Structural basis for the function of anti-idiotypic antibody in immune memory

We had earlier proposed a hypothesis to explain the mechanism of perpetuation of immunological memory based on the operation of idiotypic network in the complete absence of antigen. Experimental evidences were provided for memory maintenance through anti-idiotypic antibody (Ab(2)) carrying the internal image of the antigen. In the present work, we describe a structural basis for such memory perpetuation by molecular modeling and structural analysis studies. A three-dimensional model of Ab(2) was generated and the structure of the antigenic site on the hemagglutinin protein H of Rinderpest virus was modeled using the structural template of hemagglutinin protein of Measles virus. Our results show that a large portion of heavy chain containing the CDR regions of Ab(2) resembles the domain of the hemagglutinin housing the epitope regions. The similarity demonstrates that an internal image of the H antigen is formed in Ab(2), which provides a structural basis for functional mimicry demonstrated earlier. This work brings out the importance of the structural similarity between a domain of hemagglutinin protein to that of its corresponding Ab(2). It provides evidence that Ab(2) is indeed capable of functioning as surrogate antigen and provides support to earlier proposed relay hypothesis which has provided a mechanism for the maintenance of immunological memory.

Access path query language for relational database systems

Database management systems offer a very reliable and attractive data organization for fast and economical information storage and processing for diverse applications. It is much more important that the information should be easily accessible to users with varied backgrounds, professional as well as casual, through a suitable data sublanguage. The language adopted here (APPLE) is one such language for relational database systems and is completely nonprocedural and well suited to users with minimum or no programming background. This is supported by an access path model which permits the user to formulate completely nonprocedural queries expressed solely in terms of attribute names. The data description language (DDL) and data manipulation language (DML) features of APPLE are also discussed. The underlying relational database has been implemented with the help of the DATATRIEVE-11 utility for record and domain definition which is available on the PDP-11/35. The package is coded in Pascal and MACRO-11. Further, most of the limitations of the DATATRIEVE-11 utility have been eliminated in the interface package.

Mechanism of oxidation of α,β-unsaturated thiones by singlet oxygen

Photo-oxidation of α,β-unsaturated thiones yields the corresponding ketones as the only product. Studies carried out on three systems, namely thioketones, α,β-unsaturated thiones and thioketenes, have revealed that there exists a similarity in their mechanism of oxidation. It has been suggested that the thiocarbonyl chromophore is the site of attack by singlet oxygen in α,β-unsaturated thiones and that the adjacent C-C double bond is inert under these conditions. Absence of sulphine during the oxidation of α,β-unsaturated thiones is attributed to the electronic factors operating on the zwitterionic/diradical intermediate. While α,β-unsaturated ketones are poorly reactive, α,β-unsaturated thiones are highly reactive toward singlet oxygen.

The Evolution of Guanylyl Cyclases as Multidomain Proteins: Conserved Features of Kinase-Cyclase Domain Fusions

Guanylyl cyclases (GCs) are enzymes that generate cyclic GMP and regulate different physiologic and developmental processes in a number of organisms. GCs possess sequence similarity to class III adenylyl cyclases (ACs) and are present as either membrane-bound receptor GCs or cytosolic soluble GCs. We sought to determine the evolution of GCs using a large-scale bioinformatic analysis and found multiple lineage-specific expansions of GC genes in the genomes of many eukaryotes. Moreover, a few GC-like proteins were identified in prokaryotes, which come fused to a number of different domains, suggesting allosteric regulation of nucleotide cyclase activity Eukaryotic receptor GCs are associated with a kinase homology domain (KHD), and phylogenetic analysis of these proteins suggest coevolution of the KHD and the associated cyclase domain as well as a conservation of the sequence and the size of the linker region between the KHD and the associated cyclase domain. Finally, we also report the existence of mimiviral proteins that contain putative active kinase domains associated with a cyclase domain, which could suggest early evolution of the fusion of these two important domains involved in signa transduction.

Reflexive Incidence Matrx (RIM) Representation of Petr Nets

Although incidence matrix representation has been used to analyze the Petri net based models of a system, it has the limitation that it does not preserve reflexive properties (i.e., the presence of selfloops) of Petri nets. But in many practical applications self-loops play very important roles. This paper proposes a new representation scheme for general Petri nets. This scheme defines a matrix called "reflexive incidence matrix (RIM) c which is a combination of two matrices, a "base matrix Cb,,, and a "power matrix CP." This scheme preserves the reflexive and other properties of the Petri nets. Through a detailed analysis it is shown that the proposed scheme requires less memory space and less processing time for answering commonly encountered net queries compared to other schemes. Algorithms to generate the RIM from the given net description and to decompose RIM into input and output function matrices are also given. The proposed Petri net representation scheme is very useful to model and analyze the systems having shared resources, chemical processes, network protocols, etc., and to evaluate the performance of asynchronous concurrent systems.

Incompressible boundary layer for longitudinal flow over a cylinder with an applied magnetic field

The flow, heat and mass transfer problem for a steady laminar incompressible boundary layer flow in an electrically conducting fluid over a longitudinal cylinder with an applied magnetic field has been studied. The partial differential equations governing the flow have been solved numerically using an implicit finite-difference scheme. The results are found to be strongly dependent on the magnetic field and dissipation parameter. The effect of the mass transfer is more pronounced on the skin friction than on the heat transfer. The results have been compared with those of the series solution, the asymptotic solution, the Glauert and Lighthill's solution, local similarity, local nonsimilarity and difference-differential methods. Good agreement is found with all of them, except with the results of the local similarity and series solution methods.

Analysis of drop formation at conical tips : 1. Theory

The phenomenon of drop formation at conical tips under near zero flow conditions has been investigated using a theoretical approach. The analysis permits the prediction of drop profile and drop volume, until the onset of instability. A semiempirical approach based on the similarity of drop shapes has been adopted to predict the detaching drop volumes at conical tips. The effects of base diameter of the cone, cone angle, interfacial tension, and the densities of the drop and the surrounding fluid on the maximum and detached drop volumes are predicted.

Some Exact-Solutions Describing Unsteady Plane Gas-Flows With Shocks

A new class of exact solutions of plane gasdynamic equations is found which describes piston-driven shocks into non-uniform media. The governing equations of these flows are taken in the coordinate system used earlier by Ustinov, and their similarity form is determined by the method of infinitesimal transformations. The solutions give shocks with velocities which either decay or grown in a finite or infinite time depending on the density distribution in the ambient medium, although their strength remains constant. The results of the present study are related to earlier investigations describing the propagation of shocks of constant strength into non-uniform media.

Free convection heat transfer to mercury in vertical annuli

Data on free convection heat transfer to water and mercury are collected using a test rig in vertical annuli of three radii ratios, the walls of which are maintained at uniform temperatures. A theoretical analysis of the boundary layer equations has been attempted using local similarity transformation and double boundary layer approach. Correlations derived from the present theoretical analysis are compared with the analysis and the experimental data available in literature for non-metallic fluids and also with the present experimental data on water and mercury. Generalised correlations are set up for expressing the ratio of heat transferred by convection to the heat transferred by pure conduction and Nusselt's number, in terms of Grashof, Rayleigh and Prandtl numbers, based on the theoretical analysis and the present data on mercury and water. The present generalised correlations agree with the reported and present data for non-metallic fluids and liquid metals with an average deviation of 9% and maximum deviation of ± 13.7%.

A new method for generation of quasi-periodic structures withn fold axes: Application to five and seven folds

A new geometrical method for generating aperiodic lattices forn-fold non-crystallographic axes is described. The method is based on the self-similarity principle. It makes use of the principles of gnomons to divide the basic triangle of a regular polygon of 2n sides to appropriate isosceles triangles and to generate a minimum set of rhombi required to fill that polygon. The method is applicable to anyn-fold noncrystallographic axis. It is first shown how these regular polygons can be obtained and how these can be used to generate aperiodic structures. In particular, the application of this method to the cases of five-fold and seven-fold axes is discussed. The present method indicates that the recursion rule used by others earlier is a restricted one and that several aperiodic lattices with five fold symmetry could be generated. It is also shown how a limited array of approximately square cells with large dimensions could be detected in a quasi lattice and these are compared with the unit cell dimensions of MnAl6 suggested by Pauling. In addition, the recursion rule for sub-dividing the three basic rhombi of seven-fold structure was obtained and the aperiodic lattice thus generated is also shown.

Enzymatic cleavage of carotenoids

1. 1.|Carotene 15,15′-dioxygenase (EC 1.13.11.21) has been isolated from the intestine of guinea pig and rabbit and purified 38- and 30-fold, respectively, but subjecting the intestinal homogenate to protamine sulfate treatment, (NH4)2SO4 fractionation and acetone precipitation. 2. 2.|The guinea pig enzyme showed a pH optimum at 8.5, an optimum substrate concentration of 200 nmoles of β,β-carotene per 25 ml of reaction mixture, an apparent Km with β,β-carotene as substrate of 9.5 · 10−6 M and a V 3.3 nmoles of retinal formation/mg protein per h. The reaction was linear upto 3 h and the reaction rate increased linearly with increase in enzyme protein concentration. The enzyme was activated by GSH and Fe2+ and inhibited by sodium dodecylsulfate, sulfhydryl binding and iron chelating agents. 3. 3.|The reaction catalysed by guinea pig enzyme was strictly stoichiometric. 4. 4.|Rabbit enzyme showed a close similarity with guinea pig enzyme with respect to time course, optimum substrate concentration, activation by Fe2+ and GSH, inhibition by sodium dodecylsulfate, iron chelating and sulfhydryl binding agents. However, it showed a slightly lower pH optimum (pH 7.8). 5. 5.|The enzyme from guinea pig and rabbit showed remarkable similarity with respect to cleavage of carotenoids. The enzyme from both the species was more specific for β,β-carotene but could also cleave a number of other carotenoids at the 15,15′-double bond. 6. 6.|10′-Apo-β-carotenal and 10′-apo-β-carotenol were readily cleaved compared with other apo-β-carotenals and apo-β-carotenols tested. 7. 7.|It has been conclusively shown for the first time that mono-ring substituted carotenoids are also cleaved at the 15,15′-double bond.

Novel Biginelli dihydropyrimidines with potential anticancer activity: A parallel synthesis and CoMSIA study

Novel Biginelli dihydropyrimidines of biological interest were prepared using p-toluene sulphonic acid as an efficient catalyst. All the thirty-two synthesised dihydropyrimidines were evaluated for their in vitro antioxidant activity using DPPH method. Only, compounds 28 and 29 exhibited reasonably good antioxidant activity. Furthermore, the synthesised Biginelli compounds were subjected for their in vitro anticancer activity against MCF-7 human breast cancer cells. The title compounds were tested at the concentration of 10 μg. Compounds exhibited activity ranging from weak to moderate and, from moderate to high in terms of percentage cytotoxicity. Among them, compounds 10 and 11 exhibited significant anticancer activity. In order to elucidate the three-dimensional structure–activity relationships (3D QSAR) towards their anticancer activity, we subjected them for comparative molecular similarity indices analysis (CoMSIA). Illustration regarding their synthesis, analysis, antioxidant activity, anticancer activity and 3D QSAR study is described.

Enzymatic cleavage of carotenoids

1. 1.|Carotene 15,15′-dioxygenase (EC 1.13.11.21) has been isolated from the intestine of guinea pig and rabbit and purified 38- and 30-fold, respectively, but subjecting the intestinal homogenate to protamine sulfate treatment, (NH4)2SO4 fractionation and acetone precipitation. 2. 2.|The guinea pig enzyme showed a pH optimum at 8.5, an optimum substrate concentration of 200 nmoles of β,β-carotene per 25 ml of reaction mixture, an apparent Km with β,β-carotene as substrate of 9.5 · 10−6 M and a V 3.3 nmoles of retinal formation/mg protein per h. The reaction was linear upto 3 h and the reaction rate increased linearly with increase in enzyme protein concentration. The enzyme was activated by GSH and Fe2+ and inhibited by sodium dodecylsulfate, sulfhydryl binding and iron chelating agents. 3. 3.|The reaction catalysed by guinea pig enzyme was strictly stoichiometric. 4. 4.|Rabbit enzyme showed a close similarity with guinea pig enzyme with respect to time course, optimum substrate concentration, activation by Fe2+ and GSH, inhibition by sodium dodecylsulfate, iron chelating and sulfhydryl binding agents. However, it showed a slightly lower pH optimum (pH 7.8). 5. 5.|The enzyme from guinea pig and rabbit showed remarkable similarity with respect to cleavage of carotenoids. The enzyme from both the species was more specific for β,β-carotene but could also cleave a number of other carotenoids at the 15,15′-double bond. 6. 6.|10′-Apo-β-carotenal and 10′-apo-β-carotenol were readily cleaved compared with other apo-β-carotenals and apo-β-carotenols tested. 7. 7.|It has been conclusively shown for the first time that mono-ring substituted carotenoids are also cleaved at the 15,15′-double bond.

Similarities in Different Experiments of Erosion Caused by Cavitation and Liquid Impingement

Correlations of erosion resistances of materials tested in different equipment are reported. Analysis of the authors' data from rotating disk and venturi equipment indicates that there exists a good correlation between the erosion resistances of materials tested at different intensities. The study indicates that time effects on erosion are important in correlations of this type. The erosion resistances of materials tested in two different devices exhibit good correlations indicating a quantitative similarity between different forms of erosion. The investigations also show that the prediction of erosion resistances of materials in a field device may be made with the data from a laboratory device which may not fully reproduce the flow conditions in the field. These conclusions are also checked with data reported from other laboratories.

Turbulence measurements in an equilibrium axisymmetric wall jet

This paper reports measurements of turbulent quantities in an axisymmetric wall jet subjected to an adverse pressure gradient in a conical diffuser, in such a way that a suitably defined pressure-gradient parameter is everywhere small. Self-similarity is observed in the mean velocity profile, as well as the profiles of many turbulent quantities at sufficiently large distances from the injection slot. Autocorrelation measurements indicate that, in the region of turbulent production, the time scale of ν fluctuations is very much smaller than the time scale of u fluctuations. Based on the data on these time scales, a possible model is proposed for the Reynolds stress. One-dimensional energy spectra are obtained for the u, v and w components at several points in the wall jet. It is found that self-similarity is exhibited by the one-dimensional wavenumber spectrum of $\overline{q^2}(=\overline{u^2}+\overline{v^2}+\overline{w^2})$, if the half-width of the wall jet and the local mean velocity are used for forming the non-dimensional wavenumber. Both the autocorrelation curves and the spectra indicate the existence of periodicity in the flow. The rate of dissipation of turbulent energy is estimated from the $\overline{q^2}$ spectra, using a slightly modified version of a previously suggested method.