New hybrids of tacrine and indomethacin as multifunctional acetylcholinesterase inhibitors

A new series of hybrid compounds were designed, consisting of anti-AChE and BuChE activity components with an antiinfammatory component. A series of 9-amino-1,2,3,4-tetrahydroacridine and indomethacin derivatives were synthesized. All compounds were created using alkyldiamine with diferent chain lengths as a linker. Various biological activities were evaluated, including inhibitory activity against AChE and BuChE. The tested compounds showed high inhibitory activities against cholinesterases. The IC50 values for all compounds ranging from 10 nM to 7 µM. The potency of inhibition was much higher than well-known AChE and BuChE inhibitors (tacrine and donepezil). Compound 3h had the strongest inhibitory activity; kinetic studies showed it to have a mixed-type of acetylcholinesterase inhibition properties. The cytotoxicity of the newly-synthesized compounds against HepG2 (hepatocarcinoma cells) and EA.hy96 (human vein endothelial cells) cell lines was determined using the MTT and MTS tests. All investigated compounds presented similar cytotoxic activity against HepG2 and EA.hy926 cell line, ranged in micromolar values. Compounds with longer linkers showed higher antioxidant activity. The most active compound was 3h. Docking studies confrmed interactions with important regions of AChE and BuChE. Its multifunctional properties, i.e. high activity against AChE and BuChE, antioxidant activity and low cytotoxicity, highlight 3h as a promising agent for the treatment of AD

Prevalence of generalised joint hypermobility in relation to selected medical and training indicators in swimmers: Randomised control study

Generalised joint hypermobility (GJH) is characterised by the range of motion that exceeds normal limits in multiple joints. GJH is relatively common. When it is accompanied with other manifestations, it is defined as a health-related disorder, like Joint Hypermobility Syndrome (JHS) or the Ehlers–Danlos Syndrome - Hypermobile Type (hEDS). The prevalence of GJH is higher in sporting than in the general population. The aim of the study was to investigate the prevalence of GJH in competitive swimmers and its relation to the number and type of injuries, pain and selected anthropological and training indicators. The research group consisted of 97 competitive Polish swimmers (50 males; 47 females) aged 15-24 years. Body stature and body mass was measured. Participants completed a questionnaire to collect demographic data and information on previous injuries. Concerning joint hypermobility, participants were examined with the Beighton Scale. Spearman’s rank correlation test was applied for analysis. GJH is an often-occurring symptom among the researched group. There was no correlation between selected acute injuries nor chronic pain and GJH in the study group. Several other correlations were noted. Keywords: Generalised joint hypermobility; Swimmers; Pain; Injurie

MODELING THE OPTIMAL MEASUREMENT TIME WITH A PROBE ON THE MACHINE TOOL USING MACHINE LEARNING METHODS

This paper explores the application of various machine learning techniques to model the optimal measurement time required after machining with a probe on CNC machine tools. Specifically, the research employs four different machine learning models: Elastic Net, Neural Networks, Decision Trees, and Support Vector Machines, each chosen for their unique strengths in addressing different aspects of predictive modeling in an industrial context. The study examines as input parameters such as material type, post-processing wall thickness, cutting depth, and rotational speed over measurement time. This approach ensures that the models account for the variables that significantly affect CNC machine operations. Regression value, mean square error, root mean square error, mean absolute percentage error, and mean absolute error were used to evaluate the quality of the obtained models. As a result of the analyses, the best modeling results were obtained using neural networks. Their ability to accurately predict measurement times can significantly increase operational efficiency by optimizing schedules and reducing downtime in machining processes

Effect of Periodic Granulocyte Colony-Stimulating Factor Administration on Endothelial Progenitor Cells and Different Monocyte Subsets in Pediatric Patients with Muscular Dystrophies

Muscular dystrophies (MD) are heterogeneous group of diseases characterized by progressive muscle dysfunction. There is a large body of evidence indicating that angiogenesis is impaired in muscles of MD patients. Therefore, induction of dystrophic muscle revascularization should become a novel approach aimed at diminishing the extent of myocyte damage. Recently, we and others demonstrated that administration of granulocyte colony-stimulating factor (G-CSF) resulted in clinical improvement of patients with neuromuscular disorders. To date, however, the exact mechanisms underlying these beneficial effects of G-CSF have not been fully understood. Here we used flow cytometry to quantitate numbers of CD34+ cells, endothelial progenitor cells, and different monocyte subsets in peripheral blood of pediatric MD patients treated with repetitive courses of G-CSF administration. We showed that repetitive cycles of G-CSF administration induced efficient mobilization of above-mentioned cells including cells with proangiogenic potential. These findings contribute to better understanding the beneficial clinical effects of G-CSF in pediatric MD patients

Are rare species useful species? Obstacles to the conservation of tree diversity in the dry forest zone agro-ecosystems of Mesoamerica

Aim To test the potential to conserve rare dry forest tree and shrub species circa situm.Location Oaxaca, Mexico and Southern Honduras.Methods Local uses (timber, posts and firewood) of species were determined principally through semistructured interviews with 20 rural householders in each of four communities in Honduras and four in Oaxaca. Tree and shrub diversity inventories were carried out in a total of 227 forest patches and parcels of farmland in those eight communities. Species’ conservation priorities were determined using the star system of Hawthorne (1996) and IUCN listings.Results Despite a large number of useful species, remarkably few were also conservation priorities. Useful species were found to be substitutable as is illustrated by Bombacopsis quinata, Cordia alliodora, Guaiacum sanctum and G. coulteri.Conclusions In these areas, circa situm conservation is inhibited by the lack of species that are both rare and useful. Usefulness must be interpreted as a function of substitutability. Natural regeneration provides an abundance of diversity, farmers are unlikely to invest in the management of a species when suitable substitutes are freely available. The key to conserving rare species may be in maintaining or enhancing the value of the landscape elements in which they are found

BioTIME:a database of biodiversity time series for the Anthropocene

Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.Main types of variables included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of two, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology andcontextual information about each record.Spatial location and grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1 000 000 000 000 cm2).Time period and grain: BioTIME records span from 1874 to 2016. The minimum temporal grain across all datasets in BioTIME is year.Major taxa and level of measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton, and terrestrial invertebrates to small and large vertebrates.Software format: .csv and .SQ

BioTIME:a database of biodiversity time series for the Anthropocene

Abstract Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community‐led open‐source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. Main types of variables included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. Spatial location and grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km² (158 cm²) to 100 km² (1,000,000,000,000 cm²). Time period and grain: BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. Major taxa and level of measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates. Software format: .csv and .SQL