62 research outputs found
Ligand based pharmacophore modelling of anticancer histone deacetylase inhibitors
Histone deacetylases have emerged as an important therapeutic target for the treatment of cancer. Genome-wide histone hypoacetylation causes many cancers. Recently, inhibitors of histone deacetylases (HDAC) have emerged as an important class of anticancer agents. Various side effectslike myocardium damage and bone marrow depression even leading to cell death have been observed in the treatment of caner cells using HDAC inhibitors. The discovery and development of type-specific HDAC inhibitors is of both research and clinical interests. Ligand based pharmacophore modelling is playing a key role for the identification of ligand features for the particular targets. We present a model for designing the pharmacophore onto the set of 70 compounds of three different classes and two subclasses. The ligand based pharmacophore model has been identified in order to facilitate the discovery of type specific anticancer HDAC inhibitors. The result indicates that the in silico methodsare useful in predicting the biological activity of the compound or compound library by screening it against a predicted pharmacophore. Ligand Scout 2.02 has been used to predict the pharmacophorefeatures for anticancer HDAC inhibitors and the distances between pharmacophore features have been calculated through the software Jmol. The proposed model has been validated by docking the MS275compound into the binding pocket of Human HDAC8. Our discovery will help in the identification of more specific anticancer human HDAC inhibitors
Sustainability practices at higher education institutions in Asia
Purpose: It is still unclear how Asian universities incorporate the theory or practice of sustainable development (SD) in their research and education programmes. To address this gap, the purpose of this paper is to report on a study that has examined how universities in Asian countries handle and address matters related to SD. Design/methodology/approach: The study used a bibliometric analysis and an online survey-method. The online survey data were analysed through descriptive analysis and one-sample studentâs t-test. Findings: The study indicates that there is considerable variation among the Asian countries regarding sustainability practices in higher education institutions (HEIs). The HEIs in far eastern countries, such as Indonesia, Malaysia and Thailand are perceived to demonstrate more sustainability practices. Research limitations/implications: Even though a substantial number of participants participated in the survey, it did not cover all Asian countries. The online survey was carried out over a limited period of time, and not all HEIs in the field may have received information about the study. Practical implications: Asia is the largest continent facing a number of sustainability challenges. In this context, the contribution of HEIs is very important. The findings of the current study may serve as a baseline for Asian HEIs to take more initiatives towards SD goals, as HEIs are responsible for the education and training of hundreds of thousands of students who will be occupying key positions in industry, government or education in the coming years. Originality/value: The study contributes to the existing literature in two distinct ways. First, it was possible to develop a comprehensive instrument to measure sustainability practices in HEIs. Second, this study has filled the gap of the scarcity of studies regarding sustainability practices in HEIs in Asia
Spotting the enemy within: Targeted silencing of foreign DNA in mammalian genomes by the KrĂŒppel-associated box zinc finger protein family
3D-Printed Stationary Phases with Ordered Morphology: State of the Art and Future Development in Liquid Chromatography Chromatographia
Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)
Background
Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillinâgentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis.
Methods
In BARNARDS, consenting motherâneonates aged 0â60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokineticâpharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability.
Findings
Between Nov 12, 2015, and Feb 1, 2018, 36â285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillinâgentamicin, ceftazidimeâamikacin, piperacillinâtazobactamâamikacin, and amoxicillin clavulanateâamikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidimeâamikacin than for neonates treated with ampicillinâgentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14â0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillinâgentamicin; 286 (73·3%) to amoxicillin clavulanateâamikacin; 301 (77·2%) to ceftazidimeâamikacin; and 312 (80·0%) to piperacillinâtazobactamâamikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillinâgentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanateâamikacin; 93 (92·7% [0·24]) of 109 with ceftazidimeâamikacin; and 70 (85·3% [0·47]) of 76 with piperacillinâtazobactamâamikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis
A one-step implicit iterative method for two finite families of asymptotically nonexpansive mappings in a hyperbolic space
We introduce a one-step implicit iterative method for two finite families of asymptotically nonexpansive mappings in a hyperbolic space and use it to approximate common fixed points of these families. The results presented in this paper are new in the setting of hyperbolic spaces. On top, these are generalizations of several results in literature from Banach spaces to hyperbolic spaces. At the end of the paper, we give an example to validate our results.The author H. Fukhar-ud-din is grateful to King Fahd University of Petroleum and Minerals for supporting the research project IN121055 and the author A. Kalsoom is grateful to Higher Education Commission (HEC) of Pakistan for financial support during this research
Intelligent computing based forecasting of deforestation using fire alerts: a deep learning approach
No abstract available
Genomeâwide association study of cyanogenic glycosides, proline, sugars, and pigments in Eucalyptus cladocalyx
Millimeter-wave smart antenna solutions for URLLC in industry 4.0 and beyond
Industry 4.0 is a new paradigm of digitalization and automation that demands high data rates and real-time ultra-reliable agile communication. Industrial communication at sub-6 GHz industrial, scientific, and medical (ISM) bands has some serious impediments, such as interference, spectral congestion, and limited bandwidth. These limitations hinder the high throughput and reliability requirements of modern industrial applications and mission-critical scenarios. In this paper, we critically assess the potential of the 60 GHz millimeter-wave (mmWave) ISM band as an enabler for ultra-reliable low-latency communication (URLLC) in smart manufacturing, smart factories, and mission-critical operations in Industry 4.0 and beyond. A holistic overview of 60 GHz wireless standards and key performance indicators are discussed. Then the review of 60 GHz smart antenna systems facilitating agile communication for Industry 4.0 and beyond is presented. We envisage that the use of 60 GHz communication and smart antenna systems are crucial for modern industrial communication so that URLLC in Industry 4.0 and beyond could soar to its full potential
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