3D-QSAR and molecular docking studies of 4-methyl quinazoline derivatives as PI3Kα inhibitors

A new series of 4- methyl quinazoline derivatives was synthesized and its anti-cancer activity was assessed. It was revealed that its compounds have potent inhibition on related phosphoinositide 3-kinases alpha (PI3Kα). In this study, the three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking approaches were performed on a series of 4-methyl quinazoline derivatives with PI3Kα inhibitors. The 3D-QSAR study was applied using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods, which gave the cross-validation coefficient (Q²) values of 0.850 and 0.92, the determination coefficient (R²) values of 0.998 and 0.987, and the standard error of the estimate (SEE) values of 0.017 and 0.105, respectively. The acceptable values of determination coefficient (R² test) to CoMFA and CoMSIA respectively corresponding to values of 0.793 and 0.804 utilizing a test set of seven molecules prove the high predictive ability of this model. Using AutoDock tools, Molecular docking analysis was utilized to validate 3D-QSAR methods and to explain the binding site interactions and energy between the most active ligands and the PI3Kα (PDB ID: 4JPS) receptor. Based on these results, a novel series of 4- methyl quinazoline derivatives was predicted.     

Analysis of ambient ozone and precursor monitoring data in a densely populated residential area of Kuwait

Analysis of ozone (O₃) pollution in the Salmiyah residential area of Kuwait was conducted over a period of 12 months, from March 2008 to February 2009. Salmiyah is a densely populated area, mainly by expatriates. Apartment buildings are the dominant type of dwellings available in Salmiyah. The area is surrounded by major highways that get congested with traffic at peak hours of the day. The objectives of this work were: to monitor ambient tropospheric levels of O₃ and its precursors both for test comparing such levels to international standard limits and for assessing their health effects, to understand their diurnal behaviors, and to study their seasonal trends. The results of this study indicated that O₃, nitrogen dioxide (NO₂), and non-methane hydrocarbons (NMHC) exceeded the ambient air quality standards during specific times of the year. The diurnal patterns for NO₂ and NMHC showed three peaks which were directly dependent on high traffic density, while only two daily maxima were observed in the case of O₃. Finally, O₃ compared to its precursors exhibited a completely opposite monthly mean distribution with the highest concentration levels detected during the summer season (July and August).     

Field test studies of our infrared-based human temperature screening system embedded with a parallel measurement approach

This paper introduces a parallel measurement approach for fast infrared-based human temperature screening suitable for use in a large public area. Our key idea is based on the combination of simple image processing algorithms, infrared technology, and human flow management. With this multidisciplinary concept, we arrange as many people as possible in a two-dimensional space in front of a thermal imaging camera and then highlight all human facial areas through simple image filtering, image morphological, and particle analysis processes. In this way, an individual’s face in live thermal image can be located and the maximum facial skin temperature can be monitored and displayed. Our experiment shows a measured 1 ms processing time in highlighting all human face areas. With a thermal imaging camera having an FOV lens of 24° × 18° and 320 × 240 active pixels, the maximum facial skin temperatures from three people’s faces located at 1.3 m from the camera can also be simultaneously monitored and displayed in a measured rate of 31 fps, limited by the looping process in determining coordinates of all faces. For our 3-day test under the ambient temperature of 24–30 °C, 57–72% relative humidity, and weak wind from the outside hospital building, hyperthermic patients can be identified with 100% sensitivity and 36.4% specificity when the temperature threshold level and the offset temperature value are appropriately chosen. Appropriately locating our system away from the building doors, air conditioners and electric fans in order to eliminate wind blow coming toward the camera lens can significantly help improve our system specificity.     

Analysis of a Discrete-time Model for Periodic Diseases with Pulse Vaccination

We construct a discrete-time mathematical model for so-called periodic diseases. Most of these diseases occur during the early years of life and appear in cycles that are approximately periodic. Our three variable model effectively reduces to two variables. We study the nature of its fixed-point and its linear stability properties, and obtain an estimation of small oscillations about the fixed-point. This model, unlike many continuous-time ODE models, has an increasing total population. The major goal of this work is to examine the response of the model to a pulse vaccination strategy. We show that under the proper conditions the disease can be eliminated from the total population.     

Enzymatic determination of cholesterol and triglycerides in serum lipoprotein profiles by asymmetrical flow field-flow fractionation with on-line, dual detection

Alterations of lipoproteins (LPs) and related lipid levels in blood serum are correlated to the risk of coronary artery disease (CAD). Fast, possibly automated methods to obtain complete, multi-parametric LP profiles are therefore welcome to be developed for routine, clinical analysis practice. In this work, asymmetrical flow field-flow fractionation (AF4) with on-line, dual post-fractionation reaction detection (PFRD) is applied to develop a method for single-run, simultaneous quantification of cholesterol (CHOL) and triglycerides (TGs) in each fractionated LP class. The enzymatic reagents used for the post-fractionation reaction are available as commercial kits for certified, standard clinical protocols for the analysis of CHOL and TGs in serum. Using CHOL and glycerol as reference standards, a new procedure is applied to optimize the experimental conditions for PFRD-based, quantitative analysis. Upon optimized PFRD and AF4 conditions, results obtained for the determination of total CHOL (TC), TGs, HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C) in a set of serum samples from healthy donors are found in agreement with the values provided by a clinical laboratory. The intra-day and inter-day precisions of the method were found always lower than 10% (CV). When the method was applied to serum samples from patients affected by sepsis, differences in CHOL and TG profiles between patients and healthy donors were observed.     

Quantitative metabolic profiling of 21 endogenous corticosteroids in urine by liquid chromatography-triple quadrupole-mass spectrometry

Since corticosteroid metabolism may be affected by disease states, the accurate and precise measurement of endogenous corticosteroids in urine is necessary to understand their biochemical roles. An efficient quantitative profiling of 21 endogenous corticosteroids in urine has been validated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After enzymatic hydrolysis with β-glucuronidase, samples were purified using a solid-phase extraction cartridge and then separated through a sub-2 μm particle C18 column (2.1 mm × 50 mm, 1.9 μm) and quantified within 12.1 min using a triple quadrupole MS with electrospray ionization in positive ion mode. All corticosteroids resulted in the base-line separation, which is even achieved for stereo-isomers, such as α-/β-cortol, α-/β-cortolone, and allo-tetrahydrocortisol/tetrahydrocortisol. Overall recoveries ranged from 85% to 106% with limit of quantification ranged from 0.5 to 2.0 ng mL⁻¹ for the corticosteroids examined. The precision (% CV) and accuracy (% bias) of the assay were 1.7-7.8% and 95.1-105.4%, respectively, in 0.5-200 ng mL⁻¹ calibration ranges (r² > 0.9903), for quality-control samples containing 21 endogenous corticosteroids at three different urinary concentrations. Clinical application included quantitative analysis from patients with both prostate cancer and benign prostatic hyperplasia with altered cortisol concentrations. The described LC-MS/MS method eliminates interference from other urine components, has excellent chromatographic resolution achieved by a small particle LC column with a sufficient sensitivity to allow the profiling of both gluco- and mineralo-corticosteroids at a time.     

Synthesis of glycosaminoglycan oligosaccharides. Part 5: Synthesis of a putative heparan sulfate tetrasaccharide antigen involved in prion diseases

The synthesis of the putative prion-associated heparan sulfate tetrasaccharide containing two d-glucuronic acid units is reported. Key to the synthesis were the differentiation of the N-acetylated and N-unsubstituted glucosamine units, the high-yielding glucosylation at O-4 of an N-acetyl-d-glucosamine derivative and the α-selective glycosylation of the 4′-OH group of a β-d-GlcpA-(1→4)-d-GlcpNAc disaccharide building block with a disaccharide thioglycoside donor.     

A derivation of the discrete-time Anderson–May model for periodic diseases

We discuss the basic properties of the Anderson–May discrete-time model and its various modifications by Mickens. We then show that this model corresponds to the discretization of a pair of coupled first-order differential equations for which the step-size is selected to be the inverse of the transition rate out of the diseased population.     

Some applications of capillary gas chromatography in clinical chemistry

Profile analysis using capillary gas chromatography is applied in clinical chemistry to detect metabolic abnormalities. Examples are the increase of the urinary excretion of aromatic acids carrying a 4-hydroxyl group and the decrease of hippuric acid in liver cirrhosis, and the elevated concentrations and excretions of dicarboxylic, oxocarboxylic, and hydroxycarboxylic acids in diabetes mellitus. Gas chromatographic quantitations, in some instances using mass selective detection, are performed on clinically relevant constituents. An example is the investigation of plasma and urinary hippuric acid and 3-carboxy-4-methyl-5-pro-pyl-2-furanpropionic acid in different stages of renal diseases.