Temporal gradients in microfluidic systems to probe cellular dynamics: A review

Microfluidic devices have found a unique place in cellular studies due to the ease of fabrication, their ability to provide long-term culture, or the seamless integration of downstream measurements into the devices. The accurate and precise control of fluid flows also allows unique stimulant profiles to be applied to cells that have been difficult to perform with conventional devices. In this review, we describe and provide examples of microfluidic systems that have been used to generate temporal gradients of stimulants, such as waveforms or pulses, and how these profiles have been used to produce biological insights into mammalian cells that are not typically revealed under static concentration gradients. We also discuss the inherent analytical challenges associated with producing and maintaining temporal gradients in these devices.     

Synthesis of Privileged Scaffolds by Using Diversity‐Oriented Synthesis

An elegant reagent‐controlled strategy has been developed for the generation of a diverse range of biologically active scaffolds from a chiral bicyclic lactam. Reduction of the chiral lactam with LAH or alkylation with LHMDS to trigger different cyclization reactions have been shown to generate privileged scaffolds, such as pyrrolidines, indolines, and cyclotryptamines. Their amenability to substitution allows us to create various compound libraries by using these scaffolds. In silico studies were used to estimate the drug‐like properties of these compounds. Selected compounds were subjected to anticancer screening by using three different cell lines. In addition, all these compounds were subjected to antibacterial screening to gauge the spectrum of biological activity that was conferred by our DOS methodology. Gratifyingly, with no additional iterative cycles, our method directly generated anticancer compounds with potency at low nanomolar concentrations, as represented by spiroindoline 14 .     

Liquid-chromatographic separation and determination of process-related impurities, including a regio-specific isomer of celecoxib on reversed-phase C18 column dynamically coated with hexamethyldisilazane.

A simple and rapid reversed-phase high-performance liquid-chromatographic method for the separation and determination of process-related impurities of celecoxib (CXB) in bulk drugs and pharmaceuticals was developed. The separation of impurities viz., 4-methylacetophenone (I), 1-(4-methylphenyl)-4,4,4-trifluorobutane-1,3-dione (II), 4-hydrazinobenzene sulfonamide (III) and a regio-specific isomer [3-(4-methylphenyl)-5-trifluoromethyl-1H-pyrazole-1-yl]-benzenesulfonamide (IV), was accomplished on an Inertsil ODS-3 column dynamically coated with 0.1% hexamethyldisilazane (HMDS) in acetonitrile:water (55:45 v/v) as a mobile phase and detection at 242 nm using PDA at ambient temperature. The chromatographic conditions were optimized by studying the effects of HMDS, an organic modifier, time of silanization and column temperature. The method was validated and found to be suitable not only for monitoring the synthetic reactions, but also to evaluate the quality of CXB.     

Approximation for the mean value performance of locking algorithms for distributed database systems: a partitioned database

Concurrent access to databases must be synchronized for correct execution of transactions and preservation of data consistency. This is usually achieved through use of concurrency control algorithms, amongst which locking algorithms are the most popular both in the literature and in practice. Several analytic methods have been developed for predicting the performance of centralized database systems employing locking algorithms for concurrency control, but very few exist for distributed database systems.This paper proposes a method to approximate the mean value of various performance parameters in distributed database systems using locking for concurrency control. The main contribution of this approach is its ability to model the interaction between resource and data contention and the resulting effect on system performance. System performance is evaluated at a point where the interaction between these two factors is in equilibrium (stable state) and both the data and resource contention equations are simultaneously satisfied.The model involves the solution of a set of simultaneous polynomial equations whose order is dependent on several problem parameters such as the number of nodes and number of locks requested per transaction. These equations are solved by an iterative procedure to evaluate approximate values of relative throughput, utilization of servers and transaction response time. The small computational requirements of the analytical model permit sensitivity analysis on network parameters, and can thus be effectively used by system designers to evaluate choices of communication line speeds, processor capacity, database sizes, etc.The analytic approximations have been extensively verified against simulations for networks with up to 20 nodes. The input traffic was varied from light loads (about 5% utilization of the channels and processors) to heavy loads (about 65% utilization of the processors and channels). The discrepancies between the analytic approximation and the simulation were quite small (2–8%).This work was done while the authors were at Drexel University, Philadelphia.     

Synthesis and antibacterial activity of a new series of 2,3,5,7-substituted-pyrido[2,3-d]pyrimidin-4(3h)-one derivatives

A new series of 2,3,5,7-substituted-pyrido[2,3-d]pyrimidin-4(3H)-one derivatives were prepared from 2-amino-N,6-substituted phenyl-4-(trifluoromethyl or methyl)nicotinamides. The key intermediate 2-amino-N,6-substituted phenyl-4-(trifluoromethyl or methyl)nicotinamides were synthesized from 2-bromo-N,6-disubstituted phenyl-4-(trifluoromethyl or methyl)nicotinamides as well as from ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) coupling of 2-amino-4,6-substituted nicotinic acid and substituted arylamines. All the synthesized compounds were screened for antibacterial activity against Gram +ve and Gram -ve bacteria. Compound 7c showed better antibacterial activity against Gram +ve and Gram -ve bacteria.     

Studies on the polymerization of ethyl acrylate. II. Chain transfer studies

Transfer constants for different solvents representing hydrocarbons, halogenated compounds, alcohols, ketones, acids, and esters were determined in the thermal polymerization of ethyl acrylate at 80°C and they are compared with the available data on methyl acrylate and ethyl methacrylate. It was observed from the values of transfer constants that ethyl acrylate radicals are a little more effective than methyl acrylate or ethyl methacrylate in abstracting hydrogen atom from hydrocarbons and alcohols. In acetic and n-butyric acid media, it has been found, by the aid of endgroup analysis, that the derived solvent radicals from transfer reactions are not too efficient to start a new chain.     

Synthesis and applications of copillar[5]arene dithiols

Abstract

A novel copillar[4+1]arene incorporating alkylthiol substituents was synthesised in three steps and structurally characterised as the first example of a pillar[n]arene to incorporate two terminal thiols on the same aromatic ring. The macrocycle was attached to gold electrodes through a standard dipping technique. Cyclic voltammetry demonstrated selectivity for Li⁺ over other alkali metal cations. The copillar[4+1]arene was also used as a capping agent in the preparation of 3 nm gold nanoparticles.     

Organocatalytic oxidative synthesis of C2-functionalized benzoxazoles,naphthoxazoles, benzothiazoles and benzimidazoles

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The facile and efficient organocatalytic platform for accessing 1,2,4-selenadiazoles and thiadiazoles under aerobic conditions

The first organocatalytic approach towards synthesis of rarely explored 1,2,4-selenadiazole and thiadiazole scaffolds have been devised using corresponding carboxamides as substrates. The transformations were realized using two distinct conditions in the presence of catalytic vitamin B₃ or thiourea under aerobic conditions. Developed methods overcome the associated limitations of previous reported approaches and the desired products were obtained in high yields and selectivity without the formation of toxic side-products.