bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational protein design with explicit consideration of surface hydrophobic patches
Authors: Jacak Ron , Leaver‐Fay Andrew , Kuhlman Brian 
Published: November 2011

AbstractDe novo protein design requires the identification of amino‐acid sequences that favor the target‐folded conformation and are soluble in water. One strategy for promoting solubility is to disallow hydrophobic residues on the protein surface during design. However, naturally occurring proteins often have hydrophobic amino acids on their surface that contribute to protein stability via the partial burial of hydrophobic surface area or play a key role in the formation of protein–protein interactions. A less restrictive approach for surface design that is used by the modeling program Rosetta is to parameterize the energy function so that the number of hydrophobic amino acids designed on the protein surface is similar to what is observed in naturally occurring monomeric proteins. Previous studies with Rosetta have shown that this limits surface hydrophobics to the naturally occurring frequency (∼ 28%), but that it does not prevent the formation of hydrophobic patches that are considerably larger than those observed in naturally occurring proteins. Here, we describe a new score term that explicitly detects and penalizes the formation of hydrophobic patches during computational protein design. With the new term, we are able to design protein surfaces that include hydrophobic amino acids at naturally occurring frequencies, but do not have large hydrophobic patches. By adjusting the strength of the new score term, the emphasis of surface redesigns can be switched between maintaining solubility and maximizing folding free energy. Proteins 2011. © 2012 Wiley Periodicals, Inc.
Optimal sample sizes for phase II clinical trials and pilot studies
Authors: Stallard Nigel 
Published: November 2011

Methodology for sample size calculation for phase III clinical trials is well established and widely used. In contrast, for earlier phase clinical trials or pilot studies, although there is an acceptance that the methods used for phase III trials are not appropriate, there is little consensus over methods that should be used. This paper explores this problem from a Bayesian decision‐theoretic perspective. The aim is to obtain sample sizes that would be appropriate for studies funded by a large funder such as a public sector body or major pharmaceutical company. The sample sizes obtained are optimal in that they minimise the average number of patients required per successfully identified effective therapy or equivalently maximise the number of effective therapies successfully identified over a long period.It is indicated that the number of patients included in a phase II clinical trial should be approximately 0.03 times that planned to be included in the phase III study. This is similar to that proposed by other researchers in this area, though rather smaller than actually used for many phase II trials. Copyright © 2011 John Wiley & Sons, Ltd.
Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential
Authors: Liu Yang , Jiang Xiaohua , Zhang Xiaohu , Chen Rui , Sun Tingting , Fok Kin Lam , Dong Jianda , Tsang Lai Ling , Yi Shaoqiong , Ruan Yechun , Guo Jinghui , Yu Mei Kuen , Tian Yuemin , Chung Yiu Wa , Yang Mo , Xu Wenming , Chung Chin Man , Li Tingyu , Chan Hsiao Chang 
Published: November 2011

AbstractStem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low in vivo survival and differentiation potential of the transplanted cells limits their overall effectiveness and thus clinical usage. Here we show that, after in vitro induction of neuronal differentiation and dedifferentiation, on withdrawal of extrinsic factors, mesenchymal stem cells (MSCs) derived from bone marrow, which have already committed to neuronal lineage, revert to a primitive cell population (dedifferentiated MSCs) retaining stem cell characteristics but exhibiting a reprogrammed phenotype distinct from their original counterparts. Of therapeutic interest, the dedifferentiated MSCs exhibited enhanced cell survival and higher efficacy in neuronal differentiation compared to unmanipulated MSCs both in vitro and in vivo, with significantly improved cognition function in a neonatal hypoxic–ischemic brain damage rat model. Increased expression of bcl-2 family proteins and microRNA-34a appears to be the important mechanism giving rise to this previously undefined stem cell population that may provide a novel treatment strategy with improved therapeutic efficacy.
Behavioral dimensions of climate change: drivers, responses, barriers, and interventions
Authors: Gifford Robert , Kormos Christine , McIntyre Amanda 
Published: November 2011

AbstractThis overview describes the anthropogenic drivers of global climate change, reviews the behavioral and psychological responses to its impacts (including barriers to behavior change), considers behavior‐focused intervention strategies, and suggests future directions for research. In doing so, it demonstrates why and how behavioral science is crucial for confronting the complex challenges posed by global climate change. The human dimensions of climate change are discussed, followed by descriptions of key theoretical models for explaining and predicting climate‐relevant behavior, issues and distinctions in studying human behavior in response to global climate change, an account of psychological (as opposed to structural) adaptation and its behavioral sequelae, the many psychological barriers to behavior change in this context, and behavior‐focused intervention strategies. The overview concludes with suggestions for researchers interested in advancing knowledge about behavior change and psychological responses to climate change. When knowledge about human behavior, cognitions, and psychological adaptation is integrated with that produced by researchers in related social and natural science disciplines, the result will facilitate solutions to this massive shared challenge.WIREs Clim Change2011, 2:801–827. doi: 10.1002/wcc.143This article is categorized under:Perceptions, Behavior, and Communication of Climate Change > Behavior Change and Responses
Modeling and performance evaluation of Advanced Diffusion with Classified Data in vehicular sensor networks
Authors: Haddadou Nadia , Rachedi Abderrezak , Ghamri‐Doudane Yacine 
Published: November 2011

ABSTRACTIn this paper, we propose a newly distributed protocol called Advanced Diffusion of Classified Data (ADCD) to manage information harvesting and distribution in vehicular sensor networks. ADCD aims at reducing the generated overhead, avoiding network congestions as well as long latency to deliver the harvested information. The concept of ADCD is based on the characterization of sensed information (i.e., based on its importance, location, and time of collection) and the diffusion of this information accordingly. Furthermore, ADCD uses an adaptive broadcasting strategy to avoid overwhelming users with messages in which they have no interest. Also, we propose in this paper a new probabilistic model for ADCD based on Markov chain. This one aims to optimally tune the parameters of ADCD, such as the optimal number of broadcaster nodes. The analytical and simulation results based on different metrics, such as the overhead, the delivery ratio, the probability of a complete transmission, and the minimal number of hops, are presented. These results illustrate that ADCD allows mitigating the information redundancy and its delivery with an adequate latency while making the reception of interesting data for the drivers (related to their location) more adapted. Moreover, the ADCD protocol reduces the overhead by 90% compared with the classical broadcast and an adapted version of MobEyes. The ADCD overhead is kept stable whatever the vehicular density. Copyright © 2011 John Wiley & Sons, Ltd.
Physics for infants: characterizing the origins of knowledge about objects, substances, and number
Authors: Hespos Susan J. , vanMarle Kristy 
Published: November 2011

AbstractAdults possess a great deal of knowledge about how objects behave and interact in our every day environment, yet several puzzles remain unsolved regarding how we manage this ubiquitous skill. The notion of intuitive physics has been a central focus of research on cognitive development in infancy. This article focuses on the origins of knowledge about objects, substances, and number concepts in infancy. The article reviews common themes of solidity, continuity, cohesion, and property changes as they have been studied with regard to infants' knowledge about objects and more recently with regard to infants' knowledge about substances. In addition, we review how object and substance knowledge interfaces with number knowledge systems. The evidence supports the view that certain core principles about these domains are present as early as we can test for them and the nature of the underlying representation is best characterized as primitive initial concepts that are elaborated and refined through learning and experience. WIREs Cogn Sci 2012, 3:19–27. doi: 10.1002/wcs.157This article is categorized under:

Psychology > Development and Aging
Validations and improvements of airfoil trailing‐edge noise prediction models using detailed experimental data
Authors: Kamruzzaman M. , Lutz Th. , Würz W. , Shen W. Z. , Zhu W. J. , Hansen M. O. L. , Bertagnolio F. , Madsen H. Aa. 
Published: November 2011

ABSTRACTThis paper describes an extensive assessment and a step by step validation of different turbulent boundary‐layer trailing‐edge noise prediction schemes developed within the European Union funded wind energy project UpWind. To validate prediction models, measurements of turbulent boundary‐layer properties such as two‐point turbulent velocity correlations, the spectra of the associated wall pressure fluctuations and the emitted trailing‐edge far‐field noise were performed in the laminar wind tunnel of the Institute of Aerodynamics and Gas Dynamics, University of Stuttgart. The measurements were carried out for a NACA 643‐418 airfoil, at Re  =  2.5 ×106, angle of attack of −6° to 6°. Numerical results of different prediction schemes are extensively validated and discussed elaborately. The investigations on the TNO‐Blake noise prediction model show that the numerical wall pressure fluctuation and far‐field radiated noise models capture well the measured peak amplitude level as well as the peak position if the turbulence noise source parameters are estimated properly including turbulence anisotropy effects. Large eddy simulation based computational aeroacoustic computations show good agreements with measurements in the frequency region higher than 1 kHz, whereas they over‐predict the sound pressure level in the low‐frequency region. Copyright © 2011 John Wiley & Sons, Ltd.
Delivering a Pharmacogenetic Service: Is There a Role for Genetic Counselors?
Authors: Callard Alice , Newman William , Payne Katherine 
Published: November 2011

AbstractPharmacogenetics, the use of genetic information to direct safer and or more effective prescription of medication, is a relatively new clinical concept. Currently, there is no consensus regarding which healthcare professionals should deliver pharmacogenetic services. This study explored the opinions of genetic counselors about their potential role in delivering pharmacogenetic services. Semi‐structured face‐to‐face interviews were conducted with 14 genetic counselors. Four vignettes describing pharmacogenetic testing scenarios were used to elicit views on specific clinical applications. Data were analysed using the constant comparative method. Opinions varied, but the majority of interviewees suggested that genetic counselors could have a role. However, participants suggested that additional training would be needed due to counselors’ limited knowledge of pharmacogenetics. Employing genetic counselors in a specialist role within a multidisciplinary clinic was suggested as a model of service delivery. Service models developed for pharmacogenetic testing may need to be adapted according to the issues presented by each type of test.
Presenilin enhancer‐2 gene: Identification of a novel promoter mutation in a patient with early‐onset familial Alzheimer's disease
Authors: Andreoli Virginia , Trecroci Francesca , La Russa Antonella , Cittadella Rita , Liguori Maria , Spadafora Patrizia , Caracciolo Manuela , Di Palma Gemma , Colica Carmela , Gambardella Antonio , Quattrone Aldo 
Published: November 2011

Abstractγ‐Secretase proteins complex cleaves the amyloid precursor protein (APP) to generate amyloid‐β (Aβ) peptides. Considerable evidence suggests that alterations in genes encoding these proteins exert their influence on the pathogenesis of familial Alzheimer's disease (FAD). Presenilin enhancer‐2 gene (PEN‐2) is a necessary component of the γ‐Secretase complex. Recently, it has been shown that PEN‐2 mutations could be involved in Alzheimer's disease (AD). We performed a mutational screening of all PEN‐2 coding and promoter regions in a FAD cohort derived from Southern Italy. Four hundred and fifty‐two subjects (FAD: 97; Controls: 355) were recruited for this study. We identified for the first time in a key region necessary for the promoter activity a novel 3 bp deletion in a subject with early‐FAD. Our genetic data demonstrate that the mutant allele may influence the transcriptional activity of the PEN‐2 gene. Although the effective role of the PEN‐2 promoter deletion in AD is not entirely clear, these findings might lead to more studies on its functional and genetic role.
Is Alzheimer's disease amyloidosis the result of a repair mechanism gone astray?
Authors: Kokjohn Tyler A. , Maarouf Chera L. , Roher Alex E. 
Published: November 2011

AbstractHere, we synthesize several lines of evidence supporting the hypothesis that at least one function of amyloid‐β is to serve as a part of the acute response to brain hemodynamic disturbances intended to seal vascular leakage. Given the resilient and adhesive physicochemical properties of amyloid, an abluminal hemostatic repair system might be highly advantageous, if deployed on a limited and short‐term basis, in young individuals. However, in the aged, inevitable cardiovascular dysfunction combined with brain microvascular lesions may yield global chronic hypoperfusion that may lead to continuous amyloid deposition and consequential negative effects on neuronal viability. A large body of experimental evidence supports the hypothesis of an amyloid‐β rescue function gone astray. Preventing or inducing the removal of amyloid in Alzheimer's disease (AD) has been simultaneously successful and disappointing. Amyloid deposits clearly play major roles in AD, but they may not represent the preeminent factor in dementia pathogenesis. Successful application of AD preventative approaches may hinge on an accurate and comprehensive view of comorbidities, including cardiovascular disease, diabetes, and head trauma.
Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: A consensus paper from the Alzheimer's Biomarkers Standardization Initiative
Authors: Vanderstichele Hugo , Bibl Mirko , Engelborghs Sebastiaan , Le Bastard Nathalie , Lewczuk Piotr , Molinuevo Jose Luis , Parnetti Lucilla , Perret‐Liaudet Armand , Shaw Leslie M. , Teunissen Charlotte , Wouters Dirk , Blennow Kaj 
Published: November 2011

AbstractBackgroundNumerous studies show that the cerebrospinal fluid biomarkers total tau (T‐tau), tau phosphorylated at threonine 181 (P‐tau181P), and amyloid‐β (1‐42) (Aβ1–42) have high diagnostic accuracy for Alzheimer's disease. Variability in concentrations for Aβ1–42, T‐tau, and P‐tau181P drives the need for standardization.MethodsKey issues were identified and discussed before the first meeting of the members of the Alzheimer's Biomarkers Standardization Initiative (ABSI). Subsequent ABSI consensus meetings focused on preanalytical issues.ResultsConsensus was reached on preanalytical issues such as the effects of fasting, different tube types, centrifugation, time and temperature before storage, storage temperature, repeated freeze/thaw cycles, and length of storage on concentrations of Aβ1–42, T‐tau, and P‐tau181P in cerebrospinal fluid.ConclusionsThe consensus reached on preanalytical issues and the recommendations put forward during the ABSI consensus meetings are presented in this paper.
Countrywide strategic plans on Alzheimer's disease: Developing the framework for the international battle against Alzheimer's disease
Authors: Rosow Kyra , Holzapfel Andrew , Karlawish Jason H. , Baumgart Matthew , Bain Lisa J. , Khachaturian Ara S. 
Published: November 2011

AbstractAs the world's population ages, countries must prepare for the significant impact Alzheimer's disease will have on their health systems, their economies, and their citizens. In anticipation of major global demographic changes, many countries in the G‐20 since 2000 have begun to develop and enact plans to address Alzheimer's disease as a national priority. However, even with nearly half of these participating countries having plans in place, there has been little research done to quantify the value of enacting a countrywide plan on this disease. In this review, we summarize recent national plans (from the year 2000 and beyond) and any results stemming from their respective recommendations and activities.
Designing e‐government services: Key service attributes and citizens’ preference structures
Authors: Venkatesh Viswanath , Chan Frank K.Y. , Thong James Y.L. 
Published: November 2011

AbstractAdvances in Internet technologies have led to the popularity of technology‐based self‐services, with the design of such services becoming increasingly important. Using technology‐based services in the public sector as the setting, we identified the key service attributes driving adoption and use of transactional e‐government services, and citizens’ preference structures across these attributes. After identifying four key attributes, i.e., usability, computer resource requirement, technical support provision and security provision, we conducted a Web‐based survey and a conjoint experiment among 2465 citizens. In a two‐stage Web‐based survey, citizens reported their perceptions about a smartcard technology for transactional e‐government services before use, and their use and satisfaction 4 months later. Results showed that the key attributes (noted above) influenced citizens’ intentions, subsequent use and satisfaction. In the conjoint experiment, citizens reported their preferences for key service attributes for two transactional e‐government services. Further, a cluster analysis uncovered four distinct citizen segments, i.e., balanced, usability‐focused, risk‐conscious and resource‐conservative, that can inform efforts in designing e‐government services. A post hoc analysis confirmed the appropriateness of the market segmentation in understanding citizens’ adoption and use of transactional e‐government services.
Enhancing effects of manufacturing flexibility through operational absorptive capacity and operational ambidexterity
Authors: Patel Pankaj C. , Terjesen Siri , Li Dan 
Published: November 2011

AbstractA large body of research investigates how manufacturing flexibility in uncertain environments leads to firm performance, with mixed results. The mixed findings could be due to differences across firms in terms of the capabilities to acquire, assimilate, and transform knowledge and to simultaneously pursue both the exploitation of existing operational capabilities and the exploration for new operational capabilities. Building on the literature that suggests that manufacturing flexibility mediates the relationship between environmental uncertainty and firm performance, we explore the applicability of two organizational learning contingencies to the operations environment: operational absorptive capability and operational ambidexterity. Absorptive capacity enables the recognition and assimilation of new knowledge. Ambidexterity determines whether this knowledge will be applied for both exploration and exploitation. Using a sample of 852 manufacturing firms, we find that environmental uncertainty affects firm performance directly and indirectly through manufacturing flexibility. Furthermore, both operational absorptive capacity and operational ambidexterity moderate the relationship between environmental uncertainty and manufacturing flexibility and the relationship between manufacturing flexibility and firm performance. Theoretical and practical implications are discussed.
Rayleigh–Taylor mixing in an otherwise stable stratification
Authors: Lawrie Andrew G. W. , Dalziel Stuart B. 
Published: November 2011

AbstractWe seek to understand the distribution of irreversible energy conversions (mixing efficiency) between quiescent initial and final states in a miscible Rayleigh–Taylor driven system. The configuration we examine is a Rayleigh–Taylor unstable interface sitting between stably stratified layers with linear density profiles above and below. Our experiments in brine solution measure vertical profiles of density before and after the unstable interface is allowed to relax to a stable state. Our analysis suggests that less than half the initially available energy is irreversibly released as heat due to viscous dissipation, while more than half irreversibly changes the probability density function of the density field by scalar diffusion and therefore remains as potential energy, but in a less useful form. While similar distributions are observed in Rayleigh–Taylor driven mixing flows between homogeneous layers, our new configuration admits energetically consistent end-state density profiles that span all possible mixing efficiencies, ranging from all available energy being expended as dissipation, to none. We present experiments that show that the fluid relaxes to a state with a significantly lower mixing efficiency than the value for ideal mixing in this configuration, and deduce that this mixing efficiency more accurately characterizes Rayleigh–Taylor driven mixing than previous measurements. We argue that the physical mechanisms intrinsic to Rayleigh–Taylor instability are optimal conditions for mixing, and speculate that we have observed an upper bound to fluid mixing in general.
Global stability of the two-dimensional flow over a backward-facing step
Authors: Lanzerstorfer Daniel , Kuhlmann Hendrik C. 
Published: November 2011

AbstractThe two-dimensional, incompressible flow over a backward-facing step is considered for a systematic variation of the geometry covering expansion ratios (step to outlet height) from 0.25 to 0.975. A global temporal linear stability analysis shows that the basic flow becomes unstable to different three-dimensional modes depending on the expansion ratio. All critical modes are essentially confined to the region behind the step extending downstream up to the reattachment point of the separated eddy. An energy-transfer analysis is applied to understand the physical nature of the instabilities. If scaled appropriately, the critical Reynolds number approaches a finite asymptotic value for very large step heights. In that case centrifugal forces destabilize the flow with respect to an oscillatory critical mode. For moderately large expansion ratios an elliptical instability mechanism is identified. If the step height is further decreased the critical mode changes from oscillatory to stationary. In addition to the elliptical mechanism, the strong shear in the layer emanating from the sharp corner of the step supports the amplification process of the critical mode. For very small step heights the basic state becomes unstable due to the lift-up mechanism, which feeds back on itself via the recirculating eddy behind the step, resulting in a steady critical mode comprising pronounced slow and fast streaks.