Other articles by Amy H. Van Hove on PubMed

• Neuroleptic Malignant Syndrome in Juvenile Neuronal Ceroid Lipofuscinosis Associated with Low-dose Risperidone Therapy Journal of Inherited Metabolic Disease. 2003  |   Pubmed ID: 14605508 We present a patient with juvenile neuronal ceroid lipofuscinosis who developed a neuroleptic malignant syndrome when treated for hallucinations with a very low dose of risperidone, an atypical neuroleptic medication with usually few extrapyramidal side-effects. The loss of dopaminergic neurons in this condition may make these patients more vulnerable to this severe adverse effect.
• Chloride Channel ClCN7 Mutations Are Responsible for Severe Recessive, Dominant, and Intermediate Osteopetrosis Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. Oct, 2003  |   Pubmed ID: 14584882 Among 94 osteopetrotic patients presenting with a severe clinical picture and diagnosed early in life, 12 bore mutations in the ClCN7 gene, but only 7 of them had the expected two recessive mutations. The remaining five patients seem to be heterozygous for a ClCN7 mutation, and significant variations were observed in the clinical manifestations of their disease, even within the same family.
• Influence of the Radiographer on the Pain Felt During Mammography European Radiology. Oct, 2003  |   Pubmed ID: 14534806 Mammography is the only useful examination in screening for breast cancer. Mortality from breast cancer can be reduced if women go regularly for a screening mammography. Moreover, it is still the key examination in diagnosis of breast diseases and in the follow-up of patients treated for breast cancer. Pain with mammography can deter women from going for regular screening or follow-up; therefore, it is important to reduce pain experience or discomfort from mammography. In this study we evaluate the impact of the "radiographer" on the pain risk during mammography by analysing questionnaires filled in by women and radiographers. Study results reveal that the opinion of the radiographer, the information and communication during the examination and the number of years of experience are important factors in pain and discomfort experience. The attitude of the radiographer plays an important role in the pain experience.
• Plaque-associated Endothelial Dysfunction in Apolipoprotein E-deficient Mice on a Regular Diet. Effect of Human Apolipoprotein AI Cardiovascular Research. Jul, 2003  |   Pubmed ID: 12829190 Apolipoprotein E-deficient mice (apoE(-/-)) on a regular diet become hypercholesterolemic and develop atherosclerosis, but endothelium-dependent relaxation remains undisturbed for up to 6 months. We investigated whether vasomotor dysfunction develops in aged apoE(-/-), whether the defect was systemic (hypercholesterolemia-dependent) or focal (plaque-related), and the effect of human apolipoprotein AI transgenesis (apoAI/E(-/-)).
• Idebenone Treatment in Friedreich's Ataxia: Neurological, Cardiac, and Biochemical Monitoring Neurology. May, 2003  |   Pubmed ID: 12771265 The authors report 1-year prospective data on eight patients with Friedreich ataxia. Idebenone did not halt the progression of ataxia. At the end of therapy, cardiac ultrasound demonstrated significant reduction of cardiac hypertrophy in six of eight patients. Cardiac strain and strain rate imaging showed that the reduction of hypertrophy is preceded by an early and linear improvement in cardiac function. Idebenone reduced erythrocyte protoporphyrin IX levels in five of six patients with elevated baseline levels; however, changes did not consistently relate to cardiac improvement.
• Concerns Regarding Transience and Heterozygosity in Neonatal Hyperglycenemia Annals of Neurology. May, 2003  |   Pubmed ID: 12731008
• D,L-3-hydroxybutyrate Treatment of Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) Lancet. Apr, 2003  |   Pubmed ID: 12727399 Cardiomyopathy and leukodystrophy are life-threatening complications of multiple acyl-CoA dehydrogenase deficiency (MADD). A 2-year-old boy with this disorder developed rapidly progressive leukodystrophy resulting in complete paralysis within 4 months. Within a week of starting sodium-D,L-3-hydroxybutyrate he had improved. After 2 years, neurological function returned, including walking independently, with progressive improvement of brain MRI. Two additional infants with MADD developed life-threatening cardiomyopathy unresponsive to conventional treatment. On sodium-D,L-3-hydroxybutyrate treatment their cardiac contractility showed progressive and sustained improvement. D,L-3-hydroxybutyrate is a therapeutic option for cerebral and cardiac complications in severe fatty acid oxidation defects.
• Late-Onset Visceral Presentation with Cardiomyopathy and Without Neurological Symptoms of Adult Sanfilippo A Syndrome American Journal of Medical Genetics. Part A. May, 2003  |   Pubmed ID: 12687673 Sanfilippo A syndrome, mucopolysaccharidosis type IIIA, is caused by a deficiency of heparan sulphamidase activity, and usually presents in childhood with neurodegeneration leading to death in teenage years. Visceral symptoms are limited to coarsening and diarrhea. We now describe an adult patient who presented with cardiomyopathy. At age 45 years she had hypertension, and the next year she developed a progressively worsening cardiomyopathy with prominent apical hypertrophy and atrial fibrillation. At age 53, she had severe concentric hypertrophic nonobstructive cardiomyopathy in both ventricles. There was no coarsening of features. Neurologic function, skeleton, cornea, liver, and spleen were normal. Percutaneous endomyocardial biopsy showed ballooned cardiomyocytes with storage vacuoles, containing acid mucopolysaccharides. Leucocytes, uterus, and brain biopsy did not show this storage material. There was a slight increase in total urine mucopolysaccharides, with an increased proportion of heparan sulfates. Heparan sulphamidase activity was deficient in leukocytes and heparan sulphamidase protein and activity were reduced in cultured fibroblasts. No mutations were identified after sequencing of the heparan sulphamidase gene at the cDNA and the genomic level. This new clinical presentation expands the clinical spectrum of Sanfilippo A syndrome to include a primary visceral presentation of cardiomyopathy without neurologic symptoms in the adult. The late onset may be related to the residual heparan sulphamidase activity. The genetic basis of this new variant is still unclear. Physicians evaluating adults must remain aware of possible new adult presentations of storage conditions.
• International Council for Standardization in Haematology (ICSH) Recommendations for "surrogate Reference" Method for the Packed Cell Volume Laboratory Hematology : Official Publication of the International Society for Laboratory Hematology. 2003  |   Pubmed ID: 12661822 The spun packed cell volume (PCV, hematocrit) is a key measurement on which are based hematology instrument calibration, reference range determination, and assignment of values to calibrators/controls. In 2001, the International Council for Standardization in Haematology (ICSH) recommended a Reference PCV method, which is fully traceable to the ICSH reference hemoglobin method. Because of its complexity, however, this method is impractical for occasional use in routine laboratories and is therefore intended primarily for use by manufacturers of capillary microhematocrit tubes, liquid calibrators, and multichannel analyzers. In response to the need for a simpler method--accessible to all routine laboratories--the ICSH offers this "Surrogate Reference" PCV procedure. It is traceable to the original ICSH Reference PCV method and is based on spun PCVs obtained using borosilicate capillary tubes with an already-known relationship to this reference procedure. This ICSH "Surrogate Reference" PCV method is substantially simpler, thus putting it within the reach of most routine hematology laboratories.
• Natural History of Nonketotic Hyperglycinemia in 65 Patients Neurology. Nov, 2004  |   Pubmed ID: 15557500 Glycine encephalopathy, also known as nonketotic hyperglycinemia (NKH), is an autosomal recessive disorder caused by a defect in the glycine cleavage system. NKH is classically associated with neonatal apnea, lethargy, hypotonia, and seizures, followed by severe psychomotor retardation in those who survive.
• Monte Carlo Simulations of Segregation in Pt-Re Catalyst Nanoparticles The Journal of Chemical Physics. Sep, 2004  |   Pubmed ID: 15352835 We have investigated the segregation of Pt atoms to the surfaces of Pt-Re nanoparticles using the Monte Carlo method and modified embedded-atom method potentials that we have developed for Pt-Re alloys. The Pt(75)Re(25) nanoparticles (containing from 586 to 4,033 atoms) are assumed to have disordered fcc configurations and cubo-octahedral shapes (terminated by [111] and [100] facets), while the Pt(50)Re(50) and Pt(25)Re(75) nanoparticles (containing from 587 to 4,061 atoms) are assumed to have disordered hcp configurations and truncated hexagonal bipyramidal shapes (terminated by [0001] and [1011] facets). We predict that due to the segregation process the equilibrium Pt-Re nanoparticles would achieve a core-shell structure, with a Pt-enriched shell surrounding a Pt-deficient core. For fcc cubo-octahedral Pt(75)Re(25) nanoparticles, the shells consist of almost 100 at. % of Pt atoms. Even in the shells of hcp truncated hexagonal bipyramidal Pt(50)Re(50) nanoparticles, the concentrations of Pt atoms exceed 85 at. % (35 at. % higher than the overall concentration of Pt atoms in these nanoparticles). Most prominently, all Pt atoms will segregate to the surfaces in the hcp truncated hexagonal bipyramidal Pt(25)Re(75) nanoparticles containing less than 1000 atoms. We also find that the Pt atoms segregate preferentially to the vertex sites, less to edge sites, and least to facet sites on the shell of Pt-Re nanoparticles.
• Pharmacokinetics and Tolerability of Long-acting Risperidone in Schizophrenia Schizophrenia Research. Sep, 2004  |   Pubmed ID: 15246468 The pharmacokinetics and tolerability of long-acting risperidone (Risperdal Consta) were evaluated in a multicenter, prospective, open-label, 15-week study of 86 patients with schizophrenia. Subjects stabilized on 2, 4 or 6 mg of oral risperidone once daily for at least 4 weeks were assigned to receive i.m. injections of 25, 50 or 75 mg of risperidone, respectively, every 2 weeks for 10 weeks. The 90% confidence intervals for the i.m./oral ratios of the mean steady-state plasma-AUC, corrected for dosing interval, and of the average plasma concentration of the active moiety (risperidone plus 9-hydroxyrisperidone) were within the range of 80-125%, indicating bioequivalence of the i.m. and oral formulations. However, mean steady-state peak concentrations of the active moiety were 25-32% lower with i.m. than oral dosing (P < 0.05) and fluctuations in plasma active-moiety levels were 32-42% lower with the i.m. than oral regimen. Symptoms of schizophrenia continued to improve after switching from oral to i.m. dosing. Long-acting risperidone was well tolerated locally and systematically. Although overall bioequivalence of the two formulations was established, the differences in pharmacokinetic profiles between the two formulations indicate potential benefits for long-acting risperidone.
• Long-term Intravenous Treatment of Pompe Disease with Recombinant Human Alpha-glucosidase from Milk Pediatrics. May, 2004  |   Pubmed ID: 15121988 Recent reports warn that the worldwide cell culture capacity is insufficient to fulfill the increasing demand for human protein drugs. Production in milk of transgenic animals is an attractive alternative. Kilogram quantities of product per year can be obtained at relatively low costs, even in small animals such as rabbits. We tested the long-term safety and efficacy of recombinant human -glucosidase (rhAGLU) from rabbit milk for the treatment of the lysosomal storage disorder Pompe disease. The disease occurs with an estimated frequency of 1 in 40,000 and is designated as orphan disease. The classic infantile form leads to death at a median age of 6 to 8 months and is diagnosed by absence of alpha-glucosidase activity and presence of fully deleterious mutations in the alpha-glucosidase gene. Cardiac hypertrophy is characteristically present. Loss of muscle strength prevents infants from achieving developmental milestones such as sitting, standing, and walking. Milder forms of the disease are associated with less severe mutations and partial deficiency of alpha-glucosidase.
• Design, Synthesis, and Characterization of Peptide Nanostructures Having Ion Channel Activity Bioorganic & Medicinal Chemistry. Mar, 2004  |   Pubmed ID: 15018900 We report the synthesis and the functional studies of multiple crown alpha-helical peptides designed to form artificial ion channels. The approach combines the versatility of solid phase peptide synthesis, the conformational predictability of peptidic molecules, and the solution synthesis of crown ethers with engineerable ion-binding abilities. Several biophysical methods were employed to characterize the activity and the mode of action of these crown peptide nanostructures. The 21 residue peptides bearing six 21-EC-7 turned out to facilitate the translocation of ions in a similar fashion to natural ion channels.
• Neutrophils in Barth Syndrome (BTHS) Avidly Bind Annexin-V in the Absence of Apoptosis Blood. May, 2004  |   Pubmed ID: 14764526 Barth syndrome (BTHS) is a rare X-linked disease characterized by a triad of dilated cardiomyopathy, skeletal myopathy, and neutropenia. The disease is associated with mutations of the TAZ gene, resulting in defective cardiolipin (CL), an important inner mitochondrial membrane component. Untreated boys die in infancy or early childhood from septicemia or cardiac failure. To date, neutrophil function has never been studied. Directed motility and killing activity of neutrophils was investigated in 7 BTHS patients and found normal in those tested. The circulating neutrophils and eosinophils (but not monocytes or lymphocytes) showed annexin-V binding, suggesting phosphatidylserine (PS) exposure due to apoptosis. However, caspase activity was absent in fresh BTHS cells. Unexpectedly, the near absence of CL impacted neither the mitochondrial mass and shape in fresh BTHS neutrophils nor mitochondrial clustering and Bax translocation upon apoptosis. Annexin-V binding to BTHS neutrophils was not caused by phospholipid scrambling. Moreover, freshly purified BTHS neutrophils were not phagocytosed by macrophages. In sum, a massive number of circulating annexin-V-binding neutrophils in the absence of apoptosis can be demonstrated in BTHS. These neutrophils expose an alternative substrate for annexin-V different from PS and not recognized by macrophages, excluding early clearance as an explanation for the neutropenia.
• Surface Structures of Cubo-octahedral Pt-Mo Catalyst Nanoparticles from Monte Carlo Simulations The Journal of Physical Chemistry. B. Jun, 2005  |   Pubmed ID: 16852434 The surface structures of cubo-octahedral Pt-Mo nanoparticles have been investigated using the Monte Carlo method and modified embedded atom method potentials that we developed for Pt-Mo alloys. The cubo-octahedral Pt-Mo nanoparticles are constructed with disordered fcc configurations, with sizes from 2.5 to 5.0 nm, and with Pt concentrations from 60 to 90 atom %. The equilibrium Pt-Mo nanoparticle configurations were generated through Monte Carlo simulations allowing both atomic displacements and element exchanges at 600 K. We predict that the Pt atoms weakly segregate to the surfaces of such nanoparticles. The Pt concentrations in the surface are calculated to be 5-14 atom % higher than the Pt concentrations of the nanoparticles. Moreover, the Pt atoms preferentially segregate to the facet sites of the surface, while the Pt and Mo atoms tend to alternate along the edges and vertexes of these nanoparticles. We found that decreasing the size or increasing the Pt concentration leads to higher Pt concentrations but fewer Pt-Mo pairs in the Pt-Mo nanoparticle surfaces.
• Partnership Working Between University Researchers and Self-advocacy Organizations: 'A Way Forward for Inclusion?'in England and 'Fine Feathers Make a Fine Bird'in Flanders Journal of Intellectual Disabilities : JOID. Dec, 2005  |   Pubmed ID: 16330488 This article gives accounts of differing experiences of self-advocate partnerships in research with universities in England and Flanders. In England the partnership grew up within a local People First group built upon a personal working relationship with one support person. It is focused almost exclusively on empirical research and, because it is aimed at influencing policy and practice, questions of funding and control are to the fore. In Flanders the partnership is closely linked with the development of a national movement of self-advocates in which the university was a close ally. Research is important in both contexts but in Flanders the university is more clearly identified with the wider movement. Partnerships have their ups and downs but in both countries researchers with the label 'learning difficulties' wish to set their own agendas and place great importance on trust in their work with their support worker (England) or ally (Flanders).
• Benzoate Treatment and the Glycine Index in Nonketotic Hyperglycinaemia Journal of Inherited Metabolic Disease. 2005  |   Pubmed ID: 16151895 High-dose benzoate treatment aimed at reducing plasma glycine levels to normal reduces seizures and increases wakefulness in patients with nonketotic hyperglycinaemia (NKH). Since benzoate metabolism is dependent on the available glycine pool, and since the glycine pool is variably affected by the deficiency in the glycine cleavage enzyme system, we examined the importance of interpatient variability in benzoate requirement. To correct for the dietary glycine contribution, the glycine index was introduced as the molar requirement of benzoate dose necessary to normalize plasma glycine levels and subtracting from that the dietary glycine intake, both corrected for weight. The glycine index varied between 3.62 and 4.87 mmol/kg per day in five patients with a poor neurodevelopmental outcome and between 0.92 and 1.90 mmol/kg per day in four patients with a better neurodevelopmental outcome, and was 2.54 mmol/kg per day in a single patient with an intermediate outcome. The glycine index was stable over time within each patient. Exceeding the balance by either increasing food glycine intake or decreasing the benzoate dose resulted in increased glycine levels. Exceeding the glycine tolerance by increasing benzoate resulted in elevated and toxic levels of benzoate. The glycine index is a stable, individually specific parameter in patients with NKH. It has clinical consequences for the dose of benzoate required and the role of dietary management. Through its correlation with neurodevelopmental outcome, the glycine index points to potential genetic factors that could contribute to the psychomotor retardation in NKH.
• A Mitochondrial TRNA Aspartate Mutation Causing Isolated Mitochondrial Myopathy American Journal of Medical Genetics. Part A. Aug, 2005  |   Pubmed ID: 16059939 Several mutations in mitochondrial transfer RNA (tRNA) genes can cause mitochondrial myopathy. We describe a young girl who presented with pronounced exercise intolerance. The anaerobic threshold and the maximal oxygen consumption were decreased. She had decreased complex I and IV enzyme activity and ragged red fibers on muscle biopsy. An A to G transition at nucleotide position 7526 in tRNA Aspartate (tRNA(Asp)) gene was heteroplasmic in several of the patient's tissues. We were unable to detect the mutation in muscle tissue from the patient's mother. This case adds a new genetic etiology for mitochondrial myopathy. It also illustrates for patients with combined deficiency of the complex I and IV enzyme activity the value of sequencing in the affected tissue muscle, and not only in blood, all mitochondrial tRNA genes including those not commonly affected, such as in this case mt tRNA(Asp).
• Clinical and Molecular Characterization of the First Adult Congenital Disorder of Glycosylation (CDG) Type Ic Patient American Journal of Medical Genetics. Part A. Aug, 2005  |   Pubmed ID: 16007612 Congenital disorder of glycosylation (CDG) type Ic, the second largest subtype of CDG, is caused by mutations in human ALG6 (hALG6). This gene encodes the alpha1,3-glucosyltransferase that catalyzes transfer of the first glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. In this report, we describe the first adult patient diagnosed with CDG-Ic, carrying two previously unknown mutations. The first is a three base deletion (897-899delAAT) leading to the loss of I299, the second is an intronic mutation (IVS7 + 2T > G) that causes aberrant splicing. Wildtype hALG6, delivered by a lentiviral vector into patient's fibroblasts, clearly improves the biochemical phenotype, which confirms that the mutations are disease-causing. Striking clinical findings include limb deficiencies in the fingers, resembling brachydactyly type B, a deep vein thrombosis, pseudotumor cerebri, and endocrine disturbances with pronounced hyperandrogenism and virilization. However, even in adulthood, this patient shows normal magnetic resonance imaging of the brain.
• Long-term Treatment with the NO-donor Molsidomine Reduces Circulating ICAM-1 Levels in Patients with Stable Angina Atherosclerosis. Jun, 2005  |   Pubmed ID: 15910868 Recent clinical evidence has indicated that the severity of atherosclerosis is correlated with the level of soluble ICAM-1 (sICAM-1). Nitric oxide (NO) donors are used to treat patients with stable angina pectoris, and the aim of this study was to investigate the short- and long-term effect of molsidomine on the level of this circulating biochemical marker of endothelial function. We included 172 patients and examined the effect of the NO donor treatment on angina related parameters and on sICAM-1 levels after a 4-week- and a 1-year treatment period. After 4 weeks, angina attacks and sublingual (s.l.) isosorbide dinitrate tablet (ISDN) consumption frequency was significantly (p
• Brain Angiotensin and Anxiety-related Behavior: the Transgenic Rat TGR(ASrAOGEN)680 Brain Research. Jun, 2005  |   Pubmed ID: 15869747 The transgenic rat TGR(ASrAOGEN)680, characterized by a transgene-producing antisense RNA against angiotensinogen in the brain, provides an opportunity to study the behavioral effects of angiotensin. While exposed to the elevated plus-maze (EPM) and the light/dark box, TGR(ASrAOGEN)680 rats showed more signs of anxiety compared to parental Sprague-Dawley (SD) rats. In the EPM, they made fewer entries into the open arms, spent less time there and more time on the closed arms. Head dips were reduced and U-turns were increased. In the light/dark box, the latency to the first re-entry into the light compartment was higher in TGR(ASrAOGEN)680. They displayed more SAP out from the dark and a reduced number of transitions between the two compartments. In the social interaction test, active social contacts were reduced, further suggesting an anxious phenotype. Although there was no transgenic effect on distance traveled in the open field, the more anxious TGR(ASrAOGEN)680 spent less time in the inner zone. Self-grooming was increased in TGR(ASrAOGEN)680 during exposure to the EPM and the open field, but was decreased in the social interaction test. In TGR(ASrAOGEN)680, tissue content of 5-HT and its metabolite 5-HIAA was lower in the hippocampus, frontal, and parietal cortex. HIAA and 5-HIAA/5-HT ratios were reduced in the hypothalamus, striatum, and septum. In the open field, the anxiogenic effect of the 5-HT2C/1B receptor agonist mCPP (0.5-1 mg/kg IP) was more pronounced in TGR(ASrAOGEN)680. The data suggest an anxious phenotype in rats with low brain angiotensinogen, possibly related to secondary dysfunctions of the brain serotonergic system.
• Risperidone and Haloperidol in First-episode Psychosis: a Long-term Randomized Trial The American Journal of Psychiatry. May, 2005  |   Pubmed ID: 15863797 The first episode of psychotic illness is a key intervention point. The initial experience with medication can affect willingness to accept treatment. Further, relapse prevention is a treatment cornerstone during the first years of illness because active psychotic illness may affect lifetime outcomes. Thus, initial treatment of active symptoms and subsequent relapse prevention are central goals of pharmacotherapy. This study compared long-term effectiveness of risperidone versus haloperidol in first-episode psychosis patients.
• Intellectual Abilities and Motivation Toward Substance Abuse Treatment in Drug-involved Offenders: a Pilot Study in the Belgian Criminal Justice System International Journal of Offender Therapy and Comparative Criminology. Jun, 2005  |   Pubmed ID: 15851508 A sample of Belgian drug-involved inmates (N=116) completed the European Addiction Severity Index, the Raven Standard Progressive Matrices (SPM), and the Circumstances, Motivation, and Readiness Scales. The pilot results demonstrate that nearly 50% of the participating drug-involved offenders display low intellectual abilities (SPM score definitely below average). Legal difficulties, drug abuse, and psychological problems are identified as the most severe problem areas for the total group. The participants display low to moderately low scores regarding motivation, readiness, and external reasons to stay in or leave treatment. No to very limited correlations between motivational attributes and other variables such as the length of the prison sentence and the number of violent crimes are found. Participants with high intellectual abilities are less motivated to enter substance abuse treatment compared to their counterparts with average and low intellectual abilities. Implications for treatment are discussed.
• Short- and Long-term Efficacy and Safety of Risperidone in Adults with Disruptive Behavior Disorders Psychopharmacology. May, 2005  |   Pubmed ID: 15668818 Function in society can be severely affected by disruptive behaviors in adults.
• Monte Carlo Simulations of Segregation in Pt-Ni Catalyst Nanoparticles The Journal of Chemical Physics. Jan, 2005  |   Pubmed ID: 15638613 We have investigated the segregation of Pt atoms in the surfaces of Pt-Ni nanoparticles, using modified embedded atom method potentials and the Monte Carlo method. The nanoparticles are constructed with disordered fcc configurations at two fixed overall concentrations (50 at. % Pt and 75 at. % Pt). We use octahedral and cubo-octahedral nanoparticles terminated by {111} and {100} facets to examine the extent of the Pt segregation to the nanoparticle surfaces at T=600 K. The model particles contain between 586 and 4033 atoms (particle size ranging from 2.5 to 5 nm). Our results imply that a complete {100}-facet reconstruction could make the cubo-octahendral Pt-Ni nanoparticles most energetically favorable. We predict that at 600 K due to segregation the equilibrium cubo-octahedral Pt50Ni50 nanoparticles with fewer than 1289 atoms and Pt75Ni25 nanoparticles with fewer than 4033 atoms would achieve a surface-sandwich structure, in which the Pt atoms are enriched in the outermost and third atomic shells while the Ni atoms are enriched in the second atomic shell. We also find that, due to an order-disorder transition, the Pt50Ni50 cubo-octahedral nanoparticles containing more than 2406 atoms would form a core-shell structure with a Pt-enriched surface and a Pt-deficient homogenous core.
• Carbon Budget of Pinus Sylvestris Saplings After Four Years of Exposure to Elevated Atmospheric Carbon Dioxide Concentration Tree Physiology. Mar, 2005  |   Pubmed ID: 15631981 To study the responses of Scots pine (Pinus sylvestris L.), a commercially important tree species in Europe, to future increases in atmospheric CO2 concentration ([CO2]), we grew saplings for 4 years in the ground in open-top chambers in ambient or ambient + 400 micromol mol(-1) CO2, without supplemental addition of nutrients and water. Carbon (C) budgets were developed for trees in both CO2 treatments based on productivity and biomass data obtained from destructive harvests at the end of the third and fourth years of treatment, and simulations of annual gross photosynthesis (P(tot)) and maintenance respiration by the model MAESTRA. Simulated P(tot) was enhanced by elevated [CO2], despite significant down-regulation of photosynthetic capacity. The subsequent increase in C uptake was allocated primarily to tissues with limited longevity (needles and fine roots), which explains why the measured annual increment in woody biomass did not differ between CO2 treatments. Thus, our results suggest that accelerated stem growth only occurs in the first 2 years in the presence of elevated [CO2] and that forest rotations will not be shortened significantly in response to increasing [CO2]. In elevated [CO2], a higher proportion of available C was allocated below ground, resulting in altered biomass distribution patterns. In trees of equal size, measured ratios of fine root/needle biomass and belowground/aboveground biomass were almost twice as large in the elevated [CO2] treatment. Although there are uncertainties in scaling from saplings to mature canopies, the data indicate that, in nutrient-limited Scots pine forests, elevated [CO2] is unlikely to accelerate tree growth significantly, but is likely to increase C inputs to soil.
• Clericuzio Type Poikiloderma with Neutropenia is Distinct from Rothmund-Thomson Syndrome American Journal of Medical Genetics. Part A. Jan, 2005  |   Pubmed ID: 15558713 Two siblings from a consanguineous family presented with a poikiloderma of limbs and face, plantar keratoderma, and toenail pachyonychia. Neutropenia and neutrophil dysfunction with impairment of the respiratory burst and bacterial killing resulted in frequent respiratory tract infections. A bronchocentric granulomatous pneumonia was a fatal complication. The clinical presentation is consistent with Clericuzio type poikiloderma with neutropenia. Literature review identified several additional probable patients. Genetic linkage analysis excluded the locus of the RECQL4 gene, mutations in which have been described in some patients with the Rothmund-Thomson poikiloderma syndrome. This report confirms the clinical and genetic identity of the Clericuzio type of poikiloderma with neutropenia syndrome.
• Outcome After Three Years of Laronidase Enzyme Replacement Therapy in a Patient with Hurler Syndrome Journal of Inherited Metabolic Disease. Dec, 2006  |   Pubmed ID: 17089217 Enzyme replacement therapy (ERT) with laronidase, recombinant alpha-L-iduronidase, for mucopolysaccharidosis type I (MPS I) has been clinically available since April 2003. Pre-approval studies were performed on patients with the more attenuated forms of MPS I, Hurler-Scheie and Scheie syndromes. The clinical efficacy of laronidase on the severe form of MPS I, Hurler syndrome, is not well known. We present a patient with Hurler syndrome who has been treated with laronidase for 3 years. Clinically, the patient demonstrated improvement in urinary glycosaminoglycan (GAG) levels and hepatomegaly, but continued to experience decline in respiratory status, musculoskeletal and spinal involvement, and developmental skills. Overall, the benefit of ERT with laronidase in advanced Hurler syndrome appeared to be minimal in this patient.
• The HADHSC Gene Encoding Short-chain L-3-hydroxyacyl-CoA Dehydrogenase (SCHAD) and Type 2 Diabetes Susceptibility: the DAMAGE Study Diabetes. Nov, 2006  |   Pubmed ID: 17065362 The short-chain l-3-hydroxyacyl-CoA dehydrogenase (SCHAD) protein is involved in the penultimate step of mitochondrial fatty acid oxidation. Previously, it has been shown that mutations in the corresponding gene (HADHSC) are associated with hyperinsulinism in infancy. The presumed function of the SCHAD enzyme in glucose-stimulated insulin secretion led us to the hypothesis that common variants in HADHSC on chromosome 4q22-26 might be associated with development of type 2 diabetes. In this study, we have performed a large-scale association study in four different cohorts from the Netherlands and Denmark (n = 7,365). Direct sequencing of HADHSC cDNA and databank analysis identified four tagging single nucleotide polymorphisms (SNPs) including one missense variant (P86L). Neither the SNPs nor haplotypes investigated were associated with the disease, enzyme function, or any relevant quantitative measure (all P > 0.1). The present study provides no evidence that the specific HADHSC variants or haplotypes examined do influence susceptibility to develop type 2 diabetes. We conclude that it is unlikely that variation in HADHSC plays a major role in the pathogenesis of type 2 diabetes in the examined cohorts.
• Efficient Calculation of Electron Diffraction for the Structural Determination of Nanomaterials Physical Review Letters. Aug, 2006  |   Pubmed ID: 17026114 A critical advance in the technique of low-energy electron diffraction is presented and shown to enable determining detailed structures of nanomaterials, based on experimental methods that already exist or have been proposed. Our new cluster approach speeds up the computation to scale as n logn, rather than the current n3 or n2, with n the number of atoms, for example. Applications are illustrated for C60 molecules adsorbed on a Cu(111) surface, with and without coadsorbed metal atoms, exhibiting sensitivity to important structural features such as buckyball size and deformation.
• Comparison of Ochratoxin A and Deoxynivalenol in Organically and Conventionally Produced Beers Sold on the Belgian Market Food Additives and Contaminants. Sep, 2006  |   Pubmed ID: 16901860 Beer was chosen as a cereal-derived and homogeneous product for a comparison of organic and conventional production methods in terms of mycotoxin contamination levels. Ochratoxin A (OTA, a storage mycotoxin) and deoxynivalenol (DON, a field mycotoxin) were assessed by HPLC in organically and conventionally produced beers sold in Belgium. Immunoaffinity column (OchraTest and DONPrep) purification was used prior to HPLC analysis. For in-house validation, recovery experiments, carried out with the spiked beers in the ranges of 50-200 ng OTA l-1 and 20-100 microg DON l-1, led to the overall averages of 91% (RSD = 10%, n = 9) and 93% (RSD = 5%, n = 27), respectively. Organic beers collected during 2003-2004 were more frequently OTA-contaminated (95%, n = 40) than their conventional counterparts (50%, n = 40). Conventional beers were OTA-contaminated at a mean concentration of 25 ng l-1 (range: 19-198 ng l-1), while organic beers contained a mean level of 182 ng l-1 (range: 18-1134 ng l-1). High OTA contamination above the limit of 200 ng l-1 (up to 1134 ng l-1) occasionally occurred in organically produced beers. A complementary survey performed with the same brands in 2005 did not confirm this accidental presence of excessive OTA loads (range: 3-67 ng l-1 for 10 conventional beers and 19-158 ng l-1 for 10 organic beers). Establishing a maximum of 3 microg OTA kg-1 in malt, the application of the regulation EC No. 466/2001 (entered in force before the last sampling) may be related to the observed improvement. The overall incidence of DON was 67 and 80% in conventional and organic beers, respectively. DON concentrations ranged from 2 to 22 microg DON l-1 (mean = 6 microg DON l-1) in conventional beers, while organic beers ranged from 2 to 14 microg DON l-1 (mean=4 microg DON l-1). Thus, DON in beers does not appear to be a major matter of concern. From the statistical tests, it was concluded that the variation between different batches was significant (P < 0.0001), in contrast to that observed between different brands, showing a lack of homogeneity in the raw materials. This occurs either in organically or in conventionally produced materials. Considering these results, an optimized frequency of controls according to European Regulations EC No 466/2001 and EC No 856/2005 should be recommended to reject the irregular batches.
• The Role of Immune Tolerance in Asthma Pathogenesis Current Allergy and Asthma Reports. Sep, 2006  |   Pubmed ID: 16899207 Immune-mediated tolerance encompasses a wide spectrum of mechanisms that can prevent unnecessary and potentially harmful inflammatory responses. An increasing number of scientific publications provide proof for the concept that an impairment of immune-tolerance mechanisms might be causally related to the development of unwanted Th2-driven, allergen-induced airway diseases. In this review, we discuss immune tolerance and the evidence supporting its role in asthma pathogenesis.
• Precision Study on Capillary Electrophoresis Methods for Metacycline Electrophoresis. Jun, 2006  |   Pubmed ID: 16718715 A CE method for metacycline (MTC) determination was investigated in an inter-laboratory experiment. Many problems were encountered in this study, most of which were related to the transfer of the method to different CE equipment. The reported problems could be classified into different categories: problems related to the precision, to the parameters in the protocol, and to the MTC peak shape. As the peak shape problem was partially responsible for the poor precision, a new CE method was developed in order to obtain a good MTC peak shape on all equipment. The precision of this new method for MTC determination was examined in an intermediate precision study, where the influence of the factors "time" and "equipment" was investigated. Although the new method could be transferred to different instruments, the precision remained poor mainly due to the contributions of the between-replicate and the between-injection variances.
• MRI of the Brain and Cervical Spinal Cord in Rhizomelic Chondrodysplasia Punctata Neurology. Mar, 2006  |   Pubmed ID: 16567694 The classic rhizomelic chondrodysplasia punctata (RCDP) phenotype involves a typical facial appearance, cataracts, skeletal dysplasia causing disproportionate somatic growth failure, microcephaly, and severe psychomotor defects. Biochemical abnormalities include impaired plasmalogen biosynthesis in all forms of RCDP and accumulation of phytanic acid in RCDP type 1. A subset of patients has a milder clinical and biochemical phenotype, with less severe neurologic impairment and an incomplete deficiency in plasmalogens. The impact of plasmalogen deficiency on neurologic function is severe, causing spasticity and mental defects, but its pathomechanism is still unknown. The authors specifically focused on myelination because myelin is rich in ethanolamine plasmalogens.
• Risperidone in the Treatment of Psychosis of Alzheimer Disease: Results from a Prospective Clinical Trial The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. Mar, 2006  |   Pubmed ID: 16505133 The objective of this study was to evaluate efficacy and safety of low-dose risperidone for treating psychosis of Alzheimer disease (AD).
• Expanded Motor and Psychiatric Phenotype in Autosomal Dominant Segawa Syndrome Due to GTP Cyclohydrolase Deficiency Journal of Neurology, Neurosurgery, and Psychiatry. Jan, 2006  |   Pubmed ID: 16361586 Segawa syndrome due to GTP cyclohydrolase deficiency is an autosomal dominant disorder with variable expression, that is clinically characterised by l-dopa responsive, diurnally fluctuating dystonia and parkinsonian symptoms.
• A Daylong Clinical Laboratory: from Gaming to High-fidelity Simulators Nurse Educator. Nov-Dec, 2007  |   Pubmed ID: 17998857 Meeting required objectives in the clinical setting can be difficult because of low exposure to critical events. This has been further compounded by an increase in the number of enrolling students without a reciprocal rise in the number of field-related clinical sites. As simulation gains popularity in nursing, exploration of its use and benefits to teach nursing-related concepts is desirable. The authors discuss a variety of teaching strategies ranging from the use of games to high-fidelity simulators that have been incorporated into an all-day clinical simulation campus laboratory.
• Recruitment of Cdc42 Through the GAP Domain of RLIP Participates in Remodeling of the Actin Cytoskeleton and is Involved in Xenopus Gastrulation Developmental Biology. Dec, 2007  |   Pubmed ID: 17950267 The transduction pathways that branch out of fibroblast growth factor signaling are essential for the induction of the mesoderm and the specification of the vertebrate body plan. One of these pathways is thought to control remodeling of the actin cytoskeleton through the Ral binding protein (RLIP also known as RalBP1), an effector of the small G protein Ral. RLIP contains a region of homology with the GTPase-activating protein (GAP) domain involved in the regulation of GTPases of the Rho family. We demonstrate here that the GAP domain of RLIP is responsible for the stability of the actin cytoskeleton in Xenopus laevis embryos. We also demonstrate that the complete N-terminal domain of RLIP containing the mu2 binding domain (mu2BD) and the GAP domain induces disruption of the actin cytoskeleton when targeted to the plasma membrane. Neither domain, however, has any effect on the actin cytoskeleton when individually targeted to the plasma membrane. We also determined that Cdc42-GDP, but neither Rac-GDP nor Rho-GDP, rescues the effect of expression of the membrane-localized Xenopus RLIP on the actin cytoskeleton. We show that the GAP domain of RLIP interacts in vivo with Cdc42-GTP and Cdc42-GDP. Finally, a single mutation (K244A) in the GAP sequence prevented embryos from gastrulating. These results demonstrate that to participate in the control of the actin cytoskeleton, RLIP needs its complete N-terminal region coding for the mu2BD and the GAP domain. We suggest that RLIP, by coordinating two complementary mechanisms, the endocytosis of clathrin-coated pits and the remodeling of cortical actin, participates in the gastrulation process.
• Narrative in a Nutshell: Sharing Hopes, Fears, and Dreams with Self-advocates Intellectual and Developmental Disabilities. Oct, 2007  |   Pubmed ID: 17887909 The grand narrative of modernism is a dominating story with profound sociopolitical implications in the lives of people with the label of intellectual disabilities. In this article, we throw light on the life stories and interpretive theories of self-advocates, which usually remain hidden between the story-lines of life. Professionals in the field are being pressed to address self-advocates' existential challenges and move us, as theoretical allies, towards deeper conversations about disability theory. Here, we search for a useful theoretical framework to support the circulation of their wisdom and knowledge. We experiment with poststructuralist and feminist pointers and, in particular, some of the notions of Deleuze and Guattari's (1987) rhizome.
• Comment on "A Novel Pathway That Regulates Inflammatory Disease in the Respiratory Tract" Journal of Immunology (Baltimore, Md. : 1950). Jun, 2007  |   Pubmed ID: 17548581
• Expansion Cranioplasty with Jackscrew Distracters for Craniosynostosis and Intracranial Hypertension in Transplanted Osteopetrosis Pediatric Neurosurgery. 2007  |   Pubmed ID: 17337920 An 11-month-old boy with autosomal recessive infantile osteopetrosis presented, 7 months after bone marrow transplantation, with normal ventricular size and life-threatening intracranial hypertension due to pansynostosis.
• Prolonged Inhaled Allergen Exposure Can Induce Persistent Tolerance American Journal of Respiratory Cell and Molecular Biology. May, 2007  |   Pubmed ID: 17218615 Murine asthma models suggest that failure of immune tolerance rather than a defective T helper cell type 1 (Th1) immunity underlies the immune biology of Th2-driven allergen-induced airway disease. Intriguingly, prolonged exposures can result in a full waning of inflammation. The mechanisms underlying this observation are not understood. We hypothesized that the fading of inflammation is the result of regulatory processes, characterized by altered dendritic cell (DC)-T cell interactions. First, we implemented a model in which mice developed Th2-driven airway disease. When we subjected these mice to prolonged antigen ovalbumin (OVA) exposures (8 wk), all inflammation disappeared. Re-immunization and re-challenge showed an inability to mount Th2-skewed immune responses, with absence of airway eosinophils, IgE, and Th2 cytokines. Besides specific immune tolerance, bystander protection was observed. A decrease in CD4+CD25+Foxp3+ T-regulatory cells, PD-1, and IL-10 expression was discerned as compared with acute inflammation. In addition, suppression of ICOS and CD28 was found, along with inhibited DC maturation. This process of disease inhibition surprisingly had a long-lasting memory and was not caused by endotoxin signaling through TLR-4. In summary, our results indicate that the disappearance of Th2-driven airway disease upon persistent antigen exposure is associated with the induction of immune tolerance. The tolerant state is antigen-dependent, and extends to bystander antigens. Moreover, this tolerance is characterized by an altered DC-T cell communication and is long-lasting. Our data further suggest that the mechanism of the disease inhibition after allergic airway inflammation differs from the anti-inflammatory mechanisms observed during acute eosinophilic airway inflammation.
• Long-term Safety and Tolerability of Long-acting Injectable Risperidone in Patients with Schizophrenia or Schizoaffective Disorder European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. Jan, 2007  |   Pubmed ID: 17049818 Subjects were patients with schizophrenia or schizoaffective disorder enrolled in extension studies (Study A and Study B) after participating in 12-week studies of long-acting injectable risperidone [Kane, J.M., Eerdekens, M., Lindenmayer, J.-P., Keith, S.J., Lesem, M., Karcher, K., 2003. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am. J. Psychiatry 160, 1125-1132; Lindenmayer, J.-P., Eerdekens, L., Berry, S., Eerdekens, M., 2004. Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics. J. Clin. Psychiatry 65, 1084-1089]. Twelve months of treatment were completed by 55% of Study A patients and 52% of Study B patients. The median modal dose of long-acting injectable risperidone was 50 mg/14 days in both studies. Most frequent adverse events were psychosis, headache, insomnia, agitation, and rhinitis. EPS-related adverse events were reported in 33% of patients in Study A and 22% in Study B. Patients with Clinical Global Impressions ratings of "not ill" and "mild" increased from 14% at baseline to 54% at endpoint in Study A and from 42% to 65% in Study B. It is concluded that treatment with long-acting injectable risperidone for 1 year or longer appeared to be safe and well tolerated in patients with schizophrenia or schizoaffective disorder.
• A Proposed Method for Assessing Plasma Hypertonicity in Vivo European Journal of Clinical Nutrition. Jan, 2007  |   Pubmed ID: 16855542 Indices of plasma hypertonicity, elevated plasma concentrations of solutes that draw fluid out of cells by osmosis, are needed to pursue hypertonicity as a possible risk factor for obesity and chronic disease. This paper proposes a new index that may be more sensitive to mild hypertonicity in vivo at a point in time than traditional measures. The index compares mean corpuscular volume (MCV) estimates from diluted (in solution by automated cell counter) and nondiluted blood (calculated from manual hematocrit, MCV=Hct/RBC*10(6)). A larger Auto vs Manual MCV (>2 fl) in vitro indicates hypertonicity in vivo if the cell counter diluent is isotonic with the threshold for plasma vasopressin (PVP) release and PVP is detectable in plasma (>0.5 pg/ml). To evaluate this principle of concept, hypertonicity was induced by 24-h fluid restriction after a 20 ml/kg water load in four healthy men (20-46 years). Unlike serum and urine indices, the MCV difference-&-PVP index detected hypertonicity in all participants.
• [Economic Evaluation of Deflexible Ureteroscopy with Laser] Progrès En Urologie : Journal De L'Association Française D'urologie Et De La Société Française D'urologie. Dec, 2008  |   Pubmed ID: 19041810 The purpose of our study was to make an evaluation of the effective cost of a session of deflexible ureteroscopy with laser to cure kidney stones and kidney urothelials tumors.
• Management of a Patient with Holocarboxylase Synthetase Deficiency Molecular Genetics and Metabolism. Dec, 2008  |   Pubmed ID: 18974016 We investigated in a patient with holocarboxylase synthetase deficiency, the relation between the biochemical and genetic factors of the mutant protein with the pharmacokinetic factors of successful biotin treatment. A girl exhibited abnormal skin at birth, and developed in the first days of life neonatal respiratory distress syndrome and metabolic abnormalities diagnostic of multiple carboxylase deficiency. Enzyme assays showed low carboxylase activities. Fibroblast analysis showed poor incorporation of biotin into the carboxylases, and low transfer of biotin by the holocarboxylase synthetase enzyme. Kinetic studies identified an increased Km but a preserved Vmax. Mutation analysis showed the child to be a compound heterozygote for a new nonsense mutation Q379X and for a novel missense mutation Y663H. This mutation affects a conserved amino acid, which is located the most 3' of all recorded missense mutations thus far described, and extends the region of functional biotin interaction. Treatment with biotin 100mg/day gradually improved the biochemical abnormalities in blood and in cerebrospinal fluid (CSF), corrected the carboxylase enzyme activities, and provided clinical stability and a normal neurodevelopmental outcome. Plasma concentrations of biotin were increased to more than 500 nM, thus exceeding the increased Km of the mutant enzyme. At these pharmacological concentrations, the CSF biotin concentration was half the concentration in blood. Measuring these pharmacokinetic variables can aid in optimizing treatment, as individual tailoring of dosing to the needs of the mutation may be required.
• Chronic Inflammation in Asthma: a Contest of Persistence Vs Resolution Allergy. Sep, 2008  |   Pubmed ID: 18616676 Recent investigations have highlighted that endogenous anti-inflammatory mediators and immune regulating mechanisms are important for the resolution of inflammatory processes. A disruption of these mechanisms can be causally related not only to the initiation of unnecessary inflammation, but also to the persistence of several chronic inflammatory diseases. In asthma, chronic Th-2 driven eosinophilic inflammation of the airways is one of the central abnormalities. To date, elucidating the role of the different pro-inflammatory mediators involved in orchestrating the inflammatory processes in asthma has been the subject of intense research in both humans and animal models. However, the counter-regulatory mechanisms that co-determine the outcome in the contest of resolution vs persistence of the eosinophilic airway inflammation remain poorly understood. These are currently being investigated in animal models of chronic asthma. Elucidating these mechanisms is of relevance, since it can give rise to a new therapeutic approach in the treatment of chronic airway inflammation in asthmatics. This novel concept of treatment involves the stimulation of endogenous anti-inflammatory pathways, rather than solely antagonising the various pro-inflammatory mediators. Here, we review and discuss the current knowledge about these endogenous anti-inflammatory mediators in clinical and experimental asthma.
• Mechanical Properties of Solid C(60) Studied with Density Functional Tight Binding Method Augmented by an Empirical Dispersion Term Journal of Physics. Condensed Matter : an Institute of Physics Journal. Jul, 2008  |   Pubmed ID: 21694401 The bulk modulus of solid fcc C(60) was calculated with a density functional tight binding method, augmented by an empirical van der Waals force. The predicted modulus of 9.1 GPa is in good agreement with the experimental measurements. We found that the geometric structures of C(60) molecules in the solid fcc phase are considerably changed under strong compression, due to variations in the type of hybridization of carbon atoms. We also observed a reduction of the HOMO-LUMO gap under compression which is attributed to the overlap of π orbitals from neighboring C(60) molecules. Finally, we showed that the dispersion energy correction in the adopted scheme plays an essential role for the quantitative description of the weakly bound C(60) solid.
• Predictors of Technical Skill Acquisition Among Resident Trainees in a Laparoscopic Skills Education Program World Journal of Surgery. Sep, 2008  |   Pubmed ID: 18553192 Administrative and financial pressures on surgical education have created a need for efficient training curricula. Predictors of innate technical ability, which would guide the optimization of such a curriculum, are not well described. The goal of this study was to identify student characteristics predictive of innate pretraining skill level and response to training during the course of a four-week laparoscopic skills development program.
• Reevaluation of the Role of VEGF-B Suggests a Restricted Role in the Revascularization of the Ischemic Myocardium Arteriosclerosis, Thrombosis, and Vascular Biology. Sep, 2008  |   Pubmed ID: 18511699 The endogenous role of the VEGF family member vascular endothelial growth factor-B (VEGF-B) in pathological angiogenesis remains unclear.
• Cigarette Smoke Enhances Th-2 Driven Airway Inflammation and Delays Inhalational Tolerance Respiratory Research. 2008  |   Pubmed ID: 18489797 Active smoking increases asthma severity and is related to diminished treatment efficacy. Animal models in which inhalation of both allergen and mainstream cigarette smoke are combined can help us to understand the complex interaction between both agents. We have recently shown that, in allergic mice, the airway inflammation can be cleared by repeated allergen challenge, resulting in the establishment of a state of inhalational tolerance.
• Demographic and Socioeconomic Trends in the Use of Laparoscopic Appendectomy from 1997 to 2003 American Journal of Surgery. May, 2008  |   Pubmed ID: 18424278 Because there is conflicting evidence regarding the benefits of laparoscopic appendectomy, we hypothesized that there would be measurable differences in its use among various socioeconomic groups and geographic areas.
• Endothelial Function in Aorta Segments of Apolipoprotein E-deficient Mice Before Development of Atherosclerotic Lesions Pflügers Archiv : European Journal of Physiology. Feb, 2008  |   Pubmed ID: 17899169 Acetylcholine (ACh)-induced relaxation declines in apolipoprotein E-deficient (apoE-/-) mouse aortas, but only after atherosclerotic plaque formation. This study investigated intracellular calcium concentrations [Ca2+]i and changes in phenylephrine-induced contractions as index of baseline nitric oxide (NO) bioavailability before plaque development. Isometric contractions of thoracic aorta rings of young (4 months) apoE-/- and C57BL/6J (WT) mice were evoked by phenylephrine (3x10(-9)-3x10(-5) M) in the presence and absence of endothelial cells (ECs) or NO synthase (NOS) inhibitors. [Ca2+]i (Fura-2 AM) and endothelium-dependent relaxation were measured at baseline and after ACh stimulation. Segments of apoE-/- mice were significantly more sensitive and developed more tension than WT segments in response to phenylephrine. The differences disappeared after NOS inhibition or EC removal or upon increasing [Ca2+]i in apoE-/- strips with 10(-6) M cyclopiazonic acid or 10(-7) M Ca2+-ionophore A23187. Expression of endothelial NOS (eNOS) mRNA was similar in apoE-/- and WT aorta segments. Basal [Ca2+]i was significantly lower in apoE-/- than in WT strips. Relaxation by ACh (3x10(-9)-10(-5) M) was time- and dose-dependently related to [Ca2+]i, but neither ACh-induced relaxation nor Ca2+ mobilization were diminished in apoE-/- strips. In conclusion, basal, but not ACh-induced NO bioavailability, was compromised in lesion-free aorta of apoE-/- mice. Decreased basal NO bioavailability was not related to lower eNOS expression, but most likely related to lower basal [Ca2+]i. These findings further point to important differences between basal and stimulated eNOS activity.
• Infantile Cardiomyopathy Caused by the T14709C Mutation in the Mitochondrial TRNA Glutamic Acid Gene European Journal of Pediatrics. Jul, 2008  |   Pubmed ID: 17891417 A 6-week-old child presented with hypotonia, myopathy, and a rapidly worsening dilated cardiomyopathy with severe atrial and ventricular arrhythmias and pulmonary hypertension, which proved fatal at age 3 months. Biochemical analysis showed a combined deficiency of the enzymatic activities of complexes I and IV and molecular studies identified a T14709C mutation in the mitochondrial tRNA glutamic acid gene. A review of symptomatology in patients with this mutation shows that it mainly presents in childhood or young adults with mild myopathy and diabetes mellitus. Infants with a high, nearly homoplasmic mutant load can present with more severe symptoms including cardiomyopathy. Families with this mitochondrial DNA mutation should be aware that increased mutant load in a subsequent generation may result in severe and often fatal cardiac symptoms.
• Impaired Fibrillin-1 Function Promotes Features of Plaque Instability in Apolipoprotein E-deficient Mice Circulation. Dec, 2009  |   Pubmed ID: 19948973 Arterial stiffness has been associated with an increased cardiovascular risk. The aim of this study was to investigate the interaction between arterial stiffness and atherosclerosis.
• Stacking of Polycyclic Aromatic Hydrocarbons As Prototype for Graphene Multilayers, Studied Using Density Functional Theory Augmented with a Dispersion Term The Journal of Chemical Physics. Nov, 2009  |   Pubmed ID: 19929066 The interlayer pi-pi interaction between finite-size models of graphene sheets was investigated by using a density functional theory method, augmented with an empirical R(-6) term for the description of long-range dispersive interaction; these were calibrated by studying the pi-pi interaction between various benzene dimer configurations and comparing the results with previous calculations. For stacked bilayers (dimers) and multilayers of polyaromatic hydrocarbons, which serve as molecular models of graphene sheets, we found that binding energies and energy gaps are strongly dependent on their sizes, while the stacking order and the number of stacked layers have a minor influence. The remarkably broad variation of the energy gap, ranging from 1.0 to 2.5 eV, due mainly to variation of the model size, suggests the potential of broadband luminescence in the visible range for carbon-based nanomaterials that have pi-pi interacting.
• HF-rTMS Treatment in Medication-resistant Melancholic Depression: Results from 18FDG-PET Brain Imaging CNS Spectrums. Aug, 2009  |   Pubmed ID: 19890238 High frequency repetitive transcranial magnetic stimulation (HF-rTMS) of the left dorsolateral prefrontal cortex (DLPFC) might be a promising strategy to treat depression, but not all patients show a positive outcome.
• [Unexplained Iron-deficiency Due to Helicobacter Pylori] Nederlands Tijdschrift Voor Geneeskunde. 2009  |   Pubmed ID: 19857290 Iron-deficiency is one of the most prevalent worldwide deficiencies. In the western world, chronic, mostly occult, blood loss is a frequent cause. However, in up to 30% of patients an underlying cause is never found during routine investigations. We describe two male patients aged 20 and 62 years and a 77-year-old woman with mainly fatigue and iron-deficiency showing no abnormalities on endoscopy. In these patients, infection with H. pylori was regarded as the major cause of iron deficiency, and there was lasting normalization of iron status and haemoglobin after successful eradication therapy. Although the underlying mechanism still remains to be established, we recommend investigation for H. pylori infection and appropriate treatment in case of unexplained iron-deficiency. In a number of patients, eradication results in a clinically significant improvement of both iron-balance and status.
• Risperidone for the Treatment of Acute Mania in Children and Adolescents with Bipolar Disorder: a Randomized, Double-blind, Placebo-controlled Study Bipolar Disorders. Nov, 2009  |   Pubmed ID: 19839994 To evaluate the efficacy, safety, and tolerability of risperidone monotherapy for the treatment of an acute mixed or manic episode in children and adolescents with bipolar I disorder.
• Vasodilator Efficacy of Nitric Oxide Depends on Mechanisms of Intracellular Calcium Mobilization in Mouse Aortic Smooth Muscle Cells British Journal of Pharmacology. Oct, 2009  |   Pubmed ID: 19788496 Reduction of intracellular calcium ([Ca(2+)](i)) in smooth muscle cells (SMCs) is an important mechanism by which nitric oxide (NO) dilates blood vessels. We investigated whether modes of Ca(2+) mobilization during SMC contraction influenced NO efficacy.
• Combined Effects of Single-nucleotide Polymorphisms in GCK, GCKR, G6PC2 and MTNR1B on Fasting Plasma Glucose and Type 2 Diabetes Risk Diabetologia. Sep, 2009  |   Pubmed ID: 19533084 Variation in fasting plasma glucose (FPG) within the normal range is a known risk factor for the development of type 2 diabetes. Several reports have shown that genetic variation in the genes for glucokinase (GCK), glucokinase regulatory protein (GCKR), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2) and melatonin receptor type 1B (MTNR1B) is associated with FPG. In this study we examined whether these loci also contribute to type 2 diabetes susceptibility.
• Mouse Models of Asthma: a Comparison Between C57BL/6 and BALB/c Strains Regarding Bronchial Responsiveness, Inflammation, and Cytokine Production Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]. Dec, 2009  |   Pubmed ID: 19506803 Animal models of asthma mimic major features of human disease. Since the genetic background of experimental animals might affect hyperresponsiveness and inflammation, we studied its potential influence and the mechanisms leading to differences in strains.
• Mutation Detection in DNA Isolated from Cerebrospinal Fluid and Urine: Clinical Utility and Pitfalls of Multiple Displacement Amplification Molecular Genetics and Metabolism. Aug, 2009  |   Pubmed ID: 19501531 This study describes the use of cerebral spinal fluid (CSF) and/or urine as source of DNA for mutation analysis combined with multiple displacement amplification. The findings illustrate the opportunities and pitfalls of these methods in the search for identification of the pathogenic mutations in the case that only scarce material is available such as CSF.
• Osteocyte Morphology in Human Tibiae of Different Bone Pathologies with Different Bone Mineral Density--is There a Role for Mechanosensing? Bone. Aug, 2009  |   Pubmed ID: 19398046 Matrix strains due to external loading are different in bones of different pathologies with different bone mineral density (BMD), and are likely sensed by the osteocytes, the putative bone mechanosensors. The mechanosensitivity of osteocytes appears to be strongly influenced by their morphology. In this study, we explored the possibility that osteocyte morphology might play a role in various bone pathologies with different BMD. Confocal laser scanning microscopy and nano-CT were used to quantitatively determine 3D morphology and alignment of osteocytes and osteocyte lacunae in human proximal tibial bone with relatively low (osteopenic), medium (osteoarthritic), and high (osteopetrotic) BMD. Osteopenic osteocytes were relatively large and round (lengths 8.9:15.6:13.4 microm), osteopetrotic osteocytes were small and discoid shaped (lengths 5.5:11.1:10.8 microm), and osteoarthritic osteocytes were large and elongated (lengths 8.4:17.3:12.2 microm). Osteopenic osteocyte lacunae showed 3.5 fold larger volume and 2.2 fold larger surface area than osteoarthritic lacunae, whereas osteopetrotic lacunae were 1.9 fold larger and showed 1.5 fold larger surface area than osteoarthritic lacunae. Osteopetrotic osteocyte lacunae had lower alignment than osteopenic and osteoarthritic lacunae as indicated by their lower degree of anisotropy. The differences in 3D morphology of osteocytes and their lacunae in long bones of different pathologies with different BMD might reflect an adaptation to matrix strain due to different external loading conditions. Moreover, since direct mechanosensing of matrix strain likely occurs by the cell bodies, the differences in osteocyte morphology and their lacunae might indicate differences in osteocyte mechanosensitivity. The exact relationship between osteocyte morphology and bone architecture, however, is complex and deserves further study.
• Acute Nutrition Management in the Prevention of Metabolic Illness: a Practical Approach with Glucose Polymers Molecular Genetics and Metabolism. May, 2009  |   Pubmed ID: 19367873
• Finding Twinkle in the Eyes of a 71-year-old Lady: a Case Report and Review of the Genotypic and Phenotypic Spectrum of TWINKLE-related Dominant Disease American Journal of Medical Genetics. Part A. May, 2009  |   Pubmed ID: 19353676 Progressive external ophthalmoplegia (PEO) can be caused by a disorder characterized by multiple mitochondrial DNA (mtDNA) deletions due to mutations in the TWINKLE gene, encoding a mtDNA helicase. We describe a 71-year-old woman who had developed PEO at age 55 years. She had cataracts, diabetes, paresthesias, cognitive defects, memory problems, hearing loss, and sensory ataxia. She had muscle weakness with ragged red fibers on biopsy. MRI showed static white matter changes. A c.908G>A substitution (p.R303Q) in the TWINKLE gene was identified. Multiple mtDNA deletions were detected in muscle but not blood by a PCR-based method, but not by Southern blot analysis. MtDNA copy number was maintained in blood and muscle. A systematic literature search was used to identify the genotypic and phenotypic spectrum of dominant TWINKLE-related disease. Patients were adults with PEO and symptoms including myopathy, neuropathy, dysarthria or dysphagia, sensory ataxia, and parkinsonism. Diabetes, cataract, memory loss, hearing loss, and cardiac problems were infrequent. All reported mutations clustered between amino acids 303 and 508 with no mutations at the N-terminal half of the gene. The TWINKLE gene should be analyzed in adults with PEO even in the absence of mtDNA deletions in muscle on Southern blot analysis, and of a family history for PEO. The pathogenic mutations identified 5' beyond the linker region suggest a functional role for this part of the protein despite the absence of a primase function in humans. In our patient, the pathogenesis involved multiple mtDNA deletions without reduction in mtDNA copy number.
• Efficacy and Tolerability of Tapentadol Immediate Release and Oxycodone HCl Immediate Release in Patients Awaiting Primary Joint Replacement Surgery for End-stage Joint Disease: a 10-day, Phase III, Randomized, Double-blind, Active- and Placebo-controlled Study Clinical Therapeutics. Feb, 2009  |   Pubmed ID: 19302899 The primary objective of this study was to assess the efficacy and tolerability of tapentadol immediate release (IR) in patients who were candidates for joint replacement surgery due to end-stage joint disease. A secondary objective was to compare tapentadol IR with oxycodone HCl IR with respect to efficacy and prespecified tolerability end points.
• Wilms' Tumour Gene 1 (WT1) Positivity in Endothelial Cells Surrounding Epithelial Uterine Tumours Histopathology. Feb, 2009  |   Pubmed ID: 19236519
• Comparison of Acute Inflammatory and Chronic Structural Asthma-like Responses Between C57BL/6 and BALB/c Mice International Archives of Allergy and Immunology. 2009  |   Pubmed ID: 19218812 The interactions between airway responsiveness, structural remodelling and inflammation in allergic asthma remain poorly understood. Prolonged challenge with inhaled allergen is necessary to replicate many of the features of airway wall remodelling in mice. In both mice and humans, genetic differences can have a profound influence on allergy, inflammation, airway responsiveness and structural changes.
• Genetic Association Analysis of 13 Nuclear-encoded Mitochondrial Candidate Genes with Type II Diabetes Mellitus: the DAMAGE Study European Journal of Human Genetics : EJHG. Aug, 2009  |   Pubmed ID: 19209188 Mitochondria play an important role in many processes, like glucose metabolism, fatty acid oxidation and ATP synthesis. In this study, we aimed to identify association of common polymorphisms in nuclear-encoded genes involved in mitochondrial protein synthesis and biogenesis with type II diabetes mellitus (T2DM) using a two-stage design. In the first stage, we analyzed 62 tagging single nucleotide polymorphisms (SNPs) in the Hoorn study (n=999 participants) covering all common variation in 13 biological candidate genes. These 13 candidate genes were selected from four clusters regarded essential for correct mitochondrial protein synthesis and biogenesis: aminoacyl tRNA synthetases, translation initiation factors, tRNA modifying enzymes and mitochondrial DNA transcription and replication. SNPs showing evidence for association with T2DM were measured in second stage genotyping (n=10164 participants). After a meta-analysis, only one SNP in SIRT4 (rs2522138) remained significant (P=0.01). Extending the second stage with samples from the Danish Steno Study (n=1220 participants) resulted in a common odds ratio (OR) of 0.92 (0.85-1.00), P=0.06. Moreover, in a large meta-analysis of three genome-wide association studies, this SNP was also not associated with T2DM (P=0.72). In conclusion, we did not find evidence for association of common variants in 13 nuclear-encoded mitochondrial proteins with T2DM.
• Evaluating the Inter-respondent (consumer Vs. Staff) Reliability and Construct Validity (SIS Vs. Vineland) of the Supports Intensity Scale on a Dutch Sample Journal of Intellectual Disability Research : JIDR. Apr, 2009  |   Pubmed ID: 19207283 Despite various reliability studies on the Supports Intensity Scale (SIS), to date there has not been an evaluation of the reliability of client vs. staff judgments. Such determination is important, given the increasing consumer-driven approach to services. Additionally, there has not been an evaluation of the instrument's construct validity on a non-English speaking sample. This is important as the SIS is currently translated into 13 languages.
• A Delphi Clinical Practice Protocol for the Management of Very Long Chain Acyl-CoA Dehydrogenase Deficiency Molecular Genetics and Metabolism. Mar, 2009  |   Pubmed ID: 19157942 Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is a disorder of oxidation of long chain fat, and can present as cardiomyopathy or fasting intolerance in the first months to years of life, or as myopathy in later childhood to adulthood. Expanded newborn screening has identified a relatively high incidence of this disorder (1:31,500), but there is a dearth of evidence-based outcomes data to guide the development of clinical practice protocols. This consensus protocol is intended to assist clinicians in the diagnosis and management of screen-positive newborns for VLCAD deficiency until evidence-based guidelines are available.
• Folinic Acid-responsive Seizures Are Identical to Pyridoxine-dependent Epilepsy Annals of Neurology. May, 2009  |   Pubmed ID: 19142996 Folinic acid-responsive seizures and pyridoxine-dependent epilepsy are two treatable causes of neonatal epileptic encephalopathy. The former is diagnosed by characteristic peaks on cerebrospinal fluid (CSF) monoamine metabolite analysis; its genetic basis has remained elusive. The latter is due to alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency, associated with pathogenic mutations in the ALDH7A1 (antiquitin) gene. We report two patients whose CSF showed the marker of folinic acid-responsive seizures, but who responded clinically to pyridoxine. We performed genetic and biochemical testing of samples from these patients, and seven others, to determine the relation between these two disorders.
• High-frequency Detection of Deletions and Variable Rearrangements at the Ornithine Transcarbamylase (OTC) Locus by Oligonucleotide Array CGH Molecular Genetics and Metabolism. Mar, 2009  |   Pubmed ID: 19138872 Ornithine transcarbamylase (OTC) deficiency is an X-linked inborn error of metabolism characterized by impaired synthesis of citrulline from carbamylphosphate and ornithine. Previously reported data suggest that only approximately 80% of OTC deficiency (OTCD) patients have a mutation identified by OTC gene sequencing. To elucidate the molecular etiology in patients with clinical signs of OTCD and negative OTC sequencing, we subjected their DNA to array comparative genomic hybridization (aCGH) using a custom-designed targeted 44k oligonucleotide array. Whenever possible, parental DNA was analyzed to determine the inheritance or to rule out copy number variants in the OTC locus. DNA samples from a total of 70 OTCD patients were analyzed. Forty-three patients (43/70 or 61.5%) were found to have disease-causing point mutations in the OTC gene. The remaining 27 patients (27/70 or 38.5%) showed normal sequencing results or failure to amplify all or part of the OTC gene. Among those patients, eleven (11/70 or 15.7%) were found to have deletions ranging from 4.5kb to 10.6Mb, all involving the OTC gene. Sixteen OTCD patients (16/70 or 22.8%) had normal sequencing and oligoarray results. Analysis of the deletions did not reveal shared breakpoints, suggesting that non-homologous end joining or a replication-based mechanism might be responsible for the formation of the observed rearrangements. In summary, we demonstrate that approximately half of the patients with negative OTC sequencing may have OTC gene deletions readily identifiable by the targeted oligonucleotide-based aCGH. Thus, the test should be considered in OTC sequencing-negative patients with classic symptoms of the disease.
• Search for Quark Compositeness with the Dijet Centrality Ratio in Pp Collisions at √s=7 TeV Physical Review Letters. Dec, 2010  |   Pubmed ID: 21231646 A search for quark compositeness in the form of quark contact interactions, based on hadronic jet pairs (dijets) produced in proton-proton collisions at √s=7 TeV, is described. The data sample of the study corresponds to an integrated luminosity of 2.9 pb(-1) collected with the CMS detector at the LHC. The dijet centrality ratio, which quantifies the angular distribution of the dijets, is measured as a function of the invariant mass of the dijet system and is found to agree with the predictions of the standard model. A statistical analysis of the data provides a lower limit on the energy scale of quark contact interactions. The sensitivity of the analysis is such that the expected limit is 2.9 TeV; because the observed value of the centrality ratio at high invariant mass is below the expectation, the observed limit is 4.0 TeV at the 95% confidence level.
• Search for Dijet Resonances in 7 TeV Pp Collisions at CMS Physical Review Letters. Nov, 2010  |   Pubmed ID: 21231289 A search for narrow resonances in the dijet mass spectrum is performed using data corresponding to an integrated luminosity of 2.9 pb⁻¹ collected by the CMS experiment at the Large Hadron Collider. Upper limits at the 95% confidence level are presented on the product of the resonance cross section, branching fraction into dijets, and acceptance, separately for decays into quark-quark, quark-gluon, or gluon-gluon pairs. The data exclude new particles predicted in the following models at the 95% confidence level: string resonances, with mass less than 2.50 TeV, excited quarks, with mass less than 1.58 TeV, and axigluons, colorons, and E6 diquarks, in specific mass intervals. This extends previously published limits on these models.
• Mountain States Genetics Regional Collaborative Center's Metabolic Newborn Screening Long-term Follow-up Study: a Collaborative Multi-site Approach to Newborn Screening Outcomes Research Genetics in Medicine : Official Journal of the American College of Medical Genetics. Dec, 2010  |   Pubmed ID: 21150369 This article presents the rationale and design of the Mountain States Genetics Regional Collaborative Center's Metabolic Newborn Screening Long-Term Follow-up Study.
• Person-centered Planning: Analysis of Research and Effectiveness Intellectual and Developmental Disabilities. Dec, 2010  |   Pubmed ID: 21166549 Person-centered planning is a well known and widely used approach to individual program planning in the field of intellectual and developmental disabilities. Its purpose is to develop collaborative supports focused on community presence, community participation, positive relationships, respect, and competence. Because there is little research on its effectiveness, our purpose here was to (a) review the current status of effectiveness research; (b) describe its effectiveness in terms of outcomes or results; and (c) discuss the effectiveness of person-centered planning in relation to evidence-based practices. Analyzed studies suggest that, overall, this planning has a positive, but moderate, impact on personal outcomes for this population. The body of evidence provided in this review is weak with regard to criteria for evidence-based research.
• Pediatric Cochlear Implantation: a Qualitative Study of Parental Decision-making Processes in Flanders, Belgium American Annals of the Deaf. 2010  |   Pubmed ID: 21138046 Factors contributing to parents' decision when they choose between cochlear implantation (CI) and traditional hearing aids for their child were examined. The subjects were children with severe/profound hearing loss, born 1999-2001, registered in the universal neonatal hearing screening program in the Flanders region of Belgium. Qualitative data collected retrospectively from parents were subjected to thematic content analysis. In their responses to professional advice, parents were segmented into 3 groups: (a) those whose primary considerations were the importance of oral language development and the relative potential of CI and traditional hearing aids; (b) those for whom alternative factors (e.g., medical risks, ethical issues) were paramount, even in the face of professional advocacy of CI; (c) those who followed professional advice against CI. The researchers conclude that care professionals should be sensitive to the impact of their advice and other factors in parental decision making.
• Prospects for Resolving Chemical Structure by Atomic Force Microscopy: a First-principles Study Langmuir : the ACS Journal of Surfaces and Colloids. Nov, 2010  |   Pubmed ID: 20973578 In a recent paper, the chemical structure of a molecule was resolved by means of atomic force microscopy (AFM): using a metal tip terminated in a CO molecule, the authors could image the internal bonding arrangement of a pentacene molecule with remarkable spatial resolution (notably better than with other tip terminations), as verified by their first-principles calculations. Here we further explore with first-principles calculations the mechanisms, applicability, and capabilities of this approach for a wider range of situations, by varying the imaged molecule and the tip beyond the experimental cases. In our simulations, a high atomic resolution is found to be dominated by the electronic structure of the last two atoms on the tip apex which are set perpendicularly to the sample molecule. For example, tips terminated in CH(4) or pentacene itself (both having a C-H apex) yield similar images, while tips terminated in O(2) or CO give quite different images. While using a CO-terminated tip successfully resolves the chemical structure of pentacene and of other extended planar networks based on C(6) rings, this tip fails to resolve the structures of benzene (with its single C(6) ring) or nonplanar C(6) networks, such as C(60) or small-diameter carbon nanotubes. Defects (such as N substitution for a C-H group) were also found to significantly influence the image resolution. Our findings indicate that further application of this approach requires, for each sample, careful selection of a suitable "imaging" molecule as tip termination.
• First Measurement of Bose-Einstein Correlations in Proton-proton Collisions at √s=0.9 and 2.36 TeV at the LHC Physical Review Letters. Jul, 2010  |   Pubmed ID: 20867758 Bose-Einstein correlations have been measured using samples of proton-proton collisions at 0.9 and 2.36 TeV center-of-mass energies, recorded by the CMS experiment at the CERN Large Hadron Collider. The signal is observed in the form of an enhancement of pairs of same-sign charged particles with small relative four-momentum. The size of the correlated particle emission region is seen to increase significantly with the particle multiplicity of the event.
• Transverse-momentum and Pseudorapidity Distributions of Charged Hadrons in Pp Collisions at Square Root of S = 7 TeV Physical Review Letters. Jul, 2010  |   Pubmed ID: 20867699 Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at square root of s = 7  TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity dN(ch)/dη|(|η|
• Manipulating Localized Molecular Orbitals by Single-atom Contacts Physical Review Letters. Sep, 2010  |   Pubmed ID: 20867664 We have fabricated atom-molecule contacts by attachment of single Cu atoms to terpyridine side groups of bis-terpyridine tetra-phenyl ethylene molecules on a Cu(111) surface. By means of scanning tunneling microscopy, spectroscopy, and density functional calculations, we have found that, due to the localization characteristics of molecular orbitals, the Cu-atom contact modifies the state localized at the terpyridine side group which is in contact with the Cu atom but does not affect the states localized at other parts of the molecule. These results illustrate the contact effects at individual orbitals and offer possibilities to manipulate orbital alignments within molecules.
• The P15 - a Multinational Assessment Battery for Collecting Data on Health Indicators Relevant to Adults with Intellectual Disabilities Journal of Intellectual Disability Research : JIDR. Nov, 2010  |   Pubmed ID: 20825552 Health disparities between adults with intellectual disabilities (ID) and the general population have been well documented but, to date, no dedicated assessment battery for measuring health disparity has been available. This paper reports on the development and testing of a multinational assessment battery for collecting data on a range of health indicators relevant to adults with ID.
• The Genotypic and Phenotypic Spectrum of Pyridoxine-dependent Epilepsy Due to Mutations in ALDH7A1 Journal of Inherited Metabolic Disease. Oct, 2010  |   Pubmed ID: 20814824 Pyridoxine-dependent epilepsy is a disorder associated with severe seizures that may be caused by deficient activity of α-aminoadipic semialdehyde dehydrogenase, encoded by the ALDH7A1 gene, with accumulation of α-aminoadipic semialdehyde and piperideine-6-carboxylic acid. The latter reacts with pyridoxal-phosphate, explaining the effective treatment with pyridoxine. We report the clinical phenotype of three patients, their mutations and those of 12 additional patients identified in our clinical molecular laboratory. There were six missense, one nonsense, and five splice-site mutations, and two small deletions. Mutations c.1217_1218delAT, I431F, IVS-1(+2)T > G, IVS-2(+1)G > A, and IVS-12(+1)G > A are novel. Some disease alleles were recurring: E399Q (eight times), G477R (six times), R82X (two times), and c.1217_1218delAT (two times). A systematic review of mutations from the literature indicates that missense mutations cluster around exons 14, 15, and 16. Nine mutations represent 61% of alleles. Molecular modeling of missense mutations allows classification into three groups: those that affect NAD+ binding or catalysis, those that affect the substrate binding site, and those that affect multimerization. There are three clinical phenotypes: patients with complete seizure control with pyridoxine and normal developmental outcome (group 1) including our first patient; patients with complete seizure control with pyridoxine but with developmental delay (group 2), including our other two patients; and patients with persistent seizures despite pyridoxine treatment and with developmental delay (group 3). There is preliminary evidence for a genotype-phenotype correlation with patients from group 1 having mutations with residual activity. There is evidence from patients with similar genotypes for nongenetic factors contributing to the phenotypic spectrum.
• Electron Stimulation of Internal Torsion of a Surface-mounted Molecular Rotor ACS Nano. Aug, 2010  |   Pubmed ID: 20731465 A molecular rotor which includes a central rotator group was investigated by scanning tunneling microscopy at 4.9 K as it was grafted on a Cu(111) surface via its two terminal groups. Topographs with submolecular resolution revealed several distinct molecular conformations which we attribute to different angular orientations of the rotator and which are locally stable states according to density functional theory calculations. Time-resolved tunneling current spectra showed that the rotator undergoes a torsional motion around the molecular long axis as stimulated by tunneling electrons in a one-electron process with an excitation energy threshold of 355 meV. Calculations identified an intrinsic axial vibration mode of the rotator group at 370 meV as adsorbed on the surface, which we propose to be the channel for effectively converting the tunneling electron energy into the mechanical energy of the intramolecular torsion.
• Perceived Participation, Experiences from Persons with Spinal Cord Injury in Their Transition Period from Hospital to Home International Journal of Rehabilitation Research. Internationale Zeitschrift Für Rehabilitationsforschung. Revue Internationale De Recherches De Réadaptation. Dec, 2010  |   Pubmed ID: 20679902 It is suggested that participation should be achieved at the end of the rehabilitation process. However, there is a lack of consensus on the definition, the conceptualization and the measurement of participation. This study aims to add to the existing body of knowledge of participation by exploring the 'person perceived participation' in individuals with spinal cord injury (SCI). On the basis of the 'grounded theory' approach, in-depth, semistructured interviews were conducted with 11 SCI patients from a rehabilitation cohort in their transition period from hospital to home, to gain an insider perspective on the concept of participation. Results identified three different categories of participation: social participation, occupational participation and socio occupational participation. The participants conceptualize participation as a set of values, including experiencing free choice to perform activities, performing according to the person's identity, experiencing personal growth, belonging by experiencing trust and security, feeling validated, having a sense of control, experiencing a sense of importance and finding equal identities. In conclusion, from a client perspective, participation is a complex,multidimensional construct and can be considered asa dyad between the individual's social interactions and his specific activities performed. Participation was not experienced by the SCI patients as an objective way of performing activities within a societal context or as frequencies of activities performed, but rather as an internal process of negotiation that seemed to be based on balancing personal and societal values.
• Objective Assessment of Technical Surgical Skills The British Journal of Surgery. Jul, 2010  |   Pubmed ID: 20632260 Surgeons are increasingly being scrutinized for their performance and there is growing interest in objective assessment of technical skills. The purpose of this study was to review all evidence for these methods, in order to provide a guideline for use in clinical practice.
• Efficacy and Safety of Tapentadol Extended Release Compared with Oxycodone Controlled Release for the Management of Moderate to Severe Chronic Pain Related to Osteoarthritis of the Knee: a Randomized, Double-blind, Placebo- and Active-controlled Phase III Study Clinical Drug Investigation. 2010  |   Pubmed ID: 20586515 Tapentadol is a novel, centrally acting analgesic with mu-opioid receptor agonist and norepinephrine reuptake inhibitor activity.
• Efficacy and Safety of Tapentadol Extended Release for the Management of Chronic Low Back Pain: Results of a Prospective, Randomized, Double-blind, Placebo- and Active-controlled Phase III Study Expert Opinion on Pharmacotherapy. Aug, 2010  |   Pubmed ID: 20578811 To evaluate the efficacy and safety of tapentadol extended release (ER) for the management of moderate to severe chronic low back pain.
• Succinyl-CoA Ligase Deficiency: a Mitochondrial Hepatoencephalomyopathy Pediatric Research. Aug, 2010  |   Pubmed ID: 20453710 This patient presented on the first day of life with pronounced lactic acidosis with an elevated lactate/pyruvate ratio. Urine organic acids showed Krebs cycle metabolites and mildly elevated methylmalonate and methylcitrate. The acylcarnitine profile showed elevated propionylcarnitine and succinylcarnitine. Amino acids showed elevated glutamic acid, glutamine, proline, and alanine. From the age 2 of mo on, she had elevated transaminases and intermittent episodes of liver failure. Liver biopsy showed steatosis and a decrease of mitochondrial DNA to 50% of control. She had bilateral sensorineural hearing loss. Over the course of the first 2 y of life, she developed a progressively severe myopathy with pronounced muscle weakness eventually leading to respiratory failure, Leigh disease, and recurrent hepatic failure. The hepatic symptoms and the metabolic parameters temporarily improved on treatment with aspartate, but neither muscle symptoms nor brain lesions improved. Laboratory testing revealed a deficiency of succinyl-CoA ligase enzyme activity and protein in fibroblasts because of a novel homozygous mutation in the SUCLG1 gene: c.40A>T (p.M14L). Functional analysis suggests that this methionine is more likely to function as the translation initiator methionine, explaining the pathogenic nature of the mutation. Succinyl-CoA ligase deficiency due to an SUCLG1 mutation is a new cause for mitochondrial hepatoencephalomyopathy.
• Optimal Electron Doping of a C60 Monolayer on Cu(111) Via Interface Reconstruction Physical Review Letters. Jan, 2010  |   Pubmed ID: 20366662 We demonstrate the charge state of C60 on a Cu(111) surface can be made optimal, i.e., forming C60(3-) as required for superconductivity in bulk alkali-doped C60, purely through interface reconstruction rather than with foreign dopants. We link the origin of the C60(3-) charge state to a reconstructed interface with ordered (4x4) 7-atom vacancy holes in the surface. In contrast, C60 adsorbed on unreconstructed Cu(111) receives a much smaller amount of electrons. Our results illustrate a definitive interface effect that affects the electronic properties of molecule-electrode contact.
• Sampling and Ethical Issues in a Multicenter Study on Health of People with Intellectual Disabilities Journal of Clinical Epidemiology. Oct, 2010  |   Pubmed ID: 20304607 To study health inequalities in persons with intellectual disabilities, representative and unbiased samples are needed. Little is known about sample recruitment in this vulnerable group. This study aimed to determine differences in ethical procedures and sample recruitment in a multicenter research on health of persons with intellectual disabilities. Study questions regarded the practical sampling procedure, how ethical consent was obtained in each country, and which person gave informed consent for each study participant.
• The Association of Mitochondrial Content with Prevalent and Incident Type 2 Diabetes The Journal of Clinical Endocrinology and Metabolism. Apr, 2010  |   Pubmed ID: 20150578 It has been shown that mitochondrial DNA (mtDNA) content is associated with type 2 diabetes (T2D) and related traits. However, empirical data, often based on small samples, did not confirm this observation in all studies. Therefore, the role of mtDNA content in T2D remains elusive.
• A Novel POLG Gene Mutation in 4 Children with Alpers-like Hepatocerebral Syndromes Archives of Neurology. Feb, 2010  |   Pubmed ID: 20142534 To describe a novel POLG missense mutation (c.3218C>T; p.P1073L) that, in association with 2 previously described mutations, caused an Alpers-like hepatocerebral syndrome in 4 children.
• Neonatal Liver Failure: a Genetic and Metabolic Perspective Current Opinion in Pediatrics. Apr, 2010  |   Pubmed ID: 20090522 Liver failure in newborns can present formidable diagnostic challenges. The presentation of neonatal liver failure is variable and the initial assessment is crucial in the determination of potentially treatable causes. We present a case of neonatal hemochromatosis, review genetic and metabolic causes of neonatal liver failure, and outline an updated differential diagnosis of neonatal liver failure. In addition, we propose a comprehensive initial work-up of neonatal liver failure, and review current treatments for neonatal hemochromatosis.
• Transglutaminase 2 Deficiency Decreases Plaque Fibrosis and Increases Plaque Inflammation in Apolipoprotein-E-deficient Mice Journal of Vascular Research. 2010  |   Pubmed ID: 19893320 Transglutaminase 2 (TG2) is important for the deposition and stability of the extracellular matrix via effects on cross-linking of matrix proteins and transforming growth factor beta (TGFbeta) activity. The purpose of this study was to investigate the effect of TG2 deficiency on the composi- tion of atherosclerotic plaques.
• Genetic Association Analysis of LARS2 with Type 2 Diabetes Diabetologia. Jan, 2010  |   Pubmed ID: 19847392 LARS2 has been previously identified as a potential type 2 diabetes susceptibility gene through the low-frequency H324Q (rs71645922) variant (minor allele frequency [MAF] 3.0%). However, this association did not achieve genome-wide levels of significance. The aim of this study was to establish the true contribution of this variant and common variants in LARS2 (MAF > 5%) to type 2 diabetes risk.
• Gene Variants in the Novel Type 2 Diabetes Loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B Affect Different Aspects of Pancreatic Beta-cell Function Diabetes. Jan, 2010  |   Pubmed ID: 19833888 Recently, results from a meta-analysis of genome-wide association studies have yielded a number of novel type 2 diabetes loci. However, conflicting results have been published regarding their effects on insulin secretion and insulin sensitivity. In this study we used hyperglycemic clamps with three different stimuli to test associations between these novel loci and various measures of beta-cell function.
• Combined Risk Allele Score of Eight Type 2 Diabetes Genes is Associated with Reduced First-phase Glucose-stimulated Insulin Secretion During Hyperglycemic Clamps Diabetes. Jan, 2010  |   Pubmed ID: 19808892 At least 20 type 2 diabetes loci have now been identified, and several of these are associated with altered beta-cell function. In this study, we have investigated the combined effects of eight known beta-cell loci on insulin secretion stimulated by three different secretagogues during hyperglycemic clamps.
• Search for a Vectorlike Quark with Charge 2/3 in T+Z Events from Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Dec, 2011  |   Pubmed ID: 22243304 A search for pair-produced heavy vectorlike charge-2/3 quarks, T, in pp collisions at a center-of-mass energy of 7 TeV, is performed with the CMS detector at the LHC. Events consistent with the flavor-changing-neutral-current decay of a T quark to a top quark and a Z boson are selected by requiring two leptons from the Z-boson decay, as well as an additional isolated charged lepton. In a data sample corresponding to an integrated luminosity of 1.14  fb^{-1}, the number of observed events is found to be consistent with the standard model background prediction. Assuming a branching fraction of 100% for the decay T→tZ, a T quark with a mass less than 475  GeV/c^{2} is excluded at the 95% confidence level.
• Search for Supersymmetry at the LHC in Events with Jets and Missing Transverse Energy Physical Review Letters. Nov, 2011  |   Pubmed ID: 22182023 A search for events with jets and missing transverse energy is performed in a data sample of pp collisions collected at sqrt[s]=7  TeV by the CMS experiment at the LHC. The analyzed data sample corresponds to an integrated luminosity of 1.14  fb^{-1}. In this search, a kinematic variable α_{T} is used as the main discriminator between events with genuine and misreconstructed missing transverse energy. No excess of events over the standard model expectation is found. Exclusion limits in the parameter space of the constrained minimal supersymmetric extension of the standard model are set. In this model, squark masses below 1.1 TeV are excluded at 95% C.L. Gluino masses below 1.1 TeV are also ruled out at 95% C.L. for values of the universal scalar mass parameter below 500 GeV.
• Search for New Physics with a Monojet and Missing Transverse Energy in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Nov, 2011  |   Pubmed ID: 22181725 A study of events with missing transverse energy and an energetic jet is performed using pp collision data at a center-of-mass energy of 7 TeV. The data were collected by the CMS detector at the LHC, and correspond to an integrated luminosity of 36  pb^{-1}. An excess of these events over standard model contributions is a signature of new physics such as large extra dimensions and unparticles. The number of observed events is in good agreement with the prediction of the standard model, and significant extension of the current limits on parameters of new physics benchmark models is achieved.
• Search for B(s)(0) → μ+ μ- and B(0) → μ+ μ- Decays in Pp Collisions at Sqrt[s] = 7 TeV Physical Review Letters. Nov, 2011  |   Pubmed ID: 22181597 A search for the rare decays B(s)(0) → μ+ μ- and B(0) → μ+ μ- is performed in pp collisions at sqrt[s] = 7 TeV, with a data sample corresponding to an integrated luminosity of 1.14 fb(-1), collected by the CMS experiment at the LHC. In both cases, the number of events observed after all selection requirements is consistent with expectations from background and standard-model signal predictions. The resulting upper limits on the branching fractions are B(B(s)(0) → μ+ μ-) < 1.9 × 10(-8) and B(B(0) → μ+ μ-)
• Measurement of the Inclusive Jet Cross Section in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Sep, 2011  |   Pubmed ID: 22026843 The inclusive jet cross section is measured in pp collisions with a center-of-mass energy of 7 TeV at the Large Hadron Collider using the CMS experiment. The data sample corresponds to an integrated luminosity of 34  pb^{-1}. The measurement is made for jet transverse momenta in the range 18-1100 GeV and for absolute values of rapidity less than 3. The measured cross section extends to the highest values of jet p_{T} ever observed and, within the experimental and theoretical uncertainties, is generally in agreement with next-to-leading-order perturbative QCD predictions.
• Search for Three-Jet Resonances in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Sep, 2011  |   Pubmed ID: 21981492 A search for three-jet hadronic resonance production in pp collisions at a center-of-mass energy of 7 TeV has been conducted by the CMS Collaboration at the LHC, using a data sample corresponding to an integrated luminosity of 35  pb^{-1}. Events with high jet multiplicity and a large scalar sum of jet transverse momenta are analyzed using a signature-based approach. The number of expected standard model background events is found to be in good agreement with the observed events. Limits on the cross section times branching ratio are set in a model of gluino pair production with an R-parity-violating decay to three quarks, and the data rule out such particles within the mass range of 200 to 280  GeV/c^{2}.
• An Alternative Paper Based Tissue Washing Method for Mass Spectrometry Imaging: Localized Washing and Fragile Tissue Analysis Journal of the American Society for Mass Spectrometry. Oct, 2011  |   Pubmed ID: 21952901 Surface treatment of biological tissue sections improves detection of peptides and proteins for mass spectrometry imaging. However, liquid surface treatments can result in diffusion of surface analytes and fragile tissue sections can be easily damaged by typical washing solvents. Here, we present a new surface washing procedure for mass spectrometry imaging. This procedure uses solvent wetted fiber-free paper to enable local washing of tissue sections for mass spectrometry imaging and tissue profiling experiments. In addition, the method allows fragile tissues that cannot be treated by conventional washing techniques to be analyzed by mass spectrometry imaging.
• Lectin Activity of the Nucleocytoplasmic EUL Protein from Arabidopsis Thaliana Biochemical and Biophysical Research Communications. Oct, 2011  |   Pubmed ID: 21945438 The Euonymus lectin (EUL) domain was recognized as the structural motif for a novel class of putative carbohydrate binding proteins. Confocal microscopy demonstrated that the lectin from Euonymus europaeus (EEA) as well as the EUL protein from Arabidopsis thaliana (ArathEULS3) are located in the nucleocytoplasmic compartment of the plant cell. ArathEULS3 as well as its EUL domain were successfully expressed in Pichia pastoris and purified. The EUL domain from Arabidopsis interacts with glycan structures containing Lewis Y, Lewis X and lactosamine, indicating that it can be considered a true lectin domain. Despite the high sequence identity between the EUL domains in EEA and ArathEULS3, both domains recognize different carbohydrate structures.
• Deaf Parents and Pediatric Cochlear Implantation: an Exploration of the Decision-making Process American Annals of the Deaf. 2011  |   Pubmed ID: 21941879 The study examined factors in deaf parents' decision between cochlear implantation (CI) and traditional hearing aids for their child. The subjects were 6 Flemish children ages 5-9 years with severe/profound congenital hearing loss, with at least 1 deaf parent. The researchers, who conducted thematic content analysis of qualitative data collected through parent interviews, found that with the exception of a family with 1 hearing parent, parents gave priority to Deaf identity, sign language, and ethical issues in deciding between CI and hearing aids. Medical risks were also mentioned. The researchers conclude that the decision-making processes of the parents involved factors that have also been found among hearing parents, as well as aspects that have not been reported to play a role in hearing parents' decision making. A further conclusion is that deaf parents' perspective merits attention in professional practice and empirical research.
• Measurement of the T-channel Single Top Quark Production Cross Section in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Aug, 2011  |   Pubmed ID: 21929225 Electroweak production of the top quark is measured for the first time in pp collisions at sqrt[s]=7  TeV, using a data set collected with the CMS detector at the LHC and corresponding to an integrated luminosity of 36  pb⁻¹. With an event selection optimized for t-channel production, two complementary analyses are performed. The first one exploits the special angular properties of the signal, together with background estimates from the data. The second approach uses a multivariate analysis technique to probe the compatibility with signal topology expected from electroweak top-quark production. The combined measurement of the cross section is 83.6±29.8(stat+syst)±3.3(lumi)  pb, consistent with the standard model expectation.
• Indications of Suppression of Excited Î¥ States in Pb-Pb Collisions at √(s(NN))=2.76 TeV Physical Review Letters. Jul, 2011  |   Pubmed ID: 21867063 A comparison of the relative yields of Î¥ resonances in the μ(+)μ(-) decay channel in Pb-Pb and pp collisions at a center-of-mass energy per nucleon pair of 2.76 TeV is performed with data collected with the CMS detector at the LHC. Using muons of transverse momentum above 4  GeV/c and pseudorapidity below 2.4, the double ratio of the Î¥(2S) and Î¥(3S) excited states to the Î¥(1S) ground state in Pb-Pb and pp collisions, [Î¥(2S+3S)/Î¥(1S)](Pb-Pb)/[Î¥(2S+3S)/Î¥(1S)](pp), is found to be 0.31(-0.15)(+0.19)(stat)±0.03(syst). The probability to obtain the measured value, or lower, if the true double ratio is unity, is calculated to be less than 1%.
• Metabolic and Monogenic Causes of Seizures in Neonates and Young Infants Molecular Genetics and Metabolism. Nov, 2011  |   Pubmed ID: 21839663 Seizures in neonates or young infants present a frequent diagnostic challenge. After exclusion of acquired causes, disturbances of the internal homeostasis and brain malformations, the physician must evaluate for inborn errors of metabolism and for other non-malformative genetic disorders as the cause of seizures. The metabolic causes can be categorized into disorders of neurotransmitter metabolism, disorders of energy production, and synthetic or catabolic disorders associated with brain malformation, dysfunction and degeneration. Other genetic conditions involve channelopathies, and disorders resulting in abnormal growth, differentiation and formation of neuronal populations. These conditions are important given their potential for treatment and the risk for recurrence in the family. In this paper, we will succinctly review the metabolic and genetic non-malformative causes of seizures in neonates and infants less than 6 months of age. We will then provide differential diagnostic clues and a practical paradigm for their evaluation.
• Progression of the Prothrombotic State in Aging Bmal1-deficient Mice Arteriosclerosis, Thrombosis, and Vascular Biology. Nov, 2011  |   Pubmed ID: 21799179 The goal of this study was to examine the functional relationship between aging endothelium and thrombogenicity in a mouse model of premature aging.
• Measurement of the Polarization of W Bosons with Large Transverse Momenta in W + Jets Events at the LHC Physical Review Letters. Jul, 2011  |   Pubmed ID: 21797595 A first measurement of the polarization of W bosons with large transverse momenta in pp collisions is presented. The measurement is based on 36 pb⁻¹ of data recorded at √s = 7 TeV by the CMS detector at the LHC. The left-handed, right-handed, and longitudinal polarization fractions (f(L), f(R), and fâ‚€, respectively) of W bosons with transverse momenta larger than 50 GeV are determined by using decays to both electrons and muons. The muon final state yields the most precise measurement: (f(L) - f(R))⁻ = 0.240 ± 0.036(stat) ± 0.031(syst) and f₀⁻ = 0.183 ± 0.087(stat) ± 0.123(syst) for negatively charged W bosons and (f(L) - f(R))⁺ = 0.310 ± 0.036(stat) ± 0.017(syst) and f₀⁺ = 0.171 ± 0.085(stat) ± 0.099(syst) for positively charged W bosons. This establishes, for the first time, that W bosons produced in pp collisions with large transverse momenta are predominantly left-handed, as expected in the standard model.
• An "intermediate Curriculum" for Advanced Laparoscopic Skills Training with Virtual Reality Simulation Journal of Minimally Invasive Gynecology. Sep-Oct, 2011  |   Pubmed ID: 21783431 To estimate face and construct validity for a novel curriculum designed for intermediately skilled laparoscopic surgeons on a virtual reality simulator. It consists of 5 exercises that focus on training precision and coordination between both hands.
• Measurement of the B0 Production Cross Section in Pp Collisions at Sqrt[s] = 7 TeV Physical Review Letters. Jun, 2011  |   Pubmed ID: 21770632 Measurements of the differential production cross sections dσ/dpTB and dσ/dyB for B0 mesons produced in pp collisions at sqrt[s] = 7 TeV are presented. The data set used was collected by the CMS experiment at the LHC and corresponds to an integrated luminosity of 40 pb-1. The production cross section is measured from B0 meson decays reconstructed in the exclusive final state J/ψKS0, with the subsequent decays J/ψ → μ + μ - and KS0 → Ï€+}Ï€-. The total cross section for pTB>5 GeV and |yB|
• Search for Neutral Minimal Supersymmetric Standard Model Higgs Bosons Decaying to Tau Pairs in Pp Collisions at √s=7 TeV Physical Review Letters. Jun, 2011  |   Pubmed ID: 21770497 A search for neutral minimal supersymmetric standard model (MSSM) Higgs bosons in pp collisions at the LHC at a center-of-mass energy of 7 TeV is presented. The results are based on a data sample corresponding to an integrated luminosity of 36  pb(-1) recorded by the CMS experiment. The search uses decays of the Higgs bosons to tau pairs. No excess is observed in the tau-pair invariant-mass spectrum. The resulting upper limits on the Higgs boson production cross section times branching fraction to tau pairs, as a function of the pseudoscalar Higgs boson mass, yield stringent new bounds in the MSSM parameter space.
• Single-molecule Resolution of an Organometallic Intermediate in a Surface-supported Ullmann Coupling Reaction Journal of the American Chemical Society. Aug, 2011  |   Pubmed ID: 21761920 We have studied the organometallic intermediate of a surface-supported Ullmann coupling reaction from 4, 4″-dibromo-p-terphenyl to poly(para-phenylene) by scanning tunneling microscopy/spectroscopy and density functional theory calculations. Our study reveals at a single-molecular level that the intermediate consists of biradical terphenyl (ph)(3) units that are connected by single Cu atoms through C-Cu-C bridges. Upon further increasing the temperature, the neighboring biradical (ph)(3) units are coupled by C-C bonds forming poly(para-phenylene) oligomers while the Cu atoms are released.
• The Impact of Living Arrangements and Deinstitutionalisation in the Health Status of Persons with Intellectual Disability in Europe Journal of Intellectual Disability Research : JIDR. Sep, 2011  |   Pubmed ID: 21726319 Despite progress in the process of deinstitutionalisation, very little is known about the health conditions of people with intellectual disability (PWID) who live in large institutions and PWID living in small residential services, family homes or independent living within the community. Furthermore, there are no international comparison studies at European level of the health status and health risk factors of PWID living in fully staffed residential services with formal support and care compared with those living in unstaffed family homes or independent houses with no formal support.
• Pyridoxine Dependent Epilepsy and Antiquitin Deficiency: Clinical and Molecular Characteristics and Recommendations for Diagnosis, Treatment and Follow-up Molecular Genetics and Metabolism. Sep-Oct, 2011  |   Pubmed ID: 21704546 Antiquitin (ATQ) deficiency is the main cause of pyridoxine dependent epilepsy characterized by early onset epileptic encephalopathy responsive to large dosages of pyridoxine. Despite seizure control most patients have intellectual disability. Folinic acid responsive seizures (FARS) are genetically identical to ATQ deficiency. ATQ functions as an aldehyde dehydrogenase (ALDH7A1) in the lysine degradation pathway. Its deficiency results in accumulation of α-aminoadipic semialdehyde (AASA), piperideine-6-carboxylate (P6C) and pipecolic acid, which serve as diagnostic markers in urine, plasma, and CSF. To interrupt seizures a dose of 100 mg of pyridoxine-HCl is given intravenously, or orally/enterally with 30 mg/kg/day. First administration may result in respiratory arrest in responders, and thus treatment should be performed with support of respiratory management. To make sure that late and masked response is not missed, treatment with oral/enteral pyridoxine should be continued until ATQ deficiency is excluded by negative biochemical or genetic testing. Long-term treatment dosages vary between 15 and 30 mg/kg/day in infants or up to 200 mg/day in neonates, and 500 mg/day in adults. Oral or enteral pyridoxal phosphate (PLP), up to 30 mg/kg/day can be given alternatively. Prenatal treatment with maternal pyridoxine supplementation possibly improves outcome. PDE is an organic aciduria caused by a deficiency in the catabolic breakdown of lysine. A lysine restricted diet might address the potential toxicity of accumulating αAASA, P6C and pipecolic acid. A multicenter study on long term outcomes is needed to document potential benefits of this additional treatment. The differential diagnosis of pyridoxine or PLP responsive seizure disorders includes PLP-responsive epileptic encephalopathy due to PNPO deficiency, neonatal/infantile hypophosphatasia (TNSALP deficiency), familial hyperphosphatasia (PIGV deficiency), as well as yet unidentified conditions and nutritional vitamin B6 deficiency. Commencing treatment with PLP will not delay treatment in patients with pyridox(am)ine phosphate oxidase (PNPO) deficiency who are responsive to PLP only.
• Study of Z Boson Production in PbPb Collisions at √S(NN)=2.76 TeV Physical Review Letters. May, 2011  |   Pubmed ID: 21699291 A search for Z bosons in the μ(+)μ(-) decay channel has been performed in PbPb collisions at √S(NN)=2.76  TeV with the CMS detector at the LHC, in a 7.2 μb(-1) data sample. The number of opposite-sign muon pairs observed in the 60-120 GeV/c(2) invariant mass range is 39, corresponding to a yield per unit of rapidity (y) and per minimum bias event of [33.8±5.5(stat)±4.4(syst)]×10(-8), in the |y|
• Search for Supersymmetry in Pp Collisions at √7 TeV in Events with Two Photons and Missing Transverse Energy Physical Review Letters. May, 2011  |   Pubmed ID: 21699288 A search for supersymmetry in the context of general gauge-mediated breaking with the lightest neutralino as the next-to-lightest supersymmetric particle and the gravitino as the lightest is presented. The data sample corresponds to an integrated luminosity of 36 pb(-1) recorded by the CMS experiment at the LHC. The search is performed by using events containing two or more isolated photons, at least one hadronic jet, and significant missing transverse energy. No excess of events at high missing transverse energy is observed. Upper limits on the signal cross section for general gauge-mediated supersymmetry between 0.3 and 1.1 pb at the 95% confidence level are determined for a range of squark, gluino, and neutralino masses, excluding supersymmetry parameter space that was inaccessible to previous experiments.
• Family Quality of Life in 25 Belgian Families: Quantitative and Qualitative Exploration of Social and Professional Support Domains Journal of Intellectual Disability Research : JIDR. Dec, 2011  |   Pubmed ID: 21668801 This article reports on the results of a study conducted in Belgium on family quality of life situated within a larger project focusing on the development of support strategies for young and adolescent siblings of persons with intellectual disabilities. The objectives of this article are twofold: (1) to present the results of the measures contained in the nine domains of the Family Quality of Life Survey-2006 (FQOLS-2006) from the perspective of parents (quantitative analysis); and (2) to come to a more in-depth understanding of two important domains of the FQOLS-2006 by exploring and comparing the quantitative and qualitative data from open-ended interviews with parents.
• Measurement of Dijet Angular Distributions and Search for Quark Compositeness in Pp Collisions at √s = 7 TeV Physical Review Letters. May, 2011  |   Pubmed ID: 21668222 Dijet angular distributions are measured over a wide range of dijet invariant masses in pp collisions at √s = 7 TeV, at the CERN LHC. The event sample, recorded with the CMS detector, corresponds to an integrated luminosity of 36 pb⁻¹. The data are found to be in good agreement with the predictions of perturbative QCD, and yield no evidence of quark compositeness. With a modified frequentist approach, a lower limit on the contact interaction scale for left-handed quarks of Λ⁺ = 5.6 TeV (Λ⁻ = 6.7 TeV) for destructive (constructive) interference is obtained at the 95% confidence level.
• Search for Pair Production of Second-generation Scalar Leptoquarks in Pp Collisions at √s = 7 TeV Physical Review Letters. May, 2011  |   Pubmed ID: 21668221 A search for pair production of second-generation scalar leptoquarks in the final state with two muons and two jets is performed using proton-proton collision data at √s = 7 TeV collected by the CMS detector at the LHC. The data sample used corresponds to an integrated luminosity of 34 pb⁻¹. The number of observed events is in good agreement with the predictions from the standard model processes. An upper limit is set on the second-generation leptoquark cross section times β² as a function of the leptoquark mass, and leptoquarks with masses below 394 GeV are excluded at a 95% confidence level for β = 1, where β is the leptoquark branching fraction into a muon and a quark. These limits are the most stringent to date.
• Search for Pair Production of First-generation Scalar Leptoquarks in Pp Collisions at √s = 7 TeV Physical Review Letters. May, 2011  |   Pubmed ID: 21668220 A search for pair production of first-generation scalar leptoquarks is performed in the final state containing two electrons and two jets using proton-proton collision data at √s = 7 TeV. The data sample used corresponds to an integrated luminosity of 33 pb⁻¹ collected with the CMS detector at the CERN LHC. The number of observed events is in good agreement with the predictions for the standard model background processes, and an upper limit is set on the leptoquark pair production cross section times β² as a function of the leptoquark mass, where β is the branching fraction of the leptoquark decay to an electron and a quark. A 95% confidence level lower limit is set on the mass of a first-generation scalar leptoquark at 384 GeV for β = 1, which is the most stringent direct limit to date.
• Constitutive Induction of Pro-inflammatory and Chemotactic Cytokines in Cystathionine Beta-synthase Deficient Homocystinuria Molecular Genetics and Metabolism. Aug, 2011  |   Pubmed ID: 21601502 Cystathionine beta-synthase (CBS) deficient homocystinuria (HCU) is an inherited metabolic defect that if untreated, typically results in cognitive impairment, connective tissue disturbances, atherosclerosis and thromboembolic disease. In recent years, chronic inappropriate expression of the inflammatory response has emerged as a major driving force of both thrombosis and atherosclerotic lesion development. We report here a characterization of the abnormalities in cytokine expression induced in both a mouse model of HCU and human subjects with the disease in the presence and absence of homocysteine lowering therapy. HCU mice exhibited highly significant induction of the pro-inflammatory cytokines Il-1alpha, Il-1beta and TNF-alpha. Similarly, in untreated/poorly compliant human subjects with HCU we observed constitutive induction of multiple pro-inflammatory cytokines (IL-1alpha, IL-6, TNF-alpha, Il-17 and IL-12(p70)) and chemotactic chemokines (fractalkine, MIP-1alpha and MIP-1beta) compared to normal controls. These HCU patients also exhibited significant induction of IL-9, TGF-alpha and G-CSF. The expression levels of anti-inflammatory cytokines were unaffected in both HCU mice and human subjects with the disease. In the human subjects, homocysteine lowering therapy was associated with either normalization or significant reduction of all of the pro-inflammatory cytokines and chemokines investigated. We conclude that HCU is a disease of chronic inflammation and that aberrant cytokine expression has the potential to contribute to multiple aspects of pathogenesis. Our findings indicate that anti-inflammatory strategies could serve as a useful adjuvant therapy for this disease.
• Dijet Azimuthal Decorrelations in Pp Collisions at √s=7 TeV Physical Review Letters. Mar, 2011  |   Pubmed ID: 21517306 Measurements of dijet azimuthal decorrelations in pp collisions at √s=7 TeV using the CMS detector at the CERN LHC are presented. The analysis is based on an inclusive dijet event sample corresponding to an integrated luminosity of 2.9 pb⁻¹. The results are compared to predictions from perturbative QCD calculations and various Monte Carlo event generators. The dijet azimuthal distributions are found to be sensitive to initial-state gluon radiation.
• The Impact of HF-rTMS Treatment on Serotonin(2A) Receptors in Unipolar Melancholic Depression Brain Stimulation. Apr, 2011  |   Pubmed ID: 21511211 Currently, the underlying neurobiological mechanism as to how repetitive transcranial magnetic stimulation (rTMS) can alter depressive states remains unclear. Animal data suggest that its influence could occur at the neurotransmitter level, such as modulation of the serotonin system.
• Measurement of the B(+) Production Cross Section in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Mar, 2011  |   Pubmed ID: 21469857 Measurements of the total and differential cross sections dσ/dp(T)(B) and dσ/dy(B) for B(+) mesons produced in pp collisions at sqrt[s]=7  TeV are presented. The data correspond to an integrated luminosity of 5.8  pb(-1) collected by the CMS experiment operating at the LHC. The exclusive decay B(+)→J/ψK(+), with J/ψ→μ(+)μ(-), is used to detect B(+) mesons and to measure the production cross section as a function of p(T)(B) and y(B). The total cross section for p(T)(B)>5  GeV and |y(B)|
• Measurement of the Isolated Prompt Photon Production Cross Section in Pp Collisions at √s=7  TeV Physical Review Letters. Feb, 2011  |   Pubmed ID: 21405566 The differential cross section for the inclusive production of isolated prompt photons has been measured as a function of the photon transverse energy E(T)(γ) in pp collisions at √s=7  TeV using data recorded by the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 2.9  pb(-1). Photons are required to have a pseudorapidity |η(γ)|21  GeV, covering the kinematic region 0.006
• Changes in Yearly Birth Prevalence Rates of Children with Down Syndrome in the Period 1986-2007 in The Netherlands Journal of Intellectual Disability Research : JIDR. May, 2011  |   Pubmed ID: 21375641 The Netherlands are lacking reliable national empirical data in relation to the development of birth prevalence of Down syndrome. Our study aims at assessing valid national live birth prevalence rates for the period 1986-2007.
• Congenitally Deaf Children's Care Trajectories in the Context of Universal Neonatal Hearing Screening: a Qualitative Study of the Parental Experiences Journal of Deaf Studies and Deaf Education. 2011  |   Pubmed ID: 21367846 The objective of this study is to examine the early care trajectories of congenitally deaf children from a parental perspective, starting with universal neonatal hearing screenings. The analysis using a three-dimensional care trajectory concept is aimed at developing a basic typology of postscreening care trajectories. Children with severe/profound hearing loss, registered in the Flanders' (Belgium) universal neonatal hearing screening program, born between 1999 and 2001. Thematic content analysis of qualitative data collected retrospectively from participant's parents. Two basic types of care trajectories emerged; based on differences in care-use in the phase of further diagnosis and related parental experiences. Subtypes resulted from events related to cochlear implantation. Five trajectory phases were identified: screening, further diagnosis, care and technology, cochlear implantation, and reduction of care and were characterized by specific parental experiences such as confusion, disbelief, disappointment, and uncertainty. Those experiences relate to care professionals' acts and communication and the child's functional evolution. Early care interventions could benefit from coordinated transition between phases, parent support throughout the care trajectory, and a broad approach to deafness in professionals' communication.
• Ageing and Health Status in Adults with Intellectual Disabilities: Results of the European POMONA II Study Journal of Intellectual & Developmental Disability. Mar, 2011  |   Pubmed ID: 21314593 POMONA II was a European Commission public health-funded project. The research questions in this article focus on age-specific differences relating to environmental and lifestyle factors, and the 17 medical conditions measured by the POMONA Checklist of Health Indicators (P15).
• Ageing and Health Status in Adults with Intellectual Disabilities: Results of the European POMONA II Study Journal of Intellectual & Developmental Disability. Jan, 2011  |   Pubmed ID: 21280980 Background POMONA II was a European Commission public health-funded project. The research questions in this article focus on age-specific differences relating to environmental and lifestyle factors, and the 17 medical conditions measured by the POMONA Checklist of Health Indicators (P15). Method The P15 was completed in a cross-sectional design for a stratified sample of 1,253 adults with ID across 14 European member states. Results Older people (55+) were more likely to live in larger residential homes. Rates of smoking and use of alcohol were lower than in the general population but were higher with older age. More than 60% of older adults had a sedentary lifestyle. Cataract, hearing disorder, diabetes, hypertension, osteoarthritis/arthrosis, and osteoporosis were positively associated with advancing age; allergies and epilepsy, negatively associated. Conclusions Some evidence of health disparities was found for older people with ID, particularly in terms of underdiagnosed or inadequately managed preventable health conditions.
• Search for Stopped Gluinos in Pp Collisions at Square Root S=7 TeV Physical Review Letters. Jan, 2011  |   Pubmed ID: 21231732 The results of the first search for long-lived gluinos produced in 7 TeV pp collisions at the CERN Large Hadron Collider are presented. The search looks for evidence of long-lived particles that stop in the CMS detector and decay in the quiescent periods between beam crossings. In a dataset with a peak instantaneous luminosity of 1×10(32) cm-2 s-1, an integrated luminosity of 10 pb-1, and a search interval corresponding to 62 hours of LHC operation, no significant excess above background was observed. Limits at the 95% confidence level on gluino pair production over 13 orders of magnitude of gluino lifetime are set. For a mass difference mg - mχ1(0) >100 GeV/c2, and assuming BR(g→gχ1(0))=100%, mg < 370 GeV/c2 are excluded for lifetimes from 10 μs to 1000 s.
• Gibberella Musae (Fusarium Musae) Sp. Nov., a Recently Discovered Species from Banana is Sister to F. Verticillioides Mycologia. May-Jun, 2011  |   Pubmed ID: 21177490 Several strains of Fusarium isolated from banana were identified previously as F. verticillioides (Sacc.) Nirenberg but described as unable to produce fumonisin. Here we report biochemical and morphological evidence, as well as multilocus phylogenetic analyses based on elongation factor (EF-1α), calmodulin, β-tubulin, and the second largest subunit of RNA polymerase II (RPB2) sequences, indicating that these isolates represent a unique lineage in the Gibberella fujikuroi species complex related to but distinct from F. verticillioides. Together with previous results of molecular studies, as well as with results of metabolite analyses, crossing experiments, pathogenicity tests and morphological characterization, these new data indicate that these strains isolated from banana represent a new species, Gibberella musae Van Hove et al. sp. nov. (anamorph: Fusarium musae Van Hove et al. sp. nov.), which is described herein.
• Inhibition of Inositol Monophosphatase by Lithium Chloride Induces Selective Macrophage Apoptosis in Atherosclerotic Plaques British Journal of Pharmacology. Mar, 2011  |   Pubmed ID: 21138421 Lithium chloride (LiCl) inhibits inositol monophosphatase (IMPase) at therapeutic concentrations. Given that LiCl induces death in cultured macrophages and that macrophages play an active role in atherosclerotic plaque destabilization, we investigated whether LiCl would induce selective macrophage death to stabilize the structure of the plaque.
• Fatty Liver is Associated with Reduced SIRT3 Activity and Mitochondrial Protein Hyperacetylation The Biochemical Journal. Feb, 2011  |   Pubmed ID: 21044047 Acetylation has recently emerged as an important mechanism for controlling a broad array of proteins mediating cellular adaptation to metabolic fuels. Acetylation is governed, in part, by SIRTs (sirtuins), class III NAD(+)-dependent deacetylases that regulate lipid and glucose metabolism in liver during fasting and aging. However, the role of acetylation or SIRTs in pathogenic hepatic fuel metabolism under nutrient excess is unknown. In the present study, we isolated acetylated proteins from total liver proteome and observed 193 preferentially acetylated proteins in mice fed on an HFD (high-fat diet) compared with controls, including 11 proteins not previously identified in acetylation studies. Exposure to the HFD led to hyperacetylation of proteins involved in gluconeogenesis, mitochondrial oxidative metabolism, methionine metabolism, liver injury and the ER (endoplasmic reticulum) stress response. Livers of mice fed on the HFD had reduced SIRT3 activity, a 3-fold decrease in hepatic NAD(+) levels and increased mitochondrial protein oxidation. In contrast, neither SIRT1 nor histone acetyltransferase activities were altered, implicating SIRT3 as a dominant factor contributing to the observed phenotype. In Sirt3⁻(/)⁻ mice, exposure to the HFD further increased the acetylation status of liver proteins and reduced the activity of respiratory complexes III and IV. This is the first study to identify acetylation patterns in liver proteins of HFD-fed mice. Our results suggest that SIRT3 is an integral regulator of mitochondrial function and its depletion results in hyperacetylation of critical mitochondrial proteins that protect against hepatic lipotoxicity under conditions of nutrient excess.
• Amino Acid Uptake Profiling of Wild Type and Recombinant Streptomyces Lividans TK24 Batch Fermentations Journal of Biotechnology. Apr, 2011  |   Pubmed ID: 20797416 Streptomyces lividans is considered an interesting host for the secretory production of heterologous proteins. To obtain a good secretion yield of heterologous proteins, the availability of suitable nitrogen sources in the medium is required. Often, undefined mixtures of amino acids are used to improve protein yields. However, the understanding of amino acid utilization as well as their contribution to the heterologous protein synthesis is poor. In this paper, amino acid utilization by wild type and recombinant S. lividans TK24 growing on a minimal medium supplemented with casamino acids is profiled by intensive analysis of the exometabolome (metabolic footprint) as a function of time. Dynamics of biomass, substrates, by-products and heterologous protein are characterized, analyzed and compared. As an exemplary protein mouse Tumor Necrosis Factor Alpha (mTNF-α) is considered. Results unveil preferential glutamate and aspartate assimilation, together with glucose and ammonium, but the associated high biomass growth rate is unfavorable for protein production. Excretion of organic acids as well as alanine is observed. Pyruvate and alanine overflow point at an imbalance between carbon and nitrogen catabolism and biosynthetic fluxes. Lactate secretion is probably related to clump formation. Heterologous protein production induces a slowdown in growth, denser clump formation and a shift in metabolism, as reflected in the altered substrate requirements and overflow pattern. Besides glutamate and aspartate, most amino acids are catabolized, however, their exact contribution in heterologous protein production could not be seized from macroscopic quantities. The metabolic footprints presented in this paper provide a first insight into the impact and relevance of amino acids on biomass growth and protein production. Type and availability of substrates together with biomass growth rate and morphology affect the protein secretion efficiency and should be optimally controlled, e.g., by appropriate medium formulation and substrate dosing. Overflow metabolism as well as high biomass growth rates must be avoided because they reduce protein yields. Further investigation of the intracellular metabolic fluxes should be conducted to fully unravel and identify ways to relieve the metabolic burden of plasmid maintenance and heterologous protein production and to prevent overflow.
• Search for Heavy Neutrinos and W_{R} Bosons with Right-Handed Couplings in a Left-Right Symmetric Model in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Dec, 2012  |   Pubmed ID: 23368549 Results are presented from a search for heavy, right-handed muon neutrinos, N_{μ}, and right-handed W_{R} bosons, which arise in the left-right symmetric extensions of the standard model. The analysis is based on a 5.0  fb^{-1} sample of proton-proton collisions at a center-of-mass energy of 7 TeV, collected by the CMS detector at the Large Hadron Collider. No evidence is observed for an excess of events over the standard model expectation. For models with exact left-right symmetry, heavy right-handed neutrinos are excluded at 95% confidence level for a range of neutrino masses below the W_{R} mass, dependent on the value of M_{W_{R}}. The excluded region in the two-dimensional (M_{W_{R}}, M_{N_{μ}}) mass plane extends to M_{W_{R}}=2.5  TeV.
• Study of the Dijet Mass Spectrum in Pp→W+jets Events at Sqrt[s]=7  TeV Physical Review Letters. Dec, 2012  |   Pubmed ID: 23368450 We report an investigation of the invariant mass spectrum of the two jets with highest transverse momentum in pp→W+2-jet and W+3-jet events to look for resonant enhancement. The data sample corresponds to an integrated luminosity of 5.0  fb^{-1} collected with the CMS detector at sqrt[s]=7  TeV. We find no evidence for the anomalous structure reported by the CDF Collaboration, and establish an upper limit of 5.0 pb at 95% confidence level on the production cross section for a generic Gaussian signal with mass near 150 GeV. Additionally, we exclude two theoretical models that predict a CDF-like dijet resonance near 150 GeV.
• Observation of Sequential Î¥ Suppression in PbPb Collisions Physical Review Letters. Nov, 2012  |   Pubmed ID: 23368113 The suppression of the individual Î¥(nS) states in PbPb collisions with respect to their yields in pp data has been measured. The PbPb and pp data sets used in the analysis correspond to integrated luminosities of 150  μb^{-1} and 230  nb^{-1}, respectively, collected in 2011 by the CMS experiment at the LHC, at a center-of-mass energy per nucleon pair of 2.76 TeV. The Î¥(nS) yields are measured from the dimuon invariant mass spectra. The suppression of the Î¥(nS) yields in PbPb relative to the yields in pp, scaled by the number of nucleon-nucleon collisions, R_{AA}, is measured as a function of the collision centrality. Integrated over centrality, the R_{AA} values are 0.56±0.08(stat)±0.07(syst), 0.12±0.04(stat)±0.02(syst), and lower than 0.10 (at 95% confidence level), for the Î¥(1S), Î¥(2S), and Î¥(3S) states, respectively. The results demonstrate the sequential suppression of the Î¥(nS) states in PbPb collisions at LHC energies.
• Rediscovering Recovery: Reconceptualizing Underlying Assumptions of Citizenship and Interrelated Notions of Care and Support TheScientificWorldJournal. 2012  |   Pubmed ID: 23326216 Over the last few decades, research, policy, and practice in the field of mental health care and a complementary variety of social work and social service delivery have internationally concentrated on recovery as a promising concept. In this paper, a conceptual distinction is made between an individual approach and a social approach to recovery, and underlying assumptions of citizenship and interrelated notions and features of care and support are identified. It is argued that the conditionality of the individual approach to recovery refers to a conceptualization of citizenship as normative, based on the existence of a norm that operates in every domain of our society. We argue that these assumptions place a burden of self-governance on citizens with mental health problems and risk producing people with mental health problems as nonrecyclable citizens. The social approach to recovery embraces a different conceptualization of citizenship as relational and inclusive and embodies the myriad ways in which the belonging of people with mental health problems can be constructed in practice. As such, we hope to enable social services and professionals in the field to balance their role in the provision of care and support to service users with mental health problems.
• A Random Rotor Molecule: Vibrational Analysis and Molecular Dynamics Simulations The Journal of Chemical Physics. Dec, 2012  |   Pubmed ID: 23267481 Molecular structures that permit intramolecular rotational motion have the potential to function as molecular rotors. We have employed density functional theory and vibrational frequency analysis to study the characteristic structure and vibrational behavior of the molecule (4('),4(")-(bicyclo[2,2,2]octane-1,4-diyldi-4,1-phenylene)-bis-2,2('):6('),2(")-terpyridine. IR active vibrational modes were found that favor intramolecular rotation. To demonstrate the rotor behavior of the isolated single molecule, ab initio molecular dynamics simulations at various temperatures were carried out. This molecular rotor is expected to be thermally triggered via excitation of specific vibrational modes, which implies randomness in its direction of rotation.
• Aptamer-based Molecular Recognition of Lysergamine, Metergoline and Small Ergot Alkaloids International Journal of Molecular Sciences. 2012  |   Pubmed ID: 23242153 Ergot alkaloids are mycotoxins produced by fungi of the genus Claviceps, which infect cereal crops and grasses. The uptake of ergot alkaloid contaminated cereal products can be lethal to humans and animals. For food safety assessment, analytical techniques are currently used to determine the presence of ergot alkaloids in food and feed samples. However, the number of samples which can be analyzed is limited, due to the cost of the equipment and the need for skilled personnel. In order to compensate for the lack of rapid tests for the detection of ergot alkaloids, the aim of this study was to develop a specific recognition element for ergot alkaloids, which could be further applied to produce a colorimetric reaction in the presence of these toxins. As recognition elements, single-stranded DNA ligands were selected by using an iterative selection procedure named SELEX, i.e., Systematic Evolution of Ligands by EXponential enrichment. After several selection cycles, the resulting aptamers were cloned and sequenced. A surface plasmon resonance analysis enabled determination of the dissociation constants of the complexes of aptamers and lysergamine. Dissociation constants in the nanomolar range were obtained with three selected aptamers. One of the selected aptamers, having a dissociation constant of 44 nM, was linked to gold nanoparticles and it was possible to produce a colorimetric reaction in the presence of lysergamine. This system could also be applied to small ergot alkaloids in an ergot contaminated flour sample.
• Search for New Physics in the Multijet and Missing Transverse Momentum Final State in Proton-Proton Collisions at Sqrt[s]=7  TeV Physical Review Letters. Oct, 2012  |   Pubmed ID: 23215177 A search for physics beyond the standard model is performed in events with at least three jets and large missing transverse momentum produced in proton-proton collisions at a center-of-mass energy of sqrt[s]=7  TeV. No significant excess of events above the expected backgrounds is observed in 4.98  fb^{-1} of data collected with the CMS detector at the Large Hadron Collider. The results are presented in the context of the constrained minimal supersymmetric extension of the standard model and more generically for simplified models. For the simplified models of gluino-gluino and squark-squark production, gluino masses below 1.0 TeV and squark masses below 0.76 TeV are excluded in case the lightest supersymmetric particle mass is below 200 GeV. These results significantly extend previous searches.
• Measurement of the Pseudorapidity and Centrality Dependence of the Transverse Energy Density in Pb-Pb Collisions at Sqrt[s_{NN}]=2.76  TeV Physical Review Letters. Oct, 2012  |   Pubmed ID: 23102301 The transverse energy (E_{T}) in Pb-Pb collisions at 2.76 TeV nucleon-nucleon center-of-mass energy (sqrt[s_{NN}]) has been measured over a broad range of pseudorapidity (η) and collision centrality by using the CMS detector at the LHC. The transverse energy density per unit pseudorapidity (dE_{T}/dη) increases faster with collision energy than the charged particle multiplicity. This implies that the mean energy per particle is increasing with collision energy. At all pseudorapidities, the transverse energy per participating nucleon increases with the centrality of the collision. The ratio of transverse energy per unit pseudorapidity in peripheral to central collisions varies significantly as the pseudorapidity increases from η=0 to |η|=5.0. For the 5% most central collisions, the energy density per unit volume is estimated to be about 14  GeV/fm^{3} at a time of 1  fm/c after the collision. This is about 100 times larger than normal nuclear matter density and a factor of 2.6 times higher than the energy density reported at sqrt[s_{NN}]=200  GeV at the Relativistic Heavy Ion Collider.
• Search for a W^{'} or Techni-ρ Decaying into WZ in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Oct, 2012  |   Pubmed ID: 23083236 A search is performed in pp collisions at sqrt[s]=7  TeV for exotic particles decaying via WZ to final states with electrons and muons. The data sample corresponds to an integrated luminosity of approximately 5  fb^{-1}. No significant excess is observed in the data above the expected standard model background. Upper bounds at 95% confidence level are set on the production cross section of the W^{'} boson described by the sequential standard model and on the W^{'} WZ coupling. W^{'} bosons with masses below 1143 GeV are excluded. Limits are also set in the context of low-scale technicolor models, under a range of assumptions concerning the model parameters.
• Azimuthal Anisotropy of Charged Particles at High Transverse Momenta in Pb-Pb Collisions at Sqrt[s_{NN}]=2.76  TeV Physical Review Letters. Jul, 2012  |   Pubmed ID: 23030154 The azimuthal anisotropy of charged particles in Pb-Pb collisions at sqrt[s_{NN}]=2.76  TeV is measured with the CMS detector at the LHC over an extended transverse momentum (p_{T}) range up to approximately 60  GeV/c. The data cover both the low-p_{T} region associated with hydrodynamic flow phenomena and the high-p_{T} region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v_{2}) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v_{2} values are found to first increase with p_{T}, reaching a maximum around p_{T}=3  GeV/c, and then to gradually decrease to almost zero, with the decline persisting up to at least p_{T}=40  GeV/c over the full centrality range measured.
• Resistance and Resilience in a Life Full of Professionals and Labels: Narrative Snapshots of Chris Intellectual and Developmental Disabilities. Oct, 2012  |   Pubmed ID: 23025644 In this article, the authors relate the life of Chris through narrative snapshots. Chris asked the authors to tell her story. They decided that it could be used to provide an insight into the different ways people with labels are confronted with professional practices and rituals. Although Chris lived a "tough life," her story is full of resilience and resistance. Chris will be kept in the authors' memory as a strong woman, a teacher, and a friend.
• Selective Loss of Basal but Not Receptor-stimulated Relaxation by Endothelial Nitric Oxide Synthase After Isolation of the Mouse Aorta European Journal of Pharmacology. Dec, 2012  |   Pubmed ID: 23022329 Bioavailability of nitric oxide (NO) is mostly studied in isolated blood vessels. We investigated changes in basal and receptor-stimulated endothelial NO synthase (eNOS) activity after isolation of wild-type and Marfan mouse aorta. Starting 1h after dissection, basal NO release was assessed at hourly intervals by its ability to suppress isometric contractions in aortic segments. Relaxation induced by acetylcholine or α(2)-adrenoceptor agonist 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14304) was used to study stimulated NOS activity. One hour after dissection, phenylephrine- or prostaglandin F(2α)-induced force attained only 17 ± 4% or 31 ± 7% of maximum tension in the presence of N(Ω)-nitro-l-arginine-methylesther (l-NAME), and contractions increased to 63 ± 6% and 82 ± 11%, respectively at 5h. In contrast, acetylcholine or UK14304 relaxation curves changed minimally. l-NAME and eNOS-deficiency abolished basal NO production, unlike inhibitors of neuronal (N(Ω)-propyl-l-arginine) or inducible (1400W) NOS. Acetylcholine-induced relaxation was abolished by l-NAME, strongly suppressed by eNOS-deficiency and attenuated by N(Ω)-propyl-l-arginine. In a bioassay based on diethylamine NONOate concentration-response curves the suppression of contractile forces was interpolated into NO equivalents. This showed exponential decay of basal NO, which occurred three times faster in aortas from mice with Marfan syndrome, while acetylcholine-induced relaxation remained unaltered. Immunoblotting showed unchanged eNOS expression, or phosphorylation at Ser1177, Ser617 or Thr495 between 1h and 4h, but Akt phosphorylation declined gradually. The dramatic loss of basal NO release after tissue isolation shows that timing is crucial when studying NO responses. The preservation of receptor-induced relaxation implies differential regulation of basal and stimulated eNOS activity, and phosphoinositide-3-kinase/Akt signalling seems specifically associated with basal eNOS activity.
• Lysine Restricted Diet for Pyridoxine-dependent Epilepsy: First Evidence and Future Trials Molecular Genetics and Metabolism. Nov, 2012  |   Pubmed ID: 23022070 To evaluate the efficacy and safety of dietary lysine restriction as an adjunct to pyridoxine therapy on biochemical parameters, seizure control, and developmental/cognitive outcomes in children with pyridoxine-dependent epilepsy (PDE) caused by antiquitin (ATQ) deficiency.
• Search for New Physics with Same-sign Isolated Dilepton Events with Jets and Missing Transverse Energy Physical Review Letters. Aug, 2012  |   Pubmed ID: 23006358 A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98  fb^{-1} produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.
• Search for a Light Pseudoscalar Higgs Boson in the Dimuon Decay Channel in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Sep, 2012  |   Pubmed ID: 23005937 The dimuon invariant mass spectrum is searched in the range between 5.5 and 14 GeV for a light pseudoscalar Higgs boson a, predicted in a number of new physics models, including the next-to-minimal supersymmetric standard model. The data sample used in the search corresponds to an integrated luminosity of 1.3  fb^{-1} collected in pp collisions at sqrt[s]=7  TeV with the CMS detector at the LHC. No excess is observed above the background predictions and upper limits are set on the cross section times branching fraction σ×B(pp→a→μ^{+}μ^{-}) in the range of 1.5-7.5 pb. These results improve on existing bounds on the abb[over ¯] coupling for m_{a}m_{Î¥(3S)}. Constraints on the supersymmetric parameter space are presented in the context of the next-to-minimal model.
• Measurement of the Electron Charge Asymmetry in Inclusive W Production in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Sep, 2012  |   Pubmed ID: 23005617 A measurement of the electron charge asymmetry in inclusive pp→W+X→eν+X production at sqrt[s]=7  TeV is presented based on data recorded by the CMS detector at the LHC and corresponding to an integrated luminosity of 840  pb^{-1}. The electron charge asymmetry reflects the unequal production of W^{+} and W^{-} bosons in pp collisions. The electron charge asymmetry is measured in bins of the absolute value of electron pseudorapidity in the range of |η|
• Search for Dark Matter and Large Extra Dimensions in Pp Collisions Yielding a Photon and Missing Transverse Energy Physical Review Letters. Jun, 2012  |   Pubmed ID: 23004964 Results are presented from a search for new physics in the final state containing a photon (γ) and missing transverse energy (E̸_{T}). The data correspond to an integrated luminosity of 5.0  fb^{-1} collected in pp collisions at sqrt[s]=7  TeV by the CMS experiment. The observed event yield agrees with standard-model expectations for the γ+E̸_{T} events. Using models for the production of dark-matter particles (χ), we set 90% confidence level (C.L.) upper limits of 13.6-15.4 fb on χ production in the γ+E̸_{T} state. These provide the most sensitive upper limits for spin-dependent χ-nucleon scattering for χ masses (M_{χ}) between 1 and 100 GeV. For spin-independent contributions, the present limits are extended to M_{χ}
• Observation of a New Ξ_{b} Baryon Physical Review Letters. Jun, 2012  |   Pubmed ID: 23004588 The observation of a new b baryon via its strong decay into Ξ_{b}^{-}Ï€^{+} (plus charge conjugates) is reported. The measurement uses a data sample of pp collisions at sqrt[s]=7  TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 5.3  fb^{-1}. The known Ξ_{b}^{-} baryon is reconstructed via the decay chain Ξ_{b}^{-}→J/ψΞ^{-}→μ^{+}μ^{-}Λ^{0}Ï€^{-}, with Λ^{0}→pÏ€^{-}. A peak is observed in the distribution of the difference between the mass of the Ξ_{b}^{-}Ï€^{+} system and the sum of the masses of the Ξ_{b}^{-} and Ï€^{+}, with a significance exceeding 5 standard deviations. The mass difference of the peak is 14.84±0.74(stat)±0.28(syst)  MeV. The new state most likely corresponds to the J^{P}=3/2^{+} companion of the Ξ_{b}.
• First Information Parents Receive After UNHS Detection of Their Baby's Hearing Loss Journal of Deaf Studies and Deaf Education. 2012  |   Pubmed ID: 22960753 The first information parents receive after referral through Universal Newborn Hearing Screening (UNHS) has significant consequences for later care-related decisions they take and thus for the future of the child with a hearing loss. In this study, 11 interviews were conducted with a representative sample of Flemish service providers to discover (a) the content of the information provided to parents and (b) the service providers' assumptions and beliefs concerning deafness and care. To do this, we conducted an interpretative phenomenological analysis, followed by a discourse analysis. Results showed that parents receive diverse information, depending on the reference center to which they are referred. Moreover, all service providers used a medical discourse. We suggest that there is value to be gained from closer consideration of the nature of follow-up services provided in response to UNHS in Flanders and from auditing the professional preparation of service providers that are involved in providing information to parents.
• Contribution of Transient and Sustained Calcium Influx, and Sensitization to Depolarization-induced Contractions of the Intact Mouse Aorta BMC Physiology. 2012  |   Pubmed ID: 22943445 Electrophysiological studies of L-type Ca2+ channels in isolated vascular smooth muscle cells revealed that depolarization of these cells evoked a transient and a time-independent Ca2+ current. The sustained, non-inactivating current occurred at voltages where voltage-dependent activation and inactivation overlapped (voltage window) and its contribution to basal tone or active tension in larger multicellular blood vessel preparations is unknown at present. This study investigated whether window Ca2+ influx affects isometric contraction of multicellular C57Bl6 mouse aortic segments.
• [Use of Checklists for Laparoscopic Equipment in Dutch Hospitals] Nederlands Tijdschrift Voor Geneeskunde. 2012  |   Pubmed ID: 22894804 Descriptive study.
• Matrix Metalloproteinase-3 in the Central Nervous System: a Look on the Bright Side Journal of Neurochemistry. Oct, 2012  |   Pubmed ID: 22862420 Matrix metalloproteinases (MMPs) are a large family of proteases involved in many cell-matrix and cell-cell signalling processes through activation, inactivation or release of extracellular matrix (ECM) and non-ECM molecules, such as growth factors and receptors. Uncontrolled MMP activities underlie the pathophysiology of many disorders. Also matrix metalloproteinase-3 (MMP-3) or stromelysin-1 contributes to several pathologies, such as cancer, asthma and rheumatoid arthritis, and has also been associated with neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and multiple sclerosis. However, based on defined MMP spatiotemporal expression patterns, the identification of novel candidate molecular targets and in vitro and in vivo studies, a beneficial role for MMPs in CNS physiology and recovery is emerging. The main purpose of this review is to shed light on the recently identified roles of MMP-3 in normal brain development and in plasticity and regeneration after CNS injury and disease. As such, MMP-3 is correlated with neuronal migration and neurite outgrowth and guidance in the developing CNS and contributes to synaptic plasticity and learning in the adult CNS. Moreover, a strict spatiotemporal MMP-3 up-regulation in the injured or diseased CNS might support remyelination and neuroprotection, as well as genesis and migration of stem cells in the damaged brain.
• Search for the Standard Model Higgs Boson in the Decay Channel H→ZZ→4â„“ in Pp Collisions at √s=7 TeV Physical Review Letters. Mar, 2012  |   Pubmed ID: 22540464 A search for a Higgs boson in the four-lepton decay channel H→ZZ, with each Z boson decaying to an electron or muon pair, is reported. The search covers Higgs boson mass hypotheses in the range of 110
• Search for Signatures of Extra Dimensions in the Diphoton Mass Spectrum at the Large Hadron Collider Physical Review Letters. Mar, 2012  |   Pubmed ID: 22540461 A search for signatures of extra spatial dimensions in the diphoton invariant-mass spectrum has been performed with the CMS detector at the LHC. No excess of events above the standard model expectation is observed using a data sample collected in proton-proton collisions at √s=7 TeV corresponding to an integrated luminosity of 2.2 fb(-1). In the context of the large-extra-dimensions model, lower limits are set on the effective Planck scale in the range of 2.3-3.8 TeV at the 95% confidence level. These limits are the most restrictive bounds on virtual-graviton exchange to date. The most restrictive lower limits to date are also set on the mass of the first graviton excitation in the Randall-Sundrum model in the range of 0.86-1.84 TeV, for values of the associated coupling parameter between 0.01 and 0.10.
• Energetics and Dynamics of a New Type of Extended Line Defects in Graphene Nanoscale. Apr, 2012  |   Pubmed ID: 22434098 We revealed a novel extended line defect (ELD) containing tetragonal rings embedded in graphene, formed as a growth fault, with its energetic and dynamic behavior studied via first-principles calculations. In our finding based upon the molecular dynamics simulation, transformation between locally stable ELDs in graphene at high temperatures simultaneously with contrastive electronic properties can be applied to predetermine the formation process and reconstruction of ELDs.
• Dynamics of the Subcellular Localization of RalBP1/RLIP Through the Cell Cycle: the Role of Targeting Signals and of Protein-protein Interactions FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. May, 2012  |   Pubmed ID: 22319010 The small G protein Ras regulates many cell processes, such as gene expression, proliferation, apoptosis, and cell differentiation. Its mutations are associated with one-third of all cancers. Ras functions are mediated, at least in part, by Ral proteins and their downstream effector the Ral-binding protein 1 (RalBP1). RalBP1 is involved in endocytosis and in regulating the dynamics of the actin cytoskeleton. It also regulates early development since it is required for the completion of gastrulation in Xenopus laevis. RalBP1 has also been reported to be the main transporter of glutathione electrophiles, and it is involved in multidrug resistance. Such a variety of functions could be explained by a differential regulation of RalBP1 localization. In this study, we have detected endogenous RalBP1 in the nucleus of interphasic cells. This nuclear targeting is mediated by nuclear localization sequences that map to the N-terminal third of the protein. Moreover, in X. laevis embryos, a C-terminal coiled-coil sequence mediates RalBP1 retention in the nucleus. We have also observed RalBP1 at the level of the actin cytoskeleton, a localization that depends on interaction of the protein with active Ral. During mitosis RalBP1 also associates with the mitotic spindle and the centrosome, a localization that could be negatively regulated by active Ral. Finally, we demonstrate the presence of post-transcriptional and post-translational isoforms of RalBP1 lacking the Ral-binding domain, which opens new possibilities for the existence of Ral-independent functions.
• In Situ Monitoring of Atomic Layer Deposition in Nanoporous Thin Films Using Ellipsometric Porosimetry Langmuir : the ACS Journal of Surfaces and Colloids. Feb, 2012  |   Pubmed ID: 22304361 Ellipsometric porosimetry (EP) is a handy technique to characterize the porosity and pore size distribution of porous thin films with pore diameters in the range from below 1 nm up to 50 nm and for the characterization of porous low-k films especially. Atomic layer deposition (ALD) can be used to functionalize porous films and membranes, e.g., for the development of filtration and sensor devices and catalytic surfaces. In this work we report on the implementation of the EP technique onto an ALD reactor. This combination allowed us to employ EP for monitoring the modification of a porous thin film through ALD without removing the sample from the deposition setup. The potential of in situ EP for providing information about the effect of ALD coating on the accessible porosity, the pore radius distribution, the thickness, and mechanical properties of a porous film is demonstrated in the ALD of TiO(2) in a mesoporous silica film.
• Effect of Basic Laparoscopic Skills Courses on Essential Knowledge of Equipment Surgical Innovation. Dec, 2012  |   Pubmed ID: 22298751 This study aims to evaluate the effect of laparoscopic skills courses on the knowledge of laparoscopic equipment.
• An Aberrant Cerebellar Development in Mice Lacking Matrix Metalloproteinase-3 Molecular Neurobiology. Feb, 2012  |   Pubmed ID: 22108898 Cell-cell and cell-matrix interactions are necessary for neuronal patterning and brain wiring during development. Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of remodelling the pericellular environment and regulating signaling pathways through cleavage of a large degradome. MMPs have been suggested to affect cerebellar development, but the specific role of different MMPs in cerebellar morphogenesis remains unclear. Here, we report a role for MMP-3 in the histogenesis of the mouse cerebellar cortex. MMP-3 expression peaks during the second week of postnatal cerebellar development and is most prominently observed in Purkinje cells (PCs). In MMP-3 deficient (MMP-3(-/-)) mice, a protracted granule cell (GC) tangential migration and a delayed GC radial migration results in a thicker and persistent external granular layer, a retarded arrival of GCs in the inner granular layer, and a delayed GABAergic interneuron migration. Importantly, these neuronal migration anomalies, as well as the consequent disturbed synaptogenesis on PCs, seem to be caused by an abnormal PC dendritogenesis, which results in reduced PC dendritic trees in the adult cerebellum. Of note, these developmental and adult cerebellar defects might contribute to the aberrant motor phenotype observed in MMP-3(-/-) mice and suggest an involvement of MMP-3 in mouse cerebellar development.
• Genetic Diversity and Mycotoxin Production of Fusarium Lactis Species Complex Isolates from Sweet Pepper International Journal of Food Microbiology. Feb, 2012  |   Pubmed ID: 22098923 An internal fruit rot disease of sweet peppers was first detected in Belgium in 2003. Research conducted mostly in Canada indicates that this disease is primarily caused by Fusarium lactis Pirotta. Ninety-eight Fusarium isolates obtained from diseased sweet peppers from Belgium, as well as from other countries (Canada, the Netherlands and the United Kingdom) were identified by sequencing the translation elongation factor 1α (EF). Of these 98 isolates, 13 were identified as F. oxysporum Schltdl., nine as F. proliferatum (Matsush.) Nirenberg and two belonged to clade 3 of the F. solani species complex. Of the 74 remaining isolates, the EF sequence showed 97% to 98% similarity to F. lactis. Of these isolates, the β-tubulin (TUB), calmodulin (CAM) and the second largest subunit of RNA polymerase II (RPB2) genes were also sequenced. Analysis of the combined sequences revealed that the 74 isolates share nine combined sequences that correspond to nine multilocus sequence types (STs), while the F. lactis neotype strain and one other strain, both isolated from figs, form a separate ST. Together, these 10 STs represent a monophyletic F. lactis species complex (FLASC). An unusually high level of genetic diversity was observed between (groups of) these STs. Two of them (ST5 and ST6) fulfilled the criteria for species recognition based on genealogical exclusivity and together represent a new monophyletic species lineage (FLASC-1). The seven other STs, together with the F. lactis neotype ST, form a paraphyletic species lineage in the African clade of the Gibberella fujikuroi species complex (GFSC). From each of the 10 STs, the mycotoxin production was assessed using a multi-mycotoxin liquid chromatography mass spectrometry method. Out of the 27 analyzed mycotoxins, beauvericin and fumonisins were detected in sweet pepper tissue and in maize kernels. The 10 STs clearly differed in the amount of mycotoxin produced, but there was only limited congruence between the production profile and the phylogenetic analysis. Furthermore, the morphological characterization (based on mycelial growth rate and the length of macroconidia) showed distinct differences between the 10 STs, but again there was limited congruence with the phylogenetic results. In conclusion, the data presented in this study demonstrate that 75% of the isolates obtained from sweet pepper with internal fruit rot belong to a F. lactis species complex (FLASC), including a new FLASC-1 monophyletic species, and that the members of this complex display great genetic and phenotypic diversity.
• The Influence of Supports Strategies, Environmental Factors, and Client Characteristics on Quality of Life-related Personal Outcomes Research in Developmental Disabilities. Jan-Feb, 2012  |   Pubmed ID: 22093653 The concept of quality of life (QOL) is increasingly being used as a support provision and outcomes evaluation framework in the field of intellectual disability (ID). The present study used a hierarchical multiple regression research design to determine the role that available supports strategies, environmental factors, and client characteristics play in assessed quality of life-related personal outcomes. Data were collected in Arduin Foundation in The Netherlands. Participants were 186 individuals with an intellectual disability. Results indicated that QOL-outcomes were significantly impacted by the availability of support strategies, living arrangement, status of employment and level of ID.
• Prediction of Long-term Outcome in Glycine Encephalopathy: a Clinical Survey Journal of Inherited Metabolic Disease. Mar, 2012  |   Pubmed ID: 22002442 Glycine encephalopathy (GE) is a rare autosomal recessive inborn error of glycine degradation resulting in severe encephalopathy with ensuing poor outcome. Attenuated variants with a significantly better outcome have been reported. Early prediction of long-term outcome is not yet possible.
• Urea Cycle Disorders: Brain MRI and Neurological Outcome Pediatric Radiology. Apr, 2012  |   Pubmed ID: 21989980 Urea cycle disorders encompass several enzyme deficiencies that can result in cerebral damage, with a wide clinical spectrum from asymptomatic to severe.
• The Illusion and the Paradox of Being Autonomous, Experiences from Persons with Spinal Cord Injury in Their Transition Period from Hospital to Home Disability and Rehabilitation. 2012  |   Pubmed ID: 21978173 To open a discourse on the concept of autonomy as a precursor for participation in individuals with Spinal Cord Injury (SCI) by exploring the experiences about their perceived autonomy in their transition period from hospital to home.
• Seminal Vesicle Invasion: What is the Best Adjuvant Treatment After Radical Prostatectomy? BJU International. Feb, 2012  |   Pubmed ID: 21851534 • To evaluate the biochemical-failure free survival according to different adjuvant treatments in patients who underwent radical prostatectomy (RP) with seminal vesicle invasion (SVI).
• Identification of MMP-2 As a Novel Enhancer of Cerebellar Granule Cell Proliferation Molecular and Cellular Neurosciences. Oct, 2013  |   Pubmed ID: 24141049 During the first postnatal days in the mouse, granule cells (GCs) undergo massive proliferation, which then gradually decreases. Matrix metalloproteinase-2 (MMP-2), a Zn(2+)-dependent proteolytic enzyme, is involved in a wide variety of pathological and physiological pathways. Evidence for a role of this proteinase in cell proliferation is emerging, reporting its involvement in pathological proliferation, as well as during neurogenesis and developmental proliferation of non-CNS tissues. In this study, MMP-2 protein expression was observed within the early postnatal cerebellar cortex, predominantly in Purkinje cells and within the GC proliferative zone, i.e. the superficial external granular layer (EGL). Consistently, the spatiotemporal MMP-2 mRNA and protein profiles highly correlated with the peak of GC precursor (GCP) proliferation and detailed morphometric analyses of MMP-2 deficient cerebella revealed a thinner EGL due to a decreased GCP proliferation. BrdU cumulative experiments, performed to measure the length of different cell cycle phases, further disclosed a transiently prolonged S-phase in MMP-2 deficient GCPs during early cerebellar development. In consequence, MMP-2 deficient animals displayed a transient delay in GC migration towards the IGL. In conclusion, our findings provide important evidence for a role for MMP-2 in neuronal proliferation and cell cycle kinetics in the developing CNS.
• A New Mutation in MT-ND1 M.3928G>C P.V208L Causes Leigh Disease with Infantile Spasms Mitochondrion. Sep, 2013  |   Pubmed ID: 24063851 New mutations in mitochondrial DNA encoded genes of complex I are rarely reported. An infant developed Leigh disease with infantile spasms. Complex I enzyme activity was deficient and response to increasing coenzyme Q concentrations was reduced. Complex I assembly was intact. A new mutation in MT-ND1 m.3928G>C p,V208L, affecting a conserved amino acid in a critical domain, part of the coenzyme Q binding pocket, was present at high heteroplasmy. The unaffected mother did not carry measurable mutant mitochondrial DNA, but concern remained for gonadal mosaicism. Prenatal testing was possible for a subsequent sibling. The ND1 p.V208L mutation causes Leigh disease.
• An X-linked Cobalamin Disorder Caused by Mutations in Transcriptional Coregulator HCFC1 American Journal of Human Genetics. Sep, 2013  |   Pubmed ID: 24011988 Derivatives of vitamin B12 (cobalamin) are essential cofactors for enzymes required in intermediary metabolism. Defects in cobalamin metabolism lead to disorders characterized by the accumulation of methylmalonic acid and/or homocysteine in blood and urine. The most common inborn error of cobalamin metabolism, combined methylmalonic acidemia and hyperhomocysteinemia, cblC type, is caused by mutations in MMACHC. However, several individuals with presumed cblC based on cellular and biochemical analysis do not have mutations in MMACHC. We used exome sequencing to identify the genetic basis of an X-linked form of combined methylmalonic acidemia and hyperhomocysteinemia, designated cblX. A missense mutation in a global transcriptional coregulator, HCFC1, was identified in the index case. Additional male subjects were ascertained through two international diagnostic laboratories, and 13/17 had one of five distinct missense mutations affecting three highly conserved amino acids within the HCFC1 kelch domain. A common phenotype of severe neurological symptoms including intractable epilepsy and profound neurocognitive impairment, along with variable biochemical manifestations, was observed in all affected subjects compared to individuals with early-onset cblC. The severe reduction in MMACHC mRNA and protein within subject fibroblast lines suggested a role for HCFC1 in transcriptional regulation of MMACHC, which was further supported by the identification of consensus HCFC1 binding sites in MMACHC. Furthermore, siRNA-mediated knockdown of HCFC1 expression resulted in the coordinate downregulation of MMACHC mRNA. This X-linked disorder demonstrates a distinct disease mechanism by which transcriptional dysregulation leads to an inborn error of metabolism with a complex clinical phenotype.
• Inclusive Search for Supersymmetry Using Razor Variables in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Aug, 2013  |   Pubmed ID: 24010428 An inclusive search is presented for new heavy particle pairs produced in sqrt[s]=7  TeV proton-proton collisions at the LHC using 4.7±0.1  fb^{-1} of integrated luminosity. The selected events are analyzed in the 2D razor space of M_{R}, an event-by-event indicator of the heavy particle mass scale, and R, a dimensionless variable related to the missing transverse energy. The third-generation sector is probed using the event heavy-flavor content. The search is sensitive to generic supersymmetry models with minimal assumptions about the superpartner decay chains. No excess is observed in the number of events beyond that predicted by the standard model. Exclusion limits are derived in the CMSSM framework as well as for simplified models. Within the CMSSM parameter space considered, gluino masses up to 800 GeV and squark masses up to 1.35 TeV are excluded at 95% confidence level depending on the model parameters. The direct production of pairs of top or bottom squarks is excluded for masses as high as 400 GeV.
• Validation of an Interactive Simulation Module to Train the Use of a Laparoscopic Insufflator Surgical Innovation. Aug, 2013  |   Pubmed ID: 23945841 Background. The purpose of this study was to determine construct and face validities of an interactive Web-based module for pneumoperitoneum and insufflator. Methods. Participants were recruited from surgical departments in 2 academic hospitals and 1 large nonacademic teaching hospital. They were stratified into 3 groups based on their laparoscopic experience (A, no experience; B, experience as assistant; and C, experience as primary surgeon). Within each group the participants were randomized into a training subgroup and a control subgroup. All participants performed a theoretical and a practical test. The training participants first completed the module before they performed the tests. The control participants immediately performed the tests. Results were compared between the training and control participants. All training participants filled out a questionnaire on their opinion about the module. Results. In total, 40 participants were enrolled in the study: group A consisted of 20 participants and groups B and C both consisted of 10 participants. The trained participants answered significantly more theoretical questions correctly (8.3 vs 6.6; P < .001), correctly identified more alarm causes (91% vs 86%; P = .014) and made significantly less errors in the practical test (1.5 vs 3.6; P = .001). All 20 trained participants rated the module fairly good and indicated the module to be of additive value to surgical training programs. Conclusions. Training with the interactive web-based module on installation of a pneumoperitoneum and use of an insufflator has a positive effect on both theoretical and practical competence. Construct and face validities were established for this module.
• Birth, Death and Horizontal Transfer of the Fumonisin Biosynthetic Gene Cluster During the Evolutionary Diversification of Fusarium Molecular Microbiology. Oct, 2013  |   Pubmed ID: 23937442 Fumonisins are a family of carcinogenic secondary metabolites produced by members of the Fusarium fujikuroi species complex (FFSC) and rare strains of Fusarium oxysporum. In Fusarium, fumonisin biosynthetic genes (FUM) are clustered, and the cluster is uniform in gene organization. Here, sequence analyses indicated that the cluster exists in five different genomic contexts, defining five cluster types. In FUM gene genealogies, evolutionary relationships between fusaria with different cluster types were largely incongruent with species relationships inferred from primary-metabolism (PM) gene genealogies, and FUM cluster types are not trans-specific. In addition, synonymous site divergence analyses indicated that three FUM cluster types predate diversification of FFSC. The data are not consistent with balancing selection or interspecific hybridization, but they are consistent with two competing hypotheses: (i) multiple horizontal transfers of the cluster from unknown donors to FFSC recipients and (ii) cluster duplication and loss (birth and death). Furthermore, low levels of FUM gene divergence in F. bulbicola, an FFSC species, and F. oxysporum provide evidence for horizontal transfer of the cluster from the former, or a closely related species, to the latter. Thus, uniform gene organization within the FUM cluster belies a complex evolutionary history that has not always paralleled the evolution of Fusarium.
• Efficacy and Safety of Oral Tapentadol Extended Release in Japanese and Korean Patients with Moderate to Severe, Chronic Malignant Tumor-related Pain Current Medical Research and Opinion. Oct, 2013  |   Pubmed ID: 23937387 Abstract Objective: This phase 3 study evaluated the efficacy and safety of tapentadol extended release (ER) compared with oxycodone controlled release (CR) for the management of moderate to severe, chronic malignant tumor-related cancer pain. Research design and methods: This randomized, double-blind, active-controlled study included Japanese and Korean patients with moderate to severe, chronic malignant tumor-related pain. Patients were randomized (1:1) to receive oral tapentadol ER (25-200 mg bid) or oral oxycodone HCl CR (5-40 mg bid) for 4 weeks of double-blind treatment. ClinicalTrials.gov identifier: NCT01165281. Main outcome measures: This study was designed to evaluate the non-inferiority of the efficacy provided by tapentadol ER versus oxycodone CR, based on the mean change in average pain intensity (11 point numerical rating scale) from baseline to the last 3 days of study drug administration. Treatment-emergent adverse events (TEAEs) were recorded throughout the study. Results: Of the 374 patients who were screened, 343 were randomized and 236 completed treatment. The least-squares mean difference in the change in pain intensity from baseline to the last 3 days of study treatment between tapentadol ER and oxycodone CR was -0.06 (95% confidence interval [CI], -0.506 to 0.383). The upper limit of the 95% CI was
• Age-associated Pro-inflammatory Adaptations of the Mouse Thoracic Aorta Thrombosis and Haemostasis. Sep, 2013  |   Pubmed ID: 23925372 Arterial ageing may be associated with a reduction in vasodilation due to increased reactive oxygen species (ROS) production, whereas endothelial cell activation induces procoagulant changes. However, little is known on the effect of ageing on expression of anticoagulant endothelial markers such as endothelial protein C receptor (EPCR). To study age-associated alterations in smooth muscle cell (SMC) and endothelial cell (EC) structure and function, the aorta was isolated from 10-week- and 12- and 24-month-old C57BL/6J mice and analysed for its expression of genes involved in senescence, oxidative stress production, coagulation and matrix remodelling. In addition, vasorelaxation experiments were performed using 10-week- and 24-month-old thoracic aortic ring segments in organ chamber baths. The media thickness of the thoracic aorta progressively increased with age, associated with hypertrophy of vascular SMCs. Basal nitric oxide production and sensitivity to acetylcholine-mediated vasodilation in thoracic aorta rings was reduced with age, whereas no significant differences in ROS production could be demonstrated. Gene expression of tissue factor, EPCR and von Willebrand factor was not affected by ageing of the aorta, whereas that of thrombomodulin was mildly reduced and that of xanthine dehydrogenase, NADPH oxidase 4, tumour necrosis factor-α and vascular cell adhesion molecule-1 significantly enhanced. In conclusion, a reduction in endothelial cell-mediated vasodilation in aged thoracic aortas of C57BL/6J mice was accompanied by a shift towards a pro-inflammatory state of the endothelium.
• A Quantitative Assessment of Educational Integration of Students with Down Syndrome in the Netherlands Journal of Intellectual Disability Research : JIDR. Jun, 2013  |   Pubmed ID: 23796135 In the Netherlands, as in many other countries, there are indications of an inclusive school policy for children with Down syndrome. However, there is a lack of studies that evaluate to what extent this policy has actually succeeded in supporting the mainstreaming of these students.
• Evaluation of the Child with Suspected Mitochondrial Liver Disease Journal of Pediatric Gastroenterology and Nutrition. Sep, 2013  |   Pubmed ID: 23783016
• Measurement of Associated Production of Vector Bosons and Top Quark-antiquark Pairs in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Apr, 2013  |   Pubmed ID: 23679709 The first measurement of vector-boson production associated with a top quark-antiquark pair in proton-proton collisions at sqrt[s]=7  TeV is presented. The results are based on a data set corresponding to an integrated luminosity of 5.0  fb^{-1}, recorded by the CMS detector at the LHC in 2011. The measurement is performed in two independent channels through a trilepton analysis of tt[over ¯]Z events and a same-sign dilepton analysis of tt[over ¯]V (V=W or Z) events. In the trilepton channel a direct measurement of the tt[over ¯]Z cross section σ_{tt[over ¯]Z}=0.28_{-0.11}^{+0.14} (stat)_{-0.03}^{+0.06} (syst)  pb is obtained. In the dilepton channel a measurement of the tt[over ¯]V cross section yields σ_{tt[over ¯]V}=0.43_{-0.15}^{+0.17} (stat)_{-0.07}^{+0.09} (syst)  pb. These measurements have a significance, respectively, of 3.3 and 3.0 standard deviations from the background hypotheses and are compatible, within uncertainties, with the corresponding next-to-leading order predictions of 0.137_{-0.016}^{+0.012} and 0.306_{-0.053}^{+0.031}  pb.
• Effect of Resveratrol on Cultured Skin Fibroblasts from Patients with Oxidative Phosphorylation Defects Phytotherapy Research : PTR. Apr, 2013  |   Pubmed ID: 23620374 Few therapeutic options are available to patients with oxidative phosphorylation disorders. Administering pharmacological agents that are able to stimulate mitochondrial biogenesis have been put forward as a possible treatment, yet the approach remains in need of thorough testing. We investigated the effect of resveratrol in an in vitro setting. Mitochondrial enzymatic activities were tested in cultured skin fibroblasts from patients harboring a nuclear defect in either complex II or complex IV (n = 11), and in fibroblasts from healthy controls (n = 11). In the latter, preincubation with resveratrol resulted in a significant increase of citrate synthase, complex II and complex IV enzyme activity. In patients with complex II or complex IV deficiency, however, activity of the deficient complex could not be substantially augmented, and response was dependent upon the residual activity. We conclude that resveratrol is not capable of normalizing oxidative phosphorylation activities in deficient cell lines. Copyright © 2013 John Wiley & Sons, Ltd.
• Matrix Metalloproteinase-2 and -9 As Promising Benefactors in Development, Plasticity and Repair of the Nervous System Progress in Neurobiology. Jun, 2013  |   Pubmed ID: 23567503 It has been 50 years since Gross and Lapiere discovered collagenolytic activity during tadpole tail metamorphosis, which was later on revealed as MMP-1, the founding member of the matrix metalloproteinases (MMPs). Currently, MMPs constitute a large group of endoproteases that are not only able to cleave all protein components of the extracellular matrix, but also to activate or inactivate many other signaling molecules, such as receptors, adhesion molecules and growth factors. Elevated MMP levels are associated with an increasing number of injuries and disorders, such as cancer, inflammation and auto-immune diseases. Yet, MMP upregulation has also been implicated in many physiological functions such as embryonic development, wound healing and angiogenesis and therefore, these proteinases are considered to be crucial mediators in many biological processes. Over the past decennia, MMP research has gained considerable attention in several pathologies, most prominently in the field of cancer metastasis, and more recent investigations also focus on the nervous system, with a striking emphasis on the gelatinases, MMP-2 and MMP-9. Unfortunately, the contribution of these gelatinases to neuropathological disorders, like multiple sclerosis and Alzheimer's disease, has overshadowed their potential as modulators of fundamental nervous system functions. Within this review, we wish to highlight the currently known or suggested actions of MMP-2 and MMP-9 in the developing and adult nervous system and their potential to improve repair or regeneration after nervous system injury.
• Study of the Mass and Spin-Parity of the Higgs Boson Candidate Via Its Decays to Z Boson Pairs Physical Review Letters. Feb, 2013  |   Pubmed ID: 23473131 A study is presented of the mass and spin-parity of the new boson recently observed at the LHC at a mass near 125 GeV. An integrated luminosity of 17.3  fb^{-1}, collected by the CMS experiment in proton-proton collisions at center-of-mass energies of 7 and 8 TeV, is used. The measured mass in the ZZ channel, where both Z bosons decay to e or μ pairs, is 126.2±0.6(stat)±0.2(syst)  GeV. The angular distributions of the lepton pairs in this channel are sensitive to the spin-parity of the boson. Under the assumption of spin 0, the present data are consistent with the pure scalar hypothesis, while disfavoring the pure pseudoscalar hypothesis.
• Measurement of the Î¥(1S), Î¥(2S), and Î¥(3S) Polarizations in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Feb, 2013  |   Pubmed ID: 23473130 The polarizations of the Î¥(1S), Î¥(2S), and Î¥(3S) mesons are measured in proton-proton collisions at sqrt[s]=7  TeV, using a data sample of Î¥(nS)→μ^{+}μ^{-} decays collected by the CMS experiment, corresponding to an integrated luminosity of 4.9  fb^{-1}. The dimuon decay angular distributions are analyzed in three different polarization frames. The polarization parameters λ_{Ï‘}, λ_{φ}, and λ_{ϑφ}, as well as the frame-invariant quantity λ[over Ëœ], are presented as a function of the Î¥(nS) transverse momentum between 10 and 50 GeV, in the rapidity ranges |y|
• Search for Pair Production of Third-Generation Leptoquarks and Top Squarks in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Feb, 2013  |   Pubmed ID: 23473129 Results are presented from a search for the pair production of third-generation scalar and vector leptoquarks, as well as for top squarks in R-parity-violating supersymmetric models. In either scenario, the new, heavy particle decays into a Ï„ lepton and a b quark. The search is based on a data sample of pp collisions at sqrt[s]=7  TeV, which is collected by the CMS detector at the LHC and corresponds to an integrated luminosity of 4.8  fb^{-1}. The number of observed events is found to be in agreement with the standard model prediction, and exclusion limits on mass parameters are obtained at the 95% confidence level. Vector leptoquarks with masses below 760 GeV are excluded and, if the branching fraction of the scalar leptoquark decay to a Ï„ lepton and a b quark is assumed to be unity, third-generation scalar leptoquarks with masses below 525 GeV are ruled out. Top squarks with masses below 453 GeV are excluded for a typical benchmark scenario, and limits on the coupling between the top squark, Ï„ lepton, and b quark, λ_{333}^{'} are obtained. These results are the most stringent for these scenarios to date.
• Evidence for Associated Production of a Single Top Quark and W Boson in Pp Collisions at Sqrt[s]=7  TeV Physical Review Letters. Jan, 2013  |   Pubmed ID: 23383893 Evidence is presented for the associated production of a single top quark and W boson in pp collisions at sqrt[s]=7  TeV with the CMS experiment at the LHC. The analyzed data correspond to an integrated luminosity of 4.9  fb^{-1}. The measurement is performed using events with two leptons and a jet originated from a b quark. A multivariate analysis based on kinematic properties is utilized to separate the tt[over ¯] background from the signal. The observed signal has a significance of 4.0σ and corresponds to a cross section of 16_{-4}^{+5}  pb, in agreement with the standard model expectation of 15.6±0.4_{-1.2}^{+1.0}  pb.
• Matrix Metalloproteinase 14 in the Zebrafish: an Eye on Retinal and Retinotectal Development PloS One. 2013  |   Pubmed ID: 23326364 Matrix metalloproteinases (MMPs) are members of the metzincin superfamily of proteinases that cleave structural elements of the extracellular matrix and many molecules involved in signal transduction. Although there is evidence that MMPs promote the proper development of retinotectal projections, the nature and working mechanisms of specific MMPs in retinal development remain to be elucidated. Here, we report a role for zebrafish Mmp14a, one of the two zebrafish paralogs of human MMP14, in retinal neurogenesis and retinotectal development.
• Contribution of α-adrenoceptor Stimulation by Phenylephrine to Basal Nitric Oxide Production in the Isolated Mouse Aorta Journal of Cardiovascular Pharmacology. Apr, 2013  |   Pubmed ID: 23249678 In the mouse aorta, contractions evoked by the α(1)-adrenoceptor agonist phenylephrine are strongly suppressed by the continuous production of nitric oxide (NO). We investigated whether phenylephrine itself stimulated NO production by activating endothelial α(2)-adrenoceptors. On a prostaglandin F(2α) contraction, the α(2)-adrenoceptor agonist 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14304) induced 29.3 ± 7.4% relaxation, which was inhibited by 0.1 μM 2-[(4,5-Dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole (BRL44408) with a pKB' corresponding to α(2)-antagonism. In the presence of NO synthase blockers, UK14304 elicited small contractions above 1 μM that were inhibited by 0.1 μM prazosin, but not influenced by 0.1 μM rauwolscine. At 3 μM or higher concentrations, phenylephrine caused only modest relaxation (up to 7.4 ± 2.3%) of segments constricted with prostaglandin F(2α) in the presence of prazosin, which was abolished with 0.1 μM BRL44408. Furthermore, BRL44408 did not increase contractions induced with 1 μM phenylephrine. These results confirm that α(1)- but not α(2)-adrenoceptors are expressed on aortic smooth muscle cells, whereas endothelial cells only express α(2)-adrenoceptors. Moreover, phenylephrine exerted a very modest relaxing effect through nonspecific stimulation of α(2)-adrenoceptors, but only at concentrations higher than 1 μM. It is concluded that the high basal output of NO in the isolated mouse aorta is not due to stimulation of α-adrenoceptors.
• Impact of Geographic Access to Care on Compliance and Metabolic Control in Phenylketonuria Molecular Genetics and Metabolism. Jan, 2013  |   Pubmed ID: 23177662 To study the impact of geographic access to care on metabolic control and compliance in phenylketonuria (PKU).
• Combined MR, Fluorescence and Histology Imaging Strategy in a Human Breast Tumor Xenograft Model NMR in Biomedicine. Mar, 2013  |   Pubmed ID: 22945331 Applications of molecular imaging in cancer and other diseases frequently require the combination of in vivo imaging modalities, such as MR and optical imaging, with ex vivo optical, fluorescence, histology and immunohistochemical imaging to investigate and relate molecular and biological processes to imaging parameters within the same region of interest. We have developed a multimodal image reconstruction and fusion framework that accurately combines in vivo MRI and MRSI, ex vivo brightfield and fluorescence microscopic imaging and ex vivo histology imaging. Ex vivo brightfield microscopic imaging was used as an intermediate modality to facilitate the ultimate link between ex vivo histology and in vivo MRI/MRSI. Tissue sectioning necessary for optical and histology imaging required the generation of a three-dimensional reconstruction module for two-dimensional ex vivo optical and histology imaging data. We developed an external fiducial marker-based three-dimensional reconstruction method, which was able to fuse optical brightfield and fluorescence with histology imaging data. The registration of the three-dimensional tumor shape was pursued to combine in vivo MRI/MRSI and ex vivo optical brightfield and fluorescence imaging data. This registration strategy was applied to in vivo MRI/MRSI, ex vivo optical brightfield/fluorescence and histology imaging datasets obtained from human breast tumor models. Three-dimensional human breast tumor datasets were successfully reconstructed and fused with this platform.
• Differences in Proliferation, Differentiation, and Cytokine Production by Bone Cells Seeded on Titanium-nitride and Cobalt-chromium-molybdenum Surfaces Journal of Biomaterials Applications. Aug, 2013  |   Pubmed ID: 22614252 Titanium-nitride coating is used to improve cobalt-chromium-molybdenum implant survival in total knee arthroplasty, but its effect on osteoconduction is unknown. Chromium and cobalt ions negatively affect the growth and metabolism of cultured osteoblasts while enhancing osteoclastogenic cytokine production. Therefore, it was hypothesized that a titanium-nitride surface would enhance osteoblast proliferation and/or differentiation and reduce osteoclastogenic cytokine production compared with a cobalt-chromium-molybdenum surface. MC3T3-E1 osteoblasts showed increased proliferation and decreased differentiation on titanium-nitride, while cytokine interleukin-6 production was higher on porous cobalt-chromium-molybdenum (p 
• More Academics in Regular Schools? The Effect of Regular Versus Special School Placement on Academic Skills in Dutch Primary School Students with Down Syndrome Journal of Intellectual Disability Research : JIDR. Jan, 2013  |   Pubmed ID: 22141327 Studies from the UK have shown that children with Down syndrome acquire more academic skills in regular education. Does this likewise hold true for the Dutch situation, even after the effect of selective placement has been taken into account?