1,153 research outputs found

    Dynamics of a ball bouncing on a vibrated elastic membrane

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    International audienceWe investigate the dynamics of a ball bouncing on a vibrated elastic membrane. Beyond the classical solid/solid case, we study the effect of introducing new degrees of freedom by allowing substrate oscillations. The forcing frequency of the vibration strongly influences the different thresholds between the dynamical states. The simple model proposed gives a good agreement between the experiments and the analytical expression for the threshold at which the ball begins to bounce. Numerical simulations permit to qualitatively recover the experimental phase diagram. Finally, we discuss how this simple system can give new insights in the recent experimental studies on bouncing droplets

    Pregnancy induces a fetal antigen-specific maternal T regulatory cell response that contributes to tolerance

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    A fetus is inherently antigenic to its mother and yet is not rejected. The T regulatory (Treg) subset of CD4^+ T cells can limit immune responses and has been implicated in maternal tolerance of the fetus. Using virgin inbred mice undergoing a first syngenic pregnancy, in which only the male fetuses are antigenic, we demonstrate a maternal splenocyte proliferative response to the CD4^+ T cell restricted epitope of the male antigen (H-Y) in proportion to the fetal antigen load. A portion of the maternal immune response to fetal antigens is Treg in nature. The bystander suppressive function of pregnancy-generated Tregs requires the presence of the fetal antigen, demonstrating their inherent antigen specificity. In vivo targeting of diphtheria toxin to kill Tregs leads to a lower fraction of live male offspring and a selective reduction in mass of the surviving males. Thus, Tregs generated in the context of pregnancy function in an antigen-specific manner to limit the maternal immune response to the fetus in a successful pregnancy

    Establishment of a patient-derived orthotopic osteosarcoma mouse model

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    Background: Osteosarcoma (OS) is the most common pediatric primary malignant bone tumor. As the prognosis for patients following standard treatment did not improve for almost three decades, functional preclinical models that closely reflect important clinical cancer characteristics are urgently needed to develop and evaluate new treatment strategies. The objective of this study was to establish an orthotopic xenotransplanted mouse model using patient-derived tumor tissue. Methods: Fresh tumor tissue from an adolescent female patient with osteosarcoma after relapse was surgically xenografted into the right tibia of 6 immunodeficient BALB/c Nu/Nu mice as well as cultured into medium. Tumor growth was serially assessed by palpation and with magnetic resonance imaging (MRI). In parallel, a primary cell line of the same tumor was established. Histology and high-resolution array-based comparative genomic hybridization (aCGH) were used to investigate both phenotypic and genotypic characteristics of different passages of human xenografts and the cell line compared to the tissue of origin. Results: A primary OS cell line and a primary patient-derived orthotopic xenotranplanted mouse model were established. MRI analyses and histopathology demonstrated an identical architecture in the primary tumor and in the xenografts. Array-CGH analyses of the cell line and all xenografts showed highly comparable patterns of genomic progression. So far, three further primary patient-derived orthotopic xenotranplanted mouse models could be established. Conclusion: We report the first orthotopic OS mouse model generated by transplantation of tumor fragments directly harvested from the patient. This model represents the morphologic and genomic identity of the primary tumor and provides a preclinical platform to evaluate new treatment strategies in OS

    The Influence of the Cytoskeleton on the Development and Behavior of Viral Factories in Mammalian Orthoreovirus

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    Cytosolic viral factories (VFs) of mammalian orthoreovirus (MRV) are sites for viral genome replication and assembly of virus progeny. Despite advancements in reverse genetics, the formation and dynamics of VFs still need to be clarified. MRV exploits host cytoskeletal components like microtubules (MTs) throughout its life cycle, including cell entry, replication, and release. MRV VFs, membrane-less cytosolic inclusions, rely on the viral proteins μ2 and μNS for formation. Protein μ2 interacts and stabilizes MTs through acetylation, supporting VF formation and viral replication, while scaffold protein μNS influences cellular components to aid VF maturation. The disruption of the MT network reduces viral replication, underscoring its importance. Additionally, μ2 associates with MT-organizing centers, modulating the MT dynamics to favor viral replication. In summary, MRV subverts the cytoskeleton to facilitate VF dynamics and promote viral replication and assembly to promote VF dynamics, replication, and assembly, highlighting the critical role of the cytoskeleton in viral replication

    Erweiterung von BPMN um kontextuelle Einflüsse auf Prozesse abzubilden

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    Die Welt in der wir leben unterliegt einem stetigem Wandel, welcher vor keinem Bereich halt macht. Die Notwendigkeit auf diesen Wandel adäquat und schnell zu reagieren ist nicht neu. Ebenso bekannt ist das Konzept des Prozessmanagements. Auch hier ist die Notwendigkeit auf Veränderungen zu reagieren gegeben. Sie wird durch Schlagworte wie Flexibilität und Exception-Handling gut beschrieben und auch abgedeckt. Ein Einfluss welcher sich stets ändern kann ist der Kontext. Gemeint ist hier nicht zwangsläufig die Umgebung des Prozesses sondern weitaus mehr. Die Nutzung dieses Einflusses zur Verfeinerung oder automatisierten Generierung von Prozessen ist ein Thema mit hoher Aktualität. Ebenso aktuell ist der Siegeszug der BPMN als rozessmodellierungs- und auch Prozessausführungssprache. Wie stellt man jedoch Kontext, kontextuelle Einflüsse und die Auswirkungen dieser dar? In der vorliegenden Arbeit wurden Prozesse aus den Anwendungsdomänen Medizin und Software Engineering betrachtet und analysiert. Aus den Schlüssen die daraus gezogen werden konnten, wurde ein Konzept entwickelt, welche die bereits erwähnte Darstellung mittels BPMN ermöglicht

    Determinação de manganês em pelos, dentes e soro de ratos wistar: potenciais biomarcadores de acúmulo em um modelo de intoxicação subaguda

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    Introdução: O Manganês (Mn) é um metal essencial aos humanos por participar em processos enzimáticos de desenvolvimento, metabolismo energético e defesas antioxidantes. Em altas concentrações, pode ser potencialmente tóxico e provocar danos ao sistema nervoso central, desencadeando sintomas como distonia, bradicinesia e rigidez muscular, consequências de uma desordem neurológica chamada Manganismo. Objetivos: Mensurar a concentração de Mn nos pelos, dentes e soro de ratos Wistars adultos, machos e fêmeas, e avaliar a função motora após intoxicação subaguda ao Mn. Metodologia: Os animais receberam doses baixas ou altas de Mn, 6mg/kg ou 15mg/kg respectivamente, intraperitonealmente, cinco dias por semana, durante quatro semanas, a fim de mimetizar a intoxicação subaguda. O grupo controle recebeu solução salina 0,9% da mesma forma de administração e pelo mesmo período. A concentração de Mn nos pelos, dentes e no soro foram mensuradas por meio de espectrometria de absorção atômica e a avaliação comportamental de função motora através do Rotarod. Resultados: Não foi observado acúmulo de Mn no soro dos animais, já que há propensão de que o Mn circulante se deposite em tecidos. Assim, houve um aumento na concentração de Mn nos tecidos avaliados e em ambos os gêneros quando comparados com o grupo controle. Por outro lado, não foi observada diferença significativa na latência para a queda entre os grupos no teste do Rotarod. Conclusão: O aumento nas concentrações de Mn em pelos e dentes dos animais pode ser indicativo de potenciais biomarcadores de exposição ao Mn, mesmo antes do aparecimento dos sintomas centrais do Manganismo. Palavras-chave: Manganês. Intoxicação Subaguda. Biomarcador de exposição
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