83 research outputs found
Outline: An Extensive and Secure Personal Data Management System Using SGX
International audiencePersonal Data Management System (PDMS) solutions are currently flourishing, spurred by new privacy regulations such as GDPR and new legal concepts like data altruism. PDMSs aim to empower individuals by providing appropriate tools to collect and manage their personal data and share computed results with third parties, thus requiring (i) a secure platform protecting the userâs privacy and delivering strong guarantees on the outputs of userâs data processing, and (ii) an extensible solution that supports all types of data-driven computation
An Extensive and Secure Personal Data Management System Using SGX
International audiencePersonal Data Management System (PDMS) solutions are currently flourishing, spurred by new privacy regulations such as GDPR and new legal concepts like data altruism. PDMSs aim to empower individuals by providing appropriate tools to collect and manage their personal data and share computed results with third parties, thus requiring (i) a secure platform protecting the user's privacy and delivering strong guarantees on the outputs of user's data processing, and (ii) an extensible solution that supports all types of data-driven computations. In previous works, we analyzed these requirements and proposed an Extensive and Secure PDMS (ES-PDMS) logical architecture. This demonstration presents the first ES-PDMS prototype based on SGX enclaves, focusing on its security properties with the help of several concrete scenarios and interactive games
Advances in predicting acute GVHD
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96282/1/bjh12142.pd
NK cells produce high levels of IL-10 early after allogeneic stem cell transplantation and suppress development of acute GVHD
Natural killer (NK) cells rapidly reconstitute following allogeneic stem cell transplantation (allo-SCT), at the time when alloreactive T cell immunity is being established. We investigated very early NK cell reconstitution in 82 patients following T cell-depleted allo-SCT. NK cell number rapidly increased, exceeding T cell reconstitution such that the NK:T cell ratio was over 40 by day 14. NK cells at day 14 (NK-14) were donor-derived, intensely proliferating and expressed chemokine receptors targeted to lymphoid and peripheral tissue. Spontaneous production of the immunoregulatory cytokine IL-10 was observed in over 70% of cells and transcription of cytokines and growth factors was augmented. NK-14 cell number was inversely correlated with the incidence of grade II-IV acute graft versus host disease (GVHD). These findings reveal that robust reconstitution of immunoregulatory NK cells by day 14 after allo-SCT is an important determinant of the clinical outcome, suggesting that NK cells may suppress the development of the T cell-mediated alloreactive immune response through production of IL-10
New development in the CMS ECAL Level-1 trigger system to meet the challenges of LHC Run 2
The CMS Electromagnetic Calorimeter (ECAL) provides energy sums to the Level-1 calorimeter trigger at a rate of 40 MHz. The processing of these trigger primitives (TPs) is performed by dedicated trigger concentrator cards (TCCs) located in the CMS service cavern. Updates to the functionality of the TCCs are required to respond to the challenging experimental conditions of LHC Run 2, where the center-of-mass of proton-proton collision energy was 13 TeV and the peak instantaneous luminosity of the proton beams reached 2x10 cms. A new algorithm, termed the Cumulative Overflow Killing Engine (COKE), has been developed and implemented via software and firmware updates to the TCCs in order to automatically detect and mask noisy or problematic TPs via configurable thresholds. The auto-recovery of the TCC from Single Event Upsets (SEUs) has also been improved. This allows the detector to trigger efficiently without direct expert intervention, and the thresholds can evolve with evolving LHC conditions
Homeostatic cytokines, IL-7 and IL-15, during CSH allograft
Les mĂ©canismes assurant lâhomĂ©ostasie du compartiment lymphocytaire T pĂ©riphĂ©riqueveillent Ă prĂ©server Ă la fois le nombre, la diversitĂ© et la qualitĂ© des cellules T qui le composent. CesmĂ©canismes sont fortement sollicitĂ©s chez un receveur dâallogreffe de cellules soucheshĂ©matopoĂŻĂ©tiques puisquâune dĂ©plĂ©tion initiale plus ou moins intense de son compartimentlymphocytaire pĂ©riphĂ©rique est induite par le conditionnement prĂ©-greffe. Le retour Ă lâhomĂ©ostasie sâeffectue grĂące Ă la prolifĂ©ration homĂ©ostatique des lymphocytes du donneurapportĂ©s par le greffon non manipulĂ©, avant la reconstitution beaucoup plus tardive dâuncompartiment lymphocytaire T naĂŻf opĂ©rationnel, en fonction des capacitĂ©s de thymopoĂŻĂšse dureceveur. LâIL-7 et lâIL-15, qui jouent un rĂŽle majeur dans la survie des cellules T naĂŻves et/oumĂ©moires, participent Ă©troitement Ă lâexpansion des cellules T induite par la lymphopĂ©nie etmĂ©ritent Ă ce titre le qualificatif de cytokines homĂ©ostatiques.Des protocoles de conditionnement dâintensitĂ© variable exposent Ă un risque Ă©quivalent demaladie du greffon contre lâhĂŽte, sinon de rechute, en dĂ©pit de lâinduction dâun degrĂ© variabledâinflammation. Ceci suggĂšre que lâexpansion homĂ©ostatique pĂ©riphĂ©rique des lymphocytes T dudonneur est un facteur dĂ©terminant de lâĂ©volution bĂ©nĂ©fique ou dĂ©favorable de lâallogreffe.Une Ă©tude prospective de 107 patients rĂ©partis en deux cohortes, lâune aprĂšsconditionnement myĂ©loablatif, lâautre aprĂšs divers protocoles de conditionnement dâintensitĂ©rĂ©duite nous a permis de comparer lâimpact du degrĂ© de lymphopĂ©nie et dâinflammation sur lestaux systĂ©miques dâIL-7 et dâIL-15, lâexpression de leurs rĂ©cepteurs par les lymphocytes Tcirculants et lâĂ©volution clinique.Nous confirmons une Ă©volution en miroir des taux plasmatiques dâIL-7 et de lalymphocytose et nous montrons que la cinĂ©tique des taux dâIL-7 post-allogreffe est semblablequelque soit lâintensitĂ© des protocoles de conditionnements utilisĂ©s. En revanche, si les taux dâIL-15prĂ©sentent une cinĂ©tique en miroir similaire Ă celle de lâIL-7, la valeur au pic et lâaire sous la courbedâIL-15 diffĂšrent nettement selon le type de conditionnement, mais sont fortement corrĂ©lĂ©sĂ la CRP plasmatique.Lâincidence des maladies aiguĂ«s du greffon contre lâhĂŽte de grade 2 Ă 4 est similaire dansnos deux cohortes, mais le dĂ©lai de survenue est plus tardif aprĂšs un conditionnement rĂ©duit. AprĂšsanalyse multivariĂ©e, notre Ă©tude permet de conclure Ă lâintĂ©rĂȘt prospectif de la dĂ©terminationprĂ©coce des taux plasmatiques dâIL-7 : dans les conditionnements myĂ©loablatifs, un taux dâIL-7supĂ©rieur Ă 11,9 pg/mL Ă J+14 est prĂ©dictif, tandis que dans les conditionnements rĂ©duits, câest untaux supĂ©rieur Ă 5,9 pg/mL Ă J+30 qui sâavĂšre prĂ©dictif. Dans notre cohorte de patients sousconditionnement myĂ©loablatif, de faibles taux dâIL-15 Ă J+14 sont associĂ©s en analyse univariĂ©e etmultivariĂ©e Ă la survenue ultĂ©rieure dâune rechute de lâhĂ©mopathie maligne. Une relation similairemais plus tardive (J+90) est retrouvĂ©e chez les receveurs dâun conditionnement rĂ©duit.Outre lâintĂ©rĂȘt prospectif pour les patients de la dĂ©termination prĂ©coce des tauxplasmatiques dâIL-7 et dâIL-15, cette Ă©tude comparative a permis de cerner dâune part le rĂŽleessentiel de la lymphopĂ©nie dans lâaccumulation dâune concentration critique dâIL-7 nĂ©cessairepour piloter lâexpansion homĂ©ostatique des cellules T matures et, dâautre part lâimpact du contexteinflammatoire sur lâaugmentation de la concentration plasmatique dâIL-15. Celle-ci, par son actiondirecte sur les lâexpansion des cellules T CD8+ mĂ©moires et ses effets contributifs Ă lâexpansionhomĂ©ostatique des cellules T naĂŻves, apparaĂźt renforcer lâaction de lâIL-7 en potentialisant son rĂŽledans lâallorĂ©activitĂ©, bĂ©nĂ©fique en terme de protection vis-Ă -vis de la rechute mais dĂ©lĂ©tĂšre enterme de rĂ©action de greffon contre hĂŽte.My PhD was realised in the research team EA2686 at the Pole of Immunology in the Center of Biology Pathology of Lille under the direction of Doctor Myriam Labalette and in collaboration with Professor Ibrahim Yakoub-Agha from the department of Blood Diseases in the Hospital of Lille. The central line of the my work concern the implication of the different subpopulations of naive and memory T cells in the immune reconstitution and the main events post allograft of hematopoietic stem cells (HSC). 1)Study of factors controlling the homeostatic proliferation of T cells after allograft : By a prospective study, our team showed that the dynamic of reconstitution of subpopulations of naive and memory T cells during the immune reconstitution after allograft of HSC affects the occurrence of late events (Yakoub-Agha, 2009). The homeostatic proliferation of donor T cell provided by the graft and possibly also by the few residual recipient T cells is involved in the initial reconstitution of the lymphocyte compartment. Two main homeostatic cytokines are involved in this way of expansion of T cells after allograft, IL-7 and IL-15. We determined the precocious plasmatic level of these cytokines and the degree of expression of their receptor, IL-7Ralpha chain (CD127) and IL-15Rbeta chain (CD122) on the subpopulations of naive and memory T cells during the immune reconstitution post allograft. a) In 40 recipients of HSC with a myeloablative conditioning, our prospective study showed variations of IL-7 and IL-15 level during the first weeks post-graft. The plasmatic levels increased strongly to peak at day+14. Then, the concentrations return to a normal range around day+30. The increase of IL-7 and IL-15 levels observed during the first days post-graft could be due to an increase of production in response to the lymphopenia. However, at day+14 post-graft, we notice real important variations of IL-7 and IL-15 level among patients (range 3.8â30.2 and 14.3â66 pg/ml, respectively). A high level of IL-7 (≥11,9 pg/mL) at day+14 post-graft, when recipients are strongly lymphopenic, is a predictive factor of a risk of occurrence of acute GVHD (HR= 3.63 ; P= .014) compared to others factors known to favour independently this complication (reinfection to CMV, sex-mismatch). The relapse of disease is significantly associated to low level of IL-15 at day+14 (<33.3 pg/mL) (HR= 0.93; P= .035) (Thiant, 2010). b) In a prospective group of 45 recipients of HSC with a reduced conditioning inducing a lower degree of lymphopenia, the occurrence of acute GVHD is significantly associated to the plasmatic level of IL-7 and IL-15 at day+30 post-graft. This later lag is explained by the modalities of conditioning inducing a lower lymphopenia and the later occurrence of acute GVHD (median time= 42 days) compared to recipients with myeloablative conditioning (median time= 30 days). We also showed that levels of cytokines a month after the graft, affect the degree of expression of receptors, IL-7Rα and IL-15Rβ (Thiant, 2010). c) The increase of IL-7 could, in some conditions, suggest a failure of the receptivity by the IL-7Ralpha chain. We established a project of collaboration with the Professor Klaus MĂŒllerâs team from the Hospital of Copenhagen, which highlighted the presence of polymorphisms located on the nucleotidic sequence encoding the IL-7R alpha chain in recipients of bone marrow (Shamim, 2006). The polymorphism +510 is correlated to the level of IL-7 and represents a factor of risk of occurrence of acute GVHD (P=.049). We know that this polymorphism induces a modification of amino acid in the sequence but the consequences on the functionality of the receptor of IL-7 are not known yet. [...
Les cytokines homéostatiques, IL-7 et IL-15, au cours de l'allogreffe de CSH : leurs évolutions selon le conditionnement et leurs valeurs prédictives de la GVH aiguë et de la rechute
My PhD was realised in the research team EA2686 at the Pole of Immunology in the Center of Biology Pathology of Lille under the direction of Doctor Myriam Labalette and in collaboration with Professor Ibrahim Yakoub-Agha from the department of Blood Diseases in the Hospital of Lille. The central line of the my work concern the implication of the different subpopulations of naive and memory T cells in the immune reconstitution and the main events post allograft of hematopoietic stem cells (HSC). 1)Study of factors controlling the homeostatic proliferation of T cells after allograft : By a prospective study, our team showed that the dynamic of reconstitution of subpopulations of naive and memory T cells during the immune reconstitution after allograft of HSC affects the occurrence of late events (Yakoub-Agha, 2009). The homeostatic proliferation of donor T cell provided by the graft and possibly also by the few residual recipient T cells is involved in the initial reconstitution of the lymphocyte compartment. Two main homeostatic cytokines are involved in this way of expansion of T cells after allograft, IL-7 and IL-15. We determined the precocious plasmatic level of these cytokines and the degree of expression of their receptor, IL-7Ralpha chain (CD127) and IL-15Rbeta chain (CD122) on the subpopulations of naive and memory T cells during the immune reconstitution post allograft. a) In 40 recipients of HSC with a myeloablative conditioning, our prospective study showed variations of IL-7 and IL-15 level during the first weeks post-graft. The plasmatic levels increased strongly to peak at day+14. Then, the concentrations return to a normal range around day+30. The increase of IL-7 and IL-15 levels observed during the first days post-graft could be due to an increase of production in response to the lymphopenia. However, at day+14 post-graft, we notice real important variations of IL-7 and IL-15 level among patients (range 3.8â30.2 and 14.3â66 pg/ml, respectively). A high level of IL-7 (≥11,9 pg/mL) at day+14 post-graft, when recipients are strongly lymphopenic, is a predictive factor of a risk of occurrence of acute GVHD (HR= 3.63 ; P= .014) compared to others factors known to favour independently this complication (reinfection to CMV, sex-mismatch). The relapse of disease is significantly associated to low level of IL-15 at day+14 (<33.3 pg/mL) (HR= 0.93; P= .035) (Thiant, 2010). b) In a prospective group of 45 recipients of HSC with a reduced conditioning inducing a lower degree of lymphopenia, the occurrence of acute GVHD is significantly associated to the plasmatic level of IL-7 and IL-15 at day+30 post-graft. This later lag is explained by the modalities of conditioning inducing a lower lymphopenia and the later occurrence of acute GVHD (median time= 42 days) compared to recipients with myeloablative conditioning (median time= 30 days). We also showed that levels of cytokines a month after the graft, affect the degree of expression of receptors, IL-7Rα and IL-15Rβ (Thiant, 2010). c) The increase of IL-7 could, in some conditions, suggest a failure of the receptivity by the IL-7Ralpha chain. We established a project of collaboration with the Professor Klaus MĂŒllerâs team from the Hospital of Copenhagen, which highlighted the presence of polymorphisms located on the nucleotidic sequence encoding the IL-7R alpha chain in recipients of bone marrow (Shamim, 2006). The polymorphism +510 is correlated to the level of IL-7 and represents a factor of risk of occurrence of acute GVHD (P=.049). We know that this polymorphism induces a modification of amino acid in the sequence but the consequences on the functionality of the receptor of IL-7 are not known yet. [...]Les mĂ©canismes assurant lâhomĂ©ostasie du compartiment lymphocytaire T pĂ©riphĂ©riqueveillent Ă prĂ©server Ă la fois le nombre, la diversitĂ© et la qualitĂ© des cellules T qui le composent. CesmĂ©canismes sont fortement sollicitĂ©s chez un receveur dâallogreffe de cellules soucheshĂ©matopoĂŻĂ©tiques puisquâune dĂ©plĂ©tion initiale plus ou moins intense de son compartimentlymphocytaire pĂ©riphĂ©rique est induite par le conditionnement prĂ©-greffe. Le retour Ă lâhomĂ©ostasie sâeffectue grĂące Ă la prolifĂ©ration homĂ©ostatique des lymphocytes du donneurapportĂ©s par le greffon non manipulĂ©, avant la reconstitution beaucoup plus tardive dâuncompartiment lymphocytaire T naĂŻf opĂ©rationnel, en fonction des capacitĂ©s de thymopoĂŻĂšse dureceveur. LâIL-7 et lâIL-15, qui jouent un rĂŽle majeur dans la survie des cellules T naĂŻves et/oumĂ©moires, participent Ă©troitement Ă lâexpansion des cellules T induite par la lymphopĂ©nie etmĂ©ritent Ă ce titre le qualificatif de cytokines homĂ©ostatiques.Des protocoles de conditionnement dâintensitĂ© variable exposent Ă un risque Ă©quivalent demaladie du greffon contre lâhĂŽte, sinon de rechute, en dĂ©pit de lâinduction dâun degrĂ© variabledâinflammation. Ceci suggĂšre que lâexpansion homĂ©ostatique pĂ©riphĂ©rique des lymphocytes T dudonneur est un facteur dĂ©terminant de lâĂ©volution bĂ©nĂ©fique ou dĂ©favorable de lâallogreffe.Une Ă©tude prospective de 107 patients rĂ©partis en deux cohortes, lâune aprĂšsconditionnement myĂ©loablatif, lâautre aprĂšs divers protocoles de conditionnement dâintensitĂ©rĂ©duite nous a permis de comparer lâimpact du degrĂ© de lymphopĂ©nie et dâinflammation sur lestaux systĂ©miques dâIL-7 et dâIL-15, lâexpression de leurs rĂ©cepteurs par les lymphocytes Tcirculants et lâĂ©volution clinique.Nous confirmons une Ă©volution en miroir des taux plasmatiques dâIL-7 et de lalymphocytose et nous montrons que la cinĂ©tique des taux dâIL-7 post-allogreffe est semblablequelque soit lâintensitĂ© des protocoles de conditionnements utilisĂ©s. En revanche, si les taux dâIL-15prĂ©sentent une cinĂ©tique en miroir similaire Ă celle de lâIL-7, la valeur au pic et lâaire sous la courbedâIL-15 diffĂšrent nettement selon le type de conditionnement, mais sont fortement corrĂ©lĂ©sĂ la CRP plasmatique.Lâincidence des maladies aiguĂ«s du greffon contre lâhĂŽte de grade 2 Ă 4 est similaire dansnos deux cohortes, mais le dĂ©lai de survenue est plus tardif aprĂšs un conditionnement rĂ©duit. AprĂšsanalyse multivariĂ©e, notre Ă©tude permet de conclure Ă lâintĂ©rĂȘt prospectif de la dĂ©terminationprĂ©coce des taux plasmatiques dâIL-7 : dans les conditionnements myĂ©loablatifs, un taux dâIL-7supĂ©rieur Ă 11,9 pg/mL Ă J+14 est prĂ©dictif, tandis que dans les conditionnements rĂ©duits, câest untaux supĂ©rieur Ă 5,9 pg/mL Ă J+30 qui sâavĂšre prĂ©dictif. Dans notre cohorte de patients sousconditionnement myĂ©loablatif, de faibles taux dâIL-15 Ă J+14 sont associĂ©s en analyse univariĂ©e etmultivariĂ©e Ă la survenue ultĂ©rieure dâune rechute de lâhĂ©mopathie maligne. Une relation similairemais plus tardive (J+90) est retrouvĂ©e chez les receveurs dâun conditionnement rĂ©duit.Outre lâintĂ©rĂȘt prospectif pour les patients de la dĂ©termination prĂ©coce des tauxplasmatiques dâIL-7 et dâIL-15, cette Ă©tude comparative a permis de cerner dâune part le rĂŽleessentiel de la lymphopĂ©nie dans lâaccumulation dâune concentration critique dâIL-7 nĂ©cessairepour piloter lâexpansion homĂ©ostatique des cellules T matures et, dâautre part lâimpact du contexteinflammatoire sur lâaugmentation de la concentration plasmatique dâIL-15. Celle-ci, par son actiondirecte sur les lâexpansion des cellules T CD8+ mĂ©moires et ses effets contributifs Ă lâexpansionhomĂ©ostatique des cellules T naĂŻves, apparaĂźt renforcer lâaction de lâIL-7 en potentialisant son rĂŽledans lâallorĂ©activitĂ©, bĂ©nĂ©fique en terme de protection vis-Ă -vis de la rechute mais dĂ©lĂ©tĂšre enterme de rĂ©action de greffon contre hĂŽte
Constructions et reconstructions de pavages de dominos
PARIS-BIUSJ-ThĂšses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF
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