Reduced VDAC1, Maintained Mitochondrial Dynamics and Enhanced Mitochondrial Biogenesis in a Transgenic Tau Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most common forms of neurodegeneration, defined by reduced cognitive function, which is caused by the gradual death of neurons in the brain. Recent studies have shown an age-dependent rise in the levels of voltage-dependent anion channel 1 (VDAC1) in AD. In addition, we discovered an aberrant interaction between VDAC1 and P-TAU in the brains of AD patients, which led to abnormalities in the structural and functional integrity of the mitochondria. The purpose of our study is to understand the protective effects of reduced VDAC1 against impaired mitochondrial dynamics and defective mitochondrial biogenesis in transgenic TAU mice. Recently, we crossed heterozygote VDAC1 knockout (VDAC1^+/−) mice with transgenic TAU mice to obtain double-mutant VDAC1^+/−/TAU mice. Our goal was to evaluate whether a partial decrease in VDAC1 lessens the amount of mitochondrial toxicity in transgenic Tau (P301L) mice. We found that mitochondrial fission proteins were significantly reduced, and mitochondrial fusion and biogenesis proteins were increased in double-mutant mice compared to TAU mice. On the basis of these discoveries, the current work may have significance for the development of reduced-VDAC1-based treatments for individuals suffering from AD as well as other tauopathies.     

Metabolic Pathways for Observed Impacts of Crop Load on Floral Induction in Apple

The triggers of biennial bearing are thought to coincide with embryonic development in apple and occurs within the first 70 days after full bloom (DAFB). Strong evidence suggests hormonal signals are perceived by vegetative apple spur buds to induce flowering. The hormonal response is typically referred to as the floral induction (FI) phase in bud meristem development. To determine the metabolic pathways activated in FI, young trees of the biennial bearing cultivar ‘Nicoter’ and the less susceptible cultivar ‘Rosy Glow’ were forced into an alternate cropping cycle over five years and an inverse relationship of crop load and return bloom was established. Buds were collected over a four-week duration within 70 DAFB from trees that had maintained a four-year biennial bearing cycle. Metabolomics profiling was undertaken to determine the differentially expressed pathways and key signalling molecules associated with biennial bearing. Marked metabolic differences were observed in trees with high and low crop load treatments. Significant effects were detected in members of the phenylpropanoid pathway comprising hydroxycinnamates, salicylates, salicylic acid biosynthetic pathway intermediates and flavanols. This study identifies plant hormones associated with FI in apples using functional metabolomics analysis.     

Cost optimal, parallel reliability systems with fixed repair sanction

Optimisation methods under varied criteria for different parameters in stochastic reliability systems are being increasingly developed and have been reported in recent literature. The large interest evinced in this fascinating area is primarily due to its applicational value and operational role in the decision making process. Recently a parallel system has been considered and the optimal number of units discussed, as well as optimal replacement times for the system based on acquisition and replacement costs.In this paper we consider an improved version of the model formulation, by bringing in additionally the maintenance and per unit repair time costs, and develop a procedure to obtain the optimal number of components in the system with the condition that the system is allowed to undergo a prefixed maximum number of repairs, after which the system is to be replaced.The applicational use of the results is illustrated through numerical work, specialising to some known laws governing the system parameters and corresponding to different fixed number of repair sanctions.     

Remote sensing and GIS for locating favourable zones of lead-zinc-copper mineralization in Rajpura-Dariba area,Rajasthan, India

This paper reports the results of a pilot study carried out in RajpuraDariba area, Rajasthan, for locating favourable zones of lead-zinc-copper (Pb-Zn-Cu) mineralization using remote sensing, Geographical Information System (GIS) and geostatistical modelling techniques. Remotely sensed data, both aerial and satellite, were used to update the existing geological map. ATLAS GIS software and multivariate geostatistical techniques were used to analyse and integrate different types of geological and geophysical datasets. The Favourability Index (FI) maps prepared during this study show the occurrence of three favourable zones for Pb-Zn-Cu mineralization. They are: (i) around and north of Rawan ka Khera; (ii) isolated spots between Ruppura and Bhupalsagar; and (iii) north of Dhani. Selective geochemical sampling and resistivity profiling carried out in these favourable zones indicated the presence of geochemical anomalies (anomalous concentrations of Zn and Cu) and low/moderate resistivity zones, respectively. Recent drilling carried out by the Department of Mines and Geology (DMG), Rajasthan, at about 2.5 km north of Rawan ka Khera (one of the predicted favourable zones) indicated evidence of Cu mineralization at a depth of about 70 m.     

Strength of lime–fly ash compacts using different curing techniques and gypsum additive

Lime–fly ash mixtures are exploited for the manufacture of fly ash bricks finding applications in load bearing masonry. Lime–pozzolana reactions take place at a slow pace under ambient temperature conditions and hence very long curing durations are required to achieve meaningful strength values. The present investigation examines the improvements in strength development in lime–fly ash compacts through low temperature steam curing and use of additives like gypsum. Results of density–strength–moulding water content relationships, influence of lime–fly ash ratio, steam curing and role of gypsum on strength development, and characteristics of compacted lime–fly ash–gypsum bricks have been discussed. The test results reveal that (a) strength increases with increase in density irrespective of lime content, type of curing and moulding water content, (b) optimum lime–fly ash ratio yielding maximum strength is about 0.75 in the normal curing conditions, (c) 24 h of steam curing (at 80°C) is sufficient to achieve nearly possible maximum strength, (d) optimum gypsum content yielding maximum compressive strength is at 2%, (e) with gypsum additive it is possible to obtain lime–fly ash bricks or blocks having sufficient strength (>10 MPa) at 28 days of normal wet burlap curing.     

Fluorescence properties and energy transfer mechanism of Sm ion in lead telluroborate glasses

We report the fluorescence properties of Sm³⁺-doped lead telluroborate glasses of composition PbF₂.TeO₂.H₃BO₃.Sm₂O₃ as a function of Sm³⁺ concentration. A Judd-Ofelt scheme was used to determine the intensity parameters and radiative properties of Sm³⁺ ion. The emission and decay measurements were carried out at 402 nm excitation. Beyond 1.0 mol% Sm³⁺ concentration, the luminescence quenching is observed. The decay curves of ⁴G_5/2 level are well fitted to a single exponential function. The evaluated radiative properties suggest that the ⁴G_5/2 → ⁶H_7/2 transition is responsible for reddish-orange luminescence which might be used in the development of visible lasers.     

A new strain hardening model for rate-dependent crystal plasticity

This paper presents a crystal plasticity based finite element analysis employing the new microstructure-based strain hardening model recently presented by Saimoto and Van Houtte (2011) [7] to simulate formability and texture evolution in the commercial aluminum alloy 5754. Simulations are performed to compare the predictive capability of the new hardening model against the common work hardening models using a rate-dependent plasticity formulation. The parameters in the numerical models are calibrated using the X-ray data published by Iadicola et al. (2008) [9] for the aluminum sheet alloy 5754. The predictions of the model for balanced biaxial tension and in-plane plane-strain tests are compared against experimental observations presented in Iadicola et al. (2008) [9]. It is concluded that the new model provides the best predictions of the large strain behavior of Aluminum sheet alloy 5754 subjected to various strain paths.     

Estimation of Melt Pool Dimensions, Thermal Cycle, and Hardness Distribution in the Laser-Engineered Net Shaping Process of Austenitic Stainless Steel

Laser engineered net shaping (LENS) and other similar processes facilitate building of parts with freeform shapes by melting and deposition of metallic powders layer by layer. A-priori estimation of the layerwise variations in peak temperature, build dimension, cooling rate, and mechanical property is requisite for successful application of these processes. We present here an integrated approach to estimate these build attributes. A three-dimensional (3-D) heat transfer analysis based on the finite element method is developed to compute the layerwise variation in thermal cycles and melt pool dimensions in the single-line multilayer wall structure of austenitic stainless steel. The computed values of cooling rates during solidification are used to estimate the layerwise variation in cell spacing of the solidified structure. A Hall–Petch like relation using cell size as the structural parameter is used next to estimate the layerwise hardness distribution. The predicted values of layer widths and build heights have depicted fair agreement with the corresponding measured values in actual deposits. The estimated values of layerwise cell spacing and hardness remain underpredicted and overpredicted, respectively. The slight underprediction of the cell spacing is attributed to the possible overestimation of the cooling rates that may have resulted due to the neglect of convective heat transport within the melt pool. The overprediction of the layerwise hardness is certainly due to the underprediction of corresponding cell spacing. The application of Hall–Petch coefficients, which is strictly valid for wrought and annealed grain structures, to estimate the hardness of as-solidified cellular structures may have also contributed to the overprediction of the layerwise hardness.     

Microstructure and Mechanical Properties of Friction Stir Lap Welded Aluminum Alloy AA2014

Friction stir lap welds were produced in 3 mm thick Alclad sheets of Al alloy 2014-T4 using two different tools (with triangular and threaded taper cylindrical pins). The effects of tool geometry on weld microstructure, lap-shear performance and failure mode were investigated. The pin profile was found to significantly influence the hook geometry, which in turn strongly influenced the joint strength and the failure mode. Welds produced in alloy 2014-T4 Alclad sheets by using triangular and threaded taper cylindrical tools exhibited an average lap-shear failure load of 16.5 and 19.5 kN, respectively, while the average failure load for standard riveted joints was only 3.4 kN. Welds produced in alloy 2014-T6 Alclad sheets and in alloy 2014-T4 bare sheets (i.e., no Alclad) were comparatively evaluated with those produced in alloy 2014-T4 Alclad sheets. While the welds made (with threaded taper cylindrical tool) in T6 and T4 conditions showed very similar lap-shear failure loads, the joint efficiency of the welds made in T6 condition (43%) was considerably lower (because of the higher base material strength) than those made in T4 condition (51%). The Alclad layers were found to present no special problems in friction stir lap welding. Welds made with triangular tool in alloy 2014-T4 Alclad and bare sheets showed very similar lap-shear failure loads. The present work provides some useful insights into the use of friction stir welding for joining Al alloys in lap configuration.     

Near-Field Scanning Nanophotonic Microscopy—Breaking the Diffraction Limit Using Integrated Nano Light-Emitting Probe Tip

We introduce a novel scanning ldquonanophotonicrdquo microscope through monolithic integration of a nanoscale LED (Nano-LED) on a silicon cantilever. We review two recent trends of incorporating miniature light sources on the scanning probes for near-field scanning optical microscopy: one is to attach fluorephores at the tip to define a small light source, while the other is to integrate an LED and a nanometer aperture into scanning probes, based on silicon microfabrication techniques. The creation of Nano-LED combines the advantages of previous two approaches: no external sources are required and the reduction of the light source size directly leads to resolution improvement. Two types of Nano-LEDs have been successfully demonstrated utilizing nanofabrication and microelectromechanical systems technologies: 1) formation of thin silicon dioxide light-emitting layer between heavily doped p + and n+ silicon layers created by a focused ion beam and 2) electrostatic trapping and excitation of CdSe/ZnS core-shell nanoparticles in a nanogap. We employed these probes into a standard near-field scanning and excitation setup. The probe successfully measured optical as well as topographic images of chromium test patterns with imaging resolutions of 400 and 50 nm, respectively. In addition, the directional resolution dependence of the acquired images suggests the size and shape of the light source. To our knowledge, these results are probably the first successful near-field images directly measured by such tip-embedded light sources. With the potential emission capability from near UV to IR and additional mass producibility, the nanophotonic microscope presents exciting opportunities in near-field optics, integrated circuit technology, nanomanufacturing and molecular imaging, and sensing in biomedicine.