Long-range shooting incident reconstruction: when terrain matters

International audienc

A Phase 1 study for safety and pharmacokinetics of BIO101 (20‐hydroxyecdysone) in healthy young and older adults

Abstract Background Sarcopenia is an age‐related skeletal muscle disorder characterized by loss of muscle mass and strength leading to mobility disability. 20‐Hydroxyecdysone (20E) is a polyhydroxylated plant steroid that demonstrates pharmacological effects in many disease animal models including ageing/sarcopenia. BIO101 is a 20E purified investigational drug (≥97%) that previously demonstrated good toxicology profiles in rat and dog. BIO101 is evaluated in healthy young and older adults in a Phase 1 study. Methods This study is a Single Ascending Dose (SAD) followed by a 14‐day Multiple Ascending Dose (MAD). In SAD, BIO101 was administered orally to 16 young adults at doses from 100 to 1400 mg and to 8 older adults (age ≥65 years) at 1400 mg. In MAD, doses of 350 mg once daily (qd), 350 mg twice daily (bid) and 450 mg bid were administered to 10 older adults. The primary objective was to evaluate safety and pharmacokinetics (PK), including dosing of circulating metabolites. Pharmacodynamic effects were investigated with regard to myostatin, procollagen‐III‐amino‐terminal propeptide (PIIINP), myoglobin, creatine‐kinase Muscle Brain (CKMB), renin and aldosterone plasma/serum levels. Results BIO101 showed a good safety profile with only mild to moderate adverse events and a satisfactory pharmacokinetic profile. In SAD, at 100 mg to 1400 mg, mean Cmax and areas under the curve increased less than dose‐proportionally. Mean half‐life was short (2.4–4.9 h), and mean renal clearance was comparable in all doses (4.05–5.05 L/h). Mean plasma exposure was slightly lower in older adults (22% lower for Cmax and 13%–15% lower for AUCs) compared with young subjects. In MAD, 350 and 450 mg bid led to a slight accumulation over 14 days (mean ratio of accumulation [Rac] of 1.31 in both cohorts). Reduction of biomarkers (myoglobin, CK‐MB) mean serum levels (vs. baseline) was observed at 450 mg bid. Two major metabolites of 20E (14‐deoxy‐20‐hydroxyecdysone and 14‐deoxypoststerone) were identified and quantified. Conclusions BIO101 shows a good safety and pharmacokinetic profile that led to the selection of doses for the subsequent interventional clinical trials of Phase 2 in age‐related sarcopenia (SARA‐INT) and Phase 3 in Covid‐19 (COVA)

Fault Injection to Reverse Engineer DES-Like Cryptosystems

International audienceSecurity is a key component for information technologies and communication and is mainly provided by cryptosystems. Although Kerckhoffs' principle enunciates that such cryptosystems should be secure even if their algorithms are public knowledge, private algorithms are still used. As the secrecy of such private algorithms ensures a large part of the security of the whole system, some attacks, called ``reverse-engineering'', aim at recovering these algorithms and/or details of their implementations. Among technics used to perform such attacks, a really efficient and powerful one, called “pertubation attacks”, consists in disrupting the circuit's behavior in order to alter the correct progress of the algorithm. Our work applies such technic to recover part of a crypto-algorithm based on the DES (for Data Encryption Standard) but which only differs from the values of its substitution boxes (or Sboxes).In the first part of the talk, the different technics of fault attacks will be shortly described. Then, our working hypothesis and our attack will be detailed. Next, the result obtained on simulated experiments will be presented. We’ll show that, with our approach, about two hundred of faulty executions of the algorithm enable to retrieve all the Sboxes. Compared with state of the art reverse engineering attacks based on faults, this number is reduced by a factor two