Correction for founder effects in host-viral association studies via principal components

Viruses such as HIV and Hepatitis C (HCV) replicate rapidly and with high transcription error rates, which may facilitate their escape from immune detection through the encoding of mutations at key positions within human leukocyte antigen (HLA)-specific peptides, thus impeding T-cell recognition. Large-scale population-based host-viral association studies are conducted as hypothesis-generating analyses which aim to determine the positions within the viral sequence at which host HLA immune pressure may have led to these viral escape mutations. When transmission of the virus to the host is HLA-associated, however, standard tests of association can be confounded by the viral relatedness of contemporarily circulating viral sequences, as viral sequences descended from a common ancestor may share inherited patterns of polymorphisms, termed 'founder effects'. Recognizing the correspondence between this problem and the confounding of case-control genome-wide association studies by population stratification, we adapt methods taken from that field to the analysis of host-viral associations. In particular, we consider methods based on principal components analysis within a logistic regression framework motivated by alternative formulations in the Frisch-Waugh-Lovell Theorem. We demonstrate via simulation their utility in detecting true host-viral associations whilst minimizing confounding by associations generated by founder effects. The proposed methods incorporate relatively robust, standard statistical procedures which can be easily implemented using widely available software, and provide alternatives to the more complex computer intensive methods often implemented in this area

Geochemical analysis and modeling for an artificial aquifer recharge study in the shallow zone squifer near Pojoaque, New Mexico.

An artificial aquifer recharge project is currently being evaluated as a component of the Pojoaque Basin Regional Water System as part of the Aamodt Litigation Settlement Act. The purpose of the project is for aquifer storage, with later retrieval as drinking water. The total diversion of San Juan Chama Project Water (SJCPW) for this project is approximately 4,000 acre-feet per year. It should be noted that some of the SJCPW would be treated and put directly into the drinking water system. The goal of this project is to extract the SJCPW from the Rio Grande and pump it into two arroyos, the Arroyo Jocona and an unnamed arroyo. The hope is that the water will reach the shallow aquifer via infiltration. The United States Geological Survey (USGS) performed a geophysical study of the two above-mentioned arroyos near Pojoaque, New Mexico to determine the lithology if SJCPW will infiltrate through the vadose zone and into the shallow aquifer system. The USGS also drilled four borings and completed monitoring wells in two of the borings. The wells were used to collect water levels and water quality samples. After performing analysis of the groundwater, using both an inductively couple plasma (ICP) and ion chromatography (IC) instruments, and analysis of the sediments using acid digestion and a batch extraction, it was determined that several analytes exceed the United States Environmental Protection Agency Drinking Water Standards. These analytes include aluminum, beryllium, fluoride, iron, and arsenic. All of these analytes are found at concentrations would most likely be able to be treated using standard modern water treatment techniques

Axion perturbation spectra in string cosmologies

We discuss the semi-classical perturbation spectra produced in the massless fields of the low energy string action in a pre big bang type scenario. Axion fields may possess an almost scale-invariant spectrum on large scales dependent upon the evolution of the dilaton and moduli fields to which they are coupled. As an example we calculate the spectra for three axion fields present in a truncated type IIB model and show that they are related with at least one of the fields having a scale-invariant or red perturbation spectrum. In the simplest pre big bang scenario this may be inconsistent with the observed isotropy of the microwave background. More generally, relations between the perturbation spectra in low energy string cosmologies reflect the symmetries of the theory.Comment: 9 pages, latex with epsf, 1 figure. Revised estimate of amplitude of density perturbations and extended discussion of possible conflict with isotropy of cosmic microwave background. To appear in Physics Letters

Comparison of data acquisition methods for the identification and quantification of histone post-translational modifications on a Q Exactive HF hybrid quadrupole Orbitrap mass spectrometer.

RATIONALE: Histone PTMs play key roles in regulating eukaryotic gene expression. Mass spectrometry (MS) has emerged as a powerful method to characterize and quantify histone PTMs as it allows unbiased identification and quantification of multiple histone PTMs including combinations of the modifications present. METHODS: In this study we compared a range of data acquisition methods for the identification and quantification of the histone PTMs using a Q Exactive HF Orbitrap. We compared three different data-dependent analysis (DDA) methods with MS2 resolutions of 120K, 60K, 30K. We also compared a range of data-independent analysis (DIA) methods using MS2 isolation windows of 20 m/z and DIAvw to identify and quantify histone PTMs in Chinese Hamster Ovary (CHO) cells. RESULTS: The increased number of MS2 scans afforded by the lower resolution methods resulted in a higher number of queries, peptide sequence matches (PSMs) and a higher number of peptide proteoforms with a Mascot Ion score greater than 46. No difference in the proportion of peptide proteoforms with Delta scores >17 was observed. Comparing the data acquisition methods increased repeatability in terms of lower CVs afforded by DIA MS1 60K MS2 30K 20m/z isolation windows was observed. CONCLUSION: We observed that DIA which offers advantages in flexibility and identification of isobaric peptide proteoforms performs as well as DDA in the analysis of histone PTMs. We were able to identify 71 modified histone peptides for histone H3 and H4 and quantified 64 across each of the different acquisition methods

Templates for Convex Cone Problems with Applications to Sparse Signal Recovery

This paper develops a general framework for solving a variety of convex cone problems that frequently arise in signal processing, machine learning, statistics, and other fields. The approach works as follows: first, determine a conic formulation of the problem; second, determine its dual; third, apply smoothing; and fourth, solve using an optimal first-order method. A merit of this approach is its flexibility: for example, all compressed sensing problems can be solved via this approach. These include models with objective functionals such as the total-variation norm, ||Wx||_1 where W is arbitrary, or a combination thereof. In addition, the paper also introduces a number of technical contributions such as a novel continuation scheme, a novel approach for controlling the step size, and some new results showing that the smooth and unsmoothed problems are sometimes formally equivalent. Combined with our framework, these lead to novel, stable and computationally efficient algorithms. For instance, our general implementation is competitive with state-of-the-art methods for solving intensively studied problems such as the LASSO. Further, numerical experiments show that one can solve the Dantzig selector problem, for which no efficient large-scale solvers exist, in a few hundred iterations. Finally, the paper is accompanied with a software release. This software is not a single, monolithic solver; rather, it is a suite of programs and routines designed to serve as building blocks for constructing complete algorithms.Comment: The TFOCS software is available at http://tfocs.stanford.edu This version has updated reference

Critical current degradation in HTS wires due to cyclic mechanical strain

HTS wires, which may be used in many devices such as magnets and rotating machines, may be subjected to mechanical strains from electromagnetic, thermal and centripetal forces. In some applications these strains will be repeated several thousand times during the lifetime of the device. We have measured critical current degradation due to repeated strain cycles for both compressive and tensile strains. Results for BSCCO-2223 HTS conductor samples are presented for strain values up to 0.5% and cycle numbers up to and beyond 10/sup 4/

Optimal network topology and reliability indices to be used in the design of power distribution networks in oil and gas plants

The cost of loss of production in oil and gas plants is on average 6.5 times higher than that of plants in any other industry. Thus the reliability performance and analysis of oil and gas plants are unique. There have been many studies that have produced reliability indices for equipment that is used in industrial distribution networks, but these are all industry generic and none are specifi c to the oil and gas industry. This paper presents a set of equipment reliability indices that has been established from data collected from oil and gas plants and is suitable for use in reliability evaluations of the distribution networks of oil and gas plants. In the design of distribution networks for new oil and gas plants, engineers either do not have enough operational data, enough time or do not know how to perform the analysis required for establishing what type of network topology to use. This paper recommends the optimal network topology to use in such cases and provides evidence to support this proposal.http://www.tandfonline.com/loi/tele20hb2016Electrical, Electronic and Computer Engineerin

Conformationally restricted calpain inhibitors

The cysteine protease calpain-I is linked to several diseases and is therefore a valuable target for inhibition. Selective inhibition of calpain-I has proved difficult as most compounds target the active site and inhibit a broad spectrum of cysteine proteases as well as other calpain isoforms. Selective inhibitors might not only be potential drugs but should act as tools to explore the physiological and pathophysiological roles of calpain-I. α-Mercaptoacrylic acid based calpain inhibitors are potent, cell permeable and selective inhibitors of calpain-I and calpain-II. These inhibitors target the calcium binding domain PEF(S) of calpain-I and -II. Here X-ray diffraction analysis of co-crystals of PEF(S) revealed that the disulfide form of an α-mercaptoacrylic acid bound within a hydrophobic groove that is also targeted by a calpastatin inhibitory region and made a greater number of favourable interactions with the protein than the reduced sulfhydryl form. Measurement of the inhibitory potency of the α-mercaptoacrylic acids and X-ray crystallography revealed that the IC50 values decreased significantly on oxidation as a consequence of the stereo-electronic properties of disulfide bonds that restrict rotation around the S–S bond. Consequently, thioether analogues inhibited calpain-I with potencies similar to those of the free sulfhydryl forms of α-mercaptoacrylic acids

Cosmological scaling solutions in generalised Gauss-Bonnet gravity theories

The conditions for the existence and stability of cosmological power-law scaling solutions are established when the Einstein-Hilbert action is modified by the inclusion of a function of the Gauss-Bonnet curvature invariant. The general form of the action that leads to such solutions is determined for the case where the universe is sourced by a barotropic perfect fluid. It is shown by employing an equivalence between the Gauss-Bonnet action and a scalar-tensor theory of gravity that the cosmological field equations can be written as a plane autonomous system. It is found that stable scaling solutions exist when the parameters of the model take appropriate values.Comment: 10 pages and 5 figure