Protuupalno i analgetsko djelovanje novih derivata piridindikarbonitrila i benzopiranopiridina

In continuation of our search for new substituted pyridine based anti-inflammatories, reaction of 1-(2-thienyl or furanyl)-3-(2-hydroxyphenyl)-2-propen-1-ones (1) with malononitrile in alcoholic KOH solution afforded a mixture of 4-alkoxy-2-(2-thienyl or furanyl)-5H-[1]benzopyrano[3,4-c]pyridine-5-ones (2) and 2-alkoxy-4-amino-6-(2-thienyl or furanyl)-3,5-pyridinedicarbonitriles (3). Some of the synthesized compounds were evaluated for their anti-inflammatory and analgesic activities compared to diclofenac potassium as positive control. Detailed synthesis, spectroscopic and toxicity data are reported.U nastavku istraživanja derivata piridina s potencijalnim protuupalnim djelovanjem sintetizirani su 4-alkoksi-2-(2-tienil ili furanil)-5H-[1]benzopirano[3,4-c]piridin-5-oni (2) i 2-alkoksi-4-amino-6-(2-tienil ili furanil)-3,5-piridindikarbonitrili (3). Smjesa spojeva 2 i 3 dobivena je reakcijom 1-(2-tienil ili furanil)-3-(2-hidroksifenil)-2-propen-1-ona (1) s malononitrilom u alkoholnoj otopini KOH. Neki od sintetiziranih spojeva testirani su na protuupalno i analgetsko djelovanje, uz diklofenak kalij kao pozitivnu kontrolu. U radu su dani detaljni sintetski, spektroskopski i toksikološki podaci

Start-up delay Estimation at Signalized Intersections: Impact of Left-Turn Phasing Sequences

This paper aims to investigate the start-up delay at signalized intersections in Abu Dhabi (AD) city, UAE. Impact of external factors that may affect the start-up delay is examined including left turn phasing sequences (split/lead/lag), movement turning (through/left), intersection location (CBD/non-CBD) and day time (peak/off-peak). A new technique of data collection was applied based on the automate records of license plate of vehicles and a comparison with the traditional video recorded technique was carried out. Data covered 66 approaches of 36 signalized intersections. The analysis showed that overall estimated mean value of the start-up delay is 2.201 sec. with a standard deviation of 1.823 sec. The t-test shows significant statistical difference in start-up delay between observations at through and left movements, at CDB and non-CDB area and at split and lead/lag phasing. However, no significant differences were found between peak and off-peak periods and between split and lead phasing. In general, lead/lag phasing sequences not only improved the overall delay at signalized intersection but also improved the start-up delay.nbsp nbs

Production of Polysaccharides (Xanthan gum) by Xanthomonas campestris pv. Sesame

Many microorganisms and plants were found produce polysaccharides which are widely varying in their composition and structure. The extracellular polysaccharide produced by   Xanthomonas campestris pv. campestris, is chemically analyzed and used industrially. However, only the xanthan gum which was ranking as the best among the ten polysaccharides was used commercially in large amounts. The xanthan gum has numerous applications in food and other industries. The present study was aiming to investigate the capacity of X; campestris pv. sesami for the production of xanthan gum, using culture media containing different carbon sources. The properties of the produced material were investigated (pH, viscosity, and chromatographic analysis using thin layer chromatography).  The results showed that the weight of the product was increasing with time reaching about 9.8g at the tenth day compared to only 2.1g on the second day. The results of the effect of different carbon sources indicated that sucrose was the best giving 9.0 g in the 7th day compared to only 1.5g by raffinose. The pH was changing from 6.7 at the beginning of the experiment to 4.2 in the tenth day. However, the viscosity of the inoculated sucrose medium was found to increase from 2.4 unit at the second day to 9.7 units after ten days. Analysis on paper chromatography showed that the produced polysaccharide contains mannose, glucuronic acid, glucose, rhamnose but no ribose nor trehalose or fructose were detected. The results indicated that the investigated bacterium was producing large amounts of xanthan gum. Although, Xanthan gum was discovered in 1950s its substantial commercial production began in 1964 and in 1969, the USA, Food and Drug Administration authorized its use in food. Xanthan gum, now has numerous uses in food and other industries. Further studies should be carried on other isolates  of the bacterium   X. campestris pv. sesami and more chemical analysis are needed

Antiapoptotic and Antioxidant Properties of Orthosiphon stamineus Benth (Cat's Whiskers): Intervention in the Bcl-2-Mediated Apoptotic Pathway

Antiapoptotic and antioxidant activities of aqueous-methanolic extract (CAME) of Orthosiphonstamineus Benth(OS), and its hexane (HF), chloroform (CF), n-butanol (NBF), ethyl acetate (EAF) and water (WF) fractions were investigated. Antioxidant properties were evaluated using the assays of Folin-Ciocalteu, aluminiumtrichloride, β-carotene bleaching and DPPH. The role of OS against hydrogen peroxide induced apoptosis on MDA-M231 epithelial cells was examined using MTT assay, phase contrast microscope, colorimetric assay of caspase-3, western blot and quantitative real-time PCR. Results showed that EAF showed the highest total phenolic content followed by CAME, NBF, WF, CF and HF, respectively. Flavonoid content was in the order of the CF > EAF > HF > CAME > NBF > WF. The IC50 values on DPPH assay for different extract/fractions were 126.2 ± 23, 31.25 ± 1.2, 15.25 ± 2.3, 13.56 ± 1.9, 23.0 ± 3.2, and 16.66 ± 1.5 μg/ml for HF, CF, EAF, NBF, WF and CAME, respectively. OSreduced the oxidation of β-carotene by hydroperoxides. Cell death was dose-dependently inhibited by pretreatment with OS. Caspase-3 and distinct morphological features suggest the anti-apoptotic activities of OS. This plant not only increased the expression of Bcl-2, but also decreased Bax expression, and ultimately reduced H2O2-induced apoptosis. The current results showed that phenolics may provide health and nutritional benefits

Proposal of a modified tip apex distance for prediction of lag screw cut-out in trochanteric hip fractures

Introduction: Lag screw cut-out is a serious complication of dynamic hip screw fixation of trochanteric hip fractures. The lag screw position has been acknowledged as one of the important factors affecting the lag screw cut-out. We propose a modification of the Tip Apex Distance (TAD) and hypothesise that it could improve the reliability of predicting lag screws cut-out in these injuries. Materials and Methods: A retrospective study was conducted for hip fracture entries in the period from Jan 2018 to July 2022. A hundred and nine patients were suitable for the final analysis. The modified TAD was measured in millimetres based on the sum of the traditional TAD in the lateral view and the net value of two distances in the AP view, the first distance is from the tip of the lag screw to the opposite point on the femoral head along the axis of the lag screw while the second distance is from that point to the femoral head apex. The first distance is a positive value, whereas the second distance is positive if the lag screw is superior and negative if inferior. A receiver operating characteristic curve was used to evaluate the reliability of the different parameters assessing the lag screw position within the femoral head. Results: Reduction quality, fracture pattern as per the AO/OTA classification, TAD, Calcar Referenced TAD, Axis Blade Angle, Parker’s ration in the AP view, Cleveland Zone 1, and modified TAD were statistically associated with lag screw cut-out. Among the tested parameters, the modified TAD had 90.1% sensitivity and 90.9% specificity for lag screw cut-out at a cut-off value of 25 mm with a P-value < 0.001. Conclusion: The modified TAD had the highest reliability in the prediction of lag screw cut-out. A value ≤ 25 mm could potentially protect against lag screw cut-out in trochanteric hip fractures

Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts.

Recent studies indicated that seeded fibril formation and toxicity of α-synuclein (α-syn) play a main role in the pathogenesis of certain diseases including Parkinson's disease (PD), multiple system atrophy, and dementia with Lewy bodies. Therefore, examination of compounds that abolish the process of seeding is considered a key step towards therapy of several synucleinopathies. Using biophysical, biochemical and cell-culture-based assays, assessment of eleven compounds, extracted from Chinese medicinal herbs, was performed in this study for their effect on α-syn fibril formation and toxicity caused by the seeding process. Salvianolic acid B and dihydromyricetin were the two compounds that strongly inhibited the fibril growth and neurotoxicity of α-syn. In an in-vitro cell model, these compounds decreased the insoluble phosphorylated α-syn and aggregation. Also, in primary neuronal cells, these compounds showed a reduction in α-syn aggregates. Both compounds inhibited the seeded fibril growth with dihydromyricetin having the ability to disaggregate preformed α-syn fibrils. In order to investigate the inhibitory mechanisms of these two compounds towards fibril formation, we demonstrated that salvianolic acid B binds predominantly to monomers, while dihydromyricetin binds to oligomeric species and to a lower extent to monomers. Remarkably, these two compounds stabilized the soluble non-toxic oligomers lacking β-sheet content after subjecting them to proteinase K digestion. Eleven compounds were tested but only two showed inhibition of α-syn aggregation, seeded fibril formation and toxicity in vitro. These findings highlight an essential beginning for development of new molecules in the field of synucleinopathies treatment.The work conducted by Dr. El-Agnaf laboratory was supported by Qatar Biomedical Research Institute under the Start-up Fund SF 2017–007. Funding for this work was provided in part by NIH/NIA grant R37AG019391 to D.E. This study was made possible by NPRP grant 4–1371–1-223 from the Qatar National Research Fund (a member of Qatar Foundation). The funding bodies provided financial support for this study; they had no role in the study design, performance, data collection and analysis, decision to publish and preparation/writing of the manuscript

Feature Selection by Multiobjective Optimization: Application to Spam Detection System by Neural Networks and Grasshopper Optimization Algorithm

Networks are strained by spam, which also overloads email servers and blocks mailboxes with unwanted messages and files. Setting the protective level for spam filtering might become even more crucial for email users when malicious steps are taken since they must deal with an increase in the number of valid communications being marked as spam. By finding patterns in email communications, spam detection systems (SDS) have been developed to keep track of spammers and filter email activity. SDS has also enhanced the tool for detecting spam by reducing the rate of false positives and increasing the accuracy of detection. The difficulty with spam classifiers is the abundance of features. The importance of feature selection (FS) comes from its role in directing the feature selection algorithm’s search for ways to improve the SDS’s classification performance and accuracy. As a means of enhancing the performance of the SDS, we use a wrapper technique in this study that is based on the multi-objective grasshopper optimization algorithm (MOGOA) for feature extraction and the recently revised EGOA algorithm for multilayer perceptron (MLP) training. The suggested system’s performance was verified using the SpamBase, SpamAssassin, and UK-2011 datasets. Our research showed that our novel approach outperformed a variety of established practices in the literature by as much as 97.5%, 98.3%, and 96.4% respectively.©2022 the Authors. Published by IEEE. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License. For more information, see https://creativecommons.org/licenses/by-nc-nd/4.0/fi=vertaisarvioitu|en=peerReviewed

Mathematical modeling of temperature effect on algal growth for biodiesel application

Microalgae biomass is promising feedstock for the industrial production of biodiesel. Hence, research and development are required in various domains especially optimizations of growth conditions including temperature effect for mass scale operation (production of biomass, harvesting, extraction of lipid, etc). Since in middle east region, seasonal temperature variation and more rapid daily fluctuations are amenable to alter the growth kinetics of microalgae in outdoor culture and hence affect algae biomass production efficiency. Therefore, in this study, a mathematical model was developed to calculate how the algae sp. (Chlorella kessleri) will react at different temperatures. The model integrates Monod model and Arrhenius equation, and as such it describes the relationship of algal growth rate with culturing temperature and limiting nutrient concentration. The apparent activation energy and pre-exponential factors were calculated to be 2537 cal/mol and 0.0077 day−1, respectively. The developed models could be useful to anticipate the effective impacts of temperature on outdoor algae culture

A diabetes risk score for Qatar utilizing a novel mathematical modeling approach to identify individuals at high risk for diabetes

We developed a diabetes risk score using a novel analytical approach and tested its diagnostic performance to detect individuals at high risk of diabetes, by applying it to the Qatari population. A representative random sample of 5,000 Qataris selected at different time points was simulated using a diabetes mathematical model. Logistic regression was used to derive the score using age, sex, obesity, smoking, and physical inactivity as predictive variables. Performance diagnostics, validity, and potential yields of a diabetes testing program were evaluated. In 2020, the area under the curve (AUC) was 0.79 and sensitivity and specificity were 79.0% and 66.8%, respectively. Positive and negative predictive values (PPV and NPV) were 36.1% and 93.0%, with 42.0% of Qataris being at high diabetes risk. In 2030, projected AUC was 0.78 and sensitivity and specificity were 77.5% and 65.8%. PPV and NPV were 36.8% and 92.0%, with 43.0% of Qataris being at high diabetes risk. In 2050, AUC was 0.76 and sensitivity and specificity were 74.4% and 64.5%. PPV and NPV were 40.4% and 88.7%, with 45.0% of Qataris being at high diabetes risk. This model-based score demonstrated comparable performance to a data-derived score. The derived self-complete risk score provides an effective tool for initial diabetes screening, and for targeted lifestyle counselling and prevention programs.Peer reviewe