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Κυριακή 24 Ιουλίου 2016

Statins, familial hypercholesterolemia, and type 2 diabetes



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Response to Dr. Gerald M Reaven: good news for patients with familial hypercholesterolaemia: statins are not diabetogenic in this disease



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Sensors, Vol. 16, Pages 1163: A Sensor Array for the Detection and Discrimination of Methane and Other Environmental Pollutant Gases

We address the sensitive detection and discrimination of gases impacting the environment, such as CH4, NH3, SO2, and CO, using a sensor array and aided by principal component analysis (PCA). A 32-element chemiresistive sensor array consisting of nine different sensor materials including seven types of modified single-walled carbon nanotubes and two types of polymers has been constructed. PCA results demonstrate excellent discriminating ability of the chemiresistor sensor chip in the 1–30 ppm concentration range. The accuracy of the sensor was verified against data collected using cavity ring down spectroscopy. The sensor chip has also been integrated with a smartphone and has been shown to reproduce the sensing performance obtained with the laboratory measurement system.

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Sustainability, Vol. 8, Pages 699: Sustainable Cultural Tourism in Urban Destinations: Does Space Matter?

Policy makers and tourism developers must understand visitors' mobility behavior and how they consume space and tourism resources in order to set up sustainable cultural tourism destinations. With this in mind, it should also be pointed out that the mobility patterns of tourists in urban destinations are mainly located in the city center (spatial centrality), the analysis of which enables us to define "how central" the resources (museums, monuments, etc.) are and what the interactions between them are. Comprehending which factors influence visitors' urban mobility behavior is key to understanding tourists' consumption of space and their connections with the tourism assets of the city. Furthermore, when tourists visit a destination, they make a mental representation of the destination, constructing a mental map of it. Thus, tourists consume not only spaces but also the image of a city/destination. Moreover, the latter influences the former. The quality of surrounding architecture and urbanism plays a crucial role in enhancing the experiential value of a destination and influencing space consumption preferences. Clearly, visitors are more likely to use/consume environments that are easily navigated and mentally legible. In order to explore these patterns, a real experiment was performed based on visitor behavior in the city of Bilbao. In addition, the central places of Bilbao were determined and an analysis of the spatial interaction between cultural sites was performed, making use of a new methodology based on GPS technologies, network analysis, and surveys. This methodology is the main contribution of this work. The results suggest that (1) easy mobility (walkability, accessibility, different transport modes) of the visited space facilitates the tourist experience; (2) simple and eligible mental maps of the city that are easily perceived by visitors facilitate the rapid consumption of the tourist destination; and (3) the centrality of the tourism resources affects the mobility of visitors and the consumption of the destination. Thus, by understanding how tourist mobility works in a destination and analyzing tourism resources' centrality, policy makers may better tailor sustainable strategies for cultural tourism destinations.

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Sustainability, Vol. 8, Pages 707: New Product Development and Innovation in the Maquiladora Industry: A Causal Model

Companies seek to stand out from their competitors and react to other competitive threats. Making a difference means doing things differently in order to create a product that other companies cannot provide. This can be achieved through an innovation process. This article analyses, by means of a structural equation model, the current situation of Mexican maquiladora companies, which face the constant challenge of product innovation. The model associates three success factors for new product development (product, organization, and production process characteristics as independent latent variables) with benefits gained by customers and companies (dependent latent variables). Results show that, in the Mexican maquiladora sector, organizational characteristics and production processes characteristics explain only 31% of the variability (R2 = 0.31), and it seems necessary to integrate other aspects. The relationship between customer benefits and company benefits explains 58% of the variability, the largest proportion in the model (R2 = 0.58).

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Toxins, Vol. 8, Pages 217: Protection of the Furin Cleavage Site in Low-Toxicity Immunotoxins Based on Pseudomonas Exotoxin A

Recombinant immunotoxins (RITs) are fusions of an Fv-based targeting moiety and a toxin. Pseudomonas exotoxin A (PE) has been used to make several immunotoxins that have been evaluated in clinical trials. Immunogenicity of the bacterial toxin and off-target toxicity have limited the efficacy of these immunotoxins. To address these issues, we have previously made RITs in which the Fv is connected to domain III (PE24) by a furin cleavage site (FCS), thereby removing unneeded sequences of domain II. However, the PE24 containing RITs do not contain the naturally occurring disulfide bond around the furin cleavage sequence, because it was removed when domain II was deleted. This could potentially allow PE24 containing immunotoxins to be cleaved and inactivated before internalization by cell surface furin or other proteases in the blood stream or tumor microenvironment. Here, we describe five new RITs in which a disulfide bond is engineered to protect the FCS. The most active of these, SS1-Fab-DS3-PE24, shows a longer serum half-life than an RIT without the disulfide bond and has the same anti-tumor activity, despite being less cytotoxic in vitro. These results have significance for the production of de-immunized, low toxicity, PE24-based immunotoxins with a longer serum half-life.

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Forests, Vol. 7, Pages 152: Timber Regulation and Value Chain in Community-Based Timber Enterprise and Smallholder Forestry in the Philippines

Forest tenure reform has no doubt attained significant gains in promoting social justice and equity in the forest sector, through legal recognition of the communities' property rights over forest lands in many developing countries. This includes the right to harvest and market trees that the communities planted. Along these lines, the Philippines' community-based forest management (CBFM) and smallholder forestry have the potential to meet the country's wood demand and contribute to its poverty alleviation goal. Realities on the ground, however, make this lofty aspiration seems too far-fetched. Formal and informal barriers along the timber value chain restrict the growth and obstruct opportunities for community-based timber enterprises (CBTEs) and smallholder forestry. Using the case of CBFM and smallholder forestry in the Visayas and Mindanao Islands in the Philippines, respectively, this paper examines the hurdles posed by regulations and informal practices, such as restrictive policies and increased transaction costs, through a segment analysis of the timber value chain. It argues that failure to address these barriers would lead to the decline of CBTEs and smallholder enterprises, thus undermining the merits of the forest tenure reform.

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Cosmetics, Vol. 3, Pages 27: Overview of Skin Whitening Agents: Drugs and Cosmetic Products

Depigmentation and skin lightening products, which have been in use for ages in Asian countries where skin whiteness is a major esthetic criterion, are now also highly valued by Western populations, who expose themselves excessively to the sun and develop skin spots as a consequence. After discussing the various possible mechanisms of depigmentation, the different molecules that can be used as well as the status of the products containing them will now be presented. Hydroquinone and derivatives thereof, retinoids, alpha- and beta-hydroxy acids, ascorbic acid, divalent ion chelators, kojic acid, azelaic acid, as well as diverse herbal extracts are described in terms of their efficacy and safety. Since a genuine effect (without toxic effects) is difficult to obtain, prevention by using sunscreen products is always preferable.

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Energies, Vol. 9, Pages 578: A Review of Dangerous Dust in Fusion Reactors: from Its Creation to Its Resuspension in Case of LOCA and LOVA

The choice of materials for the future nuclear fusion reactors is a crucial issue. In the fusion reactors, the combination of very high temperatures, high radiation levels, intense production of transmuting elements and high thermomechanical loads requires very high-performance materials. Erosion of PFCs (Plasma Facing Components) determines their lifetime and generates a source of impurities (i.e., in-vessel tritium and dust inventories), which cool down and dilute the plasma. The resuspension of dust could be a consequences of LOss of Coolant Accidents (LOCA) and LOss of Vacuum Accidents (LOVA) and it can be dangerous because of dust radioactivity, toxicity, and capable of causing an explosion. These characteristics can jeopardize the plant safety and pose a serious threat to the operators. The purpose of this work is to determine the experimental and numerical steeps to develop a numerical model to predict the dust resuspension consequences in case of accidents through a comparison between the experimental results taken from campaigns carried out with STARDUST-U and the numerical simulation developed with CFD codes. The authors in this work will analyze the candidate materials for the future nuclear plants and the consequences of the resuspension of its dust in case of accidents through the experience with STARDUST-U.

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Gene activation by metazoan enhancers: Diverse mechanisms stimulate distinct steps of transcription

Enhancers can stimulate transcription by a number of different mechanisms which control different stages of the transcription cycle of their target genes, from recruitment of the transcription machinery to elongation by RNA polymerase. These mechanisms may not be mutually exclusive, as a single enhancer may act through different pathways by binding multiple transcription factors. Multiple enhancers may also work together to regulate transcription of a shared target gene. Most of the evidence supporting different enhancer mechanisms comes from the study of single genes, but new high-throughput experimental frameworks offer the opportunity to integrate and generalize disparate mechanisms identified at single genes. This effort is especially important if we are to fully understand how sequence variation within enhancers contributes to human disease.

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Enhancers are regulatory elements that bind transcription factors and activate expression of their target genes by stimulating specific steps in the RNA polymerase II transcription cycle. Here we review the mechanisms of enhancer action and highlight opportunities for new insights from high-throughput experimental technologies such as massively parallel reporter assays.



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Cosmetics, Vol. 3, Pages 26: Human Hair and the Impact of Cosmetic Procedures: A Review on Cleansing and Shape-Modulating Cosmetics

Hair can be strategically divided into two distinct parts: the hair follicle, deeply buried in the skin, and the visible hair fiber. The study of the hair follicle is mainly addressed by biological sciences while the hair fiber is mainly studied from a physicochemical perspective by cosmetic sciences. This paper reviews the key topics in hair follicle biology and hair fiber biochemistry, in particular the ones associated with the genetically determined cosmetic attributes: hair texture and shape. The traditional and widespread hair care procedures that transiently or permanently affect these hair fiber features are then described in detail. When hair is often exposed to some particularly aggressive cosmetic treatments, hair fibers become damaged. The future of hair cosmetics, which are continuously evolving based on ongoing research, will be the development of more efficient and safer procedures according to consumers' needs and concerns.

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Sensors, Vol. 16, Pages 1157: Real Time 3D Facial Movement Tracking Using a Monocular Camera

The paper proposes a robust framework for 3D facial movement tracking in real time using a monocular camera. It is designed to estimate the 3D face pose and local facial animation such as eyelid movement and mouth movement. The framework firstly utilizes the Discriminative Shape Regression method to locate the facial feature points on the 2D image and fuses the 2D data with a 3D face model using Extended Kalman Filter to yield 3D facial movement information. An alternating optimizing strategy is adopted to fit to different persons automatically. Experiments show that the proposed framework could track the 3D facial movement across various poses and illumination conditions. Given the real face scale the framework could track the eyelid with an error of 1 mm and mouth with an error of 2 mm. The tracking result is reliable for expression analysis or mental state inference.

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Energies, Vol. 9, Pages 574: Artificial Neural Network Application for Partial Discharge Recognition: Survey and Future Directions

In order to investigate how artificial neural networks (ANNs) have been applied for partial discharge (PD) pattern recognition, this paper reviews recent progress made on ANN development for PD classification by a literature survey. Contributions from several authors have been presented and discussed. High recognition rate has been recorded for several PD faults, but there are still many factors that hinder correct recognition of PD by the ANN, such as high-amplitude noise or wide spectral content typical from industrial environments, trial and error approaches in determining an optimum ANN, multiple PD sources acting simultaneously, lack of comprehensive and up to date databank of PD faults, and the appropriate selection of the characteristics that allow a correct recognition of the type of source which are currently being addressed by researchers. Several suggestions for improvement are proposed by the authors include: (1) determining the optimum weights in training the ANN; (2) using PD data captured over long stressing period in training the ANN; (3) ANN recognizing different PD degradation levels; (4) using the same resolution sizes of the PD patterns when training and testing the ANN with different PD dataset; (5) understanding the characteristics of multiple concurrent PD faults and effectively recognizing them; and (6) developing techniques in order to shorten the training time for the ANN as applied for PD recognition Finally, this paper critically assesses the suitability of ANNs for both online and offline PD detections outlining the advantages to the practitioners in the field. It is possible for the ANNs to determine the stage of degradation of the PD, thereby giving an indication of the seriousness of the fault.

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Diseases, Vol. 4, Pages 26: Human Coronaviruses: A Review of Virus–Host Interactions

Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs.

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Beverages, Vol. 2, Pages 18: Phenolic Composition and Color of Single Cultivar Young Red Wines Made with Mencia and Alicante-Bouschet Grapes in AOC Valdeorras (Galicia, NW Spain)

Single cultivar wines made with two different red grape cultivars from AOC Valdeorras (Galicia, NW Spain), Mencia and Alicante Bouschet, were studied with the aim of determining their color and phenolic composition. Two sets of analyses were made on 30 wine samples of 2014 vintage, after malolactic fermentation took place, to evaluate several physicochemical characteristics from these wines related to color and polyphenols. Several parameters related with color and the general phenolic composition of wines (total phenols index, color intensity, hue, total anthocyans, total anthocyanins, colored anthocyanins, chemical age index, and total tannins) were determined by UV-VIS spectrophotometry. Those analyses revealed that Alicante Bouschet wines presented, in general, a higher content of polyphenols and a more intense color than Mencia wines. Using HPLC-DAD, five anthocyanin monoglucosides and nine acylated anthocyanins were identified in both types of wine; each type of wine showed a distinctive anthocyanin fingerprint, as Alicante Bouschet wines contained a higher proportion of cyanidin-derived anthocyanins. Multivariate statistic studies were performed to both datasets to explore relationships among variables and among samples. These studies revealed relationships among several variables considered, and were capable to group the samples in two different classes using principal component analysis (PCA).

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Axial length, refraction, and retinal vascularization 1 year after ranibizumab or bevacizumab treatment for retinopathy of prematurity



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Clinical & Pathological Studies of Upper Gastrointestinal Carcinoma

Conditions:   Stomach Cancer;   Gastro-Esophageal(GE) Junction Cancer;   Gastric (Stomach) Cancer;   Esophageal Cancer;   Gastrointestinal Stromal Tumor (GIST)
Interventions:   Procedure: Blood draw;   Procedure: Tissue tumor biopsy
Sponsors:   Stanford University;   National Institutes of Health (NIH)
Recruiting - verified July 2016

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Mitochondria and oxidative stress in heart aging

Abstract

As average lifespan of humans increases in western countries, cardiac diseases become the first cause of death. Aging is among the most important risk factors that increase susceptibility for developing cardiovascular diseases. The heart has very aerobic metabolism, and is highly dependent on mitochondrial function, since mitochondria generate more than 90 % of the intracellular ATP consumed by cardiomyocytes. In the last few decades, several investigations have supported the relevance of mitochondria and oxidative stress both in heart aging and in the development of cardiac diseases such as heart failure, cardiac hypertrophy, and diabetic cardiomyopathy. In the current review, we compile different studies corroborating this role. Increased mitochondria DNA instability, impaired bioenergetic efficiency, enhanced apoptosis, and inflammation processes are some of the events related to mitochondria that occur in aging heart, leading to reduced cellular survival and cardiac dysfunction. Knowing the mitochondrial mechanisms involved in the aging process will provide a better understanding of them and allow finding approaches to more efficiently improve this process.



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Plant responses to tomato chlorotic mottle virus: Proteomic view of the resistance mechanisms to a bipartite begomovirus in tomato

Publication date: Available online 22 July 2016
Source:Journal of Proteomics
Author(s): Lílian S.T. Carmo, André M. Murad, Renato O. Resende, Leonardo S. Boiteux, Simone G. Ribeiro, Jesús V. Jorrín-Novo, Angela Mehta
Tomato chlorotic mottle virus (ToCMoV) is a widespread bipartite Begomovirus species found in tomato fields in Brazil. In this study, plant responses and putative mechanisms associated with the 'Tyking'-derived recessive resistance to ToCMoV were investigated. Changes in the protein profile in the inoculated plants of two near isogenic tomato lines resistant ('LAM 157') and susceptible ('Santa Clara') to ToCMoV were analyzed. Seedlings were biolistically inoculated with an infectious ToCMoV clone. Leaves from infected plants (confirmed by PCR) were sampled at 15days after inoculation. Proteins were extracted using phenol and analyzed by shotgun MS (2D-nanoUPLC/HDMSE). Out of the 534 identified proteins, 82 presented statistically significant differences in abundance, including 35 unique proteins displayed in the resistant tomato inoculated with ToCMoV. Proteins associated to chromatin structure, cytoskeleton structure, cuticle biosynthesis, and ubiquitin pathway were identified and their putative roles during virus infection process were discussed. The protein profile analysis allowed for the development of a hypothetical model showing how the resistant host cell responds to ToCMoV infection. The data obtained provide a better understanding of resistant mechanisms used by the host plant to contain viral infection and could be the basis for further investigation in other plant-begomovirus pathosystems.Biological significanceIn this study we propose a model of resistance to begomovirus in tomato and highlight host proteins, which could be targets for future investigations in plant-begomovirus pathosystems.



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Proteomic identification of putative biomarkers for early detection of sudden cardiac death in a family with a LMNA gene mutation causing dilated cardiomyopathy

Publication date: Available online 22 July 2016
Source:Journal of Proteomics
Author(s): Irene Izquierdo, Isaac Rosa, Susana Belén Bravo, Esteban Guitián, Alexandra Pérez-Serra, Oscar Campuzano, Ramon Brugada, Alipio Mangas, Ángel García, Rocio Toro
Dilated cardiomyopathy (DCM) is a severe heart disease characterized by progressive ventricular dilation and impaired systolic function of the left ventricle. We recently identified a novel pathogenic mutation in the LMNA gene in a family affected by DCM showing sudden death background. We now aimed to identify potential biomarkers of disease status, as well as sudden death predictors, in members of this family. We analysed plasma samples from 14 family members carrying the mutation, four of which (with relevant clinical symptoms) were chosen for the proteomic analysis. Plasma samples from these four patients and from four sex- and age-matched healthy controls were processed for their enrichment in low- and medium-abundance proteins (ProteoMiner™) prior to proteomic analysis by 2D-DIGE and MS. 111 spots were found to be differentially regulated between mutation carriers and control groups, 83 of which were successfully identified by MS, corresponding to 41 different ORFs. Some proteins of interest were validated either by turbidimetry or western blot in family members and healthy controls. Actin, alpha-1-antytripsin, clusterin, vitamin-D binding protein and antithrombin-III showed increased levels in plasma from the diseased group. We suggest following these proteins as putative biomarkers for the evaluation of DCM status in LMNA mutation carriers.Biological significanceWe developed a proteomic analysis of plasma samples from a family showing history of dilated cardiomyopathy caused by a LMNA mutation, which may lead to premature death or cardiac transplant. We identified a number of proteins augmented in mutation carriers that could be followed as potential biomarkers for dilated cardiomyopathy on these patients.

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Laboratory Simulation of an Iron(II)-rich Precambrian Marine Upwelling System to Explore the Growth of Photosynthetic Bacteria

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We simulated a Precambrian ferruginous marine upwelling system in a lab-scale vertical flow-through column. The goal was to understand how geochemical profiles of O2 and Fe(II) evolve as cyanobacteria produce O2. The results show the establishment of a chemocline due to Fe(II) oxidation by photosynthetically produced O2.

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Intracerebroventricular and Intravascular Injection of Viral Particles and Fluorescent Microbeads into the Neonatal Brain

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Here, we describe a simple method of intracerebroventricular and intravascular injection of viral particles or fluorescent microbeads into the neonatal mouse brain. The localization pattern of the virus and nanoparticles could be detected by microscopic evaluation or by in situ hybridization.

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Phenotypic characterization of a pair of molecules in tissues confer to classical Mendelian or non Mendelian ratios

Publication date: September 2016
Source:Medical Hypotheses, Volume 94
Author(s): L.M. Suneetha, Prasanna Marsakatla, G.V. Ravi, Aparna Sykam, R. Raju, P.P. Reddy, V.V. Hara Gopal, R. Jadhav, S. Suneetha
Studies have reported a wide range of inflammatory responses in the nerve, skin and plasma of leprosy patients. The expression levels of each biomolecule was individualistic, however could be categorized as high and low based on their statistical mean level. Here we report for the first time, expression of a set of biomolecules relating with each other in a defined proportion.The hypothesis of this paper is that the segregation of high and low combinations of a set of biomolecules follows either classical Mendelian dihybrid ratio or epistatic ratios. This hypothesis was tested for 17 molecules in three tissues; nerve, skin and plasma and were confirmed to interact in 9:7, 9:3:4, 12:3:1, 13:3, 15:1 epistatic proportions. These findings suggest that there could be a significant role of networking of molecules in defined epistatic proportions and could be important in pathophysiology of peripheral nerve.



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Watershed Planning within a Quantitative Scenario Analysis Framework

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There is a critical need for tools and methodologies capable of managing aquatic systems in the face of uncertain future conditions. We provide methods for conducting a targeted watershed assessment that enables resource managers to produce landscape-based cumulative effects models for use within a scenario analysis management framework.

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