516 research outputs found
Machine Learning Research Trends in Africa: A 30 Years Overview with Bibliometric Analysis Review
In this paper, a critical bibliometric analysis study is conducted, coupled
with an extensive literature survey on recent developments and associated
applications in machine learning research with a perspective on Africa. The
presented bibliometric analysis study consists of 2761 machine learning-related
documents, of which 98% were articles with at least 482 citations published in
903 journals during the past 30 years. Furthermore, the collated documents were
retrieved from the Science Citation Index EXPANDED, comprising research
publications from 54 African countries between 1993 and 2021. The bibliometric
study shows the visualization of the current landscape and future trends in
machine learning research and its application to facilitate future
collaborative research and knowledge exchange among authors from different
research institutions scattered across the African continent
Molecular Recognition of Ketamine by a Subset of Olfactory G Protein–coupled Receptors
Ketamine elicits various neuropharmacological effects, including sedation, analgesia, general anesthesia, and antidepressant activity. Through an in vitro screen, we identified four mouse olfactory receptors (ORs) that responded to ketamine. In addition to their presence in the olfactory epithelium, these G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) are distributed throughout the central nervous system. To better understand the molecular basis of the interactions between ketamine and ORs, we used sequence comparison and molecular modeling to design mutations that (i) increased, reduced, or abolished ketamine responsiveness in responding receptors, and (ii) rendered non-responding receptors responsive to ketamine. We showed that olfactory sensory neurons (OSNs) that expressed distinct ORs responded to ketamine in vivo, suggesting that ORs may serve as functional targets for ketamine. The ability to both abolish and introduce responsiveness to ketamine in GPCRs enabled us to identify and confirm distinct interaction loci in the binding site, which suggested a signature ketamine-binding pocket that may guide exploration of additional receptors for this general anesthetic drug
Recommended from our members
Rapid detection of BRCA1/2 recurrent mutations in Chinese breast and ovarian cancer patients with multiplex SNaPshot genotyping panels.
BRCA1/2 mutations are significant risk factors for hereditary breast and ovarian cancer (HBOC), its mutation frequency in HBOC of Chinese ethnicity is around 9%, in which nearly half are recurrent mutations. In Hong Kong and China, genetic testing and counseling are not as common as in the West. To reduce the barrier of testing, a multiplex SNaPshot genotyping panel that targeted 25 Chinese BRCA1/2 mutation hotspots was developed, and its feasibility was evaluated in a local cohort of 441 breast and 155 ovarian cancer patients. For those who tested negative, they were then subjected to full-gene testing with next-generation sequencing (NGS). BRCA mutation prevalence in this cohort was 8.05% and the yield of the recurrent panel was 3.52%, identifying over 40% of the mutation carriers. Moreover, from 79 Chinese breast cancer cases recruited overseas, 2 recurrent mutations and one novel BRCA2 mutation were detected by the panel and NGS respectively. The developed genotyping panel showed to be an easy-to-perform and more affordable testing tool that can provide important contributions to improve the healthcare of Chinese women with cancer as well as family members that harbor high risk mutations for HBOC
Recommended from our members
Cathelicidin preserves intestinal barrier function in polymicrobial sepsis.
ObjectivesThe intestinal epithelium compartmentalizes the sterile bloodstream and the commensal bacteria in the gut. Accumulating evidence suggests that this barrier is impaired in sepsis, aggravating systemic inflammation. Previous studies reported that cathelicidin is differentially expressed in various tissues in sepsis. However, its role in sepsis-induced intestinal barrier dysfunction has not been investigated.DesignTo examine the role of cathelicidin in polymicrobial sepsis, cathelicidin wild-(Cnlp+/+) and knockout (Cnlp-/-) mice underwent cecal-ligation and puncture (CLP) followed by the assessment of septic mortality and morbidity as well as histological, biochemical, immunological, and transcriptomic analyses in the ileal tissues. We also evaluated the prophylactic and therapeutic efficacies of vitamin D3 (an inducer of endogenous cathelicidin) in the CLP-induced murine polymicrobial sepsis model.ResultsThe ileal expression of cathelicidin was increased by three-fold after CLP, peaking at 4 h. Knockout of Cnlp significantly increased 7-day mortality and was associated with a higher murine sepsis score. Alcian-blue staining revealed a reduced number of mucin-positive goblet cells, accompanied by reduced mucin expression. Increased number of apoptotic cells and cleavage of caspase-3 were observed. Cnlp deletion increased intestinal permeability to 4kD fluorescein-labeled dextran and reduced the expression of tight junction proteins claudin-1 and occludin. Notably, circulating bacterial DNA load increased more than two-fold. Transcriptome analysis revealed upregulation of cytokine/inflammatory pathway. Depletion of Cnlp induced more M1 macrophages and neutrophils compared with the wild-type mice after CLP. Mice pre-treated with cholecalciferol (an inactive form of vitamin D3) or treated with 1alpha, 25-dihydroxyvitamin D3 (an active form of VD3) had decreased 7-day mortality and significantly less severe symptoms. Intriguingly, the administration of cholecalciferol after CLP led to worsened 7-day mortality and the associated symptoms.ConclusionsEndogenous cathelicidin promotes intestinal barrier integrity accompanied by modulating the infiltration of neutrophils and macrophages in polymicrobial sepsis. Our data suggested that 1alpha, 25-dihydroxyvitamin D3 but not cholecalciferol is a potential therapeutic agent for treating sepsis
The role of tank-treading motions in the transverse migration of a spheroidal vesicle in a shear flow
The behavior of a spheroidal vesicle, in a plane shear flow bounded from one
side by a wall, is analysed when the distance from the wall is much larger than
the spheroid radius. It is found that tank treading motions produce a
transverse drift away from the wall, proportional to the spheroid eccentricity
and the inverse square of the distance from the wall. This drift is independent
of inertia, and is completely determined by the characteristics of the vesicle
membrane. The relative strength of the contribution to drift from tank-treading
motions and from the presence of inertial corrections, is discussed.Comment: 16 pages, 1 figure, Latex. To appear on J. Phys. A (Math. Gen.
Quinolizidines as Novel SARS-CoV-2 Entry Inhibitors
COVID-19, caused by the highly transmissible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has rapidly spread and become a pandemic since its outbreak in 2019. We have previously discovered that aloperine is a new privileged scaffold that can be modified to become a specific antiviral compound with markedly improved potency against different viruses, such as the influenza virus. In this study, we have identified a collection of aloperine derivatives that can inhibit the entry of SARS-CoV-2 into host cells. Compound 5 is the most potent tested aloperine derivative that inhibited the entry of SARS-CoV-2 (D614G variant) spike protein-pseudotyped virus with an IC50 of 0.5 µM. The compound was also active against several other SARS-CoV-2 variants including Delta and Omicron. Results of a confocal microscopy study suggest that compound 5 inhibited the viral entry before fusion to the cell or endosomal membrane. The results are consistent with the notion that aloperine is a privileged scaffold that can be used to develop potent anti-SARS-CoV-2 entry inhibitors
Effects of Molecular Structure and Packing Order on the Stretchability of Semicrystalline Conjugated Poly(Tetrathienoacene-diketopyrrolopyrrole) Polymers
The design of polymer semiconductors possessing high charge transport performance, coupled with good ductility, remains a challenge. Understanding the distribution and behavior of both crystalline domains and amorphous regions in conjugated polymer films, upon an applied stress, shall provide general guiding principles to design stretchable organic semiconductors. Structure–property relationships (especially in both side chain and backbone engineering) are investigated for a series of poly(tetrathienoacene-diketopyrrolopyrrole) polymers. It is observed that the fused thiophene diketopyrrolopyrrole-based polymer, when incorporated with branched side chains and an additional thiophene spacer in the backbone, exhibits improved mechanical endurance and, in addition, does not show crack propagation until 40% strain. Furthermore, this polymer exhibits a hole mobility of 0.1 cm2 V−1 s−1 even at 100% strain or after recovered from strain, which reveals prominent continuity and viscoelasticity of the polymer thin film. It is also observed that the molecular packing orientations (either edge-on or face-on) significantly affect the mechanical compliance of the polymer films. The improved stretchability of the polymers is attributed to both the presence of soft amorphous regions and the intrinsic packing arrangement of its crystalline domains
The effect of carbon nanotube aspect ratio and loading on the elastic modulus of electrospun poly(vinyl alcohol)-carbon nanotube hybrid fibers
The reinforcement effect of carbon nanotubes (CNTs) has been examined as a function of their loading and aspect ratio in poly(vinyl alcohol) (PVA) based hybird fibers. Lignosulfonic acid sodium salt (LSA) was used to disperse CNTs to produce consistently high CNT loaded PVA-LSA-CNT hybrid fibers using an electrospinning process. The elastic modulus of individual fibers was measured using atomic force microscopy. The presence of CNTs significantly increased the average elastic modulus of PVA-LSA-CNT fibers compared to PVA-LSA fibers. The elastic modulus, however, exhibited no fiber diameter dependency. Transmission electron microscopy (TEM) was used to determine the loading and the aspect ratio of CNTs in each hybrid fiber. The CNT loading in PVA-LSA-CNT fibers varied widely due to non-uniform CNT dispersion and displayed no relationship with the elastic modulus. Our results also demonstrated that the average value of CNT aspect ratio significantly affected the elastic modulus of the hybrid fibers. Such a result was in agreement with theoretical prediction in which the stress transfer efficiency in a composite matrix is strongly dependent on the CNT aspect ratio.NRC publication: Ye
- …