bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mechanism by which binding of the broadly neutralizing antibody b12 unfolds the inner domain α1 helix in an engineered HIV‐1 gp120
Authors: Emileh Ali , Abrams Cameron F. 
Published: October 2010

AbstractUsing all‐atom simulations, we examine the role of the I109C/Q428C disulfide “stitch” in altering the conformational distribution of engineered HIV‐1 gp120 core relevant for binding of the broadly neutralizing recombinant antibody b12. In particular, we propose that the I109C/Q428C stitch results in a conformational distribution favoring an unfolded inner‐domain α1‐helix upon binding of b12. Using targeted molecular dynamics, we show that folded α1 in the b12‐bound conformation of gp120 is stable both with and without the stitch, but that with folded α1, the stitch requires an orientation of the β20/β21 sheet that is sterically incompatible with b12 binding. Forcing β20/β21 into the orientation displayed by the b12‐bound conformation after folding α1 with the stitch intact results in partial unfolding of α1, whereas without the stitch, β20/β21 reorientation does not affect the conformation of α1. These findings collectively support the hypothesis that the disulfide stitch shifts the conformational distribution of α1 to the unfolded state, meaning an unfolded α1 is not a strict requirement of the b12‐bound conformational ensemble of gp120's lacking the I109C/Q428C stitch. Proteins 2011. © 2010 Wiley‐Liss, Inc.
Structural basis for branching‐enzyme activity of glycoside hydrolase family 57: Structure and stability studies of a novel branching enzyme from the hyperthermophilic archaeon Thermococcus Kodakaraensis KOD1
Authors: Santos Camila R. , Tonoli Celisa C. C. , Trindade Daniel M. , Betzel Christian , Takata Hiroki , Kuriki Takashi , Kanai Tamotsu , Imanaka Tadayuki , Arni Raghuvir K. , Murakami Mário T. 
Published: October 2010

AbstractBranching enzymes (BEs) catalyze the formation of branch points in glycogen and amylopectin by cleavage of α‐1,4 glycosidic bonds and subsequent transfer to a new α‐1,6 position. BEs generally belong to glycoside hydrolase family 13 (GH13); however TK1436, isolated from the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1, is the first GH57 member, which possesses BE activity. To date, the only BE structure that had been determined is a GH13‐type from Escherichia coli. Herein, we have determined the crystal structure of TK1436 in the native state and in complex with glucose and substrate mimetics that permitted mapping of the substrate‐binding channel and identification of key residues for glucanotransferase activity. Its structure encompasses a distorted (β/α)7‐barrel juxtaposed to a C‐terminal α‐helical domain, which also participates in the formation of the active‐site cleft. The active site comprises two acidic catalytic residues (Glu183 and Asp354), the polarizer His10, aromatic gate‐keepers (Trp28, Trp270, Trp407, and Trp416) and the residue Tyr233, which is fully conserved among GH13‐ and GH57‐type BEs. Despite TK1436 displaying a completely different fold and domain organization when compared to E. coli BE, they share the same structural determinants for BE activity. Structural comparison with AmyC, a GH57 α‐amylase devoid of BE activity, revealed that the catalytic loop involved in substrate recognition and binding, is shortened in AmyC structure and it has been addressed as a key feature for its inability for glucanotransferase activity. The oligomerization has also been pointed out as a possible determinant for functional differentiation among GH57 members. Proteins 2011. © 2010 Wiley‐Liss, Inc.
In‐cell protein NMR and protein leakage
Authors: Barnes Christopher O. , Pielak Gary J. 
Published: October 2010

AbstractIn‐cell nuclear magnetic resonance spectroscopy is a tool for studying proteins under physiologically relevant conditions. In some instances, however, protein signals from leaked protein are observed in the liquid surrounding the cells. Here, we examine the expression of four proteins in Escherichia coli. We describe the controls that should be used for in‐cell NMR experiments and show that leakage is likely when the protein being studied exceeds ∼20% of the total cellular protein. Proteins 2011. © 2010 Wiley‐Liss, Inc.
Safety vs efficacy in OA: has the pendulum swung too far?
Authors: Conaghan Philip , Davenport Graham , George Emmanuel 
Published: October 2010

AbstractOsteoarthritis is a common problem in the UK and the safety of available treatment options has been under scrutiny in recent years. As a result, the management of osteoarthritis presents a considerable healthcare challenge for primary and secondary care. In this Expert Panel Discussion, the panel considers the current management guidelines and whether patients are receiving optimal pharmacological treatment. Copyright © 2010 Wiley Interface Ltd
Feeling at home: Producing and consuming things in Karenni refugee camps on the Thai‐Burma border
Authors: Dudley Sandra 
Published: October 2010

AbstractThis article concentrates on production and consumption, particularly of food and textiles, and the contribution of such processes and bodily action to feeling at home, for the highly heterogeneous population of Karenni refugees from Burma living in camps on the Thai border. Looking at eating, weaving and wearing, I examine the implications and associations of the production and consumption processes and their similarities and differences with pre‐exile life. I argue that an investigation into sensory aspects of such issues can illuminate how it feels to be a refugee, in a physical sense: to be out of one's familiar place and ecology, seeking actively to bring about a sense of being ‘at home’ in the exiled context of a border camp. Beingdisplaced inevitably alters forced migrants' connections with the physical world of places, objects and other people of which they are a part. To focus on this aspect of forced migration, rather than following the more usual emphases on causes, protection and assistance, or psychosocial impacts, facilitates exploration of the fundamentally cultural processes through which refugees make meaning out of the rupture they have experienced. It is an approach that demonstrates local agency and makes it clear that refugees are not passive victims, but active agents working hard to make the best of their circumstances. For the Karenni as for other displaced and non‐displaced peoples alike, an important part of feeling ‘at home’ is the cultivation of a sense of spatiotemporal continuity of place and of emplacement. Yet real, physical continuity of place is impossible for refugees: the camp is not and never will be the place whence they have come. I demonstrate that refugees make considerable efforts to create a sense of purpose and home in displacement, and that embodied knowledge and the opportunity for its repeated enactment, and especially, sensory experience, are central components in this. While the camp is in some ways perpetually becoming more like home, it will never quite be it. Nonetheless, repeated and active engagement in the present with the objects and actions of the past, are in a refugee setting particularly powerful and dynamic in forming and re‐forming connections with the pre‐exile past. Copyright © 2010 John Wiley & Sons, Ltd.
Detecting data fabrication in clinical trials from cluster analysis perspective
Authors: Wu Xiaoru , Carlsson Martin 
Published: October 2010

AbstractDetecting data fabrication is of great importance in clinical trials. As the role of statisticians in detecting abnormal data patterns has grown, a large number of statistical procedures have been developed, most of which are based on descriptive statistics. Based upon the fact that substantial data fabrication cases have certain clustering structures, this paper discusses the potential for the use of statistical clustering method in fraud detection. Three clustering patterns, angular, neighborhood and repeated measurements clustering, are identified and explored. Correspondingly, simple and efficient test statistics are proposed and randomization tests are carried out. The proposed methods are applied to a 12‐week multi‐center study for illustration. Extensive simulations are conducted to validate the effectiveness of the procedures. Copyright © 2010 John Wiley & Sons, Ltd.
A ratio‐to‐control Williams‐type test for trend
Authors: Hothorn Ludwig A. , Djira Gemechis D. 
Published: October 2010

AbstractUnder certain conditions, many multiple contrast tests based on the difference of treatment means can also be conveniently expressed in terms of ratios. In this paper, a Williams test for trend is defined as ratios‐to‐control for ease of interpretation and to obtain directly comparable confidence intervals. Simultaneous confidence intervals for percentages are particularly helpful for interpretations in the case of multiple endpoints. Methods for constructing simultaneous confidence intervals are discussed under both homogeneous and heterogeneous error variances. This approach is available in the R extension packagemratios. The proposed method is used to test for trend in an immunotoxicity study with several endpoints as an example. Copyright © 2010 John Wiley & Sons, Ltd.
Adjoint sensitivity of the model forecast to data assimilation system error covariance parameters
Authors: Daescu Dacian N. , Todling Ricardo 
Published: October 2010

AbstractThe development of the adjoint of the forecast model and of the adjoint of the data assimilation system (adjoint‐DAS) makes feasible the evaluation of the local sensitivity of a model forecast aspect with respect to a large number of parameters in the DAS. In this study it is shown that, by exploiting sensitivity properties that are intrinsic to the analyses derived from a minimization principle, the adjoint‐DAS software tools developed at numerical weather prediction centres for observation and background sensitivity may be used to estimate the forecast sensitivity to observation‐ and background‐error covariance parameters and for forecast impact assessment. All‐at‐once sensitivity to error covariance weighting coefficients and first‐order impact estimates are derived as a particular case of the error covariance perturbation analysis. The use of the sensitivity information as a DAS diagnostic tool and for implementing gradient‐based error covariance tuning algorithms is illustrated in idealized data assimilation experiments with the Lorenz 40‐variable model. Preliminary results of forecast sensitivity to observation‐ and background‐error covariance weight parameters are presented using the fifth‐generation NASA Goddard Earth Observing System (GEOS‐5) atmospheric DAS and its adjoint developed at the Global Modeling and Assimilation Office. Copyright © 2010 Royal Meteorological Society
Characterization of the aminated agarose nanoparticles labeled with fluorescein isothiocyanate
Authors: Zhang Ling‐Min , Huang Jian‐Yan , Zhang Ling‐Hui , Chu Bin , Tang Shun‐Qing 
Published: October 2010

AbstractIncorporating an organic fluorescence agent into nanoparticles can significantly promote its fluorescent efficiency. In this article, a novel fluorescein isothiocyanate labeling aminated agarose (FITC‐AA) was synthesized and tested as an effective fluorescent labeling agent. FITC‐AA could spontaneously form nanoparticles with a diameter less than 200 nm below 37°C due to gelling effect of the agarose. Cell culture experiments confirmed that 3T3 fibroblast cells could be marked by fluorescent FITC‐AA nanoparticles and the labeling time sustained longer than by FITC alone. This finding demonstrates that the fluorescent labeling of cells can be enhanced when fluorescent nanoparticles are used as markers. SCANNING 32: 361–368, 2010. © 2010 Wiley Periodicals, Inc.
The AT1angiotensin II receptor blockade attenuates the development of amphetamine‐induced behavioral sensitization in a two‐injection protocol
Authors: Paz Maria Constanza , Assis Maria Amparo , Cabrera Ricardo J. , Cancela Liliana M. , Bregonzio Claudia 
Published: October 2010

AbstractIt has been shown that a single exposure to amphetamine is sufficient to induce long‐term behavioral, neurochemical, and neuroendocrine sensitization in rats. Dopaminergic neurotransmission in the nucleus accumbens and the caudate‐putamen plays a critical role in the addictive properties of drugs of abuse. Angiotensin (Ang) II receptors are found on the soma and terminals of mesolimbic dopaminergic neurons and it has been shown that Ang II acting through its AT1receptors facilitates dopamine release. The hypothesis was tested that Ang II AT1receptors are involved in the neuroadaptative changes induced by a single exposure to amphetamine and that such changes are related to the development of behavioral and neurochemical sensitization. For this purpose, the study examined the expression of amphetamine‐enhanced (0.5 mg kg−1i.p.) locomotor activity in animals pretreated with candesartan, an AT1blocker, (3 mg kg−1p.o × 5 days), 3 weeks after an amphetamine injection (5 mg kg−1i.p.). Dopaminergic hyperreactivity was tested by measuring the 3H‐DA release in vitro from caudate‐putamen and nucleus accumbens slices, induced by K+stimulus. It was confirmed the behavioral sensitization in the two‐injection protocol and candesartan pretreatment attenuate this response. It was also found that AT1blockade pretreatment did not affect the locomotor response to dopamine agonists. In respect to the neurochemical sensitization tested using ex vivo 3H‐DA release experiments it was found that AT1receptor pretreatment blunted the enhanced response induced by K+stimulus. The results support the idea that the development of neuroadaptive changes induced by amphetamine involves brain AT1Ang II receptor activation. Synapse, 2011. © 2010 Wiley‐Liss, Inc.
Targeted mutations in the Na,K‐ATPase alpha 2 isoform confer ouabain resistance and result in abnormal behavior in mice
Authors: Schaefer Tori L. , Lingrel Jerry B , Moseley Amy E. , Vorhees Charles V. , Williams Michael T. 
Published: October 2010

AbstractSodium and potassium‐activated adenosine triphosphatases (Na,K‐ATPase) are ubiquitous, participate in osmotic balance and membrane potential, and are composed of α, β, and γ subunits. The α subunit is required for the catalytic and transport properties of the enzyme and contains binding sites for cations, ATP, and digitalis‐like compounds including ouabain. There are four known α isoforms; three that are expressed in the CNS in a regional and cell‐specific manner. The α2 isoform is most commonly found in astrocytes, pyramidal cells of the hippocampus in adults, and developmentally in several other neuronal types. Ouabain‐like compounds are thought to be produced endogenously in mammals, bind the Na,K‐ATPase, and function as a stress‐related hormone, however, the impact of the Na,K‐ATPase ouabain binding site on neurobehavioral function is largely unknown. To determine if the ouabain binding site of the α2 isoform plays a physiological role in CNS function, we examined knock‐in mice in which the normally ouabain‐sensitive α2 isoform was made resistant (α2R/R) while still retaining basal Na,K‐ATPase enzymatic function. Egocentric learning (Cincinnati water maze) was impaired in adult α2R/Rmice compared to wild type (WT) mice. They also exhibited decreased locomotor activity in a novel environment and increased responsiveness to a challenge with an indirect sympathomimetic agonist (methamphetamine) relative to WT mice. The α2R/Rmice also demonstrated a blunted acoustic startle reflex and a failure to habituate to repeated acoustic stimuli. The α2R/Rmice showed no evidence of altered anxiety (elevated zero maze) nor were they impaired in spatial learning or memory in the Morris water maze and neither group could learn in a large Morris maze. These results suggest that the ouabain binding site is involved in specific types of learning and the modulation of dopamine‐mediated locomotor behavior. Synapse, 2011. © 2010 Wiley‐Liss, Inc.
The grammar of graphics
Authors: Wilkinson Leland 
Published: October 2010

AbstractThe grammar of graphics (GoG) denotes a system with seven classes embedded in a data flow. This data flow specifies a strict order in which data are transformed from a raw dataset to a statistical graphic. Each class contains multiple methods, each of which is a function executed at the step in the data flow corresponding to that class. The classes are orthogonal, in the sense that the product set of all classes (every possible sequence of class methods) defines a space of graphics which is meaningful at every point. The meaning of a statistical graphic is thus determined by the mapping produced by the function chain linking data and graphic. WIREs Comp Stat 2010 2 673–677 DOI: 10.1002/wics.118This article is categorized under:

Statistical and Graphical Methods of Data Analysis > Statistical Graphics and Visualization
The use of long acting subcutaneous levonorgestrel (LNG) gel depot as an effective contraceptive option for cotton‐top tamarins (Saguinus oedipus)
Authors: Wheaton C.J. , Savage A. , Shukla A. , Neiffer D. , Qu W. , Sun Y. , Lasley B.L. 
Published: October 2010

AbstractCotton‐top tamarins (Saguinus oedipus) are a critically endangered species that have been bred successfully in captivity for many years. For two decades, the Cotton‐top Tamarin SSP© has been challenged with a high rate of reproduction combined with a history of contraceptive failures and nonrecommended births using the current Depo Provera® (medroxyprogesterone acetate) injection followed by MGA (melengestrol acetate) implant contraception combination. To address these issues we have developed and tested the use of levonorgestrel (LNG) as an effective contraception option for cotton‐top tamarins. LNG was delivered in an injectable, gel matrix consisting of polylactic‐co‐glycolic acid, triethyl citrate and N‐methylpyrrolidone. This gel matrix forms a biodegradable depot at the subcutaneous injection site providing slow release of the active ingredient. Gel matrix composition and LNG concentration were adjusted in four gel formulations to maximize the duration of contraceptive efficacy while minimizing immediate post‐injection increases in fecal LNG concentration. LNG treatment (68.44±8.61 mg/kg) successfully eliminated ovarian cycles (fecal pregnanediol‐3‐glucuronide (PdG) and estrone conjugates (E1C)) for 198.8±70.3 days (formulation four; range 19–50 weeks). It was demonstrated that subcutaneous LNG depot injection was an effective, reversible contraceptive option for the management of cotton‐top tamarins in captivity. Zoo Biol 30:498–522, 2011. © 2010 Wiley Periodicals, Inc.
Developmentally regulated expression of Sox9 and microRNAs 124,128 and 23 in neuroepithelial stem cells in the developing spinal cord
Authors: Farrell Barbara C. , Power Emmet M. , Dermott Kieran W. Mc 
Published: October 2010

AbstractCentral nervous system development is a complex process involving many interacting factors. MicroRNAs have recently been identified as playing key intrinsic roles in development however few of their specific targets have been identified in vivo. The transcription factor Sox9 has recently been identified as a target of miR‐124 in the adult mouse sub‐ventricular zone. Here we investigate the expression of the microRNAs miR‐124, miR‐128 and miR‐23 and that of transcription factor Sox9, in neuroepithelial stem cells in the developing spinal cord. Furthermore we investigate if neurogenesis in embryonic neuroepithelial cells in the spinal cord might also be regulated by the interaction of Sox9 and miR‐124. We provide evidence of the spatial and temporal regulation of miR‐124, miR‐128, miR‐23 and Sox9, and taken together with recent findings we provide evidence that Sox9 may also be target of miR‐124 in developing spinal cord neuroepithelial cells.
Zur Verzahnung von Jugendhilfe, Gesundheitssystem und Eingliederungshilfe - Ergebnisse des 13. Kinder- und Jugendberichts
Authors: Permien Hanna 
Published: October 2010

Einleitung
Der 13. Kinder- und Jugendbericht befasste sich mit der gesundheitlichen Situation von jungen Menschen und den Möglichkeiten der Kinder- und Jugendhilfe im Bereich von Gesundheitsförderung und Prävention. Gerade im psychosozialen Bereich können die sozialpädagogischen Ansätze die Gesundheit der Mädchen und Jungen fördern, erhalten sowie sie und ihre Familien motivieren, Gesundheitsrisiken zu vermeiden. Allerdings fehlt es oft an flächendeckenden und kontinuierlichen Kooperationen zwischen den verschiedenen Arbeitsfeldern (Frühe Hilfen, Familienbildung, Kindertagesbetreuung, Jugendarbeit, Erziehungshilfen) und an ausreichenden Unterstützungsmaßnahmen, damit gerade auch benachteiligte Kinder und Jugendliche unkompliziert und gezielt notwendige Hilfen erhalten.
Aktion ,,Ich geh zur U! Und Du?‘‘ – Erfahrungen auf kommunaler Ebene
Authors: Wolfram Nicole 
Published: October 2010

Einleitung
Die Früherkennungsuntersuchungen im Kindesalter erheben regelmäßig und standardisiert die körperliche, geistige und soziale Entwicklung des Kindes. Sie stellen ein wertvolles Instrument zur Steuerung der kindlichen Entwicklung dar. Um die Akzeptanz auf Seiten der Eltern, insbesondere aus bildungsfernen und sozial schwachen Schichten zu erhöhen, wurde im Jahr 2004 von der Bundeszentrale für gesundheitliche Aufklärung die Aktion „Ich geh’ zur U! Und Du?“ ins Leben gerufen. Im Beitrag wird die Umsetzung und Adaption des bundesweiten Ansatzes auf kommunaler Ebene dargelegt.
PALME – ein Präventives Elterntraining für alleinerziehende Mütter geleitet von ErzieherInnen
Authors: Franz Matthias , Weihrauch Lonja , Schäfer Ralf 
Published: October 2010

Einleitung
Auf bindungstheoretischer Grundlage wurde ein emotionszentriertes präventives Elterntraining für allein erziehende Mütter mit Kindern im Vorschulalter entwickelt. Die Wirksamkeit des Trainings wurde in einer randomisierten, kontrollierten Studie untersucht. Es zeigten sich signifikante Gruppe x Messzeitpunkt-Interaktionseffekte zugunsten der Interventionsgruppe. Angesichts des Nutzens und der geringen Kosten könnte dieses Elterntraining z.B. in kommunalen Settings angeboten werden.
Wie wirkt sich täglicher Schulsport auf den juvenilen Medienkonsum aus?
Authors: Liersch Sebastian , Bisson Susanne , Sterdt Elena , Henze Vicky , Krauth Christian , Räbl Markus , Walter Ulla 
Published: October 2010

EinleitungDie Interventionsmaßnahme „fit für pisa“ ergänzt während der gesamten 4-jährigen Grundschulzeit die obligatorischen zwei Schulstunden Sport/Woche durch drei weitere Sportstunden an fünf Grundschulen in Göttingen. Die von 2007-2010 BMBF-geförderte Evaluationsstudie soll Aufschluss darüber geben, inwieweit sich ein quantitativ gesteigerter und qualitativ verbesserter Sportunterricht auf Gesundheit und Bewegungsverhalten von Schülern nachhaltig auswirkt.
Worship and threshold obligations
Authors: GWIAZDA JEREMY 
Published: October 2010

AbstractIn this reply to Tim Bayne and Yujin Nagasawa, I defend the possibility of a maximal-excellence account of the grounding of the obligation to worship God. I do not offer my own account of the obligation to worship God; rather I argue that the major criticism (that is raised against maximal-excellence accounts) fails. Thus maximal-excellence can ground an obligation to worship God.