Bridging the Gap between Chemical Reaction Pretraining and Conditional Molecule Generation with a Unified Model

Chemical reactions are the fundamental building blocks of drug design and organic chemistry research. In recent years, there has been a growing need for a large-scale deep-learning framework that can efficiently capture the basic rules of chemical reactions. In this paper, we have proposed a unified framework that addresses both the reaction representation learning and molecule generation tasks, which allows for a more holistic approach. Inspired by the organic chemistry mechanism, we develop a novel pretraining framework that enables us to incorporate inductive biases into the model. Our framework achieves state-of-the-art results on challenging downstream tasks. By possessing chemical knowledge, our generative framework overcome the limitations of current molecule generation models that rely on a small number of reaction templates. In the extensive experiments, our model generates synthesizable drug-like structures of high quality. Overall, our work presents a significant step toward a large-scale deep-learning framework for a variety of reaction-based applications

Femtosecond laser surface structuring of silicon with Gaussian and optical vortex beams

We report an experimental analysis of femtosecond laser induced surface structuring of silicon by exploiting both Gaussian and Optical Vortex beams. In particular, we show how different surface patterns, consisting of quasi-periodic ripples and grooves, can be obtained by using different states of polarization offered by optical vortex beams. Both for Gaussian and optical vortex beams, an increase of the number of laser pulses, N, or beam energy, E-0, leads to a progressive predominance of the grooves coverage, with ripples confined in specific regions of the irradiated area at lower fluence. The average period of ripples and grooves shows a different dependence as a function of both E-0 and N, underlying important differences in mechanisms leading to the formation of ripples and grooves. In particular, our experimental characterization allows identifying a preliminary stage of grooves generation with rudimental surface structures, preferentially directed parallel to the laser polarization. This supports the idea that one possible mechanism of grooves formation lies in the progressive aggregation of clusters of nanopartides densely decorating the ripples. Our experimental findings provide important indications on the basic understanding of the processes involved in laser surface structuring with ultrashort pulses that can guide the design of the surface patterns. (C) 2016 Elsevier B.V. All rights reserved

Surface Structuring with Polarization-Singular Femtosecond Laser Beams Generated by a q-plate

In the last few years femtosecond optical vortex beams with di erent spatial distributions of the state of polarization (e.g. azimuthal, radial, spiral, etc.) have been used to generate complex, regular surface patterns on di erent materials. Here we present an experimental investigation on direct femtosecond laser surface structuring based on a larger class of vector beams generated by means of a q-plate with topological charge q = +1/2. In fact, voltage tuning of q-plate optical retardation allows generating a family of ultrashort laser beams with a continuous spatial evolution of polarization and uence distribution in the focal plane. These beams can be thought of as a controlled coherent superposition of a Gaussian beam with uniform polarization and a vortex beam with a radial or azimuthal state of polarization. The use of this family of ultrashort laser beams in surface structuring leads to a further extension of the achievable surface patterns. The comparison of theoretical predictions of the vector beam characteristics at the focal plane and the generated surface patterns is used to rationalize the dependence of the surface structures on the local state of the laser beam, thus o ering an e ective way to either design unconventional surface structures or diagnose complex ultrashort laser beams

Study on the Comprehensive Properties and Microstructures of A3-3 Matrix Graphite Related to the High Temperature Purification Treatment

At the beginning, a comparative analysis was made on the oxidation corrosion rate and ash content of A3-3 matrix graphite (MG) pebbles lathed before and after high temperature purification (HTP) treatment. Their oxidation corrosion rate and ash contents were almost identical, which indicated that the HTP process was to purify the entire MG pebbles and not limited on the surfaces. Furthermore, the multiple mechanical and thermal properties of MG treated without and with the treatment of HTP at ~1900°C were compared and their microstructure features were characterized as well. As the crush strength, oxidation corrosion rate, and erosion rate of MG without HTP treatment did not satisfy the specifications, the comprehensive properties and purity of MG with HTP were improved in various degrees through the HTP process so that all performances met the requirements of the A3-3 MG. The improvement of crush strength and erosion rate of MG in the HTP process could be mainly attributed to the upgradation of ordered microstructure and corresponding increase of density. However, the enhancement of oxidation corrosion rate was due to the synergistic effects of microstructural optimization and reduction of impurity elements, especially the transition metal elements of MG in the HTP process

Identification of the ADPR binding pocket in the NUDT9 homology domain of TRPM2

Activation of the transient receptor potential melastatin 2 (TRPM2) channel occurs during the response to oxidative stress under physiological conditions as well as in pathological processes such as ischemia and diabetes. Accumulating evidence indicates that adenosine diphosphate ribose (ADPR) is the most important endogenous ligand of TRPM2. However, although it is known that ADPR binds to the NUDT9 homology (NUDT9-H) domain in the intracellular C-terminal region, the molecular mechanism underlying ADPR binding and activation of TRPM2 remains unknown. In this study, we generate a structural model of the NUDT9-H domain and identify the binding pocket for ADPR using induced docking and molecular dynamics simulation. We find a subset of 11 residues—H1346, T1347, T1349, L1379, G1389, S1391, E1409, D1431, R1433, L1484, and H1488—that are most likely to directly interact with ADPR. Results from mutagenesis and electrophysiology approaches support the predicted binding mechanism, indicating that ADPR binds tightly to the NUDT9-H domain, and suggest that the most significant interactions are the van der Waals forces with S1391 and L1484, polar solvation interaction with E1409, and electronic interactions (including π–π interactions) with H1346, T1347, Y1349, D1431, and H1488. These findings not only clarify the roles of a range of newly identified residues involved in ADPR binding in the TRPM2 channel, but also reveal the binding pocket for ADPR in the NUDT9-H domain, which should facilitate structure-based drug design for the TRPM2 channel

Associations of Educational Attainment, Occupation, Social Class and Major Depressive Disorder among Han Chinese Women

Background The prevalence of major depressive disorder (MDD) is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years. Principal findings We report results from 3,639 Chinese women with recurrent MDD and 3,800 controls. Highly significant odds ratios (ORs) were observed between MDD and full time employment (OR = 0.36, 95% CI = 0.25–0.46, logP = 78), social status (OR = 0.83, 95% CI = 0.77–0.87, logP = 13.3) and education attainment (OR = 0.90, 95% CI = 0.86–0.90, logP = 6.8). We found a monotonic relationship between increasing age and increasing levels of educational attainment. Those with only primary school education have significantly more episodes of MDD (mean 6.5, P-value = 0.009) and have a clinically more severe disorder, while those with higher educational attainment are likely to manifest more comorbid anxiety disorders. Conclusions In China lower socioeconomic position is associated with increased rates of MDD, as it is elsewhere in the world. Significantly more episodes of MDD occur among those with lower educational attainment (rather than longer episodes of disease), consistent with the hypothesis that the lower socioeconomic position increases the likelihood of developing MDD. The phenomenology of MDD varies according to the degree of educational attainment: higher educational attainment not only appears to protect against MDD but alters its presentation, to a more anxious phenotype

Microplate analytical method for quinones by pulse photo-irradiation and chemiluminescence detection

Quinones are widely distributed in nature and have various bioactivities. Besides, quinones are also considered as toxicological intermediates which cause severe dangerous effects. Hereby, a sensitive, simple, and rapid method is reported for quinones determination. The proposed method employed time resolved fluorescence (TRF) microplate reader based chemiluminescent (CL) detection for the first time as a novel approach for measurement. Under pulse photo-irradiation, the unique photochemical characteristic of quinones is exploited to liberate reactive oxygen species (ROS) which reacted with photosensitized CL reagent. L-012, luminol analogue, was selected for its high sensitivity. Under our investigation, para-quinones showed high CL response when compared to ortho-quinones. A linear response was obtained for studied quinone concentrations in the range of 0.05-50 μM for 1,4-naphthquinone and of 0.05-150 μM for 2-methyl-1,4-naphthoquinone (menadione) and 9,10-anthraquinone with detection limit (blank + 3SD) of 0.01 μM. The proposed method allowed the rapid determination of large number of samples in very short time (96 sample/125 s). The proposed method was successfully applied for determination of menadione in spiked human serum

Intense Bessel femtosecond pulse propagation in dispersive Kerr medium

The performance of intense Bessel femtosecond pulse propagation in dispersive medium is investigated. Water is chosen as the Kerr medium with large dispersion. We find that within the dispersion length, the temporal profile integrated over the beam radius is controlled mainly by dispersion, whereas the spectral profile is nearly undistorted. We also show the energy flow between different transverse parts of the beam, which provides a reservoir for the intense part of the Bessel beam and extends the nonlinear effect length between the pulse and the Kerr medium as we have previously found in argon