Optimal promising zone designs

Clinical trials with adaptive sample size reassessment based on an unblinded analysis of interim results are perhaps the most popular class of adaptive designs (see Elsäßer et al., 2007). Such trials are typically designed by prespecifying a zone for the interim test statistic, termed the promising zone, along with a decision rule for increasing the sample size within that zone. Mehta and Pocock (2011) provided some examples of promising zone designs and discussed several procedures for controlling their type‐1 error. They did not, however, address how to choose the promising zone or the corresponding sample size reassessment rule, and proposed instead that the operating characteristics of alternative promising zone designs could be compared by simulation. Jennison and Turnbull (2015) developed an approach based on maximizing expected utility whereby one could evaluate alternative promising zone designs relative to a gold‐standard optimal design. In this paper, we show how, by eliciting a few preferences from the trial sponsor, one can construct promising zone designs that are both intuitive and achieve the Jennison and Turnbull (2015) gold‐standard for optimality.     

alpha-Alkyl-alpha-amino-beta-sulphone hydroxamates as potent MMP inhibitors that spare MMP-1

A series of alpha-alkyl-alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable.     

Segregation of the yeast plasmid: similarities and contrasts with bacterial plasmid partitioning

The high copy yeast plasmid 2 microm circle, like the well-studied low copy bacterial plasmids, utilizes two partitioning proteins and a cis-acting 'centromere'-like sequence for its stable propagation. Functionally, though, the protein and DNA constituents of the two partitioning systems are quite distinct. Key events in the yeast and bacterial segregation pathways are plasmid organization, localization, replication, 'counting' of replicated molecules and their distribution to daughter cells. We suggest that the two systems facilitate these common logistical steps by adapting to the physical, biochemical, and mechanical contexts in which the host chromosomes segregate.     

Amino acids in anthers of Milo and in cytoplasmic genetic male sterile sorghums (Sorghum bicolor L. Moench) of Indian origin

Summary Amino acid composition of proteins from anthers of milo and Indian origin male steriles were determined. Comparison of amino acid between A and B lines showed lower contents of histidine, threonine, glutamic acid, glycine, leucine and phenylalanine and higher contents of alanine, serine, proline and tyrosine in line A compared to line B. Alanine content in anthers of A lines was more than two fold higher than that in the anthers from B lines. Marked differences in amino acid composition of anthers of A and B lines are suggestive of their involvement in male sterility. Cytoplasmic male steriles of Indian origin M35-1A and M31-2A showed greater similarity but differed from milo, VZM2A and B.     

Epitope imprinting of iron binding protein of Neisseria meningitidis bacteria through multiple monomers imprinting approach

Epitope imprinting is a promising technique for fabrication of novel diagnostic tools. In this study, an epitope imprinted methodology for recognition of target epitope sequence as well as targeted protein infused by bacterial infection in blood samples of patients suffering from brain fever is developed. Template sequence chosen is a ferric iron binding fbp A protein present in Neisseria meningitidis bacteria. To orient the imprinting template peptide sequence on gold surface of electrochemical quartz crystal microbalance (EQCM), thiol chemistry was utilized to form the self‐assembled monolayer on EQCM electrode. Here, synergistic effects induced by various noncovalent interactions extended by multiple monomers (3‐sulfopropyl methacrylate potassium‐salt and benzyl methacrylate) were used in fabricating the imprinting polymeric matrix with additional firmness provided by N,N‐methylene‐bis‐acrylamide as cross‐linker and azo‐isobutyronitrile as initiator. Extraction of template molecule was carried out with phosphate buffer solution. After extraction of epitope molecules from the polymeric film, epitope molecularly imprinted polymeric films were fabricated on EQCM electrode surface. Nonimprinted polymers were also synthesized in the similar manner without epitope molecule. Detection limit of epitope molecularly imprinted polymers and imprinting factor (epitope molecularly imprinted polymers/nonimprinted polymers) was calculated 1.39 ng mL^?1 and 12.27 respectively showing high binding capacity and specific recognition behavior toward template molecule. Simplicity of present method would put forward a fast, facile, cost‐effective diagnostic tool for mass health care.     

Involvement of Boiling Stable Antioxidant Enzymes in Adaptation of Invasive Alien Plant Lantana to Abiotic Stress under Natural Conditions

Russian Journal of Plant Physiology - Lantana camara L. is noxious weed affecting ecosystem and biodiversity worldwide. However, the biochemical basis of invasiveness and adaptation to abiotic...     

An isobutyronitrile-induced bienzymatic system of Alcaligenes sp. MTCC 10674 and its application in the synthesis of α-hydroxyisobutyric acid

Alcaligenes sp. MTCC 10674 was isolated as acetone cyanohydrin hydrolyzing bacterium from soil of orchid gardens of Himachal Pradesh. Acetone cyanohydrin hydrolyzing activity of this organism comprised nitrile hydratase and amidase activities. It exhibited higher substrate specificity towards aliphatic hydroxynitrile (acetone cyanohydrin) in comparison to arylaliphatic hydroxynitrile. Isobutyronitrile (40 mM) acted as a carbon source as well as inducer for growth of Alcaligenes sp. MTCC 10674 and expression of acetone cyanohydrin hydrolyzing activity. Optimization of culture condition using response surface methodology increased acetone cyanohydrin hydrolyzing activity by 1.3-fold, while inducer mediation approach increased the activity by 1.2-fold. The half life of this enzyme was 25 h at 15 °C. V _max and K _m value for acetone cyanohydrin hydrolyzing enzyme was 0.71 μmol mg^?1 min^?1 and 14.3 mM, when acetone cyanohydrin was used as substrate. Acetone cyanohydrin hydrolyzing enzyme encountered product inhibition and IC50 and K _i value were calculated to be 28 and 10.2 mM, respectively, when product α-hydroxyisobutyric acid was added in the reaction. Under optimized reaction conditions at 40 ml fed batch scale, 3 mg dcw ml ^? resting cells of Alcaligenes sp. MTCC 10674 fully converted 0.33 M acetone cyanohydrin into α-hydroxyisobutyric acid (1.02 g) in 6 h 40 min. The characterization of acetone cyanohydrins hydrolyzing activity revealed that it comprises bienzymatic nitrile hydrolyzing system, i.e. nitrile hydratase and amidase for the production of α-hydroxyisobutyric acid from acetone cyanohydrin and maximum 70 % yield is being reported for the first time.     

The Prebiotic Provenance of Semi-Aqueous Solvents

Origins of Life and Evolution of Biospheres - The numerous and varied roles of phosphorylated organic molecules in biochemistry suggest they may have been important to the origin of life. The...