899 resultados para Recipient


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[Excerpt] Cornell University and the Baker Program in Real Estate are pleased to announce the 2016 Real Estate Industry Leader Award recipient: MaryAnne Gilmartin, President & CEO of Forest City Ratner Companies. MaryAnne’s leadership in the real estate industry has made a powerful and positive impact on society as a driving force behind several of the highest-profile, largest-scale additions to the urban landscape of New York City.

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La transplantation de cellules souches hématopoïétiques (CSH) constitue une avenue thérapeutique potentiellement curative pour plusieurs cancers hématologiques comme la leucémie. L’utilisation d’une thérapie immunosuppressive pour prévenir la maladie du greffon contre l’hôte (GvHD) est un déterminant majeur du succès de la greffe. Malgré tout, cette complication survient chez 25 à 50% des transplantés et est une cause majeure de mortalité. L’optimisation du régime d’immunosuppression est un facteur facilement modifiable qui pourrait améliorer le pronostic des patients. Particulièrement, les polymorphismes du génome du donneur ou du receveur dans les voies pharmacogénomiques des immunosuppresseurs pourraient influencer l’exposition et l’action de ces médicaments, de même que le pronostic du patient. Le profilage de 20 pharmacogènes prioritaires chez des paires de donneurs-receveurs en greffe de CSH a permis d’identifier des variations génétiques liées au risque de la GvHD aiguë. Principalement, le statut génétique du receveur pour les protéines ABCC1 et ABCC2, impliquées dans le transport du méthotrexate (MTX), ainsi que des cibles moléculaires de ce médicament (ATIC et MTHFR) ont été associées au risque de GvHD aiguë. Similairement, le NFATc1, codant pour une cible moléculaire de la cyclosporine, augmentait lui aussi le risque de la maladie. Les porteurs de deux génotypes à risque et plus étaient particulièrement prédisposés à développer cette complication. Par surcroît, le statut génétique du donneur influençait également le pronostic du receveur après la greffe. Entre autres, des allèles protecteurs ont été identifiés dans les voies liées au transport (SLC19A1) et à l’action du MTX (DHFR). Inversement, NFATc2 a été associé à une augmentation du risque de GvHD aiguë. Afin de mieux comprendre les associations observées entre ces marqueurs génétiques et le risque de GvHD aiguë, une étude prospective innovante est en cours chez des greffés de CSH. Cette étude permettra d’étudier comment la génétique du patient ou du donneur peut influencer la pharmacocinétique et la pharmacodynamie des immunosuppresseurs, de même que leurs liens avec la GvHD aiguë. Ces paramètres sont quantifiés grâce à des approches analytiques que nous avons mises au point afin de répondre aux besoins spécifiques et uniques de cette étude. Les approches proposées dans cette thèse sont complémentaires aux méthodes classiques de suivi des immunosuppresseurs et pourraient aider à optimiser la pharmacothérapie du patient. Une meilleure identification des patients à haut risque de GvHD aiguë avant la greffe, basée sur des marqueurs pharmacogénomiques identitaires, pourrait guider le choix de la prophylaxie immunosuppressive, et ainsi améliorer l’issue clinique de la greffe.

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Direct allorecognition is the process by which donor-derived major histocompatibility complex (MHC)-peptide complexes, typically presented by donor-derived ‘passenger’ dendritic cells, are recognised directly by recipient T cells. In this review, we discuss the two principle theories which have been proposed to explain why individuals possess a high-precursor frequency of T cells with direct allospecificity and how self-restricted T cells recognise allogeneic MHCpeptide complexes. These theories, both of which are supported by functional and structural data, suggest that T cells recognising allogeneic MHC-peptide complexes focus either on the allopeptides bound to the allo-MHC molecules or the allo-MHC molecules themselves. We discuss how direct alloimmune responses may be sustained long term, the consequences of this for graft outcome and highlight novel strategies which are currently being investigated as a potential means of reducing rejection mediated through this pathway.

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In the first part of this thesis, the oncogenic potential of TCL1A family genes was comparatively evaluated by using gamma-retroviral vectors to introduce human TCL1A, MTCP1, and TML1 into hematopoietic stem cells/hematopoietic progenitor cells (HSC/HPC) of wild type mice that were transplanted into wild type recipients. TCL1A and MTCP1 recipient mice predominantly developed B-cell malignancies after a median survival of 388 days and 394 days, respectively. The presented data indicates that TCL1A and MTCP1 are oncogenes with comparable oncogenic potential and shows for the first time that MTCP1 is not only a T-cell oncogene, but is able to transform B cells as well. The third family member TML1 induced the development of immature T-cell malignancies in only a few mice. This study provides first evidence for its oncogenic function. Additionally, the transforming potential of compartment-targeted TCL1A variants was evaluated by retroviral expression of a membrane localizing myristoylated (myr-TCL1A) and a nuclear localizing (nls-TCL1A) variant. Recipients of HSC/HPC transduced with myr-TCL1A and nls-TCL1A predominantly developed B-cell malignancies after a median survival of 360 days and 349 days, respectively. There was a significantly shorter latency period for nls-TCL1A compared to the previously described generic TCL1A. Gene expression analysis revealed higher similarities between expression profiles of tumors induced by TCL1A and nls-TCL1A. Together these data implicate that TCL1A’s predominant oncogenic function might rely on its nuclear presence. The second part of this thesis aims to understand if and how TCR stimulation affects the transforming potential of TCL1A. Mature OT-1 T cells carrying monoclonal TCR’s that specifically recognize ovalbumin (OVA) were retrovirally transduced with TCL1A and repeatedly stimulated in vivo with OVA-peptides. TCR stimulated recipient mice of TCL1A transduced T cells showed a significantly accelerated leukemic outgrowth and a reduced median survival of 305 days, when compared to unstimulated recipients (417 days). These data strongly implicate a pro-leukemogenic cooperation of TCL1A and TCR signals that might be actionable in upcoming interventional designs.

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Many times, moving a loved one into a long-term care facility is a true act of love and unselfishness. If the caregiver and the care recipient cannot leave the house, you have both become very isolated. Imagine mom being able to go outside her door to find someone to talk with. There are activities, meals to be shared with friends, and a barrier free area where she can roam.

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Understanding the evolution of sociality in humans and other species requires understanding how selection on social behaviour varies with group size. However, the effects of group size are frequently obscured in the theoretical literature, which often makes assumptions that are at odds with empirical findings. In particular, mechanisms are suggested as supporting large-scale cooperation when they would in fact rapidly become ineffective with increasing group size. Here we review the literature on the evolution of helping behaviours (cooperation and altruism), and frame it using a simple synthetic model that allows us to delineate how the three main components of the selection pressure on helping must vary with increasing group size. The first component is the marginal benefit of helping to group members, which determines both direct fitness benefits to the actor and indirect fitness benefits to recipients. While this is often assumed to be independent of group size, marginal benefits are in practice likely to be maximal at intermediate group sizes for many types of collective action problems, and will eventually become very small in large groups due to the law of decreasing returns. The second component is the response of social partners on the past play of an actor, which underlies conditional behaviour under repeated social interactions. We argue that under realistic conditions on the transmission of information in a population, this response on past play decreases rapidly with increasing group size so that reciprocity alone (whether direct, indirect, or generalised) cannot sustain cooperation in very large groups. The final component is the relatedness between actor and recipient, which, according to the rules of inheritance, again decreases rapidly with increasing group size. These results explain why helping behaviours in very large social groups are limited to cases where the number of reproducing individuals is small, as in social insects, or where there are social institutions that can promote (possibly through sanctioning) large-scale cooperation, as in human societies. Finally, we discuss how individually devised institutions can foster the transition from small-scale to large-scale cooperative groups in human evolution.

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Pinctada margaritifera is an economically important marine bivalve species for cultured pearl production in French Polynesian aquaculture. In order to evaluate the influence of donor oyster age on pearl quality traits, experiments were conducted over 6 years using both grafts and surgreffe operations. At harvest, 6 pearl quality traits were recorded and compared: surface defects, luster, grade, darkness level, and visual color. Analyzing the quality traits of pearls harvested in the initial graft process and those of pearls obtained from surgreffe experiments allowed a comparison of the influence of pearl sac cells originating from the initial mantle graft, which aged together with their recipient oysters. The results demonstrated a significant decrease between these successive grafts in luster, grade (A-B-C,) darkness level, and green color – traits that are of major importance in the pearl market. The duplicated graft experiment allowed the comparison of donor oyster families at 2 and 5 years old, where a mantle graft was inserted into recipient oysters aged 2.5 years old. The results showed the same tendencies to a lesser extent, with 1) an improved pearl grade, predominantly through a most important rate of 0 surface defect category, and 2) a green / grey ratio in favor of the younger donor. A comparison between the graft-surgreffe and the duplicated graft experiments also highlighted: 1) the indirect role played by the younger recipient oysters, which must be optimized for optimal pearl quality realization, and 2) the complex interplay between donor and recipient oysters.

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Spectrum Disorder (ASD), is a heterogeneous neurodevelopmental disorder with na estimated global prevalence rate of 17:10000, and a male to female ratio of 4:1. Patients with ASD presente language and communication difficulties and stereotyped behaviours. Comorbidity with other disorders, such as Intelectual Disability, Fragile-X syndrome (FXS) epilepsy and tuberous sclerosis frequently occurs. ASD presents amultifactorial etiopathology, and genetic factos alone are not suficiente to explain how the syndrome arises, with recente studies establishing ASD heritability at approximately 50%. Pre-, peri- and post-natal exposure to toxic environmental factos has been implicated in the development of ASD. Involvement of epigenetic regulatory mechanisms has been suggested, supported by the occurrence of autistic symptoms in patients with disorders aris ing from epigenetic mutations, such as FXS. A polygenic and epistatic model is a strong hypothesis to explain ASD. The main goal of this project is to identify specific exposure patterns to environmental toxicants in children diagnosed with ASD and integrate the results with genetic and epigenetic data.

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Artykuł przedstawia news telewizyjny jako akt retoryczny. News telewizyjny rozumiany jest jako relacja o wydarzeniu zbudowana zazwyczaj z zapowiedzi i krótkiego kilkuminutowego materiału filmowego (nazywanego czasem felietonem), będącego rezultatem pracy reporter-skiej, wyemitowana w telewizji, zazwyczaj jako jeden z elementów w strukturze magazynu informacyjnego, ale również jako element bloków programowych telewizji informacyjnych. Newsy telewizyjne funkcjonują w mediach jako jeden z elementów działań strategicznych nadawców medialnych nastawionych na określone cele, w tym cele wizerunkowe, polityczne i ekonomiczne. Newsy powstają jako reakcja na konkretne wydarzenia, zaspokajają potrzebę informacji, ale służą też kreowaniu obrazu świata, skupianiu uwagi na pewnych aspektach rze-czywistości, wartościowaniu jej, przekonywaniu o ważności lub nieważności pewnych zda-rzeń. Pełnią funkcje informacyjne, ale też kreacyjne, wzorcotwórcze, stymulacyjne, wartościu-jące, i w końcu estetyczne. Dla osiągnięcia tych celów są odpowiednio konstruowane, z uwzględnieniem specyfiki i potrzeb odbiorcy oraz ethosu nadawcy. W tym sensie są więc ak-tami „retorycznymi”, a więc zamierzonymi, celowymi, będącymi odpowiedzią na określoną sytuację (uwarunkowane są historycznie, społecznie i politycznie) i adresowanymi do określo-nych odbiorców.

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W artykule dowodzi się tezy, że współczesne debaty publiczne, emitowane w telewizji (takie jak emitowany od 2004 roku w TVP2 program Jana Pospieszalskiego „Warto rozmawiać”), są zdarzeniami komunikacyjnymi zasadzonymi na konflikcie destruktywnym, a więc takim, który wg L. Kriesberga, nastawiony jest nie na problem wywołujący frustrację, ale jest manifestacją agresji, a celem sporu staje się nie pokonanie różnic dzielących strony, ale pokonanie oponenta. Wynika to z sytuacji komunikacyjnej debaty telewizyjnej i nastawienia w pierwszej kolejności na zdobycie uwagi, a potem zaspokajanie potrzeb odbiorcy sekundarnego – widza. Podporządkowane są temu takie elementy, jak wybór tematu debaty, jej scenariusz, dobór uczestników, a w dalszej kolejności ich zachowania werbalne i niewerbalne. W rezultacie, w debacie telewizyjnej złamane zostają typowe dla debaty konstruktywnej reguły i strategie, i zastąpione zostają zachowaniami typowymi dla konfliktu destruktywnego, takimi jak: brak otwartości na argumenty drugiej strony, nastawienie na pokonanie antagonisty, niechęć do szukania innych rozwiązań, jak tylko moja wygrana - twoja przegrana, działania nastawione na prowokację i podważanie wiarygodności partnera, przenoszenie ciężaru debaty ze sprawy na osobę, posługiwanie się argumentacją niemerytoryczną, niezgoda na konstruowanie wspólnego stanowiska. Taki wzorzec debaty telewizyjnej, która stała się pośpieszną, bezproduktywną prezentacją rozbieżnych stanowisk, nie prowadzącą do żadnych konkluzji, nastawioną najwyżej na obrażenie rozmówcy i dostarczenie widzowi krótkotrwałych emocji, buduje powszechne przekonania o niemożności dialogu i porozumienia w dyskursie publicznym i dominującym w nim antagonizmie.

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Transplantation is one of the most beautiful achievements for humanity in the last century and became the last hope to many patients. As other beautiful achievements, it has been used by criminals. The future of transplantation will be focused on tissue and cells transplantation. Trafficking of human beings to organ removal and trafficking of human organs are an early stage of trafficking on tissues and cells comparable with slaves trafficking in the 17th and 18th century. As 400 years ago, the motive for the crime is development, economy and profit. Transplant surgery is the modern “cotton gin” to this new commerce. Poverty exploitation, unprotected people, are always the victims. Even so, there are some differences since then. The paying buyers are the patients themselves and the “cotton” transplanted is not so harmless. Unsafe tissues and cells inappropriately collected and allocated can be so dangerous to the recipient and his family, that the dreamed transplant/implant becomes a nightmare. Beyond the trafficking crime, there is a most dangerous associated crime that is the crime of spreading dangerous infectious diseases.