Interfacial Regions Governing Internal Cavities of Dendrimers. Studies of Poly(alkyl aryl ether) Dendrimers Constituted with Linkers of Varying Alkyl Chain Length

This report deals with a study of the properties of internal cavities of dendritic macromolecules that are capable Of encapsulating and mediating photoreactions of guest molecules. The internal cavity structures of dendrimers are determined by the interfacial regions between the aqueous exterior and hydrocarbon like interior constituted by the linkers that connect symmetrically sited branch points constituting the dendrimer and head groups that cap the dendrimers. Phloroglucinol-based poly(alkyl aryl ether) dendrimers constituted with a homologous series of alkyl linkers were undertaken for the current study. Twelve dendrimers within first, second, and third generations, having ethyl, n-propyl, n-butyl, and n-pentyl groups as the linkers and hydroxyl groups at peripheries in each generation, were synthesized. Encapsulation of pyrene and coumarins by aqueous basic solutions of dendrimers were monitored-by UV-vis and fluorescence spectroscopies, which showed that a lower generation dendrimer with an optimal alkyl linker presented better encapsulation abilities than a higher generation dendrimer. Norrish type I photoreaction of dibenzyl ketone was carried out within the above: series of dendrimers to probe their abilities to hold guests and reactive inthermediate radical pairs within themselves. The extent of cage effect from the series of third generation dendrimers was observed to be higher with dendrimers having an n-pentyl group as the linker.

Nucleation and growth characteristics of cavities during the early stages of tensile creep deformation in a superplastic zirconia-20 wt% alumina composite

Constant-stress tensile creep experiments on a superplastic 3-mol%-yttria-stabilized tetragonal zirconia composite with 20 wt% alumina revealed that cavities nucleate relatively early during tensile deformation. The number of cavities nucleated increases with increasing imposed stress. The cavities nucleate at triple points associated largely with an alumina grain, and then grow rapidly in a cracklike manner to attain dimensions on the order of the grain facet size. It is suggested that coarser-grained superplastic ceramics exhibit lower ductility due to the ease in formation of such grain boundary facet-cracks and their interlinkage to form a macroscopic crack of critical dimensions.

DEPTH: a web server to compute depth and predict small-molecule binding cavities in proteins

Depth measures the extent of atom/residue burial within a protein. It correlates with properties such as protein stability, hydrogen exchange rate, protein-protein interaction hot spots, post-translational modification sites and sequence variability. Our server, DEPTH, accurately computes depth and solvent-accessible surface area (SASA) values. We show that depth can be used to predict small molecule ligand binding cavities in proteins. Often, some of the residues lining a ligand binding cavity are both deep and solvent exposed. Using the depth-SASA pair values for a residue, its likelihood to form part of a small molecule binding cavity is estimated. The parameters of the method were calibrated over a training set of 900 high-resolution X-ray crystal structures of single-domain proteins bound to small molecules (molecular weight < 1.5 KDa). The prediction accuracy of DEPTH is comparable to that of other geometry-based prediction methods including LIGSITE, SURFNET and Pocket-Finder (all with Matthew's correlation coefficient of similar to 0.4) over a testing set of 225 single and multi-chain protein structures. Users have the option of tuning several parameters to detect cavities of different sizes, for example, geometrically flat binding sites. The input to the server is a protein 3D structure in PDB format. The users have the option of tuning the values of four parameters associated with the computation of residue depth and the prediction of binding cavities. The computed depths, SASA and binding cavity predictions are displayed in 2D plots and mapped onto 3D representations of the protein structure using Jmol. Links are provided to download the outputs. Our server is useful for all structural analysis based on residue depth and SASA, such as guiding site-directed mutagenesis experiments and small molecule docking exercises, in the context of protein functional annotation and drug discovery.

Dynamic Internal Cavities of Dendrimers as Constrained Media. A Study of Photochemical Isomerizations of Stilbene and Azobenzene Using Poly(alkyl aryl ether) Dendrimers

Dendritic rnicroenvironments defined by dynamic internal cavities of a dendrimer were probed through geometric isomerization of stilbene and azobenzene. A third-generation poly(alkyl aryl ether) dendrimer with hydrophilic exterior and hydrophobic interior was used as a reaction cavity in aqueous medium. The dynamic inner cavity sizes were varied by utilizing alkyl linkers that connect the branch junctures from ethyl to n-pentyl moiety (C(2)G(3)-C(5)G(3)). Dendrimers constituted with n-pentyl linker were found to afford higher solubilities of stilbene and azobenzene. Direct irradiation of trans-stilbene showed that C(5)G(3) and C(4)G(3) dendrimers afforded considerable phenanthrene formation, in addition to cis-stilbene, whereas C(3)G(3) and C(2)G(3) gave only cis-stilbene. An electron-transfer sensitized trans-cis isomerization, using cresyl violet perchlorate as the sensitizer, also led to similar results. Thermal isomerization of cis-azobenzene to trans-azobenzene within dendritic microenvironments revealed that the activation energy of the cis- to trans-isomer was increasing in the series C(5)G(3) < C(4)G(3) < C(3)G(3)

Proteomic profiling of high glucose primed monocytes identifies cyclophilin A as a potential secretory marker of inflammation in type 2 diabetes

Hyperglycemia is widely recognized to be a potent stimulator of monocyte activity, which is a crucial event in the pathogenesis of atherosclerosis. We analyzed the monocyte proteome for potential markers that would enhance the ability to screen for early inflammatory status in Type 2 diabetes mellitus (T2DM), using proteomic technologies. Monocytic cells (THP-1) were primed with high glucose (HG), their protein profiles were analyzed using 2DE and the downregulated differentially expressed spots were identified using MALDI TOF/MS. We selected five proteins that were secretory in function with the help of bioinformatic programs. A predominantly downregulated protein identified as cyclophilin A (sequence coverage 98%) was further validated by immunoblotting experiments. The cellular mRNA levels of cyclophilin A in various HG-primed cells were studied using qRT-PCR assays and it was observed to decrease in a dose-dependent manner. LC-ESI-MS was used to identify this protein in the conditioned media of HG-primed cells and confirmed by Western blotting as well as ELISA. Cyclophilin A was also detected in the plasma of patients with diabetes. We conclude that cyclophilin A is secreted by monocytes in response to HG. Given the paracrine and autocrine actions of cyclophilin A, the secreted immunophilin could be significant for progression of atherosclerosis in type 2 diabetes. Our study also provides evidence that analysis of monocyte secretome is a viable strategy for identifying candidate plasma markers in diabetes.

Natural convection in a series of thermally interacting cavities with wall mounted heaters

Laminar natural convection in a series of thermally interacting cavities is numerically studied. Each cavity consists of a conducting bottom wall with a surface mounted heater. The side walls of the cavities are isothermally cooled. Each cavity thermally interacts with its adjacent cavities through the conducting walls. Flow and heat transfer characteristics are studied in detail for various Rayleigh numbers. The convection characteristics in multiple cavities are compared with those in single independent cavity. The thermal interaction between the cavities results in lower temperatures compared with those in independent cavities. While heat is rejected into the adjacent upper cavity through some portion of the conducting wall, heat is received from the adjacent cavity through the remaining portion of the wall. The influence of substrate conductivity on heat exchange between adjacent cavities are examined. Substrate conductivity shows strong effect on temperature distribution. When cooling at both vertical sides is changed to one side cooling, the heat transfer characteristics are changed drastically and many interesting flow features are observed. Effects of cavity aspect ratio is studied and higher heat transfer rates are observed at higher aspect ratios. Correlations for dimensionless temperature maximum and average Nusselt number are presented in terms of Rayleigh number.

Depth: a web server to compute depth, cavity sizes, detect potential small-molecule ligand-binding cavities and predict the pK(a) of ionizable residues in proteins

Residue depth accurately measures burial and parameterizes local protein environment. Depth is the distance of any atom/residue to the closest bulk water. We consider the non-bulk waters to occupy cavities, whose volumes are determined using a Voronoi procedure. Our estimation of cavity sizes is statistically superior to estimates made by CASTp and VOIDOO, and on par with McVol over a data set of 40 cavities. Our calculated cavity volumes correlated best with the experimentally determined destabilization of 34 mutants from five proteins. Some of the cavities identified are capable of binding small molecule ligands. In this study, we have enhanced our depth-based predictions of binding sites by including evolutionary information. We have demonstrated that on a database (LigASite) of similar to 200 proteins, we perform on par with ConCavity and better than MetaPocket 2.0. Our predictions, while less sensitive, are more specific and precise. Finally, we use depth (and other features) to predict pK(a)s of GLU, ASP, LYS and HIS residues. Our results produce an average error of just <1 pH unit over 60 predictions. Our simple empirical method is statistically on par with two and superior to three other methods while inferior to only one. The DEPTH server (http://mspc.bii.a-star.edu.sg/depth/) is an ideal tool for rapid yet accurate structural analyses of protein structures.

Numerical study of driven flows of shear thinning viscoelastic fluids in rectangular cavities

In this work, we present a numerical study of flow of shear thinning viscoelastic fluids in rectangular lid driven cavities for a wide range of aspect ratios (depth to width ratio) varying from 1/16 to 4. In particular, the effect of elasticity, inertia, model parameters and polymer concentration on flow features in rectangular driven cavity has been studied for two shear thinning viscoelastic fluids, namely, Giesekus and linear PTT. We perform numerical simulations using the symmetric square root representation of the conformation tensor to stabilize the numerical scheme against the high Weissenberg number problem. The variation in flow structures associated with merging and splitting of elongated vortices in shallow cavities and coalescence of corner eddies to yield a second primary vortex in deep cavities with respect to the variation in flow parameters is discussed. We discuss the effect of the dominant eigenvalues and the corresponding eigenvectors on the location of the primary eddy in the cavity. We also demonstrate, by performing numerical simulations for shallow and deep cavities, that where the Deborah number (based on convective time scale) characterizes the elastic behaviour of the fluid in deep cavities, Weissenberg number (based on shear rate) should be used for shallow cavities. (C) 2016 Elsevier B.V. All rights reserved.

The strength distribution of brittle materials with a high-concentration of cavities

The maximum stress concentration factor in brittle materials with a high concentration of cavities is obtained. The interaction between the nearest cavities, in addition to the far field interactions, is taken into account to evaluate the strength distribution based on the statistical analysis of the nearest distance distribution. Through this investigation, it is found that the interaction between the nearest neighbors is much more important than the far field interactions, and one has to consider it in calculating the strength of brittle materials even if the volume fraction of cavities it contains is small. The other important conclusion is that the maximum stress concentration factor has a wide scattered distribution.

Resonant mode analysis in toroidal cavities with elliptic cross-sections

Resonant cavity modes in a torus with elliptical cross section are studied by means of a direct variational method. The nonlinear effects of toroidicity and ellipticity on the frequency of the basic mode are analyzed simply and systematically without the restriction of linear theory. It is shown that the toroidicity effect on the m = 0 transverse magnetic mode is less-than-or-equal-to 11%. The frequency of the mode shifts approximately 11-29% when the elongation of the cross section changes from 1 to 2. The effects of toroidicity and ellipticity differ for each resonant mode.

On the non-linear stability theory of spinning solid bodies with liquid-filled cavities and its application to the columbus problem

In this paper, we first present a system of differential-integral equations for the largedisturbance to the general case that any arbitrarily shaped solid body with a cavity contain-ing viscous liquid rotates uniformly around the principal axis of inertia, and then develop aweakly non-linear stability theory by the Lyapunov direct approach. Applying this theoryto the Columbus problem, we have proved the consistency between the theory and Kelvin'sexperiments.

Analysis of Behaviors of Shock Focusing in the Inner Cavities of Double Wedge and Cone

The mechanisms of shock focusing in inner cavities of double wedge and cone are compared with that of traditional curved-surface shock focusing. The results show that there are many high temperature regions just behind shock surface which appear in two place alternately, one is near the surface of wall and the other is near the centerline. Also, changes in temperature, pressure, energy and power of the high temperature regions were analyzed and the results show that energy and power per unit volume increase, but total energy and power in the high temperature regions decrease during the process of shock moving forward the apex of double wedge or cone.