Structure-Guided Synthesis and Evaluation of Small-Molecule Inhibitors Targeting Protein–Protein Interactions of BRCA1 tBRCT Domain

The tandem BRCT domains (tBRCT) of BRCA1 engage phosphoserine-containing motifs in target proteins to propagate intracellular signals initiated by DNA damage, thereby controlling cell cycle arrest and DNA repair. Recently, we identified Bractoppin, the first small-molecule inhibitor of the BRCA1 tBRCT domain, which selectively interrupts BRCA1-mediated cellular responses evoked by DNA damage. Here, we combine structure-guided chemical elaboration, protein mutagenesis and cellular assays to define the structural features responsible for Bractoppin's activity. Bractoppin fails to bind mutant forms of BRCA1 tBRCT bearing K1702A, a key residue mediating phosphopeptide recognition, or F1662R or L1701K that adjoin the pSer-recognition site. However, the M1775R mutation, which engages the Phe residue in the consensus phosphopeptide motif pSer-X-X-Phe, does not affect Bractoppin binding, confirming a binding mode distinct from the substrate phosphopeptide binding. We explored these structural features through structure-guided chemical elaboration and characterized structure–activity relationships (SARs) in biochemical assays. Two analogues, CCBT2088 and CCBT2103 were effective in abrogating BRCA1 foci formation and inhibiting G2 arrest induced by irradiation of cells. Collectively, our findings reveal structural features underlying the activity of a novel inhibitor of phosphopeptide recognition by the BRCA1 tBRCT domain, providing fresh insights to guide the development of inhibitors that target protein–protein interactions.     

Density Modulation of Embedded Nanoparticles via Spatial,Temporal, and Chemical Control Elements

Nanoparticle polymer composites have enabled material multifunctionalities that are difficult to obtain otherwise. A simple modification to a commercially available resin system enables a universal methodology to embed nanoparticles in resins via spatial, temporal, thermal, concentration, and chemical control parameters. Changes in nanoparticle density distribution are exploited to demonstrate dynamic optical and electronic properties that can be processed on‐demand, without the need for expensive equipment or cleanroom facilities. This strategy provides access to the control of optical (cooperative plasmonic effects), electronic (insulator to a conductor), and chemical parameters (multimetal patterning). Using the same composite resin system, the followings are fabricated: i) diffraction gratings with tuneable diffraction efficiencies (10–78% diffraction efficiencies), ii) organic electrochemical transistors with a low drive voltage, and iii) embedded electrodes in confined spaces for potential diagnostic applications.     

Electro‐conductive cotton fabric prepared by electron beam induced graft polymerization and electroless deposition technology

Cotton fabric has been made electro‐conductive by electroless deposition of silver from its salt solution. Preparation process involved radical graft polymerization of glycidyl methacrylate monomer on plain woven cotton fabric using 10 kGy dose of electron beam irradiation, and then hydrazination of the epoxy ring of the monomer to introduce reducing agents into the fibre chemical structure. These reducing agents are sites for metal particle deposition. The chemical modifications were characterized by infrared spectroscopic studies. From X‐ray diffraction pattern analysis, the average size of these deposited silver metallic particles is 41 nm. These are observed as heterogeneous deposition on the fibre surface in scanning electron images. From thermogravimetric analysis, around 7.5% of the metal plated fabric weight is silver. The deposited silver nanoparticles make a conductive pathway through contact network, and this network brings a drop in average value of surface resistivity of the cotton fabric from 10⁹ Ω/sq to 3.63 Ω/sq for the metallised fabric. Such prepared electro‐conductive fabric showed very good wash durability of electrical conductivity up to 15 washing cycles when carried out as per ISO‐105‐C10:2006 (E) test no. A (1) standard, indicating firm adherence of silver nanoparticles to the fabric surface. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44576.     

An LSTM-based novel near-real-time multiclass network intrusion detection system for complex cloud environments

The Internet is connected with everyone for sharing and monitoring digital information. However, securing network resources from malicious activities is critical for several applications. Numerous studies have recently used deep learning-based models in detecting intrusions and received relatively robust recognition outcomes. Nevertheless, most investigations have operated old datasets, so they could not detect the most delinquent attack information. Therefore, the current research proposes the long short-term memory (LSTM)-based near real-time multiclass network intrusion detection system (NIDS) utilizing complex cloud CSE-CICIDSS2018 datasets to secure and detect the network anomalous. The proposed strategy utilizes a random forest algorithm for dimensionality reduction and feature selection. In addition, the selected best suitable features were used in a deep learning-based LSTM model developed for detecting network intrusions. The experimental outcomes reveal that the presented LSTM model obtained 99.66% testing accuracy with 0.12% loss. Thus, the suggested approach can detect network intrusions with the highest precision and lowest rate over the earlier designs.     

Alkali,alkaline earth and transition metal doped B6H6 complexes for hydrogen storage

Alkali, alkaline earth and transition metal doped B₆H₆ complexes are considered for the hydrogen storage. Density functional theory (DFT) and second order Møller–Plesset methods with 6–311++G** basis set have been used for the study. B₆H₆Li, B₆H₆Be, B₆H₆Sc, B₆H₆Li₂, B₆H₆Be₂, B₆H₆Sc₂ complexes can interact with maximum three, two, four, six, four and eight H₂ molecules respectively with respective H₂ uptake capacity of 7.2, 4.8, 6.5, 12.5, 8.3 and 9.1 wt%. This uptake capacity is well above the target set by the U.S. Department of Energy by 2020 except for the B₆H₆Be complex. Thermo chemistry calculations are carried out to estimate the Gibbs free energy corrected H₂ adsorption energy which reveals whether adsorption of hydrogen on these complexes is favourable or not at different temperature. It is observed that H₂ adsorption on all the six complexes are unfavourable at ambient conditions where as it is favourable below 150, 135, 75, and 50 K on B₆H₆Sc, B₆H₆Be, B₆H₆Li and B₆H₆Li₂ complexes respectively. Various interaction energies in H₂ adsorbed complexes are obtained using Many-body analysis approach. The H₂ desorption temperature for the B₆H₆Li, B₆H₆Be, B₆H₆Sc, B₆H₆Li₂, B₆H₆Be₂ and B₆H₆Sc₂ complexes is found to be 25, 165, 265, 10, 265 and 373 K respectively.     

Exploration of resource and transmission expansion decisions in the Western Renewable Energy Zone initiative

The Western Renewable Energy Zone (WREZ) initiative brings together a diverse set of voices to develop data, tools, and a unique forum for coordinating transmission expansion in the Western Interconnection. In this paper we use a new tool developed in the WREZ initiative to evaluate possible renewable resource selection and transmission expansion decisions. We evaluate these decisions under a number of alternative future scenarios centered on meeting 33% of the annual load in the Western Interconnection with new renewable resources located within WREZ-identified resource hubs. Our analysis finds that wind energy is the largest source of renewable energy procured to meet the 33% RE target across nearly all scenarios analyzed (38–65%). Solar energy is almost always the second largest source (14–41%). We find several load zones where wind energy is the least cost resource under a wide range of sensitivity scenarios. Load zones in the Southwest, on the other hand, are found to switch between wind and solar, and therefore to vary transmission expansion decisions, depending on uncertainties and policies that affect the relative economics of each renewable option. Further, we find that even with total transmission expenditures of $17–34 billion these costs still represent just 10–19% of the total delivered cost of renewable energy.     

Electrospun polymeric nanofibers for dental applications

Electrospinning is an economical, efficient, and versatile process for the preparation of continuous nanofibers with desired patterns, tailored fiber diameters, and orientations. Since its invention, electrospinning has been utilized to prepare nanofibers from several natural polymers and synthetic polymers for use as scaffolds in tissue engineering, regeneration, and biomedical applications. Furthermore, complex scaffolds were prepared by electrospinning complex polymer solutions formulated by blending natural and synthetic organic polymers with bioceramics and other inorganic molecules. Lately, coaxial electrospinning has emerged as a promising technology in the preparation of drug-loaded biodegradable core-shell structured micro/nanofibers for sustained drug delivery applications. This paper will discuss the basic mechanism of electrospinning, parameters governing the electrospinning process, various materials investigated for use in the electrospinning process, and its recent advances.     

Mixing of medium viscosity liquids in a stirred tank with fractal impeller

Mixing of viscous liquids in a stirred tank is a daunting task. The present paper explores the possibility of using a fractal impeller for mixing of viscous liquids in a stirred tank. The analysis includes power consumptions characteristics, mixing characteristics and the flow patterns in the stirred tank. Ultrasonic velocity profiler (UVP) was used to measure the local velocities in the stirred tank. Fractal impeller found to exhibit different power consumption characteristics than known for conventional impellers. For the range of viscosities 0.58–0.192 Pa s, mixing time found to be directly proportional to the power consumption per unit mass. The normalised mean radial velocity profiles were found to be independent of fluid viscosities studied in the present work.     

Changing Sunshine: Analyzing the dynamics of solar electricity policies in the global context

Although solar costs have been dropping in recent years, solar power is still more expensive than conventional and other renewable energy options, and in most applications solar power still needs continuing government policy support. However, the need to achieve multiple objectives and ensure sufficient political support for solar power makes it difficult for policy makers to design an optimal solar power policy. The dynamic and uncertain nature of the solar industry, combined with the constraints imposed by broader economic, political and social conditions further complicates the task of policy making. In this paper, we present a framework to critically analyze the objectives behind different country policies, how factors such as macro-economic conditions and development paradigms affect the policy outcomes and finally, how these outcomes affect the overall cost reduction of solar energy. We find that while the extent of cost reduction through creation of large demand remains to be seen, it is essential for governments to provide adequate support for leapfrog RD&D, and exploit real comparative advantages across countries for effective solar cost reduction. Policy makers need to optimally design their policies by balancing national objectives and paying capacity with the global objective of solar power cost reduction in order to realize its full potential.     

Characteristics of aluminium metal foam for automotive applications

Closed cell aluminium foam has been examined with respect to crash protection systems, stiff and strong light weight structures and sound absorbing panels / enclosures for use in automotive systems. Monotonic compression tests revealed that the crash box made from aluminium foam-filled steel tube showed twice the energy absorption compared to empty crash box. Flexural studies on foam-filled thin walled aluminium extruded section showed higher resistance to bending (7.5 kN) against empty Al-section (5.8 kN). Differences in the mechanisms of deformation between foam filled sections and their empty counterparts were studied in compression and bend loading conditions. Acoustic behaviour was evaluated in the as-received foam and in foams post processed to increase cell interconnectivity. High sound absorption coefficients were observed in most conditions. The optimum combination of high sound absorption coefficient and frequency range occurred in a crushed foam with good cell interconnectivity.