New Preimage Attacks Against Reduced SHA-1

This paper shows preimage attacks against reduced SHA-1 up to 57 steps. The best previous attack has been presented at CRYPTO 2009 and was for 48 steps finding a two-block preimage with incorrect padding at the cost of 2159.3 evaluations of the compression function. For the same variant our attacks find a one-block preimage at 2150.6 and a correctly padded two-block preimage at 2151.1 evaluations of the compression function. The improved results come out of a differential view on the meet-in-the-middle technique originally developed by Aoki and Sasaki. The new framework closely relates meet-in-the-middle attacks to differential cryptanalysis which turns out to be particularly useful for hash functions with linear message expansion and weak diffusion properties

Differential and invertibility properties of BLAKE (full version)

BLAKE is a hash function selected by NIST as one of the 14 second round candidates for the SHA-3 Competition. In this paper, we follow a bottom-up approach to exhibit properties of BLAKE and of its building blocks: based on differential properties of the internal function G, we show that a round of BLAKE is a permutation on the message space, and present an efficient inversion algorithm. For 1.5 rounds we present an algorithm that finds preimages faster than in previous attacks. Discovered properties lead us to describe large classes of impossible differentials for two rounds of BLAKE’s internal permutation, and particular impossible differentials for five and six rounds, respectively for BLAKE- 32 and BLAKE-64. Then, using a linear and rotation-free model, we describe near-collisions for four rounds of the compression function. Finally, we discuss the problem of establishing upper bounds on the probability of differential characteristics for BLAKE

Improved Linear Differential Attacks on CubeHash

This paper presents improved collision attacks on round-reduced variants of the hash function CubeHash, one of the SHA-3 second round candidates. We apply two methods for finding linear differential trails that lead to lower estimated attack complexities when used within the framework introduced by Brier,.Khazaei, Meier and Peyrin at ASIA-CRYPT 2009. The first method yields trails that are relatively dense at the beginning and sparse towards the end. In combination with the condition function concept; such trails lead to much faster collision attacks. We demonstrate this by providing a. real collision for CubeHash-5/96. The second method randomizes the search for highly probable linear differential trails and leads to significantly better attacks for up to eight rounds

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10-10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10-10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response : a sub-study of the NEAT001/ANRS143 randomized trial

OBJECTIVES: NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. METHODS: Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5*3, CYP3A4*22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0-24 and C24 with time to virological failure was evaluated by Cox regression. RESULTS: Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P < 0.001). No significant relationship was demonstrated between darunavir AUC0-24 or C24 and time to virological failure [HR (95% CI): 2.28 (0.53-9.80), P = 0.269; and 1.82 (0.61-5.41), P = 0.279, respectively]. CONCLUSIONS: Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity