and SPECT images of small animals but requires sufficiently high radiation doses capable of causing significant DNA damage. Therefore, we described the relationship between radiation dose, biologic damage, and image quality to determine whether CT can be used without significantly compromising radiotherapy and tumor development studies.

High-Dose Therapy and Autologous Stem Cell Transplantation in First Relapse for Diffuse Large B Cell Lymphoma in the Rituximab Era: An Analysis Based on Data from the European Blood and Marrow Transplantation Registry

Autologous stem cell transplantation (ASCT) consolidation remains the treatment of choice for patients with relapsed diffuse large B cell lymphoma. The impact of rituximab combined with chemotherapy in either first- or second-line therapy on the ultimate results of ASCT remains to be determined, however. This study was designed to evaluate the benefit of ASCT in patients achieving a second complete remission after salvage chemotherapy by retrospectively comparing the disease-free survival (DFS) after ASCT for each patient with the duration of the first complete remission (CR1). Between 1990 and 2005, a total of 470 patients who had undergone ASCT and reported to the European Blood and Bone Transplantation Registry with Medical Essential Data Form B information were evaluated. Of these 470 patients, 351 (74%) had not received rituximab before ASCT, and 119 (25%) had received rituximab before ASCT. The median duration of CR1 was 11 months. The median time from diagnosis to ASCT was 24 months. The BEAM protocol was the most frequently used conditioning regimen (67%). After ASCT, the 5-year overall survival was 63% (95% confidence interval, 58%-67%) and 5-year DFS was 48% (95% confidence interval, 43%-53%) for the entire patient population. Statistical analysis showed a significant increase in DFS after ASCT compared with duration of CR1 (median, 51 months versus 11 months; P < .001). This difference was also highly significant for patients with previous exposure to rituximab (median, 10 months versus not reached; P < .001) and for patients who had experienced relapse before 1 year (median, 6 months versus 47 months; P < .001). Our data indicate that ASCT can significantly increase DFS compared with the duration of CR1 in relapsed diffuse large B cell lymphoma and can alter the disease course even in patients with high-risk disease previously treated with rituximab.

Fibrin Gel As Alternative Scaffold for Respiratory Tissue Engineering

Fibrin gel has proven a valuable scaffold for tissue engineering. Complex geometries can be produced by injection molding; it offers effective cell seeding and can be produced autologous. In order to evaluate its suitability for respiratory tissue engineering, we examined proliferation, functionality, and differentiation of respiratory epithelial cells on fibrin gel in comparison to culture on collagen-coated, microporous membranes. Respiratory epithelial cells formed a confluent layer by day 4, and proliferation showed no significant difference with respect to surface. Measurement of the transepithelial electrical resistance reflected the development of a confluent epithelial cell layer and the subsequent initiation of adequate ion-transfer processes. Appearance of ciliae could be detected at similar time points, and ciliary beating could be observed for cells on both surfaces. Histology and immunohistochemistry of cells grown on fibrin gel revealed the onset of adequate differentiation. As no significant differences in respiratory epithelial cells' proliferation, function, and differentiation could be observed between cells grown on fibrin gel compared to cells on a collagen-coated, microporous surface, we concluded that fibrin gel might prove a suitable scaffold for respiratory tissue engineering and merits further investigation to overcome the limitations associated with scaffolds currently in use.

[Neuroendocrine Pulmonary Neoplasms: Improved Diagnosis by DOTATOC- Vs. FDG-PET/CT]

Variants of the Recently Discovered Avian Gyrovirus 2 Are Detected in Southern Brazil and The Netherlands

A genome of a virus preliminarily named avian gyrovirus 2 (AGV2), a close relative to chicken anemia virus, was recently discovered in a chicken in the state of Rio Grande do Sul, Southern Brazil. To study the occurrence of AGV2 in Rio Grande do Sul and the neighboring state Santa Catarina, a number of adult chickens (n=108 and n=48, respectively) were tested for the presence of AGV2 DNA. An AGV2-specific PCR was developed, optimized and used to analyze DNA extracted from clinical samples. AGV2 DNA was detected in 98/108 (90.7%) of samples collected in the state of Rio Grande do Sul and 29/48 (60.4%) of the samples collected in the state of Santa Catarina. In order to check whether AGV2 DNA would be detected in samples from a geographically distant region, DNA from brain samples of 21 diseased chickens from the Netherlands were tested independently, by the same method. In such specimens, 9/21 (42.9%) brain tissue samples were found to contain AVG2 DNA. Sequence analysis of some of the PCR products demonstrated that the amplified AGV2 sequences could vary up to 15.8% and could preliminarily be divided in three groups. This indicated the occurrence of variants of AGV2, which may reflect differences in geographical origin and/or in biological properties. The data presented here provides evidence that AGV2 seems fairly distributed in chickens in Southern Brazil and that AGV2 also circulates in the Netherlands. Besides, circulating viruses display genetic variants whose significance should be further examined, particularly to determine whether AGV2 would play any role in chicken diseases.

CD34 and SMA Expression of Superficial Zone Cells in the Normal and Pathological Human Meniscus

The aim of this study was to evaluate histological changes in torn (0.5-27 weeks after injury) and osteoarthritic (OA) knee menisci versus normal menisci after PAS-AB, SAF-O-FG, and immunostaining for CD34, CD31, and smooth muscle actin (SMA). Cell layers in the superficial zone and the cell density in the deep zone of the menisci were counted. In the superficial zone of normal menisci, cells expressing CD34 were demonstrated. CD34(+) CD31(-) cells were absent in OA menisci and disappeared in torn menisci as a function of time. In contrast, an increase of SMA(+) cells combined with an increase of cell layers was observed in the superficial zone of torn menisci. SMA(+) cells were absent in normal and OA menisci. The predominant tissue type in torn menisci evolved from fibrocartilage-like to fibrous-like tissue as a function of time, whereas in OA menisci it became cartilage-like. The response of the superficial zone was reflected by the decrease of CD34(+) and the increase of SMA(+) cells in torn menisci and the transformation of a fibrous-like into a cartilage-like surface layer in OA menisci. These results potentially illustrate the contribution of CD34(+) cells to the homeostasis of meniscus tissue. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Hypoxia Imaging Using PET and SPECT: the Effects of Anesthetic and Carrier Gas on [Cu]-ATSM, [Tc]-HL91 and [F]-FMISO Tumor Hypoxia Accumulation

Preclinical imaging requires anaesthesia to reduce motion-related artefacts. For direct translational relevance, anaesthesia must not significantly alter experimental outcome. This study reports on the effects of both anaesthetic and carrier gas upon the uptake of [⁶⁴Cu]-CuATSM, [(⁹⁹m)Tc]-HL91 and [¹⁸F]-FMISO in a preclinical model of tumor hypoxia.

Molecular Pathogenesis of Neisseria Gonorrhoeae

Search for Dilepton Resonances in Pp Collisions at ˆs=7 TeV with the ATLAS Detector

This Letter reports on a search for narrow high-mass resonances decaying into dilepton final states. The data were recorded by the ATLAS experiment in pp collisions at √s=7  TeV at the Large Hadron Collider and correspond to a total integrated luminosity of 1.08 (1.21)  fb(-1) in the e(+)e(-) (μ(+)μ(-)) channel. No statistically significant excess above the standard model expectation is observed and upper limits are set at the 95% C.L. on the cross section times branching fraction of Z' resonances and Randall-Sundrum gravitons decaying into dileptons as a function of the resonance mass. A lower mass limit of 1.83 TeV on the sequential standard model Z' boson is set. A Randall-Sundrum graviton with coupling k/M(Pl)=0.1 is excluded at 95% C.L. for masses below 1.63 TeV.

In-situ Sorbent Amendments: A New Direction in Contaminated Sediment Management

Global Patterns of Leaf Mechanical Properties

Leaf mechanical properties strongly influence leaf lifespan, plant-herbivore interactions, litter decomposition and nutrient cycling, but global patterns in their interspecific variation and underlying mechanisms remain poorly understood. We synthesize data across the three major measurement methods, permitting the first global analyses of leaf mechanics and associated traits, for 2819 species from 90 sites worldwide. Key measures of leaf mechanical resistance varied c. 500-800-fold among species. Contrary to a long-standing hypothesis, tropical leaves were not mechanically more resistant than temperate leaves. Leaf mechanical resistance was modestly related to rainfall and local light environment. By partitioning leaf mechanical resistance into three different components we discovered that toughness per density contributed a surprisingly large fraction to variation in mechanical resistance, larger than the fractions contributed by lamina thickness and tissue density. Higher toughness per density was associated with long leaf lifespan especially in forest understory. Seldom appreciated in the past, toughness per density is a key factor in leaf mechanical resistance, which itself influences plant-animal interactions and ecosystem functions across the globe.

Sequential Energy and Electron Transfer in Polyisocyanopeptide-based Multichromophoric Arrays

We report on the synthesis and detailed photo-physical investigation of four model chromophore side chain polyisocyanopeptides: two homopolymers of platinum-porphyrin functionalized polyisocyanopeptides (Pt-porphyrin-PIC) and perylene-bis(dicarboximide) functionalized polyisocyanopeptides (PDI-PIC), and two statistical copolymers with different ratios of Pt-porphyrin and PDI molecules attached to a rigid, helical polyisocyanopeptide backbone. (1)H NMR and circular dichroism measurements confirm that our model compounds retain a chiral architecture in the presence of the chromophores. The combination of Pt-porphyrin and PDI chromophores allows charge- and/or energy transfer to happen. We observe the excitation and relaxation pathways for selective excitation of the Pt-porphyrin and PDI chromophores. Studies of photoluminescence and transient absorption on nanosecond and picosecond scales upon excitation of Pt-porphyrin chromophores in our multichromophoric assemblies show similar photophysical features to those of the Pt-porphyrin monomers. In contrast, excitation of perylene chromophores results in a series of energy and charge transfer processes with the Pt-porphyrin group and forms additional charge-transfer states, which behave as an intermediate state that facilitates electronic coupling in these multichromophoric systems.

Structure-related Distribution of PCDD/Fs, PCBs and HCB in a River-sea System

Water concentrations of PCDD/Fs, HCB, and non-ortho, mono-ortho, and non-dioxin-like PCBs were measured four times during 1 year in a coastal area of the Baltic Sea, to investigate background levels and distribution behaviour. Sampling sites included two rivers, an estuary, and the sea. Particulate and apparently dissolved concentrations were determined using active sampling (filters+PUFs), while freely dissolved concentrations were determined using passive sampling (POM-samplers). The distribution between particulate+colloidal and freely dissolved phases, in the form of TOC-normalized distribution ratios (K(TOC)), was found to be near or at equilibrium. The observed K(TOC) were not significantly different between sampling sites or seasons. For PCDD/Fs, the concentrations were significantly correlated to suspended particulate matter (SPM), while no correlation to organic carbon (TOC) was observed. In the estuary and the sea, PCB concentrations were correlated to TOC. The sorption of various congeners to SPM and TOC appeared to be related to both hydrophobicity and 3D-structure. The PCDD/F concentration in the sea decreased to one third in May, likely connected to the increased vertical flux of particles during the spring bloom.

Threshold Concentration of Easily Assimilable Organic Carbon in Feedwater for Biofouling of Spiral-Wound Membranes

Threshold Concentrations of Biomass and Iron for Pressure Drop Increase in Spiral-wound Membrane Elements

In a model feed channel for spiral-wound membranes the quantitative relationship of biomass and iron accumulation with pressure drop development was assessed. Biofouling was stimulated by the use of tap water enriched with acetate at a range of concentrations (1-1000 μgCl(-1)). Autopsies were performed to quantify biomass concentrations in the fouled feed channel at a range of Normalized Pressure Drop increase values (NPD(i)). Active biomass was determined with adenosinetriphosphate (ATP) and the concentration of bacterial cells with Total Direct Cell count (TDC). Carbohydrates (CH) were measured to include accumulated extracellular polymeric substances (EPS). The paired ATP and CH concentrations in the biofilm samples were significantly (p<0.001; R(2)=0.62) correlated and both parameters were also significantly correlated with NPD(i) (p<0.001). TDC was not correlated with the pressure drop in this study. The threshold concentration for an NPD(i) of 100% was 3.7 ng ATP cm(-2) and for CH 8.1 μg CH cm(-2). Both parameters are recommended for diagnostic membrane autopsy studies. Iron concentrations of 100-400 mg m(-2) accumulated in the biofilm by adsorption were not correlated with the observed NPD(i), thus indicating a minor role of Fe particulates at these concentrations in fouling of spiral-wound membrane.

In Situ Measurement of PCB Pore Water Concentration Profiles in Activated Carbon-amended Sediment Using Passive Samplers

Vertical pore water profiles of in situ PCBs were determined in a contaminated mudflat in San Francisco Bay, CA, 30 months after treatment using an activated carbon amendment in the upper layer of the sediment. Pore water concentrations were derived from concentrations of PCBs measured in two passive samplers; polyethylene (PE, 51 μm thick) and polyoxymethylene (POM, 17 μm thick) at different sediment depths. To calculate pore water concentrations from PCB contents in the passive samplers, an equilibrium approach and a first-order uptake model were applied, using five performance reference compounds to estimate pore water sampling rates. Vertical pore water profiles showed good agreement among the measurement and calculation methods with variations within a factor of 2, which seems reasonable for in situ measurements. The close agreements of pore water estimates for the two sampler materials (PE and POM) and the two methods used to translate uptake in samplers to pore water concentrations demonstrate the robustness and suitability of the passive sampling approach. The application of passive samplers in the sediment presents a promising method for site monitoring and remedial treatment evaluation of sorbent amendment or capping techniques that result in changes of pore water concentrations in the sediment subsurface.

An Image Statistics-Based Model for Fixation Prediction

The problem of predicting where people look at, or equivalently salient region detection, has been related to the statistics of several types of low-level image features. Among these features, contrast and edge information seem to have the highest correlation with the fixation locations. The contrast distribution of natural images can be adequately characterized using a two-parameter Weibull distribution. This distribution catches the structure of local contrast and edge frequency in a highly meaningful way. We exploit these observations and investigate whether the parameters of the Weibull distribution constitute a simple model for predicting where people fixate when viewing natural images. Using a set of images with associated eye movements, we assess the joint distribution of the Weibull parameters at fixated and non-fixated regions. Then, we build a simple classifier based on the log-likelihood ratio between these two joint distributions. Our results show that as few as two values per image region are already enough to achieve a performance comparable with the state-of-the-art in bottom-up saliency prediction.

Introduction of a Quality Management System and Outcome After Hematopoietic Stem-cell Transplantation

A comprehensive quality management system called JACIE (Joint Accreditation Committee International Society for Cellular Therapy and the European Group for Blood and Marrow Transplantation), was introduced to improve quality of care in hematopoietic stem-cell transplantation (HSCT). We therefore tested the hypothesis that the introduction of JACIE improved patient survival.

ErbB-2 Blockade and Prenyltransferase Inhibition Alter Epidermal Growth Factor and Epidermal Growth Factor Receptor Trafficking and Enhance (111)In-DTPA-hEGF Auger Electron Radiation Therapy

The intracellular distribution of Auger electron-emitting radiopharmaceuticals is a determinant of cytotoxicity. However, the mechanisms by which these agents are routed through the cell are ill understood. The aim of this study was to investigate how trafficking of (111)In-labeled human epidermal growth factor ((111)In-DTPA-hEGF) relates to that of the EGF receptor (EGFR) and whether coadministration of agents that modulate EGFR signaling alters the efficacy of (111)In-DTPA-hEGF.

Encapsulation of Phthalocyanine Supramolecular Stacks into Virus-like Particles

We report herein the encapsulation of a water-soluble phthalocyanine (Pc) into virus-like particles (VLPs) of two different sizes, depending on the conditions. At neutral pH, the cooperative encapsulation/templated assembly of the particles induces the formation of Pc stacks instead of Pc dimers, due to an increased confinement concentration. The Pc-containing VLPs may potentially be used as photosensitizer/vehicle systems for biomedical applications such as photodynamic therapy.

Azobenzene-containing Triazatriangulenium Adlayers on Au(111): Structural and Spectroscopic Characterization

Adlayers of different azobenzene-functionalized derivatives of the triazatriangulenium (TATA) platform on Au(111) surfaces were studied by scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), gap-mode surface-enhanced Raman spectroscopy (gap-mode SERS), and cyclic voltammetry (CV). The chemical composition of the adlayers is in good agreement with the molecular structure, i.e., different chemical groups attached to the azobenzene functionality were identified. Furthermore, the presence of the azobenzene moieties in the adlayers was verified by the vibration spectra and electrochemical data. These results indicate that the molecules remain intact upon adsorption with the freestanding functional groups oriented perpendicularly to the TATA platform and thus also to the substrate surface.

[Genome Instability of Pseudomonas Aeruginosa Phages of the EL Species: Examination of Virulent Mutants]

The article continues a study of pseudolysogeny in Pseudominas aeruginosa infected with phiKZ-like phages of the EL species. Analysis was performed for several newly isolated virulent mutants of EL phages (EL and RU) that were virulent (capable of causing lysis of bacteria infected with the wild-type phage) and a lower extent of opalescence of negative colonies (NCs). Wile-type recombinants were detected in crosses of virulent mutants of phages EL and RU to confirm the polygenic control of virulence. Since a deletion mutation was found in one of the virulent EL mutants and high genetic instability was characteristic of another mutant, a mobile genetic element was assumed to play a role in mutagenesis. Pseudolysogeny of bacteria provides for horizontal gene transfer between different bacterial strains. Hence, sequencing of the phage genome and demonstration of the lack of toxic gene products are insufficient for the phage to be included into a therapeutic mixture. To use live phages, it is essential to study in detail the possible consequences of their interaction with host bacteria.

Search for Diphoton Events with Large Missing Transverse Energy in 7 TeV Proton-proton Collisions with the ATLAS Detector

A search for diphoton events with large missing transverse energy is presented. The data were collected with the ATLAS detector in proton-proton collisions at √s=7 TeV at the CERN Large Hadron Collider and correspond to an integrated luminosity of 3.1 pb⁻¹. No excess of such events is observed above the standard model background prediction. In the context of a specific model with one universal extra dimension with compactification radius R and gravity-induced decays, values of 1/R<729 GeV are excluded at 95% C. L., providing the most sensitive limit on this model to date.

Search for Supersymmetry Using Final States with One Lepton, Jets, and Missing Transverse Momentum with the ATLAS Detector in ˆs=7 TeV Pp Collisions

This Letter presents the first search for supersymmetry in final states containing one isolated electron or muon, jets, and missing transverse momentum from √s=7  TeV proton-proton collisions at the LHC. The data were recorded by the ATLAS experiment during 2010 and correspond to a total integrated luminosity of 35  pb(-1). No excess above the standard model background expectation is observed. Limits are set on the parameters of the minimal supergravity framework, extending previous limits. Within this framework, for A(0)=0 GeV, tanβ=3, and μ>0 and for equal squark and gluino masses, gluino masses below 700 GeV are excluded at 95% confidence level.

Are Social Value Orientations Expressed Automatically? Decision Making in the Dictator Game

Drawing on the social intuitionist model, the authors studied the hypothesis that social value orientations are expressed automatically in behavior. They compared spontaneous and more deliberated decisions in the dictator game and confirmed that social values determine behavior when responses are based on the automatic system. By means of both mediation and experimental analyses, the authors further demonstrate that the automatic expression of social value orientations is mediated by perceptions of interpersonal closeness. A reasoning process can subsequently override these automatic responses and disconnect decisions from perceptions of interpersonal closeness. This results in lower levels of other-regarding behavior, at least for prosocials.

Use of Life Cycle Assessments to Evaluate the Environmental Footprint of Contaminated Sediment Remediation

Ecological and human risks often drive the selection of remedial alternatives for contaminated sediments. Traditional human and ecological risk assessment (HERA) includes assessing risk for benthic organisms and aquatic fauna associated with exposure to contaminated sediments before and after remediation as well as risk for human exposure but does not consider the environmental footprint associated with implementing remedial alternatives. Assessment of environmental effects over the whole life cycle (i.e., Life Cycle Assessment, LCA) could complement HERA and help in selecting the most appropriate sediment management alternative. Even though LCA has been developed and applied in multiple environmental management cases, applications to contaminated sediments and marine ecosystems are in general less frequent. This paper implements LCA methodology for the case of the polychlorinated dibenzo-p-dioxins and -furans (PCDD/F)-contaminated Grenland fjord in Norway. LCA was applied to investigate the environmental footprint of different active and passive thin-layer capping alternatives as compared to natural recovery. The results showed that capping was preferable to natural recovery when analysis is limited to effects related to the site contamination. Incorporation of impacts related to the use of resources and energy during the implementation of a thin layer cap increase the environmental footprint by over 1 order of magnitude, making capping inferior to the natural recovery alternative. Use of biomass-derived activated carbon, where carbon dioxide is sequestered during the production process, reduces the overall environmental impact to that of natural recovery. The results from this study show that LCA may be a valuable tool for assessing the environmental footprint of sediment remediation projects and for sustainable sediment management.

The T7-related Pseudomonas Putida Phage φ15 Displays Virion-associated Biofilm Degradation Properties

Formation of a protected biofilm environment is recognized as one of the major causes of the increasing antibiotic resistance development and emphasizes the need to develop alternative antibacterial strategies, like phage therapy. This study investigates the in vitro degradation of single-species Pseudomonas putida biofilms, PpG1 and RD5PR2, by the novel phage ϕ15, a 'T7-like virus' with a virion-associated exopolysaccharide (EPS) depolymerase. Phage ϕ15 forms plaques surrounded by growing opaque halo zones, indicative for EPS degradation, on seven out of 53 P. putida strains. The absence of haloes on infection resistant strains suggests that the EPS probably act as a primary bacterial receptor for phage infection. Independent of bacterial strain or biofilm age, a time and dose dependent response of ϕ15-mediated biofilm degradation was observed with generally a maximum biofilm degradation 8 h after addition of the higher phage doses (10(4) and 10(6) pfu) and resistance development after 24 h. Biofilm age, an in vivo very variable parameter, reduced markedly phage-mediated degradation of PpG1 biofilms, while degradation of RD5PR2 biofilms and ϕ15 amplification were unaffected. Killing of the planktonic culture occurred in parallel with but was always more pronounced than biofilm degradation, accentuating the need for evaluating phages for therapeutic purposes in biofilm conditions. EPS degrading activity of recombinantly expressed viral tail spike was confirmed by capsule staining. These data suggests that the addition of high initial titers of specifically selected phages with a proper EPS depolymerase are crucial criteria in the development of phage therapy.

The Innovative Osmotic Membrane Bioreactor (OMBR) for Reuse of Wastewater

An innovative osmotic membrane bioreactor (OMBR) is currently under development for the reclamation of wastewater, which combines activated sludge treatment and forward osmosis (FO) membrane separation with a RO post-treatment. The research focus is FO membrane fouling and performance using different activated sludge investigated both at laboratory scale (membrane area of 112cm2) and at on-site bench scale (flat sheet membrane area of 0.1 m2). FO performance on laboratory-scale (i) increased with temperature due to a decrease in viscosity and (ii) was independent of the type of activated sludge. Draw solution leakage increased with temperature and varied for different activated sludge. FO performance on bench-scale (i) increased with osmotic driving force, (ii) depended on the membrane orientation due to internal concentration polarization and (iii) was invariant to feed flow decrease and air injection at the feed and draw side. Draw solution leakage could not be evaluated on bench-scale due to experimental limitation. Membrane fouling was not found on laboratory scale and bench-scale, however, partially reversible fouling was found on laboratory scale for FO membranes facing the draw solution. Economic assessment indicated a minimum flux of 15L.m-2 h-1 at 0.5M NaCl for OMBR-RO to be cost effective, depending on the FO membrane price.

Measurement of the W+ W- Cross Section in Sqrt(s) = 7  TeV Pp Collisions with ATLAS

This Letter presents a measurement of the W+ W- production cross section in sqrt(s) = 7  TeV pp collisions by the ATLAS experiment, using 34  pb(-1) of integrated luminosity produced by the Large Hadron Collider at CERN. Selecting events with two isolated leptons, each either an electron or a muon, 8 candidate events are observed with an expected background of 1.7 ± 0.6 events. The measured cross section is 41(-16)(+20)(stat) ± 5(syst)±1(lumi)  pb, which is consistent with the standard model prediction of 44 ± 3  pb calculated at next-to-leading order in QCD.

Xeno-Free Plant-Derived Hydrolysate-Based Freezing of Human Embryonic Stem Cells

Human embryonic stem cells (hESCs) are one of the most interesting cell types for tissue engineering and cell therapy. The large-scale banking of hESCs for research and future clinical application requires economic, defined, and xeno-free cryopreservation protocols. In this study, the possibility to substitute knockout serum replacement (KO-SR) in the cryopreservation process with vegetal and synthetic hydrolysates was investigated. To our knowledge, the use of hydrolysates in hESC cryopreservation has not been yet explored. Initially, 3 different hydrolysates (Ultrapep Soy, Hypep 4601 and EX-CELL(®) CD Hydrolysate Fusion) were tested in the cryopreservation solution. A concentration of 8 mg/mL EX-CELL CD Hydrolysate Fusion in the cryopreservation solution leads to the highest recovery ratio; thus, this solution was selected for additional cryopreservation experiments. To ensure reproducibility of the results, 3 hESC lines (HS181, H9, and BG01) were used. The hESCs were collected prefreezing by application of collagenase IV and cell dissociation solution. Experiments showed that it was feasible to substitute the KO-SR in both the cryopreservation solution as the thawing solution. The obtained recovery ratios were comparable to those obtained with KO-SR (no statistical significant difference; Student's t-test, P<0.05). Further optimization protocols showed a doubling of the obtained recovery ratio after addition of Rock-inhibitor Y-27632 post-thawing. The expansion profile and pluripotency analysis revealed no changes in normal hESC behavior. We conclude that the application of vegetal or synthetic hydrolysates is suitable for xeno-free hESC cryopreservation.

Creating a Knowledge Translation Trainee Collaborative: from Conceptualization to Lessons Learned in the First Year

Trainees (e.g., graduate students, residents, fellows) are increasingly identifying knowledge translation as their research discipline. In Canada, a group of trainees have created a trainee-initiated and trainee-led national collaborative to provide a vehicle for trainees to examine the diversity of knowledge translation research and practice, and to link trainees from diverse geographical areas and disciplines. The aim of this paper is to describe our experience and lessons learned in creating the Knowledge Translation Trainee Collaborative. In this meeting report, we outline the process, challenges, and opportunities in planning and experiencing the collaborative's inaugural meeting as participant organizers, and present outcomes and learnings to date.

Optimization of the Isolation, Culture, and Characterization of Equine Umbilical Cord Blood Mesenchymal Stromal Cells

Mesenchymal stromal cells (MSC) represent a promising population for supporting new clinical concepts in cellular therapy. A wide diversity of isolation procedures for MSC from umbilical cord blood (UCB) has been described for humans. In contrast, a few data are available in horses. In the current study, a sedimentation method using hydroxyethyl starch and a method based on the lysis of red blood cells using ammonium chloride (NH(4)Cl) were compared with two density gradient separation methods (Ficoll-Paque and Percoll). Adherent cell colonies could be established using all four isolation methods. The mononuclear cell recovery after Percoll separation, however, resulted in significantly more putative MSC colonies; and, therefore, this isolation method was used for all further experiments. Culture conditions such as cell density and medium or serum coating of the wells did not significantly affect putative MSC recovery. Isolated MSC using Percoll were subsequently differentiated toward the osteogenic, chondrogenic, and adipogenic lineage. In addition, MSC were phenotyped by multicolor flow cytometry based on their expression of different cell protein markers. Cultured MSC were CD29, CD44, and CD90-positive and CD79α, Macrophage/Monocyte and MHC II-negative. In conclusion, this study reports optimized protocols to isolate, culture, and characterize solid equine MSC from UCB.

The CAREGENE Study: Genetic Variants of the Endothelium and Aerobic Power in Patients with Coronary Artery Disease

Aerobic phenotypes show a wide variability to similar aerobic training stimuli, which can be partly attributed to heritability. Endothelial function affects aerobic power. Various physiological pathways may influence the endothelial function. Therefore, we aimed to examine whether polymorphisms of the eNos gene, the CAT gene, the VEGF gene, the GPX1 gene, the subunit P22 phox of the NAD(P)H-odixase gene, the PPAR-alpha gene, and the PGC-alpha gene are associated with aerobic power or with its response to physical training in patients with coronary artery disease (CAD).

Impact of Resistance Training on Blood Pressure and Other Cardiovascular Risk Factors: a Meta-analysis of Randomized, Controlled Trials

We reviewed the effect of resistance training on blood pressure and other cardiovascular risk factors in adults. Randomized, controlled trials lasting ≥4 weeks investigating the effects of resistance training on blood pressure in healthy adults (age ≥18 years) and published in a peer-reviewed journal up to June 2010 were included. Random- and fixed-effects models were used for analyses, with data reported as weighted means and 95% confidence limits. We included 28 randomized, controlled trials, involving 33 study groups and 1012 participants. Overall, resistance training induced a significant blood pressure reduction in 28 normotensive or prehypertensive study groups [-3.9 (-6.4; -1.2)/-3.9 (-5.6; -2.2) mm Hg], whereas the reduction [-4.1 (-0.63; +1.4)/-1.5 (-3.4; +0.40) mm Hg] was not significant for the 5 hypertensive study groups. When study groups were divided according to the mode of training, isometric handgrip training in 3 groups resulted in a larger decrease in blood pressure [-13.5 (-16.5; -10.5)/-6.1(-8.3; -3.9) mm Hg] than dynamic resistance training in 30 groups [-2.8 (-4.3; -1.3)/-2.7 (-3.8; -1.7) mm Hg]. After dynamic resistance training, Vo(2) peak increased by 10.6% (P=0.01), whereas body fat and plasma triglycerides decreased by 0.6% (P<0.01) and 0.11 mmol/L (P<0.05), respectively. No significant effect could be observed on other blood lipids and fasting blood glucose. This meta-analysis supports the blood pressure-lowering potential of dynamic resistance training and isometric handgrip training. In addition, dynamic resistance training also favorably affects some other cardiovascular risk factors. Our results further suggest that isometric handgrip training may be more effective for reducing blood pressure than dynamic resistance training. However, given the small amount of isometric studies available, additional studies are warranted to confirm this finding.

Selection of an M184V Mutation in the Cerebrospinal Fluid of a Treatment-naive HIV-infected Individual Starting Darunavir-based Therapy

Here, we describe a newly diagnosed HIV-1-infected patient, in whom shortly after the initiation of a darunavir-based regimen, the HIV-1 virus exclusively mutated in the cerebrospinal fluid (CSF), leading to an increase in CSF HIV-1 RNA load and neurological complaints.

Ambra1: A Parkin-binding Protein Involved in Mitophagy

Mutations in the gene for the E3 ubiquitin ligase Parkin are the most prevalent cause of autosomal recessive Parkinson disease (PD), an incurable neurodegenerative disorder. Parkin surveys mitochondrial quality by translocating to depolarized mitochondria and inducing their selective macroautophagic removal (mitophagy). We recently reported that Parkin interacts with Ambra1 (activating molecule in Beclin 1-regulated autophagy), a protein that promotes autophagy in the vertebrate central nervous system. We discovered that prolonged mitochondrial depolarization strongly increases the interaction of Parkin with Ambra1. Ambra1 is recruited in a Parkin-dependent manner to perinuclear clusters of depolarized mitochondria, activates the class III phosphatidylinositol 3-kinase (PtdIns3K) complex around these mitochondria and contributes to their selective autophagic clearance. Here, we discuss these findings and suggest a model where translocated Parkin efficiently triggers mitophagy through combined recruitment of Ambra1 and ubiquitination of outer mitochondrial membrane proteins.

Semi-automatic Delineation Using Weighted CT-MRI Registered Images for Radiotherapy of Nasopharyngeal Cancer

To develop a delineation tool that refines physician-drawn contours of the gross tumor volume (GTV) in nasopharynx cancer, using combined pixel value information from x-ray computed tomography (CT) and magnetic resonance imaging (MRI) during delineation.

The Iron-repressed, AraC-like Regulator MpeR Activates Expression of FetA in Neisseria Gonorrhoeae

Neisseria gonorrhoeae is an obligate human pathogen that causes the common sexually transmitted infection gonorrhea. Gonococcal infections cause significant morbidity, particularly among women, as the organism ascends to the upper reproductive tract, resulting in pelvic inflammatory disease, ectopic pregnancy, and infertility. In the last few years, antibiotic resistance rates have risen dramatically, leading to severe restriction of treatment options for gonococcal disease. Gonococcal infections do not elicit protective immunity, nor is there an effective vaccine to prevent the disease. Thus, further understanding of the expression, function, and regulation of surface antigens could lead to better treatment and prevention modalities in the future. In the current study, we determined that an iron-repressed regulator, MpeR, interacted specifically with the DNA sequence upstream of fetA and activated FetA expression. Interestingly, MpeR was previously shown to regulate the expression of gonococcal antimicrobial efflux systems. We confirmed that the outer membrane transporter FetA allows gonococcal strain FA1090 to utilize the xenosiderophore ferric enterobactin as an iron source. However, we further demonstrated that FetA has an extended range of substrates that encompasses other catecholate xenosiderophores, including ferric salmochelin and the dimers and trimers of dihydroxybenzoylserine. We demonstrated that fetA is part of an iron-repressed, MpeR-activated operon which putatively encodes other iron transport proteins. This is the first study to describe a regulatory linkage between antimicrobial efflux and iron transport in N. gonorrhoeae. The regulatory nidus that links these systems, MpeR, is expressed exclusively by pathogenic neisseriae and is therefore expected to be an important virulence factor.

Is Leaf Dry Matter Content a Better Predictor of Soil Fertility Than Specific Leaf Area?

Specific leaf area (SLA), a key element of the 'worldwide leaf economics spectrum', is the preferred 'soft' plant trait for assessing soil fertility. SLA is a function of leaf dry matter content (LDMC) and leaf thickness (LT). The first, LDMC, defines leaf construction costs and can be used instead of SLA. However, LT identifies shade at its lowest extreme and succulence at its highest, and is not related to soil fertility. Why then is SLA more frequently used as a predictor of soil fertility than LDMC?

An Algorithm-based Topographical Biomaterials Library to Instruct Cell Fate

It is increasingly recognized that material surface topography is able to evoke specific cellular responses, endowing materials with instructive properties that were formerly reserved for growth factors. This opens the window to improve upon, in a cost-effective manner, biological performance of any surface used in the human body. Unfortunately, the interplay between surface topographies and cell behavior is complex and still incompletely understood. Rational approaches to search for bioactive surfaces will therefore omit previously unperceived interactions. Hence, in the present study, we use mathematical algorithms to design nonbiased, random surface features and produce chips of poly(lactic acid) with 2,176 different topographies. With human mesenchymal stromal cells (hMSCs) grown on the chips and using high-content imaging, we reveal unique, formerly unknown, surface topographies that are able to induce MSC proliferation or osteogenic differentiation. Moreover, we correlate parameters of the mathematical algorithms to cellular responses, which yield novel design criteria for these particular parameters. In conclusion, we demonstrate that randomized libraries of surface topographies can be broadly applied to unravel the interplay between cells and surface topography and to find improved material surfaces.

Expansion of Human Embryonic Stem Cells: a Comparative Study

Human embryonic stem cells (hESC) are promising for tissue engineering (TE) purposes due to their unique properties. However, current standard mechanical passaging techniques limit rates of possible TE experiments, as it is difficult to obtain high enough numbers of the cells for experimentation. In this study, several dissociative solutions and application methods are tested for their applicability to, and influence on, hESC culture and expansion.

Autologous Peripheral Blood Stem Cell Transplantation for Acute Myeloid Leukemia

We report the results of a prospective, randomized phase 3 trial evaluating autologous peripheral blood stem cell transplantation (ASCT) versus intensive consolidation chemotherapy in newly diagnosed AML patients in complete remission (CR1). Patients with AML (16-60 years) in CR1 after 2 cycles of intensive chemotherapy and not eligible for allogeneic SCT were randomized between intensive chemotherapy with etoposide and mitoxantrone or ASCT ater high-dose cyclophosphamide and busulfan. Of patients randomized (chemotherapy, n = 259; ASCT, n = 258), more than 90% received their assigned treatment. The 2 groups were comparable with regard to prognostic factors. The ASCT group showed a markedly reduced relapse rate (58% vs 70%, P = .02) and better relapse-free survival at 5 years (38% vs 29%, P = .065, hazard ratio = 0.82; 95% confidence interval, 0.66-1.1) with nonrelapse mortality of 4% versus 1% in the chemotherapy arm (P = .02). Overall survival was similar (44% vs 41% at 5 years, P = .86) because of more opportunities for salvage with second-line chemotherapy and stem cell transplantation in patients relapsing on the chemotherapy arm. This large study shows a relapse advantage for ASCT as postremission therapy but similar survival because more relapsing patients on the chemotherapy arm were salvaged with a late transplantation for relapse. This trial is registered at www.trialregister.nl as #NTR230 and #NTR291.

Cell Physiology Rather Than Enzyme Kinetics Can Determine the Efficiency of Cytochrome P450-catalyzed C-H-oxyfunctionalization

Cell physiology is a critical factor determining the efficiency of reactions performed by microbial biocatalysts. In order to develop an efficient biotransformation procedure for the hydroxylation of (S)-limonene to (S)-perillyl alcohol by recombinant Pseudomonas putida cells harboring the cytochrome P450 monooxygenase CYP153A6, physiological parameters were optimized. The previously reported synthesis of (S)-perillyl alcohol by P. putida GPo12 was based on complex and sensitive octane feeding strategies (van Beilen et al. in Appl Environ Microbiol 71:1737-1744, 2005), indicating the pivotal role of cell physiology. In contrast to previous findings, the screening of different carbon sources showed that glycerol and citrate are suitable alternatives to octane allowing high specific limonene hydroxylation activities. The use of P. putida KT2440 as an alternative host strain and citrate as the carbon source improved practical handling and allowed a 7.5-fold increase of the specific activity (to 22.6 U g (CDW) (-1) ). In two-liquid-phase biotransformations, 4.3 g of (S)-perillyl alcohol L (tot) (-1) were produced in 24 h, representing a sixfold improvement in productivity compared to previously reported results. It is concluded that, for selective cytochrome P450-based hydrocarbon oxyfunctionalizations by means of living microbial cells, the relationship between cell physiology and the target biotransformation is crucial, and that understanding the relationship should guide biocatalyst and bioprocess design.

Activation and Effector Functions of Human RORC+ Innate Lymphoid Cells

Innate lymphoid cells expressing the nuclear hormone receptor RORC have emerged as important players in human mucosal immunity. These cells combine innate modes of activation such as Toll-like receptor signaling with secretion of adaptive effector molecules including IL-2, BAFF and the Th17 cytokines IL-17 and IL-22. This endows these cells with the ability to rapidly respond to changes in cytokine milieu as well as changes in microbial composition and to affect both intestinal homeostasis and activation of adaptive immune cells.

Climate Change and Its Effects on Terrestrial Insects and Herbivory Patterns

Climate change and extreme weather events affect plants and animals and the direct impact of anthropogenic climate change has been documented extensively over the past years. In this review, I address the main consequences of elevated CO2 and O3 concentrations, elevated temperature and changes in rainfall patterns on the interactions between insects and their host plants. Because of their tight relationship with host plants, insect herbivores are expected to suffer direct and indirect effects of climate change through the changes experienced by their host plants, with consequences to population dynamics, community structure and ecosystem functioning.

Imaging DNA Damage in Vivo Using GammaH2AX-targeted Immunoconjugates

DNA damage responses (DDR) occur during oncogenesis and therapeutic responses to DNA damaging cytotoxic drugs. Thus, a real-time method to image DNA damage in vivo would be useful to diagnose cancer and monitor its treatment. Toward this end, we have developed fluorophore- and radioisotope-labeled immunoconjugates to target a DDR signaling protein, phosphorylated histone H2A variant H2AX (γH2AX), which forms foci at sites of DNA double-strand breaks. Anti-γH2AX antibodies were modified by the addition of diethylenetriaminepentaacetic acid (DTPA) to allow (111)In labeling or the fluorophore Cy3. The cell-penetrating peptide Tat (GRKKRRQRRRPPQGYG) was also added to the immunoconjugate to aid nuclear translocation. In irradiated breast cancer cells, confocal microscopy confirmed the expected colocalization of anti-γH2AX-Tat with γH2AX foci. In comparison with nonspecific antibody conjugates, (111)In-anti-γH2AX-Tat was retained longer in cells. Anti-γH2AX-Tat probes were also used to track in vivo DNA damage, using a mouse xenograft model of human breast cancer. After local X-ray irradiation or bleomycin treatment, the anti-γH2AX-Tat probes produced fluorescent and single photon emission computed tomography signals in the tumors that were proportionate to the delivered radiation dose and the amount of γH2AX present. Taken together, our findings establish the use of radioimmunoconjugates that target γH2AX as a noninvasive imaging method to monitor DNA damage, with many potential applications in preclinical and clinical settings.

Predicting Pore Water EPA-34 PAH Concentrations and Toxicity in Pyrogenic-impacted Sediments Using Pyrene Content

Sediment and freely dissolved pore water concentrations of the U.S. Environmental Protection Agency's list of 34 alkyl and parent PAHs (EPA-34) were measured in 335 sediment samples from 19 different sites impacted by manufactured gas plants, aluminum smelters and other pyrogenic sources. The total EPA-34 freely dissolved pore water concentration, C(pw,EPA-34), expressed as toxic units (TU) is currently considered one of the most accurate measures to assess risk at such sites; however, it is very seldom measured. With this data set, we address how accurately C(pw,EPA-34) can be estimated using limited 16 parent PAH data (EPA-16) commonly available for such sites. An exhaustive statistical analysis of the obtained data validated earlier observations that PAHs with more than 3 rings are present in similar relative abundances and their partitioning behavior typically follows Raoult's law and models developed for coal tar. As a result, sediment and freely dissolved pore water concentrations of pyrene and other 3- and 4-ring PAHs exhibit good log-log correlations (r² > 0.8) to most individual EPA-34 PAHs and also to C(pw,EPA-34). Correlations improve further by including the ratio of high to low molecular weight PAHs, as 2-ring PAHs exhibit the most variability in terms of their relative abundance. The most practical result of the current work is that log C(pw,EPA-34) estimated by the recommended pyrene-based estimation techniques was similarly well correlated to % survival of the benthic amphipods Hyalella azteca and Leptocheirus plumulosus as directly measured log C(pw,EPA-34) values (n = 211). Incorporation of the presented C(pw,EPA-34) estimation techniques could substantially improve risk assessments and guidelines for sediments impacted by pyrogenic residues, especially when limited data are available, without requiring any extra data or measurement costs.

Knowledge Translation in the Discourse of Professional Practice

Clients and practitioners desire up-to-date, safe and effective healthcare. Knowledge translation, a term used to describe the interchange of knowledge between its producers and users, aims to support this desire. Knowledge, and by extension knowledge translation, is subject to varying perspectives ranging from the objective truth-tested knowledge of empiricism, associated by some with academia, to knowledge in the practitioner realm. This latter knowledge is often based on multiple users' experiences and contexts, thus constructed to meet their needs. The goal of this paper is to compare and contrast knowledge and knowledge translation from empirical and constructivist perspectives. It then relates knowledge translation to professional practice discourse and concludes with thoughts on constructivist knowledge translation strategies, including practitioner-driven strategies derived from practice. For example, knowledge translation can be woven into processes to train/integrate new graduates into the healthcare system, it can be captured in practitioner-driven provision of continuing education, and/or it can be facilitated through practitioner collaboration in research via action research approaches. Regardless of the perspective taken, delivery of up-to-date, safe and effective care requires useful, relevant knowledge available when necessary and applicable to real-life issues as perceived, critically, by the knowledge end-user.

Predictive Impact of Allele-matching and EBMT Risk Score for Outcome After T-cell Depleted Unrelated Donor Transplantation in Poor-risk Acute Leukemia and Myelodysplasia

Many parameters predict for outcome after unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (alloSCT). High-resolution HLA-matching significantly impacts outcome and also the European Group of Blood and Marrow Transplantation (EBMT) risk score, based on patient age, disease stage, donor type, time from diagnosis to SCT and gender combination, may predict for non-relapse mortality and overall survival (OS). We evaluated the individual and combined effects of allele-matching and the EBMT risk score in 327 patients with poor-risk acute leukemia or myelodysplasia, who received a T-cell depleted URD alloSCT. Matching for HLA-A, -B, -C and -DRB1 alleles (8/8 match) was associated with a 5-year OS of 40% compared with 30% for mismatched (≤7/8) pairs (P=0.02). Patients with EBMT risk scores of 1-2, 3, 4 and 5-7 had 5-year OS estimates of 53, 43, 30 and 20%, respectively (P<0.001). The favorable prognostic impact of an 8/8 donor was most pronounced if the EBMT risk score was low (1-2). Five-year OS was 74±8% vs 39±11% for fully matched patients with a low-risk EBMT score as compared with EBMT low-risk patients with ≤7/8 donors. These data underscore the importance of incorporating both the EBMT risk score and the degree of high-resolution HLA-matching in the risk assessment prior to URD alloSCT.

Measurement of Dijet Azimuthal Decorrelations in Pp Collisions at Sqrt(s)=7  TeV

Azimuthal decorrelations between the two central jets with the largest transverse momenta are sensitive to the dynamics of events with multiple jets. We present a measurement of the normalized differential cross section based on the full data set (∫Ldt=36  pb(-1)) acquired by the ATLAS detector during the 2010 sqrt(s)=7  TeV proton-proton run of the LHC. The measured distributions include jets with transverse momenta up to 1.3 TeV, probing perturbative QCD in a high-energy regime.

An Efficient, Economical Slow-Freezing Method for Large-Scale Human Embryonic Stem Cell Banking

Human embryonic stem cells (hESCs) are one of the most interesting cell types for tissue engineering, cell therapy, basic scientific research, and drug screening. Fast advancement in these areas requires the availability of large amounts of safe and well-characterized hESCs from hESC banks. Therefore, optimized freezing protocols, allowing the cryopreservation of large amounts of hESC without direct contact with liquid nitrogen, need to be established. In this study, 6 different cryoprotector combinations [dimethylsulfoxide (DMSO), ethylene glycol, and hydroxyethylstarch (HES)] combined with 2 different application methods were screened with the VUB01 cell line, to establish a new slow-freezing protocol with high recovery rates and a good expansion capacity. Our best conditions were confirmed in 4 other hESC lines: H1, H9, 181, and UGent2. To our knowledge, this is the first time that HES is evaluated as a cryoprotector for hESCs. The use of 5% DMSO+5% HES combined with a new detachment protocol leads to efficient hESC cryopreservation. This protocol involves treating the hESC colonies with cell dissociation solution, a mild dissociation solution uncommonly used for hESC culture. A recovery ratio ranging from 45.5% to 168.2% was obtained, and these were significantly different from the other tested conditions (Student's t-test, P<0.05). The cryopreserved hESCs were morphologically comparable to control cells, exhibited a good expansion profile, were positive for pluripotent expression markers, and could still differentiate into the 3 germ layers. This new protocol allows efficient and economical hESC cryopreservation, ideal for hESC banking.

Intensified Chemotherapy Inspired by a Pediatric Regimen Combined with Allogeneic Transplantation in Adult Patients with Acute Lymphoblastic Leukemia Up to the Age of 40

Event-free survival (EFS) at 5 years in pediatric acute lymphoblastic leukemia (ALL) is >80%. Outcome in adult ALL is still unsatisfactory, which is due to less cumulative dosing of chemotherapy and less strict adherence to timing of successive cycles. In the present phase II trial, we evaluated a pediatric regimen in adult patients with ALL under the age of 40. Treatment was according to the pediatric FRALLE approach for high-risk ALL patients and characterized by increased dosages of asparaginase, steroids, methotrexate and vincristin. However, allogeneic stem cell transplantation was offered to standard risk patients with a sibling donor and to all high-risk patients in contrast to the pediatric protocol. Feasibility was defined by achieving complete remission (CR) and completion of treatment within a strict timeframe in at least 60% of patients. In all, 54 patients were included with a median age of 26. CR was achieved in 49 patients (91%), of whom 33 completed treatment as scheduled (61%). Side effects primarily consisted of infections and occurred in 40% of patients. With a median follow-up of 32 months, EFS estimated 66% at 24 months and overall survival 72%. These data show that a dose-intensive pediatric regimen is feasible in adult ALL patients up to the age of 40.

Remediation of Contaminated Marine Sediment Using Thin-layer Capping with Activated Carbon--a Field Experiment in Trondheim Harbor, Norway

In situ amendment of contaminated sediments using activated carbon (AC) is a recent remediation technique, where the strong sorption of contaminants to added AC reduces their release from sediments and uptake into organisms. The current study describes a marine underwater field pilot study in Trondheim harbor, Norway, in which powdered AC alone or in combination with sand or clay was tested as a thin-layer capping material for polycyclic aromatic hydrocarbon (PAH)-contaminated sediment. Several novel elements were included, such as measuring PAH fluxes, no active mixing of AC into the sediment, and the testing of new manners of placing a thin AC cap on sediment, such as AC+clay and AC+sand combinations. Innovative chemical and biological monitoring methods were deployed to test capping effectiveness. In situ sediment-to-water PAH fluxes were measured using recently developed benthic flux chambers. Compared to the reference field, AC capping reduced fluxes by a factor of 2-10. Pore water PAH concentration profiles were measured in situ using a new passive sampler technique, and yielded a reduction factor of 2-3 compared to the reference field. The benthic macrofauna composition and biodiversity were affected by the AC amendments, AC + clay having a lower impact on the benthic taxa than AC-only or AC + sand. In addition, AC + clay gave the highest AC recoveries (60% vs 30% for AC-only and AC + sand) and strongest reductions in sediment-to-water PAH fluxes and porewater concentrations. Thus, application of an AC-clay mixture is recommended as the optimal choice of the currently tested thin-layer capping methods for PAHs, and more research on optimizing its implementation is needed.

Hydrogen Bonding and Chemical Shift Assignments in Carbazole Functionalized Isocyanides from Solid-state NMR and First-principles Calculations

Carbazole functionalized polyisocyanides are known to exhibit excellent electronic properties (E. Schwartz, et al., Chemistry of Materials, 2010, 22, 2597). The functionalities and properties of such materials crucially depend on the organization and stability of the polymer structure. We combine solid-state Nuclear Magnetic Resonance (NMR) experiments with first-principles calculations of isotropic chemical shifts, within the recently developed converse approach, to rationalize the origin of isotropic chemical shifts in the crystalline monomer l-isocyanoalanine 2-(9H-carbazol-9-yl) ethyl amide (monomer 1) and thereby gain insight into the structural organization of its polymer (polymer 2). The use of state-of-the-art solid-state NMR experiments combined with Density Functional Theory (DFT) based calculations allows an unambiguous assignment of all proton and carbon resonances of the monomer. We were able to identify the structure stabilising interactions in the crystal and understand the influence of the molecular packing in the crystal structure on the chemical shift data observed in the NMR spectra. Here the Nuclear Independent Chemical Shift (NICS) approach allows discriminating between 'physical' interactions amongst neighboring molecules such as ring-current effects and 'chemical' interactions such as hydrogen bonding. This analysis reveals that the isocyanide monomer is stabilized by multiple hydrogen bonds such as a bifurcated hydrogen bond involving -N-H, -C-H and O=C- moieties and Ar-H···C≡N- hydrogen bonding (Ar = aromatic group). Based on the geometrical arrangement it is postulated that the carbazole units are involved in the weak σ-π interactions giving rise to a Herringbone packing of the molecules. The chemical shift analysis of the polymer spectra readily establishes the existence of N-H···O=C hydrogen bonds despite the limited resolution exhibited by the polymer spectra. It is also elucidated that the relative arrangement of the carbazole units in the polymer differs significantly from that of the monomer.

Use of Multispectral MRI to Monitor Aneurysm Sac Contents After Endovascular Abdominal Aortic Aneurysm Repair

To validate a newly developed semi-automatic multispectral magnetic resonance imaging (MRI) tool for quantitatively monitoring aneurysm sac contents in patients after endovascular aneurysm repair (EVAR).

Allogeneic Hematopoietic Stem Cell Transplantation for Isolated and Leukemic Myeloid Sarcoma in Adults: a Report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Lenalidomide Maintenance After Nonmyeloablative Allogeneic Stem Cell Transplantation in Multiple Myeloma is Not Feasible: Results of the HOVON 76 Trial

To improve the outcome of allogeneic stem cell transplantation (allo-SCT) in multiple myeloma as part of first-line treatment, we prospectively investigated the feasibility and efficacy of lenalidomide maintenance. Patients started maintenance 1 to 6 months after nonmyeloablative allo-SCT. Lenalidomide was dosed 10 mg on days 1 to 21 of a 28-day schedule for a total of 24 cycles. Peripheral blood samples were taken to evaluate immune modulating effects. Thirty-five eligible patients were enrolled, and 30 started with lenalidomide. After 2 cycles, 14 patients (47%) had to stop treatment, mainly because of the development of acute graft versus host disease (GVHD). In total, 13 patients (43%) stopped treatment because of development of GVHD, 5 patients (17%) because of other adverse events, and 5 patients (17%) because of progression. Responses improved in 37% of patients, and the estimated 1-year progression-free survival from start of maintenance was 69% (90% confidence interval, 53%-81%). Lenalidomide increased the frequency of human leukocyte antigen-DR(+) T cells and regulatory T cells, without correlation with clinical parameters. In conclusion, lenalidomide maintenance 10 mg daily after nonmyeloablative allo-SCT with unmanipulated graft in multiple myeloma patients is not feasible, mainly because of the induction of acute GVHD. This trial was registered at www.trialregister.nl as #NTR1645.

Attentional Window Set by Expected Relevance of Environmental Signals

The existence of an attentional window--a limited region in visual space at which attention is directed--has been invoked to explain why sudden visual onsets may or may not capture overt or covert attention. Here, we test the hypothesis that observers voluntarily control the size of this attentional window to regulate whether or not environmental signals can capture attention. We have used a novel approach to test this: participants eye-movements were tracked while they performed a search task that required dynamic gaze-shifts. During the search task, abrupt onsets were presented that cued the target positions at different levels of congruency. The participant knew these levels. We determined oculomotor capture efficiency for onsets that appeared at different viewing eccentricities. From these, we could derive the participant's attentional window size as a function of onset congruency. We find that the window was small during the presentation of low-congruency onsets, but increased monotonically in size with an increase in the expected congruency of the onsets. This indicates that the attentional window is under voluntary control and is set according to the expected relevance of environmental signals for the observer's momentary behavioral goals. Moreover, our approach provides a new and exciting method to directly measure the size of the attentional window.

Reproducibility and Agreement of Pharyngeal Automated Impedance Manometry with Videofluoroscopy

Automated impedance manometry analysis (AIM) measures swallow function variables that define bolus timing, intrabolus pressure, contractile vigor, and bolus presence; these are combined to derive a swallow risk index (SRI) that is correlated with pharyngeal dysfunction and aspiration. We assessed intra-rater and inter-rater reproducibility of AIM analysis-derived variables; the diagnostic accuracy of AIM-based criteria for detecting aspiration was determined by using expertly scored videofluoroscopy as the standard.

Ultraviolet B Radiation and Reactive Oxygen Species Modulate Interleukin-31 Expression in T Lymphocytes, Monocytes and Dendritic Cells

Interleukin (IL)-31 is a novel Th2 T-cell cytokine that induces pruritus and dermatitis in transgenic mice. While enhanced mRNA expression of this cytokine is detected in skin samples of inflammatory skin diseases, the regulation of IL-31 expression is poorly understood.

Long-term Outcome of Popliteal Artery Aneurysms After Ligation and Bypass

After exclusion of popliteal artery aneurysms (PAAs) through bypass surgery, there is a risk of persistent flow through collaterals and growth of the excluded aneurysmal sac. This study was conducted to evaluate this risk at long-term follow-up.

Drug-eluting Stents in the Perioperative Period: What Are the Key Aspects in Management?

[Interventional Radiological Therapies in Lung Oncology]

Interventional radiological procedures for the treatment of primary and secondary pulmonary malignancies have become increasingly important. In addition to thermally ablative treatment, selective chemoembolisation by a vascular access allows localised therapy. These treatments are considered to be palliative for patients in a reduced general condition which does not allow systemic chemotherapy. In functionally inoperable patients especially the ablative procedures are potentially curative alternatives to surgery. This article provides an overview of the currently used interventional radiological procedures in lung oncology and assesses their importance. Further studies are needed to show whether interventional radiological procedures, which are promising due to their favourable risk-benefit ratio, may represent an alternative to radiotherapy or be effective in multimodal approaches.

A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses

Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of V(H)1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the V(H)1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.

TonB-Dependent Transporters Expressed by Neisseria Gonorrhoeae

Neisseria gonorrhoeae causes the common sexually transmitted infection, gonorrhea. This microorganism is an obligate human pathogen, existing nowhere in nature except in association with humans. For growth and proliferation, N. gonorrhoeae requires iron and must acquire this nutrient from within its host. The gonococcus is well-adapted for growth in diverse niches within the human body because it expresses efficient transport systems enabling use of a diverse array of iron sources. Iron transport systems facilitating the use of transferrin, lactoferrin, and hemoglobin have two components: one TonB-dependent transporter and one lipoprotein. A single component TonB-dependent transporter also allows N. gonorrhoeae to avail itself of iron bound to heterologous siderophores produced by bacteria within the same ecological niche. Other TonB-dependent transporters are encoded by the gonococcus but have not been ascribed specific functions. The best characterized iron transport system expressed by N. gonorrhoeae enables the use of human transferrin as a sole iron source. This review summarizes the molecular mechanisms involved in gonococcal iron acquisition from human transferrin and also reviews what is currently known about the other TonB-dependent transport systems. No vaccine is available to prevent gonococcal infections and our options for treating this disease are compromised by the emergence of antibiotic resistance. Because iron transport systems are critical for the survival of the gonococcus in vivo, the surface-exposed components of these systems are attractive candidates for vaccine development or therapeutic intervention.

Differences in Eye-movement Patterns Between Anorexic and Control Observers when Judging Body Size and Attractiveness

Attentional biases may influence the eye-movements made when judging bodies and so alter the visual information sampled when making a judgment. This may lead to an overestimation of body size. We measured the eye-movements made by 16 anorexic observers and 16 age-matched controls when judging body size and attractiveness. We combined behavioural data with a novel eye-movement analysis technique that allowed us to apply spatial statistical techniques to make fine spatial discriminations in the pattern of eye-movements between our observer groups. Our behavioural results show that anorexic observers overestimate body size relative to controls and find bodies with lower body mass indexes more attractive. For both judgments, the controls' fixations centre on the stomach, but the anorexic observers show a much wider fixation pattern extending to encompass additional features such as the prominence of the hip and collar bones. This additional visual information may serve to alter their behavioural judgments towards an overestimation of body size and shift their ideal body size towards a significantly lower value.

Parkin Interacts with Ambra1 to Induce Mitophagy

Mutations in the gene encoding Parkin are a major cause of recessive Parkinson's disease. Recent work has shown that Parkin translocates from the cytosol to depolarized mitochondria and induces their autophagic removal (mitophagy). However, the molecular mechanisms underlying Parkin-mediated mitophagy are poorly understood. Here, we investigated whether Parkin interacts with autophagy-regulating proteins. We purified Parkin and associated proteins from HEK293 cells using tandem affinity purification and identified the Parkin interactors using mass spectrometry. We identified the autophagy-promoting protein Ambra1 (activating molecule in Beclin1-regulated autophagy) as a Parkin interactor. Ambra1 activates autophagy in the CNS by stimulating the activity of the class III phosphatidylinositol 3-kinase (PI3K) complex that is essential for the formation of new phagophores. We found Ambra1, like Parkin, to be widely expressed in adult mouse brain, including midbrain dopaminergic neurons. Endogenous Parkin and Ambra1 coimmunoprecipitated from HEK293 cells, SH-SY5Y cells, and adult mouse brain. We found no evidence for ubiquitination of Ambra1 by Parkin. The interaction of endogenous Parkin and Ambra1 strongly increased during prolonged mitochondrial depolarization. Ambra1 was not required for Parkin translocation to depolarized mitochondria but was critically important for subsequent mitochondrial clearance. In particular, Ambra1 was recruited to perinuclear clusters of depolarized mitochondria and activated class III PI3K in their immediate vicinity. These data identify interaction of Parkin with Ambra1 as a key mechanism for induction of the final clearance step of Parkin-mediated mitophagy.

Hierarchical Self-assembly and Optical Disassembly for Controlled Switching of Magnetoferritin Nanoparticle Magnetism

Protein cages such as ferritin and viral capsids are interesting building blocks for nanotechnology due to their monodisperse structure and ability to encapsulate various functional moieties. Here we show that recombinant ferritin protein cages encapsulating Fe(3)O(4)-γ-Fe(2)O(3) iron oxide (magnetoferritin) nanoparticles and photodegradable Newkome-type dendrons self-assemble into micrometer-sized complexes with a face-centered-cubic (fcc) superstructure and a lattice constant of 13.1 nm. The magnetic properties of the magnetoferritin particles are affected directly by the hierarchical organization. Magnetoferritin nanoparticles dispersed in water exhibit typical magnetism of single domain noninteracting nanoparticles; however, the same nanoparticles organized into fcc superstructures show clearly the effects of the altered magnetostatic (e.g., dipole-dipole) interactions by exhibiting, for example, different hysteresis of the field-dependent magnetization. The magnetoferritin-dendron assemblies can be efficiently disassembled by a short optical stimulus resulting in release of free magnetoferritin particles. After the triggered release the nanomagnetic properties of the pristine magnetoferritin nanoparticles are regained.

Search for a Heavy Particle Decaying into an Electron and a Muon with the ATLAS Detector in Sqrt[s] = 7 TeV Pp Collisions at the LHC

This Letter presents the first search for a heavy particle decaying into an e ± μ(-/+) final state in sqrt[s] = 7 TeV pp collisions at the LHC. The data were recorded by the ATLAS detector during 2010 and correspond to a total integrated luminosity of 35 pb(-1). No excess above the standard model background expectation is observed. Exclusions at 95% confidence level are placed on two representative models. In an R-parity violating supersymmetric model, tau sneutrinos with a mass below 0.75 TeV are excluded, assuming all R-parity violating couplings are zero except λ(311)' = 0.11 and λ312 = 0.07. In a lepton flavor violating model, a Z'-like vector boson with masses of 0.70-1.00 TeV and corresponding cross sections times branching ratios of 0.175-0.183 pb is excluded. These results extend to higher mass R-parity violating sneutrinos and lepton flavor violating Z's than previous constraints from the Tevatron.

Timing Nutriceuticals?

Evidence on time-dependent effects of drugs and nutrition is succinctly reviewed in order to illustrate and advocate investigations of the timing of nutriceuticals. Emphasis is placed on the merits of coordinated, individually, inferentially, statistically examined sets of N-of-1 studies.

Sphagnum-dwelling Testate Amoebae in Subarctic Bogs Are More Sensitive to Soil Warming in the Growing Season Than in Winter: the Results of Eight-year Field Climate Manipulations

Sphagnum-dwelling testate amoebae are widely used in paleoclimate reconstructions as a proxy for climate-induced changes in bogs. However, the sensitivity of proxies to seasonal climate components is an important issue when interpreting proxy records. Here, we studied the effects of summer warming, winter snow addition solely and winter snow addition together with spring warming on testate amoeba assemblages after eight years of experimental field climate manipulations. All manipulations were accomplished using open top chambers in a dry blanket bog located in the sub-Arctic (Abisko, Sweden). We estimated sensitivity of abundance, diversity and assemblage structure of living and empty shell assemblages of testate amoebae in the living and decaying layers of Sphagnum. Our results show that, in a sub-arctic climate, testate amoebae are more sensitive to climate changes in the growing season than in winter. Summer warming reduced species richness and shifted assemblage composition towards predominance of xerophilous species for the living and empty shell assemblages in both layers. The higher soil temperatures during the growing season also decreased abundance of empty shells in both layers hinting at a possible increase in their decomposition rates. Thus, although possible effects of climate changes on preservation of empty shells should always be taken into account, species diversity and structure of testate amoeba assemblages in dry subarctic bogs are sensitive proxies for climatic changes during the growing season.

24-hour Bronchodilation Following a Single Dose of the Novel β(2)-agonist Olodaterol in COPD

Current guidelines recommend long-acting bronchodilators as maintenance therapy in COPD when symptoms are not adequately controlled with short-acting agents. Olodaterol is a novel long-acting β(2)-adrenoceptor agonist with a pre-clinical profile that suggests 24-h bronchodilation may be achieved with once-daily administration.

Insufficient Recovery of Thymopoiesis Predicts for Opportunistic Infections in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Recovery of thymopoiesis after allogeneic hematopoietic stem cell transplantation is considered pivotal for full immune competence. However, it is still unclear to what extent insufficient recovery of thymopoiesis predicts for subsequent opportunistic infections and non-relapse mortality.

Stem Cell Factor Consistently Improves Thymopoiesis After Experimental Transplantation of Murine or Human Hematopoietic Stem Cells in Immunodeficient Mice

Deficient thymopoiesis is a pivotal determinant of impaired immune competence following hematopoietic stem cell transplantation (HSCT). Stem cell factor (SCF) is essentially involved in early thymopoiesis. We evaluated whether SCF administration would improve recovery of thymopoiesis following HSCT in immunodeficient mice receiving: 1) bone marrow (BM) transplantation of congenic mice; or 2) human fetal liver HSCT in the human immune system mouse model. Following murine BM transplantation, SCF significantly enhanced thymopoiesis and peripheral T cell recovery in lymph nodes and spleen. SCF did not affect BM lymphoid progenitor recovery and/or expansion. Median thymic cellularity increased from 0.9 in PBS- to 266 × 10(4)/thymus in SCF-treated mice (p = 0.05). Following human HSCT in human immune system mice, higher thymic cellularity was observed in SCF-treated mice. Double-negative and early double-positive thymocyte subsets increased, but especially late double-positive, CD4 single-positive, and CD8 single-positive thymocyte subsets were significantly enhanced (p < 0.05). These results show that exogenous supply of SCF may significantly improve murine and human posttransplant thymopoiesis, for which the effect is probably exerted by directly promoting T cell development intrathymically rather than by enhanced entry of prethymically expanded lymphoid progenitors.

A Case of Kaposi's Sarcoma During Primary HIV-1 Infection

The majority of cases of Kaposi's sarcoma (KS) occur at low CD4 counts during chronic HIV-1 infection. We present a case of KS which was diagnosed during primary HIV-1 infection. This report aims to draw attention that KS may occur early in the course of HIV-1 infection and that primary HIV-1 infection may rapidly progress to AIDS.

Influence of Historical Industrial Epochs on Pore Water and Partitioning Profiles of Polycyclic Aromatic Hydrocarbons and Polychlorinated Biphenyls in Oslo Harbor, Norway, Sediment Cores

Contaminant levels in urban harbor sediments vary with contaminant emission levels, sedimentation rates, and sediment resuspension processes such as propeller wash. Levels of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) are decreasing in many urban harbors, as heavily contaminated sediments that accumulated during past decades are being buried by less-contaminated sediments. However, PAHs and PCBs remain a concern in areas where burial is slow or resuspension processes re-expose heavily contaminated older layers. Chronostratigraphic sediment core studies typically characterize contaminant level histories by using total sediment concentrations, C(sed) , and do not determine the freely dissolved porewater concentrations, C(pw) , which provide a better measure of bioavailability. Here both C(sed) and C(pw) profiles were established for PAHs and PCBs in dated sediment cores from diverse areas of Oslo Harbor, Norway. Sediment-porewater partitioning profiles were established alongside profiles of various sorbing carbonaceous phases, including total organic carbon (TOC), black carbon, and diverse carbonaceous geosorbents identified by petrographic analysis. Stratigraphic trends in carbonaceous phases and C(sed) could be associated with different industrial epochs: hydropower (post-1960, approximately), manufactured gas (∼1925-1960), coal (∼1910-1925), and early industry (∼1860-1910). Partitioning was highly variable and correlated best with the TOC. Hydropower-epoch sediments exhibit decreasing C(sed) with time and a relatively strong sorption capacity compared with the manufactured-gas epoch. Sediments from the manufactured-gas epoch exhibit substantial PAH and metal contamination, large amounts of coke and char, and a low sorption capacity. Reexposure of sediments of this epoch increases risks to local benthic species. Implications on natural recovery as a sediment management strategy are discussed.

Highly Pathogenic or Low Pathogenic Avian Influenza Virus Subtype H7N1 Infection in Chicken Lungs: Small Differences in General Acute Responses

ABSTRACT: Avian influenza virus can be divided into two groups, highly pathogenic avian influenza virus (HPAI) and low pathogenic avian influenza virus (LPAI) based on their difference in virulence. To investigate if the difference in clinical outcome between LPAI and HPAI in chickens is due to immunological host responses in the lung within the first 24 hours post infection (hpi), chickens were infected with LPAI or HPAI of subtype H7N1. Virus was found in the caudal and cranial part of the lung. With LPAI, virus was localised around the intrapulmonary bronchus and secondary bronchi. In sharp contrast, HPAI was detected throughout the whole lung. However, based on viral RNA levels, no quantitative difference was observed between LPAI and HPAI infected birds. In infected areas of the lungs, an influx of CD8α+ cells as well as KUL01+ macrophages and dendritic cells (DC) occurred as fast as 8 hpi in both infected groups. No major difference between LPAI and HPAI infected birds in the induction of cytokines and interferons at mRNA level in lung tissue was found.In conclusion, the differences in lethality for chickens infected with LPAI or HPAI could be ascribed to difference in location of the virus. However similar amounts of viral RNA, similar cytokine mRNA levels, and similar influxes of CD8α+ and KUL01+ macrophages and DC were found between HPAI and LPAI in the lungs. A cytokine storm at mRNA level as described for mammals was not observed in the lungs of HPAI infected birds within 24 hpi.

How Do Bryophytes Govern Generative Recruitment of Vascular Plants?

Interactions between vascular plants and bryophytes determine plant community composition in many ecosystems. Yet, little is known about the importance of interspecific differences between bryophytes with respect to their effects on vascular plants. We compared the extent to which species-specific bryophyte effects on vascular plant generative recruitment depend on the following underlying mechanisms: allelopathy, mechanical obstruction, soil moisture and temperature control. We sowed 10 vascular plant species into monospecific mats of six chemically and structurally diverse bryophytes, and examined 1-yr seedling recruitment. Allelopathic effects were also assessed in a laboratory phyto-assay. Although all bryophytes suppressed vascular plant regeneration, there were significant differences between the bryophyte species. The lack of interactions indicated the absence of species-specific adaptations of vascular plants for recruitment in bryophyte mats. Differences between bryophyte species were best explained by alterations in temperature regime under bryophyte mats, mostly by reduced temperature amplitudes during germination. The temperature regime under bryophyte mats was well predicted by species-specific bryophyte cushion thickness. The fitness of established seedlings was not affected by the presence of bryophytes. Our results suggest that climatically or anthropogenically driven changes in the species' composition of bryophyte communities have knock-on effects on vascular plant populations via generative reproduction.

TGFβ1 Enhances MAD1 Expression and Stimulates Promoter-bound Pol II Phosphorylation: Basic Functions of C/EBP, SP and SMAD3 Transcription Factors

The MAD1 protein, a member of the MYC/MAX/MAD network of transcriptional regulators, controls cell proliferation, differentiation and apoptosis. MAD1 functions as a transcriptional repressor, one direct target gene being the tumor suppressor PTEN. Repression of this gene is critical to mediate the anti-apoptotic function of MAD1. Under certain conditions it also antagonizes the functions of the oncoprotein MYC. Previous studies have demonstrated that MAD1 expression is controlled by different cytokines and growth factors. Moreover we have recently demonstrated that the MAD1 promoter is controlled by the cytokine granulocyte colony-stimulating factor (G-CSF) through the activation of STAT3, MAP kinases and C/EBP transcription factors.

Paradox of Sonic Hedgehog (SHH) Transcriptional Regulation: Alternative Transcription Initiation Overrides the Effect of Downstream Promoter DNA Methylation

Recently, DNA methylation has been suggested as a potential mechanism involved in the transcriptional regulation of SHH gene expression in cancer. However, detailed analyses on the underlying transcriptional mechanisms of SHH expression have not been presented so far and were therefore the focus of this study. We found that the genomic region of SHH contains two different transcriptional start sites and four CpG islands spread from the 5' promoter region to the 3' end of the SHH gene. Based on this CpG island topology we analyzed the influence of DNA methylation within the promoter region as well as in exon 2 and exon 3 on SHH mRNA expression in a large set (n = 14) of benign and malignant human cell lines, and further elucidated the functionality of the two identified SHH transcription initiation sites. Methylation-specific PCR (MSP) clearly showed that SHH is expressed independently of DNA methylation within exon 2 and exon 3 of its genomic region, while methylation of the promoter region is able to abrogate SHH expression. Most interesting, we found activation of the upstream SHH promoter in several breast cancer cell lines when the downstream SHH promoter is methylated. These observations lead us to propose a transcriptional model for the SHH gene, in which combined mechanisms of DNA methylation and alternative promoter usage coordinate the transcriptional activity of this important developmental gene.

C14ORF179 Encoding IFT43 is Mutated in Sensenbrenner Syndrome

Sensenbrenner syndrome is a heterogeneous ciliopathy that is characterised by skeletal and ectodermal anomalies, accompanied by chronic renal failure, heart defects, liver fibrosis and other features.

Metal-ion-induced Formation and Stabilization of Protein Cages Based on the Cowpea Chlorotic Mottle Virus

The cowpea chlorotic mottle virus (CCMV) is a versatile building block for the construction of nanoreactors and functional materials. Upon RNA removal, the capsid can be reversibly assembled and disassembed by adjusting the pH. At pH 5.0 the capsid is in the native assembled conformation, while at pH 7.5 it disassembles into 90 capsid protein dimers. This special property enables the encapsulation of various molecules, such as protein and enzymes, but only at low pH. It is possible to stabilize the capsid at pH 7.5 by addition of negatively charged polyelectrolytes or negatively charged particles, but these methods all fill the interior of the capsid, leaving little or no space for other cargo molecules. This pH restriction therefore severely limits the range of enzymes that can be encapsulated, and hampers the investigation of the CCMV capsid as a nanoreactor for the study of enzymes in confined spaces. Herein, the interaction of N-terminal histidine-tag-modified capsid proteins with several metal ions is reported. Depending on the conditions used, nanometer-sized protein particles or capsidlike architectures are formed that are stable at pH 7.5. This metal-mediated stabilization methodology is employed to form stable capsids containing multiple proteins at pH 7.5, thereby greatly expanding the scope of the CCMV capsid as a nanoreactor.

Automated Morphometry of the Visual Pathway in Primary Open-angle Glaucoma

To establish whether primary open-angle glaucoma (POAG) is associated with a change in volume of the visual pathway structures between the eyes and the visual cortex.

Coherent Motion Sensitivity and Reading Development in the Transition from Prereading to Reading Stage

Evidence suggests that sensitivity to coherent motion (CM) is related to reading, but its role in the etiology of developmental dyslexia remains unclear. In this longitudinal study, CM sensitivity was measured in 31 children at family risk for dyslexia and 31 low-risk controls. Children, diagnosed with dyslexia in third grade (mean age=8 years 3 months), demonstrated reduced CM sensitivity in kindergarten (mean age=5 years 8 months), before they had learned to read. Preschool CM thresholds in controls also uniquely predicted future literacy achievement. When reassessed in first grade, CM sensitivity in the dyslexic children was age appropriate, and CM thresholds in the controls no longer predicted literacy acquisition. These findings contribute to the debate about the developmental relations between visual processing and reading acquisition.

Comparison Between RapidTEG® and Conventional Thromboelastography in Cardiac Surgery Patients

Amine-reactive PEGylated Nanoparticles for Potential Bioconjugation

Water-dispersible PEGylated nanoparticles (NPs) presenting amine-reactive conjugation sites at their surfaces were synthesized and their ability to react with amines was demonstrated. An amphiphilic block copolymer bearing an N-succinimidyl ester at its water-soluble end was synthesized by the consecutive controlled radical polymerization of poly(ethylene glycol) methacrylate and styrene from a functional halide initiator. After purification of the copolymer, NPs of approximately 40 nm were obtained by a self-assembly process in water. The reactivity of the NPs was evidenced by reacting them with primary amines, including a fluorescent dye. The activated ester remained stable throughout all synthetic steps and a nearly quantitative coupling efficiency was obtained.

Large-scale Remapping of Visual Cortex is Absent in Adult Humans with Macular Degeneration

The occipital lobe contains retinotopic representations of the visual field. The representation of the central retina in early visual areas (V1-3) is found at the occipital pole. When the central retina is lesioned in both eyes by macular degeneration, this region of visual cortex at the occipital pole is accordingly deprived of input. However, even when such lesions occur in adulthood, some visually driven activity in and around the occipital pole can be observed. It has been suggested that this activity is a result of remapping of this area so that it now responds to inputs from intact, peripheral retina. We evaluated whether or not remapping of visual cortex underlies this activity. Our functional magnetic resonance imaging results provide no evidence of remapping, questioning the contemporary view that early visual areas of the adult human brain have the capacity to reorganize extensively.

Renal Transplantation for Fibromuscular Dysplasia

This is the first report that presents renal transplantation after bilateral nephrectomy as the final treatment for severe renovascular hypertension due to fibromuscular dysplasia (FMD). We describe the history of a 1-year-old girl who suffered from renovascular hypertension due to FMD. Imaging revealed multiple bilateral stenoses of the renal artery extending into the distal branches. The hypertension proved unresponsive to pharmacologic treatment and the intrarenal peripherally located stenoses rendered a conventional approach such as transluminal or surgical angioplasty not feasible. At the age of 5 years, a unilateral nephrectomy of the most affected kidney was performed, but she remained hypertensive and developed progressive cardiomyopathy and retinopathy. At the age of 6 years the remaining kidney was removed, followed by a living related renal transplantation with a kidney donated by her mother. Posttransplantation, she developed mild hypertension due to a postanastomotic stenosis, which was easily controlled with antihypertensives. Now 8 years after transplantation, she has experienced no further blood pressure related problems. Although there is a risk of recurrence of FMD after performing a living related transplantation, our report suggests that this procedure is relatively safe, provided appropriate preoperative evaluation and follow up is performed.

Another Role for Nitric Oxide in Blood Flow Control?

In the current issue, Chen and co-authors present a mathematical model to simulate shear stress-dependent nitric oxide (NO) transport in a small reconstructed microvascular network. Here their results are discussed in the context of NO-dependent blood flow control. Furthermore, other NO-dependent blood flow control mechanisms are briefly reviewed.

Reactions Inside Nanoscale Protein Cages

Chemical reactions are traditionally carried out in bulk solution, but in nature confined spaces, like cell organelles, are used to obtain control in time and space of conversion. One way of studying these reactions in confinement is the development and use of small reaction vessels dispersed in solution, such as vesicles and micelles. The utilization of protein cages as reaction vessels is a relatively new field and very promising as these capsules are inherently monodisperse, in that way providing uniform reaction conditions, and are readily accessible to both chemical and genetic modifications. In this review, we aim to give an overview of the different kinds of nanoscale protein cages that have been employed as confined reaction spaces.

Comment on "Partition Coefficients of Organic Contaminants with Carbohydrates"

[Bronchopulmonary Sequestration As a Cause for Recurrent Pneumonia]

The Neural Basis of the Right Visual Field Advantage in Reading: an MEG Analysis Using Virtual Electrodes

Right-handed participants respond more quickly and more accurately to written words presented in the right visual field (RVF) than in the left visual field (LVF). Previous attempts to identify the neural basis of the RVF advantage have had limited success. Experiment 1 was a behavioral study of lateralized word naming which established that the words later used in Experiment 2 showed a reliable RVF advantage which persisted over multiple repetitions. In Experiment 2, the same words were interleaved with scrambled words and presented in the LVF and RVF to right-handed participants seated in an MEG scanner. Participants read the real words silently and responded "pattern" covertly to the scrambled words. A beamformer analysis created statistical maps of changes in oscillatory power within the brain. Those whole-brain maps revealed activation of the reading network by both LVF and RVF words. Virtual electrode analyses used the same beamforming method to reconstruct the responses to real and scrambled words in three regions of interest in both hemispheres. The middle occipital gyri showed faster and stronger responses to contralateral than to ipsilateral stimuli, with evidence of asymmetric channeling of information into the left hemisphere. The left mid fusiform gyrus at the site of the 'visual word form area' responded more strongly to RVF than to LVF words. Activity in speech-motor cortex was lateralized to the left hemisphere, and stronger to RVF than LVF words, which is interpreted as representing the proximal cause of the RVF advantage for naming written words.

The FbpABC Operon is Required for Ton-independent Utilization of Xenosiderophores by Neisseria Gonorrhoeae Strain FA19

Neisseria gonorrhoeae produces no known siderophores but can employ host-derived, iron-binding proteins, including transferrin and lactoferrin, as iron sources. Given the propensity of this pathogen to hijack rather than synthesize iron-sequestering molecules, we hypothesized that the ability to use siderophores produced by other bacteria, or xenosiderophores, may also play a role in the survival of the gonococcus. Among a panel of diverse siderophores, only the catecholate xenosiderophores enterobactin and salmochelin promoted growth of gonococcal strain FA19. Surprisingly, the internalization pathway was independent of TonB or any of the TonB-dependent transporters. Xenosiderophore-mediated growth was similarly independent of the pilin-extruding secretin formed by PilQ and of the hydrophobic-agent efflux system composed of MtrCDE. The fbpABC operon encodes a periplasmic-binding-protein-dependent ABC transport system that enables the gonococcus to transport iron into the cell subsequent to outer membrane translocation. We hypothesized that the FbpABC proteins, required for ferric iron transport from transferrin and lactoferrin, might also contribute to the utilization of xenosiderophores as iron sources. We created mutants that conditionally expressed FbpABC from an IPTG-inducible promoter. We determined that expression of FbpABC was required for growth of gonococcal strain FA19 in the presence of enterobactin and salmochelin. The monomeric component of enterobactin, dihydroxybenzoylserine (DHBS), and the S2 form of salmochelin specifically promoted FbpABC-dependent growth of FA19. This study demonstrated that the gonococcal FbpABC transport system is required for utilization of some xenosiderophores as iron sources and that growth promotion by these ferric siderophores can occur in the absence of TonB or individual TonB-dependent transporters.

Unusual Cluster of HIV Type 1 Dual Infections in Groningen, The Netherlands

In 2007, 14 Dutch men having sex with men (MSM) filed a criminal case against three other men, accusing them of administering sedative drugs, sexual abuse, and deliberate subcutaneous injections with HIV-1-infected blood. Medical files showed that 9 of 17 men presented with an acute HIV-1 infection syndrome during 2006-2007. Two men were not infected with HIV. Analysis of viral strains in the 12 MSM and the three alleged donors showed that one donor and six recipients were double infected with two distinct HIV-1 subtype B strains, while another five recipients and one donor were single infected with either strain. Two men were infected with unrelated strains. The finding of multiple double infections with very similar HIV-1 strains is without precedent.

Static Secondary Ion Mass Spectrometry for the Surface Characterisation of Individual Nanofibres of Polycaprolactone Functionalised with an Antibacterial Additive

Electrospinning (ES) of polymer solutions generates non-woven webs of nanofibres. The fibre diameter ranges between 10 nm and 1 μm depending on the operating conditions. Surface functionalisation can be performed by the use of suitable additives. Detailed characterisation of the molecular composition at the fibre surface is a key issue. Biodegradable nanowebs with potential antibacterial activity have been prepared by ES of solutions containing polycaprolactone (PCL) and a functionalising additive with PCL segments and hexyldimethylammonium groups (PCLhexaq). Static secondary ion mass spectrometry with Bi(3)(+) projectiles has been applied to individual nanofibres. The positive ion mass spectra contain several signals with high structural specificity allowing the presence of PCLhexaq to be traced back in spite of its low concentration (0.16-1.4% w/w relative to PCL) and its structural similarity to the PCL fibre matrix. Imaging of structural ions visualises the homogeneous distribution of PCLhexaq over the fibre surface. Quantifying the surface concentration of PCLhexaq relative to that of PCL reveals electric field-driven surface enrichment of the additive during ES. Finally, nanofibres subjected to leaching in water for up to 72 h have been analysed. The PCLhexaq surface concentration decreases almost linearly with time at a rate of 0.6% h(-1).

An ACGH Classifier Derived from BRCA1-mutated Breast Cancer and Benefit of High-dose Platinum-based Chemotherapy in HER2-negative Breast Cancer Patients

Breast cancer cells deficient for BRCA1 are hypersensitive to agents inducing DNA double-strand breaks (DSB), such as bifunctional alkylators and platinum agents. Earlier, we had developed a comparative genomic hybridisation (CGH) classifier based on BRCA1-mutated breast cancers. We hypothesised that this BRCA1-like(CGH) classifier could also detect loss of function of BRCA1 due to other causes besides mutations and, consequently, might predict sensitivity to DSB-inducing agents.

HIV Transmission Patterns Among The Netherlands, Suriname, and The Netherlands Antilles: a Molecular Epidemiological Study

We aimed to study patterns of HIV transmission among Suriname, The Netherlands Antilles, and The Netherlands. Fragments of env, gag, and pol genes of 55 HIV-infected Surinamese, Antillean, and Dutch heterosexuals living in The Netherlands and 72 HIV-infected heterosexuals living in Suriname and the Antilles were amplified and sequenced. We included 145 pol sequences of HIV-infected Surinamese, Antillean, and Dutch heterosexuals living in The Netherlands from an observational cohort. All sequences were phylogenetically analyzed by neighbor-joining. Additionally, HIV-1 mobility among ethnic groups was estimated. A phylogenetic tree of all pol sequences showed two Surinamese and three Antillean clusters of related strains, but no clustering between ethnic groups. Clusters included sequences of individuals living in Suriname and the Antilles as well as those who have migrated to The Netherlands. Similar clustering patterns were observed in env and gag. Analysis of HIV mobility among ethnic groups showed significantly lower migration between groups than expected under the hypothesis of panmixis, apart from higher HIV migration between Antilleans in The Netherlands and all other groups. Our study shows that HIV transmission mainly occurs within the ethnic group. This suggests that cultural factors could have a larger impact on HIV mobility than geographic distance.

The Influence of Early Embryo Traits on Human Embryonic Stem Cell Derivation Efficiency

Despite its prognostic value in in vitro fertilization, early embryo morphology is not reported on in the derivation of human embryonic stem cell (hESC) lines. Standard hESC derivation does rely on blastocyst development and its efficiency is highly correlated to inner cell mass (ICM) quality. Poor-quality embryos (PQEs) donated for hESC derivation may have a range of cleavage-stage abnormalities that are known to compromise further development. This study was implemented to determine whether specific PQEs traits influence the efficiency of good-quality ICMs to derive new hESC lines. We found that although the types of PQEs investigated were all able to make blastocysts with good-quality ICMs, the ICMs were unequal in their ability to derive hESCs. Good-quality ICMs from embryos with multiple poor-quality traits were unable to generate hESC lines, in contrast to good-quality ICMs from embryos with a single poor-quality trait. In addition, our data suggest a direct correlation between the number of ICM cells present in the blastocyst and its capacity to derive new hESC lines. This study is the first to demonstrate that ICM quality alone is an incomplete indicator of hESC derivation and that application of in vitro fertilization-based early embryo scoring can help predict hESC derivation efficiency. Experiments aiming to quantify, improve upon, or compare hESC derivation efficiency should thus take into consideration early embryo morphology scoring for the comparison of groups with equal developmental competence.

Focal Fatty Areas in the Myocardium of Patients with Tuberous Sclerosis Complex: a Unique Finding

With this collection of computed tomography and magnetic resonance images, we illustrate a recently described novel finding in the myocardium of patients with tuberous sclerosis complex.

Measures of Exercise Capacity in Adults with Congenital Heart Disease

Exercise capacity in grown-ups with congenital heart disease (GUCH) is mostly reported by peak oxygen consumption (peak VO(2)). Our aim was to evaluate the maximal character of exercise tests, and to investigate submaximal measures of exercise capacity.

Unexplained Hypothermia and Bradycardia in Two Pediatric Patients with Wegener's Granulomatosis

Effect of Endurance Training on Blood Pressure Regulation, Biomarkers and the Heart in Subjects at a Higher Age

We reported previously that two otherwise identical training programs at lower (LI) and higher intensity (HI) similarly reduced resting systolic blood pressure (BP) by approximately 4-6 mmHg. Here, we determined the effects of both programs on BP-regulating mechanisms, on biomarkers of systemic inflammation and prothrombotic state and on the heart. In this cross-over study (3 × 10 weeks), healthy participants exercised three times 1 h/week at, respectively, 33% and 66% of the heart rate (HR) reserve, in a random order, with a sedentary period in between. Measurements, performed at baseline and at the end of each period, involved blood sampling, HR variability, systolic BP variability (SBPV) and cardiac magnetic resonance imaging. Thirty-nine participants (18 men; mean age 59 years) completed the study. Responses were not different between both programs (P>0.05). Pooled data from LI and HI showed a reduction in HR (-4.3 ± 8.1%) and an increase in stroke volume (+11 ± 23.1%). No significant effect was seen on SBPV, plasma renin activity, basal nitric oxide and left ventricular mass. Our results suggest that the BP reduction observed appears to be due to a decrease in systemic vascular resistance; training intensity does not significantly affect the results on mechanisms, biomarkers and the heart.

Sexual Transmission of Hepatitis C Virus in Human Immunodeficiency Virus-negative Men Who Have Sex with Men: a Series of Case Reports

Hepatitis C Virus (HCV) has recently emerged as sexual transmitted infection among (human immunodeficiency virus) HIV-positive but not HIV-negative men who have sex with men (MSM). We present 4 case reports showing that HIV-infection is not an absolute prerequisite for sexual HCV transmission in MSM. HIV-negative MSM with ulcerative sexual transmitted infection, those who engage in rough sexual practices or report a HCV-positive sexual partner, should be regularly screened for HCV.

Fixation Based Event-related Fmri Analysis: Using Eye Fixations As Events in Functional Magnetic Resonance Imaging to Reveal Cortical Processing During the Free Exploration of Visual Images

Eye movements, comprising predominantly fixations and saccades, are known to reveal information about perception and cognition, and they provide an explicit measure of attention. Nevertheless, fixations have not been considered as events in the analyses of data obtained during functional magnetic resonance imaging (fMRI) experiments. Most likely, this is due to their brevity and statistical properties. Despite these limitations, we used fixations as events to model brain activation in a free viewing experiment with standard fMRI scanning parameters. First, we found that fixations on different objects in different task contexts resulted in distinct cortical patterns of activation. Second, using multivariate pattern analysis, we showed that the BOLD signal revealed meaningful information about the task context of individual fixations and about the object being inspected during these fixations. We conclude that fixation-based event-related (FIBER) fMRI analysis creates new pathways for studying human brain function by enabling researchers to explore natural viewing behavior.

Comparison of Microbial Hosts and Expression Systems for Mammalian CYP1A1 Catalysis

Mammalian cytochrome P450 enzymes are of special interest as biocatalysts for fine chemical and drug metabolite synthesis. In this study, the potential of different recombinant microorganisms expressing rat and human cyp1a1 genes is evaluated for such applications. The maximum specific activity for 7-ethoxyresorufin O-deethylation and gene expression levels were used as parameters to judge biocatalyst performance. Under comparable conditions, E. coli is shown to be superior over the use of S. cerevisiae and P. putida as hosts for biocatalysis. Of all tested E. coli strains, E. coli DH5α and E. coli JM101 harboring rat CYP1A1 showed the highest activities (0.43 and 0.42 U g (CDW) (-1) , respectively). Detection of active CYP1A1 in cell-free E. coli extracts was found to be difficult and only for E. coli DH5α, expression levels could be determined (41 nmol g (CDW) (-1) ). The presented results show that efficient expression of mammalian cyp1a1 genes in recombinant microorganisms is troublesome and host-dependent and that enhancing expression levels is crucial in order to obtain more efficient biocatalysts. Specific activities currently obtained are not sufficient yet for fine chemical production, but are sufficient for preparative-scale drug metabolite synthesis.

Keratinocyte Growth Factor and Stem Cell Factor to Improve Thymopoiesis After Autologous CD34+ Cell Transplantation in Rhesus Macaques

Deficient thymopoiesis and retarded recovery of naive CD4(+) T cells are important determinants of insufficient immune-competence following hematopoietic stem cell transplantation (HSCT). Although keratinocyte growth factor (KGF) may protect the thymic epithelium, stem cell factor (SCF) is involved in early thymopoiesis. We evaluated whether KGF alone or combined with SCF would affect thymopoiesis and hematologic recovery following myeloablative autologous HSCT into rhesus macaques. Purpose-bred adult rhesus macaques received 10(6) autologous CD34(+)-selected mononuclear bone marrow cells (BMC)/kg after 9 Gy myeloablative conditioning. Animals were treated with phosphate-buffered saline (PBS) (n = 2), KGF alone (n = 2), or KGF combined with SCF (n = 2). KGF-treated animals showed accelerated hematologic recovery, improved thymopoiesis, and enhanced naive T-cell recovery following transplantation. Improved T cell recovery was not associated with protection against cytomegalovirus reactivation nor with improved antibody response to tetanus toxoid vaccination. Animals treated with KGF and SCF experienced severe adverse events that precluded evaluation of thymopoiesis and T cell recovery. Collectively, our data confirm that KGF may enhance thymopoiesis.

Activated Carbon Amendment to Sequester PAHs in Contaminated Soil: A Lysimeter Field Trial

Activated carbon (AC) amendment is an innovative method for the in situ remediation of contaminated soils. A field-scale AC amendment of either 2% powder or granular AC (PAC and GAC) to a PAH contaminated soil was carried out in Norway. The PAH concentration in drainage water from the field plot was measured with a direct solvent extraction and by deploying polyoxymethylene (POM) passive samplers. In addition, POM samplers were dug directly in the AC amended and unamended soil in order to monitor the reduction in free aqueous PAH concentrations in the soil pore water. The total PAH concentration in the drainage water, measured by direct solvent extraction of the water, was reduced by 14% for the PAC amendment and by 59% for GAC, 12months after amendment. Measurements carried out with POM showed a reduction of 93% for PAC and 56% for GAC. The free aqueous PAH concentration in soil pore water was reduced 93% and 76%, 17 and 28months after PAC amendment, compared to 84% and 69% for GAC. PAC, in contrast to GAC, was more effective for reducing freely dissolved concentrations than total dissolved ones. This could tentatively be explained by leaching of microscopic AC particles from PAC. Secondary chemical effects of the AC amendment were monitored by considering concentration changes in dissolved organic carbon (DOC) and nutrients. DOC was bound by AC, while the concentrations of nutrients (NO(3), NO(2), NH(4), PO(4), P-total, K, Ca and Mg) were variable and likely affected by external environmental factors.

Heart Rate Variability After Heart Transplantation: A 10-year Longitudinal Follow-up Study

BACKGROUND: Cross-sectional studies suggest, by use of heart rate variability (HRV), that partial re-innervation of the sinus node may occur after heart transplantation (HTx). Our aim was to test this hypothesis by examining HRV in long-term longitudinal follow-up study of HTx recipients. METHODS AND RESULTS: 14 HTx recipients (11 men) were studied 1-48 (median 13) months (baseline) and 119-172 (median 141) months after HTx (follow-up). At baseline and follow-up, electrocardiographic RR interval was continuously recorded in the supine position for 20min. The signals were analyzed in the time domain and in the frequency domain by means of power spectral analysis. RR-interval decreased significantly from baseline to follow-up (p<0.05). This was associated with an increase of total power (p<0.001), absolute low frequency (p<0.001), and high frequency power (p<0.001), but unchanged relative low frequency and high frequency power. CONCLUSIONS: The observed changes in HRV during long-term follow-up after HTx are compatible with partial re-innervation of the cardiac sinus node, as has been suggested by cross-sectional studies.

Biocompatibility Properties of Surface-modified Poly(dimethylsiloxane) for Urinary Applications

An electronic sensor system for urinary bladder pressure monitoring requires an imbedding into a biocompatible, flexible, and liquid-impermeable material. Poly(dimethylsiloxane) (PDMS) was selected in the present set-up as packaging material because it fulfills the abovementioned requirements. However, the surface of PDMS is hydrophobic and causes undesired interactions with salts, proteins, and cells present in urine. To reduce possible interactions of urine salts in the urinary bladder, monomers, [2-(methacryloyloxy)ethyl]-dimethyl-3-sulfopropyl-ammonium hydroxide (sulfobetaine) and 2-acrylamido-2-methylpropyl sulfonic acid, were grafted onto the surface through oxygen plasma treatment. A reduction in salt deposition between the pure PDMS and the modified PDMS was observed both in vitro (artificial urine flow over the surface) and in vivo (implants into the urinary bladder of experimental pigs). Additionally, a 10-fold reduction in salt deposition was observed in vitro due to grafting of the monomers onto the surface. These modified PDMS materials proved also to be biocompatible in cell cultures, which was further confirmed by histological screening of the bladder tissue after implantation in an in vivo pig model.

Virus-based Nanocarriers for Drug Delivery

New nanocarrier platforms based on natural biological building blocks offer great promises in revolutionalizing medicine. The usage of specific protein cage structures: virus-like particles (VLPs) for drug packaging and targetted delivery is summarized here. Versatile chemical and genetic modifications on the outer surfaces and inner cavities of VLPs facilitate the preparation of new materials that could meet the biocompatibility, solubility and high uptake efficiency requirements for drug delivery. A full evaluation on the toxicity, bio-distribution and immunology of these materials are envisaged to boost their application potentials.

Impact of FLT3 Internal Tandem Duplication on the Outcome of Related and Unrelated Hematopoietic Transplantation for Adult Acute Myeloid Leukemia in First Remission: A Retrospective Analysis

PURPOSEPatients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain. PATIENTS AND METHODSWe analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning.ResultsCompared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 × 10(9)/L; P < .001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; ± standard deviation) was higher (30% ± 5% v 16% ± 5%; P = .006) and leukemia-free survival (LFS) lower (58% ± 5% v 71% ± 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR. CONCLUSIONFLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.

Sorption of PAHs and PCBs to Activated Carbon: Coal Versus Biomass-based Quality

The addition of activated carbon (AC) is an increasingly popular method for pollutant immobilization, and the AC material can be made of biomass or coal/fossil feedstock. The aim of the present study was to investigate whether there are differences between pollutant sorption to biomass and coal-based AC in the presence and absence of sediment. Through N(2) and CO(2) adsorption to probe surface area and pore size it was shown that the biomass-based AC had a stronger dominance of narrow pores in the size range 3.5-15Å than the anthracite-based material. In the absence of sediment, sorption isotherms for the probe compounds pyrene and PCB-101 showed stronger sorption for the biomass-based AC (logarithmic Freundlich coefficients 8.15 for pyrene; 9.91 for PCB-101) than for the anthracite-based one (logarithmic Freundlich coefficients 7.20 and 9.70, respectively). In the presence of sediment, the opposite trend was observed, with the stronger sorption for anthracite-based AC. Thus, the presence of competing and/or pore-blocking sediment constituents reduces sorption to a larger extent for biomass-derived AC (factor of 5 for pyrene to almost 100 for PCB-101) than for anthracite-based AC (no reduction for pyrene to factor of 5 for PCB-101). This difference is tentatively attributed to the difference in pore size distribution, narrow pores being more prone to clogging, and could have implications for remediation feasibility with AC from different sources.

Effects of Chemical, Biological, and Physical Aging As Well As Soil Addition on the Sorption of Pyrene to Activated Carbon and Biochar

Quantifying the Total and Bioavailable PAHs and Dioxins in Biochars

Biochar soil amendment is advocated to mitigate climate change and improve soil fertility. A concern though, is that during biochar preparation PAHs and dioxins are likely formed. These contaminants can possibly be present in the biochar matrix and even bioavailable to exposed organisms. Here we quantify total and bioavailable PAHs and dioxins in a suite of over 50 biochars produced via slow pyrolysis between 250 and 900 °C, using various methods and biomass from tropical, boreal and temperate areas. These slow pyrolysis biochars, which can be produced locally on farms with minimum resources, are also compared to biochar produced using the industrial methods of fast pyrolysis and gasification. Total concentrations were measured with a soxhlet extraction and bioavailable concentrations were measured with polyoxymethylene passive samplers. Total PAH concentrations ranged from 0.07 µg g-1 to 3.27 µg g-1 for the slow pyrolysis biochars and were dependant on biomass source, pyrolysis temperature and time. With increasing pyrolysis time and temperature, PAH concentrations generally decreased. These total concentrations were below existing environmental quality standards for concentrations of PAHs in soils. Total PAH concentrations in the fast pyrolysis and gasification biochar were 0.3 µg g-1 and 45 µg g-1 respectively, with maximum levels exceeding some quality standards. Concentration of bioavailable PAHs in slow pyrolysis biochars ranged from 0.17 ng L-1to 10.0 ng L-1which is lower than concentrations reported for relatively clean urban sediments. The gasification produced biochar sample had the highest bioavailable concentration (162 ± 71 ng L-1). Total dioxin concentrations were low (up to 92 pg g-1) and bioavailable concentrations were below the analytical limit of detection. No clear pattern of how strongly PAHs were bound to different biochars was found based on the biochars' physicochemical properties.

Bacterial Host Interaction of GFP-labelled Vibrio Anguillarum HI-610 with Gnotobiotic Sea Bass, Dicentrarchus Labrax (L.), Larvae

The location and cell damage caused by Vibrio anguillarum, the causative agent of classical vibriosis, within the developing gut of the newly hatched sea bass, Dicentrarchus labrax (L.), is unknown. A gnotobiotic sea bass model was used to investigate the early interactions of V. anguillarum with sea bass larvae. In the present study, germ-free sea bass larvae were orally exposed to a V. anguillarum HI-610 pathogen labelled with the green fluorescent protein (GFP-HI-610) and sampled at regular intervals. Pathogenic colonization of gut enterocytes was observed 2 h post-exposure (p.e.) and onwards, whereas bacteria within the swim bladder were visualized 48 h p.e and onwards. Ultrastructural findings demonstrated direct bacterial contact with the host cell in the oesophageal mucosa and putative attachment to microvilli of mid- and hindgut enterocytes. The present findings form a starting point for studies assessing the impact of potential candidates (probiotics, prebiotics, antimicrobial peptides) to mitigate bacterial virulence.

Neonatal Onset Autosomal Dominant Polycystic Kidney Disease (ADPKD) in a Patient Homozygous for a PKD2 Missense Mutation Due to Uniparental Disomy

Autosomal dominant polycystic kidney disease (ADPKD), due to a heterozygous mutation in PKD1 or PKD2, is usually an adult onset disease. Renal cystic disease is generally milder in PKD2 patients than in PKD1 patients. Recently, several PKD1 patients with a severe renal cystic phenotype due to a second modifying PKD1 allele, or carrying two incomplete penetrant PKD1 alleles, have been described. This study reports for the first time a patient with neonatal onset of PKD homozygous for an incomplete penetrant PKD2 missense variant due to uniparental disomy.

Relative Size Selection of a Conjugated Polyelectrolyte in Virus-like Protein Structures

A conjugated polyelectrolyte poly[(2-methoxy-5-propyloxy sulfonate)-phenyl-ene vinylene] (MPS-PPV) drives the assembly of virus capsid proteins to form single virus-like particles (VLPs) and aggregates with more than two VLPs, with a relative selection of high molecular weight polymer in the latter.

Sorption of Organic Compounds to Fresh and Field-aged Activated Carbons in Soils and Sediments

Activated carbon (AC) amendment to polluted sediment or soil is an emerging in situ treatment technique that reduces freely dissolved porewater concentrations and subsequently reduces the ecological and human health risk of hydrophobic organic compounds (HOCs). An important question is the capacity of the amended AC after prolonged exposure in the field. To address this issue, sorption of freshly spiked and native HOCs to AC aged under natural field conditions and fresh AC amendments was compared for one soil and two sediments. After 12-32 months of field aging, all AC amendments demonstrated effectiveness for reducing pore water concentrations of both native (30-95%) and spiked (10-90%) HOCs compared to unamended sediment or soil. Values of K(AC) for field-aged AC were lower than freshly added AC for spiked HOCs up to a factor of 10, while the effect was less for native HOCs. The different behavior in sorbing native HOCs compared to freshly spiked HOCs was attributed to differences in the sorption kinetics and degree of competition for sorption sites between the contaminants and pore-clogging natural organic matter. The implications of these findings are that amended AC can still be effective in sorbing additional HOCs some years following amendment in the field. Thus, a certain level of long-term sustainability of this remediation approach is observed, but conclusions for decade-long periods cannot be drawn solely based on the present study.

Complete Genome Sequence of the Giant Virus OBP and Comparative Genome Analysis of the Diverse ΦKZ-related Phages

The 283,757-bp double-stranded DNA genome of Pseudomonas fluorescens phage OBP shares a general genomic organization with Pseudomonas aeruginosa phage EL. Comparison of this genomic organization, assembled in syntenic genomic blocks interspersed with hyperplastic regions of the ΦKZ-related phages, supports the proposed division in the "EL-like viruses," and the "phiKZ-like viruses" within a larger subfamily. Identification of putative early transcription promoters scattered throughout the hyperplastic regions explains several features of the ΦKZ-related genome organization (existence of genomic islands) and evolution (multi-inversion in hyperplastic regions). When hidden Markov modeling was used, typical conserved core genes could be identified, including the portal protein, the injection needle, and two polypeptides with respective similarity to the 3'-5' exonuclease domain and the polymerase domain of the T4 DNA polymerase. While the N-terminal domains of the tail fiber module and peptidoglycan-degrading proteins are conserved, the observation of C-terminal catalytic domains typical for the different genera supports the further subdivision of the ΦKZ-related phages.

Global Assessment of Experimental Climate Warming on Tundra Vegetation: Heterogeneity over Space and Time

Understanding the sensitivity of tundra vegetation to climate warming is critical to forecasting future biodiversity and vegetation feedbacks to climate. In situ warming experiments accelerate climate change on a small scale to forecast responses of local plant communities. Limitations of this approach include the apparent site-specificity of results and uncertainty about the power of short-term studies to anticipate longer term change. We address these issues with a synthesis of 61 experimental warming studies, of up to 20 years duration, in tundra sites worldwide. The response of plant groups to warming often differed with ambient summer temperature, soil moisture and experimental duration. Shrubs increased with warming only where ambient temperature was high, whereas graminoids increased primarily in the coldest study sites. Linear increases in effect size over time were frequently observed. There was little indication of saturating or accelerating effects, as would be predicted if negative or positive vegetation feedbacks were common. These results indicate that tundra vegetation exhibits strong regional variation in response to warming, and that in vulnerable regions, cumulative effects of long-term warming on tundra vegetation - and associated ecosystem consequences - have the potential to be much greater than we have observed to date.

HIV-1 Dual Infection Is Associated With Faster CD4+ T-Cell Decline in a Cohort of Men With Primary HIV Infection

Background. In vitro, animal, and mathematical models suggest that human immunodeficiency virus (HIV) co- or superinfection would result in increased fitness of the pathogen and, possibly, increased virulence. However, in patients, the impact of dual HIV type 1 (HIV-1) infection on disease progression is unclear, because parameters relevant for disease progression have not been strictly analyzed. The objective of the present study is to analyze the effect of dual HIV-1 infections on disease progression in a well-defined cohort of men who have sex with men. Methods. Between 2000 and 2009, 37 men who had primary infection with HIV-1 subtype B, no indication for immediate need of combination antiretroviral therapy (cART), and sufficient follow-up were characterized with regard to dual infection or single infection and to coreceptor use. Patients were followed to estimate the effect of these parameters on clinical disease progression, as defined by the rate of CD4(+) T-cell decline and the time to initiation of cART. Results. Four patients presented with HIV-1 coinfection; 6 patients acquired HIV-1 superinfection, on average 8.5 months from their primary infection; and 27 patients remained infected with a single strain. Slopes of longitudinal CD4(+) T-cell counts and time-weighted changes from baseline were significantly steeper for patients with dual infection compared with patients with single infection. Multivariate analysis showed that the most important parameter associated with CD4(+) T-cell decline over time was dual infection (P = .001). Additionally, patients with HIV-1 coinfection had a significantly earlier start of cART (P < .0001). Conclusions. Dual HIV-1 infection is the main factor associated with CD4(+) T-cell decline in men who have untreated primary infection with HIV-1 subtype B.

Decellularization of Heart Valve Matrices: Search for the Ideal Balance

Abstract: Objective: Currently used decellularization procedures have negative effects on extracellular matrix (ECM) integrity. The objective of this study is to evaluate four decellularization methods and their effect on the collagen ultrastructure, mechanical behavior and antigenicity of porcine aortic valves. Methods: Aortic valves were placed in a trypsin, osmotic, trypsin-osmotic or detergent-osmotic solution. Leaflets were processed for histology and mechanical testing. Matrices were implanted subdermally in rats to evaluate immune reaction and calcification. Results: Trypsin-osmotic methodology effected near-complete decellularization. Trypsin treatment resulted in cell removal only in the spongiosa layer. Osmotic and detergent-osmotic treatments did not remove any cells from the cusps. Mechanical strength was significantly inferior in the trypsin (p50,03) and trypsin-osmotic treated group (p50,04). Trypsin and trypsin-osmotic decellularized matrices evoked a strong CD31 inflammatory cell infiltration. Conclusion: Enzymatic-osmotic decellularization appears to be the only effective method to remove cellular components. However, the near cell free scaffolds still evokes a strong CD31 T-cell inflammatory reaction.

TNF Blockade Requires 1,25(OH)2D3 to Control Human Th17-mediated Synovial Inflammation

OBJECTIVES: T helper 17 (Th17) cells from patients with early rheumatoid arthritis (RA) induce a proinflammatory feedback loop upon RA synovial fibroblast (RASF) interaction, including autocrine interleukin (IL)-17A production. A major challenge in medicine is how to control the pathogenic Th17 cell activity in human inflammatory autoimmune diseases. The objective of this study was to examine whether tumour necrosis factor (TNF) blockade and/or 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) controls Th17-mediated synovial inflammation.METHODS: Peripheral CD4+CD45RO+CCR6+ Th17 cells of patients with early RA, Th17-RASF cocultures and synovial biopsy specimens were cultured with or without 1,25(OH)(2)D(3) and/or TNFα blockade. Intracellular cytokine expression was detected by flow cytometry. Cytokine and matrix metalloprotease (MMP) production was determined by ELISA.RESULTS: The authors show that the 1,25(OH)(2)D(3), but not TNFα blockade, significantly suppressed autocrine IL-17A production in Th17-RASF and synovial biopsy cultures. Combining 1,25(OH)(2)D(3) and TNFα blockade had a significant additive effect compared with single treatment in controlling synovial inflammation, indicated by a further reduction in IL-6, IL-8, MMP-1 and MMP-3 in Th17-RASF cocultures and IL-6 and IL-8 expression in cultures of RA synovial tissue.CONCLUSIONS: These data show that TNF blockade does not suppress IL-17A and IL-22, which can be overcome by 1,25(OH)(2)D(3). The combination of neutralising TNF activity and 1,25(OH)(2)D(3) controls human Th17 activity and additively inhibits synovial inflammation. This indicates more valuable therapeutic potential of activation of Vitamin D receptorsignalling over current TNF neutralisation strategies in patients with RA and potentially other Th17-mediated inflammatory diseases.

Micro- and Macrorheology of Jellyfish Extracellular Matrix

Mechanical properties of the extracellular matrix (ECM) play a key role in tissue organization and morphogenesis. Rheological properties of jellyfish ECM (mesoglea) were measured in vivo at the cellular scale by passive microrheology techniques: microbeads were injected in jellyfish ECM and their Brownian motion was recorded to determine the mechanical properties of the surrounding medium. Microrheology results were compared with macrorheological measurements performed with a shear rheometer on slices of jellyfish mesoglea. We found that the ECM behaved as a viscoelastic gel at the macroscopic scale and as a much softer and heterogeneous viscoelastic structure at the microscopic scale. The fibrous architecture of the mesoglea, as observed by differential interference contrast and scanning electron microscopy, was in accord with these scale-dependent mechanical properties. Furthermore, the evolution of the mechanical properties of the ECM during aging was investigated by measuring microrheological properties at different jellyfish sizes. We measured that the ECM in adult jellyfish was locally stiffer than in juvenile ones. We argue that this stiffening is a consequence of local aggregations of fibers occurring gradually during aging of the jellyfish mesoglea and is enhanced by repetitive muscular contractions of the jellyfish.

Phaedra, a Protocol-Driven System for Analysis and Validation of High-Content Imaging and Flow Cytometry

High-content screening has brought new dimensions to cellular assays by generating rich data sets that characterize cell populations in great detail and detect subtle phenotypes. To derive relevant, reliable conclusions from these complex data, it is crucial to have informatics tools supporting quality control, data reduction, and data mining. These tools must reconcile the complexity of advanced analysis methods with the user-friendliness demanded by the user community. After review of existing applications, we realized the possibility of adding innovative new analysis options. Phaedra was developed to support workflows for drug screening and target discovery, interact with several laboratory information management systems, and process data generated by a range of techniques including high-content imaging, multicolor flow cytometry, and traditional high-throughput screening assays. The application is modular and flexible, with an interface that can be tuned to specific user roles. It offers user-friendly data visualization and reduction tools for HCS but also integrates Matlab for custom image analysis and the Konstanz Information Miner (KNIME) framework for data mining. Phaedra features efficient JPEG2000 compression and full drill-down functionality from dose-response curves down to individual cells, with exclusion and annotation options, cell classification, statistical quality controls, and reporting.

Persistent Subretinal Fluid After Surgery for Rhegmatogenous Retinal Detachment: Hypothesis and Review

BACKGROUND: Persistent subretinal fluid after rhegmatogenous retinal detachment (RRD) surgery is responsible for delayed recovery, and may affect the final visual outcome. Cause, consequences, and treatment remain elusive. DESIGN: Literature review and case series. METHODS: We reviewed the pathophysiological principles and therapeutic options from the literature, and we report the results from a subretinal fluid cytology study. Nine eyes from nine patients with macula-involving RRD underwent surgical repair. The cellular content of subretinal fluid (SRF) was studied by electron microscopy and anti-rhodopsin immunostaining. All eyes were assessed postoperatively with optical coherence tomography for the detection of persistent submacular fluid (PSF) (Ethics Committee Ghent University Hospital, registration number B6702006169). RESULTS: Certain patient characteristics as well as surgical methods were implicated. PSF appears to occur more frequently in patients with longstanding detachments treated with buckling surgery. Several therapeutic options have been suggested but safety and efficacy remain unclear. We found PSF in three eyes on postoperative OCT scans, which corresponded to the three cell-rich subretinal samples. CONCLUSIONS: PSF after successful RRD repair seems to be related to fluid composition. We hypothesize, in the absence of an effective treatment, that a modified surgical drainage, including a washout of the subretinal space, could evacuate the subretinal fluid more completely, and may prevent this complication.

Genetic Variants in TGFβ-1 and PAI-1 As Possible Risk Factors for Cardiovascular Disease After Radiotherapy for Breast Cancer

It has been established that radiotherapy can increase cardiovascular disease (CVD) risk. Genetic variants, which play a role in the tissue, damage response and angiogenesis regulating TGFβ pathway might give us insight into the mechanisms underlying radiation-induced CVD. We examined the effects of two polymorphisms, TGFβ1 29C>T and PAI-1 5G>4G, on CVD incidence.

Treatment, Risk Factors, and Outcome of Adults with Relapsed AML After Reduced Intensity Conditioning for Allogeneic Stem Cell Transplantation

Because information on management and outcome of AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of EBMT. Among 2815 RIC transplants performed for AML in complete remission (CR) between 1999 and 2008, cumulative incidence of relapse was 32% ± 1%. Relapsed patients (263) were included into a detailed analysis of risk factors for overall survival (OS) and building of a prognostic score. CR was reinduced in 32%; remission duration after transplantation was the only prognostic factor for response (P = .003). Estimated 2-year OS from relapse was 14%, thereby resembling results of AML relapse after standard conditioning. Among variables available at the time of relapse, remission after HSCT > 5 months (hazard ratio [HR] = 0.50, 95% confidence interval [CI], 0.37-0.67, P < .001), bone marrow blasts less than 27% (HR = 0.53, 95% CI, 0.40-0.72, P < .001), and absence of acute GVHD after HSCT (HR = 0.67, 95% CI, 0.49-0.93, P = .017) were associated with better OS. Based on these factors, 3 prognostic groups could be discriminated, showing OS of 32% ± 7%, 19% ± 4%, and 4% ± 2% at 2 years (P < .0001). Long-term survival was achieved almost exclusively after successful induction of CR by cytoreductive therapy, followed either by donor lymphocyte infusion or second HSCT for consolidation.

IL-31 Regulates Differentiation and Filaggrin Expression in Human Organotypic Skin Models

Atopic dermatitis (AD) is an inflammatory skin disease affecting 10% to 20% of children and 1% to 3% of adults in industrialized countries. Enhanced expression of IL-31 is detected in skin samples of patients with AD, but its physiological relevance is not known.

An Optimized Growth Factor Cocktail for Ovine Mesenchymal Stem Cells

Growth factors that regulate proliferation, migration, and invasion of ovine mesenchymal stem cells (oMSCs) are not well defined. In this study, we have evaluated five growth factors for their ability to initiate and support in vitro proliferation, migration, and invasion of oMSCs. oMSCs were exposed to different doses and combinations of the growth factors: basic fibroblast growth factor (bFGF), transforming growth factor-β (TGF-β), epidermal growth factor (EGF), insulin growth factor-I (IGF-I), connective tissue growth factor, and platelet-derived growth factor-AB (PDGF-AB). Cellular proliferation, motility, and invasiveness were assayed. The most proliferative stimulating growth factors are PDGF-AB+TGF-β and PDGF-AB+IGF-I. Combinations EGF+bFGF and EGF+bFGF+PDGF-AB demonstrated the greatest ability to stimulate migration. Moreover, the triple cocktail EGF+bFGF+TGF-β has the most significant effect on invasion. Different growth factor cocktails are required to enhance proliferation, migration, and invasion. These results may be useful for the development of a tissue-engineered heart valve by stimulating cellular repopulation.

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