321 research outputs found
Valoriser les processus pour élaborer des cahiers des charges: une approche innovante
Lors de la fusion de communes, l’organisation des services du feu et leur efficacité dans la lutte contre les incendies et autres sinistres est une préoccupation des autorités cantonales. L’accroissement des activités socio-économiques et des besoins humains exerce une pression grandissante sur les corps des sapeurs-pompiers (CSP), créant des difficultés de recrutement et de fonctionnement, réduisant l’efficacité d’utilisation des ressources disponibles (hommes et équipement). Le processus de collaboration ou de fusion au niveau des CSP vise à mieux identifier les problèmes et à être capable de répondre aux normes en vigueur, notamment en intervenant dans le délai stipulé (15 minutes à partir de l’alarme). Ce papier introduit un modèle de représentation des processus liés aux activités des sapeurs-pompiers (SP). La bonne compréhension de ces processus permet d’identifier les activités de chaque acteur et ainsi d’élaborer son cahier des charges (CdC). A partir de trois processus caractéristiques, les différentes étapes du modèle proposé sont explicitement mises en évidence
Finding the adequate location scenario after the merger of fire brigades thanks to Multiple Criteria Decision Analysis Methods
This paper addresses the issue of selecting a suitable location for a fire station in canton of Fribourg, as a result of a fire brigades’merger, by applying Multiple Criteria Decision Analysis (MCDA) methods. Solving the problem of determining fire station locations through various methods has been analyzed in-‐depth by researchers. However, a different approach, based on application of methods like ELECTRE and PROMETHEE is advanced in this paper. The selection of the most suitable fire station site is obtained by applying the designated methods to five distinctive alternatives (called scenarios), taking into consideration the relatively limited information and specifics, and the extensive number of relevant criteria that summed up to seventy-‐ eight. Taking the merger of the three local fire departments as an example, the proposed methods for selecting a suitable location for the fire station demonstrate and justify the reason behind this choice. Research shows that the applied methods have been proven to be useful and powerful tools that exhibited acceptable levels of consistency when selecting the best project. The main finding is that one scenario in particular proved to be strongly dominant over the others and most suitable in determining the fire station location
What economic sanctions signal : cheap talk, or putting your money where your mouth is?
Title from PDF of title page (University of Missouri--Columbia, viewed on Feb. 15, 2010 ).The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Dissertation advisor: Dr. A. Cooper Drury.Vita.Ph. D. University of Missouri--Columbia 2009.This study addresses the role of economic sanctions in foreign policy through two research questions. The first assesses the relationship between economic and military coercion, the studies of which have remained largely unlinked theoretically and empirically. My study bridges these gaps, developing a formal model of international dispute escalation beginning with the threat of a sanction, escalating through sanction imposition, and culminating with armed force. Presenting a simple argument of issue salience, the model predicts that the more the sender (challenger) values the issue under dispute, the more likely the dispute is to escalate to violence. Empirical evidence supports my theory that sender issue salience remains a key variable in determining dispute escalation. Since the end of the Cold War in particular, states have used economic coercion as a precursor to military force. My findings have significant implications for scholars and policymakers alike, as I argue that the way states use sanctions has changed dramatically since the collapse of the Soviet Union. The second research question tests a long-standing assumption in the literature. Researchers have presumed that sanctions serve as tacit signals to states other than their primary target to avoid the target's behavior that brought about the sanction. I put this assumption to the test and find no direct evidence of this signaling channel. However, I argue that further research is needed to fully uncover this signaling process.Includes bibliographical reference
Telomere length regulation: coupling DNA end processing to feedback regulation of telomerase
The conventional DNA polymerase machinery is unable to fully replicate the ends of linear chromosomes. To surmount this problem, nearly all eukaryotes use the telomerase enzyme, a specialized reverse transcriptase that utizes its own RNA template to add short TG-rich repeats to chromosome ends, thus reversing their gradual erosion occurring at each round of replication. This unique, non-DNA templated mode of telomere replication requires a regulatory mechanism to ensure that telomerase acts at telomeres whose TG tracts are too short, but not at those with long tracts, thus maintaining the protective TG repeat cap at an appropriate average length. The prevailing notion in the field is that telomere length regulation is brought about through a negative feedback mechanism that counts TG repeat-bound protein complexes to generate a signal that regulates telomerase action. This review summarizes experiments leading up to this model and then focuses on more recent experiments, primarily from yeast, that begin to suggest how this counting mechanism might work. The emerging picture is that of a complex interplay between the conventional DNA replication machinery, DNA damage response factors, and a specialized set of proteins that help to recruit and regulate the telomerase enzyme
Proteostatic Control of Telomerase Function through TRiC-Mediated Folding of TCAB1
SummaryTelomere maintenance by telomerase is impaired in the stem cell disease dyskeratosis congenita and during human aging. Telomerase depends upon a complex pathway for enzyme assembly, localization in Cajal bodies, and association with telomeres. Here, we identify the chaperonin CCT/TRiC as a critical regulator of telomerase trafficking using a high-content genome-wide siRNA screen in human cells for factors required for Cajal body localization. We find that TRiC is required for folding the telomerase cofactor TCAB1, which controls trafficking of telomerase and small Cajal body RNAs (scaRNAs). Depletion of TRiC causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. DC patient-derived mutations in TCAB1 impair folding by TRiC, disrupting telomerase function and leading to severe disease. Our findings establish a critical role for TRiC-mediated protein folding in the telomerase pathway and link proteostasis, telomere maintenance, and human disease
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Glioblastoma Mimicking an Arteriovenous Malformation
Abnormal cerebral vasculature can be a manifestation of a vascular malformation or a neoplastic process. We report the case of a patient with angiography-negative subarachnoid hemorrhage (SAH) who re-presented 3 years later with a large intraparenchymal hemorrhage. Although imaging following the intraparenchymal hemorrhage was suggestive of arteriovenous malformation, the patient was ultimately found to have an extensive glioblastoma associated with abnormal tumor vasculature. The case emphasizes the need for magnetic resonance imaging to investigate angiography-negative SAH in suspicious cases to rule out occult etiologies, such as neoplasm. We also discuss diagnostic pitfalls when brain tumors are associated with hemorrhage and abnormal vasculature
Native gel electrophoresis of human telomerase distinguishes active complexes with or without dyskerin
Telomeres, the ends of linear chromosomes, safeguard against genome instability. The enzyme responsible for extension of the telomere 3′ terminus is the ribonucleoprotein telomerase. Whereas telomerase activity can be reconstituted in vitro with only the telomerase RNA (hTR) and telomerase reverse transcriptase (TERT), additional components are required in vivo for enzyme assembly, stability and telomere extension activity. One such associated protein, dyskerin, promotes hTR stability in vivo and is the only component to co-purify with active, endogenous human telomerase. We used oligonucleotide-based affinity purification of hTR followed by native gel electrophoresis and in-gel telomerase activity detection to query the composition of telomerase at different purification stringencies. At low salt concentrations (0.1 M NaCl), affinity-purified telomerase was ‘supershifted’ with an anti-dyskerin antibody, however the association with dyskerin was lost after purification at 0.6 M NaCl, despite the retention of telomerase activity and a comparable yield of hTR. The interaction of purified hTR and dyskerin in vitro displayed a similar salt-sensitive interaction. These results demonstrate that endogenous human telomerase, once assembled and active, does not require dyskerin for catalytic activity. Native gel electrophoresis may prove useful in the characterization of telomerase complexes under various physiological conditions
TERT Promotes Epithelial Proliferation through Transcriptional Control of a Myc- and Wnt-Related Developmental Program
Telomerase serves a critical role in stem cell function and tissue homeostasis. This role depends on its ability to synthesize telomere repeats in a manner dependent on the reverse transcriptase (RT) function of its protein component telomerase RT (TERT), as well as on a novel pathway whose mechanism is poorly understood. Here, we use a TERT mutant lacking RT function (TERTci) to study the mechanism of TERT action in mammalian skin, an ideal tissue for studying progenitor cell biology. We show that TERTci retains the full activities of wild-type TERT in enhancing keratinocyte proliferation in skin and in activating resting hair follicle stem cells, which triggers initiation of a new hair follicle growth phase and promotes hair synthesis. To understand the nature of this RT-independent function for TERT, we studied the genome-wide transcriptional response to acute changes in TERT levels in mouse skin. We find that TERT facilitates activation of progenitor cells in the skin and hair follicle by triggering a rapid change in gene expression that significantly overlaps the program controlling natural hair follicle cycling in wild-type mice. Statistical comparisons to other microarray gene sets using pattern-matching algorithms revealed that the TERT transcriptional response strongly resembles those mediated by Myc and Wnt, two proteins intimately associated with stem cell function and cancer. These data show that TERT controls tissue progenitor cells via transcriptional regulation of a developmental program converging on the Myc and Wnt pathways
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Clinical features of brain metastasis from salivary gland tumors
Salivary gland tumors comprise a group of 24 tumor subtypes with a wide range of clinical behaviors and propensities for metastasis. Several prognostic factors have been identified that help predict the development of systemic metastases, most commonly to the lung, liver, or bone. Metastases to the brain are rare. To better understand the behavior of salivary gland tumors that metastasise to the brain, we performed a retrospective cohort analysis on a series of patients to highlight features of their medical and surgical management. From 2007 to 2011, a database of 4117 elective craniotomies were queried at a single institution to identify patients surgically treated for salivary gland metastases to the brain. Three patients were identified. Histologic subtypes included salivary duct carcinoma, poorly differentiated carcinoma, and papillary mucinous adenocarcinoma. They had all undergone previous treatment for their primary malignancy. The mean time to intracranial metastasis was 48 months from initial diagnosis (range, 14–91 months). Treatment for intracranial metastases included surgical resection, whole brain radiation, stereotactic radiosurgery, and chemotherapy. Intracranial metastases from salivary gland tumors are rare, present years after diagnosis of the primary tumor, and are treatable with multimodality therapy
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