Exhaustive search of the configurational space of heat-shock protein 90 with its inhibitor by multicanonical molecular dynamics based dynamic docking

Multicanonical molecular dynamics based dynamic docking was used to exhaustively search the configurational space of an inhibitor binding to the N-terminal domain of heat-shock protein 90 (Hsp90). The obtained structures at 300 K cover a wide structural ensemble, with the top two clusters ranked by their free energy coinciding with the native binding site. The representative structure of the most stable cluster reproduced the experimental binding configuration, but an interesting conformational change in Hsp90 could be observed. The combined effects of solvation and ligand binding shift the equilibrium from a preferred loop-in conformation in the unbound state to an α-helical one in the bound state for the flexible lid region of Hsp90. Thus, our dynamic docking method is effective at predicting the native binding site while exhaustively sampling a wide configurational space, modulating the protein structure upon binding.     

Steric Effect of Carboxylate Ligands on Pd‐Catalyzed Intramolecular C(sp2)–H and C(sp3)–H Arylation Reactions

A bulky carboxylic acid bearing three cyclohexylmethyl substituents at the α‐position, namely, tri(cyclohexylmethyl)acetic acid, is demonstrated to act as an efficient ligand source in Pd‐catalyzed intramolecular C(sp²)?H and C(sp³)?H arylation reactions. The reactions proceed smoothly under mild reaction conditions, even at room temperature due to the steric bulk of the carboxylate ligands, which accelerates the rate‐determining C?H bond activation step in the catalytic cycle.     

Chiral Carboxylic Acid Enabled Achiral Rhodium(III)‐Catalyzed Enantioselective C−H Functionalization

Reported is an achiral Cp^xRh^III/chiral carboxylic acid catalyzed asymmetric C?H alkylation of diarylmethanamines with a diazomalonate, followed by cyclization and decarboxylation to afford 1,4‐dihydroisoquinolin‐3(2H)‐one. Secondary alkylamines as well as nonprotected primary alkylamines underwent the transformation with high enantioselectivities (up to 98.5:1.5 e.r.) by using a newly developed chiral carboxylic acid as the sole source of chirality to achieve enantioselective C?H cleavage by a concerted metalation‐deprotonation mechanism.     

Biphenyl ether and biphenyl quinolizidine lactone alkaloids from Heimia salicifolia

Three new biphenyl ether quinolizidine lactone alkaloids (1–3) and 13 new biphenyl quinolizidine lactone alkaloids (4–16) were isolated from Heimia salicifolia (Lythraceae) together with seven known alkaloids. Their structures were determined by spectroscopic analyses and chemical conversions.     

The second-generation synthesis of BICMAP analogues

We previously reported the synthesis of BICMAP (1a) via 6-diphenylphosphino-2,3-dihydrobenzofuran as a key intermediate. However, we did not successfully synthesize BICMAP analogues via a similar synthetic route. Herein we report the second-generation synthesis of BICMAP and its derivatives via diethylphosphonate as a key intermediate.     

SCCN: A Time-Effective Hierarchical Interconnection Network for Network-On-Chip

Mobile Networks and Applications - The needed time to send and receive a message among two nodes in an interconnection network has a fundamental role in determining the performance of this network....     

Measurement of flow phenomena using the ultrasonic velocity profile method in a simulated Czochralski crystal puller

An experimental investigation of flow phenomena in a simulated Czochralski (CZ) crystal puller was conducted using an ultrasound velocity profile (UVP) probe to measure fluid velocities. To isolate the various forces that influence the fluid motion, only the crystal was rotated and a water-glycerol mixture was used as the test fluid in this experiment. Measurements of the velocity components, V_z and V_r, under the initial transient from zero rotation to a set rotation rate as well as under steady-state conditions were made. The corresponding Reynolds number based on the crystal radius and rotation varied from Re_Ω,_x ≈ 660–5000 (Ω_x ≈ 110–2000 rpm). The measured velocity profiles, V_z and V_r, were processed using a simple color image scheme based on the magnitude and direction of flow with respect to the probe. These profiles were studied to postulate flow patterns in the simulated CZ device. The measurements revealed three major regions of flow: (1) one beneath the crystal, (2) one near the free surface and crucible wall and (3) one beneath the crystal and occupying the extent of the crucible. In the initial transient, spatially symmetric outward flow beneath the crystal developed until the recirculating flow from below disturbed this pattern. At this point the apparent shear between the flow beneath the crystal and that circulating upwards from the bottom of the crucible induced flow instabilities and a non-axisymmetric flow pattern. The non-axisymmety was verified by the color-coded velocity profiles and a power spectrum analysis. The analysis revealed the critical Reynolds number for the onset of the primary instability to be Re_Ωcrit ≈ 669. The linear variation in the power of the primary peak with the Reynolds number indicates that the onset of the axisymmetry-breaking instability is due to Hopf bifurcation.     

Transmission electron microscopy observation of GaAs/Al0.3Ga0.7As T-shaped quantum well structure fabricated by glancing angle molecular beam epitaxy on GaAs(100) reverse-mesa etched substrates

GaAs/Al_0.3Ga_0.7As multi-layer structures were grown on GaAs (100) reverse-mesa etched substrates by glancing angle molecular beam epitaxy (GA-MBE). A(111)B facet was formed as a side-facet. Surface migration of Ga and Al atoms from the (100) flat region to the (111)B side-facet region has been investigated to fabricate T-shaped GaAs/AlGaAs quantum wells (QWs) under the condition that Ga and Al atoms impinge only an the (100) flat region and do not impinge on the (111)B side-facet. Observation of T-shaped GaAs/AlGaAs quantum wires (QWRs) by cross-sectional transmission electron microscopy (TEM) revealed that there is no migration of Al atoms from the (100) to the (111)B facet region at a substrate temperature (T_s) as high as 630°C, under a V/III ratio of 28 (in pressure ratio). On the other hand, very thin GaAs epitaxial layers grown on the (111)B side-facet region owing to the Ga migration were observed for substrate temperatures of 600 and 630°C. It was found that the mass flow of Ga atoms from the (100) region to the (111)B side-facet region increases, with the thermal activation energy of 2.0 eV, as the substrate temperature increases from 570 to 630°C. The GA-MBE growth on a reverse-mesa etched GaAs substrate at a low temperature 570°C or lower is desirable to fabricate a nm-scale GaAs/AlGaAs QWR structure with nm-scale precision.     

Preferential migration of indium atoms on the (411)A plane in InGaAs grown on GaAs channeled substrates by molecular beam epitaxy

Lateral profiles of In content in a 1.5 μm thick In_xGa_1−xAs (x 0.2) layer grown on GaAs channeled substrates (CSs) with (411)A side-slopes by molecular beam epitaxy (MBE) have been investigated with the use of energy dispersive X-ray spectroscopy (EDX). The observed profiles of the In content suggested that In atoms migrate preferentially in the [1 ] direction on the (411)A plane during MBE growth. This preferential migration of In atoms along [1 ] on the (411)A plane was confirmed by comparing observed lateral profiles of In content in InGaAs layers grown on GaAs CSs and simulated In profiles which are calculated by taking into account of an additional one-way flow of In atoms along [1 ].