bluuebunny/crossref_metadata_2025_split huggingface dataset:
An early origin of secondary growth: Franhueberia gerriennei gen. et sp. nov. from the Lower Devonian of Gaspé (Quebec, Canada)
Authors: Hoffman Laurel A. , Tomescu Alexandru M. F. 
Published: March 2013

• Premise of the Study: Secondary xylem (wood) produced by a vascular cambium supports increased plant size and underpins the most successful model of arborescence among tracheophytes. Woody plants established the extensive forest ecosystems that dramatically changed the Earth's biosphere. Secondary growth evolved in several lineages in the Devonian, but only two occurrences have been reported previously from the Early Devonian. The evolutionary history and phylogeny of wood production are poorly understood, and Early Devonian plants are key to illuminating them.• Methods: A fossil plant preserved anatomically by cellular permineralization in the Lower Devonian (Emsian, ca. 400–395 million years old) Battery Point Formation of Gaspé Bay (Quebec, Canada) is described using the cellulose acetate peel technique.• Key Results: The plant, Franhueberia gerriennei Hoffman et Tomescu gen. et sp. nov., is a basal euphyllophyte with a centrarch protostele and metaxylem tracheids with circular and oval to scalariform bordered multiaperturate pits (P‐type tracheids). The outer layers of xylem, consisting of larger‐diameter P‐type tracheids, exhibit the features diagnostic of secondary xylem: radial files of tracheids, multiplicative divisions, and a combination of axial and radial components.• Conclusions: Franhueberia is one of the three oldest euphyllophytes exhibiting secondary growth documented in the Early Devonian. Within the euphyllophyte clade, these plants represent basal lineages that predate the evolution of stem‐leaf‐root organography and indicate that underlying mechanisms for secondary growth became part of the euphyllophyte developmental toolkit very early in the clade's evolution.
Antivirally Active Ribavirin Analogues – 4,5-disubstituted 1,2,3-triazole Nucleosides: Biological Evaluation against Certain Respiratory Viruses and Computational Modelling
Authors: Krajczyk Anna , Kulinska Katarzyna , Kulinski Tadeusz , Hurst Brett L , Day Craig W , Smee Donald F , Ostrowski Tomasz , Januszczyk Piotr , Zeidler Joanna 
Published: March 2013

Background: Ribavirin is a broad-spectrum antiviral agent that derives some of its activity from inhibition of cellular inosine monophosphate dehydrogenase (IMPDH), resulting in lower guanosine triphosphate (GTP) levels. Here we report the biological activities of three ribavirin analogues. Methods: Antiviral activities of test compounds were performed by in vitro cytopathic effect inhibition assays against influenza A (H1N1, H3N2 and H5N1), influenza B, measles, parainfluenza type 3 (PIV-3) and respiratory syncytial viruses. Compounds were modelled into the ribavirin 5‘-monophosphate binding site of the crystallographic structure of the human type II IMPDH (hIMPDH2) ternary complex. Effects of compounds on intracellular GTP levels were performed by strong anion exchange HPLC analysis. Results: Of the three compounds evaluated, the 5-ethynyl nucleoside (ETCAR) exhibited virus-inhibitory activities (at 1.2–20 μM, depending upon the virus) against most of the viruses, except for weak activity against PIV-3 (62 μM). Antiviral activity of ETCAR was similar to ribavirin; however, cytotoxicity of ETCAR was greater than ribavirin. Replacing the 5-ethynyl group with a 5-propynyl or bromo substituent (BrCAR) considerably reduced antiviral activity. Computational studies of ternary complexes of hIMPDH2 enzyme with 5‘-monophosphates of the compounds helped rationalize the observed differences in biological activity. All compounds suppressed GTP levels in cells; additionally, BrCAR suppressed adenosine triphosphate and elevated uridine triphosphate levels. Conclusions: Three compounds related to ribavirin inhibited IMPDH and had weak to moderate antiviral activity. Cytotoxicity adversely affected the antiviral selectivity of ETCAR. As with ribavirin, reduction in intracellular GTP may play a role in virus inhibition.
L'arrivée et la demande d'asile
Authors: Gaeremynck Jean 
Published: March 2013

Le droit de l’asile et le droit des étrangers en général procèdent en principe de deux logiques différentes : celle de la protection pour le premier, celle du contrôle pour le second. Pourtant, ni en fait ni en droit cette distinction n’est aussi tranchée, si l’on se réfère à la situation de la demande et des demandeurs d’asile. Qu’il s’agisse de l’entrée en France, de l’asile à la frontière, de la détermination de l’État responsable, de la présentation de la demande d’asile ou encore des pays d’origine sûrs, les règles en vigueur composent un paysage particulièrement complexe. Il reste que, sur la base de la convention de Genève, la demande d’asile a connu un essor spectaculaire qui la place objectivement dans le courant des flux migratoires.
Réfugiés sans refuge
Authors: Laacher Smaïn 
Published: March 2013

Les victimes des conflits qui provoquent des déplacements de populations deviennent des personnes dépossédées d’un foyer. Rapportée à ces millions de personnes sans assignation, ou ne possédant comme seule identité publique et seule condition sociale que celle de « réfugié », la notion de foyer recouvre des enjeux fondamentaux souvent peu explicités.
De quoi un cas est-il le cas ?
Authors: Hamidi Camille 
Published: March 2013

Si les travaux fondés sur l’enquête ethnographique connaissent un renouveau et une légitimité croissante ces dernières décennies en France, la capacité de cette méthode à produire des résultats théoriques généralisables au-delà des cas étudiés fait toujours question. En présentant les différentes étapes d’une enquête de terrain portant sur les associations de jeunes issus de l’immigration, l’article met en évidence le caractère nécessairement itératif du processus de théorisation à partir des cas. Il s’intéresse plus spécifiquement à la question des cas limites et propose de distinguer deux façons de concevoir ceux-ci en fonction du rapport qu’ils entretiennent au processus de théorisation : l’approche en termes de cas négatifs, qui vise à tester la robustesse et le degré d’extension d’une théorie ; l’approche en termes de cas limites, qui vise à mettre la théorie à l’épreuve dans ses marges afin de spécifier ses conditions de validité et de la reconstruire.
Vers une nouvelle gouvernance des conditions d'accès à l'encadrement sportif professionnel
Authors: Pierre Jeremy 
Published: March 2013

La notion d’incertitude est devenue aujourd’hui constitutive de nos sociétés contemporaines, et son utilisation dans le domaine politique est croissante. Une des adaptations à cette caractéristique est la gouvernance au sein de laquelle des acteurs hétérogènes, privés et publics, prennent part à la formulation de la politique. Le secteur sportif n’échappe pas à ces constats. Jusqu’au tournant du XXI e siècle, les conditions d’accès à l’encadrement sportif rémunéré dans le secteur privé sont le monopole du ministère en charge des Sports via le « Brevet d’État d’Éducateur Sportif ». Cet ordre établi se trouve bouleversé au début des années 2000 par l’ouverture de ces métiers à de nouvelles natures de certifications mais aussi par l’émergence d’une branche professionnelle spécifique au sport. Les conditions d’accès à l’encadrement sportif sont ainsi partagées entre plusieurs certificateurs. D’une part, les diplômes de la filière universitaire « Sciences et Techniques des Activités Physiques et Sportives » obtiennent de nouvelles prérogatives. D’autre part, la branche sport développe le « Certificat de Qualification Professionnelle », dont les titulaires peuvent également encadrer une activité sportive, sous des conditions bien particulières. Ces reconfigurations engendrent inéluctablement des concurrences et de l’incertitude dans cette nouvelle gouvernance.
Absorption and frequency shift of GPR signals in sandy and silty soils: empirical relations between quality factor Q, complex permittivity and clay and water contents
Authors: Wunderlich Tina , Rabbel Wolfgang 
Published: March 2013

ABSTRACTThe arrival time, shape and amplitude of a reflected GPR wavelet depend mainly on the real and imaginary parts of dielectrical permittivity and electrical conductivity. All these parameters are strongly affected by the water and clay content of soils. From a comparison of the amplitude and shape of the direct and reflected wavelets the quality factor can be determined independently as an additional soil parameter. To investigate the relationships between the influencing factors, we conducted high‐frequency GPR reflection measurements on soil samples with varying clay and water contents. The factor, derived from the spectral ratio method, is found to be between 5–15 for our samples that range from about 5–90% in sand content, 5–65% in silt content, 3–63% in clay content and 0–37% in pore water content. A multivariate non‐linear empirical function linking water and clay content to agrees well with the observations. We found that the ratio of the real and imaginary parts of the dielectric permittivity depends basically on the clay content. Therefore, it may become possible to determine the clay content of soils in situ from a combination of GPR and conductivity measurements. The values determined from spectral ratios are confirmed by synthetic radargrams and agree with the observed decrease of the central frequency of GPR reflections caused by absorption.
2D and 3D ground‐penetrating radar surveys with a modular system: data processing strategies and results from archaeological field tests
Authors: Verdonck Lieven , Vermeulen Frank , Docter Roald , Meyer Cornelius , Kniess Rudolf 
Published: March 2013

ABSTRACTRecently, the use of ground‐penetrating radar (GPR) arrays with a large number of antenna elements in a fixed configuration has become more common. The investment needed for these systems is significant. In order to reduce the recording time in the field, an alternative is the use of several single GPR antennas in parallel (a ‘modular system’). Although this does not match the fast acquisition of detailed data sets by means of multi‐channel arrays, a system consisting in single antennas can gradually be expanded and investment can be spread over time. This paper presents a 2D and a full‐resolution 3D survey, conducted with a modular GPR instrument. A characteristic of these systems is that the cross‐line separation between transmitter‐receiver pairs is larger than the sampling distance prescribed by the Nyquist theorem. As a consequence, for 3D data collection, profiles have to be acquired between previously recorded ones, which requires high positioning accuracy. A completely identical response for different single GPR antennas is difficult to achieve. For the system tested, on less favourable soils this resulted in striping in the horizontal slices. Several methods (3D frequency‐wavenumber filtering, eigenimage filtering, mean profile filtering and filtering based on discrete wavelet transform, discrete ridgelet transform and linear Radon transform) were applied to two data sets exhibiting different kinds of linear noise and their capability to suppress artefacts was assessed. Although overall a reduction of the stripe patterns was achieved, mostly it was impossible to fully eliminate the noise in the time‐slices without low‐pass filtering in the cross‐line direction. For the 2D data, low‐pass filtering caused loss of some of the archaeological response and therefore was not applied. Mean profile filtering allowed the most reliable characterization of the archaeological structures.
Tolerogenic Donor-Derived Dendritic Cells Risk Sensitization In Vivo owing to Processing and Presentation by Recipient APCs
Authors: Smyth Lesley A. , Ratnasothy Kulachelvy , Moreau Aurelie , Alcock Sally , Sagoo Pervinder , Meader Lucy , Tanriver Yakup , Buckland Matthew , Lechler Robert , Lombardi Giovanna 
Published: March 2013

Abstract
Modification of allogeneic dendritic cells (DCs) through drug treatment results in DCs with in vitro hallmarks of tolerogenicity. Despite these observations, using murine MHC-mismatched skin and heart transplant models, donor-derived drug-modified DCs not only failed to induce tolerance but also accelerated graft rejection. The latter was inhibited by injecting the recipient with anti-CD8 Ab, which removed both CD8+ T cells and CD8+ DCs. The discrepancy between in vitro and in vivo data could be explained, partly, by the presentation of drug-modified donor DC MHC alloantigens by recipient APCs and activation of recipient T cells with indirect allospecificity, leading to the induction of alloantibodies. Furthermore, allogeneic MHC molecules expressed by drug-treated DCs were rapidly processed and presented in peptide form by recipient APCs in vivo within hours of DC injection. Using TCR-transgenic T cells, Ag presentation of injected OVA-pulsed DCs was detectable for ≤ 3 d, whereas indirect presentation of MHC alloantigen by recipient APCs led to activation of T cells within 14 h and was partially inhibited by reducing the numbers of CD8+ DCs in vivo. In support of this observation when mice lacking CD8+ DCs were pretreated with drug-modified DCs prior to transplantation, skin graft rejection kinetics were similar to those in non–DC-treated controls. Of interest, when the same mice were treated with anti-CD40L blockade plus drug-modified DCs, skin graft survival was prolonged, suggesting endogenous DCs were responsible for T cell priming. Altogether, these findings highlight the risks and limitations of negative vaccination using alloantigen-bearing “tolerogenic” DCs.
GITR-Dependent Regulation of 4-1BB Expression: Implications for T Cell Memory and Anti–4-1BB–Induced Pathology
Authors: Lin Gloria H. Y. , Snell Laura M. , Wortzman Michael E. , Clouthier Derek L. , Watts Tania H. 
Published: March 2013

Abstract
The TNFR family member 4-1BB plays a key role in the survival of activated and memory CD8 T cells. However, the mechanisms that regulate 4-1BB re-expression on memory CD8 T cells after Ag clearance are unknown. In unimmunized mice, ∼10% of CD8 CD44hi memory T cells in the bone marrow (BM) and liver express 4-1BB, with minimal 4-1BB expression in spleen and lymph node. IL-2, IL-15, and IL-7 are collectively dispensable for 4-1BB expression on the memory CD8 T cells. Rather, T cell–intrinsic glucocorticoid-induced TNFR-related protein (GITR) contributes to 4-1BB expression on CD8 T cells upon their entry into the BM or liver. Consistent with its role in regulation of 4-1BB, GITR is required on memory CD8 T cells for their persistence in vivo. These findings reveal site-specific effects of the BM and liver microenvironment on CD8 memory T cells. Previous work has demonstrated that 4-1BB agonists given to unimmunized mice induce splenomegaly, hepatitis, and other immune system anomalies. Moreover, severe liver pathology has been observed in a subset of anti–4-1BB–treated melanoma patients. Remarkably, the absence of GITR in mice almost completely abrogates cellular expansions, splenomegaly, and liver inflammation associated with anti–4-1BB agonist treatment of unimmunized mice. In contrast, lack of CD8 T cells selectively improves liver pathology, but not splenomegaly in the mice. Thus, the regulation of 4-1BB expression by GITR on CD8 T cells, as well as on other cells, contributes to the pathological effects of anti–4-1BB in unimmunized mice.
IL-27 Receptor Signaling Regulates CD4+ T Cell Chemotactic Responses during Infection
Authors: Gwyer Findlay Emily , Villegas-Mendez Ana , de Souza J. Brian , Inkson Colette A. , Shaw Tovah N. , Saris Christiaan J. , Hunter Christopher A. , Riley Eleanor M. , Couper Kevin N. 
Published: March 2013

Abstract
IL-27 exerts pleiotropic suppressive effects on naive and effector T cell populations during infection and inflammation. Surprisingly, however, the role of IL-27 in restricting or shaping effector CD4+ T cell chemotactic responses, as a mechanism to reduce T cell–dependent tissue inflammation, is unknown. In this study, using Plasmodium berghei NK65 as a model of a systemic, proinflammatory infection, we demonstrate that IL-27R signaling represses chemotaxis of infection-derived splenic CD4+ T cells in response to the CCR5 ligands, CCL4 and CCL5. Consistent with these observations, CCR5 was expressed on significantly higher frequencies of splenic CD4+ T cells from malaria-infected, IL-27R–deficient (WSX-1−/−) mice than from infected wild-type mice. We find that IL-27 signaling suppresses splenic CD4+ T cell CCR5-dependent chemotactic responses during infection by restricting CCR5 expression on CD4+ T cell subtypes, including Th1 cells, and also by controlling the overall composition of the CD4+ T cell compartment. Diminution of the Th1 response in infected WSX-1−/− mice in vivo by neutralization of IL-12p40 attenuated CCR5 expression by infection-derived CD4+ T cells and also reduced splenic CD4+ T cell chemotaxis toward CCL4 and CCL5. These data reveal a previously unappreciated role for IL-27 in modulating CD4+ T cell chemotactic pathways during infection, which is related to its capacity to repress Th1 effector cell development. Thus, IL-27 appears to be a key cytokine that limits the CCR5-CCL4/CCL5 axis during inflammatory settings.
Prenatally Acquired Vitamin A Deficiency Alters Innate Immune Responses to Human Rotavirus in a Gnotobiotic Pig Model
Authors: Vlasova Anastasia N. , Chattha Kuldeep S. , Kandasamy Sukumar , Siegismund Christine S. , Saif Linda J. 
Published: March 2013

Abstract
We examined how prenatally acquired vitamin A deficiency (VAD) modulates innate immune responses and human rotavirus (HRV) vaccine efficacy in a gnotobiotic (Gn) piglet model of HRV diarrhea. The VAD and vitamin A–sufficient (VAS) Gn pigs were vaccinated with attenuated HRV (AttHRV) with or without concurrent oral vitamin A supplementation (100,000 IU) and challenged with virulent HRV (VirHRV). Regardless of vaccination status, the numbers of conventional and plasmacytoid dendritic cells (cDCs and pDCs) were higher in VAD piglets prechallenge, but decreased substantially postchallenge as compared with VAS pigs. We observed significantly higher frequency of CD103 (integrin αEβ7) expressing DCs in VAS versus VAD piglets postchallenge, indicating that VAD may interfere with homing (including intestinal) phenotype acquisition. Post-VirHRV challenge, we observed longer and more pronounced diarrhea and higher VirHRV fecal titers in nonvaccinated VAD piglets. Consistent with higher VirHRV shedding titers, higher IFN-α levels were induced in control VAD versus VAS piglet sera at postchallenge day 2. Ex vivo HRV-stimulated mononuclear cells (MNCs) isolated from spleen and blood of VAD pigs prechallenge also produced more IFN-α. In contrast, at postchallenge day 10, we observed reduced IFN-α levels in VAD pigs that coincided with decreased TLR3+ MNC frequencies. Numbers of necrotic MNCs were higher in VAD pigs in spleen (coincident with splenomegaly in other VAD animals) prechallenge and intestinal tissues (coincident with higher VirHRV induced intestinal damage) postchallenge. Thus, prenatal VAD caused an imbalance in innate immune responses and exacerbated VirHRV infection, whereas vitamin A supplementation failed to compensate for these VAD effects.
Id2-Mediated Inhibition of E2A Represses Memory CD8+ T Cell Differentiation
Authors: Masson Frederick , Minnich Martina , Olshansky Moshe , Bilic Ivan , Mount Adele M. , Kallies Axel , Speed Terence P. , Busslinger Meinrad , Nutt Stephen L. , Belz Gabrielle T. 
Published: March 2013

Abstract
The transcription factor inhibitor of DNA binding (Id)2 modulates T cell fate decisions, but the molecular mechanism underpinning this regulation is unclear. In this study we show that loss of Id2 cripples effector differentiation and instead programs CD8+ T cells to adopt a memory fate with increased Eomesodermin and Tcf7 expression. We demonstrate that Id2 restrains CD8+ T cell memory differentiation by inhibiting E2A-mediated direct activation of Tcf7 and that Id2 expression level mirrors T cell memory recall capacity. As a result of the defective effector differentiation, Id2-deficient CD8+ T cells fail to induce sufficient Tbx21 expression to generate short-lived effector CD8+ T cells. Our findings reveal that the Id2/E2A axis orchestrates T cell differentiation through the induction or repression of downstream transcription factors essential for effector and memory T cell differentiation.
Nonstereotyped Lymphoma B Cell Receptors Recognize Vimentin as a Shared Autoantigen
Authors: Cha Soung-Chul , Qin Hong , Kannan Shibichakravarthy , Rawal Seema , Watkins Leticia S. , Baio Flavio E. , Wu Weiguo , Ong Juliana , Wei Jinsong , Kwak Benjamin , Kim Sang , Popescu Michael S. , Paick Daniel S. , Kim Kunhwa , Luong Amber , Davis Richard E. , Schroeder Harry W. , Kwak Larry W. , Neelapu Sattva S. 
Published: March 2013

Abstract
Ag activation of the BCR may play a role in the pathogenesis of human follicular lymphoma (FL) and other B cell malignancies. However, the nature of the Ag(s) recognized by tumor BCRs has not been well studied. In this study, we used unbiased approaches to demonstrate that 42 (19.35%) of 217 tested FL Igs recognized vimentin as a shared autoantigen. The epitope was localized to the N-terminal region of vimentin for all vimentin-reactive tumor Igs. We confirmed specific binding to vimentin by using recombinant vimentin and by performing competitive inhibition studies. Furthermore, using indirect immunofluorescence staining, we showed that the vimentin-reactive tumor Igs colocalized with an anti-vimentin mAb in HEp-2 cells. The reactivity to N-terminal vimentin of IgG FL Igs was significantly higher than that of IgM FL Igs (30.4 versus 10%; p = 0.0022). However, vimentin-reactive FL Igs did not share CDR3 motifs and were not homologous. Vimentin was expressed in the T cell–rich regions of FL, suggesting that vimentin is available for binding with tumor BCRs within the tumor microenvironment. Vimentin was also frequently recognized by mantle cell lymphoma and multiple myeloma Igs. Our results demonstrate that vimentin is a shared autoantigen recognized by nonstereotyped FL BCRs and by the Igs of mantle cell lymphoma and multiple myeloma and suggest that vimentin may play a role in the pathogenesis of multiple B cell malignancies. These findings may lead to a better understanding of the biology and natural history of FL and other B cell malignancies.
Restoring Immune Function of Tumor-Specific CD4+ T Cells during Recurrence of Melanoma
Authors: Goding Stephen R. , Wilson Kyle A. , Xie Ying , Harris Kristina M. , Baxi Aparna , Akpinarli Akgul , Fulton Amy , Tamada Koji , Strome Scott E. , Antony Paul Andrew 
Published: March 2013

Abstract
Recurrent solid malignancies are often refractory to standard therapies. Although adoptive T cell transfer may benefit select individuals, the majority of patients succumb to their disease. To address this important clinical dilemma, we developed a mouse melanoma model in which initial regression of advanced disease was followed by tumor recurrence. During recurrence, Foxp3+ tumor-specific CD4+ T cells became PD-1+ and represented &gt;60% of the tumor-specific CD4+ T cells in the host. Concomitantly, tumor-specific CD4+ T effector cells showed traits of chronic exhaustion, as evidenced by their high expression of the PD-1, TIM-3, 2B4, TIGIT, and LAG-3 inhibitory molecules. Although blockade of the PD-1/PD-L1 pathway with anti–PD-L1 Abs or depletion of tumor-specific regulatory T cells (Tregs) alone failed to reverse tumor recurrence, the combination of PD-L1 blockade with tumor-specific Treg depletion effectively mediated disease regression. Furthermore, blockade with a combination of anti–PD-L1 and anti–LAG-3 Abs overcame the requirement to deplete tumor-specific Tregs. In contrast, successful treatment of primary melanoma with adoptive cell therapy required only Treg depletion or Ab therapy, underscoring the differences in the characteristics of treatment between primary and relapsing cancer. These data highlight the need for preclinical development of combined immunotherapy approaches specifically targeting recurrent disease.