Systematic Identification of Synergistic Drug Pairs Targeting HIV

The systematic identification of effective drug combinations has been hindered by the unavailability of methods that can explore the large combinatorial search space of drug interactions. Here we present a multiplex screening method named MuSIC (Multiplex Screening for Interacting Compounds), which expedites the comprehensive assessment of pair-wise compound interactions. We examined ~500,000 drug pairs from 1000 FDA-approved or clinically tested drugs and identified drugs that synergize to inhibit HIV replication. Our analysis reveals an enrichment of anti-inflammatory drugs in drug combinations that synergize against HIV, indicating HIV benefits from inflammation that accompanies its infection. Multiple drug pairs identified in this study, including glucocorticoid and nitazoxanide, synergize by targeting different steps of the HIV life cycle. As inflammation accompanies HIV infection, our findings indicate that inhibiting inflammation could curb HIV propagation. MuSIC can be applied to a wide variety of disease-relevant screens to facilitate efficient identification of compound combinations

Could social robots facilitate children with autism spectrum disorders in learning distrust and deception?

Social robots have been increasingly involved in our daily lives and provide a new environment for children\u27s growth. The current study aimed to examine how children with and without Autism Spectrum Disorders (ASD)learned complex social rules from a social robot through distrust and deception games. Twenty children with ASD between the ages of 5–8 and 20 typically-developing (TD)peers whose age and IQ were matched participated in distrust and deception tasks along with an interview about their perception of the human-likeness of the robot. The results demonstrated that: 1)children with ASD were slower to learn to and less likely to distrust and deceive a social robot than TD children and 2)children with ASD who perceived the robot to appear more human-like had more difficulty in learning to distrust the robot. Besides, by comparing to a previous study the results showed that children with ASD appeared to have more difficulty in learning to distrust a human compared to a robot, particularly in the early phase of learning. Overall, our study verified that social robots could facilitate children with ASD\u27s learning of some social rules and showed that children\u27s perception of the robot plays an important role in their social learning, which provides insights on robot design and its clinical applications in ASD intervention

Single-cell-resolution transcriptome map revealed novel genes involved in testicular germ cell progression and somatic cells specification in Chinese tongue sole with sex reversal

19 pages, 7 figures, supporting information https://doi.org/10.1007/s11427-021-2236-4.-- Data availability: The data reported in this study are available in the CNGB Nucleotide Sequence Archive (CNSA: https://db.cngb.org/cnsa; accession number CNP0002135).Female-to-male sex reversals (pseudomales) are common in lower vertebrates and have been found in natural populations, which is a concern under rapid changes in environmental conditions. Pseudomales can exhibit altered spermatogenesis. However, the regulatory mechanisms underlying pseudomale spermatogenesis remain unclear. Here, we characterized spermatogenesis in Chinese tongue sole (Cynoglossus semilaevis), a species with genetic and environmental sex determination, based on a high-resolution single-cell RNA-seq atlas of cells derived from the testes of genotypic males and pseudomales. We identified five germ cell types and six somatic cell types and obtained a single-cell atlas of dynamic changes in gene expression during spermatogenesis in Chinese tongue sole, including alterations in pseudomales. We detected decreased levels of Ca2+ signaling pathway-related genes in spermatogonia, insufficient meiotic initiation in spermatocytes, and a malfunction of somatic niche cells in pseudomales. However, a cluster of CaSR genes and MAPK signaling factors were upregulated in undifferentiated spermatogonia of pseudomales. Additionally, we revealed that Z chromosome-specific genes, such as piwil2, dhx37, and ehmt1, were important for spermatogenesis. These results improve our understanding of reproduction after female-to-male sex-reversal and provide new insights into the adaptability of reproductive strategies in lower vertebratesThis work was supported by the National Key R&D Program of China (2018YFD0900301), the National Nature Science Foundation of China (31722058, 31802275, 31472269), the AoShan Talents Cultivation Program Supported by Qingdao National Laboratory for Marine Science and Technology (2017ASTCP-ES06), the Taishan Scholar Project Fund of Shandong of China to C.S., the National Ten-Thousands Talents Special Support Program to C.S., the Central Public-interest Scientific Institution Basal Research Fund, CAFS (2020TD19) and the China Agriculture Research System (CARS-47-G03)With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewe

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

Research for Unmanned Aerial Vehicle components reliability evaluation model considering the influences of human factors

Human operating error is one of the important factors affecting the reliable operation of unmanned aerial vehicle (UAV) components, however, people always neglect human-operating-error of the existing unmanned aircraft systems and components reliability assessment methods. This article set the problem to the most important position to search, divided the scene of UAV components assignment to the Status debugging monitoring model and Preventive maintenance type. First, analysis of two scenarios UAV components made qualitative analysis of human error using the method of failure mode and effect analysis; and then put forward the two scenarios of human reliability assessment model, used to quantify the probability of human error. In example analysis, it considers the primary factors those affect humans reliability, to calculate and compare the proportion of human error at different situation. Results show that the proposed method can quantify human error probability, and quantitative characterization of human error can affect the reliability of the UAV components

Degree of impact of factors that affect the start-up of small and medium enterprises in Singapore.

This report aims to uncover the factors that affect the start-up of SMEs in Singapore and the degree of their impact. This includes finding out in detail each of the following factors: Government, Education, Economic Conditions, Legal Environment, Technology, Infrastructure and Financial, and how they affect the start-up of SMEs in Singapore

Three-Dimensional Aerodynamic Instabilities In Multi-Stage Axial Compressors

This thesis presents the conceptualization and development of a computational model for describing three-dimensional non-linear disturbances associated with instability and inlet distortion in multistage compressors. Specifically, the model is aimed at simulating the non-linear aspects of short wavelength stall inception, part span stall cells, and compressor response to three-dimensional inlet distortions. The computed results demonstrated the first-of-a-kind capability for simulating short wavelength stall inception in multistage compressors. The adequacy of the model is demonstrated by its application to reproduce the following phenomena: (1) response of a compressor to a square-wave total pressure inlet distortion; (2) behavior of long wavelength small amplitude disturbances in compressors; (3) short wavelength stall inception in a multistage compressor and the occurrence of rotating stall inception on the negatively sloped portion of the compressor characteristic; (4) progressive stalling behavior in the first stage in a mismatched multistage compressor; (5) change of stall inception type (from modal to spike and vice versa) due to IGV stagger angle variation, and "unique rotor tip incidence" at these points where the compressor stalls through short wavelength disturbances. The model has been applied to determine the parametric dependence of instability inception behavior in terms of amplitude and spatial distribution of initial disturbance, and intra-blade-row gaps. It is found that reducing the inter-blade row gaps suppresses the growth of short wavelength disturbances. It is also concluded from these parametric investigations that each local component group (rotor and its two adjacent stators) has its own instability point (i.e. conditions at which disturbances are sustained) for short wavelength disturbances, with the instability point for the compressor set by the most unstable component group. For completeness, the methodology has been extended to describe finite amplitude disturbances in high-speed compressors. Results are presented for the response of a transonic compressor subjected to inlet distortions

A study of implicit leadership theories of Gen Y and Gen X in Singapore.

With Generation Y poised to become a large proportion of the workforce in the near future, it is crucial to understand their key characteristics and behaviours that set them apart from previous generations. This paper investigates differences in leadership perceptions between Generation X and Y in Singapore using Implicit Leadership Theories (ILTs). To measure ILTs in our context, we combined the Implicit Leadership Scale (ILS) developed by Epitropaki and Martin (2004) and Chinese Implicit Leadership Scale (CILS) developed by Ling, Chia, and Fang (2000). Of the ten dimensions from these scales, seven were hypothesized on. A survey-questionnaire methodology was chosen for data collection, and it was given to a sample of 205 Generation Yers and 108 Generation Xers via convenience sampling. We found significant evidence showing Generation Y viewing the dimensions of Personal Morality, Interpersonal Competency and Intelligence as being more characteristic of an effective leader than Generation X does. These results can be utilized by companies to modify their leadership development and selection policies, producing leaders who are perceived as being effective, thus aiding the motivation and retention of Generation Y. Individual managers can also tap onto these findings to adopt effective leadership styles to manage different generations at work. Nonetheless, our results also indicated that generational stereotypes are to be used as a form of reference and managers should not overlook the importance of individual variations within generations.BUSINES

Proanthocyanidin biosynthesis in the seed coat of yellow-seeded, canola quality Brassica napus YN01-429 is constrained at the committed step catalyzed by dihydroflavonol 4-reductase

The yellow seed characteristic in Brassica napus L. is desirable because of its association with higher oil content and better quality of oil-extracted meal. YN01-429 is a yellow-seeded canola-quality germplasm developed in Canada arising from several years of research. Seed-coat pigmentation is due to oxidized proanthocyanidins (PA; condensed tannins) derived from phenylpropanoids and malonyl CoA. We found PA accumulation to be most robust in young seed coats (20 d post anthesis; dpa) of a related black-seeded line N89-53 and only very little PA in YN01-429, which also contained much less extractable phenolics. The flavonol content, however, did not show as great a difference between these two lines. Furthermore, sinapine, a product of the general phenylpropanoid metabolism, was present at comparable levels in the embryos of both lines. Dihydroflavonol reductase (DFR) activity that commits phenolics to PA synthesis was lower in YN01-429 seed coats. The results of Southern blot and in silico analyses were indicative of two copies of the DFR gene in B. napus. Both copies were functional in YN01-429, ruling out homeoallelic repression or silencing, but together they showed very low expression levels (17-fold fewer transcripts) relative to DFR activity in N89-53 seed coats. These results collectively suggest that YN01-429 differs in regulatory circuits that impact the PA synthesis branch much more than the flavonol synthesis branch in the seed coats and such circuits do not impinge upon general phenylpropanoid metabolism in the embryos.Le jaune caracte\ub4ristique des grains du Brassica napus L. est de\ub4sirable, compte tenu de son association avec une haute teneur en huile et une meilleure qualite\ub4 de la farine extraite de l\u2019huile. Le YN01-429 constitue un germplasme a` graine jaune de qualite\ub4 canola re\ub4sultant de plusieurs anne\ub4es de recherches. La pigmentation des te\ub4guments est attribue\ub4e a` des proanthocyanidines oxyde\ub4es (PA; tannins condense\ub4s) de\ub4rive\ub4es de phe\ub4nylpropano\u131\ua8des et du CoA du malonyl. Les auteurs ont trouve\ub4 une plus forte accumulation de PA chez les jeunes te\ub4guments (20 jours apre`s l\u2019anthe`se; dpa) d\u2019une ligne\ub4e apparente\ub4e a` grains noirs N89-53 et tre`s peu de PA chez la ligne\ub4e YN01-429 qui contient a` la fois beaucoup moins de phe\ub4nols extractibles. Cependant, la teneur en flavonols ne montre pas autant de diffe\ub4rences entre ces deux ligne\ub4es. De plus, la sinapine, un produit du me\ub4tabolisme ge\ub4ne\ub4ral des phe\ub4nylpropano\u131\ua8des, se retrouve a` des teneurs comparables chez les embryons des deux ligne\ub4es. L\u2019activite\ub4 de la re\ub4ductase du dihydroflavonol (DFR) qui pousse les phe\ub4nols vers la synthe` se de PA, est plus faible dans les te\ub4guments du YN01-429. Les re\ub4sultats du transfert Southern et des analyses in silico indiquent la pre\ub4sence de deux copies du ge`ne DFR chez le B. napus. Les deux copies sont fonctionnelles chez le YN01- 429, ce qui e\ub4limine la re\ub4pression ou le silencing home\ub4oalle\ub4lique, mais ensemble elles ne montrent que de tre`s faibles degre \ub4s d\u2019expression (transcriptions 17 fois infe\ub4rieures) par rapport a` l\u2019activite\ub4 du DFR chez les te\ub4guments du N89-53. Ces re\ub4- sultats pris dans leur ensemble sugge`rent que le YN01-429 diffe`re a` l\u2019e\ub4chelle des circuits qui agissent sur la ligne de synthe`se des PA beaucoup plus que sur la ligne de synthe`se des flavonols dans les te\ub4guments, et de tels circuits n\u2019affectent pas le me\ub4tabolisme ge\ub4ne\ub4ral des phe\ub4nylpropano\u131\ua8des chez les embryons.Peer reviewed: YesNRC publication: Ye