Context. N-methylformamide, CH 3 NHCHO, may be an important molecule for interstellar pre-biotic chemistry because it contains a peptide bond, which in terrestrial chemistry is responsible for linking amino acids in proteins. The rotational spectrum of the most stable trans conformer of N-methylformamide is complicated by strong torsion-rotation interaction due to the low barrier of the methyl torsion. For this reason, the theoretical description of the rotational spectrum of the trans conformer has up to now not been accurate enough to provide a firm basis for its interstellar detection. Aims. In this context, as a prerequisite for a successful interstellar detection, our goal is to improve the characterization of the rotational spectrum of N-methylformamide. Methods. We use two absorption spectrometers in Kharkiv and Lille to measure the rotational spectra over the frequency range 45-630 GHz. The analysis is carried out using the Rho-axis method and the RAM36 code. We search for N-methylformamide toward the hot molecular core Sagittarius (Sgr) B2(N2) using a spectral line survey carried out with the Atacama Large Millimeter/submillimeter Array (ALMA). The astronomical spectra are analyzed under the assumption of local thermodynamic equilibrium. The astronomical results are put into a broader astrochemical context with the help of a gas-grain chemical kinetics model. Results. The new laboratory data set for the trans conformer of N-methylformamide consists of 9469 distinct line frequencies with J ≤ 62, including the first assignment of the rotational spectra of the first and second excited torsional states. All these lines are fitted within experimental accuracy for the first time. Based on the reliable frequency predictions obtained in this study, we report the tentative detection of N-methylformamide towards Sgr B2(N2). We find N-methylformamide to be more than one order of magnitude less abundant than formamide (NH 2 CHO), a factor of two less abundant than the unsaturated molecule methyl isocyanate (CH 3 NCO), but only slightly less abundant than acetamide (CH 3 CONH 2 ). We also report the tentative detection of the 15 N isotopologue of formamide ( 15 NH 2 CHO) toward Sgr B2(N2). The chemical models indicate that the efficient formation of HNCO via NH + CO on grains is a necessary step in the achievement of the observed gas-phase abundance of CH 3 NCO. Production of CH 3 NHCHO may plausibly occur on grains either through the direct addition of functional-group radicals or through the hydrogenation of CH 3 NCO. Conclusions. Provided the detection of N-methylformamide is confirmed, the only slight underabundance of this molecule compared to its more stable structural isomer acetamide and the sensitivity of the model abundances to the chemical kinetics parameters suggest that the formation of these two molecules is controlled by kinetics rather than thermal equilibrium.

Background: We conducted the randomized phase III double-blind EORTC 1325/ KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma. At a 1.25-year (yr) median follow-up, pembrolizumab improved recurrence-free survival (RFS) (hazard ratio [HR] 0.57, P<0.0001) as compared to placebo (Eggermont, NEJM 2018). This led to the approval of pembrolizumab adjuvant treatment by EMA and FDA.

10000 Background: We conducted the phase 3 double-blind EORTC 1325/KEYNOTE-054 trial to evaluate pembrolizumab vs placebo in patients (pts) with resected high-risk stage III melanoma. Based on 351 recurrence-free survival (RFS) events and at a median follow-up of 1.25 years (yrs), pembrolizumab improved RFS (hazard ratio (HR) 0.57, P<0.0001) as compared to placebo (Eggermont, NEJM 2018). This led to the approval of pembrolizumab adjuvant treatment by EMA and FDA. Methods: Eligible pts included those ≥18 yrs of age with complete resection of cutaneous melanoma metastatic to lymph node(s), classified as AJCC-7 stage IIIA (at least one lymph node metastasis >1 mm), IIIB or IIIC (without in-transit metastasis). A total of 1019 pts were randomized (stratification by stage and region) to pembrolizumab at a flat dose of 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses (~1 year) or until disease recurrence or unacceptable toxicity. The 2 co-primary endpoints were RFS in the intention-to-treat overall population and in pts with PD-L1-positive tumors. Here, we report an updated RFS analysis based on a longer follow-up. Results: Overall, 15%/46%/39% of pts had stage IIIA/IIIB/IIIC. At 3.05-yr median follow-up, pembrolizumab (190 RFS events) compared with placebo (283 RFS events) prolonged RFS, in the overall population and in the PD-L1 positive tumor subgroup (see Table). RFS was consistently prolonged across subgroups, in particular according to AJCC-7 staging, BRAF-V600 E/K mutation status. Conclusions: Pembrolizumab, administered at 200 mg every 3 weeks for up to 1 year as adjuvant therapy, provided, at a 3-yr median follow-up, a sustained improvement in RFS, which was clinically meaningful, in resected high-risk stage III melanoma. This improvement was consistent across subgroups. In the overall population, the 3-yr cumulative incidence of distant metastasis being the first recurrence was 22.3% (pembrolizumab group) vs 37.3% (placebo group) (HR 0.55, 95% CI 0.44-0.69). Clinical trial information: NCT02362594. [Table: see text]

On the occasion of the 100th anniversary of M. A. Lavrent'ev, it seems pertinent to summarize the longterm work on the physical foundations, design, and manufacturing of sources of high-pressure gases for hypersonic wind tunnels in the pages of a journal founded with the immediate participation from M. A. Lavrent'ev. This direction of experimental aerodynamics received invaluable support of M. A. Lavrent'ev in early 1970s, without which the scientific ideas would not, probably, be put into practice.The idea of using high (up to 20,000 atm) pressures of a gas in the plenum chamber in an aerodynamic experiment was first put forward in the late 1960s by M. A. Plotnikov [1] who worked at that time in Research Institute-1 in the group of Prof. E. I. Shchetinkov, one of the founders and proponents for using supersonic combustion in air-breathing engines of hypersonic flying vehicles (HFV) for Mach numbers from 8 to 20 [2]. At the same time, the papers of Soviet and American scientists posed the question of the necessity of developing of a reentry HFV with an aircraft-type take-off and landing, capable of taking payloads to the orbit of an Earth's satellite and back. It is expected that, with the use of these vehicles, the cost of putting payloads to orbit, which is the key economic factor of using spacecraft systems in practical activity outside of the military field, will decrease by 5 to 8 times. One of the main obstacles for the use of such systems is the absence of knowledge on the complex of fundamental phenomena that accompany and ensure the HFV flight. The existing hypersonic aerodynamic facilities do not allow one to create conditions necessary for testing the corresponding HFV models [4]. This is especially true for reproduction of Reynolds numbers and ensuring test-gas purity and run time.At the end of the 1960s, M. A. Plotnikov and his colleagues developed tables of thermodynamic functions of nitrogen [1] from which it followed that the transition to the pressure region up to 10,000-20,000 atm leads to an additional contribution to the gas enthalpy equivalent to a temperature increase by approximately 1000 K per each 10,000 atm. On the one hand, this offered a possibility of increasing the Lavrent'ev Institute