bluuebunny/crossref_metadata_2025 huggingface dataset:
AMENDING SECTION 84 PATENTS ACT 1983 TO ENCOMPASS THE HEALTH FLEXIBILITIES LEVERAGE ACCORDED BY ARTICLE 31bis TRIPS AGREEMENT
Authors: Hingun Mohsin , Mohamed Nizamuddin Rahamatthunnisa
Published: January 2021

The significance of this study lies in its proposal to insert an appropriate provision into the Patents Act 1983 to embody the provisions of Article 31bis TRIPS Agreement. The methodology adopted in this study is library-based, and relies extensively on primary sources such as the Paris Convention, TRIPS Agreement and Patents Act 1983. This is further supported through secondary sources such as articles, books, websites and newspaper reports. The research question posed in this study aims to identify the most appropriate provision that should be incorporated into the Patents Act 1983 in addressing the public health flexibilities provided under Article 31bis. The purpose of this study is to demonstrate that Article 31bis is best incorporated into the Patents Act 1983, under the right of the government mechanism rather than through the compulsory license mechanism. Furthermore, the scope of this study is limited to issues that address the abuse of monopoly, granted by the patent system, with respect to the dire needs of the public health. Hence, this paper discusses the mechanisms that address abuse of the patent system under Article 5(A) Paris Convention, Articles 31 and 31bis TRIPS Agreement, the relevant corresponding provisions under the Patents Act 1983, and subsequently formulates new proposed amendments to Section 84 Patents Act 1983 to buttress the public health flexibilities provided under Article 31bis. The outcome of this study proposes that the provisions of Article 31bis should be incorporated into the Patents Act 1983 under the right of the government mechanism, by replacing the current Section 84 Patents Act 1983 with a newly proposed Section 84.
Celebrity Endorsement, Price dan Customer Behavior terhadap Social Climber pada Generasi Melenial di Kota Denpasar
Authors: Purnama Sari Desak Made Febri , Safitri Helmy
Published: January 2021

Penelitian ini bertujuan untuk mengetahui pengaruh celebrity endorsement, price, dan customer behavior terhadap social climber pada generasi milenial di Kota Denpasar. Populasi penelitian ini generasi milenial (1982-2000) yang berusia 19 tahun sampai 37 tahun di daerah Denpasar yang berjumlah 366.700 jiwa, penelitian menyebarkan kuesioner kepada 100 orang. Kuesioner sebagai alat ukur dengan skala likert. Penelitian menggunakan teknik kuantitatif. Metode analisis pada penelitian ini adalah analisis uji validitas, uji reliabilitas, uji asumsi klasik, dan uji analisis regresi linier berganda dengan bantuan aplikasi SPSS version 20.0. Dinyatakan bahwa celebrity endorsement, price, dan customer behavior merek berpengaruh positiif dan signifiikan secara parsial dan simultan terhadap social climber pada generasi milenial. Hasil pengujuan 54,7% yang berarti bahwa variasi variable social climber mejelaskan bahwa ketiga varian variable independent celebrity endorsement, price dan customer behavior. Sedangkan sisanya (100%-54,7% = 45.3%) dijelaskan oleh sebab-sebab lain diluar model yaitu gaya hidup,lingkungan dan status sosial.
Evaluasi Rasio Keuangan Pada Kategori BUKU 3
Authors: Sihotang Ellen Theresia , Puspasari Ismayantika Dyah , Kurnia Anisa Utika
Published: January 2021

Tujuan dari penelitian ini adalah untuk mengetahui elemen rasio keuangan yang mempengaruhi ROE pada Bank Umum Kegiatan Usaha (BUKU) III. Rasio keuangan yang digunakan adalah rasio kecukupan modal (Capital Adequacy Ratio/CAR), Loan to Deposit Ratio (LDR), Loan to Asset Ratio (LAR), Non Performance Loan (NPL), Beban Operasional terhadap Pendapatan Operasional (BOPO) dan Fee Based Income Ratio (FBIR). Metode pengambilan sampel menggunakan purposive sampling. Tiga bank yang memenuhi kriteria sampel adalah PT Bank Bukopin, Tbk; PT Bank Mayapada Tbk, dan PT Bank Mega, Tbk. Periode penelitian adalah 2015-2019. Teknik analisis data menggunakan regresi berganda. Hasil penelitian ini mengungkapkan bahwa CAR, LDR, NPL, BOPO dan FBIR secara simultan berpengaruh signifikan terhadap ROE. CAR, LDR, NPL, dan BOPO memiliki pengaruh negatif signifikan terhadap ROE, sedangkan FBIR tidak berpengaruh secara signifikan terhadap ROE. CAR merupakan variabel yang berpengaruh paling dominan terhadap ROE dengan kontribusi sebesar 51,4%. Pemenuhan terhadap kecukupan modal bank mengindikasikan bahwa bank mampu menyerap sejumlah kerugian operasional secara efisien. Peningkatan CAR dapat menyebabkan penurunan laba dan ROE karena pengeluaran terhadap aset tertimbang menurut risiko lebih besar dibandingkan ketersediaan modal, sehingga perolehan laba dan ROE menurun. Penurunan nilai ROE berpengaruh juga pada menurunnya tingkat pengembalian bagi sejumlah investor.
Analisis Pengaruh Realisasi Belanja Pemerintah Terhadap Penerimaan Pajak di Indonesia
Authors: Kurniawan Tria Sandi , Sari Dyah Wulan , Irmawati Dyah Reni
Published: January 2021

This study examines the effect of the realization of government spending consisting of goods expenditure, capital expenditure and employee expenditure on tax revenue in Indonesia. In this study, we use four analytical methods that consist of  Granger Test, Partial Adjustment Model (PAM), Error Correction Model (ECM) and Vector Autoregression (VAR). The result shows that the realization of goods and employee expenditure are significant determinant of the tax revenue. Further examination shows that the shocks on goods and employee expenditure have a positive impacts toward tax revenue. However the shock effect are different on those variables. On the shock to goods expenditure, the tax revenue response will occur directly, in contrast to shock on employee expenditure that requires time lag. This study also find that between PAM and ECM, the ECM model is more appropriate to be used to explain the effect of government spending on tax revenue in Indonesia.
Determinan Kepatuhan Bendahara Pemerintah dalam Menyetorkan Penerimaan Pajak
Authors: Harjowiryono Marwanto
Published: January 2021

Penerimaan pajak yang bersumber dari aktivitas belanja APBN dan belanja APBD masih dianggap belum optimal, bertolak belakang dengan jumlah pagu APBN dan APBD yang terus meningkat setiap tahun. Peran bendahara pemerintah baik pada Satuan Kerja Pemerintah Pusat maupun Pemerintah Daerah menjadi sorotan utama. Penelitian ini bertujuan untuk menganalisis faktor-faktor yang mempengaruhi kepatuhan Bendahara Satuan Kerja Pemerintah Pusat dan Pemerintah Daerah dalam menyetor penerimaan pajak dengan mengacu pada Teori Atribusi Fritz Heider yang memiliki relevansi dalam menemukan faktor-faktor yang mempengaruhi seseorang dalam memilih suatu keputusan. Penelitian ini dilakukan dengan menyebarkan kuisioner terhadap Bendahara Satuan Kerja Pemerintah Pusat dan Bendahara Satuan Kerja Pemerintah Daerah lingkup 34 propinsi di Indonesia dengan menggunakan Kepatuhan Pajak Bendahara Pemerintah sebagai variabel terikat dan variabel bebas terdiri dari Pengetahuan Perpajakan, Sikap Terhadap Kewajiban Perpajakan,  Kualitas Pelayanan Pajak, Kemudahan Aplikasi Pajak, Efektivitas Administrasi Perpajakan dan Sertifikasi Bendahara. Setelah melalui uji validitas dan reliabilitas kuisioner, hasil kuisioner dianalisis dengan menggunakan metode regresi logistik. Hasil penelitian menunjukkan bahwa secara simultan dan secara parsial, seluruh variabel bebas berpengaruh terhadap Kepatuhan Pajak Bendahara Pemerintah Daerah. Program Sertifikasi Bendahara yang diperluas tidak hanya untuk Bendahara Satker Pemerintah Pusat, tetapi juga untuk Bendahara Satker Pemda dapat menjadi solusi untuk meningkatkan kualitas Bendahara Pemerintah.
Modelación matemática para optimizar la estructura de los cursos en las plataformas e-learning
Authors: Machín Armenteros Amaury , Vázquez Alfonso Yasser
Published: January 2021

Esta investigación se realizó en la Universidad Agraria de la Habana “Fructuoso Rodríguez Pérez” (UNAH) ubicada en la provincia de Mayabeque. Tuvo como principal objetivo modelar matemáticamente el comportamiento de los usuarios en las plataformas educativas para la optimización de la estructura de los cursos a partir de la matriz de adyacencia y bajo los supuestos que, a mayor tiempo de permanencia en una página de la misma sesión, mayor interés en ella, y que la frecuencia de uso de las interrelaciones indica una mayor utilidad de las mismas para acceder hacia la información deseada. Haciendo uso de Minería Web se extrajeron los datos necesarios para aplicar el modelo a los logs del curso Estructura de Datos II de la plataforma Moodle. El modelo propuesto permite optimizar y personalizar la estructura de los cursos en las plataformas educativas, se logra encontrar estructuras de navegación más eficientes desde el punto de la navegabilidad y usabilidad, mejorando en concreto la estructura de los cursos de las plataformas educativas en la UNAH.
La educación del talento académico en los estudiantes desde la física
Authors: León Arencibia Ariel , Dorvigny González Beatriz de la Caridad , Rodríguez Brito Bárbaro Evelio
Published: January 2021

En este trabajo se revela como problemática la insuficiente preparación de los docentes para asumir, entre sus objetivos, la educación del talento académico de los estudiantes desde la Física. Se presentan herramientas al docente para su preparación en la educación del talento académico de los estudiantes desde la Física, a partir de nuevos fundamentos semióticos que permiten utilizar los códigos culturales y cotidianos para motivar intrínsecamente a los estudiantes, se proponen principios, definiciones en que esta se sustenta, así como sus elementos condicionantes, dimensiones e indicadores, que se concretan a través de las orientaciones con pasos metodológicos.
Modelación y simulación del rendimiento del pasto estrella (C.nlemfuensis) bajo diferentes condiciones de manejo y escenarios climáticos
Authors: López Rodríguez Jorge Lázaro , Larduet Vicet Rubén
Published: January 2021

El presente trabajo tuvo como objetivos modelar y simular la producción de materia seca acumulada (RMSA) del pasto estrella (C. nlemfuensis) y estudiar la influencia de dos escenarios climáticos sobre el desempeño de esta variable y de esta forma contribuir a la toma de decisiones en condiciones ambientales desfavorables para el desarrollo de este cultivo. Los escenarios considerados fueron: temperatura media del planeta se eleve 2 ºC (A2) y que esta variable se eleve 4 ºC (B2). Para ello, se utilizó información de experimentos generados en áreas del Instituto de Ciencia Animal y de trabajos publicados acerca de la influencia del clima sobre RMSA, se encontró que el modelo Gompertz fue el de mejor ajuste del RMSA vs la edad de rebrote, con elevados coeficientes de determinación, sesgos y errores de estimación pequeños en todas las mediciones analizadas. Se obtuvieron además un grupo de indicadores notables para la toma de decisiones de productores e investigadores, tales como punto de inflexión (edad del cultivo en la cual su curva de crecimiento pasa de un tipo de concavidad a otra), valor óptimo de cosecha, que corresponde al valor de la edad en que se intersectan las curvas de incrementos corriente medio (RMSA dividida entre la edad) y diario (derivada de la función de Gompertz evaluada en la edad), entre otros. Fue seleccionado el modelo multiplicativo exponencial para estudiar el efecto del clima sobre RMSA, donde se apreció que los escenarios estudiados A2 y B2, tuvieron efectos negativos sobre el rendimiento de materia seca acumulada, debido a que ocasionaron aumento de temperatura media y disminución de las precipitaciones y radiación global. Se obtuvo un programa computacional (SERPE) que estima los rendimientos acumulados de materia seca bajo diferentes condiciones ambientales.
El enfoque comunicativo mediante el tratamiento de la gramática inglesa en la carrera de medicina y estomatología
Authors: Velasteguí López Luis Efraín
Published: January 2021

El continuo desarrollo del mundo de hoy exige de una preparación integral de los profesionales de todas las esferas de la sociedad, mostrando dominio no solo de una especialidad determinada en la cual estos se desempeñen, sino también en aspectos generales y culturales, así como el dominio de un idioma extranjero, especialmente, el inglés, dada la razón de ser el idioma universal, en tanto que no solo es la lengua materna para muchos países, sino que en otros se habla como segunda lengua.
Estimativa do desperdício das dietas hospitalares associado a satisfação e aceitação dos pacientes no Hospital Universitário Alcides Carneiro em Campina Grande -PB
Authors: Baía Sandra Regina Dantas , Souza Thaisa Abrantes da Silva , Gusmão Rennan Pereira de , Santos Rebeca Morais Silva , Pimentel Gabriela Mariana Cruz , Costa Rikaelly Vital , Medeiros Elis Dantas
Published: January 2021

Vários são os impactos causados ao meio ambiente ocasionados pelos processos de produção de refeições. A pesquisa foi realizada com o objetivo de avaliar o desperdício dos alimentos associados a aceitação e a satisfação da dieta hospitalar dos pacientes internos do Hospital Universitário em Campina Grande-PB. Trata-se de um estudo transversal quantitativo, onde foi aplicado o sistema de pesagem antes e após a refeição e posteriormente foi aplicado um questionário referente a satisfação das dietas oferecidas aos internos. Destacamos a opção de muito satisfeitos para os atributos: sabor 33,98%; aparência 33%; cor 35,92%; textura 33,98%; temperatura 46,60%; forma de distribuição 51,45%; recipiente servido 53,39% e quantidade servida 41,74%. Embora o estudo apresente uma boa satisfação na dieta ofertada, ainda assim há um desperdício com um valor de 30%, o que ultrapassa o limite aceitável de 20% para coletividade enferma, demonstrando um consumo reduzido de ingestão de energia e proteína pelo paciente, ocasionando um duplo aumento no risco de morte durante uma internação hospitalar. Em relação aos dois gêneros constatamos que o gênero masculino apresentou um menor desperdício (27,88%) em relação ao gênero feminino (32,79%). Corroborar a importância de ações educativas com intuito de amenizar esses desperdícios alimentares e evitar desnutrição nos pacientes, custos hospitalares e impactos ao meio ambiente, realizando trimestralmente uma pesquisa de satisfação com os pacientes; expor em murais a quantidade de desperdício diária dos alimentos; e doar os alimentos excedentes  a pessoas com risco alimentar e nutricional, apoiado na Lei 14016 de 23 de junho de 2020.
Functional properties of immune cells under the influence of extracts of mushrooms Ganoderma lucidum, Lentinula edodes, Boletus edulis
Authors: Duzh Еlena V. , Hancharou Аndrei Y.
Published: January 2021

Тhe water extracts of Basidiomycota division mushrooms such as Boletus edulis, Ganoderma lucidum, Lentinula edodes posessed a wide spectrum of immunomodulatory activity. It was shown that Boletus edulis enhances the expression of surface markers on lymphoid cell lines Jurkat-tat and Daudi, and also increases the expression of reactive oxygen species by dendritic cells, monocytes and peripheral blood neutrophils, activates basophils. There was observed no effect of fungal extracts on NK-cells.
Sclerotinia sclerotiorum KK-1 isolate from Belarus: pathogenicity factors and glyphosate sensitivity
Authors: Kulik Alena V. , Shukshina Margarita A. , Evtushenkov Anatoliy N.
Published: January 2021

In the presence work, mycelial growth, sclerotia formation, polygalacturonase, a-amylase and cellulase activities of a Belarusian fungal isolate Sclerotinia sclerotiorum KK-1 collected from infected сarrot (Daucus carota subsp. sativus) were analyzed. It was established that polygalacturonase was induced by pectin and subject to catabolite repression by glucose. The ability of the isolate to produce oxalic acid, an important factor of pathogenesis, was observed throughout fungus incubation on PDA medium amended with bromophenol blue. Glyphosate (commercial counterpart «Tornado») starting from its level in the medium of 200 mg/L caused a significant inhibition of mycelial growth and sclerotia formation. It was observed that a-amylase and cellulase activities were inhibited by glyphosate unlike polygalacturonase activity.
The first registration of the wintering of invasive species of coccinellid Harmonia axyridis (Pallas, 1773) in the bee hives in Belarus
Authors: Kruglova Oksana Yu. , Prischepchik Oleg V.
Published: January 2021

The first registration in Belarus of an invasive species of coccinellid Harmonia axyridis wintering in bee hives in the Galik village (Drogichinsky district, Brest region) has been established. Some structural features of the obtained sample of H. axyridis are analyzed. The sex ratio is closed to the theoretically expected (1 : 1) – 50.5 % of females and 49.5 % of males. Three of the four main phenotypic color classes of elytra are distinguished in imago – succinea, conspicua and spectabilis. The succinea phenotype is dominated with a frequency of 95.78 %. The elite crest was absent in 10 % of specimens.
Co-ocurrencia de peces fluviátiles en los ríos de Gibara, Holguín, Cuba
Authors: Reynaldo de la Cruz Enrique , Vega Cendejas María Eugenia , Vega Torres Antonio , Córdova García Elier
Published: January 2021

La estructura de los ensamblajes de peces fluviales se ha relacionado con los factores abióticos y la recolonización dinámica, en lugar de considerar las interacciones bióticas como las de mayor importancia. Este trabajo se propuso determinar patrones de coexistencia entre las especies ictiológicas dulceacuícolas en los ríos del municipio Gibara, Holguín, Cuba. El índice del puntaje-C observado fue 0.732, mayor al simulado (0.6762). Los pares de especies que presentaron más unidades de co-ocurrencia (6) correspondieron a: Joturus pichardi con Awaous banana y Cubanichthys cubensis; Sicydium plumieri con Ciprinus carpio, Cyprinodon artifrons; Eleotris pisonis y Hypophthalmichthys nobilis. El índice observado de la razón de varianza fue igual a 3.8689 permitiendo determinar que existe una fuerte covarianza entre la composición de las especies con el número de sitios. Se obtuvo dos grandes grupos en el análisis de similitud a un 75 %, no presentando diferencias estadísticas. Las especies que más contribuyeron a la disimilitud entre ambos grupos fueron las especies del género Awaous, Girardinus denticulatus y S. plumieri.
Diversidad de tardígrados (Tardigrada) asociados a briofitos en el Jardín de los Helechos en Santiago de Cuba
Authors: Muñoz-Li Rogelio Roberto , Jover Capote Abdiel
Published: January 2021

Los tardígrados u osos de agua son un grupo de invertebrados microscópicos que habitan en ambientes acuáticos y terrestres, y de manera frecuente en los briófitos. El grupo ha sido poco estudiado en Cuba, los trabajos de tardígrados son meramente taxonómicos y no evalúan los patrones de abundancia y diversidad de las comunidades. El propósito de esta investigación fue analizar la diversidad de tardígrados asociados a musgos en el Jardín de los Helechos en Santiago de Cuba. Para esto se realizaron curvas de acumulación de especies utilizando diversos estimadores de riqueza, se determinaron las diversidades alfa observada y estimadas, se estableció el orden jerárquico de la comunidad y se evaluó el patrón de abundancia mediante curvas de Whittaker. Se encontraron 34 tardígrados pertenecientes a las clases Heterotardigrada y Eutardigrada, los géneros presentes fueron Echiniscus, Milnesium, Mesobiotus y Macrobiotus con un total de 8 morfoespecies identificadas. El morfo dominante fue Macrobiotus sp. 1, mientras que Echiniscus sp., Mesobiotus sp. 2 y Mesobiotus sp. 3 resultaron ser especies raras. La curva de rango-abundancia indicó una comunidad equitativa.
Spilostethus pandurus (Hemiptera: Heteroptera: Lygaeidae), nuevo registro para República Dominicana y el Caribe insular
Authors: Bastardo Ruth H. , Perez-Gelabert Daniel E.
Published: January 2021

Se reporta por primera vez para República Dominicana y el Caribe insular la especie de chinche de semillas Spilostethus pandurus (Scopoli, 1763) originaria del Viejo Mundo. Este chinche podría representar una amenaza para múltiples plantas cultivadas pertenecientes a varias familias. Se ofrecen algunas características diagnósticas que permiten diferenciar la especie reportada de otros Lygaeidae en la Hispaniola.
A Framework for Applying the Learning Sciences to MOOC Design
Authors: Gordon Darcy G. , Wiltrout Mary Ellen
Published: January 2021

Evidence-based practices grounded in the learning sciences provide an opportunity for improved learning experiences in traditional in-person, as well as in hybrid and online environments. We advocate specifically that large-scale, online learning experiences, such as Massive Open Online Courses (MOOCs) benefit from applications of the learning sciences. To that end, we present a description of how and why we use specific learning science practices in a biochemistry MOOC with the intention to contribute to the discussion about the quality of online learning experiences and lower the barrier for other practitioners seeking a framework for implementing evidence-based course design. We believe that the application of the learning sciences makes online learning experiences more rigorous and effective, and practitioners should optimize the use of these strategies through clever tests in specific contexts.
Associations Between Morning Salivary and Blood Cortisol Concentrations in Individuals With Obstructive Sleep Apnea Syndrome: A Meta-Analysis
Authors: Imani Mohammad Moslem , Sadeghi Masoud , Khazaie Habibolah , Sanjabi Arezoo , Brand Serge , Brühl Annette , Sadeghi Bahmani Dena
Published: January 2021

Background

Obstructive sleep apnea syndrome (OSAS) may be associated with an increase in hypothalamic-pituitary-adrenocortical axis activity (HPA AA). We reviewed research comparing morning salivary and blood (serum and plasma) cortisol concentrations of individuals with OSAS to those of healthy controls.

Methods

We made a systematic search without any restrictions of the PubMed/Medline, Scopus, Cochrane Library, and Web of Science databases for relevant articles published up to August 25, 2019.

Results

Sixteen studies were analyzed in this meta-analysis; five studies compared morning salivary concentrations, five compared serum concentrations, four compared plasma cortisol concentrations, and two compared both salivary and plasma concentrations. In pediatric samples, compared to healthy controls, those with OSAS had significantly lower saliva morning cortisol concentrations (MD = -0.13 µg/dl; 95% CI: 0.21, -0.04;P= 0.003). In contrast, no significant differences were observed for serum cortisol concentrations, plasma cortisol concentrations, or salivary morning cortisol concentrations between adults with and without OSAS (p= 0.61,p= 0.17,p= 0.17).

Conclusion

Cortisol concentrations did not differ between adults with OSAS and healthy controls. In contrast, morning salivary cortisol concentrations were lower in children with OSAS, compared to healthy controls. Given that a reduced HPA AA is observed among individuals with chronic stress, it is conceivable that children with OSAS are experiencing chronic psychophysiological stress.
Human Pluripotent Stem Cells: A Unique Tool for Toxicity Testing in Pancreatic Progenitor and Endocrine Cells
Authors: MacFarlane Erin M. , Bruin Jennifer E.
Published: January 2021

Diabetes prevalence is increasing worldwide, and epidemiological studies report an association between diabetes incidence and environmental pollutant exposure. There are >84,000 chemicals in commerce, many of which are released into the environment without a clear understanding of potential adverse health consequences. While in vivo rodent studies remain an important tool for testing chemical toxicity systemically, we urgently need high-throughput screening platforms in biologically relevant models to efficiently prioritize chemicals for in depth toxicity analysis. Given the increasing global burden of obesity and diabetes, identifying chemicals that disrupt metabolism should be a high priority. Pancreatic endocrine cells are key regulators of systemic metabolism, yet often overlooked as a target tissue in toxicology studies. Immortalized β-cell lines and primary human, porcine, and rodent islets are widely used for studying the endocrine pancreas in vitro, but each have important limitations in terms of scalability, lifespan, and/or biological relevance. Human pluripotent stem cell (hPSC) culture is a powerful tool for in vitro toxicity testing that addresses many of the limitations with other β-cell models. Current in vitro differentiation protocols can efficiently generate glucose-responsive insulin-secreting β-like cells that are not fully mature, but still valuable for high-throughput toxicity screening in vitro. Furthermore, hPSCs can be applied as a model of developing pancreatic endocrine cells to screen for chemicals that influence endocrine cell formation during critical windows of differentiation. Given their versatility, we recommend using hPSCs to identify potential β-cell toxins, which can then be prioritized as chemicals of concern for metabolic disruption.
Thyroid Disrupting Effects of Old and New Generation PFAS
Authors: Coperchini Francesca , Croce Laura , Ricci Gianluca , Magri Flavia , Rotondi Mario , Imbriani Marcello , Chiovato Luca
Published: January 2021

Per- and polyfluoroalkyl substances (PFAS) represent a group of synthetic compounds widely used in industry plants due to their low grade of degradation, surfactant properties, thermic and flame resistance. These characteristics are useful for the industrial production, however they are also potentially dangerous for human health and for the environment. PFAS are persistent pollutants accumulating in waters and soil and recoverable in foods due to their release by food packaging. Humans are daily exposed to PFAS because these compounds are ubiquitous and, when assimilated, they are difficult to be eliminated, persisting for years both in humans and animals. Due to their persistence and potential danger to health, some old generation PFAS have been replaced by newly synthesized PFAS with the aim to use alternative compounds presumably safer for humans and the environment. Yet, the environmental pollution with PFAS remains a matter of concern worldwide and led to large-scale epidemiological studies both on plants’ workers and on exposed people in the general population. In this context, strong concern emerged concerning the potential adverse effects of PFAS on the thyroid gland. Thyroid hormones play a critical role in the regulation of metabolism, and thyroid function is related to cardiovascular disease, fertility, and fetal neurodevelopment. In vitro, ex vivo data, and epidemiological studies suggested that PFASs may disrupt the thyroid hormone system in humans, with possible negative repercussions on the outcome of pregnancy and fetal-child development. However, data on the thyroid disrupting effect of PFAS remain controversial, as well as their impact on human health in different ages of life. Aim of the present paper is to review recent data on the effects of old and new generation PFAS on thyroid homeostasis. To this purpose we collected information from in vitro studies, animal models, and in vivo data on exposed workers, general population, and pregnant women.
Epigenetic Memory: Lessons From iPS Cells Derived From Human β Cells
Authors: Efrat Shimon
Published: January 2021

Incomplete reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) may be responsible for the heterogeneity in differentiation capacity observed among iPSC lines. It remains unclear whether it results from stochastic reprogramming events, or reflects consistent genetic or cell-of-origin differences. Some evidence suggests that epigenetic memory predisposes iPSCs to enhanced differentiation into the parental cell type. We investigated iPSCs reprogrammed from human pancreatic islet β cells (BiPSCs), as a step in development of a robust differentiation protocol for generation of β-like cells. BiPSCs derived from multiple human donors manifested enhanced and reproducible spontaneous and induced differentiation towards insulin-producing cells, compared with iPSCs derived from isogenic non-β-cell types and fibroblast-derived iPSCs (FiPSCs). Genome-wide analyses of open chromatin in BiPSCs and FiPSCs identified thousands of differential open chromatin sites (DOCs) between the two iPSC types. DOCs more open in BiPSCs (Bi-DOCs) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites. Bi-DOCs were associated with genes related to pancreas development and β-cell function. These studies provide evidence for reproducible epigenetic memory in BiPSCs. Bi-DOCs may provide clues to genes and pathways involved in the differentiation process, which could be manipulated to increase the efficiency and reproducibility of differentiation of pluripotent stem cells from non-β-cell sources.
CD4 Inhibits Helper T Cell Activation at Lower Affinity Threshold for Full-Length T Cell Receptors Than Single Chain Signaling Constructs
Authors: Johnson Deborah K. , Magoffin Wyatt , Myers Sheldon J. , Finnell Jordan G. , Hancock John C. , Orton Taylor S. , Persaud Stephen P. , Christensen Kenneth A. , Weber K. Scott
Published: January 2021

CD4+ T cells are crucial for effective repression and elimination of cancer cells. Despite a paucity of CD4+ T cell receptor (TCR) clinical studies, CD4+T cells are primed to become important therapeutics as they help circumvent tumor antigen escape and guide multifactorial immune responses. However, because CD8+T cells directly kill tumor cells, most research has focused on the attributes of CD8+TCRs. Less is known about how TCR affinity and CD4 expression affect CD4+T cell activation in full length TCR (flTCR) and TCR single chain signaling (TCR-SCS) formats. Here, we generated an affinity panel of TCRs from CD4+T cells and expressed them in flTCR and three TCR-SCS formats modeled after chimeric antigen receptors (CARs) to understand the contributions of TCR-pMHCII affinity, TCR format, and coreceptor CD4 interactions on CD4+T cell activation. Strikingly, the coreceptor CD4 inhibited intermediate and high affinity TCR-construct activation by Lck-dependent and -independent mechanisms. These inhibition mechanisms had unique affinity thresholds dependent on the TCR format. Intracellular construct formats affected the tetramer staining for each TCR as well as IL-2 production. IL-2 production was promoted by increased TCR-pMHCII affinity and the flTCR format. Thus, CD4+ T cell therapy development should consider TCR affinity, CD4 expression, and construct format.
Gut Commensal-Induced IκBζ Expression in Dendritic Cells Influences the Th17 Response
Authors: Michaelis Lena , Treß Marcel , Löw Hanna-Christine , Klees Johanna , Klameth Christian , Lange Anna , Grießhammer Anne , Schäfer Andrea , Menz Sarah , Steimle Alex , Schulze-Osthoff Klaus , Frick Julia-Stefanie
Published: January 2021

Intestinal commensal bacteria can have a large impact on the state of health and disease of the host. Regulation of Th17 cell development by gut commensals is known to contribute to their dichotomous role in promoting gut homeostasis and host defense, or development of autoimmune diseases. Yet, the underlying mechanisms remain to be fully elucidated. One candidate factor contributing to Th17 differentiation, and the expression of which could be influenced by commensals is the atypical nuclear IκB protein IκBζ. IκBζ acts as a transcriptional regulator of the expression of Th17-related secondary response genes in many cell types including dendritic cells (DCs). Insights into the regulation of IκBζ in DCs could shed light on how these immune sentinel cells at the interface between commensals, innate and adaptive immune system drive an immune-tolerogenic or inflammatory Th17 cell response. In this study, the influence of two gut commensals of low (Bacteroides vulgatus) or high (Escherichia coli) immunogenicity on IκBζ expression in DCs and its downstream effects was analyzed. We observed that the amount of IκBζ expression and secretion of Th17-inducing cytokines correlated with the immunogenicity of these commensals. However, under immune-balanced conditions, E. coli also strongly induced an IκBζ-dependent secretion of anti-inflammatory IL-10, facilitating a counter-regulative Treg response as assessed in in vitro CD4+ T cell polarization assays. Yet, in an in vivo mouse model of T cell-induced colitis, prone to inflammatory and autoimmune conditions, administration of E. coli promoted an expansion of rather pro-inflammatory T helper cell subsets whereas administration of B. vulgatus resulted in the induction of protective T helper cell subsets. These findings might contribute to the development of new therapeutic strategies for the treatment of autoimmune diseases using commensals or commensal-derived components.
Plasma TNFSF13B and TNFSF14 Function as Inflammatory Indicators of Severe Adenovirus Pneumonia in Pediatric Patients
Authors: Fan Huifeng , Lu Bingtai , Cao Can , Li Hui , Yang Diyuan , Huang Li , Ding Tao , Wu Minhao , Lu Gen
Published: January 2021

Background

Human adenoviruses (HAdV) infection caused pneumonia remains a major threat to global children health. Currently, diagnosis of severe HAdV pneumonia in children is hampered by the lack of specific biomarkers. Also, the severity of adenovirus pneumonia in pediatric patients is generally based on clinical features and existing biomarkers do not reliably correlate to clinical severity. Here, we asked whether local and systemic inflammatory mediators could act as biomarkers predicting severe HAdV pneumonia in children.

Methods

Totally 37 common inflammatory protein levels were determined by Luminex assay in plasma and bronchoalveolar lavage (BAL) from pediatric patients who were diagnosed with HAdV pneumonia, and their correlation with the disease severity and lung lesion were assessed using statistical and bioinformatic analysis.

Results

Among 37 inflammatory cytokines, the protein levels of 4 TNF superfamily (TNFSF) members and their receptors (TNF receptor superfamily, TNFRSF) [TNFSF13B, TNFSF14, sTNF-R1 and sTNF-R2] in the plasma and 7 TNFSF/TNFRSF members [TNFSF12, TNFSF13, TNFSF13B, TNFSF14, TNFRSF8, sTNF-R1, and sTNF-R2] in the BAL were enhanced in patients with HAdV pneumonia compared with control subjects with airway foreign body. Moreover, the protein levels of all the tested TNFSF/TNFRSF members (except TNFSF12) were elevated in the BAL of severe group compared with non-severe HAdV pneumonia patients, while only TNFSF13B and TNFSF14 were dramatically increased in the plasma of severe cases, and positively related to the plasma CRP levels. In addition, ROC analysis indicated that TNFSF13B and TNFSF14 displayed a great potential to predict severe HAdV pneumonia.

Conclusion

In pediatric HAdV pneumonia, TNFSF/TNFRSF members function as key molecules in local and systemic inflammatory network, and the plasma TNFSF13B and TNFSF14 may be the potential local and systemic inflammatory indicators of severe HAdV pneumonia in pediatric patients.
The Critical Role of Head Movements for Spatial Representation During Bumblebees Learning Flight
Authors: Doussot Charlotte , Bertrand Olivier J. N. , Egelhaaf Martin
Published: January 2021

Bumblebees perform complex flight maneuvers around the barely visible entrance of their nest upon their first departures. During these flights bees learn visual information about the surroundings, possibly including its spatial layout. They rely on this information to return home. Depth information can be derived from the apparent motion of the scenery on the bees' retina. This motion is shaped by the animal's flight and orientation: Bees employ a saccadic flight and gaze strategy, where rapid turns of the head (saccades) alternate with flight segments of apparently constant gaze direction (intersaccades). When during intersaccades the gaze direction is kept relatively constant, the apparent motion contains information about the distance of the animal to environmental objects, and thus, in an egocentric reference frame. Alternatively, when the gaze direction rotates around a fixed point in space, the animal perceives the depth structure relative to this pivot point, i.e., in an allocentric reference frame. If the pivot point is at the nest-hole, the information is nest-centric. Here, we investigate in which reference frames bumblebees perceive depth information during their learning flights. By precisely tracking the head orientation, we found that half of the time, the head appears to pivot actively. However, only few of the corresponding pivot points are close to the nest entrance. Our results indicate that bumblebees perceive visual information in several reference frames when they learn about the surroundings of a behaviorally relevant location.
Treatment of Unresectable Differentiated Thyroid Carcinoma With Upfront External Radiotherapy and Salvage Surgery: A STROBE-Compliant Retrospective Cohort Study
Authors: Carrillo José F. , Flores Jesús Manuel , Espinoza Gilberto , Vázquez-Romo Rafael , Ramírez-Ortega Margarita C. , Carrillo Liliana C. , Cortés-García Beatriz Y. , Ochoa-Carrillo Francisco J. , Oñate-Ocaña Luis F.
Published: January 2021

Introduction

In patients with unresectable Differentiated thyroid cancer (DTC), the use of external beam radiation therapy (EBRT), leads mostly to palliation. Our aim is to define the role of upfront EBRT, followed or not by salvage surgery, on Progression-free survival (PFS) or Overall survival (OS) in patients with DTC.

Methods

This is a cohort study of patients with initially unresectable DTC who received EBRT. Cohort A received EBRT followed by rescue surgery and cohort B, EBRT only. The Kaplan-Meier method and Cox model were employed for survival analysis.

Results

Thirty-three patients were included; 69.6% females and 30.3% males. Mean age was 60.6 and mean tumor diameter was 10.4 cm; 17 and 16 patients were included in cohorts A and B, respectively. Belonging to cohort A (Hazard ratio [HR] 0.177, 95% CI 0.05–0.7) and use of intensity modulated radiotherapy (HR 0.177, 95% CI 0.03–1.08) were associated to better PFS, while high-risk histopathology (HR 6.6, 95% CI 0.9–50) and EBRT dose (HR 1.05, 95% CI 1.01–1.08) were independently associated with lower PFS. Patients from cohort A (HR 0.061, 95% CI 0.01–0.3) had improved OS, while high-risk histopathology (HR 5.7, 95% CI 1.1–28.6) and EBRT dose (HR 1.05, 95% CI 1.01–1.09) were independently associated to worse OS.

Conclusion

EBRT, and when feasible, salvage surgery, should be an integral part of the therapeutic strategy in initially unresectable DTC.
Silencing of KIF3B Suppresses Breast Cancer Progression by Regulating EMT and Wnt/β-Catenin Signaling
Authors: Wang Chengqin , Zhang Runze , Wang Xiao , Zheng Yan , Jia Huiqing , Li Haiyan , Wang Jin , Wang Ning , Xiang Fenggang , Li Yujun
Published: January 2021

Breast cancer is the most common malignant tumors in women. Kinesin family member 3B (KIF3B) is a critical regulator in mitotic progression. The objective of this study was to explore the expression, regulation, and mechanism of KIF3B in 103 cases of breast cancer tissues, 35 metastatic lymph nodes and breast cancer cell lines, including MDA-MB-231, MDA-MB-453, T47D, and MCF-7. The results showed that KIF3B expression was up-regulated in breast cancer tissues and cell lines, and the expression level was correlated with tumor recurrence and lymph node metastasis, while knockdown of KIF3B suppressed cell proliferation, migration, and invasion both in vivo and in vitro. In addition, UALCAN analysis showed that KIF3B expression in breast cancer is increased, and the high expression of KIF3B in breast cancer is associated with poor prognosis. Furthermore, we found that silencing of KIF3B decreased the expression of Dvl2, phospho-GSK-3β, total and nucleus β-catenin, then subsequent down-regulation of Wnt/β-catenin signaling target genes such as CyclinD1, C-myc, MMP-2, MMP-7 and MMP-9 in breast cancer cells. In addition, KIF3B depletion inhibited epithelial mesenchymal transition (EMT) in breast cancer cells. Taken together, our results revealed that KIF3B is up-regulated in breast cancer which is potentially involved in breast cancer progression and metastasis. Silencing KIF3B might suppress the Wnt/β-catenin signaling pathway and EMT in breast cancer cells.
Tedizolid, Faropenem, and Moxifloxacin Combination With Potential Activity Against Nonreplicating Mycobacterium tuberculosis
Authors: Srivastava Shashikant , Cirrincione Kayle N. , Deshpande Devyani , Gumbo Tawanda
Published: January 2021

Background:Mycobacteriumtuberculosis [Mtb] could be present in different metabolic population in the lung lesions, and nonreplicating persisters [NRP], associated with latent tuberculosis [TB], are the most difficult to kill.

Objective: Test the combination of tedizolid, moxifloxacin, and faropenem for activity against NRP using Mtb SS18b in the hollow fiber model [HFS-TB].

Methods: Tedizolid and moxifloxacin were tested as, first, two-drug combination against log-phase growth [LPG] and, second, slowly replicating bacilli [SRB] under acidic condition and with faropenem to create a three-drug combination regimen. Finally, standard regimen [isoniazid-rifampin-pyrazinamide] was used as comparator in the HFS-TB experiment with NRP Mtb. HFS-TB units were sampled for drug-concentration measurement as well as for estimation of bacterial burden using solid agar and mycobacterial growth indicator tube [MGIT] method. Linear regression was used to calculate the kill slopes with each treatment regimen and analysis of variance (ANOVA) to compare the regimen.

Results: Tedizolid at standard dose in combination with high-dose moxifloxacin killed 3.05 log10 CFU/ml LPG Mtb and 7.37 log10 CFU/ml SRB in the bactericidal and sterilizing activity HFS-TB experiments, respectively. There was no statistical difference between tedizolid-moxifloxacin-faropenem combination and the standard regimen as both killed 7.35 log10 CFU/ml NRP Mtb in 21 days. There was no emergence of resistance to any of the drugs studied in the three HFS-TB experiments.

Conclusion: The experimental regimen of tedizolid, moxifloxacin, and faropenem could effectively kill NRP population of Mtb, and given the efficacy against different metabolic population of Mtb could serve as a pan-TB regimen. Clinical studies are warranted to validate the in vitro findings.
Capturing Protein Domain Structure and Function Using Self-Supervision on Domain Architectures
Authors: Melidis Damianos P. , Nejdl Wolfgang
Published: January 2021

Predicting biological properties of unseen proteins is shown to be improved by the use of protein sequence embeddings. However, these sequence embeddings have the caveat that biological metadata do not exist for each amino acid, in order to measure the quality of each unique learned embedding vector separately. Therefore, current sequence embedding cannot be intrinsically evaluated on the degree of their captured biological information in a quantitative manner. We address this drawback by our approach, dom2vec, by learning vector representation for protein domains and not for each amino acid base, as biological metadata do exist for each domain separately. To perform a reliable quantitative intrinsic evaluation in terms of biology knowledge, we selected the metadata related to the most distinctive biological characteristics of a domain, which are its structure, enzymatic, and molecular function. Notably, dom2vec obtains an adequate level of performance in the intrinsic assessment—therefore, we can draw an analogy between the local linguistic features in natural languages and the domain structure and function information in domain architectures. Moreover, we demonstrate the dom2vec applicability on protein prediction tasks, by comparing it with state-of-the-art sequence embeddings in three downstream tasks. We show that dom2vec outperforms sequence embeddings for toxin and enzymatic function prediction and is comparable with sequence embeddings in cellular location prediction.
Estimation of Sensible and Latent Heat Fluxes Using Surface Renewal Method: Case Study of a Tea Plantation
Authors: Wang Jizhang , Buttar Noman Ali , Hu Yongguang , Lakhiar Imran Ali , Javed Qaiser , Shabbir Abdul
Published: January 2021

An experiment of sensible and latent heat flux measurement was conducted in a tea plantation near the Yangtze River within Danyang of Jiangsu Province, China. High-frequency (~10 Hz) air temperature measurement with fine-wire thermocouples (⌀ = 50 μm) was used for the estimation of sensible heat flux (H), and latent heat flux (LE) was extracted as a residual of the energy balance equation using additional measurements of net radiation (Rn) and soil heat flux (G). Results were compared against the eddy covariance (EC) system under unstable conditions only, and days with high precipitation were excluded from further analysis. Half-hourly datasets of the sensible heat flux estimated using the surface renewal method (SR) (HSR) and measured by the EC system (HEC) were analyzed. Results showed good agreement with R2 = 0.80, root mean square error (RMSE) = 27.87 W m−2, relative error (RE) = 9.02%, and a regression slope of 0.68—this slope was used for the calibration of the uncalibrated HSR estimated by SR. On the other hand, the half-hourly dataset of LESR was regressed against EC, and it showed good agreement with relatively high R2 = 0.93, RMSE = 32.99 W·m−2, and RE = 5.67%. Hence, the SR method may estimate the surface fluxes at a relatively low cost, ultimately improving calculations of evapotranspiration. Thus, the SR method could provide an economical tool for improving crop water management of tea plantations.
A Compact Weighing Lysimeter to Estimate the Water Infiltration Rate in Agricultural Soils
Authors: Ávila-Dávila Laura , Soler-Méndez Manuel , Bautista-Capetillo Carlos Francisco , González-Trinidad Julián , Júnez-Ferreira Hugo Enrique , Robles Rovelo Cruz Octavio , Molina-Martínez José Miguel
Published: January 2021

Infiltration estimation is made by tests such as concentric cylinders, which are prone to errors, such as the lateral movement under the ring. Several possibilities have been developed over the last decades to compensate these errors, which are based on physical, electronic, and mathematical principles. In this research, two approaches are proposed to measure the water infiltration rate in a silty loam soil by means of the mass values of a lysimeter weighing under rainfall conditions and different moisture contents. Based on the fact that with the lysimeter it is possible to determine acting soil flows very precisely, then with the help of mass conservation and assuming a downward vertical movement, 12 rain events were analyzed. In addition, it was possible to monitor the behavior of soil moisture and to establish the content at field capacity from the values of the weighing lysimeter, from which both approach are based. The infiltration rate of these events showed a variable rate at the beginning of the rainfall until reaching a maximum, to descend to a stable or basic rate. This basic infiltration rate was 1.49 ± 0.36 mm/h, and this is because soils with fine textures have reported low infiltration capacity. Four empirical or semi-empirical models of infiltration were calibrated with the values obtained with our approaches, showing a better fit with the Horton’s model.