323 research outputs found

    Orbit Assembly Of Unmanned Spacecraft

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    In future, the mission demands on unmanned spacecraft, (whether they be Earth orbiters or deep space probes) , will be so great and so complex as to preclude their being small enough to be launched from Earth by chemical rocket. Such spacecraft can be assembled in Earth orbit by suited astronauts, using pre-fabricated modules specifically designed for such orbital assembly. These modules could be standardized, so that any number of spacecraft and mission requirements could be accommodated without extensive need for specialized hardware

    Interaction between C/EBPβ and Tax down-regulates human T-cell leukemia virus type I transcription

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    AbstractThe human T-cell leukemia virus type I (HTLV-I) Tax protein trans-activates viral transcription through three imperfect tandem repeats of a 21-bp sequence called Tax-responsive element (TxRE). Tax regulates transcription via direct interaction with some members of the activating transcription factor/CRE-binding protein (ATF/CREB) family including CREM, CREB, and CREB-2. By interacting with their ZIP domain, Tax stimulates the binding of these cellular factors to the CRE-like sequence present in the TxREs. Recent observations have shown that CCAAT/enhancer binding protein β (C/EBPβ) forms stable complexes on the CRE site in the presence of CREB-2. Given that C/EBPβ has also been found to interact with Tax, we analyzed the effects of C/EBPβ on viral Tax-dependent transcription. We show here that C/EBPβ represses viral transcription and that Tax is no more able to form a stable complex with CREB-2 on the TxRE site in the presence of C/EBPβ. We also analyzed the physical interactions between Tax and C/EBPβ and found that the central region of C/EBPβ, excluding its ZIP domain, is required for direct interaction with Tax. It is the first time that Tax is described to interact with a basic leucine-zipper (bZIP) factor without recognizing its ZIP domain. Although unexpected, this result explains why C/EBPβ would be unable to form a stable complex with Tax on the TxRE site and could then down-regulate viral transcription. Lastly, we found that C/EBPβ was able to inhibit Tax expression in vivo from an infectious HTLV-I molecular clone. In conclusion, we propose that during cell activation events, which stimulate the Tax synthesis, C/EBPβ may down-regulate the level of HTLV-I expression to escape the cytotoxic-T-lymphocyte response

    SOD1G93A transgenic mouse CD4+ T cells mediate neuroprotection after facial nerve axotomy when removed from a suppressive peripheral microenvironment

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    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving motoneuron (MN) axonal withdrawal and cell death. Previously, we established that facial MN (FMN) survival levels in the SOD1G93A transgenic mouse model of ALS are reduced and nerve regeneration is delayed, similar to immunodeficient RAG2-/- mice, after facial nerve axotomy. The objective of this study was to examine the functionality of SOD1G93A splenic microenvironment, focusing on CD4+ T cells, with regard to defects in immune-mediated neuroprotection of injured MN. We utilized the RAG2-/- and SOD1G93A mouse models, along with the facial nerve axotomy paradigm and a variety of cellular adoptive transfers, to assess immune-mediated neuroprotection of FMN survival levels. We determined that adoptively transferred SOD1G93A unfractionated splenocytes into RAG2-/- mice were unable to support FMN survival after axotomy, but that adoptive transfer of isolated SOD1G93A CD4+ T cells could. Although WT unfractionated splenocytes adoptively transferred into SOD1G93A mice were able to maintain FMN survival levels, WT CD4+ T cells alone could not. Importantly, these results suggest that SOD1G93A CD4+ T cells retain neuroprotective functionality when removed from a dysfunctional SOD1G93A peripheral splenic microenvironment. These results also indicate that the SOD1G93A central nervous system microenvironment is able to re-activate CD4+ T cells for immune-mediated neuroprotection when a permissive peripheral microenvironment exists. We hypothesize that dysfunctional SOD1G93A peripheral splenic microenvironment may compromise neuroprotective CD4+ T cell activation and/or differentiation, which, in turn, results in impaired immune-mediated neuroprotection for MN survival after peripheral axotomy in SOD1G93A mice

    Facial Nerve Axotomy in Mice: A Model to Study Motoneuron Response to Injury

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    The goal of this surgical protocol is to expose the facial nerve, which innervates the facial musculature, at its exit from the stylomastoid foramen and either cut or crush it to induce peripheral nerve injury. Advantages of this surgery are its simplicity, high reproducibility, and the lack of effect on vital functions or mobility from the subsequent facial paralysis, thus resulting in a relatively mild surgical outcome compared to other nerve injury models. A major advantage of using a cranial nerve injury model is that the motoneurons reside in a relatively homogenous population in the facial motor nucleus in the pons, simplifying the study of the motoneuron cell bodies. Because of the symmetrical nature of facial nerve innervation and the lack of crosstalk between the facial motor nuclei, the operation can be performed unilaterally with the unaxotomized side serving as a paired internal control. A variety of analyses can be performed postoperatively to assess the physiologic response, details of which are beyond the scope of this article. For example, recovery of muscle function can serve as a behavioral marker for reinnervation, or the motoneurons can be quantified to measure cell survival. Additionally, the motoneurons can be accurately captured using laser microdissection for molecular analysis. Because the facial nerve axotomy is minimally invasive and well tolerated, it can be utilized on a wide variety of genetically modified mice. Also, this surgery model can be used to analyze the effectiveness of peripheral nerve injury treatments. Facial nerve injury provides a means for investigating not only motoneurons, but also the responses of the central and peripheral glial microenvironment, immune system, and target musculature. The facial nerve injury model is a widely accepted peripheral nerve injury model that serves as a powerful tool for studying nerve injury and regeneration

    Identification of B6SJL mSOD1(G93A) mouse subgroups with different disease progression rates

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    Disease progression rates among patients with amyotrophic lateral sclerosis (ALS) vary greatly. Although the majority of affected individuals survive 3-5 years following diagnosis, some subgroups experience a more rapidly progressing form, surviving less than 1 year, and other subgroups experience slowly progressing forms, surviving nearly 50 years. Genetic heterogeneity and environmental factors pose significant barriers in investigating patient progression rates. Similar to the case for humans, variation in survival within the mSOD1 mouse has been well documented, but different progression rates have not been investigated. The present study identifies two subgroups of B6SJL mSOD1(G93A) mice with different disease progression rates, a fast progression group (FPG) and slow progression group, as evidenced by differences in the rate of motor function decline. In addition, increased disease-associated gene expression within the FPG facial motor nucleus confirmed the presence of a more severe phenotype. We hypothesize that a more severe disease phenotype could be the result of 1) an earlier onset of axonal disconnection with a consistent degeneration rate or 2) a more severe or accelerated degenerative process. We performed a facial nerve transection axotomy in both mSOD1 subgroups prior to disease onset as a method to standardize the axonal disconnection. Instead of leading to comparable gene expression in both subgroups, this standardization did not eliminate the severe phenotype in the FPG facial nucleus, suggesting that the FPG phenotype is the result of a more severe or accelerated degenerative process. We theorize that these mSOD1 subgroups are representative of the rapid and slow disease phenotypes often experienced in ALS

    Complexity of Bradley-Manna-Sipma Lexicographic Ranking Functions

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    In this paper we turn the spotlight on a class of lexicographic ranking functions introduced by Bradley, Manna and Sipma in a seminal CAV 2005 paper, and establish for the first time the complexity of some problems involving the inference of such functions for linear-constraint loops (without precondition). We show that finding such a function, if one exists, can be done in polynomial time in a way which is sound and complete when the variables range over the rationals (or reals). We show that when variables range over the integers, the problem is harder -- deciding the existence of a ranking function is coNP-complete. Next, we study the problem of minimizing the number of components in the ranking function (a.k.a. the dimension). This number is interesting in contexts like computing iteration bounds and loop parallelization. Surprisingly, and unlike the situation for some other classes of lexicographic ranking functions, we find that even deciding whether a two-component ranking function exists is harder than the unrestricted problem: NP-complete over the rationals and ÎŁ2P\Sigma^P_2-complete over the integers.Comment: Technical report for a corresponding CAV'15 pape

    Fast and slow rates of symptom progression in the transgenic SOD1 murine model of ALS

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    poster abstractALS is a disease targeting motoneurons (MN). In the SOD1 mouse model of ALS, an axonal dieback process is initiated during the pre-symptomatic stage where MN axons withdraw from target muscle. We have used facial nerve axotomy, which resembles the axonal die-back response, in pre-symptomatic SOD1 mice to investigate aspects of the disease. Apoptotic and pro-inflammatory gene expression is upregulated in pre-symptomatic SOD1 axotomized facial nuclei in addition to significant SOD1 MN death. Disease progression in symptomatic SOD1 facial nuclei resembles the molecular response initiated by axotomy. MN survival levels in symptomatic SOD1 and axotomized, presymptomatic SOD1 facial nuclei are similar. Therefore, facial nerve axotomy produces a disease onset-like response. The current study used behavioral testing to assess motor function, and revealed two groups of SOD1 mice with differing rates of symptomatic disease progression. The slow progression group had significantly less motor impairments compared to the fast progression group, but no difference in symptom onset was seen. Fast progression group showed higher mRNA levels for genes related to axonal injury. Symptomatic severity in SOD1 mice correlates to the cellular and molecular responses to axonal injury. Therefore, research using treatments to slow disease or extend

    La préservation du patrimoine naturel littoral dans le processus de la gestion intégrée des zones côtières : éléments de réflexion pour l'élaboration d'un projet et perspectives

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    The coastal zone is an area of conflicting processes reflecting its position at the interface between the terrestrial and marine environments. This area needs further study and an enforcement of co-ordinated conservation policy for the implementation of effective protection. A multidisciplinary team (law, ecology, biology, and geography) has published a book, which assembles the elements of current politics involved with the preservation of the natural heritage of the coasts of mainland France. Part 1 deals on the definition of the coastal zone, the dispositions for the preservation of the natural heritage, the institutions concerned with its knowledge about and management and the objective criteria and methods for the choice or separation of zones to be protected. Part 2 gives the characteristic heritage aspects of the three coastal chosen regions. Part 3 gives perspectives to set up a more management model for the preservation of the natural heritage. It is necessary to have a clarification of current expertise resulting in a harmonization and institutional co-ordination of organisms linked to the coastal zone. The reform of the status of the CELRL increases its intervention in the maritime public domain. It offers prospects to consolidate this organization in its role in the protection of the littoral natural patrimonyInterface entre le milieu terrestre et le milieu marin, le littoral est une zone conflictuelle où les usages sont contradictoires, et un espace où il existe des besoins de connaissances et où il faut mettre en place une politique coordonnée de protection. Un ouvrage vient d'être réalisé par une équipe pluridisciplinaire (droit, écologie, biologie, géographie) en réponse au programme LITEAU du MATE. Il recense les éléments de la politique de préservation du patrimoine naturel de la France métropolitaine. Il prend pour exemples trois littoraux. Le Temps 1 s'ordonne autour des définitions du littoral, des institutions impliquées dans sa connaissance et sa gestion, des critères et méthodes objectives pour choisir ou délimiter des zones à préserver. Le Temps 2 traite des particularités patrimoniales des trois régions choisies. Le Temps 3 donne des perspectives pour construire un modèle de gestion satisfaisant du patrimoine naturel littoral à partir de l'analyse de l'existant. Les nombreuses interactions entre les intervenants multiples sur le littoral imposent une clarification des compétences, une harmonisation et une coordination institutionnelle. La réforme du statut du CELRL prévoit son intervention au domaine public maritime ; elle offre des perspectives pour le conforter dans son rôle d'acteur de la protection du patrimoine naturel littoral
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