894 resultados para Nucleophilic addition to carbonyl


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In vielen Bereichen der industriellen Fertigung, wie zum Beispiel in der Automobilindustrie, wer- den digitale Versuchsmodelle (sog. digital mock-ups) eingesetzt, um die Entwicklung komplexer Maschinen m ̈oglichst gut durch Computersysteme unterstu ̈tzen zu k ̈onnen. Hierbei spielen Be- wegungsplanungsalgorithmen eine wichtige Rolle, um zu gew ̈ahrleisten, dass diese digitalen Pro- totypen auch kollisionsfrei zusammengesetzt werden k ̈onnen. In den letzten Jahrzehnten haben sich hier sampling-basierte Verfahren besonders bew ̈ahrt. Diese erzeugen eine große Anzahl von zuf ̈alligen Lagen fu ̈r das ein-/auszubauende Objekt und verwenden einen Kollisionserken- nungsmechanismus, um die einzelnen Lagen auf Gu ̈ltigkeit zu u ̈berpru ̈fen. Daher spielt die Kollisionserkennung eine wesentliche Rolle beim Design effizienter Bewegungsplanungsalgorith- men. Eine Schwierigkeit fu ̈r diese Klasse von Planern stellen sogenannte “narrow passages” dar, schmale Passagen also, die immer dort auftreten, wo die Bewegungsfreiheit der zu planenden Objekte stark eingeschr ̈ankt ist. An solchen Stellen kann es schwierig sein, eine ausreichende Anzahl von kollisionsfreien Samples zu finden. Es ist dann m ̈oglicherweise n ̈otig, ausgeklu ̈geltere Techniken einzusetzen, um eine gute Performance der Algorithmen zu erreichen.rnDie vorliegende Arbeit gliedert sich in zwei Teile: Im ersten Teil untersuchen wir parallele Kollisionserkennungsalgorithmen. Da wir auf eine Anwendung bei sampling-basierten Bewe- gungsplanern abzielen, w ̈ahlen wir hier eine Problemstellung, bei der wir stets die selben zwei Objekte, aber in einer großen Anzahl von unterschiedlichen Lagen auf Kollision testen. Wir im- plementieren und vergleichen verschiedene Verfahren, die auf Hu ̈llk ̈operhierarchien (BVHs) und hierarchische Grids als Beschleunigungsstrukturen zuru ̈ckgreifen. Alle beschriebenen Verfahren wurden auf mehreren CPU-Kernen parallelisiert. Daru ̈ber hinaus vergleichen wir verschiedene CUDA Kernels zur Durchfu ̈hrung BVH-basierter Kollisionstests auf der GPU. Neben einer un- terschiedlichen Verteilung der Arbeit auf die parallelen GPU Threads untersuchen wir hier die Auswirkung verschiedener Speicherzugriffsmuster auf die Performance der resultierenden Algo- rithmen. Weiter stellen wir eine Reihe von approximativen Kollisionstests vor, die auf den beschriebenen Verfahren basieren. Wenn eine geringere Genauigkeit der Tests tolerierbar ist, kann so eine weitere Verbesserung der Performance erzielt werden.rnIm zweiten Teil der Arbeit beschreiben wir einen von uns entworfenen parallelen, sampling- basierten Bewegungsplaner zur Behandlung hochkomplexer Probleme mit mehreren “narrow passages”. Das Verfahren arbeitet in zwei Phasen. Die grundlegende Idee ist hierbei, in der er- sten Planungsphase konzeptionell kleinere Fehler zuzulassen, um die Planungseffizienz zu erh ̈ohen und den resultierenden Pfad dann in einer zweiten Phase zu reparieren. Der hierzu in Phase I eingesetzte Planer basiert auf sogenannten Expansive Space Trees. Zus ̈atzlich haben wir den Planer mit einer Freidru ̈ckoperation ausgestattet, die es erlaubt, kleinere Kollisionen aufzul ̈osen und so die Effizienz in Bereichen mit eingeschr ̈ankter Bewegungsfreiheit zu erh ̈ohen. Optional erlaubt unsere Implementierung den Einsatz von approximativen Kollisionstests. Dies setzt die Genauigkeit der ersten Planungsphase weiter herab, fu ̈hrt aber auch zu einer weiteren Perfor- mancesteigerung. Die aus Phase I resultierenden Bewegungspfade sind dann unter Umst ̈anden nicht komplett kollisionsfrei. Um diese Pfade zu reparieren, haben wir einen neuartigen Pla- nungsalgorithmus entworfen, der lokal beschr ̈ankt auf eine kleine Umgebung um den bestehenden Pfad einen neuen, kollisionsfreien Bewegungspfad plant.rnWir haben den beschriebenen Algorithmus mit einer Klasse von neuen, schwierigen Metall- Puzzlen getestet, die zum Teil mehrere “narrow passages” aufweisen. Unseres Wissens nach ist eine Sammlung vergleichbar komplexer Benchmarks nicht ̈offentlich zug ̈anglich und wir fan- den auch keine Beschreibung von vergleichbar komplexen Benchmarks in der Motion-Planning Literatur.

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Virgin olive oil(VOO) is a product characterized by high economic and nutritional values, because of its superior sensory characteristics and minor compounds (phenols and tocopherols) contents. Since the original quality of VOO may change during its storage, this study aimed to investigate the influence of different storage and shipment conditions on the quality of VOO, by studying different solutions such as filtration, dark storage and shipment inside insulated containers to protect it. Different analytical techniques were used to follow-up the quality changes during virgin olive oil storage and simulated shipments, in terms of basic quality parameters, sensory analysis and evaluation of minor components (phenolic compounds, diglycerides, volatile compounds). Four main research streams were presented in this PhD thesis: The results obtained from the first experimental section revealed that the application of filtration and/or clarification can decrease the unavoidable quality loss of the oil samples during storage, in comparison with unfiltered oil samples. The second section indicated that the virgin olive oil freshness, evaluated by diglycerides content, was mainly affected by the storage time and temperature. The third section revealed that fluctuation in temperature during storage may adversely affect the virgin olive oil quality, in terms of hydrolytic rancidity and oxidation quality. The fourth section showed that virgin olive oil shipped inside insulated containers showed lower hydrolytic and oxidation degradation than those without insulation cover. Overall, this PhD thesis highlighted that application of adequate treatment, such as filtration or clarification, in addition to a good protection against other external variables, such as temperature and light, will improve the stability of virgin olive oil during storage.

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Heart diseases are the leading cause of death worldwide, both for men and women. However, the ionic mechanisms underlying many cardiac arrhythmias and genetic disorders are not completely understood, thus leading to a limited efficacy of the current available therapies and leaving many open questions for cardiac electrophysiologists. On the other hand, experimental data availability is still a great issue in this field: most of the experiments are performed in vitro and/or using animal models (e.g. rabbit, dog and mouse), even when the final aim is to better understand the electrical behaviour of in vivo human heart either in physiological or pathological conditions. Computational modelling constitutes a primary tool in cardiac electrophysiology: in silico simulations, based on the available experimental data, may help to understand the electrical properties of the heart and the ionic mechanisms underlying a specific phenomenon. Once validated, mathematical models can be used for making predictions and testing hypotheses, thus suggesting potential therapeutic targets. This PhD thesis aims to apply computational cardiac modelling of human single cell action potential (AP) to three clinical scenarios, in order to gain new insights into the ionic mechanisms involved in the electrophysiological changes observed in vitro and/or in vivo. The first context is blood electrolyte variations, which may occur in patients due to different pathologies and/or therapies. In particular, we focused on extracellular Ca2+ and its effect on the AP duration (APD). The second context is haemodialysis (HD) therapy: in addition to blood electrolyte variations, patients undergo a lot of other different changes during HD, e.g. heart rate, cell volume, pH, and sympatho-vagal balance. The third context is human hypertrophic cardiomyopathy (HCM), a genetic disorder characterised by an increased arrhythmic risk, and still lacking a specific pharmacological treatment.

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In the CNS, myelinating oligodendrocytes and axons form a functional unit based on intimate cell-cell interactions. In addition to axonal insulation serving to increase the conduction velocity of electrical impulses, oligodendrocytes provide trophic support to neurons essential for the long-term functional integrity of axons. The glial signals maintaining axonal functions are just at the beginning to become uncovered. Yet, their determination is highly relevant for all types of demyelinating diseases, where lack of glial support significantly contributes to pathology. rnThe present PhD thesis uncovers exosomes as a novel signaling entity in the CNS by which cargo can be transferred from oligodendrocytes to neurons. Exosomes are small membranous vesicles of endocytic origin, which are released by almost every cell type and have been implicated in intercellular communication. Oligodendrocytes secrete exosomes containing a distinct set of proteins as well as mRNA and microRNA. Intriguingly, oligodendroglial exosome release is stimulated by the neurotransmitter glutamate indicating that neuronal electrical activity controls glial exosome release. In this study, the role of exosomes in neuron-glia communication and their implications on glial support was examined. Cortical neurons internalized and accumulated oligodendroglial exosomes in the neuronal cell soma in a time-dependent manner. Moreover, uptake occurred likewise at the somatodendritic and axonal compartment of the neurons via dynamin and clathrin dependent endocytosis. Intriguingly, neuronal internalization of exosomes resulted in functional retrieval of exosomal cargo in vitro and in vivo upon stereotactic injection of Cre recombinase bearing exosomes. Functional recovery of Cre recombinase from transferred exosomes was indicated by acquired reporter recombination in the target cell. Electrophysiological analysis showed an increased firing rate in neurons exposed to oligodendroglial exosomes. Moreover, microarray analysis revealed differentially expressed genes after exosome treatment, indicating functional implications on neuronal gene expression and activity. rnTaken together, the results of this PhD thesis represent a proof of principle for exosome transmission from oligodendrocytes to neurons suggesting a new route of horizontal transfer in the CNS.rn

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Removal of miniplates is a controversial topic in oral and maxillofacial surgery. Originally, miniplates were designed to be removed on completion of bone healing. The introduction of low profile titanium miniplates has led to the routine removal of miniplates becoming comparatively rare in many parts of the world. Few studies have investigated the reasons for non-routine removal of miniplates and the factors that affect osteosynthesis after osteotomy in large numbers of patients. The aim of the present study was to investigate complications related to osteosynthesis after bilateral sagittal split osteotomy (BSSO) in a large number (n=153) of patients. In addition to the rates of removal, emphasis was placed on investigating the reasons and risk factors associated with symptomatic miniplate removal. The rate of plate removal per patient was 18.6%, the corresponding rate per plate being 18.2%. Reasons for plate removal included plate-related complications in 16 patients and subjective discomfort in 13 patients. Half of the plates were removed during the first postoperative year. Smoking was the only significant predictor for plate removal. Patients undergoing orthognathic surgery should be screened with regard to smoking and encouraged and assisted to cease smoking, at least perioperatively.

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Objective: Significant others are central to patients' experience and management of their cancer illness. Building on our validation of the Distress Thermometer (DT) for family members, this investigation examines individual and collective distress in a sample of cancer patients and their matched partners, accounting for the aspects of gender and role. Method: Questionnaires including the DT were completed by a heterogeneous sample of 224 couples taking part in a multisite study. Results: Our investigation showed that male patients (34.2%), female patients (31.9%), and male partners (29.1%) exhibited very similar levels of distress, while female partners (50.5%) exhibited much higher levels of distress according to the DT. At the dyad level just over half the total sample contained at least one individual reporting significant levels of distress. Among dyads with at least one distressed person, the proportion of dyads where both individuals reported distress was greatest (23.6%). Gender and role analyses revealed that males and females were not equally distributed among the four categories of dyads (i.e. dyads with no distress; dyads where solely the patient or dyads where solely the partner is distressed; dyads where both are distressed). Conclusion: A remarkable number of dyads reported distress in one or both partners. Diverse patterns of distress within dyads suggest varying risks of psychosocial strain. Screening patients' partners in addition to patients themselves may enable earlier identification of risk settings. The support offered to either member of such dyads should account for their role- and gender-specific needs. Copyright © 2010 John Wiley ; Sons, Ltd.

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Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. The present study evaluated the effect of atorvastatin added to interferon beta-1b in multiple sclerosis (MS) in a multicenter, randomized, parallel-group, rater-blinded study performed in eight Swiss hospitals. Seventy-seven patients with relapsing-remitting MS started interferon beta-1b every other day. After 3 months, they were randomized 1:1 to receive atorvastatin 40 mg/day or not in addition to interferon beta-1b until month 15. The primary endpoint was the proportion of patients with new lesions on T2-weighted images at month 15 compared to baseline at month three. At study end, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.14; 95 % CI 0.36-3.56; p = 0.81). All predefined secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of new Gd-enhancing lesions on T1-weighted images, total brain volume, volume of grey matter, volume of white matter, EDSS, MSFC, relapse rate, time to first relapse, number of relapse-free patients and neutralizing antibodies did not show any significant differences (all p values >0.1). Transient elevations of liver enzymes were more frequent with atorvastatin (p = 0.02). In conclusion, atorvastatin 40 mg/day in addition to interferon beta-1b did not have a beneficial effect on relapsing-remitting MS compared to interferon beta-1b monotherapy over a 12-month period.

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The purpose of this research project is to continue exploring the Montandon Long-Term Hydrologic Research Site(LTHR) by using multiple geophysical methods to obtain more accurate and precise information regarding subsurface hydrologic properties of a local gravel ridge,which are important to both the health of surrounding ecosystems and local agriculture. Through using non-invasive geophysical methods such as seismic refraction, Direct Current resistivity and ground penetrating radar (GPR) instead of invasive methods such as boreholedrilling which displace sediment and may alter water flow, data collection is less likely to bias the data itself. In addition to imaging the gravel ridge subsurface, another important researchpurpose is to observe how both water table elevation and the moisture gradient (moisture content of the unsaturated zone) change over a seasonal time period and directly after storm events. The combination of three types of data collection allows the strengths of each method combine together and provide a relatively strongly supported conclusions compared to previous research. Precipitation and geophysical data suggest that an overall increase in precipitation during the summer months causes a sharp decrease in subsurface resistivity within the unsaturated zone. GPR velocity data indicate significant immediate increase in moisture content within the shallow vadose zone (< 1m), suggesting that rain water was infiltrating into the shallow subsurface. Furthermore, the combination of resistivity and GPR results suggest that the decreased resistivity within the shallow layers is due to increased ion content within groundwater. This is unexpected as rainwater is assumed to have a DC resistivity value of 3.33*105 ohm-m. These results may suggest that ions within the sediment must beincorporated into the infiltrating water.

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The inflammatory response is a critical component of ischemic stroke. In addition to its physiological role, the mechanisms behind transendothelial recruitment of immune cells also offer a unique therapeutic opportunity for translational stem cell therapies. Recent reports have demonstrated homing of neural stem cells (NSC) into the injured brain areas after intravascular delivery. However, the mechanisms underlying the process of transendothelial recruitment remain largely unknown. Here we describe the critical role of the chemokine CCL2 and its receptor CCR2 in targeted homing of NSC after ischemia.

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Pulmonary disease is the most important cause of morbidity and mortality in cystic fibrosis (CF). Most patients with CF die from respiratory failure with extensive airway destruction. Airway remodelling, defined as structural airway wall changes, begins early in life in CF but the sequence of remodelling events in the disease process is poorly understood. Airway remodelling in CF has traditionally been thought to be solely the consequence of repeated cycles of inflammation and infection. However, new evidence obtained from developmental, physiological and histopathological studies suggests that there might instead be multiple mechanisms leading to airway remodelling in CF including (1) changes related to infection and inflammation; (2) changes specific to CF as a result of CF transmembrane conductance regulator (CFTR) dysfunction in the airway wall, independent of infection and inflammation; and (3) protective responses to (1) and/or (2). Recent advances in bronchoscopic techniques have allowed airway mucosal (endobronchial) biopsies to be taken in children and even infants. Endobronchial biopsy studies may provide insight into the role and relative contribution of the different mechanisms of airway remodelling in CF, with the main limitation that they assess only changes in proximal large airways and not in peripheral small airways from where CF disease is thought to originate. Findings from biopsy studies could encourage the development of novel therapeutic strategies targeting structural changes in addition to infection and inflammation.

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Ocean acidification might reduce the ability of calcifying plankton to produce and maintain their shells of calcite, or of aragonite, the more soluble form of CaCO3. In addition to possibly large biological impacts, reduced CaCO3 production corresponds to a negative feedback on atmospheric CO2. In order to explore the sensitivity of the ocean carbon cycle to increasing concentrations of atmospheric CO2, we use the new biogeochemical Bern3D/PISCES model. The model reproduces the large scale distributions of biogeochemical tracers. With a range of sensitivity studies, we explore the effect of (i) using different parameterizations of CaCO3 production fitted to available laboratory and field experiments, of (ii) letting calcite and aragonite be produced by auto- and heterotrophic plankton groups, and of (iii) using carbon emissions from the range of the most recent IPCC Representative Concentration Pathways (RCP). Under a high-emission scenario, the CaCO3 production of all the model versions decreases from ~1 Pg C yr−1 to between 0.36 and 0.82 Pg C yr−1 by the year 2100. The changes in CaCO3 production and dissolution resulting from ocean acidification provide only a small feedback on atmospheric CO2 of −1 to −11 ppm by the year 2100, despite the wide range of parameterizations, model versions and scenarios included in our study. A potential upper limit of the CO2-calcification/dissolution feedback of −30 ppm by the year 2100 is computed by setting calcification to zero after 2000 in a high 21st century emission scenario. The similarity of feedback estimates yielded by the model version with calcite produced by nanophytoplankton and the one with calcite, respectively aragonite produced by mesozooplankton suggests that expending biogeochemical models to calcifying zooplankton might not be needed to simulate biogeochemical impacts on the marine carbonate cycle. The changes in saturation state confirm previous studies indicating that future anthropogenic CO2 emissions may lead to irreversible changes in ΩA for several centuries. Furthermore, due to the long-term changes in the deep ocean, the ratio of open water CaCO3 dissolution to production stabilizes by the year 2500 at a value that is 30–50% higher than at pre-industrial times when carbon emissions are set to zero after 2100.

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Trypanosoma brucei is the causative agent of human African sleeping sickness and Nagana in cattle. In addition to being an important pathogen T. brucei has developed into a model system in cell biology.

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Utilization of biogas can provide a source of renewable energy in both heat and power generation. Combustion of biogas in land-based gas turbines for power generation is a promising approach to reducing greenhouse gases and US dependence on foreign-source fossil fuels. Biogas is a byproduct from the decomposition of organic matter and consists primarily of CH4 and large amounts of CO2. The focus of this research was to design a combustion device and investigate the effects of increasing levels of CO2 addition to the combustion of pure CH4 with air. Using an atmospheric-pressure, swirl-stabilized dump combustor, emissions data and flame stability limitations were measured and analyzed. In particular, CO2, CO, and NOx emissions were the main focus of the combustion products. Additionally, the occurrence of lean blowout and combustion pressure oscillations, which impose significant limitations in operation ranges for actual gas turbines, was observed. Preliminary kinetic and equilibrium modeling was performed using Cantera and CEA for the CH4/CO2/Air combustion systems to analyze the effect of CO2 upon adiabatic flame temperature and emission levels. The numerical and experimental results show similar dependence of emissions on equivalence ratio, CO2 addition, inlet air temperature, and combustor residence time. (C) 2014 Elsevier Ltd. All rights reserved.

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Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H (CTSH) and Tumor necrosis factor (ligand) superfamily member 4 (TNFSF4, also called OX40L), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease.

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BACKGROUND: Several approaches can be used to determine the order of loci on chromosomes and hence develop maps of the genome. However, all mapping approaches are prone to errors either arising from technical deficiencies or lack of statistical support to distinguish between alternative orders of loci. The accuracy of the genome maps could be improved, in principle, if information from different sources was combined to produce integrated maps. The publicly available bovine genomic sequence assembly with 6x coverage (Btau_2.0) is based on whole genome shotgun sequence data and limited mapping data however, it is recognised that this assembly is a draft that contains errors. Correcting the sequence assembly requires extensive additional mapping information to improve the reliability of the ordering of sequence scaffolds on chromosomes. The radiation hybrid (RH) map described here has been contributed to the international sequencing project to aid this process. RESULTS: An RH map for the 30 bovine chromosomes is presented. The map was built using the Roslin 3000-rad RH panel (BovGen RH map) and contains 3966 markers including 2473 new loci in addition to 262 amplified fragment-length polymorphisms (AFLP) and 1231 markers previously published with the first generation RH map. Sequences of the mapped loci were aligned with published bovine genome maps to identify inconsistencies. In addition to differences in the order of loci, several cases were observed where the chromosomal assignment of loci differed between maps. All the chromosome maps were aligned with the current 6x bovine assembly (Btau_2.0) and 2898 loci were unambiguously located in the bovine sequence. The order of loci on the RH map for BTA 5, 7, 16, 22, 25 and 29 differed substantially from the assembled bovine sequence. From the 2898 loci unambiguously identified in the bovine sequence assembly, 131 mapped to different chromosomes in the BovGen RH map. CONCLUSION: Alignment of the BovGen RH map with other published RH and genetic maps showed higher consistency in marker order and chromosome assignment than with the current 6x sequence assembly. This suggests that the bovine sequence assembly could be significantly improved by incorporating additional independent mapping information.