Organophosphorus Compounds. Part 43. A Molecular Mechanics Study: the Structural Effect of Cyclic Esters of Phosphorus-based Acids in Hydrolytic Reaction

Hydrolytic reactions of some cyclic esters of alkylphosphates and phosphonates have been studied using molecular mechanics calculations A great deal of attention has been devoted to the hydrolytic behaviour of cyclic esters of phosphorus acids. Interest in this reaction has been largely associated with the understanding of the mechanism of enzymatic hydrolysis'-3 and the pseudorotation process4,' of these physiologically active phosphorus Unfortunately, there are few reports concerned with quantitative or semiquantitative studies of the hydrolytic reaction of cyclic organophosphorus esters. ' The electronegativity and HMO investigations provide a good explanation of the observed product ratio of the ring opening and retention in the hydrolysis of 2-methoxy-2-0x0-1,3,2-dioxaphospholane (1) and 2-methoxy-2-0x0-1,2-oxaphospholane (2), but these methods are unable to rationalize the effects of ring size and endocyclic substituent on the hydrolytic rate constant. The substituent effect on the alkaline hydrolysis of both cyclic and acyclic phosphonyl chlorides has been investigated successfully by us12-14 using Allinger's 1977 force field, MM2 1985 program. However, the effect of the ring size and endocyclic substituents has not been considered in that treatment. In this paper, molecular mechanics calculations (MM2 1985) are used to investigate the hydrolysis reaction of the following cyclic phosphorus compounds including (l), (2), 2-ethoxy-2-oxo-1,2-oxaphospholane (3), 2-ethoxy-2-0x0-1,2-oxaphosphorinane (4), 2-ethoxy-2-oxo-1,2-oxaphosphepane (5), diethyl ethylphosphonate (6), l-methoxy-l-oxo-2,2,3-trimethylphosphetane (7), and 1-methoxy-1-oxo-2,2,3,4,4-pentamethylphosphetane (8). The calculation results indicate that the ratio of the ring opening and retention products in the hydrolysis of (1) and (2), and the effect of the ring size and the endocyclic substituents are mainly controlled by the steric energy difference (AE or AAE) between the substrate and its pentaco-ordinated transition state. Calculations Allinger's 1977 force field and MM2 1985 program" were used and all calculations were carried out on a Vax-780 computer at Shanghai Institute of Organic Chemistry, Chinese Academy of Science. Since only van der Waals parameters are used in the program, the other parameters for the tetraco-ordinated and pentaco-ordinated phosphorus compounds were calibrated in our laboratory. ' For the calculations of pentaco-ordinated phosphorus compounds the MM2 force field was modified by us.12 In order to evaluate the difference in stability of trigonal bipyramid (TBP) and square pyramid (SP), 1,3-van der Waals (VDW) interactions between the atoms directly bonded to the pentaco-ordinated phosphorus atom were added into the MM2 force field. A similar method has been used to modify the MM1 force field by Holmes.'6 In the present treatment the VDW radius for 1,3-VDW interactions is different and larger than that for 1,4-or longer VDW interactions. This not only gives a reliable energy difference value between TBP and SPY but also the correct bond angles around the pentaco-ordinated phosphorus atom bonding with different atoms. If the initial conformation is assigned as trigonal bipyramidal or square pyramidal, after minimization the structure will basically remain TBP or SP because different natural bond length and bond angle parameters for TBP and SP are assigned in the program. However, the minimization structure may deviate slightly from the standard TBP or SP owing to steric interactions. In the present case only TBP or SP were considered since they are two well studied geometries in crystal structures. Also the leaving group in the alkaline hydrolysis reaction of phosphorus esters is usually considered to be located in the axial position of a trigonal bipyramid. Some parameters for particular groups are so far not available owing to a lack of experimental data. In such cases some approximation was made, for example, the calculation parameters for the bonds P-0-and P-OH2 were replaced by these for P-OH. The geometry of each compound and transition state was optimized by using the MM2 1985 program, and the most stable conformation was selected for comparison purposes. However, the general molecular mechanics calculations are only representative of the gas-phase conditions. In order to study the reactions in solution, the solvent effect should be taken into consideration, but this effect is very difficult to evaluate in a simple way. Fortunately, in the present investigation the reactions proceed through the TBP intermediates from the same substrate and in the same solvent and the difference is onl

Quantifying efficiency of remote excitation for surface enhanced Raman spectroscopy in molecular junctions

Surface-enhanced Raman spectroscopy (SERS) is enabled by local surface plasmon resonances (LSPRs) in metallic nanogaps. When SERS is excited by direct illumination of the nanogap, the background heating of lattice and electrons can prevent further manipulation of the molecules. To overcome this issue, we report SERS in electromigrated gold molecular junctions excited remotely: surface plasmon polaritons (SPPs) are excited at nearby gratings, propagate to the junction, and couple to the local nanogap plasmon modes. Like direct excitation, remote excitation of the nanogap can generate both SERS emission and an open-circuit photovoltage (OCPV). We compare SERS intensity and OCPV in both direct and remote illumination configurations. SERS spectra obtained by remote excitation are much more stable than those obtained through direct excitation when photon count rates are comparable. By statistical analysis of 33 devices, coupling efficiency of remote excitation is calculated to be around 10%, consistent with the simulated energy flow.Comment: 20 pages, 4 figures, plus 19 pages, 11 figures supporting informatio

Weakly-Supervised Action Localization by Hierarchically-structured Latent Attention Modeling

Weakly-supervised action localization aims to recognize and localize action instancese in untrimmed videos with only video-level labels. Most existing models rely on multiple instance learning(MIL), where the predictions of unlabeled instances are supervised by classifying labeled bags. The MIL-based methods are relatively well studied with cogent performance achieved on classification but not on localization. Generally, they locate temporal regions by the video-level classification but overlook the temporal variations of feature semantics. To address this problem, we propose a novel attention-based hierarchically-structured latent model to learn the temporal variations of feature semantics. Specifically, our model entails two components, the first is an unsupervised change-points detection module that detects change-points by learning the latent representations of video features in a temporal hierarchy based on their rates of change, and the second is an attention-based classification model that selects the change-points of the foreground as the boundaries. To evaluate the effectiveness of our model, we conduct extensive experiments on two benchmark datasets, THUMOS-14 and ActivityNet-v1.3. The experiments show that our method outperforms current state-of-the-art methods, and even achieves comparable performance with fully-supervised methods.Comment: Accepted to ICCV 2023. arXiv admin note: text overlap with arXiv:2203.15187, arXiv:2003.12424, arXiv:2104.02967 by other author

Effects of Al-Ti-C Refiner and Forming Processes on the Microstructure and Properties of Al-Zn-Mg-Cu Alloys

In this paper, the refinement effect of Al-5Ti-0.2C refiner on Al-Zn-Mg-Cu alloys was first investigated, and then the effects of three forming processes, i.e., Gravity Casting (GC), Squeeze Casting (SC), and Squeeze Casting after Ultrasonic Treatment (UT-SC), on microstructure and properties of Al-Zn-Mg-Cu alloys were studied. The results show that the refining effect of Al-5Ti-0.2C refiner is obvious; first, the average grain size of the alloy decreases and then increases with the increase in Ti content from 0.15 wt.% to 0.3 wt.%. The optimal amount of added Al-5Ti-0.2C is 0.2 wt.% Ti content. The good refining effect is attributed to the formation of TiC particles and Al3Ti compounds by the refiner, which can all be the nucleus of solidification. The poor refining effect when the Ti content was more than 0.2 wt.% is due to the formation of coarse Al3Ti particles. The results of three forming processes that cast Al-Zn-Mg-Cu alloys under the addition of Al-5Ti-0.2C with 0.2 wt.% Ti content show that the mechanical properties under the UT-SC process are the best; the tensile strength in the as-cast state reaches 367 MPa, and the elongation is 3.84%. The effect of tiny TiC particles in the refiner on the microstructure and properties of Al-Zn-Mg-Cu alloys is also discussed

Porcine deltacoronavirus resists antibody neutralization through cell-to-cell transmission

ABSTRACTPorcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that has been reported to infect a variety of animals and even humans. Cell–cell fusion has been identified as an alternative pathway for the cell-to-cell transmission of certain viruses, but the ability of PDCoV to exploit this transmission model, and the relevant mechanisms, have not been fully elucidated. Herein, we provide evidence that cell-to-cell transmission is the main mechanism supporting PDCoV spread in cell culture and that this efficient spread model is mediated by spike glycoprotein-driven cell–cell fusion. We found that PDCoV efficiently spread to non-susceptible cells via cell-to-cell transmission, and demonstrated that functional receptor porcine aminopeptidase N and cathepsins in endosomes are involved in the cell-to-cell transmission of PDCoV. Most importantly, compared with non-cell-to-cell infection, the cell-to-cell transmission of PDCoV was resistant to neutralizing antibodies and immune sera that potently neutralized free viruses. Taken together, our study revealed key characteristics of the cell-to-cell transmission of PDCoV and provided new insights into the mechanism of PDCoV infection

Quantifying Efficiency of Remote Excitation for Surface-Enhanced Raman Spectroscopy in Molecular Junctions

Surface-enhanced Raman spectroscopy (SERS) is enabled by local surface plasmon resonances (LSPRs) in metallic nanogaps. When SERS is excited by direct illumination of the nanogap, the background heating of the lattice and electrons can prevent further manipulation of the molecules. To overcome this issue, we report SERS in electromigrated gold molecular junctions excited remotely: surface plasmon polaritons (SPPs) are excited at nearby gratings, propagate to the junction, and couple to the local nanogap plasmon modes. Like direct excitation, remote excitation of the nanogap can generate both SERS emission and an open-circuit photovoltage (OCPV). We compare the SERS intensity and the OCPV in both direct and remote illumination configurations. SERS spectra obtained by remote excitation are much more stable than those obtained through direct excitation when the photon count rates are comparable. By statistical analysis of 33 devices, the coupling efficiency of remote excitation is calculated to be around 10%, consistent with the simulated energy flow

Germline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes

 Abstract Genetic testing for germline mutations in BRCA1/2 of patients with breast cancer (BC) is part of routine patient care. However, BRCA1/2 mutations account only for a fraction of familial BC. A custom panel of 22 gene sequencing was performed on each patient. Among the 481 female patients, 135 patients were detected to carry pathogenic (P)/likely pathogenic (LP) mutations (28.1%), which corresponded to 12 different cancer predisposition genes [14.6% (70/481) on BRCA1 gene, 5.0% (24/481) on BRCA2 gene, 8.5% (41/481) on non‐BRCA1/2 genes]. Moreover, 24.7% (119/481) of patients had mutation of unknown significance (VUS) in these genes. The most common (8/481) pathogenic mutation is BRCA1 c.5470_5477del, while BRIP1 2392 C > T of patients was detected. All the mutations detected were mainly seen in the homologous recombinant repair pathway. Compared to BRCA2 mutation, BRCA1 mutation is higher in younger female patients (P < 0.01). Some pathogenic mutations were detected in the patients’ familiy members without the past history of tumor and 92 novel mutations were detected (31 on BRCA including 2 P, 16 LP, 13 VUS; 61 on non‐BRCA1/2 including 9 LP, 52 VUS). The detection rate of BRCA1/2 mutations was higher in patients with three or more cancer family members than those with one or two. However, the difference was not statistically different. The results suggest that multigene panel testing can increase mutation detection rate for high‐risk BC patients. Detailed family history can help to categorize new mutations