bluuebunny/crossref_metadata_2025_split huggingface dataset:
TCR-Induced Activation of Ras Proceeds at the Plasma Membrane and Requires Palmitoylation of N-Ras
Authors: Rubio Ignacio , Grund Stefan , Song Shu-Ping , Biskup Christoph , Bandemer Sabine , Fricke Melanie , Förster Martin , Graziani Andrea , Wittig Ute , Kliche Stefanie 
Published: August 2010

Abstract
Ras transmits manifold signals from the TCR at various crossroads in the life of a T cell. For example, selection programs in the thymus or the acquisition of a state of hypo-responsiveness known as anergy are just some of the T cell features known to be controlled by TCR-sparked signals that are intracellularly propagated by Ras. These findings raise the question of how Ras can transmit such a variety of signals leading to the shaping of equally many T cell traits. Because Ras proteins transit through endomembrane compartments on their way to the plasma membrane (PM), compartmentalized Ras activation at distinct subcellular sites represents a potential mechanism for signal diversification in TCR signaling. This hypothesis has been nurtured by studies in T cells engineered to overexpress Ras that reported distinct activation of Ras at the PM and Golgi. Contrary to this scenario, we report in this study that activation of endogenous Ras, imaged in live Jurkat T cells using novel affinity probes for Ras-GTP, proceeds only at the PM even upon enforced signal flux through the diacylglycerol/RasGRP1 pathway. Physiological engagement of the TCR at the immunological synapse in primary T cells caused focalized Ras-GTP accumulation also only at the PM. Analysis of palmitoylation-deficient Ras mutants, which are confined to endomembranes, confirmed that the TCR does not activate Ras in that compartment and revealed a critical function for palmitoylation in N-Ras/H-Ras activation. These findings identify the PM as the only site of TCR-driven Ras activation and document that endomembranes are not a signaling platform for Ras in T cells.
T-bet and Eomesodermin Are Required for T Cell-Mediated Antitumor Immune Responses
Authors: Zhu Yibei , Ju Songguang , Chen Elizabeth , Dai Shao , Li Changyou , Morel Penelope , Liu Lin , Zhang Xueguang , Lu Binfeng 
Published: August 2010

Abstract
Cell-mediated adaptive immunity is very important in tumor immune surveillance and tumor vaccination. However, the genetic program underlying an effective adaptive antitumor immunity is elusive. T-bet and Eomesodermin (Eomes) have been suggested to be master regulators of Th1 cells and CD8+ T cells. However, whether they are important for T cell-mediated antitumor immunity is controversial. In this paper, we show that the combined germline deletion of T-bet and T cell-specific deletion of Eomes resulted in profound defects in adaptive antitumor immune responses. T-bet and Eomes drive Tc1 differentiation by preventing alternative CD8+ T cell differentiation to Tc17 or Tc2 cells. Surprisingly, T-bet and Eomes are not critical for the generation of systemic CTL activities against cancer cells. Instead, T-bet and Eomes are crucial for tumor infiltration by CD8+ T cells. This study defines T-bet and Eomes as critical regulators of T cell-mediated immune responses against tumor.
Nonsteroidal Anti-Inflammatory Drugs Increase TNF Production in Rheumatoid Synovial Membrane Cultures and Whole Blood
Authors: Page Theresa H. , Turner Jeremy J. O. , Brown Anthony C. , Timms Emma M. , Inglis Julia J. , Brennan Fionula M. , Foxwell Brian M. J. , Ray Keith P. , Feldmann Marc 
Published: August 2010

AbstractNonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase activity and hence PG production. However, the ability of NSAIDs to ameliorate pain and tenderness does not prevent disease progression in rheumatoid arthritis, a disease whose pathogenesis is linked to the presence of proinflammatory cytokines, such as TNF-α. To understand this observation, we have examined the effect of NSAIDs on the production of clinically validated proinflammatory cytokines. We show that a variety of NSAIDs superinduce production of TNF from human peripheral blood monocytes and rheumatoid synovial membrane cultures. A randomized, double-blinded, crossover, placebo-controlled trial in healthy human volunteers also revealed that the NSAID drug celecoxib increased LPS-induced TNF production in whole blood. NSAID-mediated increases in TNF are reversed by either the addition of exogenous PGE2 or by a PGE2 EP2 receptor agonist, revealing that PGE2 signaling via its EP2 receptor provides a valuable mechanism for controlling excess TNF production. Thus, by reducing the level of PGE2, NSAIDs can increase TNF production and may exacerbate the proinflammatory environment both within the rheumatoid arthritis joint and the systemic environment.
Restricted TCR-α CDR3 Diversity Disadvantages Natural Regulatory T Cell Development in the B6.2.16 β-Chain Transgenic Mouse
Authors: Singh Yogesh , Ferreira Cristina , Chan Andrew C. Y. , Dyson Julian , Garden Oliver A. 
Published: August 2010

Abstract
To date, analysis of mice expressing TCR-β transgenes derived from CD4+ T cell clones has demonstrated equivalent or higher TCR diversity in naturally occurring regulatory CD4+ T cells (Tregs) versus conventional CD4+ T cells (Tcons). However, TCR-α–chain diversity in these mice may be influenced by the inherent bias toward the CD4+ lineage in the selected repertoires. We wished to determine whether the choice of TCR-β–chain influences the relative diversity of the Treg and Tcon repertoires, examining as a model the B6.2.16β-transgenic mouse, in which the fixed β-chain is derived from a CD8+ T cell clone. B6.2.16β Treg thymocytes showed significantly lower TRAV17 (AV9) CDR3 sequence diversity than both syngeneic Tcon thymocytes, and Treg and Tcon thymocytes from wild-type C57BL/6 (B6) mice. The ratio of single-positive CD4+/single-positive CD8+ thymocytes in B6.2.16β mice was similar to that in B6, yet both the proportional frequency and absolute number of CD4+Foxp3+ cells was significantly lower in the thymi and peripheral lymph nodes of B6.2.16β mice. Furthermore, B6 + B6.2.16β→B6 mixed bone marrow chimeras revealed that the transgenic β-chain disadvantaged Treg development in a competitive environment. These data underline the importance of the β-chain in assessments of Treg α-chain diversity and provide further support for the notion that interclonal competition for entry into the Treg lineage is a significant factor in determining the composition of this lineage.
IL-10 Restricts Memory T Cell Inflation during Cytomegalovirus Infection
Authors: Jones Morgan , Ladell Kristin , Wynn Katherine K. , Stacey Maria A. , Quigley Máire F. , Gostick Emma , Price David A. , Humphreys Ian R. 
Published: August 2010

AbstractThe β-herpesvirus CMV induces a substantial and progressive expansion of virus-specific memory CD8 T cells, which protect the host against viral reactivation from latency. In this paper, we report that this expansion, or “inflation,” of memory T cells is amplified dramatically during mouse CMV infection of IL-10 knockout (IL-10−/−) mice. T cells from IL-10−/− mice were oligoclonal, exhibited a highly activated phenotype, expressed antiviral cytokines, and degranulated in response to cognate Ag encounter ex vivo. Moreover, latent viral load was reduced in IL-10−/− mice. Importantly, these results were recapitulated by IL-10R blockade during chronic/latent infection of wild-type mice. These data demonstrate that regulatory immune mechanisms can influence CMV-specific T cell memory and suggest a possible rationale for the acquisition of functional IL-10 orthologs by herpesviruses.
Directly Transfected Langerin+ Dermal Dendritic Cells Potentiate CD8+ T Cell Responses following Intradermal Plasmid DNA Immunization
Authors: Elnekave Mazal , Furmanov Karina , Nudel Itay , Arizon Moran , Clausen Björn E. , Hovav Avi-Hai 
Published: August 2010

Abstract
Dendritic cells (DCs) play a critical role in CD8+ T cell priming following DNA vaccination. In contrast to other DNA injection routes or immunization with viral vectors, Ag presentation is delayed following needle injection of plasmid DNA into the skin. The contribution of various skin DC subsets to this process is not known. In this study, we show that dermal CD11c+ cells are the most important transgene-expressing cells following immunization. Using langerin- diphtheria toxin receptor mice we demonstrated that langerin+ dermal DCs (Ln+dDCs) were crucial for generating an optimal CD8+ T cell response. Blocking migration of skin cells to the lymph node (LN) ablated immunogenicity, suggesting that migration of dDC subsets to the LN is essential for generating immunity. This migration generated a weak Ag-presenting activity in vivo until day 5 postimmunization, which then increased dramatically. We further found that Ln+dDCs and dDCs were the only DC populations directly presenting Ag to CD8+ T cells ex vivo during the initial 8-d period postimmunization. This activity changed on the following days, when both skin DCs and LN-resident DCs were able to present Ag to CD8+ T cells. Taken together, our in vivo and ex vivo results suggest that activation of CD8+ T cells following intradermal plasmid DNA immunization depends on directly transfected Ln+dDCs and dDCs. Moreover, the type of DCs presenting Ag changed over time, with Ln+dDCs playing the major role in potentiating the initial CD8+ T cell response.
Asymptotic Formulae for Pairs of Diagonal Cubic Equations
Authors: Brüdern Jörg , Wooley Trevor D. 
Published: August 2010

Abstract We investigate the number of integral solutions possessed by a pair of diagonal cubic equations in a large box. Provided that the number of variables in the system is at least fourteen, and in addition the number of variables in any non-trivial linear combination of the underlying forms is at least eight, we obtain an asymptotic formula for the number of integral solutions consistent with the product of local densities associated with the system.
Externalizing problems and problematic sexual behaviors: same etiology?
Authors: Lévesque Mireille , Bigras Marc , Pauzé Robert 
Published: August 2010

AbstractThe study sought to determine whether maltreatment subtypes, family sexuality, and personal characteristics predicted and distinguished child problematic sexual behaviors (PSB) and externalizing problems (EP). Participants were families of 188 children, 6–11 years old, referred by child welfare services in four Quebec districts. Caregivers completed interviews and questionnaires. Results suggested that family environment and maltreatment subtypes had partially different impacts on PSB and EP. When EP and gender were controlled, younger children in a sexualized family environment and those verbally victimized were more likely to exhibit PSB. When PSB and gender were controlled, verbal abuse and neglect emerged as predictors of EP. Potential implications for child PSB research and interventions are discussed. Aggr. Behav. 36:358–370, 2010. © 2010 Wiley‐Liss, Inc.
Direct Observation of Capacitor Switching Using Planar Electrodes
Authors: Balke Nina , Gajek Martin , Tagantsev Alexander K. , Martin Lane W. , Chu Ying‐Hao , Ramesh Ramamoorthy , Kalinin Sergei V. 
Published: August 2010

AbstractFerroelectric polarization switching in epitaxial (110) BiFeO3 films is studied using piezoresponse force microscopy of a model in‐plane capacitor structure. The electrode orientation is chosen such that only two active domain variants exist. Studies of the kinetics of domain evolution allows clear visualization of nucleation sites, as well as forward and lateral growth stages of domain formation. It is found that the location of the reverse‐domain nucleation is correlated with the direction of switching in a way that the polarization in the domains nucleated at an electrode is always directed away from it. The role of interface charge injection and surface screening charge on switching mechanisms is explored, and the nucleation is shown to be controllable by the bias history of the sample. Finally, the manipulation of domain nucleation through domain structure engineering is illustrated. These studies pave the way for the engineering and design of the ferroelectric device structures through control of individual steps of the switching process.
High Breakdown Field Dielectric Elastomer Actuators Using Encapsulated Polyaniline as High Dielectric Constant Filler
Authors: Molberg Martin , Crespy Daniel , Rupper Patrick , Nüesch Frank , Månson Jan‐Anders E. , Löwe Christiane , Opris Dorina M. 
Published: August 2010

AbstractA novel method allowing rapid production of reliable composites with increased dielectric constant and high dielectric strength for dielectric elastomer actuators (DEA) is reported. The promising approach using composites of conductive particles and insulating polymers generally suffers from low breakdown fields when applied to DEA devices. The present publication shows how to overcome this deficiency by using conductive polyaniline (PANI) particles encapsulated into an insulating polymer shell prior to dispersion. PANI particles are encapsulated using miniemulsion polymerization (MP) of divinylbenzene (DVB). The encapsulation process is scaled up to approximately 20 g particles per batch. The resulting particles are used as high dielectric constant (ϵ′) fillers. Composites in a polydimethylsiloxane (PDMS) matrix are prepared and the resulting films characterized by dielectric spectroscopy and tensile tests, and evaluated in electromechanical actuators. The composite films show a more than threefold increase in ϵ′, breakdown field strengths above 50 V μm−1, and increased strain at break. These novel materials allow tuning the actuation strain or stress output and have potential as materials for energy harvesting.
Formation of Nickel Oxide Nanotubes with Uniform Wall Thickness by Low‐Temperature Thermal Oxidation Through Understanding the Limiting Effect of Vacancy Diffusion and the Kirkendall Phenomenon
Authors: Ren Yi , Chim Wai Kin , Chiam Sing Yang , Huang Jin Quan , Pi Can , Pan Ji Sheng 
Published: August 2010

AbstractIn this work, the step‐wise oxidation mechanism of nickel (Ni) nanowires is elucidated. Rapid vacancy diffusion plays a significant role at low temperatures in forming heterostructures of nickel oxide (NiO) nanotubes with Ni nanowires. Subsequent investigations of Ni nanowire oxidation at higher temperatures and faster temperature ramp rates show that it is difficult to bypass this rapid vacancy diffusion stage, which affects the formation of the final structure. Therefore, it is unlikely to form solid NiO nanowires or NiO nanotubes with uniform wall thickness through the conventional annealing/oxidation process of Ni nanowires. Instead, a step‐wise oxidation process by combining low temperature oxidation with a chemical etching step is utilized to produce for the first time NiO nanotubes with uniform wall thickness from Ni nanowires.
Polymer–Fullerene Bulk‐Heterojunction Solar Cells
Authors: Brabec Christoph J. , Gowrisanker Srinivas , Halls Jonathan J. M. , Laird Darin , Jia Shijun , Williams Shawn P. 
Published: August 2010

AbstractSolution‐processed bulk heterojunction organic photovoltaic (OPV) devices have gained serious attention during the last few years and are established as one of the leading next generation photovoltaic technologies for low cost power production. This article reviews the OPV development highlights of the last two decades, and summarizes the key milestones that have brought the technology to today’s efficiency performance of over 7%. An outlook is presented on what will be required to drive this young photovoltaic technology towards the next major milestone, a 10% power conversion efficiency, considered by many to represent the efficiency at which OPV can be adopted in wide‐spread applications. With first products already entering the market, sufficient lifetime for the intended application becomes more and more critical, and the status of OPV stability as well as the current understanding of degradation mechanisms will be reviewed in the second part of this article.
Carbon Nanotubes in the Biological Interphase: The Relevance of Noncovalence
Authors: Lee Yeonju , Geckeler Kurt E. 
Published: August 2010

AbstractWith the increasing interest in the biological applications of carbon nanotubes, their interactions in the biological interphase and their general cytotoxicity have become major issues. In spite of their salient properties, major hurdles still exist for their use in biological applications, due to their main characteristics, including their hydrophobic surfaces and tendency to aggregate, as well as their unknown interactions in the cellular interphase. In this Research News, these characteristics of carbon nanotubes, a model nanomaterial, are investigated. Thus, the cytotoxicity of carbon nanotubes, the influence of functionalization, as well as their interactions with different mammalian cell lines are studied. Moreover, suggestions for the improvement of their biocompatibility and the design of biocompatible carbon nanotube‐based systems are provided.
Tiered exposure‐assessment strategy in the semiconductor health study
Authors: Hammond S. Katharine , Hammond S. Katharine , Hines Cynthia J. , Hallock Marilyn F. , Woskle Susan R. , Abdollahzadeh Sassan , Iden C. Robert , Anson Ellen , Ramsey Fred , Schenker Marc B. 
Published: August 2010

AbstractThe Semiconductor Health Study included 14 U.S. companies with 82 silicon‐based wafer‐fabrication rooms and a complex array of processes and chemicals. Its epidemiologic components were a historical examination of spontaneous abortion rates among 902 women, a prospective evaluation of reproductive outcomes in 483 women, and a cross‐sectional review of MAle fertility and of respiratory, ergonomic, neurologic, or gastrointestinal problems among 3,175 men and women. Designing an exposure assessment strategy presented unique problems, and multiple agents had to be evaluated. A three‐tiered approach to exposure assessment was developed to reflect increasing specificity of exposures. At the first tier, employees were divided into fabrication and nonfabrication groups. At the second tier, work groups with qualitatively different exposures were determined. At the third tier, intensity of exposures to specific chemical, physical, and ergonomic agents was evaluated. Evaluations were based on worker reports of tasks performed, moderated by fabrication‐specific factors observed by study industrial hygienists during site visits.
Algorithms for estimating personal exposures to chemical agents in the semiconductor health study
Authors: Woskie Susan R. , Hammond S. Katharine , Hines Cynthia J. , Hallock Marilyn F. , Schenker Marc B. 
Published: August 2010

AbstractFor exposure assessment in a series of epidemiologic studies of semiconductor industry workers, estimates of potential personal exposures to selected chemical agents were developed using a set of algorithms. A worker's total exposure to each agent was defined as the sum of task scores for each task using that agent. Task scores were calculated as the intensity and frequency score for each task, modified by a factor indicating degree of presence of the target agent and a process‐specific emission factor representing degree of emission control present for that process. The algorithms used multiple sources of information to generate an exposure score for each worker‐process‐agent combination. Exposure scores were then placed into ordinal categories of exposure (0–3) for use in the epidemiologic analysis.
Historical cohort investigation of spontaneous abortion in the semiconductor health study: Epidemiologic methods and analyses of risk in fabrication overall and in fabrication work groups
Authors: Beaumont James J. , Swan Shanna H. , Hammond S. Katharine , Samuels Steven J. , Green Rochelle S. , Hallock Marilyn F. , Dominguez Carol , Boyd Peggy , Schenker Marc B. 
Published: August 2010

AbstractThe risk of spontaneous abortion (SAB) in the semiconductor industry was examined in a historical cohort study of pregnancies at 14 companies. We identified Female employees who had worked for at least 6 months and whose ages ranged from 18 to 44 years during the 1986–1989 study period. Using company records, we included all fabrication‐room (fab) employees and an Approximately equal number of nonfabrication (non‐fab) employees, for a total sample of 7,269. Telephone interviews with 6,088 women (84%) identified 904 eligible pregnancies and 113 SABs. Exposure classification was based on questionnaire and industrial hygiene assessments of tasks the women performed during the first trimester of pregnancy. Using logistic regression to control for age, smoking, ethnicity, education, income, year of pregnancy, and stress, we found a higher risk of SAB in fab employees than in nonfab employees (15.0% of fab pregnancies ended in SAB vs. 10.4% of nonfab pregnancies, adjusted relative risk [RR] = 1.43, 95% CI = 0.95‐2.09). Analysis of fab work groups showed that the highest relative risk was in MAsking employees (17.5% SAB rate, adjusted RR = 1.78, 95% CI = 1.17‐2.62 in comparison with nonfab employees). Within MAsking, the highest risk was found in etching‐related process employees (22.2% SAB rate, adjusted RR = 2.08, 95% CI = 1.27‐3.19 in comparison to nonfab employees)
Historical cohort study of spontaneous abortion among fabrication workers in the semiconductor health study: Agent‐level analysis
Authors: Swan Shanna H. , Beaumont James J. , Hammond S. Katharine , Vonbehren Julie , Green Rochelle S. , Hallock Marilyn F. , Woskie Susan R. , Hines Cynthia J. , Schenker Marc B. 
Published: August 2010

AbstractRisk of spontaneous abortion (SAB) was examined in relation to chemical and physical agents in a retrospective study of employees of 14 seminconductor MAnufacturers: After screening over 6,000 employees, 506 current and 385 former workers were eligible. If a woman had multiple eligible pregnancies, one was selected at random. Telephone interviews provided data on demographics and occupational and other exposures during the first trimester. Two groups of chemicals accounted for the 45% excess risk of SAB among fabrication‐room (fab) workers: photoresist and developed solvents (PDS), including glycol ethers, and fluoride compounds used in etching. Women exposed to high levels of both these agents were at greater risk (RR = 3.21, 95% confidence interval [CI] = 1.29–5.96). In fab workers without these exposures, SAB rates were not elevated (adjusted relative risk [RR] = 0.98, 95% CI = 0.55‐1.69). An association was seen with workplace stress, which was not limited to women exposed to PDS or fluoride, nor did stress explain the associations between these chemicals and SAB.