Testing High-dimensional Multinomials with Applications to Text Analysis

Motivated by applications in text mining and discrete distribution inference, we investigate the testing for equality of probability mass functions of $K$ groups of high-dimensional multinomial distributions. A test statistic, which is shown to have an asymptotic standard normal distribution under the null, is proposed. The optimal detection boundary is established, and the proposed test is shown to achieve this optimal detection boundary across the entire parameter space of interest. The proposed method is demonstrated in simulation studies and applied to analyze two real-world datasets to examine variation among consumer reviews of Amazon movies and diversity of statistical paper abstracts

Activation of Extracellular-signal Regulated Kinase (ERK1/2) by Fluid Shear is Ca\u3csup\u3e2+\u3c/sup\u3e- and ATP-dependent in MC3T3-E1 Osteoblasts

To determine the role of Ca2+ signaling in activation of the Mitogen-Activated Protein Kinase (MAPK) pathway, we subjected MC3T3-E1 pre-osteoblastic cells to inhibitors of Ca2+ signaling during application of fluid shear stress (FSS). FSS only activated ERK1/2, rapidly inducing phosphorylation within 5 min of the onset of shear. Phosphorylation of ERK1/2 (pERK1/2) was significantly reduced when Cai2+ was chelated with BAPTA or when Ca2+ was removed from the flow media. Inhibition of both the L-type voltage-sensitive Ca2+ channel and the mechanosensitive cation-selective channel blocked FSS-induced pERK1/2. Inhibition of phospholipase C with U73122 significantly reduced pERK1/2. This inhibition did not result from blockage of intracellular Ca2+ release, but a loss of PKC activation. Recent data suggests a role of ATP release and purinergic receptor activation in mechanotransduction. Apyrase-mediated hydrolysis of extracellular ATP completely blocked FSS-induced phosphorylation of ERK1/2, while the addition of exogenous ATP to static cells mimicked the effects of FSS on pERK1/2. Two P2 receptors, P2Y2 and P2X7, have been associated with the anabolic responses of bone to mechanical loading. Using both iRNA techniques and primary osteoblasts isolated from P2X7 knockout mice, we found that the P2X7, but not the P2Y2, purinergic receptor was involved in ERK1/2 activation under FSS. These data suggest that FSS-induced ERK1/2 phosphorylation requires Ca2+-dependent ATP release, however both increased Cai2+ and PKC activation are needed for complete activation. Further, this ATP-dependent ERK1/2 phosphorylation is mediated through P2X7, but not P2Y2, purinergic receptors

Cardiac fibroblast-specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin-6 signaling mechanism

Recent studies suggest that cardiac fibroblast-specific p38α MAPK contributes to the development of cardiac hypertrophy, but the underlying mechanism is unknown. Our study used a novel fibroblast-specific, tamoxifen-inducible p38α knockout (KO) mouse line to characterize the role of fibroblast p38α in modulating cardiac hypertrophy, and we elucidated the mechanism. Myocardial injury was induced in tamoxifen-treated Cre-positive p38α KO mice or control littermates via chronic infusion of the β-adrenergic receptor agonist isoproterenol. Cardiac function was assessed by pressure-volume conductance catheter analysis and was evaluated for cardiac hypertrophy at tissue, cellular, and molecular levels. Isoproterenol infusion in control mice promoted overt cardiac hypertrophy and dysfunction (reduced ejection fraction, increased end systolic volume, increased cardiac weight index, increased cardiomyocyte area, increased fibrosis, and up-regulation of myocyte fetal genes and hypertrophy-associated microRNAs). Fibroblast-specific p38α KO mice exhibited marked protection against myocardial injury, with isoproterenol-induced alterations in cardiac function, histology, and molecular markers all being attenuated. In vitro mechanistic studies determined that cardiac fibroblasts responded to damaged myocardium by secreting several paracrine factors known to induce cardiomyocyte hypertrophy, including IL-6, whose secretion was dependent upon p38α activity. In conclusion, cardiac fibroblast p38α contributes to cardiomyocyte hypertrophy and cardiac dysfunction, potentially via a mechanism involving paracrine fibroblast-to-myocyte IL-6 signaling.-Bageghni, S. A., Hemmings, K. E., Zava, N., Denton, C. P., Porter, K. E., Ainscough, J. F. X., Drinkhill, M. J., Turner, N. A. Cardiac fibroblast-specific p38α MAP kinase promotes cardiac hypertrophy via a putative paracrine interleukin-6 signaling mechanism

Peer-reviewed Library Teaching: Reflections, Background and Practicalities

Information Literacy Instruction & Teaching are among the increasing variety of roles librarians undertake (Vassilakaki & Moniarou-Papaconstantinou, 2015). However, many in the profession must learn and develop the necessary skills when in post as teaching development is a missing component in the majority of library courses (Levene & Frank, 1993; Alabi & Weare, 2014). This workshop explores Peer Observation (a learning technique many librarians are unfamiliar with (Alabi et al, 2012)) and considers how information professionals could potentially use it to improve their teaching practice to more effectively deliver Information Literacy Instruction & Support and develop and enhance students’ skills

Herschel far-infrared photometric monitoring of protostars in the Orion Nebula Cluster

We have obtained time series observations of the Orion Nebula Cluster at 70 microns and 160 microns from the Herschel/PACS Photometer. This represents the first wide-field far-infrared photometric monitoring of a young star forming region. The acquired 35'x35' maps show complex extended structures, with unprecedented details, that trace the interaction between the molecular gas and the young hot stars. We detect 43 protostars, most of which are situated along the integral-shaped filament extending from the Orion nebula, through OMC2 and to OMC3. We present high-reliability light curves for some of these objects using the first six epochs of our observing program spread over 6 weeks. We find amplitude variations in excess of 20% for a fraction of the detected protostars over periods as short as a few weeks. This is inconsistent with the dynamical time-scales of cool far-IR emitting material that orbits at hundreds of AU from the protostar, and it suggests that the mechanism(s) responsible for the observed variability originates from the inner region of the protostars, likely driven by variable mass accretion.Comment: 14 pages, 3 figures, 2 table

Commercial-off-the-shelf simulation package interoperability: Issues and futures

Commercial-Off-The-Shelf Simulation Packages (CSPs) are widely used in industry to simulate discrete-event models. Interoperability of CSPs requires the use of distributed simulation techniques. Literature presents us with many examples of achieving CSP interoperability using bespoke solutions. However, for the wider adoption of CSP-based distributed simulation it is essential that, first and foremost, a standard for CSP interoperability be created, and secondly, these standards are adhered to by the CSP vendors. This advanced tutorial is on an emerging standard relating to CSP interoperability. It gives an overview of this standard and presents case studies that implement some of the proposed standards. Furthermore, interoperability is discussed in relation to large and complex models developed using CSPs that require large amount of computing resources. It is hoped that this tutorial will inform the simulation community of the issues associated with CSP interoperability, the importance of these standards and its future

The application of Bayesian change point detection in UAV fuel systems

AbstractA significant amount of research has been undertaken in statistics to develop and implement various change point detection techniques for different industrial applications. One of the successful change point detection techniques is Bayesian approach because of its strength to cope with uncertainties in the recorded data. The Bayesian Change Point (BCP) detection technique has the ability to overcome the uncertainty in estimating the number and location of change point due to its probabilistic theory. In this paper we implement the BCP detection technique to a laboratory based fuel rig system to detect the change in the pre-valve pressure signal due to a failure in the valve. The laboratory test-bed represents a Unmanned Aerial Vehicle (UAV) fuel system and its associated electrical power supply, control system and sensing capabilities. It is specifically designed in order to replicate a number of component degradation faults with high accuracy and repeatability so that it can produce benchmark datasets to demonstrate and assess the efficiency of the BCP algorithm. Simulation shows satisfactory results of implementing the proposed BCP approach. However, the computational complexity, and the high sensitivity due to the prior distribution on the number and location of the change points are the main disadvantages of the BCP approac

Mapping the methylation status of the miR-145 promoter in saphenous vein smooth muscle cells from individuals with type 2 diabetes

Type 2 diabetes mellitus prevalence is growing globally, and the leading cause of mortality in these patients is cardiovascular disease. Epigenetic mechanisms such as microRNAs (miRs) and DNA methylation may contribute to complications of type 2 diabetes mellitus. We discovered an aberrant type 2 diabetes mellitus–smooth muscle cell phenotype driven by persistent up-regulation of miR-145. This study aimed to determine whether elevated expression was due to changes in methylation at the miR-145 promoter. Smooth muscle cells were cultured from saphenous veins of 22 non-diabetic and 22 type 2 diabetes mellitus donors. DNA was extracted, bisulphite treated and pyrosequencing used to interrogate methylation at 11 CpG sites within the miR-145 promoter. Inter-patient variation was high irrespective of type 2 diabetes mellitus. Differential methylation trends were apparent between non-diabetic and type 2 diabetes mellitus–smooth muscle cells at most sites but were not statistically significant. Methylation at CpGs −112 and −106 was consistently lower than all other sites explored in non-diabetic and type 2 diabetes mellitus–smooth muscle cells. Finally, miR-145 expression per se was not correlated with methylation levels observed at any site. The persistent up-regulation of miR-145 observed in type 2 diabetes mellitus–smooth muscle cells is not related to methylation at the miR-145 promoter. Crucially, miR-145 methylation is highly variable between patients, serving as a cautionary note for future studies of this region in primary human cell types