Formal Safety and Security Assessment of an Avionic Architecture with Alloy

We propose an approach based on Alloy to formally model and assess a system architecture with respect to safety and security requirements. We illustrate this approach by considering as a case study an avionic system developed by Thales, which provides guidance to aircraft. We show how to define in Alloy a metamodel of avionic architectures with a focus on failure propagations. We then express the specific architecture of the case study in Alloy. Finally, we express and check properties that refer to the robustness of the architecture to failures and attacks.Comment: In Proceedings ESSS 2014, arXiv:1405.055

Evidence for Interlayer Electronic Coupling in Multilayer Epitaxial Graphene from Polarization Dependent Coherently Controlled Photocurrent Generation

Most experimental studies to date of multilayer epitaxial graphene on C-face SiC have indicated that the electronic states of different layers are decoupled as a consequence of rotational stacking. We have measured the third order nonlinear tensor in epitaxial graphene as a novel approach to probe interlayer electronic coupling, by studying THz emission from coherently controlled photocurrents as a function of the optical pump and THz beam polarizations. We find that the polarization dependence of the coherently controlled THz emission expected from perfectly uncoupled layers, i.e. a single graphene sheet, is not observed. We hypothesize that the observed angular dependence arises from weak coupling between the layers; a model calculation of the angular dependence treating the multilayer structure as a stack of independent bilayers with variable interlayer coupling qualitatively reproduces the polarization dependence, providing evidence for coupling.Comment: submitted to Nano Letter

Coherent Control of Ballistic Photocurrents in Multilayer Epitaxial Graphene Using Quantum Interference

International audienceWe report generation of ballistic electric currents in unbiased epitaxial graphene at 300 K via quantum interference between phase-controlled cross-polarized fundamental and second harmonic 220 fs pulses. The transient currents are detected via the emitted terahertz radiation. Because of graphene's special structure symmetry, the injected current direction can be well controlled by the polarization of the pump beam in epitaxial graphene. This all optical injection of current provides not only a noncontact way of injecting directional current in graphene but also new insight into optical and transport process in epitaxial graphene

Cytogénétique des carcinomes rénaux [Cytogenetics profiles of renal carcinoma]

National audienc

Cytoplasmic PAR-3 protein expression is associated with adverse prognostic factors in clear cell renal cell carcinoma and independently impacts survival.

International audienceClear cell renal cell carcinomas (ccRCCs) represent 70% of renal cancers, and several clinical and histolopathological factors are implicated in their prognosis. We recently demonstrated that the overexpression of PAR-3 protein encoded by the PARD3 gene could be implicated in renal oncogenesis. The object of this work was to study the association of intratumoral PAR-3 expression with known prognostic parameters and clinical outcome. In this aim, PAR-3 expression was assessed by immunohistochemistry in ccRCC tumors of 101 patients from 2003 to 2005. The immunostaining of PAR-3 was scored either as membranous (mPAR-3) or as both membranous and cytoplasmic (cPAR-3). Cytoplasmic PAR-3 was significantly associated with worse histopathological and clinical prognostic factors: Fuhrman grades 3 and 4, tumor necrosis, sarcomatoid component, adrenal invasion, renal and hilar fat invasion, eosinophilic component, a noninactivated VHL gene, higher tumor grade, lymph node involvement, metastasis, and worse clinical Eastern Cooperative Oncology Group and S classification scores. After multivariate analysis, 2 parameters were independently associated with cPAR-3: necrosis and eosinophilic components. In addition, cPAR-3 patients had shorter overall and progression-free survivals independently from strong prognostic validated factors like metastases. A cytoplasmic expression of PAR-3 is therefore implicated in worse clinical and pathological cancer features in ccRCC and could be useful to identify patients with high-risk tumors

CD95 recruits PLCγ1 to trigger a calcium response promoting Th17 accumulation in inflamed organs of lupus mice

CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L, and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase Cγ1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway may be attractive therapeutic approach for SLE treatment

Wild-type VHL Clear Cell Renal Cell Carcinomas Are a Distinct Clinical and Histologic Entity: A 10-Year Follow-up

International audienceBackground: Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with 50% risk of metastases at initial diagnosis or at follow-up. An inactivation of the tumor-suppressor gene von Hippel-Lindau (VHL) is present in >70% of sporadic cases by two of three different mechanisms: locus deletion, gene mutation, or promoter hypermethylation. Objective: To correlate the complete status of the VHL gene with clinical and pathologic criteria. Design, setting, and participants We retrospectively included 98 patients with ccRCC who underwent surgery between 2002 and 2005. VHL gene deletions (71 of 98; 72.4%), mutations (68 of 98; 69.4%), and promoter hypermethylations (13 of 98; 13.3%) were screened by gene copy analysis, gene sequencing, and methylation-specific multiplex ligation-dependent probe amplification, respectively. Outcome measurements and statistical analysis Relationships between VHL subgroups and the studied criteria were analyzed using chi-square and Student t tests. Survival was analyzed with the log-rank test and Kaplan-Meier curves. Results and limitations: Compared with ccRCCs with two events (66.3%), tumors with no or one genetic event (33.6%) were associated with a higher nuclear grade IV (p = 0.02), metastases (p = 0.04), sarcomatoid component (p = 0.01), dense lymphocyte infiltrate (p = 0.013), and vascular endothelial growth factor overexpression (>30%) (p = 0.003), which was also an independent factor after multivariate analysis. Furthermore, wild-type VHL tumors (no inactivating event, 11.2%) were associated with nodal involvement (p = 0.019), and patients with this type of tumor had a specific survival of 33 mo compared with patients with ccRCCs having one or two VHL inactivating events (107 mo; p = 0.016). The retrospective design with small number of wild-type tumors was a limitation of this work. Conclusions: This long-term study (10-yr clinical follow-up) confirms that ccRCCs with wild-type VHL are highly aggressive tumors that need to be formally identified. Patient summary Among activated VHL tumors, the wild-type subgroup defines an aggressive phenotype with worse survival rates, suggesting that these tumors must be more thoroughly screene

CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice

CD95 ligand (CD95L) is expressed by immune cells and triggers apoptotic death. Metalloprotease-cleaved CD95L (cl-CD95L) is released into the bloodstream but does not trigger apoptotic signaling. Hence, the pathophysiological role of cl-CD95L remains unclear. We observed that skin-derived endothelial cells from systemic lupus erythematosus (SLE) patients expressed CD95L and that after cleavage, cl-CD95L promoted T helper 17 (Th17) lymphocyte transmigration across the endothelial barrier at the expense of T regulatory cells. T cell migration relied on a direct interaction between the CD95 domain called calcium-inducing domain (CID) and the Src homology 3 domain of phospholipase Cγ1. Th17 cells stimulated with cl-CD95L produced sphingosine-1-phosphate (S1P), which promoted endothelial transmigration by activating the S1P receptor 3. We generated a cell-penetrating CID peptide that prevented Th17 cell transmigration and alleviated clinical symptoms in lupus mice. Therefore, neutralizing the CD95 non-apoptotic signaling pathway could be an attractive therapeutic approach for SLE treatment

Full-band Structure Calculations of Optical Injection in Semiconductors: Investigations of One-color, Two-color, and Pump-probe Scenarios

Carrier, spin, charge current, and spin current injection by one- and two-color optical schemes are investigated within 30-band k·p theory. Parameters of the band model are optimized to give full-Brillouin zone band structures for GaAs and Ge that give accurate Γ-point effective masses and gyromagnetic factors and give access to the L valley, and to the E₁ and E₁+Δ₁ critical points in the linear optical absorption. Calculations of one- and two-photon carrier and spin injection and two-color current injection are performed for excitation energies in the range of 0—4 eV in GaAs and 0—3.5 eV in Ge. Significant spin and spin current injection occurs with 30% spin polarization in GaAs and Ge at photon energy matching the E₁ critical point. Further, the anisotropy and disparity of the current injection between parallel and perpendicular linearly-polarized beam configurations are calculated. For light propagating along a crystal axis, anisotropic contributions in coherent current control and two-photon spin injection give rise to normal current components and in-plane spin components. In Ge, contributions from the holes to spin, electrical current, and spin current injection are investigated. Optical orientation results in 83% spin-polarized holes at the band edge. The effects of carrier dynamics in Ge are treated within a rate-equation model. The detection of spin dynamics in a pump-probe setup is considered, and the Fermi-factor approach is justified for electrons but not for holes. Carrier and current injection are further investigated in single-layer and bilayer graphene within the tight-binding model. In single-layer graphene, the linear-circular dichroism in two-photon absorption yields an absorption coefficient that is twice as large for circularly polarized light compared to linearly polarized light. Coherent current injection is largest for co-circularly polarized beams and zero for cross-circularly polarized beams. For linearly polarized beams, the magnitude of the injected current is independent of beam polarizations. In contrast, the injected current in bilayer graphene shows disparity between parallel and perpendicular configurations of the beams. The resulting angular dependence of the current is a macroscopic, measurable consequence of interlayer coupling in the bilayer.Ph

Carcinomes à cellules rénales et facteurs pronostiques. [Renal cell carcinoma and prognostic factors]

International audienceHistological and prognostic patterns of renal cell carcinoma vary greatly, sometimes hindering accurate prognosis. Classical histological prognostic factors have emerged during the last 25 years, the two predominant factors being TNM stage and nuclear Fuhrman grade. However, the use of new treatment strategies, targeting tumoral angiogenesis, make it necessary to develop new prognostic markers. Microvascular density, plasmatic and tissue expression of VEGF, such as intratumoral expression of VHL, HIF and CA IX can be useful to further evaluate prognosis and outcome. Future study as predictive factors of response or non-response to antiangiogenic therapies is of major interest for clinicians