Local Structural and Environmental Factors Define the Efficiency of an RNA Pseudoknot Involved in Programmed Ribosomal Frameshift Process

In programmed -1 ribosomal frameshift, an RNA pseudoknot stalls the ribosome at specific sequence and restarts translation in a new reading frame. A precise understanding of structural characteristics of these pseudoknots and their PRF inducing ability has not been clear to date. To investigate this phenomenon, we have studied various structural aspects of a -1 PRF inducing RNA pseudoknot from BWYV using extensive molecular dynamics simulations. A set of functional and poorly functional forms, for which previous mutational data were available, were chosen for analysis. These structures differ from each other by either single base substitutions or base-pair replacements from the native structure. We have rationalized how certain mutations in RNA pseudoknot affect its function; e.g., a specific base substitution in loop 2 stabilizes the junction geometry by forming multiple noncanonical hydrogen bonds, leading to a highly rigid structure that could effectively resist ribosome-induced unfolding, thereby increasing efficiency. While, a CG to AU pair substitution in stem 1 leads to loss of noncanonical hydrogen bonds between stems and loop, resulting in a less stable structure and reduced PRF inducing ability, inversion of a pair in stem 2 alters specific base-pair geometry that might be required in ribosomal recognition of nucleobase groups, negatively affecting pseudoknot functioning. These observations illustrate that the ability of an RNA pseudoknot to induce -1 PRF with an optimal rate depends on several independent factors that contribute to either the local conformational variability or geometry

Effect of inductive effect on the formation of cocrystals and eutectics

There is a growing need to understand the factors that control the formation of different yet related multicomponent adducts such as cocrystals, solid solutions and eutectics from both fundamental and application perspectives. Benzoic acid and its structural analogues, having gradation in inductive force strengths, are found to serve as excellent coformers to comprehend the formation of above adducts with the antiprotozoal drug ornidazole. The combination of the drug with para-amino and -hydroxybenzoic acids resulted in cocrystals in accordance with the induction strength complementarity between the participant hydrogen bond donor-acceptor groups. The lack of adequate inductive forces for combinations with benzoic acid and other coformers was exploited to make eutectics of the drug. The isomorphous/isostructural relationship between para-amino and -hydroxybenzoic acid-drug cocrystals was utilized to make solid solutions, i.e. solid solutions of cocrystals. All in all, we successfully steered and expanded the supramolecular solid-form space of ornidazole.

Hydrophobic hydration driven self-assembly of curcumin in water: Similarities to nucleation and growth under large metastability, and an analysis of water dynamics at heterogeneous surfaces

As the beneficial effects of curcumin have often been reported to be limited to its small concentrations, we have undertaken a study to find the aggregation properties of curcumin in water by varying the number of monomers. Our molecular dynamics simulation results show that the equilibrated structure is always an aggregated state with remarkable structural rearrangements as we vary the number of curcumin monomers from 4 to 16 monomers. We find that the curcumin monomers form clusters in a very definite pattern where they tend to aggregate both in parallel and anti-parallel orientation of the phenyl rings, often seen in the formation of beta-sheet in proteins. A considerable enhancement in the population of parallel alignments is observed with increasing the system size from 12 to 16 curcumin monomers. Due to the prevalence of such parallel alignment for large system size, a more closely packed cluster is formed with maximum number of hydrophobic contacts. We also follow the pathway of cluster growth, in particular the transition from the initial segregated to the final aggregated state. We find the existence of a metastable structural intermediate involving a number of intermediate-sized clusters dispersed in the solution. We have constructed a free energy landscape of aggregation where the metatsable state has been identified. The course of aggregation bears similarity to nucleation and growth in highly metastable state. The final aggregated form remains stable with the total exclusion of water from its sequestered hydrophobic core. We also investigate water structure near the cluster surface along with their orientation. We find that water molecules form a distorted tetrahedral geometry in the 1st solvation layer of the cluster, interacting rather strongly with the hydrophilic groups at the surface of the curcumin. The dynamics of such quasi-bound water molecules near the surface of curcumin cluster is considerably slower than the bulk signifying a restricted motion as often found in protein hydration layer. (C) 2014 AIP Publishing LLC.

Mining Unit Tests for Discovery and Migration of Math APIs

Today's programming languages are supported by powerful third-party APIs. For a given application domain, it is common to have many competing APIs that provide similar functionality. Programmer productivity therefore depends heavily on the programmer's ability to discover suitable APIs both during an initial coding phase, as well as during software maintenance. The aim of this work is to support the discovery and migration of math APIs. Math APIs are at the heart of many application domains ranging from machine learning to scientific computations. Our approach, called MATHFINDER, combines executable specifications of mathematical computations with unit tests (operational specifications) of API methods. Given a math expression, MATHFINDER synthesizes pseudo-code comprised of API methods to compute the expression by mining unit tests of the API methods. We present a sequential version of our unit test mining algorithm and also design a more scalable data-parallel version. We perform extensive evaluation of MATHFINDER (1) for API discovery, where math algorithms are to be implemented from scratch and (2) for API migration, where client programs utilizing a math API are to be migrated to another API. We evaluated the precision and recall of MATHFINDER on a diverse collection of math expressions, culled from algorithms used in a wide range of application areas such as control systems and structural dynamics. In a user study to evaluate the productivity gains obtained by using MATHFINDER for API discovery, the programmers who used MATHFINDER finished their programming tasks twice as fast as their counterparts who used the usual techniques like web and code search, IDE code completion, and manual inspection of library documentation. For the problem of API migration, as a case study, we used MATHFINDER to migrate Weka, a popular machine learning library. Overall, our evaluation shows that MATHFINDER is easy to use, provides highly precise results across several math APIs and application domains even with a small number of unit tests per method, and scales to large collections of unit tests.

Effect of functional groups on separating carbon dioxide from CO2/N-2 gas mixtures using edge functionalized graphene nanoribbons

Development of microporous adsorbents for separation and sequestration of carbon dioxide from flue gas streams is an area of active research. In this study, we assess the influence of specific functional groups on the adsorption selectivity of CO2/N-2 mixtures through Grand Canonical Monte Carlo (GCMC) simulations. Our model system consists of a bilayer graphene nanoribbon that has been edge functionalized with OH, NH2, NO2, CH3 and COOH. Ab initio Moller-Plesset (MP2) calculations with functionalized benzenes are used to obtain binding energies and optimized geometries for CO2 and N-2. This information is used to validate the choice classical forcefields in GCMC simulations. In addition to simulations of adsorption from binary mixtures of CO2 and N-2, the ideal adsorbed solution theory (IAST) is used to predict mixture isotherms. Our study reveals that functionalization always leads to an increase in the adsorption of both CO2 and N-2 with the highest for COOH. However, significant enhancement in the selectivity for CO2 is only seen with COOH functionalized nanoribbons. The COOH functionalization gives a 28% increase in selectivity compared to H terminated nanoribbons, whereas the improvement in the selectivity for other functional groups are much Enure modest. Our study suggests that specific functionalization with COOH groups can provide a material's design strategy to improve CO2 selectivity in microporous adsorbents. Synthesis of graphene nanoplatelets with edge functionalized COOH, which has the potential for large scale production, has recently been reported (Jeon el, al., 2012). (C) 2014 Elsevier Ltd. All rights reserved,

An Expeditious Asymmetric Synthesis of the Polyketide Unit Present in HIV-Inhibitory Depsipeptides Aetheramide A and B

The enantioselective synthesis of the polyketide unit present in depsipeptides aetheramide A and B, which possess potent HIV-inhibitory activity, is accomplished from a chiral furyl carbinol.

Solution processable diketopyrrolopyrrole (DPP) cored small molecules with BODIPY end groups as novel donors for organic solar cells

Two novel triads based on a diketopyrrolopyrrole (DPP) central core and two 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) units attached by thiophene rings have been synthesised having high molar extinction coefficients. These triads were characterised and used as donor materials in small molecule, solution processable organic solar cells. Both triads were blended with PC71BM as an acceptor in different ratios by wt% and their photovoltaic properties were studied. For both the triads a modest photovoltaic performance was observed, having an efficiency of 0.65%. Moreover, in order to understand the ground and excited state properties and vertical absorption profile of DPP and BODIPY units within the triads, theoretical DFT and TDDFT calculations were performed.

Graded IR Filters: Distinguishing Between Single and Multipoint NO2 center dot center dot center dot I Halogen Bonded Supramolecular Synthons (P, Q, and R Synthons)

The NO2 center dot center dot center dot I supramolecular synthon is a halogen bonded recognition pattern that is present in the crystal structures of many compounds that contain these functional groups. These synthons have been previously distinguished as P, Q, and R types using topological and geometrical criteria. A five step IR spectroscopic sequence is proposed here to distinguish between these synthon types in solid samples. Sets of known compounds that contain the P, Q, and R synthons are first taken to develop IR spectroscopic identifiers for them. The identifiers are then used to create graded IR filters that sieve the synthons. These filters contain signatures of the individual NO2 center dot center dot center dot I synthons and may be applied to distinguish between P, Q, and R synthon varieties. They are also useful to identify synthons that are of a borderline character, synthons in disordered structures wherein the crystal structure in itself is not sufficient to distinguish synthon types, and in the identification of the NO2 center dot center dot center dot I synthons in compounds with unknown crystal structures. This study establishes clear differences for the three different geometries P, Q, and Rand in the chemical differences in the intermolecular interactions contained in the synthons. Our IR method can be conveniently employed when single crystals are not readily available also in high throughput analysis. It is possible that such identification may also be adopted as an input for crystal structure prediction analysis of compounds with unknown crystal structures.

Synthesis, crystal structure and spectroscopic and electrochemical properties of bridged trisbenzoato copper-zinc heterobinuclear complex of 2,2 `-bipyridine

The synthesis of the heterobinuclear copper-zinc complex CuZn(bz)(3)(bpy)(2)]ClO4 (bz = benzoate) from benzoic acid and bipyridine is described. Single crystal X-ray diffraction studies of the heterobinuclear complex reveals the geometry of the benzoato bridged Cu(II)-Zn(II) centre. The copper or zinc atom is pentacoordinate, with two oxygen atoms from bridging benzoato groups and two nitrogen atoms from one bipyridine forming an approximate plane and a bridging oxygen atom from a monodentate benzoate group. The Cu-Zn distance is 3.345 angstrom. The complex is normal paramagnetic having mu(eff) value equal to 1.75 BM, ruling out the possibility of Cu-Cu interaction in the structural unit. The ESR spectrum of the complex in CH3CN at RT exhibit an isotropic four line spectrum centred at g = 2.142 and hyperfine coupling constants A(av) = 63 x 10(-4) cm(-1), characteristic of a mononuclear square-pyramidal copper(II) complexes. At LNT, the complex shows an isotropic spectrum with g(parallel to) = 2.254 and g(perpendicular to) =2.071 and A(parallel to) = 160 x 10(-4) cm(-1). The Hamiltonian parameters are characteristic of distorted square pyramidal geometry. Cyclic voltammetric studies of the complex have indicated quasi-reversible behaviour in acetonitrile solution. (C) 2014 Elsevier B.V. All rights reserved.

IR spectroscopy as a probe for C-H center dot center dot center dot X hydrogen bonded supramolecular synthons

Weak hydrogen bonds of the type C-H center dot center dot center dot X (X: N, O, S and halogens) have evoked considerable interest over the years, especially in the context of crystal engineering. However, association patterns of weak hydrogen bonds are generally difficult to characterize, and yet the identification of such patterns is of interest, especially in high throughput work or where single crystal X-ray analysis is difficult or impossible. To obtain structural information on such assemblies, we describe here a five step IR spectroscopic method that identifies supramolecular synthons in weak hydrogen bonded dimer assemblies, bifurcated systems, and p-electron mediated synthons. The synthons studied here contain C-H groups as hydrogen bond donors. The method involves: (i) identifying simple compounds/cocrystals/salts that contain the hydrogen bonded dimer synthon of interest or linear hydrogen bonded assemblies between the same functionalities; (ii) scanning infrared (IR) spectra of the compounds; (iii) identifying characteristic spectral differences between dimer and linear; (iv) assigning identified bands as marker bands for identification of the supramolecular synthon, and finally (v) identifying synthons in compounds whose crystal structures are not known. The method has been effectively implemented for assemblies involving dimer/linear weak hydrogen bonds in nitrobenzenes (C-H center dot center dot center dot O-NO), nitro-dimethylamino compounds (NMe2 center dot center dot center dot O2N), chalcones (C-H center dot center dot center dot O=C), benzonitriles (C-H center dot center dot center dot N C) and fluorobenzoic acids (C-H center dot center dot center dot F-C). Two other special cases of C-H center dot center dot center dot pi and N-H center dot center dot center dot pi synthons were studied in which the band shape of the C-H stretch in hydrocarbons and the N-H deformation in aminobenzenes was examined.

Differential Cocrystallization Behavior of Isomeric Pyridine Carboxamides toward Antitubercular Drug Pyrazinoic Acid

Pyrazinoic acid, the active form of the antitubercular pro-drug Pyrazinamide, is an amphiprotic molecule containing carboxylic acid and pyridine groups and therefore can form both salts and cocrystals with relevant partner molecules. Cocrystallization of pyrazinoic acid with isomeric pyridine carboxamide series resulted in a dimorphic mixed-ionic complex with isonicotinamide and in eutectics with nicotinamide and picolinamide, respectively. It is observed that with alteration of the carboxamide position, steric and electrostatic compatibility issues between molecules of the combination emerge and affect intermolecular interactions and supramolecular growth, thus leading to either cocrystal or eutectic for different pyrazinoic acid-pyridine carboxamide combinations. Intermolecular interaction energy calculations have been performed to understand the role of underlying energetics on the formation of cocrystal/eutectic in different combinations. On the other hand, two molecular salts with piperazine and cytosine and a gallic acid cocrystal of the drug were obtained, and their X-ray crystal structures were also determined in this work.

Design of an Automated Dispenser Unit

This paper presents our work on developing an automated micro positioner and a low cost disposable dispenser module having a disposable dispenser core. The dispenser core is made up of Polydimethylsiloxane (PDMS). Once the user specifies the dispensing location in the Graphical User Interface (GUI), the movement of the micropositioner is automatic. The design, fabrication and characterization results of the dispenser module are also presented. The dispensing experiments are performed with Di-Ethanol Amine as the working reagent. The minimum dispensed volume achieved is about 4 nL.

Controlled synthesis of tunable nanoporous carbons for gas storage and supercapacitor application

A simple methodology has been developed for the synthesis of functional nanoporous carbon (NPC) materials using a metal-organic framework (IRMOF-3) that can act as a template for external carbon precursor (viz, sucrose) and also a self-sacrificing carbon source. The resultant graphitic NPC samples (abbreviated as NPC-0, NPC-150, NPC-300, NPC-500 and NPC-1000 based on sucrose loading) obtained through loading different amounts of sucrose exhibit tunable textural parameters. Among these, NPC-300 shows very high surface area (BET approximate to 3119 m(2)/g, Langmuir approximate to 4031 m(2)/g) with a large pore volume of 1.93 cm(3)/g. High degree of porosity coupled with polar surface functional groups, make NPC-300 remarkable candidate for the uptake of H-2 (2.54 wt% at 1 bar, and 5.1 wt% at 50 bar, 77 K) and CO2 (64 wt% at 1 bar, 195 K and 16.9 wt% at 30 bar, 298 K). As a working electrode in a supercapacitor cell, NPC-300 shows excellent reversible charge storage thus, demonstrating multifunctional usage of the carbon materials. (C) 2015 Elsevier Inc. All rights reserved.

Composition dependent non-ideality in aqueous binary mixtures as a signature of avoided spinodal decomposition

We explore the potential energy landscape of structure breaking binary mixtures (SBBM) where two constituents dislike each other, yet remain macroscopically homogeneous at intermediate to high temperatures. Interestingly, we find that the origin of strong composition dependent non-ideal behaviour lies in its phase separated inherent structure. The inherent structure (IS) of SBBM exhibits bi-continuous phase as is usually formed during spinodal decomposition. We draw analogy of this correlation between non-ideality and phase separation in IS to explain observation of non-ideality in real aqueous mixtures of small amphiphilic solutes, containing both hydrophilic and hydrophobic groups. Although we have not been able to obtain IS of these liquids, we find that even at room temperature these liquids sustain formation of fluctuating, transient bi-continuous phase, with limited lifetime (tau less than or similar to 20 ps). While in the model (A, B) binary mixture, the non-ideal composition dependence can be considered as a fluctuation from a phase separated state, a similar scenario is expected to be responsible for the unusually strong non-ideality in these aqueous binary mixtures.

A Time-based Low Voltage Body Temperature Monitoring Unit

A neonatal temperature monitoring system operating in subthreshold regime that utilizes time mode signal processing is presented. Resistance deviations in a thermistor due to temperature variations are converted to delay variations that are subsequently quantized by a Delay measurement unit (DMU). The DMU does away with the need for any analog circuitry and is synthesizable entirely from digital logic. An FPGA implementation of the system demonstrates the viability of employing time mode signal processing, and measured results show that temperature resolution better than 0.1 degrees C can be achieved using this approach.