bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sublingual Immunization with Nonreplicating Antigens Induces Antibody-Forming Cells and Cytotoxic T Cells in the Female Genital Tract Mucosa and Protects against Genital Papillomavirus Infection
Authors: Çuburu Nicolas , Kweon Mi-Na , Hervouet Catherine , Cha Hye-Ran , Pang Yuk-Ying S. , Holmgren Jan , Stadler Konrad , Schiller John T. , Anjuère Fabienne , Czerkinsky Cecil 
Published: November 2009

Abstract
We have recently reported that the sublingual (s.l.) mucosa is an efficient site for inducing systemic and mucosal immune responses. In this study, the potential of s.l. immunization to induce remote Ab responses and CD8+ cytotoxic responses in the female genital tract was examined in mice by using a nonreplicating Ag, OVA, and cholera toxin (CT) as an adjuvant. Sublingual administration of OVA and CT induced Ag-specific IgA and IgG Abs in blood and in cervicovaginal secretions. These responses were associated with large numbers of IgA Ab-secreting cells (ASCs) in the genital mucosa. Genital ASC responses were similar in magnitude and isotype distribution after s.l., intranasal, or vaginal immunization and were superior to those seen after intragastric immunization. Genital, but not blood or spleen, IgA ASC responses were inhibited by treatment with anti-CCL28 Abs, suggesting that the chemokine CCL28 plays a major role in the migration of IgA ASC progenitors to the reproductive tract mucosa. Furthermore, s.l. immunization with OVA induced OVA-specific effector CD8+ cytolytic T cells in the genital mucosa, and these responses required coadministration of the CT adjuvant. Furthermore, s.l. administration of human papillomavirus virus-like particles with or without the CT adjuvant conferred protection against genital challenge with human papillomavirus pseudovirions. Taken together, these findings underscore the potential of s.l. immunization as an efficient vaccination strategy for inducing genital immune responses and should impact on the development of vaccines against sexually transmitted diseases.
B7-1/2 (CD80/CD86) Direct Signaling to B Cells Enhances IgG Secretion
Authors: Rau Friederike C. , Dieter Jacquelyn , Luo Zhang , Priest Stephen O. , Baumgarth Nicole 
Published: November 2009

AbstractB cell responses are regulated by Ag recognition, costimulatory signals provided by interaction with helper T cells, and by innate signals. We recently provided evidence for a link between the effects of innate and costimulatory signals on B cells during influenza virus infection, by demonstrating that most B cells in the regional lymph nodes of the respiratory tract enhance surface expression of the costimulator B7-2 (CD86) within 24–48 h following infection via a type I IFNR-dependent mechanisms, a finding we are confirming here. While the role of B7-1/2 for helper T cell activation is well documented, its role in direct B cell regulation is poorly understood. Here, our in vivo studies with mixed bone marrow irradiation chimeric mice, lacking B7-1/2 only on B cells, demonstrated that B7-1/2 expression is crucial for induction of maximal local, but to a lesser extent systemic, IgG Ab responses following influenza virus infection. In contrast to mice that completely lack B7-1/2 expression, loss of B7-1/2 on B cells alone did not significantly affect germinal center formation or the extent of CD4+ T cell activation and IFN-γ secretion. Instead, our in vitro studies identify a dramatic effect of B7-2 engagement on IgG, but not IgM secretion by already class-switched B cells. Concomitantly, B7-2 engagement induced expression of X-box binding protein 1 (XBP-1) and spliced XBP1, evidence for increased protein synthesis by these cells. Taken together, these results identify direct signaling through B7-1/2 as a potent regulator of IgG secretion by previously activated B cells.
Activation, Immune Polarization, and Graft-versus-Leukemia Activity of Donor T Cells Are Regulated by Specific Subsets of Donor Bone Marrow Antigen-Presenting Cells in Allogeneic Hemopoietic Stem Cell Transplantation
Authors: Li Jian-Ming , Southerland Lauren T. , Lu Ying , Darlak Kataryna A. , Giver Cynthia R. , McMillin Douglas W. , Harris Wayne A. C. , Jaye David L. , Waller Edmund K. 
Published: November 2009

AbstractWe investigated the roles of specific subsets of donor APCs purified from bone marrow in donor T cell activation and graft-vs-leukemia (GvL) activity in murine models of hemopoietic stem cell transplantation. Lineage−CD11c+ APC precursors were separated from donor bone marrow based on expression of CD11b. Transplanting lineage−CD11c+CD11b− APC (CD11b− APC) in combination with c-kit+Sca-1+lineage− hemopoietic stem cells (HSC) and congenic donor T cells led to increased donor CD4+ and CD8+ T cell proliferation and higher donor T cell chimerism than with transplanting grafts containing HSC, T cells, and lineage−CD11c+CD11b+ APCs (CD11b+ APC), or grafts containing only HSC and T cells. Transplanting CD11b− APCs induced Th1/type 1 cytotoxic T lymphocyte donor T cell immune polarization and enhanced GvL activity of donor T cells without increased graft-vs-host disease in both MHC- and minor histocompatibility Ag-mismatched murine hemopoietic stem cell transplantation models, whereas CD11b+ APCs led to Th2/type 2 cytotoxic T lymphocyte donor T cell immune polarization. Donor CD11b− APCs were plasmacytoid dendritic cell progenitors (&gt;90% CD317; PDCA-1+) and up-regulated CD80, CD86, and IL-12 during alloantigen presentation, whereas CD11b+ APCs expressed Gr-1 and up-regulated expression of programmed death ligands-1 and 2 after activation. These results are the first to show that manipulation of the content of donor APCs in allogeneic HSC grafts can regulate donor T cell immunity and enhance GvL without increasing graft-vs-host disease activity.
Human Activated T Lymphocytes Modulate IDO Expression in Tumors through Th1/Th2 Balance
Authors: Godin-Ethier Jessica , Pelletier Sandy , Hanafi Laïla-Aïcha , Gannon Philippe O. , Forget Marie-Andrée , Routy Jean-Pierre , Boulassel Mohamed-Rachid , Krzemien Urszula , Tanguay Simon , Lattouf Jean-Baptiste , Arbour Nathalie , Lapointe Réjean 
Published: November 2009

Abstract
Previous cancer vaccination approaches have shown some efficiency in generating measurable immune responses, but they have rarely led to tumor regression. It is therefore possible that tumors emerge with the capacity to down-regulate immune counterparts, through the local production of immunosuppressive molecules, such as IDO. Although it is known that IDO exerts suppressive effects on T cell functions, the mechanisms of IDO regulation in tumor cells remain to be characterized. Here, we demonstrate that activated T cells can induce functional IDO expression in breast and kidney tumor cell lines, and that this is partly attributable to IFN-γ. Moreover, we found that IL-13, a Th2 cytokine, has a negative modulatory effect on IDO expression. Furthermore, we report IDO expression in the majority of breast and kidney carcinoma samples, with infiltration of activated Th1-polarized T cells in human tumors. These findings demonstrate complex control of immune activity within tumors. Future immune therapeutic interventions should thus include strategies to counteract these negative mechanisms.
RasGRP1 Is Required for Human NK Cell Function
Authors: Lee Suk Hyung , Yun Sohyun , Lee Jiwon , Kim Mi Jeong , Piao Zheng-Hao , Jeong Mira , Chung Jin Woong , Kim Tae-Don , Yoon Suk Ran , Greenberg Philip D. , Choi Inpyo 
Published: November 2009

Abstract
Cross-linking of NK activating receptors activates phospholipase-γ and subsequently induces diacylglycerol and Ca2+ as second messengers of signal transduction. Previous studies reported that Ras guanyl nucleotide-releasing protein (RasGRP) 1, which is activated by diacylglycerol and Ca2+, is crucial for TCR-mediated Ras-ERK activation. We now report that RasGRP1, which can also be detected in human NK cells, plays an essential role in NK cell effector functions. To examine the role of RasGRP1 in NK cell functions, the expression of RasGRP1 was suppressed using RNA interference. Knockdown of RasGRP1 significantly blocked ITAM-dependent cytokine production as well as NK cytotoxicity. Biochemically, RasGRP1-knockdown NK cells showed markedly decreased ability to activate Ras, ERK, and JNK. Activation of the Ras-MAPK pathway was independently shown to be indispensable for NK cell effector functions via the use of specific pharmacological inhibitors. Our results reveal that RasGRP1 is required for the activation of the Ras-MAPK pathway leading to NK cell effector functions. Moreover, our data suggest that RasGRP1 might act as an important bridge between phospholipase-γ activation and NK cell effector functions via the Ras-MAPK pathway.
Bim-Mediated Apoptosis Is Not Necessary for Thymic Negative Selection to Ubiquitous Self-Antigens
Authors: Hu Qian , Sader Alyssa , Parkman Julia C. , Baldwin Troy A. 
Published: November 2009

Abstract
T cell education in the thymus is critical for establishing a functional, yet self-tolerant, T cell repertoire. Negative selection is a key process in enforcing self-tolerance. There are many questions that surround the mechanism of negative selection, but it is currently held that apoptosis initiated by Bim and/or Nur77 is critical for negative selection. Recent studies, however, have questioned the necessity of Bim in maintaining both central and peripheral T cell tolerance. To reconcile these apparently contradictory findings, we examined the role of Bim in negative selection in the well-characterized, physiological HYcd4 mouse model. We found that while Bim expression was required for CD4+CD8+ double-positive thymocyte apoptosis, it was not required for negative selection. Furthermore, Bim deficiency did not alter the frequency or affinity of male reactive cells that escape negative selection in an oligoclonal repertoire. Collectively, these studies indicate that negative selection occurs efficiently in the absence of apoptosis and suggest that the current paradigm of negative selection requiring apoptosis be revisited.
Thymus-Blood Protein Interactions Are Highly Effective in Negative Selection and Regulatory T Cell Induction
Authors: Atibalentja Danielle F. , Byersdorfer Craig A. , Unanue Emil R. 
Published: November 2009

AbstractUsing hen egg-white lysozyme, the effect of blood proteins on CD4 thymic cells was examined. A small fraction of i.v. injected hen egg-white lysozyme rapidly entered the thymus into the medulla. There it was captured and presented by dendritic cells (DCs) to thymocytes from two TCR transgenic mice, one directed to a dominant peptide and a second to a poorly displayed peptide, both presented by MHC class II molecules I-Ak. Presentation by DC led to negative selection and induction of regulatory T cells, independent of epithelial cells. Presentation took place at very low levels, less than 100 peptide-MHC complexes per DC. Such low levels could induce negative selection, but even lower levels could induce regulatory T cells. The anatomy of the thymus-blood barrier, the highly efficient presentation by DC, together with the high sensitivity of thymic T cells to peptide-MHC complexes, results in blood protein Ags having a profound effect on thymic T cells.
Tracking the Total CD8 T Cell Response to Infection Reveals Substantial Discordance in Magnitude and Kinetics between Inbred and Outbred Hosts
Authors: Rai Deepa , Pham Nhat-Long L. , Harty John T. , Badovinac Vladimir P. 
Published: November 2009

Abstract
Determining the magnitude and kinetics, together with the phenotypic and functional characteristics of responding CD8 T cells, is critical for understanding the regulation of adaptive immunity as well as in evaluating vaccine candidates. Recent technical advances have allowed tracking of some CD8 T cells responding to infection, and a body of information now exists describing phenotypic changes that occur in CD8 T cells of known Ag-specificity during their activation, expansion, and memory generation in inbred mice. In this study, we demonstrate that Ag but not inflammation-driven changes in expression of CD11a and CD8α can be used to distinguish naive from Ag-experienced (effector and memory) CD8 T cells after infection or vaccination. Interestingly and in contrast to inbred mice, tracking polyclonal CD8 T cell responses with this approach after bacterial and viral infections revealed substantial discordance in the magnitude and kinetics of CD8 T cell responses in outbred hosts. These data reveal limitations to the use of inbred mouse strains as preclinical models at vaccine development and suggest the same dose of infection or vaccination can lead to substantial differences in the magnitude and timing of Ag-specific CD8 expansion as well in differences in protective memory CD8 T cell numbers in outbred individuals. This concept has direct relevance to development of vaccines in outbred humans.
Finite Cohen–Macaulay Type and Smooth Non-Commutative Schemes
Authors: Jørgensen Peter 
Published: November 2009

AbstractA commutative local Cohen–Macaulay ring R of finite Cohen–Macaulay type is known to be an isolated singularity; that is, Spec(R) \ ﹛m﹜ is smooth. This paper proves a non-commutative analogue. Namely, if A is a (non-commutative) graded Artin–Schelter Cohen–Macaulay algebra which is fully bounded Noetherian and has finite Cohen–Macaulay type, then the non-commutative projective scheme determined by A is smooth.
Heegner Points and the Rank of Elliptic Curves over Large Extensions of Global Fields
Authors: Breuer Florian , Im Bo-Hae 
Published: November 2009

AbstractLetkbe a global field,a separable closure ofk, andGkthe absolute Galois groupofoverk. For everyσ ∈ Gk, letbe the fixed subfield ofunderσ. LetE/kbe an elliptic curve overk. It is known that the Mordell–Weil grouphas infinite rank. We present a new proof of this fact in the following two cases. First, when k is a global function field of odd characteristic andEis parametrized by a Drinfeld modular curve, and secondly whenkis a totally real number field andE/kis parametrized by a Shimura curve. In both cases our approach uses the non-triviality of a sequence of Heegner points onEdefined over ring class fields.
A Multi-Frey Approach to Some Multi-Parameter Families of Diophantine Equations
Authors: Bugeaud Yann , Mignotte Maurice , Siksek Samir 
Published: November 2009

AbstractWe solve several multi-parameter families of binomial Thue equations of arbitrary degree; for example, we solve the equation5uxn − 2r3s yn = ±1,in non-zero integers x, y and positive integers u, r, s and n ≥ 3. Our approach uses several Frey curves simultaneously, Galois representations and level-lowering, new lower bounds for linear forms in 3 logarithms due to Mignotte and a famous theorem of Bennett on binomial Thue equations.
Non-Selfadjoint Perturbations of Selfadjoint Operators in Two Dimensions IIIa. One Branching Point
Authors: Hitrik Michael , Sjöstrand Johannes 
Published: November 2009

AbstractThis is the third in a series of works devoted to spectral asymptotics for non-selfadjoint perturbations of selfadjointh-pseudodifferential operators in dimension 2, having a periodic classical flow. Assuming that the strength ॉ of the perturbation is in the rangeh2≪ ॉ ≪ h1/2(and may sometimes reach even smaller values), we get an asymptotic description of the eigenvalues in rectangles [−1/C, 1/C] +iॉ[F0− 1/C,F0 + 1/C],C≫ 1, when ॉF0is a saddle point value of the flow average of the leading perturbation.
Uniform Linear Bound in Chevalley’s Lemma
Authors: Adamus J. , Bierstone E. , Milman P. D. 
Published: November 2009

AbstractWe obtain a uniform linear bound for the Chevalley function at a point in the source of an analytic mapping that is regular in the sense of Gabrielov. There is a version of Chevalley’s lemma also along a fibre, or at a point of the image of a proper analytic mapping. We get a uniform linear bound for the Chevalley function of a closed Nash (or formally Nash) subanalytic set.
Genus 2 Curves with Quaternionic Multiplication
Authors: Baba Srinath , Granath Håkan 
Published: November 2009

AbstractWe explicitly construct the canonical rational models of Shimura curves, both analytically in terms of modular forms and algebraically in terms of coefficients of genus 2 curves, in the cases of quaternion algebras of discriminant 6 and 10. This emulates the classical construction in the elliptic curve case. We also give families of genus 2 QMcurves, whose Jacobians are the corresponding abelian surfaces on the Shimura curve, and with coefficients that are modular forms of weight 12. We apply these results to show that our j-functions are supported exactly at those primes where the genus 2 curve does not admit potentially good reduction, and construct fields where this potentially good reduction is attained. Finally, using j, we construct the fields ofmoduli and definition for somemoduli problems associated to the Atkin–Lehner group actions.
Maximum Principles for Subharmonic Functions Via Local Semi-Dirichlet Forms
Authors: Kuwae Kazuhiro 
Published: November 2009

AbstractMaximum principles for subharmonic functions in the framework of quasi-regular local semi-Dirichlet forms admitting lower bounds are presented. As applications, we give weak and strong maximum principles for (local) subsolutions of a second order elliptic differential operator on the domain of Euclidean space under conditions on coefficients, which partially generalize the results by Stampacchia.
H∞ Functional Calculus and Mikhlin-Type Multiplier Conditions
Authors: Galé José E. , Miana Pedro J. 
Published: November 2009

AbstractLet T be a sectorial operator. It is known that the existence of a bounded (suitably scaled) H∞ calculus for T, on every sector containing the positive half-line, is equivalent to the existence of a bounded functional calculus on the Besov algebra . Such an algebra includes functions defined byMikhlin-type conditions and so the Besov calculus can be seen as a result on multipliers for T. In this paper, we use fractional derivation to analyse in detail the relationship between and Banach algebras of Mikhlin-type. As a result, we obtain a new version of the quoted equivalence.
On Types for Unramified p-Adic Unitary Groups
Authors: Kariyama Kazutoshi 
Published: November 2009

AbstractLet F be a non-archimedean local field of residue characteristic neither 2 nor 3 equipped with a galois involution with fixed field F0, and let G be a symplectic group over F or an unramified unitary group over F0. Following the methods of Bushnell–Kutzko for GL(N, F), we define an analogue of a simple type attached to a certain skew simple stratum, and realize a type in G. In particular, we obtain an irreducible supercuspidal representation of G like GL(N, F).
A Classification of Tsirelson Type Spaces
Authors: Lopez-Abad J. , Manoussakis A. 
Published: November 2009

AbstractWe give a complete classification of mixed Tsirelson spacesfor finitely many pairs of given compact and hereditary familiesof finite sets of integers and 0 <θi< 1 in terms of the Cantor–Bendixson indices of the families, andθi(1 ≤i≤r). We prove that there are unique countable ordinalαand 0 <θ< 1 such that every block sequence ofhas a subsequence equivalent to a subsequence of the natural basis of the. Finally, we give a complete criterion of comparison in between two of these mixed Tsirelson spaces.
Short Time Behavior of Solutions to Linear and Nonlinear Schrödinger Equations
Authors: Taylor Michael 
Published: November 2009

AbstractWe examine the fine structure of the short time behavior of solutions to various linear and nonlinear Schrödinger equations ut = iΔu+q(u) on I×ℝn, with initial data u(0, x) = f (x). Particular attention is paid to cases where f is piecewise smooth, with jump across an (n−1)-dimensional surface. We give detailed analyses of Gibbs-like phenomena and also focusing effects, including analogues of the Pinsky phenomenon. We give results for general n in the linear case. We also have detailed analyses for a broad class of nonlinear equations when n = 1 and 2, with emphasis on the analysis of the first order correction to the solution of the corresponding linear equation. This work complements estimates on the error in this approximation.
Remarks on Littlewood–Paley Analysis
Authors: Ho Kwok-Pun 
Published: November 2009

AbstractLittlewood–Paley analysis is generalized in this article. We show that the compactness of the Fourier support imposed on the analyzing function can be removed. We also prove that the Littlewood–Paley decomposition of tempered distributions converges under a topology stronger than the weak-star topology, namely, the inductive limit topology. Finally, we construct a multiparameter Littlewood–Paley analysis and obtain the corresponding “renormalization” for the convergence of this multiparameter Littlewood–Paley analysis.
Case series of liver failure associated with rosiglitazone and pioglitazone
Authors: Floyd James S. , Barbehenn Elizabeth , Lurie Peter , Wolfe Sidney M. 
Published: November 2009

AbstractPurposeThe thiazolidinedione drugs rosiglitazone and pioglitazone are not widely known to be hepatotoxic. We evaluated the FDA Adverse Event Reporting System (AERS) to determine the number of reported cases of liver failure associated with rosiglitazone and pioglitazone between 1997 and 2006, and described their clinical characteristics.MethodsAdverse event reports spontaneously submitted to the FDA AERS from 1997 to 2006 were examined. Liver failure associated with rosiglitazone or pioglitazone was defined as liver injury accompanied by hepatic encephalopathy, liver transplantation, placement on a liver transplant list, or death in which all other likely etiologies were excluded. Using prescribing data, the number of reported cases of liver failure per million patient‐years of exposure was calculated for each drug.ResultsTwenty‐one cases met our case definition. Clinical characteristics, outcomes, and pathologic data were similar between cases of liver failure associated with rosiglitazone and with pioglitazone. The median duration of therapy was 9 weeks and 85% of cases were acute, defined as symptom onset to liver failure in less than 26 weeks. The case‐fatality rate was 81% (17/21), and only 14% (3/21) spontaneously recovered. Accounting for underreporting, the number needed to harm (NNH) for each case of liver failure was 44 000 patient‐years of exposure for rosiglitazone and 52 000 patient‐years of exposure for pioglitazone.ConclusionsThis is the largest case series of liver failure associated with rosiglitazone or pioglitazone reported to date, strengthening the evidence that these drugs can cause severe hepatotoxicity. Copyright © 2009 John Wiley & Sons, Ltd.
COSMOPEN: dynamic reverse engineering on a budget. How cheap observation techniques can be used to reconstruct complex multi‐level behaviour
Authors: Taïani François , Killijian Marc‐Olivier , Fabre Jean‐Charles 
Published: November 2009

AbstractIn this paper we present COSMOPEN, a reverse‐engineering tool optimized for the behavioural analysis of complex layered software. COSMOPENcombines cheap and non‐intrusive observation techniques with a versatile graph manipulation engine. By programming different graph manipulation scripts, the ‘focal length’ of our tool can be adapted to different abstraction levels. We illustrate how our tool can be used to extract high‐level behavioural models from a complex multi‐threaded platform (GNU/Linux, CORBA middleware). Copyright © 2009 John Wiley & Sons, Ltd.