Scaffold-based molecular design with a graph generative model

Searching for new molecules in areas like drug discovery often starts from the core structures of known molecules. Such a method has called for a strategy of designing derivative compounds retaining a particular scaffold as a substructure. On this account, our present work proposes a graph generative model that targets its use in scaffold-based molecular design. Our model accepts a molecular scaffold as input and extends it by sequentially adding atoms and bonds. The generated molecules are then guaranteed to contain the scaffold with certainty, and their properties can be controlled by conditioning the generation process on desired properties. The learned rule of extending molecules can well generalize to arbitrary kinds of scaffolds, including those unseen during learning. In the conditional generation of molecules, our model can simultaneously control multiple chemical properties despite the search space constrained by fixing the substructure. As a demonstration, we applied our model to designing inhibitors of the epidermal growth factor receptor and show that our model can employ a simple semi-supervised extension to broaden its applicability to situations where only a small amount of data is available.

We propose a scaffold-based graph generative model for designing novel drug candidates that include the desired scaffold as a substructure.     

Lewis-Base Adducts of Group 11 Metal(I) Compounds. LXXVI Structural Studies in the Copper(I) Halide : Norbornadiene System

The structural characterizations of some copper(I) halide (CuX) adducts with norbornadiene (nbd) are recorded. CuCl : nbd (1:1)₄ (a redetermination), (2:1)_2(|), are systems both based around Cu₄Cl₄ cubane-type cluster arrays. CuBr : nbd (7:3)_(|)( 0.5 MeOH), a complex polymer with 3-symmetry, is believed to be the complex previously described as an adduct of 2:1 stoichiometry. Attempts to obtain an iodide counterpart have resulted in the definition of an ephemeral adduct CuI : MeCN (3:2)_(|). 0.5 C₇H₈ in which, remarkably, the nbd is uncoordinated; the complex is a polymer, related to the [AgX(quinoline)]_(|) (X = Cl, Br) saddle polymer.     

Medical Positron Imaging with a Dense Drift Space MultiWire Proportional Chamber

A multiplanar positron camera is proposed, made of six MWPC modules, arranged to form the lateral surface of a hexagonal prism. Each 50 x 50 cm(2) module has a single MWPC sandwiched by two 2-cm thick lead glass tube converters. The experimental results for a 15 x 15 cm(2) test module are reported. For 511 keV gamma-rays incident almost perpendicular onto a 1.0-cm thick converter, a detection efficiency of 4.3%, a time resolution of 130 ns (FWHM) and a spatial resolution of 2.8 mm (FWHM) have been measured with a standard Argon-Methane (70-30) mixture at 1.2 atm. The chamber may also be operated in high resolution mode: 1.2-mm (FWHM) spatial resolution has been measured at a 50% lower efficiency. The use of fast delay lines (specific delay 8 ns/cm) for the position read-out ensures a high rate capability. The expected performance of the six-module MWPC camera is discussed and compared with that of a BGO crystal ring camera. The MWPC solution seems very attractive not only for its low cost and simplicity of construction, but also for its fully three-dimensional imaging capability.     

A facile synthesis of (6S,1′S)-(+)-hernandulcin and (6S,1′R)-(+)-epihernandulcin

A facile total synthesis of (+)-hernandulcin (1) was accomplished from (−)-isopulegol in 6 steps with 15% overall yield. Epoxidation of (−)-isopulegol with m-chloroperbenzoic acid followed by opening of the epoxide 3a with prenyl Grignard afforded the tertiary alcohol 4a with correct C-6 and C-1′ stereochemistry as a major product. Oxidation of the secondary alcohol in compound 4a to the ketone 5a was accomplished in high yield by using TPAP and N-methylmorpholine N-oxide. Conversion of the ketone 5a to α,β-unsaturated ketone via organoselenium intermediate gave (+)-hernandulcin (1). This method was also successfully applied to the synthesis of (+)-epihernandulcin (2).     

Effect of steps on the decomposition of CH3O at PdZn alloy surfaces

The decomposition of methoxide (CH(3)O) on a PdZn alloy is considered to be the rate-limiting step of steam re-forming of methanol over a Pd/ZnO catalyst. Our previous density functional (DF) studies (Langmuir 2004, 20, 8068; Phys. Chem. Chem. Phys. 2004, 6, 4499) revealed only a very low propensity of defect-free flat (111) and (100) PdZn surfaces to promote C-H or C-O bond breaking of CH(3)O. Thus, we applied the same DF periodic slab-model approach to investigate these two routes of CH(3)O decomposition on PdZn(221) surfaces that expose Pd, (221)(Pd), and Zn, (221)(Zn), steps. C-H bond cleavage of CH(3)O is greatly facilitated on (221)(Pd): the calculated activation energy is dramatically reduced, to approximately 50 kJ mol(-1) from approximately 90 kJ mol(-1) on flat PdZn surfaces, increasing the rate constant by a factor of 10(8). The lower barrier is mainly due to a weaker interaction of the reactant CH(3)O and an enhanced interaction of the product CH(2)O with the substrate. The activation energy for C-O bond scission did not decrease on the (221)(Pd) step. On the (221)(Zn) step, the calculated reaction barriers of both decomposition routes are even higher than on flat surfaces, because of the stronger adsorption of CH(3)O. Steps (and other defects) appear to be crucial for methanol steam re-forming on Pd/ZnO catalyst; the stepped surface PdZn(221)(Pd) is a realistic model for studying the reactivity of this catalyst.     

Synthesis, characterization and protein adsorption behaviors of PLGA/PEG di-block co-polymer blend films

A series of poly(D,L-lactic-co-glycolic acid) (PLGA)/poly(ethyleneglycol) (PEG) di-block copolymers were synthesized by ring-opening polymerization of D,L-lactide and glycolide with different molecular weights of monomethoxy polyethyleneglycol (mPEG) 750, 2000 and 5000 as an initiator. The bulk properties of these co-polymers were characterized by using 1H NMR spectroscopy, gel permeation chromatography, differential scanning calorimetry (DSC). Electron spectroscopy for chemical analysis (ESCA) results, in which the blend films with the di-block copolymers showed increasing surface oxygen atomic percentage with increasing PEG chain length, indicate that PEG chain segment in the di-block copolymers is surface oriented and enriched onto the surface of the blend films. The extent of protein adsorption onto the surface of these blend films was studied, using iodine radio-labeled human serum albumin, gamma globulin and human growth hormone. The protein adsorption amount was reduced for the blend films prepared with PLGA/PEG 750 and 2000 di-block copolymers, but increased to a great extent for PLGA/PEG 5000 di-block copolymer. This is due to the increased water uptake capacity of the blend film, which absorbed more protein molecules into a swollen polymer matrix in addition to surface adsorption.     

Selective wet etching of p-GaN for efficient GaN-based light-emitting diodes

The selective wet etching of a p-GaN layer by using a solution of KOH in ethylene glycol (KE) was studied to enhance the optical and electrical performance of the GaN-based light-emitting diodes (LEDs). The surface of the p-GaN, which was selectively etched in the KE solution, showed hexagonal-shaped etch pits. The light-output power of etched LEDs was improved by 29.4% compared to that of the nonetched LED. This improvement was attributed to the increase in the probability of photons to escape due to the increased surface area of textured surface and the reduction in contact resistance of the ohmic layer resulting from the increased contact area and hole concentration on the textured p-GaN. The reverse leakage current of the LED was also greatly decreased due to the surface passivation and the removal of defective regions from the p-GaN.     

Advances in Vapor Pressure Modeling for Electronic Packaging

Two advanced techniques have been developed for modeling vapor pressure within the plastic IC packages during solder reflow. The first involves the extension of the "wetness" technique to delamination along multimaterial interface and during dynamic solder reflow. Despite its simplicity, this technique is capable of offering reliable and accurate prediction for packages with high flexural rigidity. For packages with low flexural rigidity, the new "decoupling" technique that integrates thermodynamics, moisture diffusion, and structural analysis into a unified procedure has been shown to be more useful. The rigorous technique has been validated on both leadframe-based as well as laminate-based packages. With high accuracy and computational efficiency, these dynamic modeling tools will be valuable for optimization of package construction, materials, and solder reflow profile against popcorn cracking for both SnPb and Pb-free solders     

Symbol error rate of selection amplify-and-forward relay systems

Cooperative diversity schemes significantly improve the performance of wireless networks by transmitting the same information through several nodes. The amplify-and-forward (AF) relaying method is one of the most attractive cooperative diversity schemes due to its low complexity. Selection AF relaying has recently been proven to achieve the same diversity order as and lower outage probability than all-participate relays. In this letter, we present an asymptotic analysis of the symbol error rates of a selection AF network, and compare it with the conventional all-participate scheme