Synthesis, Structure and Biological Activity of CIA and CIB, Two α-Conotoxins from the Predation-Evoked Venom of Conus catus

Cone snails produce a fast-acting and often paralyzing venom that is usually injected into their prey or predator through a hypodermic needle-like modified radula tooth. Many diverse compounds are found in their venom including small molecules, peptides and enzymes. However, peptidic toxins called conotoxins (10-40 residues and 2-4 disulfide bonds) largely dominate these cocktails. These disulfide rich toxins are very valuable pharmacological tools for investigating the function of ions channels, G-protein coupled receptors, transporters and enzymes. Here, we report on the synthesis, structure determination and biological activities of two -conotoxins, CIA and CIB, found in the predatory venom of the piscivorous species Conus catus. CIA is a typical 3/5 -conotoxin that blocks the rat muscle type nAChR with an IC50 of 5.7 nM. Interestingly, CIA also inhibits the neuronal rat nAChR subtype 32 with an IC50 of 2.06 M. CIB is a 4/7 -conotoxin that blocks rat neuronal nAChR subtypes, including 32 (IC50 = 128.9 nM) and 7 (IC50 = 1.51 M). High resolution NMR structures revealed typical -conotoxin folds for both peptides. We also investigated the in vivo effects of these toxins on fish, since both peptides were identified in the predatory venom of C. catus. Consistent with their pharmacology, CIA was highly paralytic to zebrafish (ED50 = 110 g/kg), whereas CIB did not affect the mobility of the fish. In conclusion, CIA likely participates in prey capture through muscle paralysis, while the putative ecological role of CIB remains to be elucidated

Wave Equation Numerical Resolution: a Comprehensive Mechanized Proof of a C Program

We formally prove correct a C program that implements a numerical scheme for the resolution of the one-dimensional acoustic wave equation. Such an implementation introduces errors at several levels: the numerical scheme introduces method errors, and floating-point computations lead to round-off errors. We annotate this C program to specify both method error and round-off error. We use Frama-C to generate theorems that guarantee the soundness of the code. We discharge these theorems using SMT solvers, Gappa, and Coq. This involves a large Coq development to prove the adequacy of the C program to the numerical scheme and to bound errors. To our knowledge, this is the first time such a numerical analysis program is fully machine-checked.Comment: No. RR-7826 (2011

Impact of photovoltaic power plants on far-field effects of UVCEs

International audiencePhotovoltaic power stations are developing worldwide as they emit no greenhouse gases while producing electricity. In France, industries such as Total plan to install such stations in fields surrounding their chemical and refining plants. The risk analyses performed for these plants often highlighted Unconfined Vapor Cloud Explosions scenarios, related to heavy gases releases, for which characteristic overpressure effect distances were computed The present work aims at quantifying the impact of the presence of a photovoltaic power station in a potential flammable cloud. It is nevertheless limited to a station geometry provided by Total. The problem is not straightforward as two main physical trends appear: flame acceleration due to panels obstruction and flame extinction when the flame reaches the top of the flammable cloud. It has first to be determined if explosion runaway is possible, this one due to the obstacles repetition on the flame path. Then, characteristic overpressure effects distances can be computed for photovoltaic power plants of any size. To this goal, a CFD-based method is proposed and detailed. The open-source CFD code OpenFoam is used as well as phenomenological considerations for computing characteristic overpressure effects distances

Proteomic Analysis of the Predatory Venom of Conus striatus Reveals Novel and Population-Specific κA-Conotoxin SIVC

Animal venoms are a rich source of pharmacological compounds with ecological and evolutionary significance, as well as with therapeutic and biotechnological potentials. Among the most promising venomous animals, cone snails produce potent neurotoxic venom to facilitate prey capture and defend against aggressors. Conus striatus, one of the largest piscivorous species, is widely distributed, from east African coasts to remote Polynesian Islands. In this study, we investigated potential intraspecific differences in venom composition between distinct geographical populations from Mayotte Island (Indian Ocean) and Australia (Pacific Ocean). Significant variations were noted among the most abundant components, namely the κA-conotoxins, which contain three disulfide bridges and complex glycosylations. The amino acid sequence of a novel κA-conotoxin SIVC, including its N-terminal acetylated variant, was deciphered using tandem mass spectrometry (MS/MS). In addition, the glycosylation pattern was found to be consisting of two HexNAc and four Hex for the Mayotte population, which diverge from the previously characterized two HexNAc and three Hex combinations for this species, collected elsewhere. Whereas the biological and ecological roles of these modifications remain to be investigated, population-specific glycosylation patterns provide, for the first time, a new level of intraspecific variations in cone snail venoms

Discours et signature de l'acte constitutionnel par le roi, suivis de la réponse du président, lors de la séance du 14 septembre 1791

Duport-Dutertre Marguerite Louis François, Thouret Jacques Guillaume. Discours et signature de l'acte constitutionnel par le roi, suivis de la réponse du président, lors de la séance du 14 septembre 1791. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XXX - Du 28 août au 17 septembre 1791. Paris : Librairie Administrative P. Dupont, 1888. pp. 635-636

Discours et signature de l'acte constitutionnel par le roi, suivis de la réponse du président, lors de la séance du 14 septembre 1791

Duport-Dutertre Marguerite Louis François, Thouret Jacques Guillaume. Discours et signature de l'acte constitutionnel par le roi, suivis de la réponse du président, lors de la séance du 14 septembre 1791. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XXX - Du 28 août au 17 septembre 1791. Paris : Librairie Administrative P. Dupont, 1888. pp. 635-636

Evidence of a larger EM-induced fault model

International audienceElectromagnetic waves have been recently pointed out as a medium for fault injection within circuits featuring cryptographic mod- ules. Indeed, it has been experimentally demonstrated by A. Dehbaoui et al. (Injection of transient faults using electromagnetic pulses - practical results on a cryptographic system, IACR Cryptology ePrint Archive 2012) that an electromagnetic pulse, produced with a high voltage pulse generator and a probe similar to that used to perform EM analyses, was susceptible to create faults exploitable from a cryptanalysis viewpoint. An analysis of the induced faults (Dehbaoui et al., Electro-magnetic transient faults injection on a hardware and a software implementations of aes. In FDTC, 2012) revealed that they originated from timing constraint violations. This paper experimentally demonstrates that EM injection, performed with enhanced probes is very local and can produce not only timing faults but also bit-set and bit-reset faults. This result clearly extends the range of the threats associated with EM fault injection

Further Analysis of Laser-induced IR-drop

International audienceStudies on laser induced IR-drop are recent and still not much covered. Since laser-induced IR-drop can amplify the well-known effects of induced photoelectric currents in ICs, this work aims to present important characteristics of such effect. Understanding the characteristics and effects of laser induced IRdrop in ICs allows the elaboration of more accurate simulation models, and consequently helps in the design of countermeasures that mitigate the effects of laser illumination. Simulations and experiments were performed in order to understand the relationship of the laser pulse width and the decoupling capacitance of the power supply network with the induced IR-drop. The results showed that the maximum variation of the supply voltage depends on the laser pulse duration, and on other circuit characteristics, such as RLC parameters of the supply network. It was possible to observe by simulations and experiments that, for the proposed circuit, the maximum variation of the supply voltage occurred for a laser pulse greater than or equal to 1 μs. Regarding the decoupling capacitance variation, the results showed that for a decoupling capacitor up to 100 pF, the IR-drop becomes even more relevant with a variation up to 97% of VDD

An experimentally tuned compact electrical model for laser fault injection simulation

International audienceThis work reports LFI experiments carried out on custom CMOS 65 nm digital test gates, aiming at tuning the parameters of a compact electrical model. Like in previous works, we observed a difference in behavior in the induced faults when using nanosecond and picosecond range laser pulse duration. However, our experimental results showed that the laser-sensitive areas were restricted to the PMOS transistors for ns laser pulses, contrary to what was previously stated in the literature. For ps pulse duration, these works outline the sensitivity of both the NMOS and PMOS of an SRAM cell following the theoretical model of LFI. These experiments help to calibrate the parameters of a compact electrical model, allowing the simulation of LFI attacks (using SPICE-like CAD tools). This compact model is built upon previous works, with simplifications to facilitate its use. Once tuned, simulations using the proposed compact model exhibit a good correlation with the experimental results

Olecranon bursitis secondary to Mycobacterium europaeum infection in a patient receiving immunosuppressive drugs for rheumatoid arthritis

International audienceMycobacterium europaeum is one of the 16 slow-growing non-tuberculous mycobacterial species belonging to the Mycobacterium simiae complex. It was first described in 2011, after the polyphasic analyses of five strains collected in various European countriesfromsputumsamples and a jaw gland biopsy between 1995 and 2009 [1]. Only three cases of M. europaeum infections involving the respiratory tract have been reported in immunocompromised patients from Iran and France [2,3]. We report a case of M. europaeum infection involving the periarticularstructuresin an immunocompromised adult and describe its successful management