Bounded-time fault-tolerant rule-based systems

We introduce two systems concepts: bounded response-time and self-stabilization in the context of rule-based programs. These concepts are essential for the design of rule-based programs that must be highly fault-tolerant and perform in a real-time environment. The mechanical analysis of programs for these two properties will be discussed. We have also applied our techniques to analyze a NASA application.     

Maximizable routing metrics

We present a simple theory for maximizable routing metrics. First, we give a formal definition of routing metrics and identify two important properties: boundedness and monotonicity. We show that these two properties are both necessary and sufficient for a routing metric to be maximizable in any network. We show how to combine two (or more) routing metrics into a single composite metric such that if the original metrics are both bounded and monotonic (and, hence, maximizable), then the composite metric is also bounded and monotonic (and, hence, maximizable). We present several applications of our theory. We show that the composite routing metric used in the inter-gateway routing protocol (IGRP) is not maximizable and we show that enhanced IGRP (EIGRP) does not behave as expected for nonmonotonic metrics. We also show that a technique for scalable link-state routing does not work correctly when applied to composite metrics. A common theme throughout the paper is that the intuitions generated by using distance metrics to produce shortest paths do not carry over to other routing metrics.     

Synthesis and Antioxidant Evaluation of Some Nicotinonitriles

One‐pot condensation of malononitrile 1 , furan‐2‐carbaldehyde 2 , butan‐2‐one 3 , and ammonium acetate in ethanol, followed by cyanoacetylation of the formed nicotinonitrile 4 with 3‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐3‐oxopropanenitrile 5 afforded the cyanoacetamide 6 . Compound 6 was used as a key intermediate for synthesis of nicotinonitriles via reaction with different reagents.     

Overview of the synthetic routes to tadalafil and its analogues

The biological and medicinal properties of tadalafil and its analogues have prompted enormous research aimed at developing synthetic routes to these heterocyclic analogues. This review focuses on the chemical properties associated with this system.     

Spectrophotometric determination of gatifloxacin in pure form and in pharmaceutical formulation

Simple, rapid, and extractive spectrophotometric methods were developed for the determination of gatifloxacin (GT) in bulk and pharmaceutical dosage form. These methods are based on the formation of yellow ion-pair complexes between the basic nitrogen of the drug and three sulphonphthalein acid dyes, namely; bromocresol green (BCG), bromocresol purple (BCP), bromophenol blue (BPB) and bromothymol blue (BTB) in phthalate buffer pH 3.0, 3.4 and 3.2, using BCG, BCP and (BPB or BTB), respectively. The formed complexes were extracted with chloroform and measured at 415, 417, 412 and 414 nm for BCG, BPB, BCP and BTB, respectively. The analytical parameters and their effects on the reported systems are investigated. The reactions were extremely rapid at room temperature and the absorbance values remains unchanged at 48 h for all reactions. Beer's law was obeyed in the ranges 2.0-20, 2.0-14 and 2.0-16 microg mL(-1) for BCG, BCP and (BPB or BTB), respectively. The composition of the ion pairs was found 1:1 by Job's method. Beer's law validation, accuracy, precision, limits of detection, limits of quantification. The proposed methods have been applied successfully for the analysis of the drug bulk form and its dosage form. The results were in good agreement with those obtained by the official and reported methods.     

Application of an Artificial Neural Network for Modelling the Thermal Dynamics of a Building’s Space and its Heating System

Artificial neural networks (ANNs) have been used for modelling the thermal dynamics of a building’s space, its water heating system and the influence of solar radiation. A multi-layer feed-forward neural network, using a Levenberg-Marquardt backpropagation-training algorithm, has been applied to predict the future internal temperature. Real weather data for a number of winter months, together with a validated building model (based on the building constructions data), were used to train the network in order to generate a mapping between the easily measurable inputs (outdoor temperature, solar irradiance, heating valve position and the building indoor temperature) and the desired output, i.e., the predicted indoor temperature. The objective of this work was to investigate the potential of using an ANN with singular value decomposition method (SVD) to predict the indoor temperature to shut down the heating system controller early for saving the energy consumption for heating inside the building.     

Synthesis and Antioxidant Activity of Some Novel Nicotinonitrile Derivatives Bearing a Furan Moiety

As a part of ongoing studies in developing new potent antioxidant agents, 2‐amino‐4‐(furan‐2‐yl)‐5,6‐dimethylnicotinonitrile 4 was utilized as a key intermediate for the synthesis of some new pyrimidines 5 and 11 , form (acet)amide 6 , 7 , urea and thiourea 9 , 10 , 1,8‐naphthyridines 12 , 13 , and 14 . Moreover, condensation of 4 with 5,5‐dimethyl‐1,3‐cyclohexanedione and cyclohexanone in ethanol furnished the pyridine derivatives 16 and 17 , respectively. Furthermore, refluxing of 4 with ethylenediamine in carbon disulfide afforded the 4,5‐dihydro‐1H‐imidazol‐2‐yl pyridine derivative 19 . In addition, refluxing of 4 with carbon disulfide and concentrated sulfuric acid furnished the pyridine derivatives 20 and 21 , respectively. The reaction of 4 with phenacyl chloride and ethyl chloroacetate in dimethylformamide in the presence of catalytic amount of triethylamine afforded the pyridine derivatives 22 and 23 , respectively. Finally, heating of 4 with 1‐phenyl‐3‐(piperidin‐1‐yl)propan‐1‐one hydrochloride in glacial acetic acid afforded phenylpropylamino pyridine derivative 24 . The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, ¹H‐NMR, and mass spectral data. Representative compounds of the synthesized products were evaluated as antioxidant agents. Compounds 8 , 19 , and 22 are promising compounds.     

Globally Approved EGFR Inhibitors: Insights into Their Syntheses,Target Kinases,Biological Activities,Receptor Interactions,and Metabolism

Targeting the EGFR with small-molecule inhibitors is a confirmed valid strategy in cancer therapy. Since the FDA approval of the first EGFR-TKI, erlotinib, great efforts have been devoted to the discovery of new potent inhibitors. Until now, fourteen EGFR small-molecule inhibitors have been globally approved for the treatment of different types of cancers. Although these drugs showed high efficacy in cancer therapy, EGFR mutations have emerged as a big challenge for these drugs. In this review, we focus on the EGFR small-molecule inhibitors that have been approved for clinical uses in cancer therapy. These drugs are classified based on their chemical structures, target kinases, and pharmacological uses. The synthetic routes of these drugs are also discussed. The crystal structures of these drugs with their target kinases are also summarized and their bonding modes and interactions are visualized. Based on their binding interactions with the EGFR, these drugs are also classified into reversible and irreversible inhibitors. The cytotoxicity of these drugs against different types of cancer cell lines is also summarized. In addition, the proposed metabolic pathways and metabolites of the fourteen drugs are discussed, with a primary focus on the active and reactive metabolites. Taken together, this review highlights the syntheses, target kinases, crystal structures, binding interactions, cytotoxicity, and metabolism of the fourteen globally approved EGFR inhibitors. These data should greatly help in the design of new EGFR inhibitors.     

Pyrrolizine/Indolizine-NSAID Hybrids: Design,Synthesis, Biological Evaluation,and Molecular Docking Studies

In the current study, eight new hybrids of the NSAIDs, ibuprofen and ketoprofen with five pyrrolizine/indolizine derivatives were designed and synthesized. The chemical structures of these hybrids were confirmed by spectral and elemental analyses. The antiproliferative activities of these hybrids (5 μM) was investigated against MCF-7, A549, and HT-29 cancer cell lines using the cell viability assay, MTT assay. The results revealed 4–71% inhibition of the growth of the three cancer cell lines, where 8a,e,f were the most active. In addition, an investigation of the antiproliferative activity of 8a,e,f against MCF-7 cells revealed IC₅₀ values of 7.61, 1.07, and 3.16 μM, respectively. Cell cycle analysis of MCF-7 cells treated with the three hybrids at 5 μM revealed a pro-apoptotic increase in cells at preG1 and cell cycle arrest at the G1 and S phases. In addition, the three hybrids induced early apoptotic events in MCF-7 cells. The results of the molecular docking of the three hybrids into COX-1/2 revealed higher binding free energies than their parent compounds 5a,c and the co-crystallized ligands, ibuprofen and SC-558. The results also indicated higher binding free energies toward COX-2 over COX-1. Moreover, analysis of the binding modes of 8a,e,f into COX-2 revealed partial superposition with the co-crystallized ligand, SC-558 with the formation of essential hydrogen bonds, electrostatic, or hydrophobic interactions with the key amino acid His90 and Arg513. The new hybrids also showed drug-likeness scores in the range of 1.06–2.03 compared to ibuprofen (0.65) and ketoprofen (0.57). These results above indicated that compounds 8a,e,f deserve additional investigation as potential anticancer candidates.     

Spectrophotometric Determination of Dextromethorphan Hydrobromide and Ketamine Hydrochloride in Pure and Dosage Forms

Three simple, sensitive and accurate spectrophotometric methods have been developed for the determination of dextromethorphan hydrobromide (DEX) and ketamine hydrochloride (KET) in dosage forms. These methods are based on the formation of ion‐pair complexes with bromocresol green (BCG), bromocresol purple (BCP), and bromophenol blue (BPB) in acidic medium. The coloured ion‐pair products are measured at 419, 409 and 417 nm for DEX and at 417, 408 and 416 nm for KET using BCG, BCP and BPB, respectively. Beer's law was obeyed in the range of 2.0–22 μg mL^?1 for DEX and 2.0–16 μg mL^?1 for KET. The composition of the ion‐pair was established by continuous variation and molar ratio methods. The proposed methods were applied successfully for the determination of DEX and KET in dosage forms applying the standard addition technique and compared statistically with the official methods. The molar absorptivity, Sandell sensitivity, detection and quantification limits were also calculated.