Probing to Minimize

We develop approximation algorithms for set-selection problems with deterministic constraints, but random objective values, i.e., stochastic probing problems. When the goal is to maximize the objective, approximation algorithms for probing problems are well-studied. On the other hand, few techniques are known for minimizing the objective, especially in the adaptive setting, where information about the random objective is revealed during the set-selection process and allowed to influence it. For minimization problems in particular, incorporating adaptivity can have a considerable effect on performance. In this work, we seek approximation algorithms that compare well to the optimal adaptive policy. We develop new techniques for adaptive minimization, applying them to a few problems of interest. The core technique we develop here is an approximate reduction from an adaptive expectation minimization problem to a set of adaptive probability minimization problems which we call threshold problems. By providing near-optimal solutions to these threshold problems, we obtain bicriteria adaptive policies. We apply this method to obtain an adaptive approximation algorithm for the Min-Element problem, where the goal is to adaptively pick random variables to minimize the expected minimum value seen among them, subject to a knapsack constraint. This partially resolves an open problem raised in [Goel et al., 2010]. We further consider three extensions on the Min-Element problem, where our objective is the sum of the smallest k element-weights, or the weight of the min-weight basis of a given matroid, or where the constraint is not given by a knapsack but by a matroid constraint. For all three of the variations we explore, we develop adaptive approximation algorithms for their corresponding threshold problems, and prove their near-optimality via coupling arguments

Charge-transfer nanostructures through noncovalent amphiphilic self-assembly: extended cofacial donor-acceptor arrays

Charge‐transfer (CT) assemblies with mixed‐stack (MS) arrays of donor (D) and acceptor (A) molecules are important class of functional organic materials owing to their interesting optoelectronic properties. Construction of charge‐transfer nanostructures comprising cofacially stacked perylene/tetrathiafulvalene (TTF) donors and viologen acceptors by an efficient, noncovalent, amphiphilic approach is described. Optical properties were used to probe the CT coassembly and stoichiometry of molecular D/A components, whereas <SUP>1</SUP>H NMR and X‐ray diffraction studies provided insights into their face‐to‐face organization. The efficient equimolar coassembly between ionic D (perylene salt (PS) and TTF salt (TTFS)) and A (dodecylmethyl viologen (DMV) and hexadecylmethyl viologen (HDMV)) molecules in water through ground state CT interactions results in the formation of noncovalent amphiphiles. Microscopic studies provided structural insight into the hierarchical organization of these charge‐transfer D‐A amphiphiles into bilayers and one‐dimensional nanostructures. In addition, at higher concentrations PS‐HDMV amphiphiles form hydrogels due to strong hydrophobic interactions caused by the long hydrocarbon tails. Two probe devices fabricated from these CT nanostructures as channel elements showed impressive conductivity values without any external doping, thus validating the CT design for conducting organic wires

Oral Lining Mucosa Development Depends on Mesenchymal microRNAs

The oral mucosa plays critical roles in protection, sensation, and secretion and can be classified into masticatory, lining, and specialized mucosa that are known to be functionally, histologically, and clinically distinct. Each type of oral mucosa is believed to develop through discrete molecular mechanisms, which remain unclear. MicroRNAs (miRNAs) are 19 to 25nt non-coding small single-stranded RNAs that negatively regulate gene expression by binding target mRNAs. miRNAs are crucial for fine-tuning of molecular mechanisms. To investigate the role of miRNAs in oral mucosa development, we examined mice with mesenchymal (Wnt1Cre; Dicer(fl/fl)) conditional deletion of Dicer. Wnt1Cre; Dicer(fl/fl) mice showed trans-differentiation of lining mucosa into an epithelium with masticatory mucosa/skin-specific characteristics. Up-regulation of Fgf signaling was found in mutant lining mucosal epithelium that was accompanied by an increase in Fgf7 expression in mutant mesenchyme. Mesenchyme miRNAs thus have an indirect effect on lining mucosal epithelial cell growth/differentiation.</p

Stability-indicating assay method for determination of actarit, its process related impurities and degradation products: Insight into stability profile and degradation pathwaysâ

The stability of the drug actarit was studied under different stress conditions like hydrolysis (acid, alkaline and neutral), oxidation, photolysis and thermal degradation as recommended by International Conference on Harmonization (ICH) guidelines. Drug was found to be unstable in acidic, basic and photolytic conditions and produced a common degradation product while oxidative stress condition produced three additional degradation products. Drug was impassive to neutral hydrolysis, dry thermal and accelerated stability conditions. Degradation products were identified, isolated and characterized by different spectroscopic analyses. Drug and the degradation products were synthesized by a new route using green chemistry. The chromatographic separation of the drug and its impurities was achieved in a phenomenex luna C18 column employing a step gradient elution by high performance liquid chromatography coupled to photodiode array and mass spectrometry detectors (HPLCâPDAâMS). A specific and sensitive stability-indicating assay method for the simultaneous determination of the drug actarit, its process related impurities and degradation products was developed and validated. Keywords: Actarit, Forced degradation, Stability-indicating assay metho

Discovery of 2-aminoimidazole and 2-amino imidazolyl-thiazoles as non-xanthine human adenosine A 3 receptor antagonists: SAR and molecular modeling studies

A small-molecule combinatorial library of 24 compounds with 2-aminoimidazole and 2-aminoimidazolyl-thiazole derivatives was synthesized using a 2-chloro trityl resin. The generated compound library was tested against all the human adenosine receptors subtypes. The 2-aminoimidazole derivatives (6a-6l) showed weak to moderate affinity towards the human adenosine receptors. Further modification to 2-aminoimidazolyl-thiazole derivatives (12a-12l) resulted in an improvement of affinity at adenosine A 1 , A 2A and A 3 receptor subtypes. Compound 12b was the most potent and selective non-xanthine human adenosine A 3 receptor antagonist of this series. A receptor-based modeling study was performed to explore the possible binding mode of these novel 2-aminoimidazole and 2-aminoimidazolyl-thiazole derivatives into human adenosine A 1 , A 2A and A 3 receptor subtypes