Three-point correlators for giant magnons

Three-point correlation functions in the strong-coupling regime of the AdS/CFT correspondence can be analyzed within a semiclassical approximation when two of the vertex operators correspond to heavy string states having large quantum numbers while the third vertex corresponds to a light state with fixed charges. We consider the case where the heavy string states are chosen to be giant magnon solitons with either a single or two different angular momenta, for various different choices of light string states.Comment: 15 pages. Latex. v2: Misprints corrected. Published versio

HEALTH SIMULATOR: um simulador de casos de estudo para a área da saúde

Este artigo apresenta o desenvolvimento de um simulador de casos de estudo em saúde denominado Health Simulator. Um aporte teórico embasa o desenvolvimento. O simulador foi concebido com uma estrutura robusta que permite a especialistas inserir conhecimentos específicos de cada área da saúde em um formalismo denominado rede bayesiana. Os casos de estudo são escritos em um sistema de fácil manipulação por profissionais que não são da área da computação, sendo transformados, de forma automática em um jogo sério para os alunos. Na execução do jogo os alunos são acompanhados de um agente que recomenda conteúdos e novos casos de estudo, reforçando e/ou instigando o aluno a aprender.   PALAVRAS-CHAVE: Health Simulator; Simulador; Casos de estudo; Ensino na Saúde.     ABSTRACT This paper presents the development of a health simulator case study called Health Simulator. A theoretical contribution supports the development. The simulator was designed with a robust structure that allows specialists to insert specific knowledge of each area of health in a formalism called the Bayesian network. Case studies are written in a easy system to manipulate by professionals who aren’t from the field of computing, and are automatically transformed into a serious game for students. In the execution of the game the students are accompanied by an agent who recommends contents and new cases of study, reinforcing and / or instigating the student to learn.   KEYWORDS: Health Simulator; Simulator; Case studies; Teaching in Health.     RESUMEN Este artículo presenta el desarrollo de un simulador de casos de estudio en salud denominado Health Simulator. El desarrollo se basa en un aporte teórico. El simulador fue concebido con una estructura robusta que permite a especialistas insertar conocimientos específicos de cada área de la salud en un formalismo denominado red bayesiana. Los casos de estudio se escriben en un sistema de fácil manipulación por profesionales que no son del área de la computación, siendo transformados, de forma automática en un juego serio para los alumnos. En la ejecución del juego los alumnos van acompañados de un agente que recomiende contenidos y nuevos casos de estudio, reforzando y / o instigando al alumno a aprender.   PALABRAS CLAVE: Simulador de Salud; Simulador; Casos de estudio; Ensino en la Saúde

Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

PENGARUH HARGA DAN DESAIN PRODUK TERHADAP KEPUTUSAN PEMBELIAN MEBEL PADA UD. JEPARA INDAH KOTA PASURUAN

The purpose of this research is to examine the influence of price, and product design on furniture purchasing decision at UD. Jepara Indah Pasuruan City. This study uses multiple linier regression analysis on 100 respondents that have been determined using purposive sampling technique as a method of sampling by using questionnaires for data collection. The results of this study revealed that prices have a positive and significant effect on purchasing decision of furniture in UD. Jepara Indah and product design have a positive and significant impact on purchasing decision of furniture in UD. Jepara Indah

Global analysis of gene expression in mineralizing fish vertebra-derived cell lines: new insights into anti-mineralogenic effect of vanadate

<p>Abstract</p> <p>Background</p> <p>Fish has been deemed suitable to study the complex mechanisms of vertebrate skeletogenesis and gilthead seabream (<it>Sparus aurata</it>), a marine teleost with acellular bone, has been successfully used in recent years to study the function and regulation of bone and cartilage related genes during development and in adult animals. Tools recently developed for gilthead seabream, <it>e.g. </it>mineralogenic cell lines and a 4 × 44K Agilent oligo-array, were used to identify molecular determinants of <it>in vitro </it>mineralization and genes involved in anti-mineralogenic action of vanadate.</p> <p>Results</p> <p>Global analysis of gene expression identified 4,223 and 4,147 genes differentially expressed (fold change - FC > 1.5) during <it>in vitro </it>mineralization of VSa13 (pre-chondrocyte) and VSa16 (pre-osteoblast) cells, respectively. Comparative analysis indicated that nearly 45% of these genes are common to both cell lines and gene ontology (GO) classification is also similar for both cell types. Up-regulated genes (FC > 10) were mainly associated with transport, matrix/membrane, metabolism and signaling, while down-regulated genes were mainly associated with metabolism, calcium binding, transport and signaling. Analysis of gene expression in proliferative and mineralizing cells exposed to vanadate revealed 1,779 and 1,136 differentially expressed genes, respectively. Of these genes, 67 exhibited reverse patterns of expression upon vanadate treatment during proliferation or mineralization.</p> <p>Conclusions</p> <p>Comparative analysis of expression data from fish and data available in the literature for mammalian cell systems (bone-derived cells undergoing differentiation) indicate that the same type of genes, and in some cases the same orthologs, are involved in mechanisms of <it>in vitro </it>mineralization, suggesting their conservation throughout vertebrate evolution and across cell types. Array technology also allowed identification of genes differentially expressed upon exposure of fish cell lines to vanadate and likely involved in its anti-mineralogenic activity. Many were found to be unknown or they were never associated to bone homeostasis previously, thus providing a set of potential candidates whose study will likely bring insights into the complex mechanisms of tissue mineralization and bone formation.</p

The use of PBPK/PD to establish clinically relevant dissolution specifications for zolpidem immediate release tablets

Background: Zolpidem is a non-benzodiazepine hypnotic agent which has been shown to be effective in inducing and maintaining sleep in adults and is one of the most frequently prescribed hypnotics in the world. For drugs that are used to treat sleeping disorders, the time to reach the maximum concentration (Tmax) of the drug in plasma is important to achieving a fast onset of action and this must be maintained when switching from one product to another. Objectives: The main objective of the present work was to create a PBPK/PD model for zolpidem and establish a clinically relevant “safe space” for dissolution of zolpidem from the commercial immediate release (IR) formulation. A second objective was to analyze literature pharmacokinetic data to verify the negative food effect ascribed to zolpidem and consider its ramifications in terms of the “safe space” for dissolution. Methods: Using dissolution, pharmacokinetic and pharmacodynamic data, an integrated PBPK/PD model for immediate release zolpidem tablets was constructed in Simcyp®. This model was used to identify the clinically relevant dissolution specifications necessary to ensure efficacy. Results: According to the simulations, as long as 85% of the drug is released in 45 minutes or less, the impact on the PK and PD profiles of zolpidem would be minimal. According to the FDA, the drug has to dissolve from the test and reference products at a similar rate and to an extent of 85% in not more than 30 minutes to pass bioequivalence via the BCS-biowaiver test. Thus, the BCS-biowaiver specifications are somewhat more stringent than the “safe space” based on the PBPK/PD model. Published data from fasted and fed state pharmacokinetic studies suggest but do not prove a negative food effect of zolpidem. Conclusions: A PBPK/PD model indicates that current BCS biowaiver criteria are more restrictive for immediate release zolpidem tablets than they need to be. In view of the close relationship between PK and PD, it remains advisable to avoid taking zolpidem tablets with or immediately after a meal, as indicated by the Stilnox® labeling