SimShiftDB; local conformational restraints derived from chemical shift similarity searches on a large synthetic database

We present SimShiftDB, a new program to extract conformational data from protein chemical shifts using structural alignments. The alignments are obtained in searches of a large database containing 13,000 structures and corresponding back-calculated chemical shifts. SimShiftDB makes use of chemical shift data to provide accurate results even in the case of low sequence similarity, and with even coverage of the conformational search space. We compare SimShiftDB to HHSearch, a state-of-the-art sequence-based search tool, and to TALOS, the current standard tool for the task. We show that for a significant fraction of the predicted similarities, SimShiftDB outperforms the other two methods. Particularly, the high coverage afforded by the larger database often allows predictions to be made for residues not involved in canonical secondary structure, where TALOS predictions are both less frequent and more error prone. Thus SimShiftDB can be seen as a complement to currently available methods

The Evolution of Ga and as Core Levels in the Formation of Fe/GaAs (001): A High Resolution Soft X-Ray Photoelectron Spectroscopic Study

A high resolution soft x-ray photoelectron spectroscopic study of Ga and as 3d core levels has been conducted for Fe/GaAs (001) as a function of Fe thickness. This work has provided unambiguous evidence of substrate disrupting chemical reactions induced by the Fe overlayer—a quantitative analysis of the acquired spectra indicates significantly differing behavior of Ga and as during Fe growth, and our observations have been compared with existing theoretical models. Our results demonstrate that the outdiffusing Ga and as remain largely confined to the interface region, forming a thin intermixed layer. Whereas at low coverages Fe has little influence on the underlying GaAs substrate, the onset of substrate disruption when the Fe thickness reaches 3.5 Å results in major changes in the energy distribution curves (EDCs) of both as and Ga 3d cores. Our quantitative analysis suggests the presence of two additional as environments of metallic character: one bound to the interfacial region and another which, as confirmed by in situ oxidation experiments, surface segregates and persists over a wide range of overlayer thickness. Analysis of the corresponding Ga 3d EDCs found not two, but three additional environments—also metallic in nature. Two of the three are interface resident whereas the third undergoes outdiffusion at low Fe coverages. Based on the variations of the integrated intensities of each component, we present a schematic of the proposed chemical makeup of the Fe/GaAs (001) system

The Bolocam Galactic Plane Survey: Survey Description and Data Reduction

We present the Bolocam Galactic Plane Survey (BGPS), a 1.1 mm continuum survey at 33" effective resolution of 170 square degrees of the Galactic Plane visible from the northern hemisphere. The survey is contiguous over the range -10.5 < l < 90.5, |b| < 0.5 and encompasses 133 square degrees, including some extended regions |b| < 1.5. In addition to the contiguous region, four targeted regions in the outer Galaxy were observed: IC1396, a region towards the Perseus Arm, W3/4/5, and Gem OB1. The BGPS has detected approximately 8400 clumps over the entire area to a limiting non-uniform 1-sigma noise level in the range 11 to 53 mJy/beam in the inner Galaxy. The BGPS source catalog is presented in a companion paper (Rosolowsky et al. 2010). This paper details the survey observations and data reduction methods for the images. We discuss in detail the determination of astrometric and flux density calibration uncertainties and compare our results to the literature. Data processing algorithms that separate astronomical signals from time-variable atmospheric fluctuations in the data time-stream are presented. These algorithms reproduce the structure of the astronomical sky over a limited range of angular scales and produce artifacts in the vicinity of bright sources. Based on simulations, we find that extended emission on scales larger than about 5.9' is nearly completely attenuated (> 90%) and the linear scale at which the attenuation reaches 50% is 3.8'. Comparison with other millimeter-wave data sets implies a possible systematic offset in flux calibration, for which no cause has been discovered. This presentation serves as a companion and guide to the public data release through NASA's Infrared Processing and Analysis Center (IPAC) Infrared Science Archive (IRSA). New data releases will be provided through IPAC IRSA with any future improvements in the reduction.Comment: Accepted for publication in Astrophysical Journal Supplemen

Engineering restoration and gaseous carbon uptake on a degraded bog: the role of Eriophorum angustifolium and micropropagated Sphagnum

Degraded peatlands are significant sources of carbon greenhouse gases (CGHG), and their recovery can make significant contributions to climate change mitigation as well as deliver biodiversity benefits. Sphagnum mosses are key species for northern peatland formation and re-introduction is often needed for successful ecohydrological restoration of degraded bogs, but natural sources are scarce and often protected. Micropropagated Sphagnum moss products (BeadaMoss®) were developed to alleviate this constraint. This research explored in detail, for the first time, the CGHG fluxes on a cut-over lowland peatland restoration site where micropropagated Sphagnum was introduced to an existing ‘nurse crop’ of Eriophorum angustifolium, and tested the influence of vegetation maturity. Ecosystem CGHG flux was measured using closed chambers at plot scale in areas of both mature and immature E. angustifolium with and without application of BeadaGel™ Sphagnum, with control plots on bare peat. Studies were conducted over two years of contrasting weather patterns. In Year 1, mean net (CO2e) CGHG uptake on vegetated plots was -2.33 (minimum 1.55, maximum -5.55) t ha-1 yr-1 with increasing CGHG uptake as vegetation matured. In Year 2, gross photosynthesis reduced significantly during the 2018 summer drought resulting in a small mean net CGHG emission of 0.11 (minimum 2.21 maximum -1.22) t ha-1 yr-1 . Sphagnum application within immature vegetation resulted in greater CGHG uptake in both years, but was not as beneficial within mature vegetation. CGHG emission from bare peat (3.79 t ha-1 yr-1 overall) showed the magnitude of avoided losses. Methane flux contributed significantly to CGHG emission but was not closely related to water table depth. Application of Sphagnum within E. angustifolium can deliver good CGHG flux results in the early stages of degraded lowland bog recovery but cannot fully mitigate vulnerability to climate change scenarios

Infinite factorization of multiple non-parametric views

Combined analysis of multiple data sources has increasing application interest, in particular for distinguishing shared and source-specific aspects. We extend this rationale of classical canonical correlation analysis into a flexible, generative and non-parametric clustering setting, by introducing a novel non-parametric hierarchical mixture model. The lower level of the model describes each source with a flexible non-parametric mixture, and the top level combines these to describe commonalities of the sources. The lower-level clusters arise from hierarchical Dirichlet Processes, inducing an infinite-dimensional contingency table between the views. The commonalities between the sources are modeled by an infinite block model of the contingency table, interpretable as non-negative factorization of infinite matrices, or as a prior for infinite contingency tables. With Gaussian mixture components plugged in for continuous measurements, the model is applied to two views of genes, mRNA expression and abundance of the produced proteins, to expose groups of genes that are co-regulated in either or both of the views. Cluster analysis of co-expression is a standard simple way of screening for co-regulation, and the two-view analysis extends the approach to distinguishing between pre- and post-translational regulation

Metabolic rate and rates of protein turnover in food-deprived cuttlefish, Sepia officinalis (Linnaeus 1758)

To determine the metabolic response to food deprivation, cuttlefish (Sepia officinalis) juveniles were either fed, fasted (3 to 5 days food deprivation), or starved (12 days food deprivation). Fasting resulted in a decrease in triglyceride levels in the digestive gland, and after 12 days, these lipid reserves were essentially depleted. Oxygen consumption was decreased to 53% and NH4 excretion to 36% of the fed group following 3-5 days of food deprivation. Oxygen consumption remained low in the starved group, but NH4 excretion returned to the level recorded for fed animals during starvation. The fractional rate of protein synthesis of fasting animals decreased to 25% in both mantle and gill compared with fed animals and remained low in the mantle with the onset of starvation. In gill, however, protein synthesis rate increased to a level that was 45% of the fed group during starvation. In mantle, starvation led to an increase in cathepsin A-, B-, H-, and L-like enzyme activity and a 2.3-fold increase in polyubiquitin mRNA that suggested an increase in ubiquitin-proteasome activity. In gill, there was a transient increase in the polyubiquitin transcript levels in the transition from fed through fasted to the starved state and cathepsin A-, B-, H-, and L-like activity was lower in starved compared with fed animals. The response in gill appears more complex, as they better maintain rates of protein synthesis and show no evidence of enhanced protein breakdown through recognized catabolic processes

Risk factors for delay in symptomatic presentation: a survey of cancer patients

Background: Delay in symptomatic presentation leading to advanced stage at diagnosis may contribute to poor cancer survival. To inform public health approaches to promoting early symptomatic presentation, we aimed to identify risk factors for delay in presentation across several cancers. Methods: We surveyed 2371 patients with 15 cancers about nature and duration of symptoms using a postal questionnaire. We calculated relative risks for delay in presentation (time from symptom onset to first presentation >3 months) by cancer, symptoms leading to diagnosis and reasons for putting off going to the doctor, controlling for age, sex and deprivation group. Results: Among 1999 cancer patients reporting symptoms, 21% delayed presentation for >3 months. Delay was associated with greater socioeconomic deprivation but not age or sex. Patients with prostate (44%) and rectal cancer (37%) were most likely to delay and patients with breast cancer least likely to delay (8%). Urinary difficulties, change of bowel habit, systemic symptoms (fatigue, weight loss and loss of appetite) and skin symptoms were all common and associated with delay. Overall, patients with bleeding symptoms were no more likely to delay presentation than patients who did not have bleeding symptoms. However, within the group of patients with bleeding symptoms, there were significant differences in risk of delay by source of bleeding: 35% of patients with rectal bleeding delayed presentation, but only 9% of patients with urinary bleeding. A lump was a common symptom but not associated with delay in presentation. Twenty-eight percent had not recognised their symptoms as serious and this was associated with a doubling in risk of delay. Embarrassment, worry about what the doctor might find, being too busy to go to the doctor and worry about wasting the doctor’s time were also strong risk factors for delay, but were much less commonly reported (<6%). Interpretation: Approaches to promote early presentation should aim to increase awareness of the significance of cancer symptoms and should be designed to work for people of the lowest socioeconomic status. In particular, awareness that rectal bleeding is a possible symptom of cancer should be raised

Professionalism, Golf Coaching and a Master of Science Degree: A commentary

As a point of reference I congratulate Simon Jenkins on tackling the issue of professionalism in coaching. As he points out coaching is not a profession, but this does not mean that coaching would not benefit from going through a professionalization process. As things stand I find that the stimulus article unpacks some critically important issues of professionalism, broadly within the context of golf coaching. However, I am not sure enough is made of understanding what professional (golf) coaching actually is nor how the development of a professional golf coach can be facilitated by a Master of Science Degree (M.Sc.). I will focus my commentary on these two issues

Nucleon-nucleon elastic scattering analysis to 2.5 GeV

A partial-wave analysis of NN elastic scattering data has been completed. This analysis covers an expanded energy range, from threshold to a laboratory kinetic energy of 2.5 GeV, in order to include recent elastic pp scattering data from the EDDA collaboration. The results of both single-energy and energy-dependent analyses are described.Comment: 23 pages of text. Postscript files for the figures are available from ftp://clsaid.phys.vt.edu/pub/said/n

HES5 silencing is an early and recurrent change in prostate tumourigenesis.

Prostate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation profiling in a series of multi-focal prostate tumours, we identify promoter methylation of the transcription factor HES5 as an early event in prostate tumourigenesis. We confirm that this epigenetic alteration occurs in 86-97% of cases in two independent prostate cancer cohorts (n=49 and n=39 tumour-normal pairs). Treatment of prostate cancer cells with the demethylating agent 5-aza-2'-deoxycytidine increased HES5 expression and downregulated its transcriptional target HES6, consistent with functional silencing of the HES5 gene in prostate cancer. Finally, we identify and test a transcriptional module involving the AR, ERG, HES1 and HES6 and propose a model for the impact of HES5 silencing on tumourigenesis as a starting point for future functional studies.The authors are grateful to study volunteers for their participation and staff at the Welcome Trust Clinical Research Facility, Addenbrooke’s Clinical Research Centre, Cambridge. They also thank the NIHR Cambridge Biomedical Research Centre, the DOH HTA (ProtecT grant), and the NCRI/MRC (ProMPT grant) for help with the bio-repository, The University of Cambridge, Hutchison Whampoa Limited and Cancer Research UK for funding. They are grateful to the CRUK Cambridge Institute Genomics and Bioinformatics Core Facilities. Cross-validation of HES5 methylation includes the use of data generated by the TCGA Research Network.This is the final version of the article. It was originally published in the Endocrine-Related Cancer, April 1, 2015 22 131-144 doi: 10.1530/ERC-14-0454