100,398 research outputs found
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Pelevin’s Trinity in the novel “t”: author – protagonist – reader
No full textThe article attempts to interpret Pelevin's artistic strategy in the novel "T" by exploring its subject organization and addressing the key problems of the author, the protagonist, and the reader as they are seen by the researcher. The article analyzes the peculiarities of constructing the narrative reality in the novel "T", and goes on to discuss Pelevin's philosophic models of the development of the humankind, and the emergence of his new anthropology
Measuring industry-science links through inventor-author relations: A profiling method
No full textIn this pilot study we examine the performance of text-based profiling in recovering a set of validated inventor-author links. In a first step we match patents and publications solely based on their similarity in content. Next, we compare inventor and author names on the highest ranked matches for the occurrence of name matches. Finally, we compare these candidate matches with the names listed in a validated set of inventor-author names. Our text-based profile methodology performs significantly better than a random matching of patents and publications, suggesting that text-based profiling is a valuable complementary tool to the name searches used in previous studies.innovation; industry-science links; text-based profiling;
Wave turbulence of a rotating array of quantized vortices in the T → 0 temperature limit
No full textThe dynamics of quantized vortices in the zero temperature limit is currently of great interest, particularly in the case of the Fermi superfluid He-B. Here we study wave turbulence, generated by the librating motion of a rotating cylindrical container filled with He-B, in the limit of vanishing viscous forces at temperatures . The polarization of the quantized vortices with respect to the axis of rotation is measured using non-invasive NMR techniques. We observe a decrease of the polarization when the librating motion is started, and a two-stage relaxation process when the modulation of the rotation velocity is stopped. The first relaxation process is associated with the dissipation of large-scale flow stored in inertial waves and the solid body rotation of the vortex array. From the decay of these energy reservoirs we determine the rate of energy dissipation of large-scale flow. The later second process is related to the relaxation of Kelvin waves on individual vortices. This process is monitored by the recovery of the polarization. The existence of a Kelvin wave cascade at the lowest temperatures is currently a central open question. We supply some evidence for the cascade
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
No full textThe majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire
Characterization of endothelial stem/progenitor cells in postnatal vasculogenesis
No full textLa thérapie cellulaire dans l'artériopathie oblitérante des membres inférieurs (AOMI) est un domaine de recherche visant la régénération vasculaire notamment au stade d'ischémie critique où le membre inférieur est à risque d'amputation. Les succès mitigés des essais thérapeutiques réalisés peuvent provenir du produit de thérapie cellulaire utilisé, comme par exemple la moelle osseuse autologue supposée contenir les progéniteurs vasculaires. L'origine des Endothelial Colony-Forming Cells (ECFCs), le sous-type vasculogénique des cellules progénitrices endothéliales, reste encore inconnu. Dans un 1er article (1), nous avons rapporté que les very small embryonic-like stem cells (VSELs) présentes chez l'adulte sont capables d'auto-renouvèlement et de différenciation vers les 3 lignées germinales et seraient un bon candidat. L'équipe du Pr Smadja a démontré que les VSELs issues de moelle osseuse humaine pouvaient se différentier en cellules endothéliales et contribuer à la vasculogénèse. Dans un 2ème article en écriture j'ai participé à la caractérisation par cytométrie en flux des cellules immatures circulantes de patients porteurs d'un coeur artificiel CARMAT. L'existence d'une néo-endothélialisation au sein de ce coeur témoigne d'une colonisation par des progéniteurs cellulaires et nous avons démontré une mobilisation de cellules immatures circulantes dont des VSELs un mois après implantation. A l'aide du panel d'anticorps mis au point dans le travail précédent, afin de quantifier, isoler et expandre des VSELs circulantes chez des patients avec AOMI nous avons mis en place la collection biologique prospective monocentrique VESSELS (VEry Small embryonic like cellS Expandability in Lower limb arterial diSease), stratifiée sur les stades d'ischémie d'effort ou ischémie critique et associé ou non au diabète. Seuls 55 patients ont été inclus en lien avec les difficultés d'inclusion liée à l'épidémie COVID-19. Par ailleurs, les VSELs sont apparentées aux cellules germinales primordiales migratrices et prolifèrent ainsi sous l'action de gonadotrophines : l'hormone folliculo-stimulante (FSH) et l'hormone lutéinisante (LH). Le 3ème article soumis à Journal of Thrombosis and Haemostasis(2), vise à tester les propriétés angiogéniques des ECFCs issus de sang de cordon traités par FSH et LH. Nous avons pu montrer qu'elles augmentaient le potentiel angiogénique des ECFCs in vitro mais pas leur prolifération ni l'engagement en ECFCs des cellules mononuclées de sang de cordon. Par ailleurs, la génération de thrombine était accrue après culture par FSH et ces gonadotrophines étaient plus élevées chez les hommes avec AOMI comparés à leurs contrôles. Ces hormones pourraient ainsi jouer un rôle dans la physiopathologie de l'AOMI. Enfin dans un 4ème article en cours d'écriture, j'ai comparé les caractéristiques distinguant les hommes et les femmes hospitalisés pour AOMI. A la ménopause les gonadotrophines restent élevées en plateau et n'ont plus les variations liées aux cycles menstruels. Les femmes nécessitent une hospitalisation pour AOMI à un âge plus avancé que les hommes, et leur athérosclérose est plus diffuse. Nous allons ajouter l'analyse des profils hormonaux dans la collection biologique VESSELS afin de mieux comprendre l'implication des gonadotrophines dans l'AOMI. En perspective, VESSELS permettra d'appliquer les techniques de caractérisation des cellules immatures développées au cours de ma thèse, puis d'isoler et expandre les VSELs afin de pouvoir tester ces cellules comme produit de thérapie cellulaire. Références : 1. Detriche, G., Guerin, C. L., Gendron, N., Mirault, T. & Smadja, D. M. Do Endothelial Colony'forming Cells Come From Bone Marrow or Vessels/VSELs? Stem Cell Rev. Rep. (2021) doi:10.1007/s12015-021-10140-y. 2. Détriché, G. et al. Gonadotropins as new active partners in vascular diseases: insight from endothelial colony-forming cells angiogenic properties and thrombotic potential. J. Thromb. Haemost. submittedCell therapy in peripheral arterial disease of the lower limbs (PAD) is an area of research aimed at vascular regeneration, particularly at the stage of critical limb ischemia where the lower limb is at risk of amputation. The mixed successes of the therapeutic trials carried out may be due to the cell therapy product used, like bone marrow supposedly containing vascular progenitors. The origin of Endothelial Colony-Forming Cells (ECFCs), the vasculogenic subtype of endothelial progenitor cells, remains unknown. In a first article(1) we reported that very small embryonic-like stem cells (VSELs), present in adult bone marrow are capable of self-renewal and differentiation into the 3 germinal lineages and would be a good candidate. Pr Smadja's team demonstrated that VSELs derived from human bone marrow could differentiate into endothelial cells and contribute to vasculogenesis. In a 2nd article in progress, I participated in the characterization by flow cytometry of immature circulating cells from patients with a CARMAT artificial heart. The existence of an endothelialization of their implant testifies to a colonization by progenitor cells and we were able to demonstrate a mobilization of circulating immature cells including VSELs 1 month after implantation. With the help of the antibody panel developed in the previous work, in order to quantify, isolate and then expand circulating VSELs in PAD, I set up the prospective biological collection VESSELS (VEry Small embryonic-like cellS Expandability in Lower limb arterial diSease) stratified on the stages of ischemia: claudication or critical limb ischemia and with associated diabetes or not. Only 55 patients were included but the COVID19 pandemic delayed inclusion capabilities.VSELs are related to migrating primordial germ cells and thus proliferate under the action of gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The 3rd article submitted to the Journal of Thrombosis and Haemostasis(2) aims at testing the angiogenic properties of ECFCs derived from cord blood and treated by FSH and LH. We demonstrated that they increased the angiogenic potential of ECFCs in vitro but not their proliferation or the commitment of cord blood mononuclear cells to ECFCs. Moreover, thrombin generation was increased by FSH and these gonadotropins were higher in men with PAD than in their controls. These hormones could thus play a role in the pathophysiology of PAD. Finally, in a 4th article in process, I compared the characteristics distinguishing men and women hospitalized for PAD. At menopause gonadotropins remain elevated in a plateau and have no longer the pulses associated with menstrual cycles. Women require hospitalization for PAD at a later age than men, and their atherosclerosis is more diffuse. Thus, we will add the analysis of hormonal profiles in the VESSELS biological collection to better understand the involvement of gonadotropins in PAD. In perspective, VESSELS will allow us to apply the characterization techniques of immature cells developed during my thesis, and then to isolate and expand VSELs in order to test these cells as a cell therapy product. References : 1. Detriche, G., Guerin, C. L., Gendron, N., Mirault, T. & Smadja, D. M. Do Endothelial Colony'forming Cells Come From Bone Marrow or Vessels/VSELs? Stem Cell Rev. Rep. (2021) doi:10.1007/s12015-021-10140-y. 2. Détriché, G. et al. Gonadotropins as new active partners in vascular diseases: insight from endothelial colony-forming cells angiogenic properties and thrombotic potential. J. Thromb. Haemost. submitted (2021)
Acoustic radiation due to scattering of T-S wave by the mean-flow distortion induced by steady local suction
No full textSubstantial sound waves can be generated by boundary-layer instability modes when the latter are scattered by a rapid mean-flow distortion. This is a rather generic mechanism and operates when an oncoming T-S wave is scattered by a steady local suction slot. This paper focuses on this problem by extending a recently developed Local Scattering Theory (Wu & Dong, J. Fluid Mech. submitted), where a so-called transmission coefficient, defined as the ratio of the T-S wave amplitude downstream of the scatter to that upstream, is introduced to characterize the effect of a local scatter on boundary-layer instability and transition. As in the earlier work, the mathematical formulation is based on triple-deck formulism, but in order to accommodate the acoustic far field, which was not considered in the paper mentioned, the unsteady terms in the upper deck, which play a leading-order role in radiation, are retained, and the influence of the radiated sound on the near-wall perturbation is included. The upper deck equation for the pressure is the Helmholtz equation rather than the Laplace equation. This leads to a modified pressure-displacement relation, which is coupled with the linearized boundary-layer equations in the lower deck. Discretization of the whole system formulates a generalized eigenvalue problem, which is solved numerically. It is found that suction suppresses oncoming T-S waves, and this effect increases with the suction velocity and the slot width. The directivity is ndependent of the flow parameters only when the Mach number is low. The intensity of the radiated sound in general increases with the frequency, the suction velocity and the width of the suction slot. Interestingly, for O(1) suction velocities, the radiated sound is very weak, indicating that the gain of stabilizing effect does not cause aeroacoustic penalty
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