Modeling the Evolution of Regulatory Elements by Simultaneous Detection and Alignment with Phylogenetic Pair HMMs

The computational detection of regulatory elements in DNA is a difficult but important problem impacting our progress in understanding the complex nature of eukaryotic gene regulation. Attempts to utilize cross-species conservation for this task have been hampered both by evolutionary changes of functional sites and poor performance of general-purpose alignment programs when applied to non-coding sequence. We describe a new and flexible framework for modeling binding site evolution in multiple related genomes, based on phylogenetic pair hidden Markov models which explicitly model the gain and loss of binding sites along a phylogeny. We demonstrate the value of this framework for both the alignment of regulatory regions and the inference of precise binding-site locations within those regions. As the underlying formalism is a stochastic, generative model, it can also be used to simulate the evolution of regulatory elements. Our implementation is scalable in terms of numbers of species and sequence lengths and can produce alignments and binding-site predictions with accuracy rivaling or exceeding current systems that specialize in only alignment or only binding-site prediction. We demonstrate the validity and power of various model components on extensive simulations of realistic sequence data and apply a specific model to study Drosophila enhancers in as many as ten related genomes and in the presence of gain and loss of binding sites. Different models and modeling assumptions can be easily specified, thus providing an invaluable tool for the exploration of biological hypotheses that can drive improvements in our understanding of the mechanisms and evolution of gene regulation

Angiostrongylosis-related restrictive pneumopathy assessed by arterial blood gas analysis in a dog

Pulmonary angiostrongylosis was diagnosed by the Baermann method and larval identification from faecal and bronchoalveolar lavage samples in a five-month- old male mongrel dog with dyspnoea and cough. Arterial blood gas analysis indicated arterial hypoxaemia and restrictive pneumopathy. In addition to the palliative treatment, fenbendazole was administered (50 mg/kg/24 h per os) for 14 days. The respiratory signs subsided within a short time clinically, but serial arterial blood gas analysis demonstrated an ongoing ventilation disorder. Repeated haematology, thoracic radiography, bronchoscopy and blood gas analysis were performed to follow the course of the disease. The most severe eosinophilia was detected after the beginning of the anthelmintic therapy, and the arterial pO2 level was permanently low. Arterial blood gas analysis provided the most adequate information about the course of the pneumopathy and it greatly facilitated the patient’s medical management

Thermal Diffusion and Quench Propagation in YBCO Pancake Coils Wound with ZnO-and Mylar Insulations

The thermal diffusion properties of several different kinds of YBCO insulations and the quench properties of pancake coils made using these insulations were studied. Insulations investigated include Nomex, Kapton, and Mylar, as well as insulations based on ZnO, Zn2GeO4, and ZnO-Cu. Initially, short stacks of YBCO conductors with interlayer insulation, epoxy, and a central heater strip were made and later measured for thermal conductivity in liquid nitrogen. Subsequently, three different pancake coils were made. The first two were smaller, each using one meter total of YBCO tape present as four turns around a G-10 former. One of these smaller coils used Mylar insulation co-wound with the YBCO tape, the other used YBCO tape onto which ZnO based insulation had been deposited. One larger coil was made which used 12 total meters of ZnO-insulated tape and had 45 turns. The results for all short sample and coil thermal conductivities were ~1-3 Wm-1K-1. Finally, quench propagation velocity measurements were performed on the coils (77 K, self field) by applying a DC current and then using a heater pulse to initiate a quench. Normal zone propagation velocity (NZP) values were obtained for the coils both in the radial direction and in the azimuthal direction. Radial NZP values (0.05-0.7 mm/s) were two orders of magnitude lower than axial values (~14-17 mm/s). Nevertheless, the quenches were generally seen to propagate radially within the coils, in the sense that any given layer in the coil is driven normal by the layer underneath it.Comment: 58 pages, 5 tables, 16 fig

Anisotropic Connectivity and its Influence on Critical Current Densities, Irreversibility Fields, and Flux Creep in In-Situ-Processed MgB2 Strands

The anisotropy of the critical current density (Jc) and its influence on measurement of irreversibility field (Birr) has been investigated for high quality, in-situ MgB2 strands. Comparison of transport and magnetization measurements has revealed the onset of a regime where large differences exist between transport and magnetically measured values of the critical current density and Birr. These effects, initially unexpected due to the lack of crystalline texture in these in-situ processed strands, appear to be due to a fibrous microstructure, connected with the details of the wire fabrication and MgB2 formation reactions. Scanning electron micrographs of in-situ-processed MgB2 monocore strands have revealed a fibrous microstructure. Grains (~100 nm) are randomly oriented, and there is no apparent local texture of the grains. However, this randomly oriented polycrystalline material has a fibrous texture at a larger length scale, with stringers of MgB2 (~ 60 {\mu}m long and ~5 {\mu}m in diameter) partially separated by elongated pores -- the spaces previously occupied by stringers of elemental Mg. This leads to an interpretation of the differences observed in transport and magnetically determined critical currents, in particular a large deviation between the two at higher fields, in terms of different transverse and longitudinal connectivities within the strand. The different values of connectivity also lead to different resistive transition widths, and thus irreversibility field values, as measured by transport and magnetic techniques. Finally, these considerations are seen to influence estimated pinning potentials for the strands.Comment: 43 Pages, 11 Figures, accepted by Supercon. Sci. Tec

Nuclear dependence of the transverse single-spin asymmetry in the production of charged hadrons at forward rapidity in polarized p+pp+p, p+p+Al, and p+p+Au collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

We report on the nuclear dependence of transverse single-spin asymmetries (TSSAs) in the production of positively-charged hadrons in polarized $p^{\uparrow}+p$, $p^{\uparrow}+$Al and $p^{\uparrow}+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV. The measurements have been performed at forward rapidity ($1.4<\eta<2.4$) over the range of $1.8<p_{T}<7.0$ GeV$/c$ and $0.1<x_{F}<0.2$. We observed a positive asymmetry $A_{N}$ for positively-charged hadrons in \polpp collisions, and a significantly reduced asymmetry in $p^{\uparrow}$+$A$ collisions. These results reveal a nuclear dependence of charged hadron $A_N$ in a regime where perturbative techniques are relevant. These results provide new opportunities to use \polpA collisions as a tool to investigate the rich phenomena behind TSSAs in hadronic collisions and to use TSSA as a new handle in studying small-system collisions.Comment: 303 authors from 66 institutions, 9 pages, 2 figures, 1 table. v1 is version accepted for publication in Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Nuclear dependence of the transverse-single-spin asymmetry for forward neutron production in polarized pp++AA collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

During 2015 the Relativistic Heavy Ion Collider (RHIC) provided collisions of transversely polarized protons with Au and Al nuclei for the first time, enabling the exploration of transverse-single-spin asymmetries with heavy nuclei. Large single-spin asymmetries in very forward neutron production have been previously observed in transversely polarized $p$$+$$p$ collisions at RHIC, and the existing theoretical framework that was successful in describing the single-spin asymmetry in $p$$+$$p$ collisions predicts only a moderate atomic-mass-number ($A$) dependence. In contrast, the asymmetries observed at RHIC in $p$$+$$A$ collisions showed a surprisingly strong $A$ dependence in inclusive forward neutron production. The observed asymmetry in $p$$+$Al collisions is much smaller, while the asymmetry in $p$$+$Au collisions is a factor of three larger in absolute value and of opposite sign. The interplay of different neutron production mechanisms is discussed as a possible explanation of the observed $A$ dependence.Comment: 315 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for publication in Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm