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.

A C-0 Interior Penalty Method for a Fourth-order Variational Inequality of the Second Kind

In this article, we propose a C-0 interior penalty ((CIP)-I-0) method for the frictional plate contact problem and derive both a priori and a posteriori error estimates. We derive an abstract error estimate in the energy norm without additional regularity assumption on the exact solution. The a priori error estimate is of optimal order whenever the solution is regular. Further, we derive a reliable and efficient a posteriori error estimator. Numerical experiments are presented to illustrate the theoretical results. (c) 2015Wiley Periodicals, Inc.

Crack problems of piezoelectric materials

This paper presents an analysis of crack problems in homogeneous piezoelectrics or on the interfaces between two dissimilar piezoelectric materials based on the continuity of normal electric displacement and electric potential across the crack faces. The explicit analytic solutions are obtained for a single crack in piezoelectrics or on the interfaces of piezoelectric bimaterials. A class of boundary problems involving many cracks is also solved. For homogeneous materials it is found that the normal electric displacement D-2 induced by the crack is constant along the crack faces which depends only on the applied remote stress field. Within the crack slit, the electric fields induced by the crack are also constant and not affected by the applied electric field. For the bimaterials with real H, the normal electric displacement D-2 is constant along the crack faces and electric field E-2 has the singularity ahead of the crack tip and a jump across the interface.

A Passage to India: from novel to film. Some problems of "translation"

Eguíluz, Federico; Merino, Raquel; Olsen, Vickie; Pajares, Eterio; Santamaría, José Miguel (eds.)

Problems of industrial fisheries development in the Cross River State

The industrial fisheries as opposed to artisanal fisheries in Cross River State, Nigeria, is discussed, considering the prospect of industrial fisheries in the State and identifying the major fish and shrimp resources within the coastal waters. Industrial fishing was introduced in 1973 when the state government invited a Japaneese company to carry out a joint exploratory shrimp fishing venture. The contributions made by the Seastate Seafoods Company, the Eyib's Nutritional Food and the Arawak Fishing Companies towards the increase in the number of fishing fleet in the state are noted.

Evidence of dopant type-inversion and other radiation damage effects of the CDF silicon detectors

xix, 213 p.