789 research outputs found

    Generic searches for alternative gravitational wave polarizations with networks of interferometric detectors

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    The detection of gravitational wave signals by Advanced LIGO and Advanced Virgo enables us to probe the polarization content of gravitational waves. In general relativity, only tensor modes are present, while in a variety of alternative theories one can also have vector or scalar modes. Recently test were performed which compared Bayesian evidences for the hypotheses that either purely tensor, purely vector, or purely scalar polarizations were present. Indeed, with only three detectors in a network and allowing for mixtures of tensor polarizations and alternative polarization states, it is not possible to identify precisely which nonstandard polarizations might be in the signal and by what amounts. However, we demonstrate that one can still infer whether, in addition to tensor polarizations, alternative polarizations are present in the first place, irrespective of the detailed polarization content. We develop two methods to do this for sources with electromagnetic counterparts, both based on the so-called null stream. Apart from being able to detect mixtures of tensor and alternative polarizations, these have the added advantage that no waveform models are needed, and signals from any kind of transient source with known sky position can be used. Both formalisms allow us to combine information from multiple sources so as to arrive at increasingly more stringent bounds. For now we apply these on the binary neutron star signal GW170817, showing consistency with the tensor-only hypothesis with p-values of 0.315 and 0.790 for the two methods

    Generic searches for alternative gravitational wave polarizations with networks of interferometric detectors

    Get PDF
    The detection of gravitational wave signals by Advanced LIGO and Advanced Virgo enables us to probe the polarization content of gravitational waves. In general relativity, only tensor modes are present, while in a variety of alternative theories one can also have vector or scalar modes. Recently test were performed which compared Bayesian evidences for the hypotheses that either purely tensor, purely vector, or purely scalar polarizations were present. Indeed, with only three detectors in a network and allowing for mixtures of tensor polarizations and alternative polarization states, it is not possible to identify precisely which non-standard polarizations might be in the signal and by what amounts. However, we demonstrate that one can still infer whether, in addition to tensor polarizations, alternative polarizations are present in the first place, irrespective of the detailed polarization content. We develop two methods to do this for sources with electromagnetic counterparts, both based on the so-called null stream. Apart from being able to detect mixtures of tensor and alternative polarizations, these have the added advantage that no waveform models are needed, and signals from any kind of transient source with known sky position can be used. Both formalisms allow us to combine information from multiple sources so as to arrive at increasingly more stringent bounds. For now we apply these on the binary neutron star signal GW170817, showing consistency with the tensor-only hypothesis with p-values of 0.315 and 0.790 for the two methods.Comment: 8 pages, 3 figure

    Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

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    BACKGROUND: Recent studies indicate that microRNAs (miRNAs) are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA. RESULTS: Comparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R(2 )= 0.81); and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03); as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index). CONCLUSION: In sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast and prostate cancer biopsies

    Using machine learning to infer reasoning provenance from user interaction log data: based on the data/frame theory of sensemaking

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    The reconstruction of analysts’ reasoning processes (reasoning provenance) during complex sensemaking tasks can support reflection and decision making. One potential approach to such reconstruction is to automatically infer reasoning from low-level user interaction logs. We explore a novel method for doing this using machine learning. Two user studies were conducted in which participants performed similar intelligence analysis tasks. In one study, participants used a standard web browser and word processor; in the other, they used a system called INVISQUE (Interactive Visual Search and Query Environment). Interaction logs were manually coded for cognitive actions based on captured think-aloud protocol and posttask interviews based on Klein, Phillips, Rall, and Pelusos’s data/frame model of sensemaking as a conceptual framework. This analysis was then used to train an interaction frame mapper, which employed multiple machine learning models to learn relationships between the interaction logs and the codings. Our results show that, for one study at least, classification accuracy was significantly better than chance and compared reasonably to a reported manual provenance reconstruction method. We discuss our results in terms of variations in feature sets from the two studies and what this means for the development of the method for provenance capture and the evaluation of sensemaking systems

    N-WASP Is Required for Structural Integrity of the Blood-Testis Barrier

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    During spermatogenesis, the blood-testis barrier (BTB) segregates the adluminal (apical) and basal compartments in the seminiferous epithelium, thereby creating a privileged adluminal environment that allows post-meiotic spermatid development to proceed without interference of the host immune system. A key feature of the BTB is its continuous remodeling within the Sertoli cells, the major somatic component of the seminiferous epithelium. This remodeling is necessary to allow the transport of germ cells towards the seminiferous tubule interior, while maintaining intact barrier properties. Here we demonstrate that the actin nucleation promoting factor Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) provides an essential function necessary for BTB restructuring, and for maintaining spermatogenesis. Our data suggests that the N-WASP-Arp2/3 actin polymerization machinery generates branched-actin arrays at an advanced stage of BTB remodeling. These arrays are proposed to mediate the restructuring process through endocytic recycling of BTB components. Disruption of N-WASP in Sertoli cells results in major structural abnormalities to the BTB, including mis-localization of critical junctional and cytoskeletal elements, and leads to disruption of barrier function. These impairments result in a complete arrest of spermatogenesis, underscoring the critical involvement of the somatic compartment of the seminiferous tubules in germ cell maturation

    Study protocol: the effects of work-site exercise on the physical fitness and work-ability of older workers

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    BACKGROUND: Older workers have a higher rate and cost of injury than younger workers and with a rapidly ageing work force there is a need to identify strategies to address this problem. Older workers are less physically active and fit than younger workers and so have reduced work ability. The reduced work ability means they are more likely to be fatigued at work and so at greater risk of injury. Exercise could potentially assist this problem. Exercise training has been previously shown to improve fitness in older people however there has been no evaluation of workplace exercise program for older workers. We do not know if the programs are feasible and can improve the fitness and work ability of older workers. We have designed a randomised controlled trial to evaluate whether exercise improves fitness and perceived work-ability of older workers. METHODS/DESIGN: This paper describes the protocol for a trial examining the effects of a 12-week physical training program in workers over the age of 45. Participants will be randomized to an exercise or no-intervention control group. The primary outcomes are cardiorespiratory endurance, lifting capacity, upper and lower limb strength and perceived work-ability. DISCUSSION: This trial will test the feasibility of implementing a worksite-based exercise program as a means of improving the physical fitness and work-ability of older workers performing physically demanding work. If we demonstrate the feasibility of the program we will conduct a larger trial that additionally measures injury outcomes

    Ginsenoside-Rg1 mediates a hypoxia-independent upregulation of hypoxia-inducible factor-1α to promote angiogenesis

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    Hypoxia-inducible factor (HIF-1) is the key transcription regulator for multiple angiogenic factors and is an appealing target. Ginsenoside-Rg1, a nontoxic saponin isolated from the rhizome of Panax ginseng, exhibits potent proangiogenic activity and has the potential to be developed as a new angiotherapeutic agent. However, the mechanisms by which Rg1 promotes angiogenesis are not fully understood. Here, we show that Rg1 is an effective stimulator of HIF-1α under normal cellular oxygen conditions in human umbilical vein endothelial cells. HIF-1α steady-state mRNA was not affected by Rg1. Rather, HIF-1α protein synthesis was stimulated by Rg1. This effect was associated with constitutive activation of phosphatidylinositol 3-kinase (PI3K)/Akt and its effector p70 S6 kinase (p70S6K), but not extracellular-signal regulated kinase 1/2. We further revealed that HIF-1α induction triggered the expression of target genes, including vascular endothelial growth factor (VEGF). The use of small molecule inhibitors LY294002 or rapamycin to inhibit PI3K/Akt and p70S6K activities, respectively, resulted in diminished HIF-1α activation and subsequent VEGF expression. RNA interference-mediated knockdown of HIF-1α suppressed Rg1-induced VEGF synthesis and angiogenic tube formation, confirming that the effect was HIF-1α specific. Similarly, the angiogenic phenotype could be reversed by inhibition of PI3K/Akt and p70S6K. These results define a hypoxia-independent activation of HIF-1α, uncovering a novel mechanism for Rg1 that could play a major role in angiogenesis and vascular remodeling

    The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents:Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project

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    Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age.Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age.Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable.Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.</p

    The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents:Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project

    Get PDF
    Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age.Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age.Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable.Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.</p
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