Showing papers by "University of Duisburg-Essen published in 2007"

Size-Dependent Cytotoxicity of Gold Nanoparticles

Abstract: Gold nanoparticles are widely used in biomedical imaging and diagnostic tests. Based on their established use in the laboratory and the chemical stability of Au(0), gold nanoparticles were expected to be safe. The recent literature, however, contains conflicting data regarding the cytotoxicity of gold nanoparticles. Against this background a systematic study of water-soluble gold nanoparticles stabilized by triphenylphosphine derivatives ranging in size from 0.8 to 15 nm is made. The cytotoxicity of these particles in four cell lines representing major functional cell types with barrier and phagocyte function are tested. Connective tissue fibroblasts, epithelial cells, macrophages, and melanoma cells prove most sensitive to gold particles 1.4 nm in size, which results in IC(50) values ranging from 30 to 56 microM depending on the particular 1.4-nm Au compound-cell line combination. In contrast, gold particles 15 nm in size and Tauredon (gold thiomalate) are nontoxic at up to 60-fold and 100-fold higher concentrations, respectively. The cellular response is size dependent, in that 1.4-nm particles cause predominantly rapid cell death by necrosis within 12 h while closely related particles 1.2 nm in diameter effect predominantly programmed cell death by apoptosis.

The EPS Matrix: The “House of Biofilm Cells”

Abstract: In response to a suggestion by the Biofilms 2007 organizing committee to hold an evening session on biofilm extracellular polymeric substances (EPS), an exceptionally inspiring event followed contributions by Ken Bayles, Alan Decho, Martina Hausner, Jan Kreft, Thomas Neu, Per Nielsen, Ute Romling,

Max Weber, Wirtschaft und Gesellschaft. Grundriss der verstehenden Soziologie, Tübingen 1922

Abstract: „Wirtschaft und Gesellschaft“ ist eine Zusammenstellung von Schriften Max Webers, die seine Frau Marianne 1922 aus dem Nachlass veroffentlichte. Weber hatte vor dem Ersten Weltkrieg eine gewaltige wissenschaftliche Kollektivanstrengung initiiert und herausgegeben, die unter dem Titel „Grundriss der Sozialokonomik“ im Bereich von Politik, Wirtschaft und Gesellschaft alle hierfur relevanten normativen, theoretischen und empirischen Aspekte verbinden wollte. Max Webers eigener Beitrag war als erster Band fur die III. Abteilung mit dem Titel „Wirtschaft und Gesellschaft“ gedacht. Er sollte „Die Wirtschaft und ihre gesellschaftlichen Ordnungen und Machte“ heisen. Die heutige Gestalt beruht auf der Neuausgabe Johannes Winckelmanns. Er versuchte, den Stoff in der von Weber moglicherweise intendierten Gliederung vorzulegen und erganzte die fur „Wirtschaft und Gesellschaft“ noch nicht ausgefuhrten Abschnitte um Stucke aus anderen Veroffentlichungen Webers.

Sleep-disordered breathing in patients with symptomatic heart failure: a contemporary study of prevalence in and characteristics of 700 patients.

Abstract: Aim: Evaluation of the prevalence and nature of sleep-disordered breathing (SDB) in patients with symptomatic chronic heart failure (CHF) receiving therapy according to current guidelines. Methods and results: We prospectively screened 700 patients with CHF (NYHA class ≥II, LV-EF ≤40%) for SDB using cardiorespiratory polygraphy (Embletta™). Furthermore, echocardiography, cardiopulmonary exercise and 6-min walk testing were performed. Medication included ACE-inhibitors and/or AT1-receptor blockers in at least 94%, diuretics in 87%, β-blockers in 85%, digitalis in 61% and spironolactone in 62% of patients. SDB was present in 76% of patients (40% central (CSA), 36% obstructive sleep apnoea (OSA)). CSA patients were more symptomatic (NYHA class 2.9±0.5 vs. no SDB 2.57±0.5 or OSA 2.57±0.5; pb0.05) and had a lower LV-EF (27.4±6.6% vs. 29.3±2.6%, pb0.05) than OSA patients. Oxygen uptake (VO2) was lowest in CSA patients: predicted peak VO2 57±16% vs. 64±18% in OSA and 63±17% in no SDB, pb0.05. 6-min walking distances were 331±111 m in CSA, 373±108 m in OSA and 377±118 m in no SDB (pb0.05). Conclusions: This study confirms the high prevalence of SDB, particularly CSA in CHF patients. CSA seems to be a marker of heart failure severity.

Within-plant signaling by volatiles leads to induction and priming of an indirect plant defense in nature.

Abstract: Plants respond to herbivore attack with the release of volatile organic compounds (VOCs), which can attract predatory arthropods and/or repel herbivores and thus serve as a means of defense against herbivores. Such VOCs might also be perceived by neighboring plants to adjust their defensive phenotype according to the present risk of attack. We exposed lima bean plants at their natural growing site to volatiles of beetle-damaged conspecific shoots. This reduced herbivore damage and increased the growth rate of the exposed plants. To investigate whether VOCs also can serve in signaling processes within the same individual plant we focused on undamaged “receiver” leaves that were either exposed or not exposed to VOCs released by induced “emitter” leaves. Extrafloral nectar secretion by receiver leaves increased when they were exposed to VOCs of induced emitters of neighboring plants or of the same shoot, yet not when VOCs were removed from the system. Extrafloral nectar attracts predatory arthropods and represents an induced defense mechanism. The volatiles also primed extrafloral nectar secretion to show an augmented response to subsequent damage. Herbivore-induced VOCs elicit a defensive response in undamaged plants (or parts of plants) under natural conditions, and they function as external signal for within-plant communication, thus serving also a physiological role in the systemic response of a plant to local damage.

Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution

Abstract: We recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism.

Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants.

Abstract: Background Obesity is a major health problem. Although heritability is substantial, genetic mechanisms predisposing to obesity are not very well understood. We have performed a genome wide association study (GWA) for early onset (extreme) obesity. Methodology/Principal Findings a) GWA (Genome-Wide Human SNP Array 5.0 comprising 440,794 single nucleotide polymorphisms) for early onset extreme obesity based on 487 extremely obese young German individuals and 442 healthy lean German controls; b) confirmatory analyses on 644 independent families with at least one obese offspring and both parents. We aimed to identify and subsequently confirm the 15 SNPs (minor allele frequency ≥10%) with the lowest p-values of the GWA by four genetic models: additive, recessive, dominant and allelic. Six single nucleotide polymorphisms (SNPs) in FTO (fat mass and obesity associated gene) within one linkage disequilibrium (LD) block including the GWA SNP rendering the lowest p-value (rs1121980; log-additive model: nominal p = 1.13×10−7, corrected p = 0.0494; odds ratio (OR)CT 1.67, 95% confidence interval (CI) 1.22–2.27; ORTT 2.76, 95% CI 1.88–4.03) belonged to the 15 SNPs showing the strongest evidence for association with obesity. For confirmation we genotyped 11 of these in the 644 independent families (of the six FTO SNPs we chose only two representing the LD bock). For both FTO SNPs the initial association was confirmed (both Bonferroni corrected p<0.01). However, none of the nine non-FTO SNPs revealed significant transmission disequilibrium. Conclusions/Significance Our GWA for extreme early onset obesity substantiates that variation in FTO strongly contributes to early onset obesity. This is a further proof of concept for GWA to detect genes relevant for highly complex phenotypes. We concurrently show that nine additional SNPs with initially low p-values in the GWA were not confirmed in our family study, thus suggesting that of the best 15 SNPs in the GWA only the FTO SNPs represent true positive findings.

Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study.

Abstract: The aim of this study was to evaluate the efficacy and tolerability of topiramate for the prevention of chronic migraine in a randomized, double-blind, placebo-controlled trial. Chronic migraine is a common form of disabling headache presenting in headache subspecialty practice. Preventive treatments are essential for chronic migraine management, although there are few or no controlled empirical trial data on their use in this patient population. Topiramate is approved for the prophylaxis of migraine headache in adults. Patients (18-65 years) who experienced chronic migraine (defined as > or =15 monthly migraine days) for > or =3 months prior to trial entry and had > or =12 migraine days during the 4-week (28-day) baseline phase were randomized to topiramate or placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly) to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200 mg/day, according to patient need. Existing migraine preventive treatments, except for antiepileptic drugs, were continued throughout the trial. The primary efficacy measure was the change in number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population, which consisted of all patients who received at least one dose of study medication and had one outcome assessment during the double-blind phase. Health-related quality of life was evaluated with the Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was assessed by adverse event (AE) reports and early trial discontinuations. Eighty-two patients were screened. Thirty-two patients in the intent-to-treat population (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most patients (78%) met the definition for acute medication overuse at baseline. The mean duration of treatment was 100 and 92 days for topiramate- and placebo-treated patients, respectively. Study completion rates for topiramate- and placebo-treated patients were 75% and 52%, respectively. Topiramate significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7, P < 0.05). No significant intergroup differences were found for MSQ and HIT-6. MIDAS showed improvement with the topiramate treatment group (P = 0.042 vs. placebo). Treatment emergent adverse events were reported by 75% of topiramate-treated patients (37%, placebo). The most common AEs, paraesthesia, nausea, dizziness, dyspepsia, fatigue, anorexia and disturbance in attention, were reported by 53%, 9%, 6%, 6%, 6%, 6% and 6% of topiramate-treated patients, respectively, vs. 7%, 0%, 0%, 0%, 0%, 4% and 4% of placebo-treated patients. This randomized, double-blind, placebo-controlled trial demonstrates that topiramate is effective and reasonably well tolerated when used for the preventive treatment of chronic migraine, even in the presence of medication overuse.

Magnetic superelasticity and inverse magnetocaloric effect in Ni-Mn-In

Abstract: Applying a magnetic field to a ferromagnetic Ni{sub 50}Mn{sub 34}In{sub 16} alloy in the martensitic state induces a structural phase transition to the austenitic state. This is accompanied by a strain which recovers on removing the magnetic field, giving the system a magnetically superelastic character. A further property of this alloy is that it also shows the inverse magnetocaloric effect. The magnetic superelasticity and the inverse magnetocaloric effect in Ni-Mn-In and their association with the first-order structural transition are studied by magnetization, strain, and neutron-diffraction studies under magnetic field.

Definitions of terms relating to the structure and processing of sols, gels, networks, and inorganic-organic hybrid materials (IUPAC Recommendations 2007)

Abstract: This document defines terms related to the structure and processing of inorganic, polymeric, and inorganic-organic hybrid materials from precursors, through gels to solid products. It is divided into four sections-precursors, gels, solids, and processes- and the terms have been restricted to those most commonly encountered. For the sake of completeness and where they are already satisfactorily defined for the scope of this document, terms from other IUPAC publications have been used. Otherwise, the terms and their definitions have been assembled in consultation with experts in the relevant fields. The definitions are intended to assist the reader who is unfamiliar with sol-gel processing, ceramization, and related technologies and materials, and to serve as a guide to the use of standard terminology by those researching in these areas.

Liver cell death and anemia in Wilson disease involve acid sphingomyelinase and ceramide.

Abstract: Wilson disease is caused by accumulation of Cu(2+) in cells, which results in liver cirrhosis and, occasionally, anemia. Here, we show that Cu(2+) triggers hepatocyte apoptosis through activation of acid sphingomyelinase (Asm) and release of ceramide. Genetic deficiency or pharmacological inhibition of Asm prevented Cu(2+)-induced hepatocyte apoptosis and protected rats, genetically prone to develop Wilson disease, from acute hepatocyte death, liver failure and early death. Cu(2+) induced the secretion of activated Asm from leukocytes, leading to ceramide release in and phosphatidylserine exposure on erythrocytes, events also prevented by inhibition of Asm. Phosphatidylserine exposure resulted in immediate clearance of affected erythrocytes from the blood in mice. Accordingly, individuals with Wilson disease showed elevated plasma levels of Asm, and displayed a constitutive increase of ceramide- and phosphatidylserine-positive erythrocytes. Our data suggest a previously unidentified mechanism for liver cirrhosis and anemia in Wilson disease.

Superradiance of quantum dots

Abstract: In 1954, Dicke pointed out that the description of a spontaneously radiating gas has to include the fact that all atoms or molecules interact with a common radiation field1. Consequently, the individual particles may not be considered as independent sources of radiation. In this regard, the question arises of whether quantum dot (QD) systems may also exhibit signatures of cooperative radiation and hence have to be considered as coupled quantum systems. Here, we present experimental evidence for a long-range electromagnetic interaction between laterally arranged QDs. The experimental results suggest that the QDs do not behave like independent objects as long as they form an ensemble of QDs. By removing QDs from the sample, we found that the coupling was reduced. The range of interaction is shown to be at least 150 nm. This may therefore provide a mechanism to couple discrete quantum objects on a large scale.

A novel, self-expanding, nitinol stent in medically refractory intracranial atherosclerotic stenoses: the Wingspan study.

Abstract: Background and Purpose— The purpose of this study was to assess the safety and performance of the Wingspan stent system and Gateway percutaneous transluminal angioplasty balloon catheter in the treatment of high-grade, intracranial atherosclerotic lesions in patients who had failed medical therapy. Methods— In this prospective, multicenter, single-arm study, medically refractory patients with a modified Rankin score ≤3 and recurrent symptoms attributable to angiographically demonstrated intracranial stenosis ≥50% in a vessel 2.5 to 4.5 mm in diameter were enrolled. Intracranial lesions were predilated with an undersized Gateway balloon catheter to 80% of the native vessel diameter, followed by deployment of the self-expanding Wingspan stent to facilitate further remodeling of the atherosclerotic plaque and to maintain vessel patency. Neurologic examinations and angiograms were performed at 6 months after the procedure. Results— Among the 45 patients enrolled, the degree of stenosis was reduced from a baseline of 74.9±9.8% to 31.9±13.6% after stenting and 28±23.2% at the 6-month follow-up. The 30-day composite ipsilateral stroke/death rate was 4.5% (2/44); at the 6-month follow-up, the ipsilateral stroke/death rate was 7.0%, the rate for all strokes was 9.7%, and all-cause mortality was 2.3%. Physician-reported follow-up in 43 patients (average of 13 months) conducted outside the study protocol (not adjudicated by the clinical event committee) reported 1 additional ipsilateral stroke. Conclusions— In medically refractory patients with high-grade intracranial atherosclerotic stenoses, a new treatment paradigm involving predilation with an undersized Gateway percutaneous transluminal angioplasty balloon catheter and placement of a self-expanding Wingspan stent system appears to be safe, may facilitate remodeling, and may contribute to favorable angiographic outcomes.

Outcome parameters for trials in atrial fibrillation: executive summary.

Abstract: Atrial fibrillation (AF), the most common atrial arrhythmia, has a complex aetiology and causes relevant morbidity and mortality due to different mechanisms, including but not limited to stroke, heart failure, and tachy- or bradyarrhythmia. Current therapeutic options (rate control, rhythm control, antithrombotic therapy, ‘upstream therapy’) only prevent a part of this burden of disease. Several new treatment modalities are therefore under evaluation in controlled trials. Given the multifold clinical consequences of AF, trials in AF patients should assess the effect of therapy in each of the main outcome domains. This paper describes an expert consensus of required outcome parameters in seven relevant outcome domains, namely death, stroke, symptoms and quality of life, rhythm, left ventricular function, cost, and emerging outcome parameters. In addition to these ‘requirements’ for outcome assessment in AF trials, further, more detailed outcome parameters are described. In addition to a careful selection of a relevant primary outcome parameter, coverage of outcomes in all major domains of AF-related morbidity and mortality is desirable for any clinical trial in AF.

Specifying Computer-Supported Collaboration Scripts

Abstract: Collaboration scripts are activity programs which aim to foster collaborative learning by structuring interaction between learners. Computer-supported collaboration scripts generally suffer from the problem of being restrained to a specific learning platform and learning context. A standardization of collaboration scripts first requires a specification of collaboration scripts that integrates multiple perspectives from computer science, education and psychology. So far, only few and limited attempts at such specifications have been made. This paper aims to consolidate and expand these approaches in light of recent findings and to propose a generic framework for the specification of collaboration scripts. The framework enables a description of collaboration scripts using a small number of components (participants, activities, roles, resources and groups) and mechanisms (task distribution, group formation and sequencing). (http://www.springerlink.com/content/6286w8235q818664/)

Substrate-induced magnetic ordering and switching of iron porphyrin molecules.

Abstract: To realize molecular spintronic devices, it is important to externally control the magnetization of a molecular magnet. One class of materials particularly promising as building blocks for molecular electronic devices is the paramagnetic porphyrin molecule in contact with a metallic substrate. Here, we study the structural orientation and the magnetic coupling of in-situ-sublimated Fe porphyrin molecules on ferromagnetic Ni and Co films on Cu(100). Our studies involve X-ray absorption spectroscopy and X-ray magnetic circular dichroism experiments. In a combined experimental and computational study we demonstrate that owing to an indirect, superexchange interaction between Fe atoms in the molecules and atoms in the substrate (Co or Ni) the paramagnetic molecules can be made to order ferromagnetically. The Fe magnetic moment can be rotated along directions in plane as well as out of plane by a magnetization reversal of the substrate, thereby opening up an avenue for spin-dependent molecular electronics.

Social support during pregnancy: effects on maternal depressive symptoms, smoking and pregnancy outcome

Abstract: BACKGROUND: The goal was to study the effects of social support during pregnancy on maternal depressive symptoms, quality of life and pregnancy outcomes. METHODS: Eight hundred ninety-six women were prospectively studied in the first trimester of pregnancy and following completion of the pregnancy. The sample was divided into quartiles yielding groups of low, medium and high social support based on perceived social support. RESULTS: Pregnant women with low support reported increased depressive symptoms and reduced quality of life. The effects of social support on pregnancy outcomes were particularly pronounced in women who had smoked during pregnancy, with significant main effects of social support in a two-way analysis of variance (smoking status and social support) for child body length (F = 4.26, P = 0.04; 50.43 ± 2.81 cm with low support versus 51.76 ± 2.31 cm with high support) and birthweight (F = 11.35, P = 0.001; 3175 ± 453 g with low support versus 3571 ± 409 g with high support). In smokers, pregnancy complications occurred more frequently when given low support {34 versus 10.3% with high support, c 2 = 5.49, P = 0.019; relative risk (RR) = 3.3 [95% confidence interval (95% CI) = 1.1–10.2]}, and the proportion of preterm deliveries was greater given low support (10.0 versus 0% with high support, c 2 = 3.84, P = 0.05, odds ratio = 8.1).

Cognitive English Grammar

Abstract: Cognitive English Grammar is designed to be used as a textbook in courses of English and general linguistics. It introduces the reader to cognitive linguistic theory and shows that Cognitive Grammar helps us to gain a better understanding of the grammar of English. The notions of motivation and meaningfulness are central to the approach adopted in the book. In four major parts comprising 12 chapters, Cognitive English Grammar integrates recent cognitive approaches into one coherent model, allowing the analysis of the most central constructions of English. Part I presents the cognitive framework: conceptual and linguistic categories, their combination in situations, the cognitive operations applied to them, and the organisation of conceptual structures into linguistic constructions. Part II deals with the category of ‘things’ and their linguistic structuring as nouns and noun phrases. It shows how things are grounded in reality by means of reference, quantified by set and scalar quantifiers, and qualified by modifiers. Part III describes situations as temporal units of various layers: internally, as types of situations; and externally, as located relative to the time of speech and grounded in reality or potentiality. Part IV looks at situations as relational units and their structuring as sentences. Its two chapters are devoted to event schemas and space and metaphorical extensions of space. Cognitive English Grammar offers a wealth of linguistic data and explanations. The didactic quality is guaranteed by the frequent use of definitions and examples, a glossary of the terms used, overviews and chapter summaries, suggestions for further reading, and study questions. For the Key to Study Questions click here .

Ultrafast Bond Softening in Bismuth: Mapping a Solid's Interatomic Potential with X-rays

Abstract: Intense femtosecond laser excitation can produce transient states of matter that would otherwise be inaccessible to laboratory investigation. At high excitation densities, the interatomic forces that bind solids and determine many of their properties can be substantially altered. Here, we present the detailed mapping of the carrier density–dependent interatomic potential of bismuth approaching a solid-solid phase transition. Our experiments combine stroboscopic techniques that use a high-brightness linear electron accelerator–based x-ray source with pulse-by-pulse timing reconstruction for femtosecond resolution, allowing quantitative characterization of the interatomic potential energy surface of the highly excited solid.

Prevalence and complications of uveitis in juvenile idiopathic arthritis in a population-based nation-wide study in Germany: suggested modification of the current screening guidelines

Abstract: patients with uveitis were significantly younger at onset of arthritis (3.8 vs 7.0yrs) or ANA-positive (86% vs 42%) than the patients without uveitis. Predictors of uveitis included age at onset (P ¼0.03) and ANA-positivity (P <0.01) besides the presence of a certain JIA subgroup (P ¼0.04). Uveitis was clinically silent in 75% of the oligoarthritis but in none of the enthesitis-related arthritis patients. The median onset of uveitis was 5.5 months after arthritis manifestation. In 73%, 77% and 90%, uveitis developed within 1, 2 and 4yrs after arthritis, respectively. Anterior uveitis was the most common anatomic type of uveitis (83%). Uveitis complications at mean follow-up of 5.6yrs were common (56%), and predictors for complications included presence of complications at first visit (P <0.001) and uveitis manifestation before arthritis (P ¼0.001), but not ANA positivity. Conclusions. The JIA subgroups markedly differ with respect to the prevalence and course of associated uveitis. Ophthalmological screening should be initiated early after arthritis onset and the intervals be related to the JIA subgroup. A modification of the current screening guidelines is suggested.

Understanding the interaction between psychosocial stress and immune-related diseases: a stepwise progression.

Abstract: For many years, anecdotal evidence and clinical observations have suggested that exposure to psychosocial stress can affect disease outcomes in immune-related disorders such as viral infections, chronic autoimmune diseases and tumors. Experimental evidence in humans supporting these observations was, however, lacking. Studies published in the last 2 decades in Brain, Behavior and Immunity and other journals have demonstrated that acute and chronic psychological stress can induce pronounced changes in innate and adaptive immune responses and that these changes are predominantly mediated via neuroendocrine mediators from the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal axis. In addition, psychological stress has predicted disease outcomes using sophisticated models such as viral challenge, response to vaccination, tracking of herpesvirus latency, exploration of tumor metastasis and healing of experimental wounds, as well as epidemiological investigations of disease progression and mortality. These studies have contributed significantly to our understanding that the neuroendocrine-immune interaction is disturbed in many pathophysiological conditions, that stress can contribute to this disturbance, and that malfunction in these communication pathways can play a significant role in the progression of disease processes. There are, however, significant gaps in the extant literature. In the coming decade(s), it will be essential to further analyze neuroendocrine-immune communication during disease states and to define the specific pathways linking the central nervous system to the molecular events that control important disease-relevant processes. This knowledge will provide the basis for new therapeutic pharmacological and non-pharmacological behavioral approaches to the treatment of chronic diseases via specific modulation of nervous system-immune system communication.

Suicidal erythrocyte death in sepsis

Abstract: Sequelae of sepsis include anemia which presumably results from accelerated clearance of erythrocytes from circulating blood. The underlying mechanisms, however, remained hitherto elusive. Most recent studies disclosed that increased cytosolic Ca2+ activity and ceramide both trigger suicidal erythrocyte death (i.e., eryptosis), which is characterized by lipid scrambling of the cell membrane leading to phosphatidylserine exposure at the erythrocyte surface. Phosphatidylserine exposing erythrocytes may adhere to vascular walls or may be engulfed by macrophages equipped with phosphatidylserine receptors. To explore whether sepsis leads to eryptosis, erythrocytes from healthy volunteers were exposed to plasma of patients suffering from sepsis, or to supernatants from sepsis producing pathogens. Then, phosphatidylserine exposure (annexin V binding), cell volume (forward scatter), cytosolic Ca2+ activity (Fluo3 fluorescence), and ceramide formation (anti-ceramide antibody) were determined by flow cytometry. Challenge of erythrocytes with plasma from the patients but not with plasma from healthy individuals triggered annexin V binding. The effect of patient plasma on erythrocyte annexin V binding was paralleled by formation of ceramide and a significant increase of cytosolic Ca2+ activity. Exposure of erythrocytes to supernatant of pathogens similarly induced eryptosis, an effect correlating with sphingomyelinase activity. The present observations disclose a novel pathophysiological mechanism leading to anemia and derangement of microcirculation during sepsis. Exposure to plasma from septic patients triggers phosphatidylserine exposure leading to adherence to the vascular wall and clearance from circulating blood.

Modeling of Wind Turbines Based on Doubly-Fed Induction Generators for Power System Stability Studies

Abstract: This paper deals with modeling of the doubly-fed induction generator (DFIG) and the corresponding converter for stability studies. To enable efficient computation, a reduced-order DFIG model is developed that restricts the calculation to the fundamental frequency component. However, the model enhancement introduced in this paper allows the consideration of the alternating components of the rotor current as well, which is necessary for triggering the crowbar operation. Suitable models are presented for the rotor and grid side converters as well as the dc-link, taking into account all four possible operating modes. The proposed model for speed and pitch angle control can be used when wind and rotor speed variations are significant. Simulation results are presented for model verification purposes and also for demonstrating the dynamic behavior of a large offshore wind farm connected through a long undersea cable to the high voltage grid.

Outcome parameters for trials in atrial fibrillation: recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork and the European Heart Rhythm Association.

Abstract: Atrial fibrillation (AF), the most common atrial arrhythmia, has a complex aetiology and causes relevant morbidity and mortality due to different mechanisms, including but not limited to stroke, heart failure, and tachy- or bradyarrhythmia. Current therapeutic options (rate control, rhythm control, antithrombotic therapy, ‘upstream therapy’) only prevent a part of this burden of disease. New treatment modalities are therefore currently under evaluation in clinical trials. Given the multifold clinical consequences of AF, controlled trials in AF patients should assess the effect of therapy in each of the main outcome domains. This paper describes an expert consensus of required outcome parameters in seven relevant outcome domains, namely death, stroke, symptoms and quality of life, rhythm, left ventricular function, cost, and emerging outcome parameters. In addition to these ‘requirements’ for outcome assessment in AF trials, further outcome parameters are described in each outcome domain. In addition to a careful selection of a relevant primary outcome parameter, coverage of outcomes in all major domains of AF-related morbidity and mortality is desirable for any clinical trial in AF.