Le rôle de la spatialité dans la mise en place du New Model Worker : du projet Valmy aux tours de la Défense de la Société Générale

Willing to turn a tremendous item of expenditure into a real organizational resource, organizations usually perceive their spaces as potential management tools, but from conceived spaces to lived ones, a noticeable gap is often to be found. This thesis aims at understanding what an organizational space can reveal about the ongoing management practices: what can we understand from the way space is organized, beyond official discourses? Our research is focused on a case: an international bank's headquarter, from its original architectural project document (written in 1989) to 2014, that is to say: six years of construction (as the towers were delivered in 1995) and nineteen years of spatial practice. This is particularly interesting for those towers were supposed to help implement a "New Model Worker" through a particular spatial setting, favorable to informal communication. From our collected data, we've been able to build up a fresh perspective - an analysis grid gathering space, place, and artefacts - to better understand organizational spaces.Les organisations, tentées par la perspective de transformer un poste de dépense considérable en véritable ressource organisationnelle, envisagent généralement leur espace comme un potentiel outil de management, mais de l'espace conçu à l'espace vécu, on observe souvent un décalage remarquable. Cette thèse pose la question de ce que peut révéler un espace organisationnel du management pratiqué en son sein : au-delà des déclarations d'intention, que peut-on comprendre de l'espace? De la façon dont il est administré? Notre terrain d'observation est le siège social d'une grande banque internationale, de son projet architectural initial (rédigé en 1989) jusqu'à nos jours, soit six ans de construction (livraison des tours en 1995), et dix-neuf années de pratique spatiale. Ce cas emblématique a retenu notre attention car le projet consistait à faciliter la mise en place d'un "New Model Worker" par un aménagement spatial particulier, propice à la communication informelle. L'analyse de nos données nous a finalement permis de mettre au point une grille de lecture - regroupant la territorialisation, la valorisation et la localisation - pour mieux appréhender l'espace des organisations

Making music in the radial mainstream: representations of creative practice in UK-based pop/rock

Popular music is one of the United Kingdom’s most readily engaged with and exported cultural forms. Commensurate with such a positioning, there exists a wealth of academic literature on the subject across a breadth of interests and research focus. However, there also appears to be a somewhat lower level of attention to the experience of the professional practitioners who are engaged in creating this cultural form. An attention to creators’ discourses and how they may represent their experiences of practice will then be of value in adding some additional ‘real world’ context and content to existing thought on popular music. Drawing on an original data set from interviews with leading practitioners, this thesis is the production of such a work. Through the application of relevant sociological models, the study forms a participant-based characterization of creative practice in UK-­‐‑based pop/rock in an area that I have termed the ‘radial mainstream’. Themes drawn from the research participants and my own experiences of professional practice characterize creative work as being an assemblage of activities that are informed by the lived environment, mediating forces, musical influences, and creators’ ideals of practice. Underpinned by tenets of phenomenology and ethnographic inquiry, this is also a multi.. .voiced representation of how specific professionals think and feel about their practice and the contexts within which they operate. The wider study of popular music may benefit from the production of a ‘micro’ representation of creative practice, wherein subsequent thought can be more properly attentive to the depictions and preoccupations that emerge in this discourse on creating UK-­‐‑based pop/rock in the ‘radial mainstream’

Iron Homeostasis And Anemia In Hiv And Tuberculosis

Background: Evidence supports a role for iron homeostasis in the pathogenesis of HIV and tuberculosis. The iron regulatory peptide, hepcidin, inhibits both dietary iron absorption and iron efflux leading to macrophage iron retention. Conditions associated with elevated hepcidin, which include altered concentrations of ferritin, transferrin and hemoglobin, may favor Mycobacterium tuberculosis iron acquisition, HIV progression and anemia. In light of this, we investigated iron homeostasis biomarkers as risk factors for incident TB and mortality in an HIVseropositive cohort and also for progression to TB in an HIV-seromixed cohort. In addition, we characterized iron homeostasis during TB therapy in order to identify causes of anemia and inform selection of safe, effective and well-timed treatments for anemia. Methods: Clinical and demographic data and archived plasma and serum samples from two research platforms were utilized in this work: the Medical Research Council (MRC) HIV clinical cohort and the MRC TB case contact study. Analysis of iron homeostasis biomarker concentrations was conducted at MRC laboratories in The Gambia. Results: During HIV Clinical Cohort follow up, 32 incident tuberculosis cases were identified and 64% of the 196 participants died. Greater hepcidin was associated with significantly increased likelihood of tuberculosis and greater all-cause mortality. This was consistent with observed higher ferritin and hepcidin concentrations in HIV-seromixed contacts of infectious TB cases that progressed to TB earlier. Analysis of biomarkers and anemia during TB therapy revealed that anemia of inflammation was predominant TB diagnosis, declining significantly after six months of treatment; however, a corresponding reduction was not evident for anemia with iron-responsive components. Hepcidin concentrations significantly declined after 2 months of TB treatment. Conclusions: Changes in iron homeostasis biomarkers are associated with incident TB and mortality in HIV and progression to TB disease among contacts of infectious TB cases. Further studies are needed to elucidate mechanisms and determine the clinical utility of monitoring iron homeostasis biomarkers. TB therapy is associated with significant reductions in anemia of inflammation, but iron-based interventions are needed for anemia with iron responsive components. Monitoring hepcidin reveals a window for intervention opening as early as two months into TB treatment

Business plan for a general contractor in the New York City public sector

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 1995.Includes bibliographical references (leaves 93-95).by Antonio Minchella.M.S

Analysis of regulatory protease sequences identified through bioinformatic data mining of the Schistosoma mansoni genome

<p>Abstract</p> <p>Background</p> <p>New chemotherapeutic agents against <it>Schistosoma mansoni</it>, an etiological agent of human schistosomiasis, are a priority due to the emerging drug resistance and the inability of current drug treatments to prevent reinfection. Proteases have been under scrutiny as targets of immunological or chemotherapeutic anti-<it>Schistosoma </it>agents because of their vital role in many stages of the parasitic life cycle. Function has been established for only a handful of identified <it>S. mansoni </it>proteases, and the vast majority of these are the digestive proteases; very few of the conserved classes of regulatory proteases have been identified from <it>Schistosoma </it>species, despite their vital role in numerous cellular processes. To that end, we identified protease protein coding genes from the <it>S. mansoni </it>genome project and EST library.</p> <p>Results</p> <p>We identified 255 protease sequences from five catalytic classes using predicted proteins of the <it>S. mansoni </it>genome. The vast majority of these show significant similarity to proteins in KEGG and the Conserved Domain Database. Proteases include calpains, caspases, cytosolic and mitochondrial signal peptidases, proteases that interact with ubiquitin and ubiquitin-like molecules, and proteases that perform regulated intramembrane proteolysis. Comparative analysis of classes of important regulatory proteases find conserved active site domains, and where appropriate, signal peptides and transmembrane helices. Phylogenetic analysis provides support for inferring functional divergence among regulatory aspartic, cysteine, and serine proteases.</p> <p>Conclusion</p> <p>Numerous proteases are identified for the first time in <it>S. mansoni</it>. We characterized important regulatory proteases and focus analysis on these proteases to complement the growing knowledge base of digestive proteases. This work provides a foundation for expanding knowledge of proteases in <it>Schistosoma </it>species and examining their diverse function and potential as targets for new chemotherapies.</p

developing an effective breast cancer vaccine challenges to achieving sterile immunity versus resetting equilibrium

Abstract Introduction Evading immune destruction is an emerging hallmark of cancer. Immunotherapy of cancer is categorized as either specific stimulation of the immune system by active immunization, with cancer vaccines, or passive transfer of humor or cellular materials, such as, tumor specific antibodies (including immunomodulators) or adoptive cell therapy that inhibit the function of- or directly kill tumor cells. Modulation of immune response in cancer patients is the result of a balanced activity of T regulators and T effector cells. Methods and results We will present the current information and the prospects for the future of immunotherapy in patients with breast cancer including tumor antigens for vaccines and targets for monoclonal antibodies and adoptive T-cell therapy. Discussion Active immunotherapy in breast cancer and its implementation into clinical trials has largely been a frustrating experience in the last decades. After many years of controversy, the concept that the immune system regulates cancer development is experiencing a new resurgence. It is clear that the cancer immunosurveillance process indeed exists and potentially acts as an extrinsic tumor suppressor. It has been also clear that the immune system can facilitate tumor progression by sculpting the immunogenic phenotype of tumors as they develop. Cancer immunoediting represents a refinement of the cancer immunosurveillance hypothesis and resumes the complex interaction between tumor and immune system into three phases: elimination, equilibrium, and escape. Conclusion What do we know about tumor immunogenicity and how might we therapeutically improve tumor immunogenicity? The first vaccine and the first immunomodulating agent were recently approved by the US Food and Drug Administration (FDA) for the treatment of prostate cancer (sipuleucel-T) and melanoma (ipilimumab), respectively. The success of future immunotherapy strategies will depend on the identification of additional immunogenic antigens that can serve as the best tumor-rejection targets. Therapeutic success will depend on developing the best antigen delivery systems and on the elucidation of the entire network of immune signalingsignaling pathways that regulate immune responses in the tumor microenvironment

Empirical Support for Optimal Virulence in a Castrating Parasite

The trade-off hypothesis for the evolution of virulence predicts that parasite transmission stage production and host exploitation are balanced such that lifetime transmission success (LTS) is maximised. However, the experimental evidence for this prediction is weak, mainly because LTS, which indicates parasite fitness, has been difficult to measure. For castrating parasites, this simple model has been modified to take into account that parasites convert host reproductive resources into transmission stages. Parasites that kill the host too early will hardly benefit from these resources, while postponing the killing of the host results in diminished returns. As predicted from optimality models, a parasite inducing castration should therefore castrate early, but show intermediate levels of virulence, where virulence is measured as time to host killing. We studied virulence in an experimental system where a bacterial parasite castrates its host and produces spores that are not released until after host death. This permits estimating the LTS of the parasite, which can then be related to its virulence. We exposed replicate individual Daphnia magna (Crustacea) of one host clone to the same amount of bacterial spores and followed individuals until their death. We found that the parasite shows strong variation in the time to kill its host and that transmission stage production peaks at an intermediate level of virulence. A further experiment tested for the genetic basis of variation in virulence by comparing survival curves of daphniids infected with parasite spores obtained from early killing versus late killing infections. Hosts infected with early killer spores had a significantly higher death rate as compared to those infected with late killers, indicating that variation in time to death was at least in part caused by genetic differences among parasites. We speculate that the clear peak in lifetime reproductive success at intermediate killing times may be caused by the exceptionally strong physiological trade-off between host and parasite reproduction. This is the first experimental study to demonstrate that the production of propagules is highest at intermediate levels of virulence and that parasite genetic variability is available to drive the evolution of virulence in this system

Elevated Hepcidin Is Part of a Complex Relation That Links Mortality with Iron Homeostasis and Anemia in Men and Women with HIV Infection.

BACKGROUND: Early and chronic inflammation is a hallmark of HIV infection, and inflammation is known to increase hepcidin expression. Consequently, hepcidin may be a key determinant of the iron homeostasis and anemia associated with poorer HIV prognoses. OBJECTIVE: The objective of this study was to understand how hepcidin is related to anemia, iron homeostasis, and inflammation at HIV diagnosis and to investigate associations between hepcidin and all-cause mortality in HIV infection. METHODS: In a retrospective cohort, baseline plasma hepcidin was measured by competitive enzyme immunoassay within 3 mo of HIV diagnosis in 196 antiretroviral-naive Gambians. Iron homeostasis [hemoglobin, plasma transferrin, ferritin, iron, soluble transferrin receptor (sTfR)] and inflammation [α1-antichymotrypsin (ACT)] from the same plasma sample were available, as were absolute CD4 cell counts, age, gender, body mass index (BMI), and HIV type. RESULTS: Anemia was common across the spectrum of immunosuppression [CD4 cell counts (prevalence of anemia): >500 cells/μL (68%), 200-500 cells/μL (73%), and <200 cells/μL (89%); P = 0.032] and in men (81%) and women (76%). Increasing hepcidin was associated with iron homeostasis biomarkers (higher ferritin and lower transferrin, hemoglobin, and sTfR), inflammation (higher ACT), and key health indicators (lower CD4 or BMI, advancing age, and male gender; P < 0.001 except for hemoglobin, P = 0.021). Elevated hepcidin was associated with greater all-cause mortality in a dose-dependent manner [intermediate vs. lowest tertile: unadjusted HR (95% CI), 1.95 (1.22, 3.10); upper vs. lowest tertile: 3.02 (1.91, 4.78)]. Principal components analysis identified 2 patterns composed of hepcidin-ferritin-transferrin, with or without ACT, and iron-sTfR-hemoglobin that may distinguish inflammation and erythropoiesis iron functions. CONCLUSIONS: Elevated hepcidin is independently associated with greater mortality in men and women with HIV infection, and hepcidin is also part of a complex relation linking iron homeostasis, anemia, and HIV. Understanding the mechanisms and role of hepcidin modulation may further guide evidence-based interventions needed to counter detrimental iron homeostasis and anemia in HIV infection

preoperative therapy with trastuzumab and oral vinorelbine endocrine therapy in patients with her2 positive breast cancer

Abstract Background Combined trastuzumab and intravenous vinorelbine yielded high clinical activity as preoperative treatment in patients (pts) with HER 2/ neu positive breast cancer. Patients and methods We tested a preoperative combination of trastuzumab with oral vinorelbine (oV) in pts with locally advanced (T2-T4 N0-3 M0) HER2-positive breast cancer. Trastuzumab was administered i.v q 3 wks and oV was administered at the dose of 55 mg/sqm on days 1 and 3 q 3 wks, for 8 courses. Pts with ER ≥ 10% tumors received endocrine therapy with letrozole 2.5 mg/day, plus monthly triptorelin if premenopausal. Results Forty-five pts entered the study. The overall response rate (CR + PR) was 76% (95% CI: 60%–87%). pCR was observed in 4 pts (10%). Among ER-positive tumors 21/25 pts obtained a clinical response (84%) and two pts obtained a pCR (8%). Conclusions The combination of trastuzumab and oral vinorelbine demonstrated encouraging activity in patients with HER 2 positive ER-positive tumors. Alternative strategies should be investigated in patients with endocrine non responsive disease