Comparative kinomics of human and chimpanzee reveal unique kinship and functional diversity generated by new domain combinations

Background: Phosphorylation by protein kinases is a common event in many cellular processes. Further, many kinases perform specialized roles and are regulated by non-kinase domains tethered to kinase domain. Perturbation in the regulation of kinases leads to malignancy. We have identified and analysed putative protein kinases encoded in the genome of chimpanzee which is a close evolutionary relative of human. Result: The shared core biology between chimpanzee and human is characterized by many orthologous protein kinases which are involved in conserved pathways. Domain architectures specific to chimp/human kinases have been observed. Chimp kinases with unique domain architectures are characterized by deletion of one or more non-kinase domains in the human kinases. Interestingly, counterparts of some of the multi-domain human kinases in chimp are characterized by identical domain architectures but with kinase-like non-kinase domain. Remarkably, out of 587 chimpanzee kinases no human orthologue with greater than 95% sequence identity could be identified for 160 kinases. Variations in chimpanzee kinases compared to human kinases are brought about also by differences in functions of domains tethered to the catalytic kinase domain. For example, the heterodimer forming PB1 domain related to the fold of ubiquitin/Ras-binding domain is seen uniquely tethered to PKC-like chimpanzee kinase. Conclusion: Though the chimpanzee and human are evolutionary very close, there are chimpanzee kinases with no close counterpart in the human suggesting differences in their functions. This analysis provides a direction for experimental analysis of human and chimpanzee protein kinases in order to enhance our understanding on their specific biological roles.

SHAMP: An experimental shared memory multimicroprocessor system for performance evaluation of parallel algorithms

In this paper, the design and implementation of a single shared bus, shared memory multiprocessing system using Intel's single board computers is presented. The hardware configuration and the operating system developed to execute the parallel algorithms are discussed. The performance evaluation studies carried out on Image are outlined.

Rotating Beams and Nonrotating Beams With Shared Eigenpair

In this paper, we look for rotating beams whose eigenpair (frequency and mode-shape) is the same as that of uniform nonrotating beams for a particular mode. It is found that, for any given mode, there exist flexural stiffness functions (FSFs) for which the jth mode eigenpair of a rotating beam, with uniform mass distribution, is identical to that of a corresponding nonrotating uniform beam with the same length and mass distribution. By putting the derived FSF in the finite element analysis of a rotating cantilever beam, the frequencies and mode-shapes of a nonrotating cantilever beam are obtained. For the first mode, a physically feasible equivalent rotating beam exists, but for higher modes, the flexural stiffness has internal singularities. Strategies for addressing the singularities in the FSF for finite element analysis are provided. The proposed functions can be used as test-functions for rotating beam codes and for targeted destiffening of rotating beams.

Parallel polygon scan conversion algorithms: Performance evaluation on a shared bus architecture

In this paper, three parallel polygon scan conversion algorithms have been proposed, and their performance when executed on a shared bus architecture has been compared. It has been shown that the parallel algorithm that does not use edge coherence performs better than those that use edge coherence. Further, a multiprocessing architecture has been proposed to execute the parallel polygon scan conversion algorithms more efficiently than a single shared bus architecture.

Design and evaluation of a dual-microcomputer shared memory system with a shared I/O bus

The design, implementation and evaluation are described of a dual-microcomputer system based on the concept of shared memory. Shared memory is useful for passing large blocks of data and it also provides a means to hold and work with shared data. In addition to the shared memory, a separate bus between the I/O ports of the microcomputers is provided. This bus is utilized for interprocessor synchronization. Software routines helpful in applying the dual-microcomputer system to realistic problems are presented. Performance evaluation of the system is carried out using benchmarks.

Understanding Protein Structure from a Percolation Perspective

Underlying the unique structures and diverse functions of proteins area vast range of amino-acid sequences and a highly limited number of folds taken up by the polypeptide backbone. By investigating the role of noncovalent connections at the backbone level and at the detailed side-chain level, we show that these unique structures emerge from interplay between random and selected features. Primarily, the protein structure network formed by these connections shows simple (bond) and higher order (clique) percolation behavior distinctly reminiscent of random network models. However, the clique percolation specific to the side-chain interaction network bears signatures unique to proteins characterized by a larger degree of connectivity than in random networks. These studies reflect some salient features of the manner in which amino acid sequences select the unique structure of proteins from the pool of a limited number of available folds.

Understanding solvent effects on structure and reactivity of organic intermediates: a Raman study

The effect of solvent on chemical reactivity has generally been explained on the basis of the dielectric constant and viscosity. However a number of spectroscopic studies, including UV-VIS, IR and Raman, has led to numerous empirical parameters to define solvent effect based on either solvating ability or polarity scale. These parameters include solvent polarizability, dipolarity, Lewis acidity and Lewis basicity, E-T(30), pi*, alpha, beta etc. However, from a structural point of view, we can separate solvation as static and dynamic processes. The static solvation basically relates to stabilization of the molecular structure by the solvent to attain the equilibrium structure, both in the intermediate and ground state. Dynamic solvation relates to solvent reorganization-induced dynamics prior to the structural reorganization to reach the equilibrium state. In this paper, we present (a) structural distortions induced by the solvent due to preferential solvation of the triplet excited state, and (b) the importance of dynamic solvation induced by vibronic coupling (pseudo-Jahn-Teller coupling). The examples include the effect of solvent on structure and reactivity of excited states of 2,2,2-trifluoroacetophenone (TFA). Based on the comparison of time resolved resonance Raman (TR3) data of TFA and other substituted acetophenone systems, it was found that change in solvent polarity indeed results in electronic state switching and structural changes in the excited state, which explains the trend in reactivity. Further, a TR3 study of fluoranil (FA) in the triplet excited state in solvents of varying polarities indicates that the structure of FA in the triplet excited state is determined by vibronic coupling effects and thus distorted structure. These experimental results have been well supported by density functional theoretical computational studies.

Understanding the folding process of synthetic polymers by small-molecule folding agents

Two acceptor containing polyimides PDI and NDI carrying pyromellitic diimide units and 1,4,5,8-naphthalene tetracarboxy diimide units, respectively, along with hexa(oxyethylene) (EO6) segments as linkers, were prepared from the corresponding dianhydrides and diamines. These polyimides were made to fold by interaction with specifically designed folding agents containing a dialkoxynaphtha-lene (DAN) donor linked to a carboxylic acid group. The alkali-metal counter-ion of the donor carboxylic acid upon complexation with the EO6 segment brings the DAN unit in the right location to induce a charge-transfer complex formation with acceptor units in the polymer backbone. This two-point interaction between the folding agent and the polymer backbone leads to a folding of the polymer chain, which was readily monitored by NMR titrations. The effect of various parameters, such as structures of the folding agent and polymer, and the solvent composition, on the folding propensities of the polymer was studied.

Understanding the Knowledge Needs of Designers During Design Process in Industry

Product success is substantially influenced by satisfaction of knowledge needs of designers, and many tools and methods have been proposed to support these needs. However, adoption of these methods in industry is minimal. This may be due to an inadequate understanding of the knowledge needs of designers in industry. This research attempts to develop a better understanding of these needs by undertaking descriptive studies in an industry. We propose a taxonomy of knowledge, and evaluate this by analyzing the questions asked by the designers involved in the study during their interactions. Using the taxonomy, we converted the questions asked into a generic form. The generic questions provide an understanding about what knowledge must be captured during design, and what its structure should be.

Understanding Membranes through the Molecular Design of Lipids

Lipids are amphiphilic molecules that are composed of hydrophilic and hydrophobic regions. A typical membranous aggregate (vesicles, water-filled lipid nanospheres) is formed upon the self-organization of lipids in water from a diverse collection of amphiphiles producing a dynamic supramolecular structure that shows phase behavior and ordering as required for specific biological functions. The determination of various physical properties of lipid aggregates is the key to determining structure-function relationships. Over the years, we have designed and synthesized a wide variety of lipid molecular systems for the investigation of their membrane-forming properties and have used them for purposes such as gene delivery and enzyme activation. In this feature article, we focus on our work on various types of lipids including ion-paired amphiphiles, cholesterol-based lipids, aromatic lipids, macrocyclic lipids containing disulfide tethers; cationic dimeric lipids, and so forth. The emphasis is oil experimental design and bottom-line conclusions.

An automated framework for understanding structural variations in the binding grooves of MHC class II molecules

Background: MHC/HLA class II molecules are important components of the immune system and play a critical role in processes such as phagocytosis. Understanding peptide recognition properties of the hundreds of MHC class II alleles is essential to appreciate determinants of antigenicity and ultimately to predict epitopes. While there are several methods for epitope prediction, each differing in their success rates, there are no reports so far in the literature to systematically characterize the binding sites at the structural level and infer recognition profiles from them. Results: Here we report a new approach to compare the binding sites of MHC class II molecules using their three dimensional structures. We use a specifically tuned version of our recent algorithm, PocketMatch. We show that our methodology is useful for classification of MHC class II molecules based on similarities or differences among their binding sites. A new module has been used to define binding sites in MHC molecules. Comparison of binding sites of 103 MHC molecules, both at the whole groove and individual sub-pocket levels has been carried out, and their clustering patterns analyzed. While clusters largely agree with serotypic classification, deviations from it and several new insights are obtained from our study. We also present how differences in sub-pockets of molecules associated with a pair of autoimmune diseases, narcolepsy and rheumatoid arthritis, were captured by PocketMatch(13). Conclusion: The systematic framework for understanding structuralvariations in MHC class II molecules enables large scale comparison of binding grooves and sub-pockets, which is likely to have direct implications towards predicting epitopes and understanding peptide binding preferences.

An automated framework for understanding structural variations in the binding grooves of MHC class II molecules

Background: MHC/HLA class II molecules are important components of the immune system and play a critical role in processes such as phagocytosis. Understanding peptide recognition properties of the hundreds of MHC class II alleles is essential to appreciate determinants of antigenicity and ultimately to predict epitopes. While there are several methods for epitope prediction, each differing in their success rates, there are no reports so far in the literature to systematically characterize the binding sites at the structural level and infer recognition profiles from them. Results: Here we report a new approach to compare the binding sites of MHC class II molecules using their three dimensional structures. We use a specifically tuned version of our recent algorithm, PocketMatch. We show that our methodology is useful for classification of MHC class II molecules based on similarities or differences among their binding sites. A new module has been used to define binding sites in MHC molecules. Comparison of binding sites of 103 MHC molecules, both at the whole groove and individual sub-pocket levels has been carried out, and their clustering patterns analyzed. While clusters largely agree with serotypic classification, deviations from it and several new insights are obtained from our study. We also present how differences in sub-pockets of molecules associated with a pair of autoimmune diseases, narcolepsy and rheumatoid arthritis, were captured by PocketMatch(13). Conclusion: The systematic framework for understanding structural variations in MHC class II molecules enables large scale comparison of binding grooves and sub-pockets, which is likely to have direct implications towards predicting epitopes and understanding peptide binding preferences.

A chemical approach to an understanding of the fast ion conduction in silver iodide-silver oxysalt glasses

A number of AgI based fast ion conducting glasses, with a general formula AgI---Ag2O---MxOy (MxOy=MoO3, SeO3, WO3, V2O5, P2O5, GeO2, B2O3, As2O3, CrO3) have been studied. A chemical approach is made to investigate the origin of fast ion conduction in these glasses. An index known as Image tructural Image npinning Image umber, SUN (S), has been defined for the purpose, based on the unscreened nuclear charge of silver ions and the equilibrium lectronegativities of the halide-oxyanion matrix in these glasses. The variation of the glass transition temperature, Tg, conductivity, σ, and the energy of activation, Ea, with the concentration of AgI are discussed in the light of the structural unpinning number. Conductivities increase uniformly in any given glass series as a smooth function of S and level off at very high values. The entire range of conductivity appears to vary as ln Image , where ln σ0 corresponds roughly to the conductivity of the hypothetical AgI glass and “a” is a constant which could be obtained as the slope in the graph of ln Ea versus S. It is suggested that the increase in the concentration of AgI beyond 75–80 mole% in the glass is not advantageous from the conductivity point of view.

A general thermodynamic framework for understanding the behaviour of absorption chillers

In this article, a general definition of the process average temperature has been developed, and the impact of the various dissipative mechanisms on 1/COP of the chiller evaluated. The present component-by-component black box analysis removes the assumptions regarding the generator outlet temperature(s) and the component effective thermal conductances. Mass transfer resistance is also incorporated into the absorber analysis to arrive at a more realistic upper limit to the cooling capacity. Finally, the theoretical foundation for the absorption chiller T-s diagram is derived. This diagrammatic approach only requires the inlet and outlet conditions of the chiller components and can be employed as a practical tool for system analysis and comparison. (C) 2000 Elsevier Science Ltd and IIR. All rights reserved.