Miracle-dz/UniFAR-FTUs huggingface dataset:
Brd/BET Proteins Influence the Genome-Wide Localization of the Kaposi’s Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus Major Latency Proteins

The rhadinoviruses Kaposi’s Sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus (MHV-68) persist in infected hosts in a latent state that is characterized by the absence of virus production and by restricted viral gene expression. Their major latency protein, the latency-associated nuclear antigen (kLANA for KSHV and mLANA for MHV-68), is essential for viral genome maintenance and replication and involved in transcriptional regulation. Both kLANA and mLANA interact with cellular chromatin-associated proteins, among them the Bromodomain and Extra Terminal domain (Brd/BET) proteins, which recruit cellular and viral proteins to acetylated histones through their bromodomains and modulate cellular gene expression. Brd/BET proteins also play a role in the tethering, replication, segregation or integration of a diverse group of viral DNA genomes. In this study we explored if Brd/BET proteins influence the localization of the LANAs to preferential regions in the host chromatin and thereby contribute to kLANA- or mLANA-mediated transcriptional regulation. Using ChIP-Seq, we revealed a genome-wide co-enrichment of kLANA with Brd2/4 near cellular and viral transcriptional start sites (TSS). Treatment with I-BET151, an inhibitor of Brd/BET, displaced kLANA and Brd2/4 from TSS in the viral and host chromatin, but did not affect the direct binding of kLANA to kLANA-binding sites (LBS) in the KSHV latent origin of replication. Similarly, mLANA, but not a mLANA mutant deficient for binding to Brd2/4, also associated with cellular TSS. We compared the transcriptome of KSHV-infected with uninfected and kLANA-expressing human B cell lines, as well as a murine B cell line expressing mLANA or a Brd2/4-binding deficient mLANA mutant. We found that only a minority of cellular genes, whose TSS are occupied by kLANA or mLANA, is transcriptionally regulated by these latency proteins. Our findings extend previous reports on a preferential deposition of kLANA on cellular TSS and show that this characteristic chromatin association pattern is at least partially determined by the interaction of these viral latency proteins with members of the Brd/BET family of chromatin modulators.
Online Conversation Disentanglement with Pointer Networks

Huge amounts of textual conversations occur online every day, where multiple conversations take place concurrently. Interleaved conversations lead to difficulties in not only following the ongoing discussions but also extracting relevant information from simultaneous messages. Conversation disentanglement aims to separate intermingled messages into detached conversations. However, existing disentanglement methods rely mostly on handcrafted features that are dataset specific, which hinders generalization and adaptability. In this work, we propose an end-to-end online framework for conversation disentanglement that avoids time-consuming domain-specific feature engineering. We design a novel way to embed the whole utterance that comprises timestamp, speaker, and message text, and proposes a custom attention mechanism that models disentanglement as a pointing problem while effectively capturing inter-utterance interactions in an end-to-end fashion. We also introduce a joint-learning objective to better capture contextual information. Our experiments on the Ubuntu IRC dataset show that our method achieves state-of-the-art performance in both link and conversation prediction tasks.
A Search for Ultra-high-energy Neutrinos from TXS 0506+056 Using the Pierre Auger Observatory

Results of a search for ultra-high-energy neutrinos with the Pierre Auger Observatory from the direction of the blazar TXS 0506+056 are presented. They were obtained as part of the follow-up that stemmed from the detection of high-energy neutrinos and gamma rays with IceCube, Fermi-LAT, MAGIC, and other detectors of electromagnetic radiation in several bands. The Pierre Auger Observatory is sensitive to neutrinos in the energy range from 100 PeV to 100 EeV and in the zenith-angle range from θ = 60° to θ = 95°, where the zenith angle is measured from the vertical direction. No neutrinos from the direction of TXS 0506+056 have been found. The results were analyzed in three periods: one of 6 months around the detection of IceCube-170922 A, coinciding with a flare period of TXS 0506+056, a second one of 110 days during which the IceCube collaboration found an excess of 13 neutrinos from a direction compatible with TXS 0506+056, and a third one from 2004 January 1 up to 2018 August 31, over which the Pierre Auger Observatory has been taking data. The sensitivity of the Observatory is addressed for different spectral indices by considering the fluxes that would induce a single expected event during the observation period. For indices compatible with those measured by the IceCube collaboration the expected number of neutrinos at the Observatory is well below one. Spectral indices as hard as 1.5 would have to apply in this energy range to expect a single event to have been detected.
Promise for Whom? “Free-College” Programs and Enrollments by Race and Gender Classifications at Public, 2-Year Colleges

Promise programs are proliferating across the United States, with wide variation in their design. Using national data on 33 Promise programs affecting single, 2-year colleges, this study examines program effects on first-time, full-time college enrollments of students by race/ethnicity and gender classification. Results suggest Promise programs are associated with large percent increases in enrollments of Black and Hispanic students, especially students classified as females, at eligible colleges. Promise programs with merit requirements are associated with higher enrollment of White and Asian, Native Hawaiian, or Pacific Islander female students; those with income requirements are negatively associated with enrollment of most demographic groups. More generous Promise programs are associated with greater enrollment increases among demographic groups with historically higher levels of postsecondary attainment.
Subcellular relocalization and nuclear redistribution of the RNA methyltransferases TRMT1 and TRMT1L upon neuronal activation

RNA modifications are dynamic chemical entities that regulate RNA fate, and an avenue for environmental response in neuronal function. However, which RNA modifications may be playing a role in neuronal plasticity and environmental responses is largely unknown. Here we characterize the biochemical function and cellular dynamics of two human RNA methyltransferases previously associated with neurological dysfunction, TRMT1 and its homolog, TRMT1-like (TRMT1L). Using a combination of next-generation sequencing, LC-MS/MS, patient-derived cell lines and knockout mouse models, we confirm the previously reported dimethylguanosine (m 2,2 G) activity of TRMT1 in tRNAs, as well as reveal that TRMT1L, whose activity was unknown, is responsible for methylating a subset of cytosolic tRNA Ala (AGC) isoacceptors at position 26. Using a cellular in vitro model that mimics neuronal activation and long term potentiation, we find that both TRMT1 and TRMT1L change their subcellular localization upon neuronal activation. Specifically, we observe a major subcellular relocalization from mitochondria and other cytoplasmic domains (TRMT1) and nucleoli (TRMT1L) to different small punctate compartments in the nucleus, which are as yet uncharacterized. This phenomenon does not occur upon heat shock, suggesting that the relocalization of TRMT1 and TRMT1L is not a general reaction to stress, but rather a specific response to neuronal activation. Our results suggest that subcellular relocalization of RNA modification enzymes play a role in neuronal plasticity and transmission of information, presumably by addressing new targets.
COVID-19-Related Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a common and severe neurological disorder and is associated with high rates of mortality and morbidity. ICH is associated with old age and underlying conditions such as hypertension and diabetes mellitus. The COVID-19 pandemic is associated with neurological symptoms and complications including ICH. For instance, the mechanisms by which COVID-19 may contribute to hemorrhagic stroke may include both depletion of angiotensin converting enzyme 2 (ACE2) receptor and overactive immune response. In this study, we herein report three patients (0.25%) out of 1200 admissions with COVID-19 to our center between 1 May and August 4, 2020, who developed ICH. In addition, we will briefly discuss the possible pathophysiological mechanisms of COVID-19 infection in patients with ICH.
Shark conservation risks associated with the use of shark liver oil in SARS-CoV-2 vaccine development

The COVID-19 pandemic may create new demand for wildlife-generated products for human health, including a shark-derived ingredient used in some vaccines. Adjuvants are a vaccine component that increases efficacy, and some adjuvants contain squalene, a natural compound derived from shark liver oil which is found most abundantly in deep-sea sharks. In recent decades, there has been growing conservation concern associated with the sustainability of many shark fisheries. The need for a potentially massive number of adjuvant-containing SARS-CoV-2 vaccines may increase global demand for shark-derived squalene, with possible consequences for shark conservation, especially of vulnerable and understudied deep-sea species. A shift to non-animal-derived sources of squalene, which are similar in cost and identical in effectiveness, or an emphasis on increasing traceability and sustainability of shark-derived squalene from existing well-managed fisheries, could better support conservation and public health goals.
Deep Neural Networks Are Congestion Games: From Loss Landscape to Wardrop Equilibrium and Beyond

The theoretical analysis of deep neural networks (DNN) is arguably among the most challenging research directions in machine learning (ML) right now, as it requires from scientists to lay novel statistical learning foundations to explain their behaviour in practice. While some success has been achieved recently in this endeavour, the question on whether DNNs can be analyzed using the tools from other scientific fields outside the ML community has not received the attention it may well have deserved. In this paper, we explore the interplay between DNNs and game theory (GT), and show how one can benefit from the classic readily available results from the latter when analyzing the former. In particular, we consider the widely studied class of congestion games, and illustrate their intrinsic relatedness to both linear and non-linear DNNs and to the properties of their loss surface. Beyond retrieving the state-of-the-art results from the literature, we argue that our work provides a very promising novel tool for analyzing the DNNs and support this claim by proposing concrete open problems that can advance significantly our understanding of DNNs when solved.
OPA1 deficiency accelerates hippocampal synaptic remodelling and age-related deficits in learning and memory

Abstract A healthy mitochondrial network is essential for the maintenance of neuronal synaptic integrity. Mitochondrial and metabolic dysfunction contributes to the pathogenesis of many neurodegenerative diseases including dementia. OPA1 is the master regulator of mitochondrial fusion and fission and is likely to play an important role during neurodegenerative events. To explore this, we quantified hippocampal dendritic and synaptic integrity and the learning and memory performance of aged Opa1 haploinsufficient mice carrying the Opa1Q285X mutation (B6; C3-Opa1Q285STOP; Opa1+/−). We demonstrate that heterozygous loss of Opa1 results in premature age-related loss of spines in hippocampal pyramidal CA1 neurons and a reduction in synaptic density in the hippocampus. This loss is associated with subtle memory deficits in both spatial novelty and object recognition. We hypothesize that metabolic failure to maintain normal neuronal activity at the level of a single spine leads to premature age-related memory deficits. These results highlight the importance of mitochondrial homeostasis for maintenance of neuronal function during ageing.
Finite-size corrections in critical symmetry-resolved entanglement

In the presence of a conserved quantity, symmetry-resolved entanglement entropies are a refinement of the usual notion of entanglement entropy of a subsystem. For critical 1d quantum systems, it was recently shown in various contexts that these quantities generally obey entropy equipartition in the scaling limit, i.e. they become independent of the symmetry sector. In this paper, we examine the finite-size corrections to the entropy equipartition phenomenon, and show that the nature of the symmetry group plays a crucial role. In the case of a discrete symmetry group, the corrections decay algebraically with system size, with exponents related to the operators' scaling dimensions. In contrast, in the case of a U(1) symmetry group, the corrections only decay logarithmically with system size, with model-dependent prefactors. We show that the determination of these prefactors boils down to the computation of twisted overlaps.
On Offline Evaluation of Recommender Systems

In academic research, recommender models are often evaluated offline on benchmark datasets. The offline dataset is first split to train and test instances. All training instances are then modeled in a user-item interaction matrix, and supervised learning models are trained. Many such offline evaluations ignore the global timeline in the data, which leads to "data leakage": a model learns from future data to predict a current value, making the evaluation unrealistic. In this paper, we evaluate the impact of "data leakage" using two widely adopted baseline models, BPR and NeuMF, on MovieLens dataset. We show that accessing to different amount of future data may improve or deteriorate a model's recommendation accuracy. That is, ignoring the global timeline in offline evaluation makes the performance among recommendation models not comparable. Our experiments also show that more historical data in training set does not necessarily lead to better recommendation accuracy. We share our understanding of these observations and highlight the importance of preserving the global timeline. We also call for a revisit of recommender system offline evaluation.
Improving SMEs performance through supply chain flexibility and market agility: IT orchestration perspective

ABSTRACT In a context of competitive pressure and uncertain socioeconomic change, this research examines a key component of successful business performance: the capacity to orchestrate information technologies (IT) resources. The study also explores the effect of supply chain flexibility and market agility and their role in SME performance, including responsiveness to customer needs and the speed of new product launches. Lastly, this study focuses on e-procurement application development given the strategic position of purchasing activity in companies. The conceptual framework is tested using data gathered from 126 French SMEs. Drawing upon resource orchestration theory, the empirical results provide useful guidelines for SMEs that wish to invest in e-procurement tools to enhance competitiveness and performance.
The Impact of Video Gaming Terminals on Casinos and State and Local Tax Revenue

In 2012, Illinois passed legislation allowing video gaming terminals (VGTs) outside of casinos. This legislation was passed to increase tax revenues from gambling in a market that had seen decreases in revenues and admissions over the past 8 years. VGTs may substitute for casino gambling and have a negative impact on casino and tax revenue. Using ordinary least squares and vector autoregressive models, we find that casino slot revenues decrease by about 0.05 percent for each 1 percent increase in VGT revenues. Admissions decrease by about eleven people per VGT. A Granger causality test suggests causation is running from VGTs to admissions. Thus, there is substitution between VGTs and casino gambling but not so large as to reduce tax revenue. Overall tax revenue from gambling, both casino and VGT, has increased for Illinois. However, local communities where casinos are located have experienced declines in casino tax revenue that have exceeded the gains from VGT revenue.
Markov chains on finite fields with deterministic jumps

We study the Markov chain on $\mathbf{F}_p$ obtained by applying a function $f$ and adding $\pm\gamma$ with equal probability. When $f$ is a linear function, this is the well-studied Chung--Diaconis--Graham process. We consider two cases: when $f$ is the extension of a rational function which is bijective, and when $f(x)=x^2$. In the latter case, the stationary distribution is not uniform and we characterize it when $p=3\pmod{4}$. In both cases, we give an almost linear bound on the mixing time, showing that the deterministic function dramatically speeds up mixing. The proofs involve establishing bounds on exponential sums over the union of short intervals.
Entropy and the Brain: An Overview

Entropy is a powerful tool for quantification of the brain function and its information processing capacity. This is evident in its broad domain of applications that range from functional interactivity between the brain regions to quantification of the state of consciousness. A number of previous reviews summarized the use of entropic measures in neuroscience. However, these studies either focused on the overall use of nonlinear analytical methodologies for quantification of the brain activity or their contents pertained to a particular area of neuroscientific research. The present study aims at complementing these previous reviews in two ways. First, by covering the literature that specifically makes use of entropy for studying the brain function. Second, by highlighting the three fields of research in which the use of entropy has yielded highly promising results: the (altered) state of consciousness, the ageing brain, and the quantification of the brain networks’ information processing. In so doing, the present overview identifies that the use of entropic measures for the study of consciousness and its (altered) states led the field to substantially advance the previous findings. Moreover, it realizes that the use of these measures for the study of the ageing brain resulted in significant insights on various ways that the process of ageing may affect the dynamics and information processing capacity of the brain. It further reveals that their utilization for analysis of the brain regional interactivity formed a bridge between the previous two research areas, thereby providing further evidence in support of their results. It concludes by highlighting some potential considerations that may help future research to refine the use of entropic measures for the study of brain complexity and its function. The present study helps realize that (despite their seemingly differing lines of inquiry) the study of consciousness, the ageing brain, and the brain networks’ information processing are highly interrelated. Specifically, it identifies that the complexity, as quantified by entropy, is a fundamental property of conscious experience, which also plays a vital role in the brain’s capacity for adaptation and therefore whose loss by ageing constitutes a basis for diseases and disorders. Interestingly, these two perspectives neatly come together through the association of entropy and the brain capacity for information processing.
Covid-19: Suicidal thoughts increased in young adults during lockdown, UK study finds

Rates of suicidal thoughts have increased during lockdown, especially among young adults, a longitudinal study has found.1 Research published in the British Journal of Psychiatry found that women, young adults, socially disadvantaged people, and people with pre-existing mental health problems reported the worst mental health outcomes in the initial six week period of national lockdown. The study—funded by the Samaritans, the Scottish Association for Mental Health, and the Mindstep Foundation—claims to be the most detailed examination to date of the mental health of UK adults in the weeks after they were instructed to stay at home, on 23 March 2020. Researchers surveyed a national …
Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa

Objective: Dolutegravir exposure at conception was associated with a preliminary signal of increased infant neural tube defect risk. As low maternal folate levels are linked with neural tube defects, we aimed to assess serum folate concentrations in women starting dolutegravir. Design: We analysed serum folate concentrations from stored plasma among women enrolled in the South African ADVANCE trial. Methods: We compared changes in mean serum folate and occurrence of low serum folate (<14.0 nmol/l) at weeks 0, 12 and 24 across study arms. In ADVANCE, 1053 treatment-naïve participants were randomized to initiate tenofovir–alafenamide/emtricitabine + dolutegravir (TAF/FTC + DTG), tenofovir–disoproxil–fumarate (TDF)/FTC + DTG or TDF/FTC/efavirenz (EFV). Results: Analysis includes 406 females, mean age 31.5 years and baseline CD4+ cell count 356 cells/μl. At baseline, folate concentrations were similar across treatment arms. However, serum folate increased over 12 weeks in the TAF/FTC + DTG arm (+4.0 ± 8.1 nmol/l), while folate concentrations decreased slightly in the TDF/FTC + DTG arm (−1.8 ± 8.9 nmol/l) and decreased in the TDF/FTC/EFV arm (−5.9 ± 8.1 nmol/l). Women taking TDF/FTC/EFV had low folate concentrations at both 12 and 24 weeks compared with the other arms (P < 0.001). Of 26 women who became pregnant on study before week 24, folate concentrations increased between baseline and 12 weeks by a mean 2.4 ± 7.1 nmol/l in the TAF/FTC + DTG arm and 2.3 ± 8.4 nmol/l in the TDF/FTC + DTG arm, but decreased by −3.3 ± 8.1 with TDF/FTC/EFV arm. Conclusion: Unexpectedly, no declines were noted in the dolutegravir-containing arms, and concentrations were considerably higher than in the EFV arm. The possibility that dolutegravir may block cellular uptake of folate warrants investigation.