419 research outputs found
Experiments on the Flow Field and Acoustic Properties of a Mach number 0·75 Turbulent Air Jet at a Low Reynolds Number
Pathways to Care: Duration of Untreated Psychosis from Karachi, Pakistan
Background: Substantial amount of time is lost before initiation of treatment in Schizophrenia. The delay in treatment is labelled as Duration of Untreated Psychosis (DUP). Most of these estimates come from western countries, where health systems are relatively better developed. There is dearth of information on pathway to care from developing countries. Methods And Results: Patients with ICD-10 based diagnosis of Schizophrenia were enrolled by convenient method of sampling. The pathway to care was explored through a semi-structured questionnaire. Onset, course and symptoms of psychosis were assessed using Interview for the Retrospective Assessment of the Onset of Schizophrenia (IRAOS). Ethical approval of the project was taken from The Aga Khan University, Ethics Review Committee. Of the enrolled 93 subjects, 55 (59%) were males and 38 (41%) were females. In our sample, 1.56 mean (median, 2) attempts were made prior to successful help seeking. The duration of untreated psychosis was 14.8 months (St. Deviation, 29.4). DUP was 16.8 months (St. Deviation, 34.9) for males and 11.8 months (St. Deviation, 18.9) for females. In the pathway to care, psychiatrists featured prominently as initial care providers. In the first attempt at help-seeking, 43% Patients were initially taken to psychiatrists. After the initial consultation, 45% were prescribed psychotropic medication while 7% were hospitalized. Only 9% subjects were given the diagnosis of schizophrenia initially. When participants were inquired about the reasons for delay, 29% reported financial difficulties as the barrier to care. Positive symptoms of psychosis were present in 57% subjects while negative symptoms were present in 30% subjects. There was a statistically significant difference (Chi-square, 7.928, df: 1, Sig 0.005) between DUP and the positive and negative symptoms category. Conclusion: In the absence of well developed primary care health system in Pakistan, majority of Patients present to psychiatrists as a first contact. DUP, as a measurement of help seeking behaviour, tends to be shorter with positive symptoms of Schizophrenia. Substantial amount of time is lost due to non recognition of disease and subsequently, inadequate treatment. Secondary prevention strategies should focus on families, which play an important role in the treatment-seeking process of psychotic Patients
A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz
Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector
This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}4.6\;{\rm f}{{{\rm b}}^{-1}}{{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}|\eta |\lt 1.9{{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques
Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV
The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV
Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector
The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV
Predicting Cellular Growth from Gene Expression Signatures
Maintaining balanced growth in a changing environment is a fundamental
systems-level challenge for cellular physiology, particularly in microorganisms.
While the complete set of regulatory and functional pathways supporting growth
and cellular proliferation are not yet known, portions of them are well
understood. In particular, cellular proliferation is governed by mechanisms that
are highly conserved from unicellular to multicellular organisms, and the
disruption of these processes in metazoans is a major factor in the development
of cancer. In this paper, we develop statistical methodology to identify
quantitative aspects of the regulatory mechanisms underlying cellular
proliferation in Saccharomyces cerevisiae. We find that the
expression levels of a small set of genes can be exploited to predict the
instantaneous growth rate of any cellular culture with high accuracy. The
predictions obtained in this fashion are robust to changing biological
conditions, experimental methods, and technological platforms. The proposed
model is also effective in predicting growth rates for the related yeast
Saccharomyces bayanus and the highly diverged yeast
Schizosaccharomyces pombe, suggesting that the underlying
regulatory signature is conserved across a wide range of unicellular evolution.
We investigate the biological significance of the gene expression signature that
the predictions are based upon from multiple perspectives: by perturbing the
regulatory network through the Ras/PKA pathway, observing strong upregulation of
growth rate even in the absence of appropriate nutrients, and discovering
putative transcription factor binding sites, observing enrichment in
growth-correlated genes. More broadly, the proposed methodology enables
biological insights about growth at an instantaneous time scale, inaccessible by
direct experimental methods. Data and tools enabling others to apply our methods
are available at http://function.princeton.edu/growthrate
Measurements of Elastic Moduli of Silicone Gel Substrates with a Microfluidic Device
Thin layers of gels with mechanical properties mimicking animal tissues are widely used to study the rigidity sensing of adherent animal cells and to measure forces applied by cells to their substrate with traction force microscopy. The gels are usually based on polyacrylamide and their elastic modulus is measured with an atomic force microscope (AFM). Here we present a simple microfluidic device that generates high shear stresses in a laminar flow above a gel-coated substrate and apply the device to gels with elastic moduli in a range from 0.4 to 300 kPa that are all prepared by mixing two components of a transparent commercial silicone Sylgard 184. The elastic modulus is measured by tracking beads on the gel surface under a wide-field fluorescence microscope without any other specialized equipment. The measurements have small and simple to estimate errors and their results are confirmed by conventional tensile tests. A master curve is obtained relating the mixing ratios of the two components of Sylgard 184 with the resulting elastic moduli of the gels. The rigidity of the silicone gels is less susceptible to effects from drying, swelling, and aging than polyacrylamide gels and can be easily coated with fluorescent tracer particles and with molecules promoting cellular adhesion. This work can lead to broader use of silicone gels in the cell biology laboratory and to improved repeatability and accuracy of cell traction force microscopy and rigidity sensing experiments
Environmental and Genetic Determinants of Colony Morphology in Yeast
Nutrient stresses trigger a variety of developmental switches in the budding yeast Saccharomyces cerevisiae. One of the least understood of such responses is the development of complex colony morphology, characterized by intricate, organized, and strain-specific patterns of colony growth and architecture. The genetic bases of this phenotype and the key environmental signals involved in its induction have heretofore remained poorly understood. By surveying multiple strain backgrounds and a large number of growth conditions, we show that limitation for fermentable carbon sources coupled with a rich nitrogen source is the primary trigger for the colony morphology response in budding yeast. Using knockout mutants and transposon-mediated mutagenesis, we demonstrate that two key signaling networks regulating this response are the filamentous growth MAP kinase cascade and the Ras-cAMP-PKA pathway. We further show synergistic epistasis between Rim15, a kinase involved in integration of nutrient signals, and other genes in these pathways. Ploidy, mating-type, and genotype-by-environment interactions also appear to play a role in the controlling colony morphology. Our study highlights the high degree of network reuse in this model eukaryote; yeast use the same core signaling pathways in multiple contexts to integrate information about environmental and physiological states and generate diverse developmental outputs
Molecular Biomechanics: The Molecular Basis of How Forces Regulate Cellular Function
Recent advances have led to the emergence of molecular biomechanics as an essential element of modern biology. These efforts focus on theoretical and experimental studies of the mechanics of proteins and nucleic acids, and the understanding of the molecular mechanisms of stress transmission, mechanosensing and mechanotransduction in living cells. In particular, single-molecule biomechanics studies of proteins and DNA, and mechanochemical coupling in biomolecular motors have demonstrated the critical importance of molecular mechanics as a new frontier in bioengineering and life sciences. To stimulate a more systematic study of the basic issues in molecular biomechanics, and attract a broader range of researchers to enter this emerging field, here we discuss its significance and relevance, describe the important issues to be addressed and the most critical questions to be answered, summarize both experimental and theoretical/computational challenges, and identify some short-term and long-term goals for the field. The needs to train young researchers in molecular biomechanics with a broader knowledge base, and to bridge and integrate molecular, subcellular and cellular level studies of biomechanics are articulated.National Institutes of Health (U.S.) (grant UO1HL80711-05 to GB)National Institutes of Health (U.S.) (grant R01GM076689-01)National Institutes of Health (U.S.) (grant R01AR033236-26)National Institutes of Health (U.S.) (grant R01GM087677-01A1)National Institutes of Health (U.S.) (grant R01AI44902)National Institutes of Health (U.S.) (grant R01AI38282)National Science Foundation (U.S.) (grant CMMI-0645054)National Science Foundation (U.S.) (grant CBET-0829205)National Science Foundation (U.S.) (grant CAREER-0955291
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