Miracle-dz/UniFAR-FTUs huggingface dataset:
Borrelia burgdorferi-Induced Changes in the Class II Self-Immunopeptidome Displayed on HLA-DR Molecules Expressed by Dendritic Cells

The MHC class II antigen processing and presentation pathway has evolved to derive short amino acid peptides from proteins that enter the endocytic pathway, load them onto MHC class II molecules and display them on the surface of antigen presenting cells for recognition by CD4+ T cells. Under normal circumstances, peptides bound to MHC class II molecules are derived from host (self) proteins and not recognized by T cells due to tolerance mechanisms. Pathogens induce significant changes in the biology of antigen presenting cells, including upregulation of MHC processing and presentation. We therefore hypothesized that exposure to pathogens may alter the repertoire of self-peptides bound to MHC class II molecules. To test this hypothesis, we isolated monocyte-derived dendritic cells from healthy subjects, exposed them to the TLR-2 agonist lipoteichoic acid or live Borrelia burgdorferi, the causative agent of Lyme disease, and isolated and characterized HLA-DR associated peptides using mass spectrometry. Our results show that lipoteichoic acid-stimulated, B. burgdorferi-stimulated and unstimulated monocyte-derived dendritic cells largely derive their self-peptides from similar overlapping sets of host proteins. However, lipoteichoic acid and B. burgdorferi stimulation promote the processing and presentation of new sets of HLA-DR associated self-peptides derived from unique protein sources. Examination of processes and compartments these proteins reside in, indicate that activation of monocyte-derived dendritic cells changes the range of host self-proteins available for processing and presentation on MHC class II molecules. These findings reveal that the HLA-DR-bound self-immunopeptidome presented by mo-DCs is dynamic in nature and changes with activation state reflective of cellular function. In addition, among the repertoire of self-peptides bound to HLA-DR are several epitopes known to be recognized by autoreactive T cells. These studies are relevant to our basic understanding of pathogen-induced changes in monocyte-derived dendritic cell function, and the mechanisms involved in infection-induced autoimmune illnesses such as Lyme arthritis.
RegX3 Activates whiB3 Under Acid Stress and Subverts Lysosomal Trafficking of Mycobacterium tuberculosis in a WhiB3-Dependent Manner

Two-component systems (TCSs) are central to the ability of Mycobacterium tuberculosis to respond to stress. One such paired TCS is SenX3-RegX3, which responds to phosphate starvation. Here we show that RegX3 is required for M. tuberculosis to withstand low pH, one of the challenges encountered by the bacterium in the host environment, and that RegX3 activates the cytosolic redox sensor WhiB3 to launch an appropriate response to acid stress. We show that the whiB3 promoter of M. tuberculosis harbors a RegX3 binding motif. Electrophoretic mobility shift assays (EMSAs) show that phosphorylated RegX3 (RegX3-P) (but not its unphosphorylated counterpart) binds to this motif, whereas a DNA binding mutant, RegX3 (K204A) fails to do so. Mutation of the putative RegX3 binding motif on the whiB3 promoter, abrogates the binding of RegX3-P. The significance of this binding is established by demonstrating that the expression of whiB3 is significantly attenuated under phosphate starvation or under acid stress in the regX3-inactivated mutant, ΔregX3. Green fluorescent protein (GFP)-based reporter assays further confirm the requirement of RegX3 for the activation of the whiB3 promoter. The compromised survival of ΔregX3 under acid stress and its increased trafficking to the lysosomal compartment are reversed upon complementation with either regX3 or whiB3, suggesting that RegX3 exerts its effects in a WhiB3-dependent manner. Finally, using an in vitro granuloma model, we show that granuloma formation is compromised in the absence of regX3, but restored upon complementation with either regX3 or whiB3. Our findings provide insight into an important role of RegX3 in the network that regulates the survival of M. tuberculosis under acid stress similar to that encountered in its intracellular niche. Our results argue strongly in favor of a role of the RegX3-WhiB3 axis in establishment of M. tuberculosis infection.
Deep Autoencoders and Feedforward Networks Based on a New Regularization for Anomaly Detection

Anomaly detection is a problem with roots dating back over 30 years. The NSL-KDD dataset has become the convention for testing and comparing new or improved models in this domain. In the field of network intrusion detection, the UNSW-NB15 dataset has recently gained significant attention over the NSL-KDD because it contains more modern attacks. In the present paper, we outline two cutting-edge architectures that push the boundaries of model accuracy for these datasets, both framed in the context of anomaly detection and intrusion classification. We summarize training methodologies, hyperparameters, regularization, and other aspects of model architecture. Moreover, we also utilize the standard deviation of weight values to design a new regularization technique. Then, we embed it on both models and report the models’ performance. Finally, we detail potential improvements aimed at increasing models’ accuracy.
METRICaL EvaLUaTIon oF SPaTIaL ConTEnT FoR SEgMEnTaTIon­BaSED IMagE RETRIEvaL

Interest in the image content analysis has been motivated by expansion of imaging in manifold scopes of activity, the availability of large image libraries, growth of multimedia applications, etc. One of the ways for partial elimination of a semantic gap between low-level visual features and high-level human concept is to analyze spatial properties of image parts specifically induced by segmentation. To provide a region-based image retrieval with a query ‘ad exemplum’ (to wide extent), a new metric to compare arbitrary nested partitions is proposed. Studied metrical properties of partially ordered quotient sets provide e.g. the objects search independent on the background.
In silico prediction of COVID-19 test efficiency with DinoKnot

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus spreading across the world causing the disease COVID-19. The diagnosis of COVID-19 is done by quantitative reverse-transcription polymer chain reaction (qRT-PCR) testing which utilizes different primer-probe sets depending on the assay used. Using in silico analysis we aimed to determine how the secondary structure of the SARS-CoV-2 RNA genome affects the interaction between the reverse primer during qRT-PCR and how it relates to the experimental primer-probe test efficiencies. We introduce the program DinoKnot (Duplex Interaction of Nucleic acids with pseudoKnots) that follows the hierarchical folding hypothesis to predict the secondary structure of two interacting nucleic acid strands (DNA/RNA) of similar or different type. DinoKnot is the first program that utilizes stable stems in both strands as a guide to find the structure of their interaction. Using DinoKnot we predicted the interaction of the reverse primers used in four common COVID-19 qRT-PCR tests with the SARS-CoV-2 RNA genome. In addition, we predicted how 12 mutations in the primer/probe binding region may affect the primer/probe ability and subsequent SARS-CoV-2 detection. While we found all reverse primers are capable of interacting with their target area, we identified partial mismatching between the SARS-CoV-2 genome and some reverse primers. We predicted three mutations that may prevent primer binding, reducing the ability for SARS-CoV-2 detection. We believe our contributions can aid in the design of a more sensitive SARS-CoV-2 test. Author summary The current testing for the disease COVID-19 that is caused by the novel cornonavirus SARS-CoV-2 uses oligonucleotides called primers that bind to specific target regions on the SARS-CoV-2 genome to detect the virus. Our goal was to use computational tools to predict how the structure of the SARS-CoV-2 RNA genome affects the ability of the primers to bind to their target region. We introduce the program DinoKnot (Duplex interaction of nucleic acids with pseudoknots) that is able to predict the interactions between two DNA or RNA molecules. We used DinoKnot to predict the efficiency of four common COVID-19 tests, and the effect of mutations in the SARS-CoV-2 virus on ability of the COVID-19 tests in detecting those strains. We predict partial mismatching between some primers and the SARS-CoV-2 genome but that all primers are capable of interacting with their target areas. We also predict three mutations that prevent primer binding and thus SARS-CoV-2 detection. We discuss the limitations of the current COVID-19 testing and suggest the design of a more sensitive COVID-19 test that can be aided by our findings.
Time and space in segmentation

Arthropod segmentation and vertebrate somitogenesis are leading fields in the experimental and theoretical interrogation of developmental patterning. However, despite the sophistication of current research, basic conceptual issues remain unresolved. These include (1) the mechanistic origins of spatial organisation within the segment addition zone (SAZ); (2) the mechanistic origins of segment polarisation; (3) the mechanistic origins of axial variation; and (4) the evolutionary origins of simultaneous patterning. Here, I explore these problems using coarse-grained models of cross-regulating dynamical processes. In the morphogenetic framework of a row of cells undergoing axial elongation, I simulate interactions between an “oscillator”, a “switch”, and up to three “timers”, successfully reproducing essential patterning behaviours of segmenting systems. I also compare the output of these largely cell-autonomous models to variants that incorporate positional information. I find that scaling relationships, wave patterns, and patterning dynamics all depend on whether the SAZ is regulated by temporal or spatial information. I also identify three mechanisms for polarising oscillator output, all of which functionally implicate the oscillator frequency profile. Finally, I demonstrate significant dynamical and regulatory continuity between sequential and simultaneous modes of segmentation. I discuss these results in the context of the experimental literature.
ERWR: Predicting Efficacious Drug Combinations in Cancer Based on Random Walk with Restart

(1) Background Compared with monotherapy, efficacious drug combinations can increase the therapeutic effect, decrease drug resistance of experimental subjects and the side effects of drugs. Therefore, efficacious drug combinations are widely used in the treatment of complex diseases, such as various cancers. However, compared with the mathematical model and computational method, experimental screening efficacious drug combinations is time-consuming, costly, laborious, and inefficient; (2) Methods we predicted efficacious drug combinations in cancer based on random walk with restart (ERWR). An efficacious score can be obtained between any two individual drugs by ERWR; (3) Results As a result, we analyzed the rationality of the efficacious score first. Besides, compared with the other methods by leave-one-out cross-validation, all the Area Under Receiver Operating Characteristic Curves (AUROCs) of ERWR were higher for data sets of breast cancer, colorectal cancer, and lung cancer. Moreover, the case study of breast cancer showed that ERWR could discover potential efficacious drug combinations; (4) Conclusions These results suggest that ERWR is a novel way to discover efficacious drug combinations in cancer, which provides new prospects for cancer treatment. Furthermore, ERWR is a semi-supervised learning framework that can be used to predict combinations of drugs for other complex diseases.
A model of patent trolls

This paper develops a model of patent trolls to understand various litigation strategies employed by nonpracticing entities (NPE). We show that when a NPE faces multiple potential infringers who use related technologies, it can gain a credible threat to litigate even when it has no such credibility vis-‡-vis any single potential infringer in isolation. This is due to an information externality generated by an early litigation outcome for subsequent litigation. Successful litigation creates an option value against future potential infringers through Bayesian updating. This renders a credible litigation threat against the initial defendant and allows the NPE to extract more rents. We discuss policy implications including the adoption of the British system of ìloser-paysî fee shifting and the use of injunctive relief.
Epidemiology of High Ankle Sprains: A Systematic Review

Syndesmotic sprains or high ankle sprains are reported to be associated with increasing morbidity and time loss. The aim of this study was to critically appraise literature on epidemiology of syndesmotic sprains through systematic review of published literatures. A systematic review was conducted online for literature published in English using PubMed and Google Scholar, as per PRISMA guidelines up to April 30, 2019. Predefined eligibility criteria were applied, and the data thus compiled were analyzed. A total of 26 studies were found to be eligible, of which three-fourths involved sporting population. Considerable inconsistency in assessment procedure reporting, injury and injury severity definition with variable unit measures used to describe incidence or injury rate was observed. Meta-analysis and intra- and intersports comparison could not be performed owing to the study heterogeneity and methodological variability. There is a need for standardization in future research, specifically with regard to injury assessment and reporting, demanding heightened awareness and improved diagnostic modalities, as injury epidemiology is integral to the overall injury-prevention conundrum. Levels of Evidence: Systematic review, Level III
V OICE C ONVERSION B ASED ON S PECTRAL E NVELOPE T RANSFORMATION

: In this paper a new voice conversion algorithm is presented, which transforms the utterance of a source speaker into the utterance of a target speaker or into the utterance of a new unknown speaker. The voice conversion algorithm is based on spectral speech analysis, frequency transformation, spectral envelope warping, spectrum interpolation and parametrical high quality IIR or FIR cepstral speech synthesis. The cepstral speech model is realized using short time discrete Fourier transform of overlapping pitch-asynchronous speech frames and on speech deconvolution in the cepstral domain. Cepstral speech synthesis is implemented pitch-synchronous and in contrary to the LPC speech model, the cepstral speech model is of the pole/zero type and contains also information about the vocal tract excitation. Several approaches to frequency transformation of the speech spectrum are compared, e.g. linear frequency scaling, piecewise linear frequency warping and nonlinear lowpass to lowpass frequency transformation. The type of spectral warping depends on the wanted accuracy of the formant mapping of the source into the target spectrum. Prosodic transformations, i.e. fundamental frequency, time and intensity scale modifications are also shortly mentioned.
How to Treat the Use of Grey Literature in Software Engineering

Context: Following on other scientific disciplines, such as health sciences, the use of grey literature (GL) is becoming widespread in Software Engineering (SE) research. Whilst the number of papers incorporating GL on SE is increasing, there is little empirically known about different aspects of the use of GL in SE research. In particular, there is a lack of excellent evaluation standard for the quality of GL.Aim: Our research is aimed at systematically reviewing the use of GL in SE, empirically exploring SE researchers’ views on GL and providing a guide for using GL in SE and for quality assessment of the GL to be included.Method: We used a mixed-methods approach for this research. We carried out a Systematic Literature Review (SLR) of the use of GL in SE. Then we surveyed the authors of the papers included in the SLR (as GL users) and the invited experts in the SE community on the use of GL in SE research.Results: We systematically selected and reviewed 102 SE secondary studies that incorporate GL in SE research, from which we identified two groups based on their reporting: 1) 76 reviews only claim their use of GL; 2) 26 reviews report the results by including GL. We also obtained 20 replies from the GL users and 24 replies from the invited SE experts.Conclusion: There is no common understanding of the meaning of GL in SE. Researchers define the scopes and the definitions of GL in a variety of ways. We found five main reasons of using GL in SE research. The findings have enabled us to propose a conceptual model for how GL works in SE research lifecycle. In the next work There is a need for research to develop guidelines for using GL in SE and for assessing quality of GL.
The Study of Some Physical and Chemical Characteristics of Soil Cultivated with Olive Trees (Olea Europaea), in Three Fields with Different Ages Under Organic and Conventional Agricultural Systems at Al-Jouf Saudi Arabia

This study was carried out at Al-Jouf region, north eastern Saudi Arabia, to investigate differences in soil physical and chemical characteristics under three olive (Olea europaea) fields (9, 17, 27 years old) under organic agricultural system (OAS), and three similar olive fields under conventional agricultural system (CAS). There were significant differences in averages of organic carbon percentage (OC%) and organic matter (OM%) under the organic and conventional agricultural systems and CAS attained the highest percentages. However, the values of other characteristics did not show significant differences between the two systems. The results indicated no significant differences between the two agricultural systems (OAS and CAS) as regared to soil pH, EC, cation exchange capacity (CEC), CaCO3. The regarding the soil macro-elements were significant differences between the two systems in soil total nitrogen content (TN) and P in which CAS dominated giving the highest soil content, with no significant difference as regard to K content. For the microelements (Cu, Fe, Mn, Zn) and the heavy metals (Ni, Pb, Cd) there were no significant differences between the two systems. For soil field capacity (FC) the water content under FC was significantly high in soil under organic fertilization compared to conventional system, and FC, wilting point (WP) and available water (AW) increased significantly with increase in age of fields under both systems. Due to scarcity of information regarding soil properties under the organic and conventional systems at Al-Jouf region in the Kingdom of Saudi Arabia, this study was conducted.
O możliwości zastosowania stymulacji magnetycznej TMS w terapii schizofrenii

Transcranial magnetic stimulation TMS is the technique using the strong time varying magnetic field to activate or inhibition of cortical brain structures. TMS is applied in the neurological diagnostics and in basic research on various neuropsychological functions. The investigations on utilization of TMS stimulation in the psychiatric therapy were also undertaken. The most studies over the therapeutic activity were conducted in patients with depression. Schizophrenia is the second psychiatric diagnosis (regarding to the numbers of publications) in which the effectiveness of TMS was studied. The paper presents the results of hitherto existing investigations on the TMS use in this indication. It was showed, that the low frequency stimulation of the neighborhood area of the appropriate sensory cortex (auditory cortex in the case „hearing the voices”; visual cortex for visual hallucinations) is the best method for reducing of productive symptoms of the type of hallucinations. It the case of negative symptoms most profitable effects was acquired with help of the high-frequency stimulation of the left dorsolateral prefrontal cortex. Hitherto existing investigations despite certain positive effects have rather cognitive than practice character. Studied groups of patients were numerical little; specific problems exist with the assurance of the blind conditions; there is not studies on the effects of long-term of TMS stimulation.
Evaluation of anti-diarrhoeal properties of methanolic Root extract of Piliostigma reticulatum in rats

Piliostigma reticulatum (DC) Hoechst (Leguminosae) is an evergreen shrub reputed to possess a number of medicinal properties. The methanolic extract of Piliostigma reticulatum root (Leguminosae) was evaluated for anti-diarrhoeal activity in rats using castor oilinduced diarrhoea and fluid accumulation and activated charcoal test models. Phytochemical screening revealed the presence of tannins, glycosides, saponins, sterols, alkaloid and balsam. The extract (at doses of 100 and 200 mg/kg) and atropine (3 mg/kg) significantly inhibited castor oil-induced diarrhoea (53.5 72.1%) and fluid accumulation (35.17 71.03%) and small intestinal transit (9.38 21.74%) in the rats. The results obtained in this study revealed that the extract has remarkable anti-diarrhoeal effect, which may be due to the presence of the tannins, alkaloids and saponins constituents and can thus be used in the treatment of non-specific diarrhoea.
Long noncoding RNAs, ENST00000598996 and ENST00000524265, are correlated with favorable prognosis and act as potential tumor suppressors in bladder cancer

Bladder cancer (BC) is a serious malignancy worldwide due to its distant metastasis and high recurrence rates. Increasing evidence has indicated that dysregulated long non-coding RNAs (lncRNAs) are involved in tumorigenesis and progression in multiple malignancies. However, their clinical significances, biological functions and molecular mechanisms in BC remain poorly understood. Hence, the present study investigated the expression profile of lncRNAs and mRNAs in five BC tissues and the corresponding adjacent normal specimens using high-throughput RNA sequencing (RNA-seq). A total of 103 differentially expressed (DE) lncRNAs were identified, including 35 upregulated and 68 downregulated ones in BC tissues. Similarly, a total of 2,756 DE-mRNAs were detected, including 1,467 upregulated and 1,289 downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, and lncRNA-miRNA-mRNA network analyses suggested that these dysregulated lncRNAs are potentially implicated in the onset and progression of BC. Subsequently, four lncRNAs (upregulated ENST00000433108; downregulated ENST00000598996, ENST00000524265 and ENST00000398461) and two mRNAs (upregulated CCNB1 and CDK1) in 64 pairs of BC and adjacent normal tissues and four BC cell lines were detected using reverse transcription-quantitative PCR and these results were consistent with the sequencing data. Additionally, Fisher's exact test, Kaplan-Meier plots, and Cox regression analyses were used for elucidating the clinical values of ENST00000598996 and ENST00000524265. Furthermore, a receiver operating characteristic curve was constructed to assess their diagnostic values. The low expression level of ENST00000598996 and ENST00000524265 was correlated with unfavorable clinicopathological parameters, and shorter progression-free and overall survival time, whereas, ENST00000433108 was not associated with either. The in vitro functional experiments also revealed that the overexpression of ENST00000598996 and ENST00000524265 decreased the proliferation, migration, and invasion abilities of BC cells. Collectively, the results of the present study provide a novel landscape of lncRNA and mRNA expression profiles in BC. In addition, the results also indicated that ENST00000598996 and ENST00000524265 may serve as tumor suppressors, potential diagnostic biomarkers and prognostic predictors for patients with BC.