Call Sequence Prediction through Probabilistic Calling Automata

Predicting a sequence of upcoming function calls is important for optimizing programs written in modern managed languages (e.g., Java, Javascript, C#.) Existing function call predictions are mainly built on statistical patterns, suitable for predicting a single call but not a sequence of calls. This paper presents a new way to enable call sequence prediction, which exploits program structures through Probabilistic Calling Automata (PCA), a new program representation that captures both the inherent ensuing relations among function calls, and the probabilistic nature of execution paths. It shows that PCA-based prediction outperforms existing predictions, yielding substantial speedup when being applied to guide Just-In-Time compilation. By enabling accurate, efficient call sequence prediction for the first time, PCA-based predictors open up many new opportunities for dynamic program optimizations

Task-Based Cognitive Fatigability for Older Adults and Validation of Mental Fatigability Subscore of Pittsburgh Fatigability Scale

Cognitive fatigue and cognitive fatigability are distinct constructs. Cognitive fatigue reflects perception of cognitive fatigue outside of the context of activity level and duration and can be reliably assessed via established instruments such as the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). In contrast, cognitive fatigability reflects change in fatigue levels quantified within the context of the level and duration of cognitive activity, and currently there are no reliable measures of cognitive fatigability. A recently published scale, the Pittsburgh Fatigability Scale (PFS), attempts to remedy this problem with a focus on the aged population. While the physical fatigability subscore of PFS has been validated using physical activity derived measures, the mental fatigability subscore of PFS remains to be tested against equivalent measures derived from cognitive activities. To this end, we recruited 35 older, healthy adult participants (mean age 73.77 ± 5.9) to complete the PFS as well as a prolonged continuous performance of a Stroop task (>2 h). Task-based assessments included time-on-task changes in self-reported fatigue scores (every 20 min), reaction time, and pupil diameter. Defining subjective fatigability, behavioral fatigability, and physiologic/autonomic fatigability to be the slope of change over time-on-task in the above three assessed variables, we found that the PFS mental subscore was not correlated with any of the three task-based fatigability measures. Instead, the PFS mental subscore was correlated with trait level fatigue measures FSS (ρ = 0.63, p < 0.001), and MFIS cognitive subsection (ρ = 0.36, p = 0.03). This finding suggested that the PFS mental fatigability subscore may not be an adequate measure of how fatigued one becomes after a given amount of mental work. Further development efforts are needed to create a self-report scale that reliably captures cognitive fatigability in older adults

Up-Converting Nanoparticle-Based Immunochromatographic Strip for Multi-Residue Detection of Three Organophosphorus Pesticides in Food

Organophosphorus (OP) pesticides are widely used to control pests because of their high activity. This study described a rapid and sensitive lateral flow immunochromatographic (LFIC) assay based on up-converting nanoparticles (UCNPs) for multi-residue detection of three OP pesticides. The developed assay integrated novel fluorescent material UCNPs labeled with a broad-specific monoclonal antibody. Based on the competitive platform by immobilized antigen in the test zone, the optimized UCNPs-LFIC assay enabled sensitive detection for parathion, parathion-methyl, and fenitrothion with IC50 of 3.44, 3.98, and 12.49 ng/mL (R2 ≥ 0.9776) within 40 min. The detectable ability ranged from 0.98 to 250 ng/mL. There was no cross-reactivity with fenthion, phoxim, isocarbophos, chlorpyrifos, or triazophos, even at a high concentration of 500 ng/mL. Matrix interference from various agricultural products was also studied in food sample detection. In the spiked test, recoveries of the three OP pesticides ranged from 67 to 120% and relative standard deviations were below 19.54%. These results indicated that the proposed strip assay can be an alternative screening tool for rapid detection of the three OP pesticides in food samples

A compendium of genetic regulatory effects across pig tissues

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.</p

Genomic data for 78 chickens from 14 populations

Background: Since the domestication of the red jungle fowls (Gallus gallus; dating back to~10 000 B.P.) in Asia, domestic chickens (Gallus gallus domesticus) have been subjected to the combined effects of natural selection and human-driven artificial selection; this has resulted in marked phenotypic diversity in a number of traits, including behavior, body composition, egg production, and skin color. Population genomic variations through diversifying selection have not been fully investigated. Findings: The whole genomes of 78 domestic chickens were sequenced to an average of 18-fold coverage for each bird. By combining this data with publicly available genomes of five wild red jungle fowls and eight Xishuangbanna game fowls, we conducted a comprehensive comparative genomics analysis of 91 chickens from 17 populations. After aligning ~21.30 gigabases (Gb) of high-quality data from each individual to the reference chicken genome, we identified ~6.44 million (M) single nucleotide polymorphisms (SNPs) for each population. These SNPs included 1.10 M novel SNPs in 17 populations that were absent in the current chicken dbSNP (Build 145) entries. Conclusions: The current data is important for population genetics and further studies in chickens and will serve as a valuable resource for investigating diversifying selection and candidate genes for selective breeding in chickens.Peer reviewedAnimal Scienc

PigBiobank: a valuable resource for understanding genetic and biological mechanisms of diverse complex traits in pigs

© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] fully unlock the potential of pigs as both agricultural species for animal-based protein food and biomedical models for human biology and disease, a comprehensive understanding of molecular and cellular mechanisms underlying various complex phenotypes in pigs and how the findings can be translated to other species, especially humans, are urgently needed. Here, within the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we build the PigBiobank (http://pigbiobank.farmgtex.org) to systematically investigate the relationships among genomic variants, regulatory elements, genes, molecular networks, tissues and complex traits in pigs. This first version of the PigBiobank curates 71 885 pigs with both genotypes and phenotypes from over 100 pig breeds worldwide, covering 264 distinct complex traits. The PigBiobank has the following functions: (i) imputed sequence-based genotype-phenotype associations via a standardized and uniform pipeline, (ii) molecular and cellular mechanisms underlying trait-associations via integrating multi-omics data, (iii) cross-species gene mapping of complex traits via transcriptome-wide association studies, and (iv) high-quality results display and visualization. The PigBiobank will be updated timely with the development of the FarmGTEx-PigGTEx project, serving as an open-access and easy-to-use resource for genetically and biologically dissecting complex traits in pigs and translating the findings to other species.National Natural Science Foundation of China [32022078]; National Key R&D Program of China [2022YFF1000900]; Local Innovative and Research Teams Project of Guangdong Province [2019BT02N630]; China Agriculture Research System [CARS-35]. Funding for open access charge: National Natural Science Foundation of China [32022078].Peer reviewe

Causal interactions in brain networks predict pain levels in trigeminal neuralgia

Trigeminal neuralgia (TN) is a highly debilitating facial pain condition. Magnetic resonance imaging (MRI) is the main method for generating insights into the central mechanisms of TN pain in humans. Studies have found both structural and functional abnormalities in various brain structures in TN patients as compared with healthy controls. Whereas studies have also examined aberrations in brain networks in TN, no studies have to date investigated causal interactions in these brain networks and related these causal interactions to the levels of TN pain. We recorded fMRI data from 39 TN patients who either rested comfortably in the scanner during the resting state session or tracked their pain levels during the pain tracking session. Applying Granger causality to analyze the data and requiring consistent findings across the two scanning sessions, we found 5 causal interactions, including: (1) Thalamus → dACC, (2) Caudate → Inferior temporal gyrus, (3) Precentral gyrus → Inferior temporal gyrus, (4) Supramarginal gyrus → Inferior temporal gyrus, and (5) Bankssts → Inferior temporal gyrus, that were consistently associated with the levels of pain experienced by the patients. Utilizing these 5 causal interactions as predictor variables and the pain score as the predicted variable in a linear multiple regression model, we found that in both pain tracking and resting state sessions, the model was able to explain ∼36 % of the variance in pain levels, and importantly, the model trained on the 5 causal interaction values from one session was able to predict pain levels using the 5 causal interaction values from the other session, thereby cross-validating the models. These results, obtained by applying novel analytical methods to neuroimaging data, provide important insights into the pathophysiology of TN and could inform future studies aimed at developing innovative therapies for treating TN

miR-93-5p knockdown repressed hepatocellular carcinoma progression via increasing ERBB4 and TETs-dependent DNA demethylation

Background microRNAs (miRNAs) are involved in hepatocellular carcinoma (HCC) development and can control gene expression via directly targeting or regulating DNA methylation. This research aims to analyse the mechanism of miR-93-5p on HCC progression. Methods miR-93-5p, Erb-B2 receptor tyrosine kinase 4 (ERBB4) and ten-eleven translocation methyl-cytosine dioxygenases (TET1, TET2 and TET3) abundances were measured via quantitative reverse transcription polymerase chain reaction and Western blotting. The binding interaction was examined by dual-luciferase reporter analysis and chromatin immunoprecipitation. Cell proliferation and apoptosis were assessed via Cell Counting Kit-8, colony formation and flow cytometry. The DNA methylation of ERBB4 was detected via specific polymerase chain reaction. SNU-449 cells were subcutaneously inoculated into the BALB/c nude mice to establish the in vivo model for HCC, and the in vivo function of miR-93-5p was analysed by intratumoral injections of miR-93-5p antogomir. Results miR-93-5p abundance was enhanced and ERBB4 level was reduced in HCC tumour tissues of 62 patients and HCC cell lines, in contrast with that in paired normal tissues of 62 patients and normal cell lines. ERBB4 was targeted by miR-93-5p. miR-93-5p knockdown or ERBB4 overexpression repressed HCC cell proliferation and promoted apoptosis via decreasing cell viability and colony ability and inducing cycle arrest. ERBB4 silence attenuated the influence of miR-93-5p knockdown on cell proliferation and apoptosis. ERBB4 promoter DNA methylation level was enhanced in HCC samples and cell lines, and ERBB4 abundance was increased via TETs (TET1, TET2 and TET3). miR-93-5p targeted TETs to modulate ERBB4 abundance. TETs silence relieved the influence of miR-93-5p knockdown on cell proliferation and apoptosis. miR-93-5p knockdown decreased HCC growth in a xenograft model. Conclusion miR-93-5p knockdown repressed the progression of HCC via increasing ERBB4 and TETs-dependent DNA demethylation