bluuebunny/crossref_metadata_2025 huggingface dataset:
Value Estimation Of California Bearing Ratio From Hand Cone Penetrometer Test For Pekanbaru Soils
Authors: Nugroho Soewignjo Agus , Yusa Muhammad , Satibi Syawal
Published: August 2019

In practice, the design of pavement is commonly based on the California Bearing Ratio (CBR) test. This research was performed to study local correlation between Hand Cone Penetrometer (HCP) tests to the field CBR value. The local correlation is determined based on comparisons of HCP and CBR test results for the same density of soil taken from several locations in Pekanbaru City, Indonesia. It was found that there is an approximate linear relation in log scale between HCP test results to CBR values for a certain density of soil. Correlation for HCP and density to CBR has been put forward for the local correlation between the two values. Verification of the formula shows that the correlation can be used relatively accurately for predicting the field CBR values from the HCP test for inorganic soils. For organic soil, the formula need to be further researched.Pada praktiknya, perancangan perkerasan jalan didasarkan pada tes California Bearing Ratio (CBR). Studi ini dilakukan untuk mengetahui korelasi lokal antara tes Hand Cone Penetrometer (HCP) dan tes CBR untuk tanah dengan berat jenis yang sama, yang diambil pada beberapa titik di kota Pekanbaru, Indonesia. Berdasarkan analisis, diketahui bahwa terdapat hubungan linear, dalam skala log, antara nilai tes HCP dan CBR untuk tanah dengan berat jenis tertentu. Studi ini kemudian mendefinisikan persamaan korelasi dari HCP dan berat jenis terhadap CBR untuk korelasi lokal antara nilai HCP dan CBR. Dari hasil verifikasi persamaan, diketahui bahwa persamaan korelasi tersebut cukup akurat dan dapat digunakan untuk memprediksi nilai CBR lapangan dengan menggunakan nilai tes HCP untuk tanah inorganik. Penelitian lebih lanjut perlu dilakukan untuk mendefinisikan formula korelasi untuk tanah organic.
Certification of Ochratoxin A Reference Materials: Calibration Solutions OTAN-1 and OTAL-1 and a Mycotoxin-Contaminated Rye Flour MYCO-1
Authors: Bates Jennifer , Bahadoor Adilah , Cui Yi , Meija Juris , Windust Anthony , Melanson Jeremy E.
Published: August 2019

Background: Among the regulated mycotoxins that contaminate global food supplies, ochratoxin A is particularly harmful as a nephrotoxin and suspected carcinogen. Objective: To support global measurement comparability, certified calibration solutions for ochratoxin A and
[13C6]-ochratoxin A (OTAN-1 and OTAL-1, respectively) as well as a mycotoxin-contaminated rye flour certified reference material (CRM) known as MYCO-1 were developed. Methods: Quantitative proton NMR was used along with maleic acid as an external standard traceable
to the Système international (SI) to measure the concentration of ochratoxin A and [13C6]-ochratoxin A for the calibration solutions. OTAN-1 and OTAL-1 were then used as a pair in double isotope dilution MS to certify the mass fraction of ochratoxin A in MYCO-1.
The natural ochratoxin A CRM served as the primary standard for traceable quantitation, while the synthetic [13C6]-ochratoxin A CRM served as the internal standard. Results: The certified mass fraction of ochratoxin A or [13C6]-ochratoxin
A in the two mycotoxin calibration solution standards was established to be 11.03 ± 0.32 µg/g (k = 2) for OTAN-1 and 4.89 ± 0.18 µg/g (k = 2) for OTAL-1. The mass fraction of ochratoxin A in the rye flour standard MYCO-1 was certified at 4.05 ±
0.88 µg/kg (k = 2). Conclusions: These CRMs will support regulatory testing as they can be used in the method development, validation, calibration, and QC analysis of ochratoxin A. Highlights: This report highlights the methods used to certify OTAN-1, OTAL-1, and
MYCO-1 as well as the challenges associated with producing such materials, which can be applied to a wide variety of other CRMs.
Evaluation of the GENE-UP®Cronobacter Method for the Detection of Cronobacter Species in Select Foods and Environmental Surfaces: Collaborative Study, First Action 2019.01
Authors: Johnson Ronald , Mills John , Pittet Jean-Louis , Rannou Maryse , Bird Patrick , Nelson Maria
Published: August 2019

Background: The GENE-UP®Cronobacter assay (Performance Tested MethodSM 081801) is a real-time PCR technology for the rapid detection of Cronobacter species in select foods and environmental surfaces. Objective: The purpose of this validation was to evaluate the method’s interlaboratory performance and submit the result to AOAC INTERNATIONAL for adoption as a First Action Official MethodSM for the detection of Cronobacter species in select foods and environmental surfaces. Method: The GENE-UP method was evaluated in a multilaboratory study as part of the AFNOR NF VALIDATION certification process (NF102) following ISO 16140-2:2016 using unpaired test portions for one food matrix, reconstituted infant formula containing probiotics. The candidate method was compared to the ISO 22964:2017 reference method. Sixteen participants from fifteen laboratories throughout the European Union participated. Three levels of contamination were evaluated: a noninoculated control level (0 CFU/target test portion), a low contamination level (approximately 2 CFU/target test portion), and a high contamination level (approximately 10 CFU/target test portion). Data from that study were analyzed according to the probability of detection (POD) statistical model as presented in the AOAC validation guidelines. The difference in laboratory POD (dLPODC) values with 95% confidence intervals across collaborators was calculated for each level between the candidate and reference method results and between the candidate presumptive and confirmed results. Results: The dLPODC values with 95% confidence intervals were 0.00 (–0.03, 0.03), –0.08 (–0.19, 0.02), and 0.00 (–0.03, 0.03) for the noninoculated, low, and high contamination levels, respectively. Conclusions: The dLPODC results indicate no significant difference between the candidate method and the reference method or between presumptive and confirmed results for all three levels of contamination. Highlights: The GENE-UP Cronobacter assay provides industry with a rapid, easy to use method for the rapid detection of Cronobacter in a wide range of products and environmental samples.
Simultaneous Determination of 12 Bioactive Constituents in Bupi Yiqi No. 1 Recipe by Ultrahigh-Performance Liquid Chromatography Tandem Mass Spectrometry
Authors: Xie Qingling , Li Bin , Huang Feibing , Cao Mengru , Yuan Hanwen , Liu Yongbei , Li Wei , Qiu Yixing , Zhou Xiaoling , Man Rongyong , Wang Wei , Zhang Weining
Published: August 2019

Background: Bupi Yiqi No. 1 Recipe (BPYQ), a traditional Chinese medicine formula, has been widely used as a treatment of multidrug resistance during chemotherapy in colorectal cancer and for the prevention of gastrointestinal cancer recurrence for decades. Objective: In this study, a rapid, reliable, and accurate ultrahigh-performance LC (UHPLC) coupled with electrospray ionization (ESI)–tandem MS (MS/MS) method was developed for the simultaneous determination of 12 major bioactive components, including protocatechuic acid, astilbin, rutin, calycosin-7-O-β-D-glucoside, ginsenoside Re, ononin, isoliquiritigenin, calycosin, apigenin, ginsenoside Rb1, formononetin, and glycyrrhizic acid in BPYQ. Methods: The chromatographic separation of the analytes was achieved on a Poroshell 120 SB-Aq column (50 × 2.1 mm, 1.7 µm) with a mobile phase of acetonitrile and 0.1% (v/v) formic acid aqueous solution. The flow rate and column temperature were set at 0.4 mL/min and 30°C, respectively. Mass spectrometric detection of the analyses was performed on multiple reaction monitoring mode in positive and negative ESI mode. Results: The established UHPLC–ESI–MS/MS method was validated in terms of the linearity, precision, repeatability, stability, and accuracy. All calibration curves of the 12 compounds showed good linearity, with correlation coefficients (r) greater than 0.9980 within the test ranges. The LODs and LOQs for the 12 compounds were in the ranges of 0.08–1.32 and 0.27–5.28 ng/mL, respectively. The average recoveries of all the standard compounds were between 98.4 and 102.9%, and their relative SD values ranged from 1.24 to 3.78%. Conclusions: The proposed method can provide a meaningful basis for the QC of BPYQ. Highlights: The established UHPLC-ESI-MS/MS method was demonstrated to be a powerful tool for quantifying the 12 compounds in BPYQ.
Et in Florentina ego: Luigi Fiacchi e o Locus amoenus
Authors: Cairus Henrique Fortuna , Paiva Jeannie Bressan Annibolete de
Published: August 2019

Busca-se, neste artigo, trazer à discussão o conceito de locus amoenus, uma denominação corrente do locus communis (tópos, para os gregos) que remete à paisagem ideal, conforme os preceitos da poesia idílica antiga. O locus amoenus será aqui descrito e analisado, a partir da poesia italiana do setecentos, mais especificamente nas fábulas de Luigi Fiacchi, poeta e sacerdote católico do século XVIII, privilegiando as referências, diretas ou não, à Antiguidade que seu autor, conhecido pelo epíteto “Il Clasio”, permite entrever nas próprias fábulas.
“My Soul’s Imaginary Sight”: renaissance poetics and the notion of imagination
Authors: Silvares Lavinia
Published: August 2019

Nos séculos XVI e XVII, o significado conceitual de “imaginação” atrelava-se sobretudo à teoria aristotélica da phantasia, traduzida como imaginatio, em latim, e amplamente discutida em tratados sobre poesia e retórica. Neste artigo, propõe-se explorar brevemente algumas ideias relativas à especificidade histórica da noção de “imaginação” na poética renascentista, com vistas a evitar as abordagens transistóricas da poesia e de sua interpretação. Para tanto, serão comentados trechos específicos dos tratados The Defense of Poetry (1595), de Philip Sidney, Advancement of Learning (1605), de Francis Bacon, bem como algumas passagens das obras de William Shakespeare.
Gestão sustentável de resíduos sólidos em propriedades rurais do interior do RS
Authors: Fão Josiele Maria , Kohler Romualdo , Zaluski Felipe Cavalheiro , Oliveira Tarcisio Dorn de , Thesing Nelson José
Published: August 2019

O presente estudo teve por intuito elucidar a situação das propriedades rurais de municípios do interior do Estado do Rio Grande do Sul, mas especificadamente da região do Médio Alto Uruguai, quanto à gestão dos resíduos. Verificar qual o nível de conhecimento quanto aos efeitos do descarte dos resíduos e a conscientização dos donos de propriedades rurais é o prelúdio de ações que possam contribuir para uma gestão rural mais sustentável e que possa ser, além de lucrativa, não nociva ao meio ambiente. A partir da abordagem qualitativa com metodologia exploratória e descritiva, os resultados coletados por meio da pesquisa de levantamento elucidaram que os proprietários admitem que o descarte dos resíduos muitas vezes é realizado de maneira incorreta, o que pode ser justificado pela falta de conhecimento específico dos malefícios desses atos para o meio ambiente e para própria saúde dos que habitam a propriedade e imediações. Seria interessante que houvesse palestras dos sindicatos e órgãos relativos a esses produtores referente a conscientização da importância do descarte dos resíduos nas propriedades rurais, pois muitos afirmam que existe falta de conhecimento e conscientização referente ao assunto. Ações no gerenciamento de resíduos do meio rural são necessárias para que a sustentabilidade aconteça. O prolongamento dos recursos naturais é responsabilidade de todos os âmbitos sociais, pois favorece o desenvolvimento. Portanto, conclui-se que, ainda, algumas pessoas agem de maneira incorreta no descarte de resíduos sólidos em propriedades rurais por falta de direcionamento, o que conduz o pensamento de que a educação sustentável e a percepção de busca da preservação do meio ambiente ainda são a melhor solução para mudar esse atual contexto.
Microalgas como uma matriz para biodiesel na perspectiva de estudantes do semiárido
Authors: Nascimento Elaine Cristina Rodrigues do , Moreira Sueli Aparecida , Silva Allyne do Nascimento Eufrásio , Lichston Juliana Espada
Published: August 2019

A crescente preocupação com o ambiente vem despertando a humanidade para o desenvolvimento de produtos e técnicas mais sustentáveis. A energia proveniente de biomassa se mostra uma alternativa promissora na substituição das energias fósseis para alcançar o tão promissor ‘desenvolvimento sustentável’. Neste contexto, as microalgas constituem uma excelente alternativa, pois apresentam aplicações ambientais no uso de águas residuais, captação de gás carbônico e produção de oxigênio e geram vários produtos para a indústria, inclusive os biocombustíveis. No entanto, é importante saber o que a aprendizagem escolar transmite de conhecimento a respeito deste tema dentro das escolas técnicas. Dessa forma, o objetivo desse estudo é avaliar o conhecimento de estudantes do curso Técnico de Nível Médio em Biocombustíveis IFRN-Apodi sobre a definição, o uso, a sustentabilidade do cultivo de microalgas e a aplicação no setor de biocombustíveis. Para isso foram aplicados questionários com perguntas semi-estruturadas para 86 estudantes. A partir da análise dos dados, constatou-se que 44% dos alunos ouviram falar a respeito de microalgas, mas apresentavam conhecimento superficial sobre o tema. Concluiu-se que seria importante que esse tema fosse abordado nas disciplinas iniciais assim como a cultura de outras matrizes vegetais energéticas e que os estudantes necessitam ampliar seus conhecimentos sobre toda a gama de produtos e benefícios que as microalgas podem gerar, além do biodiesel.
Stress Measurements in Alumina by Optical Fluorescence: Revisited
Authors: Cook Robert F. , Michaels Chris A.
Published: August 2019

Stress measurements in single-crystal and polycrystalline alumina are revisited
using a recently developed optical fluorescence energy shift method. The method
simultaneously utilizes the R1 and R2 Cr-related ruby line shifts in alumina to
determine two components of the stress tensor in crystallographic coordinates,
independent of the intended or assumed stress state. Measurements from a range of
experimental conditions, including high-pressure, shock, quasi-static, and bulk
polycrystals containing thermal expansion anisotropy effects, are analyzed. In many
cases, the new analysis suggests stress states and stress magnitudes significantly
different from those inferred previously, particularly for shock experiments. An
implication is that atomistic models relating stress state to fluorescence shift
require significant refinement for use in materials-based residual stress
distribution analyses. Conversely, the earliest measurements of fluorescence in
polycrystalline alumina are shown to be consistent with recent detailed measurements
of stress equilibrium and dispersion.
Diez años de investigación en las principales revistas científicas de comunicación. Tendencias y temáticas en las publicaciones de mayor impacto en JCR y SJR.
Authors: Vizoso Ángel , Pérez-Seijo Sara , López-García Xosé
Published: August 2019

La comunicación, entendida como campo de estudio y como disciplina, aunque es relativamente joven, ha conseguido una importante madurez en la primera década del siglo XXI como muestra la producción científica y la centralidad que ha conseguido en las sociedades actuales. Este artículo es el resultado de la realización de una Revisión Sistemática de la Literatura científica en las trece revistas académicas del área de la comunicación que ocupan los dos principales rankings de indexación: Journal Citation Reports (JCR) y Scimago Journal & Country Rank (SJR). Tras el análisis de 5.291 textos, ha sido posible encontrar algunos de los patrones y tendencias que se siguen en la publicación de investigaciones académicas en el campo de la comunicación. De este modo, este artículo muestra cómo algunas de las publicaciones privilegian algunos temas frente a otros. Al mismo tiempo, se ha identificado un notable crecimiento de la producción académica gracias, en parte, a la facilidad de difusión a través de la incorporación de plataformas de publicación en línea por parte de las revistas científicas. Además, se ha identificado la presencia y evolución de determinadas temáticas a lo largo de los últimos diez años para entender su desarrollo e importancia. Este texto contribuye a la literatura científica centrada en la comprensión de los patrones de publicación y cita entre investigadores mostrando las principales tendencias en la investigación de la comunicación a lo largo de la última década.
Hábitos de uso y consumo de la generación millennial en sus teléfonos móviles
Authors: Cabrera García-Ochoa Yolanda
Published: August 2019

El uso de la telefonía móvil ha experimentado en los últimos años un crecimiento insólito a nivel mundial. Esto ha tenido consecuencias que afectan a los hábitos de consumo, de entretenimiento, el intercambio de contenidos y ha obligado a los expertos de marketing y a las agencias de publicidad a poner el foco en un consumidor que se ha convertido en la generación clave que apuntalará las nuevas formas de consumo del siglo XXI. Se trata de la denominada generación Y, también conocidos como los millennials. Aunque hay cierta discrepancia en torno a la franja de años que aglutina a este grupo de edad, los demógrafos William Straus y Neil Howe, quienes acuñan el término, les definen como los nacidos entre 1982 y 2004 (1991). Una generación surgida en plena prosperidad económica pero que llega a su mayoría de edad haciendo frente a una fuerte recesión económica, lo que les lleva a estar mejor preparados que sus predecesores pero sin embargo, tener peores expectativas laborales y verse afectados por una alta tasa de desempleo. Tomamos como muestra de nuestra investigación a este grupo de edad por ser nativos digitales para analizar los usos y las motivaciones que marcan la utilización de sus teléfonos móviles, analizar sus hábitos de consumo y ver qué características de uso definen a este grupo de edad y pueden verse afectadas en función de parámetros como el género, la formación o la edad de las personas encuestadas.
Publicidad de la publicidad. Las redes sociales como soportes de comunicación de las agencias de publicidad
Authors: Hidalgo-Marí Tatiana , Segarra-Saavedra Jesús
Published: August 2019

La naturaleza de la actividad publicitaria trae consigo una dedicación centrada en el anunciante, para el cual, las agencias de publicidad definen, planifican y ejecutan estrategias de comunicación a todos los niveles. Sin embargo, poco se ha hablado de cómo las propias agencias de publicidad trabajan y perfilan su comunicación, en aras de captar y conseguir tanto clientes como su posicionamiento de marca en el mercado. La comunicación de las agencias se ha limitado, tradicionalmente, a obtener posicionamiento y reconocimiento en festivales y certámenes destinados a valorar su trabajo, evitando anunciarse en medios convencionales, para no entrar en conflicto con sus propios clientes. Sin embargo, con el surgimiento de las redes sociales y los medios digitales, el escenario de comunicación ha cambiado significativamente y las agencias han encontrado un espacio virtual en el que poder trabajar su comunicación, hacer autopublicidad y trabajar sus valores de marca. El presente trabajo realiza un análisis descriptivo sobre la presencia y uso de redes sociales de las agencias españolas de publicidad asociadas a la Asociación Española de Agencias de Comunicación Publicitaria (AEACP), que se complementa con una revisión de los mensajes difundidos por las mismas en redes sociales. Los resultados apuntan a que las agencias buscan su presencia en redes sociales, a pesar de que todavía no se están explotando todas las posibilidades que ofrecen estos canales. Además, se detecta un proceso de cambio tímido pero existente en base al uso de las redes sociales como soportes corporativos para las agencias.
Qu’est-ce que la nature qu’on cherche à conserver? Une approche sémiologique de l’action écologique
Authors: Ducarme Frédéric
Published: August 2019

L’écologie est passée au cours du XXe siècle de science descriptive à science de l’action. Cette métamorphose contraint à adapter tout un vocabulaire théorique à l’épreuve du concret. Or, cette translation n’est pas facile. Si la large majorité des acteurs sociaux s’accordent quant à la nécessité de « protéger la nature », des controverses profondes s’élèvent dès qu’il s’agit de mettre en action cette préservation : que doit-on faire, sur quoi doit-on agir quand on veut protéger « la nature »? Qu’est-ce que la « nature », en somme? C’est à cette question que ce texte propose de répondre, en retraçant tout d’abord la généalogie de ce terme dont le sens n’a jamais été clair, puis en isolant un certain nombre de définitions dominantes, renvoyant chacune à une conception de la nature bien spécifique, et supposant donc des actions de protection distinctes. Plutôt que d’arbitrer de manière jupitérienne (comme s’y sont essayés sans succès de nombreux penseurs), nous proposons d’intégrer toute cette complexité du phénomène nature dans les démarches de protection de la nature, qui doit être pensée dans une acception large, transdisciplinaire et transculturelle.
La importancia del feedback en un entorno virtual de aprendizaje
Authors: Batalla-Busquets Josep-Maria , Plana Erta Dolors , Martínez Argüelles María Jesús
Published: August 2019

Existe un amplio consenso en que uno de los elementos clave para garantizar un buen proceso de aprendizaje en un contexto universitario no presencial es la existencia de procesos que pauten y dirijan el aprendizaje, y que permitan a los estudiantes evaluar periódicamente su grado de logro de los conocimientos. Una estrategia habitual para facilitar esta pauta es el uso del feeback entre el estudiante y el profesor. Pero en entornos con grupos de estudiantes de gran dimensión, la realización de este feedback puede convertirse en un trabajo demasiado laborioso y no sostenible.

En este artículo presentamos los resultados de tres proyectos piloto centrados en el contexto del grado de Administración y Dirección de empresas (ADE) de la UOC, donde hemos explorado varias herramientas TIC (audio, vídeo y capturas de pantalla) y distintas estrategias para realizar el feedback con el objetivo de hacerlo sostenible en grupos grandes y mejorar la eficacia y eficiencia del proceso de regulación de los aprendizajes.
Governance planning for sustainable oceans in a small island state
Authors: Singh Gerald G , Oduber Marck , Cisneros-Montemayor Andres , Ridderstaat Jorge
Published: August 2019

Achieving the Sustainable Development Goals (SDGs) will require coordinated policymaking for achievement. Aruba is a Small Island State (SIDS) with 90% of its jobs and GDP dependent on the oceans has prioritized SDG 14 – life below water, or the SDG Ocean goal – for achievement. We have developed a planning process, building off of the the literature on SDG interactions and stratetic policy planning literatures, to guide SDG policy development and implemented it in Aruba. We used a structured expert elicitation process to carry out the analysis for this process. The process involves first identifying priority areas based on determining which SDG Ocean target provides the most co-benefit across other SDGs. Next we determine the SDG areas that most contribute to key SDG Ocean targets. Using this information we determine the key policy areas important for promoting sustainable oceans. Finally, we determine the Aruban ministries and institutions responsible for the various SDG areas and based on which SDG areas are most important for SDG Ocean achievement we visualize a new institutional network to support the achievement of SDG Oceans. First, we determined that while increasing economic benfits for SIDS (SDG 14.7) was the most important SDG Ocean target when considering direct impacts, reducing marine pollution (SDG 14.1), restoring marine habitats (SDG 14.2), and marine protection (SDG 14.5) were the most important SDG Ocean targets when considering indirect impacts. SDG areas with the most beneficial consequences for the SDG Ocean targets were mitigating climate impacts (SDG 13), international partnerships (SDG 17), jobs and economy (SDG 8), conserving terrestrial area (SDG 15), strengthening institutions (SDG 16), and promoting sustainable consumption and production practices (SDG 12). When links between SDGs are not considered, the institutional network supporting sustainable oceans is relatively simple, with the Department of Nature and the Environment most central: it coordinates across the largest number of relevant institutions supporting the SDG Oceans goal. However, when SDG relationships are considered, the institutional network is relatively complex, and the Social and Economic Council is determined to be the most central and important in coordinating activities across the largest number of Aruban instutions that support the SDG Ocean goal. Transitioning to a sustainable future requires policymaking that works across social-ecological dimensions, and need to design coherent and integrative institutional structures with which to do this.
The social context for conservation: amphibians in human-shaped landscapes
Authors: Hartel Tibor , Scheele Ben C , Rozylowicz Laurentiu , Horcea-Milcu Andra , Cogalniceanu Dan
Published: August 2019

Many human-shaped landscapes support viable amphibian populations due to the habitats created and/or maintained as a consequence of human actions. The challenges and approaches required to achieve the persistence of amphibians in human-shaped landscapes are markedly different from approaches commonly applied in protected areas. Contrary to protected areas or natural landscapes where amphibian conservationists can have direct control over management, in human-shaped landscapes, management options are best approached through understanding local communities’ values and socio-economic aspirations. However, consideration of the social aspects of amphibian conservation are vastly under-represented in the amphibian conservation literature. We propose that amphibian conservationists should: (i) assess the controllability of their mitigation actions for achieving long-term sustainability, (ii) understand the values and attitudes of individual landowners towards amphibians and amphibian-friendly management (local scale) and land stewardship on which amphibian conservation initiatives can be built (landscape scale), and (iii) understand the social and economic drivers of land-use change operating at regional levels, which is crucial for building adaptive potential in conservation programs. Since targeted amphibian conservation initiatives are limited in many human-shaped landscapes, consideration of the socio-economic context conducive to amphibian persistence is crucial.
Mutationally-activated PI3’-kinase-α promotes de-differentiation of lung tumors initiated by the BRAFV600E oncoprotein kinase
Authors: van Veen J Edward , Scherzer Michael , Boshuizen Julia , Chu Mollee , Liu Annie , Landman Allison , Green Shon , Trejo Christy , McMahon Martin
Published: August 2019

Human lung adenocarcinoma exhibits a propensity for de-differentiation, complicating diagnosis and treatment, and predicting poorer patient survival. In genetically engineered mouse models of lung cancer, expression of the BRAFV600E oncoprotein kinase initiates the growth of benign tumors retaining characteristics of their cell of origin, AT2 pneumocytes. Cooperating alterations that activate PI3’-lipid signaling promote progression of BRAFV600E-driven benign tumors to malignant adenocarcinoma. However, the mechanism(s) by which this cooperation occurs remains unclear. To address this, we generated mice carrying a conditional BrafCAT allele in which CRE-mediated recombination leads to co-expression of BRAFV600E and tdTomato. We demonstrate that co-expression of BRAFV600E and PIK3CAH1047R in AT2 pneumocytes leads to rapid cell de-differentiation, without decreased expression of the transcription factors NKX2-1, FOXA1, or FOXA2. Instead, we propose a novel role for PGC1α in maintaining AT2 pneumocyte identity. These findings provide insight into how these pathways may cooperate in the pathogenesis of human lung adenocarcinoma.
Tailored tetravalent antibodies potently and specifically activate Wnt/Frizzled pathways in cells, organoids and mice
Authors: Tao Yuyong , Mis Monika , Blazer Levi , Ustav Mart , Steinhart Zachary , Chidiac Rony , Kubarakos Elli , O'Brien Siobhan , Wang Xiaomei , Jarvik Nick , Patel Nish , Adams Jarrett , Moffat Jason , Angers Stephane , Sidhu Sachdev S
Published: August 2019

Secreted Wnt proteins regulate development and adult tissue homeostasis by binding and activating cell-surface Frizzled receptors and co-receptors including LRP5/6. The hydrophobicity of Wnt proteins has complicated their purification and limited their use in basic research and as therapeutics. We describe modular tetravalent antibodies that can recruit Frizzled and LRP5/6 in a manner that phenocopies the activities of Wnts both in vitro and in vivo. The modular nature of these synthetic Frizzled and LRP5/6 Agonists, called FLAgs, enables tailored engineering of specificity for one, two or multiple members of the Frizzled family. We show that FLAgs underlie differentiation of pluripotent stem cells, sustain organoid growth, and activate stem cells in vivo. Activation of Wnt signaling circuits with tailored FLAgs will enable precise delineation of functional outcomes directed by distinct receptor combinations and could provide a new class of therapeutics to unlock the promise of regenerative medicine.
Seasonal variation and etiologic inferences of childhood pneumonia and diarrhea mortality in India
Authors: Farrar Daniel S , Awasthi Shally , Fadel Shaza A , Kumar Rajesh , Sinha Anju , Fu Sze Hang , Wahl Brian , Morris Shaun K , Jha Prabhat
Published: August 2019

Control of pneumonia and diarrhea mortality in India requires understanding of their etiologies. We combined time series analysis of seasonality, climate region, and clinical syndromes from 243,000 verbal autopsies in the nationally representative Million Death Study. Pneumonia mortality at 1 month-14 years was greatest in January (Rate ratio (RR) 1.66, 99% CI 1.51–1.82; versus the April minimum). Higher RRs at 1–11 months suggested respiratory syncytial virus (RSV) etiology. India’s humid subtropical region experienced a unique summer pneumonia mortality. Diarrhea mortality peaked in July (RR 1.66, 1.48–1.85) and January (RR 1.37, 1.23–1.48), while deaths with fever and bloody diarrhea (indicating enteroinvasive bacterial etiology) showed little seasonality. Combining mortality at ages 1–59 months with prevalence surveys, we estimate 40,600 pneumonia deaths from Streptococcus pneumoniae, 20,700 from RSV, 12,600 from influenza, and 7200 from Haemophilus influenzae type b and 24,700 diarrheal deaths from rotavirus occurred in 2015. Careful mortality studies can elucidate etiologies and inform vaccine introduction.
A nuclear role for the DEAD-box protein Dbp5 in tRNA export
Authors: Lari Azra , Arul Nambi Rajan Arvind , Sandhu Rima , Reiter Taylor , Montpetit Rachel , Young Barry P , Loewen Chris JR , Montpetit Ben
Published: August 2019

Dbp5 is an essential DEAD-box protein that mediates nuclear mRNP export. Dbp5 also shuttles between nuclear and cytoplasmic compartments with reported roles in transcription, ribosomal subunit export, and translation; however, the mechanism(s) by which nucleocytoplasmic transport occurs and how Dbp5 specifically contributes to each of these processes remains unclear. Towards understanding the functions and transport of Dbp5 in Saccharomyces cerevisiae, alanine scanning mutagenesis was used to generate point mutants at all possible residues within a GFP-Dbp5 reporter. Characterization of the 456 viable mutants led to the identification of an N-terminal Xpo1-dependent nuclear export signal in Dbp5, in addition to other separation-of-function alleles, which together provide evidence that Dbp5 nuclear shuttling is not essential for mRNP export. Rather, disruptions in Dbp5 nucleocytoplasmic transport result in tRNA export defects, including changes in tRNA shuttling dynamics during recovery from nutrient stress.
Humans can efficiently look for but not select multiple visual objects
Authors: Ort Eduard , Fahrenfort Johannes Jacobus , ten Cate Tuomas , Eimer Martin , Olivers Christian NL
Published: August 2019

The human brain recurrently prioritizes task-relevant over task-irrelevant visual information. A central question is whether multiple objects can be prioritized simultaneously. To answer this, we let observers search for two colored targets among distractors. Crucially, we independently varied the number of target colors that observers anticipated, and the number of target colors actually used to distinguish the targets in the display. This enabled us to dissociate the preparation of selection mechanisms from the actual engagement of such mechanisms. Multivariate classification of electroencephalographic activity allowed us to track selection of each target separately across time. The results revealed only small neural and behavioral costs associated with preparing for selecting two objects, but substantial costs when engaging in selection. Further analyses suggest this cost is the consequence of neural competition resulting in limited parallel processing, rather than a serial bottleneck. The findings bridge diverging theoretical perspectives on capacity limitations of feature-based attention.
Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin
Authors: Lee Juhye M , Eguia Rachel , Zost Seth J , Choudhary Saket , Wilson Patrick C , Bedford Trevor , Stevens-Ayers Terry , Boeckh Michael , Hurt Aeron C , Lakdawala Seema S , Hensley Scott E , Bloom Jesse D
Published: August 2019

A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza’s major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.
A comprehensive molecular phylogeny of Geometridae (Lepidoptera) with a focus on enigmatic small subfamilies
Authors: Murillo-Ramos Leidys , Brehm Gunnar , Sihvonen Pasi , Hausmann Axel , Holm Sille , Reza Ghanavi Hamid , Õunap Erki , Truuverk Andro , Staude Hermann , Friedrich Egbert , Tammaru Toomas , Wahlberg Niklas
Published: August 2019

Our study aims to investigate the relationships of the major lineages within the moth family Geometridae, with a focus on the poorly studied Oenochrominae-Desmobathrinae complex, and to translate some of the results into a coherent subfamilial and tribal level classification for the family. We analyzed a molecular dataset of 1,206 Geometroidea terminal taxa from all biogeographical regions comprising up to 11 molecular markers that includes one mitochondrial (COI) and 10 protein-coding nuclear gene regions (wingless, ArgK, MDH, RpS5, GAPDH, IDH, Ca-ATPase, Nex9, EF-1alpha, CAD). The molecular data set was analyzed using maximum likelihood as implemented in IQ-TREE and RAxML. We found high support for the subfamilies Larentiinae, Geometrinae and Ennominae in their traditional scopes. Sterrhinae becomes monophyletic only ifErgaviaWalker,AmetrisHübner andMacrotesWestwood, which are currently placed in Oenochrominae, are formally transferred to Sterrhinae. Desmobathrinae and Oenochrominae are found to be polyphyletic. The concepts of Oenochrominae and Desmobathrinae required major revision and, after appropriate rearrangements, these groups also form monophyletic subfamily-level entities. Oenochrominaes.str. as originally conceived by Guenée is phylogenetically distant fromEpidesmiaand its close relatives. The latter is hereby described as the subfamily Epidesmiinae Murillo-Ramos, Sihvonen & Brehm,subfam. nov.Epidesmiinae are a lineage of “slender-bodied Oenochrominae” that include the generaEcphyasTurner,SystaticaTurner,AdeixisWarren,DichromodesGuenée,PhrixocomesTurner,AbraxaphantesWarren,EpidesmiaDuncan & Westwood andPhratariaWalker. Archiearinae are monophyletic whenDirceandAcalyphesare formally transferred to Ennominae. We also found that many tribes were para- or polyphyletic and therefore propose tens of taxonomic changes at the tribe and subfamily levels. Archaeobalbinistat. rev.Viidalepp (Geometrinae) is raised from synonymy with Pseudoterpnini Warren to tribal rank. Chlorodontoperini Murillo-Ramos, Sihvonen & Brehm,trib. nov.and Drepanogynini Murillo-Ramos, Sihvonen & Brehm,trib. nov.are described as new tribes in Geometrinae and Ennominae, respectively.
Genome-resolved insights into a novelSpiroplasmasymbiont of the Wheat Stem Sawfly (Cephus cinctus)
Authors: Yeoman Carl J. , Brutscher Laura M. , Esen Özcan C. , Ibaoglu Furkan , Fowler Curtis , Eren A. Murat , Wanner Kevin , Weaver David K.
Published: August 2019

Arthropods often have obligate relationships with symbiotic microbes, and recent investigations have demonstrated that such host-microbe relationships could be exploited to suppress natural populations of vector carrying mosquitos. Strategies that target the interplay between agricultural pests and their symbionts could decrease the burden caused by agricultural pests; however, the lack of comprehensive genomic insights into naturally occurring microbial symbionts presents a significant bottleneck. Here we employed amplicon surveys, genome-resolved metagenomics, and scanning electron microscopy to investigate symbionts of the wheat stem sawfly (Cephus cinctus), a major pest that causes an estimated $350 million dollars or more in wheat yield losses in the northwestern United States annually. Through 16S rRNA gene sequencing of two major haplotypes and life stages of wheat stem sawfly, we show a novelSpiroplasmaspecies is ever-present and predominant, with phylogenomic analyses placing it as a member of the ixodetis clade of mollicutes. Using state-of-the-art metagenomic assembly and binning strategies we were able to reconstruct a 714 Kb, 72.7%-completeSpiroplasmagenome, which represents just the second draft genome from the ixodetis clade of mollicutes. Functional annotation of theSpiroplasmagenome indicated carbohydrate-metabolism involved PTS-mediated import of glucose and fructose followed by glycolysis to lactate, acetate, and propionoate. The bacterium also encoded biosynthetic pathways for essential vitamins B2, B3, and B9. We identified putativeSpiroplasmavirulence genes: cardiolipin and chitinase. These results identify a previously undescribed symbiosis between wheat stem sawfly and a novelSpiroplasmasp., availing insight into their molecular relationship, and may yield new opportunities for microbially-mediated pest control strategies.
Prevalence of near-death experiences in people with and without REM sleep intrusion
Authors: Kondziella Daniel , Dreier Jens P. , Olsen Markus Harboe
Published: August 2019

Background

The origin and prevalence of near-death experiences are unknown. A recent study suggested a link with REM sleep intrusion but was criticized for its selection of control participants. We therefore assessed the association of REM intrusion and near-death experiences with different methods.

Methods

Using a crowd-sourcing platform, we recruited 1,034 lay people from 35 countries to investigate the prevalence of near-death experiences and self-reported REM sleep intrusion. Reports were validated using the Greyson Near-Death Experiences Scale (GNDES) with ≥7 points as cut-off for near-death experiences.

Results

Near-death experiences were reported by 106 of 1,034 participants (10%; 95% CI [8.5–12%]). Evidence of REM intrusion was more common in people with near-death experiences (n = 50∕106; 47%) than in people with experiences with 6 points or less on the GNDES (n = 47∕183; 26%) or in those without such experiences (n = 107∕744; 14%; p =  < 0.0001). Following multivariate regression analysis to adjust for age, gender, place of residence, employment and perceived danger, this association remained highly significant; people with REM intrusion were more likely to exhibit near-death experiences than those without (OR 2.85; 95% CI [1.68–4.88]; p = 0.0001).

Discussion

Using a crowd-sourcing approach, we found a prevalence of near-death experiences of 10%. While age, gender, place of residence, employment status and perceived threat do not seem to influence the prevalence of near-death experiences, we confirmed a possible association with REM sleep intrusion.
Insights from the proteome profile of Phytophthora capsici in response to the novel fungicide SYP-14288
Authors: Cai Meng , Wang Zhiwen , Ni Xiaoxia , Hou Yanhua , Peng Qin , Gao Xiang , Liu Xili
Published: August 2019

Phytophthora capsica is a destructive oomycete plant pathogen that causes huge losses to crop production worldwide. However, the novel fungicide SYP-14288 has shown excellent activity against various stages of the oomycete life cycle as well against fungal plant pathogens. The current study utilized isobaric tags for relative and absolute quantitation technology to generate proteome profiles of P. capsici in the presence or absence of SYP-14288 in order to gain a greater understanding of the SYP-14288 mode of action. A total of 1,443 individual proteins were identified during the investigation, of which 599 were considered to have significantly altered expression. Further investigation using Cluster of Orthologous Groups of proteins analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated most of the proteins with altered expression were associated with carbohydrate metabolism, energy metabolism and their downstream biological functions, especially with regard to oxidoreductase activity and subsequent adenosine triphosphate (ATP) production associated pathways. Quantitative expression analysis using qRT-PCR validated the proteomic data. These results seem to indicate that SYP-14288 treatment caused a shift in energy metabolism that resulted in the activation of compensatory mechanisms affecting carbohydrate and lipid metabolism. The study also found evidence that the up-regulation of transmembrane transporters and proteins associated with stress response might also be coopted to compensate for the disrupted proton gradient and other downstream effects. Taken together these results provide strong evidence that SYP-14288 has a similar mode of action to the oxidative phosphorylation uncoupler Fluazinam but further investigation, including molecular studies, is required to completely characterize the SYP-14288 mode of action in P. capsici. However, the proteomic data collected in the current study does provide important insight into the overall effect of SYP-14288 in P. capsici, which could be useful for the registration and application of this novel fungicide.
Characterization of Polyphenols and Mineral Contents in Three Medicinal Weeds
Authors: Sahu Yaman Kumar , Patel Khageshwar Singh , Martín-Ramos Pablo , Towett Erick K.
Published: August 2019

Aims: Common weeds Rorippa palustris (L.) Besser, Euphorbia rothiana Spreng. and Schoenoplectiella articulata (L.) Lye are used for food, medicinal, green biofertilizer and biosorbent applications. In this work, their polyphenol and mineral contents have been characterized.

Methodology: Samples from aforementioned three plants were manually collected in Raipur city (CG, India) and processed for the analyses. Folin-Ciocalteu and aluminum chloride were used for the spectrophotometric determination of polyphenols. The mineral contents were quantified by X-ray fluorescence.

Results: The total concentration of 20 elements (viz. P, S, Cl, As, Se, K, Rb, Mg, Ca, Sr, Ba, Al, Ti, Cr, Mn, Fe, Co, Zn, Mo and Pb), total polyphenol and flavonoid contents in the leaves ranged from 46372 to 71501, from 47877 to 73791 and from 1950 to 9400 mg/kg, respectively. Remarkable concentrations of several nutrients (P, S, Cl, K, Mg, Ca and Fe) were observed.

Conclusion: The biomass from medicinal weeds R. palustris, E. rothiana and S. articulata featured very high K, Ca and Fe contents. Other nutrients (polyphenols, flavonoids, P, S, Cl and Mg) were identified at moderate levels. These species may hold promise as bioindicators.
Neural networks associated with body composition in frontotemporal dementia
Authors: Ahmed Rebekah M. , Landin‐Romero Ramon , Liang Cheng T. , Keogh Julia M. , Henning Elana , Strikwerda‐Brown Cherie , Devenney Emma M. , Hodges John R. , Kiernan Matthew C. , Farooqi I. Sadaf , Piguet Olivier
Published: August 2019

Background

Frontotemporal dementia (FTD) is associated with complex changes in eating behavior and metabolism, which potentially affect disease pathogenesis and survival. It is currently not known if body composition changes and changes in fat deposition also exist in FTD, the relationship of these changes in eating behavior and appetite, and whether these changes are centrally mediated.

Methods

Body composition was measured in 28 people with behavioral‐variant frontotemporal dementia (bvFTD), 16 with Alzheimer’s disease (AD), and 19 healthy controls, using dual energy x‐ray absorptiometry. Changes in body composition were correlated to brain grey matter atrophy using voxel‐based morphometry on high‐resolution magnetic resonance imaging.

Results

Behavioral‐variant FTD was characterized by changes in body composition, with increased total fat mass, visceral adipose tissue area (VAT area), and android: gynoid ratio compared to control and AD participants (all P values < 0.05). Changes in body composition correlated to abnormal eating behavior and behavioral change (P < 0.01) and functional decline (P < 0.01). Changes in body composition also correlated to grey matter atrophy involving a distributed neural network that included the hippocampus, amygdala, nucleus accumbens, insula, cingulate, and cerebellum – structures known to be central to autonomic control – as well as the thalamus, putamen, accumbens, and caudate, which are involved in reward processing.

Conclusions

Changes in body composition and fat deposition extend the clinical phenomenology in bvFTD beyond cognition and behavior, with changes associated with changes in reward and autonomic processing suggesting that these deficits may be central in FTD
Exosome‐Guided Phenotypic Switch of M1 to M2 Macrophages for Cutaneous Wound Healing
Authors: Kim Hyosuk , Wang Sun Young , Kwak Gijung , Yang Yoosoo , Kwon Ick Chan , Kim Sun Hwa
Published: August 2019

Macrophages (Mϕs) critically contribute to wound healing by coordinating inflammatory, proliferative, and angiogenic processes. A proper switch from proinflammatory M1 to anti‐inflammatory M2 dominant Mϕs accelerates the wound healing processes leading to favorable wound‐care outcomes. Herein, an exosome‐guided cell reprogramming technique is proposed to directly convert M1 to M2 Mϕs for effective wound management. The M2 Mϕ‐derived exosomes (M2‐Exo) induce a complete conversion of M1 to M2 Mϕs in vitro. The reprogrammed M2 Mϕs turn Arginase (M2‐marker) and iNOS (M1‐marker) on and off, respectively, and exhibit distinct phenotypic and functional features of M2 Mϕs. M2‐Exo has not only Mϕ reprogramming factors but also various cytokines and growth factors promoting wound repair. After subcutaneous administration of M2‐Exo into the wound edge, the local populations of M1 and M2 Mϕs are markedly decreased and increased, respectively, showing a successful exosome‐guided switch to M2 Mϕ polarization. The direct conversion of M1 to M2 Mϕs at the wound site accelerates wound healing by enhancing angiogenesis, re‐epithelialization, and collagen deposition. The Mϕ phenotype switching induced by exosomes possessing the excellent cell reprogramming capability and innate biocompatibility can be a promising therapeutic approach for various inflammation‐associated disorders by regulating the balance between pro‐ versus anti‐inflammatory Mϕs.