bluuebunny/crossref_metadata_2025 huggingface dataset:
Sop‐GPU: Accelerating biomolecular simulations in the centisecond timescale using graphics processors
Authors: Zhmurov A. , Dima R. I. , Kholodov Y. , Barsegov V.
Published: July 2010

Theoretical exploration of fundamental biological processes involving the forced unraveling of multimeric proteins, the sliding motion in protein fibers and the mechanical deformation of biomolecular assemblies under physiological force loads is challenging even for distributed computing systems. Using aCα‐based coarse‐grained self organized polymer (SOP) model, we implemented the Langevin simulations of proteins on graphics processing units (SOP‐GPU program). We assessed the computational performance of an end‐to‐end application of the program, where all the steps of the algorithm are running on a GPU, by profiling the simulation time and memory usage for a number of test systems. The ∼90‐fold computational speedup on a GPU, compared with an optimized central processing unit program, enabled us to follow the dynamics in the centisecond timescale, and to obtain the force‐extension profiles using experimental pulling speeds (vf= 1–10 μm/s) employed in atomic force microscopy and in optical tweezers‐based dynamic force spectroscopy. We found that the mechanical molecular response critically depends on the conditions of force application and that the kinetics and pathways for unfolding change drastically even upon a modest 10‐fold increase invf. This implies that, to resolve accurately the free energy landscape and to relate the results of single‐molecule experimentsin vitroandin silico, molecular simulations should be carried out under the experimentally relevant force loads. This can be accomplished in reasonable wall‐clock time for biomolecules of size as large as 105residues using the SOP‐GPU package. Proteins 2010; © 2010 Wiley‐Liss, Inc.
Structural origins of pH‐dependent chemical shifts in the B1 domain of protein G
Authors: Tomlinson Jennifer H. , Green Victoria L. , Baker Patrick J. , Williamson Mike P.
Published: July 2010

We report chemical shifts for HN, N, and C′ nuclei in the His‐tagged B1 domain of protein G (GB1) over a range of pH values from pH 2.0 to 9.0, which fit well to standard pH‐dependent equations. We also report a 1.2 Å resolution crystal structure of GB1 at pH 3.0. Comparison of this crystal structure with published crystal structures at higher pHs provides details of the structural changes in GB1 associated with protonation of the carboxylate groups, in particular a conformational change in the C‐terminus of the protein at low pH. An additional change described recently is not seen in the crystal structure because of crystal contacts. We show that the pH‐dependent changes in chemical shifts can be almost entirely understood based on structural changes, thereby providing insight into the relationship between structure and chemical shift. In particular, we describe through‐bond effects extending up to five bonds, affecting N and C′ but not HN; through‐space effects of carboxylates, which fit well to a simple electric field model; and effects due to conformational change, which have a similar magnitude to many of the direct effects. Finally, we discuss cooperative effects, demonstrating a lack of cooperative unfolding in the helix, and the existence of a β‐sheet “iceberg” extending over three of the four strands. This study therefore extends the application of chemical shifts to understanding protein structure. Proteins 2010; © 2010 Wiley‐Liss, Inc.
Structural facets of disease‐linked human prion protein mutants: A molecular dynamic study
Authors: Rossetti Giulia , Giachin Gabriele , Legname Giuseppe , Carloni Paolo
Published: July 2010

Prion propagation in transmissible spongiform encephalopathies involves the conversion of the cellular prion protein, PrPC, into the pathogenic conformer PrPSc. Human familial forms of the disease are linked to specific mutations in the PrP gene, PRNP, and include Gerstmann‐Sträussler‐Scheinker syndrome (GSS), familial Creutzfeldt‐Jakob disease (fCJD), and fatal familial insomnia. To gain insights into the molecular basis of these disorders, we performed 200 ns of classical molecular dynamic simulations in aqueous solution on wild type (WT) human PrP (HuPrP), and on three HuPrP variants located in the globular HuPrP domain: two pathological mutations, HuPrP(Q212P) and HuPrP(E200K), linked to GSS and to fCJD respectively, and one protective polymorphism, HuPrP(E219K) (total time‐scale simulated 800 ns). A comparison between the predicted structural determinants of WT HuPrP and HuPrP(E200K) with their NMR structures established the accuracy of the methods used. Strikingly, the analyzed disease‐linked variants produced their major effect on the α2‐α3 region and the β2‐α2 loop, regardless of the mutation position. The conformational change of the latter might affect the interactions with cellular partners in the fibrillation process. The protocol proposed here represents a powerful approach for reproducing the structural effects of genetic mutations located in the globular domain of HuPrP, such as the GSS‐related HuPrP(Q212P) and the protective polymorphism HuPrP(E219K). Proteins 2010. © 2010 Wiley‐Liss, Inc.
Achieving reliability and high accuracy in automated protein docking: Cluspro, PIPER, SDU, and stability analysis in CAPRI rounds 13–19
Authors: Kozakov Dima , Hall David R. , Beglov Dmitri , Brenke Ryan , Comeau Stephen R. , Shen Yang , Li Keyong , Zheng Jiefu , Vakili Pirooz , Paschalidis Ioannis Ch. , Vajda Sandor
Published: July 2010

Our approach to protein—protein docking includes three main steps. First, we run PIPER, a rigid body docking program based on the Fast Fourier Transform (FFT) correlation approach, extended to use pairwise interactions potentials. Second, the 1000 best energy conformations are clustered, and the 30 largest clusters are retained for refinement. Third, the stability of the clusters is analyzed by short Monte Carlo simulations, and the structures are refined by the medium‐range optimization method SDU. The first two steps of this approach are implemented in the ClusPro 2.0 protein–protein docking server. Despite being fully automated, the last step is computationally too expensive to be included in the server. When comparing the models obtained in CAPRI rounds 13–19 by ClusPro, by the refinement of the ClusPro predictions and by all predictor groups, we arrived at three conclusions. First, for the first time in the CAPRI history, our automated ClusPro server was able to compete with the best human predictor groups. Second, selecting the top ranked models, our current protocol reliably generates high‐quality structures of protein–protein complexes from the structures of separately crystallized proteins, even in the absence of biological information, provided that there is limited backbone conformational change. Third, despite occasional successes, homology modeling requires further improvement to achieve reliable docking results. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Liquiritigenin induces mitochondria‐mediated apoptosis via cytochrome c release and caspases activation in heLa Cells
Authors: Liu Changwei , Wang Yu , Xie Sirou , Zhou Yijing , Ren Xiangmei , Li Xiaoting , Cai Yunqing
Published: July 2010

It has been demonstrated that many flavonoids possess a potent and broad spectrum of antitumor activity. Liquiritigenin is a flavanone extracted from Glycyrrhizae. This study investigated the effects of liquiritigenin on cell viability and apoptosis induction in human cervical carcinoma (HeLa) cells. The results show that liquiritigenin significantly suppressed cell proliferation in a dose‐ and time‐dependent manner in HeLa cells. In addition, liquiritigenin promoted apoptosis in HeLa cells, evidenced by apoptotic morphological changes and Annexin‐V binding. The apoptosis induction with liquiritigenin is associated with the up‐regulation of p53 and Bax, along with down‐regulation of Bcl‐2 and survivin. Finally, examination of the mitochondrial pathway of apoptosis revealed that cytochrome c is released from mitochondria to cytosol, associated with the activation of caspase‐9 and ‐3, and the cleavage of poly (ADP‐ribose) polymerase (PARP). Overall, the results indicate that liquiritigenin induces apoptosis in part via the mitochondrial pathway, which is associated with p53 up‐regulation, release of cytochrome c and elevated activity of caspase‐9 and ‐3 in HeLa cells. Copyright © 2010 John Wiley & Sons, Ltd.
Sensitivity study for mesoscale simulations of gravity waves above Antarctica during Vorcore
Authors: Plougonven Riwal , Arsac Antonin , Hertzog Albert , Guez Lionel , Vial François
Published: July 2010

The observations from the Vorcore campaign (September 2005– January 2006) provide a unique dataset for the study of gravity waves in the lower stratosphere because of their wide coverage (150 000 observations from the South Pole to about 40°S) and of the quasi‐Lagrangian nature of the superpressure balloons used. Numerical simulations with a mesoscale model are undertaken in order to investigate further the observed gravity waves, their sources and the induced momentum fluxes. The need for a high spatial resolution makes it necessary to find a compromise between the size of the model domain and the length of the simulations. We describe preliminary simulations used to determine the best configuration of the model for this purpose, and show that the simulations compare reasonably well with the observations. Model results complement the observations and provide new insights into orographic and non‐orographic wave sources. Copyright © 2010 Royal Meteorological Society
Additional information from array comparative genomic hybridization technology over conventional karyotyping in prenatal diagnosis: a systematic review and meta‐analysis
Authors: Hillman S. C. , Pretlove S. , Coomarasamy A. , Mcmullan D. J. , Davison E. V. , Maher E. R. , Kilby M. D.
Published: July 2010

Objective

Array comparative genomic hybridization (CGH) is transforming clinical cytogenetics with its ability to interrogate the human genome at increasingly high resolution. The aim of this study was to determine whether array CGH testing in the prenatal population provides diagnostic information over conventional karyotyping.

Methods

MEDLINE (1970 to December 2009), EMBASE (1980 to December 2009) and CINAHL (1982 to December 2009) databases were searched electronically. Studies were selected if array CGH was used on prenatal samples or if array CGH was used on postnatal samples following termination of pregnancy for structural abnormalities that were detected on an ultrasound scan. Of the 135 potential articles, 10 were included in this systematic review and eight were included in the meta‐analysis. The pooled rate of extra information detected by array CGH when the prenatal karyotype was normal was meta‐analyzed using a random‐effects model. The pooled rate of receiving an array CGH result of unknown significance was also meta‐analyzed.

Results

Array CGH detected 3.6% (95% CI, 1.5–8.5) additional genomic imbalances when conventional karyo‐typing was ‘normal’, regardless of referral indication. This increased to 5.2% (95% CI, 1.9–13.9) more than karyotyping when the referral indication was a structural malformation on ultrasound.

Conclusions

There appears to be an increased detection rate of chromosomal imbalances, compared with conventional karyotyping, when array CGH techniques are employed in the prenatal population. However, some are copy number imbalances that are not clinically significant. This carries implications for prenatal counseling and maternal anxiety. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.
First‐trimester combined screening for trisomy 21 at 7–14 weeks' gestation
Authors: Wright D. , Spencer K. , Kagan K K. , Tørring N. , Petersen O. B. , Christou A. , Kallikas J. , Nicolaides K. H.
Published: July 2010

Objective

To establish an algorithm for first‐trimester combined screening for trisomy 21 with biochemical testing from 7 to 14 weeks' gestation and ultrasound testing at 11–13 weeks.

Methods

This was a multicenter study of 886 pregnancies with trisomy 21 and 222 475 unaffected pregnancies with measurements of free β‐human chorionic gonadotropin (β‐hCG) and pregnancy‐associated plasma protein‐A (PAPP‐A) at 7–14 weeks' gestation. Multiple regression modeling of log‐transformed marker values was used to produce log multiples of the median (MoM) values for PAPP‐A and free β‐hCG. The models included terms for the center attended and the machine used for biochemical analysis, gestational age, maternal racial origin, maternal weight, smoking status and method of conception. Bivariate Gaussian distributions were fitted to log MoM PAPP‐A and log MoM free β‐hCG in trisomy 21 and in unaffected pregnancies. In each case the patient‐specific risk for trisomy 21 was estimated by multiplying the individual maternal age‐related risk with the likelihood ratio (LR) for fetal nuchal translucency (NT) according to the mixture model and the combined LR for maternal serum free β‐hCG and PAPP‐A. Estimates of detection rates for trisomy 21 and false‐positive rates were calculated for combined screening with measurements of NT at 12 weeks together with measurements of free β‐hCG and PAPP‐A from 8 to 13 weeks.

Results

In trisomy 21 pregnancies the mean log MoM free β‐hCG increased linearly with gestation between 7 and 14 weeks, whereas the relation between log MoM PAPP‐A and gestation was fitted by a quadratic equation such that the maximum separation between trisomy 21 and unaffected pregnancies occurs at 9–10 weeks. At a false‐positive rate of 3% the detection rate of combined screening at 12 weeks was 86% and this increased to 90% by biochemical testing at 9 weeks and ultrasound scanning at 12 weeks. The detection rate increased to 92% by measuring PAPP‐A at 9 weeks and free β‐hCG at the time of the scan at 12 weeks.

Conclusion

The performance of first‐trimester biochemical screening for trisomy 21 is best at 9–10 weeks rather than at 7–8 or 11–14 weeks. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.
A frequency distribution approach to hotspot identification
Authors: Bartolino Valerio , Maiorano Luigi , Colloca Francesco
Published: July 2010

We present a new global method for the identification of hotspots in conservation and ecology. The method is based on the identification of spatial structure properties through cumulative relative frequency distributions curves, and is tested with two case studies, the identification of fish density hotspots and terrestrial vertebrate species diversity hotspots. Results from the frequency distribution method are compared with those from standard techniques among local, partially local and global methods. Our approach offers the main advantage to be independent from the selection of any threshold, neighborhood, or other parameter that affect most of the currently available methods for hotspot analysis. The two case studies show how such elements of arbitrariness of the traditional methods influence both size and location of the identified hotspots, and how this new global method can be used for a more objective selection of hotspots.
miR‐1/miR‐206 regulate Hsp60 expression contributing to glucose‐mediated apoptosis in cardiomyocytes
Authors: Shan Zhi-Xin , Lin Qiu-Xiong , Deng Chun-Yu , Zhu Jie-Ning , Mai Li-Ping , Liu Ju-Li , Fu Yong-Heng , Liu Xiao-Ying , Li Yang-Xin , Zhang You-Yi , Lin Shu-Guang , Yu Xi-Yong
Published: July 2010

Hsp60 is an important component of defense mechanisms against diabetic myocardial injury; however, the cause of Hsp60 reduction in the diabetic myocardium remains unknown. After stimulation of cardiomyocytes with high glucose in vivo and in vitro, significant up‐regulation of miR‐1/miR‐206 and post‐transcriptional modulation of Hsp 60 were observed. Serum response factor (SRF) and the MEK1/2 pathway were involved in miR‐1 and miR‐206 expression in cardiomyocytes. miR‐1 and miR‐206 regulated Hsp60 expression post‐transcriptionally and accelerated cardiomyocyte apoptosis through Hsp60. These results revealed that miR‐1 and miR‐206 regulate Hsp60 expression, contributing to high glucose‐mediated apoptosis in cardiomyocytes.
The Devonian magmatism in the Kropotkin Ridge (East Sayan) and sources of basites: geological, geochemical, and Sr-Nd isotope data
Authors: Vorontsov A.A. , Sandimirov I.V.
Published: July 2010

In the east of the Tuvinian trough within the Kropotkin Ridge, the formation of Devonian volcanic associations was intimately conjugate with rifting on the southwestern framing of the Siberian Platform. The associations include picrite-like basalts, trachybasalts, basaltic trachyandesites, trachyandesites, trachytes, trachyrhyodacites, trachyrhyolites, comendites, and subvolcanic dolerites. The basic and normal-basic rocks are subdivided into two groups by TiO2 contents: high-Ti (TiO2 ∼ 2.2–4.2 wt.%) and medium-Ti (TiO2 ∼ 1.3–2.0 wt.%). Compared with the high-Ti basites, the medium-Ti ones are depleted in K, Rb, REE, Nb, Ta, Th, and U and have features of magmatic series of active continental margins. The high-Ti rocks are similar in composition to within-plate basalts. But in the isotopic compositions of Sr and Nd the above groups of basites are similar and correspond to mantle sources forming enriched within-plate basalts of the OIB type. This combination of within-plate and continent-marginal geochemical features in the basites localized in the same structure-geologic conditions might indicate the formation of rock associations in the rift zone at the rear of active continental paleomargin during the evolution of their common plume source. Its interaction with the suprasubductional lithospheric mantle determined the geochemistry of rocks.
Cost–benefit of a 13-week multidiciplinary rehabilitation course for chronic non-malignant pain patients
Authors: Meineche-Schmidt Villy
Published: July 2010

Background

Economy is an important part of chronic pain.

Aim

To describe the economy in chronic non-malignant pain patients attending a 13-week Rehabilitation Program (RP).

Methods

All patients participating in the RP 2006–2008 were evaluated at baseline (BL) and at follow-up (FU) after an observation period of mean … month in relation to: (1) work-income (WI) or (2) transfer income (TI), comprised by: (a) sick-leave (SL), (b) sick pension (SP), (c) social benefit (SB) and (d) rehabilitation benefit (RB). The economic impact on state and county and the time to age pension was calculated.

Results

117 patients attended the RP. At BL 23 patients had WI and 19 maintained this at FU (3 were on SP and 1 on RB). 90 patients were on TI at BL: 58 on SL at BL changed to 20 on SP + 23 on WI + 6 on SB + 1 on RB + 6 maintained SL, 12 on SB at BL changed to 6 on WI+ 1 on SP + 5 still on SB. 7 on RB at BL changed to 6 on WI + 1 on RB. The economic situation was concluded for 97 patients (83%). State expenses were increased by 540,000 Euro and county savings was 698,000 Euro. The societal savings were 158,000 Euro. The total costs for the RP was 421,000 Euro. Costs balanced savings after 2.7 years. The average time to age pension for the participating patients was 25 years. The potential accumulated savings thus amounted to 3.5 million Euros.

Conclusions

The 13-week Rehabilitation Program was highly cost effective: expenses for the program balanced savings after 3 years and the time to age pension for the participating patients was 25 years. The potential accumulated saving per patient was 30,000 Euro.
Bayesian Logical Data Analysis for the Physical Sciences
Authors: Gregory Phil
Published: July 2010

Bayesian inference provides a simple and unified approach to data analysis, allowing experimenters to assign probabilities to competing hypotheses of interest, on the basis of the current state of knowledge. By incorporating relevant prior information, it can sometimes improve model parameter estimates by many orders of magnitude. This book provides a clear exposition of the underlying concepts with many worked examples and problem sets. It also discusses implementation, including an introduction to Markov chain Monte-Carlo integration and linear and nonlinear model fitting. Particularly extensive coverage of spectral analysis (detecting and measuring periodic signals) includes a self-contained introduction to Fourier and discrete Fourier methods. There is a chapter devoted to Bayesian inference with Poisson sampling, and three chapters on frequentist methods help to bridge the gap between the frequentist and Bayesian approaches. Supporting Mathematica® notebooks with solutions to selected problems, additional worked examples, and a Mathematica tutorial are available at www.cambridge.org/9780521150125.
The Cambridge Introduction to Michel Foucault
Authors: Downing Lisa
Published: July 2010

French philosopher and historian Michel Foucault is essential reading for students in departments of literature, history, sociology and cultural studies. His work on the institutions of mental health and medicine, the history of systems of knowledge, literature and literary theory, criminality and the prison system, and sexuality, has had a profound and enduring impact across the humanities and social sciences. This introductory book, written for students, offers in-depth critical and contextual perspectives on all of Foucault's major published works. It provides ways in to understanding Foucault's key concepts of subjectivity, discourse, and power and explains the problems of translation encountered in reading Foucault in English. The book also explores the critical reception of Foucault's works and acquaints the reader with the afterlives of some of his theories, particularly his influence on feminist and queer studies. This book offers the ideal introduction to a famously complex, controversial and important thinker.
The Cambridge Introduction to Walter Benjamin
Authors: Ferris David S.
Published: July 2010

For students of modern criticism and theory, Walter Benjamin's writings have become essential reading. His analyses of photography, film, language, history, allegory, material culture, the poet Charles Baudelaire, and his vast examination of the social, political and historical significance of the Arcades of nineteenth-century Paris have left an enduring and important critical legacy. This volume examines in detail a substantial selection of his important critical writings on these topics from 1916 to 1940 and outlines his life in pre-war Germany, his association with the Frankfurt School, and the dissemination of his ideas and methodologies into a variety of academic disciplines since his death. David Ferris traces the development of Benjamin's key critical concepts and provides students with an accessible overview of the life, work and thought of one of the twentieth-century's most important literary and cultural critics.
PARACONSISTENT LOGICS INCLUDED IN LEWIS’ S4
Authors: ROBLES GEMMA , MÉNDEZ JOSÉ M.
Published: July 2010

As is known, a logic S is paraconsistent if the rule ECQ (E contradictione quodlibet) is not a rule of S. Not less well known is the fact that Lewis’ modal logics are not paraconsistent. Actually, Lewis vindicates the validity of ECQ in a famous proof currently known as the “Lewis’ proof” or “Lewis’ argument.” This proof essentially leans on the Disjunctive Syllogism as a rule of inference. The aim of this paper is to define a series of paraconsistent logics included in S4 where the Disjunctive Syllogism is valid only as a rule of proof.
Seismic layer 2A variations in the Lucky Strike segment at the Mid‐Atlantic Ridge from reflection measurements
Authors: Seher Tim , Crawford Wayne C. , Singh Satish C. , Cannat Mathilde
Published: July 2010

The SISMOMAR experiment carried out seismic measurements of the slow spreading Lucky Strike segment of the Mid‐Atlantic Ridge, located approximately 300 km south of the Azores platform. We present results from a segment scale reflection study of seismic layer 2A that is centered on the Lucky Strike volcano and covers the central 54 km of the 70 km long segment and extends 30 km on both sides of the ridge axis. Our study allows new conclusions about the role of tectonic, magmatic and hydrothermal processes in shaping the upper crustal structure of the Lucky Strike segment. The seismic reflection measurements show an almost constant layer 2A two‐way time within the median valley and an abrupt layer 2A two‐way time decrease off‐axis. This two‐way time decrease is caused by a layer 2A velocity increase on the order of 1 km/s. The uniform two‐way time in the median valley results from a constant thickness layer 2A, which could be caused by the existence of a porosity threshold linked to the lithologic lava/dike boundary. The regularity of the layer 2A/2B interface within the median valley indicates that layer 2A is built entirely inside the median valley. The off‐axis velocity increase is consistent with hydrothermal alteration and the aging of the crust.
Synthesis of satellite (MODIS), aircraft (ICARTT), and surface (IMPROVE, EPA‐AQS, AERONET) aerosol observations over eastern North America to improve MODIS aerosol retrievals and constrain surface aerosol concentrations and sources
Authors: Drury Easan , Jacob Daniel J. , Spurr Robert J. D. , Wang Jun , Shinozuka Yohei , Anderson Bruce E. , Clarke Antony D. , Dibb Jack , McNaughton Cameron , Weber Rodney
Published: July 2010

We use an ensemble of satellite (MODIS), aircraft, and ground‐based aerosol observations during the ICARTT field campaign over eastern North America in summer 2004 to (1) examine the consistency between different aerosol measurements, (2) evaluate a new retrieval of aerosol optical depths (AODs) and inferred surface aerosol concentrations (PM2.5) from the MODIS satellite instrument, and (3) apply this collective information to improve our understanding of aerosol sources. The GEOS‐Chem global chemical transport model (CTM) provides a transfer platform between the different data sets, allowing us to evaluate the consistency between different aerosol parameters observed at different times and locations. We use an improved MODIS AOD retrieval based on locally derived visible surface reflectances and aerosol properties calculated from GEOS‐Chem. Use of GEOS‐Chem aerosol optical properties in the MODIS retrieval not only results in an improved AOD product but also allows quantitative evaluation of model aerosol mass from the comparison of simulated and observed AODs. The aircraft measurements show narrower aerosol size distributions than those usually assumed in models, and this has important implications for AOD retrievals. Our MODIS AOD retrieval compares well to the ground‐based AERONET data (R = 0.84, slope = 1.02), significantly improving on the MODIS c005 operational product. Inference of surface PM2.5 from our MODIS AOD retrieval shows good correlation to the EPA‐AQS data (R = 0.78) but a high regression slope (slope = 1.48). The high slope is seen in all AOD‐inferred PM2.5 concentrations (AERONET: slope = 2.04; MODIS c005: slope = 1.51) and could reflect a clear‐sky bias in the AOD observations. The ensemble of MODIS, aircraft, and surface data are consistent in pointing to a model overestimate of sulfate in the mid‐Atlantic and an underestimate of organic and dust aerosol in the southeastern United States. The sulfate overestimate could reflect an excessive contribution from aqueous‐phase production in clouds, while the organic carbon underestimate could possibly be resolved by a new secondary pathway involving dicarbonyls.
Regional trends of daily precipitation indices in northwest Mexico and southwest United States
Authors: Arriaga‐Ramírez Sarahí , Cavazos Tereza
Published: July 2010

A regionalization based on a rotated principal component analysis (PCA) was used to produce six precipitation regions in northwest Mexico and the southwest United States. Monthly precipitation data from 184 meteorological stations for the 1960–1997 period were used in the PCA. The aim of this study was to estimate annual and seasonal trends of 10 daily precipitation indices in the six regions, including four indices related with extreme precipitation. The annual indices show a larger number of statistically significant trends than the seasonal indices, especially in Arizona‐New Mexico and in the monsoon region in northwest Mexico (MON). Significant positive trends common to these two contiguous regions are extreme precipitation exceeding the 95th (R95p) and 99th (R99p) percentiles. The analysis of summer (June–October) daily precipitation indices also reveals the occurrence of significant positive trends in R95p in MON, mainly due to tropical cyclone activity. With the exception of the trends in MON, the most important contribution to the annual trends comes from the winter indices. Four of the six regions in the study area show significant positive trends in extreme winter precipitation (R10mm, R95p or R99p) during the study period. The variability of the annual indices that show statistically significant trends in extreme precipitation are partially linked to natural variations resulting from the combined effects of El Niño/Southern Oscillation and the Pacific decadal oscillation (PDO) and, in most cases, the trends are explained by the PDO.
Semianalytical analysis of hyporheic flow induced by alternate bars
Authors: Marzadri A. , Tonina D. , Bellin A. , Vignoli G. , Tubino M.
Published: July 2010

We investigate the effects of alternate bar morphology on the hyporheic flow in gravel bed rivers. Our goal is to investigate the relations between residence time distribution of a conservative tracer and the parameters controlling bed form morphology. We assume homogeneous, isotropic or anisotropic hydraulic properties of the streambed sediment and constant flow regime in equilibrium with the bed form, which is considered fixed because its formation timescale is much longer than that of the subsurface flow. Under these assumptions, we solve the in‐stream and hyporheic flow fields analytically in a three‐dimensional domain. We approximate the former with the shallow water equations and model the latter as a Darcian flow. The two systems are linked through the hydraulic head distribution, which is predicted at the streambed by the surface model and applied as a boundary condition to the hyporheic flow model. We solve the solute transport equation in the hyporheic zone for a conservative tracer by means of particle tracking. Our model predicts that the mean value and variance of the hyporheic residence time depend on the alternate bar amplitude at equilibrium. This result is found to be applicable also to discharges that are lower (70% in our simulations) than the formative and submerge the bars entirely. Moreover, our analysis shows that 95% of the hyporheic flow is confined in a near‐bed layer, whose depth is about the width of the channel and shallows from low to steep gradient streams. This causes the hyporheic mean residence time to reach a threshold when the alluvial depth is deeper than the channel width. Our results also show that as the stream slope increases, the streamlines compact near to the streambed, thereby reducing the mean residence time and its variance. Finally, we observe that the hyporheic residence time of pulse injections of passive solutes is lognormally distributed, with the mean value depending in a simple manner on the amplitude of the alternate bars.
Coupling of ice‐shelf melting and buttressing is a key process in ice‐sheets dynamics
Authors: Gagliardini O. , Durand G. , Zwinger T. , Hindmarsh R. C. A. , Le Meur E.
Published: July 2010

Increase in ice‐shelf melting is generally presumed to have triggered recent coastal ice‐sheet thinning. Using a full‐Stokes finite element model which includes a proper description of the grounding line dynamics, we investigate the impact of melting below ice shelves. We argue that the influence of ice‐shelf melting on the ice‐sheet dynamics induces a complex response, and the first naive view that melting inevitably leads to loss of grounded ice is erroneous. We demonstrate that melting acts directly on the magnitude of the buttressing force by modifying both the area experiencing lateral resistance and the ice‐shelf velocity, indicating that the decrease of back stress imposed by the ice‐shelf is the prevailing cause of inland dynamical thinning. We further show that feedback from melting and buttressing forces can lead to nontrivial results, as an increase in the average melt rate may lead to inland ice thickening and grounding line advance.
Northern Hemisphere winter snow anomalies: ENSO, NAO and the winter of 2009/10
Authors: Seager R. , Kushnir Y. , Nakamura J. , Ting M. , Naik N.
Published: July 2010

Winter 2009/10 had anomalously large snowfall in the central parts of the United States and in northwestern Europe. Connections between seasonal snow anomalies and the large scale atmospheric circulation are explored. An El Niño state is associated with positive snowfall anomalies in the southern and central United States and along the eastern seaboard and negative anomalies to the north. A negative NAO causes positive snow anomalies across eastern North America and in northern Europe. It is argued that increased snowfall in the southern U.S. is contributed to by a southward displaced storm track but further north, in the eastern U.S. and northern Europe, positive snow anomalies arise from the cold temperature anomalies of a negative NAO. These relations are used with observed values of NINO3 and the NAO to conclude that the negative NAO and El Niño event were responsible for the northern hemisphere snow anomalies of winter 2009/10.
Intronic hammerhead ribozymes are ultraconserved in the human genome
Authors: de la Peña Marcos , García‐Robles Inmaculada
Published: July 2010

Small ribozymes have been regarded as living fossils of a prebiotic RNA world that would have remained in the genomes of modern organisms. In this study, we report the ultraconserved occurrence of hammerhead ribozymes in Amniota genomes (reptiles, birds and mammals, including humans), similar to those described previously in amphibians and platyhelminth parasites. The ribozymes mapped to intronic regions of different genes, such as the tumour suppressor RECK in birds and mammals, a mammalian tumour antigen and the dystrobrevin beta in lizards and birds. In vitro characterization confirmed a high self‐cleavage activity, whereas analysis of RECK‐expressed sequence tags revealed fusion events between the in vivo self‐cleaved intron and U5 or U6 small nuclear RNA fragments. Together, these results suggest a conserved role for these ribozymes in messenger RNA biogenesis.
Acetylation‐dependent oncogenic activity of metastasis‐associated protein 1 co‐regulator
Authors: Ohshiro Kazufumi , Rayala Suresh K , Wigerup Caroline , Pakala Suresh B , Natha Reddy S Divijendra , Gururaj Anupama E , Molli Poonam R , Månsson Sofie Svensson , Ramezani Ali , Hawley Robert G , Landberg Goran , Lee Norman H , Kumar Rakesh
Published: July 2010

High expression of metastasis‐associated protein 1 co‐regulator (MTA1), a component of the nuclear remodelling and histone deacetylase complex, has been associated with human tumours. However, the precise role of MTA1 in tumorigenesis remains unknown. In this study, we show that induced levels of MTA1 are sufficient to transform Rat1 fibroblasts and that the transforming potential of MTA1 is dependent on its acetylation at Lys626. Underlying mechanisms of MTA1‐mediated transformation include activation of the Ras–Raf pathway by MTA1 but not by acetylation‐inactive MTA1; this was due to the repression of Gαi2 transcription, which negatively influences Ras activation. We observed that acetylated MTA1–histone deacetylase (HDAC) interaction was required for the recruitment of the MTA1–HDAC complex to the Gαi2 regulatory element and consequently for the repression of Gαi2 transcription and expression leading to activation of the Ras–Raf pathway. The findings presented in this study provide for the first time—to the best of our knowledge—evidence of acetylation‐dependent oncogenic activity of a cancer‐relevant gene product.
Tackling the pathogenesis of RNA nuclear retention in myotonic dystrophy
Authors: Mastroyiannopoulos Nikolas P. , Shammas Christos , Phylactou Leonidas A.
Published: July 2010

DM1 (myotonic dystrophy type I) is a common form of muscular dystrophy that affects mainly adults. It is a disease that belongs to the group of defective RNA export diseases, since a major part of the pathogenic mechanism of the disease is the retention of the mutant transcripts in the cell nucleus. The presence of an expanded CUG trinucleotide repeat in the 3′‐UTR (3′‐untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene causes the attraction of RNA‐binding proteins by the nuclear‐located mutant transcripts. As a result of the occupation of the RNA‐binding proteins, there is defective mis‐splicing of several cellular transcripts. This is believed to be a major pathogenic mechanism of the disease and any attempt to repair the activities of the RNA‐binding proteins or target the mutant transcripts should be beneficial for the patients. Certain approaches have been described in the literature and they demonstrate progress in various directions. The purpose of the present review is to summarize the successful attempts to tackle the pathogenesis caused by nuclear retention of mutant transcripts in myotonic dystrophy and to discuss the possible gains from such approaches.
Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser910/Ser935, disruption of 14-3-3 binding and altered cytoplasmic localization
Authors: Dzamko Nicolas , Deak Maria , Hentati Faycal , Reith Alastair D. , Prescott Alan R. , Alessi Dario R. , Nichols R. Jeremy
Published: July 2010

LRRK2 (leucine-rich repeat protein kinase 2) is mutated in a significant number of Parkinson's disease patients. Since a common mutation that replaces Gly2019 with a serine residue enhances kinase catalytic activity, small-molecule LRRK2 inhibitors might have utility in treating Parkinson's disease. However, the effectiveness of inhibitors is difficult to assess, as no physiological substrates or downstream effectors have been identified that could be exploited to develop a robust cell-based assay. We recently established that LRRK2 bound 14-3-3 protein isoforms via its phosphorylation of Ser910 and Ser935. In the present study we show that treatment of Swiss 3T3 cells or lymphoblastoid cells derived from control or a Parkinson's disease patient harbouring a homozygous LRRK2(G2019S) mutation with two structurally unrelated inhibitors of LRRK2 (H-1152 or sunitinib) induced dephosphorylation of endogenous LRRK2 at Ser910 and Ser935, thereby disrupting 14-3-3 interaction. Our results suggest that H-1152 and sunitinib induce dephosphorylation of Ser910 and Ser935 by inhibiting LRRK2 kinase activity, as these compounds failed to induce significant dephosphorylation of a drug-resistant LRRK2(A2016T) mutant. Moreover, consistent with the finding that non-14-3-3-binding mutants of LRRK2 accumulated within discrete cytoplasmic pools resembling inclusion bodies, we observed that H-1152 causes LRRK2 to accumulate within inclusion bodies. These findings indicate that dephosphorylation of Ser910/Ser935, disruption of 14-3-3 binding and/or monitoring LRRK2 cytoplasmic localization can be used as an assay to assess the relative activity of LRRK2 inhibitors in vivo. These results will aid the elaboration and evaluation of LRRK2 inhibitors. They will also stimulate further research to understand how phosphorylation of Ser910 and Ser935 is controlled by LRRK2, and establish any relationship to development of Parkinson's disease.
Stability of a hybrid mean velocity profile and its relevance to cavity resonance suppression
Authors: Sarpotdar Shekhar , Panickar Praveen , Raman Ganesh
Published: July 2010

A rod in crossflow is a technique known for its simple and effective means of suppressing cavity tones. Although several hypotheses have been put forward regarding its working principle, no validated explanation exists. In the present study we investigate whether the cylinder, through its wake, changes the stability characteristics of the shear layer that develops over the cavity. The present study pertains to a cavity of length to depth ratio L/D=2, for subsonic Mach numbers ranging from 0.5 to 0.8. The upstream boundary layer was found to be turbulent for all cases considered. We use linear stability theory in the spatial, compressible and inviscid formulation for our study. We construct artificial velocity profiles that are prototypical of the experimentally measured velocity profiles, to investigate how the wake of the cylinder influences the stability of the shear layer. Parametric analysis of these profiles revealed several interesting stability characteristics, viz., different stability modes, the dominant feature of the velocity profile that influences the stability characteristics of the shear layer. We also calculate integrated growth rates, based on a series of profiles measured along the length of the cavity, for a variety of baseline and control configurations. Comparison of these integrated growth rates with the acoustic suppression data showed that the link between the two is weak. Thus the ability of the rod to suppress the cavity resonance is not directly explained by linear stability analysis of the modified shear layer, for the configurations considered.
An experimental investigation of bending wave instability modes in a generic four-vortex wake
Authors: Babie Brian M. , Nelson Robert C.
Published: July 2010

An experimental study of a planar wake consisting of four vortices that simulate the trailing vortex wakes generated by transport airplanes in either takeoff or landing configurations is presented. The objective of this study was to examine naturally occurring wake instabilities. Specifically, the focus of the study was centered on bending wave instabilities of which the Crow instability represents a particular case. A unique method of generating a four-vortex wake was developed for this study. The four-vortex wake generating device permitted direct variation of the spacing between vortices as well as control over the vortex circulation strength. Two quantitative flow visualization experiments were instrumental in identifying wake configurations that were conducive to the rapid growth of bending wave modes and in the identification of the long-wavelength mode. Detailed experiments were also conducted to examine the flow structure in the near-field or roll-up region using a four sensor, hot-wire probe that could measure all three velocity components in the wake simultaneously. The results of both the flow visualization and hot-wire experiments indicate that the long-wavelength mode and the first short-wavelength mode likely dominate the far-field wake physics and may potentially be utilized in a wake control strategy.
Multi-Jastrow trial wavefunctions for electronic structure calculations with quantum Monte Carlo
Authors: Bouabça Thomas , Braïda Benoît , Caffarel Michel
Published: July 2010

A new type of electronic trial wavefunction suitable for quantum Monte Carlo calculations of molecular systems is presented. In contrast with the standard Jastrow–Slater form built with a unique global Jastrow term, it is proposed to introduce individual Jastrow factors attached to molecular orbitals. Such a form is expected to be more physical since it allows to describe differently the local electronic correlations associated with various molecular environments (1s-core orbitals, 3d-magnetic orbitals, localized two-center σ-orbitals, delocalized π-orbitals, atomic lone pairs, etc.). In contrast with the standard form, introducing different Jastrow terms allows us to change the nodal structure of the wavefunction, a point which is important in the context of building better nodes for more accurate fixed-node diffusion Monte Carlo (FN-DMC) calculations. Another important aspect resulting from the use of local Jastrow terms is the possibility of defining and preoptimizing local and transferable correlated units for building complex trial wavefunctions from simple parts. The practical aspects associated with the computation of the intricate derivatives of the multi-Jastrow trial function are presented in detail. Some first illustrative applications for atoms of increasing size (O, S, and Cu) and for the potential energy curve and spectroscopic constants of the FH molecule are presented. In the case of the copper atom, the use of the multi-Jastrow form at the variational Monte Carlo level has allowed us to improve significantly the value of the total ground-state energy (about 75% of the correlation energy with only one determinant and three atomic orbital Jastrow factors). In the case of the FH molecule (fluorine hydride), it has been found that the multi-Jastrow nodes lead to an almost exact FN-DMC value of the dissociation energy [D0=−140.7(4) kcal/mol instead of the estimated nonrelativistic Born–Oppenheimer exact value of −141.1], which is not the case with standard nodes, D0=−138.3(4) kcal/mol.
Multiscale dynamic analysis of blast furnace system based on intensive signal processing
Authors: Chu Yanxu , Gao Chuanhou , Liu Xiangguan
Published: July 2010

In this paper, the Hilbert–Huang transform method and time delay embedding method are applied to multiscale dynamic analysis on the time series of silicon content in hot metal collected from a medium-sized blast furnace with the inner volume of 2500 m3. The results provide clear evidence of multiscale features in blast furnace ironmaking process. Ten intrinsic mode functions (IMFs) are decomposed from the silicon content time series; the presence of noninteger fractal dimension, positive finite Kolmogorov entropy, and positive finite maximum Lyapunov exponent are found in some IMF components. In addition, the coupling of subscale structures of blast furnace system is studied using the dimension of interaction dynamics and a robust algorithm for detecting interdependence. It is found that IMF(3) is the main driver in the coupling system IMF(2) and IMF(3) while for the coupling system IMF(3) and IMF(4) neither subsystem can act as the driver. All these provide a guideline for studying blast furnace ironmaking process with multiscale theory and methods, and may open way for more candidate tools to model and control blast furnace system in the future.