Cell detection and counting through cell lysate impedance spectroscopy in microfluidic devices

Cell-based microfluidic devices have attracted interest for a wide range of applications. While optical cell counting and flow cytometry-type devices have been reported extensively, sensitive and efficient non-optical methods to detect and quantify cells attached over large surface areas within microdevices are generally lacking. We describe an electrical method for counting cells based on the measurement of changes in conductivity of the surrounding medium due to ions released from surface-immobilized cells within a microfluidic channel. Immobilized cells are lysed using a low conductivity, hypotonic media and the resulting change in impedance is measured using surface patterned electrodes to detect and quantify the number of cells. We found that the bulk solution conductance increases linearly with the number of isolated cells contributing to solution ion concentration. The method of cell lysate impedance spectroscopy is sensitive enough to detect 20 cells microL(-1), and offers a simple and efficient method for detecting and enumerating cells within microfluidic devices for many applications including measurement of CD4 cell counts in HIV patients in resource-limited settings. To our knowledge, this is the most sensitive approach using non-optical setups to enumerate immobilized cells. The microfluidic device, capable of isolating specific cell types from a complex bio-fluidic and quantifying cell number, can serve as a single use cartridge for a hand-held instrument to provide simple, fast and affordable cell counting in point-of-care settings.     

Stereoselective synthesis of a MCHr1 antagonist

Melanin-concentrating hormone (MCH) is implicated in the feeding behavior in mammals affording a potential target to control overeating in people. Compound 1 (AMG 076) has been identified as a potent MCHr1 antagonist for the treatment of obesity. A synthesis suitable for the large-scale preparation of this lead candidate was developed to support preclinical studies. A Robinson annulation of benzylpiperidone and resolution of the desired enone from a mixture of the diastereomers afforded key intermediate 6 after a stereoselective hydrogenation. Subsequent Fischer indole synthesis with hydrazine 5 then provided the advanced intermediate, indole 2. Two complementary reductive amination strategies employing either aldehyde 3 or lactol 4 led to the synthesis of title compound 1.     

Antioxidant and Anti-Inflammatory Effects of Peganum harmala Extracts: An In Vitro and In Vivo Study

Peganum harmala (P. harmala) belongs to the family Zygophyllaceae, and is utilized in the traditional medicinal systems of Pakistan, China, Morocco, Algeria, and Spain to treat several chronic health disorders. The aim of the present study was to identify the chemical constituents and to evaluate the antioxidant, anti-inflammatory, and toxicity effects of P. harmala extracts both in vitro and in vivo. Sequential crude extracts including 100% dichloromethane, 100% methanol, and 70% aqueous methanol were obtained and their antioxidant and anti-inflammatory effects evaluated both in vitro and in vivo. The anti-inflammatory effect of the extract was investigated using the carrageenan-induced paw edema method in mice, whereas the toxicity of the most active extract was evaluated using an acute and subacute toxicity rat model. In addition, we have used the bioassay-guided approach to obtain potent fractions, using solvent–solvent partitioning and reversed phase high performance liquid chromatography from active crude extracts; identification and quantification of compounds from the active fractions was achieved using electrospray ionization mass spectrometry and high performance liquid chromatography techniques. Results revealed that the 100% methanol extract of P. harmala exhibits significant in vitro antioxidant activity in DPPH assay with an IC₅₀ of 49 µg/mL as compared to the standard quercetin with an IC₅₀ of 25.4 µg/mL. The same extract exhibited 63.0% inhibition against serum albumin denaturation as compared to 97% inhibition by the standard diclofenac sodium in an in vitro anti-inflammatory assay, and in vivo anti-inflammatory against carrageenan-induced paw edema (75.14% inhibition) as compared to 86.1% inhibition caused by the standard indomethacin. Furthermore, this extract was not toxic during a 14 day trial of acute toxicity when given at a dose of 3 g/kg, indicating that the lethal dose (LD₅₀) of P. harmala methanol extract was greater than 3 g/kg. P. harmala methanolic fraction 2 obtained using bioassay-guided fractionation showed the presence of quinic acid, peganine, harmol, harmaline, and harmine, confirmed by electrospray ionization mass spectrometry and quantified using external standards on high performance liquid chromatography. Taken all together, the current investigation further confirms the antioxidant, anti-inflammatory, and safety aspects of P. harmala, which justifies its use in folk medicine.     

New features in the class of association models

The most common association models are the U-, R-, C- and RC-models, achieved when only one dimension on the association is considered as significant (M = 1). Whenever more than one dimensions are significant (M > 1), the only kind of association assumed for each dimension is of the RC-type with the exception of Goodman's R + C + RC, R + RC, C + RC, U + RC and R + C models. Extending the idea of U-, R-, and C-models to association models with M > 1, relaxing the equidistance principle for successive categories for the known scores and using orthogonal polynomials, some new models are developed. Two classical sets of data are used to illustrate the advantages of the newly introduced models. Comparisons in terms of chi-square goodness of fit indicate that some of the newly introduced models perform better than the models fitted so far on these data sets. © 1998 John Wiley & Sons, Ltd.     

Generalized holographic dark energy model

In this paper, the model of the holographic Chaplygin gas has been extended to two general cases: first the case of a modified variable Chaplygin gas and second the case of the viscous generalized Chaplygin gas. The dynamics of the model is expressed by the use of scalar fields and scalar potentials.     

A mild,efficient and selective iodination of aromatic compounds using iodine and 1,4-bis(triphenylphosphonium)-2-butene peroxodisulfate

A simple and efficient method for the iodination of aromatic compounds has been achieved in the presence of iodine and 1,4-bis(triphenylphosphonium)-2-butene peroxodisulfate.     

On the commutativity degree of compact groups

In any finite group G, the commutativity degree of G (denoted by d(G)) is the probability that two randomly chosen elements of G commute. More generally, for every n ≥ 2 the nth commutativity degree (denoted by d _n (G)) is the probability that a randomly chosen ordered (n + 1)-tuple of the group elements is mutually commuting. The aim of this paper is to generalize the definition of d(G) and d _n (G) to every compact group G (infinite and even uncountable). We shall state some results concerning compact groups and we will extend some results in Erfanian et al. (Comm. Algebra 35 (2007), 4183–4197) and Lescot (J. Algebra 177 (1995), 847–869).     

Fixed point for set-valued mappings satisfying an implicit relation in partially ordered metric spaces

Let (X,?) be a partially ordered set and d be a complete metric on X. Let F,G be two set-valued mappings on X. We obtained sufficient conditions for the existence of common fixed point of F and G satisfying an implicit relation in partially ordered set X.