Miracle-dz/UniFAR-FTUs huggingface dataset:
Visualization of Latin Textual Variants using a Pixel-Based Text Analysis Tool

One of the most important activities of Latin scholars is to analyze fragmentary copies of a Classical text and assemble an annotated reconstruction as a conjecture about its original form. We have developed a pixel-based visual text analysis tool to help Latin scholars visualize the evolution of historic copies and analyze the details of alterations and errors introduced in transcription. Coordination of pixel-based visualizations with focus +context navigation across multiple views allows compact representation of text variation across scales of text structure. This approach helps scholars validate the accuracy of variations and assess subtle differences across fragmentary copies as well as past reconstructions. In this paper, we describe the central design features of the tool that help scholars analyze the density and distribution of variants by interacting with text at the granularities of words, lines, and pages simultaneously. We present the results of a user study on our initial multiple view focus+context design and discuss how the results motivate a more visually integrated focus+context design using tiered views.
Effectiveness of First-Line Bevacizumab in Metastatic Colorectal Cancer: The Observational Cohort Study GRETA.

BACKGROUND Scant real-world data exist on the clinical outcomes associated with the use of bevacizumab-containing chemotherapy (B+CT) in patients with metastatic colorectal cancer (mCRC). The primary objective of the GRETA cohort study was to compare the overall survival (OS) of patients with mCRC treated with first-line B+CT versus chemotherapy (CT) alone, in an Italian clinical practice setting. MATERIALS AND METHODS Incident patients with mCRC were identified during the period 2010-2012 from five population-based cancer registries in Italy. Cases were linked to regional health care utilization databases to obtain the entire spectrum of health services provided to each patient. Patients starting a first-line treatment with B+CT or CT alone within 90 days from the diagnosis were included in the study cohort. A propensity score (PS) method was applied to account for residual confounding. RESULTS Of 480 patients with mCRC included in the study cohort, 21.0 received first-line B+CT, and 79.0% received CT. Patients receiving B+CT were younger (p < .001) and underwent surgery more frequently (p = .001). The median OS was 22.5 and 14.6 months for B+CT and CT, respectively (p = .011). The corresponding hazard ratios adjusted by multivariate modeling and PS matched analysis were 0.82 (95% confidence interval [CI], 0.62-1.08) and 0.86 (95% CI, 0.56-1.33), respectively. Similar results were observed after subgrouping by age and surgery. CONCLUSION In this Italian real-world setting of unselected mCRC, the OS of patients treated with B+CT was consistent with previous observational and patient-registry studies. However, definitive evidence of an improvement in OS cannot be drawn. IMPLICATIONS FOR PRACTICE Bevacizumab is a well-established first-line treatment for metastatic colorectal cancer. However, there is scarce evidence in the literature about its effectiveness in clinical practice. Evaluating this topic should be of interest for both clinicians and regulatory agencies. In this study, the median overall survival of the bevacizumab cohort was strikingly coherent with that reported in large observational series of unselected patients, thus suggesting a consistent and reproducible effect of the drug in clinical practice. Although consistent results were observed both in the overall population and in age and surgery subgroups, the present study did not offer definitive evidence of an improvement in OS.
Neurokinin-1 Receptor Deficiency Improves Survival in Murine Polymicrobial Sepsis Through Multiple Mechanisms in Aged Mice.

OBJECTIVE Substance P (SP) is a neuropeptide that contributes to a proinflammatory state by binding to the neurokinin 1 receptor (NK-1R). Limiting this interaction has been shown to attenuate the acute inflammation. Our hypothesis was that NK-1R activation would contribute to the morbidity and mortality of sepsis in a model using mice genetically deficient in the NK-1R. METHODS To investigate the role of the SP/NK-1R axis in a murine model of sepsis, cecal ligation and puncture (CLP) in NK-1R deficient and wild type (WT) aged mice was performed. Acute inflammation was assessed by measuring circulating cytokines and clinical parameters. RESULTS Deletion of the NK-1R results in improved survival following CLP (NK-1R knockout mice survival = 100% vs. WT = 14%). A reduction in the inflammatory cytokines interleukin (IL) 6, macrophage inflammatory peptide 2, and IL-1 receptor antagonist, improved hemodynamic parameters, and increased neutrophilia were present in the NK-1R-deficient mice after CLP compared with WT mice. CONCLUSIONS These data confirm the hypothesis that eliminating the SP/NK-1R interaction in a highly lethal murine model of sepsis leads to decreased morbidity and mortality through multiple mechanisms.
Rho GTPases in A549 and Caco-2 cells dominating the endocytic pathways of nanocarbons with different morphologies

Introduction Endocytosis of nanomaterials is the first step of nano-bio interaction and current regulation is mostly by nanomaterials but seldom by intracellular signaling proteins. Materials and methods Herein, we synthesized tubular nanocarbon (oxMWCNT) and lamellar-like nanocarbon (oxGRAPHENE) and formulated their aqueous dispersion. A549 and Caco-2 cells were selected as the models of tumor and intestinal epithelial cells, respectively. After knocking down three members of Rho GTPases (Cdc42, Rac1, RhoA) in these two cell lines, their silencing effects on the uptake pathways of nanomaterials with different morphologies were investigated. Results An unexpected finding was that the knock-down led to opposite uptake trends in different types of cells. The endocytosis of carbon nanomaterials increased in Caco-2 cells when Rho GTPases were inactivated, while that in A549 cells decreased. For nanomaterials with different shapes, the involved GTPase member of Rho family, or regulating protein molecule, was different. Concretely, Cdc42 and Rac1 were involved in oxMWCNT endocytosis, while all three GTPases participated in oxGRAPHENE internalization. More interestingly, such difference induced different uptake pathways, namely, the cellular uptake of oxMWCNT was clathrin-mediated and oxGRAPHENE was caveolin-modulated, both with the involvement of dynamin. Conclusion In conclusion, this study provides new insights for the potential intervention in nano-bio interplay.
Using virtual reality to counter extremism

Extremism presents a significant danger to safe and healthy environment of communities. In recent times, some extremist groups are treacherously using informational content to influence public perception. More seriously, these groups are targeting youth using religiously significant terms described with distorted interpretations. The discourse of these groups presents a romanticized view of destruction, trivializes loss of life and breeds hatred to anyone adhering to a different set of values. These extremist groups pose three important risks to communities: (1) influencing public perception and gaining silent sympathizers, (2) creating a sense of us versus them which then leads to discord and identity conflicts and (3) radicalizing and/or recruiting youth. This research presents a digital prototype developed in a 3D‐environment, based on research concerning informational and affective properties of extremists' content, with an objective to educate youth against extremism.
The Response of Vegetation Phenology and Productivity to Drought in Semi-Arid Regions of Northern China

A major disturbance in nature, drought, has a significant impact on the vulnerability and resilience of semi-arid ecosystems by shifting phenology and productivity. However, due to the various disturbance mechanisms, phenology and primary productivity have remained largely ambiguous until now. This paper evaluated the spatio-temporal changes of phenology and productivity based on GIMMS NDVI3g time series data, and demonstrated the responses of vegetation phenology and productivity to drought disturbances with the standardized precipitation evapotranspiration index (SPEI) in semi-arid ecosystems of northern China. The results showed that (1): vegetation phenology exhibited dramatic spatial heterogeneity with different rates, mostly presented in the regions with high chances of land cover type variation. The delayed onset of growing season (SOS) and advanced end of growing season (EOS) occurred in Horqin Sandy Land and the eastern Ordos Plateau with a one to three days/decade (p < 0.05) rate and in the middle and east of Inner Mongolia with a two days/decade rate, respectively. Vegetation productivity presented a clear pattern: south increased and north decreased. (2) Spring drought delayed SOS in grassland, barren/sparsely vegetated land, and cropland, while autumn drought significantly advanced EOS in grassland and barren/sparsely vegetated lands. Annual drought reduced vegetation productivity and the sensitivity of productivity regarding drought disturbance was higher than that of phenology.
Discovery of a Human Testis-specific Protein Complex TEX101-DPEP3 and Selection of Its Disrupting Antibodies*

The interactome of human TEX101 protein in testicular tissues and spermatozoa was identified by applying a quantitative co-immunoprecipitation-MS approach. DPEP3 emerged as the top hit, and TEX101-DPEP3 complex was validated by using hybrid immunoassays. Combinations of antibodies against different epitopes of TEX101 and DPEP3 facilitated selection of clones which disrupted the native TEX101-DPEP3 complex. Graphical Abstract Highlights Quantitative co-IP-MS approach to discover the human TEX101 interactome. Validation of the human testis-specific protein complex TEX101-DPEP3. Development of a hybrid immunoassay to screen for disruptors of TEX101-DPEP3 complex. TEX101 is a testis-specific protein expressed exclusively in male germ cells and is a validated biomarker of male infertility. Studies in mice suggest that TEX101 is a cell-surface chaperone which regulates, through protein-protein interactions, the maturation of proteins involved in spermatozoa transit and oocyte binding. Male TEX101-null mice are sterile. Here, we identified by co-immunoprecipitation-mass spectrometry the interactome of human TEX101 in testicular tissues and spermatozoa. The testis-specific cell-surface dipeptidase 3 (DPEP3) emerged as the top hit. We further validated the TEX101-DPEP3 complex by using hybrid immunoassays. Combinations of antibodies recognizing different epitopes of TEX101 and DPEP3 facilitated development of a simple immunoassay to screen for disruptors of TEX101-DPEP3 complex. As a proof-of-a-concept, we demonstrated that anti-TEX101 antibody T4 disrupted the native TEX101-DPEP3 complex. Disrupting antibodies may be used to study the human TEX101-DPEP3 complex, and to develop modulators for male fertility.
Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial).

Blood cell membranes in sickle cell disease (SCD) have low docosahexaenoic acid (DHA). DHA treatment reduces sickle cell crisis (SCC) rate and ameliorates the inflammation, oxidative stress, and hypercoagulable state of SCD. SC411 is a novel DHA ethyl ester formulation with a proprietary delivery platform (Advanced Lipid Technology) that enhances DHA bioavailability. The SCOT trial investigated the effect of 3 different doses of SC411 on clinical and biochemical endpoints in 67 children with SCD (5-17 years old). Seventy-six percent of subjects were also receiving hydroxyurea. After 4 weeks of treatment with SC411 at 20, 36, and 60 mg DHA/kg per day or placebo a statistically significant (P < .001) mean percentage increase of blood cell membrane DHA and eicosapentaenoic acid was seen vs baseline: 109.0% (confidence interval [CI], 46.7-171.3), 163.8% (CI, 108.3-219.2), 170.8% (CI, 90.2-251.4), and 28.6% (CI, 250.1 to 107.3), respectively. After 8 weeks of treatment, statistically significant changes vs placebo were also observed in D-dimer (P = .025) and soluble E-selectin (P = .0219) in subjects exposed to 36 mg/kg. A significant increase in hemoglobin was observed against placebo in subjects receiving 20 mg DHA/kg per day (P = .039). SC411 significantly reduced electronic diary recorded SCC, analgesic use at home, and days absent from school because of sickle cell pain. The lower rate of clinical SCC observed in the pooled active groups vs placebo did not reach statistical significance (rate ratio, 0.47; 95% CI, 0.20-1.11; P = .07). All tested doses were safe and well tolerated. This trial was registered at www.clinicaltrials. gov as #NCT02973360.
Improvement of SSA Approach for Numerical Simulation of Sea Surface Scattering at High Microwave Bands

: Small slope approximation (SSA) is a widely accepted approach in sea surface electromagnetic (EM) scattering studies. Nevertheless, the spatial sample interval used for sea surface should be around or even smaller than one-eighth of the incident wavelength to ensure EM scattering calculation accuracy, which requires a huge amount of computation, creating an obstacle to scattering numerical simulation, especially for high microwave band incident waves and large sea surface scenes. In this paper, a novel realization approach for SSA is proposed to signiﬁcantly decrease the computation demands and computer memory requirements in sea surface scattering simulation. First, the sea surface is decomposed into two scales, and each scale has its own spatial sample interval. Then, the inclination state of the large-scale sea surface is determined under a speciﬁc wind speed. After that, scattering calculations of a typical surface cell with a ﬁnely sampled structure are completed and saved in all possible situations. Finally, scattering results for all the cells of a concrete sea surface are extracted from the saved cell scattering data base. From the different kinds of scattering result comparisons, it is demonstrated that this novel SSA realization approach can attain almost similar scattering results to exact SSA. This approach can be broadly applied in composite scattering studies, and remote sense imaging simulation of large sea surfaces with multiple targets.
Diagnostic Testing and Decision-Making: Beauty Is Not Just in the Eye of the Beholder

To use a diagnostic test effectively and consistently in their practice, clinicians need to know how well the test distinguishes between those patients who have the suspected acute or chronic disease and those patients who do not. Clinicians are equally interested and usually more concerned whether, based on the results of a screening test, a given patient actually: (1) does or does not have the suspected disease; or (2) will or will not subsequently experience the adverse event or outcome. Medical tests that are performed to screen for a risk factor, diagnose a disease, or to estimate a patient’s prognosis are frequently a key component of a clinical research study. Like therapeutic interventions, medical tests require proper analysis and demonstrated efficacy before being incorporated into routine clinical practice. This basic statistical tutorial, thus, discusses the fundamental concepts and techniques related to diagnostic testing and medical decision-making, including sensitivity and specificity, positive predictive value and negative predictive value, positive and negative likelihood ratio, receiver operating characteristic curve, diagnostic accuracy, choosing a best cut-point for a continuous variable biomarker, comparing methods on diagnostic accuracy, and design of a diagnostic accuracy study.
Tousled-like kinases stabilize replication forks and show synthetic lethality with checkpoint and PARP inhibitors

TLKs promote nucleosome assembly and prevent fork collapse and DNA damage upon checkpoint or PARP inhibition. DNA sequence and epigenetic information embedded in chromatin must be faithfully duplicated and transmitted to daughter cells during cell division. However, how chromatin assembly and DNA replication are integrated remains unclear. We examined the contribution of the Tousled-like kinases 1 and 2 (TLK1/TLK2) to chromatin assembly and maintenance of replication fork integrity. We show that TLK activity is required for DNA replication and replication-coupled nucleosome assembly and that lack of TLK activity leads to replication fork stalling and the accumulation of single-stranded DNA, a phenotype distinct from ASF1 depletion. Consistent with these results, sustained TLK depletion gives rise to replication-dependent DNA damage and p53-dependent cell cycle arrest in G1. We find that deficient replication-coupled de novo nucleosome assembly renders replication forks unstable and highly dependent on the ATR and CHK1 checkpoint kinases, as well as poly(adenosine 5′-diphosphate–ribose) polymerase (PARP) activity, to avoid collapse. Human cancer data revealed frequent up-regulation of TLK genes and an association with poor patient outcome in multiple types of cancer, and depletion of TLK activity leads to increased replication stress and DNA damage in a panel of cancer cells. Our results reveal a critical role for TLKs in chromatin replication and suppression of replication stress and identify a synergistic lethal relationship with checkpoint signaling and PARP that could be exploited in treatment of a broad range of cancers.
Exploring prestigious citations sourced from top universities across disciplines

There have been many studies on the factors influencing paper citation counts. A number of studies have focused on the citing papers, and corresponding methods were proposed to measure the prestige of citations based on the journal impact factors, the total citation counts and the PageRank algorithm values. However, there are drawbacks to these methods. In this paper, we propose a novel method to identify prestigious citations from the affiliation of the citing paper. Specifically, if the authors of the citing paper are affiliated with a prestigious university, the citing paper could be counted as a prestigious citation. As a pilot, we used the top 200 universities on the QS World University Rankings 2015 to identify the prestigious universities so that the prestigious citations, named as QS citations, were identified accordingly. Experimental results validated that QS citations have more important impact on the cited papers than other citations. Papers with QS citations have better performance across most disciplines not only in total citation counts, but also in altmetrics such as the Altmetric Attension Score and Mendeley reader counts.
PCDC - On the Highway to Data - A Tool for the Fast Generation of Large Synthetic Data Sets

In this paper, we present Parallel Coordinates for Data Creation (PCDC), a new visual-interactive method for the fast generation of labeled multidimensional data sets. Multivariate data need to be analyzed in various domains such as ﬁnance, biology or medicine using complex data mining techniques. For the evaluation or presentation of the techniques, e.g., for assessing their sensitivity to speciﬁc data properties, test data need to be generated. PCDC allows for a fast and intuitive creation of multivariate data with several classes. It is based on interactive deﬁnition of data regions and data distributions in a parallel coordinates view. It offers a quick deﬁnition of data regions over several dimensions in one interface. Moreover, the users can directly see the outcome of their settings in the same view without the need for switching between data generation and output visualization. Our tool enables also an easy adjustment of the data generation parameters for creating additional similar datasets. Categories and Subject Descriptors (according to ACM CCS) : Computer Graphics [I.3. 3]: Viewing Algorithms— Computer Graphics [I.3. 6]: Methodology and Techniques—Graphics data structures and data types
Identifying the inserted locus of randomly integrated expression plasmids by whole-genome sequencing of Aspergillus strains

ABSTRACT Whole-genome sequencing was conducted on two Aspergillus oryzae strains used for the manufacturing of food enzymes, Acrylaway® and Shearzyme®, with the aim of identifying the inserted locus of randomly integrated expression plasmid and obtaining flanking sequences for safety assessment. Illumina paired-end sequencing was employed, and the obtained reads were mapped to two references: the public genome sequence of Aspergillus oryzae RIB40 and the in-house sequence of the used expression plasmid. Introducing the concept of linking-reads, one locus for each was successfully identified as the integrated site. In the case of Acrylaway®, the obtained sequences suggested that the expression plasmid had been integrated as multiple copies in tandem form. In the case of Shearzyme®, however, information on one edge of the insert was missing, which required extra polymerase chain reaction (PCR) cloning for safety assessment. A 4-kb deletion was detected at the integrated site. There was also evidence of rearrangement occurring in Shearzyme® strain. Graphical Abstract Concept of linking reads made the identification of inserted locus possible.
Vocal One Switch (VOS) Selection Interfaces for Virtual and Augmented Reality Hands-free Tasks

Several virtual and augmented reality tasks involve users in hands-free interactions; in this case, speech-based systems are often preferred for their intuitiveness and naturalness. On the other hand, the robustness of this kind of interfaces can be an issue, thus affecting both the usability and the user experience, when they are used in noisy environments. This paper proposes a comparison of a traditional multiword interface with a one switch interface triggered by vocal commands: three different scanning algorithms are tested. With one switch scanning interfaces users can sequentially select the desired command, thus improving the robustness of traditional multiword speech recognition-based interfaces. Latency time is an issue for one switch interfaces, but it is shown how a bidirectional scanning algorithm based on a non binary switch can strongly mitigate this problem. The comparison considered both objectively (robustness and efficiency) and subjectively (user feedback) parameters.
Small RNAs detected in exosomes derived from the MH7A synovial fibroblast cell line with TNF-α stimulation

Rheumatoid arthritis (RA) is an autoimmune disease that causes the chronic inflammation of the joints. Intercellular communication containing synovial fibroblasts seems to play a major role in RA pathogenesis. In this study, to better understand intercellular communication related to RA pathogenesis, we identified exosomal microRNAs (miRNAs) derived from synovial fibroblasts. Exosomes were collected from an RA synovial fibroblast (RASF) cell line, namely, MH7A, with or without stimulation by tumor necrosis factor alpha (TNF-α). We used small RNA sequencing to analyze the profile of small RNAs, including miRNAs, in MH7A exosomes and cells. By using differential expression analysis, we identified four miRNAs (miR-155-5p, miR-146a-5p, miR-323a-5p, and miR-1307-3p) that are upregulated in exosomes with TNF-α stimulation. The identification of miR-155-5p and miR-146a-5p which have been reported in RA patients demonstrated the validity of our experimental model. Other two miRNAs were newly identified. miR-323a-5p was predicted to target the protein encoding gene CD6, which attenuates T-cell activation signals, and miR-1307-3p was predicted to target the protein encoding gene N-myc downstream-regulated gene 2 (NDRG2), which inhibits osteoclast-related gene expression. The results suggested that these miRNAs might be involved in RA pathogenesis. We hope our results will help us understand the role of RASF exosomes in RA pathogenesis.