Epigenetic silencing of SOCS3 expression contributes to fibrosis in Crohn’s disease

Identified risk polymorphisms affecting the Jak-STAT3 pathway in patients with Crohn’s disease could affect TGF-β1 and collagen I expression and in the pathway’s negative regulator, SOCS3. Genetic factors, however, account for only ~25% of disease. Epigenetic events also shape gene expression. Recent experiments showed that autocrine IL-6 production in mesenchymal cells, subepithelial myofibroblasts (SEMF) and muscle cells, of patients with fibrostenotic Crohn’s disease causes sustained Jak-STAT3 activity, excess TGF-β1 and Collagen I production and fibrosis. SOCS3 paradoxically decreased in these cells. We now identify epigenetic mechanisms that silence SOCS3 expression in SEMF of patients with fibrostenotic Crohn’s disease. In a previous experiment, using isolated SEMF of normal ileum and affected ileum from patients with each Crohn’s phenotype, inflammatory (Montreal B1), fibrostenotic (B2) and penetrating (B3), we confirmed decreased SOCS3 protein levels were unique to B2 patients. Expression of miR-19b increased in SEMF of affected ileum. SOCS3 transcriptional activity decreased after transfection of miR-19b mimic and increased when antagomiR-19b was expressed. Epigenetic silencing of SOCS3 in ileal SEMF of patients with fibrostenotic Crohn’s disease occurs by increased miR-19b mediated inhibition of SOCS3

An Online Decision-Theoretic Pipeline for Responder Dispatch

The problem of dispatching emergency responders to service traffic accidents, fire, distress calls and crimes plagues urban areas across the globe. While such problems have been extensively looked at, most approaches are offline. Such methodologies fail to capture the dynamically changing environments under which critical emergency response occurs, and therefore, fail to be implemented in practice. Any holistic approach towards creating a pipeline for effective emergency response must also look at other challenges that it subsumes - predicting when and where incidents happen and understanding the changing environmental dynamics. We describe a system that collectively deals with all these problems in an online manner, meaning that the models get updated with streaming data sources. We highlight why such an approach is crucial to the effectiveness of emergency response, and present an algorithmic framework that can compute promising actions for a given decision-theoretic model for responder dispatch. We argue that carefully crafted heuristic measures can balance the trade-off between computational time and the quality of solutions achieved and highlight why such an approach is more scalable and tractable than traditional approaches. We also present an online mechanism for incident prediction, as well as an approach based on recurrent neural networks for learning and predicting environmental features that affect responder dispatch. We compare our methodology with prior state-of-the-art and existing dispatch strategies in the field, which show that our approach results in a reduction in response time with a drastic reduction in computational time.Comment: Appeared in ICCPS 201

Facilities for the Energy Frontier of Nuclear Physics

The Relativistic Heavy Ion Collider at BNL has been exploring the energy frontier of nuclear physics since 2001. Its performance, flexibility and continued innovative upgrading can sustain its physics output for years to come. Now, the Large Hadron Collider at CERN is about to extend the frontier energy of laboratory nuclear collisions by more than an order of magnitude. In the coming years, its physics reach will evolve towards still higher energy, luminosity and varying collision species, within performance bounds set by accelerator technology and by nuclear physics itself. Complementary high-energy facilities will include fixed-target collisions at the CERN SPS, the FAIR complex at GSI and possible electron-ion colliders based on CEBAF at JLAB, RHIC at BNL or the LHC at CERN.Comment: Invited talk at the International Nuclear Physics Conference, Vancouver, Canada, 4-9 July 2010, to be published in Journal of Physics: Conference Series. http://inpc2010.triumf.ca

Multistate Assessment of Public Health Surveillance Relevant to American Indians and Alaska Natives, 2007

Improving the health of American Indian and Alaska Native (AI/AN) populations involves multiple agencies, levels of government, and jurisdictions. We assessed collaboration between state health departments and AI/AN Tribes and agencies through an online survey of State Epidemiologists. Frequencies and percentages of responses were examined by univariate and bivariate analyses. Among 39 states with federally recognized or state-recognized Tribes or federally funded urban Indian health centers, 25 (64%) participated. Nineteen had discussed public health surveillance with an AI/ AN government or nongovernment entity in the past 2 years (10 (53%) of these had ongoing, regular discussions about public health surveillance; nine (47%) had these discussions as needed). Nine (36%) responding states have a point person for working with AI/AN communities and/or agencies on public health surveillance. Four (16%) states have an active memorandum of understanding or other formal agreement with an AI/AN government or nongovernment entity regarding surveillance. To prepare for public health emergencies, six (24%) states involve the Indian Health Service, and eight (47%) involve another AI/AN entity. Functional relationships between state health departments and AI/AN agencies have not been consistently established. Strengthening these relationships will facilitate surveillance and response capacity to address continuing and emerging public health problems

Models and estimators linking individual-based and sample-based rarefaction, extrapolation and comparison of assemblages

Aims: In ecology and conservation biology, the number of species counted in a biodiversity study is a key metric but is usually a biased underestimate of total species richness because many rare species are not detected. Moreover, comparing species richness among sites or samples is a statistical challenge because the observed number of species is sensitive to the number of individuals counted or the area sampled. For individual-based data, we treat a single, empirical sample of species abundances from an investigator-defined species assemblage or community as a reference point for two estimation objectives under two sampling models: estimating the expected number of species (and its unconditional variance) in a random sample of (i) a smaller number of individuals (multinomial model) or a smaller area sampled (Poisson model) and (ii) a larger number of individuals or a larger area sampled. For sample-based incidence (presence-absence) data, under a Bernoulli product model, we treat a single set of species incidence frequencies as the reference point to estimate richness for smaller and larger numbers of sampling units. Methods: The first objective is a problem in interpolation that we address with classical rarefaction (multinomial model) and Coleman rarefaction (Poisson model) for individual-based data and with sample-based rarefaction (Bernoulli product model) for incidence frequencies. The second is a problem in extrapolation that we address with sampling-theoretic predictors for the number of species in a larger sample (multinomial model), a larger area (Poisson model) or a larger number of sampling units (Bernoulli product model), based on an estimate of asymptotic species richness. Although published methods exist for many of these objectives, we bring them together here with some new estimators under a unified statistical and notational framework. This novel integration of mathematically distinct approaches allowed us to link interpolated (rarefaction) curves and extrapolated curves to plot a unified species accumulation curve for empirical examples. We provide new, unconditional variance estimators for classical, individual-based rarefaction and for Coleman rarefaction, long missing from the toolkit of biodiversity measurement. We illustrate these methods with datasets for tropical beetles, tropical trees and tropical ants. Important Findings: Surprisingly, for all datasets we examined, the interpolation (rarefaction) curve and the extrapolation curve meet smoothly at the reference sample, yielding a single curve. Moreover, curves representing 95% confidence intervals for interpolated and extrapolated richness estimates also meet smoothly, allowing rigorous statistical comparison of samples not only for rarefaction but also for extrapolated richness values. The confidence intervals widen as the extrapolation moves further beyond the reference sample, but the method gives reasonable results for extrapolations up to about double or triple the original abundance or area of the reference sample. We found that the multinomial and Poisson models produced indistinguishable results, in units of estimated species, for all estimators and datasets. For sample-based abundance data, which allows the comparison of all three models, the Bernoulli product model generally yields lower richness estimates for rarefied data than either the multinomial or the Poisson models because of the ubiquity of non-random spatial distributions in nature. © 2012 The Author. Published by Oxford University Press on behalf of the Institute of Botany, Chinese Academy of Sciences and the Botanical Society of China. All rights reserved

CMB polarimetry with BICEP: instrument characterization, calibration, and performance

BICEP is a ground-based millimeter-wave bolometric array designed to target the primordial gravity wave signature on the polarization of the cosmic microwave background (CMB) at degree angular scales. Currently in its third year of operation at the South Pole, BICEP is measuring the CMB polarization with unprecedented sensitivity at 100 and 150 GHz in the cleanest available 2% of the sky, as well as deriving independent constraints on the diffuse polarized foregrounds with select observations on and off the Galactic plane. Instrument calibrations are discussed in the context of rigorous control of systematic errors, and the performance during the first two years of the experiment is reviewed.Comment: 12 pages, 15 figures, updated version of a paper accepted for Millimeter and Submillimeter Detectors and Instrumentation for Astronomy IV, Proceedings of SPIE, 7020, 200

4-Amino­pyridinium hydrogen succinate

In the title salt, C5H7N2 +·C4H5O4 −, the asymmetric unit comprises an amino­pyridinium cation and a hydrogen succinate anion as protonation of the aromatic N atom of the 4-amino­pyridine mol­ecule has occurred. The crystal packing is stabilized by inter­molecular O—H⋯O and N—H⋯O hydrogen bonds that lead to a two-dimensional array. Short C—H⋯O contacts are also present

Bis(4-amino­pyridinium) bis(hydrogen oxalate) monohydrate

In the title compound, 2C5H7N2 +·2C2HO4 −·H2O, the asymmetric unit consists of an amino­pyridinium cation, an oxalic actetate anion and a half-molecule of water, which lies on a two-fold rotation axis. The crystal packing is consolidated by inter­molecular O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds. The mol­ecules are linked into an infinite one dimensional chain along [010]