Calibration of DFT-based Models with Experimental Data

JAS thanks David Ponting and co‐workers at Lhasa Limited for useful suggestions and discussions. This work was also supported by the National Natural Science Foundation of China [Grant number 21875061, 21975066] and the program for Science & Technology Innovation Team in Universities of Henan Province [Grant number 19IRTSTHN029]. Publisher Copyright: © 2022 The Authors. Molecular Informatics published by Wiley-VCH GmbH.Random Forest (RF) QSPR models were developed with a data set of homolytic bond dissociation energies (BDE) previously calculated by B3LYP/6-311++G(d,p)//DFTB for 2263 sp3C−H covalent bonds. The best set of attributes consisted in 114 descriptors of the carbon atom (counts of atom types in 5 spheres around the kernel atom and ring descriptors). The optimized model predicted the DFT-calculated BDE of an independent test set of 224 bonds with MAE=2.86 kcal/mol. A new data set of 409 bonds from the iBonD database (http://ibond.nankai.edu.cn) was predicted by the RF with a modest MAE (5.36 kcal/mol) but a relatively high R2 (0.75) against experimental energies. A prediction scheme was explored that corrects the RF prediction with the average deviation observed for the k nearest neighbours (KNN) in an additional memory of experimental data. The corrected predictions achieved MAE=2.22 kcal/mol for an independent test set of 145 bonds and the corresponding experimental bond energies.publishersversionpublishe

MicroRNAs show diverse and dynamic expression patterns in multiple tissues of Bombyx mori

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) repress target genes at the post-transcriptional level, and function in the development and cell-lineage pathways of host species. Tissue-specific expression of miRNAs is highly relevant to their physiological roles in the corresponding tissues. However, to date, few miRNAs have been spatially identified in the silkworm.</p> <p>Results</p> <p>We establish for the first time the spatial expression patterns of nearly 100 miRNAs in multiple normal tissues (organs) of <it>Bombyx mori </it>females and males using microarray and Northern-blotting analyses. In all, only 10 miRNAs were universally distributed (including bmo-let-7 and bmo-bantam), while the majority were expressed exclusively or preferentially in specific tissue types (e.g., bmo-miR-275 and bmo-miR-1). Additionally, we examined the developmental patterns of miRNA expression during metamorphosis of the body wall, silk glands, midgut and fat body. In total, 63 miRNAs displayed significant alterations in abundance in at least 1 tissue during the developmental transition from larvae to pupae (e.g., bmo-miR-263b and bmo-miR-124). Expression patterns of five miRNAs were significantly increased during metamorphosis in all four tissues (e.g., bmo-miR-275 and bmo-miR-305), and two miRNA pairs, bmo-miR-10b-3p/5p and bmo-miR-281-3p/5p, showed coordinate expression.</p> <p>Conclusions</p> <p>In this study, we conducted preliminary spatial measurements of several miRNAs in the silkworm. Periods of rapid morphological change were associated with alterations in miRNA expression patterns in the body wall, silk glands, midgut and fat body during metamorphosis. Accordingly, we propose that corresponding ubiquitous or tissue-specific expression of miRNAs supports their critical roles in tissue specification. These results should facilitate future functional analyses.</p

MicroRNA expression profiling during the life cycle of the silkworm (Bombyx mori)

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are expressed by a wide range of eukaryotic organisms, and function in diverse biological processes. Numerous miRNAs have been identified in <it>Bombyx mori</it>, but the temporal expression profiles of miRNAs corresponding to each stage transition over the entire life cycle of the silkworm remain to be established. To obtain a comprehensive overview of the correlation between miRNA expression and stage transitions, we performed a whole-life test and subsequent stage-by-stage examinations on nearly one hundred miRNAs in the silkworm.</p> <p>Results</p> <p>Our results show that miRNAs display a wide variety of expression profiles over the whole life of the silkworm, including continuous expression from embryo to adult (miR-184), up-regulation over the entire life cycle (let-7 and miR-100), down-regulation over the entire life cycle (miR-124), expression associated with embryogenesis (miR-29 and miR-92), up-regulation from early 3^rdinstar to pupa (miR-275), and complementary pulses in expression between miR-34b and miR-275. Stage-by-stage examinations revealed further expression patterns, such as emergence at specific time-points during embryogenesis and up-regulation of miRNA groups in late embryos (miR-1 and bantam), expression associated with stage transition between instar and molt larval stages (miR-34b), expression associated with silk gland growth and spinning activity (miR-274), continuous high expression from the spinning larval to pupal and adult stages (miR-252 and miR-31a), a coordinate expression trough in day 3 pupae of both sexes (miR-10b and miR-281), up-regulation in pupal metamorphosis of both sexes (miR-29b), and down-regulation in pupal metamorphosis of both sexes (miR-275).</p> <p>Conclusion</p> <p>We present the full-scale expression profiles of miRNAs throughout the life cycle of <it>Bombyx mori</it>. The whole-life expression profile was further investigated via stage-by-stage analysis. Our data provide an important resource for more detailed functional analysis of miRNAs in this animal.</p

The Effect of Impurities on the Processing of Aluminum Alloys

For this Aluminum Industry of the Future (IOF) project, the effect of impurities on the processing of aluminum alloys was systematically investigated. The work was carried out as a collaborative effort between the Pennsylvania State University and Oak Ridge National Laboratory. Industrial support was provided by ALCOA and ThermoCalc, Inc. The achievements described below were made. A method that combines first-principles calculation and calculation of phase diagrams (CALPHAD) was used to develop the multicomponent database Al-Ca-K-Li-Mg-Na. This method was extensively used in this project for the development of a thermodynamic database. The first-principles approach provided some thermodynamic property data that are not available in the open literature. These calculated results were used in the thermodynamic modeling as experimental data. Some of the thermodynamic property data are difficult, if not impossible, to measure. The method developed and used in this project allows the estimation of these data for thermodynamic database development. The multicomponent database Al-Ca-K-Li-Mg-Na was developed. Elements such as Ca, Li, Na, and K are impurities that strongly affect the formability and corrosion behavior of aluminum alloys. However, these impurity elements are not included in the commercial aluminum alloy database. The process of thermodynamic modeling began from Al-Na, Ca-Li, Li-Na, K-Na, and Li-K sub-binary systems. Then ternary and higher systems were extrapolated because of the lack of experimental information. Databases for five binary alloy systems and two ternary systems were developed. Along with other existing binary and ternary databases, the full database of the multicomponent Al-Ca-K-Li-Mg-Na system was completed in this project. The methodology in integrating with commercial or other aluminum alloy databases can be developed. The mechanism of sodium-induced high-temperature embrittlement (HTE) of Al-Mg is now understood. Using the thermodynamic database developed in this project, thermodynamic simulations were carried out to investigate the effect of sodium on the HTE of Al-Mg alloys. The simulation results indicated that the liquid miscibility gap resulting from the dissolved sodium in the molten material plays an important role in HTE. A liquid phase forms from the solid face-centered cubic (fcc) phase (most likely at grain boundaries) during cooling, resulting in the occurrence of HTE. Comparison of the thermodynamic simulation results with experimental measurements on the high-temperature ductility of an Al-5Mg-Na alloy shows that HTE occurs in the temperature range at which the liquid phase exists. Based on this fundamental understanding of the HTE mechanism during processing of aluminum alloy, an HTE sensitive zone and a hot-rolling safe zone of the Al-Mg-Na alloys are defined as functions of processing temperature and alloy composition. The tendency of HTE was evaluated based on thermodynamic simulations of the fraction of the intergranular sodium-rich liquid phase. Methods of avoiding HTE during rolling/extrusion of Al-Mg-based alloys were suggested. Energy and environmental benefits from the results of this project could occur through a number of avenues: (1) energy benefits accruing from reduced rejection rates of the aluminum sheet and bar, (2) reduced dross formation during the remelting of the aluminum rejects, and (3) reduced CO2 emission related to the energy savings. The sheet and extruded bar quantities produced in the United States during 2000 were 10,822 and 4,546 million pounds, respectively. It is assumed that 50% of the sheet and 10% of the bar will be affected by implementing the results of this project. With the current process, the rejection rate of sheet and bar is estimated at 5%. Assuming that at least half of the 5% rejection of sheet and bar will be eliminated by using the results of this project and that 4% of the aluminum will be lost through dross (Al2O3) during remelting of the rejects, the full-scale industrial implementation of the project results would lead to energy savings in excess of 6.2 trillion Btu/year and cost savings of $42.7 million by 2020

Multiplex genomic structure variation mediated by TALEN and ssODN

BACKGROUND: Genomic structure variation (GSV) is widely distributed in various organisms and is an important contributor to human diversity and disease susceptibility. Efficient approaches to induce targeted genomic structure variation are crucial for both analytic and therapeutic studies of GSV. Here, we presented an efficient strategy to induce targeted GSV including chromosomal deletions, duplications and inversions in a precise manner. RESULTS: Utilizing Transcription Activator-Like Effector Nucleases (TALEN) designed to target two distinct sites, we demonstrated targeted deletions, duplications and inversions of an 8.9 Mb chromosomal segment, which is about one third of the entire chromosome. We developed a novel method by combining TALEN-induced GSV and single stranded oligodeoxynucleotide (ssODN) mediated gene modifications to reduce unwanted mutations occurring during the targeted GSV using TALEN or Zinc finger nuclease (ZFN). Furthermore, we showed that co-introduction of TALEN and ssODN generated unwanted complex structure variation other than the expected chromosomal deletion. CONCLUSIONS: We demonstrated the ability of TALEN to induce targeted GSV and provided an efficient strategy to perform GSV precisely. Furthermore, it is the first time to show that co-introduction of TALEN and ssODN generated unwanted complex structure variation. It is plausible to believe that the strategies developed in this study can be applied to other organisms, and will help understand the biological roles of GSV and therapeutic applications of TALEN and ssODN. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-41) contains supplementary material, which is available to authorized users

Microarray-based gene expression profiles in multiple tissues of the domesticated silkworm, Bombyx mori

Using a genome-wide oligonucleotide microarray, gene expression was surveyed in multiple silkworm tissues on day 3 of the fifth instar, providing a new resource for annotating the silkworm genome

Plasma Homocysteine Level in Children With Postural Tachycardia Syndrome

The study was designed to evaluate the changes of plasma homocysteine (Hcy) level in children with postural tachycardia syndrome (POTS) and explore its significance. A total of 65 subjects were recruited in our study, of whom 35 children were in the POTS group and 30 healthy children were in the control group. Plasma Hcy levels were determined in all subjects. The relationship between the plasma Hcy level and the symptom score was analyzed in the 35 POTS patients. The relationship between the plasma Hcy level and the change in heart rate from the supine to upright position (ΔHR) and between the plasma Hcy level and the rate of increase in heart rate from the supine to upright position (ΔHR/sHR × 100%) were analyzed in all subjects. The plasma Hcy levels were significantly higher in the children with POTS than those in the control group (9.78 [7.68, 15.31] μmol/L vs. 7.79 [7.46, 9.63] μmol/L, P &lt; 0.05). The plasma Hcy levels were positively correlated with symptom scores in the POTS patients (n = 35, r = 0.522, P &lt; 0.01). The plasma Hcy levels were also positively correlated with ΔHR (n = 65, r = 0.332, P &lt; 0.01) and ΔHR/sHR × 100% (n = 65, r = 0.341, P &lt; 0.01) in all the subjects. In conclusion, the plasma Hcy levels were elevated in the children with POTS positively correlated with the severity of POTS, suggesting that Hcy might be involved in the pathogenesis of POTS

Circadian regulation of night feeding and daytime detoxification in a formidable Asian pest Spodoptera litura

Voracious feeding, trans-continental migration and insecticide resistance make Spodoptera litura among the most difficult Asian agricultural pests to control. Larvae exhibit strong circadian behavior, feeding actively at night and hiding in soil during daytime. The daily pattern of larval metabolism was reversed, with higher transcription levels of genes for digestion (amylase, protease, lipase) and detoxification (CYP450s, GSTs, COEs) in daytime than at night. To investigate the control of these processes, we annotated nine essential clock genes and analyzed their transcription patterns, followed by functional analysis of their coupling using siRNA knockdown of interlocked negative feedback system core and repressor genes (SlituClk, SlituBmal1 and SlituCwo). Based on phase relationships and overexpression in cultured cells the controlling mechanism seems to involve direct coupling of the circadian processes to E-boxes in responding promoters. Additional manipulations involving exposure to the neonicotinoid imidacloprid suggested that insecticide application must be based on chronotoxicological considerations for optimal effectiveness

BmILF and I-motif Structure Are Involved in Transcriptional Regulation of \u3cem\u3eBmPOUM2\u3c/em\u3e in \u3cem\u3eBombyx mori\u3c/em\u3e

Guanine-rich and cytosine-rich DNA can form four-stranded DNA secondary structures called G-quadruplex (G4) and i-motif, respectively. These structures widely exist in genomes and play important roles in transcription, replication, translation and protection of telomeres. In this study, G4 and i-motif structures were identified in the promoter of the transcription factor gene BmPOUM2, which regulates the expression of the wing disc cuticle protein gene (BmWCP4) during metamorphosis. Disruption of the i-motif structure by base mutation, anti-sense oligonucleotides (ASOs) or inhibitory ligands resulted in significant decrease in the activity of the BmPOUM2 promoter. A novel i-motif binding protein (BmILF) was identified by pull-down experiment. BmILF specifically bound to the i-motif and activated the transcription of BmPOUM2. The promoter activity of BmPOUM2 was enhanced when BmILF was over-expressed and decreased when BmILF was knocked-down by RNA interference. This study for the first time demonstrated that BmILF and the i-motif structure participated in the regulation of gene transcription in insect metamorphosis and provides new insights into the molecular mechanism of the secondary structures in epigenetic regulation of gene transcription