bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of clinical efficacy of Derinat® in form of spray in practice of district therapist
Authors: Babkin A. P. , Zuikova A. A. , Krasnorutskaya O. N. , Kotova Yu. A. , Bugrimov D. Yu. , Kashaeva O. V. , Sizova N. M.
Published: November 2019

The widespread worldwide spread of acute respiratory diseases is an urgent problem in health care. Expressed polyetiology of respiratory diseases does not allow to limit the use of specific vaccine preparations and dictates the need to use to combat them a variety of non-specific means that stimulate the natural resistance of the human body. The main pharmacological action of sodium deoxyribonucleate is the stimulation of phagocytic activity of T-helpers and T-killers, increasing the functional activity of neutrophils and monocytes/ macrophages, providing regeneration and repair processes in the epithelial component of antiviral protection of the body. Based on the above, the study of the clinical efficacy of Derinat® in the form of spray in the treatment of acute respiratory viral infections is relevant.
Emotional Intelligence in Malaysian Police: A Review
Authors: Kanesan, P.
Published: November 2019

This article discussed the findings of previous studies on emotional intelligence in Royal Malaysia Police. Based on the review, emotional intelligence related to job stress, job satisfaction, job commitment, work-life balance, and psychological well-being of police officers. Review concludes that no significant differences in emotional intelligence by demographic factors like salary, working department, age, marital status, length of service, and job position. Police department has to organise training and seminars to enhance the emotional intelligence level of police officers. More studies have to be done on emotional intelligence in the police department, thus the findings will be helpful for the organisation’s development.

 

Keywords: Demographic factors; Police job nature; Job stress; Royal Malaysia Police
Öva och pröva - Hur kan fritidspedagogik stärka teknikundervisningen?
Authors: Karlsson Marie , Jeppsson Fredrik
Published: November 2019

I de senaste styrdokumenten för fritidshem framgår att fritidshem ska bedriva undervisning samt att det finns ett kompletterande uppdrag där verksamheten ska planeras och genomföras så att eleverna tränar vissa förmågor. Men undervisning är inte detsamma som lärande. Om undervisningen ska bidra till lärande måste fritidsläraren vara medveten om hur elever lär sig, besitta vissa ämneskunskaper samt bedriva en undervisning som ökar elevers förståelse. Denna artikel baseras på ett empiriskt material som samlades in till en studie inom ramen för en masterkurs i yngre barns lärande i naturvetenskap, teknik och hållbar utveckling.
Influencia de la administración del capital de trabajo en la rentabilidad empresarial
Authors: Duque Espinoza Gabriela Monserrath , Espinoza Flores Orlando , González Soto Karla , Sigüencia Muñoz Adrián
Published: November 2019

El capital de trabajo es relevante en la administración empresarial, pues proporciona a las firmas los recursos necesarios para llevar a cabo sus operaciones de forma regular, buscando una gestión eficiente que ayude a generar mayores niveles de rentabilidad. La presente investigación tiene por objeto determinar la eficiencia en la administración del capital de trabajo y su relación con la rentabilidad en las empresas del sector textil del Ecuador, y su evolución en el tiempo. Mediante una metodología de análisis cuantitativo, a través de datos de panel, se estudia la relación entre la eficiencia en la administración del capital de trabajo y la rentabilidad, de acuerdo con el nivel de actividad de 425 sociedades. Se evidencia que las firmas que utilizaron de manera más eficiente su capital de trabajo para la generación de ventas fueron las pequeñas y micro empresas. Las empresas pequeñas evidencian una relación positiva entre la variable de estudio y el ROA, lo que demuestra que tener una mayor eficiencia en la administración de capital de trabajo permite a las firmas obtener mayores niveles de rentabilidad.
Inmigrantes venezolanos en el contexto ecuatoriano: análisis de las relaciones interculturales
Authors: González Martínez Elier , Velez Arteaga Maria Fernanda
Published: November 2019

En la actualidad, Ecuador recibe inmigrantes de varios continentes. Refiriéndose a la nacionalidad venezolana, a principios de 2018 aproximadamente 547.000 venezolanos ingresaron a Ecuador a través de la frontera colombiana, eso equivale un promedio diario de entre 2.700 y 3.000 hombres, mujeres y niños. Con posturas a favor y en contra, los venezolanos han enfrentado en el territorio ecuatoriano disimiles dificultades para su integración social, por lo que el objetivo de esta investigación fue analizar las relaciones interculturales de los inmigrantes venezolanos en Ecuador. El enfoque de la investigación fue cuantitativo y se escogió el cuestionario “Relaciones Interculturales en Sociedades Plurales” (versión: grupo ecuatoriano) que se encuentra en el sitio oficial Centre for Applied Cross-cultural Research. Participaron 190 venezolanos en la investigación que residen en la ciudad de Quito y Guayaquil. Los resultados evidenciaron que los mayores problemas están vinculados a actos de discriminación social percibida y lo vinculado con su seguridad. La competencia sociocultural que indagó sobre la actitud de ellos para integrase mostró valores significativos de interés y disposición de ellos para formar parte de la sociedad ecuatoriana.
La ciudad de las oportunidades. Turistificación y emprendimientos del Centro Histórico de Quito
Authors: Llugsha Guijarro Víctor Elías
Published: November 2019

La conservación del patrimonio del Centro Histórico de Quito se encuentra relacionado de forma próxima a las actividades turísticas.  Durante las recientes administraciones municipales, la peatonización de varias calles y la creación de terrazas turísticas, se justifican en criterios de seguridad, disminución de los niveles de contaminación ambiental, el mejoramiento de la calidad del aire y brindar mejores condiciones para la llegada de turistas. Estas acciones sobre el territorio han generado el aparecimiento de nuevos stakeholders que se benefician de las condiciones que el destino les ofrece, remplazando actividades económicas tradicionales, por nuevas que responden a un enfoque de boutiquización (hoteles, restaurantes, tiendas de recuerdos). Por otra parte la conformación de colectivos locales y la participación de nuevos emprendedores que también buscan beneficiarse de las nuevas condiciones que les ofrece el territorio. El documento aborda los conflictos que se generan alrededor de la turistificación del Centro Histórico de Quito, donde la construcción de mejores espacios para el desarrollo de actividades turísticas, llevan a la ciudad a procesos de cambios de actividades económicas y aceleración de la pérdida de población local.
Propuesta de un modelo contextualizado de capacitación para promover un turismo comunitario sustentable: Estudio de caso de la asociación ASORUTACHAGRA
Authors: Ortega Vásconez Daniela Pilar , Cajas Quishpe Diego Christian
Published: November 2019

El turismo comunitario en el Ecuador es una actividad reconocida y regulada legalmente. Estas regulaciones también establecen las actividades y el tipo de capacitación con las que deben contar las comunidades indígenas o rurales  que han tenido la iniciativa por emprender en este sector para garantizar la calidad de los servicios turísticos ofertados.

 El requisito de capacitación y formación se vuelve problemático para los miembros de los emprendimientos comunitarios por diferentes razones, por ejemplo: capacitadores con conocimientos limitados de la comunidad, capacitadores que no poseen las herramientas pedagógicas y metodológicas necesarias para motivar una participación activa de las personas asistentes a las capacitaciones y contenidos de aprendizaje que sean pertinentes con el contexto de la comunidad.  Por este motivo se propone un modelo de co-capacitación de los miembros de la comunidad en el que con el soporte de un facilitador, y utilizando una metodología didáctica basada en problemas (PBL) sean los mismos miembros de la comunidad que compartan sus conocimientos para lograr un aprendizaje común con el objetivo de lograr que sus emprendimientos de turismo comunitario sean rentables y se mantengan en el tiempo.

Palabras clave: turismo comunitario; sostenibilidad; capacitación; pedagogía; metodología.
Estrategias para aumentar el compromiso organizacional en el área de ventas de una empresa de la industria cosmética y cuidado personal
Authors: López Bravo Noli Jhasmeth , Dondero Cassano Pietro Pablo Guissepi
Published: November 2019

La presente investigación desarrollada tiene como objetivo proponer estrategias para mejorar el compromiso organizacional del área de ventas de una empresa de la industria cosmética y cuidado personal. El estudio se trabajó mediante el sintagma holístico, enfoque mixto, de tipo proyectiva, nivel comprensivo, método inductivo y deductivo, para la recopilación de datos se utilizó un cuestionario correspondiente a 18 ítems, la población estuvo constituida por 15 asesores de ventas, mientras que las entrevistas se aplicaron a las tres gerentes. El procesamiento y análisis de la información cuantitativo se realizó con el apoyo del diagrama de Pareto, software Spss.24 y Atlas.ti para la cualitativa. El compromiso organizacional se logró medir a través de tres componentes: compromiso afectivo, de continuidad y normativo, teniendo como resultados por parte del personal la falta de involucramiento, falta de motivación y la rotación continua, es por ello que se planteó el Modelo IML que implica actividades de involucramiento, motivación y una línea de carrera para lograr elevar el compromiso organizacional que es importante el logro de los objetivos organizacionales.
Naturaleza ontológica de la investigación socioeducativa: Elementos orientadores
Authors: Colina Vargas Alejandra Mercedes
Published: November 2019

El presente artículo propone la exploración y revisión de forma sistemática la naturaleza ontológica de la investigación socioeducativa, la cual parte de concebir a la educación como un fenómeno social, delineando con ello el ámbito epistemológico del fenómeno educativo, en la cual se considera la simbiosis entre la naturaleza de la realidad y las características que las rodean. Para ello se realizó un análisis teórico de los componentes y elementos esenciales que conforman la investigación, haciendo énfasis a los aspectos filosóficos, científicos y técnicos que delinean las relaciones entre esos elementos, los cuales perfilan al final en un diseño de investigación de los fenómenos socioeducativos. Dentro de las reflexiones finales destaca el hecho de la existencia de vacíos al emprender una investigación socioeducativa, pues se intenta la producción y reproducción del proceso de investigación social de manera lineal, sin tomar en cuenta las relaciones analíticas, hermenéuticas y reflexivas que circundan sobre los fenómenos educativos estudiados con perspectiva científica.
Estrategias financieras para incrementar la rentabilidad. Caso: Empresa Indema Perú S.A.C
Authors: Zurita Farceque Trinidad , Pucutay Perez Jen Alexis , Córdova Jaime Iduvina , León Sánchez Liliana Yolanda
Published: November 2019

El objetivo de la investigación fue proponer la implementación de estrategias financieras para incrementar la rentabilidad de la empresa Indema Perú S.A.C. Las principales causas del estancamiento en el desarrollo económico empresarial están constituidas por el elevado costo de ventas y la falta de control en los gastos que afectan de manera directa a la utilidad, reflejándose en los respectivos índices. La investigación fue de enfoque mixto, método analítico e inductivo, en la recopilación de datos se aplicó la guía de entrevista a tres unidades informantes que fueron el gerente general, la contadora y el jefe de finanzas, también se aplicó la ficha de análisis documental, los datos se triangularon con el software Atlas. Ti. Los resultados evidenciaron que la rentabilidad sobre los activos disminuyó año tras año, para el año 2016 la empresa tuvo un rendimiento de 0.86% sobre la inversión, en el 2017, generó pérdidas; sin embargo, para el año 2018, obtuvo un 0.08% de rendimiento sobre la inversión. Los factores que influyen de manera directa en la rentabilidad es el alto costo de ventas, que en el 2018 representó un 85% del nivel de ventas y se espera reducir al 70% en los próximos 5 años; los gastos operativos representan el 12%, el cual hace que la utilidad sea escasa.  Por lo tanto, se plantean las siguientes estrategias: a) Incrementar las ventas, b) Reducción de los costos de venta, c) Incrementar la liquidez.
Factores de apoyo de la Academia para generar emprendimientos, caso de estudio Facultad de Hospitalidad y Servicios de la Universidad UTE
Authors: Balarezo Noboa Mauricio Alberto , Cumbal Flores Héctor Silvio
Published: November 2019

El 27.6% de desempleados pertenecen a jóvenes con estudios superiores. El emprendimiento es una oportunidad de trabajo para quienes sueñan en tener una empresa, pero no es fácil, considerando que las IES no cuentan con las estrategias para convertirse en un aliado eficiente. Como objetivos se plantearon: conocer la actitud emprendedora de los estudiantes y descubrir aquellos factores de apoyo provenientes de la academia para que un proyecto estudiantil se convierta en empresa. Se utilizó el método exploratorio descriptivo, estudio de caso en la Facultad de Hospitalidad y Servicios, de la Universidad UTE, como técnicas: encuestas a 316 estudiantes; el cuestionario se basó en el Entrepreneurial Attitude Orientation (EAO) Scale. Como resultados, el 63% de los estudiantes indicaron que están dispuestos a desarrollar nuevas oportunidades, el 43% señalaron que el mayor impedimento para emprender es la capacidad económica, el apoyo más importante que esperan de la universidad es capital de preincubación 38%. Los resultados obtenidos suponen que la facultad debe implementar estrategias para el desarrollo de una cultura emprendedora como base para la generación de proyectos innovadores. Estudiantes, universidad, empresa y gobierno deben interactuar en el marco de un ecosistema de negocios y redes con alcance nacional y regional.

Palabras Claves: negocio; empresa; desarrollo económico y social; gestión
Influence of Farm Management for Calves on Growth Performance and Meat Quality Traits Duration Fattening of Simmental Bulls and Heifers
Authors: Kučević Denis , Papović Tamara , Tomović Vladimir , Plavšić Miroslav , Jajić Igor , Krstović Saša , Stanojević Dragan
Published: November 2019

This study assessed the effects of farm management during rearing practices in the first months of a calf’s life on growth performance and meat quality traits during the fattening period. A total of 48 Simmental calves were divided into two groups at a commercial cattle feedlot. In the first group were calves from the same farm and herd (n = 12 male and n = 12 female). The second group included calves from several different herds and farms (n = 12 male and n= 12 female). Calves were transferred to a feedlot and fed with a commercial feedlot ration at three to four months of age. The aim was to determine if identical fattening conditions at feedlot can reduce initial calf rearing differences between cattle during the fattening period. Bulls grew faster than heifers reaching higher total gain and showed significantly higher slaughter weight than heifers. Meat samples of heifers from the same herd had the highest intramuscular fat content and reddest color with significant differences among cattle groups. The most abundant fatty acid was oleic acid (C18:1), followed by palmitic (C16:0), stearic (C18:0), linoleic (C18:2), and myristic acid (C14:0). Meat samples of heifers from different herds were darkest with highest content of iron (Fe) with significant differences among cattle groups.
The Selection of Reference Genes for Quantitative Real-Time PCR in the Ashidan Yak Mammary Gland During Lactation and Dry Period
Authors: Wu Xiaoyun , Zhou Xuelan , Ding Xuezhi , Chu Min , Liang Chunnian , Pei Jie , Xiong Lin , Bao Pengjia , Guo Xian , Yan Ping
Published: November 2019

Investigating the critical genes related to milk synthesis is essential for the improvement of the milk yield of the yak. Real-time quantitative polymerase chain reaction (RT-qPCR) is a reliable and widely used method to measure and evaluate gene expression levels. Selection of suitable reference genes is mandatory to acquire accurate normalization of gene expression results from RT-qPCR. To select the most stable reference genes for reliable normalization of mRNA expression by RT-qPCR in the mammary gland of the Ashidan yak, we selected 16 candidate reference genes and analyzed their expression stability at different physiological stages (lactation and dry period). The expression stability of the candidate reference genes was assessed using geNorm, NormFinder, BestKeeper, Delta Ct, and RefFinder methods. The results showed that the hydroxymethylbilane synthase gene (HMBS) and the tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide gene (YWHAZ) were the most stable genes across all treatment samples. The reliability of selected reference genes was validated by normalizing relative expression of the lactation-related 60S ribosomal protein L35 gene (RPL35). The relative expression of RPL35 varied considerably according to the different reference genes. This work provides valuable information to further promote research in the molecular mechanisms involved in lactation and mammary gland development and provides a foundation for the improvement of the milk yield and quality of the Ashidan yak.
Do Prenatally-Conditioned Flavor Preferences Affect Consumption of Creep Feed by Piglets?
Authors: Figueroa Jaime , Marchant Ignacio , Morales Pía , Salazar Laura C.
Published: November 2019

Piglets can prefer flavors that are presented to pregnant sows, hence this study intended to estimate the effect of prenatal exposure of piglets to flavors on the intake of flavored creep feed and performance. Gestational sows were fed either a flavored (garlic or aniseed; n24) or an unflavored diet (n24) from days 90 to 114 of gestation. Their litters were offered either garlic, aniseed, or unflavored creep feed during the suckling period, and its intake was measured as well as animal’s final body weight (BW) and average daily gain (ADG). Data was analyzed taking into account the diet offered to both sows and piglets, as well as the interaction between these variables. As previous experiments have shown, flavor learning did not affect a piglet’s performance during the suckling period, finding no differences for creep feed intake, ADG, or BW according to diets (p > 0.05). Repeated exposure of piglets to previously learned flavors without clear post-ingestive benefits could nullify the strategies proposed. Moreover, milk and creep feed diets show a great reward contrast that may accelerate learning extinction. Results of the present and previous experiments suggest that current flavor continuity strategies that are proposed for pig production systems need to be reconsidered.
Principles and Clinical Uses of Real-Time Ultrasonography in Female Swine Reproduction
Authors: Kauffold Johannes , Peltoniemi Olli , Wehrend Axel , Althouse Gary C.
Published: November 2019

Within the past 30 years, through ongoing technology and portability developments, real-time (b-mode) ultrasonography (RTU) has increasingly become a valuable diagnostic tool in assessing the female reproductive tract in swine. Initially applied in swine production to visually determine pregnancy status, RTU use has expanded to include assessment of the peri-pubertal and mature non-pregnant females as well. Transabdominal and transrectal modalities to visualizing the reproductive tract in swine have been reported with the transabdominal approach more common due to the fact of its ease of accessibility, animal/personnel safety, and reduced time to perform. Adjustable frequency transducers are preferred as they allow optimization of image quality at various depths. If a single transducer frequency must be selected, a 5 MHz probe provides the best versatility for visualizing the reproductive tract in swine. Other basic requirements for ultrasound equipment which will be used on commercial swine farms include being light weight and easy to handle, readily cleanable and disinfectable, long battery-life, and good durability. When using RTU for pregnancy determination, diagnosis is based upon a combination of the animal’s breeding records, the presence of embryonic fluid, and, depending upon gestational stage, fetal structures. If RTU is used as a diagnostic tool in assessing reproductive problems in an individual or a group of animals, sonographic evaluation of both the uterus and ovaries is performed. Tissues are delineated and assessed based upon their echogenicity, echotexture, and size. Uses of RTU in clinical practice may include assessment of delayed puberty, prolonged wean-to-estrus interval, absence of post-weaning estrus, herd disruptions in conception and farrowing rates, vulval discharge, peripartum and puerperal disorders. This review aims to provide an overview on principles and clinical uses of RTU with respect to application to address female reproductive performance issues in commercial swine operations.
Linear Response in Topological Materials
Authors: Noky Jonathan , Sun Yan
Published: November 2019

The discovery of topological insulators and semimetals has opened up a new perspective to understand materials. Owing to the special band structure and enlarged Berry curvature, the linear responses are strongly enhanced in topological materials. The interplay of topological band structure and symmetries plays a crucial role for designing new materials with strong and exotic new electromagnetic responses and provides promising mechanisms and new materials for the next generation of technological applications. We review the fundamental concept of linear responses in topological materials from the symmetry point of view and discuss their potential applications.
Understanding Household Energy Transitions: From Evaluating Single Cookstoves to “Clean Stacking” Alternatives
Authors: Medina Paulo , Berrueta Victor , Cinco Lourdes , Ruiz-García Victor , Edwards Rufus , Olaya Belén , Schilmann Astrid , Masera Omar
Published: November 2019

The pervasiveness of “stacking” between traditional and clean fuels/stoves is moving the household clean cooking research and policy agenda from programs that are centered on one-fuel or stove, to multi-clean fuel/device interventions that could result in a more effective displacement of traditional biomass stoves. However, there is little recognition and knowledge of the benefits realistic clean-stacking cooking solutions can have on indoor air quality and health. In this paper, particulate matter (PM2.5) and carbon monoxide (CO) concentration levels that are associated with stove-stacking options (Patsari-U-shaped open fire (U-type), Patsari-liquefied petroleum gas (LPG) stove, U-type-LPG, and Patsari-U-type-LPG) common within rural Mexico were evaluated while using a controlled cooking cycle (CCC) from the Purepecha Highlands, which mimics the most common dishes prepared daily within the region as well as their sequential arrangement. The results confirms that the WHO Interim Target-1 (IT1) of 35 μg/m3 for PM2.5 is exceeded whenever woodburning open fires are part of the stacking combination (Patsari-U-type 107 ± 9 μg/m3, U-type-LPG 131 ± 55 μg/m3 and Patsari-U-type-LPG 107 ± 22 μg/m3). However, well-designed and properly operated woodburning chimney stoves, such as the Patsari can meet the IT1, either used exclusively (21 ± 8 μg/m3) or as a “clean stacking” option with LPG (24 ± 5 μg/m3). Given stove stacking patterns, evaluating the health and environmental consequences of stove transitions while assuming the total replacement of traditional fires by clean cooking options will lead to misplaced expectations, and programs should evaluate more realistic “clean-stacking” options.
C-Fiber Assays in the Cornea vs. Skin
Authors: Moulton Eric A. , Borsook David
Published: November 2019

C-fibers are unmyelinated nerve fibers that transmit high threshold mechanical, thermal, and chemical signals that are associated with pain sensations. This review examines current literature on measuring altered peripheral nerve morphology and discusses the most relevant aspects of corneal microscopy, especially whether corneal imaging presents significant method advantages over skin biopsy. Given its relative merits, corneal confocal microscopy would seem to be a more practical and patient-centric approach than utilizing skin biopsies.
Irrigation Combined with Aeration Promoted Soil Respiration through Increasing Soil Microbes, Enzymes, and Crop Growth in Tomato Fields
Authors: Chen Hui , Shang Zihui , Cai Huanjie , Zhu Yan
Published: November 2019

Soil respiration (Rs) is one of the major components controlling the carbon budget of terrestrial ecosystems. Aerated irrigation has been proven to increase Rs compared with the control, but the mechanisms of CO2 release remain poorly understood. The objective of this study was (1) to test the effects of irrigation, aeration, and their interaction on Rs, soil physical and biotic properties (soil water-filled pore space, temperature, bacteria, fungi, actinomycetes, microbial biomass carbon, cellulose activity, dehydrogenase activity, root morphology, and dry biomass of tomato), and (2) to assess how soil physical and biotic variables control Rs. Therefore, three irrigation levels were included (60%, 80%, and 100% of full irrigation). Each irrigation level contained aeration and control. A total of six treatments were included. The results showed that aeration significantly increased total root length, dry biomass of leaf, stem, and fruit compared with the control (p < 0.05). The positive effect of irrigation on dry biomass of leaf, fruit, and root was significant (p < 0.05). With respect to the control, greater Rs under aeration (averaging 6.2% increase) was mainly driven by soil water-filled pore space, soil bacteria, and soil fungi. The results of this study are helpful for understanding the mechanisms of soil CO2 release under aerated subsurface drip irrigation.
Kinetic Monte-Carlo Simulation of Methane Steam Reforming over a Nickel Surface
Authors: Unruean Palawat , Plianwong Teetuch , Pruksawan Sirawit , Kitiyanan Boonyarach , Ziff Robert M.
Published: November 2019

A kinetic Monte-Carlo model was developed in order to simulate the methane steam reforming and kinetic behavior of this reaction. There were 34 elementary step reactions that were used, based on the Langmuir–Hinshelwood mechanism, over a nickel catalyst. The simulation was investigated at a mole fraction of methane between 0.1 and 0.9, temperature of 600 to 1123 K, and total pressure of up to 40 bar. The simulated results were collected at a steady state and were compared with the previously reported experiments. The fractional coverages of the adsorbed species and the production rates of H2, CO, and CO2 were evaluated, and the effects of the reaction temperature, feed concentration, and total pressure of reactants were also investigated. The simulation results showed a similar trend with previous experimental results, and suggested the appropriate conditions for this reaction, which were a total pressure of 10 bar, with the mole fraction of methane in a range of 0.4–0.5.
Systemic Toxicity Reported for CDK8/19 Inhibitors CCT251921 and MSC2530818 Is Not Due to Target Inhibition
Authors: Chen Mengqian , Li Jing , Liang Jiaxin , Thompson Zanshé S. , Kathrein Katie , Broude Eugenia V. , Roninson Igor B.
Published: November 2019

CDK8/19 kinases, which mediate transcriptional reprogramming, have become an active target for cancer drug discovery. Several small-molecule CDK8/19 inhibitors showed in vivo efficacy and two have entered clinical trials, with no significant toxicities reported. However, Clarke et al. (eLife 2016; 5; e20722) found severe systemic toxicity associated with two potent CDK8/19 inhibitors, Cmpd3 (CCT251921) and Cmpd4 (MSC2530818), and suggested that their toxicity was due to on-target effects. Here, we compared five CDK8/19 inhibitors: Cmpd3, Cmpd4, Senexin B, 16-didehydro-cortistatin A (dCA) and 15w, in different assays. Only Cmpd4 showed striking toxicity in developing zebrafish. In cell-based assays for CDK8 and CDK19 inhibition, Cmpd3, Cmpd4, dCA and 15w showed similar low-nanomolar potency and efficacy against CDK8 and CDK19, while Senexin B was less potent. Only dCA produced sustained inhibition of CDK8/19-dependent gene expression. While toxicity of different compounds did not correlate with their effects on CDK8 and CDK19, kinome profiling identified several off-target kinases for both Cmpd3 and Cmpd4, which could be responsible for their toxicity. Off-target activities could have been achieved in the study of Clarke et al. due to high in vivo doses of Cmpd3 and Cmpd4, chosen for the ability to inhibit STAT1 S727 phosphorylation in tumor xenografts. We show here that STAT1 S727 phosphorylation is induced by various cytokines and stress stimuli in CDK8/19-independent manner, indicating that it is not a reliable pharmacodynamic marker of CDK8/19 activity. These results illustrate the need for careful off-target analysis and dose selection in the development of CDK8/19 inhibitors.
MiR-21, MiR-29a, GATA4, and MEF2c Expression Changes in Endothelin-1 and Angiotensin II Cardiac Hypertrophy Stimulated Isl-1+Sca-1+c-kit+ Porcine Cardiac Progenitor Cells In Vitro
Authors: Zlabinger Katrin , Spannbauer Andreas , Traxler Denise , Gugerell Alfred , Lukovic Dominika , Winkler Johannes , Mester-Tonczar Julia , Podesser Bruno , Gyöngyösi Mariann
Published: November 2019

Cost- and time-intensive porcine translational disease models offer great opportunities to test drugs and therapies for pathological cardiac hypertrophy and can be supported by porcine cell culture models that provide further insights into basic disease mechanisms. Cardiac progenitor cells (CPCs) residing in the adult heart have been shown to differentiate in vitro into cardiomyocytes and could contribute to cardiac regeneration. Therefore, it is important to evaluate their changes on the cellular level caused by disease. We successfully isolated Isl1+Sca1+cKit+ porcine CPCs (pCPCs) from pig hearts and stimulated them with endothelin-1 (ET-1) and angiotensin II (Ang II) in vitro. We also performed a cardiac reprogramming transfection and tested the same conditions. Our results show that undifferentiated Isl1+Sca1+cKit+ pCPCs were significantly upregulated in GATA4, MEF2c, and miR-29a gene expressions and in BNP and MCP-1 protein expressions with Ang II stimulation, but they showed no significant changes in miR-29a and MCP-1 when stimulated with ET-1. Differentiated Isl1+Sca1+cKit+ pCPCs exhibited significantly higher levels of MEF2c, GATA4, miR-29a, and miR-21 as well as Cx43 and BNP with Ang II stimulation. pMx-MGT-transfected Isl1+Sca1+cKit+ pCPCs showed significant elevations in MEF2c, GATA4, and BNP expressions when stimulated with ET-1. Our model demonstrates that in vitro stimulation leads to successful Isl1+Sca1+cKit+ pCPC hypertrophy with upregulation of cardiac remodeling associated genes and profibrotic miRNAs and offers great possibilities for further investigations of disease mechanisms and treatment.
Influence of Substrate Shape and Roughness on Coating Microstructure in Suspension Plasma Spray
Authors: Caio Fernanda , Moreau Christian
Published: November 2019

This study investigated the influence of the substrate shape and roughness on the microstructure of suspension plasma spray (SPS) coatings. For this purpose, an yttria-stabilized zirconia (YSZ) suspension was sprayed on flat and curved stainless-steel substrates by SPS. The suspension was composed of 20 wt.% YSZ particles in ethanol. After spraying, the morphology of the coatings was characterized by scanning electron microscopy (SEM). The results showed that the substrate shape influences the amount of coating material deposited and microstructural features of the coating. The amount of coating material deposited was seen to decrease as the radius of curvature decreased. Finally, the roughness was found to influence the formation of columnar structure.
X-ray Assisted Scanning Tunneling Microscopy and Its Applications for Materials Science: The First Results on Cu Doped ZrTe3
Authors: Yan Hui , Shirato Nozomi , Zhu Xiangde , Rosenmann Daniel , Tong Xiao , Xu Weihe , Petrovic Cedomir , Rose Volker , Nazaretski Evgeny
Published: November 2019

Synchrotron X-ray Scanning Tunneling Microscopy (SX-STM) is a novel imaging technique capable of providing real space chemically specific mapping with a potential of reaching atomic resolution. Determination of chemical composition along with ultra-high resolution imaging by SX-STM can be realized through excitation of core electrons by incident X-rays when their energy is tuned to an absorption edge of a particular atom during raster scanning, as is done in the conventional STM experiments. In this work, we provide a brief summary and the current status of SX-STM and discuss its applications for material science. In particular, we discuss instrumentation challenges associated with the SX-STM technique and present early experiments on Cu doped ZrTe3 single crystals.
Ovarian Cancer Targeting Phage for In Vivo Near-Infrared Optical Imaging
Authors: Asar Mallika , Newton-Northup Jessica , Deutscher Susan , Soendergaard Mette
Published: November 2019

Ovarian cancer is often diagnosed at late stages due to current inadequate detection. Therefore, the development of new detection methods of ovarian cancer is needed. This may be achieved by phage nanoparticles that display targeting peptides for optical imaging. Here, two such phage clones are reported. Ovarian cancer binding and specificity of phage clones (pJ18, pJ24) and peptides (J18, J24) were investigated using fluorescent microscopy and modified ELISA. Further, AF680-labeled phage particles were subjected to biodistribution and optical imaging studies in SKOV-3 xenografted mice. Fluorescent microscopy and ELISA of phage and peptides showed significantly increased binding to SKOV-3 cells compared to controls. Additionally, these studies revealed that J18 exhibits specificity for ovarian cancer SKOV-3 and OVCAR-3 cell lines. Further, peptides displayed increased SKOV-3 binding compared to N35 (non-relevant peptide) with EC50 values of 22.2 ± 10.6 μM and 29.0 ± 6.9 (mean ± SE), respectively. Biodistribution studies of AF680-labeled phage particles showed tumor uptake after 4 h and excretion through the reticuloendothelial system. Importantly, SKOV-3 tumors were easily localized by optical imaging after 2 h and 4 h and displayed good tumor-to-background contrast. The fluorescent tumor signal intensity was significantly higher for pJ18 compared to wild type (WT) after 2 h.
Impact of Heating Control Strategy and Occupant Behavior on the Energy Consumption in a Building with Natural Ventilation in Poland
Authors: Kaminska Aniela
Published: November 2019

This study aims to provide an experimental assessment of energy consumption in an existing public building in Poland, in order to analyze the impact of occupant behavior on that consumption. The building is naturally ventilated and the occupants have the freedom to change the temperature set point and open or close the windows. The energy consumption is calculated and the calculation results are compared with the experimental data. An analysis of occupants’ behavior has revealed that they choose temperature set points in a wide range recognized as thermal comfort, and window opening is accidental and difficult to predict. The implemented heating control algorithms take into account the strong influence of individual occupant preferences on the feeling of comfort. The energy consumption assessment has revealed that the lowering of temperature set point by 1 °C results in an energy saving of about 5%. Comparisons of energy consumption with heating control and without any controls showed that the potential for energy reduction due to heating control reached approximately 10%. The use of windows control, which allows to turn off the heating after opening the window and its impact on energy savings have been discussed as well.
The Combined Role of Retention Pattern and Post-Harvest Site Preparation in Regulating Plant Functional Diversity: A Case Study in Boreal Forest Ecosystems
Authors: Wei Liping , Fenton Nicole J. , Lafleur Benoit , Bergeron Yves
Published: November 2019

Changes in the light availability in forests generated by diversified retention patterns (e.g., clear cut, partial harvest) have been shown to strongly filter the plant species present. Modified soil microsite conditions due to post-harvest site preparation (e.g., mechanical site preparation, prescribed fire) might also be an important determinant of plant diversity. The objective here was to detect how retention pattern and post-harvest site preparation act as filters that explain the understory functional diversity in boreal forests. We also assessed whether these effects were dependent on forest attributes (stand type, time since fire, and time since harvest). We retrieved data from seven different studies within 101 sites in boreal forests in Eastern Canada. Our data included forests harvested with two retention patterns: careful logging and clear cut, plus unharvested control forests. Three post-harvest site preparation techniques were applied: plow or disk trenching after careful logging, and prescribed fire after clear cut. We collected trait data (10 traits) representing plant morphology, regeneration strategy, or resource utilization for common species. Our results demonstrated significant variation in functional diversity after harvest. The combined effect of retention pattern and site preparation was the most important factor explaining understory diversity compared to retention pattern only and forest attributes. According to RLQ analysis, harvested forests with site preparation favored traits reflecting resistance or resilience ability after disturbance (clonal guerilla species, geophytes, and species with higher seed weight). Yet harvested forests without site preparation mainly affected understory plant species via their light requirements. Forest attributes did not play significant roles in affecting the relationship between site preparation and functional diversity or traits. Our results indicated the importance of the compounding effects of light variation and soil disturbance in filtering understory diversity and composition in boreal forests. Whether these results are also valid for other ecosystems still needs to be demonstrated.
Comparative Characterization of Protein Hydrolysates from Three Edible Insects: Mealworm Larvae, Adult Crickets, and Silkworm Pupae
Authors: Yoon Sungwon , Wong Nathan A. K. , Chae Minki , Auh Joong-Hyuck
Published: November 2019

A comparative characterization of proteins from three edible insects—Tenebrio molitor (mealworm) larvae, Gryllus bimaculatus (cricket), and Bombyx mori (silkworm) pupae—was performed in this study. Proteins were extracted from edible insects and their hydrolysates were prepared through enzymatic hydrolysis with commercial enzymes (Flavourzyme: 12%; Alcalase: 3%). Solubility was significantly higher following enzymatic hydrolysis, while foamability was lower compared to those of the protein control. Angiotensin-converting enzyme was significantly inhibited after enzymatic hydrolysis, especially following Alcalase treatment, with IC50 values of 0.047, 0.066, and 0.065 mg/mL for G. bimaculatus, T. molitor larvae, and B. mori pupae, respectively. Moreover, the Alcalase-treated group of B. mori pupae and the T. molitor larvae group treated with a mixture of enzymes showed the effective inhibition of α-glucosidase activity. The anti-inflammatory activity of the insect hydrolysates was assessed via nitric oxide production from macrophages, and B. mori pupae samples exhibited significant activity regardless of the method of hydrolysis. These results indicate the functional properties of protein and hydrolysates from three species of edible insects, which may be useful in their future exploitation.
Wnt-11 Expression Promotes Invasiveness and Correlates with Survival in Human Pancreatic Ductal Adeno Carcinoma
Authors: Dart Dafydd A. , Arisan Damla E , Owen Sioned , Hao Chunyi , Jiang Wen G. , Uysal-Onganer Pinar
Published: November 2019

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer, proving difficult to manage clinically. Wnt-11, a developmentally regulated gene producing a secreted protein, has been associated with various carcinomas but has not previously been studied in PDAC. The present study aimed to elucidate these aspects first in vitro and then in a clinical setting in vivo. Molecular analyses of Wnt-11 expression as well as other biomarkers involved qRT-PCR, RNA-seq and siRNA. Proliferation was measured by MTT; invasiveness was quantified by Boyden chamber (Matrigel) assay. Wnt-11 mRNA was present in three different human PDAC cell lines. Wnt-11 loss affected epithelial-mesenchymal transition and expression of neuronal and stemness biomarkers associated with metastasis. Indeed, silencing Wnt-11 in Panc-1 cells significantly inhibited their Matrigel invasiveness without affecting their proliferative activity. Consistently with the in vitro data, human biopsies of PDAC showed significantly higher Wnt-11 mRNA levels compared with matched adjacent tissues. Expression was significantly upregulated during PDAC progression (TNM stage I to II) and maintained (TNM stages III and IV). Wnt-11 is expressed in PDAC in vitro and in vivo and plays a significant role in the pathophysiology of the disease; this evidence leads to the conclusion that Wnt-11 could serve as a novel, functional biomarker PDAC.
The Role of Shear Wave Velocity and Non-Linearity of Soil in the Seismic Response of a Coupled Tunnel-Soil-Above Ground Building System
Authors: Abate Glenda , Grasso Salvatore , Massimino Maria Rossella
Published: November 2019

The presence of tunnels close to aboveground structures may modify the response of these structures, while the contrary is also true, the presence of aboveground structures may modify the dynamic response of tunnels. In this context, the dynamic properties of the soil through which the aboveground and underground structures are “connected” could play an important role. The paper reports dynamic FEM (Finite Element Method) analyses of a coupled tunnel-soil-above ground structure system (TSS system), which differ in regards to the soil shear wave velocity and in turns for the damping ratio, in order to investigate the role of these parameters in the full-coupled TSS system response. The analyses were performed using three different seismic inputs. Moreover, the soil non-linearity was taken into account adopting two different constitutive models: i) an equivalent linear visco-elastic model, characterized by degraded soil shear moduli and damping ratios, according to suggestions given by EC8 in 2003; and ii) a visco-elasto-plastic constitutive model, characterized by isotropic and kinematic hardening and a non-associated flow rule. The seismic response of the system was investigated in the time and frequency domains, in terms of: acceleration ratios; amplification ratios and response spectra; and bending moments in the tunnel.
VEGFR-1 Regulates EGF-R to Promote Proliferation in Colon Cancer Cells
Authors: Nagano Hikaru , Tomida Chisato , Yamagishi Naoko , Teshima-Kondo Shigetada
Published: November 2019

The relationship between epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) pathways in tumor growth is well established. EGF induces VEGF production in cancer cells, and the paracrine VEGF activates vascular endothelial cells to promote tumor angiogenesis and thus supports tumor cell growth in an angiogenesis-dependent manner. In this study, we found angiogenesis-independent novel crosstalk between the VEGF and the EGF pathways in the regulation of colon cancer cell proliferation. Stimulation of colon cancer cells with VEGF-A and placental growth factor (PlGF) activated VEGF receptor-1 (VEGFR-1) and increased proliferation activity in an autocrine EGF/EGF receptor (EGF-R)-dependent manner. Mechanistically, VEGFR-1 interacted with and stabilized EGF-R, leading to increased EGF-R protein levels and prolonged its expression on cell surface plasma membrane. In contrast, VEGFR-1 blockade by a neutralizing antibody and an antagonistic peptide of VEGFR-1 suppressed the complex formation of VEGFR-1 and EGF-R and decreased EGF-R expression via a lysosome-dependent pathway, resulting in the suppression of proliferation activity. Our results indicated that VEGFR-1 regulated EGF-R expression to promote proliferation activity in a cell-autonomous-dependent manner.
Assessing the Resilience Potential of Inshore and Offshore Coral Communities in the Western Gulf of Thailand
Authors: Sutthacheep Makamas , Chamchoy Charernmee , Pengsakun Sittiporn , Klinthong Wanlaya , Yeemin Thamasak
Published: November 2019

Coral reefs in the Gulf of Thailand have experienced severe coral bleaching events and anthropogenic disturbances during the last two decades. This study assessed the resilience potential of coral communities at Ko Losin offshore reef sites and Mu Ko Chumphon nearshore coral reefs, in the south of Thailand, by conducting field surveys on the live coral cover, hard substratum composition and diversity and density of juvenile corals. Most study sites had higher percentages of live coral cover compared to dead coral cover. Some inshore and offshore reef sites showed low resilience to coral bleaching events. The total densities of juvenile corals at the study sites were in the range of 0.89–3.73 colonies/m2. The density of the juvenile corals at most reef sites was not dependent on the live coral cover of adult colonies in a reef, particularly for the Acropora communities. We suggest that Ko Losin should be established as a marine protected area, and Mu Ko Chumphon National Park should implement its management plans properly to enhance coral recovery and promote marine ecotourism. Other measures, such as shading, should be also applied at some coral reefs during bleaching periods.
A Study of Tenselessness in Rengma (Western)
Authors: Longmailai Monali
Published: November 2019

Rengma is a Tibeto–Burman language from the Naga group (Angami–Pochuri) spoken in Northeast India. The paper is one of the first attempts in documenting the Western Rengma language, a variety of Rengma found in Karbi Anglong district, Assam. It makes attempts to study the tense, aspect and mood features present in Western Rengma in comparison to related neighbouring Tibeto-Burman (TB) languages such as Angami and Sema and thereby, seek to identify the aspect of tenselessness in this language. The study further examines the serial verb construction (SVC) as pivotal in determining time in relation to tense–aspect–mood (TAM). Throughout the paper, we observe the semantic-pragmatic features to probe the verbal features and later validate if time in Rengma is a genetic or an areal feature.