Forming Networks of Strategic Agents with Desired Topologies

Many networks such as social networks and organizational networks in global companies consist of self-interested agents. The topology of these networks often plays a crucial role in important tasks such as information diffusion and information extraction. Consequently, growing a stable network having a certain topology is of interest. Motivated by this, we study the following important problem: given a certain desired network topology, under what conditions would best response (link addition/deletion) strategies played by self-interested agents lead to formation of a stable network having that topology. We study this interesting reverse engineering problem by proposing a natural model of recursive network formation and a utility model that captures many key features. Based on this model, we analyze relevant network topologies and derive a set of sufficient conditions under which these topologies emerge as pairwise stable networks, wherein no node wants to delete any of its links and no two nodes would want to create a link between them.

Redox regulation of protein tyrosine phosphatase 1B (PTP1B): Importance of steric and electronic effects on the unusual cyclization of the sulfenic acid intermediate to a sulfenyl amide

The redox regulation of protein tyrosine phosphatase 1B (PTP1B) via the unusual transformation of its sulfenic acid (PTP1B-SOH) to a cyclic sulfenyl amide intermediate is studied by using small molecule chemical models. These studies suggest that the sulfenic acids derived from the H2O2-mediated reactions o-amido thiophenols do not efficiently cyclize to sulfenyl amides and the sulfenic acids produced in situ can be trapped by using methyl iodide. Theoretical calculations suggest that the most stable conformer of such sulfenic acids are stabilized by n(O) -> sigma* (S-OH) orbital interactions, which force the -OH group to adopt a position trans to the S center dot center dot center dot O interaction, leading to an almost linear arrangement of the O center dot center dot center dot S-O moiety and this may be the reason for the slow cyclization of such sulfenic acids to their corresponding sulfenyl amides. On the other hand, additional substituents at the 6-position of o-amido phenylsulfenic acids that can induce steric environment and alter the electronic properties around the sulfenic acid moiety by S center dot center dot center dot N or S center dot center dot center dot O nonbonded interactions destabilize the sulfenic acids by inducing strain in the molecule. This may lead to efficient the cyclization of such sulfenic acids. This model study suggests that the amino acid residues in the close proximity of the sulfenic acid moiety in PTP1B may play an important role in the cyclization of PTP1B-SOH to produce the corresponding sulfenyl amide.

Design and synthesis of positional isomers of 5 and 6-bromo-1-(phenyl)sulfonyl]-2-(4-nitrophenoxy)methyl]-1H-benzimida zoles as possible antimicrobial and antitubercular agents

In this Letter, we report the structure activity relationship (SAR) studies on series of positional isomers of 5(6)-bromo-1-(phenyl)sulfonyl]-2-(4-nitrophenoxy)methyl]-1H-benzim idazoles derivatives 7(a-j) and 8(a j) synthesized in good yields and characterized by H-1 NMR, C-13 NMR and mass spectral analyses. The crystal structure of 7a was evidenced by X-ray diffraction study. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coil and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7b, 7e and 7h displayed significant activity against Mycobacterium tuberculosis H37Rv strain.

Synthesis and evaluation of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles as anti-cancer agents

A series of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles 9a-j were obtained via multistep synthesis from hydroxybenzophenones 4a-e. The cytotoxicity of compounds 9a-j was evaluated against human leukemia cell lilies (K562 and CEM). The compounds exhibited moderate to good anti-cancer activity with compounds 9b and 9i having a chloro group exhibiting the best activity (IC50 = 10 mu M). Compound 9i exhibited activity against both the cell lines and 9b only exhibited activity against CEM. Further, a lactate dehydrogenase (LDH) assay and DNA fragmentation studies of the compounds 9a-j were also performed. (C) 2013 Elsevier Masson SAS. All rights reserved.

Sufficient conditions for formation of a network topology by self-interested agents

Networks such as organizational network of a global company play an important role in a variety of knowledge management and information diffusion tasks. The nodes in these networks correspond to individuals who are self-interested. The topology of these networks often plays a crucial role in deciding the ease and speed with which certain tasks can be accomplished using these networks. Consequently, growing a stable network having a certain topology is of interest. Motivated by this, we study the following important problem: given a certain desired network topology, under what conditions would best response (link addition/deletion) strategies played by self-interested agents lead to formation of a pairwise stable network with only that topology. We study this interesting reverse engineering problem by proposing a natural model of recursive network formation. In this model, nodes enter the network sequentially and the utility of a node captures principal determinants of network formation, namely (1) benefits from immediate neighbors, (2) costs of maintaining links with immediate neighbors, (3) benefits from indirect neighbors, (4) bridging benefits, and (5) network entry fee. Based on this model, we analyze relevant network topologies such as star graph, complete graph, bipartite Turan graph, and multiple stars with interconnected centers, and derive a set of sufficient conditions under which these topologies emerge as pairwise stable networks. We also study the social welfare properties of the above topologies.

Nucleation of a Stable Solid from Melt in the Presence of Multiple Metastable Intermediate Phases: Wetting, Ostwald's Step Rule, and Vanishing Polymorphs

In many systems, nucleation of a stable solid may occur in the presence of other (often more than one) metastable phases. These may be polymorphic solids or even liquid phases. Sometimes, the metastable phase might have a lower free energy minimum than the liquid but higher than the stable-solid-phase minimum and have characteristics in between the parent liquid and the globally stable solid phase. In such cases, nucleation of the solid phase from the melt may be facilitated by the metastable phase because the latter can ``wet'' the interface between the parent and the daughter phases, even though there may be no signature of the existence of metastable phase in the thermodynamic properties of the parent liquid and the stable solid phase. Straightforward application of classical nucleation theory (CNT) is flawed here as it overestimates the nucleation barrier because surface tension is overestimated (by neglecting the metastable phases of intermediate order) while the thermodynamic free energy gap between daughter and parent phases remains unchanged. In this work, we discuss a density functional theory (DFT)-based statistical mechanical approach to explore and quantify such facilitation. We construct a simple order-parameter-dependent free energy surface that we then use in DFT to calculate (i) the order parameter profile, (ii) the overall nucleation free energy barrier, and (iii) the surface tension between the parent liquid and the metastable solid and also parent liquid and stable solid phases. The theory indeed finds that the nucleation free energy barrier can decrease significantly in the presence of wetting. This approach can provide a microscopic explanation of the Ostwald step rule and the well-known phenomenon of ``disappearing polymorphs'' that depends on temperature and other thermodynamic conditions. Theory reveals a diverse scenario for phase transformation kinetics, some of which may be explored via modem nanoscopic synthetic methods.

Antithyroid drugs and their analogues: synthesis, structure, and mechanism of action

Thyroid hormones are essential for the development and differentiation of all cells of the human body. They regulate protein, fat, and carbohydrate metabolism. In this Account, we discuss the synthesis, structure, and mechanism of action of thyroid hormones and their analogues. The prohormone thyroxine (14) is synthesized on thyroglobulin by thyroid peroxidase (TPO), a heme enzyme that uses iodide and hydrogen peroxide to perform iodination and phenolic coupling reactions. The monodeiodination of T4 to 3,3',5-triiodothyronine (13) by selenium-containing deiodinases (ID-1, ID-2) is a key step in the activation of thyroid hormones. The type 3 deiodinase (ID-3) catalyzes the deactivation of thyroid hormone in a process that removes iodine selectively from the tyrosyl ring of T4 to produce 3,3',5'-triiodothyronine (rT3). Several physiological and pathological stimuli influence thyroid hormone synthesis. The overproduction of thyroid hormones leads to hyperthyroidism, which is treated by antithyroid drugs that either inhibit the thyroid hormone biosynthesis and/or decrease the conversion of T4 to T3. Antithyroid drugs are thiourea-based compounds, which indude propylthiouracil (PTU), methimazole (MM I), and carbimazole (CBZ). The thyroid gland actively concentrates these heterocyclic compounds against a concentration gradient Recently, the selenium analogues of PTU, MMI, and CBZ attracted significant attention because the selenium moiety in these compounds has a higher nucleophilicity than that of the sulfur moiety. Researchers have developed new methods for the synthesis of the selenium compounds. Several experimental and theoretical investigations revealed that the selone (C=Se) in the selenium analogues is more polarized than the thione (C=S) in the sulfur compounds, and the selones exist predominantly in their zwitterionic forms. Although the thionamide-based antithyroid drugs have been used for almost 70 years, the mechanism of their action is not completely understood. Most investigations have revealed that MMI and PTU irreversibly inhibit TPO. PTU, MTU, and their selenium analogues also inhibit ID-1, most likely by reacting with the selenenyl iodide intermediate. The good ID-1 inhibitory activity of Pill and its analogues can be ascribed to the presence of the -N(H)-C(=O)- functionality that can form hydrogen bonds with nearby amino add residues in the selenenyl sulfide state. In addition to the TPO and ID-1 inhibition, the selenium analogues are very good antioxidants. In the presence of cellular reducing agents such as GSH, these compounds catalytically reduce hydrogen peroxide. They can also efficiently scavenge peroxynitrite, a potent biological oxidant and nitrating agent.

Aptamers as Theranostic Agents: Modifications, Serum Stability and Functionalisation

Aptamers, and the selection process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX) used to generate them, were first described more than twenty years ago. Since then, there have been numerous modifications to the selection procedures. This review discusses the use of modified bases as a means of enhancing serum stability and producing effective therapeutic tools, as well as functionalising these nucleic acids to be used as potential diagnostic agents.

Hypersensitivity of hypoxia grown Mycobacterium smegmatis to DNA damaging agents: Implications of the DNA repair deficiencies in attenuation of mycobacteria

Mycobacteria are an important group of pathogenic bacteria. We generated a series of DNA repair deficient strains of Mycobacterium smegmatis, a model organism, to understand the importance of various DNA repair proteins (UvrB, Ung, UdgB, MutY and Fpg) in survival of the pathogenic strains. Here, we compared tolerance of the M. smegmatis strains to genotoxic stress (ROS and RNI) under aerobic, hypoxic and recovery conditions of growth by monitoring their survival. We show an increased susceptibility of mycobacteria to genotoxic stress under hypoxia. UvrB deficiency led to high susceptibility of M. smegmatis to the DNA damaging agents. Ung was second in importance in strains with single deficiencies. Interestingly, we observed that while deficiency of UdgB had only a minor impact on the strain's susceptibility, its combination with Ung deficiency resulted in severe consequences on the strain's survival under genotoxic stress suggesting a strong interdependence of different DNA repair pathways in safeguarding genomic integrity. Our observations reinforce the possibility of targeting DNA repair processes in mycobacteria for therapeutic intervention during active growth and latency phase of the pathogen. High susceptibility of the UvrB, or the Ung/UdgB deficient strains to genotoxic stress may be exploited in generation of attenuated strains of mycobacteria. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Evidence of an intermediate phase in a quaternary Ag bearing telluride glass system using alternating DSC

Alternating Differential Scanning Calorimetric (ADSC) studies on quaternary Ge15Te80-xIn5Agx glasses show the non-reversing enthalpy (Delta H-NR) at T-g to exhibit a broad global minimum in the 8% <= x <= 16% range of Ag, an observation that is taken evidence for existence of an Intermediate Phase (IP) in that range. Glasses at x < 8% are in the flexible phase while those at x > 16% in the stressed-rigid phase. The nature of crystalline phases formed upon crystallization of bulk glasses are elucidated by XRD studies, and reveal presence of Te, GeTe, Ag8GeTe6, AgTe, In2Te3 and In4Te3 phases. These experiments also reveal that the fraction of Ag- bearing phases increases while those of Te- bearing ones decreases with increasing x, suggesting progressive replacement of Te-Te bonds by Ag-Te bonds. (C) 2013 Elsevier Ltd. All rights reserved.

Metal nanoparticles as better protein-aggregation prevention agents than chaperones

Prevention or suppression of protein aggregation is of great importance in the context of protein storage, transportation and delivery. Traditionally chaperones or other chemically active agents are used to stop or diffuse native protein aggregation. We have used gold nanoparticles to prevent thermal aggregation of alcohol dehydrogenase (ADH), a protein that maintains the alcohol level in the liver and stomach. A light-scattering assay has been used to investigate the effect of gold nanoparticles on thermal aggregation of ADH and the result of our study has been summarized in Fig. 1. The scattered light intensity from the solution containing ADH decreases when 45 nm gold nanoparticles are added prior to heating (thermal denaturation) the solution, which indicates prevention of aggregation. The aggregation of the protein is suppressed to the extent of 96% with picomolar concentration of 45 nm gold nanoparticles while micromolar amounts of other proteins and biological substances are necessary to achieve the same effect. The extent varies with the size and the concentration of the gold NPs for the same protein concentration.

Identification and characterization of novel indole based small molecules as anticancer agents through SIRT1 inhibition

In our pursuit to develop new potential anticancer leads, we designed a combination of structural units of indole and substituted triazole; and a library of 1-{1-methyl-2-4-phenyl-5-(propan-2-ylsulfanyl)-4H-1,2,4-triazol-3-yl ]-1H-indol-3-yl}methanamine derivatives was synthesized and characterized. Cytotoxic evaluations of these molecules over a panel of three human cancer cell lines were carried out. Few molecules exhibited potent growth inhibitory action against the treated cancer cell lines at lower micro molar concentration. An in vitro assay investigation of these active compounds using recombinant human SIRT1 enzyme showed that one of the compounds (IT-14) inhibited the deacetylation activity of the enzyme. The in vivo study of IT-14 exemplified its promising action by reducing the prostate weight to the body weight ratio in prostate hyperplasia animal models. A remarkable decrease in the disruption of histoarchitecture of the prostate tissues isolated from IT-14 treated animal compared to that of the positive control was observed. The molecular interactions with SIRT1 enzyme were also supported by molecular docking simulations. Hence this compound can act as a lead molecule to treat prostatic hyperplasia. (C) 2013 Elsevier Masson SAS. All rights reserved.

Investigation on the Sr-doped ceria Ce1-xSrO2-delta (x=0.05-0.2) as an electrolyte for intermediate temperature SOFC

The effect of Sr doping in CeO2 for its use as solid electrolytes for intermediate temperature solid oxide fuel cells (IT-SOFCs) has been explored here. Ce1-xSrxO2-delta (x = 0.05-0.2) are successfully synthesized by citrate-complexation method. XRD, Raman, FT-IR, FE-SEM/EDX and electrochemical impedance spectra are used for structural and electrical characterizations. The formation of well crystalline cubic fluorite structured solid solution is observed for x = 0.05 based on XRD and Raman spectra. For compositions i.e., x > 0.05, however, a secondary phase of SrCeO3 is confirmed by the peak at 342 cm(-1) in Raman spectra. Although the oxygen ion conductivity was found to decrease with increase in x, based on ac-impedance studies, conductivity of Ce0.95Sr0.05O2-delta was found to be higher than of Ce0.95Gd0.1O2-delta and Ce0.8Gd0.2O2-delta. The decrease in conductivity of Ce1-xSrxO2-delta with increasing dopant concentration is ascribed to formation of impurity phase SrCeO3 as well as the formation of neutral associated pairs, Se `' Ce V-o. The activation energies are found to be 0.77, 0.83, 0.85 and 0.90 eV for x = 0.05, 0.1, 0.15 and 0.20, respectively. (C) 2014 Elsevier B.V. All rights reserved.

Raman signatures of intermediate phase in quaternary Ge15Te80 (-) xIn5Agx glasses

Micro-Raman studies are conducted on as-quenched and annealed Ge15Te80 -_xIn5Agx glasses to probe the structural network and its evolution with composition. These studies reveal the presence of tetrahedral GeTe4 structural units in as-quenched samples. Specific signatures of the intermediate phase (IP) are observed in the composition dependence of Raman frequencies and corresponding intensities of different modes in the composition range, 8 <= x <= 16. In addition, the Raman peak positions are found to shift with silver doping. Apart from the Raman results, the compositional dependence of density, molar volume and thermal diffusivity, observed in the present study, confirms the presence of the intermediate phase. In thermally annealed samples, a unique variation of Raman wave-numbers in the intermediate region is observed due to the retention of some of the local structure even after the sample is crystallized. The observed Raman peaks are attributed to crystalline tellurium and silver lattice vibrational modes. Based on our present and earlier studies, we propose the occurrence of three thresholds in Ge15Te80 - xIn5Agx glasses, namely percolation of rigidity, percolation of stress and the onset of chemical phase separation on a nanoscale at 8%, 16% and 20% of silver concentration respectively. (C) 2014 Elsevier B.V. All rights reserved.