bluuebunny/crossref_metadata_2025 huggingface dataset:
Resource brokering using a multi‐site resource allocation strategy for computational grids
Authors: Yang Chao‐Tung , Leu Fang‐Yie , Chen Sung‐Yi
Published: November 2010

Grid computing employs heterogeneous resources which may be installed on different platforms, hardware/software, computer architectures, and perhaps using different computer languages to solve large‐scale computational problems. As many more Grids are being developed worldwide, the number of multi‐institutional collaborations is growing rapidly. However, to realize Grid computing's full potential, it is expected that Grid participants must be able to share one another's resources. This paper presents a resource broker that employs the multi‐site resource allocation (MSRA) strategy and the dynamic domain‐based network information model that we propose to allocate Grid resources to submitted jobs, where the Grid resources may be dispersed at different sites, and owned and governed by different organizations or institutes. The jobs and resources may also belong to different clusters/sites. Resource statuses collected by the Ganglia, and network bandwidths gathered by the Network Weather Service, are both considered in the proposed scheduling approach. A dynamic domain‐based model for network information measurement is also proposed to choose the most appropriate resources that meet the jobs' execution requirements. Experimental results show that MSRA outperformed the other tested strategies. Copyright © 2010 John Wiley & Sons, Ltd.
Fault tolerance for data parallel programs
Authors: Bertolli C. , Vanneschi M.
Published: November 2010

The main issues when supporting fault tolerance based on checkpointing and rollback recovery for High‐Performance applications are related to the scalability of the introduced support, the possibility of analyzing the induced overhead and, in more general terms, the optimization of the trade‐off between failure‐free and recovery performances. In this paper we describe our contribution in fault tolerance for high‐level structured parallelism models. We take a different viewpoint w.r.t. existing contributions, by introducing a methodology to derive interesting properties to support fault tolerance. We show how to apply this methodology to a general data parallel model, deriving useful properties to introduce a class of checkpointing protocols. Thanks to this methodology, this class of protocols is not affected by the described issues. We exemplify two checkpointing protocols and the related rollback recovery techniques. For each protocol we also derive cost models statically describing the failure‐free performance, which can be used for performance tuning or to target some Quality of Service parameter. To assess the innovation of the results we analytically and experimentally compare the introduced protocols with two literature protocols. Results show that while the protocols introduced in this paper permit the definition of cost models and have a good scalability, the literature protocols do not always have these properties. Copyright © 2010 John Wiley & Sons, Ltd.
Secure SCADA framework for the protection of energy control systems
Authors: Alcaraz Cristina , Lopez Javier , Zhou Jianying , Roman Rodrigo
Published: November 2010

Energy distribution systems are becoming increasingly widespread in today's society. One of the elements that are used to monitor and control these systems are SCADA (Supervisory Control and Data Acquisition) systems. In particular, these control systems and their complexities, together with the emerging use of the Internet and wireless technologies, bring new challenges that must be carefully considered. Examples of such challenges are the particular benefits of the integration of those new technologies, and also the effects they may have on the overall SCADA security. The main task of this paper is to provide a framework that shows how the integration of different state‐of‐the‐art technologies in an energy control system, such as wireless sensor networks, mobilead hocnetworks, and the Internet, can bring some interesting benefits, such as status management and anomaly prevention, while maintaining the security of the whole system. Copyright © 2010 John Wiley & Sons, Ltd.
A grid portal with robot certificates for bioinformatics phylogenetic analyses
Authors: Barbera R. , Andronico G. , Donvito G. , Falzone A. , Keijser J. J. , Rocca G. La , Milanesi L. , Maggi G. P. , Vicario S.
Published: November 2010

Grid technology and ICT‐based infrastructures play a crucial role in the development of transnational multi‐disciplinary collaborations and allow scientists to share a wide range of distributed computational resources, regardless of their geographical location, and address new global scientific challenges. Till now, the strict security policy requested in order to access distributed computing resources has been a limiting factor when trying to broaden the adoption of Grids by wide communities of users. There is a steep learning curve to climb before starting to gain some benefits from this new technology. Grid security is indeed based on the Public Key Infrastructure (PKI) of X.509 certificate although the procedure to get and manage those certificates is unfortunately not straightforward. A first step to make Grids more appealing for new users has recently been achieved with the adoption of robot certificates. In this paper, the solution proposed by the Italian National Institute of Nuclear Physics to go through the complexity of Grid security and allow bioinformaticians to perform large‐scale Bayesian Phylogenetic analyses on the Grid by means of a web portal enabled by a robot certificate is presented. Copyright © 2010 John Wiley & Sons, Ltd.
Improved static and dynamic performances of a two‐cell DC–DC buck converter using a digital dynamic time‐delayed control
Authors: Kaoubaâ Karama , Pelaez‐Restrepo J. , Feki M. , Robert B. G. M. , Aroudi A. El
Published: November 2010

Multi‐cell converters have been developed to overcome shortcomings in usual switching devices. The control system in these circuits is twofold: first, to balance voltages of the switches and second to regulate the load current to a desired value. However, with a purely proportional controller, the system presents a static error. With a PI controller the static error is annihilated, but at the expense of shortening the stability region and increasing settling time. In this work, a zero static error dynamic controller for a two‐cell DC–DC buck converter is designed. To achieve zero current error, we propose a generalized scheme of a dynamic controller. Then, using nonlinear analysis and Lyapunov stability theory and bifurcation prediction tools, we prove that zero static error is achieved. The proposed controller outperforms the PI controller in terms of settling time in the presence of saturating effect during the start‐up transients. Numerical simulations in the form of time domain waveforms and bifurcation diagrams from switched circuit‐based model are presented to confirm our theoretical results. Copyright © 2010 John Wiley & Sons, Ltd.
Analog filter pair design on the basis of a gyrator–capacitor prototype circuit
Authors: Handkiewicz Andrzej , Katarzyński Piotr , Szczȩsny Szymon , Wencel Jarosław , Śniatała Paweł
Published: November 2010

The paper presents an algorithmic approach to a low‐sensitivity design strategy for analog filter pairs based on a gyrator–capacitor prototype circuit. The general structure of the prototype circuit is proposed. It assumed that the generic structure of the prototype circuit can evolve, with the use of additional gyrators, into a circuit with increased redundancy. It is shown that symbolic analysis of the prototype circuit, used to formulate a set of nonlinear algebraic equations, is necessary to achieve a sufficiently high algorithm operation speed. To find a solution to this specific system of nonlinear algebraic equations, different numerical methods are compared. The modified Hooke and Jeeves algorithm is found to be the most effective. The elaborated algorithms and programs are illustrated with the seventh‐order filter pair example. The obtained filter is better than the filter obtained using LC ladder structures with respect to chip area and power consumption, and these improvements are obtained without loss of sensitivity properties. Copyright © 2010 John Wiley & Sons, Ltd.
Prenatal treatment with glucocorticoids sensitizes the hpa axis response to stress among full‐term infants
Authors: Davis Elysia Poggi , Waffarn Feizal , Sandman Curt A.
Published: November 2010

The objective of this study was to determine the consequences for HPA axis functioning among healthy full‐term newborns of prenatal treatment with the synthetic glucocorticoid (GC), betamethasone, which is the routine treatment for threatened preterm delivery. Ninety full‐term infants were recruited into two study groups (30 betamethasone treated; 60 comparison group matched for GA at birth and sex). The cortisol and behavioral response to the painful stress of a heel‐stick blood draw was assessed 24 hr after birth. Full‐term infants exposed to prenatal betamethasone displayed a larger cortisol response to the heel‐stick procedure, despite no differences in baseline levels. Further, within the recommended window of betamethasone administration (24–34 gestational weeks), infants exposed to betamethasone earlier in gestation displayed the largest cortisol response to the heel‐stick. These data add to accumulating evidence that prenatal exposure to elevated GCs programs the development of the HPA axis. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 53:175–183, 2011
Head orientation and handedness trajectory in rhesus monkey infants (Macaca mulatta)
Authors: Nelson Eliza L. , Emery Michelle S. , Babcock Samantha M. , Novak Matthew F.S.X. , Suomi Stephen J. , Novak Melinda A.
Published: November 2010

In human and chimpanzee infants, neonatal rightward supine head orientation bias predicts later right hand use preference. In an evolutionarily older primate species such as the rhesus monkey, a left hand preference has been reported, but there are no data on head orientation biases. Supine head orientation bias was measured experimentally in 16 rhesus monkey neonates and compared with prone head orientation bias as well as with various measures of hand use preference. A group‐level leftward supine head bias was found that corresponded to greater activity in the left hand while supine; however, supine head orientation did not predict later hand preference as measured by reaching or manipulation on a coordinated bimanual task. These data suggest that a trajectory for handedness in rhesus monkeys may be different from that of humans and chimpanzees. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 53:246–255, 2011.
Hydrolytic Decomposition of Tetramethylammonium Bis(trifluoromethyl)aurate(I), [NMe4][Au(CF3)2]: A Route for the Synthesis of Gold Nanoparticles in Aqueous Medium
Authors: Zopes David , Kremer Silke , Scherer Harald , Belkoura Lhoussaine , Pantenburg Ingo , Tyrra Wieland , Mathur Sanjay
Published: November 2010

Monodisperse gold nanoparticles (AuNPs) were obtained by hydrolytic decomposition of a new molecular precursor, tetramethylammonium bis(trifluoromethyl)aurate(I), [NMe4][Au(CF3)2], which has been characterised by spectroscopic and single‐crystal X‐ray diffraction analyses. On account of the simple and high‐yield synthesis, the title compound represents a versatile synthon and an alternative to the commonly used chloroauric acid (HAuCl4).
The Mechanism of the ortho‐Methylation of Nitrobenzenes by Dimethylsulfonium Methylide
Authors: Haiss Peter , Zeller Klaus‐Peter
Published: November 2010

Nitrobenzenes carrying an ortho substituent are selectively methylated at the free ortho position by reaction with dimethylsulfonium methylide. The importance of the ortho substituent is demonstrated by the failure of the methylation of nitrobenzene and 3‐ and 4‐nitroanisole. This is explained by the out‐of‐plane geometry of the nitro group in the ortho‐substituted derivative, which enables a specific interaction between the ylide and the nitro group favourable for attack of the methylide C atom at the neighbouring free ortho position. As shown by appropriate deuterium‐labelling studies, the addition is followed by an E1‐like β‐elimination with displacement of dimethyl sulfide and subsequent protonation of the elimination product.
Experimental and numerical investigation of fire development in a real fire in a five‐storey apartment building
Authors: Hofmann Anja , Muehlnikel Ruediger
Published: November 2010

A fire in a five‐storey apartment building was investigated experimentally and numerically. The room of origin of the fire was a living room in the second floor and the fire was started by a candle on a television set. The fire spread externally over the building faccade and internally along the staircase and affected all the flats above leading to two fatalities. It is estimated that the fire was discovered minutes after ignition and the fire service was called very shortly after the detection and was at the scene 9 min after the call. By this time large sections of the façade were on fire already. The rapid fire that spread over the façade and the staircase necessitated detailed investigations. Compliance of building products with the building regulations was investigated. One conclusion of the investigations was that the person who caused the fire by leaving the candle on the TV set unattended should not be held responsible for the two fatalities in the upper floors. Copyright © 2010 John Wiley & Sons, Ltd.
Hydrological field data from a modeller's perspective: Part 1. Diagnostic tests for model structure
Authors: McMillan Hilary K. , Clark Martyn P. , Bowden William B. , Duncan Maurice , Woods Ross A.
Published: November 2010

Hydrological scientists develop perceptual models of the catchments they study, using field measurements and observations to build an understanding of the dominant processes controlling the hydrological response. However, conceptual and numerical models used to simulate catchment behaviour often fail to take advantage of this knowledge. It is common instead to use a pre‐defined model structure which can only be fitted to the catchment via parameter calibration. In this article, we suggest an alternative approach where different sources of field data are used to build a synthesis of dominant hydrological processes and hence provide recommendations for representing those processes in a time‐stepping simulation model. Using analysis of precipitation, flow and soil moisture data, recommendations are made for a comprehensive set of modelling decisions, including Evapotranspiration (ET) parameterization, vertical drainage threshold and behaviour, depth and water holding capacity of the active soil zone, unsaturated and saturated zone model architecture and deep groundwater flow behaviour. The second article in this two‐part series implements those recommendations and tests the capability of different model sub‐components to represent the observed hydrological processes. Copyright © 2010 John Wiley & Sons, Ltd.
Projection of climate change for daily precipitation: a case study in Shih‐Men reservoir catchment in Taiwan
Authors: Yang Tao‐Chang , Yu Pao‐Shan , Wei Chi‐Ma , Chen Shien‐Tsung
Published: November 2010

A statistical downscaling model, based on the outputs of general circulation models (GCMs) as predictors, was proposed to simulate the daily precipitations in the Shih‐Men reservoir catchment in Taiwan. The structure of the proposed downscaling model is composed of two parts: classification and regression. Predictors of classification and regression models were selected from the large‐scale weather variables in the National Centers for Environmental Prediction (NECP) reanalysis data based on statistical tests. Discriminant analysis and support vector regression (SVR) were applied to build the classification and regression models. The outputs of five atmosphere‐ocean GCMs, which are reported to have properly considered tropical cyclone information and East Asian Monsoon modelling, were used for projecting future precipitations. Data from four grids covering Taiwan were used for developing the downscaling model. The potential of the downscaling models in simulating local precipitations was evaluated, and downscaling results reveal that the proposed downscaling model can reproduce local daily precipitations from large‐scale weather variables. Projected local precipitations under two emission scenarios show that the precipitations in the study area tend to decrease. Copyright © 2010 John Wiley & Sons, Ltd.
A distributed thermodynamic model for energy and mass balance computation: FEST–EWB
Authors: Corbari Chiara , Ravazzani Giovanni , Mancini Marco
Published: November 2010

This article presents the development of distributed thermodynamic model for energy and mass balance computation between soil surface and shallow atmospheric layers and its inclusion into the hydrological model FEST–EWB (Flash–flood Event–based Spatially distributed rainfall–runoff Transformation–Energy Water Balance). This model is also thought for a synergic use of hydrological model with remote sensing data. In particular, the energy budget is solved looking for the representative thermodynamic equilibrium temperature (RET) defined as the land surface temperature (LST) that closes the energy balance equation for any pixel of basin surface. So using this approach, through the system between the mass and energy equations, soil moisture (SM) is linked to the latent heat flux (LE) and then to LST. The RET thermodynamic approach solves most of the problems of the actual evapotranspiration (ET) and SM computation. In fact, it permits to avoid computing the effective ET as an empirical fraction of the potential one. This approach, based on the RET, has been tested at field scale (10 ha) with energy fluxes and LST measured with an eddy covariance station in Landriano (Italy). Copyright © 2010 John Wiley & Sons, Ltd.
Evaluation of linear regression methods as downscaling tools in temperature projections over the Pichola Lake Basin in India
Authors: Goyal Manish Kumar , Ojha C. S. P.
Published: November 2010

In this paper, downscaling models are developed using various linear regression approaches, namely direct, forward, backward and stepwise regression, for obtaining projections of mean monthly maximum and minimum temperatures (Tmax and Tmin) to lake‐basin scale in an arid region in India. The effectiveness of these regression approaches is evaluated through application to downscale the predictands for the Pichola lake region in the state of Rajasthan in India, which is considered to be a climatically sensitive region. The predictor variables are extracted from (i) the National Centers for Environmental Prediction (NCEP) reanalysis dataset for the period 1948–2000 and (ii) the simulations from the third‐generation Canadian Coupled Global Climate Model (CGCM3) for emission scenarios A1B, A2, B1 and COMMIT for the period 2001–2100. The selection of important predictor variables becomes a crucial issue for developing downscaling models as reanalysis data are based on a wide range of meteorological measurements and observations. A simple multiplicative shift was used for correcting predictand values. Direct regression was found to yield better performance among all other regression techniques for the training data set, while the forward regression technique performed better in the validation data set, explored in the present study. For trend analysis, the Mann–Kendall non‐parametric test was performed. The results of downscaling models show that an increasing trend is observed for Tmax and Tmin for A1B, A2 and B1 scenarios, whereas no trend is discerned with the COMMIT scenario by using predictors. Copyright © 2010 John Wiley & Sons, Ltd.
Shared and unique predictors of post‐traumatic growth and distress
Authors: Dekel Sharon , Mandl Christine , Solomon Zahava
Published: November 2010

This prospective longitudinal study compared pretraumatic, peritraumatic, and post‐traumatic predictors of post‐traumatic growth (PTG) and post‐traumatic stress disorder (PTSD). A total of 103 Israeli former prisoners of the Yom Kippur War were followed over 30 years. Sociodemographic variables, trauma exposure, reactions in captivity, world assumptions, social support, and personality factors were assessed in 1991, and PTG and PTSD symptoms in 2003. Hierarchical regression modeling showed that although some predictors, namely, loss of control and active coping during captivity, predicted both PTG and PTSD, others predicted one outcome and not the other. Self‐controllability predicted PTG while sociodemographic factors predicted PTSD when controlling for PTSD and PTG, respectively. The findings indicate that salutary and pathogenic trauma outcomes share some but not all precursors, underscoring their multifaceted relationship. © 2010 Wiley Periodicals, Inc. J Clin Psychol 00:1–12, 2010.
Culture
Authors: Smith Timothy B. , Rodríguez Melanie Domenech , Bernal Guillermo
Published: November 2010

This article summarizes the definitions, means, and research of adapting psychotherapy to clients' cultural backgrounds. We begin by reviewing the prevailing definitions of cultural adaptation and providing a clinical example. We present an original meta‐analysis of 65 experimental and quasi‐experimental studies involving 8,620 participants. The omnibus effect size of d = .46 indicates that treatments specifically adapted for clients of color were moderately more effective with that clientele than traditional treatments. The most effective treatments tended to be those with greater numbers of cultural adaptations. Mental health services targeted to a specific cultural group were several times more effective than those provided to clients from a variety of cultural backgrounds. We recommend a series of research‐supported therapeutic practices that account for clients' culture, with culture‐specific treatments being more effective than generally culture‐sensitive treatments. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 67:166–175, 2011.
Circulating carotenoid concentrations are positively correlated with later clutch initiation in Florida Scrub‐Jays (Aphelocoma coerulescens)
Authors: Heiss Rebecca S. , Cohen Alan A. , Bowman Reed , Boughton Raoul K. , Bridge Eli , McGraw Kevin J. , Schoech Stephan J.
Published: November 2010

Antioxidants play key roles in preventing free radical damage to various molecules, cells, and tissues, but it is not well understood how variation in antioxidant levels may relate to the reproductive success or health of wild animals. We explored the relationship between circulating antioxidant concentrations and both body condition and timing of reproduction in male and female Florida Scrub‐Jays (Aphelocoma coerulescens), a cooperatively breeding passerine bird. We examined whether levels of uric acid, vitamin E, and carotenoids (all potentially important antioxidants) were linked to body condition and timing of reproduction, two measures that are directly related to reproductive success. Antioxidant concentrations were not correlated with body condition, but they were related to timing of first clutch initiation, though not always in the predicted direction. Elevated circulating levels of carotenoids were associated with delayed clutch initiation in female breeders. Relatively higher vitamin E levels in control birds were associated with earlier clutch initiation, whereas male breeders that received long‐term food supplementation had elevated levels of vitamin E and delayed reproduction. Several potential explanations for the link between elevated levels of antioxidants and delayed clutch initiation are discussed. Separate explanations for each sex include, but are not limited to, oxidative stress as a result of territory defense efforts in males, different dietary regimes due to supplementation, and mobilized plasma antioxidants in females that were coping with a stressor. J. Exp. Zool. 315:101–110, 2011. © 2010 Wiley‐Liss, Inc.
Structural components and morphogenetic mechanics of the zebrafish yolk extension, a developmental module
Authors: Virta Valerie Christine , Cooper Mark Scott
Published: November 2010

The yolk extension (YE) appears to be a novel developmental module that has been inserted into the phylotypic period of teleostean development, specifically in the order Cypriniformes. The zebrafish YE informs the study of morphogenetic movements reshaping ventral tissues because (1) this trait is easily visible, so disruptions are easy to score; (2) its ontogenesis occurs quickly; and (3) the yolk cell isolates the tissues elongating the ventrum from the rest of the embryo, serving as a three‐dimensional in vivo “tissue culture.” We determined that three histological compartments comprise the structural components of the YE: (1) the internal yolk cell; (2) the mesendodermal mantle external to the yolk cell; and (3) the external embryonic integument, consisting of an embryonic epidermis plus enveloping layer cells. These structural components interact with one another in a hierarchical manner, resulting in the morphogenesis of the elongated and tubular embryonic zebrafish ventrum as the cylindrical YE forms. Time‐lapse videomicroscopy and experimental manipulation show that the yolk mass is a cohesive, viscoelastic foam, which resists compression. Moreover, as the mesodermal mantle participates in tubulation of the posterior trunk, Kupffer's Vesicle, the organ of laterality in teleosts, separates from the posterior pole of the yolk syncytial layer. Additionally, the embryonic integument becomes contractile over the posterior yolk cell, constricting the yolk mass to form the YE. These findings constitute an initial assessment of the morphogenetic mechanics underlying formation of the YE developmental module in zebrafish. J. Exp. Zool. (Mol. Dev. Evol.) 316:76–92, 2011. © 2010 Wiley‐Liss, Inc.
Evolution of developmental pattern for vertebrate dentitions: an oro‐pharyngeal specific mechanism
Authors: Fraser Gareth J. , Meredith Smith Moya
Published: November 2010

Classically the oral dentition with teeth regulated into a successional iterative order was thought to have evolved from the superficial skin denticles migrating into the mouth at the stage when jaws evolved. The canonical view is that the initiation of a pattern order for teeth at the mouth margin required development of a sub‐epithelial, permanent dental lamina. This provided regulated tooth production in advance of functional need, as exemplified by the Chondrichthyes. It had been assumed that teeth in the Osteichthyes form in this way as in tetrapods. However, this has been shown not to be true for many osteichthyan fish where a dental lamina of this kind does not form, but teeth are regularly patterned and replaced. We question the evolutionary origin of pattern information for the dentition driven by new morphological data on spatial initiation of skin denticles in the catshark. We review recent gene expression data for spatio‐temporal order of tooth initiation for Scyliorhinus canicula, selected teleosts in both oral and pharyngeal dentitions, and Neoceratodus forsteri. Although denticles in the chondrichthyan skin appear not to follow a strict pattern order in space and time, tooth replacement in a functional system occurs with precise timing and spatial order. We suggest that the patterning mechanism observed for the oral and pharyngeal dentition is unique to the vertebrate oro‐pharynx and independent of the skin system. Therefore, co‐option of a successional iterative pattern occurred in evolution not from the skin but from mechanisms existing in the oro‐pharynx of now extinct agnathans. J. Exp. Zool. (Mol. Dev. Evol.) 316:99–112, 2011. © 2010 Wiley‐Liss, Inc.
Antibody‐directed lentiviral gene transduction in early immature hematopoietic progenitor cells
Authors: Zhang Xia , Roth Monica J.
Published: November 2010

Background

The specific and efficient transduction of retroviral particles remains problematic for in vivo and ex vivo gene therapy studies, where the targeting cell population is a heterogeneous bulk population.

Methods

Pseudotyping lentiviral particles with Sindbis virus envelope (Env) proteins modified with an immunoglobulin Fc‐binding domain presents a method of selecting cells within a mixed population through antibody (Ab)‐mediated targeting. Conditions were tested for targeted lentiviral gene delivery to hematopoietic progenitor cells via Ab‐conjugated envelopes independent of CD34.

Results

Conditions to optimize the efficiency of gene delivery were established using the ABCG2 multidrug resistance protein, associated with stem cell phenotypes, as the cell surface target. By varying the proportion of ABCG2 expressing cells in a population, ABCG2‐targeted gene delivery was detectable by flow cytometry when ABCG2+ cells comprised greater than 5% of the population. Conditions that increased the efficiency of gene transfer, including cholesterol independent Env proteins and pH, increased nonspecific gene delivery. The feasibility of this cell‐Ab‐virus sandwich system in targeting transduction in a mixed population was tested in cells derived from human cord blood (CB). Conjugation of viral particles with anti‐CD133 and anti‐ABCG2 hematopoietic stem cell‐associated Ab resulted in targeted gene transfer into early immature hematopoietic progenitor cells. Enhancement was found when the hematopoietic progenitor cells were enriched from CB cells via the depletion of lineage+ committed cells.

Conclusions

Gene transfer to lineage− early immature hematopoietic progenitors from human umbilical CB was obtained using CD133, ABCG2 or HLA‐1 antibodies conjugated to lentiviruses pseudotyped with modified Sindbis viral Env proteins. Copyright © 2010 John Wiley & Sons, Ltd.
Novel tumour‐specific promoters for transcriptional targeting of hepatocellular carcinoma by herpes simplex virus vectors
Authors: Foka Pelagia , Pourchet Aldo , Hernandez‐Alcoceba Ruben , Doumba Polyxeni P. , Pissas George , Kouvatsis Vlassis , Dalagiorgou Georgia , Kazazi Dorothea , Marconi Peggy , Foschini Mariagiovanna , Manservigi Roberto , Konstadoulakis Manousos M. , Koskinas John , Epstein Alberto L. , Mavromara Penelope
Published: November 2010

Background

Hepatocellular carcinoma (HCC) is a cancer of poor prognosis, with limited success in patient treatment, which it makes an excellent target for gene therapy and viral oncolysis. Accordingly, herpes virus simplex type‐1 (HSV‐1) is one of the most promising viral platforms for transferring therapeutic genes and the development of oncolytic vectors that can target, multiply in, and eradicate hepatoma cells via their lytic cycle. Enhanced efficacy and specificity of HSV‐1‐based vectors towards HCC may be achieved by using HCC‐specific gene promoters to drive selective viral gene expression and accomplish conditional replication and/or to control the expression of therapeutic genes. However, careful verification of promoter function in the context of the replication‐competent HSV‐1 vectors is required. The present study aimed to identify novel HCC‐specific promoters that could efficiently direct transgene expression to HCC cells and maintain their activity during active viral replication.

Methods

Publicly available microarray data from human HCC biopsies were analysed in order to detect novel candidate genes induced primarily in HCC compared to normal liver. HCC specificity and promoter activity were evaluated by RT‐PCR and chromatin immunoprecipitation. Additionally, transcriptional activity of promoters was further evaluated in the context of HSV‐1 genome, using luciferase assays in cultured cells and animal models.

Results

Eight HCC‐specific genes were characterised in this study: Angiopoietin‐like‐3, Cytochrome P450, family 2, subfamily C, polypeptide 8, Vitronectin, Alcohol dehydrogenase 6‐class V, Apolipoprotein B, Fibrinogen beta chain, Inter‐alpha‐globulin‐inhibitor H3 and Inter‐alpha‐globulin‐inhibitor H1. Specific HCC expression and active gene transcription were confirmed in human liver and non‐liver cell lines and further evaluated in primary neoplastic cells from hepatitis C and B virus (HCV‐ and HBV)‐associated HCC patients. High promoter activity and specificity in the presence of HSV‐1 infection and from within the viral genome, was validated, both in vitro and in vivo.

Conclusions

We identified and experimentally characterized novel hepatoma‐specific promoters, which were valuable for cancer‐specific gene therapy, using HSV‐1 vectors. Copyright © 2010 John Wiley & Sons, Ltd.
Retinal release from opsin in molecular dynamics simulations
Authors: Wang Ting , Duan Yong
Published: November 2010

The crystal structures of opsin in the ligand‐free and the G‐protein‐interacting states showed two inter‐helical openings between transmembrane (TM) helices TM1 and TM7 and between TM5 and TM6 near the extracellular side that were thought to serve as the retinal uptake and release gates. However, it is unclear which opening is for 11‐cis‐retinal uptake or all‐trans‐retinal release although speculations have been proposed based on the structural features of opsin and retinal. In this work, we simulated the exit process of all‐trans‐retinal from the ligand‐free opsin structure by the classical molecular dynamics (MD) and random acceleration molecular dynamics (RAMD). In the 64 ns classical MD simulation, retinal remained in the receptor but moved significantly toward the TM5‐TM6 opening and almost inserted into the opening after 50 ns. Complete exit was observed in 114 out of 160 RAMD trajectories with the TM5‐TM6 opening being the predominant egress gate while egress from the TM1‐TM7 opening was observed in only a few trajectories when relatively large acceleration was applied and large structural alteration of the protein resulted. These results suggest that photolyzed all‐trans‐retinal is likely released through the TM5‐TM6 opening. Based on the unidirectional mechanism of retinal exchange suggested by experiment, we speculate that the TM1‐TM7 opening serves as the 11‐cis‐retinal uptake gate. The spatial occupancy maps of retinal computed from the 160 RAMD trajectories further indicated that retinal experienced significant interactions with the receptor during the exit process. The implications of these findings for disease mechanisms of rhodopsin mutants are discussed. Copyright © 2010 John Wiley & Sons, Ltd.
The combined effects of salinity and nitrogen forms on Catharanthus roseus: The role of internal ammonium and free amino acids during salt stress
Authors: Zhonghua Tang , Yanju Liu , Xiaorui Guo , Yuangang Zu
Published: November 2010

Catharanthus roseus is widely cultivated at the seaside of Hainan island of China for production of vinblastine with anticancer activity. Improving growth of this plant and vinblastine content under saline conditions is one of the agronomic challenges. In this study, we compare the responses of C. rosesus upon nitrate (N1) or ammonium nitrate (N2) nutrition to salinity. Biomass accumulation, reproductive growth, photosynthetic gas exchange, and the concentrations of soluble sugars (SS), free amino acids (FAA), ammonium (NH$ _4^+ $), sodium (Na+), and vinblastine were determined during 3 weeks of treatment in N1‐control, N1‐salt, N2‐control, and N2‐salt plants. The retarded growth caused by salt stress was largely ameliorated by the N2 nitrogen form. One of the reasons for this improved salt resistance in N2‐salt plants was related to the competitive uptake of NH$ _4^+ $ and Na+. The N2‐salt plants displayed a more rapid response to salinity, leading to decreased transpiration rate, well‐kept water relations, and reduced uptake of Na+. The N2‐control plants rapidly increased the concentrations of soluble sugars and free amino acids, such as sucrose, glucose, proline, and threonine in the first week. These compounds may act as compatible solutes to adjust osmotic stress and retain ion homeostasis in salt‐stressed plants. The increased FAA was found to be at the expense of glutamate accumulation, and the activities of nitrogen assimilation enzymes were tightly linked with this process. The medical alkaloid vinblastine in C. roseus was significantly increased in N2‐salt plants in the first week and in N1‐salt ones in the third week compared to their controls. It is concluded that the supplied nitrogen regime modified salinity‐induced vinblastine production in a time‐dependent way, and this process was tightly related to NH$ _4^+ $ status.
Timing and duration of growth hiatuses in mid Holocene massive Porites corals from the northern South China Sea
Authors: Yu Ke‐Fu , Zhao Jian‐Xin , Lawrence Michael G. , Feng Yuexing
Published: November 2010

Growth hiatuses in massive corals are usually indicative of past ecological or environmental stresses. Among 37 fossil Porites colonies surveyed from the reef flat of Dadonghai fringing reef at Sanya, Hainan Island, northern South China Sea, seven of them were found to show clear evidence of past mortality, representing a population of ∼19%. Among these samples, two of them (SYO‐13 and SYO‐28) display clear growth hiatuses reflecting mortality followed by subsequent recruitment, and five others exhibit a well‐preserved mortality surface and no subsequent recruitment. The growth hiatuses were dated using high‐precision thermal ionisation mass spectrometry U‐series techniques. The age results suggest all the dated corals formed and died in the mid Holocene. Multiple dates below the growth hiatuses suggest that SYO‐13 and SYO‐28 died at 6298 ± 11 and 6929 ± 19 a BP (i.e. years before AD 1950), respectively. Multiple dates above the growth hiatuses indicate that growth in SYO‐13 and SYO‐28 resumed at 6257 ± 14 and 6898 ± 20 a BP, respectively. The calculated durations of growth hiatuses are therefore 41 ± 18 a for SYO‐13 and 31 ± 28 a for SYO‐28, respectively, implying growth resumed within decades after the mortality events. U‐series dating of four other samples with dead heads suggests that they died at 6035 ± 53, 6059 ± 23, 6127 ± 22 and 6474 ± 24 a BP, respectively. In addition, using solution inductively coupled plasma mass spectrometry (ICP‐MS), monthly resolution Sr/Ca and Mg/Ca ratios were determined for the annual growth bands below and above the growth hiatuses for three of the dated samples. The Sr/Ca and Mg/Ca profiles indicate that the three corals probably died in different seasons (from spring to autumn), and the mortality appears to be unrelated to anomalous sea surface temperature‐induced bleaching. Copyright © 2010 John Wiley & Sons, Ltd.
Evidence of marked glycogen variations in the characteristic Raman signatures of human embryonic stem cells
Authors: Konorov Stanislav O. , Schulze H. Georg , Piret James M. , Turner Robin F. B. , Blades Michael W.
Published: November 2010

Human embryonic stem cells (hESCs) have typical Raman signatures, but specific factors that contribute to variations in these signatures have not been reported to date. Furthermore, variations due to the passaging that is necessary for hESC culture maintenance could potentially distort these signatures. It is therefore important to characterize the impact of these culture manipulations on the Raman spectra to gain a better understanding of the origins and nature of their variations. Here we report on the Raman microspectroscopy of hESCs samples from maintenance cultures, complemented with periodic acid Schiff (PAS, carbohydrates) and 4′‐6‐diamidino‐2‐phenlyindol (DAPI, nuclei) staining. The component predominantly responsible for variations between spectra was spectrally identified as glycogen. Variations in the Raman map of the 480 cm−1 glycogen marker band corresponded with those of a PAS stain of the same sample area. The 785‐nm Raman microspectra of hESC cultures examined daily after passaging showed that the same nonrandom spectral variances occurred at all time points after passaging. The pattern of these variances was identified as being due to glycogen spectral components. Our results help validate the previously observed spectral signatures of hESCs and further delineate and characterize the variations that can be expected in these signatures under normal maintenance culture conditions, and aid distinguishing them from those corresponding to differentiation, thus providing a benchmark for future studies. Copyright © 2010 John Wiley & Sons, Ltd.
Is the need for an arterial resection a contraindication to pancreatic resection for locally advanced pancreatic adenocarcinoma? a case‐matched controlled study
Authors: Bachellier Philippe , Rosso Edoardo , Lucescu Ionut , Oussoultzoglou Elie , Tracey Jacky , Pessaux Patrick , Ferreira Nelio , Jaeck Daniel
Published: November 2010

Background and Objectives

Arterial resection (AR) has traditionally been considered as a contraindication to pancreatic resection for locally advanced pancreatic adenocarcinoma. The objective was to evaluate if pancreatic resection with AR was worthwhile.

Methods

Between January 1990 and December 2008 the records of 26 consecutive patients who underwent a curative‐intent pancreatic resection for adenocarcinoma of the pancreas with AR (AR+ group) were matched 1:1 to those of the whole series of pancreatic resection performed in our institution. The final study population (n = 52) included two groups of patients: the study group AR+ = 26 and the control group AR− = 26.

Results

The 1‐ and 3‐year survival rates were similar in the two groups (65.9% and 22.1%, median 17 months for the group AR + , versus 50.0% and 17.6%, median 12 months, for the group AR−; P = 0.581). The multivariate analysis showed that: arterial wall invasion at the site of AR, the total number of resected lymph nodes of ≤15, and perineural invasion were independent prognostic factors for survival.

Conclusion

Pancreatic resections with AR for adenocarcinoma allowed to obtain a 3‐survival rate similar to that of a matched group of patients not requiring AR. J. Surg. Oncol. 2011;103:75–84. © 2010 Wiley‐Liss, Inc.
Methanol exposure does not lead to accumulation of oxidative DNA damage in bone marrow and spleen of mice, rabbits or primates
Authors: McCallum Gordon P. , Siu Michelle , Ondovcik Stephanie L. , Sweeting J. Nicole , Wells Peter G.
Published: November 2010

Genotoxicity tests indicate methanol (MeOH) is not mutagenic, but a rodent study has suggested carcinogenic potential, which could result from free radical‐initiated oxidative DNA damage. To investigate this possibility we treated male CD‐1 mice, New Zealand white rabbits, and cynomolgus monkeys with MeOH (2.0 g/kg ip) and assessed tissue oxidative DNA damage 6 h post‐dose, measured as 8‐hydroxy‐2′‐deoxyguanosine (8‐oxodG). We found no MeOH‐dependent increases in 8‐oxodG in bone marrow or spleen of any species. Chronic treatment of CD‐1 mice with MeOH (2.0 g/kg ip) daily for 15 d also did not increase 8‐oxodG levels in these organs. Further studies in the DNA repair deficient oxoguanine glycosylase 1 (Ogg1) knockout (KO) mice supported these findings. Fibroblasts fromOgg1KO mice accumulated 8‐oxodG following acute exposure to the renal carcinogen potassium bromate (KBrO3; 2.0 mM) but did not accumulate 8‐oxodG following exposure to 125 mM MeOH 6 h post‐treatment.Ogg1KO mice accumulated 8‐oxodG in bone marrow and spleen with age but not following exposure to MeOH. In addition, free radical‐mediated hydroxynonenal‐histidine protein adducts were not enhanced by MeOH in primate bone marrow or spleen, or in rabbit bone marrow or mouse spleen, although modest increases were observed in rabbit spleen and mouse bone marrow. Taken together these observations suggest that MeOH exposure does not promote the accumulation of oxidative DNA damage in bone marrow and spleen, and it is unlikely that human environmental exposure to MeOH would lead to lymphomas via this mechanism. Mol. Carcinog. © 2010 Wiley‐Liss, Inc.
Ah receptor antagonism inhibits constitutive and cytokine inducible IL6 production in head and neck tumor cell lines
Authors: DiNatale Brett C. , Schroeder Jennifer C. , Perdew Gary H.
Published: November 2010

There is increasing evidence that the aryl hydrocarbon receptor (AHR) plays a role in tumor progression through numerous mechanisms. We have previously shown that, in certain cancer cell lines that are typically nonresponsive to cytokine‐mediated IL6 induction, activation of the AHR with the agonist 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin derepresses the IL6 promoter and allows for synergistic induction following IL1β treatment. The mechanism by which this occurs involves liganded AHR binding upstream from the transcription start site and dismissing HDAC‐containing corepressor complexes, giving rise to a promoter structure that is more amenable to NF‐κB activation. This fact, combined with observations of multiple endogenously produced chemicals activating the AHR, led us to study its role in basal expression among high cytokine‐producing cancer cell lines. The current study provides evidence that several head and neck squamous cell carcinoma cell lines have a level of constitutively bound AHR at the IL6 promoter, allowing for higher basal and readily inducible IL6 transcription. Treatment of these cell lines with an AHR antagonist led to dismissal of the AHR from the IL6 promoter and recruitment of corepressor complexes, thus diminishing cytokine expression. Head and neck squamous cell carcinoma is typically a high cytokine‐producing tumor type, with IL6 expression levels correlating with disease aggressiveness. For this reason, AHR antagonist treatment could represent a novel adjuvant therapy for patients, lowering pro‐growth and antiapoptotic signaling with minimal systemic side effects. Mol. Carcinog. © 2010 Wiley‐Liss, Inc.
Critical evaluation of folate data in European and international databases: Recommendations for standardization in international nutritional studies
Authors: Bouckaert Kimberley P. , Slimani Nadia , Nicolas Geneviève , Vignat Jérôme , Wright Anthony J. A. , Roe Mark , Witthöft Cornelia M. , Finglas Paul M.
Published: November 2010

Scope: The objective was to perform an inventory and critical evaluation of folate data in selected European and international databases. The ultimate aim was to establish guidelines for compiling standardized folate databases for international nutritional studies.

Methods and results: An ad hoc questionnaire was prepared to critically compare and evaluate folate data completeness, quantification, terminologies, and documentation of 18 European and international databases, and national fortification regulations. Selected countries participated in the European Prospective Investigation into Nutrition and Cancer project and European Food Information Resource Network (EuroFIR). Folate completeness was generally high. “Total folate” was the most common terminology and microbiological assay was the most frequently reported quantification method. There is a lack of comparability within and between databases due to a lack of value documentation, the use of generic or non‐appropriate terminologies, folate value conversions, and/or lack of identification of synthetic folic acid.

Conclusion: Full value documentation and the use of EuroFIR component identifiers and/or INFOODS tagnames for total folate (“FOL”) and synthetic folic acid (“FOLAC”), with the additional use of individual folates, will increase comparability between databases. For now, the standardized microbiological assay for total folate and HPLC for synthetic folic acid are the recommended quantification methods.