bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lineage Divergence at the First TCR-Dependent Checkpoint: Preferential γδ and Impaired αβ T Cell Development in Nonobese Diabetic Mice
Authors: Feng Ni , Vegh Patricia , Rothenberg Ellen V. , Yui Mary A. 
Published: December 2010

Abstract
The first TCR-dependent checkpoint in the thymus determines αβ versus γδ T lineage fate and sets the stage for later T cell differentiation decisions. We had previously shown that early T cells in NOD mice that are unable to rearrange a TCR exhibit a defect in checkpoint enforcement at this stage. To determine if T cell progenitors from wild-type NOD mice also exhibit cell-autonomous defects in development, we investigated their differentiation in the Notch-ligand–presenting OP9-DL1 coculture system, as well as by analysis of T cell development in vivo. Cultured CD4 and CD8 double-negative cells from NOD mice exhibited major defects in the generation of CD4 and CD8 double-positive αβ T cells, whereas γδ T cell development from bipotent precursors was enhanced. Limiting dilution and single-cell experiments show that the divergent effects on αβ and γδ T cell development did not spring from biased lineage choice but from increased proliferation of γδ T cells and impaired accumulation of αβ T lineage double-positive cells. In vivo, NOD early T cell subsets in the thymus also show characteristics indicative of defective β-selection, and peripheral αβ T cells are poorly established in mixed bone marrow chimeras, contrasting with strong γδ T as well as B cell repopulation. Thus, NOD T cell precursors reveal divergent, lineage-specific differentiation abnormalities in vitro and in vivo from the first TCR-dependent developmental choice point, which may have consequences for subsequent lineage decisions and effector functions.
Loss of IL-17–Producing CD8 T Cells during Late Chronic Stage of Pathogenic Simian Immunodeficiency Virus Infection
Authors: Nigam Pragati , Kwa Suefen , Velu Vijayakumar , Amara Rama Rao 
Published: December 2010

Abstract
Progressive disease caused by pathogenic SIV/HIV infections is marked by systemic hyperimmune activation, immune dysregulation, and profound depletion of CD4+ T cells in lymphoid and gastrointestinal mucosal tissues. IL-17 is important for protective immunity against extracellular bacterial infections at mucosa and for maintenance of mucosal barrier. Although IL-17–secreting CD4 (Th17) and CD8 (Tc17) T cells have been reported, very little is known about the latter subset for any infectious disease. In this study, we characterized the anatomical distribution, phenotype, and functional quality of Tc17 and Th17 cells in healthy (SIV−) and SIV+ rhesus macaques. In healthy macaques, Tc17 and Th17 cells were present in all lymphoid and gastrointestinal tissues studied with predominance in small intestine. About 50% of these cells coexpressed TNF-α and IL-2. Notably, ∼50% of Tc17 cells also expressed the co-inhibitory molecule CTLA-4, and only a minority (&lt;20%) expressed granzyme B suggesting that these cells possess more of a regulatory than cytotoxic phenotype. After SIV infection, unlike Th17 cells, Tc17 cells were not depleted during the acute phase of infection. However, the frequency of Tc17 cells in SIV-infected macaques with AIDS was lower compared with that in healthy macaques demonstrating the loss of these cells during end-stage disease. Antiretroviral therapy partially restored the frequency of Tc17 and Th17 cells in the colorectal mucosa. Depletion of Tc17 cells was not observed in colorectal mucosa of chronically infected SIV+ sooty mangabeys. In conclusion, our results suggest a role for Tc17 cells in regulating disease progression during pathogenic SIV infection.
Bcl-2–Interacting Mediator of Cell Death Influences Autoantigen-Driven Deletion and TCR Revision
Authors: Hale J. Scott , Nelson Lisa T. , Simmons Kalynn B. , Fink Pamela J. 
Published: December 2010

Abstract
Peripheral CD4+Vβ5+ T cells are tolerized to an endogenous mouse mammary tumor virus superantigen either by deletion or TCR revision. Through TCR revision, RAG reexpression mediates extrathymic TCRβ rearrangement and results in a population of postrevision CD4+Vβ5− T cells expressing revised TCRβ chains. We have hypothesized that cell death pathways regulate the selection of cells undergoing TCR revision to ensure the safety and utility of the postrevision population. In this study, we investigate the role of Bcl-2–interacting mediator of cell death (Bim)-mediated cell death in autoantigen-driven deletion and TCR revision. Bim deficiency and Bcl-2 overexpression in Vβ5 transgenic (Tg) mice both impair peripheral deletion. Vβ5 Tg Bim-deficient and Bcl-2 Tg mice exhibit an elevated frequency of CD4+ T cells expressing both the transgene-encoded Vβ5 chain and a revised TCRβ chain. We now show that these dual-TCR–expressing cells are TCR revision intermediates and that the population of RAG-expressing, revising CD4+ T cells is increased in Bim-deficient Vβ5 Tg mice. These findings support a role for Bim and Bcl-2 in regulating the balance of survival versus apoptosis in peripheral T cells undergoing RAG-dependent TCR rearrangements during TCR revision, thereby ensuring the utility of the postrevision repertoire.
A Role for Immature Myeloid Cells in Immune Senescence
Authors: Enioutina Elena Y. , Bareyan Diana , Daynes Raymond A. 
Published: December 2010

Abstract
The reduced efficiency of the mammalian immune system with aging increases host susceptibility to infectious and autoimmune diseases. However, the mechanisms responsible for these pathologic changes are not well understood. In this study, we demonstrate that the bone marrow, blood, and secondary lymphoid organs of healthy aged mice possess increased numbers of immature myeloid cells that are phenotypically similar to myeloid-derived suppressor cells found in lymphoid organs of mice with progressive tumors and other pathologic conditions associated with chronic inflammation. These cells are characterized by the presence of Gr1 and CD11b markers on their surfaces. Gr1+CD11b+ cells isolated from aged mice possess an ability to suppress T cell proliferation/activation and produce heightened levels of proinflammatory cytokines, both constitutively and upon activation, including IL-12, which promotes an excessive production of IFN-γ. IFN-γ priming is essential for excessive proinflammatory cytokine production and the suppressive activities by Gr1+CD11b+ cells from aged mice. These cells suppress T cell proliferation through an NO-dependent mechanism, as depletion of splenic Gr1+ cells reduces NO levels and restores T cell proliferation. Insights into mechanisms responsible for the proinflammatory and immune suppressive activities of Gr1+CD11b+ cells from aged mice have uncovered a defective PI3K–Akt signaling pathway, leading to a reduced Akt-dependent inactivation of GSK3β. Our data demonstrate that abnormal activities of the Gr1+CD11b+ myeloid cell population from aged mice could play a significant role in the mechanisms responsible for immune senescence.
“Everybody had a piece …”: Collaborative practice and shared decision making at the Open Book
Authors: Gordon John , Ramdeholl Dianne 
Published: December 2010

AbstractIn an attempt to preserve the field's collective historical memory, the authors in this chapter explore participatory practices at the Open Book, an adult literacy program in Brooklyn, from 1985–2002. Students' roles in shaping those practices are examined and reflections on the possibilities for building democratic communities in literacy programs, particularly in the current context, are included.
Rett syndrome: Revised diagnostic criteria and nomenclature
Authors: Jeffrey L. Neul  , Kaufmann Walter E. , Glaze Daniel G. , Christodoulou John , Clarke Angus J. , Bahi‐Buisson Nadia , Leonard Helen , Bailey Mark E. S. , Schanen N. Carolyn , Zappella Michele , Renieri Alessandra , Huppke Peter , Percy Alan K. ,   for the RettSearch Consortium (Members listed in the Appendix)
Published: December 2010

AbstractObjectiveRett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl‐CpG‐binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was to revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials.MethodRettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT.ResultsThe clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed.InterpretationThese revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research. Ann Neurol 2010
Highly phosphomannosylated enzyme replacement therapy for GM2 gangliosidosis
Authors: Tsuji Daisuke , Akeboshi Hiromi , Matsuoka Kazuhiko , Yasuoka Hiroko , Miyasaki Eri , Kasahara Yoshiko , Kawashima Ikuo , Chiba Yasunori , Jigami Yoshifumi , Taki Takao , Sakuraba Hitoshi , Itoh Kohji 
Published: December 2010

AbstractObjective:Novel recombinant human lysosomal β‐hexosaminidase A (HexA) was developed for enzyme replacement therapy (ERT) for Tay‐Sachs and Sandhoff diseases, ie, autosomal recessive GM2 gangliosidoses, caused by HexA deficiency.Methods:A recombinant human HexA (Om4HexA) with a high mannose 6‐phosphate (M6P)‐type‐N‐glycan content, which was produced by a methylotrophic yeast strain, Ogataea minuta, overexpressing the OmMNN4 gene, was intracerebroventricularly (ICV) administered to Sandhoff disease model mice (Hexb−/− mice) at different doses (0.5–2.5mg/kg), and then the replacement and therapeutic effects were examined.Results:The Om4HexA was widely distributed across the ependymal cell layer, dose‐dependently restored the enzyme activity due to uptake via cell surface cation‐independent M6P receptor (CI‐M6PR) on neural cells, and reduced substrates, including GM2 ganglioside (GM2), asialo GM2 (GA2), and oligosaccharides with terminal N‐acetylglucosamine residues (GlcNAc‐oligosaccharides), accumulated in brain parenchyma. A significant inhibition of chemokine macrophage inflammatory protein‐1 α (MIP‐1α) induction was also revealed, especially in the hindbrain (<63%). The decrease in central neural storage correlated with an improvement of motor dysfunction as well as prolongation of the lifespan.Interpretation:This lysosome‐directed recombinant human enzyme drug derived from methylotrophic yeast has the high therapeutic potential to improve the motor dysfunction and quality of life of the lysosomal storage diseases (LSDs) patients with neurological manifestations. We emphasize the importance of neural cell surface M6P receptor as a delivery target of neural cell‐directed enzyme replacement therapy (NCDERT) for neurodegenerative metabolic diseases. ANN NEUROL 2010
Kopplungseffekte in optischen Metamaterialien
Authors: Liu Na , Giessen Harald 
Published: December 2010

AbstractMetamaterialien haben sich zu einem sehr interessanten Gebiet der Photonik entwickelt, seit John Pendry seine Arbeiten über den negativen Brechungsindex, Tarnkappen und Unsichtbarkeit sowie über perfekte Linsen veröffentlichte. Für jegliche praktischen Anwendungen werden dreidimensionale Metamaterialien benötigt. In diesen Materialien spielen bei den optischen und elektronischen Eigenschaften Kopplungseffekte zwischen individuellen Konstituenten eine Schlüsselrolle. Metamaterialien weisen sowohl elektronische wie auch magnetische Resonanzen bei optischen Frequenzen auf. Deswegen stellen elektrische und magnetische Dipol‐Dipol‐Wechselwirkungen wie auch Multipole höherer Ordnung den essenziellen Wechselwirkungsmechanismus dar. Je nach strukturellem Aufbau können sowohl longitudinale als auch transversale Kopplungseffekte auftreten. Das detaillierte Zusammenspiel zwischen den verschiedenen Kopplungsmechanismen bei der Plasmonenhybridisierung ist ein nützliches Hilfsmittel, um den Übergang von eher molekülartigen Zuständen bis hin zu festkörperartigen Banden zu verstehen.
Influence of backbone rigidity on the curing and the dielectric relaxations of unsaturated polyesters
Authors: Simitzis J. , Triantou D. , Soulis S. , Tsangaris G. , Zoumpoulakis L. , Manolopoulos E. 
Published: December 2010

AbstractUnsaturated polyesters with maleic acid and different molar ratio of phthalic anhydride to adipic acid were produced, mixed with styrene, and cured. The degree of double bonds conversion, determined by differential scanning calorimetry (αDSC), indicating the initial curing, increases significantly with the molar ratio of phthalic anhydride. On the other hand, the degree of double bonds conversion of maleate (αUP,FTIR) and styrene (αSt,FTIR) units determined by Fourier transform infrared spectroscopy after prolonged curing are considerably higher than αDSC and increase slightly with the molar ratio of phthalic anhydride. Polyester containing phthalic anhydride without adipic acid (M5P5) has the lowest tetrahydrofuran uptake and diffusion parameter D/α2 due to its more rigid segments, in opposite to polyester containing adipic acid (M5A5) having the highest values. According to dielectric spectroscopy measurements, two different relaxations were determined, one beginning above 130°C (with peak above 180°C) attributed to α‐relaxation (dielectric glass transition) and a second one at lower temperatures, attributed to β‐relaxation. The peak of β‐relaxation is at around 130, 75–80, and 30°C for the rigid, intermediate rigidity/flexibility, and flexible polyesters, respectively. The α‐relaxation is determined at low frequencies and the β‐relaxation at intermediate or high frequencies. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Novel Aspergillus hemicellulases enhance performance of commercial cellulases in lignocellulose hydrolysis
Authors: Shin Hyun‐Dong , Vo Trinh , Chen Rachel 
Published: December 2010

AbstractA novel hemicellulase‐producing fungal strain was isolated from a local soil sample. The organism is identified as Aspergillus fumigatus based on ribosomal RNA analyses. The Aspergillus strain, designated as 2NB, produces both enzymes acting on xylan backbone (xylanase and β‐xylosidase), and those acting on side chains (or accessory enzymes) notably α‐arabinofuranosidase and acetyl‐xylan esterase. The Asperigillus hemicellulases are characterized as having relatively low xylanase and β‐xylosidase activities but high side chain removal activities. The activity ratio of side‐chain acting enzymes to xylanase is higher than that of the Multifect enzyme, a commercial hemicellulase product. The potential of the novel hemicellulases in lignocelluloses bioprocessing was demonstrated with alkaline‐pretreated switchgrass as lignocellulose substrate with hemicellulase supplemented with a ratio of xylanase activity to filter paper unit of 2:1. Supplement of Aspergillus hemicellulases to commercial cellulases significantly enhanced the hydrolysis of lignocellulose, achieving a 94% hydrolysis yield based on reducing sugar measurement, compared to 60% when no hemicellulase or 75% when Multifect enzyme was used under otherwise identical conditions. The significant improvement resulting from supplementing a hemicellulase mix with high side‐chain removal activities suggests the importance of accessory hemicellulases in lignocellulose processing. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Championing the interface between mental health and child protection: evaluation of a service initiative to improve joint working in northern Ireland
Authors: Davidson Gavin , Duffy Joe , Barry Liz , Curry Patsy , Darragh Eithne , Lees Judith 
Published: December 2010

The importance of establishing effective inter‐agency working between adult mental health services and child care services in order to safeguard children has been repeatedly identified by research, policy, inquiries and inspection reports. This article reports on the evaluation of an initiative in one health and social care trust in Northern Ireland that aimed to facilitate joint working and so improve service provision and protection for children and families. The Champions Initiative involved identifying a Champion in each multidisciplinary community mental health team and in each family and child care team that would have responsibility for providing information, promoting joint working and identifying any obstacles to better cooperation. The evaluation of this Initiative assessed levels of experience, training, confidence, understanding and awareness in the Champions and their team members at baseline. The Champions and their Team Leaders were then followed up after six months to obtain their qualitative views of the impact of the initiative. The results include comparisons between mental health and child care staff, and crucially, views about whether the initiative has had any impact on working together. This study also generated recommendations for further service development in this complex and important area of practice. Copyright © 2010 John Wiley & Sons, Ltd.‘Identifying a Champion in each multidisciplinary community mental health team and in each family and child care team’
Synthesis and Characterization of Titanium Dioxide Phases in Mesostructured Silica Matrices with Photocatalytic Activity
Authors: Gopala Divakara Soorly , Bhattacharjee Rama Ranjan , Haerr Robert , Yeginoglu Bener , Pavel Octavian Dumitru , Cojocaru Bogdan , Parvulescu Vasile I. , Richards Ryan M. 
Published: December 2010

AbstractAn imidazole type ionic liquid (IL), 1‐hexadecyl‐3‐methylimidazolium chloride (I16IL) was used as a template in the preparation of mesoporous silica with incorporated titanium dioxide. In this process, the IL is the structural template as well as the source of the Ti. The steps leading to the formation of the nanocrystalline metal oxide include: a) formation of metal‐containing IL (M‐IL); b) using the M‐IL as a template for the mesoporous silica; c) calcination of the sample to remove the organic moiety, while leaving the metal centers to form oxides on the porous framework. By varying the TiO2–SiO2 calcination temperature, the particle size and phase of TiO2 have been studied. These TiO2–SiO2 hybrid materials were characterized by using various physicochemical techniques, such as UV/Vis diffuse‐reflectance spectroscopy, Raman spectroscopy, X‐ray diffraction, N2 adsorption‐desorption isotherm measurement, Fourier transform infrared spectroscopy, and transmission electron microscopy. The resultant hybrid silica demonstrated effective photocatalytic activity for the oxidation of cyclohexene and styrene.
The diagnostic utility of CK5/6 and p63 in fine‐needle aspiration of the breast lesions diagnosed as proliferative fibrocystic lesion
Authors: Al‐Maghraby Hatem , Ghorab Zeina , Khalbuss Walid , Wong John , Silverman Jan F. , Saad Reda S. 
Published: December 2010

AbstractFine‐needle aspiration (FNA) biopsy (FNAB) in the preoperative assessment of breast lesions has shown diagnostic limitations with false‐positive and false‐negative diagnoses. We investigated the diagnostic value of cytokeratin 5/6 (CK5/6) and p63 in a series of breast FNABs, diagnosed as proliferative breast lesions with or without atypia, to see whether these ancillary studies enhance the ability to make an accurate diagnosis by FNAB. Sixty‐four breast FNABs were retrieved between January 2000 and December 2005 and included in the study as follows: 29/64 (45%) cases as proliferative with atypia and 35/64 (55%) without atypia. We also included 10 cases of fibroadenoma. All cases had histological follow‐up available for correlation. Immunostaining for CK5/6 and p63 was performed on the cell block material in all cases. The percentage of staining cells in the specimen was graded as 0 (0–10%), 1 (11–25%), 2 (26–50%), and 3 (>50%). There were 9/29 (31%) cases in the atypical group that were found to be malignant on resection, compared with 6/35 (17%) in the cases without atypia. In histologically proven malignant cases, CK5/6 was negative in 11/15 (73%) or showed 1+ stain in 2/15 (13%) cases. In benign breast lesions, CK5/6 stained more than 25% of cell proliferation in 44/49 (90%). p63 showed characteristic staining for single naked bipolar nuclei in the background of the specimen (not appreciated by CK5/6) in all fibroadenoma cases. In conclusion, CK5/6 may enhance the ability to differentiate between benign and malignant epithelial proliferations in breast FNABs. In fibroepithelial lesions, p63 may be more useful than CK5/6. Diagn. Cytopathol. 2011. © 2010 Wiley Periodicals, Inc.
Using an iterative approach to economic evaluation in the drug development process
Authors: Boyd Kathleen Anne , Fenwick Elisabeth , Briggs Andrew 
Published: December 2010

AbstractThe pharmaceutical industry has a well‐known and formally recognized process for drug development, consisting of four distinct phases of clinical assessment. Similar to this drug development process, there is a five‐stage iterative process for economic evaluation, beginning with early indicative studies and progressing toward more rigorous assessment as data become available. This overview outlines the four phases of drug development and the five‐stage iterative approach to economic evaluation. The commonalities of the two approaches are discussed, drawing parallels in support of the case for incorporating an iterative economic process into the drug development process. Both frameworks support a process of information gathering and reducing uncertainty in order to improve decision making. In the context of commercial and public funding for economic evaluation, it is more efficient and beneficial to invest in an iterative approach to economic evaluation throughout the drug or technology lifecycle rather than using a restrictive, one‐off trial‐based approach, which provides limited information on the true cost‐effectiveness of the technology. Drug Dev Res 71: 470–477, 2010. © 2010 Wiley‐Liss, Inc.
How does NICE value innovation?
Authors: Garner Sarah 
Published: December 2010

AbstractNo country can afford all the health care interventions that might benefit patients. Demand will always outstrip available resources, so priorities have to be agreed upon. Such decisions are controversial, making it vital that they are underpinned by robust transparent processes and methods. In the United Kingdom, this is the responsibility of the National Institute for Health and Clinical Excellence (NICE). In 2009, in response to challenges that NICE was not giving sufficient value to innovation, an independent enquiry was undertaken by Sir Ian Kennedy. The enquiry raised important questions about whether NICE should only offer incentives for innovation when the benefits are actually seen by the National Health Service (NHS) as improved outcomes for patients, or whether future, but as yet unrealized, benefits such as the subsequent development of the next generation of drugs should be taken into account. There is a UK government commitment to value‐based pricing but questions remain about how this could value innovation. Potential solutions are an increased use of NICE's “only in research” recommendations and exploration of novel trial designs. Drug Dev Res 71: 449–456, 2010. © 2010 Wiley‐Liss, Inc.