Preparation of nano/micro-bimodal Ti/Al/(Mo, W, Cu) powders by simultaneous electrical explosion of dissimilar metal wires

Novel mixtures of micro- and nanoparticles have been obtained by simultaneous electrical explosion of three intertwisted wires (EEW). The possibility of obtaining of titanium‑aluminum micro- and nanoparticles alloyed with molybdenum, tungsten and copper by the electrical explosion of Ti/Al/(Mo, W, Cu – up to 6 at. %) wires has been shown. Spherical particle with sizes from 20 nm to 7 μm are formed under condition of introducing the electric energy at the level of 0.57–0.77 of the total sublimation energy. The mass content of particles with sizes less than 100 nm does not exceed 10%. The phase composition of powders includes double and triple intermetallic phases, titanium oxide (TiO) as well as phases of the initial metals. The study of the phase composition of bulk materials obtained by sintering powders Ti-Al-Mo, Ti-Al-W and Ti-Al-Cu for 2 h at 1000 °C showed the increase in the content of intermetallic phases, providing enhanced physical and mechanical properties of the titanium‑aluminum alloys. The results of the studies show that the obtained powders alloys can be used to produce feedstocks of TiAl alloys

Cherednik algebras and Zhelobenko operators

We study canonical intertwining operators between induced modules of the trigonometric Cherednik algebra. We demonstrate that these operators correspond to the Zhelobenko operators for the affine Lie algebra of type A. To establish the correspondence, we use the functor of Arakawa, Suzuki and Tsuchiya which maps certain modules of the affine Lie algebra to modules of the Cherednik algebra

Virtual screening of ultra-large chemical libraries identifies cell-permeable small-molecule inhibitors of a “non-druggable” target, STAT3 N-terminal domain

STAT3 N-terminal domain is a promising molecular target for cancer treatment and modulation of immune responses. However, STAT3 is localized in the cytoplasm, mitochondria, and nuclei, and thus, is inaccessible to therapeutic antibodies. Its N-terminal domain lacks deep pockets on the surface and represents a typical “non-druggable” protein. In order to successfully identify potent and selective inhibitors of the domain, we have used virtual screening of billion structure-sized virtual libraries of make-on-demand screening samples. The results suggest that the expansion of accessible chemical space by cutting-edge ultra-large virtual compound databases can lead to successful development of small molecule drugs for hard-to-target intracellular proteins

Genome Sequencing and Comparative Analysis of Saccharomyces cerevisiae Strains of the Peterhof Genetic Collection

The Peterhof genetic collection of Saccharomyces cerevisiae strains (PGC) is a large laboratory stock that has accumulated several thousands of strains for over than half a century. It originated independently of other common laboratory stocks from a distillery lineage (race XII). Several PGC strains have been extensively used in certain fields of yeast research but their genomes have not been thoroughly explored yet. Here we employed whole genome sequencing to characterize five selected PGC strains including one of the closest to the progenitor, 15V-P4, and several strains that have been used to study translation termination and prions in yeast (25-25-2V-P3982, 1B-D1606, 74-D694, and 6P-33G-D373). The genetic distance between the PGC progenitor and S288C is comparable to that between two geographically isolated populations. The PGC seems to be closer to two bakery strains than to S288C-related laboratory stocks or European wine strains. In genomes of the PGC strains, we found several loci which are absent from the S288C genome; 15V-P4 harbors a rare combination of the gene cluster characteristic for wine strains and the RTM1 cluster. We closely examined known and previously uncharacterized gene variants of particular strains and were able to establish the molecular basis for known phenotypes including phenylalanine auxotrophy, clumping behavior and galactose utilization. Finally, we made sequencing data and results of the analysis available for the yeast community. Our data widen the knowledge about genetic variation between Saccharomyces cerevisiae strains and can form the basis for planning future work in PGC-related strains and with PGC-derived alleles.PBD acknowledges the Russian Foundation for Basic Research (www.rfbr.ru) for grant 14-04-31265. OVT and SGIV acknowledge the Russian Foundation for Basic Research for grant 15-29-02526. JVS acknowledges the Russian Science Foundation (www.rscf.ru) for grant 14-50-00069 and the Saint-Petersburg State University for grant 1.38.426.2015. PBD, AGM, EAR, and JVS acknowledge the Saint-Petersburg State University for research grant 1.37.291.2015. PBD and OVT acknowledge the Saint-Petersburg City Committee on Science and High School (knvsh.gov.spb.ru/) for grants 15404 and 15919, respectively. PBD, AGM, JVS, and SGIV acknowledge the Saint-Petersburg State University for research grant 15.61.2218.2013. PBD acknowledges the Saint-Petersburg State University for research grant 1.42.1394.2015

Structural basis for RNA recognition by NusB and NusE in the initiation of transcription antitermination

Processive transcription antitermination requires the assembly of the complete antitermination complex, which is initiated by the formation of the ternary NusB–NusE–BoxA RNA complex. We have elucidated the crystal structure of this complex, demonstrating that the BoxA RNA is composed of 8 nt that are recognized by the NusB–NusE heterodimer. Functional biologic and biophysical data support the structural observations and establish the relative significance of key protein–protein and protein–RNA interactions. Further crystallographic investigation of a NusB–NusE–dsRNA complex reveals a heretofore unobserved dsRNA binding site contiguous with the BoxA binding site. We propose that the observed dsRNA represents BoxB RNA, as both single-stranded BoxA and double-stranded BoxB components are present in the classical lambda antitermination site. Combining these data with known interactions amongst antitermination factors suggests a specific model for the assembly of the complete antitermination complex

Detection of Pionium with DIRAC

The aim of the DIRAC experiment at CERN is to provide an accurate determination of S-wave pion-pion scattering lengths from the measurement of the lifetime of the pi+ pi- atom. The measurement will be done with precision comparable to the level of accuracy of theoretical predictions, formulated in the context of Chiral Perturbation Theory. Therefore, the understanding of chiral symmetry breaking of QCD will be submitted to a stringent test

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

A Theory of Monopolistic Competition with Horizontally Heterogeneous Consumers

Our novel approach to modeling monopolistic competition with heterogeneous consumers involves a space of characteristics of a differentiated good (consumers' ideal points), alike Hotelling (1929). Firms have heterogeneous costs à la Melitz (2003). In addition to price setting, each firm also chooses its optimal location/niche in this space. We formulate conditions for positive sorting: more efficient firms serve larger market segments and face tougher competition in the equilibrium. Our framework entails rich equilibrium patterns displaying non-monotonic markups, high in the most and least populated niches, and the unequal gains from trade across different consumers