A mathematical model of measurement uncertainty of single substrate enzyme assays

Clinical laboratory tests provide critical information at every stage of the medical decision‐making process, and measurement of the activity levels of enzymes such as alkaline phosphatase, lactate dehydrogenase, etc. provide information regarding various body functions such as the liver and gastrointestinal tract. The uncertainty associated with these enzyme measurement processes describes the quality of the measurement process, and therefore methods to improve the quality of the measurement process require minimizing the measurement uncertainty of the enzyme assay. In this study, we develop a mathematical model of the lactate dehydrogenase measurement process, with uncertainty introduced into its parameters that represent the sources of variation in the different components and stages of the measurement process. The Monte Carlo method is then utilized to estimate the uncertainty associated with the model, and therefore the measurement process. An empirical function used to generate estimates of uncertainty for patient samples with unknown activity levels is constructed using the model. The model is then used to quantify the contributions of the individual sources of uncertainty to the net measurement uncertainty and also quantify the effect of uncertainty within the calibration process on the distribution of the measurement result. Copyright © 2014 John Wiley & Sons, Ltd.     

Copper(II)-mediated cross-coupling of arylboronic acids and 2(1H)-pyrazinones facilitated by microwave irradiation with simultaneous cooling

[reaction: see text] Optimized conditions for the decoration of the 2(1H)-pyrazinone scaffold were developed by applying the Chan-Lam protocol. It was demonstrated that this Cu(II)-mediated cross-coupling reaction resulted in significantly improved yields and rates when performed under microwave irradiation with simultaneous cooling at 0 degrees C, applying a mixture of bases Et(3)N/pyridine.     

On the inapproximability of <Emphasis Type="Italic">M</Emphasis>/<Emphasis Type="Italic">G</Emphasis>/<Emphasis Type="Italic">K</Emphasis>: why two moments of job size distribution are not enough

The M/G/K queueing system is one of the oldest models for multiserver systems and has been the topic of performance papers for almost half a century. However, even now, only coarse approximations exist for its mean waiting time. All the closed-form (nonnumerical) approximations in the literature are based on (at most) the first two moments of the job size distribution. In this paper we prove that no approximation based on only the first two moments can be accurate for all job size distributions, and we provide a lower bound on the inapproximability ratio, which we refer to as “the gap.” This is the first such result in the literature to address “the gap.” The proof technique behind this result is novel as well and combines mean value analysis, sample path techniques, scheduling, regenerative arguments, and asymptotic estimates. Finally, our work provides insight into the effect of higher moments of the job size distribution on the mean waiting time.     

Anticancer Properties of Highly Purified l-Asparaginase from Withania somnifera L. against Acute Lymphoblastic Leukemia

Withania somnifera L. has been traditionally used as a sedative and hypnotic. The present study was carried out for the purification, characterization, and in vitro cytotoxicity of l-asparaginase from W. somnifera L. l-Asparaginase was purified from the fruits of W. somnifera L. up to 95% through chromatography. The purified l-asparaginase was characterized by size exclusion chromatography, polyacrylamide gel electrophoresis (PAGE), and 2D PAGE. The antitumor and growth inhibition effect of the l-asparaginase was assessed using [3-(4, 5-dimethyl-thiazol-2yl)-2, 5-diphenyl-tetrazolium bromide] (MTT) colorimetric dye reduction method. The purified enzyme is a homodimer, with a molecular mass of 72 ± 0.5 kDa, and the pI value of the enzyme was around 5.1. This is the first report of the plant containing l-asparaginase with antitumor activity. Data obtained from the MTT assay showed a LD₅₀ value of 1.45 ± 0.05 IU/ml. W. somnifera L. proved to be an effective and a novel source of l-asparaginase. Furthermore, it shows a lot of similarity with bacterial l-asparaginases EC-2.     

Microwave mediated synthesis of spiro-(indoline-isoxazolidines): mechanistic study and biological activity evaluation

Regioisomeric spiro-(indoline-isoxazolidines) have been synthesized in moderate yields by the cycloaddition reaction between ethyl (3-indolylidene)acetate and various substituted α,N-diphenylnitrones, using environmentally benign microwave technology. A novel concerted reaction mechanism is described that explains the preferential formation of the regioisomeric spiro-(indoline-isoxazolidine) analogs 6 over 5. These compounds were screened for anti-mycobacterial and anti-invasive activities against tumor cells.     

Monoamine oxidase and succinate dehydrogenase inhibitory properties of substituted mercaptoquinazolones

Twelve 6-substituted-2-(1′-mercaptoacetyl-3′-arylurea)-3-phenyl-4-quinazolones were synthesized by condensation of 6-substituted anthranilic acids and aryl isothiocyanates followed by reaction with chloroacetyl arylurea. These compounds were characterized by their sharp melting points and elemental analyses. All compounds were evaluated for their enzyme inhibitory activity. It was found that all substituted quinazolones at a final concentration of 2 × 10^?4 M inhibited in vitro monoamine oxidase and succinate dehydrogenase activity of rat brain homogenates and the degree of inhibition ranged from 11–77% and 25–53%, respectively.     

Substituted 5-aryl- or 5-diphenylmethyl-3-alkyl-2-oxazolidones as anticonvulsants

Several 5-aryl- or 5-diphenylmethylhydracrylyl hydrazides were synthesized and converted into 5-aryl- or diphenylmethyl-2-oxazolidones. The latter compounds were further alkylated into their corresponding 5-aryl- or 5-diphenylmethyl-3-alkyl-2-oxazolidones as possible anticon-vusants.     

Synthesis of substituted 2-ethyl-3-(4-hydrazinocarbonylphenyl)-4-quinazo-lones and 2-ethyl-3-(4-hydrazinocarbonylmethylphenyl)-4-quinazolones

Some substituted 2-ethyl-3-(4-hydrazinocarbonylphenyl)-4-quinazolones and 2-ethyl-3-(4-hydrazinocarbonylmethylphenyl)-4-quinazolones were synthesized and characterized by their sharp melting points, elemental analyses and spectral data.     

Metal complexes of hybrid oxygen-arsenic ligands—III : Complexes of 2-tertiary arsinobenzoic acids with zinc(II), cadmium(II) and mercury(II). Discovery of a novel chelating system

This paper describes the preparation of the halogeno complexes, HgX₂(o-R₂AsC₆H₄CO₂H) (X = Cl, Br, I, and R = Et; X = Br, I, and R-C₆H₁₁) and the carboxylate complexes, M(o-R₂-AsC₆H₄CO₂)₂nL(M = Cd, R = Et, C₆H₁₁ and n = O; M = Zn; R = Et; nL = H₂O; M = Zn, R = C₆H₁₁, nL = 3H₂O; M = Hg, R = p-tolyl, nL = 2H₂O; M = Hg, R = Me, Ph; C₆H₁₁ and nL = EtOH). The structures already reported for the halogeno complexes with R = Ph, Me, p-tolyl and X = Cl, Br, I, have been revised on the basis of detailed scrutiny of the IR spectral data and all these complexes have been divided into four structural types out of which three retain the acid dimer unit of the free ligand. In the carboxylate complexes the lowering of ν_s, CO₂ band and the marginal change in the ν_as CO₂ band with respect to those of the corresponding ligand sodium salts have been attributed to the existence of a novel resonating chelating system with the possibility of having a ring current.