172 research outputs found
Management Tools for RetD Project Portfolios in Complex Organizations â the case of an international pharmaceutical firm
Project Portfolio Management (PPM) is a growing issue in both professional and academic circles. The typology of Cooper et al. (1998) has pictured the variety of PPM formalized approaches into four types (financial, strategic, scoring and âbubble diagramâ). While the use of formalized methods by top performers is clearly attested, the choice of a specific approach and the precise benefits and limits of different instruments are still in debate. The present paper formalizes more precise contingency hypotheses between PPM practices and organizational variables such as R&D strategy, the structure and history of a firm's development, partnership policy and learning track in the project domain. Where managerial implications are concerned, the paper puts forward an analytical framework for the adjustment of portfolio instruments to fit specific situations and develops the conclusions of that framework for an international pharmaceutical group, Merck Lipha. The research underlying this paper adopts an interactive and experimental case-based methodology which has been on-going since 1997.Project; portfolios; pharmaceuticals; decision; processes; interactive research
Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders.
In the present study, we have investigated the functional profile of CD4 T cells from patients with common variable immunodeficiency (CVID), including production of cytokines and proliferation in response to bacteria and virus-derived antigens. We show that the functional impairment of CD4 T cells, including the reduced capacity to proliferate and to produce IFN-Îł and IL-2, was restricted to bacteria-specific and not virus-specific CD4 T cells. High levels of endotoxins were found in the plasma of patients with CVID, suggesting that CD4 T cell dysfunction might be caused by bacterial translocation. Of note, endotoxemia was associated with significantly higher expression of programmed death 1 (PD-1) on CD4 T cells. The blockade of the PD-1-PD-L1/2 axis in vitro restored CD4 T cell proliferation capacity, thus indicating that PD-1 signaling negatively regulates CD4 T cell functions. Finally, we showed that intravenous immunoglobulin G (IVIG) treatment significantly reduced endotoxemia and the percentage of PD-1(+) CD4 T cells, and restored bacteria-specific CD4 T cell cytokine production and proliferation. In conclusion, the present study demonstrates that the CD4 T cell exhaustion and functional impairment observed in CVID patients is associated with bacterial translocation and that IVIG treatment resolves bacterial translocation and restores CD4 T cell functions
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Non-structural carbohydrates in woody plants compared among laboratories
Non-structural carbohydrates (NSC) in plant tissue are frequently quantified to make inferences about plant responses to environmental conditions. Laboratories publishing estimates of NSC of woody plants use many different methods to evaluate NSC. We asked whether NSC estimates in the recent literature could be quantitatively compared among studies. We also asked whether any differences among laboratories were related to the extraction and quantification methods used to determine starch and sugar concentrations. These questions were addressed by sending sub-samples collected from five woody plant tissues, which varied in NSC content and chemical composition, to 29 laboratories. Each laboratory analyzed the samples with their laboratory-specific protocols, based on recent publications, to determine concentrations of soluble sugars, starch and their sum, total NSC. Laboratory estimates differed substantially for all samples. For example, estimates for Eucalyptus globulus leaves (EGL) varied from 23 to 116 (mean = 56) mg gâ»Âč for soluble sugars, 6â533 (mean = 94) mg gâ»Âč for starch and 53â649 (mean = 153) mg gâ»Âč for total NSC. Mixed model analysis of variance showed that much of the variability among laboratories was unrelated to the categories we used for extraction and quantification methods (method category RÂČ = 0.05â0.12 for soluble sugars, 0.10â0.33 for starch and 0.01â0.09 for total NSC). For EGL, the difference between the highest and lowest least squares means for categories in the mixed model analysis was 33 mg gâ»Âč for total NSC, compared with the range of laboratory estimates of 596 mg gâ»Âč. Laboratories were reasonably consistent in their ranks of estimates among tissues for starch (r = 0.41â0.91), but less so for total NSC (r = 0.45â0.84) and soluble sugars (r = 0.11â0.83). Our results show that NSC estimates for woody plant tissues cannot be compared among laboratories. The relative changes in NSC between treatments measured within a laboratory may be comparable within and between laboratories, especially for starch. To obtain comparable NSC estimates, we suggest that users can either adopt the reference method given in this publication, or report estimates for a portion of samples using the reference method, and report estimates for a standard reference material. Researchers interested in NSC estimates should work to identify and adopt standard methods.This is the publisherâs final pdf. The published article is copyrighted by the author(s) and published by Oxford University Press. The published article can be found at: http://treephys.oxfordjournals.org/Keywords: soluble sugars, starch, particle size, reference method, standardization, non-structural carbohydrate chemical analysis, extraction and quantification consistenc
Use of hRORalpha receptors for screening substances useful for the treatment of atherosclerosis
Patent apllication WO9950660 (A1)info:eu-repo/semantics/publishe
Use of Rev-erb family of receptors in screening
Patent application EP1090292 (A1)info:eu-repo/semantics/publishe
DiffĂ©rences entre âbig pharmasâ et âbiotechsâ â Quâen disent leurs brevets ?
Lâindustrie pharmaceutique a connu au cours des deux derniĂšres dĂ©cennies une trĂšs forte Ă©volution. Outre une augmentation des accords entre grands laboratoires pharmaceutiques, elle a vu Ă©merger un ensemble de jeunes entreprises fondĂ©es sur des technologies de recherche innovantes, que lâon a tendance, de maniĂšre assez imprĂ©cise Ă rassembler sous lâĂ©tiquette dâentreprises de biotechnologies. Le fonctionnement de ces derniĂšres entreprises nous semble ĂȘtre diffĂ©rent : fortes relations avec la science fondamentale, nombreux accords de coopĂ©ration entre start-ups et entre start-ups et laboratoires « traditionnels ». Il nous a donc semblĂ© intĂ©ressant de comparer les citations de brevets des principales entreprises des deux catĂ©gories. Quel en est le principe de cette mĂ©thode ? Chaque brevet comprend un certain nombre de citations destinĂ©es Ă reflĂ©ter lâĂ©tat de lâart au moment de sa publication, sur le mĂȘme modĂšle que les rĂ©fĂ©rences bibliographiques dâun article acadĂ©mique. Notre travail a consistĂ© Ă analyser ces citations.Cette recherche sâest dĂ©roulĂ©e dans un esprit dâexploration des possibilitĂ©s et des limites de la mĂ©thode. Les points Ă mesurer ont donc Ă©mergĂ© « chemin faisant ». LâĂ©chantillon est restĂ©, pour des raisons pratiques, relativement limitĂ© : 4 laboratoires que nous pouvons qualifier de « traditionnels » et 3 grandes entreprises de biotechnologies. Notre Ă©tude a permis de faire Ă©merger des diffĂ©rences entre ces deux types dâentreprises : - Les laboratoires pharmaceutiques citent des entreprises dont lâactivitĂ© principale est la chimie plus abondamment que les « biotechs », ce qui semble indiquer quâelles nâont pas perdu leur ancrage dans ce secteur. - Les entreprises de biotechnologies conjuguent un nombre moyen de citations plus Ă©levĂ© et un moindre taux dâautocitation. Les deux indicateurs rĂ©unis peuvent indiquer une plus forte ouverture du processus de recherche de ces entreprises. - Les entreprises de biotechnologies citent davantage des brevets dĂ©posĂ©s par des universitĂ©s ou des institutions de recherche fondamentale, confirmant le rĂŽle des partenariats avec ce type dâorganisations.Ces diffĂ©rences sont cohĂ©rentes avec ce que lâon pouvait attendre compte tenu de la littĂ©rature sur le sujet. Elles permettent dâalimenter la rĂ©flexion sur la maniĂšre dont les entreprises en place peuvent gĂ©rer une rĂ©volution technologique comme lâĂ©mergence des biotechnologies : dans quelle mesure intĂšgrent-elles les mĂ©thodes des nouveaux entrants (citation des entreprises de biotechnologies) ? Dans quelle mesure cela les conduit-elles Ă sâĂ©loigner de leur mĂ©tier dâorigine (citations des entreprises de chimie) ? Tissent-elles le mĂȘme type de lien avec les organisations productrices de connaissances de nature fondamentale (citation des universitĂ©s et institutions de recherche) ?... Elles permettent Ă©galement dâalimenter les rĂ©flexions sur les apports potentiels et les limites dâune telle mĂ©thode dâinvestigation
Le rĂŽle de la PI dans les relations entre laboratoires publics et industriels
Sâil existe de nombreuses Ă©tudes ayant pour but dâĂ©valuer les activitĂ©s de valorisation de la recherche dans les universitĂ©s et les organismes publics de recherche, il nâexistait pas, Ă notre connaissance, dâĂ©tude visant Ă comprendre de maniĂšre approfondie le rĂŽle de la PI dans les relations entre ces derniers et les industriels. Ce rapport est fondĂ© sur 14 entretiens menĂ©s avec des responsables de structures de valorisation et dans les entreprises.La premiĂšre partie prĂ©sente le contexte dans lequel se dĂ©roulent ces partenariats, notamment en termes de PI. Les entreprises en attendent lâutilisation de compĂ©tences pointues pour explorer des voies qui se situent trop en amont pour pouvoir ĂȘtre prises en charge Ă 100% par leurs services de R&D.Le but principal du dĂ©pĂŽt de droits de PI, notamment de brevets, est de permettre aux industriels de rentabiliser les investissements importants qui restent Ă rĂ©aliser pour transformer une invention issue dâun partenariat acadĂ©mique en innovation commercialisable. Bien sĂ»r, les organismes publics de recherche ont aussi pour ambition dâen tirer des revenus financiers, mais ce nâest pas le but qui est citĂ© en premier.Les structures de valorisation ont Ă©tĂ© crĂ©Ă©es pour servir dâintermĂ©diaires entre le monde acadĂ©mique et le monde industriel. Elles exercent leur rĂŽle dans un systĂšme de contraintes assez fortes : pression sur les indicateurs de valorisation, lĂ©gitimitĂ© Ă construire au sein de lâorganisation, ressources limitĂ©es et difficultĂ©s Ă Ă©quilibrer les budgets. La mutualisation des ressources pourrait constituer une solution mais elle est difficile Ă mettre en Ćuvre dans un contexte oĂč le poids des indicateurs conduit plutĂŽt Ă la compĂ©tition.Les rĂ©sistances soulevĂ©es par la PI au sein des laboratoires publics semblent assez limitĂ©es et plutĂŽt en baisse. La « culture PI » nây est pas encore trĂšs dĂ©veloppĂ©e mais lâattention croissante qui y est portĂ©e, les incitations financiĂšres individuelles (par ailleurs trĂšs critiquĂ©es pour leurs effets pervers) et parfois lâattrait pour la crĂ©ation dâentreprise conduisent Ă une prise en compte croissante de ce type de problĂ©matique. Le dilemme publication / brevet peut quant-Ă -lui tout Ă fait ĂȘtre surmontĂ© mĂȘme si cela nĂ©cessite une grande rĂ©activitĂ© de la part des structures de valorisation.La deuxiĂšme partie dĂ©taille davantage la nature des relations entre organismes publics de recherche et industriels, en commençant par les aspects contractuels. De ce point de vue, câest la copropriĂ©tĂ© qui pose le plus de problĂšmes. La plupart de nos interlocuteurs semblent toutefois parvenir Ă surmonter ces difficultĂ©s en Ă©tablissant un contrat laissant une grande libertĂ© Ă lâindustriel dans lâexploitation de ces droits. Une autre difficultĂ© est la dĂ©finition du niveau de royalties du fait des liens parfois indirects entre lâinvention brevetĂ©e et un produit qui arrive souvent sur le marchĂ© longtemps aprĂšs.La satisfaction des industriels concernant les prestations elles-mĂȘmes est assez Ă©levĂ©e (en dĂ©pit de diffĂ©rences dans les façons de travailler pouvant donner lieu Ă des incomprĂ©hensions). En revanche, les difficultĂ©s et les dĂ©lais de nĂ©gociation, notamment en matiĂšre de PI, sont souvent citĂ©s comme les principales limites de ces partenariats. Ces derniĂšres sont probablement rendues plus difficiles encore du fait de certaines reprĂ©sentations parfois vĂ©hiculĂ©es sur lâautre partie. Plusieurs indices nous conduisent toutefois Ă penser que ces reprĂ©sentations parfois un peu tranchĂ©es tendent Ă se nuancer au fil des collaborations rĂ©ussies
Management Tools for RetD Project Portfolios in Complex Organizations â the case of an international pharmaceutical firm
Project Portfolio Management (PPM) is a growing issue in both professional and academic circles. The typology of Cooper et al. (1998) has pictured the variety of PPM formalized approaches into four types (financial, strategic, scoring and âbubble diagramâ). While the use of formalized methods by top performers is clearly attested, the choice of a specific approach and the precise benefits and limits of different instruments are still in debate. The present paper formalizes more precise contingency hypotheses between PPM practices and organizational variables such as R&D strategy, the structure and history of a firm's development, partnership policy and learning track in the project domain. Where managerial implications are concerned, the paper puts forward an analytical framework for the adjustment of portfolio instruments to fit specific situations and develops the conclusions of that framework for an international pharmaceutical group, Merck Lipha. The research underlying this paper adopts an interactive and experimental case-based methodology which has been on-going since 1997
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