bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Responses to Avian Influenza H5 by Human CD4 T Cells
Authors: Cusick Matthew F. , Wang Shuping , Eckels David D. 
Published: October 2009

Abstract
To address the question of whether human T cells are capable of recognizing novel isolates of influenza virus, in vitro responses to recombinant Ags and synthetic peptides derived from the sequences of H1, H3, and H5 were examined in a cohort of 64 individuals selected from a healthy blood donor population. Humans respond in vitro to H1 and H3 following exposure through natural infection and vaccination. Responses to H5 were well correlated with those to H1 or H3, and thus, a significant repertoire of H5-responsive T cells is present in many individuals; clear nonresponders to H1, H3, and H5, however, do exist. Differences were observed in the cytokine responses to H1, H3, and H5, whereas both IL-2 and IFN-γ production characteristic of memory responses were observed for H1 and H3, and H5-specific responses elicited primarily IL-2 and little or no IFN-γ, consistent with a naive T cell phenotype. Responses to all influenza HA were restricted by HLA-DR molecules. To address the structural basis for T cell recognition of H1 and H5, overlapping synthetic peptides were used to identify epitopes and to determine whether recognition of H5 was limited to homologous sequences in H1, the most closely related HA phylogenetically. Although responses were generally correlated, no complete structural overlap was observed. These results suggest that helper T cell cross reactivity between different influenza strains may impart cross-protection to H5N1 strain of influenza.
Activation-Induced CD154 Expression Abrogates Tolerance Induced by Apoptotic Cells
Authors: Gurung Prajwal , Kucaba Tamara A. , Ferguson Thomas A. , Griffith Thomas S. 
Published: October 2009

Abstract
The decision to generate a productive immune response or tolerance often depends on the context in which T cells first see Ag. Using a classical system of tolerance induction, we examined the immunological consequence of Ag encountered in the presence of naive or activated apoptotic cells. Naive apoptotic cells induced tolerance when injected i.v.; however, previously activated apoptotic cells induced immunity. Further analysis revealed a key role for CD154, as tolerance resulted after i.v. injection of either naive or activated apoptotic CD154−/− T cells, while coinjection of an agonistic anti-CD40 mAb with naive apoptotic T cells induced robust immunity. Dendritic cells fed activated apoptotic T cells in vitro produced IL-12p40 in a CD154-dependent manner, and the use of IL-12p40−/− mice or mAb-mediated neutralization of IL-12 revealed a link between CD154, IL-12, and the ability of activated apoptotic T cells to induce immunity rather than tolerance. Collectively, these results show that CD154 expression on apoptotic T cells can determine the outcome of an immune response to Ag recognized within the context of the apoptotic cells and suggest that the balance between naive and activated apoptotic T cells may dictate whether a productive immune response is encouraged.
Antibodies to the Desmoglein 1 Precursor Proprotein but Not to the Mature Cell Surface Protein Cloned from Individuals without Pemphigus
Authors: Yamagami Jun , Kacir Stephen , Ishii Ken , Payne Aimee S. , Siegel Don L. , Stanley John R. 
Published: October 2009

Abstract
In pemphigus foliaceus (PF), autoantibodies against desmoglein 1 (Dsg1) cause blisters. Using Ab phage display, we have cloned mAbs from a PF patient. These mAbs, like those from a previous patient, were directed against mature Dsg1 (matDsg1) on the cell surface of keratinocytes and precursor Dsg1 (preDsg1) in the cytoplasm. To determine whether individuals without pemphigus have B cell tolerance to Dsg1, we cloned mAbs from two patients with thrombotic thrombocytopenic purpura and a healthy person. We found mAbs against preDsg1, but not matDsg1. All but 1 of the 23 anti-preDsg1 mAbs from PF patients and those without PF used the VH3-09 (or closely related VH3-20) H chain gene, whereas no PF anti-matDsg1 used these genes. VH cDNA encoding anti-preDsg1 had significantly fewer somatic mutations than did anti-matDsg1 cDNA, consistent with chronic Ag-driven hypermutation of the latter compared with the former. These data indicate that individuals without PF do not have B cell tolerance to preDsg1 and that loss of tolerance to matDsg1 is not due to epitope shifting of anti-preDsg1 B cells (because of different VH gene usage). However, presentation of peptides from Dsg1 by preDsg1-specific B cells may be one step in developing autoimmunity in PF.
Regulatory T Cell (Treg) Subsets Return in Patients with Refractory Lupus following Stem Cell Transplantation, and TGF-β-Producing CD8+ Treg Cells Are Associated with Immunological Remission of Lupus
Authors: Zhang Li , Bertucci Anne M. , Ramsey-Goldman Rosalind , Burt Richard K. , Datta Syamal K. 
Published: October 2009

Abstract
Compared with conventional drug therapy, autologous hemopoietic stem cell transplantation (HSCT) can induce very-long-term remission in refractory lupus patients. Herein, we show that in posttransplant patients, both CD4+CD25highFoxP3+ and an unusual CD8+FoxP3+ Treg subset return to levels seen in normal subjects; accompanied by almost complete inhibition of pathogenic T cell response to critical peptide autoepitopes from histones in nucleosomes, the major lupus autoantigen from apoptotic cells. In addition to a stably sustained elevation of FoxP3, posttransplant CD8 T cells also maintained markedly higher expression levels of latency-associated peptide (LAP), CD103, PD-1, PD-L1, and CTLA-4, as compared with pretransplant CD8 T cells that were identically treated by a one-time activation and rest in short-term culture. The posttransplant CD8 regulatory T cells (Treg) have autoantigen-specific and nonspecific suppressive activity, which is contact independent and predominantly TGF-β dependent. By contrast, the pretransplant CD8 T cells have helper activity, which is cell contact dependent. Although CD4+CD25high Treg cells return during clinical remission of conventional drug-treated lupus, the posttransplant patient’s CD8 Treg cells are considerably more potent, and they are absent in drug-treated patients in whom CD4 T cell autoreactivity to nucleosomal epitopes persists even during clinical remission. Therefore, unlike conventional drug therapy, hemopoietic stem cell transplantation generates a newly differentiated population of LAPhighCD103high CD8TGF-β Treg cells, which repairs the Treg deficiency in human lupus to maintain patients in true immunological remission.
FCRL3, an Autoimmune Susceptibility Gene, Has Inhibitory Potential on B-Cell Receptor-Mediated Signaling
Authors: Kochi Yuta , Myouzen Keiko , Yamada Ryo , Suzuki Akari , Kurosaki Tomohiro , Nakamura Yusuke , Yamamoto Kazuhiko 
Published: October 2009

Abstract
A polymorphism that up-regulates the expression of Fc receptor-like 3 (FCRL3) gene has recently been described as predisposing for several human autoimmune diseases. FCRL3 is preferentially expressed on B cells and is unique in displaying both an ITAM and an ITIM in the cytosolic domain, suggesting signaling functions. Herein, we show that FCRL3 potentially inhibits BCR-mediated signaling, using murine FcγRIIB/human FCRL3 chimeric protein. Coligation of the chimeric protein with BCR leads to phosphorylation of tyrosine residues in the cytosolic domain. This coligation inhibits cell tyrosine phosphorylation and calcium mobilization in addition to activation-induced cell death mediated by BCR signaling. Mutational analysis showed the tyrosine residues in two potential ITIMs at 662 and 692 offer the main contributions to this inhibition, which is further supported by strong associations of SH-2 domain-containing phosphatases with the following phosphotyrosine motifs: SHIP with the ITIM-like motif at 662; and SHP-1 and -2 with the canonical ITIM at 692. These results, together with previous genetic data, suggest that augmented inhibition of BCR-mediated signaling by FCRL3 with the disease-risk genotype alter the activation threshold and promote tolerance breakdown in B cells.
Fas Apoptosis Inhibitory Molecule Expression in B Cells Is Regulated through IRF4 in a Feed-Forward Mechanism
Authors: Kaku Hiroaki , Rothstein Thomas L. 
Published: October 2009

Abstract
Fas apoptosis inhibitory molecule (FAIM) was originally cloned as an inhibitor of Fas-mediated apoptosis in B cells that has been reported to affect multiple cell types. Recently, we found that FAIM enhances CD40L-mediated signal transduction, including induction of IFN regulatory factor (IRF)4, in vitro and augments plasma cell production in vivo. These results have keyed interest in the regulation of FAIM expression, about which little is known. Here, we show that Faim is regulated by IRF4. The Faim promoter contains three IRF binding sites, any two of which promote Faim expression. Faim promoter activity is lost following mutation of all three IRF binding sites, whereas activity of the full promoter is enhanced by concurrent expression of IRF4. In stimulated primary B cells, IRF4 expression precedes FAIM expression, IRF4 binds directly to the Faim promoter, and loss of IRF4 results in the failure of stimulated Faim up-regulation. Finally, FAIM is preferentially expressed in germinal center B cells. Taken together, these results indicate that FAIM expression is regulated through IRF4 and that this most likely occurs as part of germinal center formation. Because FAIM enhances CD40-induced IRF4 expression in B cells, these results suggest that induction of FAIM initiates a positive reinforcing (i.e., feed-forward) system in which IRF4 expression is both enhanced by FAIM and promotes FAIM expression.
Human Late Memory CD8+ T Cells Have a Distinct Cytokine Signature Characterized by CC Chemokine Production without IL-2 Production
Authors: Kim Tae Kon , St. John Lisa S. , Wieder Eric D. , Khalili Jahan , Ma Qing , Komanduri Krishna V. 
Published: October 2009

Abstract
Late memory T cell skewing is observed in the setting of immune recovery after cord blood transplantation, and may be associated with inferior control of viral reactivation and cancers. Therefore, we sought to understand how late memory cells differ functionally from earlier stage memory T cells, and whether surface phenotypes associated with differentiation stages were predictably associated with functional signatures. Higher order cytokine flow cytometry allows characterization of human T cells based on complex phenotypic markers and their differential capacity to simultaneously secrete effector proteins, including cytokines and chemokines. We used 8-color, 10-parameter cytokine flow cytometry to characterize the functional activation of human late memory CD8+ T cells defined by CD45RA and CD27 expression (CD27−CD45RA+). We assessed the 15 possible functional signatures of cells defined by production of IL-2, IFN-γ, TNF-α, and MIP-1β alone or in combination, following activation with Ags stimulating bypassing surface proteins (PMA:ionomycin) or through the TCR (e.g., viral Ags). Late memory CD8+ T cells produced abundant amounts of CC chemokines (MIP-1β, MIP-1α, and RANTES) but not IL-2. IL-2/IFN-γ coproduction, characteristic of protective immune responses to viral infections, was absent in late memory CD8+ T cells. These data demonstrate that functional cytokine signatures are predictably associated with CD8+ maturation stages, and that the polarization of late memory CD8+ T cells toward CC chemokine production and away from IL-2 production suggests a unique functional role for this subset.
On ℤ-Modules of Algebraic Integers
Authors: Bell J. P. , Hare K. G. 
Published: October 2009

Abstract. Let q be an algebraic integer of degree d ≥ 2. Consider the rank of the multiplicative subgroup of ℂ* generated by the conjugates of q. We say q is of full rank if either the rank is d − 1 and q has norm ±1, or the rank is d. In this paper we study some properties of ℤ[q] where q is an algebraic integer of full rank. The special cases of when q is a Pisot number and when q is a Pisot-cyclotomic number are also studied. There are four main results.(1)If q is an algebraic integer of full rank and n is a fixed positive integer, then there are only finitely many m such that disc `ℤ[qm]´ = disc `ℤ[qn]´.(2)If q and r are algebraic integers of degree d of full rank and ℤ[qn] = ℤ[rn] for infinitely many n, then either q = ωr′ or q = Norm(r)2/dω/r′ , where r ′ is some conjugate of r and ω is some root of unity.(3)Let r be an algebraic integer of degree at most 3. Then there are at most 40 Pisot numbers q such that ℤ[q] = ℤ[r].(4)There are only finitely many Pisot-cyclotomic numbers of any fixed order.
Subspaces of de Branges Spaces Generated by Majorants
Authors: Baranov Anton , Woracek Harald 
Published: October 2009

Abstract.For a given de Branges space ℋ (E ) we investigate de Branges subspaces defined in terms of majorants on the real axis. If ω is a nonnegative function on ℝ, we consider the subspaceWe show that ℛω (E ) is a de Branges subspace and describe all subspaces of this form. Moreover, we give a criterion for the existence of positive minimal majorants.
Characterization of Parallel Isometric Immersions of Space Forms into Space Forms in the Class of Isotropic Immersions
Authors: Maeda Sadahiro , Udagawa Seiichi 
Published: October 2009

Abstract.For an isotropic submanifold Mn (n ≧ 3) of a space form of constant sectional curvature c, we show that if the mean curvature vector of Mn is parallel and the sectional curvature K of Mn satisfies some inequality, then the second fundamental form of Mn in is parallel and our manifold Mn is a space form.
In search of dialogue and discourse in applied clinical informatics
Authors: Kim G. R. , Lehmann C. U. 
Published: October 2009

SummaryWe present a model of applied clinical informatics in the context of medical informatics in general, across the domain of health sciences and the continuum of information technology development and its adoption into workflow. The distinct challenges of applied clinical informatics present an opportunity to improve efforts through collaboration of the growing number of physicians, health institutional leaders and other health workers in successfully implementing working systems. This journal will be a forum for discussion regarding approaches to design, implement, deploy and evaluate systems and importantly, how to present experiences in a way to maximize sharing of those experiences.
Did you see the unicycling clown? Inattentional blindness while walking and talking on a cell phone
Authors: Hyman Ira E. , Boss S. Matthew , Wise Breanne M. , McKenzie Kira E. , Caggiano Jenna M. 
Published: October 2009

AbstractWe investigated the effects of divided attention during walking. Individuals were classified based on whether they were walking while talking on a cell phone, listening to an MP3 player, walking without any electronics or walking in a pair. In the first study, we found that cell phone users walked more slowly, changed directions more frequently, and were less likely to acknowledge other people than individuals in the other conditions. In the second study, we found that cell phone users were less likely to notice an unusual activity along their walking route (a unicycling clown). Cell phone usage may cause inattentional blindness even during a simple activity that should require few cognitive resources. Copyright © 2009 John Wiley & Sons, Ltd.
Passive vacuum solar flash desalination
Authors: Abutayeh Mohammad , Goswami D. Yogi 
Published: October 2009

AbstractA model for a sustainable desalination process has been developed. The simulated process consists of pumping seawater through a solar heater before flashing it under a passively created vacuum in an elevated chamber. The vacuum enhances evaporation and is maintained by the balance between the hydrostatic pressure inside the elevated flash chamber and the atmospheric pressure. The developed model uses theoretical thermodynamic relations to describe the process setting it apart from previous empirical correlations. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Progeroid syndrome with scleroderma‐like skin changes associated with homozygous R435C LMNA mutation
Authors: Madej‐Pilarczyk Agnieszka , Rosińska‐Borkowska Danuta , Rękawek Joanna , Marchel Michał , Szaluś Ewa , Jabłońska Stefania , Hausmanowa‐Petrusewicz Irena 
Published: October 2009

AbstractHutchinson–Gilford progeria is a rare genetic disorder resulting from mutations in the LMNA gene encoding lamin A/C. In addition to the classical phenotype usually caused by the 1824C>T mutation of LMNA, a number of atypical progeroid syndromes have been described. They have some distinct features, such as skeletal deformities or scleroderma‐like skin changes. The underlying defect is usually a homozygous mutation of LMNA, or a combined defect of LMNA and another gene, for example, ZMPSTE‐24. We present a 2‐year‐old girl born to consanguineous parents affected by progeroid syndrome with scleroderma‐like skin changes. Genetic analysis revealed the homozygous LMNA mutation 1303C>T (R435C). The same heterozygous mutation was found in the patient's parents and 11 other family members. The progeroid syndrome in our patient shares the signs of two laminopathies: progeria and restrictive dermatopathy. Two other children in the family died at the age of 2 due to a disease similar to that in the proposita. On the basis of the family pedigree we presume that these children probably had the same homozygous LMNA mutation. Scleroderma‐like skin changes in infants, associated with growth retardation and dysmorphic features, suggest premature aging syndrome, requiring genetic testing and counseling of asymptomatic carriers of LMNA mutations. © 2009 Wiley‐Liss, Inc.
Three novel mutations of the IRF6 gene with one associated with an unusual feature in Van der Woude syndrome
Authors: Yeetong Patra , Mahatumarat Charan , Siriwan Pichit , Rojvachiranonda Nond , Suphapeetiporn Kanya , Shotelersuk Vorasuk 
Published: October 2009

AbstractVan der Woude syndrome (VWS) is a dominantly inherited disorder characterized by cleft lip with or without cleft palate and lip pits. It remains the most common syndromic form of oral clefts. Mutations in the interferon regulatory factor 6 (IRF6) gene have been identified in patients with VWS. We reported three unrelated families with lower lip anomalies. Two had lower lip pits, a cardinal sign of VWS, but the other had a heart‐shaped mass on lower lip without pits, oral clefts, or hypodontia. This isolated anomaly has not been previously observed in VWS. We performed mutation analysis by PCR‐sequencing the entire coding region of the IRF6 gene. Three potentially pathogenic mutations, c.145C>T (p.Q49X), c.171T>G (p.F57L), and 1306C>G (p.L436V) were successfully identified. All the missense mutations were not detected in 100 unaffected ethnic‐matched control chromosomes and have never been previously reported. The p.Q49X and p.F57L mutations were located in the highly conserved DNA binding domain while the p.L436V was located at the carboxy‐terminal region. This study reported an undescribed clinical feature of VWS and three novel mutations, expanding the phenotypic spectrum of VWS and mutational spectrum of IRF6. © 2009 Wiley‐Liss, Inc.
Molecular characterization of a monosomy 1p36 presenting as an Aicardi syndrome phenocopy
Authors: Bursztejn Anne‐Claire , Bronner Myriam , Peudenier Sylviane , Grégoire Marie‐José , Jonveaux Philippe , Nemos Christophe 
Published: October 2009

AbstractMonosomy 1p36 is the most frequent terminal deletion known in Humans. Typical craniofacial features, developmental delay/mental retardation, seizures and sensorineural defects characterize 1p36 deletion syndrome. Aicardi syndrome (AIS) is a rare genetic disorder characterized by chorioretinal lacunae, corpus callosum agenesis and infantile spasms responsible for mental retardation. By screening DNA from diagnosed AIS patients with oligonucleotide array‐based comparative genomic hybridization (aCGH), we report a 1p36 monosomy in this study. There were no other deletions or duplications. Regarding clinical criteria, the patient did not have the typical facial appearance commonly described for 1p36 monosomy patients. We showed that this 1p36 monosomy corresponded to combined interstitial and terminal de novo deletions of the chromosome 1 leading to an 11.73 Mb deletion confirmed with qPCR. By microsatellite markers and FISH analyses, we have concluded that this deletion occurred on maternal chromosome 1 during oogenesis. We did find some clinical features shared by the 1p36 monosomy and AIS: infantile spasms, corpus callosum dysgenesis, ophthalmological abnormalities, and skeletal malformations. To date, no relationship between these two phenotypes has been established. We conclude that the monosomy 1p36 should be considered in the differential diagnosis of AIS. © 2009 Wiley‐Liss, Inc.
The development and evaluation of a survey to measure user engagement
Authors: O'Brien Heather L. , Toms Elaine G. 
Published: October 2009

AbstractFacilitating engaging user experiences is essential in the design of interactive systems. To accomplish this, it is necessary to understand the composition of this construct and how to evaluate it. Building on previous work that posited a theory of engagement and identified a core set of attributes that operationalized this construct, we constructed and evaluated a multidimensional scale to measure user engagement. In this paper we describe the development of the scale, as well as two large‐scale studies (N=440 and N=802) that were undertaken to assess its reliability and validity in online shopping environments. In the first we used Reliability Analysis and Exploratory Factor Analysis to identify six attributes of engagement: Perceived Usability, Aesthetics, Focused Attention, Felt Involvement, Novelty, and Endurability. In the second we tested the validity of and relationships among those attributes using Structural Equation Modeling. The result of this research is a multidimensional scale that may be used to test the engagement of software applications. In addition, findings indicate that attributes of engagement are highly intertwined, a complex interplay of user‐system interaction variables. Notably, Perceived Usability played a mediating role in the relationship between Endurability and Novelty, Aesthetics, Felt Involvement, and Focused Attention.