Terahertz epsilon-near-zero graded-index lens

An epsilon-near-zero graded-index converging lens with planar faces is proposed and analyzed. Each perfectly-electric conducting (PEC) waveguide comprising the lens operates slightly above its cut-off frequency and has the same length but different cross-sectional dimensions. This allows controlling individually the propagation constant and the normalized characteristic impedance of each waveguide for the desired phase front at the lens output while Fresnel reflection losses are minimized. A complete theoretical analysis based on the waveguide theory and Fermat’s principle is provided. This is complemented with numerical simulation results of two-dimensional and three-dimensional lenses, made of PEC and aluminum, respectively, and working in the terahertz regime, which show good agreement with the analytical work.Effort sponsored by Spanish Government under contracts Consolider “Engineering Metamaterials” CSD2008-00066 and TEC2011-28664-C02-01. P.R.-U. is sponsored by the Government of Navarra under funding program “Formación de tecnólogos” 055/01/11. M.N.- C. is supported by the Imperial College Junior Research Fellowship. M. B. acknowledges funding by the Spanish Government under the research contract program Ramon y Cajal RYC-2011-08221. N.E. acknowledges the support from the US Office of Naval Research (ONR) Multidisciplinary University Research Initiatives (MURI) grant number N00014-10-1- 0942

A Further Unique Chondroitin Sulfate from the shrimp Litopenaeus vannamei with Antithrombin Activity that Modulates Acute Inflammation

The detailed structure of a further Chondroitin Sulfate from Litopenaeus vannamei shrimp (sCS) is described. The backbone structure was established by 1H/13C NMR, which identified 3-O-sulfated GlcA, 4-O-sulfated GalNAc, 6-O-sulfated GalNAc, and 4,6-di-O-sulfated GalNAc residues. GlcA is linked to GalNAc 4,6 di S and GlcA 3S is linked to GalNAc 4S, GalNAc 4,6 di-S and GalNAc6S residues. The anticoagulant properties of this sCS were evaluated by activated partial thromboplastin time, anti-IIa, anti-Xa and anti-heparin cofactor II-mediated activities, and sCS failed to stabilise antithrombin in a fluoresence shift assay. The anti-inflammatory effect of sCS was explored using a model of acute peritonitis, followed by leukocyte count and measurement of the cytokines, IL-1β, IL-6 and TNF-α. The compound showed low clotting effects, but high anti-IIa activity and HCII-mediated thrombin inhibition. Its anti-inflammatory effect was shown by leukocyte recruitment inhibition and a decrease in pro-inflammatory cytokine levels. Although the biological role of sCS remains unknown, its properties indicate that it is suitable for studies of multi-potent molecules obtained from natural sources

Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis.

Despite substantial evidence for sex differences in addiction epidemiology, addiction-relevant behaviors and associated neurobiological phenomena, the mechanisms and implications of these differences remain unknown. Genetic analysis in model organism is a potentially powerful and effective means of discovering the mechanisms that underlie sex differences in addiction. Human genetic studies are beginning to show precise risk variants that influence the mechanisms of addiction but typically lack sufficient power or neurobiological mechanistic access, particularly for the discovery of the mechanisms that underlie sex differences. Our thesis in this review is that genetic variation in model organisms are a promising approach that can complement these investigations to show the biological mechanisms that underlie sex differences in addiction

Approximate affine linear relationship between L1 norm objective functional values and L2 norm constraint bounds

For an optimization problem with an norm objective function subject to an norm inequality constraint, this paper shows that there is an approximately linear relationship between the norm objective functional values and the norm specifications. This relationship is verified through the use of random and real world industrial data. The obtained results can be employed for 1) estimating the norm output objective functional value without solving the optimization problem numerically; 2) providing an insight for defining the norm specification in which a simple method is proposed in this paper; and 3) testing whether the obtained solutions are the globally optimal solutions or not. These advantages are demonstrated via the use of random data

Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex

Mucopolysaccharidosis type I (MPS I) is caused by genetic deficiency of alpha-l-iduronidase and impairment of lysosomal catabolism of heparan sulfate and dermatan sulfate. In the brain, these substrates accumulate in the lysosomes of neurons and glial cells, leading to neuroinflammation and neurodegeneration. Their storage also affects lysosomal homeostasis-inducing activity of several lysosomal proteases including cathepsin B (CATB). In the central nervous system, increased CATB activity has been associated with the deposition of amyloid plaques due to an alternative pro-amyloidogenic processing of the amyloid precursor protein (APP), suggesting a potential role of this enzyme in the neuropathology of MPS I. In this study, we report elevated levels of protein expression and activity of CATB in cortex tissues of 6-month-old MPS I (Idua -/- mice. Besides, increased CATB leakage from lysosomes to the cytoplasm of Idua -/- cortical pyramidal neurons was indicative of damaged lysosomal membranes. The increased CATB activity coincided with an elevated level of the 16-kDa C-terminal APP fragment, which together with unchanged levels of beta-secretase 1 was suggestive for the role of this enzyme in the amyloidogenic APP processing. Neuronal accumulation of Thioflavin-S-positive misfolded protein aggregates and drastically increased levels of neuroinflammatory glial fibrillary acidic protein (GFAP)-positive astrocytes and CD11b-positive activated microglia were observed in Idua -/- cortex by confocal fluorescent microscopy. Together, our results point to the existence of a novel CATB-associated alternative amyloidogenic pathway in MPS I brain induced by lysosomal storage and potentially leading to neurodegeneration

Isospin violation and the proton's neutral weak magnetic form factor

The effects of isospin violation on the neutral weak magnetic form factor of the proton are studied using two-flavour chiral perturbation theory. The first nonzero contributions appear at O(p^4) in the small-momentum expansion, and the O(p^5) corrections are also calculated. The leading contributions from an explicit Delta(1232) isomultiplet are included as well. At such a high order in the chiral expansion, one might have expected a large number of unknown parameters to contribute. However, it is found that no unknown parameters can appear within loop diagrams, and a single tree-level counterterm at O(p^4) is sufficient to absorb all divergences. The momentum dependence of the neutral weak magnetic form factor is not affected by this counterterm.Comment: 26 pages including 9 figure

Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants

Nowadays, pharmaceutical heparin is purified from porcine and bovine intestinal mucosa. In the past decade there has been an ongoing concern about the safety of heparin, since in 2008, adverse effects associated with the presence of an oversulfated chondroitin sulfate (OSCS) were observed in preparations of pharmaceutical porcine heparin, which led to the death of patients, causing a global public health crisis. However, it has not been clarified whether OSCS has been added to the purified heparin preparation, or whether it has already been introduced during the production of the raw heparin. Using a combination of different analytical methods, we investigate both crude and final heparin products and we are able to demonstrate that the sulfated contaminants are intentionally introduced in the initial steps of heparin preparation. Furthermore, the results show that the oversulfated compounds are not structurally homogeneous. In addition, we show that these contaminants are able to bind to cells in using well known heparin binding sites. Together, the data highlights the importance of heparin quality control even at the initial stages of its production

Optimality conditions in convex multiobjective SIP

The purpose of this paper is to characterize the weak efficient solutions, the efficient solutions, and the isolated efficient solutions of a given vector optimization problem with finitely many convex objective functions and infinitely many convex constraints. To do this, we introduce new and already known data qualifications (conditions involving the constraints and/or the objectives) in order to get optimality conditions which are expressed in terms of either Karusk–Kuhn–Tucker multipliers or a new gap function associated with the given problem.This research was partially cosponsored by the Ministry of Economy and Competitiveness (MINECO) of Spain, and by the European Regional Development Fund (ERDF) of the European Commission, Project MTM2014-59179-C2-1-P

Post-translational allosteric activation of the P2X 7 receptor through glycosaminoglycan chains of CD44 proteoglycans

Here, we present evidence for the positive allosteric modulation of the P2X7 receptor through glycosaminoglycans (GAGs) in CHO (cell line derived from the ovary of the Chinese hamster) cells. The marked potentiation of P2X7 activity through GAGs in the presence of non-saturating agonists concentrations was evident with the endogenous expression of the receptor in CHO cells. The presence of GAGs on the surface of CHO cells greatly increased the sensitivity to adenosine 5′-triphosphate and changed the main P2X7 receptor kinetic parameters EC50, Hill coefficient and Emax. GAGs decreased the allosteric inhibition of P2X7 receptor through Mg2+. GAGs activated P2X7 receptor-mediated cytoplasmic Ca2+ influx and pore formation. Consequently, wild-type CHO-K1 cells were 2.5-fold more sensitive to cell death induced through P2X7 agonists than mutant CHO-745 cells defective in GAGs biosynthesis. In the present study, we provide the first evidence that the P2X7 receptor interacts with CD44 on the CHO-K1 cell surface. Thus, these data demonstrated that GAGs positively modulate the P2X7 receptor, and sCD44 is a part of a regulatory positive feedback loop linking P2X7 receptor activation for the intracellular response mediated through P2X7 receptor stimulation

P2X 7 receptor activity regulation: the role of CD44 proteoglycan GAG chains

P2X7 receptors have received special attention in the literature for their involvement in several diseases characterized by inflammatory processes such as cancer, arthritis, neurodegenerative pathologies and chronic pains