151 research outputs found
EvEval: A Comprehensive Evaluation of Event Semantics for Large Language Models
Events serve as fundamental units of occurrence within various contexts. The
processing of event semantics in textual information forms the basis of
numerous natural language processing (NLP) applications. Recent studies have
begun leveraging large language models (LLMs) to address event semantic
processing. However, the extent that LLMs can effectively tackle these
challenges remains uncertain. Furthermore, the lack of a comprehensive
evaluation framework for event semantic processing poses a significant
challenge in evaluating these capabilities. In this paper, we propose an
overarching framework for event semantic processing, encompassing
understanding, reasoning, and prediction, along with their fine-grained
aspects. To comprehensively evaluate the event semantic processing abilities of
models, we introduce a novel benchmark called EVEVAL. We collect 8 datasets
that cover all aspects of event semantic processing. Extensive experiments are
conducted on EVEVAL, leading to several noteworthy findings based on the
obtained results
Orsay virus CP-δ adopts a novel β-bracelet structural fold and incorporates into virions as a head fiber
Fiber proteins are commonly found in eukaryotic and prokaryotic viruses, where they play important roles in mediating viral attachment and host cell entry. They typically form trimeric structures and are incorporated into virions via noncovalent interactions. Orsay virus, a small RNA virus which specifically infects the laboratory model nematod
Rapid Identification of Major QTLS Associated With Near- Freezing Temperature Tolerance in Saccharomyces cerevisiae
Temperatures had a strong effect on many life history traits, including growth, development and reproduction. At near-freezing temperatures (0–4°C), yeast cells could trigger series of biochemical reactions to respond and adapt to the stress, protect them against sever cold and freeze injury. Different Saccharomyces cerevisiae strains vary greatly in their ability to grow at near-freezing temperatures. However, the molecular mechanisms that allow yeast cells to sustain this response are not yet fully understood and the genetic basis of tolerance and sensitivity to near-freeze stress remains unclear. Uncovering the genetic determinants of this trait is, therefore, of is of significant interest. In order to investigate the genetic basis that underlies near-freezing temperature tolerance in S. cerevisiae, we mapped the major quantitative trait loci (QTLs) using bulk segregant analysis (BSA) in the F2 segregant population of two Chinese indigenous S. cerevisiae strains with divergent tolerance capability at 4°C. By genome-wide comparison of single-nucleotide polymorphism (SNP) profiles between two bulks of segregants with high and low tolerance to near-freezing temperature, a hot region located on chromosome IV was identified tightly associated with the near-freezing temperature tolerance. The Reciprocal hemizygosity analysis (RHA) and gene deletion was used to validate the genes involved in the trait, showed that the gene NAT1 plays a role in the near-freezing temperature tolerance. This study improved our understanding of the genetic basis of the variability of near-freezing temperature tolerance in yeasts. The superior allele identified could be used to genetically improve the near-freezing stress adaptation of industrial yeast strains
Potential implementation strategies, acceptability, and feasibility of new and repurposed TB vaccines
Recently, two Phase 2B tuberculosis vaccine trials reported positive efficacy results in adolescents and adults. However, experience in vaccinating these age groups is limited. We identified potential implementation strategies for the M72/AS01E vaccination and BCG-revaccination-like candidates and explored their acceptability and feasibility. We conducted in-depth semi-structured interviews among key decision makers to identify implementation strategies and target groups in South Africa, India, and China. Thematic and deductive analysis using a coding framework were used to identify themes across and within settings. In all three countries there was interest in novel TB vaccines, with school-attending adolescents named as a likely target group. In China and India, older people were also identified as a target group. Routine vaccination was preferred in all countries due to stigma and logistical issues with targeted mass campaigns. Perceived benefits for implementation of M72/AS01E were the likely efficacy in individuals with Mycobacterium tuberculosis (Mtb) infection and efficacy for people living with HIV. Perceived challenges for M72/AS01E included the infrastructure and the two-dose regimen required. Stakeholders valued the familiarity of BCG but were concerned about the adverse effects in people living with HIV, a particular concern in South Africa. Implementation challenges and opportunities were identified in all three countries. Our study provides crucial information for implementing novel TB vaccines in specific target groups and on country specific acceptability and feasibility. Key groups for vaccine implementation in these settings were identified, and should be included in clinical trials and implementation planning
Functional interplay between SA1 and TRF1 in telomeric DNA binding and DNA-DNA pairing
Proper chromosome alignment and segregation during mitosis depend on cohesion between sister chromatids. Cohesion is thought to occur through the entrapment of DNA within the tripartite ring (Smc1, Smc3 and Rad21) with enforcement from a fourth subunit (SA1/SA2). Surprisingly, cohesin rings do not play a major role in sister telomere cohesion. Instead, this role is replaced by SA1 and telomere binding proteins (TRF1 and TIN2). Neither the DNA binding property of SA1 nor this unique telomere cohesion mechanism is understood. Here, using single-molecule fluorescence imaging, we discover that SA1 displays two-state binding on DNA: searching by one-dimensional (1D) free diffusion versus recognition through subdiffusive sliding at telomeric regions. The AT-hook motif in SA1 plays dual roles in modulating non-specific DNA binding and subdiffusive dynamics over telomeric regions. TRF1 tethers SA1 within telomeric regions that SA1 transiently interacts with. SA1 and TRF1 together form longer DNA-DNA pairing tracts than with TRF1 alone, as revealed by atomic force microscopy imaging. These results suggest that at telomeres cohesion relies on the molecular interplay between TRF1 and SA1 to promote DNA-DNA pairing, while along chromosomal arms the core cohesin assembly might also depend on SA1 1D diffusion on DNA and sequence-specific DNA binding
Potential implementation strategies, acceptability, and feasibility of new and repurposed TB vaccines
Recently, two Phase 2B tuberculosis vaccine trials reported positive efficacy results in adolescents and adults. However, experience in vaccinating these age groups is limited. We identified potential implementation strategies for the M72/AS01 vaccination and BCG-revaccination-like candidates and explored their acceptability and feasibility. We conducted in-depth semi-structured interviews among key decision makers to identify implementation strategies and target groups in South Africa, India, and China. Thematic and deductive analysis using a coding framework were used to identify themes across and within settings. In all three countries there was interest in novel TB vaccines, with school-attending adolescents named as a likely target group. In China and India, older people were also identified as a target group. Routine vaccination was preferred in all countries due to stigma and logistical issues with targeted mass campaigns. Perceived benefits for implementation of M72/AS01 were the likely efficacy in individuals with Mycobacterium tuberculosis (Mtb) infection and efficacy for people living with HIV. Perceived challenges for M72/AS01 included the infrastructure and the two-dose regimen required. Stakeholders valued the familiarity of BCG but were concerned about the adverse effects in people living with HIV, a particular concern in South Africa. Implementation challenges and opportunities were identified in all three countries. Our study provides crucial information for implementing novel TB vaccines in specific target groups and on country specific acceptability and feasibility. Key groups for vaccine implementation in these settings were identified, and should be included in clinical trials and implementation planning
ATM-Mediated Phosphorylation of Cortactin Involved in Actin Polymerization Promotes Breast Cancer Cells Migration and Invasion
Background/Aims: The ataxia-telangiectasia mutated (ATM) protein kinase is critical for the maintenance of genomic stability and acts as tumor suppressor. Although evidence shows that a DNA damage-independent ATM (oxidized ATM) may be involved in cancer progression, the underlying mechanism is still unclear. Methods: Immunohistochemistry, immunofluorescence and western blotting were applied to detect the levels of oxidized ATM. Transwell assay was used to detect the cell migration and invasion abilities in different treatments. Quantitative phosphoproteome analysis was performed using hypoxic BT549 cells, in the presence or absence of Ku60019, a specific inhibitor of ATM kinase. The phosphorylated cortactin, the target protein of oxidized ATM, was confirmed by immunoprecipitation-western blots and in vitro kinase assay. The functions of phosphorylated cortactin were studied by specific short hairpin RNA, site-directed mutation, transwell assay, and actin polymerization assay. Results: Enhanced oxidized ATM proteins were present not only in the advanced and invasive breast tumor tissues but also malignant hypoxic breast cancer cells, in the absence of DNA damage. Loss of ATM expression or inhibiting oxidized ATM kinase activity reduced breast cancer cell migration and invasion. Using quantitative phosphoproteomics approach, 333 oxidized ATM target proteins were identified, some of these proteins govern key signaling associated with gap junction, focal adhesion, actin cytoskeleton rearrangement. Cortactin, one of the biggest changed phospho-protein, is a novel oxidized ATM-dependent target in response to hypoxia. Mechanically, we reveal that hypoxia-activated ATM can enhance the binding affinity of cortactin with Arp2/3 complex by phosphorylating cortactin at serine 113, and as a result, in favor of breast cancer cell migration and invasion. Conclusion: Oxidized ATM can phosphorylate cortactin at serine 113, playing a critical role in promoting breast tumor cell mobility and invasion via actin polymerization
Substantial transition to clean household energy mix in rural China
The household energy mix has significant impacts on human health and climate, as it contributes greatly to many health- and climate-relevant air pollutants. Compared to the well-established urban energy statistical system, the rural household energy statistical system is incomplete and is often associated with high biases. Via a nationwide investigation, this study revealed high contributions to energy supply from coal and biomass fuels in the rural household energy sector, while electricity comprised ∼20%. Stacking (the use of multiple sources of energy) is significant, and the average number of energy types was 2.8 per household. Compared to 2012, the consumption of biomass and coals in 2017 decreased by 45% and 12%, respectively, while the gas consumption amount increased by 204%. Increased gas and decreased coal consumptions were mainly in cooking, while decreased biomass was in both cooking (41%) and heating (59%). The time-sharing fraction of electricity and gases (E&G) for daily cooking grew, reaching 69% in 2017, but for space heating, traditional solid fuels were still dominant, with the national average shared fraction of E&G being only 20%. The non-uniform spatial distribution and the non-linear increase in the fraction of E&G indicated challenges to achieving universal access to modern cooking energy by 2030, particularly in less-developed rural and mountainous areas. In some non-typical heating zones, the increased share of E&G for heating was significant and largely driven by income growth, but in typical heating zones, the time-sharing fraction was <5% and was not significantly increased, except in areas with policy intervention. The intervention policy not only led to dramatic increases in the clean energy fraction for heating but also accelerated the clean cooking transition. Higher income, higher education, younger age, less energy/stove stacking and smaller family size positively impacted the clean energy transition
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