Mid-Infrared Properties of Luminous Infrared Galaxies II: Probing the Dust and Gas Physics of the GOALS Sample

The Great Observatories All-Sky LIRG Survey (GOALS) is a comprehensive, multiwavelength study of luminous infrared galaxies (LIRGs) in the local universe. Here we present the results of a multi-component, spectral decomposition analysis of the low resolution mid-IR Spitzer IRS spectra from 5-38um of 244 LIRG nuclei. The detailed fits and high quality spectra allow for characterization of the individual PAH features, warm molecular hydrogen emission, and optical depths for silicate dust grains and water ices. We find that starbursting LIRGs, which make up the majority of GOALS, are very consistent in their MIR properties (i.e. tau_9.7um, tau_ice, neon line and PAH feature ratios). However, as their PAH EQW decreases, usually an indicator of an increasingly dominant AGN, LIRGs cover a larger spread in these MIR parameters. The contribution from PAHs to the total L(IR) in LIRGs varies from 2-29% and LIRGs prior to their first encounter show higher L(PAH)/L(IR) ratios on average. We observe a correlation between the strength of the starburst (IR8) and the PAH fraction at 8um but not with the 7.7 to 11.3 PAH ratio, suggesting the fractional PDR emission, and not the overall grain properties, is associated with the rise in IR8 for galaxies off the starburst main sequence. We detect crystalline silicate features in 6% of the sample but only in the most obscured sources (s_9.7um < -1.24). Ice absorption features are observed in 11% (56%) of GOALS LIRGs (ULIRGs). Most GOALS LIRGs have L(H2)/L(PAH) ratios elevated above those observed for normal star-forming galaxies and exhibit a trend for increasing L(H2)/L(PAH) ratio with increasing L(H2). While star formation appears to be the dominant process responsible for exciting the H2 in most of the GOALS galaxies, a subset of LIRGs (10%) show excess H2 emission that is inconsistent with PDR models and may be excited by shocks or AGN-induced outflows.Comment: 21 pages with 20 figures plus 2 table

A Century on the Northern Plains: the University of North Dakota at 100

This is the Centennial History of the University of North Dakota, published in 1983.https://commons.und.edu/und-books/1001/thumbnail.jp

Herpes Simplex Virus-1 Infection in Human Primary Corneal Epithelial Cells is Blocked by a Stapled Peptide that Targets Processive DNA Synthesis

Purpose: Acyclovir is most commonly used for treating ocular Herpes Keratitis, a leading cause of infectious blindness. However, emerging resistance to Acyclovir resulting from mutations in the thymidine kinase gene of Herpes Simplex Virus −1 (HSV-1), has prompted the need for new therapeutics directed against a different viral protein. One novel target is the HSV-1 Processivity Factor which is essential for tethering HSV-1 Polymerase to the viral genome to enable long-chain DNA synthesis. Methods: A series of peptides, based on the crystal structure of the C-terminus of HSV-1 Polymerase, were constructed with hydrocarbon staples to retain their alpha-helical conformation. The stapled peptides were tested for blocking both HSV-1 DNA synthesis and infection. The most effective peptide was further optimized by replacing its negative N-terminus with two hydrophobic valine residues. This di-valine stapled peptide was tested for inhibiting HSV-1 infection of human primary corneal epithelial cells. Results: The stapled peptides blocked HSV-1 DNA synthesis and HSV-1 infection. The unstapled control peptide had no inhibitory effects. Specificity of the stapled peptides was confirmed by their inabilities to block infection by an unrelated virus. Significantly, the optimized di-valine stapled peptide effectively blocked HSV-1 infection in human primary corneal epithelial cells with selectivity index of 11.6. Conclusions: Hydrocarbon stapled peptides that simulate the α-helix from the C-terminus of HSV-1 DNA polymerase can specifically block DNA synthesis and infection of HSV-1 in human primary corneal epithelial cells. These stapled peptides provide a foundation for developing a topical therapeutic for treating human ocular Herpes Keratitis. © 202

Genetic validation of bipolar disorder identified by automated phenotyping using electronic health records

Bipolar disorder (BD) is a heritable mood disorder characterized by episodes of mania and depression. Although genomewide association studies (GWAS) have successfully identified genetic loci contributing to BD risk, sample size has become a rate-limiting obstacle to genetic discovery. Electronic health records (EHRs) represent a vast but relatively untapped resource for high-throughput phenotyping. As part of the International Cohort Collection for Bipolar Disorder (ICCBD), we previously validated automated EHR-based phenotyping algorithms for BD against in-person diagnostic interviews (Castro et al. Am J Psychiatry 172:363–372, 2015). Here, we establish the genetic validity of these phenotypes by determining their genetic correlation with traditionally ascertained samples. Case and control algorithms were derived from structured and narrative text in the Partners Healthcare system comprising more than 4.6 million patients over 20 years. Genomewide genotype data for 3330 BD cases and 3952 controls of European ancestry were used to estimate SNP-based heritability (h2g) and genetic correlation (rg) between EHR-based phenotype definitions and traditionally ascertained BD cases in GWAS by the ICCBD and Psychiatric Genomics Consortium (PGC) using LD score regression. We evaluated BD cases identified using 4 EHR-based algorithms: an NLP-based algorithm (95-NLP) and three rule-based algorithms using codified EHR with decreasing levels of stringency—“coded-strict”, “coded-broad”, and “coded-broad based on a single clinical encounter” (coded-broad-SV). The analytic sample comprised 862 95-NLP, 1968 coded-strict, 2581 coded-broad, 408 coded-broad-SV BD cases, and 3 952 controls. The estimated h2g were 0.24 (p = 0.015), 0.09 (p = 0.064), 0.13 (p = 0.003), 0.00 (p = 0.591) for 95-NLP, coded-strict, coded-broad and coded-broad-SV BD, respectively. The h2g for all EHR-based cases combined except coded-broad-SV (excluded due to 0 h2g) was 0.12 (p = 0.004). These h2g were lower or similar to the h2g observed by the ICCBD + PGCBD (0.23, p = 3.17E−80, total N = 33,181). However, the rg between ICCBD + PGCBD and the EHR-based cases were high for 95-NLP (0.66, p = 3.69 × 10–5), coded-strict (1.00, p = 2.40 × 10−4), and coded-broad (0.74, p = 8.11 × 10–7). The rg between EHR-based BD definitions ranged from 0.90 to 0.98. These results provide the first genetic validation of automated EHR-based phenotyping for BD and suggest that this approach identifies cases that are highly genetically correlated with those ascertained through conventional methods. High throughput phenotyping using the large data resources available in EHRs represents a viable method for accelerating psychiatric genetic research

A systematic review of the effectiveness of qigong exercise in supportive cancer care

PURPOSE: Qigong as a complementary and alternative modality of traditional Chinese medicine is often used by cancer patients to manage their symptoms. The aim of this systematic review is to critically evaluate the effectiveness of qigong exercise in cancer care. METHODS: Thirteen databases were searched from their inceptions through November 2010. All controlled clinical trials of qigong exercise among cancer patients were included. The strength of the evidence was evaluated for all included studies using the Oxford Centre for Evidence-based Medicine Levels of Evidence. The validity of randomized controlled trials (RCTs) was also evaluated using the Jadad Scale. RESULTS: Twenty-three studies including eight RCTs and fifteen non-randomized controlled clinical trials (CCTs) were identified. The effects of qigong on physical and psychosocial outcomes were examined in 14 studies and the effects on biomedical outcomes were examined in 15 studies. For physical and psychosocial outcomes, it is difficult to draw a conclusion due to heterogeneity of outcome measures and variability of the results in the included studies. Among reviewed studies on biomedical outcomes, a consistent tendency appears to emerge which suggests that the patients treated with qigong exercise in combination with conventional methods had significant improvement in immune function than the patients treated with conventional methods alone. CONCLUSIONS: Due to high risk of bias and methodological problems in the majority of included studies, it is still too early to draw conclusive statements. Further vigorously designed large-scale RCTs with validated outcome measures are needed.published_or_final_versio

Methods to Develop an Electronic Medical Record Phenotype Algorithm to Compare the Risk of Coronary Artery Disease across 3 Chronic Disease Cohorts

Background Typically, algorithms to classify phenotypes using electronic medical record (EMR) data were developed to perform well in a specific patient population. There is increasing interest in analyses which can allow study of a specific outcome across different diseases. Such a study in the EMR would require an algorithm that can be applied across different patient populations. Our objectives were: (1) to develop an algorithm that would enable the study of coronary artery disease (CAD) across diverse patient populations; (2) to study the impact of adding narrative data extracted using natural language processing (NLP) in the algorithm. Additionally, we demonstrate how to implement CAD algorithm to compare risk across 3 chronic diseases in a preliminary study. Methods and Results We studied 3 established EMR based patient cohorts: diabetes mellitus (DM, n = 65,099), inflammatory bowel disease (IBD, n = 10,974), and rheumatoid arthritis (RA, n = 4,453) from two large academic centers. We developed a CAD algorithm using NLP in addition to structured data (e.g. ICD9 codes) in the RA cohort and validated it in the DM and IBD cohorts. The CAD algorithm using NLP in addition to structured data achieved specificity >95% with a positive predictive value (PPV) 90% in the training (RA) and validation sets (IBD and DM). The addition of NLP data improved the sensitivity for all cohorts, classifying an additional 17% of CAD subjects in IBD and 10% in DM while maintaining PPV of 90%. The algorithm classified 16,488 DM (26.1%), 457 IBD (4.2%), and 245 RA (5.0%) with CAD. In a cross-sectional analysis, CAD risk was 63% lower in RA and 68% lower in IBD compared to DM (p<0.0001) after adjusting for traditional cardiovascular risk factors. Conclusions We developed and validated a CAD algorithm that performed well across diverse patient populations. The addition of NLP into the CAD algorithm improved the sensitivity of the algorithm, particularly in cohorts where the prevalence of CAD was low. Preliminary data suggest that CAD risk was significantly lower in RA and IBD compared to DM.National Institutes of Health (U.S.). Informatics for Integrating Biology and the Bedside Project (U54LM008748

Neutrino Propagation in a Strongly Magnetized Medium

We derive general expressions at the one-loop level for the coefficients of the covariant structure of the neutrino self-energy in the presence of a constant magnetic field. The neutrino energy spectrum and index of refraction are obtained for neutral and charged media in the strong-field limit ($M_{W}\gg \sqrt{B}\gg m_{e},T,\mu ,| \mathbf{p}|$) using the lowest Landau level approximation. The results found within the lowest Landau level approximation are numerically validated, summing in all Landau levels, for strong $B\gg T^{2}$ and weakly-strong $B \gtrsim T^{2}$ fields. The neutrino energy in leading order of the Fermi coupling constant is expressed as the sum of three terms: a kinetic-energy term, a term of interaction between the magnetic field and an induced neutrino magnetic moment, and a rest-energy term. The leading radiative correction to the kinetic-energy term depends linearly on the magnetic field strength and is independent of the chemical potential. The other two terms are only present in a charged medium. For strong and weakly-strong fields, it is found that the field-dependent correction to the neutrino energy in a neutral medium is much larger than the thermal one. Possible applications to cosmology and astrophysics are considered.Comment: 23 pages, 4 figures. Corrected misprints in reference

Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS