Miracle-dz/UniFAR-FTUs huggingface dataset:
Folded Circuit Synthesis

The area required by combinational logic of a sequential circuit based on standard flip-flops can be reduced by identifying subcircuits that are identical. Pairs of matching subcircuits can then be replaced by circuits in which dual-edge-triggered flip-flops operate on multiplexed data at the rising and falling edges of the clock signal. We show how to modify the Boolean network describing a combinational logic to increase the opportunities for folding, without affecting its function. Experiments with benchmark circuits achieved an average reduction in circuit area of 18%.
Quantifying the prognostic significance of microRNA-17/17-5P in cancers: a meta-analysis based on published studies

Objective The aim of this study was to investigate the prognostic value of mircoRNA-17 and mircoRNA-17-5P (miR-17/17-5P) in patients with cancer. Materials and methods We conducted a comprehensive search on published literature following the guidelines of the meta-analysis of observational studies in epidemiology group for design, implementation, and reporting. The methodological qualities for included studies were assessed using the quality in prognosis studies. The pooled hazard ratios (HRs) with 95% CIs for overall survival (OS) and progression-free survival/recurrence-free survival/disease-free survival (PFS/RFS/DFS) were calculated to appraise the associations between miR-17/17-5P expression and cancer prognosis. Results A total of 21 studies involving 2099 subjects were analyzed in evidence synthesis. The results showed that high expression of miR-17 was associated with poor OS (HR=2.14; 95% CI: 1.69–2.71, P<0.001) in patients with cancer, especially in Caucasian (HR=2.23; 95% CI: 1.58–3.14, P<0.001) and digestive tract cancer (HR=1.29, 95% CI: 1.03–1.63, P=0.03), and miR-17 expression was significantly correlated with PFS/RFS in cancer patients (HR=1.69, 95% CI: 1.29–2.22, P<0.001). miR-17-5P overexpression was significantly linked with poor OS in cancer patients (HR=1.66; 95% CI: 1.31–2.09, P=0.00), especially in Asian (HR=1.81; 95% CI: 1.37–2.40, P<0.001), digestive tract cancer (HR=1.80; 95% CI: 1.29–2.50, P<0.001), and serum sample (HR=1.76; 95% CI: 1.29–2.41, P<0.001). miR-17-5P expression was significantly associated with DFS in cancer patients (HR=1.58, 95% CI: 1.07–2.35, P=0.02). Conclusion High expression of miR-17 and miR-17-5P are significantly associated with poor survival in patients with cancer. This indicated that miR-17/17-5P may be a novel prognostic indicator in cancer.
The ATPase activity of E. coli RecA prevents accumulation of toxic complexes formed by erroneous binding to undamaged double stranded DNA

The E. coli RecA protein catalyzes the central step of homologous recombination using its homology search and strand exchange activity. RecA is a DNA-dependent ATPase, but its homology search and strand exchange activities are independent of its ATPase activity. ATP hydrolysis converts a high affinity DNA binding form, RecA-ATP, to a low affinity form RecA-ADP, thereby supporting an ATP hydrolysis-dependent dynamic cycle of DNA binding and dissociation. We provide evidence for a novel function of RecA’s dynamic behavior; RecA’s ATPase activity prevents accumulation of toxic complexes caused by direct binding of RecA to undamaged regions of dsDNA. We show that a mutant form of RecA, RecA-K250N, previously shown to be toxic to E. coli, is a loss-of-function ATPase-defective mutant. We use a new method for detecting RecA complexes involving nucleoid surface spreading and immunostaining. The method allows detection of damage-induced RecA foci; STED microscopy revealed these to typically be between 50 and 200 nm in length. RecA-K250N, and other toxic variants of RecA, form spontaneous DNA-bound complexes that are independent of replication and of accessory proteins required to load RecA onto tracts of ssDNA in vivo, supporting the hypothesis that RecA’s expenditure of ATP serves an error correction function.
Ubiquitin A-52 residue ribosomal protein fusion product 1 (Uba52) is essential for preimplantation embryo development

ABSTRACT Ubiquitin A-52 residue ribosomal protein fusion product 1 (Uba52), a ubiquitin-ribosomal fusion gene, is a major source of ubiquitin protein for covalent modification of proteinaceous substrates recycled by ubiquitin-proteasome system (UPS). Its role in early embryo development has not been studied. Using the CRISPR/Cas9 gene editing tool, the objective of this study was to determine if UBA52 protein is required for mammalian embryogenesis. Matured metaphase II porcine oocytes were injected with CRISPR Cas9+guide RNAs (Uba52 gRNA) or Cas9 without gRNAs as control, followed by in vitro fertilization (IVF) and embryo culture to day 7. Injection of Cas9+gRNAs affected embryo development. On day 4 of embryo culture, the proportion of 2-, 4- and 8-cell stage embryos was significantly different between the Uba52 gRNA and control group (P<0.05), with more 8-cell stage embryos in the control and more 4- and 2-cell stage embryos in the Uba52g RNA group. This delay in the development of Uba52 gRNA embryos occurred at the transition from the 4- to 8-cell stages, around the time of major zygotic genomic activation. The percentage of blastocyst formation on day 7 and the cell number per blastocyst were significantly lower in the Uba52 gRNA group than in the control (P<0.05). Genotyping by PCR and DNA gel electrophoresis analysis showed that 91.8% of embryos that failed to develop to blastocyst had either a monoallelic or a biallelic modification of the Uba52 gene. In comparison, only 24.4% of embryos that reached blastocyst had a monoallelic modification and biallelic editing was not found in any of the blastocysts. Based on immuno-labeling intensity, both UBA52 and proteasome protein levels on days 4 and 7 of culture were significantly lower in the Uba52 gRNA group than in the control (P<0.05), in agreement with UBA52 western blotting-densitometry of day 4 embryos. Morphological examination of blastomere nuclei revealed abnormal nuclear structure in the Uba52 gRNA group, such as reduced size, irregular shapes, nucleus fragmentation and uneven DNA distribution at all stages of embryo development. Nuclear morphology studies of embryos injected with Cas9+gRNAs and co-injected with plasmid DNA encoding nuclear localized GFP further supported these observations. In conclusion, our data indicate that the Uba52 gene is essential in early embryogenesis. Summary: Ubiquitin A-52 residue ribosomal protein fusion product 1 (Uba52), a ubiquitin-ribosomal fusion gene, is a major source of ubiquitin protein for covalent modification of proteinaceous substrates recycled by ubiquitin-proteasome system. Using CRISPR/cas9 gene editing tool, we demonstrate that that Uba52 gene is essential in early embryogenesis in mammals.
OpenDaylight vs. Floodlight: Comparative Analysis of a Load Balancing Algorithm for Software Defined Networking

This paper presents the proposal of a load balancing algorithm implemented in two of the most popular controllers for Software Defined Networks (SDN): OpenDaylight and Floodlight. A comparative study in terms of the available bandwidth and delay time of the packet forwarding was performed by means of simulation modeling in a base network in which a shortest path algorithm was implemented as well. The results show that the proposed load balancing algorithm improves significantly the performance of a SDN in terms of the offered QoS of a OpenDaylight based controller. The effect of the proposed load balancing algorithm in the Floodlight controller shows a smaller impact mainly on the bandwidth allocation due to its in-build modules that by default perform specific routing and forwarding operations efficiently according to the traffic demand.
Comparative Evaluation of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus in Diagnosis of Latent Tuberculosis Infection in Immunocompromised Patients

QuantiFERON-TB Gold Plus (QFT-Plus) is a new-generation QuantiFERON-TB Gold In-Tube (QFT-GIT) assay which has two antigen-coated tubes called TB1, which contains long peptides derived from ESAT-6 and CFP-10, and TB2, which contains the same components as TB1 and additional short peptides which potentially stimulate CD8+ T cells through the presentation of major histocompatibility complex class I. This is the first study to compare QFT-Plus and QFT-GIT for use in the diagnosis of latent tuberculosis infection (LTBI) among immunocompromised patients in the Republic of Korea. ABSTRACT QuantiFERON-TB Gold Plus (QFT-Plus) is a new-generation QuantiFERON-TB Gold In-Tube (QFT-GIT) assay which has two antigen-coated tubes called TB1, which contains long peptides derived from ESAT-6 and CFP-10, and TB2, which contains the same components as TB1 and additional short peptides which potentially stimulate CD8+ T cells through the presentation of major histocompatibility complex class I. This is the first study to compare QFT-Plus and QFT-GIT for use in the diagnosis of latent tuberculosis infection (LTBI) among immunocompromised patients in the Republic of Korea. Among 317 consecutive patients who underwent screening for LTBI before solid organ or hematopoietic stem cell transplantation and tumor necrosis factor alpha inhibitor treatment, LTBI was identified in 92 (29.0%) and 88 (27.8%) patients by QFT-GIT and QFT-Plus, respectively. The rate of concordance between QFT-GIT and QFT-Plus was 93.7% (κ value, 0.860), and the indeterminate rate (3.2%) was similar between QFT-GIT and QFT-Plus. Of 20 (6.3%) samples with discordant results, 11 (55.0%) and 7 (35.0%) were positive by QFT-GIT alone and QFT-Plus alone, respectively, and 2 (15.0%) were indeterminate by each assay. The interferon gamma level in samples with discordant results ranged from 0.39 to 1.10 IU/ml, except for one sample, in which the gamma interferon level was 2.97 IU/ml only in TB2. Conclusively, there was a high degree of agreement between the results of QFT-GIT and QFT-Plus for the screening of immunocompromised patients for LTBI. The reactivity in TB2 contributed substantially to the difference between QFT-GIT and QFT-Plus, particularly in solid organ transplant candidates. The significance of the discrete responses in TB1 and TB2 of QFT-Plus needs to be explored further by means of an immunological and clinical approach in different patient groups and clinical settings.
Double Guided Surgery in All-on-4® Concept: When Ostectomy Is Needed

Background The rehabilitation of edentulous jaws with guided and flapless surgery applied to the All-on-4 concepts is a predictable treatment with a high implant and prosthetic survival rates, but there are several contraindications for this technique like when bone reduction is needed due to a high smile line in the maxilla or when there is an irregular or thin bone crest. Purpose To report a technique with double guided surgery for bone reduction and implant placement with the All-on-4 concept. Materials and Methods 7 patients were included in the study. Guided implant planning was performed using CBCT, and the virtual templates were created with three dedicated software. Custom surgical templates were made for the ostectomy and for implants positioning. Results 28 implants were placed using a double bone-supported surgical guide. The mean angular errors between the preoperative-planned implant and the postoperative-placed implant were 2.155° ± 2.03°; the mean distance errors between the planned and the placed implants were 0.763 mm ± 0.55 mm on the shoulder implant and 0.570 mm ± 0.40 mm on the apex implant. Conclusions The results of our study indicate that this treatment is predictable with an excellent survival rate allowing excellent results even when bone reduction is mandatory.
The TAB1-p38α complex aggravates myocardial injury and can be targeted by small molecules

Inhibiting MAPK14 (p38α) diminishes cardiac damage in myocardial ischemia. During myocardial ischemia, p38α interacts with TAB1, a scaffold protein, which promotes p38α autoactivation; active p38α (pp38α) then transphosphorylates TAB1. Previously, we solved the X-ray structure of the p38α-TAB1 (residues 384–412) complex. Here, we further characterize the interaction by solving the structure of the pp38α-TAB1 (residues 1–438) complex in the active state. Based on this information, we created a global knock-in (KI) mouse with substitution of 4 residues on TAB1 that we show are required for docking onto p38α. Whereas ablating p38α or TAB1 resulted in early embryonal lethality, the TAB1-KI mice were viable and had no appreciable alteration in their lymphocyte repertoire or myocardial transcriptional profile; nonetheless, following in vivo regional myocardial ischemia, infarction volume was significantly reduced and the transphosphorylation of TAB1 was disabled. Unexpectedly, the activation of myocardial p38α during ischemia was only mildly attenuated in TAB1-KI hearts. We also identified a group of fragments able to disrupt the interaction between p38α and TAB1. We conclude that the interaction between the 2 proteins can be targeted with small molecules. The data reveal that it is possible to selectively inhibit signaling downstream of p38α to attenuate ischemic injury.
Spleen Tyrosine Kinase Inhibitor TAK-659 Prevents Splenomegaly and Tumor Development in a Murine Model of Epstein-Barr Virus-Associated Lymphoma

The novel SYK and FLT3 inhibitor TAK-659 prevents the enlargement of spleen and tumor development in a mouse model of EBV-associated lymphoma by counteracting the activation of cellular kinase SYK through the viral LMP2A gene by inducing cell death in tumor cells but not in nontumor cells. These findings indicate that TAK-659 may be a very effective nontoxic therapeutic molecule especially for EBV-positive hematologic malignancies. ABSTRACT Epstein-Barr virus (EBV) is associated with several B and epithelial cell cancers. EBV-encoded latent membrane protein 2A (LMP2A) contributes to cellular transformation by mimicking B cell receptor signaling. LMP2A/MYC double transgenic mice develop splenomegaly and B cell lymphoma much faster than MYC transgenic mice do. In this study, we explored the potential therapeutic efficacy of a novel spleen tyrosine kinase (SYK) and FLT3 inhibitor TAK-659 for development of a treatment option for EBV-associated malignancies. In our transgenic model, TAK-659 treatment totally abrogated splenomegaly and tumor development in LMP2A/MYC mice in both pretumor and tumor cell transfer experiments. TAK-659 treatment killed tumor cells, but not host cells within the spleen and tumors. Furthermore, TAK-659 treatment abrogated metastasis of tumor cells into bone marrow. Our data also show that TAK-659 inhibits SYK phosphorylation and induces apoptosis in LMP2A/MYC tumor cells at low nanomolar concentrations. Therefore, TAK-659 may provide an effective therapeutic option for treatment of LMP2A-positive EBV-associated malignancies and should be explored further in clinical trials. IMPORTANCE The novel SYK and FLT3 inhibitor TAK-659 prevents the enlargement of spleen and tumor development in a mouse model of EBV-associated lymphoma by counteracting the activation of cellular kinase SYK through the viral LMP2A gene by inducing cell death in tumor cells but not in nontumor cells. These findings indicate that TAK-659 may be a very effective nontoxic therapeutic molecule especially for EBV-positive hematologic malignancies.
Brain activity mediates the relation between emotional but not instrumental support and trait loneliness

Abstract Loneliness results from lacking satisfied social connections. However, little is known how trait loneliness, which is a stable personal characteristic, is influenced by different types of social support (i.e. emotional and instrumental support) through the brain activity associated with loneliness. To explore these questions, data of resting‐state functional magnetic resonance imaging (R‐fMRI) of 92 healthy participants were analyzed. We identified loneliness‐related brain regions by correlating participants’ loneliness scores with amplitudes of low‐frequency fluctuation (ALFF) of R‐fMRI data. We then conducted mediation analyses to test whether the negative relation between each type of social support and loneliness was explained via the neural activity in the loneliness‐related brain regions. The results showed that loneliness was positively related to the mean ALFF value within right inferior temporal gyrus (ITG). In addition, the negative relation between emotional support and loneliness was explained by a decrease in the spontaneous neural activity within right ITG but this pattern was not observed for instrumental support. These results suggest the importance of social information processing on trait loneliness and highlight the need to differentiate the functions of different types of social support on mental health from a neural perspective.
High prevalence and autochtonous transmission of human pegivirus (HPgV‐1) in blood donors in the extreme southern of Brazil

Recent studies have suggested that human pegivirus 1 (HPgV‐1) may have some pathogenic potential. In the southernmost region of Brazil, studies on HPgV‐1 are scarce, and circulating genotypes have not yet been identified. The current study aimed to evaluate the prevalence of HPgV‐1 among blood donors from the southernmost region of Brazil and identify the genotypes involved with associated factors. A cross‐sectional study was conducted with 281 blood donors, who had their plasma subjected to RNA extraction, complementary DNA synthesis, HPgV‐1 detection by nested polymerase chain reaction, and subsequent genotyping. The observed prevalence of HPgV‐1‐RNA was 21.7%. The only variable that was significantly associated with virus infection was the relationship status of the donor. Single or no fixed partner blood donors were twice as likely to have HPgV‐1 (95% CI, 1.12 to 4.56; P = 0.02). Genotype 2—subtypes 2b (69%) and 2a (29%)—was the most prevalent. In the absence of risk factors for parenteral transmission, it is likely that sexual transmission was the route of infection in the individuals studied. Further work will be needed to determine whether this virus is inert in the population, or if there are potential deleterious effects in infected individuals.
Large-Scale Adversarial Sports Play Retrieval with Learning to Rank

As teams of professional leagues are becoming more and more analytically driven, the interest in effective data management and access of sports plays has dramatically increased. In this article, we present a retrieval system that can quickly find the most relevant plays from historical games given an input query. To search through a large number of games at an interactive speed, our system is built upon a distributed framework so that each query-result pair is evaluated in parallel. We also propose a pairwise learning to rank approach to improve search ranking based on users’ clickthrough behavior. The similarity metric in training the rank function is based on automatically learnt features from a convolutional autoencoder. Finally, we showcase the efficacy of our learning to rank approach by demonstrating rank quality in a user study.
Capacity-Achieving Private Information Retrieval Codes with Optimal Message Size and Upload Cost

We propose a new capacity-achieving code for the private information retrieval (PIR) problem, and show that it has the minimum message size (being one less than the number of servers) and the minimum upload cost (being roughly linear in the number of messages) among a general class of capacity-achieving codes, and in particular, among all capacity-achieving linear codes. Different from existing code constructions, the proposed code is asymmetric, and this asymmetry appears to be the key factor leading to the optimal message size and the optimal upload cost. The converse results on the message size and the upload cost are obtained by a strategic analysis of the information theoretic proof of the PIR capacity, from which a set of critical properties of any capacity-achieving code in the code class of interest is extracted.
How Dark Personalities Perpetrate Partner and General Aggression in Sweden and the United Kingdom

Research has demonstrated, in Western nations, men and women are both perpetrators and victims of intimate partner violence (IPV). However, to the best of our knowledge, IPV and the Dark Tetrad (Machiavellianism, subclinical narcissism, subclinical psychopathy, and subclinical sadism) have not been included in this research fully. We investigated how these dark personalities influenced the perpetration of IPV in a cross-cultural study between Sweden and the United Kingdom through surveys with university students. We furthermore compared IPV perpetration with same-sex aggression of a non-romantic partner to explore sex- and aggression-specific effects. In a sample of 342 participants, our main findings were the following: (a) the only significant difference in IPV perpetration was women were more verbally aggressive; (b) men reported more verbal and physical same-sex aggression of a non-romantic partner; (c) men scored higher on all the Dark Tetrad personalities regardless of culture, while the Swedish sample scored significantly higher on subclinical narcissism and sadism; (d) the Dark Tetrad and aggression perpetration were significantly correlated; (e) different Dark Tetrad personalities predicted different forms of aggression perpetration with some gender differences; and (f) being high on subclinical psychopathy predicted most types of aggression regardless of target. Our study highlights that dark personalities engage in particular types of aggression, which helps to determine how and when distinctive personalities aggress for potential interventions.
Strategies of data layout and cache writing for input-output optimization in high performance scientific computing: Applications to the forward electrocardiographic problem

Input-output (I/O) optimization at the low-level design of data layout on disk drastically impacts the efficiency of high performance computing (HPC) applications. However, such a low-level optimization is in general challenging, especially when using popular scientific file formats designed with an emphasis on portability and flexibility. To reconcile these two aspects, we present a novel low-level data layout for HPC applications, fully independent of the number of dimensions in the dataset. The new data layout improves reading and writing efficiency in large HPC applications using many processors, and in particular during parallel post-processing. Furthermore, its combination with a cached write mode, in order to aggregate multiple writes into larger ones, substantially decreased the writing times of the proposed strategy. When applied to our simulation framework for the forward calculation of the human electrocardiogram, the combined strategy resulted in drastic improvements in I/O performance, of up to 40% in writing and 93–98% in reading for post-processing tasks. Given the generality of the proposed strategies and scientific file formats used, our results may represent significant improvements in I/O performance of HPC applications across multiple disciplines, reducing execution and post-processing times and leading to a more efficient use of HPC resource envelopes.