Saeed, Muhammad*
Dotaz
Zobrazit nápovědu
Flap endonuclease is a structure-specific nuclease which cleaves 5'-flap of bifurcated DNA substrates. Genome sequence of Thermococcus kodakarensis harbors an open reading frame, Tk1281, exhibiting high homology with archaeal flap endonucleases 1. The corresponding gene was cloned and expressed in Escherichia coli, and the gene product was purified to apparent homogeneity. Tk1281 was a monomer of 38 kDa and catalyzed the cleavage of 5'-flap from double-stranded DNA substrate containing single-stranded DNA flap. The highest cleavage activity was observed at 80 °C and pH 7.5. Under optimal conditions, Tk1281 exhibited apparent Vmax and Km values of 278 nmol/min/mg and 37 μM, respectively, against a 54-nucleotide double-stranded substrate containing a single-stranded 5'-flap of 27 nucleotides. A unique feature of Tk1281 is its highest activation in the presence of Co2+ and no activation with Mn2+. To the best of our knowledge, this is the first cloning and characterization of a flap endonuclease from the genus Thermococcus.
- MeSH
- "flap" endonukleasy chemie genetika metabolismus MeSH
- bakteriální proteiny chemie genetika metabolismus MeSH
- kinetika MeSH
- klonování DNA * MeSH
- molekulová hmotnost MeSH
- stabilita enzymů MeSH
- substrátová specifita MeSH
- Thermococcus chemie enzymologie genetika MeSH
- Publikační typ
- časopisecké články MeSH
Real-time gait event detection (GED) system can be utilized for gait analysis and tracking fitness activities. GED for various types of terrains (e.g., stair-walk, uneven surfaces, etc.) is still an open research problem. This study presents an inertial sensor-based approach for real-time GED system that works for diverse terrains in an uncontrolled environment. The GED system classifies three types of terrains, i.e., flat-walk, stair-ascend and stair-descend, with an average classification accuracy of 99%. It also accurately detects various gait events, including, toe-strike, heel-rise, toe-off, and heel-strike. It is computationally efficient, implemented on a low-cost microcontroller, works in real-time and can be used in portable rehabilitation devices for use in dynamic environments.
- Publikační typ
- časopisecké články MeSH
Electroencephalography (EEG) has emerged as a primary non-invasive and mobile modality for understanding the complex workings of the human brain, providing invaluable insights into cognitive processes, neurological disorders, and brain-computer interfaces. Nevertheless, the volume of EEG data, the presence of artifacts, the selection of optimal channels, and the need for feature extraction from EEG data present considerable challenges in achieving meaningful and distinguishing outcomes for machine learning algorithms utilized to process EEG data. Consequently, the demand for sophisticated optimization techniques has become imperative to overcome these hurdles effectively. Evolutionary algorithms (EAs) and other nature-inspired metaheuristics have been applied as powerful design and optimization tools in recent years, showcasing their significance in addressing various design and optimization problems relevant to brain EEG-based applications. This paper presents a comprehensive survey highlighting the importance of EAs and other metaheuristics in EEG-based applications. The survey is organized according to the main areas where EAs have been applied, namely artifact mitigation, channel selection, feature extraction, feature selection, and signal classification. Finally, the current challenges and future aspects of EAs in the context of EEG-based applications are discussed.
- MeSH
- algoritmy * MeSH
- artefakty MeSH
- elektroencefalografie * metody MeSH
- lidé MeSH
- mozek * fyziologie MeSH
- rozhraní mozek-počítač MeSH
- strojové učení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The increasing resistance of pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilization in agricultural applications, has stimulated the development of novel classes of molecules that target urease as an enzyme. In this context, the newly developed compounds on the basis of 1-heptanoyl-3-arylthiourea family were evaluated for Jack bean urease enzyme inhibition activity to validate their role as potent inhibitors of this enzyme. 1-Heptanoyl-3-arylthioureas were obtained in excellent yield and characterized through spectral and elemental analysis. All the compounds displayed remarkable potency against urease inhibition as compared to thiourea standard. It was found that novel compounds fulfill the criteria of drug-likeness by obeying Lipinski's rule of five. Particularly compound 4a and 4c can serve as lead molecules in 4D (drug designing discovery and development). Kinetic mechanism and molecular docking studies also carried out to delineate the mode of inhibition and binding affinity of the molecules.
- MeSH
- Canavalia enzymologie MeSH
- inhibitory enzymů chemie farmakologie MeSH
- kinetika MeSH
- molekulární struktura MeSH
- simulace molekulového dockingu * MeSH
- thiomočovina chemie farmakologie MeSH
- ureasa antagonisté a inhibitory metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.
- MeSH
- celosvětové zdraví * MeSH
- globální zátěž nemocemi * MeSH
- incidence MeSH
- kvalitativně upravené roky života MeSH
- lidé MeSH
- morbidita MeSH
- naděje dožití MeSH
- rány a poranění * mortalita MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
