On Radiative Weak Annihilation Decays

We discuss a little-studied class of weak decay modes sensitive to only one quark topology at leading order in G_F: M --> m gamma, where M,m are mesons with completely distinct flavor quantum numbers. Specifically, they proceed via the annihilation of the valence quarks through a W and the emission of a single hard photon, and thus provide a clear separation between CKM and strong interaction physics. We survey relevant calculations performed to date, discuss experimental discovery potential, and indicate interesting future directions.Comment: 10 pages LaTeX, includes macros file and 9 .eps figures. Invited talk at RADCOR 2000 (5th Int. Symp. on Radiative Corrections), Carmel, CA, Sept. 200

Polyurethane Based Inhibition for High Flame Temperature Nitramine Based Composite Modified Double Base propellant

The findings for polypropylene glycol (PPG) and hydroxyl-terminated polybutadiene (HTPB)-based inhibition systems are reported. These findings established that the inhibition system comprising HTPB-IPDI-IDP binder and Sb/sub 2/O/sub 3/-C black filler is most suitable for advanced nitramine-based composite modified double-base propellants in terms of mechanical properties and processibility. The promising composition was characterised for glass-transition behaviour and propellant-inhibition bond strength. Propellant grains inhibited with selected formulations were subjected to static evaluation at extreme temperatures and limited aging studies to obtain data of practical value

Template Entrance Channel as Possible Allosteric Inhibition and Resistance Site for Quinolines Tricyclic Derivatives in RNA Dependent RNA Polymerase of Bovine Viral Diarrhea Virus

The development of potent non-nucleoside inhibitors (NNIs) could be an alternate strategy to combating infectious bovine viral diarrhea virus (BVDV), other than the traditional vaccination. RNA-dependent RNA polymerase (RdRp) is an essential enzyme for viral replication; therefore, it is one of the primary targets for countermeasures against infectious diseases. The reported NNIs, belonging to the classes of quinolines (2h: imidazo[4,5-g]quinolines and 5m: pyrido[2,3-g] quinoxalines), displayed activity in cell-based and enzyme-based assays. Nevertheless, the RdRp binding site and microscopic mechanistic action are still elusive, and can be explored at a molecular level. Here, we employed a varied computational arsenal, including conventional and accelerated methods, to identify quinoline compounds' most likely binding sites. Our study revealed A392 and I261 as the mutations that can render RdRp resistant against quinoline compounds. In particular, for ligand 2h, mutation of A392E is the most probable mutation. The loop L1 and linker of the fingertip is recognized as a pivotal structural determinant for the stability and escape of quinoline compounds. Overall, this work demonstrates that the quinoline inhibitors bind at the template entrance channel, which is governed by conformational dynamics of interactions with loops and linker residues, and reveals structural and mechanistic insights into inhibition phenomena, for the discovery of improved antivirals

Risk-Averse Matchings over Uncertain Graph Databases

A large number of applications such as querying sensor networks, and analyzing protein-protein interaction (PPI) networks, rely on mining uncertain graph and hypergraph databases. In this work we study the following problem: given an uncertain, weighted (hyper)graph, how can we efficiently find a (hyper)matching with high expected reward, and low risk? This problem naturally arises in the context of several important applications, such as online dating, kidney exchanges, and team formation. We introduce a novel formulation for finding matchings with maximum expected reward and bounded risk under a general model of uncertain weighted (hyper)graphs that we introduce in this work. Our model generalizes probabilistic models used in prior work, and captures both continuous and discrete probability distributions, thus allowing to handle privacy related applications that inject appropriately distributed noise to (hyper)edge weights. Given that our optimization problem is NP-hard, we turn our attention to designing efficient approximation algorithms. For the case of uncertain weighted graphs, we provide a $\frac{1}{3}$-approximation algorithm, and a $\frac{1}{5}$-approximation algorithm with near optimal run time. For the case of uncertain weighted hypergraphs, we provide a $\Omega(\frac{1}{k})$-approximation algorithm, where $k$ is the rank of the hypergraph (i.e., any hyperedge includes at most $k$ nodes), that runs in almost (modulo log factors) linear time. We complement our theoretical results by testing our approximation algorithms on a wide variety of synthetic experiments, where we observe in a controlled setting interesting findings on the trade-off between reward, and risk. We also provide an application of our formulation for providing recommendations of teams that are likely to collaborate, and have high impact.Comment: 25 page

Design of 3-Phenylcoumarins and 3-Thienylcoumarins as Potent Xanthine Oxidase Inhibitors: Synthesis, Biological Evaluation, and Docking Studies

Coumarin scaffold has proven to be promising in the development of bioactive agents, such as xanthine oxidase (XO) inhibitors. Novel hydroxylated 3-arylcoumarins were designed, synthesized, and evaluated for their XO inhibition and antioxidant properties. 3-(3’-Bromophenyl)-5,7-dihydroxycoumarin (compound 11) proved to be the most potent XO inhibitor, with an IC50 of 91 nM, being 162 times better than allopurinol, one of the reference controls. Kinetic analysis of compound 11 and compound 5 [3-(4’-bromothien-2’-yl)-5,7-dihydroxycoumarin], the second-best compound within the series (IC50 of 280 nM), has been performed, and both compounds showed a mixed-type inhibition. Both compounds present good antioxidant activity (ability to scavenge ABTS radical) and are able to reduce reactive oxygen species (ROS) levels in H2O2-treated cells. In addition, they proved to be non-cytotoxic in a Caco-2 cells viability assay. Molecular docking studies have been carried out to correlate the compounds’ theoretical and experimental binding affinity to the XO binding pocket

Modelling Conformational Flexibility in a Spectrally Addressable Molecular Multi-Qubit Model System

Dipolar coupled multi-spin systems have the potential to be used as molecular qubits. Herein we report the synthesis of a molecular multi-qubit model system with three individually addressable, weakly interacting, spin (Formula presented.) centres of differing g-values. We use pulsed Electron Paramagnetic Resonance (EPR) techniques to characterise and separately address the individual electron spin qubits; CuII, Cr7Ni ring and a nitroxide, to determine the strength of the inter-qubit dipolar interaction. Orientation selective Relaxation-Induced Dipolar Modulation Enhancement (os-RIDME) detecting across the CuII spectrum revealed a strongly correlated CuII-Cr7Ni ring relationship; detecting on the nitroxide resonance measured both the nitroxide and CuII or nitroxide and Cr7Ni ring correlations, with switchability of the interaction based on differing relaxation dynamics, indicating a handle for implementing EPR-based quantum information processing (QIP) algorithms

Collaborative action for person-centred coordinated care (P3C): an approach to support the development of a comprehensive system-wide solution to fragmented care

BACKGROUND: Fragmented care results in poor outcomes for individuals with complexity of need. Person-centred coordinated care (P3C) is perceived to be a potential solution, but an absence of accessible evidence and the lack of a scalable 'blue print' mean that services are 'experimenting' with new models of care with little guidance and support. This paper presents an approach to the implementation of P3C using collaborative action, providing examples of early developments across this programme of work, the core aim of which is to accelerate the spread and adoption of P3C in United Kingdom primary care settings. METHODS: Two centrally funded United Kingdom organisations (South West Collaboration for Leadership in Applied Health Research and Care and South West Academic Health Science Network) are leading this initiative to narrow the gap between research and practice in this urgent area of improvement through a programme of service change, evaluation and research. Multi-stakeholder engagement and co-design are core to the approach. A whole system measurement framework combines outcomes of importance to patients, practitioners and health organisations. Iterative and multi-level feedback helps to shape service change while collecting practice-based data to generate implementation knowledge for the delivery of P3C. The role of the research team is proving vital to support informed change and challenge organisational practice. The bidirectional flow of knowledge and evidence relies on the transitional positioning of researchers and research organisations. RESULTS: Extensive engagement and embedded researchers have led to strong collaborations across the region. Practice is beginning to show signs of change and data flow and exchange is taking place. However, working in this way is not without its challenges; progress has been slow in the development of a linked data set to allow us to assess impact innovations from a cost perspective. Trust is vital, takes time to establish and is dependent on the exchange of services and interactions. If collaborative action can foster P3C it will require sustained commitment from both research and practice. This approach is a radical departure from how policy, research and practice traditionally work, but one that we argue is now necessary to deal with the most complex health and social problems

Influence of Cr and W alloying on the fiber-matrix interfacial shear strength in cast and directionally solidified sapphire NiAl composites

Sapphire-reinforced NiAl matrix composites with chromium or tungsten as alloying additions were synthesized using casting and zone directional solidification (DS) techniques and characterized by a fiber pushout test as well as by microhardness measurements. The sapphire-NiAl(Cr) specimens exhibited an interlayer of Cr rich eutectic at the fiber-matrix interface and a higher interfacial shear strength compared to unalloyed sapphire-NiAl specimens processed under identical conditions. In contrast, the sapphire-NiAl(W) specimens did not show interfacial excess of tungsten rich phases, although the interfacial shear strength was high and comparable to that of sapphire-NiAl(Cr). The postdebond sliding stress was higher in sapphire-NiAl(Cr) than in sapphire-NiAl(W) due to interface enrichment with chromium particles. The matrix microhardness progressively decreased with increasing distance from the interface in both DS NiAl and NiAl(Cr) specimens. The study highlights the potential of casting and DS techniques to improve the toughness and strength of NiAl by designing dual-phase microstructures in NiAl alloys reinforced with sapphire fibers

Long distance c→uγc \to u \gamma effects in weak radiative decays of D-mesons

We present a detailed analysis of the $D \to V \gamma$ transitions, using a model which combines heavy quark effective theory and the chiral Lagrangian approach and includes symmetry breaking. We notice that in addition to the previously considered s - channel annihilation and t - channel W - exchange, there is a long distance penguin - like $c \to u \gamma$ contribution in the t - channel of Cabibbo - suppressed modes. Its magnitude is determined by the size of symmetry breaking which we calculate with a vector dominance approach. Although smaller in magnitude, the penguin - like contribution would lead to sizeable effects in case of cancellations among the other contributions to the amplitude. Thus, it may invalidate suggested tests for beyond the standard model effects in these decays. We also indicate the range of expectations for the branching ratios of various $D \to V \gamma$ modes.Comment: 28 pages, Latex, 2 Figure