The SWISS‐MODEL Repository is a database of annotated three‐dimensional comparative protein structure models generated by the fully automated homology‐modelling pipeline SWISS‐MODEL. The Repository ...currently contains about 300 000 three‐dimensional models for sequences from the Swiss‐Prot and TrEMBL databases. The content of the Repository is updated on a regular basis incorporating new sequences, taking advantage of new template structures becoming available and reflecting improvements in the underlying modelling algorithms. Each entry consists of one or more three‐dimensional protein models, the superposed template structures, the alignments on which the models are based, a summary of the modelling process and a force field based quality assessment. The SWISS‐MODEL Repository can be queried via an interactive website at http://swissmodel.expasy. org/repository/. Annotation and cross‐linking of the models with other databases, e.g. Swiss‐Prot on the ExPASy server, allow for seamless navigation between protein sequence and structure information. The aim of the SWISS‐MODEL Repository is to provide access to an up‐to‐date collection of annotated three‐dimensional protein models generated by automated homology modelling, bridging the gap between sequence and structure databases.
Focal segmental glomerulosclerosis (FSGS) is a glomerular disease characterized by proteinuria, frequent progression to end‐stage renal disease, and recurrence after kidney transplantation in ∼25% of ...patients, which negatively impacts long‐term allograft survival. Experimental studies suggest that abnormalities in T and, possibly, B cells may represent one initial pathogenic trigger, leading to podocyte injury and progressive loss. New data also support the existence of circulating permeability factors able to damage the podocytes, but no single molecule has been consistently identified as the causal pathogenic element in FSGS recurrence. Unfortunately, major progress from mechanistic studies has not translated into substantial advancements in patient treatment, with plasmapheresis (PP) and high doses of cyclosporine (CsA) remaining the mainstays of therapy. Despite consistent experimental and clinical evidence that treatment of proteinuria slows renal function decline in proteinuric nephropathies, maximal use of antiproteinuric agents such as renin angiotensin system antagonists is not routine in the management of FSGS recurrence. More recently, encouraging results have been reported with anti‐CD20 depleting antibody rituximab, but further studies are needed to establish its safety/efficacy profile.
The authors review recent advancements in understanding the pathophysiology of focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplant and critically discuss the current therapeutic options.
Energy Resources and Global Development Chow, Jeffrey; Kopp, Raymond J.; Portney, Paul R.
Science (American Association for the Advancement of Science),
11/2003, Letnik:
302, Številka:
5650
Journal Article
Recenzirano
In order to address the economic and environmental consequences of our global energy system, we consider the availability and consumption of energy resources. Problems arise from our dependence on ...combustible fuels, the environmental risks associated with their extraction, and the environmental damage caused by their emissions. Yet no primary energy source, be it renewable or nonrenewable, is free of environmental or economic limitations. As developed and developing economies continue to grow, conversion to and adoption of environmentally benign energy technology will depend on political and economic realities.
In this paper a theoretical analysis of crack initiation and propagation conditions in a bonded specimen loaded under pure mode II condition is proposed. The end-loaded-split (ELS) test response is ...evaluated using a semi-analytical model where the adherends are modeled as two deformable Timoshenko beams and considering non-linear behaviour of the adhesive. Bi-linear elastic-plastic, elastic-softening and trapezoidal adhesive layer shear behaviours (ALSBs) have been implemented and studied. From the results we observed that the load–displacement curve does not permit accurate evaluation of the adhesive layer shear behaviour. An alternative procedure consisting of analyzing the strain energy release rate versus shear displacement at the crack tip is proposed for data reduction of ELS test results.
The aim of this study is to evaluate the temperature effect on the mechanical properties and damage mechanisms of a Glass/Elium 150 laminate composite. Quasi-static indentation tests are carried out ...at different temperatures to highlight the temperature dependency of different parameters of the samples (stiffness, maximum load, stored elastic energy, and applied energy). The different damage mechanisms involved in the collapse of the composite are observed at the macro-, meso-, and micro-scopic scales using optical and scanning electron microscopy. The influence of temperature on these damage mechanisms is discussed based on post-mortem observations. It has been highlighted that the kind and the severity of damage are strongly temperature dependent. Below 20℃, fiber breakage, strand failure, intra- and inter-laminar crack propagation are identified. At 60℃, plastic flow of the polymer matrix is observed, which modifies micro-crack propagation at the fiber/matrix interface. Above 90℃, only intra-laminar micro-cracking occurs. To conclude, based on all these observations the kinetics of damage appearance are discussed.
Objectif Le syndrôme MODY5 (Maturity Onset Diabetes of the Young 5) associé à des mutations hétérozygotes du gène HNF1B (Hepatocyte Nuclear Factor 1), est caractérisé en particulier par un diabète et ...une hypoplasie pancréatique. Nous avons précédemment montré que l’invalidation d’Hnf1B chez la souris conduit notamment à une agénésie du pancréas, associée à un défaut de régionalisation de l’intestin primitif. L’objectif de cette étude est d’étudier les fonctions du facteur de transcription HNF1B au cours du développement pancréatique. Matériels et méthodes Nous avons généré une délétion d’HNF1B spécifiquement dans les progéniteurs pancréatiques par invalidation conditionnelle chez la souris, en utilisant une lignée Hnf1b floxée et les lignées Pdx1-Cre et Sox9-CreERT2. Résultats Nous avons observé une hypoplasie pancréatique majeure (réduction de ∼90 % de la masse du pancréas à E18,5), chez les mutants (Pdx1-Cre+/- ; Hnf1bfl/-) comparé aux contrôles (Pdx1-Cre-/- ; Hnf1bfl/-), engendrant une létalité périnatale. Les analyses histologiques et immunohistochimiques révèlent une diminution importante des acinis (∼75 % à E16,5), des canaux kystiques, et une absence de cellules endocrines. Ceci est corrélé avec une diminution drastique de l’expression de marqueurs des lignages exocrines et endocrines par Q-PCR. En particulier, nous avons observé une réduction de ∼85 % de l’expression de NGN3, et découvert NGN3 comme cible directe d’HNF1B par ChIP. Les progéniteurs présentent une diminution de ∼20 % de la prolifération et nos analyses par Q-PCR et ChIP montrent qu’HNF1B est impliqué dans la régulation de la voie Notch. Conclusion Nos résultats démontrent qu’HNF1B est requis pour la prolifération et la survie des progéniteurs pancréatiques, pour la morphogenèse des canaux et pour l’induction des précurseurs endocrines. Notre étude révèle de nouvelles régulations dans le réseau qui contrôle l’organogenèse du pancréas, ce qui est important pour mieux comprendre la maladie MODY5 et contribuer à de nouveaux traitements par modulation de l’activité d’HNF1B ou de ses cibles.
In this paper, the flattened disk Brazilian test was used to evaluate the critical fracture parameter of a pharmaceutical tablet made of compressed anhydrous lactose powder. Following previous works, ...the energy release rate function was build thanks to experimental tests and numerical simulations. During the experimental tests, a high speed camera was used to capture the crack tip location during the dynamic propagation and Rapid Crack Propagation mechanisms were observed. A numerical analysis was thus used to evaluate the dynamic correction factor needed to take into account the inertia effects due to the crack tip velocity. The results were then compared to those obtained with the classical analytic relation related to a crack propagation in a semi-infinite plate. After giving a range of fracture energy for the material, the necessity to take into account inertia effects in the estimate of the fracture energy of the material was finally discussed in the case of the Brazilian test.
OBJECTIVE:To determine the incidence and preventability of medication errors and potential/actual adverse drug events. To evaluate system failures leading to error occurrence.
DESIGN:Prospective, ...direct observation study.
SETTING:Tertiary care academic medical center.
PATIENTS:Patients in a medical/surgical intensive care unit.
INTERVENTIONS:Observers would intervene only in the event that the medication error would cause substantial patient harm or discomfort.
MEASUREMENTS AND MAIN RESULTS:The observers identified 185 incidents during a pilot period and four phases totaling 16.5 days (33 12-hr shifts). Two independent evaluators concluded that 13 of 35 (37%) actual adverse drug events were nonpreventable (i.e., not medication errors). An additional 40 of the remaining 172 medication errors were judged not to be clinically important. Of the 132 medication errors classified as clinically important, 110 (83%) led to potential adverse drug events and 22 (17%) led to actual, preventable adverse drug events. There was one error (i.e., resulting in a potential or actual, preventable adverse drug event) for every five doses of medication administered. The potential adverse drug events mostly occurred in the administration and dispensing stages of the medication use process (34% in each); all of the actual, preventable adverse drug events occurred in the prescribing (77%) and administration (23%) stages. Errors of omission accounted for the majority of potential and actual, preventable adverse drug events (23%), followed by errors due to wrong dose (20%), wrong drug (16%), wrong administration technique (15%), and drug-drug interaction (10%).
CONCLUSIONS:Using a direct observation approach, we found a higher incidence of potential and actual, preventable adverse drug events and an increased ratio of potential to actual, preventable adverse drug events compared with studies that used chart reviews and solicited incident reporting. All of the potential adverse drug events and approximately two thirds of the actual adverse drug events were judged to be preventable. There was one preventable error for every five doses of medication administered; most errors were due to dose omission, wrong dose, wrong drug, wrong technique, or interactions.
The SWISS-MODEL Repository is a database of annotated 3D protein structure models generated by the SWISS-MODEL homology-modelling pipeline. As of September 2005, the repository contained 675 000 ...models for 604 000 different protein sequences of the UniProt database. Regular updates ensure that the content of the repository reflects the current state of sequence and structure databases, integrating new or modified target sequences, and making use of new template structures. Each Repository entry consists of one or more 3D models accompanied by detailed information about the target protein and the model building process: functional annotation, a detailed template selection log, target-template alignment, summary of the model building and model quality assessment. The SWISS-MODEL Repository is freely accessible at http://swissmodel.expasy.org/repository/.
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