Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control

Pollack, Samuela,Igo Jr., Robert P.,Jensen, Richard A.,Christiansen, Mark,Li, Xiaohui,Cheng, Ching-Yu,Ng, Maggie C.Y.,Smith, Albert V.,Rossin, Elizabeth J.,Segrè,, Ayellet V.,Davoudi, Samaneh,Ta American Diabetes Association 2019 Diabetes Vol.68 No.2

<P>To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (<I>n</I> = 3,246) and seven African American cohorts (<I>n</I> = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a <I>P</I> value <1 × 10<SUP>−5</SUP> were investigated in replication cohorts that included 18,545 European, 16,453 Asian, and 2,710 Hispanic subjects. After correction for multiple testing, the C allele of rs142293996 in an intron of nuclear VCP-like (<I>NVL</I>) was associated with DR in European discovery cohorts (<I>P</I> = 2.1 × 10<SUP>−9</SUP>), but did not reach genome-wide significance after meta-analysis with replication cohorts. We applied the Disease Association Protein-Protein Link Evaluator (DAPPLE) to our discovery results to test for evidence of risk being spread across underlying molecular pathways. One protein–protein interaction network built from genes in regions associated with proliferative DR was found to have significant connectivity (<I>P</I> = 0.0009) and corroborated with gene set enrichment analyses. These findings suggest that genetic variation in <I>NVL,</I> as well as variation within a protein–protein interaction network that includes genes implicated in inflammation, may influence risk for DR.</P>

Breathing-Dependent Redox Activity in a Tetrathiafulvalene-Based Metal–Organic Framework

Souto, Manuel,Romero, Jorge,Calbo, Joaquí,n,Vitó,rica-Yrezá,bal, Iñ,igo J.,Zafra, José,L.,Casado, Juan,Ortí,, Enrique,Walsh, Aron,Mí,nguez Espallargas, Guille American Chemical Society 2018 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.140 No.33

<P/><P>“Breathing” metal–organic frameworks (MOFs) that involve changes in their structural and physical properties upon an external stimulus are an interesting class of crystalline materials due to their range of potential applications including chemical sensors. The addition of redox activity opens up a new pathway for multifunctional “breathing” frameworks. Herein, we report the continuous breathing behavior of a tetrathiafulvalene (TTF)-based MOF, namely <B>MUV-2</B>, showing a reversible swelling (up to ca. 40% of the volume cell) upon solvent adsorption. Importantly, the planarity of the TTF linkers is influenced by the breathing behavior of the MOF, directly impacting on its electrochemical properties and thus opening the way for the development of new electrochemical sensors. Quantum chemical calculations and Raman spectroscopy have been used to provide insights into the tunability of the oxidation potential.</P>

Bacterial Hash Function Using DNA-Based XOR Logic Reveals Unexpected Behavior of the LuxR Promoter

Pearson, Brianna,Lau, Kin H.,Allen, Alicia,Barron, James,Cool, Robert,Davis, Kelly,DeLoache, Will,Feeney, Erin,Gordon, Andrew,Igo, John,Lewis, Aaron,Muscalino, Kristi,Parra, Madeline,Penumetcha, Palla Korean Society for Bioinformatics 2011 Interdisciplinary Bio Central (IBC) Vol.3 No.3

Introduction: Hash functions are computer algorithms that protect information and secure transactions. In response to the NIST's "International Call for Hash Function", we developed a biological hash function using the computing capabilities of bacteria. We designed a DNA-based XOR logic gate that allows bacterial colonies arranged in a series on an agar plate to perform hash function calculations. Results and Discussion: In order to provide each colony with adequate time to process inputs and perform XOR logic, we designed and successfully demonstrated a system for time-delayed bacterial growth. Our system is based on the diffusion of ${\ss}$-lactamase, resulting in destruction of ampicillin. Our DNA-based XOR logic gate design is based on the op-position of two promoters. Our results showed that $P_{lux}$ and $P_{OmpC}$ functioned as expected individually, but $P_{lux}$ did not behave as expected in the XOR construct. Our data showed that, contrary to literature reports, the $P_{lux}$ promoter is bidirectional. In the absence of the 3OC6 inducer, the LuxR activator can bind to the $P_{lux}$ promoter and induce backwards transcription. Conclusion and Prospects: Our system of time delayed bacterial growth allows for the successive processing of a bacterial hash function, and is expected to have utility in other synthetic biology applications. While testing our DNA-based XOR logic gate, we uncovered a novel function of $P_{lux}$. In the absence of autoinducer 3OC6, LuxR binds to $P_{lux}$ and activates backwards transcription. This result advances basic research and has important implications for the widespread use of the $P_{lux}$ promoter.

Mouse Models as a Tool for Understanding Progression in BrafV600E-Driven Thyroid Cancers

Iñigo Landa,Jeffrey A Knauf 대한내분비학회 2019 Endocrinology and metabolism Vol.34 No.1

The development of next generation sequencing (NGS) has led to marked advancement of our understanding of genetic events mediating the initiation and progression of thyroid cancers. The NGS studies have confirmed the previously reported high frequency ofmutually-exclusive oncogenic alterations affecting BRAF and RAS proto-oncogenes in all stages of thyroid cancer. Initially identifiedby traditional sequencing approaches, the NGS studies also confirmed the acquisition of alterations that inactivate tumor protein p53(TP53) and activate phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in advanced thyroid cancers. Novel alterations, such as those in telomerase reverse transcriptase (TERT) promoter and mating-type switching/sucrose non-fermenting (SWI/SNF) complex, are also likely to promote progression of the BRAFV600E-driven thyroid cancers. A number of genetically engineered mouse models (GEMM) of BRAFV600E-driven thyroid cancer have been developed to investigate thyroid tumorigenesis mediated by oncogenic BRAF and to explore the role of genetic alterations identified in the genomic analyses of advancedthyroid cancer to promote tumor progression. This review will discuss the various GEMMs that have been developed to investigateoncogenic BRAFV600E-driven thyroid cancers.

DEAGRARIANIZATION AND DIVERSIFICATION OF SOCIO-LABOUR AND ECONOMIC STRATEGIES IN THE MEXICAN COUNTRYSIDE

Hernán Salas Quintanal,Iñigo González de la Fuente Institute of Iberoamerican Studies Pusan Universit 2013 International Journal of Latin American Studies Vol.3 No.1

Abstract. In recent decades, the Latin America’s rural economy and society has been transformed as a result of its dependence on capitalist relationships and the integration of agriculture and food production to world markets, to forms of modernization favoring agro-industrial groups, capitalistic farm businessmen and a few peasant family units. Most peasants and rural workers are now employed in temporary, precarious and flexible contractual conditions. This article examines changes in the institutions regulating socio-economic life and their effect on the rural lifestyle in the Nativitas municipality, Tlaxcala, Mexico. By observing communities under study, the authors propose that rural changes have not turned these regions into totally urban settings. Rurality, as it has been known traditionally, have been altered since it is the current trend that family members work in varied sectors and milieus, whereupon it is necessary to ask what remains of that rurality and how it is defined in this context. Resumen. En las últimas décadas, la economía y sociedad rural, en toda América Latina, se ha transformado como consecuencia de la dependencia de las relaciones capitalistas, la incorporación de la agricultura y la producción de alimentos a los mercados de la economía mundial, a formas de modernización que han beneficiado a grupos de agroindustriales, empresarios agrícolas capitalistas y algunas unidades campesinas familiares. La mayoría de los campesinos y trabajadores rurales se emplean en condiciones contractuales temporales, precarias y flexibles. Este artículo tiene por objeto conocer las transformaciones de las instituciones que han regulado la vida socioeconómica y sus efectos en el modo de vida rural de la población del municipio de Natívitas al sur del estado de Tlaxcala. Estas evidencias nos llevan a proponer que las transformaciones rurales no han convertido estas regiones en espacios totalmente urbanos. La ruralidad, como la hemos conocido tradicionalmente se ha alterado, siendo la tendencia actual que los miembros de las familias se empleen en diferentes ámbitos y sectores, de manera que es necesario preguntarnos qué queda de aquella ruralidad y cómo se define en este contexto lo rural. Key words: New Rurality, Deagrarianization, Globalization, Labour pluriactivity, Mexico Palabras clave: Nueva Ruralidad, Desagrarización, Globalización, Pluriactividad laboral, México.

The fire-risks of cost-optimized steel structures: Fire-resistant and hot-rolled carbon steel

Harkaitz García,Jesús Cuadrado,María V. Biezma,Iñigo Calderón 국제구조공학회 2021 Structural Engineering and Mechanics, An Int'l Jou Vol.78 No.1

This work studies the behaviour of a steel portal frame selection under fire exposure, considering both span lengths and fire exposure times as variables. Such structures combine carbon steel (S275), fireproof micro-alloyed steel (FR), and coatings of intumescent paint with variable thicknesses, improving thereby the flame retardant behaviour of the steel structure. Thus, the main contribution of this study is the optimization of the portal frames by combining both steels, analysing the resulting costs influence on the final dimensions. Besides, the topological optimization of each steel component within the structure is also defined, in accordance with the following variables: weather conditions, span, paint thickness, and cost of steel. The results mainly confirmed that using both FR and S275 grades with intumescent painting is the Pareto optimum when considering performance, feasibility and costs of such portal frames widely used for industrial facilities.

Analysis of a preliminary configuration for a floating wind turbine

H.F. Wang,Y.H. Fan,Iñigo Moreno 국제구조공학회 2016 Structural Engineering and Mechanics, An Int'l Jou Vol.59 No.3

There are many theoretical analyses and experimental studies of the hydrodynamics for the tension leg platform (TLP) of a floating wind turbine. However, there has been little research on the arrangement of the TLP’s internal structure. In this study, a TLP model and a 5-MW wind turbine model as proposed by the Minstitute of Technology and the National Renewable Energy Laboratory have been adopted, respectively, to comprehensively analyze wind effects and wave and current combinations. The external additional coupling loads on the TLP and the effects of the loads on variables of the internal structure have been calculated. The study investigates preliminary layout parameters-namely, the thickness of the tension leg body, the contact mode of the top tower on the tension leg, the internal stiffening arrangement, and the formation of the spoke structure-and conducts sensitivity analyses of the TLP internal structure. Stress is found to be at a maximum at the top of the tension leg structure and the maximum stress has low sensitivity to the load application point. Different methods of reducing maximum stress have been researched and analyzed, and the effectiveness of these methods is analyzed. Filling of the spoke structure with concrete is discussed. Since the TLP structure for offshore wind power is still under early exploration, arrangements and the configuration of the internal structure, exploration and improvements are ongoing. With regard to its research and analysis process, this paper aims to guide future applications of tension leg structures for floating wind turbine.

Assessment of the Antibacterial Behavior of Polyester Fabric Pre-treated with Atmospheric Discharge Plasma

Z. Špitalský,D. Rástočná Illová,O. Žigo,M. Mičušík,Z. Nógellová,M. Procházka,A. Kleinová,M. Kováčová,I. Novák 한국섬유공학회 2019 Fibers and polymers Vol.20 No.8

Polyester (PES) fabrics were pre-treated with atmospheric discharge plasma, and the surface properties, chemicalcomposition, and physical changes on the surfaces of the PES fabrics were investigated. The hydrophobic recovery of theplasma-modified surface during aging of the PES fabrics treated with plasma was also investigated. The glycerin contactangles were determined along with the chemical composition changes in the PES fabric using X-ray photoelectronspectroscopy, Fourier-transform infrared spectroscopy, and iodometric analyses. The physical changes in the topography androughness of the plasma-modified PES were studied using scanning electron microscopy and nanoindentation. The relationbetween the hydrophilicity and hydroperoxide concentration on the surface of the plasma-treated PES fabrics was analyzedand the antibacterial behavior of the fabrics with respect to selected two bacterial strains was monitored.

Design Optimization and Investigation of Aerodynamic Characteristics of Low Reynolds Number Airfoils

Arshad Ali,Rodrigues Lucas Brandão,López Iñigo Martínez 한국항공우주학회 2021 International Journal of Aeronautical and Space Sc Vol.22 No.4

This study aims to develop a simple and efficient design optimization methodology for the low Reynolds number airfoils. XFOIL is used as an aerodynamic solver while modeFRONTIER workflow is employed for the design optimization purpose. The airfoil SG6043 is used as the reference airfoil for optimization due to its common applications when long-endurance characteristics are desired. A simple design optimization methodology with the integration of XFOIL in the modeFRONTIER workflow environment is proposed in this study. The proposed “software integration methodology” demonstrated up to 10% improvement in the optimization parameter which makes it more efficient by reducing the optimization time and steps without unnecessary user intervention which are the limitations conventionally associated with the optimization process. The optimization results are further compared with the results of the numerical simulations. The use of the transition-sensitive turbulence model allowed the evaluation of the behavior of the laminar separation bubble for different angles of attack, observing that it shifts towards the leading edge and has its length reduced as the angle of attack increases. The newly generated airfoil exhibits improved aerodynamic characteristics as compared to the base airfoil. The optimized airfoil can be used in the applications of UAVs as well as in general aviation. Further validation of the airfoil using wind tunnel testing is recommended and planned.

Simulation of the Electrical Resistance Sintering of Hardmetal Powders

Juan Manuel Montes,Francisco J. de la Viña,Íñigo Agote,Thomas Schubert,Francisco G. Cuevas,Yadir Torres,José María Gallardo,Jesús Cintas 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.2

The simulation of the electrical resistance sintering (ERS) of hardmetal powders has been studied. The ERS process canproduce a quick consolidation of electrical conductive powders by the simultaneous application of pressure and electricalcurrent. A model of the process has been developed, integrating three actions, namely, thermal, mechanical and electrical,and taking into account the nature of both the powders and the die where powders are placed. The model has been implementedin COMSOL Multiphysics, a finite element commercial program. This paper deals with the model fundamentals andhardmetal particular aspects, such as modelling properties of mixed powders and its thermal behaviour. Other parameters inthe model have been tuned to optimally fit the initial experimental data. To check simulation results, measurable parametershave been monitored during experimental tests with WC–6 wt% Co. Once the model was completed and put to work, resultsare discussed.