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31.
    
Liquid biopsy is a minimally-invasive diagnostic method that may improve access to molecular profiling for non-small cell lung cancer (NSCLC) patients. Although cell-free DNA (cf-DNA) isolation from plasma is the standard liquid biopsy method for detecting DNA mutations in cancer patients, the sensitivity can be highly variable. Vn96 is a peptide with an affinity for both extracellular vesicles (EVs) and circulating cf-DNA. In this study, we evaluated whether peptide-affinity (PA) precipitation of EVs and cf-DNA from NSCLC patient plasma improves the sensitivity of single nucleotide variants (SNVs) detection and compared observed SNVs with those reported in the matched tissue biopsy. NSCLC patient plasma was subjected to either PA precipitation or cell-free methods and total nucleic acid (TNA) was extracted; SNVs were then detected by next-generation sequencing (NGS). PA led to increased recovery of DNA as well as an improvement in NGS sequencing parameters when compared to cf-TNA. Reduced concordance with tissue was observed in PA-TNA (62%) compared to cf-TNA (81%), mainly due to identification of SNVs in PA-TNA that were not observed in tissue. EGFR mutations were detected in PA-TNA with 83% sensitivity and 100% specificity. In conclusion, PA-TNA may improve the detection limits of low-abundance alleles using NGS.  相似文献   
32.
Initiation of an Ab response requires interaction between dendritic cells (DC), T cells, and B cells in a T cell area. We demonstrate that rat DC and B cells form T cell-independent clusters in vitro and in vivo. In vitro clusters form within 1 h and dissociate within 24 to 48 h. Clustering is restricted to resting B cells, is energy, cytoskeleton, and protein kinase C dependent, and is inhibited by anti-LFA-1 but not anti-ICAM-1 mAbs. Spleen and lymph node B cells cluster more strongly than those from lymph or blood, suggesting up-regulation of adhesiveness during transendothelial migration. Bone marrow B cells do not form clusters. DC from spleen and lymph nodes show the most clustering, lymph-borne DC are intermediate, and DC from lamina propria, Peyer's patches, and those grown from bone marrow form the fewest clusters. Clustering is stimulated by cross-linking MHC class II (whole mAb or F(ab')2) on DC or B cells or Thy-1 on DC, but not MHC class I, CD45, or CD44. Stimulation by mAb is energy, cytoskeletal, and protein kinase C dependent, but is not inhibited by anti-LFA-1 mAbs, suggesting involvement of other, unidentified adhesion molecules. We suggest that interactions between DC and B cells will occur regularly during B cell recirculation. Cross-linking of MHC class II-peptide molecules on DC by specific T cells would increase binding avidity, causing retention of Ag-specific B cells on DC long enough for the B cells to process Ag, thereby facilitating cognate interactions between T and B cells.  相似文献   
33.
The effects of a novel prolyl endopeptidase inhibitor (PEP), (S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl)- 1-pyrrolidinecar-boxamide (JTP-4819), on performance of the Morris water maze task and on central cholinergic function were investigated in aged rats. Spatial memory (escape latency, path length, and swimming speed to the platform) was impaired in aged rats performing the Morris water maze task when compared to young rats. Administration of JTP-4819 (1 mg/kg, p.o.) for 14 days improved this memory deficit in aged rats, as shown by the decrease in escape latency and path length. In addition, when JTP-4819 (at doses of 1 and 3 mg/kg, p.o.) was administered for 3 wk, it reversed the age-related increase of ChAT activity in the cerebral cortex and the decrease of 3H-choline uptake in the hippocampus. These data suggest that JTP-4819 ameliorates age-related impairment of spatial memory and partly reverses central cholinergic dysfunction, possibly due to the enhancement of neuropeptide function by inhibition of PEP mediated degradation of substance P, arginine-vasopressin, and thyrotropin-releasing hormone.  相似文献   
34.
This study was designed to evaluate whether hair calcium concentration reflects the mortality from coronary heart disease on a UK-wide basis and to determine the effect--if any--of environmental factors which might affect calcium metabolism on this relationship. The study was based on our earlier findings of an inverse relationship between hair calcium concentration and that in the intima of the aorta and the association of high aorta calcium with severe alterations to the vessel walls which was found never to co-exist with hair calcium concentrations greater than 700 ppm. Hair samples were collected from 4393 males in an ethically approved study in 40 different health districts. These covered the range in known prevalence of heart disease as reflected in the published standardised mortality ratios (SMR). Data on water hardness were obtained from the Water Authorities and on mean annual sunshine hours from the Meteorological Office. Statistical analysis was by regression and multivariate regression techniques. Hair calcium was determined by XRF analysis and the accuracy validated by means of certified reference samples. Significant relationships were found between health district and county SMR and their respective mean hair calcium concentrations accounting for 37 and 55% of their respective variances in SMR. Water hardness and sunshine hours accounted for 39 and 49% of the variance in mortality from CHD. In combination they accounted for 54% of the variance and with the inclusion of hair calcium 65%. South-east England had the highest hair calcium, the hardest water and the most sunshine hours and the lowest mortality from CHD. The converse was true of Scotland. Hair calcium concentration did reflect the risk of CHD on a population basis and was strongly influenced by both the hardness of the water supply and the annual sunshine hours which also independently affected the SMR for CHD.  相似文献   
35.
The oxygen isotopic compositions of two calcium-aluminum-rich inclusions (CAIs) from the unequilibrated ordinary chondrite meteorites Quinyambie and Semarkona are enriched in 16O by an amount similar to that in CAIs from carbonaceous chondrites. This may indicate that most CAIs formed in a restricted region of the solar nebula and were then unevenly distributed throughout the various chondrite accretion regions. The Semarkona CAI is isotopically homogeneous and contains highly 16O-enriched melilite, supporting the hypothesis that all CAI minerals were originally 16O-rich, but that in most carbonaceous chondrite inclusions some minerals exchanged oxygen isotopes with an external reservoir following crystallization.  相似文献   
36.
A procedure is described for estimating the free fatty acids in wort and beer by gas liquid chromatography. The free fatty acids with carbon number 8 to 18 are estimated simultaneously from one injection, and by including two internal standards the reproducibility of the method is maintained over the whole range. It has been demonstrated that other lipid materials such as glycerides and esters of fatty acids do not interfere with the assay. Compared with other methods, this procedure is fairly rapid and is suitable for routine purposes. The reproducibility of the method has been assessed by analysing replicate samples of wort and beer and the precision in estimating individual fatty acids is given.  相似文献   
37.
Experiments have been performed with 19- and 61-pin test assemblies in the Thermal-Hydraulic Out-of-Reactor Safety (THORS) Facility at the Oak Ridge National Laboratory (ORNL) since 1971. The THORS Facility is a high-temperature sodium system operated for the US Liquid-Metal Fast Breeder Reactor (LMFBR) Safety Program. The facility is used primarily for testing simulated LMFBR fuel subassemblies (pin (bundles). High-performance, electrically heated fuel pin simulators (FPSs) duplicate the heat generating capabilities and the dimensional characteristics of the nuclear fuel pins. A number of test bundles have been built and operated to obtain base thermal-hydraulic data, inlet and heated zone blockage data, and transient boiling data. Five of these bundles have been operated under two-phase conditions. Sodium boiling for periods up to twelve minutes were sustained in one bundle. (The lengths of the periods were limited only by automatic data recording capability). Clad dryout occurred in several tests. Tests were run at widely varying conditions of flow and power density. Testing with nonuniform power distribution across the bundle was also a part of the program.A 19-pin bundle with 12 peripheral guard heaters and a 6-subchannel blockage around the center pin in the heated zone was tested. The test program for this bundle was designed to determine if local boiling in the wake of the blockage propagates radially or axially during quasi-steady-state conditions. Post-test inspection revealed that significant helical distortion of the FPSs occurred in the vicinity of the blockage plate. This distortion probably influenced the boiling behavior. In the more severe tests, boiling initiated at the outlet of the heated zone and propagated radially into the unblocked subchannels after it had progressed upstream to the blockage. The subchannel analysis codes, SABRE and COBRA, accurately predict the extent of the boiling region.Experimental and analytical studies of sodium boiling behavior in unblocked 19- and 61-pin bundles indicate that cooling can be maintained for a significant period of time beyond boiling inception in a flow-power transient. Quasi-steady-state boiling occurred under natural-convection conditions.Investigations of the temperature data indicate that the thermal-hydraulic behavior during boiling transients is determined by two-dimensional effects, and that one-dimensional models cannot accurately predict the important phenomena associated with sodium boiling in test bundles. The subchannel code SABRE-2P (with a simple two-phase multiplier boiling model) and the two-region equilibrium mixture code THORAX (developed at ORNL) accurately predict the two-dimensional behavior between boiling inception and dryout.Extrapolation of the data from the smaller bundle tests to full-size fuel assemblies shows that the time between boiling inception and dryout would be lower for a 217-pin bundle than for a 61-pin bundle for a comparable transient. However, the time delay would still be significant, especially in a heterogeneous reactor core.  相似文献   
38.
Efficient navigation of our social world depends on the generation, interpretation, and combination of social signals within different sensory systems. However, the influence of healthy adult aging on multisensory integration of emotional stimuli remains poorly explored. This article comprises 2 studies that directly address issues of age differences on cross-modal emotional matching and explicit identification. The first study compared 25 younger adults (19–40 years) and 25 older adults (60–80 years) on their ability to match cross-modal congruent and incongruent emotional stimuli. The second study looked at performance of 20 younger (19–40) and 20 older adults (60–80) on explicit emotion identification when information was presented congruently in faces and voices or only in faces or in voices. In Study 1, older adults performed as well as younger adults on tasks in which congruent auditory and visual emotional information were presented concurrently, but there were age-related differences in matching incongruent cross-modal information. Results from Study 2 indicated that though older adults were impaired at identifying emotions from 1 modality (faces or voices alone), they benefited from congruent multisensory information as age differences were eliminated. The findings are discussed in relation to social, emotional, and cognitive changes with age. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
39.
The advent of trusts within the NHS brought a new dimension to the role of nurses in management, in that each trust must appoint an executive nurse director to sit on the trust board. The function and potential function of this role is, I believe, pivotal to the development of clinical services within the NHS.  相似文献   
40.
Will a new and, some say, improved FDA improve the conditions, financial and otherwise, of patient care? Many argue that the acceleration of the FDA approval process comes at a high price. As new drugs hit the market faster--and with less proof of their long-term benefits--health care costs are going up, up, up, and society is facing painful rationing decisions.  相似文献   
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