599 research outputs found
Зовнішнє незалежне оцінювання з математики як вступний іспит до вищих навчальних закладів
В даній статті мова йде про Зовнішнє незалежне оцінювання як вступний іспит до вищих навчальних закладів. Обговорюється питання ефективності тестування та питання повного відображення знань абітурієнта при складанні іспиту в такій формі.In this article we are talking about external independent testing as entrance examinations to higher educational institutions. The question efektivnosti testing and issue a complete mapping of knowledge entrant at zdachi exam in this form
Structural and functional aspects of the multidrug efflux pump AcrB
The tripartite efflux system AcrA/AcrB/TolC is the main pump in Escherichia coli for the efflux of multiple antibiotics, dyes, bile salts and detergents. The inner membrane component AcrB is central to substrate recognition and energy transduction and acts as a proton/drug antiporter. Recent structural studies show that homotrimeric AcrB can adopt different monomer conformations representing consecutive states in an allosteric functional rotation transport cycle. The conformational changes create an alternate access drug transport tunnel including a hydrophobic substrate binding pocket in one of the cycle intermediate
Structure, mechanism and cooperation of bacterial multidrug transporters.
Cells from all domains of life encode energy-dependent trans-membrane transporters that can expel harmful substances including clinically applied therapeutic agents. As a collective body, these transporters perform as a super-system that confers tolerance to an enormous range of harmful compounds and consequently aid survival in hazardous environments. In the Gram-negative bacteria, some of these transporters serve as energy-transducing components of tripartite assemblies that actively efflux drugs and other harmful compounds, as well as deliver virulence agents across the entire cell envelope. We draw together recent structural and functional data to present the current models for the transport mechanisms for the main classes of multi-drug transporters and their higher-order assemblies.BL and DD are supported by the Medical Research Council (MRC), Human Frontiers Science Program (HFSP), and the Wellcome Trust. Work in the Van Veen lab is supported by the Biotechnology and Biological Sciences Research Council (BBSRC), MRC, HFSP, Royal Society, Society for Antimicrobial Chemotherapy (BSAC), Herchel Smith Foundation, and Commonwealth Trust. Work in the Pos lab is supported by the German Research Foundation (SFB 807, Transport and Communication across Biological Membranes and FOR2251, Adaptation and persistence of the emerging pathogen Acinetobacter baumannii), the DFG-EXC115 (Cluster of Excellence Macromolecular Complexes at the Goethe-University Frankfurt), Innovative Medicines Initiative Joint Undertaking Project Translocation (IMI-Translocation), EU Marie Curie Actions ITN, HFSP and the German-Israeli Foundation (GIF). The SM laboratory is supported by ERATO Murata Lipid Active Structure Project, Japan Science and Technology Agency, the Advanced Research for Medical Products Mining Program of the National Institute of Biomedical Innovation (NIBIO) and HFSP.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.sbi.2015.07.01
Independent position correction on tumor and lymph nodes; consequences for bladder cancer irradiation with two combined IMRT plans
Abstract Background The application of lipiodol injections as markers around bladder tumors combined with the use of CBCT for image guidance enables daily on-line position correction based on the position of the bladder tumor. However, this might introduce the risk of underdosing the pelvic lymph nodes. In this study several correction strategies were compared. Methods For this study set-up errors and tumor displacements for ten complete treatments were generated; both were based on the data of 10 bladder cancer patients. Besides, two IMRT plans were made for 20 patients, one for the elective field and a boost plan for the tumor. For each patient 10 complete treatments were simulated. For each treatment the dose was calculated without position correction (option 1), correction on bony anatomy (option 2), on tumor only (option 3) and separately on bone for the elective field (option 4). For each method we analyzed the D99% for the tumor, bladder and lymph nodes and the V95% for the small intestines, rectum, healthy part of the bladder and femoral heads. Results CTV coverage was significantly lower with options 1 and 2. With option 3 the tumor coverage was not significantly different from the treatment plan. The ΔD99% (D99%, option n - D99%, treatment plan) for option 4 was small, but significant. For the lymph nodes the results from option 1 differed not significantly from the treatment plan. The median ΔD99% of the other options were small, but significant. ΔD99% for PTVbladder was small for options 1, 2 and 4, but decreased up to -8.5 Gy when option 3 was applied. Option 4 is the only method where the difference with the treatment plan never exceeds 2 Gy. The V95% for the rectum, femoral heads and small intestines was small in the treatment plan and this remained so after applying the correction options, indicating that no additional hot spots occurred. Conclusions Applying independent position correction on bone for the elective field and on tumor for the boost separately gives on average the best target coverage, without introducing additional hot spots in the healthy tissue.</p
Purification and Reconstitution of the Glutamate Carrier GltT of the Thermophilic Bacterium Bacillus stearothermophilus
An affinity tag consisting of six adjacent histidine residues followed by an enterokinase cleavage site was genetically engineered at the N-terminus of the glutamate transport protein GltT of the thermophilic bacterium Bacillus stearothermophilus. The fusion protein was expressed in Escherichia coli and shown to transport glutamate. The highest levels of expression were observed in E. coli strain DH5α grown on rich medium. The protein could be purified in a single step by Ni2+-NTA affinity chromatography after solubilization of the cytoplasmic membranes with the detergent Triton X100. Purified GltT was reconstituted in an active state in liposomes prepared from E. coli phospholipids. The protein was reconstituted in detergent-treated preformed liposomes, followed by removal of the detergent with polystyrene beads. Active reconstitution was realized with a wide range of Triton X100 concentrations. Neither the presence of glycerol, phospholipids, nor substrates of the transporter was necessary during the purification and reconstitution procedure to keep the enzyme in an active state. In B. stearothermophilus, GltT translocates glutamate in symport with protons or sodium ions. In membrane vesicles derived from E. coli cells expressing GltT, the Na+ ion dependency seems to be lost, suggesting a role for the lipid environment in the cation specificity. In agreement with the last observation, glutamate transport catalyzed by purified GltT reconstituted in E. coli phospholipid is driven by an electrochemical gradient of H+ but not of Na+.
PO-0935: Correcting diffusion weighted MR images for signal pile-up and distortions near gas pockets
Differential responses of plasmacytoid dendritic cells to influenza virus and distinct viral pathogens.
Plasmacytoid dendritic cells (pDCs) are key components of the innate immune response that are capable of synthesizing and rapidly releasing vast amounts of type I interferons (IFNs), particularly IFN-α. Here we investigated whether pDCs, often regarded as a mere source of IFN, discriminate between various functionally discrete stimuli and to what extent this reflects differences in pDC responses other than IFN-α release. To examine the ability of pDCs to differentially respond to various doses of intact and infectious HIV, hepatitis C virus, and H1N1 influenza virus, whole-genome gene expression analysis, enzyme-linked immunosorbent assays, and flow cytometry were used to investigate pDC responses at the transcriptional, protein, and cellular levels. Our data demonstrate that pDCs respond differentially to various viral stimuli with significant changes in gene expression, including those involved in pDC activation, migration, viral endocytosis, survival, or apoptosis. In some cases, the expression of these genes was induced even at levels comparable to that of IFN-α. Interestingly, we also found that depending on the viral entity and the viral titer used for stimulation, induction of IFN-α gene expression and the actual release of IFN-α are not necessarily temporally coordinated. In addition, our data suggest that high-titer influenza A (H1N1) virus infection can stimulate rapid pDC apoptosis.
IMPORTANCE
Plasmacytoid dendritic cells (pDCs) are key players in the viral immune response. With the host response to viral infection being dependent on specific virus characteristics, a thorough examination and comparison of pDC responses to various viruses at various titers is beneficial for the field of virology. Our study illustrates that pDC infection with influenza virus, HIV, or hepatitis C virus results in a unique and differential response to each virus. These results have implications for future virology research, vaccine development, and virology as a whole
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