Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of MEF2B, EBF1, and IL6R as Direct Gene Targets of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Critical for EBV-Infected B-Lymphocyte Survival

ABSTRACT Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is the EBV-encoded nuclear antigen and sequence-specific DNA binding protein required for viral origin binding and episome maintenance during latency. EBNA1 can also bind to numerous sites in the cellular genome and can provide a host cell survival function, but it is not yet known how EBNA1 sequence-specific binding is responsible for host cell survival. Here, we integrate EBNA1 chromatin immunoprecipitation sequencing (ChIP-Seq) with transcriptome sequencing (RNA-Seq) after EBNA1 depletion to identify cellular genes directly regulated by EBNA1 that are also essential for B-cell survival. We first compared EBNA1 ChIP-Seq patterns in four different EBV-positive cell types, including Burkitt lymphoma (BL) cells, nasopharyngeal carcinoma (NPC) cells, and lymphoblastoid cell lines (LCLs). EBNA1 binds to ∼1,000 sites that are mostly invariant among cell types and share a consensus recognition motif. We found that a large subset of EBNA1 binding sites are located proximal to transcription start sites and correlate genome-wide with transcription activity. EBNA1 bound to genes of high significance for B-cell growth and function, including MEF2B, IL6R, and EBF1. EBNA1 depletion from latently infected LCLs results in the loss of cell proliferation and the loss of gene expression for some EBNA1-bound genes, including MEF2B, EBF1, and IL6R. Depletion of MEF2B, EBF1, or IL6R partially phenocopies EBNA1 depletion by decreasing the cell growth and viability of cells latently infected with EBV. These findings suggest that EBNA1 binds to a large cohort of cellular genes important for cell viability and implicates EBNA1 as a critical regulator of transcription of host cell genes important for enhanced survival of latently infected cells. IMPORTANCE Epstein-Barr virus (EBV) latent infection is responsible for a variety of lymphoid and epithelial cell malignancies. EBNA1 is the EBV-encoded nuclear antigen that is consistently expressed in all EBV-associated cancers. EBNA1 is known to provide a host cell survival function, but the mechanism is not known. EBNA1 is a sequence-specific binding protein important for viral genome maintenance during latency. Here, by integrating ChIP-Seq and RNA-Seq, we demonstrate that EBNA1 binds directly to the promoter regulatory regions and upregulates the transcription of host genes that are important for the survival of EBV-infected cells. Identification of EBNA1 target genes provides potential new targets for therapeutic intervention in EBV-associated disease.
A Trust Reputation Architecture for Cloud Computing Environment

Cloud computing provides computational resources (processing, storage, software, network) to users in a scalable and dynamic way over the Internet. The use of these resources are impacted by issues related to privacy, security and trust. In this sense, this paper presents a trust reputation architecture applied in the cloud computing environment. The reputed trust is based on two trust indicators: objective and subjective ones. The objective trust indicator is based on the historical QoS indicators of a cloud provider. Then, the subjective trust indicator is composed of the users' feedbacks to the cloud providers. In order to evaluate the proposed architecture, simulations were performed using a P2P Network Simulator in order to emulate cloud providers and their clients. The evaluation results show the architecture applicability with low overhead.
Diminished Social Motivation Negatively Impacts Reputation Management: Autism Spectrum Disorders as a Case in Point

Human beings are endowed with a unique motivation to be included in social interactions. This natural social motivation, in turn, is thought to encourage behaviours such as flattery or self-deprecation aimed to ease interaction and to enhance the reputation of the individual who produces them. If this is the case, diminished social interest should affect reputation management. Here, we use Autism Spectrum Disorders (ASDs) –primarily characterised by pervasive social disinterest– as a model to investigate the effect of social motivation on reputation management. Children first rated a set of pictures and were then given the opportunity to inflate their initial ratings in front of an experimenter who declared that she had drawn the picture. Contrary to the controls, children with ASD did not enhance their ratings in the drawer's presence. Moreover, participants' flattery behaviour correlated with self-reports of social enjoyment. Our findings point to a link between diminished social interest and reputation management.
An improved P300 pattern in BCI to catch user’s attention

Objective. Brain-computer interfaces (BCIs) can help patients who have lost control over most muscles but are still conscious and able to communicate or interact with the environment. One of the most popular types of BCI is the P300-based BCI. With this BCI, users are asked to count the number of appearances of target stimuli in an experiment. To date, the majority of visual P300-based BCI systems developed have used the same character or picture as the target for every stimulus presentation, which can bore users. Consequently, users attention may decrease or be negatively affected by adjacent stimuli. Approach. In this study, a new stimulus is presented to increase user concentration. Honeycomb-shaped figures with 1–3 red dots were used as stimuli. The number and the positions of the red dots in the honeycomb-shaped figure were randomly changed during BCI control. The user was asked to count the number of the dots presented in each flash instead of the number of times they flashed. To assess the performance of this new stimulus, another honeycomb-shaped stimulus, without red dots, was used as a control condition. Main results. The results showed that the honeycomb-shaped stimuli with red dots obtained significantly higher classification accuracies and information transfer rates (p < 0.05) compared to the honeycomb-shaped stimulus without red dots. Significance. The results indicate that this proposed method can be a promising approach to improve the performance of the BCI system and can be an efficient method in daily application.
Virologic, Immunologic and Clinical Responses in Foreign-Born versus US-Born HIV-1 Infected Adults Initiating Antiretroviral Therapy: An Observational Cohort Study

Introduction Mortality rates within the first year of combination antiretroviral therapy (cART) initiation are several-fold higher in resource-limited countries than in resource-replete settings. However studies in western countries examining virologic, immunologic and clinical responses after cART initiation in indigenous versus non-indigenous populations have shown mixed results. This study aimed to determine whether there is a difference in these outcomes in a United States setting between foreign-born and US-born patients. Methods This retrospective observational cohort study of HIV-1 infected adults in one urban clinic in the United States compared virologic suppression, immune recovery and rates of AIDS defining events (ADEs) within the first year of cART using linear mixed effect models, log rank tests and Cox proportional hazard models. Data were analyzed for 94 foreign-born and 1242 US-born patients. Results Foreign-born patients were younger (31.7 years versus 38.5 years), more often female (38.3% versus 27.1%), less often injection drug users (3.2% versus 9.5%) or men who have sex with men (19.0% versus 54.5%), and had higher loss to follow-up rates (14.9% versus 6.2%). No significant differences were detected between the groups in suppression of plasma HIV-1 RNA, CD4+ cell recovery or development of ADEs. Conclusions During the first year on cART, virologic suppression, immune recovery and development of ADEs were comparable between foreign-born and US-born patients in care in a US clinic. Differential rates of loss to follow-up warrant further investigation in the foreign-born population.
Youth engagement in developing an implementation science research agenda on adolescent HIV testing and care linkages in sub-Saharan Africa

Background: The importance of youth engagement in designing, implementing and evaluating programs has garnered more attention as international initiatives seek to address the HIV crisis among this population. Adolescents, however, are not often included in HIV implementation science research and have not had opportunities to contribute to the development of HIV-related research agendas. Project Supporting Operational AIDS Research (SOAR), a United States Agency for International Development-funded global operations research project, involved youth living with HIV in a meeting to develop a strategic implementation science research agenda to improve adolescent HIV care continuum outcomes, including HIV testing and counseling (HTC) and linkage to care. Methods: Project SOAR convened a 2-day meeting of 50 experts, including four youth living with HIV. Participants examined the literature, developed research questions, and voted to prioritize these questions for the implementation science research agenda. This article presents the process of involving youth, how they shaped the course of discussions, and the resulting priority research gaps identified at the meeting. Results: Youth participation influenced working group discussions and the development of the implementation science agenda. Research gaps identified included how to engage vulnerable adolescents, determining the role that stigma, peers, and self-testing have in shaping adolescent HTC behaviors, and examining the costs of different HTC and linkage to care strategies. Conclusion: The meeting participants developed the research agenda to guide future implementation science research to improve HIV outcomes among adolescents in sub-Saharan Africa. This process highlighted the importance of youth in shaping implementation science research agendas and the need for greater youth engagement.
Kinetics of transmitter release at the calyx of Held synapse

Synaptic contacts mediate information transfer between neurons. The calyx of Held, a large synapse in the mammalian auditory brainstem, has been used as a model system for the mechanism of transmitter release from the presynaptic terminal for the last 20 years. By applying simultaneous recordings from pre- and postsynaptic compartments, the calcium-dependence of the kinetics of transmitter release has been quantified. A single pool of readily releasable vesicles cannot explain the time course of release during repetitive activity. Rather, multiple pools of vesicles have to be postulated that are replenished with distinct kinetics after depletion. The physical identity of vesicle replenishment has been unknown. Recently, it has become possible to apply total internal reflection fluorescent microscopy to the calyx terminal. This technique allowed the visualization of the dynamics of individual synaptic vesicles. Rather than recruitment of vesicles to the transmitter release sites, priming of tethered vesicles in the total internal reflection fluorescent field limited the number of readily releasable vesicles during sustained activity.
Reactive Oxygen Species Contribute to the Bactericidal Effects of the Fluoroquinolone Moxifloxacin in Streptococcus pneumoniae

ABSTRACT We studied the transcriptomic response of Streptococcus pneumoniae to the fluoroquinolone moxifloxacin at a concentration that inhibits DNA gyrase. Treatment of the wild-type strain R6, at a concentration of 10× the MIC, triggered a response involving 132 genes after 30 min of treatment. Genes from several metabolic pathways involved in the production of pyruvate were upregulated. These included 3 glycolytic enzymes, which ultimately convert fructose 6-phosphate to pyruvate, and 2 enzymes that funnel phosphate sugars into the glycolytic pathway. In addition, acetyl coenzyme A (acetyl-CoA) carboxylase was downregulated, likely leading to an increase in acetyl-CoA. When coupled with an upregulation in formate acetyltransferase, an increase in acetyl-CoA would raise the production of pyruvate. Since pyruvate is converted by pyruvate oxidase (SpxB) into hydrogen peroxide (H2O2), an increase in pyruvate would augment intracellular H2O2. Here, we confirm a 21-fold increase in the production of H2O2 and a 55-fold increase in the amount of hydroxyl radical in cultures treated during 4 h with moxifloxacin. This increase in hydroxyl radical through the Fenton reaction would damage DNA, lipids, and proteins. These reactive oxygen species contributed to the lethality of the drug, a conclusion supported by the observed protective effects of an SpxB deletion. These results support the model whereby fluoroquinolones cause redox alterations. The transcriptional response of S. pneumoniae to moxifloxacin is compared with the response to levofloxacin, an inhibitor of topoisomerase IV. Levofloxacin triggers the transcriptional activation of iron transport genes and also enhances the Fenton reaction.
Immune Investment Is Explained by Sexual Selection and Pace-of-Life, but Not Longevity in Parrots (Psittaciformes)

Investment in current reproduction should come at the expense of traits promoting future reproduction, such as immunity and longevity. To date, comparative studies of pace-of-life traits have provided some support for this, with slower paced species having greater immune function. Another means of investment in current reproduction is through secondary sexual characters (SSC). Investment in SSC's is considered costly, both in terms of immunity and longevity, with greater costs being borne by species with more elaborate traits. Yet within species, females prefer more ornate males and those males are typically immunologically superior. Because of this, predictions about the relationship between immunity and SSC's across species are not clear. If traits are costly, brighter species should have reduced immune function, but the opposite is true if SSC's arise from selection for more immunocompetent individuals. My approach was to investigate immune investment in relation to SSC's, pace-of-life and longevity while considering potentially confounding ecological factors. To do so I assessed leukocyte counts from in a novel group, the Psittaciformes. Investment in SSC's best explained investment in immunity: species with brighter plumage had higher leukocyte counts and those with a greater degree of sexual dichromatism had fewer. Ecological variables and pace-of-life models tended to be poor predictors of immune investment. However, shorter incubation periods were associated with lower leukocyte counts supporting the notion that species with a fast pace-of-life invest less in immunity. These results suggest that investment in reproduction in terms of fast pace-of-life and sexual dichromatism results in reduced immunity; however, investment in plumage colour per se does not impose a cost on immunity across species.
Using Grouped Linear Prediction and Accelerated Reinforcement Learning for Online Content Caching

Proactive caching is an effective way to alleviate peak-hour traffic congestion by prefetching popular contents at the wireless network edge. To maximize the caching efficiency requires the knowledge of content popularity profile, which however is often unavailable in advance. In this paper, we first propose a new linear prediction model, named grouped linear model (GLM) to estimate the future content requests based on historical data. Unlike many existing works that assumed the static content popularity profile, our model can adapt to the temporal variation of the content popularity in practical systems due to the arrival of new contents and dynamics of user preference. Based on the predicted content requests, we then propose a reinforcement learning approach with model-free acceleration (RLMA) for online cache replacement by taking into account both the cache hits and replacement cost. This approach accelerates the learning process in non-stationary environment by generating imaginary samples for Q-value updates. Numerical results based on real-world traces show that the proposed prediction and learning based online caching policy outperform all considered existing schemes.
Generalised joint hypermobility and neurodevelopmental traits in a non-clinical adult population

Background Generalised joint hypermobility (GJH) is reportedly overrepresented among clinical cases of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and developmental coordination disorder (DCD). It is unknown if these associations are dimensional and, therefore, also relevant among non-clinical populations. Aims To investigate if GJH correlates with sub-syndromal neurodevelopmental symptoms in a normal population. Method Hakim-Grahame's 5-part questionnaire (5PQ) on GJH, neuropsychiatric screening scales measuring ADHD and ASD traits, and a DCD-related question concerning clumsiness were distributed to a non-clinical, adult, Swedish population (n=1039). Results In total, 887 individuals met our entry criteria. We found no associations between GJH and sub-syndromal symptoms of ADHD, ASD or DCD. Conclusions Although GJH is overrepresented in clinical cases with neurodevelopmental disorders, such an association seems absent in a normal population. Thus, if GJH serves as a biomarker cutting across diagnostic boundaries, this association is presumably limited to clinical populations.
Ontogeny of Social Relations and Coalition Formation in Common Ravens (Corvus corax)

The social intelligence hypothesis, originally developed for primates to explain their high intelligence and large relative brain size, assumes that challenges posed by social life in complex societies with many group members lead to the evolution of advanced cognitive abilities. In birds, pair-bonded species have larger brains than non-pair bonded species, indicating that the quality of social relationships better predicts social complexity than group size. Ravens are a long-term monogamous and territorial species, renowned for their sophisticated socio-cognitive skills and complex social relationships. Notably, during their early years they live in fission-fusion-like non-breeder societies in which social relationships could be of particular importance. Here we observed the development of dominance and affiliative relationships in 12 hand-raised captive ravens, examining the influence of age, sex and kinship on social interactions. Furthermore, we investigated at which developmental step a stable hierarchy emerged, whether third-party interventions played a role and how selectively birds intervened in others’ conflicts. At 4-5 months post-fledging, we found an increase in socio-positive behaviour and a decrease in aggression, along with the establishment of a linear dominance rank hierarchy. In line with kin selection theory, siblings exhibited a greater degree of tolerance and engaged in more socio-positive behaviour. In their first few months, ravens frequently intervened in others’ conflicts but supported mainly the aggressor; later on, their support became more selective towards kin and close social partners. These findings indicate that ravens engage in sophisticated social behaviours and form stable relationships already in their first year of life.
Successful treatment of chromoblastomycosis of 10‐year duration due to Fonsecaea nubica

We report a case of chromoblastomycosis due to the presence of large plaque and verrucous hyperplasia lesions on the left upper limb, with elbow abnormal activities, in a 56‐year‐old male. The diagnosis of chromoblastomycosis was based on gross and microscopic morphologies, histopathological examination and clinical manifestation. Molecular tools were applied to identifying the causative agent Fonsecaea nubica, which is rarely reported to be associated with chromoblastomycosis. The patient was initially treated orally with terbinafine (250 mg/day) and itraconazole (200 mg/day), subsequently patient received thermotherapy (45‐50°C, 3 h/day) for 1 month. The patient was successfully cured. A literature review was performed to assess general features, treatment and outcome of chromoblastomycosis due to F. nubica. All the 5 reviewed patients were male, over 30 years old and their lesions occurred after traumatic inoculation.
Efficacy and safety of biologics in relapsing polychondritis: a French national multicentre study

Objectives To assess the efficacy and the safety of biologics in a cohort of patients with relapsing polychondritis (RP). Methods We conducted a French multicentre retrospective cohort study including patients treated with biologics for RP. Efficacy outcomes were clinical response (partial or complete) and complete response during the first 6 months of exposure, plus daily corticosteroid dose at 6 months. Other outcomes were adverse drug reactions (ADRs), persistence of biologics and factors associated with a response. Results This study included 41 patients exposed to 105 biologics (tumour-necrosis factor (TNF) inhibitors, n=60; tocilizumab, n=17; anakinra, n=15; rituximab, n=7; abatacept, n=6). Overall response rate during the first 6 months of exposure was 62.9%. Complete response rate was 19.0%. Reduced corticosteroid doses were highly variable among patients. ADRs were mostly infections (n=42). Reasons for biologic withdrawal (73.3%) were insufficient efficacy (34.3%; ranging from 23.5% for tocilizumab to 72.7% for etanercept), loss of efficacy (18.1%) and ADRs (20.9%; mostly for anakinra: 46.7%). Persistence was comparable among biologic classes. Among TNF inhibitors, the highest persistence was observed with adalimumab. Differences in clinical response rates were observed depending on biologics and organ involvement. There were trends towards a lower response rate in cases with associated myelodysplastic syndrome and for a higher response rate for nasal/auricular chondritis, sternal chondritis and concomitant exposure to non-biologic disease-modifying antirheumatic drugs. Conclusions This study describes the efficacy of biologics for refractory RP. However, the number of complete responses was low and there were concerns about the risk of ADRs, particularly infections.
3D-simulation of the turbulent wake behind a wind turbine

The paper relates to the simulation of the airflow around a wind turbine (WT) of the type ENERCON E66 with emphasis on the turbulent wake. The simulations were undertaken with the Computational Fluid Dynamics (CFD) software ANSYS FLUENT 6.3 using the LES technique for turbulence modeling. It is the aim of the work to capture the full three- dimensional turbulent flow behind a WT in a sufficient spatial and temporal resolution to generate information for wind loads of WTs in wind farm configuration. This information shall help to optimize wind farm layouts in the future. Using an incoming wind field that matches the requirements of the IEC-61400 for wind fields used in load calculations it was possible to simulate a full meandering turbulent wake. The turbulent features of the WT wake could be reproduced with numerical methods not using further assumptions but solely based on the WT geometry and the solution of the governing physical equations. The project is supported by ENERCON GmbH, Germany.
The Impact of Jump Distributions on the Implied Volatility of Variance

We consider a tractable affine stochastic volatility model that generalizes the seminal Heston model by augmenting it with jumps in the instantaneous variance process. In this framework, we consider both realized variance options and VIX options, and we examine the impact of the distribution of jumps on the associated implied volatility smile. We provide sufficient conditions for the asymptotic behavior of the implied volatility of variance for small and large strikes. In particular, by selecting alternative jump distributions, we show that one can obtain fundamentally different shapes of the implied volatility of variance smile---some clearly at odds with the upward-sloping volatility skew observed in variance markets.