Apc mutation induces resistance of colonic cells to lipoperoxide-triggered apoptosis induced by faecal water from haem-fed rats

Recent epidemiological studies suggest that high meat intake is associated with promotion of colon cancer linked to haem-iron intake. We previously reported that dietary haem, in the form of either haemoglobin or meat, promotes precancerous lesions in the colon of rats given a low-calcium diet. The mechanism of promotion by haem is not known, but is associated with increased lipid peroxidation in faecal water and strong cytotoxic activity of faecal water on a cancerous mouse colonic epithelial cell line. To better understand the involvement of faecal water components of haem-fed rats in colon cancer promotion, we explored the effect of faecal water on normal (Apc +/+) or premalignant cells (Apc Min/+). Further, we tested if this effect was correlated to lipoperoxidation and 4-hydroxynonenal (HNE). We show here for the first time that heterozygote Apc mutation represents a strong selective advantage, via resistance to apoptosis induction (caspase 3 pathway), for colonic cells exposed to a haem-iron induced lipoperoxidation. The fact that HNE treatment of the cells provoked the same effects as the faecal water of rats fed the haem-rich diet suggests that this compound triggers apoptosis in those cells. We propose that this mechanism could be involved in the promotion of colon carcinogenesis by haem in vivo

Vers une méthode d aide à la décision pour l intégration d innovations dès la conception préliminaire des architectures de systèmes complexes

L objectif de ce travail de recherche est de proposer une méthode d aide à l intégration d innovations dès la conception préliminaire des systèmes complexes. Cette étape de la conception a en effet de forts impacts sur le reste de cycle de vie du produit. En se focalisant sur l aide à la génération d architectures de système complexe, cette méthode utilise un réseau Bayésien combiné à un problème de satisfaction de contraintes (CSP) pour générer et évaluer automatiquement des architectures de systèmes complexes. Le modèle de réseau Bayésien proposé est utilisé pour représenter le problème de conception de l architecture en termes de variables de décision, de contraintes et de performances. Un algorithme parcourt le graphe ainsi défini afin de générer les solutions d architecture qui sont considérées comme faisables et qui présentent un niveau de confiance acceptable. Ce niveau de confiance estime l incertitude associée à chaque architecture générée. Les performances des architectures sont aussi calculées grâce au réseau bayésien. Une fois les architectures générées, un modèle de problème de satisfaction de contraintes permet d optimiser le placement des composants au vu des contraintes de placement et des objectifs d optimisation préalablement définis par les concepteurs. Un logiciel a été développé pour faciliter la modélisation du problème et la visualisation des solutions. Deux cas industriels ont permis de tester la méthode et de nombreuses solutions d architecture ont été générées. Afin de tester la faisabilité de l étape de sélection d architectures dans un cadre industriel, un atelier de sélection d architectures a été organisé afin d être par la suite analysé. Il a impliqué quatre concepteurs de Thales et portait sur un des cas industriels précédents. Cette dernière étude a souligné des difficultés dans la définition des critères de sélection des architectures et propose des recommandations pour un futur support à la sélection d architecture système.The aim of this research work is to propose a method allowing innovation integration in early design stages and supporting architecture design of complex systems that have significant implications for the rest of overall system life-cycle. Focusing on system architectures generation support, this method proposes to use Bayesian networks combined with Constraint Satisfaction Problem (CSP) techniques in order to semi-automatically generate and evaluate complex systems architectures. Bayesian network model is used to represent the design problem in terms of decision variables, constraints and performances. Furthermore, an architecture generation algorithm is proposed to generate feasible solutions and to cluster them with regard to a given confidence level threshold. This confidence level is representing the estimation of the uncertainty on the overall system. Estimation of architecture performances are also calculated within the Bayesian network. Once the system architectures are generated, a CSP model optimises the component placement regarding placement constraints and optimisation objectives defined by designers. Software has been developed for the purpose of problem modelling and solutions visualisation. Two industrial implementations yielded in a generation of a high number of architecture solutions. In order to test the feasibility of architecture selection in an industrial environment, a study was conducted integrating four system designers. This study underlined the difficulties in defining architecture selection criteria and provides recommendations for the future system architecture selection support.CHATENAY MALABRY-Ecole centrale (920192301) / SudocSudocFranceF

Differential Power Analysis against the Miller Algorithm

Article en cours de publicationPairings permit several protocol simplications and original scheme creation, for example Identity Based Cryptography protocols. Initially, the use of pairings did not involve any secret entry, consequently, side channel attacks were not a threat for pairing based cryptography. On the contrary, in an Identity Based Cryptographic protocol, one of the two entries to the pairing is secret. Side Channel Attacks can be therefore applied to nd this secret. We realize a Differential Power Analysis(DPA) against the Miller algorithm, the central step to compute the Weil, Tate and Ate pairing. Keywords: Pairing, Miller Algorithm, Pairing Based Cryptography, SCA, DPA

A hepatitis A, B, C and HIV prevalence and risk factor study in ever injecting and non-injecting drug users in Luxembourg associated with HAV and HBV immunisations

<p>Abstract</p> <p>Background</p> <p>In Luxembourg, viral hepatitis and HIV infection data in problem drug users (PDUs) are primarily based on self-reporting. Our study aimed to determine the prevalence of HAV, HBV, HCV and HIV infections in ever injecting (IDUs) and non-injecting drug users (nIDUs) including inherent risk factors analysis for IDUs. Secondary objectives were immunisation against HAV and HBV, referral to care and treatment facilities as well as reduction in risk behaviour.</p> <p>Methods</p> <p>A nationwide, cross-sectional multi-site survey, involving 5 in-, 8 out-treatment and 2 prison centres, included both an assisted questionnaire (n = 368) and serological detection of HIV and Hepatitis A, B, C (n = 334). A response rate of 31% resulted in the participation of 310 IDUs and 58 nIDUs.</p> <p>Risk factors such as drug use, sexual behaviour, imprisonment, protection and health knowledge (HAV, HBV status and immunisations, HCV, HIV), piercing/tattoo and use of social and medical services were studied by means of chi2 and logistic models.</p> <p>Results</p> <p>Seroprevalence results for IDUs were 81.3% (218/268, 95%CI=[76.6; 86.0]) for HCV, 29.1% (74/254, 95%CI=[25.5;34.7 ]) for HBV (acute/chronic infection or past cured infection), 2.5% (5/202, 95%CI=[0.3; 4.6]) for HIV-1 and 57.1% (108/189, 95%CI=[50.0; 64.1]) for HAV (cured infections or past vaccinations). Seroprevalence results for nIDUs were 19.1% (9/47, 95%CI=[7.9;30.3]) for HCV, 8.9% (4/45, 95%CI=[0.6;17.2]) for HBV (acute/chronic infection or past cured infection), 4.8% (2/42, 95%CI=[-1.7;11.3]) for HIV-1 and 65.9% (27/41, 95%CI=[51.4;80.4]) for HAV. Prisoners showed the highest rates for all infections. Age, imprisonment and setting of recruitment were statistically associated with HCV seropositivity. Age, speedball career and nationality were significantly associated with HBV seropositivity. Only 56% of the participants in outpatient centres collected their serology results and 43 doses of vaccine against HAV and/or HBV were administered.</p> <p>Conclusions</p> <p>Despite the existing national risk-reduction strategies implemented since 1993, high prevalence of HCV and HBV infections in injecting drug users is observed. Our study showed that implementing risk-prevention strategies, including immunisation remains difficult with PDUs. Improvement should be looked for by the provision of field healthcare structures providing tests with immediate results, advice, immunisation or treatment if appropriate.</p

Endogenous Neurotrophins and Trk Signaling in Diffuse Large B Cell Lymphoma Cell Lines Are Involved in Sensitivity to Rituximab-Induced Apoptosis

International audienceBACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common and often fatal malignancy. Immunochemotherapy, a combination of rituximab to standard chemotherapy, has resulted in improved survival. However a substantial proportion of patients still fail to reach sustained remission. We have previously demonstrated that autocrine brain-derived neurotrophic factor (BDNF) production plays a function in human B cell survival, at least partly via sortilin expression. As neurotrophin receptor (Trks) signaling involved activation of survival pathways that are inhibited by rituximab, we speculated that neurotrophins may provide additional support for tumour cell survival and therapeutic resistance in DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used two DLBCL cell lines, SUDHL4 and SUDHL6, known to be respectively less and more sensitive to rituximab. We found by RT-PCR, western blotting, cytometry and confocal microscopy that both cell lines expressed, in normal culture conditions, BDNF and to a lesser extent NGF, as well as truncated TrkB and p75(NTR)/sortilin death neurotrophin receptors. Furthermore, BDNF secretion was detected in cell supernatants. NGF and BDNF production and Trk receptor expression, including TrkA, are regulated by apoptotic conditions (serum deprivation or rituximab exposure). Indeed, we show for the first time that rituximab exposure of DLBCL cell lines induces NGF secretion and that differences in rituximab sensitivity are associated with differential expression patterns of neurotrophins and their receptors (TrkA). Finally, these cells are sensitive to the Trk-inhibitor, K252a, as shown by the induction of apoptosis. Furthermore, K252a exhibits additive cytotoxic effects with rituximab. CONCLUSIONS/SIGNIFICANCE: Collectively, these data strongly suggest that a neurotrophin axis, such NGF/TrkA pathway, may contribute to malignant cell survival and rituximab resistance in DLBCL

Priority interventions to improve the management of chronic non-cancer pain in primary care: a participatory research of the ACCORD program

Purpose: There is evidence that the management of chronic non-cancer pain (CNCP) in primary care is far from being optimal. A 1-day workshop was held to explore the perceptions of key actors regarding the challenges and priority interventions to improve CNCP management in primary care. Methods: Using the Chronic Care Model as a conceptual framework, physicians (n=6), pharmacists (n=6), nurses (n=6), physiotherapists (n=6), psychologists (n=6), pain specialists (n=6), patients (n=3), family members (n=3), decision makers and managers (n=4), and pain researchers (n=7) took part in seven focus groups and five nominal groups. Results: Challenges identified in focus group discussions were related to five dimensions: knowledge gap, “work in silos”, lack of awareness that CNCP represents an important clinical problem, difficulties in access to health professionals and services, and patient empowerment needs. Based on the nominal group discussions, the following priority interventions were identified: interdisciplinary continuing education, interdisciplinary treatment approach, regional expert leadership, creation and definition of care paths, and patient education programs. Conclusion: Barriers to optimal management of CNCP in primary care are numerous. Improving its management cannot be envisioned without considering multifaceted interventions targeting several dimensions of the Chronic Care Model and focusing on both clinicians and patients

The geography of metapopulation synchrony in dendritic river networks

Dendritic habitats, such as river ecosystems, promote the persistence of species by favouring spatial asynchronous dynamics among branches. Yet, our understanding of how network topology influences metapopulation synchrony in these ecosystems remains limited. Here, we introduce the concept of fluvial synchrogram to formulate and test expectations regarding the geography of metapopulation synchrony across watersheds. By combining theoretical simulations and an extensive fish population time-series dataset across Europe, we provide evidence that fish metapopulations can be buffered against synchronous dynamics as a direct consequence of network connectivity and branching complexity. Synchrony was higher between populations connected by direct water flow and decayed faster with distance over the Euclidean than the watercourse dimension. Likewise, synchrony decayed faster with distance in headwater than mainstem populations of the same basin. As network topology and flow directionality generate fundamental spatial patterns of synchrony in fish metapopulations, empirical synchrograms can aid knowledge advancement and inform conservation strategies in complex habitats

Examining the international bushmeat traffic in Belgium: A threat to conservation and public health.

peer reviewedThe carriage of bushmeat into the European Union is an infringement of EU Animal Health and Wildlife Trade legislation and poses a threat to biodiversity and public health. To explore the nature and scale of the international bushmeat trade, seized leaking luggage and passengers arriving at Brussels Zaventem airport from sub-Saharan Africa between 2017 and 2018 were searched for "meat" (bushmeat and livestock) by border control authorities. Visual identification, radiography and genetic analysis were applied to derive information from seized specimens, including at least ten CITES-listed species. We estimate that an average of 3.9 t of bushmeat is smuggled monthly through Brussels. The average consignment of meat seized per passenger was 2.8 kg and 4 kg of bushmeat or domestic livestock meat, respectively. The international trafficking of bushmeat is evidently active, yet penalties are rarely enforced; hence we provide suggestions to simplify law enforcement procedures