Curcumin Pyrazole and its derivative (N-(3-Nitrophenylpyrazole) Curcumin inhibit aggregation, disrupt fibrils and modulate toxicity of Wild type and Mutant alpha-Synuclein

Accumulating evidence suggests that deposition of neurotoxic a-synuclein aggregates in the brain during the development of neurodegenerative diseases like Parkinson's disease can be curbed by anti-aggregation strategies that either disrupt or eliminate toxic aggregates. Curcumin, a dietary polyphenol exhibits anti-amyloid activity but the use of this polyphenol is limited owing to its instability. As chemical modifications in curcumin confiscate this limitation, such efforts are intensively performed to discover molecules with similar but enhanced stability and superior properties. This study focuses on the inhibitory effect of two stable analogs of curcumin viz. curcumin pyrazole and curcumin isoxazole and their derivatives against a-synuclein aggregation, fibrillization and toxicity. Employing biochemical, biophysical and cell based assays we discovered that curcumin pyrazole (3) and its derivative N-(3-Nitrophenylpyrazole) curcumin (15) exhibit remarkable potency in not only arresting fibrillization and disrupting preformed fibrils but also preventing formation of A11 conformation in the protein that imparts toxic effects. Compounds 3 and 15 also decreased neurotoxicity associated with fast aggregating A53T mutant form of a-synuclein. These two analogues of curcumin described here may therefore be useful therapeutic inhibitors for the treatment of a-synuclein amyloidosis and toxicity in Parkinson's disease and other synucleinopathies.

Influence of soil type on the properties of termite mound nests in Southern India

Termite mounds are conspicuous features in many tropical ecosystems. Their shape and soil physicochemical properties have been suggested to result from the termites ecological need to control the temperature and humidity within their nests and protect themselves from predators. This study aimed to determine the influence of the parent soil properties on the shape and soil physical and chemical properties of termite mounds. Termite mounds built by the fungus-growing termite species Odontotermes obesus were compared in two forests with different soil properties (Ferralsol or Luvisol) in Southern India. Our findings confirm that soil properties influence the physicochemical characteristics of mound material and may affect the shape, but these impacts are mostly independent of the size of the mounds (i.e., the age of the colonies). Mound walls were more enriched in clay and impoverished in C and N in the Luvisol than the Ferralsol. However, their shape was more complex in the Ferralsol than the Luvisol, suggesting a possible link between the clay content in soil and the shape of termite mounds. The results also suggest that clay becomes enriched in O. obesus mound walls through a more passive process rather than solely by particle selection, and that termite mound shape results from the soil properties rather than the ecological needs of termites. In conclusion, although ecologists have mainly focused upon the influence of termite ecological needs on their nest properties, this study highlights the need for a better understanding about the role of the soil pedological properties and, as a consequence, how these properties drive the establishment and survival of termites in tropical ecosystems. (C) 2015 Elsevier B.V. All rights reserved.

Part I: Physical Insights Into the Two-Stage Breakdown Characteristics of STI-Type Drain-Extended pMOS Device

In this paper, we study breakdown characteristics in shallow-trench isolation (STI)-type drain-extended MOSFETs (DeMOS) fabricated using a low-power 65-nm triple-well CMOS process with a thin gate oxide. Experimental data of p-type STI-DeMOS device showed distinct two-stage behavior in breakdown characteristics in both OFF-and ON-states, unlike the n-type device, causing a reduction in the breakdown voltage and safe operating area. The first-stage breakdown occurs due to punchthrough in the vertical structure formed by p-well, deep n-well, and p-substrate, whereas the second-stage breakdown occurs due to avalanche breakdown of lateral n-well/p-well junction. The breakdown characteristics are also compared with the STI-DeNMOS device structure. Using the experimental results and advanced TCAD simulations, a complete understanding of breakdown mechanisms is provided in this paper for STI-DeMOS devices in advanced CMOS processes.

Part II: Design of Well Doping Profile for Improved Breakdown and Mixed-Signal Performance of STI-Type DePMOS Device

Shallow-trench isolation drain extended pMOS (STI-DePMOS) devices show a distinct two-stage breakdown. The impact of p-well and deep-n-well doping profile on breakdown characteristics is investigated based on TCAD simulations. Design guidelines for p-well and deep-n-well doping profile are developed to shift the onset of the first-stage breakdown to a higher drain voltage and to avoid vertical punch-through leading to early breakdown. An optimal ratio between the OFF-state breakdown voltage and the ON-state resistance could be obtained. Furthermore, the impact of p-well/deep-n-well doping profile on the figure of merits of analog and digital performance is studied. This paper aids in the design of STI drain extended MOSFET devices for widest safe operating area and optimal mixed-signal performance in advanced system-on-chip input-output process technologies.

Numerical solution of the incompressible Navier-Stokes equations with an upwind compact difference scheme

A new finite difference method for the discretization of the incompressible Navier-Stokes equations is presented. The scheme is constructed on a staggered-mesh grid system. The convection terms are discretized with a fifth-order-accurate upwind compact difference approximation, the viscous terms are discretized with a sixth-order symmetrical compact difference approximation, the continuity equation and the pressure gradient in the momentum equations are discretized with a fourth-order difference approximation on a cell-centered mesh. Time advancement uses a three-stage Runge-Kutta method. The Poisson equation for computing the pressure is solved with preconditioning. Accuracy analysis shows that the new method has high resolving efficiency. Validation of the method by computation of Taylor's vortex array is presented.

Characteristics and Sub-Characteristics of Two-Dimensional Parabolized Stability Equations

特征分析表明：对原始扰动量的抛物化稳定性方程组(PSE),它在亚超音速区分别具有椭圆和抛物特性,给出PSE特征对马赫数的依赖关系,阐明PSE仅把信息对流-扩散传播特性抛物化,而保留了信息对流-扰动传播特性,因此PSE应称为扩散抛物化稳定性方程(DPSE)。

Closed form solutions of T-stress in plane elasticity crack problems

The T-stress is considered as an important parameter in linear elastic fracture mechanics. In this paper, several closed form solutions of T-stress in plane elasticity crack problems in an infinite plate are investigated using the complex potential theory. In the line crack case, if the applied loading is the remote stress or the concentrated forces, the T-stress can be derived from the basic field. Here, the basic field is defined as the field caused by the applied loading in the infinite plate without the crack. For the circular are crack, the T-stress can be abstracted from a known solution. For the cusp crack problems, the T-stress can be separated from the obtained stress solution for which the conformal mapping technique is used.

Character of simplified Navier-Stokes (SNS) equations near separation point for two-dimensional laminar flow over a flat plate

It is proved that the simplified Navier-Stokes (SNS) equations presented by Gao Zhi[1], Davis and Golowachof-Kuzbmin-Popof (GKP)[3] are respectively regular and singular near a separation point for a two-dimensional laminar flow over a flat plate. The order of the algebraic singularity of Davis and GKP equation[2,3] near the separation point is indicated. A comparison among the classical boundary layer (CBL) equations, Davis and GKP equations, Gao Zhi equations and the complete Navier-Stokes (NS) equations near the separation point is given.

Hierarchal structure of the simplified Navier-Stokes equations (SNSE) and its mechanical connotation and application

The hierarchial structure and mathematical property of the simplified Navier-Stokesequations (SNSE) are studied for viscous flow over a sphere and a jet of compressible flu-id. All kinds of the hierarchial SNSE can be divided into three types according to theirmathematical property and also into five groups according to their physical content. Amultilayers structure model for viscous shear flow with a main stream direction is pre-sented. For the example of viscous incompressible flow over a flat plate there existthree layers for both the separated flow and the attached flow; the character of thetransition from the three layers of attached flow to those of separated flow is elucidated.A concept of transition layer being situated between the viscous layer and inviscidlayer is introduced. The transition layer features the interaction between viscous flow andinviscid flow. The inner-outer-layers-matched SNSE proposed by the present author inthe past is developed into the layers matched (LsM)-SNSE.

Simplified Navier-Stokes equations (SNSE)

Ten kinds of the simplified Navier-Stokes equations (SNSE) are reviewed and also used to calculate the Jeffery-Hamel flow as well as to analyze briefly the seven kinds of flows to which the exact solutions of the complete Navier-Stokes equations (CNSE) have been found. Analysis shows that the actual differences among the solutions of the different SNSE can go beyond the range of the order of magnitude of Re-1/2 and result even in different flow patterns, therefore, how to choose the viscous terms included in the SNSE is worthy of notice where Re=S∞u∞ L/μ∞ is the Reynolds numbers. For the aforesaid eight kinds of flows, the solutions to the inner-outer-layer-matched SNSE and to the thin-layer-2-order SNSE agree completely with the exact solutions to CNSE. But the solutions to all the other SNSE are not completely consistent with the exact solutions to CNSE and not a few of them are actually the solutions of the classical boundary layer theory. The innerouter-layer-matched SNSE contains the shear stress causing angular displacement of the inormal axis with respect to the streamwise axis and the normal stress causing expansion-contraction in the direction of the normal axis and the viscous terms being of the order of magnitude of the normal stress; and it can also reasonably treat the inertial terms as well as the relation between the viscous and inertial terms. Therefore, it seems promising in respects of both mechanics and mathematics.