Global Competition Versus Regional Interests: FDI and Pharmaceuticals in India

This essay explores the economic dynamics of global competition versus regional interests corresponding to the treatment of intellectual property rights (IPRs) in India and the relative effects of such policies on its domestic pharmaceutical industry. The scope of considerations are formally limited to variables implicative of the transnational flow of capital within the pharmaceuticals industry, most specifically those pertaining to foreign direct investment (FDI).   India, as the second most populated country in the world, has been the focus of much discussion regarding patent violations in its pharmaceutical industry. International pressures and membership covenants of the World Trade Organization (WTO) have succeeded in structuring policy such that process patents are now legitimized. This has brought dilemmas between global and regional conflicts of interest to open discussion, and has become a pressing political agenda among various industry stakeholders. This paper discusses the history of Indian internal protection in the pharmaceutical industry and suggests ways in which India may continue to benefit when regulatory barriers are reduced and global trade covenants are abided. The  essay  first examines trends in global FDI and Knowledge Process Outsourcing (KPO). It highlights changes to Indian policy, and subsequently discusses other matters associated with the protection of IPRs including parallel imports, price discrimination, and corruption. Lastly, suggestions are made for viable ways of enabling India to comply with WTO mandates for participation in the global marketplace, while concurrently attending to its domestic needs as well.

The validity of eight neoclassical facial canons in the Turkish adults

The neoclassical canons were used to define the proportions between various areas of the head and face. Therefore, this study was done to establish the neoclassical canons of facial proportions in Turkish adults. A total of 200 healthy adults 20 to 35 years of age were examined. Using anthropometric landmarks, 5 horizontal and 9 vertical direct measurements were made on the faces with a sliding calliper. Results have been compared with 8 neoclassical facial canons. When comparing between sexes, a significant difference has been found in all measurements except the upper facial width, left eye-fissure width, forehead height I and II (p < 0.005). The nasofacial proportion has been found to include the most proportional subjects (33%) followed by the orbito-nasal (30%), the orbital proportion (25%) and the naso-oral proportion (17%) in the female. Considering the male, the orbital proportion has been found to include the most proportional subjects (23%) followed by the orbito-nasal proportion (21%), naso-facial proportion (19%) and the naso-oral proportion (17%). The neoclassical canons have been shown to rarely be applicable to Turkish adults and our results may contribute to determine the concepts of transcultural facial structures

A composite sandwich plate with a novel core design

© 2018 Elsevier Ltd In this study, a new core design is introduced for sandwich composite structures. Its strength and failure behavior are investigated via three-point bending tests. E-glass-fiber-reinforced epoxy resin is selected as the material for both the core and the face sheets. The core has an egg-crate shape. Acoustic emission (AE) method is used to detect the progression of damage. Signals due to elastic waves caused by activated damage mechanisms are investigated in order to identify the corresponding failure modes. A finite element model of the sandwich structure is developed to predict the failure behavior of the specimens under the loading conditions in the tests. A promising agreement between the results of the finite element model and the experiments is observed. The force-deflection-relation, the failure load as well as the region where damage initiates are accurately predicted

Deep brain stimulation, histone deacetylase inhibitors and glutamatergic drugs rescue resistance to fear extinction in a genetic mouse model

Anxiety disorders are characterized by persistent, excessive fear. Therapeutic interventions that reverse deficits in fear extinction represent a tractable approach to treating these disorders. We previously reported that 129S1/SvImJ (S1) mice show no extinction learning following normal fear conditioning. We now demonstrate that weak fear conditioning does permit fear reduction during massed extinction training in S1 mice, but reveals specific deficiency in extinction memory consolidation/retrieval. Rescue of this impaired extinction consolidation/retrieval was achieved with d-cycloserine (N-methly-d-aspartate partial agonist) or MS-275 (histone deacetylase (HDAC) inhibitor), applied after extinction training. We next examined the ability of different drugs and non-pharmacological manipulations to rescue the extreme fear extinction deficit in S1 following normal fear conditioning with the ultimate aim to produce low fear levels in extinction retrieval tests. Results showed that deep brain stimulation (DBS) by applying high frequency stimulation to the nucleus accumbens (ventral striatum) during extinction training, indeed significantly reduced fear during extinction retrieval compared to sham stimulation controls. Rescue of both impaired extinction acquisition and deficient extinction consolidation/retrieval was achieved with prior extinction training administration of valproic acid (a GABAergic enhancer and HDAC inhibitor) or AMN082 [metabotropic glutamate receptor 7 (mGlu7) agonist], while MS-275 or PEPA (AMPA receptor potentiator) failed to affect extinction acquisition in S1 mice. Collectively, these data identify potential beneficial effects of DBS and various drug treatments, including those with HDAC inhibiting or mGlu7 agonism properties, as adjuncts to overcome treatment resistance in exposure-based therapies. This article is part of a Special Issue entitled 'Cognitive Enhancers'. © 2012 Elsevier Ltd. All rights reserved

Failure behavior of composite laminates under four-point bending

In this study, failure behavior of fiber-reinforced composites under four-point bending is investigated. First, the tests are modeled analytically using the classical lamination theory (CLT). The maximum allowable moment resultants of [ 12]Toffaxis laminate as well as balanced and symmetric angle-ply [ 3/ 3]s composite laminates as a function of fiber orientation angle, , are obtained using Tsai-Wu, maximum stress, maximum strain, Hashin, Tsai-Hill, Hoffman, quadric surfaces, modified quadric surfaces, and Norris failure criteria. Second, the same tests are simulated using the finite element method (FEM). Thermal residual stresses are calculated and accounted for in the failure analysis. An analysis is conducted for optimal positioning of the supports so as to ensure that intralaminar failure modes dominate interlaminar (delamination) failure mode. A test setup is then constructed accordingly and experiments are conducted. The correlation of the predicted failure loads and the experimental results is discussed. The quadric surfaces criterion is found to correlate better with the experimental results among the chosen failure criteria for the selected configurations

Increased anxiety-like behavior following circuit-specific catecholamine denervation in mice

Parkinson's disease (PD) presents with a constellation of non-motor symptoms, notably increased anxiety, which are currently poorly treated and underrepresented in animal models of the disease. Human post-mortem studies report loss of catecholaminergic neurons in the pre-symptomatic phases of PD when anxiety symptoms emerge, and a large literature from rodent and human studies indicate that catecholamines are important mediators of anxiety via their modulatory effects on limbic regions such as the amygdala. On the basis of these observations, we hypothesized that anxiety in PD could result from an early loss of catecholaminergic inputs to the amygdala and/or other limbic structures. To interrogate this hypothesis, we bilaterally injected the neurotoxin 6-OHDA in the mouse basolateral amygdala (BL). This produced a restricted pattern of catecholaminergic (tyrosine-hydroxylase-labeled) denervation in the BL, intercalated cell masses and ventral hippocampus, but not the central amygdala or prefrontal cortex. We found that this circuit-specific lesion did not compromise performance on multiple measures of motor function (home cage, accelerating rotarod, beam balance, pole climbing), but did increase anxiety-like behavior in the elevated plus-maze and light-dark exploration tests. Fear behavior in the pavlovian cued conditioning and passive avoidance assays was, by contrast, unaffected; possibly due to preservation of catecholamine innervation of the central amygdala from the periaqueductal gray. These data provide some of the first evidence implicating loss of catecholaminergic neurotransmission in midbrain-amygdala circuits to increased anxiety-like behavior. Our findings offer an initial step towards identifying the neural substrates for pre-motor anxiety symptoms in PD

Amyloid Inspired Self-Assembled Peptide Nanofibers

Cataloged from PDF version of article.Amyloid peptides are important components in many degenerative diseases as well as in maintaining cellular metabolism. Their unique stable structure provides new insights in developing new materials. Designing bioinspired selfassembling peptides is essential to generate new forms of hierarchical nanostructures. Here we present oppositely charged amyloid inspired peptides (AIPs), which rapidly self-assemble into nanofibers at pH 7 upon mixing in water caused by noncovalent interactions. Mechanical properties of the gels formed by selfassembled AIP nanofibers were analyzed with oscillatory rheology. AIP gels exhibited strong mechanical characteristics superior to gels formed by self-assembly of previously reported synthetic short peptides. Rheological studies of gels composed of oppositely charged mixed AIP molecules (AIP-1 + 2) revealed superior mechanical stability compared to individual peptide networks (AIP-1 and AIP-2) formed by neutralization of net charges through pH change. Adhesion and elasticity properties of AIP mixed nanofibers and charge neutralized AIP-1, AIP-2 nanofibers were analyzed by high resolution force− distance mapping using atomic force microscopy (AFM). Nanomechanical characterization of self-assembled AIP-1 + 2, AIP-1, and AIP-2 nanofibers also confirmed macroscopic rheology results, and mechanical stability of AIP mixed nanofibers was higher compared to individual AIP-1 and AIP-2 nanofibers self-assembled at acidic and basic pH, respectively. Experimental results were supported with molecular dynamics simulations by considering potential noncovalent interactions between the amino acid residues and possible aggregate forms. In addition, HUVEC cells were cultured on AIP mixed nanofibers at pH 7 and biocompatibility and collagen mimetic scaffold properties of the nanofibrous system were observed. Encapsulation of a zwitterionic dye (rhodamine B) within AIP nanofiber network was accomplished at physiological conditions to demonstrate that this network can be utilized for inclusion of soluble factors as a scaffold for cell culture studies. Copyright © 2012 American Chemical Societ

Noncovalent functionalization of a nanofibrous network with a bio-inspired heavy metal binding peptide

Peptide-polymer nanofibrous networks can be developed to obtain hybrid systems providing both functionalities of peptides and stability and processability of the polymers. In this work, a bio-inspired heavy metal binding peptide was synthesized and noncovalently immobilized on water-insoluble electrospun hydroxypropyl-beta-cyclodextrin nanofibers (CDNF). The peptide functionalized hybrid nanofibers were able to bind to heavy metal ions and facilitated removal of metal ions from water. The peptide-polymer scavenging system has potential for development of further molecular recognition systems with various peptide sequences or host-guest inclusion complexes. © 2013 The Royal Society of Chemistry