Miracle-dz/UniFAR-FTUs huggingface dataset:
Elastic Scheduling of Parallel Real-Time Tasks with Discrete Utilizations

Elastic scheduling allows for online adaptation of real-time tasks' utilizations (via manipulation of each task's computational workload or period) in order to maintain system schedulability in case the utilization demand of one or more tasks changes. This is done currently by assigning each task a utilization (and therefore period or workload) from within a continuous range of acceptable values. While this works well for anytime tasks whose quality of service improves with duration or for tasks that can run at any rate within a given range, many computationally-elastic tasks have a specific workload for each distinct mode of operation and therefore cannot perform arbitrary amounts of work. Similarly, some period-elastic tasks must run at specific (e.g. harmonic) rates. Therefore, a discrete set of candidate utilizations per task must be accommodated in such cases. This paper provides a new elastic task model in which each task has a discrete set of possible utilizations (instead of a continuous range). This allows users to specify only relevant candidate periods and workloads for each task. The discrete nature of this model also allows each task to modify its workload and/or its period when changing its mode of operation, instead of adapting in only one dimension of task utilization. Elastic tasks thus can exploit both period elasticity and computational elasticity. This greatly increases both the diversity of adaptations available to each task and the kinds of real-time tasks relevant to elastic scheduling. We use the real-world example of real-time hybrid simulation as a motivating application domain with discretely computationally-elastic, period-elastic, and combined-elastic parallel real-time tasks under the Federated Scheduling paradigm. We prove the scheduling of these tasks to be NP-hard, and provide a pseudo-polynomial time scheduling algorithm. We then use this scheduling algorithm to implement the first virtual real-time hybrid simulation experiment in which discrete elastic adaptation of platform resource utilizations enables adaptive switching between controllers with differing computational demands. We also study the effects of scheduling tasks with discretized vs. continuous candidate utilizations.
Quantitative nascent proteome profiling by dual pulse labeling with O-propargyl-puromycin and stable isotope labeled amino acids

Monitoring translational regulation in response to environmental signals is crucial for understanding cellular proteostasis. However, only limited approaches are currently available for quantifying acute changes in protein synthesis induced by stimuli. Recently, a clickable puromycin analog, O-propargyl-puromycin (OPP), was developed and applied to label the C-termini of nascent polypeptide chains (NPCs). Following affinity purification via a click reaction, OPP allows for a proteomic analysis of NPCs. Despite its advantage, the affinity purification of NPCs using magnetic beads or resins inherently suffers from significant non-specific protein binding, which hinders accurate quantification of the nascent proteins. To address this issue, we employed dual pulse labeling of NPCs with both OPP and stable isotope labeled amino acids to distinguish bona fide NPCs from non-specific proteins, thereby enabling the accurate quantitative profiling of NPCs. We applied this method to dissecting the transcription-coupled translation responses and quantified ~3,000 nascent proteins. We found that the translation of a subset of ribosomal proteins (e.g., RPSA, RPLP0) as well as signaling proteins (e.g., BCAR3, EFNA1, DUSP1) was significantly repressed by transcription inhibition. Together, the present method provides an accurate and broadly applicable nascent proteome profiling for many biological applications at the level of translation.
Monocyte-specific changes in gene expression implicate LACTB2 and PLIN2 in Alzheimer’s disease

More than 50 genetic loci have been identified as being associated with Alzheimer’s disease (AD) from genome-wide association studies (GWAS) and many of these are involved in immune pathways and lipid metabolism. Therefore, we performed a transcriptome-wide association study (TWAS) of immune-relevant cells, to study the mis-regulation of genes implicated in AD. We used expression and genetic data from naive and induced CD14+ monocytes and two GWAS of AD to study genetically controlled gene expression in monocytes at different stages of differentiation and compared the results with those from TWAS of brain and blood. We identified nine genes with statistically independent TWAS signals, seven are known AD risk genes from GWAS: BIN1, PTK2B, SPI1, MS4A4A, MS4A6E, APOE and PVR and two, LACTB2 and PLIN2/ADRP, are novel candidate genes for AD. Three genes, SPI1, PLIN2 and LACTB2, are TWAS significant specifically in monocytes. LACTB2 is a mitochondrial endoribonuclease and PLIN2/ADRP associates with intracellular neutral lipid storage droplets (LSDs) which have been shown to play a role in the regulation of the immune response. Notably, LACTB2 and PLIN2 were not detected from GWAS alone.
Differences in metabolic and liver pathobiology induced by two dietary mouse models of nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic associated with key aspects of metabolic disease such as obesity and diabetes. The first stage of NAFLD is characterized by lipid accumulation in hepatocytes, but this can further progress into non-alcoholic steatohepatitis (NASH), fibrosis or cirrhosis, and hepatocellular carcinoma (HCC). A western diet, high in fats, sugars and cholesterol is linked to NAFLD development. Murine models are often used to experimentally study NAFLD, as they can display similar histopathological features as humans; however, there remains debate on which diet-induced model most appropriately and consistently mimics both human disease progression and pathogenesis. In this study, we performed a side-by-side comparison of two popular diet models of murine NAFLD/NASH and associated HCC: a high fat diet supplemented with 30% fructose water (HFHF) and a western diet high in cholesterol (WDHC), comparing them to a common grain-based chow diet (GBD). Mice on both experimental diets developed liver steatosis, while WDHC-fed mice had greater levels of hepatic inflammation and fibrosis than HFHF-fed mice. In contrast, HFHF-fed mice were more obese and developed more severe metabolic syndrome, with less pronounced liver disease. Despite these differences, WDHC-fed and HFHF-fed mice had similar tumour burdens in a model of diet-potentiated liver cancer. Response to diet and resulting phenotypes were generally similar between sexes, albeit delayed in females. Notably, although metabolic and liver disease phenotypes are often thought to progress in parallel, this study shows that modest differences in diet can significantly uncouple glucose homeostasis and liver damage. In conclusion, long-term feeding of either HFHF or WDHC are reliable methods to induce NASH and diet-potentiated liver cancer in mice of both sexes; however, the choice of diet involves a trade-off between severity of metabolic syndrome and liver damage.
Characterization of the condensed tannin (proanthocyanidin) from a group II sorghum

Most of the tannin in seeds of high-tannin bird-resistant group III sorghums [Sorghum bicolor] extracts readily into methanol or aqueous acetone. In contrast, tannin of group II sorghums is not extracted by these solvents but is extracted by methanol containing 1% (v/v) HCl. Group II sorghums have been reported to be nutritionally less harmful than group III types, presumably due to differences in their tannins. Purified tannin from a group II sorghum (IS 8768) was compared with tannin purified from a group III sorghum (DeKalb BR 64). No significant differences were found in the properties of the purified tannins. Tannin extractable only in acidic methanol is present along with methanol-extractable tannin in most group III sorghums, especially in immature grain. The differentially extractable tannins do not appear to have a precursor/product relationship
Germline APOBEC3B deletion in Asian women increases somatic hypermutation in breast cancer that is associated with Her2 subtype, PIK3CA mutations, immune activation, and increased survival

A 30-kb deletion that eliminates the coding region of APOBEC3B (A3B) is >5 times more common in women of Asian compared to European descent. This polymorphism creates a chimera with the APOBEC3A (A3A) coding region and A3B 3’UTR, and is associated with an increased risk for breast cancer in Asian women. Here, we explored the relationship between the A3B deletion polymorphism with tumour characteristics in Asian women. Using whole exome and whole transcriptome sequencing data of 527 breast tumours, we report that germline A3B deletion polymorphism leads to expression of the A3A-B hybrid isoform and increased APOBEC-associated somatic hypermutation. Hypermutated tumours, regardless of A3B germline status, were associated with the Her2 molecular subtype and PIK3CA mutations. Compared to non-hypermutated tumours, hypermutated tumours also had higher neoantigen burden, tumour heterogeneity and immune activation. Taken together, our results suggest that the germline A3B deletion polymorphism, via the A3A-B hybrid isoform, contributes to APOBEC-mutagenesis in a significant proportion of Asian breast cancers. In addition, APOBEC somatic hypermutation, regardless of A3B background, may be an important clinical biomarker for Asian breast cancers. Graphical Abstract
Rapid purification and metabolomic profiling of synaptic vesicles from mammalian brain

Neurons communicate by the activity-dependent release of small-molecule neurotransmitters packaged into synaptic vesicles (SVs). Although many molecules have been identified as neurotransmitters, technical limitations have precluded a full metabolomic analysis of synaptic vesicle content. Here, we present a workflow to rapidly isolate SVs and to interrogate their metabolic contents at a high-resolution using mass spectrometry. We validated the enrichment of glutamate in SVs of primary cortical neurons using targeted polar metabolomics. Unbiased and extensive global profiling of SVs isolated from these neurons revealed that the only detectable polar metabolites they contain are the established neurotransmitters glutamate and GABA. Finally, we adapted the approach to enable quick capture of SVs directly from brain tissue and determined the neurotransmitter profiles of diverse brain regions in a cell-type specific manner. The speed, robustness, and precision of this method to interrogate SV contents will facilitate novel insights into the chemical basis of neurotransmission.
Postural constraints recruit shorter-timescale processes into the non-Gaussian cascade processes

Healthy human postural sway exhibits strong intermittency, reflecting a richly interactive foundation of postural control. From a linear perspective, intermittent fluctuations might be interpreted as engagement and disengagement of complementary control processes at distinct timescales or from a nonlinear perspective, as cascade-like interactions across many timescales at once. The diverse control processes entailed by cascade-like multiplicative dynamics suggest specific non-Gaussian distributional properties at different timescales. Multiscale probability density function (PDF) analysis showed that when standing quietly while balancing a sand-filled tube with the two arms elicited non-Gaussianity profiles showing a negative-quadratic crossover between short and long timescales. A more stringent task of balancing a water-filled tube elicited simpler monotonic decreases in non-Gaussianity, that is, a positive-quadratic cancellation of the negative-quadratic crossover. Multiple known indices of postural sway governed the appearance or disappearance of the crossover. Finally, both tasks elicited lognormal distributions over progressively larger timescales. These results provide the first evidence that more stringent postural constraints recruit shorter-timescale processes into the non-Gaussian cascade processes, that indices of postural sway moderate this recruitment, and that more stringent postural constraints show stronger statistical hallmarks of cascade structure.
A generative modeling approach for interpreting population-level variability in brain structure

Understanding how neural structure varies across individuals is critical for characterizing the effects of disease, learning, and aging on the brain. However, disentangling the different factors that give rise to individual variability is still an outstanding challenge. In this paper, we introduce a deep generative modeling approach to find different modes of variation across many individuals. To do this, we start by training a variational autoencoder on a collection of auto-fluorescence images from a little over 1,700 mouse brains at 25 micron resolution. To then tap into the learned factors and validate the model’s expressiveness, we developed a novel bi-directional technique to interpret the latent space–by making structured perturbations to both, the high-dimensional inputs of the network, as well as the low-dimensional latent variables in its bottleneck. Our results demonstrate that through coupling generative modeling frameworks with structured perturbations, it is possible to probe the latent space to provide insights into the representations of brain structure formed in deep neural networks.
Cooperative interactions among females and even more extraordinary sex ratios

Hamilton’s local mate competition theory provided an explanation for extraordinary female biased sex ratios in a range of organisms. When mating takes place locally, in structured populations, a female biased sex ratio is favoured to reduce competition between related males, and to provide more mates for males. However, there are a number of wasp species where the sex ratios appear to more female biased than predicted by Hamilton’s theory. We investigated theoretically the extent to which cooperative interactions between related females can interact with local mate competition to favour even more female biased sex ratios. We found that: (i) cooperative interactions between females can lead to sex ratios that are more female biased than predicted by local competition theory alone; (ii) sex ratios can be more female biased when the cooperative interactions are offspring helping parents before dispersal, rather than cooperation between siblings after dispersal. Our results can be applied to a range of organisms, and provide an explanation for the extreme sex ratio biases that have been observed in Sclerodermus and Melittobia wasps.
Akt is required for artery formation during embryonic vascular development

One of the first events in the development of the cardiovascular system is morphogenesis of the main embryonic artery, the dorsal aorta (DA). The DA forms via a conserved genetic process mediated by the migration, specification, and organization of endothelial progenitor cells into a distinct arterial lineage and vessel type. Several angiogenic factors activate different signaling pathways to control DA formation, however the physiological relevance of distinct kinases in this complex process remains unclear. Here, we identify the role of Akt during early vascular development by generating mutant zebrafish lines that lack expression of akt isoforms. Live cell imaging coupled with single cell RNA sequencing of akt mutants reveal that Akt is required for proper development of the DA by sustaining arterial cell progenitor specification and segregation. Mechanistically, inhibition of active FOXO in akt mutants rescues impaired arterial development but not the expression of arterial markers, whereas Notch activation rescues arterial marker expression. Our work suggests that Akt activity is critical for early artery development, in part via FOXO and Notch-mediated regulation.
Elemental composition of phytoplankton in a subtropical lake: X-ray microanalytical studies on the dominant algae Spirulina platensis (Cyanophyta) and Cyclotella meneghiniana (Bacillariophyceae)

Studies were carried out on the phytoplankton of a subtropical polluted lake (Lake Maryut, Egypt) over a 1 year sampling period. The elemental composition of two major algal constituents-Spirulina platensis (Cyanophyta) and Cyclotella meneghiniana (Bacillariophyceae)—was determined from mixed plankton samples using electron-probe X-ray microanalysis. X-ray emission spectra obtained from S. platensis revealed a wide range of detectable elements. Clear positive (e.g. K-P, Na-Cl) and negative (e.g. Na-S, P-Cl) statistical correlations were interpreted in terms of elemental associations and compartmentation within the cell. C. meneghiniana had a broadly similar range of elements, but differed in the additional presence of Al and frequent peaks of Fe and Cu. The high concentration of Si reduced the detectability of other elements, causing a general reduction in mass fraction levels. Comparison of correlation coefficients derived from four sets of data revealed a clear pattern of elemental occurrence in the cel.
Introgression from Oryza meridionalis into domesticated rice Oryza sativa results in shoot-based iron tolerance

Iron (Fe) toxicity is one of the most common mineral disorders affecting rice (Oryza sativa) production in flooded lowland fields. Oryza meridionalis is endemic from Northern Australia and grows in regions with Fe rich soils, making it a candidate for use in adaptive breeding. Aiming to understand tolerance mechanisms in rice, we screened a population of interspecific introgression lines (IL) from a cross between O. sativa and O. meridionalis for the identification of QTLs contributing to Fe toxicity tolerance. Six putative QTLs were identified. A line carrying one introgression from O. meridionalis on chromosome 9 associated with one QTL was highly tolerant despite very high shoot Fe concentrations. Physiological, biochemical, ionomic and transcriptomic analyses showed that the IL tolerance could partly be explained by Fe retention in the leaf sheath and culm. We constructed the interspecific hybrid genome in silico for transcriptomic analysis, and identified differentially regulated introgressed genes from O. meridionalis that could be involved in shoot-based Fe tolerance, such as metallothioneins, glutathione S-transferases and transporters from ABC and MFS families. This is the first work to demonstrate that introgressions of O. meridionalis into the O. sativa genome can confer increased tolerance to excess Fe. Highlight We identified QTLs associated with iron tolerance derived from O. meridionalis, and characterized their physiological basis in O. sativa.
A Deep Learning Semiparametric Regression for Adjusting Complex Confounding Structures

Deep Treatment Learning (deepTL), a robust yet efficient deep learning-based semiparametric regression approach, is proposed to adjust the complex confounding structures in comparative effectiveness analysis of observational data, e.g. electronic health record (EHR) data, in which complex confounding structures are often embedded. Specifically, we develop a deep learning neural network with a score-based ensembling scheme for flexible function approximation. An improved semiparametric procedure is further developed to enhance the performance of the proposed method under finite sample settings. Comprehensive numerical studies have demonstrated the superior performance of the proposed methods as compared with existing methods, with a remarkably reduced bias and mean squared error in parameter estimates. The proposed research is motivated by a post-surgery pain study, which is also used to illustrate the practical application of deepTL. Finally, an R package, “deepTL”, is developed to implement the proposed method.
Differences in Belowground Heterogeneity Within a Restoration of a Dewatered Reservoir in Southwestern Wisconsin

Integrating belowground properties into ecological restoration is critical for understanding aboveground response. We investigated a recently dewatered basin in southwestern Wisconsin to test hypotheses related to the magnitude, heterogeneity, and spatial dependence of physicochemical properties between sediments and buried soils. A spatial grid was established in a 2.4‐ha basin to sample 7 physical and 13 chemical properties. Sediment depth (Sd) averaged 43 cm (std dev = 15) across the study area. The mean bulk density (BD) of the buried soils (1.41 g/cm3) was significantly greater than the sediments (0.97 g/cm3), which corresponded with a significantly higher soil moisture content (SMC) and hydraulic conductivity (Ks) of the sediments. Relative to one another, buried soils had significantly higher concentrations of Bray P, Cu, and Mn, whereas sediments had higher concentrations of Bray K, K, total phosphorus, Na, S, Al, and Ca and thus had a higher pH; Fe and B concentrations were similar between the sediments and the buried soil. Sediments were consistently less spatially heterogeneous than the buried soils. Using geostatistics, sediment BD and SMC displayed both small‐scale spatial structures and large‐scale trends, whereas Sd and the buried soil SMC displayed only small‐scale variability. Distance from the former dam was positively related to nine physicochemical properties and negatively related to only S, SMC, and the percentage of clay; no trends were found in the buried soils. These results demonstrate that damming, inundation, and dewatering due to dam removal yielded a spatially distinct and homogenized substrate relative to the soils that were buried.
Mega-phylogeny sheds light on SARS-CoV-2 spatial phylogenetic structure

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent RNA virus that spread around the planet in about 4 months. The consequences of this rapid spread on the virus evolution are under investigation. In this work, we analyzed ca. 9,000 SARS-CoV-2 genomes from Africa, America, Asia, Europe, and Oceania. We show that the virus is a complex of slightly different genetic variants that are unevenly distributed on Earth. Furthermore, we demonstrate that SARS-CoV-2 phylogeny is spatially structured. We hypothesize this could be the result of founder effects occurring as a consequence of, and local evolution occurring after, long-distance dispersal. In light of our results, we discuss how dispersal may constitute an opportunity for the virus to fix otherwise rare, and/or develop new, mutations. Based on previous studies, the possibility that this could significantly affect the virus phenotype is not remote.
Zuloagocardamum (Brassicaceae: Thelypodieae) a New Genus from the Andes Highlands of Northern Argentina

Abstract Zuloagocardamum jujuyensis , a new genus and species of Brassicaceae from fujuy Province in Argentina, is described and illustrated, and its phylogenetic relationships to nearest relatives are demonstrated. It resembles some genera of the tribe Thelypodieae, such as Chilocardamum and Weberbauera, but differs mainly by having a well-developed woody caudex with reduced leafless stems, rosulate, awl-shaped or linear, sessile, parallel-veined basal leaves conspicuously ciliate with simple trichomes, racemes much shorter than the basal leaves, torulose fruits, and mucilaginous seeds. Phylogenetic analyses, based on DNA sequences of nuclear ITS and plastid ndhF and trnL-F regions, place Z. jujuyensis in the tribe Thelypodieae, where it is related to species of Weberbauera, Englerocharis, and Parodiodoxa. However, it is morphologically different from species of all four genera by the character combinations above.