726 research outputs found

    Recovery - Air Force Ballistic Weapons Systems

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    The postflight recovery of a Ballistic Missile Re-entry Vehicle is perhaps one of the best ways of gathering data to verify the adequacy of design. The data obtained is indisputable. Since the beginning of re-entry vehicle flight testing, many attempts have been made to recover data that identified performance of the re-entry vehicle while being exposed to an operational flight environment. Telemetered instrumentation has been the mainstay of this need for data, although postflight recovery of the hardware, which would offer final proof of performance has been the desire. Trying to reach this goal, the Air Force in the past has devised various methods such as, ejecting capsules during flight that contain data recorders, and deploying parachutes during flight to decrease the forces of impact on the reentry vehicle so that meaningful data could be gathered. Systems such as these work, however, each either produce only a recording of happenings or impair the true flight conditions. The United States, acknowledging the importance of physical recovery, has developed two locations in the Pacific Ocean that are capable of recovering a re-entry vehicle that has been exposed to true flight environments and permitted to re-enter the atmosphere and impact under normal flight conditions. The capabilities and techniques employed to locate and retrieve a vehicle after impact are in part, operations used in other places to perform other tasks, but when used in combination they can accomplish the task of physical recovery of a Ballistic Missile Re-entry Vehicle

    Extra-renal locations of the a4 subunit of H+ATPase

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    Abstract Background Vacuolar-type proton pumps help maintain acid–base homeostasis either within intracellular compartments or at specialised plasma membranes. In mammals they are made up of 13 subunits, which form two functional domains. A number of the subunits have variants that display tissue restricted expression patterns such that in specialised cell types they replace the generic subunits at some sub-cellular locations. The tissue restricted a4 subunit has previously been reported at the plasma membrane in the kidney, inner ear, olfactory epithelium and male reproductive tract. Results In this study novel locations of the a4 subunit were investigated using an Atp6v0a4 knockout mouse line in which a LacZ reporter cassette replaced part of the gene. The presence of a4 in the olfactory epithelium was further investigated and the additional presence of C2 and d2 subunits identified. The a4 subunit was found in the uterus of pregnant animals and a4 was identified along with d2 and C2 in the embryonic visceral yolk sac. In the male reproductive tract a4 was seen in the novel locations of the prostatic alveoli and the ampullary glands as well as the previously reported epididymis and vas deferens. Conclusions The identification of novel locations for the a4 subunit and other tissue-restricted subunits increases the range of unique subunit combinations making up the proton pump. These studies suggest additional roles of the proton pump, indicating a further range of homologue-specific functions for tissue-restricted subunits

    Renal peroxiredoxin 6 interacts with anion exchanger 1 and plays a novel role in pH homeostasis.

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    Peroxiredoxin 6 (PRDX6) is one of the six members of the PRDX family, which have peroxidase and antioxidant activity. PRDX6 is unique, containing only one conserved cysteine residue (C47) rather than the two found in other PRDXs. A yeast two-hybrid screen found PRDX6 to be a potential binding partner of the C-terminal tail of anion exchanger 1 (AE1), a Cl(-)/HCO(3)(-) exchanger basolaterally expressed in renal α-intercalated cells. PRDX6 immunostaining in human kidney was both cytoplasmic and peripheral and colocalized with AE1. Analysis of native protein showed that it was largely monomeric, whereas expressed tagged protein was more dimeric. Two methionine oxidation sites were identified. In vitro and ex vivo pull-downs and immunoprecipitation assays confirmed interaction with AE1, but mutation of the conserved cysteine resulted in loss of interaction. Prdx6 knockout mice had a baseline acidosis with a major respiratory component and greater AE1 expression than wild-type animals. After an oral acid challenge, PRDX6 expression increased in wild-type mice, with preservation of AE1. However, AE1 expression was significantly decreased in knockout animals. Kidneys from acidified mice showed widespread proximal tubular vacuolation in wild-type but not knockout animals. Knockdown of PRDX6 by siRNA in mammalian cells reduced both total and cell membrane AE1 levels. Thus, PRDX6-AE1 interaction contributes to the maintenance of AE1 during cellular stress such as during metabolic acidosis.Human kidney sections were prepared by Suzy Haward, Addenbrooke's Human Research Tissue Bank, which is supported by the Cambridge Biomedical Research Centre. We thank Dr. Aron Fisher (Institute for Environmental Science, University of Pennsylvania) for the kind gift of Prdx6−/− mice and reagents, Carsten Wagner (Zurich) for antisera, Jane Clarke (University of Cambridge) for modified pRSET-A vector, and Kamburapola Jayawardena for mass spectrometry (CIMR). This work was funded by the Wellcome Trust (award 088489/Z/09/Z to FEKF and Strategic award 100140/Z/12/Z to the Cambridge Institute for Medical Research), and the Jack Kent Cooke Foundation (scholarship to SLS).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ki.2015.27

    Reporting of Adverse Events in Published and Unpublished Studies of Health Care Interventions : A Systematic Review

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    BACKGROUND: We performed a systematic review to assess whether we can quantify the underreporting of adverse events (AEs) in the published medical literature documenting the results of clinical trials as compared with other nonpublished sources, and whether we can measure the impact this underreporting has on systematic reviews of adverse events. METHODS AND FINDINGS: Studies were identified from 15 databases (including MEDLINE and Embase) and by handsearching, reference checking, internet searches, and contacting experts. The last database searches were conducted in July 2016. There were 28 methodological evaluations that met the inclusion criteria. Of these, 9 studies compared the proportion of trials reporting adverse events by publication status. The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies. A total of 11 studies compared the numbers of adverse events in matched published and unpublished documents. The percentage of adverse events that would have been missed had each analysis relied only on the published versions varied between 43% and 100%, with a median of 64%. Within these 11 studies, 24 comparisons of named adverse events such as death, suicide, or respiratory adverse events were undertaken. In 18 of the 24 comparisons, the number of named adverse events was higher in unpublished than published documents. Additionally, 2 other studies demonstrated that there are substantially more types of adverse events reported in matched unpublished than published documents. There were 20 meta-analyses that reported the odds ratios (ORs) and/or risk ratios (RRs) for adverse events with and without unpublished data. Inclusion of unpublished data increased the precision of the pooled estimates (narrower 95% confidence intervals) in 15 of the 20 pooled analyses, but did not markedly change the direction or statistical significance of the risk in most cases. The main limitations of this review are that the included case examples represent only a small number amongst thousands of meta-analyses of harms and that the included studies may suffer from publication bias, whereby substantial differences between published and unpublished data are more likely to be published. CONCLUSIONS: There is strong evidence that much of the information on adverse events remains unpublished and that the number and range of adverse events is higher in unpublished than in published versions of the same study. The inclusion of unpublished data can also reduce the imprecision of pooled effect estimates during meta-analysis of adverse events

    A complementary view on the growth of directory trees

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    Trees are a special sub-class of networks with unique properties, such as the level distribution which has often been overlooked. We analyse a general tree growth model proposed by Klemm {\em et. al.} (2005) to explain the growth of user-generated directory structures in computers. The model has a single parameter qq which interpolates between preferential attachment and random growth. Our analysis results in three contributions: First, we propose a more efficient estimation method for qq based on the degree distribution, which is one specific representation of the model. Next, we introduce the concept of a level distribution and analytically solve the model for this representation. This allows for an alternative and independent measure of qq. We argue that, to capture real growth processes, the qq estimations from the degree and the level distributions should coincide. Thus, we finally apply both representations to validate the model with synthetically generated tree structures, as well as with collected data of user directories. In the case of real directory structures, we show that qq measured from the level distribution are incompatible with qq measured from the degree distribution. In contrast to this, we find perfect agreement in the case of simulated data. Thus, we conclude that the model is an incomplete description of the growth of real directory structures as it fails to reproduce the level distribution. This insight can be generalised to point out the importance of the level distribution for modeling tree growth.Comment: 16 pages, 7 figure

    Increasing Feed Conversion Efficiency in Automatic Milking Systems: The Impact of Grain-Based Concentrate Allocation and Kikuyu (\u3cem\u3ePennisetum clandestinum\u3c/em\u3e) Pasture State on Milk Production

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    Pasture is typically offered to dairy cows in three allocations in pasture-based automatic milking systems (AMS). However, due to voluntary cow movement and distribution of milkings, some dairy cows access fresh pasture and other cows access depleted (stale) pasture. The first cows moving to an allocation of fresh pasture are offered ad-libitum, high quality pasture as opposed to cows arriving to the same allocation during the middle or end of the day accessing poorer quality, high fibre (neutral detergent fibre, NDF) pasture. In addition, grain-based concentrate (GBC) is allocated independently to this pasture state. The ability to increase feed conversion efficiency and AMS herd milk production by targetedGBC supplementation to cows accessing differing pasture states is unknown. Therefore, the aim of the current experiment was to determine the impact of pasture state and GBC allocation on dairy cow milk production

    Increasing Feed Conversion Efficiency in Automatic Milking Systems: The Impact of Grain-Based Concentrate Allocation and Kikuyu (\u3cem\u3ePennisetum clandestinum\u3c/em\u3e) Pasture State on Kikuyu Pasture Digestibility

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    Automatic milking system (AMS) farms, rely upon voluntary cow traffic (the voluntary movement of cattle around a farm) for milk harvesting and feed consumption. Dairy cows on a pasture-based AMS farm typically move from depleted to fresh allocations of pasture in small groups, or individually, at differing times. The first cows moving to an allocation of fresh pasture get access to rapidly fermentable, ad libitum, high quality pasture in contrast to those cows accessing the same allocation towards the end of the access period. At the same time, grain-based concentrate (GBC) is allocated independent of the pasture state that cows access. Inclusion of a high level of GBC in the diet with high or low nutritive value forage, or variable states of forage, may create dramatic variations in rumen fluid pH, which may induce subacute ruminal acidosis (Bramley 2004), reduce feed conversion efficiency and negatively impact animal health. The aim of the current study was to determine the impact of pasture state and GBC allocation on the digestibility of kikuyu pasture

    International recruitment of radiographers and the development of a workplace integration support package: Project evaluation

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    Introduction In October 2020, a regional workforce action group was established jointly by Health Education England (HEE) and NHS England and Improvement (NHSEI) in the South West to work collaboratively to address the workforce challenges within diagnostic imaging. Fifty-eight internationally recruited radiographers were offered employment in departments across the region, the majority of them taking up their posts in the UK in early 2021. The aim of the study presented here was to evaluate the efficacy of a training resource developed by Plymouth Marjon University, with input from HEE and NHSEI, to support workplace and cultural integration for the new recruits. Methods The training package to help newly recruited radiographers from outside the UK integrate into their host departments was developed using flexible learning opportunities centred on reusable digital learning assets. Self-paced e-learning sessions were augmented by group ‘connected’ sessions online. Two surveys were undertaken, exploring the impact of this workforce integration programme for International radiographers joining the NHS. Results Survey results indicate that the integration programme's three-phase strategy has seen an impact on 6 out of 12 self-efficacy measures, raised awareness of challenges, and increased personal awareness of implications for practice. By the end of the programme, delegates were in the top two quintiles for their average well-being score. Conclusion Principal recommendations include ensuring digital accessibility for new recruits as part of the on-boarding process, considering the timing of delivery of any online connected support sessions, the provision of long-term pastoral support; and mandating the training requirement for managers and team leaders. Implications for practice Success of international recruitment campaigns can be enhanced through the implementation of an online integration packag
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