555 resultados para swd: Imam-bara
Resumo:
Ataulla Bajazitov (1846-1911) fulfilled a social double role by serving his Tatar community in St. Petersburg as imam and the Russian state as military Muslim ‘cleric’, translator and teacher. By founding Russia’s first monolingual Tatar newspaper, initiating St. Petersburg’s first Friday mosque and presenting scriptural and rational arguments for the compatibility of Islam and the modern Civilization to a Russian-speaking public as early as 1883, he has been a pioneer among the Muslims in Russia in several respects. In contrast though to similar activities of his Russian contemporary, the Krim Tatar Ismail Gasprinskii (1851-1914), Bajazitov’s endeavours have remained almost unnoticed in Western scholarship. Also in Tatarstan, his books have been only recently reprinted. The present study analyzes Bajazitov’s three monographs written in Russian, namely A Response to Ernest Renan’s lecture “Islam and Science” (1883), The Relationship of Islam towards Science and People of Different Faith (1887) and Islam and Progress (1898). There, he exposes many positions that around that time started to become key arguments of Muslim reformers in the Near East for the progressivness of Islam. The study takes also into account reactions to Bajazitov’s monographs by Russian officers in Tashkent who tried to demonstrate the backwardness of Islam, especially Nikolai Petrovič Ostroumov’s (1846-1930) response in his book entitled Quran and Progress – On the intellectual awakening of today’s Russian Muslims (1901/1903).
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BACKGROUND A single non-invasive gene expression profiling (GEP) test (AlloMap®) is often used to discriminate if a heart transplant recipient is at a low risk of acute cellular rejection at time of testing. In a randomized trial, use of the test (a GEP score from 0-40) has been shown to be non-inferior to a routine endomyocardial biopsy for surveillance after heart transplantation in selected low-risk patients with respect to clinical outcomes. Recently, it was suggested that the within-patient variability of consecutive GEP scores may be used to independently predict future clinical events; however, future studies were recommended. Here we performed an analysis of an independent patient population to determine the prognostic utility of within-patient variability of GEP scores in predicting future clinical events. METHODS We defined the GEP score variability as the standard deviation of four GEP scores collected ≥315 days post-transplantation. Of the 737 patients from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) II trial, 36 were assigned to the composite event group (death, re-transplantation or graft failure ≥315 days post-transplantation and within 3 years of the final GEP test) and 55 were assigned to the control group (non-event patients). In this case-controlled study, the performance of GEP score variability to predict future events was evaluated by the area under the receiver operator characteristics curve (AUC ROC). The negative predictive values (NPV) and positive predictive values (PPV) including 95 % confidence intervals (CI) of GEP score variability were calculated. RESULTS The estimated prevalence of events was 17 %. Events occurred at a median of 391 (inter-quartile range 376) days after the final GEP test. The GEP variability AUC ROC for the prediction of a composite event was 0.72 (95 % CI 0.6-0.8). The NPV for GEP score variability of 0.6 was 97 % (95 % CI 91.4-100.0); the PPV for GEP score variability of 1.5 was 35.4 % (95 % CI 13.5-75.8). CONCLUSION In heart transplant recipients, a GEP score variability may be used to predict the probability that a composite event will occur within 3 years after the last GEP score. TRIAL REGISTRATION Clinicaltrials.gov identifier NCT00761787.
Resumo:
AIMS A non-invasive gene-expression profiling (GEP) test for rejection surveillance of heart transplant recipients originated in the USA. A European-based study, Cardiac Allograft Rejection Gene Expression Observational II Study (CARGO II), was conducted to further clinically validate the GEP test performance. METHODS AND RESULTS Blood samples for GEP testing (AlloMap(®), CareDx, Brisbane, CA, USA) were collected during post-transplant surveillance. The reference standard for rejection status was based on histopathology grading of tissue from endomyocardial biopsy. The area under the receiver operating characteristic curve (AUC-ROC), negative (NPVs), and positive predictive values (PPVs) for the GEP scores (range 0-39) were computed. Considering the GEP score of 34 as a cut-off (>6 months post-transplantation), 95.5% (381/399) of GEP tests were true negatives, 4.5% (18/399) were false negatives, 10.2% (6/59) were true positives, and 89.8% (53/59) were false positives. Based on 938 paired biopsies, the GEP test score AUC-ROC for distinguishing ≥3A rejection was 0.70 and 0.69 for ≥2-6 and >6 months post-transplantation, respectively. Depending on the chosen threshold score, the NPV and PPV range from 98.1 to 100% and 2.0 to 4.7%, respectively. CONCLUSION For ≥2-6 and >6 months post-transplantation, CARGO II GEP score performance (AUC-ROC = 0.70 and 0.69) is similar to the CARGO study results (AUC-ROC = 0.71 and 0.67). The low prevalence of ACR contributes to the high NPV and limited PPV of GEP testing. The choice of threshold score for practical use of GEP testing should consider overall clinical assessment of the patient's baseline risk for rejection.
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BACKGROUND AIMS The diverse phenotypic changes and clinical and economic disadvantages associated with the monolayer expansion of bone marrow-derived mesenchymal stromal cells (MSCs) have focused attention on the development of one-step intraoperative cells therapies and homing strategies. The mononuclear cell fraction of bone marrow, inclusive of discrete stem cell populations, is not well characterized, and we currently lack suitable cell culture systems in which to culture and investigate the behavior of these cells. METHODS Human bone marrow-derived mononuclear cells were cultured within fibrin for 2 weeks with or without fibroblast growth factor-2 supplementation. DNA content and cell viability of enzymatically retrieved cells were determined at days 7 and 14. Cell surface marker profiling and cell cycle analysis were performed by means of multi-color flow cytometry and a 5-ethynyl-2'-deoxyuridine incorporation assay, respectively. RESULTS Total mononuclear cell fractions, isolated from whole human bone marrow, was successfully cultured in fibrin gels for up to 14 days under static conditions. Discrete niche cell populations including MSCs, pericytes and hematopoietic stem cells were maintained in relative quiescence for 7 days in proportions similar to that in freshly isolated cells. Colony-forming unit efficiency of enzymatically retrieved MSCs was significantly higher at day 14 compared to day 0; and in accordance with previously published works, it was fibroblast growth factor-2-dependant. CONCLUSIONS Fibrin gels provide a simple, novel system in which to culture and study the complete fraction of bone marrow-derived mononuclear cells and may support the development of improved bone marrow cell-based therapies.
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Translation termination as a result of premature nonsense codon-incorporation in a RNA transcript can lead to the production of aberrant proteins with gain-of-function or dominant negative properties that could have deletrious effects on the cell. T-cell Receptor (TCR) genes acquire premature termination codons two-thirds of the time as a result of the error-prone programmed rearrangement events that normally occur during T-cell development. My studies have focused on the fate of TCR precursor mRNAs in response to in-frame nonsense mutations. ^ Previous published studies from our laboratory have shown that TCR precursor mRNAs are subject to nonsense mediated upregulation of pre-mRNA (NMUP). In this dissertation, I performed substitution and deletion analysis to characterize specific regions of TCR which are required to elicit NMUP. I performed frame- and factor-dependence studies to determine its relationship with other nonsense codon induced responses using several approaches including (i) translation dependence studies (ii) deletion and mutational analysis, as well as (iii) siRNA mediated knockdown of proteins involved. I also addressed the underlying molecular mechanism for this pre-mRNA upregulation by (i) RNA half-life studies using a c-fos inducible promoter, and (ii) a variety of assays to determine pre-mRNA splicing efficiency. ^ Using these approaches, I have identified a region of TCR that is both necessary and sufficient to elicit (NMUP). I have also found that neither cytoplasmic translation machinery nor the protein UPF1 are involved in eliciting this nuclear event. I have shown that the NMUP can be induced not only by nonsense and frameshift mutations, but also missense mutations that disrupt a cis splicing element in the exon that contains the mutation. However, the effect of nonsense mutations on pre-mRNA is unique and distinguishable from that of missense mutations in that nonsense mutations can upregulate pre-mRNA in a frame-dependent manner. Lastly, I provide evidence that NMUP occurs by a mechanism in which nonsense mutations inhibit the splicing of introns. In summary, I have found that TCR precursor mRNAs are subject to multiple forces involving both RNA splicing and translation that can either increase or decrease the levels of these precursor mRNAs. ^
Neocortical hyperexcitability defect in a mutant mouse model of spike-wave epilepsy, {\it stargazer}
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Single-locus mutations in mice can express epileptic phenotypes and provide critical insights into the naturally occurring defects that alter excitability and mediate synchronization in the central nervous system (CNS). One such recessive mutation (on chromosome (Chr) 15), stargazer(stg/stg) expresses frequent bilateral 6-7 cycles per second (c/sec) spike-wave seizures associated with behavioral arrest, and provides a valuable opportunity to examine the inherited lesion associated with spike-wave synchronization.^ The existence of distinct and heterogeneous defects mediating spike-wave discharge (SWD) generation has been demonstrated by the presence of multiple genetic loci expressing generalized spike-wave activity and the differential effects of pharmacological agents on SWDs in different spike-wave epilepsy models. Attempts at understanding the different basic mechanisms underlying spike-wave synchronization have focused on $\gamma$-aminobutyric acid (GABA) receptor-, low threshold T-type Ca$\sp{2+}$ channel-, and N-methyl-D-aspartate receptor (NMDA-R)-mediated transmission. It is believed that defects in these modes of transmission can mediate the conversion of normal oscillations in a trisynaptic circuit, which includes the neocortex, reticular nucleus and thalamus, into spike-wave activity. However, the underlying lesions involved in spike-wave synchronization have not been clearly identified.^ The purpose of this research project was to locate and characterize a distinct neuronal hyperexcitability defect favoring spike-wave synchronization in the stargazer brain. One experimental approach for anatomically locating areas of synchronization and hyperexcitability involved an attempt to map patterns of hypersynchronous activity with antibodies to activity-induced proteins.^ A second approach to characterizing the neuronal defect involved examining the neuronal responses in the mutant following application of pharmacological agents with well known sites of action.^ In order to test the hypothesis that an NMDA receptor mediated hyperexcitability defect exists in stargazer neocortex, extracellular field recordings were used to examine the effects of CPP and MK-801 on coronal neocortical brain slices of stargazer and wild type perfused with 0 Mg$\sp{2+}$ artificial cerebral spinal fluid (aCSF).^ To study how NMDA receptor antagonists might promote increased excitability in stargazer neocortex, two basic hypotheses were tested: (1) NMDA receptor antagonists directly activate deep layer principal pyramidal cells in the neocortex of stargazer, presumably by opening NMDA receptor channels altered by the stg mutation; and (2) NMDA receptor antagonists disinhibit the neocortical network by blocking recurrent excitatory synaptic inputs onto inhibitory interneurons in the deep layers of stargazer neocortex.^ In order to test whether CPP might disinhibit the 0 Mg$\sp{2+}$ bursting network in the mutant by acting on inhibitory interneurons, the inhibitory inputs were pharmacologically removed by application of GABA receptor antagonists to the cortical network, and the effects of CPP under 0 Mg$\sp{2+}$aCSF perfusion in layer V of stg/stg were then compared with those found in +/+ neocortex using in vitro extracellular field recordings. (Abstract shortened by UMI.) ^
Resumo:
An integrated instrument package for measuring and understanding the surface radiation budget of sea ice is presented, along with results from its first deployment. The setup simultaneously measures broadband fluxes of upwelling and downwelling terrestrial and solar radiation (four components separately), spectral fluxes of incident and reflected solar radiation, and supporting data such as air temperature and humidity, surface temperature, and location (GPS), in addition to photographing the sky and observed surface during each measurement. The instruments are mounted on a small sled, allowing measurements of the radiation budget to be made at many locations in the study area to see the effect of small-scale surface processes on the large-scale radiation budget. Such observations have many applications, from calibration and validation of remote sensing products to improving our understanding of surface processes that affect atmosphere-snow-ice interactions and drive feedbacks, ultimately leading to the potential to improve climate modelling of ice-covered regions of the ocean. The photographs, spectral data, and other observations allow for improved analysis of the broadband data. An example of this is shown by using the observations made during a partly cloudy day, which show erratic variations due to passing clouds, and creating a careful estimate of what the radiation budget along the observed line would have been under uniform sky conditions, clear or overcast. Other data from the setup's first deployment, in June 2011 on fast ice near Point Barrow, Alaska, are also shown; these illustrate the rapid changes of the radiation budget during a cold period that led to refreezing and new snow well into the melt season.
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In the Arctic, under-ice primary production is limited to summer months and is not only restricted by ice thickness and snow cover but also by the stratification of the water column, which constrains nutrient supply for algal growth. RV Polarstern visited the ice-covered Eastern Central basins between 82 to 89°N and 30 to 130°E in summer 2012 when Arctic sea ice declined to a record minimum. During this cruise, we observed a widespread deposition of ice algal biomass of on average 9 g C per m**2 to the deep-sea floor of the Central Arctic basins. Data from this cruise will contribute to assessing the impact of current climate change on Arctic productivity, biodiversity, and ecological function.
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This dataset present result from the DFG- funded Arctic-Turbulence-Experiment (ARCTEX-2006) performed by the University of Bayreuth on the island of Svalbard, Norway, during the winter/spring transition 2006. From May 5 to May 19, 2006 turbulent flux and meteorological measurements were performed on the monitoring field near Ny-Ålesund, at 78°55'24'' N, 11°55'15'' E Kongsfjord, Svalbard (Spitsbergen), Norway. The ARCTEX-2006 campaign site was located about 200 m southeast of the settlement on flat snow covered tundra, 11 m to 14 m above sea level. The permanent sites used for this study consisted of the 10 m meteorological tower of the Alfred Wegener Institute for Polar- and Marine Research (AWI), the international standardized radiation measurement site of the Baseline Surface Radiation Network (BSRN), the radiosonde launch site and the AWI tethered balloon launch sites. The temporary sites - set up by the University of Bayreuth - were a 6 m meteorological gradient tower, an eddy-flux measurement complex (EF), and a laser-scintillometer section (SLS). A quality assessment and data correction was applied to detect and eliminate specific measurement errors common at a high arctic landscape. In addition, the quality checked sensible heat flux measurements are compared with bulk aerodynamic formulas that are widely used in atmosphere-ocean/land-ice models for polar regions as described in Ebert and Curry (1993, doi:10.1029/93JC00656) and Launiainen and Cheng (1995). These parameterization approaches easily allow estimation of the turbulent surface fluxes from routine meteorological measurements. The data show: - the role of the intermittency of the turbulent atmospheric fluctuation of momentum and scalars, - the existence of a disturbed vertical temperature profile (sharp inversion layer) close to the surface, - the relevance of possible free convection events for the snow or ice melt in the Arctic spring at Svalbard, and - the relevance of meso-scale atmospheric circulation pattern and air-mass advection for the near-surface turbulent heat exchange in the Arctic spring at Svalbard. Recommendations and improvements regarding the interpretation of eddy-flux and laser-scintillometer data as well as the arrangement of the instrumentation under polar distinct exchange conditions and (extreme) weather situations could be derived.
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Basal melt of ice shelves may lead to an accumulation of disc-shaped ice platelets underneath nearby sea ice, to form a sub-ice platelet layer. Here we present the seasonal cycle of sea ice attached to the Ekström Ice Shelf, Antarctica, and the underlying platelet layer in 2012. Ice platelets emerged from the cavity and interacted with the fast-ice cover of Atka Bay as early as June. Episodic accumulations throughout winter and spring led to an average platelet-layer thickness of 4 m by December 2012, with local maxima of up to 10 m. The additional buoyancy partly prevented surface flooding and snow-ice formation, despite a thick snow cover. Subsequent thinning of the platelet layer from December onwards was associated with an inflow of warm surface water. The combination of model studies with observed fast-ice thickness revealed an average ice-volume fraction in the platelet layer of 0.25 +/- 0.1. We found that nearly half of the combined solid sea-ice and ice-platelet volume in this area is generated by heat transfer to the ocean rather than to the atmosphere. The total ice-platelet volume underlying Atka Bay fast ice was equivalent to more than one-fifth of the annual basal melt volume under the Ekström Ice Shelf.