Typical and atypical domain combinations in human protein kinases: functions, disease causing mutations and conservation in other primates

Ser/Thr and Tyr protein kinases orchestrate many signalling pathways and hence loss in this balance leads to many disease phenotypes. Due to their high abundance, diversity and importance, efforts have been made in the past to classify kinases and annotate their functions at both gross and fine levels. These kinases are conventionally classified into subfamilies based on the sequences of catalytic domains. Usually the domain architecture of a full-length kinase is consistent with the subfamily classification made based on the sequence of kinase domain. Important contributions of modular domains to the overall function of the kinase are well known. Recently occurrence of two kinds of outlier kinases-''Hybrid'' and ``Rogue'' has been reported. These show considerable deviations in their domain architectures from the typical domain architecture known for the classical kinase subfamilies. This article provides an overview of the different subfamilies of human kinases and the role of non-kinase domains in functions and diseases. Importantly this article provides analysis of hybrid and rogue kinases encoded in the human genome and highlights their conservation in closely related primate species. These kinases are examples of elegant rewiring to bring about subtle functional differences compared to canonical variants.

Modeling of solar radiation management: a comparison of simulations using reduced solar constant and stratospheric sulphate aerosols

The climatic effects of Solar Radiation Management (SRM) geoengineering have been often modeled by simply reducing the solar constant. This is most likely valid only for space sunshades and not for atmosphere and surface based SRM methods. In this study, a global climate model is used to evaluate the differences in the climate response to SRM by uniform solar constant reduction and stratospheric aerosols. Our analysis shows that when global mean warming from a doubling of CO2 is nearly cancelled by both these methods, they are similar when important surface and tropospheric climate variables are considered. However, a difference of 1 K in the global mean stratospheric (61-9.8 hPa) temperature is simulated between the two SRM methods. Further, while the global mean surface diffuse radiation increases by similar to 23 % and direct radiation decreases by about 9 % in the case of sulphate aerosol SRM method, both direct and diffuse radiation decrease by similar fractional amounts (similar to 1.0 %) when solar constant is reduced. When CO2 fertilization effects from elevated CO2 concentration levels are removed, the contribution from shaded leaves to gross primary productivity (GPP) increases by 1.8 % in aerosol SRM because of increased diffuse light. However, this increase is almost offset by a 15.2 % decline in sunlit contribution due to reduced direct light. Overall both the SRM simulations show similar decrease in GPP (similar to 8 %) and net primary productivity (similar to 3 %). Based on our results we conclude that the climate states produced by a reduction in solar constant and addition of aerosols into the stratosphere can be considered almost similar except for two important aspects: stratospheric temperature change and the consequent implications for the dynamics and the chemistry of the stratosphere and the partitioning of direct versus diffuse radiation reaching the surface. Further, the likely dependence of global hydrological cycle response on aerosol particle size and the latitudinal and height distribution of aerosols is discussed.

Economic tradeoffs in mitigation, due to different atmospheric lifetimes of CO2 and black carbon

Tradeoffs are examined between mitigating black carbon (BC) and carbon dioxide (CO2) for limiting peak global mean warming, using the following set of methods. A two-box climate model is used to simulate temperatures of the atmosphere and ocean for different rates of mitigation. Mitigation rates for BC and CO2 are characterized by respective timescales for e-folding reduction in emissions intensity of gross global product. There are respective emissions models that force the box model. Lastly there is a simple economics model, with cost of mitigation varying inversely with emission intensity. Constant mitigation timescale corresponds to mitigation at a constant annual rate, for example an e-folding timescale of 40 years corresponds to 2.5% reduction each year. Discounted present cost depends only on respective mitigation timescale and respective mitigation cost at present levels of emission intensity. Least-cost mitigation is posed as choosing respective e-folding timescales, to minimize total mitigation cost under a temperature constraint (e.g. within 2 degrees C above preindustrial). Peak warming is more sensitive to mitigation timescale for CO2 than for BC. Therefore rapid mitigation of CO2 emission intensity is essential to limiting peak warming, but simultaneous mitigation of BC can reduce total mitigation expenditure. (c) 2015 Elsevier B.V. All rights reserved.

Conformal perturbation theory and higher spin entanglement entropy on the torus

We study the free fermion theory in 1+1 dimensions deformed by chemical potentials for holomorphic, conserved currents at finite temperature and on a spatial circle. For a spin-three chemical potential mu, the deformation is related at high temperatures to a higher spin black hole in hs0] theory on AdS(3) spacetime. We calculate the order mu(2) corrections to the single interval Renyi and entanglement entropies on the torus using the bosonized formulation. A consistent result, satisfying all checks, emerges upon carefully accounting for both perturbative and winding mode contributions in the bosonized language. The order mu(2) corrections involve integrals that are finite but potentially sensitive to contact term singularities. We propose and apply a prescription for defining such integrals which matches the Hamiltonian picture and passes several non-trivial checks for both thermal corrections and the Renyi entropies at this order. The thermal corrections are given by a weight six quasi-modular form, whilst the Renyi entropies are controlled by quasi-elliptic functions of the interval length with modular weight six. We also point out the well known connection between the perturbative expansion of the partition function in powers of the spin-three chemical potential and the Gross-Taylor genus expansion of large-N Yang-Mills theory on the torus. We note the absence of winding mode contributions in this connection, which suggests qualitatively different entanglement entropies for the two systems.

Structure-Based Phylogenetic Analysis of the Lipocalin Superfamily

Lipocalins constitute a superfamily of extracellular proteins that are found in all three kingdoms of life. Although very divergent in their sequences and functions, they show remarkable similarity in 3-D structures. Lipocalins bind and transport small hydrophobic molecules. Earlier sequence-based phylogenetic studies of lipocalins highlighted that they have a long evolutionary history. However the molecular and structural basis of their functional diversity is not completely understood. The main objective of the present study is to understand functional diversity of the lipocalins using a structure-based phylogenetic approach. The present study with 39 protein domains from the lipocalin superfamily suggests that the clusters of lipocalins obtained by structure-based phylogeny correspond well with the functional diversity. The detailed analysis on each of the clusters and sub-clusters reveals that the 39 lipocalin domains cluster based on their mode of ligand binding though the clustering was performed on the basis of gross domain structure. The outliers in the phylogenetic tree are often from single member families. Also structure-based phylogenetic approach has provided pointers to assign putative function for the domains of unknown function in lipocalin family. The approach employed in the present study can be used in the future for the functional identification of new lipocalin proteins and may be extended to other protein families where members show poor sequence similarity but high structural similarity.

Effect of Chalcogens on Electronic and Photophysical Properties of Vinylene-Based Diketopyrrolopyrrole Copolymers

Three vinylene linked diketopyrrolopyrrole based donor acceptor (D-A) copolymers have been synthesized with phenyl, thienyl, and selenyl units as donors. Optical and electronic properties were investigated with UV-vis absorption spectroscopy, cyclic voltammetry, near edge X-ray absorption spectroscopy, organic field effect transistor (OFET) measurements, and density functional theory (DFT) calculations. Optical and electrochemical band gaps decrease in the order phenyl, thienyl, and selenyl. Only phenyl-based polymers are nonplanar, but the main contributor to the larger band gap is electronic, not structural effects. Thienyl and selenyl polymers exhibit ambipolar charge transport but with higher hole than electron mobility. Experimental and theoretical results predict the selenyl system to have the best transport properties, but OFET measurements prove the thienyl system to be superior with p-channel mobility as high as 0.1 cm(2) V-1 s(-1).

Evolutionary and structural analyses of heterodimeric proteins composed of subunits with same fold

Heterodimeric proteins with homologous subunits of same fold are involved in various biological processes. The objective of this study is to understand the evolution of structural and functional features of such heterodimers. Using a non-redundant dataset of 70 such heterodimers of known 3D structure and an independent dataset of 173 heterodimers from yeast, we note that the mean sequence identity between interacting homologous subunits is only 23-24% suggesting that, generally, highly diverged paralogues assemble to form such a heterodimer. We also note that the functional roles of interacting subunits/domains are generally quite different. This suggests that, though the interacting subunits/domains are homologous, the high evolutionary divergence characterize their high functional divergence which contributes to a gross function for the heterodimer considered as a whole. The inverse relationship between sequence identity and RMSD of interacting homologues in heterodimers is not followed. We also addressed the question of formation of homodimers of the subunits of heterodimers by generating models of fictitious homodimers on the basis of the 3D structures of the heterodimers. Interaction energies associated with these homodimers suggests that, in overwhelming majority of the cases, such homodimers are unlikely to be stable. Majority of the homologues of heterodimers of known structures form heterodimers (51.8%) and a small proportion (14.6%) form homodimers. Comparison of 3D structures of heterodimers with homologous homodimers suggests that interfacial nature of residues is not well conserved. In over 90% of the cases we note that the interacting subunits of heterodimers are co-localized in the cell. Proteins 2015; 83:1766-1786. (c) 2015 Wiley Periodicals, Inc.

MOMENT ANALYSIS OF A SCROLL EXPANDER USED IN AN ORGANIC RANKINE CYCLE

Recent studies on small-scale power generation with the organic Rankine cycle suggest superior performance of positive displacement type of expanders compared to turbines. Scroll expanders in particular achieve high isentropic efficiencies due to lower leakage and frictional losses. Performance of scroll machines may be enhanced by the use of non-circular involute curves in place of the circular involutes resulting non-uniform wall thickness. In this paper, a detailed moment analysis is performed for such an expander having volumetric expansion ratio of 5 using thermodynamic models proposed earlier by one of the present authors. The working fluid considered in the power cycle is R-245fa with scroll inlet temperature of 125 degrees C for a gross power output of similar to 3.5 kW. The model developed in this paper is verified with an air scroll compressor available in the literature and then applied to an expander Prediction of small variation of moment with scroll motion recommends use of scroll expander without a flywheel over other positive displacement type of expanders, e.g. reciprocating, where a flywheel is an essential component.

Quantum stochastic calculus associated with quadratic quantum noises

We first study a class of fundamental quantum stochastic processes induced by the generators of a six dimensional non-solvable Lie dagger-algebra consisting of all linear combinations of the generalized Gross Laplacian and its adjoint, annihilation operator, creation operator, conservation, and time, and then we study the quantum stochastic integrals associated with the class of fundamental quantum stochastic processes, and the quantum Ito formula is revisited. The existence and uniqueness of solution of a quantum stochastic differential equation is proved. The unitarity conditions of solutions of quantum stochastic differential equations associated with the fundamental processes are examined. The quantum stochastic calculus extends the Hudson-Parthasarathy quantum stochastic calculus. (C) 2016 AIP Publishing LLC.

Efficient simulation and rendering of realistic motion of one-dimensional flexible objects

In gross motion of flexible one-dimensional (1D) objects such as cables, ropes, chains, ribbons and hair, the assumption of constant length is realistic and reasonable. The motion of the object also appears more natural if the motion or disturbance given at one end attenuates along the length of the object. In an earlier work, variational calculus was used to derive natural and length-preserving transformation of planar and spatial curves and implemented for flexible 1D objects discretized with a large number of straight segments. This paper proposes a novel idea to reduce computational effort and enable real-time and realistic simulation of the motion of flexible 1D objects. The key idea is to represent the flexible 1D object as a spline and move the underlying control polygon with much smaller number of segments. To preserve the length of the curve to within a prescribed tolerance as the control polygon is moved, the control polygon is adaptively modified by subdivision and merging. New theoretical results relating the length of the curve and the angle between the adjacent segments of the control polygon are derived for quadratic and cubic splines. Depending on the prescribed tolerance on length error, the theoretical results are used to obtain threshold angles for subdivision and merging. Simulation results for arbitrarily chosen planar and spatial curves whose one end is subjected to generic input motions are provided to illustrate the approach. (C) 2016 Elsevier Ltd. All rights reserved.