bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the limits of time reweighting and Kramers’ rate theory to obtain correct kinetics from accelerated molecular dynamics
Authors: Xin Yao , Doshi Urmi , Hamelberg Donald
Published: June 2010

Accelerated molecular dynamics simulations are routinely being used to recover the correct canonical probability distributions corresponding to the original potential energy landscape of biomolecular systems. However, the limits of time reweighting, based on transition state theory, in obtaining true kinetic rates from accelerated molecular dynamics for biomolecular systems are less obvious. Here, we investigate this issue by studying the kinetics of cis-trans isomerization of peptidic ω bond by accelerated molecular dynamics. We find that time reweighting is valid for obtaining true kinetics when the original potential is not altered at the transition state regions, as expected. When the original potential landscape is modified such that the applied boost potential alters the transition state regions, time reweighting fails to reproduce correct kinetics and the reweighted rate is much slower than the true rate. By adopting the overdamped limit of Kramers’ rate theory, we are successful in recovering correct kinetics irrespective of whether or not the transition state regions are modified. Furthermore, we tested the validity of the acceleration weight factor from the path integral formalism for obtaining the correct kinetics of cis-trans isomerization. It was found that this formulation of the weight factor is not suitable for long time scale processes such as cis-trans isomerization with high energy barriers.
Holomorphic vector bundles on Sasakian threefolds and parabolic vector bundles
Authors: Biswas Indranil
Published: June 2010

A bijective correspondence is constructed between the parabolic vector bundles with rational parabolic weights on a Riemann surface X and the holomorphic vector bundles on quasiregular Sasakian threefolds over X. This bijective correspondence preserves the stable objects.
Comprehensive study of a detection mechanism and optimization strategies to improve sensitivity in a nanogap-embedded biotransistor
Authors: Kim Sungho , Ahn Jae-Hyuk , Park Tae Jung , Lee Sang Yup , Choi Yang-Kyu
Published: June 2010

A novel biomolecular detection method, charge pumping, is investigated comprehensively as a biosensing mechanism. Tunneling electrons located in channel interface are responsible for a charge pumping current (Icp) in a biosensing operation. The maximum tunneling distance (dtunnel) of the electrons is the dominant factor to determine the amount of generated Icp, which is closely correlated with the sensitivity in a proposed nanogap-embedded biotransistor structure. Using an analytical model in which biomolecules are considered as a trap-included insulator, the effects of the key parameters that govern dtunnel, in this case the nanogap height, frequency of the applied pulse, and maximum pulse level, are analyzed.
Extraction of the β-factor for single quantum dots coupled to a photonic crystal waveguide
Authors: Thyrrestrup Henri , Sapienza Luca , Lodahl Peter
Published: June 2010

We present measurements of the β-factor, describing the coupling efficiency of light emitted by single InAs/GaAs semiconductor quantum dots into a photonic crystal waveguide mode. The β-factor is evaluated by means of time-resolved frequency-dependent photoluminescence spectroscopy. The emission wavelength of single quantum dots is temperature tuned across the band edge of a photonic crystal waveguide and the spontaneous emission rate is recorded. Decay rates up to 5.7 ns−1, corresponding to a Purcell factor of 5.2, are measured and β-factors up to 85% are extracted. These results prove the potential of photonic crystal waveguides in the realization of on-chip single-photon sources.
Performance improvement of longwave infrared photodetector based on type-II InAs/GaSb superlattices using unipolar current blocking layers
Authors: Gautam N. , Kim H. S. , Kutty M. N. , Plis E. , Dawson L. R. , Krishna S.
Published: June 2010

We report here a heterojunction band gap engineered type-II InAs/GaSb strained layer superlattice photodiode for longwave infrared detection. The reported PbIbN architecture shows improved performance over conventional PIN design due to unipolar current blocking layers. At 77 K and Vb=−0.25 V, responsivity of 1.8 A/W, dark current density of 1.2 mA/cm2, single pass quantum efficiency of 23%, and shot noise limited detectivity (D∗) of 8.7×1010 cm Hz1/2 W−1 (λc=10.8 μm) were measured. The device demonstrated background limited performance at 100 K under 300 K for 2π field of view.
Anisotropic mean free path in simulations of fluids traveling down a density gradient
Authors: Whitman Jessica R. , Aranovich Gregory L. , Donohue Marc D.
Published: June 2010

Hard sphere molecular dynamics simulations are used to study the mean free path of molecules traveling down a density gradient at fluid densities ranging between 0.05σ−3 and 0.7σ−3. Gradients are developed using semipermeable boundaries in the x-direction and, as a result, a net flow develops in the positive x-direction. Over the course of the simulation, the free paths of colliding molecules are calculated and it was determined that the mean free path in the positive x-direction is greater than the mean free path in the negative x-direction at each density studied. These results are compared to the mean free paths in the positive and negative y- and z-directions (in which there is no net flow) and the distribution of free paths for molecules traveling in the positive and negative x-directions gives insight into the physics of the system. In addition, the dependency of the mean free path on speed is studied and compared to kinetic theory predictions. The results have application in the modification of the classical model of diffusion for low density systems undergoing flow in which the mean free path is finite, large, and can be anisotropic.
Effects of dust size distribution on instability of obliquely propagating waves in a magnetized dusty plasma
Authors: Chen Jian-hong , Duan Wen-shan
Published: June 2010

In the present paper, the obliquely propagating solitary waves are investigated in a magnetized dusty plasma considering vortexlike ion distribution and dust size distribution. A plane solitary traveling-wave solution propagating at an arbitrary angle to the magnetic field is considered. The growth rate caused by small perturbations of any direction to a solitary traveling waves is studied. The effects of the dust size distribution and perturbations on the growth rate are discussed in detail.
Beneath the Surface: Intranational Institutions and Management of the United States — Mexico Transboundary Santa Cruz Aquifer
Authors: Milman Anita , Scott Christopher A
Published: June 2010

As reliance on groundwater increases, the impact of groundwater-intensive use in internationally shared aquifers threatens not only to create negative environmental and economic externalities, but also to generate tensions between neighboring nations. Through an investigation of the shared Santa Cruz aquifer, located along the United States—Mexico border, we aim to understand factors leading to effective management of transboundary groundwaters. Specifically, we find that purely state-centric approaches provide limited explanatory value, and instead examine how national (domestic) arrangements for water management condition a country's position vis-à-vis its shared groundwaters. Polycentricism in national and subnational institutional regimes leads to gaps and overlaps in authority, limiting binational groundwater management. Concurrently, evolving institutional arrangements lead to ambiguity in decision making, yet crucially also provide opportunities for innovation in binational agenda setting and data sharing, which in turn aid in the alignment of both countries' priorities for the transboundary Santa Cruz aquifer.
Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase
Authors: Mankouri Jamel , Tedbury Philip R. , Gretton Sarah , Hughes Mair E. , Griffin Stephen D. C. , Dallas Mark. L. , Green Kevin A. , Hardie D. Grahame , Peers Chris , Harris Mark
Published: June 2010

Hepatitis C virus (HCV) infection is associated with dysregulation of both lipid and glucose metabolism. As well as contributing to viral replication, these perturbations influence the pathogenesis associated with the virus, including steatosis, insulin resistance, and type 2 diabetes. AMP-activated protein kinase (AMPK) plays a key role in regulation of both lipid and glucose metabolism. We show here that, in cells either infected with HCV or harboring an HCV subgenomic replicon, phosphorylation of AMPK at threonine 172 and concomitant AMPK activity are dramatically reduced. We demonstrate that this effect is mediated by activation of the serine/threonine kinase, protein kinase B, which inhibits AMPK by phosphorylating serine 485. The physiological significance of this inhibition is demonstrated by the observation that pharmacological restoration of AMPK activity not only abrogates the lipid accumulation observed in virus-infected and subgenomic replicon-harboring cells but also efficiently inhibits viral replication. These data demonstrate that inhibition of AMPK is required for HCV replication and that the restoration of AMPK activity may present a target for much needed anti-HCV therapies.
E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the circadian heme receptor Rev-erbα
Authors: Yin Lei , Joshi Shree , Wu Nan , Tong Xin , Lazar Mitchell A.
Published: June 2010

The metazoan circadian clock mechanism involves cyclic transcriptional activation and repression by proteins whose degradation is highly regulated via the ubiquitin-proteasome pathway. The heme receptor Rev-erbα, a core negative component of the circadian network, controls circadian oscillation of several clock genes, including Bmal1 Rev-erbα protein degradation can be triggered by inhibitors of glycogen synthase kinase 3β, such as lithium, and also by serum shock, which synchronizes circadian rhythms in cultured cells. Here we report that two E3 ligases, Arf-bp1 and Pam (Myc-bp2), are copurified with Rev-erbα and required for its ubiquitination. RNA-interference–mediated depletion of Arf-bp1 and Pam stabilizes the Rev-erbα protein and protects Rev-erbα from degradation triggered by either lithium or serum shock treatment. This degradation pathway modulates the expression of Rev-erbα–regulated
Clock
gene and circadian function in mouse hepatoma cells. Thus, Arf-bp1 and Pam are novel regulators of circadian gene expression that target Rev-erbα for degradation.
Fidelity of adaptive phototaxis
Authors: Drescher Knut , Goldstein Raymond E. , Tuval Idan
Published: June 2010

Along the evolutionary path from single cells to multicellular organisms with a central nervous system are species of intermediate complexity that move in ways suggesting high-level coordination, yet have none. Instead, organisms of this type possess many autonomous cells endowed with programs that have evolved to achieve concerted responses to environmental stimuli. Here experiment and theory are used to develop a quantitative understanding of how cells of such organisms coordinate to achieve phototaxis, by using the colonial alga
Volvox carteri
as a model. It is shown that the surface somatic cells act as individuals but are orchestrated by their relative position in the spherical extracellular matrix and their common photoresponse function to achieve colony-level coordination. Analysis of models that range from the minimal to the biologically faithful shows that, because the flagellar beating displays an adaptive down-regulation in response to light, the colony needs to spin around its swimming direction and that the response kinetics and natural spinning frequency of the colony appear to be mutually tuned to give the maximum photoresponse. These models further predict that the phototactic ability decreases dramatically when the colony does not spin at its natural frequency, a result confirmed by phototaxis assays in which colony rotation was slowed by increasing the fluid viscosity.
Regulation of blood–testis barrier dynamics by TGF-β3 is a Cdc42-dependent protein trafficking event
Authors: Wong Elissa W. P. , Mruk Dolores D. , Lee Will M. , Cheng C. Yan
Published: June 2010

In the testis, the blood–testis barrier (BTB) is constituted by specialized junctions between adjacent Sertoli cells in the seminiferous epithelium near the basement membrane. Although the BTB is one of the tightest blood–tissue barriers in the mammalian body, it undergoes extensive restructuring at stage VIII of the seminiferous epithelial cycle to facilitate the transit of preleptotene spermatocytes. Thus, meiosis and postmeiotic germ cell development take place in the seminiferous epithelium behind the BTB. Cytokines (e.g., TGF-β3) are known to regulate BTB dynamics by enhancing the endocytosis of integral membrane proteins and their intracellular degradation. This thus reduces the levels of proteins above the spermatocytes in transit at the BTB, causing its disruption after testosterone-induced new tight junction (TJ) fibrils are formed behind these cells. By using Sertoli cells cultured in vitro with an established TJ permeability barrier that mimicked the BTB in vivo, Cdc42 was shown to be a crucial regulator that mediated the TGF-β3–induced BTB disruption. TGF-β3 was shown to activate Cdc42 to its active GTP-bound form. However, an inactivation of Cdc42 by overexpressing its dominant-negative mutant T17N in Sertoli cell epithelium was shown to block the TGF-β3–induced acceleration in protein endocytosis. Consequently, this prevented the disruption of Sertoli cell TJ permeability barrier and redistribution of TJ proteins (e.g., CAR and ZO-1) from the cell–cell interface to cell cytosol caused by TGF-β3. In summary, Cdc42 is a crucial regulatory component in the TGF-β3–mediated cascade of events that leads to the disruption of the TJ fibrils above the preleptotene spermatocytes to facilitate their transit.
The boundary between the Indian and Asian tectonic plates below Tibet
Authors: Zhao Junmeng , Yuan Xiaohui , Liu Hongbing , Kumar Prakash , Pei Shunping , Kind Rainer , Zhang Zhongjie , Teng Jiwen , Ding Lin , Gao Xing , Xu Qiang , Wang Wei
Published: June 2010

The fate of the colliding Indian and Asian tectonic plates below the Tibetan high plateau may be visualized by, in addition to seismic tomography, mapping the deep seismic discontinuities, like the crust-mantle boundary (Moho), the lithosphere-asthenosphere boundary (LAB), or the discontinuities at 410 and 660 km depth. We herein present observations of seismic discontinuities with the P and S receiver function techniques beneath central and western Tibet along two new profiles and discuss the results in connection with results from earlier profiles, which did observe the LAB. The LAB of the Indian and Asian plates is well-imaged by several profiles and suggests a changing mode of India-Asia collision in the east-west direction. From eastern Himalayan syntaxis to the western edge of the Tarim Basin, the Indian lithosphere is underthrusting Tibet at an increasingly shallower angle and reaching progressively further to the north. A particular lithospheric region was formed in northern and eastern Tibet as a crush zone between the two colliding plates, the existence of which is marked by high temperature, low mantle seismic wavespeed (correlating with late arriving signals from the 410 discontinuity), poor Sn propagation, east and southeast oriented global positioning system displacements, and strikingly larger seismic (SKS) anisotropy.
Identification of an IL-27/osteopontin axis in dendritic cells and its modulation by IFN-γ limits IL-17–mediated autoimmune inflammation
Authors: Murugaiyan Gopal , Mittal Akanksha , Weiner Howard L.
Published: June 2010

Dendritic cells (DCs) play a central role in determining the induction of T cell responses. IL-27 production by DCs favors induction of IL-10–producing regulatory T cells, whereas osteopontin (OPN) promotes pathogenic IL-17 T cell responses. The regulatory mechanisms in DCs that control these two cells types are not understood well. Here, we show that IFN-γ induces IL-27 while inhibiting OPN expression in DCs both in vitro and in vivo and that engagement of IFN-γR expressed by DCs leads to suppression of IL-17 production while inducing IL-10 from T cells. DCs modified by IFN-γ acquire IL-27–dependent regulatory function, promote IL-10–mediated T cell tolerance, and suppress autoimmune inflammation. Thus, our results identify a previously unknown pathway by which IFN-γ limits IL-17–mediated autoimmune inflammation through differential regulation of OPN and IL-27 expression in DCs.
Stereoselective transbilayer translocation of mannosyl phosphoryl dolichol by an endoplasmic reticulum flippase
Authors: Sanyal Sumana , Menon Anant K.
Published: June 2010

Mannose-phosphate-dolichol (MPD) is a multifunctional glycolipid that is synthesized on the cytoplasmic face of the endoplasmic reticulum (ER) and used on the opposite side of the membrane in the ER lumen as a mannose donor for protein
N
-glycosylation, glycosylphosphatidylinositol-anchoring, and
C
- and
O
-mannosylation. For this, it must be translocated, i.e., flipped, across the ER membrane. The molecular identity of the MPD translocator (MPD flippase) is not known. Here we show that MPD-flippase activity can be reconstituted in large unilamellar proteoliposomes prepared from phosphatidylcholine and Triton X-100-solubilized rat liver ER-membrane proteins. Using carboxy-2,2,6,6-tetramethylpiperidine 1-oxyl NO
+
as a topological probe to selectively oxidize MPD molecules in the outer leaflet of the reconstituted vesicles, we demonstrate rapid, protein-dependent, ATP-independent transbilayer translocation of MPD from the inner to the outer leaflet. MPD flipping is highly specific. A stereoisomer of MPD was weakly translocated (> 10-fold lower rate) compared with natural MPD. Competition experiments with water-soluble isoprenyl monophosphates showed that MPD flippase recognizes the dolichol chain of MPD, preferring a saturated α-isoprene to unsaturated
trans
- or
cis
- α-isoprene units. Chromatography of the detergent-solubilized ER protein mixture prior to reconstitution indicated that MPD flippase (
i
) is not a Con A-binding glycoprotein and (
ii
) can be resolved from the oligosaccharide-diphosphate dolichol flippase that translocates Man
5
GlcNAc
2
-PP-dolichol, a lipid intermediate of
N
-glycosylation. These data provide a mechanistic framework for understanding MPD flipping, as well as a biochemical basis for identifying MPD flippase.
Dynamic interactions between microbubbles in water
Authors: Vakarelski Ivan U. , Manica Rogerio , Tang Xiaosong , O’Shea Sean J. , Stevens Geoffrey W. , Grieser Franz , Dagastine Raymond R. , Chan Derek Y. C.
Published: June 2010

The interaction between moving bubbles, vapor voids in liquid, can arguably represent the simplest dynamical system in continuum mechanics as only a liquid and its vapor phase are involved. Surprisingly, and perhaps because of the ephemeral nature of bubbles, there has been no direct measurement of the time-dependent force between colliding bubbles which probes the effects of surface deformations and hydrodynamic flow on length scales down to nanometers. Using ultrasonically generated microbubbles (∼100 μm size) that have been accurately positioned in an atomic force microscope, we have made direct measurements of the force between two bubbles in water under controlled collision conditions that are similar to Brownian particles in solution. The experimental results together with detailed modeling reveal the nature of hydrodynamic boundary conditions at the air/water interface, the importance of the coupling of hydrodynamic flow, attractive van der Waals–Lifshitz forces, and bubble deformation in determining the conditions and mechanisms that lead to bubble coalescence. The observed behavior differs from intuitions gained from previous studies conducted using rigid particles. These direct force measurements reveal no specific ion effects at high ionic strengths or any special role of thermal fluctuations in film thickness in triggering the onset of bubble coalescence.
Tracking differentiating neural progenitors in pluripotent cultures using microRNA-regulated lentiviral vectors
Authors: Sachdeva Rohit , Jönsson Marie E. , Nelander Jenny , Kirkeby Agnete , Guibentif Carolina , Gentner Bernhard , Naldini Luigi , Björklund Anders , Parmar Malin , Jakobsson Johan
Published: June 2010

In this study, we have used a microRNA-regulated lentiviral reporter system to visualize and segregate differentiating neuronal cells in pluripotent cultures. Efficient suppression of transgene expression, specifically in undifferentiated pluripotent cells, was achieved by using a lentiviral vector expressing a fluorescent reporter gene regulated by microRNA-292. Using this strategy, it was possible to track progeny from murine ES, human ES cells, and induced pluripotent stem cells as they differentiated toward the neural lineage. In addition, this strategy was successfully used to FACS purify neuronal progenitors for molecular analysis and transplantation. FACS enrichment reduced tumor formation and increased survival of ES cell–derived neuronal progenitors after transplantation. The properties and versatility of the microRNA-regulated vectors allows broad use of these vectors in stem cell applications.
IRAK1BP1 inhibits inflammation by promoting nuclear translocation of NF-κB p50
Authors: Conner James R. , Smirnova Irina I. , Moseman Annie Park , Poltorak Alexander
Published: June 2010

An orchestrated balance of pro- and antiinflammatory cytokine release is critical for an innate immune response sufficient for pathogen defense without excessive detriment to host tissues. By using an unbiased forward genetic approach, we previously reported that IL-1R–associated kinase 1 binding protein 1 (IRAK1BP1) down-modulates Toll-like receptor-mediated transcription of several proinflammatory cytokines. To gain insights into the physiological relevance of the inhibitory role of IRAK1BP1 in inflammation, we generated mutant mice lacking IRAK1BP1. Here we report that IRAK1BP1 does not inhibit signaling pathways generally but rather changes the transcriptional profile of activated cells, leading to an increase in IL-10 production and promoting LPS tolerance. This shift in cytokine transcription correlates with an increased ratio of functional NF-κB subunit dimers comprised of p50/p50 homodimers relative to p50/p65 heterodimers. The increase in nuclear p50/p50 was consistent with the ability of IRAK1BP1 to bind to the p50 precursor molecule and IκB family member p105. We conclude that IRAK1BP1 functions through its effects on NF-κB as a molecular switch to bias innate immune pathways toward the resolution of inflammation.
In search of lost timing
Authors: Short Ben
Published: June 2010

Researchers learn more about how cells schedule DNA replication by determining when they tear up the timetable.
Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms
Authors: Hammond Jennetta W. , Blasius T. Lynne , Soppina Virupakshi , Cai Dawen , Verhey Kristen J.
Published: June 2010

Long-distance transport in cells is driven by kinesin and dynein motors that move along microtubule tracks. These motors must be tightly regulated to ensure the spatial and temporal fidelity of their transport events. Transport motors of the kinesin-1 and kinesin-3 families are regulated by autoinhibition, but little is known about the mechanisms that regulate kinesin-2 motors. We show that the homodimeric kinesin-2 motor KIF17 is kept in an inactive state in the absence of cargo. Autoinhibition is caused by a folded conformation that enables nonmotor regions to directly contact and inhibit the enzymatic activity of the motor domain. We define two molecular mechanisms that contribute to autoinhibition of KIF17. First, the C-terminal tail interferes with microtubule binding; and second, a coiled-coil segment blocks processive motility. The latter is a new mechanism for regulation of kinesin motors. This work supports the model that autoinhibition is a general mechanism for regulation of kinesin motors involved in intracellular trafficking events.
G2 phase chromatin lacks determinants of replication timing
Authors: Lu Junjie , Li Feng , Murphy Christopher S. , Davidson Michael W. , Gilbert David M.
Published: June 2010

DNA replication in all eukaryotes follows a defined replication timing program, the molecular mechanism of which remains elusive. Using a Xenopus laevis egg extract replication system, we previously demonstrated that replication timing is established during early G1 phase of the cell cycle (timing decision point [TDP]), which is coincident with the repositioning and anchorage of chromatin in the newly formed nucleus. In this study, we use this same system to show that G2 phase chromatin lacks determinants of replication timing but maintains the overall spatial organization of chromatin domains, and we confirm this finding by genome-wide analysis of rereplication in vivo. In contrast, chromatin from quiescent cells retains replication timing but exhibits disrupted spatial organization. These data support a model in which events at the TDP, facilitated by chromatin spatial organization, establish determinants of replication timing that persist independent of spatial organization until the process of chromatin replication during S phase erases those determinants.
IL-10 production differentially influences the magnitude, quality, and protective capacity of Th1 responses depending on the vaccine platform
Authors: Darrah Patricia A. , Hegde Sonia T. , Patel Dipti T. , Lindsay Ross W. B. , Chen Linda , Roederer Mario , Seder Robert A.
Published: June 2010

The quality of a Th1 response can be a prospective correlate of vaccine-mediated protection against certain intracellular pathogens. Using two distinct vaccine platforms, we evaluate the influence of interleukin (IL) 10 production on the magnitude, quality, and protective capacity of CD4+ T cell responses in the mouse model of Leishmania major infection. Multiparameter flow cytometry was used to delineate the CD4+ T cell production of interferon (IFN) γ, IL-2, tumor necrosis factor (TNF), and IL-10 (or combinations thereof) after vaccination. Immunization with a high dose of adenovirus (ADV) expressing leishmanial proteins (MML-ADV) elicited a limited proportion of multifunctional IFN-γ+IL-2+TNF+ Th1 cells, a high frequency of IL-10–producing CD4+ T cells, and did not protect against subsequent challenge. Surprisingly, in the absence of IL-10, there was no change in the magnitude, quality, or protective capacity of the Th1 response elicited by high-dose MML-ADV. In contrast, after immunization with MML protein and CpG (MML + CpG), IL-10 limited the production of IL-12 by DCs in vivo, thereby decreasing the generation of multifunctional Th1 cells. Consequently, three immunizations with MML + CpG were required for full protection. However, inhibiting IL-10 at the time of immunization enhanced the magnitude and quality of the Th1 response sufficiently to mediate protection after only a single immunization. Overall, we delineate distinct mechanisms by which vaccines elicit protective Th1 responses and underscore the importance of multifunctional CD4+ T cells.
Measuring Agricultural Policy Bias: General Equilibrium Analysis of Fifteen Developing Countries
Authors: Jensen Henning Tarp , Robinson Sherman , Tarp Finn
Published: June 2010

Measurement is a key issue in the literature on price incentive bias induced by trade policy. We introduce a general equilibrium measure of the relative effective rate of protection, which generalizes earlier protection measures. For our fifteen sample countries, results indicate that the agricultural price incentive bias generally perceived to exist during the 1980s was largely eliminated during the 1990s. Results also demonstrate that general equilibrium effects and country‐specific characteristics are crucial for determining the sign and magnitude of agricultural bias. Our comprehensive protection measure is therefore uniquely suited to capture the full impact of trade policies on relative agricultural price incentives.
Applying the Naïve Bayes classifier with kernel density estimation to the prediction of protein–protein interaction sites
Authors: Murakami Yoichi , Mizuguchi Kenji
Published: June 2010

Motivation: The limited availability of protein structures often restricts the functional annotation of proteins and the identification of their protein–protein interaction sites. Computational methods to identify interaction sites from protein sequences alone are, therefore, required for unraveling the functions of many proteins. This article describes a new method (PSIVER) to predict interaction sites, i.e. residues binding to other proteins, in protein sequences. Only sequence features (position-specific scoring matrix and predicted accessibility) are used for training a Naïve Bayes classifier (NBC), and conditional probabilities of each sequence feature are estimated using a kernel density estimation method (KDE).

Results: The leave-one out cross-validation of PSIVER achieved a Matthews correlation coefficient (MCC) of 0.151, an F-measure of 35.3%, a precision of 30.6% and a recall of 41.6% on a non-redundant set of 186 protein sequences extracted from 105 heterodimers in the Protein Data Bank (consisting of 36 219 residues, of which 15.2% were known interface residues). Even though the dataset used for training was highly imbalanced, a randomization test demonstrated that the proposed method managed to avoid overfitting. PSIVER was also tested on 72 sequences not used in training (consisting of 18 140 residues, of which 10.6% were known interface residues), and achieved an MCC of 0.135, an F-measure of 31.5%, a precision of 25.0% and a recall of 46.5%, outperforming other publicly available servers tested on the same dataset. PSIVER enables experimental biologists to identify potential interface residues in unknown proteins from sequence information alone, and to mutate those residues selectively in order to unravel protein functions.

Availability: Freely available on the web at http://tardis.nibio.go.jp/PSIVER/

Contact:  yoichi@nibio.go.jp; kenji@nibio.go.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
COMA server for protein distant homology search
Authors: Margelevičius Mindaugas , Laganeckas Mindaugas , Venclovas Česlovas
Published: June 2010

Summary: Detection of distant homology is a widely used computational approach for studying protein evolution, structure and function. Here, we report a homology search web server based on sequence profile–profile comparison. The user may perform searches in one of several regularly updated profile databases using either a single sequence or a multiple sequence alignment as an input. The same profile databases can also be downloaded for local use. The capabilities of the server are illustrated with the identification of new members of the highly diverse PD-(D/E)XK nuclease superfamily.

Availability:  http://www.ibt.lt/bioinformatics/coma/

Contact:  venclovas@ibt.lt

Supplementary information:  Supplementary data are available at Bioinformatics online.
Large aggregations of pelagic squid near the ocean surface at the Antarctic Polar Front, and their capture by grey-headed albatrosses
Authors: Rodhouse Paul G. , Boyle Peter R.
Published: June 2010

Rodhouse, P. G., and Boyle, P. R. 2010. Large aggregations of pelagic squid near the ocean surface at the Antarctic Polar Front, and their capture by grey-headed albatrosses. – ICES Journal of Marine Science, 67: 1432–1435. Satellite-tracked squid predators and fish-finding acoustics were used to locate squid concentrations at the Antarctic Polar Front, then to sample them with a midwater trawl. Near-surface hauls were dominated by the squid Martialia hyadesi similar in size to those fed to grey-headed albatross chicks. The characteristics of the squid and their proximity to the surface suggest that the birds locate squid concentrations by olfaction and catch them by plunging.
A Customized Gene Expression Microarray Reveals That the Brittle Stem Phenotypefs2of Barley Is Attributable to a Retroelement in theHvCesA4Cellulose Synthase Gene
Authors: Burton Rachel A. , Ma Gang , Baumann Ute , Harvey Andrew J. , Shirley Neil J. , Taylor Jillian , Pettolino Filomena , Bacic Antony , Beatty Mary , Simmons Carl R. , Dhugga Kanwarpal S. , Rafalski J. Antoni , Tingey Scott V. , Fincher Geoffrey B.
Published: June 2010

The barley (Hordeum vulgare) brittle stem mutants, fs2, designated X054 and M245, have reduced levels of crystalline cellulose compared with their parental lines Ohichi and Shiroseto. A custom-designed microarray, based on long oligonucleotide technology and including genes involved in cell wall metabolism, revealed that transcript levels of very few genes were altered in the elongation zone of stem internodes, but these included a marked decrease in mRNA for the HvCesA4 cellulose synthase gene of both mutants. In contrast, the abundance of several hundred transcripts changed in the upper, maturation zones of stem internodes, which presumably reflected pleiotropic responses to a weakened cell wall that resulted from the primary genetic lesion. Sequencing of the HvCesA4 genes revealed the presence of a 964-bp solo long terminal repeat of a Copia-like retroelement in the first intron of the HvCesA4 genes of both mutant lines. The retroelement appears to interfere with transcription of the HvCesA4 gene or with processing of the mRNA, and this is likely to account for the lower crystalline cellulose content and lower stem strength of the mutants. The HvCesA4 gene maps to a position on chromosome 1H of barley that coincides with the previously reported position of fs2.
Areca nut dependence among chewers in a South Indian community who do not also use tobacco
Authors: Bhat Shrihari J. S. , Blank Melissa D. , Balster Robert L. , Nichter Mimi , Nichter Mark
Published: June 2010

Aims Previously reported research suggests a dependence syndrome for areca nut use, though well‐designed studies are virtually non‐existent. The goal of this study was to examine evidence of areca dependence in a sample of areca‐only (i.e. no tobacco) chewers using modified measurement scales.

Design A purposive sample of chewers, identified via local informants and advertisements, was surveyed from January to March of 2005.

Setting Six villages in Dakshina Kannada District, Karnataka State, India.

Participants Fifty‐nine daily areca chewers who do not also currently use any form of tobacco.

Measurements Questionnaires included modified versions of the Fagerström Tolerance Questionnaire, Cigarette Dependence Scale (CDS‐5) and the Smokeless Tobacco Dependence Scale (STDS). Additional questions assessed demographic characteristics and patterns of use.

Findings Approximately half of respondents reported 1–3 chews/day (mean = 1.9; SD = 0.98). The average number of chewing episodes/day was 4.4 (SD = 3.4) and the average number of nuts/day was 1.2 (SD = 1.1). Users’ typical chew lasts up to 20 minutes and includes spitting out the juices and rinsing the mouth with water. Overall, the levels of reported dependence symptoms were quite low, but approximately 44% of chewers endorsed at least one of the following items: continued use despite illness or mouth wounds, difficulty refraining from chewing in forbidden places, or craving during periods of abstinence. Approximately 15.4% of chewers reported at least one intentional quit attempt and a subset had summary scores indicative of dependence (13.6% had scores >16 on the CDS‐5 and 5.3% had scores >11 on the STDS). Dependence scores were positively correlated with frequency of chews/day.

Conclusions The symptoms of dependence observed in a subset of areca‐only chewers warrant further investigation. Next steps should include well‐controlled laboratory evaluation of dependence features.
Effect of an antismoking advertisement on cinema patrons' perception of smoking and intention to smoke: a quasi‐experimental study
Authors: Hanewinkel Reiner , Isensee Barbara , Sargent James D. , Morgenstern Matthis
Published: June 2010

Aims  To assess the effect of an antismoking advertisement under real‐world conditions.

Design  Quasi‐experimental study.

Setting/participants  Multiplex cinema in Kiel, Germany; 4073 patrons were surveyed after having viewed a movie. Some 4005 patrons were ≥10 years old (28.7% between 10 and 17 years). A total of 654 subjects (16.3%) were smokers.

Intervention  In the intervention condition (weeks 1 and 3), a 30‐second antismoking advertisement—accentuating long‐term health consequences of smoking and promoting cessation—was shown prior to all movies; in the control condition (weeks 2 and 4) no such spot was shown.

Main outcome measures  (i) Awareness of smoking in the movie, (ii) approval of smoking in the movie, (iii) attitude towards smoking, (iv) intention to smoke in the future and (v) desire to smoke among smokers.

Findings  Patrons who were exposed to the antismoking advertisement were more likely to be female, but did not differ with respect to smoking status. After controlling for gender differences, patrons exposed to the antismoking advertisement had (i) higher awareness of smoking in the movies, (ii) lower levels of approval of smoking in the movies, and (iii) a more negative attitude towards smoking in general compared with those not exposed. Among smokers, smoking in the movies increased urge to smoke, but there was no interaction between smoking in the movies and experimental condition.

Conclusions  Study results suggest that placing an antismoking advertisement before movies can affect attitudes towards smoking, bolstering evidence in support of such policies.
Unplanned attempts to quit smoking: a qualitative exploration
Authors: Murray Rachael L. , McNeill Ann , Lewis Sarah , Britton John , Coleman Tim
Published: June 2010

Aims  To gain a greater understanding of the process of unplanned attempts to quit smoking and the use of support in such attempts.

Design  Qualitative study using semi‐structured interviews with 20 smokers and ex‐smokers.

Setting  Twenty‐four general practices in Nottinghamshire, UK.

Participants  Smokers and ex‐smokers who reported that their most recent attempt to quit smoking was unplanned.

Measurements  Descriptions of the unplanned quit attempts and reported use of support within these.

Findings  Smokers who report making ‘unplanned’ quit attempts exhibit substantial variation in what they mean by this; many quit attempts reported as ‘unplanned’ were actually delayed and involved some planning and use of cessation support.

Conclusions  Reported ‘unplanned’ quit attempts often involve elements of planning and delay for quitters to access to cessation support. It is important, therefore, that smoking cessation services offer flexible and adaptable support which can be used readily by potential quitters.
First‐trimester fetal heart rate in mothers with opioid addiction
Authors: Schmid Maximilian , Kuessel Lorenz , Klein Katharina , Metz Verena , Fischer Gabriele , Krampl‐Bettelheim Elisabeth
Published: June 2010

Aim  To investigate the difference in fetal heart rate of opioid‐dependent mothers compared to non‐dependent mothers in the first trimester of pregnancy.

Design  The data of 74 consecutive singleton pregnancies of mothers enrolled in a maintenance programme for opioid‐dependent women was matched to 74 non‐exposed singleton pregnancies by maternal age, crown–rump length, smoking status, ethnic background and mode of conception.

Measurement  Fetal heart rate measured as part of first‐trimester screening by Doppler ultrasound between 11+0 and 13+6 gestational weeks was compared retrospectively.

Findings  The mean fetal heart rate in opioid‐dependent mothers was 156.0 beats per minute (standard deviation 7.3) compared to 159.6 (6.5) in controls. The difference in fetal heart rate was significant (P = 0.02). There was a significant difference in mean maternal body mass index (P = 0.01) but not in mean nuchal translucency (P = 0.3), gestational age (0.5), fetal gender (P = 0.3) and parity (P = 0.3) between both groups. Fifty‐five per cent (41 of 74) of cases were taking methadone, 30% (22 of 74) buprenorphine and 15% (11 of 74) were taking slow‐release morphines throughout the pregnancy.

Conclusions  In fetuses of opioid‐dependent mothers a decreased fetal heart rate can already be observed between 11+0 and 13+6 gestational weeks. The effect of opioid intake needs to be taken into consideration when interpreting fetal heart rate in opioid‐dependent mothers at first‐trimester screening.
Pharmacokinetics of enteric‐coated cysteamine bitartrate in healthy adults: a pilot study
Authors: Gangoiti Jon A. , Fidler Meredith , Cabrera Betty L. , Schneider Jerry A. , Barshop Bruce A. , Dohil Ranjan
Published: June 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Cysteamine bitartrate is taken lifelong, every 6 h and for the treatment of cystinosis. Recent studies using cysteamine for for other diseases such as neurodegenerative disorders adopt the same dosing regimen for cysteamine. Regular cysteamine bitartrate (Cystagon) may cause upper gastrointestinal symptoms in some patients.

WHAT THIS STUDY ADDS

• This is the only study that provides pharmacokinetic data for cysteamine delivered in an enteric‐release preparation in normal subjects. EC‐cysteamine is very well tolerated and does not cause increased gastrin concentrations, even at relatively high doses.

• EC‐cysteamine at the higher dose results in better drug uptake as measured by Cmax and AUC and is more likely to be effective.

AIMS

Cysteamine bitartrate (Cystagon®) is the approved treatment for cystinosis. Poor compliance and patient outcome may occur because the drug needs to be taken every 6 h and in some patients causes gastrointestinal symptoms due to hypergastrinaemia. A formulation of cysteamine requiring twice daily ingestion would improve the quality of life for these patients. This study compares the pharmacokinetics and gastrin production following cysteamine bitartrate non‐enteric‐coated and cysteamine bitartrate enteric‐coated in normal healthy subjects.

METHODS

Enteric‐coated cysteamine was prepared. Following single doses of cysteamine bitartrate non‐enteric‐coated 450 mg and cysteamine bitartrate enteric‐coated 450 mg and 900 mg, serial plasma cysteamine and gastrin concentrations were measured. Two subjects also received cysteamine bitartrate non‐enteric‐coated 900 mg. Gastrointestinal (GI) symptoms were recorded.

RESULTS

Six healthy adults (mean age 20.7 years, range 18–24 years; mean weight 59.3 kg) received drug. All post‐dose gastrin concentrations were within the normal range (<100 pg ml–1). The tmax following cysteamine bitartrate non‐enteric‐coated (mean and SD is 75 ± 19 min) was shorter than cysteamine bitartrate enteric‐coated (220 ± 74 min) (P= 0.001), but only the Cmax and AUC estimates following 900 mg cysteamine bitartrate enteric‐coated were significantly greater than any of the other preparations or doses (P < 0.05). One patient had GI symptoms following both 900 mg cysteamine bitartrate non‐enteric‐coated and cysteamine bitartrate enteric‐coated.

CONCLUSION

Although patient numbers were low, single high doses of cysteamine bitartrate enteric‐coated were better tolerated than similar doses of cysteamine bitartrate non‐enteric‐coated in the healthy subjects and all had normal gastrin concentrations. The delayed tmax following cysteamine bitartrate enteric‐coated suggested that the cysteamine was released enterically.
Pro/Con debate: is occupational asthma induced by isocyanates an immunoglobulin E‐mediated disease?
Authors: Wisnewski A. V. , Jones M.
Published: June 2010

Isocyanates, low‐molecular weight chemicals essential to polyurethane production, are one of the most common causes of occupational asthma, yet the mechanisms by which exposure leads to disease remain unclear. While isocyanate asthma closely mirrors other Type I Immune Hypersensitivity (Allergic) disorders, one important characteristic of hypersensitivity (‘allergen’‐specific IgE) is reportedly absent in a large portion of affected individuals. This variation from common environmental asthma (which typically is induced by high‐molecular weight allergens) is important for two reasons. (1) Allergen‐specific IgE is an important mediator of many of the symptoms of bronchial hyper‐reactivity in ‘allergic asthma’. Lack of allergen‐specific IgE in isocyanate hypersensitive individuals suggests differences in pathogenic mechanisms, with potentially unique targets for prevention and therapy. (2) Allergen‐specific IgE forms the basis of the most commonly used diagnostic tests for hypersensitivity (skin prick and RAST). Without allergen‐specific IgE, isocyanates may go unrecognized as the cause of asthma. In hypersensitive individuals, chronic exposure can lead to bronchial hyperreactivity that persists years after exposure ceases. Thus, the question of whether or not isocyanate asthma is an IgE‐mediated disease, has important implications for disease screening/surveillance, diagnosis, treatment and prevention. The present Pro/Con Debate, addresses contemporary, controversial issues regarding IgE in isocyanate asthma.

Cite this as: A. V. Wisnewski and M. Jones, Clinical & Experimental Allergy, 2010 (40) 1155–1162.
Influence of fish assemblage and shallow lake productivity on waterfowl communities in the Boreal Transition Zone of western Canada
Authors: EPNERS C. A. , BAYLEY S. E. , THOMPSON J. E. , TONN W. M.
Published: June 2010

1. Shallow lakes in the Boreal Transition Zone (BTZ) in Alberta, Canada are naturally productive systems that provide important breeding and moulting habitat for many waterfowl (Anseriformes). To examine the relative importance of biotic and abiotic factors on waterfowl population densities, species richness and community composition, we surveyed 30 shallow lakes and evaluated the relationships among fish communities, lake characteristics and waterfowl in both breeding and moulting habitat. Shallow lakes were either fishless (n = 15), contained only small‐bodied fishes (n = 10) or contained large‐bodied, mostly predatory, fish in addition to small‐bodied fish (n = 5).

2. Environmental factors, including water colour, submerged aquatic vegetation, lake area and potassium, explained 24.3% of the variation in breeding waterfowl communities. Fish assemblage contributed independently to a small but significant proportion (13.4%) of the variation, while 13.8% of the explained variation was shared between environmental factors and fish assemblage. In total, 51.5% of the variation in breeding waterfowl communities was explained.

3. Overall, 55.5% of the total variation in moulting waterfowl communities was explained. Environment alone [especially total phosphorus, lake area, maximum depth and dissolved organic carbon (DOC)] and variation shared by fish and environment similarly accounted for most of the explained variation in moulting waterfowl communities (21.7% and 25.7% respectively), while fish assemblage was only one‐third as important (8.1%).

4. Both breeding and moulting waterfowl densities increased with lake productivity, even in eutrophic and hypereutrophic lakes. Breeding waterfowl density was also twice as great in fishless lakes than in lakes with fish, after accounting for lake area.

5. Certain waterfowl taxa were linked to fishless lakes, especially in the moulting season. Canvasback and moulting ring‐necked ducks were linked to small‐bodied fish lakes, whereas moulting common goldeneye were indicators of large‐bodied fish lakes. Knowledge of fish presence and species composition can therefore help guide conservation and management of waterfowl habitat in western Canada. Our results suggest that management efforts to maintain the most productive waterfowl habitat in the BTZ should focus on smaller, shallow, fishless lakes, particularly given that larger fish‐bearing systems have greater regulatory protection.