Software countermeasures for control flow integrity of smart card C codes

International audienceFault attacks can target smart card programs in order to disrupt an execution and gain an advantage over the data or the embedded functionalities. Among all possible attacks, control flow attacks aim at disrupting the normal execution flow. Identifying harmful control flow attacks as well as designing countermeasures at software level are tedious and tricky for developers. In this paper, we propose a methodology to detect harmful intra-procedural jump attacks at source code level and to automatically inject formally-proven countermeasures. The proposed software countermeasures defeat 100% of attacks that jump over at least two C source code statements or beyond. Experiments show that the resulting code is also hardened against unexpected function calls and jump attacks at assembly level

Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene

The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes

Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis

Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH

Transverse momentum spectra of charged particles in proton-proton collisions at s=900\sqrt{s} = 900 GeV with ALICE at the LHC

The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at $\sqrt{s} = 900$ GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region $(|\eta|<0.8)$ over the transverse momentum range $0.15<p_{\rm T}<10$ GeV/$c$. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for $|\eta|<0.8$ is $\left<p_{\rm T}\right>_{\rm INEL}=0.483\pm0.001$ (stat.) $\pm0.007$ (syst.) GeV/$c$ and \left_{\rm NSD}=0.489\pm0.001 (stat.) $\pm0.007$ (syst.) GeV/$c$, respectively. The data exhibit a slightly larger $\left<p_{\rm T}\right>$ than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.Comment: 20 pages, 8 figures, 2 tables, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/390

Randomized Open-Label Phase II Trial of Apitolisib (GDC-0980), a Novel Inhibitor of the PI3K/Mammalian Target of Rapamycin Pathway, Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma

Purpose This study is the first to compare dual inhibition of PI3K/mTOR by apitolisib (GDC-0980) against single inhibition of mTORC1 by everolimus in metastatic renal cell carcinoma (mRCC). Patients and Methods Clear cell mRCC patients who progressed on or after VEGF-targeted therapy were randomized to apitolisib (40 mg QD) or everolimus (10 mg QD). Endpoint included progression-free survival (PFS), safety, overall survival (OS), and objective response rate (ORR). Biomarker assessments were conducted. Results Eighty-five patients were randomized. After 62 events, stratified analysis revealed median PFS was significantly shorter for apitolisib than everolimus (3.7 vs. 6.1 mo: HR 2.04 [95%CI: 1.18-3.54; p<0.01]); apitolisib was not favored in any stratification subgroup. Median OS was not significantly different but trended in favor of everolimus (11.9 vs. 14.6 mo: HR 1.73 [95%CI: 0.87-3.43; p=0.12]). ORR was 7.1% for apitolisib and 11.6% for everolimus. Patients on apitolisib with greater incidences of grade 3-4 adverse events were more likely to discontinue treatment (31% vs. 12% for everolimus). No drug related deaths were observed. Apitolisib in comparison to everolimus was associated with substantially more high-grade hyperglycemia (40% vs. 7%) and rash (24% vs. 5%). Apitolisib pharmacokinetics suggested a relationship between exposure, and rash and hyperglycemia. Retrospective biomarker analyses revealed a relationship between VHL mutation status and outcome with everolimus but not with apitolisib. High HIF1α protein expression was associated with better outcome in both arms. Conclusion This study demonstrated that dual PI3K/mTOR inhibition by apitolisib was less effective than everolimus in mRCC, likely because full blockade of Pi3K/mTOR signaling resulted in multiple on-target adverse events. VHL mutation and HIF1α expression may be predictive of mTOR inhibitor benefit, although prospective validation is required