bluuebunny/crossref_metadata_2025 huggingface dataset:
The Life of Sir Humphry Davy
Authors: Paris John Ayrton
Published: October 2011

Sir Humphry Davy (1778–1829) was a hugely influential chemist, inventor, and public lecturer who is recognised as one of the first professional scientists. He was apprenticed to an apothecary in 1795, which formed his introduction to chemical experiments. A chance meeting with Davis Giddy in 1798 introduced Davy into the wider scientific community, and in 1800 he was invited to a post at the Royal Institution, where he lectured to great acclaim. These volumes, first published in 1831, contain Davy's official biography. Researched and written by John Ayrton Paris, the work describes in detail Davy's life and his scientific studies. Organised chronologically with excerpts from his private correspondence, Davy's early life and his experiments and lectures at the Royal Institution and his Presidency of the Royal Society between 1820 and 1827 are explored in vivid detail. Volume 2 describes his life and work between 1812 and 1829.
Duels and Duets
Authors: Locke John L.
Published: October 2011

Why do men and women talk so differently? And how do these differences interfere with communication between the sexes? In search of an answer to these and other questions, John Locke takes the reader on a fascinating journey, from human evolution through ancient history to the present, revealing why men speak as they do when attempting to impress or seduce women, and why women adopt a very different way of talking when bonding with each other, or discussing rivals. When men talk to men, Locke argues, they frequently engage in a type of 'dueling', locking verbal horns with their rivals in a way that enables them to compete for the things they need, mainly status and sex. By contrast, much of women's talk sounds more like a verbal 'duet', a harmonious way of achieving their goals by sharing intimate thoughts and feelings in private.
Shakespeare, Rhetoric and Cognition
Authors: Lyne Raphael
Published: October 2011

Raphael Lyne addresses a crucial Shakespearean question: why do characters in the grip of emotional crises deliver such extraordinarily beautiful and ambitious speeches? How do they manage to be so inventive when they are perplexed? Their dense, complex, articulate speeches at intensely dramatic moments are often seen as psychological - they uncover and investigate inwardness, character and motivation - and as rhetorical - they involve heightened language, deploying recognisable techniques. Focusing on A Midsummer Night's Dream, Othello, Cymbeline and the Sonnets, Lyne explores both the psychological and rhetorical elements of Shakespeare's language. In the light of cognitive linguistics and cognitive literary theory he shows how Renaissance rhetoric could be considered a kind of cognitive science, an attempt to map out the patterns of thinking. His study reveals how Shakespeare's metaphors and similes work to think, interpret and resolve, and how their struggle to do so results in extraordinary poetry.
Principles of Applied Statistics
Authors: Cox D. R. , Donnelly Christl A.
Published: October 2011

Applied statistics is more than data analysis, but it is easy to lose sight of the big picture. David Cox and Christl Donnelly distil decades of scientific experience into usable principles for the successful application of statistics, showing how good statistical strategy shapes every stage of an investigation. As you advance from research or policy question, to study design, through modelling and interpretation, and finally to meaningful conclusions, this book will be a valuable guide. Over a hundred illustrations from a wide variety of real applications make the conceptual points concrete, illuminating your path and deepening your understanding. This book is essential reading for anyone who makes extensive use of statistical methods in their work.
The History of a Slave
Authors: Johnston Harry Hamilton
Published: October 2011

Sir Harry Hamilton Johnston (1858–1927) was an explorer, colonial administrator and main participant in the British expansion in Africa, along with his friend Cecil Rhodes. Johnston published several accounts of his expeditions, as well as surveying native languages and culture. This text is Johnston's fictionalised account of the life of a slave, based on anecdotes he gathered on his travels. The protagonist describes his early life as the warrior son of the village chief in a brutal society where cannibalism and allegations of witchcraft were commonplace. When slavers attacked his village and captured him, 'Abu' faced a long journey across the country, survived by few, before serving a succession of masters. A vivid and eventful history of one man's survival through escape attempts, attacks by wild animals and relentless violence, which Johnston described as his attempt to give 'a realistic sketch of life in the Western Sudan'.
The Friendship of Books
Authors: Maurice Frederick Denison
Published: October 2011

F. D. Maurice (1805–72), the widely published theologian and Christian socialist, served as both Professor of English Literature at King's College, London, and Professor of Moral Philosophy at Cambridge. He was a founding member of the Cambridge Apostles and later founded the Working Men's College in London. Most of Maurice's publications derive from his sermons and lectures. This book serves as an instructional guide to students of literature. The title is taken from the first lecture, in which Maurice argues that books 'help us in knowing ourselves - the part of history of our land, the people we are continually meeting. And any book that does that is surely a friend.' Subsequent chapters include 'On words', 'Ancient history' and 'On Christian civilization' as well as those with a more literary focus, on Spenser, Milton and Burke. The work was published posthumously in 1873; this third edition appeared in 1880.
Campaigning in Kaffirland, or, Scenes and Adventures in the Kaffir War of 1851–2
Authors: King William Ross
Published: October 2011

First published in 1853, this book chronicles the personal experience of the 'Kaffir' war of 1851–2 (now known as the eighth Xhosa or frontier war), between the European settlers and the native inhabitants of the Eastern Cape in South Africa. Serving as a lieutenant, William Ross King (1822–90) sailed to South Africa from Cork with the 74th Highlanders in March 1851 and remained there until late 1852. His memoir was not intended as a detailed history of military operations in the Kaffir war and in fact encompasses all of King's experiences in South Africa rather than focusing solely on the conflict. The book is especially notable for its extremely one-sided account of events: King exhibits a particularly scathing attitude towards the Xhosa people, who were 'committing the most deliberate outrages and murders' and displaying 'cowardly treachery' towards the European settlers.
America
Authors: Buckingham James Silk
Published: October 2011

James Silk Buckingham (1786–1855) was a writer who travelled extensively throughout the world and published accounts of his adventures in places such as India, Persia, Egypt, and Palestine. In addition, he was a supporter of political reform and served as the first MP for Sheffield, from 1832 to 1837. On retiring from Parliament, he left for North America, where he spent nearly four years, saying, 'I had a strong desire to add to the knowledge … acquired of the Old World, by examining for myself the most favoured portion of the New'. He recounts part of his time in America - during which he visited every state in the Union except Florida and Arkansas, as well as some of the provinces of Canada - in this three-volume work, published in 1841. Volume 2 follows his travels through Pennsylvania, Delaware, and upstate New York before he heads to Niagara Falls.
Modules over Endomorphism Rings
Authors: Faticoni Theodore G.
Published: October 2011

This is an extensive synthesis of recent work in the study of endomorphism rings and their modules, bringing together direct sum decompositions of modules, the class number of an algebraic number field, point set topological spaces, and classical noncommutative localization. The main idea behind the book is to study modules G over a ring R via their endomorphism ring EndR(G). The author discusses a wealth of results that classify G and EndR(G) via numerous properties, and in particular results from point set topology are used to provide a complete characterization of the direct sum decomposition properties of G. For graduate students this is a useful introduction, while the more experienced mathematician will discover that the book contains results that are not otherwise available. Each chapter contains a list of exercises and problems for future research, which provide a springboard for students entering modern professional mathematics.
Stochastic Control and Mathematical Modeling
Authors: Morimoto Hiroaki
Published: October 2011

This is a concise and elementary introduction to stochastic control and mathematical modelling. This book is designed for researchers in stochastic control theory studying its application in mathematical economics and those in economics who are interested in mathematical theory in control. It is also a good guide for graduate students studying applied mathematics, mathematical economics, and non-linear PDE theory. Contents include the basics of analysis and probability, the theory of stochastic differential equations, variational problems, problems in optimal consumption and in optimal stopping, optimal pollution control, and solving the Hamilton-Jacobi-Bellman (HJB) equation with boundary conditions. Major mathematical prerequisites are contained in the preliminary chapters or in the appendix so that readers can proceed without referring to other materials.
Evolution of vortex-surface fields in viscous Taylor–Green and Kida–Pelz flows
Authors: Yang Yue , Pullin D. I.
Published: October 2011

In order to investigate continuous vortex dynamics based on a Lagrangian-like formulation, we develop a theoretical framework and a numerical method for computation of the evolution of a vortex-surface field (VSF) in viscous incompressible flows with simple topology and geometry. Equations describing the continuous, timewise evolution of a VSF from an existing VSF at an initial time are first reviewed. Non-uniqueness in this formulation is resolved by the introduction of a pseudo-time and a corresponding pseudo-evolution in which the evolved field is ‘advected’ by frozen vorticity onto a VSF. A weighted essentially non-oscillatory (WENO) method is used to solve the pseudo-evolution equations in pseudo-time, providing a dissipative-like regularization. Vortex surfaces are then extracted as iso-surfaces of the VSFs at different real physical times. The method is applied to two viscous flows with Taylor–Green and Kida–Pelz initial conditions respectively. Results show the collapse of vortex surfaces, vortex reconnection, the formation and roll-up of vortex tubes, vorticity intensification between anti-parallel vortex tubes, and vortex stretching and twisting. A possible scenario for understanding the transition from a smooth laminar flow to turbulent flow in terms of topology of vortex surfaces is discussed.
Seasonal Synechococcus and Thaumarchaeal population dynamics examined with high resolution with remote in situ instrumentation
Authors: Robidart Julie C , Preston Christina M , Paerl Ryan W , Turk Kendra A , Mosier Annika C , Francis Christopher A , Scholin Christopher A , Zehr Jonathan P
Published: October 2011

Monterey Bay, CA is an Eastern boundary upwelling system that is nitrogen limited much of the year. In order to resolve population dynamics of microorganisms important for nutrient cycling in this region, we deployed the Environmental Sample Processor with quantitative PCR assays targeting both ribosomal RNA genes and functional genes for subclades of cyanobacteria (Synechococcus) and ammonia-oxidizing Archaea (Thaumarchaeota) populations. Results showed a strong correlation between Thaumarchaea abundances and nitrate during the spring upwelling but not the fall sampling period. In relatively stratified fall waters, the Thaumarchaeota community reached higher numbers than in the spring, and an unexpected positive correlation with chlorophyll concentration was observed. Further, we detected drops in Synechococcus abundance that occurred on short (that is, daily) time scales. Upwelling intensity and blooms of eukaryotic phytoplankton strongly influenced Synechococcus distributions in the spring and fall, revealing what appear to be the environmental limitations of Synechococcus populations in this region. Each of these findings has implications for Monterey Bay biogeochemistry. High-resolution sampling provides a better-resolved framework within which to observe changes in the plankton community. We conclude that controls on these ecosystems change on smaller scales than are routinely assessed, and that more predictable trends will be uncovered if they are evaluated within seasonal (monthly), rather than on annual or interannual scales.
Characterization of the cellular action of the MSK inhibitor SB-747651A
Authors: Naqvi Shaista , Macdonald Andrew , McCoy Claire E. , Darragh Joanne , Reith Alastair D. , Arthur J. Simon C.
Published: October 2011

MSK1 (mitogen- and stress-activated kinase 1) and MSK2 are nuclear protein kinases that regulate transcription downstream of the ERK1/2 (extracellular-signal-regulated kinase 1/2) and p38α MAPKs (mitogen-activated protein kinases) via the phosphorylation of CREB (cAMP-response-element-binding protein) and histone H3. Previous studies on the function of MSKs have used two inhibitors, H89 and Ro 31-8220, both of which have multiple off-target effects. In the present study, we report the characterization of the in vitro and cellular properties of an improved MSK1 inhibitor, SB-747651A. In vitro, SB-747651A inhibits MSK1 with an IC50 value of 11 nM. Screening of an in vitro panel of 117 protein kinases revealed that, at 1 μM, SB-747651A inhibited four other kinases, PRK2 (double-stranded-RNA-dependent protein kinase 2), RSK1 (ribosomal S6 kinase 1), p70S6K (S6K is S6 kinase) (p70RSK) and ROCK-II (Rho-associated protein kinase 2), with a similar potency to MSK1. In cells, SB-747651A fully inhibited MSK activity at 5–10 μM. SB-747651A was found to inhibit the production of the anti-inflammatory cytokine IL-10 (interleukin-10) in wild-type, but not MSK1/2-knockout, macrophages following LPS (lipopolysaccharide) stimulation. Both SB-747651A and MSK1/2 knockout resulted in elevated pro-inflammatory cytokine production by macrophages in response to LPS. Comparison of the effects of SB-747651A, both in vitro and in cells, demonstrated that SB-747651A exhibited improved selectivity over H89 and Ro 31-8220 and therefore represents a useful tool to study MSK function in cells.
An Oral, Motor, Medical, and Behavioral Approach to Pediatric Feeding and Swallowing Disorders: An Interdisciplinary Model
Authors: Roche William J. , Eicher Peggy S. , Martorana Pamela , Berkowitz Merrill , Petronchak JoAnn , Dzioba Jessica , Vitello Louise
Published: October 2011

Feeding and swallowing problems are reported in 10-25% of all children, 40-70% in premature infants, and 70-90% in children with medical/developmental delays (Graham, 1985; Rogers & Arvedson, 2005; Sullivan et al., 2000). The etiologies of feeding disorders are as varied as the multiple disciplines, approaches, and interventions available. This paper illustrates, through case presentation, an interdisciplinary feeding team model that incorporates an oral, motor, medical, and behavioral approach to treating children with feeding disorders.
Techniques for the measurement of disruption halo currents in the National Spherical Torus Experiment
Authors: Gerhardt S. P. , Fredrickson E. , Guttadora L. , Kaita R. , Kugel H. , Menard J. , Takahashi H.
Published: October 2011

This paper describes techniques for measuring halo currents, and their associated toroidal peaking, in the National Spherical Torus Experiments [M. Ono et al., Nucl. Fusion 40, 557 (2000)10.1088/0029-5515/40/3Y/316]. The measurements are based on three techniques: (1) measurement of the toroidal field created by the poloidal halo current, either with segmented Rogowski coils or discrete toroidal field sensors, (2) the direct measurement of halo currents into specially instrument tiles, and (3) small Rogowski coils placed on the mechanical supports of in-vessel components. For the segmented Rogowski coils and discrete toroidal field detectors, it is shown that the toroidal peaking factor inferred from the data is significantly less than the peaking factor of the underlying halo current distribution, and a simple model is developed to relate the two. For the array of discrete toroidal field detectors and small Rogowski sensors, the compensation steps that are used to isolate the halo current signal are described. The electrical and mechanical design of compact under-tile resistive shunts and mini-Rogowski coils is described. Example data from the various systems are shown.
Response of water to electric fields at temperatures below the glass transition: A molecular dynamics analysis
Authors: Hu Xiaohu , Elghobashi-Meinhardt Nadia , Gembris Daniel , Smith Jeremy C.
Published: October 2011

The electric field dependence of the structure and dynamics of water at 77 K, i.e., below the glass transition temperature (136 K), is investigated using molecular dynamics simulations. Transitions are found at two critical field strengths, denoted \documentclass[12pt]{minimal}\begin{document}$\mathcal {E}_{1}$\end{document}E1 and \documentclass[12pt]{minimal}\begin{document}$\mathcal {E}_{2}$\end{document}E2. The transition around \documentclass[12pt]{minimal}\begin{document}$\mathcal {E}_{1}\approx 3.5$\end{document}E1≈3.5 V/nm is characterized by the onset of significant structural disorder, a rapid increase in the orientational polarization, and a maximum in the dynamical fluctuations. At \documentclass[12pt]{minimal}\begin{document}$\mathcal {E}_{2}\approx 40$\end{document}E2≈40 V/nm, the system crystallizes in discrete steps into a body-centered-cubic unit cell that minimizes the potential energy by simultaneous superpolarization of the water molecular dipoles and maximization of the intermolecular hydrogen bonds. The stepwise and discontinuous increase of the orientational polarization with the increasing electric field indicates that the dipole relaxation in the electric field is highly cooperative.
Thermodynamic stability boundaries of “classical” noble-gas crystals and the polymorphism problem
Authors: Bondarev V. N. , Tarasevych D. V.
Published: October 2011

The equations of statistical crystal theory with the pair interaction by Lennard-Jones are applied to the calculation of a thermodynamic stability region of hypothetical bcc phase discussed in the literature for crystals of a type similar to Ar. It is shown that this region is completely within a similar region previously calculated by authors for a real fcc phase of such crystals. This result makes improbable the realization of the bcc modification, predicted by a group of authors in computer “experiments” on Xe at high temperatures and pressures, and provoked a critical discussion in the literature. The quantum corrections to the thermodynamic functions of “classical” noble-gas crystals were also taken into consideration and the deviation of the spinodal line of Ne from the “universal” curve is calculated. A good quantitative agreement of obtained results with the data of numerical “experiments” on model (with the Lennard-Jones interaction) “crystals” of Ar, Kr, Xe, as well as of Ne in the “exotic” region of negative pressures is found. Although, at present, the indications of the polymorphic transformation of neon to a modification different than fcc have not been experimentally observed, the discovery of this phenomenon in the predicted range of temperatures T < 70 K and pressures > 0.3 GPa would be of principal interest.
A theoretical study of Ne3 using hyperspherical coordinates and a slow variable discretization approach
Authors: Suno Hiroya
Published: October 2011

We study theoretically the ground and excited bound states of the bosonic rare gas van der Waals trimer Ne3. A slow variable discretization approach is adopted to solve the nuclear Schrödinger equation, in which the Schrödinger equation in hyperangular coordinates is solved using basis splines at a series of fixed finite-element methods discrete variable representation hyper-radii. We consider not only zero total nuclear orbital angular momentum, J = 0, states but also J > 0 states. By using the best empirical neon dimer interaction potentials, all the bound state energy levels of Ne3 will be calculated for total angular momenta up to J = 6, as well as their average root-mean-square radii. We also analyze the wave functions in hyperspherical coordinates for several selected bound states.
Zirconia grafted carbon nanotubes based biosensor for M. Tuberculosis detection
Authors: Das Maumita , Dhand Chetna , Sumana G. , Srivastava A. K. , Vijayan N. , Nagarajan R. , Malhotra B. D.
Published: October 2011

Zirconia (ZrO2) grafted multiwalled carbon nanotubes (CNTs) (crystallite size of ZrO2 ∼ 28.63 nm), obtained via isothermal hydrolysis of zirconium oxychloride in presence of CNT, have been electrophoretically deposited onto indium-tin-oxide (ITO) coated glass plate. High resolution electron microscopic investigations reveal assemblage of the ZrO2 nanostructure inside and around CNT cavities. Electrochemical impedance spectroscopic studies indicate ∼3.5 fold enhancement in charge transfer behaviour of NanoZrO2-CNT/ITO electrode compared to that of NanoZrO2/ITO electrode. Considering the synergy between biocompatible ZrO2 and electrochemically superior CNT, this nanobiocomposite has been explored to develop an impedimetric nucleic acid biosensor for M. Tuberculosis detection.
Simulating infrared spectra and hydrogen bonding in cellulose Iβ at elevated temperatures
Authors: Agarwal Vishal , Huber George W. , Conner W. Curtis , Auerbach Scott M.
Published: October 2011

We have modeled the transformation of cellulose Iβ to a high temperature (550 K) structure, which is considered to be the first step in cellulose pyrolysis. We have performed molecular dynamics simulations at constant pressure using the GROMOS 45a4 united atom forcefield. To test the forcefield, we computed the density, thermal expansion coefficient, total dipole moment, and dielectric constant of cellulose Iβ, finding broad agreement with experimental results. We computed infrared (IR) spectra of cellulose Iβ over the range 300–550 K as a probe of hydrogen bonding. Computed IR spectra were found to agree semi-quantitatively with experiment, especially in the O–H stretching region. We assigned O–H stretches using a novel synthesis of normal mode analysis and power spectrum methods. Simulated IR spectra at elevated temperatures suggest a structural transformation above 450 K, a result in agreement with experimental IR results. The low-temperature (300–400 K) structure of cellulose Iβ is dominated by intrachain hydrogen bonds, whereas in the high-temperature structure (450–550 K), many of these transform to longer, weaker interchain hydrogen bonds. A three-dimensional hydrogen bonding network emerges at high temperatures due to formation of new interchain hydrogen bonds, which may explain the stability of the cellulose structure at such high temperatures.
Mesoscale hydrodynamic modeling of a colloid in shear-thinning viscoelastic fluids under shear flow
Authors: Ji Shichen , Jiang Run , Winkler Roland G. , Gompper Gerhard
Published: October 2011

In order to study the dynamics of colloidal suspensions with viscoelastic solvents, a simple mesoscopic model of the solvent is required. We propose to extend the multiparticle collision dynamics (MPC) technique—a particle-based simulation method, which has been successfully applied to study the hydrodynamic behavior of many complex fluids with Newtonian solvent—to shear-thinning viscoelastic solvents. Here, the normal MPC particles are replaced by dumbbells with finite-extensible nonlinear elastic (FENE) springs. We have studied the properties of FENE-dumbbell fluids under simple shear flow with shear rate \documentclass[12pt]{minimal}\begin{document}$\dot{\gamma }$\end{document}γ̇. The stress tensor is calculated, and the viscosity η and the first normal-stress coefficient Ψ1 are obtained. Shear-thinning behavior is found for reduced shear rates \documentclass[12pt]{minimal}\begin{document}$\Gamma =\dot{\gamma }\tau > 1$\end{document}Γ=γ̇τ>1, where τ is a characteristic dumbbell relaxation time. Here, both η and Ψ1 display power-law behavior in the shear-thinning regime. Thus, the FENE-dumbbell fluid with MPC collisions provides a good description of viscoelastic fluids. As a first application, we study the flow behavior of a colloid in a shear-thinning viscoelastic fluid in two dimensions. A slowing down of the colloid rotation in a viscoelastic fluid compared to a Newtonian fluid is obtained, in agreement with recent numerical calculations and experimental results.
Magnetisation reversal in permalloy nanowires controlled by near-field charge interactions
Authors: Beguivin A. , O’Brien L. A. , Jausovec A. V. , Petit D. , Cowburn R. P.
Published: October 2011

This study investigates the interaction between transverse head-to-head domain walls (THHDWs) in permalloy nanowires and magnetostatic charges located within a tripod structure in close proximity. This interaction enables remote pinning of the THHDW. Eight different interactions are measurable, depending on the initialising field sequence. The pinning strengths of an attractive potential well and a repulsive barrier are compared in this paper. Based on experimental measurements, micromagnetic simulations, and a monopolar analytical model, we demonstrate that pinning strength depends on the inhomogeneous charge distribution within the tripod and the relative orientation of the THHDW which faces the tripod.
Correlation between dielectric properties and chemical composition of the tourmaline single crystals
Authors: Shekhar Pandey Chandra , Jodlauk Sven , Schreuer Jürgen
Published: October 2011

Dielectric responses were studied on piezoelectric tourmaline single crystals of widely varying chemical composition from different geological origins. The dielectric constants at constants stress, and dissipation factor were measured as a function of frequency (100-1000 kHz) using method of substitution. A correlation between two independent dielectric constants (along and perpendicular to crystallographic c-axis) is observed, and dependence of dielectric constants on chemical composition is presented.
Effects of electrical contacts on the photoconductive gain of nanowire photodetectors
Authors: Park Hongsik , Kim Jin Ho , Beresford Roderic , Xu Jimmy
Published: October 2011

The mechanism of the photoconductive gains of nanowire (NW) photodetectors has not been clearly explained yet, although it is generally thought to be the result of a long excess carrier lifetime due to a large trap density. Here, we demonstrate that the photoconductive gain of a Bi2S3 NW photodetector can be contributed by optical modulation of the electrical injection through contacts. We propose a quantitative model to explain the results based on a model of metal-nanowire contacts. The study shows that optically generated excess carriers can modify the barrier structure at the metal-nanowire interface and thereby increase photoconductivity.
Priming of hypoxia-inducible factor by neuronal nitric oxide synthase is essential for adaptive responses to severe anemia
Authors: Tsui Albert K. Y. , Marsden Philip A. , Mazer C. David , Adamson S. Lee , Henkelman R. Mark , Ho J. J. David , Wilson David F. , Heximer Scott P. , Connelly Kim A. , Bolz Steffen-Sebastian , Lidington Darcy , El-Beheiry Mostafa H. , Dattani Neil D. , Chen Kevin M. , Hare Gregory M. T.
Published: October 2011

Cells sense and respond to changes in oxygen concentration through gene regulatory processes that are fundamental to survival. Surprisingly, little is known about how anemia affects hypoxia signaling. Because nitric oxide synthases (NOSs) figure prominently in the cellular responses to acute hypoxia, we defined the effects of NOS deficiency in acute anemia. In contrast to endothelial NOS or inducible NOS deficiency, neuronal NOS (nNOS)
−/−
mice demonstrated increased mortality during anemia. Unlike wild-type (WT) animals, anemia did not increase cardiac output (CO) or reduce systemic vascular resistance (SVR) in nNOS
−/−
mice. At the cellular level, anemia increased expression of HIF-1α protein and HIF-responsive mRNA levels (EPO, VEGF, GLUT1, PDK1) in the brain of WT, but not nNOS
−/−
mice, despite comparable reductions in tissue PO
2
. Paradoxically, nNOS
−/−
mice survived longer during hypoxia, retained the ability to regulate CO and SVR, and increased brain HIF-α protein levels and HIF-responsive mRNA transcripts. Real-time imaging of transgenic animals expressing a reporter HIF-α(ODD)-luciferase chimeric protein confirmed that nNOS was essential for anemia-mediated increases in HIF-α protein stability in vivo.
S
-nitrosylation effects the functional interaction between HIF and pVHL. We found that anemia led to nNOS-dependent
S
-nitrosylation of pVHL in vivo and, of interest, led to decreased expression of GSNO reductase. These findings identify nNOS effects on the HIF/pVHL signaling pathway as critically important in the physiological responses to anemia in vivo and provide essential mechanistic insight into the differences between anemia and hypoxia.
Stocking Success of Paddlefish in Lake Francis Case, South Dakota: Population Characteristics and Sport Fishery Potential
Authors: Pierce Landon L. , Graeb Brian D. S. , Willis David W. , Sorensen Jason S. , Pegg Mark A.
Published: October 2011

Lake Francis Case, South Dakota, a Missouri River reservoir, supported a paddlefish Polyodon spathula sport fishery shortly after impoundment, but this fishery closed in 1986 owing to a lack of natural recruitment. Lake Francis Case has been stocked intermittently since 1974 and annually since 1990 to maintain the population and potentially sustain a sport harvest. To evaluate the success of these stockings, we assessed the current status of the Lake Francis Case paddlefish population (i.e., population characteristics and dynamics) and evaluated the potential effects of exploitation on this population. Advanced fingerling stockings have been effective, as 56% of sampled fish were of hatchery origin (indicated by coded wire tags), and may sustain a harvestable population. Year‐class strength was negatively correlated to water temperature inputs from Big Bend Dam and positively correlated to White River discharge. Downstream emigration is probably responsible for most of the variability in year‐class strength, and the rate of downstream emigration may be greater during years with warmer water temperatures. Harvest simulations suggested that growth overfishing was possible under a 660‐mm minimum length limit but not under 840‐mm and 1,016‐mm minimum length limits. The proportional size distribution of memorable‐length fish (PSD‐M) was reduced 28.6% and 14.3%, respectively, by 5% exploitation under simulated 660‐mm and 840‐mm minimum length limits. Under a simulated 1,016‐mm minimum length limit, PSD‐M was unchanged by 10% exploitation. At 5% exploitation, broodstock availability was reduced by more than 30% under the simulated 660‐mm and 840‐mm minimum length regulations and was reduced 16% under the 1,016‐mm minimum length limit. Our results suggest that this population could support a limited (e.g., 5% exploitation) sport fishery under a high (e.g., 1,016‐mm) minimum length limit without substantial changes in size structure or the availability of broodstock if stockings are continued.
Role for a Cindr–Arf6 axis in patterning emerging epithelia
Authors: Johnson Ruth I. , Sedgwick Alanna , D'Souza-Schorey Crislyn , Cagan Ross L.
Published: October 2011

Patterning of the Drosophila pupal eye is characterized by precise cell movements. In this paper, we demonstrate that these movements require an Arf regulatory cycle that connects surface receptors to actin-based movement. dArf6 activity—regulated by the Arf GTPase–activating proteins (ArfGAPs) dAsap and dArfGAP3 and the Arf GTP exchange factors Schizo and dPsd—promoted large cellular extensions; time-lapse microscopy indicated that these extensions presage cell rearrangements into correct epithelial niches. During this process, the Drosophila eye also requires interactions between surface Neph1/nephrin adhesion receptors Roughest and Hibris, which bind the adaptor protein Cindr (CD2AP). We provide evidence that Cindr forms a physical complex with dArfGAP3 and dAsap. Our data suggest this interaction sequesters ArfGAP function to liberate active dArf6 elsewhere in the cell. We propose that a Neph1/nephrin–Cindr/ArfGAP complex accumulates to limit local Arf6 activity and stabilize adherens junctions. Our model therefore links surface adhesion via an Arf6 regulatory cascade to dynamic modeling of the cytoskeleton, accounting for precise cell movements that organize the functional retinal field. Further, we demonstrate a similar relationship between the mammalian Cindr orthologue CD2AP and Arf6 activity in cell motility assays. We propose that this Cindr/CD2AP-mediated regulation of Arf6 is a widely used mechanism in emerging epithelia.
RNA-Seq analysis in MeV
Authors: Howe Eleanor A. , Sinha Raktim , Schlauch Daniel , Quackenbush John
Published: October 2011

Summary: RNA-Seq is an exciting methodology that leverages the power of high-throughput sequencing to measure RNA transcript counts at an unprecedented accuracy. However, the data generated from this process are extremely large and biologist-friendly tools with which to analyze it are sorely lacking. MultiExperiment Viewer (MeV) is a Java-based desktop application that allows advanced analysis of gene expression data through an intuitive graphical user interface. Here, we report a significant enhancement to MeV that allows analysis of RNA-Seq data with these familiar, powerful tools. We also report the addition to MeV of several RNA-Seq-specific functions, addressing the differences in analysis requirements between this data type and traditional gene expression data. These tools include automatic conversion functions from raw count data to processed RPKM or FPKM values and differential expression detection and functional annotation enrichment detection based on published methods.

Availability: MeV version 4.7 is written in Java and is freely available for download under the terms of the open-source Artistic License version 2.0. The website (http://mev.tm4.org/) hosts a full user manual as well as a short quick-start guide suitable for new users.

Contact:  johnq@jimmy.harvard.edu
Probabilistic alignments with quality scores: an application to short-read mapping toward accurate SNP/indel detection
Authors: Hamada Michiaki , Wijaya Edward , Frith Martin C. , Asai Kiyoshi
Published: October 2011

Motivation: Recent studies have revealed the importance of considering quality scores of reads generated by next-generation sequence (NGS) platforms in various downstream analyses. It is also known that probabilistic alignments based on marginal probabilities (e.g. aligned-column and/or gap probabilities) provide more accurate alignment than conventional maximum score-based alignment. There exists, however, no study about probabilistic alignment that considers quality scores explicitly, although the method is expected to be useful in SNP/indel callers and bisulfite mapping, because accurate estimation of aligned columns or gaps is important in those analyses.

Results: In this study, we propose methods of probabilistic alignment that consider quality scores of (one of) the sequences as well as a usual score matrix. The method is based on posterior decoding techniques in which various marginal probabilities are computed from a probabilistic model of alignments with quality scores, and can arbitrarily trade-off sensitivity and positive predictive value (PPV) of prediction (aligned columns and gaps). The method is directly applicable to read mapping (alignment) toward accurate detection of SNPs and indels. Several computational experiments indicated that probabilistic alignments can estimate aligned columns and gaps accurately, compared with other mapping algorithms e.g. SHRiMP2, Stampy, BWA and Novoalign. The study also suggested that our approach yields favorable precision for SNP/indel calling.

Availability: The method described in this article is implemented in LAST, which is freely available from: http://last.cbrc.jp.

Contact:  mhamada@k.u-tokyo.ac.jp

Supplementary Information:  Supplementary data are available at Bioinformatics online.
The dynamic nature of autophagy in cancer
Authors: Kimmelman Alec C.
Published: October 2011

Macroautophagy (referred to hereafter as autophagy) is a highly regulated cellular process that serves to remove damaged proteins and organelles from the cell. Autophagy contributes to an array of normal and pathological processes, and has recently emerged as a key regulator of multiple aspects of cancer biology. The role of autophagy in cancer is complex and is likely dependent on tumor type, stage, and genetic context. This complexity is illustrated by the identification of settings where autophagy acts potently to either promote or inhibit tumorigenesis. In this review, I discuss the underlying basis for these opposing functions and propose a model suggesting a dynamic role for autophagy in malignancy. Collectively, the data point to autophagy as serving as a barrier to limit tumor initiation. Once neoplastic lesions are established, it appears that adaptive changes occur that now result in positive roles for autophagy in malignant progression and in subsequent tumor maintenance. Remarkably, constitutive activation of autophagy is critical for continued growth of some tumors, serving to both reduce oxidative stress and provide key intermediates to sustain cell metabolism. Autophagy is also induced in response to cancer therapies where it can function as a survival mechanism that limits drug efficacy. These findings have inspired significant interest in applying anti-autophagy therapies as an entirely new approach to cancer treatment. It is now apparent that aberrant control of autophagy is among the key hallmarks of cancer. While much needs to be learned about the regulation and context-dependent biological functions of autophagy, it seems clear that modulation of this process will be an attractive avenue for future cancer therapeutic approaches.
Tunisian Potato virus Y isolates with unnecessary pathogenicity towards pepper: support for the matching allele model in eIF4E resistance–potyvirus interactions
Authors: Ben Khalifa M. , Simon V. , Fakhfakh H. , Moury B.
Published: October 2011

The pathogenic properties of Potato virus Y (PVY; genus Potyvirus, family Potyviridae) isolates collected in naturally infected pepper (Capsicum annuum) fields in Tunisia were evaluated against recessive resistance alleles at the pvr2 locus of pepper. Two pathotypes were observed. Pathotype (0,1,3) isolates were able to infect plants carrying the susceptibility allele pvr2+, together with pvr21/pvr21 and pvr23/pvr23 plants, but not pvr22/pvr22 plants. Pathotype (0) isolates were only able to infect pvr2+/pvr2+ plants. On the other hand, sequence data and phylogenetic analyses revealed three major groups of isolates, each characterized by particular amino acid residues in the central part of the VPg, the pathogenicity factor towards pvr2. Correspondence between pathogenic properties and phylogeny suggested a single evolutionary step for pathogenicity towards the pvr21 and pvr23 resistances, possibly under the selective pressure of pvr21. Indeed, 23% of the pepper plants in this area were shown to carry the pvr21 resistance, while pvr23 was not detected. The data suggested that pathogenicity towards pvr21 and pvr23 were not costly for PVY to infect susceptible pepper genotypes and supported the matching allele model for pepper–PVY interactions.
Estimation of variance components for postpartum dysgalactia syndrome in sows
Authors: Preissler R. , Hinrichs D. , Reiners K. , Looft H. , Kemper N.
Published: October 2011

The postpartum dysgalactia syndrome (PDS) represents one of the most important diseases after parturition in sows. The genetic background of the disease has been investigated some time ago and heritability estimates around 0.10 have been obtained. To compute current estimates, a dataset of 1680 sampled sows and their 2001 clinically examined litters was used for variance components estimation with a threshold liability model. Affected sows were defined through clinical examination 12–48 h after parturition. Posterior mean of additive genetic variance was 0.10 and estimated heritability for PDS averaged 0.0879 with a 95% confidence interval of 0.0876 and 0.0881. The results are in agreement with those of other studies and emphasize the importance of considering the genetic predisposition for susceptibility to PDS as well as of additional factors including hygiene and management conditions.
Effects of a single post‐partum injection of a high dose of vitamin D on glucose tolerance and insulin resistance in mothers with first‐time gestational diabetes mellitus
Authors: Mozaffari‐Khosravi H. , Hosseinzadeh‐Shamsi‐Anar M. , Salami M.‐A. , Hadinedoushan H. , Mozayan M. R.
Published: October 2011

Diabet. Med. 29, 36–42 (2012)

Aim  This study was performed to determine the effect of a single, large, intramuscular injection of vitamin D post‐partum on glucose tolerance and insulin resistance in women with gestational diabetes.

Methods  Forty‐five participants in a randomized controlled trial on gestational diabetes mellitus were divided into an intervention group and a control group. Only subjects in the intervention group received one intramuscular injection of 300 000 IU of vitamin D3. HbA1c, serum 25‐hydroxyvitamin D3, fasting insulin and blood glucose, C‐peptide, homeostasis model assessment insulin resistance index (HOMA‐IR), β‐cell function, insulin sensitivity and the Quantitative Insulin Sensitivity Check Index (QUICKI) were measured at baseline and after 3 months of intervention.

Results  Approximately 80% of the mothers had a degree of vitamin D deficiency. Post‐intervention, this was found in 4.2 and 71.4% in the intervention and control groups, respectively. The medians of HOMA‐IR indices before and after intervention were 0.6 and 0.5 (P = 0.7), respectively, in subjects in the intervention group, and 0.5 and 0.9 (P = 0.01) in subjects in the control group. The mean of the QUICKI fell only in the control group (P = 0.008). In the control group, β‐cell function increased by ∼8% (P = 0.01) and insulin sensitivity decreased after 3 months (P = 0.002). Post‐intervention, the median C‐peptide decreased in the intervention group and increased in the control group, but the change was significant only in the control group (P = 0.03).

Conclusions  A single injection of 300 000 IU of vitamin D3 achieves a 3‐month serum 25‐hydroxyvitamin D range of 50–80 nmol/l and is an efficient, effective and safe procedure for improving the vitamin status and indices of insulin resistance in mothers with gestational diabetes after delivery.
Neural response to the second stimulus associated with poor speed discrimination performance in schizophrenia
Authors: Wang Jun , Dobkins Karen R. , McDowell Jennifer E. , Clementz Brett A.
Published: October 2011

Visual motion processing is compromised in schizophrenia (SZ), but it is uncertain what neural deviations account for their motion analysis abnormalities. Neural activations were measured with dense‐array electroencephalography while 14 medicated SZ and 14 healthy persons performed a paired‐stimuli forced choice speed discrimination task. SZ had (a) worse‐at‐speed discrimination, replicating previous findings, (b) normal early extrastriate neural activity (N1) to both motion stimuli, (c) reduced later extrastriate activity (P2) specifically to the second stimulus, and (d) following P2, an enhanced later N2 over parietal cortex. Stronger P2 and N2 responses were associated with better speed discrimination performance across groups. These findings indicate that the neural correlates of poor motion analysis in SZ may not be an early visual analysis abnormality but a problem with efficient use of speed information later in cognitive processing.
Fitness Costs of Neighborhood Disruption in Translocations of a Solitary Mammal
Authors: SHIER DEBRA M. , SWAISGOOD RONALD R.
Published: October 2011

Abstract:  Translocation is used to reestablish wild populations of animals, but translocation projects often do not meet their objectives because postrelease mortality of animals is high. One reason for translocation failure is that the behavioral or ecological requirements of released animals are unmet. Maintaining founder‐group social relationships during release can affect reestablishment of social species. Solitary territorial species with stable neighbors (restricted dispersal and lifetime occupation of a home range) of the same species may also benefit from the maintenance of these social relationships during translocation. We translocated Stephens’ kangaroo rats (Dipodomys stephensi), a solitary species listed as endangered under the U.S. Endangered Species Act, with and without neighboring kangaroo rats. We compared the settlement (establishment of a stable home range) decisions and fitness of kangaroo rats between the 2 treatments. Kangaroo rats translocated with neighbors traveled shorter distances before establishing territories, had higher survival rates, and had significantly higher reproductive success than kangaroo rats translocated without neighbors. Number of offspring was 24‐fold higher for kangaroo rats translocated with neighbors than those translocated without neighbors. Differences in behavior following release may partially explain differences in survival between the 2 groups. Immediately following release, animals translocated with neighbors fought less and spent significantly more time foraging and digging burrows than animals translocated without neighbors. Our results indicate that even for solitary species, maintaining relationships among members of a translocated group of animals can influence translocation success. This study is the first empirical demonstration of the fitness consequences of disrupting social relationships among territorial neighbors.
Dose‐Response Assessment for Influenza A Virus Based on Data Sets of Infection with its Live Attenuated Reassortants
Authors: Watanabe Toru , Bartrand Timothy A. , Omura Tatsuo , Haas Charles N.
Published: October 2011

Reported data sets on infection of volunteers challenged with wild‐type influenza A virus at graded doses are few. Alternatively, we aimed at developing a dose‐response assessment for this virus based on the data sets for its live attenuated reassortants. Eleven data sets for live attenuated reassortants that were fit to beta‐Poisson and exponential dose‐response models. Dose‐response relationships for those reassortants were characterized by pooling analysis of the data sets with respect to virus subtype (H1N1 or H3N2), attenuation method (cold‐adapted or avian‐human gene reassortment), and human age (adults or children). Furthermore, by comparing the above data sets to a limited number of reported data sets for wild‐type virus, we quantified the degree of attenuation of wild‐type virus with gene reassortment and estimated its infectivity. As a result, dose‐response relationships of all reassortants were best described by a beta‐Poisson model. Virus subtype and human age were significant factors determining the dose‐response relationship, whereas attenuation method affected only the relationship of H1N1 virus infection to adults. The data sets for H3N2 wild‐type virus could be pooled with those for its reassortants on the assumption that the gene reassortment attenuates wild‐type virus by at least 63 times and most likely 1,070 times. Considering this most likely degree of attenuation, 10% infectious dose of H3N2 wild‐type virus for adults was estimated at 18 TCID50 (95% CI = 8.8–35 TCID50). The infectivity of wild‐type H1N1 virus remains unknown as the data set pooling was unsuccessful.