bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting of a T Cell Agonist Peptide to Lysosomes by DNA Vaccination Induces Tolerance in the Nonobese Diabetic Mouse
Authors: Rivas Elisa I. , Driver John P. , Garabatos Nahir , Presa Maximiliano , Mora Conchi , Rodriguez Fernando , Serreze David V. , Stratmann Thomas 
Published: February 2011

Abstract
CD4 T cells are crucial effectors in the pathology of type 1 diabetes (T1D). Successful therapeutic interventions for prevention and cure of T1D in humans are still elusive. Recent research efforts have focused on the manipulation of T cells by treatment with DNA. In this paper, we studied the effects of a DNA treatment strategy designed to target antigenic peptides to the lysosomal compartment on a monospecific T cell population termed 2.5mi+ T cells that shares reactivity with the diabetogenic T cell clone BDC-2.5 in the NOD mouse. MHC class II tetramer analysis showed that repeated administrations were necessary to expand 2.5mi+ T cells in vivo. This expansion was independent of Ag presentation by B cells. A single peptide epitope was sufficient to induce protection against T1D, which was not due to Ag-specific T cell anergy. Typical Th2 cytokines such as IL-10 or IL-4 were undetectable in 2.5mi+ T cells, arguing against a mechanism of immune deviation. Instead, the expanded 2.5mi+ T cell population produced IFN-γ similar to 2.5mi+ T cells from naive mice. Protection against T1D by DNA treatment was completely lost in NOD.CD28−/− mice which are largely deficient of natural regulatory T cells (Treg). Although Ag-specific Foxp3+ Treg did not expand in response to DNA treatment, diabetes onset was delayed in Treg-reconstituted and DNA-treated NOD.SCID mice. These observations provide evidence for a Treg-mediated protective mechanism that is independent of the expansion or de novo generation of Ag-specific Treg.
Promoter Hypomethylation Results in Increased Expression of Protein Phosphatase 2A in T Cells from Patients with Systemic Lupus Erythematosus
Authors: Sunahori Katsue , Juang Yuang-Taung , Kyttaris Vasileios C. , Tsokos George C. 
Published: February 2011

Abstract
The catalytic subunit α isoform of protein phosphatase 2A (PP2Acα) activity, protein, and mRNA have been found increased in systemic lupus erythematosus (SLE) T cells and to contribute to decreased IL-2 production. The PP2Acα promoter activity is controlled epigenetically through the methylation of a CpG within a cAMP response element (CRE) motif defined by its promoter. We considered that hypomethylation may account for the increased expression of PP2Acα in patients with SLE. Using bisulfite sequencing, we found that SLE T cells displayed decreased DNA methylation in the promoter region compared with normal T cells. More importantly, we found that the CRE-defined CpG, which binds p-CREB, is significantly less methylated in SLE compared with normal T cells, and the levels of methylation correlated with decreased amounts of DNA methyltransferase 1 transcripts. Methylation intensity correlated inversely with levels of PP2Acα mRNA and SLE disease activity. Chromatin immunoprecipitation assays revealed more binding of p-CREB to the CRE site in SLE T cells, resulting in increased expression of PP2Acα. We propose that PP2Acα represents a new methylation-sensitive gene that, like the previously reported CD70 and CD11a, contributes to the pathogenesis of SLE.
A Novel Tumor-Associated Pancreatic Glycoprotein Is Internalized by Human Dendritic Cells and Induces Their Maturation
Authors: Franceschi Cécile , Collignon Aurélie , Isnardon Daniel , Benkoel Liliane , Vérine Alain , Silvy Françoise , Bernard Jean-Paul , Lombardo Dominique , Beraud Evelyne , Olive Daniel , Mas Eric 
Published: February 2011

Abstract
Aberrant glycosylation or overexpression of cell-surface glycosylated tumor-associated Ags (TAA) distinguish neoplastic from normal cells. Interactions of TAA MUC1 and HER2/neu with dendritic cells (DC) preclude efficient processing, which impairs immune responses. It is thus important to define the mechanisms of interactions between DC and glycosylated TAA and their trafficking and processing for further T cell activation. In this work, we study interactions between DC and the oncofetal fucose-rich glycovariants of bile salt-dependent lipase (BSDL), expressed in pancreatic cancer tissues and referred to as pathological BSDL carrying the fucosylated J28 glycotope (pBSDL-J28) because it is characterized by the mAb J28. The expression of pBSDL-J28 was assessed by immunohistochemistry and quantified by confocal microscopy. Nontumoral pancreatic tissues and cells do not express pBSDL-J28. Using multidisciplinary approaches and functional studies, we provide the first evidence, to our knowledge, that this tumoral glycoprotein is rapidly internalized by human DC through macropinocytosis and endocytosis via mannose receptors and then transported to late endosomes for processing. Interestingly, pBSDL-J28 per se induced DC maturation with increased expression of costimulatory and CD83 molecules associated with cytokine secretion (IL-8 and IL-6). Surprisingly, DC retained their full ability to internalize Ags, making this maturation atypical. Finally, the allogeneic pBSDL-J28–treated DC stimulated lymphocyte proliferation. Besides, pulsing DC with pBSDL-J28 C-terminal glycopolypeptide and maturation with CD40L triggered CD4+ and CD8+ T cell proliferation. Therefore, interactions of pBSDL-J28, expressed on tumoral pancreatic tissue, with DC may lead to adequate Ag trafficking and processing and result in T cell activation.
Fear of Falling Among People Who Have Sustained a Stroke: A 6-Month Longitudinal Pilot Study
Authors: Schmid Arlene A. , Van Puymbroeck Marieke , Knies Kasie , Spangler-Morris Carrie , Watts Kathryn , Damush Teresa , Williams Linda S. 
Published: February 2011

Abstract
OBJECTIVE. Fear of falling (FoF) after stroke is not well understood. We assessed change in FoF over the first 6 mo after a stroke and compared 6-mo anxiety, depression, balance, and quality of life (QoL) scores between people with and without baseline FoF (at the time of hospital discharge).
METHOD. Data for this longitudinal study were collected at baseline and 6 mo. Of the 28 people included at baseline, 18 remained in the study 6 mo later.
RESULTS. FoF significantly decreased over time (p = .015). Participants with baseline FoF had higher 6-mo anxiety and depression scores (s = .002 and .005, respectively) and lower QoL scores (p &lt; .001) than did those without baseline FoF.
CONCLUSION. The results are suggestive of the need for occupational therapists and their colleagues to consider anxiety and depression variables in managing the needs of poststroke participants experiencing FoF.
Wanted: Entrepreneurs in Occupational Therapy
Authors: Anderson Kristin M. , Nelson David L. 
Published: February 2011

Abstract
The American Occupational Therapy Association (AOTA) has challenged occupational therapy practitioners to advance the profession so that we may become more “powerful” and “widely recognized” by the year 2017 (AOTA, 2007a). To fully achieve this vision, this article argues that the profession should encourage occupational therapy entrepreneurship. As Herz, Bondoc, Richmond, Richman, and Kroll (2005, p. 2) stated, “Entrepreneurship may provide us with the means to achieve the outcomes we need to succeed in the current health care environment.” This article also argues the urgency of seizing the many opportunities that entrepreneurship offers and recommends specific actions to be taken by AOTA and by therapists.
Interfacial and Substrate Effects on Local Elastic Properties of Polymers Using Coupled Experiments and Modeling of Nanoindentation
Authors: Watcharotone Supinda , Wood Charles D. , Friedrich Robert , Chen Xinqi , Qiao Rui , Putz Karl , Brinson L. Catherine 
Published: February 2011

AbstractThe mechanical properties of polymers near interfaces are important in a number of different fields. For almost two decades, the local dynamics of thin polymer films have been studied in great detail. However, development of an understanding of local mechanical properties has been hindered by the necessary proximity of stiff substrates: mechanical measurements are confounded by interaction with the substrate, convoluting polymer, and substrate properties. In this paper, local elastic properties of thin polymer films near interfaces are directly probed for the first time via nanoindentation experiments on thin films coupled with finite element modeling. A comprehensive set of experimental and numerical modeling results are presented for poly(methyl methacrylate) (PMMA) revealing separately the effects of substrate and interphase polymer. Results indicate the attractive surface significantly affects the properties up to hundreds of nanometers. This new, direct approach to measure local mechanical properties provides new fundamental understanding of interfacial and small‐scale behaviors in polymers and soft matter for application advances in nanocomposites, microelectronics, and biopolymers.
Annual Clinical Updates in Hematological Malignancies: A Continuing Medical Education Series: Polycythemia vera and essential thrombocythemia: 2011 update on diagnosis, risk‐stratification, and management
Authors: Tefferi Ayalew 
Published: February 2011

AbstractDisease overview:Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms primarily characterized by erythrocytosis and thrombocytosis, respectively. Other disease features include leukocytosis, splenomegaly, thrombohemorrhagic complications, vasomotor disturbances, pruritus, and a small risk of disease progression into acute leukemia or myelofibrosis.Diagnosis:Diagnosis is based onJAK2mutation status (PV and ET), serum erythropoietin (Epo) level (PV), and bone marrow histopathology (ET). The presence of aJAK2mutation and subnormal serum Epo level confirm a diagnosis of PV. Differential diagnosis in ET should include chronic myelogenous leukemia and prefibrotic myelofibrosis.Risk stratification:Current risk stratification in PV and ET is designed to estimate the likelihood of thrombotic complications: high‐risk‐age >60 years or presence of thrombosis history; low‐risk‐absence of both of these two risk factors. Presence of extreme thrombocytosis (platelet count >1,000 × 109/L) might be associated with acquired von Willebrand syndrome (AvWS) and, therefore, risk of bleeding. Risk factors for shortened survival in both PV and ET include age >60 years, leukocytosis, history of thrombosis, and anemia.Risk‐adapted therapy:Survival is near‐normal in ET and reasonably long in PV. The 10‐year risk of leukemic/fibrotic transformation is <1%/1% in ET and <5%/10% in PV. In contrast, the risk of thrombosis exceeds 20%. The main goal of therapy is therefore to prevent thrombohemorrhagic complications and this is effectively and safely accomplished by the use of low‐dose aspirin (PV and ET), phlebotomy (PV), and hydroxyurea (high risk PV and ET). Treatment with busulfan or interferon‐α is usually effective in hydroxyurea failures. Am. J. Hematol. 86:293–301, 2011. © 2011 Wiley‐Liss, Inc.
Town vs. gown: A direct comparison of community residents and student mock jurors
Authors: Hosch Harmon M. , Culhane Scott E. , Tubb V. Anne , Granillo Edgar A. 
Published: February 2011

AbstractThe use of students as mock jurors in the majority of legal psychology studies on jury behavior has been criticized (e.g., Bray & Kerr, 1979; Diamond, 1997). This study examined the degree to which student mock jurors' decisions were generalizable to those of real jurors. The participants of the study included 297 jury‐eligible university students and 297 volunteers from the venire in the same community as that in which the students resided. All participants viewed one of six versions of a videotaped criminal trial. The defendant testified in English or in Spanish. In addition, the race of defendant was varied. Three bilingual individuals served as defendants with one appearing to be of northern European origin, one of Latino background, and one of African origin. Dependent variables included verdict and, for those who found the defendant guilty, the number of years to which he should be sentenced, and whether he should be fined. Student mock jurors differed reliably from their community counterparts on several demographic characteristics. However, the two groups had mixed results in relation to decision‐making tasks. There was no difference in individual verdict preferences, but the students' sentence recommendations were more punitive. These results are interpreted in the context of the generalizability of mock juror studies. Copyright © 2011 John Wiley & Sons, Ltd.
Amidases Have a Hydrogen Bond that Facilitates Nitrogen Inversion, but Esterases Have Not
Authors: Syrén Per‐Olof , Hult Karl 
Published: February 2011

AbstractThe fact that proteases/amidases can hydrolyze amides efficiently whereas esterases can not has been discussed during the last decades. By using molecular modeling we have found a hydrogen bond in the transition state for protease/amidase catalyzed hydrolysis of peptides and amides donated by the scissile NH‐group of the substrate. The hydrogen‐bond acceptor was found either in the enzyme (enzyme assisted) or in the substrate (substrate assisted). This new interaction with the NH‐hydrogen in the transition state (TS) was found in sixteen proteases/amidases, which represent ten different reaction mechanisms and eleven different folding families. Esterases lack this interaction and, therefore, they are slow in hydrolyzing amides. By mimicking the substrate‐assisted catalysis found in amidases we were able to shift reaction specificity of amide over ester synthesis of Candida antarctica lipase B one hundred fold. We propose that the hydrogen bond facilitates nitrogen inversion in amidases.
The Construction of Quaternary Stereocenters by the Henry Reaction: Circumventing the Usual Reactivity of Substituted Glyoxals
Authors: Blay Gonzalo , Hernández‐Olmos Víctor , Pedro José R. 
Published: February 2011

AbstractThe enantioselective Henry reaction between alkyl‐ and arylglyoxal hydrates and nitromethane catalyzed by CuII–iminopyridine complexes takes place regioselectively on the ketone carbonyl group to give chiral tertiary nitroaldols with high functional group density and enantiomeric excesses of up to 96 %. Both aromatic and aliphatic glyoxals are suitable substrates for this reaction.
Surface‐Enhanced Fluorescence from Fluorophore‐Assembled Monolayers by Using Ag@SiO2 Nanoparticles
Authors: Zhang Ruohu , Wang Zhuyuan , Song Chunyuan , Yang Jing , Li Jin , Sadaf Asma , Cui Yiping 
Published: February 2011

AbstractA new and simple procedure to enhance the fluorescence of analytes on the surfaces of a solid substrate is demonstrated based on Ag@SiO2 nanoparticles. Two kinds of silver–silica core–shell nanoparticles with shell thicknesses of around 3 and 15 nm have been prepared and used as enhancing agents, respectively. By simply pipetting drops of the enhancing agents onto substrate surfaces with Rose Bengal monolayers, an enhancement of about 27 times, compared with the control sample, is achieved by using the Ag@SiO2 nanoparticles with shells of about 3 nm, whereas an enhancement of around 11.7 times is obtained when using those with thicker shells. The effects of shell thickness and surface density of the enhancing agents on the enhancement have been investigated experimentally. The results show that this method can be potentially helpful in fluorescence‐based surface analysis.
Electrochemical Biosensor Assay of the Interaction between [PtCln(NH3)4–n](2–n) (n = 0–4) Complexes and ds‐DNA
Authors: Ravera Mauro , Gabano Elisabetta , Sardi Manuele , Alessio Manuela , Osella Domenico 
Published: February 2011

AbstractWe report on the results of electrochemical DNA biosensor assay of the interaction between double‐stranded DNA (ds‐DNA) and a series of six neutral, anionic or cationic Pt complexes of the general formula [PtCln(NH3)4–n](2–n) [n = 4, 1; n = 3, 2; n = 2, isomers cisplatin (3) and transplatin (4); n = 1, 5; n = 0, 6]. The ability of the electrophilic PtII agents generated in solution to interact with DNA, and hence to form Pt–DNA adducts, was measured as a function of the decrease in the guanine oxidation signal recorded on a screen‐printed electrode by using square wave voltammetry. Hydrolysis of the platinum complexes was studied by using time‐resolved RP‐HPLC and conductivity measurements to determine the aquation rate, which modulates the formation of the electrophilic agent prone to quickly interact with DNA. Our findings indicate that, if time is allowed for sufficient hydrolysis to occur, the interaction of these PtII complexes with ds‐DNA follows the order 2 > 1 > 3 ≈ 4 > 5 >> 6.
Food insecurity and the relationship between household income and children's health and nutrition in Brazil
Authors: Reis Mauricio 
Published: February 2011

SUMMARYEmpirical evidence indicates that children living in wealthier households have better health. Food insecurity could be related to lack of adequate nutrition experienced by poor children and may be pointed out as one of the possible explanations for this relationship. This paper investigates the association between food insecurity and children's health and nutrition and the role of the former in the child health income gradient. Using data from the 2006 Brazilian Demographic and Health Survey, the results show that children living in households with food insecurity have worse nutrition and health indicators. In addition, the relationship between household income and many children's health and nutrition measures weakens but remains significant when controlling for food insecurity. Copyright © 2011 John Wiley & Sons, Ltd.
A systematic review of salicylates in foods: Estimated daily intake of a Scottish population
Authors: Wood Adrian , Baxter Gwen , Thies Frank , Kyle Janet , Duthie Garry 
Published: February 2011

AbstractSeveral studies suggest that natural salicylates in plant‐based foods may benefit health. However, large variation in published values of the salicylate content of foods means that relating dietary intakes to disease risk is problematical. Consequently, we have systematically reviewed the available literature using prescribed selection criteria. By combining these literature values with in‐house analysis, we have constructed a food composition database describing median salicylate values for 27 different types of fruits, 21 vegetables, 28 herbs, spices and condiments, 2 soups and 11 beverages. Application of a validated food frequency questionnaire estimated median dietary intakes of 4.42 (range 2.90–6.27) and 3.16 (2.35–4.89) mg/day for Scottish males and females, respectively. Major dietary sources of salicylates were alcoholic beverages (22%), herbs and spices (17%), fruits (16%), non‐alcoholic beverages including fruit juices (13%), tomato‐based sauces (12%) and vegetables (9%). Application of the database to populations with differing dietary habits and disease risk profiles may provide further evidence for the role of dietary salicylates in the prevention of chronic diseases.
Oxidative metabolism of the mycotoxins alternariol and alternariol‐9‐methyl ether in precision‐cut rat liver slices in vitro
Authors: Burkhardt Britta , Wittenauer Judith , Pfeiffer Erika , Schauer Ute M. D. , Metzler Manfred 
Published: February 2011

AbstractScope: Monohydroxylation of alternariol (AOH) and alternariol‐9‐methyl ether (AME) has previously been reported as a prominent metabolic route under cell‐free conditions. This pathway gives rise to several catechol metabolites and may therefore be of toxicological relevance.Methods and results: To clarify whether hydroxylation of AOH and AME occurs under in vivo‐like conditions in the presence of conjugation reactions, the metabolism of the Alternaria toxins has now been studied in precision‐cut rat liver slices. Four catechol metabolites of AOH and two of AME, together with several of their O‐methylation products, as catalyzed by catechol‐O‐methyl transferase, were clearly identified after incubation of the liver slices with AOH and AME. These metabolites were predominantly present as conjugates with glucuronic acid and/or sulfate. In preliminary studies with bile duct‐cannulated male rats dosed with AOH by gavage, the four monohydroxylated metabolites of AOH could also be demonstrated in the bile either as catechols or as O‐methyl ethers.Conclusion: These experiments clearly show that AOH and AME undergo catechol formation in vivo and warrant closer examination of the toxicological significance of this metabolic pathway.
Multiple testing of treatment‐effect‐modifying biomarkers in a randomized clinical trial with a survival endpoint
Authors: Michiels Stefan , Potthoff Richard F. , George Stephen L. 
Published: February 2011

AbstractThe recent revolution in genomics and the advent of targeted therapies have increased interest in biomarker‐defined subgroups of patients who respond to therapy or exhibit specific toxicities. Such biomarker‐defined subgroups are also being investigated for non‐targeted therapies (e.g. chemotherapy and statins). However, even when the targeting pathway has been identified, a broadly available test to identify the appropriate subgroup will rarely exist prior to the launch of the pivotal phase III trial.Our aim in this paper is to provide guidance for the analysis of a phase III clinical trial with a survival endpoint, in order to ascertain whether a therapy is more effective in the biomarker‐positive patients as compared with biomarker‐negative patients, when the trial is conducted on the entire population and when there are multiple candidate biomarkers. We studied treatment‐by‐biomarker interactions in a Weibull regression model. Different permutation procedures, using single‐biomarker statistics and novel composite statistics, are proposed in order to control the family‐wise error rate accounting for dependence structures among the biomarkers. A simulation study was performed to compare the operational characteristics of the permutation tests under different scenarios. The tests were applied to a phase III trial of adjuvant chemotherapy in early breast cancer, for which 10 biomarkers were measured in tumor samples from 798 patients.These permutation tests can be applied to retrospective biomarker studies and to prospective phase III trials of new drugs for which a few clues are known about the targeting pathway at the start of the trial. Copyright © 2011 John Wiley & Sons, Ltd.
Proportional odds model for dose‐finding clinical trial designs with ordinal toxicity grading
Authors: Meter Emily M. Van , Garrett‐Mayer Elizabeth , Bandyopadhyay Dipankar 
Published: February 2011

AbstractCurrently many dose‐finding clinical trial designs, including the continual reassessment method (CRM) and the standard ‘ 3 + 3’ design, dichotomize toxicity outcomes based on the pre‐specified dose‐limiting toxicity (DLT) criteria. This loss of information is particularly inefficient due to the small sample sizes in phase I trials. Common Toxicity Criteria (CTCAEv3.0) classify adverse events into grades 1–5, which range from 1 as a mild adverse event to 5 as death related to an adverse event. In this paper, we extend the CRM to include ordinal toxicity outcomes as specified by CTCAEv3.0 using the proportional odds model (POM) and compare results with the dichotomous CRM. A sensitivity analysis of the new design compares various target DLT rates, sample sizes, and cohort sizes. This design is also assessed under various dose–toxicity relationship models including POMs as well as those that violate the proportional odds assumption. A simulation study shows that the proportional odds CRM performs as well as the dichotomous CRM on all criteria compared (including safety criteria such as percentage of patients treated at highly toxic or suboptimal dose levels) and with improved estimation of the maximum tolerated dose when the PO assumption is not violated. These findings suggest that it is beneficial to incorporate ordinal toxicity endpoints into phase I trial designs. Copyright © 2011 John Wiley & Sons, Ltd.