879 research outputs found

    Determination of high temperature strains using a PC based vision system

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    With the widespread availability of video digitizers and cheap personal computers, the use of computer vision as an experimental tool is becoming common place. These systems are being used to make a wide variety of measurements that range from simple surface characterization to velocity profiles. The Sub-Pixel Digital Image Correlation technique has been developed to measure full field displacement and gradients of the surface of an object subjected to a driving force. The technique has shown its utility by measuring the deformation and movement of objects that range from simple translation to fluid velocity profiles to crack tip deformation of solid rocket fuel. This technique has recently been improved and used to measure the surface displacement field of an object at high temperature. The development of a PC based Sub-Pixel Digital Image Correlation system has yielded an accurate and easy to use system for measuring surface displacements and gradients. Experiments have been performed to show the system is viable for measuring thermal strain

    An exploration of the missing data mechanism in an Internet based smoking cessation trial.

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    BACKGROUND: Missing outcome data are very common in smoking cessation trials. It is often assumed that all such missing data are from participants who have been unsuccessful in giving up smoking ("missing=smoking"). Here we use data from a recent Internet based smoking cessation trial in order to investigate which of a set of a priori chosen baseline variables are predictive of missingness, and the evidence for and against the "missing=smoking" assumption. METHODS: We use a selection model, which models the probability that the outcome is observed given the outcome and other variables. The selection model includes a parameter for which zero indicates that the data are Missing at Random (MAR) and large values indicate "missing=smoking". We examine the evidence for the predictive power of baseline variables in the context of a sensitivity analysis. We use data on the number and type of attempts made to obtain outcome data in order to estimate the association between smoking status and the missing data indicator. RESULTS: We apply our methods to the iQuit smoking cessation trial data. From the sensitivity analysis, we obtain strong evidence that older participants are more likely to provide outcome data. The model for the number and type of attempts to obtain outcome data confirms that age is a good predictor of missing data. There is weak evidence from this model that participants who have successfully given up smoking are more likely to provide outcome data but this evidence does not support the "missing=smoking" assumption. The probability that participants with missing outcome data are not smoking at the end of the trial is estimated to be between 0.14 and 0.19. CONCLUSIONS: Those conducting smoking cessation trials, and wishing to perform an analysis that assumes the data are MAR, should collect and incorporate baseline variables into their models that are thought to be good predictors of missing data in order to make this assumption more plausible. However they should also consider the possibility of Missing Not at Random (MNAR) models that make or allow for less extreme assumptions than "missing=smoking".RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    A general method for elicitation, imputation, and sensitivity analysis for incomplete repeated binary data.

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    We develop and demonstrate methods to perform sensitivity analyses to assess sensitivity to plausible departures from missing at random in incomplete repeated binary outcome data. We use multiple imputation in the not at random fully conditional specification framework, which includes one or more sensitivity parameters (SPs) for each incomplete variable. The use of an online elicitation questionnaire is demonstrated to obtain expert opinion on the SPs, and highest prior density regions are used alongside opinion pooling methods to display credible regions for SPs. We demonstrate that substantive conclusions can be far more sensitive to departures from the missing at random assumption (MAR) when control and intervention nonresponders depart from MAR differently, and show that the correlation of arm specific SPs in expert opinion is particularly important. We illustrate these methods on the iQuit in Practice smoking cessation trial, which compared the impact of a tailored text messaging system versus standard care on smoking cessation. We show that conclusions about the effect of intervention on smoking cessation outcomes at 8 week and 6 months are broadly insensitive to departures from MAR, with conclusions significantly affected only when the differences in behavior between the nonresponders in the two trial arms is larger than expert opinion judges to be realistic

    A general method for handling missing binary outcome data in randomized controlled trials.

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    AIMS: The analysis of randomized controlled trials with incomplete binary outcome data is challenging. We develop a general method for exploring the impact of missing data in such trials, with a focus on abstinence outcomes. DESIGN: We propose a sensitivity analysis where standard analyses, which could include 'missing = smoking' and 'last observation carried forward', are embedded in a wider class of models. SETTING: We apply our general method to data from two smoking cessation trials. PARTICIPANTS: A total of 489 and 1758 participants from two smoking cessation trials. MEASUREMENTS: The abstinence outcomes were obtained using telephone interviews. FINDINGS: The estimated intervention effects from both trials depend on the sensitivity parameters used. The findings differ considerably in magnitude and statistical significance under quite extreme assumptions about the missing data, but are reasonably consistent under more moderate assumptions. CONCLUSIONS: A new method for undertaking sensitivity analyses when handling missing data in trials with binary outcomes allows a wide range of assumptions about the missing data to be assessed. In two smoking cessation trials the results were insensitive to all but extreme assumptions

    Structure of the protein kinase Cb phospholipid-binding C2 domain complexed with Ca 2+

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    Background: Conventional isoforms (α, β and γ) of protein kinase C (PKC) are synergistically activated by phosphatidylserine and Ca 2+ ; both bind to C2 domains located within the PKC amino-terminal regulatory regions. C2 domains contain a bipartite or tripartite Ca 2+ -binding site formed by opposing loops at one end of the protein. Neither the structural basis for cooperativity between phosphatidylserine and Ca 2+ , nor the binding site for phosphatidylserine are known. Results: The structure of the C2 domain from PKCβ complexed with Ca 2+ and o-phospho-L-serine has been determined to 2.7 Å resolution using X-ray crystallography. The eight-stranded, Greek key β-sandwich fold of PKCβ-C2 is similar to that of the synaptotagmin I type I C2 domain. Three Ca 2+ ions, one at a novel site, were located, each sharing common aspartate ligands. One of these ligands is donated by a dyad-related C2 molecule. A phosphoserine molecule binds to a lysine-rich cluster in C2. Conclusions: Shared ligation among the three Ca 2+ ions suggests that they bind cooperatively to PKCβ-C2. Cooperativity may be compromised by the accumulation of positive charge in the binding site as successive ions are bound. Model building shows that the C1 domain could provide carboxylate and carbonyl ligands for two of the three Ca 2+ sites. Ca 2+ -mediated interactions between the two domains could contribute to enzyme activation as well as to the creation of a positively charged phosphatidylserine-binding site

    Punctuated chromatin states regulate Plasmodium falciparum antigenic variation at the intron and 2 kb upstream regions

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    2 kb upstream region FAIRE-Seq signal comparison between var genes and different gene families (P-value is calculated based on Wilcoxon-Rank-Sum test, FDR indicates false discovery rate). (XLSX 53 kb

    Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

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    STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized

    Properties of filamentary sublimation residues from dispersions of clay in ice

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    During vacuum sublimation experiments on simulated Martian polar deposits and cometary dirty ices, a fluffy filamentary sublimate residue material with unique physical properties was produced. The silica-to-silica bonds that we believe join the particles together are the result of conditions that may exist in some Martian polar deposits and on some cometary surfaces. Submicron particles of montmorillonite clay thinly dispersed (1: 1000 clay/water) and not contacting one another in water ice can form very-low-density structures (density as low as 10-3 g cm-3) during sublimation of the ice. The lightweight constructs, when viewed in scanning electron microscopy micrographs, are composed of long network chains of the clay particles. The material is sufficiently electrically conductive to drain away the scanning electron microscopy charge. It is also resistant (no change in electronic properties are apparent) to scanning electron microscopy electron-beam heating for hours in vacuo. Infrared spectra and X-ray diffraction patterns of the sublimate residues show little difference from spectra and patterns of the original minerals. Heating in an oven, in air, to 370[deg]C produces little change in the structure of the sublimate residual material. The particle bonding forces are strong and produce a resilient, elastic lightweight material. The particle bonding will allow vapors to diffuse through it, and its thermal conductivity is very low. These properties produce a high-performance vacuum insulation. This material may have applications for insulating ice bodies (solid cryogens) in space. The incoming heat is partially carried away by the out-flowing water vapor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26207/1/0000287.pd

    Status of the joint LIGO--TAMA300 inspiral analysis

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    We present the status of the joint search for gravitational waves from inspiraling neutron star binaries in the LIGO Science Run 2 and TAMA300 Data Taking Run 8 data, which was taken from February 14 to April 14, 2003, by the LIGO and TAMA collaborations. In this paper we discuss what has been learned from an analysis of a subset of the data sample reserved as a ``playground''. We determine the coincidence conditions for parameters such as the coalescence time and chirp mass by injecting simulated Galactic binary neutron star signals into the data stream. We select coincidence conditions so as to maximize our efficiency of detecting simulated signals. We obtain an efficiency for our coincident search of 78 %, and show that we are missing primarily very distant signals for TAMA300. We perform a time slide analysis to estimate the background due to accidental coincidence of noise triggers. We find that the background triggers have a very different character from the triggers of simulated signals.Comment: 10 page, 8 figures, accepted for publication in Classical and Quantum Gravity for the special issue of the GWDAW9 Proceedings ; Corrected typos, minor change
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