Miracle-dz/UniFAR-FTUs huggingface dataset:
jPREdictor: a versatile tool for the prediction of cis-regulatory elements

Gene regulation is the process through which an organism effects spatial and temporal differences in gene expression levels. Knowledge of cis-regulatory elements as key players in gene regulation is indispensable for the understanding of the latter and of the development of organisms. Here we present the tool jPREdictor for the fast and versatile prediction of cis-regulatory elements on a genome-wide scale. The prediction is based on clusters of individual motifs and any combination of these into multi-motifs with selectable minimal and maximal distances. Individual motifs can be of heterogenous classes, such as simple sequence motifs or position-specific scoring matrices. Cluster scores are weighted occurrences of multi-motifs, where the weights are derived from positive and negative training sets. We illustrate the flexibility of the jPREdictor with a new predic-tion of Polycomb/Trithorax Response Elements in Drosophila melanogaster. jPREdictor is available as a graphical user interface for online use and for download at .
Deep-Reinforcement-Learning-Based Optimization for Cache-Enabled Opportunistic Interference Alignment Wireless Networks

Both caching and interference alignment (IA) are promising techniques for next-generation wireless networks. Nevertheless, most of the existing works on cache-enabled IA wireless networks assume that the channel is invariant, which is unrealistic considering the time-varying nature of practical wireless environments. In this paper, we consider realistic time-varying channels. Specifically, the channel is formulated as a finite-state Markov channel (FSMC). The complexity of the system is very high when we consider realistic FSMC models. Therefore, in this paper, we propose a novel deep reinforcement learning approach, which is an advanced reinforcement learning algorithm that uses a deep <inline-formula><tex-math notation="LaTeX">$Q$</tex-math></inline-formula> network to approximate the <inline-formula><tex-math notation="LaTeX">$Q$</tex-math></inline-formula> value-action function. We use Google TensorFlow to implement deep reinforcement learning in this paper to obtain the optimal IA user selection policy in cache-enabled opportunistic IA wireless networks. Simulation results are presented to show that the performance of cache-enabled opportunistic IA networks in terms of the network's sum rate and energy efficiency can be significantly improved by using the proposed approach.
Morphology and Rheology of Polypropylene/Polystyrene/Clay Nanocomposites in Batch and Continuous Melt Mixing Processes

The addition of organically modified layered silicates (organoclay) to highly immiscible polypropylene/polystyrene, PP/PS, blends leads to a significant change in blend morphology and rheology. In this study, the kinetics for morphological development of the blend nanocomposites was studied by two mixing methods (internal batch mixing and continuous mixing), with a focus on the mechanism of dispersion of the silicate layers and its dependence on mixing conditions. Through the use of a twin-screw co-rotating extruder specially modified with sampling ports along its length it was possible to study, for the first time, the kinetics of morphology developed upon mixing. The results show that the evolution of silicate layer dispersion during morphology occurs by and large relatively early in the mixing process and that the most favorable breaking process of the dispersed phase occurs initially due to the breaking up of the initial silicate tactoids into thinner ones and also due to their presence inside it. As a consequence of these sequential processes, the organoclay layers end up at the interface between the PP and the polystyrene phases and stabilize the morphology.
Sphingosine Kinase 2 Modulates Retinal Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy.

Purpose Neovascularization is a major cause of blindness in various ocular diseases. Bioactive sphingosine 1-phosphate (S1P), synthesized by two sphingosine kinases (Sphk1, Sphk2), emerged as a key player in a multitude of cellular processes, including cell survival, proliferation, inflammation, migration, and angiogenesis. We investigated the role of Sphk2, S1P, and S1P receptors (S1PR) during retinal neovascularization using the oxygen-induced retinopathy mouse model (OIR). Methods Sphk2 overexpressing (tgSphk2) and Sphk2 knockout (Sphk2-/-) mice were used in the OIR model, exposed to 75% O2 over 5 days from postnatal day (P)7 to 12 to initiate vessel regression. After returning to room air, these mice developed a marked neovascularization. Retinae recovered from untreated and treated eyes at P7, P12, P14, and P17 were used for lectin-stained retinal whole mounts, mass spectrometry, and quantitative real-time PCR. Results tgSphk2 mice showed higher retinal S1P concentrations, accelerated retinal angiogenesis, and increased neovascularization. Expression of S1PR, vascular endothelial growth factor α (VEGFα), and angiopoietin 1 and 2 was differentially regulated during the course of OIR in the different genotypes. Sphk2-/- displayed a markedly reduced retinal angiogenesis and neovascularization as well as decreased VEGFα and angiopoietin expression. Conclusions Using genetic models of Sphk2 overexpression or deletion we demonstrate a strong impact of Sphk2/S1P on retinal vasculopathy and expression of vascular growth factors like VEGF and angiopoietin in the retina. Consequently, Sphk2, S1P, and S1PR may offer attractive novel therapeutic targets for ischemic retinopathies.
Biodegradable Polymer Nanocylinders Fabricated by Transverse Fragmentation of Electrospun Nanofibers through Aminolysis

Biodegradable polymeric nanocylinders were fabricated by segmental degradation of electrospun nanofibers. Poly(L-lactic acid) (PLA) was electrospun to produce non-crystalline nanofibers that were immediately treated with amino group-containing strong bases to fabricate semicrystalline PLA nanocylinders with tunable aspect ratio. The formation of PLA nanocylinders was attributed to two concurrent events occurring during the aminolysis reaction: (i) development of stacked lamellae and (ii) transversely oriented degradation and fragmentation of the amorphous gaps between lamellae, both responsible for the fragmentation of PLA nanofibers into uniformly shaped nanocylinders. The aspect ratio of PLA nanocylinders was tunable by varying aminolysis time and controlling nanofiber diameter.
Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterization of HIV-infected patients undergoing HSCT is warranted. Methods: We studied 3 patients who underwent HSCT after either reduced intensity conditioning or myeloablative conditioning regimen. We measured HIV antigens and antibodies (Ag/Ab), HIV-specific CD4+ T-cell responses, HIV RNA, and DNA in plasma, peripheral blood mononuclear cells, isolated CD4+ T cells from peripheral blood, and lymph node cells. The patients remained on antiretroviral therapy throughout the follow-up period. Results: All patients have been in continued remission for 4–6 years post-HSCT. Analyses of HIV RNA and DNA levels showed substantial reductions in HIV reservoir–related measurements in all 3 patients, changes in immune response varied with pronounced reductions in 2 patients and a less dramatic reduction in 1 patient. One patient experienced unexpected viral rebound 4 years after HSCT. Conclusions: These 3 cases highlight the substantial changes to the HIV reservoir and the HIV immune response in patients undergoing allogeneic HSCT. The viral rebound observed in 1 patient indicates that replication competent HIV can re-emerge several years after HSCT despite these marked changes.
Local Buckling Analysis of Aluminum I Section Beams

Low elastic modulus of aluminum alloy gives prominence to lateral and local buckling of members, especially when thin walled sections are adopted to save material usage. Under certain conditions of loads and constraint, local buckling would occur in aluminum beams. A numerical study to assess the local stability of aluminum I section beams is presented in this paper. The study focused on two aspects: the local buckling of aluminum flange plate under compression, the local buckling of aluminum web plate under bending and shear. An extensive parameter analysis including width-to-thickness ratio, initial imperfection, material constitutive relation and restriction effect from adjacent plates was carried out with the purpose of extracting several governing parameters and investigating their effects on the local buckling of aluminum plate. Based upon the results of finite element analysis (FEA), a new design method in connection with the local stability of aluminum I section beams has been developed. By virtue of the proposed design method, three key indicators that include the critical value of width-to-thickness ratio to prevent local buckling of aluminum flange plate under compression, the local stability of aluminum web plate under bending/shear and the bearing capacity of aluminum I section beams under the condition that the post buckling strength of web is taken into account, could be obtained to provide more rational and efficient designs. The proposed design method is different from the current Eurocode but acts in accordance with Chinese code for design of steel structures (Chinese steel code) in order to satisfy applicability.
Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry

Background There are very few data about the mutational profile of families at-risk for hereditary breast and ovarian cancer (HBOC) from Latin America (LA) and especially from Brazil, the largest and most populated country in LA. Results Of the 349 probands analyzed, 21.5% were BRCA1/BRCA2 mutated, 65.3% at BRCA1 and 34.7% at BRCA2 gene. The mutation c.5266dupC (former 5382insC) was the most frequent alteration, representing 36.7% of the BRCA1 mutations and 24.0% of all mutations identified. Together with the BRCA1 c. 3331_3334delCAAG mutation, these mutations constitutes about 35% of the identified mutations and more than 50% of the BRCA1 pathogenic mutations. Interestingly, six new mutations were identified. Additionally, 39 out of the 44 pathogenic mutations identified were not previously reported in the Brazilian population. Besides, 36 different variants of unknown significance (VUS) were identified. Regarding ancestry, average ancestry proportions were 70.6% European, 14.5% African, 8.0% Native American and 6.8% East Asian. Materials and methods This study characterized 349 Brazilian families at-risk for HBOC regarding their germline BRCA1/BRCA2 status and genetic ancestry. Conclusions This is the largest report of BRCA1/BRCA2 assessment in an at-risk HBOC Brazilian population. We identified 21.5% of patients harboring BRCA1/BRCA2 mutations and characterized the genetic ancestry of a sample group at-risk for hereditary breast cancer showing once again how admixed is the Brazilian population. No association was found between genetic ancestry and mutational status. The knowledge of the mutational profile in a population can contribute to the definition of more cost-effective strategies for the identification of HBOC families.
A combined inductive and deductive sense data extraction and visualisation service

Wireless sensor networks (WSNs) have an intimate interaction, via sensors, with the physical environment they operate within. Application domains have a significant effect on applications performance because WSNs are usually deployed to perform application specific tasks. The part of the world with which an application is concerned is defined as that application's domain. The application domain may help scientists to leverage computational power to simulate, visualise, manipulate, predict and gain intuition about monitored phenomenon. In this paper we propose a new visualisation framework, called Multi-Dimensional Application Domain-driven (M-DAD), that elevates the capabilities of the sense data extraction and visualisation mapping service proposed in [1]. M- DAD exploits the application domain to dynamically minimise the mapping service predictive error. It is capable of visualising an arbitrary number of sense modalities. In M-DAD the visualisation performance is improved by utilising the relations between independent sense modalities as well as other parameters of the application domain. M-DAD can meet the goal of reliability and reactivity, and demonstrates satisfactory robustness using the information they collect about the environment they operate within to adapt its behaviour to changes in the environment. Self-adaptation is a fundamental capability of M-DAD which is required to operate in dynamic environments that impose varying functional and performance requirements on WSNs applications. This self-adaptation scheme makes M-DAD more resilient to faults by substituting for faulty nodes, auto-calibrate sensors, and recover form modelling errors. The experimental results demonstrate that M-DAD performs as well or better than mapping services without its extended capabilities.
The Application of Event Studies in Evaluation of Teaching Quality

Computer science is integrated with the practice closely. It has become consensus of scholars that coding ability is important to computer science education, and programming exercises can improve teaching quality efficiently. However, this consensus more relies on the expert's experience and intuition. It¿s lack of quantifiable indicators or empirical data to support the consensus. In this paper, event studies are used to analysis the effect of programming exercises to teaching quality. The results show that the improvement of students¿ coding ability can effectively improve teaching quality of computer science courses.
Revisiting routing control platforms with the eyes and muscles of software-defined networking

Prior work on centralized Routing Control Platform (RCP) has shown many benefits in flexible routing, enhanced security, and ISP connectivity management tasks. In this paper, we discuss RCPs in the context of OpenFlow/SDN, describing potential use cases and identifying deployment challenges and advantages. We propose a controller-centric hybrid networking model and present the design of the RouteFlow Control Platform (RFCP) along the prototype implementation of an AS-wide abstract BGP routing service.
Efficient generation of antigen-specific CTLs by the BAFF-activated human B Lymphocytes as APCs: a novel approach for immunotherapy

Efficient antigen presentation is indispensable for cytotoxic T lymphocyte (CTL)-mediated immunotherapy. B-lymphocytes propagated with CD40L have been developed as antigen-presenting cells (APCs), but this capacity needs further optimization. Here, we aimed to expand human B-lymphocytes on a large scale while maintaining their antigen-presenting ability by using both CD40L and B-cell activating factor (BAFF). The addition of BAFF enhanced the expansion efficiency and prolonged the culture time without causing apoptosis of the expanded B-cells. This method thus provided an almost unlimited source of cellular adjuvant to achieve sufficient expansion of CTLs in cases where several rounds of stimulation are required. We also showed that the addition of BAFF significantly enhanced the expression of major costimulatory molecules, CD80 and CD86. Subsequently, the antigen-presenting ability of the B-lymphocytes also increased. Consequently, these B-lymphocytes showed robust CTL responses to inhibit tumor growth after tumor-specific peptide pulses. A similar method induced potent antigen-specific CTL responses, which effectively eradicated human immunodeficiency virus type 1 (HIV-1) latency in CD4 T-lymphocytes isolated from patients receiving suppressive anti-retroviral therapy (ART). Together, our findings indicate that potent antigen-specific CTLs can be generated using BAFF-activated B-lymphocytes as APCs ex vivo. This approach can be applied for CTL-mediated immunotherapy in patients with cancers or chronic viral infections.
CREDO: A Protein–Ligand Interaction Database for Drug Discovery

Harnessing data from the growing number of protein–ligand complexes in the Protein Data Bank is an important task in drug discovery. In order to benefit from the abundance of three‐dimensional structures, structural data must be integrated with sequence as well as chemical data and the protein–small molecule interactions characterized structurally at the inter‐atomic level. In this study, we present CREDO, a new publicly available database of protein–ligand interactions, which represents contacts as structural interaction fingerprints, implements novel features and is completely scriptable through its application programming interface. Features of CREDO include implementation of molecular shape descriptors with ultrafast shape recognition, fragmentation of ligands in the Protein Data Bank, sequence‐to‐structure mapping and the identification of approved drugs. Selected analyses of these key features are presented to highlight a range of potential applications of CREDO. The CREDO dataset has been released into the public domain together with the application programming interface under a Creative Commons license at http://www‐cryst.bioc. cam.ac. uk/credo. We believe that the free availability and numerous features of CREDO database will be useful not only for commercial but also for academia‐driven drug discovery programmes.
Application of Anova to pulse detonation engine ground demonstrator's dynamic performance measurements

Application of Anova to Pulse Detonation Engine ground demonstrator's dynamic performance measurement is being explored due its large data of chamber pressure at station 1 (Pi) fluctuations resulting in thrust deteriorations. It has lead to quantifying engine functionality, while operating at varied frequencies during various phases of engine operations. After evaluating the performance, the causes of chamber pressure fluctuations were identified using multiple independent analysis techniques. Further, procedures of improving it by applying corrections were enforced in the areas of relevant area, which are also covered in the paper. This produced encouraging results in improving P1 and helped in upscaling efforts in a significant manner in short span of time. The current paper deals in the details of Anova implementation and systematic identification of key areas of improvements. These enhancements were carried out after careful selection of plans in the engine ground demonstrator, ground rig and instrumentation setup etc. It also yielded better reproducibility of performance and optimization of main subsystems of PDE. Further, this will also contribute to reduce the development cycle and trial complexity also, if researchers continue to extract concern areas to be addressed.
Mitigation of NADPH Oxidase 2 Activity as a Strategy to Inhibit Peroxynitrite Formation*

Using high throughput screening-compatible assays for superoxide and hydrogen peroxide, we identified potential inhibitors of the NADPH oxidase (Nox2) isoform from a small library of bioactive compounds. By using multiple probes (hydroethidine, hydropropidine, Amplex Red, and coumarin boronate) with well defined redox chemistry that form highly diagnostic marker products upon reaction with superoxide (O2̇̄), hydrogen peroxide (H2O2), and peroxynitrite (ONOO−), the number of false positives was greatly decreased. Selected hits for Nox2 were further screened for their ability to inhibit ONOO− formation in activated macrophages. A new diagnostic marker product for ONOO− is reported. We conclude that the newly developed high throughput screening/reactive oxygen species assays could also be used to identify potential inhibitors of ONOO− formed from Nox2-derived O2̇̄ and nitric oxide synthase-derived nitric oxide.
Association of combined cigarette smoking and ARMS2/LOC387715 A69S polymorphisms with age-related macular degeneration: A meta-analysis

ABSTRACT Purpose: The age-related maculopathy susceptibility2 (ARMS2)/LOC387715 A69S (rs10490924) polymorphism and cigarette smoking have been shown to have significant association with AMD. In this meta-analysis we used the results of available association studies of combined ARMS2/LOC387715 genotypes and cigarette smoking with AMD to estimate the possible synergistic or multiplicative effects. Methods: Heterogeneity of studies was evaluated using the Cochran Q-test and the I-square index. To compensate for the heterogeneity of the variables in the study we used a random effects model. Meta-analysis was performed using STATA. To estimate the additive or supra-additive effects, we calculated relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), synergy index (S), and multiplicative index (V). Results: We could include four studies with 1982 AMD patients and 1797 control subjects. Considering the GG-no smoking as a reference line the meta-analysis result of AMD odds ratios for stratified combined factors was 3.05 (95% CI 2.32–4.02) for nonGG-no smoking, 2.24 (95% CI 1.39–3.63) for GG-smoking and 4.59 (95% CI 3.51–6.01) for nonGG-smoking. The meta-analysis of synergy analysis revealed RERI = 2.01 (95% CI 1.01–3.25), AP = 0.40 (95% CI 0.22–0.54), S = 2.02 (95% CI 1.35–3.01), and V = 1.31 (95% CI 0.94–1.83). Conclusion: This analysis revealed the synergistic effect of these two factors indicating that there is a common pathway of ARMS2/LOC387715 and smoking in AMD pathogenesis which may be the complement system pathway.
Constructing Cross-Linked Polymer Networks Using Monte Carlo Simulated Annealing Technique for Atomistic Molecular Simulations

Abstract : A method for constructing atomistic models of cross-linked polymer networks using Monte Carlo simulated annealing polymerization is described in detail. The simulated annealing method is appealing because it is computationally efficient and, therefore, allows the construction of larger cross-linked networks at higher conversion than is feasible with other methods. We demonstrate the application of this method to cross-linked networks of poly(dicyclopentadiene) with varying cross-link density. The instructions are not specific to this chemistry and can easily be used to construct atomistic models of cross-linked networks with any type of chemistry. The ability to quickly and easily build computational models of cross-linked polymer networks with varying chemistry will aid in the rational design of improved materials.
Metallographic Preparation for Electron Backscattered Diffraction

Electron Backscatter Diffraction measurement can provide much analytical information, such as the phase orientation or material identification. The “Quality” rating of the backscatter diffraction depends on the success rate of indexing. To achieve this, a deformation-free preparation is essential. In recent years most preparation methods have been optimized to contain on average only three to four sample preparation steps. The sample quality is excellent when reflected light microscopy is used. Due to the low information depth of the EBSD measurement (20-100nm), the standard method must be modified. The preparation method must remove the scratches and the underlying damage in order to obtain a high quality EBSD pattern. The optimization can be done by chemo-mechanical polishing, electrolytic polishing or vibratory polishing. Examples are used to show where the limits of the technologies are and to give helpful ‘Hints’ for EBSD sample preparation.