Discovery of an Allosteric Ligand Binding Site in SMYD3 Lysine Methyltransferase

SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (K_D=42 and 84 μM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3–HSP90 binding was confirmed (K_D=13 μM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action.     

Densification of nanocrystalline Y2O3 ceramic powder by spark plasma sintering

Nanocrystalline Y₂O₃ powders with 18 nm crystallite size were sintered using spark plasma sintering (SPS) at different conditions between 1100 and 1600 °C. Dense specimens were fabricated at 100 MPa and 1400 °C for 5 min duration. A maximum in density was observed at 1400 °C. The grain size continuously increased with the SPS temperature into the micrometer size range. The maximum in density arises from competition between densification and grain growth. Retarded densification above 1400 °C is associated with enhanced grain growth that resulted in residual pores within the grains. Analysis of the grain growth kinetics resulted in activation energy of 150 kJ mol^?1 and associated diffusion coefficients higher by 10³ than expected for Y³⁺ grain boundary diffusion. The enhanced diffusion may be explained by combined surface diffusion and particle coarsening during the heating up with grain boundary diffusion at the SPS temperature.     

Atomic snapshots using lattice agreement

Summary Thesnapshot object is an important tool for constructing wait-free asynchronous algorithms. We relate the snapshot object to thelattice agreement decision problem. It is shown that any algorithm for solving lattice agreement can be transformed into an implementation of a snapshot object. The overhead cost of this transformation is only a linear number of read and write operations on atomic single-writer multi-reader registers. The transformation uses an unbounded amount of shared memory. We present a deterministic algorithm for lattice agreement that usedO (log² n) operations on 2-processorTest & Set registers, plusO (n) operations on atomic single-writer multi-reader registers. The shared objects are used by the algorithm in adynamic mode, that is, the identity of the processors that access each of the shared objects is determined dynamically during the execution of the algorithm. By a randomized implementation of 2-processorsTest & Set registers from atomic registers, this algorithm implies a randomized algorthm for lattice agreement that uses an expected number ofO (n) operations on (dynamic) atomic single-writer multi-reader registers. Combined with our transformation this yields implementations of atomic snapshots with the same complexity.Cambridge Research Laboratory, Digital Equipment Corporation Hagit Attiya received the B.Sc. degreeiin Mathematics and Computer Science from the Hebrew University of Jerusalem, in 1981, the M.Sc. and Ph.D. degrees in Computer Science from the Hebrew University of Jerusalem, in 1983 and 1987, respectively. She is presently a senior lecturer at the departtment of Computer Science at the Technion, Israel Institute of Technology. Prior to this, she has been a post-doctoral research associate at the Laboratory for Computer Science at M.I.T. Her general research interests are distributed computation and theoretical computer science. More specific interests include fault-tolerance, timing-based and asynchronous algorithms. Maurice Herlihy received the A.B. degree in Mathematics from Harvard University, and the M.S. and the Ph.D. degrees in Computer Science from M.I.T. From 1984 to 1989 he was a faculty member in the Computer Science Department at Carnegie Mellon University in Pittsburgh, PA. In 1989 he joined the research staff at the Digital Equipment Corporation's Cambridge Research Laboratory in Cambridge MA. Since 1994, he has been on the faculty at the Computer Science Department at Brown University. Dr. Herlihy's research interests encompass practical and theoretical aspects of distributed and concurrent computation. Ophir achman received a B.A. in computer science from the Technion, Haifa, Israel in 1989 and M.Sc. in computer science from the Technion, Haifa, Israel, in 1992. He is now studying for a D.Sc. in computer science at the Technion. His currentarea of research is distributed computing, and in particular, asynchronous shared memory systems.This work appeared in preliminary form in proceedings ofthe 6th International Workshop on Distributed Algorithms [12]. This research was partially supported by grant No. 92-0233 from the United States-Israel Binational Science Foundation (BSF), Jerusalem, Technion V.P.R. funds — B. and G. Greenberg Research Fund (Ottawa), and the fund for the promotion of research in the TechnionPart of the work of this author was performed while visiting DEC Cambridge Research Laboratory     

Abnormal Hall–Petch behavior in nanocrystalline MgO ceramic

Pure and dense nanocrystalline MgO with grain size ranging between 25 and 500 nm were prepared by hot-pressing. Vickers microhardness was found to increase with decrease in the grain size down to 130 nm, following the Hall–Petch relation. Further decrease in the grain size was followed by continuous decrease in microhardness. A composite model was used to describe the microhardness behavior in terms of plastic yield of the nanocrystalline grains accompanied by strain accommodation and nanocracking at the grain boundaries (gb’s). Good agreement between the experimental and the calculated values indicates that gb’s may have significant effect on strengthening and ductility of nanocrystalline-MgO ceramics in the nanometer size range. Critical grain size exists below which limited plastic deformation within the grains and nanocracking at gb’s enhance the brittleness of the ceramic.     

Plastic deformation of dense nanocrystalline yttrium oxide at elevated temperatures

Nanocrystalline yttrium oxide, Y₂O₃ with 110 nm average grain size was plastically deformed between 800 °C and 1100 °C by compression at different strain rates and by creep at different stresses. The onset temperature for plasticity was at 1000 °C. Yield stress was strongly temperature dependent and the strain hardening disappeared at 1100 °C. The polyhedral and equiaxed grain morphology were preserved in the deformed specimens. The experimentally measured and theoretically calculated stress exponent n = 2 was consistent with the plastic deformation by grain boundary sliding. Decrease in the grain size was consistent with decrease in the brittle to ductile transition temperature.     

Electrochemical Chromium(III) Oxide Coatings on Non-oxide Ceramic Substrates

SiC and TiB₂ were electrochemically coated with Cr₂O₃ from a 0.1 M aqueous solution of chromium nitrate hydrate with ethanol additives. On both substrate materials poly-crystalline Cr₂O₃ was formed at current densities from 5 to 50 mA/cm² and deposition durations of 5 to 30 min. The coating weight increased with current density and with deposition time. The as-deposited coatings contained microcracks due to drying shrinkage. Microstructural observations indicate that sintering of the Cr₂O₃ coatings on TiB₂ at 1100°C for 1 n in a reducing atmosphere in a closed graphite crucible causes the densification of the coating via a liquid phase, which forms by oxidation of TiB₂. Under similar conditions, the Cr₂O₃ coatings on SiC may be sintered via an evaporation–condensation mechanism.     

Gluten-free pasta production from banana and cassava flours with egg white protein and soy protein addition

Egg white protein and soy protein were incorporated into a banana and cassava flour blend (75:25) to produce gluten-free pasta. The objectives of study were to investigate the effects of the different protein sources on the physico-chemical properties of gluten-free pasta. The levels of protein inclusion were 0%, 5%, 10% and 15% of composite flour (w/w) for each type of protein. Pasta made from 100% durum wheat semolina was used as controls. The protein fortification affected the total starch, resistant starch and protein content of gluten-free pasta compared to semolina pasta. No significant effects of soy/egg white protein addition were found in either insoluble or soluble dietary fibre content. Cooking properties of pasta (optimum cooking time, swelling index, water adsorption index and cooking loss) and texture properties (firmness and extensibility) were affected by the level of protein addition and the type of protein. Results showed the utilisation of 25% cassava flour and protein inclusion have a promising application in gluten-free pasta production.     

On thermal runaway and local endothermic/exothermic reactions during flash sintering of ceramic nanoparticles

Numerical analysis of the heat balance at the flash event during flash sintering of granular ceramic nanoparticles was performed assuming continuum solid state as well as simultaneous surface softening/liquid formation and current percolation through the nanoparticle contacts. Assuming inter-particle radiations in the specimen volume, the electric Joule heat generated at the nanoparticle contacts partially lost by radiation from the specimen external surfaces. Considering the thermal effects due to rapid heating rate and free-molecular heat conduction regime, high-temperature gradients between the nanoparticle surfaces and the surrounding gas were developed. The attractive capillary forces, induced by the particle surface softening/liquid at the percolation threshold, lead to rapid rearrangement and densification of the nanoparticles. The excess Joule heat, already at the flash event, suffices the excess internal heat that is necessary for partial or full melting. Particle surface softening/liquid formation is a transient process, hence followed by crystallization immediate after the nanoparticle rearrangement. Thermal runaway is associated with local surface softening/melting and its solidification.