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.

High Li storage capacity of poorly crystalline porous delta-MnO2 prepared by hydrothermal route

Poorly crystalline porous delta-MnO2 is synthesized by hydrothermal route from a neutral aqueous solution of KMnO4 at 180 degrees C and the reaction time of 24 h. The as-synthesized sample and also the sample heated at 300 degrees C have nanopetals morphology with large surface area. On heating at temperatures 400 degrees C, there is a decrease in BET surface area and also a change in morphology from nanopetals to clusters of nanorods. Furthermore, the poorly crystalline delta-MnO2 converts into well crystalline alpha-MnO2 phase. The electrochemical lithium intercalation and de-intercalation studies in a non-aqueous electrolyte provide a high discharge specific capacity (275 mAh g(-1)) at a specific current of 40 mA g(-1) for the poorly crystalline delta-MnO2 samples. The rate capability is also high. There is a decrease in capacity on repeated charge-discharge cycling. The specific capacity values of the crystalline alpha-MnO2 samples are considerably less than the values of poorly crystalline delta-MnO2 samples. Thus, the hydrothermal route facilitates preparation of poorly crystalline electrochemically active porous MnO2.

N-Terminal disordered domain of saccharomyces cerevisiae Hop1 protein Is dispensable for DNA binding, bridging, and synapsis of double-stranded DNA molecules but is ecessary for spore formation

The cytological architecture of the synaptonemal complex (SC), a meiosis-specific proteinaceous structure, is evolutionarily conserved among eukaryotes. However, little is known about the biochemical properties of SC components or the mechanisms underlying their roles in meiotic chromosome synapsis and recombination. Functional analysis of Saccharomyces cerevisiae Hop1, a key structural component of SC, has begun to reveal important insights into its function in interhomolog recombination. Previously, we showed that Hop1 is a structure-specific DNA-binding protein, exhibits higher binding affinity for the Holliday junction, and induces structural distortion at the core of the junction. Furthermore, Hop1 promotes DNA condensation and intra- and intermolecular synapsis between duplex DNA molecules. Here, we show that Hop1 possesses a modular domain organization, consisting of an intrinsically disordered N-terminal domain and a protease-resistant C-terminal domain (Hop1CTD). Furthermore, we found that Hop1CTD exhibits strong homotypic as well as heterotypic protein protein interactions, and its biochemical activities were similar to those of the full-length Hop1 protein. However, Hop1CTD failed to complement the meiotic recombination defects of the Delta hop1 strain, indicating that both N- and C-terminal domains of Hop1 are essential for meiosis and spore formation. Altogether, our findings reveal novel insights into the structure-function relationships of Hop1 and help to further our understanding of its role in meiotic chromosome synapsis and recombination.

Maltose Binding Protein Is Partially Structured in Its Molten Globule State

Seven double cysteine mutants of maltose binding protein (MBP) were generated with one each in the active cleft at position 298 and the second cysteine distributed over both domains of the protein. These cysteines were spin labeled and distances between the labels in biradical pairs determined by pulsed double electron-electron resonance (DEER) measurements. The values were compared with theoretical predictions of distances between the labels in biradicals constructed by molecular modeling from the crystal structure of MBP without maltose and were found to be in excellent agreement. MBP is in a molten globule state at pH 3.3 and is known to still bind its substrate maltose. The nitroxide spin label was sufficiently stable under these conditions. In preliminary experiments, DEER measurements were carried out with one of the mutants yielding a broad distance distribution as was to be expected if there is no explicit tertiary structure and the individual helices pointing into all possible directions.

Horizontal pullout capacity of a group of two vertical plate anchors in clay

The horizontal pullout capacity of a group of two vertical strip plate anchors, placed along the same vertical plane, in a fully cohesive soil has been computed by using the lower bound finite element limit analysis. The effect of spacing between the plate anchors on the magnitude of total group failure load (P-uT) has been evaluated. An increase of soil cohesion with depth has also been incorporated in the analysis. For a weightless medium, the total pullout resistance of the group becomes maximum corresponding to a certain optimum spacing between the anchor plates which has been found to vary generally between 0.5B and B; where B is the width of the anchor plate. As compared to a single plate anchor, the increase in the pullout resistance for a group of two anchors becomes greater at a higher embedment ratio. The effect of soil unit weight has also been analyzed. It is noted that the interference effect on the pullout resistance increases further with an increase in the unit weight of soil mass.

Approach for the use of MSW settlement predictions in the assessment of landfill capacity based on reliability analysis

In the analysis and design of municipal solid waste (MSW) landfills, there are many uncertainties associated with the properties of MSW during and after MSW placement. Several studies are performed involving different laboratory and field tests to understand the complex behavior and properties of MSW, and based on these studies, different models are proposed for the analysis of time dependent settlement response of MSW. For the analysis of MSW settlement, it is very important to account for the variability of model parameters that reflect different processes such as primary compression under loading, mechanical creep and biodegradation. In this paper, regression equations based on response surface method (RSM) are used to represent the complex behavior of MSW using a newly developed constitutive model. An approach to assess landfill capacities and develop landfill closure plans based on prediction of landfill settlements is proposed. The variability associated with model parameters relating to primary compression, mechanical creep and biodegradation are used to examine their influence on MSW settlement using reliability analysis framework and influence of various parameters on the settlement of MSW are estimated through sensitivity analysis. (C) 2013 Elsevier Ltd. All rights reserved.

Seismic Bearing Capacity of Foundations on Cohesionless Slopes

By applying the lower bound theorem of limit analysis in conjunction with finite elements and nonlinear optimization, the bearing capacity factor N has been computed for a rough strip footing by incorporating pseudostatic horizontal seismic body forces. As compared with different existing approaches, the present analysis is more rigorous, because it does not require an assumption of either the failure mechanism or the variation of the ratio of the shear to the normal stress along the footing-soil interface. The magnitude of N decreases considerably with an increase in the horizontal seismic acceleration coefficient (kh). With an increase in kh, a continuous spread in the extent of the plastic zone toward the direction of the horizontal seismic body force is noted. The results obtained from this paper have been found to compare well with the solutions reported in the literature. (C) 2013 American Society of Civil Engineers.

Bearing Capacity of Foundations with Inclined Groundwater Seepage

The ultimate bearing capacity of strip foundations in the presence of inclined groundwater flow, considering both upward and downward flow directions, has been determined by using the lower bound finite-element limit analysis. A numerical solution has been generated for both smooth and rough footings placed on frictional soils. A correction factor (f gamma), which needs to be multiplied with the N gamma-term, has been computed to account for groundwater seepage. The variation of f gamma has been obtained as a function of the hydraulic gradient (i) for various inclinations of groundwater flow. For a given magnitude of i, there exists a certain critical inclination of the flow for which the value of f gamma is minimized. With an upward flow, for all flow inclinations, the magnitude of f gamma always reduces with an increase in the value of i. An example has also been provided to illustrate the application of the obtained results when designing foundations in the presence of groundwater seepage.

On secrecy above secrecy capacity

We consider secrecy obtained when one transmits on a Gaussian Wiretap channel above the secrecy capacity. Instead of equivocation, we consider probability of error as the criterion of secrecy. The usual channel codes are considered for transmission. The rates obtained can reach the channel capacity. We show that the “confusion” caused to the Eve when the rate of transmission is above capacity of the Eve's channel is similar to the confusion caused by using the wiretap channel codes used below the secrecy capacity.

Synergistic Lewis base and anion-binding catalysis for the enantioselective vinylogous addition of deconjugated butenolides to allenoates

An enantioselective vinylogous umpolung addition of deconjugated butenolides to allenoates has been developed for the first time with the help of synergistic combination of an achiral phosphine and a chiral squaramide, and represents the first example of a catalytic enantioselective C gamma-C gamma bond formation between two different carbonyl partners.

Optimal capacity relay node placement in a multi-hop network on a line

We use information theoretic achievable rate formulas for the multi-relay channel to study the problem of optimal placement of relay nodes along the straight line joining a source node and a destination node. The achievable rate formulas that we utilize are for full-duplex radios at the relays and decode-and-forward relaying. For the single relay case, and individual power constraints at the source node and the relay node, we provide explicit formulas for the optimal relay location and the optimal power allocation to the source-relay channel, for the exponential and the power-law path-loss channel models. For the multiple relay case, we consider exponential path-loss and a total power constraint over the source and the relays, and derive an optimization problem, the solution of which provides the optimal relay locations. Numerical results suggest that at low attenuation the relays are mostly clustered close to the source in order to be able to cooperate among themselves, whereas at high attenuation they are uniformly placed and work as repeaters. We also prove that a constant rate independent of the attenuation in the network can be achieved by placing a large enough number of relay nodes uniformly between the source and the destination, under the exponential path-loss model with total power constraint.

Capacity of a Gaussian MAC with energy harvesting transmit nodes

We consider a Gaussian multiple access channel (GMAC) where the users are sensor nodes powered by energy harvesters. The energy harvesters may have finite or infinite buffer to store the harvested energy. First, we find the capacity region of a GMAC powered by transmit nodes with an infinite energy buffer. Next, we consider a GMAC with the transmitting nodes equipped with a finite energy buffer. Initially we assume perfect knowledge of the buffer state information at both the encoders and the decoder. We provide an achievable region for this case. We also generalize the achievable region when only partial information about buffer state is available at both the encoders and the decoder.

Universal binding energy relation for cleaved and structurally relaxed surfaces

The universal binding energy relation (UBER), derived earlier to describe the cohesion between two rigid atomic planes, does not accurately capture the cohesive properties when the cleaved surfaces are allowed to relax. We suggest a modified functional form of UBER that is analytical and at the same time accurately models the properties of surfaces relaxed during cleavage. We demonstrate the generality as well as the validity of this modified UBER through first-principles density functional theory calculations of cleavage in a number of crystal systems. Our results show that the total energies of all the relaxed surfaces lie on a single (universal) energy surface, that is given by the proposed functional form which contains an additional length-scale associated with structural relaxation. This functional form could be used in modelling the cohesive zones in crack growth simulation studies. We find that the cohesive law (stress-displacement relation) differs significantly in the case where cracked surfaces are allowed to relax, with lower peak stresses occurring at higher displacements.

Insulin like growth factor binding protein 4 promotes GBM progression and regulates key factors involved in EMT and invasion

Insulin like growth factor binding protein 4 (IGFBP4) regulates growth and development of tissues and organs by negatively regulating IGF signaling. Among most cancers, IGFBP4 has growth inhibitory role and reported as a down-regulated gene, except for renal cell carcinoma, wherein IGFBP4 promotes tumor progression. IGFBP4 expression has been shown to be higher in increasing grades of astrocytoma. However, the functional role of IGFBP4 in gliomas has not been explored. Surgical biopsies of 20 normal brain and 198 astrocytoma samples were analyzed for IGFBP4 expression by qRT-PCR. Highest expression of IGFBP4 mRNA was seen in GBM tumors compared to control brain tissues (median log2 of 2.035, p < 0.0001). Immunohistochemical analysis of 53 tissue samples revealed predominant nuclear staining of IGFBP4, seen maximally in GBMs when compared to DA and AA tumors (median LI = 29.12 +/- A 16.943, p < 0.001). Over expression of IGFBP4 in U343 glioma cells resulted in up-regulation of molecules involved in tumor growth, EMT and invasion such as pAkt, pErk, Vimentin, and N-cadherin and down-regulation of E-cadherin. Functionally, IGFBP4 over expression in these cells resulted in increased proliferation, migration and invasion as assessed by MTT, transwell migration, and Matrigel invasion assays. These findings were confirmed upon IGFBP4 knockdown in U251 glioma cells. Our data suggest a pro-tumorigenic role for IGFBP4 in glioma.

Polymer Template Assisted Synthesis of Porous Li1.2Mn0.53Ni0.13Co0.13O2 as a High Capacity and High Rate Capability Positive Electrode Material

A porous layered composite of Li2MnO3 and LiMn1/3Co1/3Ni1/3O2 (composition: Li1.2Mn0.53Ni0.13Co0.13O2) is prepared by reverse microemulsion method employing a soft polymer template and studied as a positive electrode material. The precursor is heated at several temperatures between 500 and 900 degrees C. The product samples possess mesoporosity with broadly distributed pores of about 30 nm diameters. There is a decrease in pore volume as well as in surface area by increasing the temperature of preparation. Nevertheless, the electrochemical activity of the composite increases with an increase in temperature. The discharge capacity values of the samples prepared at 800 and 900 degrees C are about 250 mAh g(-1) at a specific current of 40 mA g(-1) with an excellent cycling stability. A value of 225 mAh g(-1) is obtained at the end of 30 charge-discharge cycles. Both these composite samples possess high rate capability, but the 800 degrees C sample is marginally superior to the 900 degrees C sample. A discharge capacity of 100 mAh g(-1) is obtained at a specific current of 1000 mA g(-1). The high rate capability is attributed to porous nature of the composite samples. (C) 2013 The Electrochemical Society. All rights reserved.