Simulation of stochastic blockchain models

International audienceThis paper build the foundations of a simulation tool for blockchain-based applications. It takes advantage of the huge expressiveness and extensibility of PyCATSHOO framework to deal with the important variability of blockchain implementations and properties of interest. A simple stochastic model of generic blockchain-style distributed consensus system and associated performance indicators are proposed (performance in terms of consistency and ability to discard double-spending attacks). Monte Carlo simulations are applied to assess the indicators and determine their sensitivity to the variation of input parameters

Dynamic Compaction Using Select Fill Displacement Methods

Since its development as a full-fledged soil compaction technique by Louis Menard in the late 1960s, the Dynamic Compaction method has evolved considerably and has become an increasingly efficient ground improvement system. Among the special techniques borne out of this evolution is the use of Dynamic Compaction to create large-diameter columns using select granular material. This method serves to not only provide increased support and better distribution of imposed loads through the columns themselves, but also augments the capability of the process in improving the host soils to a depth and degree not possible using conventional DC methods. Three case histories are presented to illustrate this technique and its benefits in terms of increased effectiveness and range of application

Conditions d'ergodicité de l'anneau de Cambridge et de certaines de ses faces. Limites fluides

Dans cet article, on étudie les conditions d'ergodicité d'un modèle défini par un anneau de Cambridge en utilisant la méthode des limites fluides. On se place dans le cas où les taux d'arrivées des messages pour chacune des des files d'attente sont identiques. Les limites fluides sont obtenues comme limites de processus stochastiques construits à partir de modèles saturés. On peut ainsi définir une modélisation macroscopique et obtenir de facon simplifiée les équations régissant la dynamique établie par l'anneau. On examine, enfin pour certains modèles ergodiques, le comportement des differentes files d'attente lors du retour à l'équilibre

Evaluation of the efficacy of prolonged administration of azithromycin in a murine model of chronic toxoplasmosis

The efficacy of prolonged administration of azithromycin was evaluated in a murine model of lethal chronic toxoplasmosis. Mice were challenged intraperitoneally with cysts of a moderately virulent strain of Toxoplasma gondii, observed for 4 weeks and then allocated to the treatment or control group. All 26 animals given azithromycin 100 mg/kg/day for 100 days were protected compared with 19 of 25 control animals which died (P < 0.001). Nineteen of the 20 mice in the treatment group survived for an additional month while receiving the same azithriomycin regiment but viable cysts were indentified in the brain tissue of these animals when they were killed. Although there was no significant difference between the groups in terms of the number of cysts in the brain, the administration of azithromycin was associated with a reduction in brain inflammation. The concentrations of azithromycin in the brains of five animals ranged from 0.7 to 2.3 μ/g; there was no evidence of accumulation even after 100 doses. Azithromycin merits further evaluation as primary or secondary prophylaxis against toxoplasma encephalitis in individuals at risk of developing this complicatio

The transmembrane protein bacterioopsin affects the polarity of the hydrophobic core of the host lipid bilayer

AbstractInfluence of the transmembrane protein bacterioopsin (the retinal-free form of bacteriorhodopsin) on the polarity of egg-phosphatidylcholine bilayers was studied by means of a steady-state and time-resolved fluorescence approach exploiting the solvatochromic properties of the 2-anthroyl fluorophore. Introduced in phosphatidylcholine molecules in the form of 8-(2-anthroyl)octanoic acid, this fluorophore probed the hydrocarbon core of the lipid bilayer. As previously shown (E. Pérochon et al., Biochemistry 31 (1992) 7672–7682), water molecules were detected in this region of the terminal part of the lipid acyl chains. Their number was considerably reduced upon addition of bacterioopsin to the lipids. This was assessed by a blue shift in the fluorescence emission spectra of the probe and a marked decrease in the fractional population of fluorophores interacting with water, to the benefit of those experiencing a hydrophobic environment. In agreement with current theories, this decrease in the hydration of the bilayer may be linked to an increase in the acyl chain order and a decrease in the lateral diffusion coefficient of lipids near the protein. The data obtained at high protein concentration accounts for a protein/lipid interface which is much less hydrated than the hydrophobic core of a protein-free lipid bilayer

Regulation of hepatic cardiolipin metabolism by TNFα: Implication in cancer cachexia

International audienceCardiolipin (CL) content accumulation leads to an increase in energy wasting in liver mitochondria in a rat model of cancer cachexia in which tumor necrosis factor alpha (TNFα) is highly expressed. In this study we investigated the mechanisms involved in liver mitochondria CL accumulation in cancer cachexia and examined if TNFα was involved in this process leading to mitochondrial bioenergetics alterations. We studied gene, protein expression and activity of the main enzymes involved in CL metabolism in liver mitochondria from a rat model of cancer cachexia and in HepaRG hepatocyte-like cells exposed to 20 ng/ml of TNFα for 12 h. Phosphatidylglycerolphosphate synthase (PGPS) gene expression was increased 2.3-fold (p < 0.02) and cardiolipin synthase (CLS) activity decreased 44% (p < 0.03) in cachectic rat livers compared to controls. CL remodeling enzymes monolysocardiolipin acyltransferase (MLCL AT-1) activity and tafazzin (TAZ) gene expression were increased 30% (p < 0.01) and 50% (p < 0.02), respectively, in cachectic rat livers compared to controls. Incubation of hepatocytes with TNFα increased CL content 15% (p < 0.05), mitochondrial oxygen consumption 33% (p < 0.05), PGPS gene expression 44% (p < 0.05) and MLCL AT-1 activity 20% (p < 0.05) compared to controls. These above findings strongly suggest that in cancer cachexia, TNFα induces a higher energy wasting in liver mitochondria by increasing CL content via upregulation of PGPS expression

Security Architecture for Point-to-Point Splitting Protocols

International audienceThe security of industrial supervisory control and data acquisition systems (SCADA) has become a major concern since the Stuxnet worm in 2010. As these systems are connected to the physical world, this makes them possibly hazardous if a malicious attacker is able to take over their control. SCADA can live up to 40 years, are particularly hard to patch, and quite often have no security feature at all. Thus, rather than securing them, network segregation is often used to prevent attackers from entering the industrial system. In this paper, we propose a generic solution: embed a point-to-point splitting protocol within a physical device, thus able to physically isolate networks, perform deep packet inspection and also provide encryption if necessary. We obtain a kind of next generation firewall, encompassing at least both diode and firewall features, for which conformity to security policies can be ensured. Then we define a set of associated security properties for such devices and the requirements for such a device's security architecture and filtering rules. Finally, we propose a secure hardware implementation

The Expression of Myeloproliferative Neoplasm-Associated Calreticulin Variants Depends on the Functionality of ER-Associated Degradation

BACKGROUND: Mutations in CALR observed in myeloproliferative neoplasms (MPN) were recently shown to be pathogenic via their interaction with MPL and the subsequent activation of the Janus Kinase - Signal Transducer and Activator of Transcription (JAK-STAT) pathway. However, little is known on the impact of those variant CALR proteins on endoplasmic reticulum (ER) homeostasis. METHODS: The impact of the expression of Wild Type (WT) or mutant CALR on ER homeostasis was assessed by quantifying the expression level of Unfolded Protein Response (UPR) target genes, splicing of X-box Binding Protein 1 (XBP1), and the expression level of endogenous lectins. Pharmacological and molecular (siRNA) screens were used to identify mechanisms involved in CALR mutant proteins degradation. Coimmunoprecipitations were performed to define more precisely actors involved in CALR proteins disposal. RESULTS: We showed that the expression of CALR mutants alters neither ER homeostasis nor the sensitivity of hematopoietic cells towards ER stress-induced apoptosis. In contrast, the expression of CALR variants is generally low because of a combination of secretion and protein degradation mechanisms mostly mediated through the ER-Associated Degradation (ERAD)-proteasome pathway. Moreover, we identified a specific ERAD network involved in the degradation of CALR variants. CONCLUSIONS: We propose that this ERAD network could be considered as a potential therapeutic target for selectively inhibiting CALR mutant-dependent proliferation associated with MPN, and therefore attenuate the associated pathogenic outcomes