Miracle-dz/UniFAR-FTUs huggingface dataset:
Interferon Regulatory Factor 2 Binding Protein 2 Is a New NFAT1 Partner and Represses Its Transcriptional Activity

ABSTRACT The nuclear factor of activated T cells (NFAT) family of transcription factors is expressed in a wide range of cell types and regulates genes involved in cell cycle, differentiation, and apoptosis. NFAT proteins share two well-conserved regions, the regulatory domain and the DNA binding domain. The N- and C-terminal ends are transactivation sites and show less sequence similarity, whereas their molecular functions remain poorly understood. Here, we identified a transcriptional repressor, interferon regulatory factor 2 binding protein 2 (IRF-2BP2), which specifically interacts with the C-terminal domain of NFAT1 among the NFAT family members. IRF-2BP2 was described as a corepressor by inhibiting both enhancer-activated and basal transcription. Gene reporter assays demonstrated that IRF-2BP2 represses the NFAT1-dependent transactivation of NFAT-responsive promoters. The ectopic expression of IRF-2BP2 in CD4 T cells resulted in decreased interleukin-2 (IL-2) and IL-4 production, supporting a repressive function of IRF-2BP2 for NFAT target genes. Furthermore, NFAT1 and IRF-2BP2 colocalized in the nucleus in activated cells, and the mutation of a newly identified nuclear localization signal in the IRF-2BP2 rendered it cytoplasmic, abolishing its repressive effect on NFAT1 activity. Collectively, our data demonstrate that IRF-2BP2 is a negative regulator of the NFAT1 transcription factor and suggest that NFAT1 repression occurs at the transcriptional level.
Zero-Determinant Strategy for Resource Sharing in Wireless Cooperations

Cooperation in resource sharing among wireless users and network operators has been widely studied in wireless communication. However, because of the limited coordination capability or cheating strategies, each participant of the cooperation may cease its cooperative behavior or duties unilaterally during the resource sharing, resulting in unsatisfying quality of services (QoSs) for all other participants. In this paper, we model the resource sharing among participants as an iterated game. Specifically, we first define the participant who is responsible for maintaining the social welfare as an administrator of cooperation (AoC), and other selfish participants as the regular participants of cooperation (PoCs). Then we consider three scenarios, i.e., with two-player applying discrete strategy, two-player applying continuous strategy, and multi-player applying continuous strategy, Finally, we investigate the power control problem in each of scenarios, and apply the zero-determinant strategies for the AoC to find the maximum social welfare that the AoC can achieve with existence of PoCs. Simulation results show that the high and stable social welfare can be maintained by the the AoC with the proposed zero-determinant algorithm.
Peers as Facilitators of Medication Adherence Interventions

Background: Difficulty taking essential medications as prescribed is a prevalent problem among people living with chronic diseases. Numerous interventions to enhance medication adherence have been developed; the majority facilitated by health care professionals. Objective: This review examined medication adherence interventions delivered by peers (ie, lay individuals living with the same chronic disease) and reports what is known about the impact of peer-facilitated interventions. Data Sources: PubMed, CINAHL, Google Scholar, Google, and PsychInfo, and ancestry searches. Study Selection: Solely peers delivered the intervention and follow-up occurred for at least 24 weeks postintervention. Electronic databases were searched from their start date to December 31, 2014. Results: Eleven studies were located that reported 10 different interventions focused on 6 chronic disease conditions. Most interventions were delivered in clinical settings and grounded in a theoretical framework. Formats were evenly split between individual and group level, with one intervention using both. Length of training for the interventionists and the number of intervention sessions that subjects received varied across studies. Limitations: Self-report was frequently used as a measure of adherence. Biomarkers were sometimes used to assess medication adherence; however, lifestyle modification may have also affected biomarker levels. Conclusions: Overall, the interventions had positive effects and attrition was quite low. Peer-facilitated interventions appear to enhance medication adherence as well as other healthful behaviors, such as exercise.
Cluster-Based Radio Resource Management for D2D-Supported Safety-Critical V2X Communications

Deploying direct device-to-device (D2D) links is a promising technology for vehicle-to-X (V2X) applications. However, intracell interference, along with stringent requirements on latency and reliability, are challenging issues. In this paper, we study the radio resource management problem for D2D-based safety-critical V2X communications. We first transform the V2X requirements into the constraints that are computable using slowly varying channel state information only. Secondly, we formulate an optimization problem, taking into account the requirements of both vehicular users (V-UEs) and cellular users (C-UEs), where resource sharing can take place not only between a V-UE and a C-UE but also among different V-UEs. The NP-hardness of the problem is rigorously proved. Moreover, a heuristic algorithm, called Cluster-based Resource block sharing and pOWer allocatioN (CROWN), is proposed to solve this problem. Finally, simulation results indicate promising performance of the CROWN scheme.
A New Segmentation Method of SAR Image Based on Multi-polarization information Fusion

Segmentation is a fundamental issue in synthetic aperture radar (SAR) image analysis. When contrast results against the true landscape, multi-polarization SAR images can provide more information, and obtain more correct segmentation than only single polarization SAR image. This paper presented a new SAR image segmentation method based on the multi-polarization SAR images fusion. The method built the whole image segmentation gradually by the segmentation algorithm framework based on ratio of averages (ROA), and the fusion processing was applied at the ROA gradient computing and the region merging step. A new method for ROA computing was proposed to generate gradient for each polarization image, and the first fusion processing was applied to build the gradient image by all of the gradients of multi-polarization SAR images. Then the initial segmentation of the gradient image was obtained by watershed algorithm. Finally, the final segmentation was provided by region merging using multi-polarization information as the second fusion step. Experimental results on the NASA/JPL multi-polarization SAR image showed that the method can improve the segmentation and have good performance.
On the Performance Analysis of Dual-Hop Mixed FSO/RF Systems

This paper presents novel results for the performance analysis of dual-hop free-space optical/radio frequency (FSO/RF) transmission systems where the FSO link is modeled by the Gamma-Gamma distribution with pointing error impairments and under both heterodyne detection and intensity modulation with direct detection (IM/DD), and the RF link experiences the generalized Nakagami-$m$ fading. Using amplify-and-forward fixed-gain relaying as well as channel-state-information(CSI)-assisted relaying, we derive closed-form expressions for the outage probability, the average bit-error rate (BER), and the ergodic capacity in terms of the bivariate H-Fox function. For a special case, we obtain simplified results for Nakagami-$m$ fading channels in the RF link. Furthermore, new asymptotic results for the outage probability and the average BER at high signal-to-noise ratio (SNR) regime are presented in terms of simple functions. Numerical and Monte-Carlo simulation results are provided to verify the accuracy of the newly proposed results, and a perfect agreement is observed.
Multiple Interferon Regulatory Factor and NF-κB Sites Cooperate in Mediating Cell-Type- and Maturation-Specific Activation of the Human CD83 Promoter in Dendritic Cells

ABSTRACT CD83 is one of the best-known surface markers for fully mature dendritic cells (mature DCs), and its cell-type- and maturation-specific regulation makes the CD83 promoter an interesting tool for the genetic modulation of DCs. To determine the mechanisms regulating this DC- and maturation-specific CD83 expression, chromatin immunoprecipitation (ChIP)-on-chip microarray, biocomputational, reporter, electrophoretic mobility shift assay (EMSA), and ChIP analyses were performed. These studies led to the identification of a ternary transcriptional activation complex composed of an upstream regulatory element, a minimal promoter, and an enhancer, which have not been reported in this arrangement for any other gene so far. Notably, these DNA regions contain a complex framework of interferon regulatory factor (IRF)- and NF-κB transcription factor-binding sites mediating their arrangement. Mutation of any of the IRF-binding sites resulted in a significant loss of promoter activity, whereas overexpression of NF-κB transcription factors clearly enhanced transcription. We identified IRF-1, IRF-2, IRF-5, p50, p65, and cRel to be involved in regulating maturation-specific CD83 expression in DCs. Therefore, the characterization of this promoter complex not only contributes to the knowledge of DC-specific gene regulation but also suggests the involvement of a transcriptional module with binding sites separated into distinct regions in transcriptional activation as well as cell-type- and maturation-specific transcriptional targeting of DCs.
Continued DNA Synthesis in Replication Checkpoint Mutants Leads to Fork Collapse

ABSTRACT Hydroxyurea (HU) treatment activates the intra-S phase checkpoint proteins Cds1 and Mrc1 to prevent replication fork collapse. We found that prolonged DNA synthesis occurs in cds1Δ and mrc1Δ checkpoint mutants in the presence of HU and continues after release. This is coincident with increased DNA damage measured by phosphorylated histone H2A in whole cells during release. High-resolution live-cell imaging shows that mutants first accumulate extensive replication protein A (RPA) foci, followed by increased Rad52. Both DNA synthesis and RPA accumulation require the MCM helicase. We propose that a replication fork “collapse point” in HU-treated cells describes the point at which accumulated DNA damage and instability at individual forks prevent further replication. After this point, cds1Δ and mrc1Δ forks cannot complete genome replication. These observations establish replication fork collapse as a dynamic process that continues after release from HU block.
Initial Access in Millimeter Wave Cellular Systems

Millimeter wave (mmWave) bands have attracted considerable recent interest for next-generation cellular systems due to the massive available spectrum at these frequencies. However, a key challenge in designing mmWave cellular systems is initial access-the procedure by which a mobile device establishes an initial link-layer connection to a cell. MmWave communication relies on highly directional transmissions and the initial access procedure must thus provide a mechanism by which initial transmission directions can be searched in a potentially large angular space. Design options are compared considering different scanning and signaling procedures to evaluate access delay and system overhead. The channel structure and multiple access issues are also considered. The results of our analysis demonstrate significant benefits of low-resolution fully digital architectures in comparison with single stream analog beamforming.
Intrusion of a DNA Repair Protein in the RNome World: Is This the Beginning of a New Era?

ABSTRACT Apurinic/apyrimidinic endonuclease 1 (APE1), an essential protein in mammals, is known to be involved in base excision DNA repair, acting as the major abasic endonuclease; the protein also functions as a redox coactivator of several transcription factors that regulate gene expression. Recent findings highlight a novel role for APE1 in RNA metabolism. The new findings are as follows: (i) APE1 interacts with rRNA and ribosome processing protein NPM1 within the nucleolus; (ii) APE1 interacts with proteins involved in ribosome assembly (i.e., RLA0, RSSA) and RNA maturation (i.e., PRP19, MEP50) within the cytoplasm; (iii) APE1 cleaves abasic RNA; and (iv) APE1 cleaves a specific coding region of c-myc mRNA in vitro and influences c-myc mRNA level and half-life in cells. Such findings on the role of APE1 in the posttranscriptional control of gene expression could explain its ability to influence diverse biological processes and its relocalization to cytoplasmic compartments in some tissues and tumors. In addition, we propose that APE1 serves as a “cleansing” factor for oxidatively damaged abasic RNA, establishing a novel connection between DNA and RNA surveillance mechanisms. In this review, we introduce questions and speculations concerning the role of APE1 in RNA metabolism and discuss the implications of these findings in a broader evolutionary context.
Ligand Promiscuity of Aryl Hydrocarbon Receptor Agonists and Antagonists Revealed by Site-Directed Mutagenesis

ABSTRACT The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that can be activated by structurally diverse chemicals. To examine the mechanisms responsible for the promiscuity in AhR ligand binding, we determined the effects of mutations within the AhR ligand-binding domain (LBD) on the activity of diverse AhR ligands. Site-directed mutagenesis identified Ile319 of the mouse AhR and, to a lesser extent, Phe318 as residues involved in ligand-selective modulation of AhR transformation using a panel of 12 AhR ligands. These ligands could be categorized into four distinct structurally related groups based on their ability to activate AhR mutants at position 319 in vitro. The mutation I319K was selectively activated by FICZ and not by other examined ligands in vitro and in cell culture. F318L and F318A mutations resulted in the conversion of AhR agonists β-naphthoflavone and 3-methylcholanthrene, respectively, into partial agonists/antagonists. Hsp90 binding to the AhR was decreased with several mutations and was inversely correlated with AhR ligand-binding promiscuity. Together, these data define overlapping amino acid residues within the AhR LBD involved in the selectivity of ligand binding, the agonist or antagonist mode of ligand binding, and hsp90 binding and provide insights into the ligand diversity of AhR activators.
Senataxin, Defective in the Neurodegenerative Disorder Ataxia with Oculomotor Apraxia 2, Lies at the Interface of Transcription and the DNA Damage Response

ABSTRACT The neurodegenerative disorder ataxia with oculomotor apraxia 2 (AOA-2) is caused by defects in senataxin, a putative RNA/DNA helicase thought to be involved in the termination of transcription at RNA polymerase pause sites. RNA/DNA hybrids (R loops) that arise during transcription pausing lead to genome instability unless they are resolved efficiently. We found that senataxin forms distinct nuclear foci in S/G2-phase human cells and that the number of these foci increases in response to impaired DNA replication or DNA damage. Senataxin colocalizes with 53BP1, a key DNA damage response protein, and with other factors involved in DNA repair. Inhibition of transcription using α-amanitin, or the dissolution of R loops by transient expression of RNase H1, leads to the loss of senataxin foci. These results indicate that senataxin localizes to sites of collision between components of the replisome and the transcription apparatus and that it is targeted to R loops, where it plays an important role at the interface of transcription and the DNA damage response.
Effects of the Paf1 Complex and Histone Modifications on snoRNA 3′-End Formation Reveal Broad and Locus-Specific Regulation

ABSTRACT Across diverse eukaryotes, the Paf1 complex (Paf1C) plays critical roles in RNA polymerase II transcription elongation and regulation of histone modifications. Beyond these roles, the human and Saccharomyces cerevisiae Paf1 complexes also interact with RNA 3′-end processing components to affect transcript 3′-end formation. Specifically, the Saccharomyces cerevisiae Paf1C functions with the RNA binding proteins Nrd1 and Nab3 to regulate the termination of at least two small nucleolar RNAs (snoRNAs). To determine how Paf1C-dependent functions regulate snoRNA formation, we used high-density tiling arrays to analyze transcripts in paf1Δ cells and uncover new snoRNA targets of Paf1. Detailed examination of Paf1-regulated snoRNA genes revealed locus-specific requirements for Paf1-dependent posttranslational histone modifications. We also discovered roles for the transcriptional regulators Bur1-Bur2, Rad6, and Set2 in snoRNA 3′-end formation. Surprisingly, at some snoRNAs, this function of Rad6 appears to be primarily independent of its role in histone H2B monoubiquitylation. Cumulatively, our work reveals a broad requirement for the Paf1C in snoRNA 3′-end formation in S. cerevisiae, implicates the participation of transcriptional proteins and histone modifications in this process, and suggests that the Paf1C contributes to the fine tuning of nuanced levels of regulation that exist at individual loci.
Immunization of Pregnant Women with a Polysaccharide Vaccine of Group B Streptococcus

Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus is a promising strategy for the prevention of perinatal infections caused by group B streptococci. To explore the feasibility of this strategy, we vaccinated 40 pregnant women at a mean gestation of 31 weeks with a single 50-microgram dose of the Type III capsular polysaccharide of group B streptococcus. The only adverse effect detected was a mild local reaction in nine women (22 percent). Of the 35 women with low or unprotective antibody levels before immunization (less than 2 micrograms per milliliter), 20 (57 percent) responded to the vaccine. The geometric mean antibody level rose from 1.3 to 7.1 micrograms per milliliter four weeks after vaccination (P less than 0.02), and these levels persisted at delivery and three months post partum. Sixty-two percent of the vaccine-induced immunoglobulin in the mothers was IgG, which readily crosses the placenta. Infant antibody levels in cord serum correlated directly with maternal antibody levels at delivery (r = 0.913, P less than 0.001). Of the 25 infants born to women who responded to the vaccine, 80 percent continued to have protective levels of antibody at one month of age and 64 percent had protective levels at three months. Serum samples from infants with greater than or equal to 2 micrograms of antibody to Type III group B streptococcus per milliliter uniformly promoted efficient opsonization, phagocytosis, and bacterial killing in vitro of Type III strains. This effect could be mediated exclusively by the alternative complement pathway. Although this vaccine with an overall response rate of 63 percent is not optimally immunogenic, we conclude that maternal immunization is feasible and can provide passive immunity against systemic infection with Type III group B streptococcus in the majority of newborns. Larger trials with better vaccines will be required to evaluate the safety and clinical effectiveness of this strategy.
RasGAP Promotes Autophagy and Thereby Suppresses Platelet-Derived Growth Factor Receptor-Mediated Signaling Events, Cellular Responses, and Pathology

ABSTRACT Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) make profound contributions to both physiology and pathology. While it is widely believed that direct (PDGF-mediated) activation is the primary mode of activating PDGFRs, the discovery that they can also be activated indirectly begs the question of the relevance of the indirect mode of activating PDGFRs. In the context of a blinding eye disease, indirect activation of PDGFRα results in persistent signaling, which suppresses the level of p53 and thereby promotes viability of cells that drive pathogenesis. Under the same conditions, PDGFRβ fails to undergo indirect activation. In this paper, we report that RasGAP (GTPase-activating protein of Ras) prevented indirect activation of PDGFRβ. RasGAP, which associates with PDGFRβ but not PDGFRα, reduced the level of mitochondrion-derived reactive oxygen species, which are required for enduring activation of PDGFRs. Furthermore, preventing PDGFRβ from associating with RasGAP allowed it to signal enduringly and drive pathogenesis of a blinding eye disease. These results indicate a previously unappreciated role of RasGAP in antagonizing indirect activation of PDGFRβ, define the underlying mechanism, and raise the possibility that PDGFRβ-mediated diseases involve indirect activation of PDGFRβ.
Joint Precoder and Artificial Noise Design for MIMO Wiretap Channels With Finite-Alphabet Inputs Based on the Cut-Off Rate

We consider precoder and artificial noise (AN) design for multi-antenna wiretap channels under the finite-alphabet input assumption. We assume that the transmitter has access to the channel coefficients of the legitimate receiver and knows the statistics of the eavesdropper’s channel. Accordingly, we propose a secrecy rate maximization algorithm using a gradient descent-based optimization of the precoder matrix and an exhaustive search over the power levels allocated to the AN. We also propose algorithms to reduce the complexities of direct ergodic secrecy rate maximization by: 1) maximizing a cut-off rate-based approximation for the ergodic secrecy rate, simplifying the mutual information expression, which lacks a closed-form and 2) diagonalizing the channels toward the legitimate receiver and the eavesdropper, which allows for employing a per-group precoding-based technique. Our numerical results reveal that jointly optimizing the precoder and the AN outperforms the existing solutions in the literature, which rely on the precoder optimization only. We also demonstrate that the proposed low complexity alternatives result in a small loss in performance while offering a significant reduction in computational complexity.
Challenges in designing a disease surveillance plan: What we have and what we need?

The early detection of disease for public health inventions presents many research challenges involving data integration and simulation, multivariate spatio-temporal clustering, non-stationary incidences and related disease groups. These present researchers with many opportunities for new methodology to meet the challenges of integrating severity of outcomes, using several sources of data relating to disease counts (e.g., presentations at emergency departments and related medication sales) and a number of dimensions of geography (e.g., home residence and workplace/school of people with the disease) into a single plan. This paper reviews some of the current challenges.