180 research outputs found
Reciprocal Recommendation System for Online Dating
Online dating sites have become popular platforms for people to look for
potential romantic partners. Different from traditional user-item
recommendations where the goal is to match items (e.g., books, videos, etc)
with a user's interests, a recommendation system for online dating aims to
match people who are mutually interested in and likely to communicate with each
other. We introduce similarity measures that capture the unique features and
characteristics of the online dating network, for example, the interest
similarity between two users if they send messages to same users, and
attractiveness similarity if they receive messages from same users. A
reciprocal score that measures the compatibility between a user and each
potential dating candidate is computed and the recommendation list is generated
to include users with top scores. The performance of our proposed
recommendation system is evaluated on a real-world dataset from a major online
dating site in China. The results show that our recommendation algorithms
significantly outperform previously proposed approaches, and the collaborative
filtering-based algorithms achieve much better performance than content-based
algorithms in both precision and recall. Our results also reveal interesting
behavioral difference between male and female users when it comes to looking
for potential dates. In particular, males tend to be focused on their own
interest and oblivious towards their attractiveness to potential dates, while
females are more conscientious to their own attractiveness to the other side of
the line
Potential complementary therapy for adverse drug reactions to sulfonamides: Chemoprotection against oxidative and nitrosative stress by TCM constituents and defined mixtures
PURPOSE: Our working hypothesis is that bioactive phytochemicals that are important constituents of Traditional Chinese Medicine and their defined mixtures have potential as complementary therapy for chemoprotection against adverse drug reactions whose toxicity is not related to the pharmacological action of the drug but where oxidative and nitrosative stress are causative factors. METHODS: In this investigation we measured cytotoxicity, lipid peroxidation, protein carbonylation and ROS/NOS-mediated changes in the disulfide proteome of Jurkat E6.1 cells resulting from exposure to sulfamethoxazole N-hydroxylamine with or without pretreatment with low µM concentrations of baicalein, crocetin, resveratrol and schisanhenol alone and in defined mixtures to compare the ability of these treatment regimens to protect against ROS/RNS toxicity to Jurkat E6.1 cells in culture. RESULTS: Each of the Traditional Chinese Medicine constituents and defined mixtures tested had significant chemoprotective effects against the toxicity of ROS/RNS formed by exposure of Jurkat E6.1 cells to reactive metabolites of sulfamethoxazole implicated as the causative factors in adverse drug reactions to sulfa drugs used for therapy. At equimolar concentrations, the defined mixtures tended to be more effective chemoprotectants overall than any of the single constituents against ROS/RNs toxicity in this context. CONCLUSIONS: At low µM concentrations, defined mixtures of TCM constituents that contain ingredients with varied structures and multiple mechanisms for chemoprotection have excellent potential for complementary therapy with sulfa drugs to attenuate adverse effects caused by oxidative/nitrosative stress. Typically, such mixtures will have a combination of immediate activity due to short in vivo half-lives of some ingredients cleared rapidly following metabolism by phase 2 conjugation enzymes; and some ingredients with more prolonged halflives and activity reliant on phase 1 oxidation enzymes for their metabolic clearance
Pharmacogenomic Variants May Influence the Urinary Excretion of Novel Kidney Injury Biomarkers in Patients Receiving Cisplatin
Nephrotoxicity is a dose limiting side effect associated with the use of cisplatin in the treatment of solid tumors. The degree of nephrotoxicity is dictated by the selective accumulation of cisplatin in renal tubule cells due to: (1) uptake by organic cation transporter 2 (OCT2) and copper transporter 1 (CTR1); (2) metabolism by glutathione S-transferases (GSTs) and γ-glutamyltransferase 1 (GGT1); and (3) efflux by multidrug resistance-associated protein 2 (MRP2) and multidrug and toxin extrusion protein 1 (MATE1). The purpose of this study was to determine the significance of single nucleotide polymorphisms that regulate the expression and function of transporters and metabolism genes implicated in development of acute kidney injury (AKI) in cisplatin treated patients. Changes in the kidney function were assessed using novel urinary protein biomarkers and traditional markers. Genotyping was conducted by the QuantStudio 12K Flex Real-Time PCR System using a custom open array chip with metabolism, transport, and transcription factor polymorphisms of interest to cisplatin disposition and toxicity. Traditional and novel biomarker assays for kidney toxicity were assessed for differences according to genotype by ANOVA. Allele and genotype frequencies were determined based on Caucasian population frequencies. The polymorphisms rs596881 (SLC22A2/OCT2), and rs12686377 and rs7851395 (SLC31A1/CTR1) were associated with renoprotection and maintenance of estimated glomerular filtration rate (eGFR). Polymorphisms in SLC22A2/OCT2, SLC31A1/CTRI, SLC47A1/MATE1, ABCC2/MRP2, and GSTP1 were significantly associated with increases in the urinary excretion of novel AKI biomarkers: KIM-1, TFF3, MCP1, NGAL, clusterin, cystatin C, and calbindin. Knowledge concerning which genotypes in drug transporters are associated with cisplatin-induced nephrotoxicity may help to identify at-risk patients and initiate strategies, such as using lower or fractionated cisplatin doses or avoiding cisplatin altogether, in order to prevent AKI
Neonatal outcome in 29 pregnant women with COVID-19 : A retrospective study in Wuhan, China
Funding: YTW: National Key Research and Development Program of China (2018YFC1002804), http://www.most.gov.cn; YTW: National Key Research and Development Program of China (2016YFC1000203), http://www.most.gov.cn. CL: COVID-19 Prevention and Control Program of International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University (2020-COVID-19-04), https://www.ipmch.com.cn. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability: All the research data are available at the ResMen Manager of Chinese Clinical Trial Registry (www.medresman.org), and the registration number is ChiCTR2000031954 (http://www.medresman.org.cn/pub/cn/proj/projectshshow.aspx?proj=1810).Peer reviewedPublisher PD
Debugging and consolidating multiple synthetic chromosomes reveals combinatorial genetic interactions
The Sc2.0 project is building a eukaryotic synthetic genome from scratch. A major milestone has been achieved with all individual Sc2.0 chromosomes assembled. Here, we describe the consolidation of multiple synthetic chromosomes using advanced endoreduplication intercrossing with tRNA expression cassettes to generate a strain with 6.5 synthetic chromosomes. The 3D chromosome organization and transcript isoform profiles were evaluated using Hi-C and long-read direct RNA sequencing. We developed CRISPR Directed Biallelic URA3-assisted Genome Scan, or ‘‘CRISPR D-BUGS,’’ to map phenotypic variants caused by specific designer modifications, known as ‘‘bugs.’’ We first fine-mapped a bug in synthetic chromosome II (synII) and then discovered a combinatorial interaction associated with synIII and synX, revealing an unexpected genetic interaction that links transcriptional regulation, inositol metabolism, and tRNASer CGA abundance. Finally, to expedite consolidation, we employed chromosome substitution to incorporate the largest chromosome (synIV), thereby consolidating >50% of the Sc2.0 genome in one strain </p
Identifying long-term stable refugia for dominant Castanopsis species of evergreen broad-leaved forests in East Asia: A tool for ensuring their conservation
Identifying and protecting refugia is a priority for conservation management under projected anthropogenic climate change. We have two main objectives: the first is to explore the spatial (East Asia) and temporal (Last Glacial Maximum to year 2070) distribution patterns of dominant Castanopsis species of evergreen broad-leaved forests, also the relation with their niche breadths; the second is to identify long-term stable refugia for preserving these species and provide a framework of conservation strategies. We find that there is an extraordinary richness with 32 dominant Castanopsis species, and they form both a geographically and climatically almost unbroken connection from ca. 5°N to 38°N, having thus ecological significance. During the Mid-Holocene and, particularly, the Last Glacial Maximum, the predicted suitable areas of the species as a whole were larger than those in the present. By 2070, potentially suitable areas with high richness of dominant Castanopsis species will be reduced by 94.5 % on average. No correlation between species niche breadths and distribution ranges is found, which could be due to regional climate stability. Mountains of southwestern and southern Yunnan in China are identified as climatically long-term stable refugia for 7¿9 Castanopsis species. We recommend that these refugia have the highest priority of conservation to prevent their extinction. Our suggested urgent measures include improving the effectiveness of currently protected Castanopsis species and expanding the network of protected areas to cover a larger fraction of the refugia, as well as ensuring Castanopsis species natural regeneration potential in fragmented and natural secondary forest areas.This study received financial support from the Major Program for Basic Research Project of Yunnan Province, China (202101BC070002), the Science and Technology Department of Yunnan University, China (2019YNU002), the Ministry of Science and Technology of China (2015FY210200-15), the Spanish Ministry of Science and Innovation (grant PID2020-119163GB-I00 funded by MCIN/AEI/10.13039/501100011033), the Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency of Japan (JPMEERF20202002), and the Northeastern Research Institute of Petrified Wood and Mineral Resources, Nakhon Ratchasima Rajabhat University, Thailand.Keywords
1. Introduction
2. Materials and methods
2.1. Data collection and notations
2.2. Ecological niche modeling
2.3. Data analyses
3. Results
3.1. Dominant Castanopsis species in East Asia today: richness and distribution patterns
3.2. Richness of dominant Castanopsis species shaped by climate change
3.3. Niche groups and niche breadths of dominant Castanopsis species
3.4. Climatically long-term stable refugia
4. Discussion
4.1. Richness of dominant Castanopsis species shaped by climate change
4.2. Niche groups and niche breadths of dominant Castanopsis species
4.3. Long-term stable refugia and conservation strategies
5. Conclusions
CRediT authorship contribution statement
Declaration of competing interest
Acknowledgements
Appendix A. Supplementary material
Reference
Induction of Antibodies in Rhesus Macaques That Recognize a Fusion-Intermediate Conformation of HIV-1 gp41
A component to the problem of inducing broad neutralizing HIV-1 gp41 membrane proximal external region (MPER) antibodies is the need to focus the antibody response to the transiently exposed MPER pre-hairpin intermediate neutralization epitope. Here we describe a HIV-1 envelope (Env) gp140 oligomer prime followed by MPER peptide-liposomes boost strategy for eliciting serum antibody responses in rhesus macaques that bind to a gp41 fusion intermediate protein. This Env-liposome immunization strategy induced antibodies to the 2F5 neutralizing epitope 664DKW residues, and these antibodies preferentially bound to a gp41 fusion intermediate construct as well as to MPER scaffolds stabilized in the 2F5-bound conformation. However, no serum lipid binding activity was observed nor was serum neutralizing activity for HIV-1 pseudoviruses present. Nonetheless, the Env-liposome prime-boost immunization strategy induced antibodies that recognized a gp41 fusion intermediate protein and was successful in focusing the antibody response to the desired epitope
Amino acid changes in the HIV-1 gp41 membrane proximal region control virus neutralization sensitivity.
CAPRISA, 2016.Abstract available in pdf
A Genome-wide Drosophila Screen for Heat Nociception Identifies α2δ3 as an Evolutionarily Conserved Pain Gene
Worldwide, acute and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knock-down in Drosophila, we report a global screen for an innate behavior and identify hundreds of novel genes implicated in heat nociception, including the α2δ-family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (α2δ3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, α2δ3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in α2δ3 mutant mice revealed impaired transmission of thermal pain evoked signals from the thalamus to higher order pain centers. Intriguingly, in α2δ3 mutant mice thermal pain and tactile stimulation triggered strong cross-activation or synesthesia of brain regions involved in vision, olfaction, and hearing
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