Optimization of Millet Axial Flow Threshing and Separation Device Based on Discrete Element Method

The difficulties of threshing and separation of millet have not been solved yet which has restricted the development of the millet industry because of the special biological structure and lack of professional agricultural machinery. In order to improve the quality of millet harvest and meet the market demand for millet, in this paper, according to the branching structure of millet, the millet earhead model was established by Discrete Element Method. Using virtual models of millet and device, the simulation tests were carried out whose results have shown that the threshing effect of the rasp-bar threshing element is better than that of the teeth threshing element. Then the rotor structure was optimized into a combined type of the rasp-bar and the teeth. A three-factor five-level quadratic orthogonal rotation combination test was carried out whose results have shown that the combined rotor can meet the requirements of millet harvest

Design, Synthesis, and Pharmacological Evaluation of Haloperidol Derivatives as Novel Potent Calcium Channel Blockers with Vasodilator Activity

Several haloperidol derivatives with a piperidine scaffold that was decorated at the nitrogen atom with different alkyl, benzyl, or substituted benzyl moieties were synthesized at our laboratory to establish a library of compounds with vasodilator activity. Compounds were screened for vasodilatory activity on isolated thoracic aorta rings from rats, and their quantitative structure–activity relationships (QSAR) were examined. Based on the result of QSAR, N-4-tert-butyl benzyl haloperidol chloride (16c) was synthesized and showed the most potent vasodilatory activity of all designed compounds. 16c dose-dependently inhibited the contraction caused by the influx of extracellular Ca2+ in isolated thoracic aorta rings from rats. It concentration-dependently attenuated the calcium channel current and extracellular Ca2+ influx, without affecting the intracellular Ca2+ mobilization, in vascular smooth muscle cells from rats. 16c, possessing the N-4-tert-butyl benzyl piperidine structure, as a novel calcium antagonist, may be effective as a calcium channel blocker in cardiovascular disease

HMGN1 Modulates Nucleosome Occupancy and DNase I Hypersensitivity at the CpG Island Promoters of Embryonic Stem Cells

Chromatin structure plays a key role in regulating gene expression and embryonic differentiation; however, the factors that determine the organization of chromatin around regulatory sites are not fully known. Here we show that HMGN1, a nucleosome-binding protein ubiquitously expressed in vertebrate cells, preferentially binds to CpG island-containing promoters and affects the organization of nucleosomes, DNase I hypersensitivity, and the transcriptional profile of mouse embryonic stem cells and neural progenitors. Loss of HMGN1 alters the organization of an unstable nucleosome at transcription start sites, reduces the number of DNase I-hypersensitive sites genome wide, and decreases the number of nestin-positive neural progenitors in the subventricular zone (SVZ) region of mouse brain. Thus, architectural chromatin-binding proteins affect the transcription profile and chromatin structure during embryonic stem cell differentiation

RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals

DNA Topoisomerases are essential to resolve topological problems during DNA metabolism in all species. However, the prevalence and function of RNA topoisomerases remain uncertain. Here, we show that RNA topoisomerase activity is prevalent in Type IA topoisomerases from bacteria, archaea, and eukarya. Moreover, this activity always requires the conserved Type IA core domains and the same catalytic residue used in DNA topoisomerase reaction; however, it does not absolutely require the non-conserved carboxyl-terminal domain (CTD), which is necessary for relaxation reactions of supercoiled DNA. The RNA topoisomerase activity of human Top3β differs from that of Escherichia coli topoisomerase I in that the former but not the latter requires the CTD, indicating that topoisomerases have developed distinct mechanisms during evolution to catalyze RNA topoisomerase reactions. Notably, Top3β proteins from several animals associate with polyribosomes, which are units of mRNA translation, whereas the Top3 homologs from E. coli and yeast lack the association. The Top3β-polyribosome association requires TDRD3, which directly interacts with Top3β and is present in animals but not bacteria or yeast. We propose that RNA topoisomerases arose in the early RNA world, and that they are retained through all domains of DNA-based life, where they mediate mRNA translation as part of polyribosomes in animals

Dynamics and Regulation of RecA Polymerization and De-Polymerization on Double-Stranded DNA

10.1371/journal.pone.0066712PLoS ONE86

Species-selective killing of bacteria by antimicrobial peptide-PNAs

This is an open-access article distributed under the terms of the Creative Commons Attribution License, CC BY 4.0 which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Broad-spectrum antimicrobials kill indiscriminately, a property that can lead to negative clinical consequences and an increase in the incidence of resistance. Species-specific antimicrobials that could selectively kill pathogenic bacteria without targeting other species in the microbiome could limit these problems. The pathogen genome presents an excellent target for the development of such antimicrobials. In this study we report the design and evaluation of species-selective peptide nucleic acid (PNA) antibacterials. Selective growth inhibition of B. subtilis, E. coli, K. pnuemoniae and S. enterica serovar Typhimurium in axenic or mixed culture could be achieved with PNAs that exploit species differences in the translation initiation region of essential genes. An S. Typhimurium-specific PNA targeting ftsZ resulted in elongated cells that were not observed in E. coli, providing phenotypic evidence of the selectivity of PNA-based antimicrobials. Analysis of the genomes of E. coli and S. Typhimurium gave a conservative estimate of >150 PNA targets that could potentially discriminate between these two closely related species. This work provides a basis for the development of a new class of antimicrobial with a tuneable spectrum of activity.Peer reviewedFinal Published versio

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

A descent modified HS conjugate gradient method with an optimal property

In this paper, by minimizing the distance between the CG direction and the direction of the improved Perry conjugate gradient method [Yao et al., Numer. Algorithms 78 (2018) 1255–1269], we propose a descent modified HS conjugate gradient method. A remarkable property of the modified HS method is that it can produce sufficient descent property, which is independent of the line search used. Under suitable conditions, we prove that the modified HS method with the standard Armijo line search is globally convergent for uniformly convex functions and the modified HS+ method with standard Wolfe line search is globally convergent for general nonlinear functions. Extensive numerical experiments show that the proposed method is efficient

Comparison of Carbon Emissions in Different Sludge Treatment Pathways - a Case Study of Jiaxing, China

Sludge management strategy is essential to future carbon reduction in wastewater plants since the treatment and disposal of sludge contribute significantly to the carbon emissions. Using the method proposed by intergovernmental Panel on Climate Change(IPCC), the three sludge treatment paths of a typical wastewater treatment plant in Jiaxing were investigated. The result showed that net carbon emission is negative at -588kgCO2/tDS thanks to R3 which is characterized by centrifugal dehydrator, coal blending incineration with combined heat and power generation and cement substitute by slag is the rout with lowest carbon missions. The carbon emission of R1 is the highest at 699.87 kgCO2/tDS because of the chemical reagents. Process unit with larger carbon emissions was identified to be dewatering in which chemical reagent contributed the most. The main carbon offsets was the combined heat and power cogeneration which should be widely advocated