188 research outputs found

    Optical-fiber Preamplifiers for Ladar Detection and Associated Measurements for Improving the Signal-to-noise Ratio

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    In an effort to increase achievable postdetection signal-tonoise ratios (SNRs) of continuous-wave, 1-gm all-solid-state ladar systems, a prototype rare-earth-doped optical-fiber amplifier has been included in the optical return signal path of both a heterodyne and a directdetection ladar system. We provide numerical predictions for SNR increases according to our previously developed theory. We also detail our experimental efforts and provide the results of SNR measurements for four distinct cases: direct ladar detection with and without a fiber amplifier, and heterodyne ladar detection with and without a fiber amplifier. Experimentally measured increases in SNRs for ladar systems incorporating an optical-fiber amplifier are then compared with our earlier predictions. Specifically, we have found that for direct detection with a fiber amplifier in place, the predicted SNR increase is 42.0 dB, and we have measured an increase of 36.5 dB. Similarly, for heterodyne ladar detection with a fiber amplifier, the predicted SNR increase is 3.8 dB, and we have measured an increase of 8.0 dB

    Sensitivity Improvement of a 1-μm Ladar System Incorporating an Active Optical Fiber Preamplifier

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    In an effort to increase the SNR of a continuous wave, 1-μm all solid state ladar system, a rare-earth-doped optical fiber amplifier is investigated as a preamplifier for ladar return signals. The experimental system is detailed and a theoretical analysis of the fiber amplifier\u27s effect on both heterodyne and direct detection schemes is provided. Beginning with the optical powers incident on the detector, the signal and noises are analyzed, through the detector electronics, to predict the SNR. The SNR is then plotted as a function of the return signal power, and a SNR threshold is defined to determine a minimum detectable signal power. The return signals required to attain the SNR threshold are then compared for four cases: direct detection with and without the fiber amplifier and heterodyne detection with and without the fiber amplifier. For the direct detection scheme considered, our results predict a sensitivity increase of 20.6 dB with the addition of the fiber amplifier, yet for heterodyne detection the predicted sensitivity increase is only 3.1 dB

    Exercise rehabilitation following intensive care unit discharge for recovery from critical illness:executive summary of a Cochrane Collaboration systematic review

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    Skeletal muscle wasting and weakness are major complications of critical illness and underlie the profound physical and func-\ud tional impairments experienced by survivors after discharge from the intensive care unit (ICU). Exercise-based rehabilitation\ud has been shown to be bene\ud fi\ud cial when delivered during ICU admission. This review aimed to determine the effectiveness of\ud exercise rehabilitation initiated after ICU discharge on primary outcomes of functional exercise capacity and health-related\ud quality of life. We sought randomized controlled trials, quasi-randomized controlled trials, and controlled clinical trials compar-\ud ing an exercise intervention commenced after ICU discharge vs. any other intervention or a control or\ud ‘\ud usual care\ud ’\ud programme\ud in adult survivors of critical illness. Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval Sys-\ud tem Online (MEDLINE), Excerpta Medica Database, and Cumulative Index to Nursing and Allied Health Literature databases\ud were searched up to February 2015. Dual, independent screening of results, data extraction, and quality appraisal were per-\ud formed. We included six trials involving 483 patients. Overall quality of evidence for both outcomes was very low. All studies\ud evaluated functional exercise capacity, with three reporting positive effects in favour of the intervention. Only two studies\ud evaluated health-related quality of life and neither reported differences between intervention and control groups. Meta-\ud analyses of data were precluded due to variation in study design, types of interventions, and selection and reporting of out-\ud come measurements. We were unable to determine an overall effect on functional exercise capacity or health-related quality\ud of life of interventions initiated after ICU discharge for survivors of critical illness. Findings from ongoing studies are awaited.\ud Future studies need to address methodological aspects of study design and conduct to enhance rigour, quality, and synthesis

    Venom kinematics during prey capture in Conus: the biomechanics of a rapid injection system

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    Cone snails use an extensile, tubular proboscis as a conduit to deliver a potent cocktail of bioactive venom peptides into their prey. Previous studies have focused mainly on understanding the venom's role in prey capture but successful prey capture requires both rapid physiological and biomechanical mechanisms

    The acceptability to patients of PhysioDirect telephone assessment and advice services; a qualitative interview study

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    Background: In response to long waiting lists and problems with access to primary care physiotherapy, several Primary Care Trusts (PCTs) (now Clinical Commissioning Groups CCGs) developed physiotherapy-led telephone assessment and treatment services. The Medical Research Council (MRC) funded PhysioDirect trial was a randomised control trial (RCT) in four PCTs, with a total of 2252 patients that compared this approach with usual physiotherapy care. This nested qualitative study aimed to explore the acceptability of the PhysioDirect telephone assessment and advice service to patients with musculoskeletal conditions. Methods: We conducted 57 semi-structured interviews with adults from 4 PCTs who were referred from general practice to physiotherapy with musculoskeletal conditions and were participating in the PhysioDirect trial. The Framework method was used to analyse the qualitative data. Results: The PhysioDirect service was largely viewed as acceptable although some saw it as a first step to subsequent face-to-face physiotherapy. Most participants found accessing the PhysioDirect service straightforward and smooth, and they valued the faster access to physiotherapy advice offered by the telephone service. Participants generally viewed both the PhysioDirect service and the physiotherapists providing the service as helpful. Participants’ preferences and priorities for treatment defined the acceptable features of PhysioDirect but the acceptable features were traded off against less acceptable features. Some participants felt that the PhysioDirect service was impersonal and impaired the development of a good relationship with their physiotherapist, which made the service feel remote and less valuable. Conclusion: The PhysioDirect service was broadly acceptable to participants since it provided faster access to physiotherapy advice for their musculoskeletal conditions. Participants felt that it is best placed as one method of accessing physiotherapy services, in addition to, rather than as a replacement for, more traditional face-to-face physiotherapy assessment and treatment

    Mitsui-7, heat-treated, and nitrogen-doped multi-walled carbon nanotubes elicit genotoxicity in human lung epithelial cells

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    Background: The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT. Previously, MWCNT exposed to high temperature (MWCNT-HT) or synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their genotoxic and carcinogenic potential are not known. Our aim was to measure the genotoxicity of MWCNT-7 compared to these two physicochemically-altered MWCNTs in human lung epithelial cells (BEAS-2B & SAEC). Results: Dose-dependent partitioning of individual nanotubes in the cell nuclei was observed for each MWCNT material and was greatest for MWCNT-7. Exposure to each MWCNT led to significantly increased mitotic aberrations with multi- and monopolar spindle morphologies and fragmented centrosomes. Quantitative analysis of the spindle pole demonstrated significantly increased centrosome fragmentation from 0.024–2.4 μg/mL of each MWCNT. Significant aneuploidy was measured in a dose-response from each MWCNT-7, HT, and ND; the highest dose of 24 μg/mL produced 67, 61, and 55%, respectively. Chromosome analysis demonstrated significantly increased centromere fragmentation and translocations from each MWCNT at each dose. Following 24 h of exposure to MWCNT-7, ND and/or HT in BEAS-2B a significant arrest in the G1/S phase in the cell cycle occurred, whereas the MWCNT-ND also induced a G2 arrest. Primary SAEC exposed for 24 h to each MWCNT elicited a significantly greater arrest in the G1 and G2 phases. However, SAEC arrested in the G1/S phase after 72 h of exposure. Lastly, a significant increase in clonal growth was observed one month after exposure to 0.024 μg/mL MWCNT-HT & ND. Conclusions: Although MWCNT-HT & ND cause a lower incidence of genotoxicity, all three MWCNTs cause the same type of mitotic and chromosomal disruptions. Chromosomal fragmentation and translocations have not been observed with other nanomaterials. Because in vitro genotoxicity is correlated with in vivo genotoxic response, these studies in primary human lung cells may predict the genotoxic potency in exposed human populations

    Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

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    Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis

    Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs.

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    Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding YxxØ motifs, including four that are present within two immunoreceptor tyrosine-based activation motifs (ITAMs). Using a combination of in vitro and in situ approaches, we establish that the sole mediator of AP2-dependent BCR internalization is the membrane proximal ITAM YxxØ motif in CD79b, which is a major target of mutation in ABC DLBCL. In addition, we establish that BCR internalization can be regulated at a minimum of two different levels: regulation of YxxØ AP2 binding in cis by downstream ITAM-embedded DCSM and QTAT regulatory elements and regulation in trans by the partner cytoplasmic domain of the CD79 heterodimer. Beyond establishing the basic rules governing BCR internalization, these results illustrate an underappreciated role for ITAM residues in controlling clathrin-dependent endocytosis and highlight the complex mechanisms that control the activity of AP2 binding motifs in this receptor system
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