Search For Candidates Research Articles

Recent advances in understanding and combatting Neisseria gonorrhoeae: a genomic perspective.

The sexually transmitted infection (STI) gonorrhoea remains a major global public health concern. The World Health Organization (WHO) estimates that 87 million new cases in individuals who were 15 to 49 years of age occurred in 2016. The growing number of gonorrhoea cases is concerning given the rise in gonococci developing antimicrobial resistance (AMR). Therefore, a global action plan is needed to facilitate surveillance. Indeed, the WHO has made surveillance leading to the elimination of STIs (including gonorrhoea) a global health priority. The availability of whole genome sequence data offers new opportunities to combat gonorrhoea. This can be through (i) enhanced surveillance of the global prevalence of AMR, (ii) improved understanding of the population biology of the gonococcus, and (iii) opportunities to mine sequence data in the search for vaccine candidates. Here, we review the current status in Neisseria gonorrhoeae genomics. In particular, we explore how genomics continues to advance our understanding of this complex pathogen.

Infrared dust echoes from neutron star mergers

ABSTRACT A significant fraction of binary neutron star mergers occur in star-forming galaxies where the UV-optical and soft X-ray emission from the relativistic jet may be absorbed by dust and re-emitted at longer wavelengths. We show that, for mergers occurring in gas-rich environment ($n_{\rm H}\gtrsim 0.5\rm \, cm^{-3}$ at a few to tens of pc) and when the viewing angle is less than about 30°, the emission from heated dust should be detectable by James Webb Space Telescope (JWST), with a detection rate of $\sim 1\rm \, yr^{-1}$. The spatial separation between the dust emission and the merger site is a few to 10 milli-arcsecs (for a source distance of 150 Mpc), which may be astrometrically resolved by JWST for sufficiently high signal-noise-ratio detections. Measuring the superluminal apparent speed of the flux centroid directly gives the orbital inclination of the merger, which can be combined with gravitational wave data to measure the Hubble constant. For a line of sight within the jet opening angle, the dust echoes are much brighter and may contaminate the search for kilonova candidates from short gamma-ray bursts, such as the case of GRB 130603B.

Exemplification in research articles: Structural, semantic and metadiscursive properties across disciplines

Examples are forms of code glosses similar to reformulations that help readers understand writers' intended meanings (Hyland, 2007) and contribute to the process of argumentation in texts (Triki, 2017). This paper investigates examples in research articles across the so-called soft and hard disciplines and aims to structurally and semantically explore the link between the building units of examples and how they could constrain the choices made across disciplines. To reach this end, the study investigates examples in a corpus of 80 research articles that cover four disciplines in the ‘soft’ sciences and four disciplines in the ‘hard’ sciences. Annotation was based on an automatic search of potential candidates then a manual annotation was performed using the UAM Corpus Tool (O'Donnell, 2008). Results suggest that (1) the structural features of exemplified units impose constraints on the choice of markers and exemplifying units (2) exemplifying clauses are more elaborative than exemplifying nominal groups and (3) the equivalence between the units exemplified and those exemplifying seems to be governed by the degree to which exemplifying units are expanding or compacting. The main conclusion is that the soft-hard distinction between academic disciplines is not always the major parameter triggering writers' choices.

Search for Crystal Structure Candidates by Applying the Generalized Scaled Hypersphere Search Method to Volume of Unit Cell Containing Quasi Rigid Body Approximated Atoms and Molecules

The volume function was employed to predict crystal structures. Face-centered cubic and hexagonal close-packed structures were identified as minima on the function. The optimization of the function with the actual ethane crystal resulted in largely similar orientations of the molecules. Searching on the function from a random structure resulted in some minima, including a structure similar to the actual structure.

Effect of Alkali Treatment on the Properties of Acacia Caesia Bark Fibres

As possible substitutes for non-biodegradable synthetic fibre, ligno-cellulosic fibres have attracted much interest for their eco-friendliness; a large number of them are already used for the production of green polymer composites. The search for further green candidates brings into focus other fibres not previously considered, yet part of other production systems, therefore available as by-products or refuse. The purpose of this study is to explore the potential of alkali treatment with 5% sodium hydroxide (NaOH) to enhance the properties of bark-extracted Acacia Caesia Bark (ACB) fibres. The microscopic structure of the treated fibres was elucidated using scanning electron microscopy (SEM). Moreover, the fibres were characterised in terms of chemical composition and density and subjected to single-fibre tensile tests (SFTT). Following their physico-chemical characterisation, fibre samples underwent thermal characterisation by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), and their crystallinity was assessed using X-ray diffraction (XRD). This level of alkali treatment only marginally modified the structure of the fibres and offered some improvement in their tensile strength. This suggested that they compare well with other bark fibres and that their thermal profile showed some increase of degradation onset temperature with respect to untreated ACB fibres. Their crystallinity would allow their application in the form of fibres with an average length of approximately 150 mm, even in thermoplastic biocomposites.

Searching for TeV Candidates in 4LAC High-synchrotron- peaked Frequency BL Lac Objects

Abstract The next generation of TeV detectors is expected to have significantly enhanced performance. It is therefore constructive to search for new TeV candidates for observation. This paper focuses on TeV candidates among the high-synchrotron-peaked BL Lacertae objects (HBLs) reported in the fourth catalog of active galactic nuclei detected by Fermi’s Large Area Telescope, i.e., 4LAC. By cross-matching the Fermi data with radio and optical observations, we collected the multiwavelength features of 180 HBLs with known redshifts. The data set contains 39 confirmed TeV sources and 141 objects whose TeV detection has not yet been reported (either not yet observed, or observed but not detected). Using two kinds of supervised machine-learning (SML) methods, we searched for new possible TeV candidates (PTCs) among the nondetected objects by assessing the similarity of their multi-wavelength properties to existing TeV-detected objects. The classification results of the two SML classifiers were combined and the 24 highest-confidence PTCs were proposed as the best candidates. We calculate, here, the 12 year averaged Fermi spectra of these PTCs and estimate their detectability by extrapolating the Fermi spectra and including the extragalactic background light attenuation. Four candidates are suggested to have a high likelihood of being detected by the Large High Altitude Air Shower Observatory, and 24 are candidates for Cherenkov Telescope Array observations.

SERR Spectroelectrochemistry as a Guide for Rational Design of DyP-Based Bioelectronics Devices.

Immobilised dye-decolorizing peroxidases (DyPs) are promising biocatalysts for the development of biotechnological devices such as biosensors for the detection of H2O2. To this end, these enzymes have to preserve native, solution properties upon immobilisation on the electrode surface. In this work, DyPs from Cellulomonas bogoriensis (CboDyP), Streptomyces coelicolor (ScoDyP) and Thermobifida fusca (TfuDyP) are immobilised on biocompatible silver electrodes functionalized with alkanethiols. Their structural, redox and catalytic properties upon immobilisation are evaluated by surface-enhanced resonance Raman (SERR) spectroelectrochemistry and cyclic voltammetry. Among the studied electrode/DyP constructs, only CboDyP shows preserved native structure upon attachment to the electrode. However, a comparison of the redox potentials of the enzyme in solution and immobilised states reveals a large discrepancy, and the enzyme shows no electrocatalytic activity in the presence of H2O2. While some immobilised DyPs outperform existing peroxidase-based biosensors, others fail to fulfil the essential requirements that guarantee their applicability in the immobilised state. The capacity of SERR spectroelectrochemistry for fast screening of the performance of immobilised heme enzymes places it in the front-line of experimental approaches that can advance the search for promising DyP candidates.

Current Status of Baricitinib as a Repurposed Therapy for COVID-19.

The emergence of the COVID-19 pandemic has mandated the instant (re)search for potential drug candidates. In response to the unprecedented situation, it was recognized early that repurposing of available drugs in the market could timely save lives, by skipping the lengthy phases of preclinical and initial safety studies. BenevolentAI’s large knowledge graph repository of structured medical information suggested baricitinib, a Janus-associated kinase inhibitor, as a potential repurposed medicine with a dual mechanism; hindering SARS-CoV2 entry and combatting the cytokine storm; the leading cause of mortality in COVID-19. However, the recently-published Adaptive COVID-19 Treatment Trial-2 (ACTT-2) positioned baricitinib only in combination with remdesivir for treatment of a specific category of COVID-19 patients, whereas the drug is not recommended to be used alone except in clinical trials. The increased pace of data output in all life sciences fields has changed our understanding of data processing and manipulation. For the purpose of drug design, development, or repurposing, the integration of different disciplines of life sciences is highly recommended to achieve the ultimate benefit of using new technologies to mine BIG data, however, the final say remains to be concluded after the drug is used in clinical practice. This review demonstrates different bioinformatics, chemical, pharmacological, and clinical aspects of baricitinib to highlight the repurposing journey of the drug and evaluates its placement in the current guidelines for COVID-19 treatment.

Plausible role of Arq Ajīb in combating COVID-19: A multi-faceted review

The current pandemic caused by SARS-CoV-2 has led to a massive change in every aspect of our lives. It has grossly affected the healthcare system, business and world trade, disruption of movement and supply of essential goods and has crippled the global economy. Although few vaccines have been approved for the control of disease, targeted therapy options for this virulent disease still remain limited and elusive. Exhaustive search for potent therapeutic candidate is in progress, for which herbal armory are also being explored. Medicinal plants and their products play a vital role in alleviating various diseases and have been reported to exhibit a wide range of biological activities. Plant-based drugs with antiviral, anti-inflammatory and immunomodulotry activities were hypothetically considered as potential drugs to prevent and mitigate the prevailing situation caused by SARS-CoV-2. Arq Ajīb ‘a Unani formulation’ presents compelling approach in treating numerous diseases. The ingredients of Arq Ajīb and their phytocompounds have been reported for wide-ranging pharmaco-biological activities including antiviral, anti-inflammatory, immunomodulotry, anti-allergic, antitussive and bronchodilatory activities. Scientific data available on the formulation ingredients and their phytocompounds indicates that the formulation may have a significant role in augmenting the immune status of individual, protecting them from infection and providing symptomatic relief to patients affected with COVID-19. Hence, it may be considered as a potential drug for the development of novel therapeutic candidate for SARS-CoV-2 infection. This multi-faceted review highlights the therapeutic significance and pharmacological actions of Arq Ajīb and its ingredients to demonstrate the plausible role of the formulation in combating COVID-19.
 Keywords: Arq Ajīb, COVID-19, Pudina, Ajwain, Camphor, Unani formulation

Post-pancreatitis diabetes mellitus: investigational drugs in preclinical and clinical development and therapeutic implications

Introduction The need for new drugs for diabetes is obvious. Albeit type 2 diabetes is the most common type of diabetes, it is fundamentally a disease of exclusion. Post-pancreatitis diabetes mellitus is one of the most common types of secondary diabetes. The pharmaceutical armamentarium in the field of diabetology can be broadened if the design of novel drugs is informed by pathogenetic insights from studies on post-pancreatitis diabetes mellitus. Areas covered The article provides an overview of preclinical and clinical studies of compounds selectively antagonising the gastric inhibitory peptide receptor, simultaneously stimulating both the glucagon-like peptide-1 and glucagon receptors, and activating ketogenesis. Expert opinion The current pharmacotherapy for post-pancreatitis diabetes mellitus is relatively ineffective. This type of diabetes represents a unique platform for rigorous, efficient, and practical search for glucose-lowering therapeutic candidates. Various methods of gastric inhibitory peptide receptor (expressed in the pancreas) antagonism have undergone extensive preclinical testing in diabetes, with promising compounds being trialled in man. Molecular mimicry with oxyntomodulin ─ an extra-pancreatic hormone homologous with pancreatic hormone glucagon and involved in the regulation of exocrine pancreatic function ─ could be harnessed. The emerging findings of a salutary effect of ketosis mimetics in people with prediabetes or obesity set the stage for a novel approach to preventing diabetes.

A systematic mapping protocol for understanding knowledge exchange in forest science

Abstract When making decisions about forest and environmental management, managers and policymakers often rely upon scientific knowledge. There is a well‐documented ‘knowledge–integration gap’ where often the production of knowledge and its use are not aligned. Though there are several theoretical frameworks that conceptualize how knowledge is exchanged between producers of scientific knowledge and users of that information, there has been little attention to documenting knowledge exchange practices and their effectiveness, especially about forests. In the systematic map, we will examine the peer‐reviewed academic and grey literature to document and classify the knowledge exchange techniques suggested and adopted by knowledge producers and users in the forest sciences globally. Characterizing this knowledge exchange landscape will provide new information about which techniques are used and their frequency, if there is evidence of effectiveness for particular techniques, and recommendations for best practices. This map will also show whether approaches to knowledge exchange differ between sectors (e.g. academia, government). We will create a systematic literature map as defined by the Collaboration for Environmental Evidence to capture case studies of, or theories about, knowledge exchange related to forest science. The search of peer‐reviewed academic and grey literature will be conducted in English and French in two academic databases (BASE and Scopus) and one specialist database (ResearchGate). Candidate search strings will be evaluated against a test list of documents to determine strings with maximum sensitivity and specificity. Eligibility criteria will be applied to items at two screening stages: (1) title and abstract and (2) full‐text. All screening decisions will be recorded in a database with 15% of full‐text screening decisions validated. Items retained for inclusion will have data extracted according to a standardized strategy. Each reviewer conducting data extraction will have at least three of their extractions validated. The systematic map will employ a narrative synthesis approach that includes descriptive statistics, tables, and figures which describe the types and frequency of knowledge exchange techniques theorized or described, a network map displaying the institutions within and between which knowledge exchange occurs, as well as summarizing any available evidence of effectiveness for particular knowledge exchange techniques.

Warm Jupiters in TESS Full-frame Images: A Catalog and Observed Eccentricity Distribution for Year 1

Abstract Warm Jupiters—defined here as planets larger than 6 Earth radii with orbital periods of 8–200 days—are a key missing piece in our understanding of how planetary systems form and evolve. It is currently debated whether Warm Jupiters form in situ, undergo disk or high-eccentricity tidal migration, or have a mixture of origin channels. These different classes of origin channels lead to different expectations for Warm Jupiters’ properties, which are currently difficult to evaluate due to the small sample size. We take advantage of the Transiting Exoplanet Survey Satellite (TESS) survey and systematically search for Warm Jupiter candidates around main-sequence host stars brighter than the TESS-band magnitude of 12 in the full-frame images in Year 1 of the TESS Prime Mission data. We introduce a catalog of 55 Warm Jupiter candidates, including 19 candidates that were not originally released as TESS objects of interest by the TESS team. We fit their TESS light curves, characterize their eccentricities and transit-timing variations, and prioritize a list for ground-based follow-up and TESS Extended Mission observations. Using hierarchical Bayesian modeling, we find the preliminary eccentricity distributions of our Warm-Jupiter-candidate catalog using a beta distribution, a Rayleigh distribution, and a two-component Gaussian distribution as the functional forms of the eccentricity distribution. Additional follow-up observations will be required to clean the sample of false positives for a full statistical study, derive the orbital solutions to break the eccentricity degeneracy, and provide mass measurements.

3CLpro and PLpro affinity, a docking study to fight COVID19 based on 900 compounds from PubChem and literature. Are there new drugs to be found?

The spread of a novel coronavirus SARS-CoV-2 and a resulting COVID19 disease in late 2019 has transformed into a worldwide pandemic and has effectively brought the world to a halt. Proteases 3CLpro and PLpro, responsible for proteolysis of new virions, represent vital inhibition targets for the COVID19 treatment. Herein, we report an in silico docking study of more than 860 COVID19-related compounds from the PubChem database. Molecular dynamic simulations were carried out to validate the conformation stability of compound-ligand complexes with best docking scores. The MM-PBSA approach was employed to calculate binding free energies. The comparison with ca. 50 previously reported potential SARS-CoV-2′s proteases inhibitors show a number of new compounds with excellent binding affinities. Anti-inflammatory drugs Montelukast, Ebastine and Solumedrol, the anti-migraine drug Vazegepant or the anti-MRSA pro-drug TAK-599, among many others, all show remarkable affinities to 3CLpro and with known side effects present candidates for immediate clinical trials. This study reports thorough docking scores summary of COVID19-related compounds found in the PubChem database and illustrates the asset of computational screening methods in search for possible drug-like candidates. Several yet-untested compounds show affinities on par with reported inhibitors and warrant further attention. Furthermore, the submitted work provides readers with ADME data, ZINC and PubChem IDs, as well as docking scores of all studied compounds for further comparisons.

Optical counterparts of ULXs in two dwarf galaxies: NGC 4861 and NGC 4449

ABSTRACT We present the results of a search for optical candidates of ultraluminous X-ray sources (ULXs) in two dwarf galaxies, NGC 4861 and NGC 4449, using Hubble Space Telescope (HST) archival data. With precise astrometry, we confirm that NGC 4861 X1 is associated with an H ii complex and we conclude that NGC 4861 X2 resides in a young star group of mass 400 ± 80 M⊙. We also find that NGC 4449 X7 is associated with three optical candidates within an error radius of 0.2 arcsec at the 90 ${{\ \rm per\ cent}}$ confidence level. Absolute magnitudes (Mv) of these candidates are determined as −5.0 and −4.1. The age and mass values for the three candidates are estimated as 40–50 Myr and ∼8 M⊙, respectively, using stellar evolutionary tracks. The locations of optical candidates suggest a possible association with a nearby group of stars. In addition, we analysed previously unused archival data of XMM–Newton, Chandra, and Swift where the sources were detected. Although the X-ray spectral data do not allow us to discriminate between physical models, long-term data at hand are consistent with the sources being in luminous hard states.

Recent Developments in Vaccines for Bovine Mycoplasmoses Caused by Mycoplasma bovis and Mycoplasma mycoides subsp. mycoides.

Two of the most important diseases of cattle are caused by mycoplasmas. Mycoplasma bovis is a world-wide bovine pathogen that can cause pneumonia, mastitis and arthritis. It has now spread to most, if not all, cattle-rearing countries. Due to its increasing resistance to antimicrobial therapy, vaccination is the principal focus of the control of infection, but effective vaccines are currently lacking. Despite being eradicated from most parts of the world, Mycoplasma mycoides subsp. mycoides, the cause of contagious bovine pleuropneumonia (CBPP), continues to plague sub-Saharan Africa, affecting at least 25 countries. Numerous new experimental vaccines have been developed over the last 20 years to improve on protection afforded by the T1/44, a live vaccine in continuous use in Africa for over 60 years, but none so far have succeeded; indeed, many have exacerbated the disease. Tools for diagnosis and control are adequate for eradication but what is necessary are resources to improve vaccine coverage to levels last seen in the 1970s, when CBPP was restricted to a few countries in Africa. This paper summarizes the results of the main studies in the field of experimental mycoplasma vaccines, reviews data on commercially available bacterin vaccines and addresses issues relating to the search for new candidates for effective vaccines to reduce economic losses in the cattle industry caused by these two mycoplasmas.

A rational in silico approach to identify inhibitors of Batroxrhagin from Bothrops atrox

Bothrops atrox venom comprises several types of bioactive molecules, enzymatic and non-enzymatic, among those, Batroxrhagin is the most predominant SVMP P-III enzyme, which are responsible for induction of local and systemic hemorrhage and muscle fibers damage, impairing regeneration. Due to great difficulties in establishing an antibothropic drug, new strategies must be addressed to achieve a more effective and efficient treatment. There are no studies of specific catalytic inhibitors of Batroxrhagin. However, there are in vitro studies that have described similar metalloprotease inhibitors. The inhibitor batimastat was used as a leading compound for the search and selection of similar candidates. This molecule is widely cited as a metalloprotease inhibitor and as an antimetastatic. In addition to batimastat-like molecules, four other reported metalloprotease inhibitors were included to compose the study's positive control group. Hence, 580 molecules were tested. The three-dimensional structure of B. atrox Batroxrhagin was predicted based on homologous structures using Modeller 9.20. Molecular docking calculation was performed using Autodock 4.2 and molecular surfaces and interactions were analyzed using Biovia/Discovery Studio 2017. Among 576 molecules, 42 similar to batismast resulted in a better energy of interaction than all positive controls, including batimastat itself. The batimastat-like molecules with lowest energy and positive controls were subjected to molecular dynamics for 30 ns in Gromacs 2019.4. This batimastat-like molecule produced better stability among all the Batroxrhagin-ligand complexes analyzed. Overall, the proposed compounds present justifiable evidence for future in vitro tests aiming to inhibit Batroxrhagin. Communicated by Ramaswamy H. Sarma

Identification of benzamide inhibitors of histone deacetylase 1 from Babesia and Theileria species via high-throughput virtual screening and molecular dynamics simulations.

Theileria and Babesia species are eukaryotic protozoan parasites classified under the order Piroplasmida of the phylum Apicomplexa. Tick vectors transmit these microorganisms in tropical and subtropical regions to a wide range of animals, including ruminants, causing fatal and life-threatening diseases such as bovine babesiosis and theileriosis. Resistance to commercially available drugs requires the search for new drug candidates. Histone deacetylase (HDAC) has a potential to be utilized as a drug target; therefore, it may be considered as an effective alternative. Previous studies revealed that HDAC inhibitors, identified for human use, show promising anti-parasitic effects. We have herein focused on the class I HDAC enzyme, HDAC1, of the Babesia and Theileria species to discover potential benzamide inhibitors by following a streamlined workflow of computer-aided drug design methodology. Molecular docking and molecular dynamics simulations revealed that benzamide derivatives stably interacted with the HDAC1 active site in both parasites as hypothesized. Furthermore, specific residue insertions at the entry point of the active site cleft of parasitic HDAC1 could enable ways to design parasite-specific drugs without adversely affecting host enzymes.

Biomarkers of vascular cognitive impairment

There is currently no approved list of vascular cognitive impairment biomarkers. The main problem for the practitioner in identifying cognitive impairment in patients is the differential diagnosis of Alzheimer's disease, vascular cognitive impairment, and other diseases, which are much less common. Vascular cognitive impairment includes post-stroke dementia, cognitive dysfunction in cardio-and cerebrovascular diseases. Without etiology identification, it is impossible to prescribe adequate treatment. Another challenge is identifying cognitive impairment before dementia develops. This literature review is devoted to the search and critical analysis of candidates for biomarkers of vascular cognitive impairment and the establishment of markers of moderate cognitive dysfunction. The papers were searched for in the Web of Science and PubMed databases. A list of cerebrospinal fluid, plasma, serum and genetic biomarkers was made, allowing for differential diagnosis between vascular impairment and Alzheimer's disease. The markers of moderate cognitive dysfunction, which make it possible to identify cognitive impairment at the pre-dementia stage, were also identified.

Mean-shift Object Tracking Algorithm with Systematic Sampling Technique

Mean shift is a fast object tracking algorithm that only considers pixels in an object area, hence its relatively small computational load. This algorithm is suitable for use in real-time conditions in terms of execution time. The use of histograms causes this algorithm to be relatively resistant to rotation and changes in object size. However, its resistance to lighting changes is not optimal. This study aims to improve the performance of the algorithm under lighting changes and reduce its processing time. The proposed technique involves the use of sampling techniques to reduce the number of iterations, optimization of candidate search object locations using simulated annealing, and addition of tolerance parameter to optimize object location search and area-based weighting instead of the Epanechnikov kernel. The results of the one-tail t-test with two independent sample groups reveal that the average performance of the proposed algorithm is significantly better than that of the traditional mean-shift algorithm in terms of resistance to lighting changes and processing time per video frame. In the test involving 999 frames of video images, the average processing time of the proposed algorithm is 83.66 ms, whereas that of the traditional mean-shift algorithm is 116.86 ms.

Beyond Tripeptides Two-Step Active Machine Learning for Very Large Data sets.

Self-assembling peptide nanostructures have been shown to be of great importance in nature and have presented many promising applications, for example, in medicine as drug-delivery vehicles, biosensors, and antivirals. Being very promising candidates for the growing field of bottom-up manufacture of functional nanomaterials, previous work (Frederix, et al. 2011 and 2015) has screened all possible amino acid combinations for di- and tripeptides in search of such materials. However, the enormous complexity and variety of linear combinations of the 20 amino acids make exhaustive simulation of all combinations of tetrapeptides and above infeasible. Therefore, we have developed an active machine-learning method (also known as “iterative learning” and “evolutionary search method”) which leverages a lower-resolution data set encompassing the whole search space and a just-in-time high-resolution data set which further analyzes those target peptides selected by the lower-resolution model. This model uses newly generated data upon each iteration to improve both lower- and higher-resolution models in the search for ideal candidates. Curation of the lower-resolution data set is explored as a method to control the selected candidates, based on criteria such as log P. A major aim of this method is to produce the best results in the least computationally demanding way. This model has been developed to be broadly applicable to other search spaces with minor changes to the algorithm, allowing its use in other areas of research.