Structural Integrity of the Greek Key Motif in beta gamma-Crystallins Is Vital for Central Eye Lens Transparency

Background: We highlight an unrecognized physiological role for the Greek key motif, an evolutionarily conserved super-secondary structural topology of the beta gamma-crystallins. These proteins constitute the bulk of the human eye lens, packed at very high concentrations in a compact, globular, short-range order, generating transparency. Congenital cataract (affecting 400,000 newborns yearly worldwide), associated with 54 mutations in beta gamma-crystallins, occurs in two major phenotypes nuclear cataract, which blocks the central visual axis, hampering the development of the growing eye and demanding earliest intervention, and the milder peripheral progressive cataract where surgery can wait. In order to understand this phenotypic dichotomy at the molecular level, we have studied the structural and aggregation features of representative mutations. Methods: Wild type and several representative mutant proteins were cloned, expressed and purified and their secondary and tertiary structural details, as well as structural stability, were compared in solution, using spectroscopy. Their tendencies to aggregate in vitro and in cellulo were also compared. In addition, we analyzed their structural differences by molecular modeling in silico. Results: Based on their properties, mutants are seen to fall into two classes. Mutants A36P, L45PL54P, R140X, and G165fs display lowered solubility and structural stability, expose several buried residues to the surface, aggregate in vitro and in cellulo, and disturb/distort the Greek key motif. And they are associated with nuclear cataract. In contrast, mutants P24T and R77S, associated with peripheral cataract, behave quite similar to the wild type molecule, and do not affect the Greek key topology. Conclusion: When a mutation distorts even one of the four Greek key motifs, the protein readily self-aggregates and precipitates, consistent with the phenotype of nuclear cataract, while mutations not affecting the motif display `native state aggregation', leading to peripheral cataract, thus offering a protein structural rationale for the cataract phenotypic dichotomy ``distort motif, lose central vision''.

Evidence of an intermediate phase in a quaternary Ag bearing telluride glass system using alternating DSC

Alternating Differential Scanning Calorimetric (ADSC) studies on quaternary Ge15Te80-xIn5Agx glasses show the non-reversing enthalpy (Delta H-NR) at T-g to exhibit a broad global minimum in the 8% <= x <= 16% range of Ag, an observation that is taken evidence for existence of an Intermediate Phase (IP) in that range. Glasses at x < 8% are in the flexible phase while those at x > 16% in the stressed-rigid phase. The nature of crystalline phases formed upon crystallization of bulk glasses are elucidated by XRD studies, and reveal presence of Te, GeTe, Ag8GeTe6, AgTe, In2Te3 and In4Te3 phases. These experiments also reveal that the fraction of Ag- bearing phases increases while those of Te- bearing ones decreases with increasing x, suggesting progressive replacement of Te-Te bonds by Ag-Te bonds. (C) 2013 Elsevier Ltd. All rights reserved.

Better early osteogenesis of electroconductive hydroxyapatite-calcium titanate composites in a rabbit animal model

In view of the fact that bone healing can be enhanced due to external electric field application, it is important to assess the influence of the implant conductivity on the bone regeneration in vivo. To address this issue, this study reports the in vivo biocompatibility property of multistage spark plasma sintered hydroxyapatite (HA)-80 wt % calcium titanate (CaTiO3) composites and monolithic HA, which have widely different conductivity property (14 orders of magnitude difference). The ability of bone regeneration was assessed by implantation in cylindrical femoral bone defects of rabbit animal model for varying time period of 1, 4, and 12 weeks. The overall assessment of the histology results suggests that the progressive healing of bone defects around HA-80 wt % CaTiO3 is associated with a better efficacy with respect to (w.r.t) early stage neobone formation, which is histomorphometrically around 140% higher than monolithic HA. Overall, this study demonstrates that the in vivo biocompatibility property of HA-80 wt % CaTiO3 with respect to local effects after 12 weeks of implantation is not compromised both qualitatively and quantitatively, and a comparison with control implant (HA) points toward the critical role of electrical conductivity on better early stage bone regeneration. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 842-851, 2014.

Spatial variations of effective elastic thickness over the Ninetyeast Ridge and implications for its structure and tectonic evolution

We present new data on the strength of oceanic lithosphere along the Ninetyeast Ridge (NER) from two independent methods: spectral analysis (Bouguer coherence) using the fan wavelet transform technique, and spatial analysis (flexure inversion) with the convolution method. The two methods provide effective elastic thickness (T-e) patterns that broadly complement each other, and correlate well with known surface structures and regional-scale features. Furthermore, our study presents a new high resolution database on the Moho configuration, which obeys flexural isostasy, and exhibit regional correlations with the T-e variations. A continuous ridge structure with a much lower T-e value than that of normal oceanic lithosphere provides strong support for the hotspot theory. The derived T-e values vary over the northern (higher T-e similar to 10-20 km), central (anomalously low T-e similar to 0-5 km), and southern (low T-e similar to 5 km) segments of the NER. The lack of correlation of the T-e value with the progressive aging of the lithosphere implies differences in thermo-mechanical setting of the crust and underlying mantle in different parts of the NER, again indicating diversity in their evolution. The anomalously low T-e and deeper Moho (similar to 22 km) estimates of the central NER (between 0.5 degrees N and 17 degrees S) are attributed to the interaction of a hotspot with the Wharton spreading ridge that caused significant thermal rejuvenation and hence weakening of the lithosphere. The higher mechanical strength values in the northern NER (north of 0.5 degrees N) may support the idea of off-ridge emplacement and a relatively large plate motion at the time of volcanism. The low T-e and deeper Moho (similar to 22 km) estimates in the southern part (south of 17 degrees S) suggest that the lithosphere was weak and therefore younger at the time of volcanism, and this supports the idea that the southern NER was emplaced on the edge of the Indian plate. (C) 2013 Elsevier B.V. All rights reserved.

Low embodied energy cement stabilised rammed earth building-A case study

Rammed earth is a monolithic construction and the construction process involves compaction of processed soil in progressive layers in a rigid formwork. Durable and thinner load bearing walls can be built using stabilised rammed earth. Use of inorganic additives such as cement for rammed earth walls has been in practice since the last 5-6 decades and cement stabilised rammed earth (CSRE) buildings can be seen across the world. The paper deals with the construction aspects, structural design and embodied energy analysis of a three storey load bearing school building complex. The CSRE school complex consists of 15 classrooms, an open air theatre and a service block. The complex has a built-up area of 1691.3 m(2) and was constructed employing manual construction techniques. This case study shows low embodied energy of 1.15 GJ/m(2) for the CSRE building as against 3-4 GJ/m(2) for conventional burnt clay brick load bearing masonry buildings. (C) 2013 Elsevier B.V. All rights reserved.

Synthesis, Characterization and Properties of Single-Walled Carbon Nanohorns

Single-walled nanohorns (SWNHs) have been prepared by sub-merged arc discharge of graphite electrodes in liquid nitrogen. The samples were examined by scanning electron microscopy, transmission electron microscopy and Raman spectroscopy. Nitrogen and boron doped SWNHs have been prepared by the sub-merged arc discharge method using melamine and elemental boron as precursors. Intensification of Raman D-band and stiffening of G-band has been observed in the doped samples. The electrical resistance of the SWNHs varies in opposite directions with nitrogen and boron doping. Functionalization of SWNHs through amidation has been carried out for solubilizing them in non-polar solvents. Water-soluble SWNHs have been produced by acid treatment and non-covalent functionalization with a coronene salt. SWNHs have been decorated with nanoparticles of Au, Ag and Pt. Interaction of electron donor (tetrathiafulvalene, TTF) and acceptor molecules (tetracyanoethylene, TCNE) with SWNHs has been investigated by Raman spectroscopy. Progressive softening and stiffening of Raman G-band has been observed respectively with increase in the concentration of TTF and TCNE.

Analysis of fatigue crack growth in reinforced concrete beams

Mechanical behavior of reinforced concrete members is influenced by the action of unknown crack bridging reactions of rebars. Under cyclic loading, due to progressive growth of cracks, this bridging action contributes to the overall strength, stiffness and hysteretic behavior of the member. In this work, fatigue behavior of reinforced concrete beams are studied using a crack propagation law, developed using dimensional analysis for plain concrete with the effect of reinforcement being simulated through constraint exerted on the crack opening. The parameters considered in the model are fracture toughness, crack length, loading ratio and structural size. A numerical procedure is followed to compute fatigue life of RC beams and the dissipated energy in the steel reinforcement due to the shake down phenomenon under cyclic loading. Through a sensitivity study, it is concluded that the structural size is the most sensitive parameter in the fatigue crack propagation phenomenon. Furthermore, the residual moment carrying capacity of an RC member is determined as a function of crack extension by including the bond-slip mechanism.

Vertical Uplift Resistance of Pipes Buried in Sand

By incorporating the variation of peak soil friction angle (phi) with mean principal stress (sigma(m)), the effect of pipe diameter (D) on the vertical uplift resistance of a long horizontal pipeline embedded in sand has been investigated. The analysis has been performed by using the lower bound finite-element limit analysis in combination with nonlinear optimization. Three well-defined phi versus sigma(m) curves reported from literature for different sands have been used. It is observed that for a given embedment ratio, with an increase in pipe diameter, the magnitude of the uplift factor (F-gamma) reduces quite significantly, which indicates the importance of considering scale effects while designing buried pipe lines. The scale effects have been found to become even more substantial with an increase in the embedment ratio. The analysis compares well with various theoretical results reported from literature. On the other hand, as compared to available centrifuge test results, the present analysis has been found to provide quite a higher magnitude of the uplift resistance when the theoretical prediction is based on peak soil friction angle. However, if the theoretical analysis is performed by using the friction angle that accounts for the progressive shear failure, the difference between the theoretical and centrifuge test results decreases quite significantly.(C) 2013 American Society of Civil Engineers.

Do stable isotopes in carbonate cement of Mio-Pleistocene Himalayan sediments record paleoecological and paleoclimatic changes?

Non-pedogenic carbonates, such as carbonate cement and nodules in the sandstones, are quite common in the terrestrial geological record. Unlike pedogenic carbonates, their stable isotope ratios lack investigations for paleo-climatic reconstructions. The present investigation therefore, explores the possibility of use of stable isotope studies of non-pedogenic carbonates from the Mb-Pleistocene Siwalik Group of sediments exposed in the Ramnagar sub-basin of the NW Himalaya. Petrographic studies reveal the dominance of micrite fabric in carbonate nodules both of pedogenic and non-pedogenic samples irrespective of specific stratigraphic unit However, calcite as cement in the sandstones shows the dominance of micrite fabric in the younger in age sediments. Seventy-two non-pedogenic carbonate samples from the carbonate nodules and cement in the Siwalik sandstones, ranging in age between similar to 1 Ma and 12.2 Ma, were analyzed for delta C-13 and delta O-18 values. The delta C-13 values vary from -24.77 parts per thousand to -1.1 parts per thousand and delta O-18 values vary from -15.34 parts per thousand to -7.81 parts per thousand. Pedogenic and non-pedogenic carbonates ranging in age between similar to 1 Ma and 6 Ma have largely similar delta C-13 values and the range of delta C-13 values indicate the dominance of C-4 type of vegetation. However, unlike pedogenic carbonates which showed the dominance of C-3 type of vegetation pre- 7 Ma on the basis of delta C-13 -depleted isotopic values (Singh et al., 2011), delta C-13 values are largely enriched in the corresponding aged non-pedogenic carbonates revealing no information on specific type of vegetation. Likewise, paleoprecipitational reconstructions from delta O-18 values in pedogenic carbonates showed a progressive increase in aridity from similar to 12 Ma to recent excluding short term increases in rainfall/monsoon intensity at around 10 Ma, 5 Ma, and 1.8 Ma (Singh et al., 2012). On the contrary, such reconstructions are not possible from the delta O-18 values of non-pedogenic carbonates and indeed the delta O-18 values of non-pedogenic carbonates are largely depleted to as much as 6 parts per thousand from the corresponding pedogenic carbonates. Such differences in delta C-13 and delta O-18 values of non-pedogenic carbonates from pedogenic carbonates are primarily due to the dependence of the former on groundwater conditions responsible for precipitating carbonate. Further, a comparison of isotopic values between non-pedogenic and pedogenic carbonates can be interpreted that post-6 Ma and pre-6 Ma non-pedogenic carbonates were largely formed by shallow and deep groundwater conditions respectively. The result of these investigative studies therefore, suggests that the stable delta C-13 and delta O-18 values of non-pedogenic carbonates, unlike the pedogenic carbonates and irrespective of nature of calcite fabric, showed their little importance in paleoclimatic and paleoecological reconstructions. (C) 2014 Elsevier B.V. All rights reserved.

In vitro osteogenic cell proliferation, mineralization, and in vivo osseointegration of injection molded high-density polyethylene-based hybrid composites in rabbit animal model

The present work reports the biocompatibility property of injection molded HDPE-HA-Al2O3 hybrid composites. In vitro cytocompatibility results reveal that osteogenic cell viability and bone mineralization are favorably supported in a statistically significant manner on HDPE-20% HA-20% Al2O3 composite, in comparison to HDPE-40 wt.% HA or HDPE-40 wt.% Al2O3. The difference in cytocompatibility property is explained in terms of difference in substrate wettability/surface energy and importantly, both the cell proliferation at 7 days or bone mineralization at 21 days on HDPE-20% HA-20% Al2O3 composite are either comparable or better than sintered HA. The progressive healing of cylindrical femoral bone defects in rabbit animal model was assessed by implantation experiments over 1, 4 and 12 weeks. Based on the histological analysis as well as histomorphometrical evaluation, a better efficacy of HDPE-20% HA-20% Al2O3 over high-density polyethylene (HDPE) for bone regeneration and neobone formation at host bone-implant interface was established. Taken together, the present study unequivocally establishes that despite the presence of 20% Al2O3, HDPE-based hybrid composites are as biocompatible as HA in vitro or better than HDPE in vivo.

SUSTAINABILITY IN TRADITIONAL HANDLOOMS

The handloom sector constitutes a distinct feature of the rich cultural heritage of India and plays a vital role in the economy and cultural identity of the country. It is an ancient industry and is source of livelihood for many villages in India. Its spread varies in style, practice and scale throughout the country - in certain regions it is has a proficient industry, while in others its establishment is localized, where it is a family-based activity. While, hand-woven fabrics are well-sought after both nationally and globally, weavers currently remain marginalized and often impoverished. The well-set power loom industry has further added to their woes. Given the progressive failure of centralized production and distribution ideologies, handlooms represent a decentralized distributed means of livelihood security, environmental consonance, employment generation, skill enhancement, cultural (diversity, identity and) integrity and sustainability. The fabrics and dyes used in the handloom industry are environment-friendly and often unique to a region (based on available skill and resources). The paper comprehensively evaluates and forecasts sustainability in the context of traditional handlooms in India. Results of the study and recommendations are presented in this paper.

Sensitivity of polarization fluctuations to the nature of protein-water interactions: Study of biological water in four different protein-water systems

Since the time of Kirkwood, observed deviations in magnitude of the dielectric constant of aqueous protein solution from that of neat water (similar to 80) and slower decay of polarization have been subjects of enormous interest, controversy, and debate. Most of the common proteins have large permanent dipole moments (often more than 100 D) that can influence structure and dynamics of even distant water molecules, thereby affecting collective polarization fluctuation of the solution, which in turn can significantly alter solution's dielectric constant. Therefore, distance dependence of polarization fluctuation can provide important insight into the nature of biological water. We explore these aspects by studying aqueous solutions of four different proteins of different characteristics and varying sizes, chicken villin headpiece subdomain (HP-36), immunoglobulin binding domain protein G (GB1), hen-egg white lysozyme (LYS), and Myoglobin (MYO). We simulate fairly large systems consisting of single protein molecule and 20000-30000 water molecules (varied according to the protein size), providing a concentration in the range of similar to 2-3 mM. We find that the calculated dielectric constant of the system shows a noticeable increment in all the cases compared to that of neat water. Total dipole moment auto time correlation function of water < dM(W) (0)delta M-W (t) > is found to be sensitive to the nature of the protein. Surprisingly, dipole moment of the protein and total dipole moment of the water molecules are found to be only weakly coupled. Shellwise decomposition of water molecules around protein reveals higher density of first layer compared to the succeeding ones. We also calculate heuristic effective dielectric constant of successive layers and find that the layer adjacent to protein has much lower value (similar to 50). However, progressive layers exhibit successive increment of dielectric constant, finally reaching a value close to that of bulk 4-5 layers away. We also calculate shellwise orientational correlation function and tetrahedral order parameter to understand the local dynamics and structural re-arrangement of water. Theoretical analysis providing simple method for calculation of shellwise local dielectric constant and implication of these findings are elaborately discussed in the present work. (C) 2014 AIP Publishing LLC.

Structural, magnetic and electrochemical investigation of novel binary Na2-x(Fe1-yMny)P2O7 (0 <= y <= 1) pyrophosphate compounds for rechargeable sodium-ion batteries

Pyrophosphate cathodes have been recently reported as a competent family of insertion compounds for sodium-ion batteries. In the current study, we have investigated the binary Na2 - x(Fe1 - yMny)P2O7 (0 <= y <= 1) pyrophosphate family, synthesized by the classical solid-state method. They form a continuous solid solution maintaining triclinic P-1 (#2) symmetry. The local structural coordination differs mainly by different degrees of Na site occupancy and preferential occupation of the Fe2 site by Mn. The structural and magnetic properties of these mixed-metal pyrophosphate phases have been studied. In each case, complete Fe3+/Fe2+ redox activity has been obtained centered at 3 V vs. Na. The Fe3+/Fe2+ redox process involves multiple steps between 2.5 and 3 V owing to Na-cation ordering during electrochemical cycling, which merge to form a broad single Fe3+/Fe2+ redox peak upon progressive Mn-doping. (C) 2014 Elsevier B.V. All rights reserved.

Dendritic atrophy constricts functional maps in resonance and impedance properties of hippocampal model neurons

A gradient in the density of hyperpolarization-activated cyclic-nucleotide gated (HCN) channels is necessary for the emergence of several functional maps within hippocampal pyramidal neurons. Here, we systematically analyzed the impact of dendritic atrophy on nine such functional maps, related to input resistance and local/transfer impedance properties, using conductance-based models of hippocampal pyramidal neurons. We introduced progressive dendritic atrophy in a CA1 pyramidal neuron reconstruction through a pruning algorithm, measured all functional maps in each pruned reconstruction, and arrived at functional forms for the dependence of underlying measurements on dendritic length. We found that, across frequencies, atrophied neurons responded with higher efficiency to incoming inputs, and the transfer of signals across the dendritic tree was more effective in an atrophied reconstruction. Importantly, despite the presence of identical HCN-channel density gradients, spatial gradients in input resistance, local/transfer resonance frequencies and impedance profiles were significantly constricted in reconstructions with dendrite atrophy, where these physiological measurements across dendritic locations converged to similar values. These results revealed that, in atrophied dendritic structures, the presence of an ion channel density gradient alone was insufficient to sustain homologous functional maps along the same neuronal topograph. We assessed the biophysical basis for these conclusions and found that this atrophy-induced constriction of functional maps was mediated by an enhanced spatial spread of the influence of an HCN-channel cluster in atrophied trees. These results demonstrated that the influence fields of ion channel conductances need to be localized for channel gradients to express themselves as homologous functional maps, suggesting that ion channel gradients are necessary but not sufficient for the emergence of functional maps within single neurons.

Changes in the expression of DNA double strand break repair genes in primordial follicles from immature and aged rats

Oocytes present at birth undergo a progressive process of apoptosis in humans and other mammals as they age. Accepted opinion is that no fresh oocytes are produced other than those present at the time of birth. Studies have shown that DNA repair genes in oocytes of mice and women decline with age, and lack of these genes show higher DNA breaks and increased oocyte death rates. In contrast to the ethical problems associated with monitoring the changes in DNA double-strand breaks in oocytes from young and old humans, it is relatively easy to carry out such a study using a rodent model. In this study, the mRNA levels of DNA repair genes are compared with protein products of some of the genes in the primordial follicles isolated from immature (18-20 days) and aged (400-450 days) female rats. Results revealed a significant decline in mRNA levels of BRAC1 (P < 0.01), RAD51 (P < 0.05), ERCC2 (P < 0.05), and H2AX (P < 0.01) of DNA repair genes and phospho-protein levels of BRAC1 (P < 0.01) and H2AX (P < 0.05) in primordial follicles of aged rats. Impaired DNA repair is confirmed as a mechanism of oocyte ageing. (C) 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.