bluuebunny/crossref_metadata_2025 huggingface dataset:
El derecho del trabajador al aire puro: contaminación atmosférica, salud y empresas en las cuencas de minerales no ferrosos (1800-1945)
Authors: Pérez-Cebada Juan Diego
Published: April 2020

Objective/context: Social conflicts caused by air pollution gave rise to an intense debate around health in the European and North American non-ferrous mineral basins during the 19th century. Contemporary scholars classified it as a public health problem, since it ultimately affected the entire mining community, encompassing what we know today as environmental and occupational hazards. This article uses selected case studies to analyze institutional regulations, and the scientific and technical solutions that were applied in response to them. However, in the first half of the twentieth century, health problems associated with smelter smoke evolved to become an industrial hygiene issue and were therefore limited to the field of industrial relations. Institutional, scientific and technical factors behind this change are closely related to the role of the social agents concerned, particularly large corporations. Methodology: This research, which is comparative from a temporal and spatial perspective, relies on an analysis of both current literature and contemporary sources. Originality: Air pollution derived from mining activities triggered a process of closely interrelated institutional, scientific and technical innovations. In the late nineteenth century, the ensuing debate became international, spreading from European to American mining basins. Conclusions: The smelter smoke controversy deeply divided the non-ferrous mineral basins of Europe, the United States and Canada, and science provided the foundation for the institutional and technical measures implemented to address it. In that process, particularly since the late nineteenth century, mining companies developed the capacity to successfully adapt the science to their needs.
La Transición como un espejo. La influencia de la Transición española en la oposición moderada chilena
Authors: Araya Gómez Rodrigo
Published: April 2020

Objective/Context: This article seeks to analyze the influence exerted by the transition to democracy in Spain in sectors of the Chilean opposition to the civil-military dictatorship led by General Pinochet. This influence manifested through visits by Spanish politicians to Chile, and also by the positive view of the Spanish transition to democracy by a large part of the Chilean opposition. Originality: This article contributes to our understanding of transitional processes from a multidimensional perspective. In this case, it examines the degree to which an external factor can influence the positions of the leading political actors in a democratic transition. Methodology: To do this, we will review periodical publications that provide accounts of visits by Spanish politicians to Chile, as well as examining the documentation at the Eduardo Frei Montalva Foundation Archive and memoirs by Chilean politicians involved with the Spanish transitional experience. Conclusions: We conclude that, in general terms, during democratization or other forms of political opening led by sectors of the political elites, the influence of international actors becomes relevant in determining political positions or in forming alliances. In the Chilean case, the Spanish experience was seen as a successful model of a peaceful regime change, and the majority of the Chilean opposition would have considered it as a point of reference in their own discussions on exit alternatives for dictatorship.
Fitness benefits and costs of shelters to the sea urchin Glyptocidaris crenularis
Authors: Chi Xiaomei , Sun Jiangnan , Yu Yushi , Luo Jia , Zhao Bao , Han Feng , Chang Yaqing , Zhao Chong
Published: April 2020

Understanding the ecological role of shelters is greatly hampered by the scarcity of long-term laboratory experiments on the trade-off between fitness benefits and costs. This lack probably leads to an underestimation of the negative and/or positive effects on behaviors and growth of marine invertebrates in benthic ecosystems. Although our previous study revealed a significant effect on fitness-related traits of Glyptocidaris crenularis after 31 months, the present study extended it and investigated fitness benefits and/or costs of long-term sheltering on sea urchins to over 7 years. The present long-term study suggests that the previously reported reduction in feeding rate probably resulted from a reduction in reflexive feeding motions (Aristotle’s lantern reflex) rather than changes in foraging behavior. Actively seeking sheltering behavior was negatively impacted in individuals with continuous access to shelters. However, covering and righting behaviors did not differ in sheltered sea urchins, indicating that these behaviors are maintained to escape from adverse environments regardless of shelter. Body size of sea urchins in the group with shelters was significantly lower than those without shelters after 7 years. Weights of gonads and gut were not significantly different after 7 years despite previous observations of differences after ~2.5 years. The present study provides valuable information on the trade-off between fitness benefits and costs to sea urchins residing in shelters. However, the present study is only a laboratory investigation for one urchin species (G. crenularis) which does not consider the complexity of natural environments. Field studies should be carried out with G. crenularis and other sea urchin species, before a more universal conclusion can be drawn.
Performance Evaluation of Vetch Varieties/Genotypes for Their Agronomic Performance and Nutritive Value in Selected Midland of East Guji Zone, Adola, Southern Oromia and Ethiopia
Authors: Jabessa Teshale , Amare Zinash , Dejene Genet
Published: April 2020

A study was conducted to identify adaptability, high biomass and dry matter and grain yielder of vetch varieties/genotypes at Bore Agricultural Research Center Adola sub-site. The three vetch varieties/genotypes tested were Vicia dasycarpa, Lalisa and 5187. Randomized complete block design (RCBD) with three replications was employed to evaluate the variety. The result revealed that date of 50% flowering, date of maturity, pod length per plant and plant height was significantly different (at p<0.05) between treatments. The early flowered genotype was 5187 (62 days) and late flowered variety was recorded from Vicia dasycarpa (79.9 days). The highest value of plant height was measured from Lalisa variety, while the shortest plant height was recorded from 5187 genotypes (67.7 cm). Date of 50% emergency, pod per plant, fresh biomass yield and grain yield and chemical composition dry matter (DM), crude protein (CP), neutral detergent (NDF), acid detergent lignin (ADL), acid detergent fiber (ADF), total ash content (TASH) and organic matter (OM) did not show significant difference between treatments at (P>0.05). Numerically had different values. Both the highest fresh biomass yield and grain yield was obtained from Lalisa variety (2.9 t/ha) and 22.7 qt/ha respectively. The lowest value of biomass and grain yielder was produced from 5187 accessions (1.9 t/ha) and Vicia dasycarpa 11.3 qt/ha. Lalisa variety was highest in organic matter (OM), total ash content (TASH), crude protein (CP) and less in neutral detergent (NDF) and acid detergent fibre (ADF) content while, Vicia dayscarpa was highest in crude protein (CP) and neutral detergent (NDF) and less in organic matter (OM), content total ash content (TASH) and crude protein (CP) content, 5187 genotype had the highest in dry matter (DM) and acid detergent fiber (ADF) and less in crude protein (CP) and acid detergent lignin (ADL) content than the rest accessions. The result of this study implied that Lalisa variety was well adapted and being productive regarding the plant height, biomass yield and seed yield. Lalisa variety, which is hopeful to fill the gap of low quantity ruminant feed supply of the community in the study area. Based on its adaptable, high biomass, high plant height, high grain yield, good CP and OM Lalisa is recommended for further promotion in the midland of East Guji zone.
Chemical Analysis and in Vitro Antiproliferative Potential of Eugenia uniflora L. (Myrtaceae)
Authors: Gomes Denise Bianchin , Zanchet Barbara , Serpa Patrícia Zanotelli , Locateli Gelvani , Miorando Daniela , Steffler Amanda Maria , Zanatta Maria Eduarda de Costa , Predebon Ana Júlia , Carteri Camila Sans , Lutinski Junir , Ruiz Ana Lúcia Tasca Góis , Santos Maria de Fátima da Costa , Barison Andersson , Junior Walter Antônio Roman
Published: April 2020

Natural products and especially medicinal plants, have been extensively studied and have exhibited antiproliferative effects. The species Eugenia uniflora L. (Myrtaceae) is native to Brazil and distributed throughout Australia, East Asia, and the Americas. The leaves are commonly used for the treatment of diarrhea, fever, and hypertension. However, the chemical properties and antiproliferative potential of the extracts remain to be elucidated. In this work, the antiproliferative effects of hydroethanolic (HEE) and dichloromethane (DEE) extracts of leaves from E. uniflora against a panel of human tumor cell lines in vitro were evaluated. Quercetin was identified using an HPLC, and the chemical component β-sitosterol was isolated. The HEE was an inactive extract, whereas the DEE extract showed antiproliferative activity against OVCAR-3 ovarian cells. In a bioassay-guided process, more pronounced antiproliferative effects were found for β-sitosterol isolated from DEE, which demonstrated potent antiproliferative effects against glioblastoma (U-251 cells) and leukemia (K-562 cells). This study contributes to the knowledge of E. uniflora and suggests that β-sitosterol is a potential chemotherapeutic compound.
e
Portfolios
Authors: Arispe Kelly
Published: April 2020

Electronic portfolios (ePortfolios) are generally defined as an electronic showcase of the learner's process and product for any given learning objective, course, or both. Cummins and Davesne call it the “learner empowering alternative to computer‐based testing.” Portfolios—in the traditional sense as a collection of student learning outcomes—are not new to K‐16 environments, however, ePortfolios have come forth at an opportune time to align with educational shifts from teacher‐centered to learner‐centered, constructivist pedagogies. Furthermore, the expanse of Web 2.0 tools used for learning have been essential in encouraging this shift from paper to online. Specifically, ePortfolios encourage holistic, personalized ways to evaluate and reflect learning, however, this change requires careful implementation as well as teacher and learner training. While ePortfolios can be of benefit for any educational context, they offer unique affordances for language learners to continue working on second language (L2) development and intercultural competence.
Move Analysis
Authors: Cotos Elena
Published: April 2020

Move analysis is an approach to discourse analysis used in the research and teaching of genres within the area of language for specific purposes (LSP). Grounded in Swales's genre theory, this approach focuses on communicative purposes referred to as moves and rhetorical strategies called steps. Moves and steps are used to describe and study the rhetorical composition of texts within a genre and the linguistic means used within discourse communities to accomplish rhetorical actions. This entry presents move analysis from the perspectives of research and pedagogy, also addressing its potential value outside of LSP.
Machine Learning in Applied Linguistics
Authors: Vajjala Sowmya
Published: April 2020

This entry introduces the topic of machine learning and provides an overview of its relevance for applied linguistics and language education. A basic overview of machine learning is given, followed by an introduction to three areas of language education where machine learning methods are used: language assessment, language learning, and learning analytics.
Translanguaging
Authors: García Ofelia , Wei Li
Published: April 2020

As a critical sociolinguistic theory, translanguaging has had the most application in language education, especially in the education of language‐minoritized students and in bilingual education and increasingly in what are considered foreign language programs. It has been seen to have the capacity and potential to transform the way we see, use, and teach language, literacy, and other subjects. This entry first discusses the meanings of translanguaging theory and its implications for a theory of language. It focuses on how translanguaging transforms our understandings of bilingual/multilingual people as well as the familiar concepts that have been used to study them. The second part then turns to how translanguaging has impacted language education, transforming how we teach students for bilingualism as well as how bilingual students learn. The focus then shifts to how translanguaging informs and can transform language policies in classrooms as well as pedagogies.
Engineered Microneedles for Interstitial Fluid Cell‐Free DNA Capture and Sensing Using Iontophoretic Dual‐Extraction Wearable Patch
Authors: Yang Bin , Fang Xueen , Kong Jilie
Published: April 2020

Interstitial fluid (ISF), as an emerging source of biomarkers, is unmistakably significant for disease diagnosis. Microneedles (MNs) provide a minimally invasive approach for extracting the desired molecules from ISF. However, existing MNs are limited by their capture efficiency and sensitivity, which impedes early disease diagnosis. Herein, an engineered wearable epidermal system is presented with a combination of reverse iontophoresis and MNs for rapid capture and sensing of Epstein‐Barr virus cell‐free DNA (an important biomarker of nasopharyngeal carcinoma). Owing to a dual‐extraction effect demonstrated by reverse iontophoresis and MNs, the engineered wearable platform successfully isolates the cell‐free DNA target from ISF within 10 min, with a threshold of 5 copies per µL and a maximum capture efficiency of 95.4%. The captured cell‐free DNA is also directly used in a recombinase polymerase amplification electrochemical microfluidic biosensor with a detection limit of 1.1 copies per µL (or a single copy). The experimental data from immunodeficient mouse models rationalizes the feasibility and practicality of the wearable system. Collectively, the developed method opens an innovative route for minimally invasive sampling of ISF for cell‐free DNA‐related cancer screening and prognosis.
Electrochemical Methods for Lithium Recovery: A Comprehensive and Critical Review
Authors: Battistel Alberto , Palagonia Maria Sofia , Brogioli Doriano , La Mantia Fabio , Trócoli Rafael
Published: April 2020

Due to the ubiquitous presence of lithium‐ion batteries in portable applications, and their implementation in the transportation and large‐scale energy sectors, the future cost and availability of lithium is currently under debate. Lithium demand is expected to grow in the near future, up to 900 ktons per year in 2025. Lithium utilization would depend on a strong increase in production. However, the currently most extended lithium extraction method, the lime‐soda evaporation process, requires a period of time in the range of 1–2 years and depends on weather conditions. The actual global production of lithium by this technology will soon be far exceeded by market demand. Alternative production methods have recently attracted great attention. Among them, electrochemical lithium recovery, based on electrochemical ion‐pumping technology, offers higher capacity production, it does not require the use of chemicals for the regeneration of the materials, reduces the consumption of water and the production of chemical wastes, and allows the production rate to be controlled, attending to the market demand. Here, this technology is analyzed with a special focus on the methodology, materials employed, and reactor designs. The state‐of‐the‐art is reevaluated from a critical perspective and the viability of the different proposed methodologies analyzed.
Morphology and Magneto‐Transport in Exfoliated Graphene on Ultrathin Crystalline β‐Si3N4(0001)/Si(111)
Authors: Salimian Sedighe , Xiang Shaohua , Colonna Stefano , Ronci Fabio , Fosca Marco , Rossella Francesco , Beltram Fabio , Flammini Roberto , Heun Stefan
Published: April 2020

This work reports the first experimental study of graphene transferred on β‐Si3N4(0001)/Si(111). A comprehensive quantitative understanding of the physics of ultrathin Si3N4 as a gate dielectric for graphene‐based devices is provided. The Si3N4 film is grown on Si(111) under ultra‐high vacuum (UHV) conditions and investigated by scanning tunneling microscopy (STM). Subsequently, a graphene flake is deposited on top of it by a polymer‐based transfer technique, and a Hall bar device is fabricated from the graphene flake. STM is employed again to study the graphene flake under UHV conditions after device fabrication and shows that the surface quality is preserved. Electrical transport measurements, carried out at low temperature in magnetic field, reveal back gate modulation of carrier density in the graphene channel and show the occurrence of weak localization. Under these experimental conditions, no leakage current between back gate and graphene channel is detected.
Mie Resonator Color Inks of Monodispersed and Perfectly Spherical Crystalline Silicon Nanoparticles
Authors: Sugimoto Hiroshi , Okazaki Takuma , Fujii Minoru
Published: April 2020

A crystalline silicon (Si) nanoparticle (NP) of 100–200 nm in diameter exhibits a highly saturated color owing to Mie resonance, and can be a component to realize angle‐insensitive structural color covering the entire visible range. However, to date, coloring a substrate by Si nanostructures has only been achieved in a very small area by using electron beam lithography and dry etching processes. In this work, a Si NP color ink capable of coloring a flexible substrate by a painting process is developed. The sphericity of Si NPs is very high; the circularity factor obtained from a transmission electron microscope image reaches 0.97. The average diameter of Si nanospheres is controlled from 95 to 200 nm, and the polydispersity defined by the standard deviation divided by the average diameter is as small as 6%. Because of the high sphericity, high crystallinity, high size purity, and perfect dispersion in solution, the Si nanosphere solutions exhibit vivid colors recognizable by naked eye in a range of blue to orange. The Si nanosphere color inks combined with a polymer binder are capable of coloring flexible substrates by a painting process.
High Efficiency Up‐Conversion Random Lasing from Formamidinium Lead Bromide/Amino‐Mediated Silica Spheres Composites
Authors: Yang Jie , Liu Zhengzheng , Pi Mingyu , Lin Hao , Zeng Fanju , Bian Yao , Shi Tongchao , Du Juan , Leng Yuxin , Tang Xiaosheng
Published: April 2020

Formamidinium (HC(NH2)+; FA) lead halide perovskites have emerged as potential candidates for solar cells, light‐emitting diodes, and lasing applications. However, the severely poor photostability of this material under UV irradiation seriously restricts the application on optoelectronic devices. In this paper, formamidinium lead halide (FAPbX3) quantum dots (QDs) adhered uniformly on the surface of amino‐mediated silica (A‐SiO2) spheres are successfully synthesized using a facile ligand‐assisted reprecipitation (LARP) method. Amazingly, the FAPbBr3/A‐SiO2 composites demonstrate excellent photostability after continuous illumination under UV lamps due to the effective suppression of the interactions and mutual contact between FAPbBr3 particles. In addition, the up‐conversion random lasing with a high quality (Q) factor of 1307 and low threshold of 413.7 µJ cm‐2 is successfully achieved from the FAPbBr3/A‐SiO2 composites at room‐temperature, which originates from the multiple random scattering of light and photon recycling provided by the silica spheres and the high gain characteristic of FAPbBr3 QDs. Moreover, different from regular lasers, random lasing does not rely on a laser cavity, which is promising in angle‐unlimited optical performance and easy/low‐cost fabrication. This work will open the window of high‐performance random lasers for digital light projector, high speed imaging, and speckle‐free full‐field imaging application.
Cellulose‐Conducting Polymer Aerogels for Efficient Solar Steam Generation
Authors: Han Shaobo , Ruoko Tero‐Petri , Gladisch Johannes , Erlandsson Johan , Wågberg Lars , Crispin Xavier , Fabiano Simone
Published: April 2020

Seawater desalination and wastewater purification technologies are the main strategies against the global fresh water shortage. Among these technologies, solar‐driven evaporation is effective in extracting fresh water by efficiently exploiting solar energy. However, building a sustainable and low‐cost solar steam generator with high conversion efficiency is still a challenge. Here, pure organic aerogels comprising a cellulose scaffold decorated with an organic conducting polymer absorbing in the infrared are employed to establish a high performance solar steam generator. The low density of the aerogel ensures minimal material requirements, while simultaneously satisfying efficient water transport. To localize the absorbed solar energy and make the system floatable, a porous floating and thermal‐insulating foam is placed between the water and the aerogel. Thanks to the high absorbance of the aerogel and the thermal‐localization performance of the foam, the system exhibits a high water evaporation rate of 1.61 kg m−2 h−1 at 1 kW m−2 under 1 sun irradiation, which is higher than most reported solar steam generation devices.
Hyperthermia‐Triggered On‐Demand Biomimetic Nanocarriers for Synergetic Photothermal and Chemotherapy
Authors: Gao Junbin , Wang Fei , Wang Shuanghu , Liu Lu , Liu Kun , Ye Yicheng , Wang Zhen , Wang Hong , Chen Bin , Jiang Jiamiao , Ou Juanfeng , van Hest Jan C. M. , Peng Fei , Tu Yingfeng
Published: April 2020

Nanoparticle‐based drug delivery systems with low side effects and enhanced efficacy hold great potential in the treatment of various malignancies, in particular cancer; however, they are still challenging to attain. Herein, an anticancer drug delivery system based on a cisplatin (CDDP) containing nanogel, functionalized with photothermal gold nanorods (GNRs) which are electrostatically decorated with doxorubicin (DOX) is reported. The nanoparticles are formed via the crosslinking reaction of hyaluronic acid with the ancillary anticarcinogen CDDP in the presence of DOX‐decorated GNRs. The nanogel is furthermore cloaked with a cancer cell membrane, and the resulting biomimetic nanocarrier (4T1‐HANG‐GNR‐DC) shows efficient accumulation by homologous tumor targeting and possesses long‐time retention in the tumor microenvironment. Upon near‐infrared (NIR) laser irradiation, in situ photothermal therapy is conducted which further induces hyperthermia‐triggered on‐demand drug release from the nanogel reservoir to achieve a synergistic photothermal/chemo‐therapy. The as‐developed biomimetic nanocarriers, with their dual‐drug delivery features, homotypic tumor targeting and synergetic photothermal/chemo‐therapy, show much promise as a potential platform for cancer treatment.
A Precise Microfluidic Assay in Single‐Cell Profile for Screening of Transient Receptor Potential Channel Modulators
Authors: Ai Xiaoni , Wu Yang , Lu Wenbo , Zhang Xinran , Zhao Lin , Tu Pengfei , Wang KeWei , Jiang Yong
Published: April 2020

Transient receptor potential (TRP) channels are emerging drug targets, and TRP channel modulators possess therapeutic potential for many indications. However, there is a lack of intellectual and robust screening assays against TRP channels utilizing the least amount of compounds. Here, a precise microfluidic assay in single‐cell profile is developed for the screening of TRP channel modulators. The geometrically optimized microchip is designed for both trapping single cells and utilizing passive pumping for sequential media replacement with low shear stress. The microfluidic chip exhibits superior performance in screening, repeatable compound administration, and improved reproducibility. Using this screening platform, the false‐positive and negative rate of the commonly used Ca2+ imaging is reduced from 76.2% to 4.8% and four coumarin derivatives isolated from Murraya species that inhibit TRP channels are identified. One coumarin derivative B‐304 reverses TRPA1‐mediated inflammatory pain in vivo. Taken together, the data demonstrate that the established microfluidic assay in single‐cell profile could be used for the screening of TRP channel modulators that may have therapeutic potential for the channelopathies.
Enhanced Potassium Ion Battery by Inducing Interlayer Anionic Ligands in MoS1.5Se0.5 Nanosheets with Exploration of the Mechanism
Authors: Fan Hai‐Ning , Wang Xing‐Yong , Yu Hai‐Bo , Gu Qin‐Fen , Chen Shan‐Liang , Liu Zheng , Chen Xiao‐Hua , Luo Wen‐Bin , Liu Hua‐Kun
Published: April 2020

The strategy of inducing interlayer anionic ligands in 2D MoS1.5Se0.5 nanosheets is employed to consolidate the interlayer band gap and optimize the electronic structure for the potassium ion battery. It combines complementary advantages from two kinds of anionic ligands with high conductivity and good affinity with potassium ions. The potassium ion diffusion rate is accelerated as well by an optimized lower energy barrier for ion diffusion pathways, with the formation of highly reversible KMo3Se3 crystal other than K0.4MoS2/K2MoS4, which encounters a much slower electro/ion diffusion rate upon discharging. These advances deliver enhanced potassium storage properties with excellent cycling stability, with retained specific capacity of 531.6 mAh g−1 at a current density of 200 mA g−1 even after 1000 cycles, and high rate capability with specific capacity of 270.1 mAh g−1 at 5 A g−1. The insertion and conversion mechanism are also elucidated by a combination of density functional theory computations and in situ synchrotron measurements.
Warm‐season forage options in Northern Dryland Regions
Authors: Carr Patrick M. , Boss Darrin L. , Chen Chengci , Dafoe Julia M. , Eberly Jed O. , Fordyce Simon , Hydner Roger M. , Fryer Heather K. , Lachowiec Jennifer A. , Lamb Peggy F. , McVay Kent A. , Khan Qasim A. , Miller Perry R. , Miller Zachariah J. , Torrion Jessica A.
Published: April 2020

Rotating summer fallow with wheat (Triticum spp.) is done in dryland grain farming at upper latitudes to stabilize yields over time and to prevent crop failure. However, summer fallow is costly since weeds must be controlled and crops are not grown. Replacing summer fallow with grain crops can generate low economic returns. Previous research indicated that annual cool‐season forages can be substituted for summer fallow in dryland cropping systems. Our objective was to determine if annual warm‐season species were suited for forage production in monocultures and polycultures in the U.S. northern Great Plains. Dry matter (DM) production by 20 warm‐ and cool‐season crop monocultures and 4 polycultures was determined across six environments during 2016, and by 25 warm‐ and cool‐season crop monocultures and polycultures across four environments from 2016 through 2018. Maize (Zea mays L.) monoculture produced forage DM in amounts equal to, or greater than, those produced by other warm‐ and cool‐season crop treatments (P < 0.05). Maize DM production averaged 2.5 to 5.7 Mg ha−1, depending on the study and environment. Sorghum (Sorghum bicolor L.), foxtail millet [Setaria italica (L.) P. Beauv.] and sunflower (Helianthus annuus L.) also produced relatively large amounts of forage DM. Polycultures failed to produce more DM than monocultures consistently (P > 0.40). These results indicate that maize and other warm‐season crops are adapted for dryland forage production in cool regions at upper latitudes. Additional research is needed to determine the impacts of annual warm‐season forages on grain yield in a forage‐wheat crop sequence.
A multi‐institutional comparison of mitoxantrone, etoposide, and cytarabine vs high‐dose cytarabine and mitoxantrone therapy for patients with relapsed or refractory acute myeloid leukemia
Authors: Christian Sonia , Arain Saad , Patel Pritesh , Khan Irum , Calip Gregory S. , Agrawal Vaibhav , Sweiss Karen , Griffin Shawn , Cahill Kirk , Konig Heiko , Esen Aysenur , Shergill Ardaman , Odenike Olatoyosi , Stock Wendy , Quigley John G.
Published: April 2020

Relapsed or refractory acute myeloid leukemia (R/R AML) has a poor prognosis and is best treated with salvage chemotherapy as a bridge to allogeneic stem cell transplant (alloSCT). However, the optimal salvage therapy remains unknown. Here we compared two salvage regimens; mitoxantrone, etoposide, and cytarabine (MEC) and mitoxantrone and high‐dose Ara‐C (Ara‐C couplets). We analyzed 155 patients treated at three academic institutions between 1998 and 2017; 87 patients received MEC and 68 received Ara‐C couplets. The primary endpoint was overall response (OR). Secondary endpoints included progression‐free survival (PFS), overall survival (OS), duration of hospitalization, hematologic and nonhematologic toxicities, and success in proceeding to alloSCT. Baseline characteristics of the cohorts were well matched, though patients receiving Ara‐C couplets had more co‐morbidities (48.5% vs 33%; P = .07). OR was achieved in 43.7% of MEC and 54.4% of Ara‐C couplets patients (P = .10). Ara‐C couplets patients also trended towards a longer OS and PFS, more frequently proceeded to alloSCT (31% vs 54.4%; P = .003), and experienced less febrile neutropenia (94% vs 72%; P < .001) and grade 3/4 gastrointestinal toxicities (17.2% vs 2.94%; P = .005). No significant differences in other toxicities or median duration of hospitalization were noted. This is the first multi‐institutional study directly comparing these regimens in a racially diverse population of R/R AML patients. Although these regimens have equivalent efficacy in terms of achieving OR, Ara‐C couplets use is associated with significant reductions in toxicities, suggesting it should be used more frequently in these patients.
Patients with paroxysmal nocturnal hemoglobinuria demonstrate a prothrombotic clotting phenotype which is improved by complement inhibition with eculizumab
Authors: Macrae Fraser L. , Peacock‐Young Barnaby , Bowman Polly , Baker Stephen R. , Quested Sam , Linton Emma , Hillmen Peter , Griffin Morag , Munir Talha , Payne Daniel , McKinley Claire , Clarke Deborah , Newton Darren J , Hill Anita , Ariëns Robert A. S.
Published: April 2020

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder, characterized by complement‐mediated intravascular hemolysis and thrombosis. The increased incidence of PNH‐driven thrombosis is still poorly understood, but unlike other thrombotic disorders, is thought to largely occur through complement‐mediated mechanisms. Treatment with a C5 inhibitor, eculizumab, has been shown to significantly reduce the number of thromboembolic events in these patients. Based on previously described links between changes in fibrin clot structure and thrombosis in other disorders, our aim was to investigate clot structure as a possible mechanism of thrombosis in patients with PNH and the anti‐thrombotic effects of eculizumab treatment on clot structure. Clot structure, fibrinogen levels and thrombin generation were examined in plasma samples from 82 patients from the National PNH Service in Leeds, UK. Untreated PNH patients were found to have increased levels of fibrinogen and thrombin generation, with subsequent prothrombotic changes in clot structure. No link was found between increasing disease severity and fibrinogen levels, thrombin generation, clot formation or structure. However, eculizumab treated patients showed decreased fibrinogen levels, thrombin generation and clot density, with increasing time spent on treatment augmenting these antithrombotic effects. These data suggest that PNH patients have a prothrombotic clot phenotype due to increased fibrinogen levels and thrombin generation, and that the antithrombotic effects of eculizumab are, in‐part, due to reductions in fibrinogen and thrombin generation with downstream effects on clot structure.
The effects of data collection and observation methods on uncertainty of social networks in wild primates
Authors: Canteloup Charlotte , Puga‐Gonzalez Ivan , Sueur Cédric , van de Waal Erica
Published: April 2020

In social species, network centralities of group members shape social transmission and other social phenomena. Different factors have been found to influence the measurement of social networks, such as data collection and observation methods. In this study, we collected data on adults and juveniles and examined the effect of data collection method (ad libitum sampling vs. focal animal sampling) and observation method (interaction—grooming; play—vs. association—arm‐length; 2 m; 5 m proximities—) on social networks in wild vervet monkeys. First, we showed using a bootstrapping method, that uncertainty of ad libitum grooming and play matrices were lesser than uncertainty of focal matrices. Nevertheless, grooming and play networks constructed from ad libitum and focal animal sampling were very similar and highly correlated. We improved the certainty of both grooming and play networks by pooling focal and ad libitum matrices. Second, we reported a high correlation between the proximity arm‐length network and the focal grooming one making an arm‐length proximity network a reasonable proxy for a grooming one in vervet monkeys. However, we did not find such a correlation between proximity networks and the play one. Studying the effects of methodological issues as data collection and observation methods can help improve understanding of what shapes social networks and which data collection method to choose to study sociality.
Isolation and Characterization of the Free Phenylphosphinidene Chalcogenides C6H5P=O and C6H5P=S, the Phosphorous Analogues of Nitrosobenzene and Thionitrosobenzene
Authors: Mardyukov Artur , Keul Felix , Schreiner Peter R.
Published: April 2020

The structures and reactivities of organic phosphinidene chalcogenides have been mainly inferred from trapping or complexation experiments. Phosphinidene chalcogenide derivatives appear to be an elusive family of molecules that have been suggested as reactive intermediates in multiple organophosphorus reactions. The quest to isolate “free” phosphinidene chalcogenides remains a challenge in the field. Here, we present the synthesis, IR, and UV/Vis spectroscopic identification of hitherto elusive phenylphosphinidene oxide and phenylphosphinidene sulfide from the corresponding phosphonic diazide precursors. We isolated these higher congeners of nitroso‐ and thionitrosobenzene in argon matrices at 10 K. The spectral assignments are supported by B3LYP/6–311++G(3df,3pd) and MP2/cc‐pVTZ computations.
Synthesis, cytotoxicity, and molecular docking of substituted 3‐(2‐methylbenzofuran‐3‐yl)‐5‐(phenoxymethyl)‐1,2,4‐oxadiazoles
Authors: Mokenapelli Sudhakar , Thalari Gangadhar , Vadiyaala Naveen , Yerrabelli Jayaprakash R. , Irlapati Vamshi K. , Gorityala Neelima , Sagurthi Someswar R. , Chitneni Prasad R.
Published: April 2020

A series of new benzofuran/oxadiazole hybrids (8a–n) was synthesized from 2H‐chromene‐3‐carbonitriles (3a–c) through the multistep synthetic methodology, and these hybrids are known to exhibit anticancer activities. All the compounds were evaluated for their in vitro cytotoxicity against the HCT116 and MIA PaCa2 cell lines. Compounds 6a (IC50: 9.71 ± 1.9 μM), 6b (IC50: 7.48 ± 0.6 μM), and 6c (IC50: 3.27 ± 1.1 μM) displayed a significant cytotoxic activity, whereas compounds 8d and 8e exhibited good activity against both cell lines. The depletion of glycogen synthase kinase‐3β (GSK3β) induces apoptosis through the inhibition of basal NF‐κB activity in HCT116 colon cancer cells and MIA PaCa2 pancreatic cancer cells. Molecular docking of compounds 6a, 6b, 6c, 8d, and 8e with GSK3β demonstrated the best binding affinity, correlating with the biological activity assay. Furthermore, the structure–activity relationship of these novel compounds reveals promising features for their use in anticancer therapy.
Application of grey system theory to phosphorite sinter process: From modeling to control
Authors: Toktassynova Nigina , Fourati Hassen , Suleimenov Batyrbek
Published: April 2020

The sintering process of phosphorite ore occurs with a large amount of return caused by untimely process control. The control task of phosphorite ore sintering is to regulate the parameters of the process to obtain a high quality sinter. The parameter clearly responsible for sinter quality is the temperature in the wind box. Therefore, in order to solve the control task, it is necessary to predict the highest temperature of the charge (also known as the burn through point (BTP)). In this paper, the theory of grey systems is used as a predictive model, which makes it possible to obtain an adequate model that uses a small number of initial samples of real temperature data. Based on the grey model GMC(1,n) a new optimal model is presented, which is constructed by using optimization algorithm. Optimal model predicts the BTP, and to establish an optimal regulation, a control synthesis is carried out through an optimization of the prediction according to the “particle swarm” algorithm.
The potential for uncertainty in Numerical Weather Prediction model verification when using solid precipitation observations
Authors: Buisán Samuel T. , Smith Craig D. , Ross Amber , Kochendorfer John , Collado José Luís , Alastrué Javier , Wolff Mareile , Roulet Yves‐Alain , Earle Michael E. , Laine Timo , Rasmussen Roy , Nitu Rodica
Published: April 2020

Precipitation forecasts made by Numerical Weather Prediction (NWP) models are typically verified using precipitation gauge observations that are often prone to the wind‐induced undercatch of solid precipitation. Therefore, apparent model biases in solid precipitation forecasts may be due in part to the measurements and not the model. To reduce solid precipitation measurement biases, adjustments in the form of transfer functions were derived within the framework of the World Meteorological Organization Solid Precipitation Inter‐Comparison Experiment (WMO‐SPICE). These transfer functions were applied to single‐Alter shielded gauge measurements at selected SPICE sites during two winter seasons (2015–2016 and 2016–2017). Along with measurements from the WMO automated field reference configuration at each of these SPICE sites, the adjusted and unadjusted gauge observations were used to analyze the bias in a Global NWP model precipitation forecast. The verification of NWP winter precipitation using operational gauges may be subject to verification uncertainty, the magnitude and sign of which varies with the gauge‐shield configuration and the relation between model and site‐specific local climatologies. The application of a transfer function to alter‐shielded gauge measurements increases the amount of solid precipitation reported by the gauge and therefore reduces the NWP precipitation bias at sites where the model tends to overestimate precipitation, and increases the bias at sites where the model underestimates the precipitation. This complicates model verification when only operational (non‐reference) gauge observations are available. Modelers, forecasters, and climatologists must consider this when comparing modeled and observed precipitation.
Testing bias adjustment methods for regional climate change applications under observational uncertainty and resolution mismatch
Authors: Casanueva Ana , Herrera Sixto , Iturbide Maialen , Lange Stefan , Jury Martin , Dosio Alessandro , Maraun Douglas , Gutiérrez José M.
Published: April 2020

Systematic biases in climate models hamper their direct use in impact studies and, as a consequence, many statistical bias adjustment methods have been developed to calibrate model outputs against observations. The application of these methods in a climate change context is problematic since there is no clear understanding on how these methods may affect key magnitudes, for example, the climate change signal or trend, under different sources of uncertainty. Two relevant sources of uncertainty, often overlooked, are the sensitivity to the observational reference used to calibrate the method and the effect of the resolution mismatch between model and observations (downscaling effect). In the present work, we assess the impact of these factors on the climate change signal of temperature and precipitation considering marginal, temporal and extreme aspects. We use eight standard and state‐of‐the‐art bias adjustment methods (spanning a variety of methods regarding their nature—empirical or parametric—, fitted parameters and trend‐preservation) for a case study in the Iberian Peninsula. The quantile trend‐preserving methods (namely quantile delta mapping (QDM), scaled distribution mapping (SDM) and the method from the third phase of ISIMIP‐ISIMIP3) preserve better the raw signals for the different indices and variables considered (not all preserved by construction). However, they rely largely on the reference dataset used for calibration, thus presenting a larger sensitivity to the observations, especially for precipitation intensity, spells and extreme indices. Thus, high‐quality observational datasets are essential for comprehensive analyses in larger (continental) domains. Similar conclusions hold for experiments carried out at high (approximately 20 km) and low (approximately 120 km) spatial resolutions.
Sequencing Strategies for Fusion Gene Detection
Authors: Heyer Erin E. , Blackburn James
Published: April 2020

Fusion genes formed by chromosomal rearrangements are common drivers of cancer. Recent innovations in the field of next‐generation sequencing (NGS) have seen a dynamic shift from traditional fusion detection approaches, such as visual characterization by fluorescence, to more precise multiplexed methods. There are many different NGS‐based approaches to fusion gene detection and deciding on the most appropriate method can be difficult. Beyond the experimental approach, consideration needs to be given to factors such as the ease of implementation, processing time, associated costs, and the level of expertise required for data analysis. Here, the different NGS‐based methods for fusion gene detection, the basic principles underlying the techniques, and the benefits and limitations of each approach are reviewed. This article concludes with a discussion of how NGS will impact fusion gene detection in a clinical context and from where the next innovations are evolving.
Production of the bioactive plant‐derived triterpenoid morolic acid in engineered Saccharomyces cerevisiae
Authors: Srisawat Pisanee , Yasumoto Shuhei , Fukushima Ery O. , Robertlee Jekson , Seki Hikaru , Muranaka Toshiya
Published: April 2020

Morolic acid is a plant‐derived triterpenoid that possesses pharmacological properties such as cytotoxicity, as well as anti‐HIV, anti‐HSV, anti‐inflammatory, and antidiabetic effects. The significant therapeutic properties of morolic acid are desirable in the context of pharmacological and drug development research, but the low accessibility of morolic acid from natural resources limits its applications. In the present study, we developed a microbial system for the production of morolic acid. Using a combinatorial biosynthesis approach, a novel production pathway was constructed in Saccharomycescerevisiae by coexpressing BfOSC2 (germanicol synthase) from Bauhinia forficata and CYP716A49 (triterpene C‐28 oxidase) from Beta vulgaris. Moreover, we reconstructed the cellular galactose regulatory network by introducing a chimeric transcriptional activator (fusion of Gal4dbd.ER.VP16) to overdrive the genes under the control of the galactose promoter. We also overexpressed truncated HMG1, encoding feedback‐inhibition‐resistant form of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase 1 and sterol‐regulating transcription factor upc2‐1, to increase the isoprenoid precursors in the mevalonate pathway. Using this yeast system, we achieved morolic acid production up to 20.7 ± 1.8 mg/L in batch culture. To our knowledge, this is the highest morolic acid titer reported from a heterologous host, indicating a promising approach for obtaining rare natural triterpenoids.
LC–MS/MS assay for the quantification of foretinib in rat plasma and its application to preclinical pharmacokinetic study
Authors: Guo Nan , Zhang Aiying , Zhuang Hui , Zhang Changzhen
Published: April 2020

A simple and sensitive ultra‐high‐performance liquid chromatography tandem mass spectrometric method was developed and validated for the determination of foretinib in rat plasma. The analyte and internal standard were extracted from the bio‐samples with acetonitrile and then separated on an Acquity UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm) using 0.1% formic acid aqueous and acetonitrile as mobile phase, at a flow rate of 0.4 ml/min. The mass detection was performed in positive selected reaction monitoring mode with precursor‐to‐product transitions at m/z 317.1 > 128.1 for foretinib and m/z 502.2 > 323.1 for internal standard. The assay was demonstrated to be linear in the concentration range of 0.5–1000 ng/ml, with correlation coefficient >0.999. The mean extraction recovery of foretinib from rat plasma was within the range of 84.55–88.09%, while the matrix effect was in the range of 88.56–99.21%. The intra‐ and inter‐day precisions were <12.95% and the accuracy ranged from −7.55 to 8.57%. Foretinib was stable in rat plasma under the tested storage conditions. The validated assay was successfully applied to the pharmacokinetic study of foretinib in the rats. The results revealed that foretinib showed moderate elimination half‐life, low clearance and dose‐independent pharmacokinetic profiles inrats.
Mechanism of microRNA‐22 in regulating neuroinflammation in Alzheimer’s disease
Authors: Han Chenyang , Guo Li , Yang Yi , Guan Qiaobing , Shen Heping , Sheng Yongjia , Jiao Qingcai
Published: April 2020

Background

Study on the expression of miRNA‐22 in serum of Alzheimer's disease (AD) patients and the mechanism of neuroinflammation regulation.

Methods

ELISA assay was used to detect the serum level of inflammatory factors, including interleukin‐1β (IL‐1β), interleukin‐18 (IL‐18), and tumor necrosis factor‐α in AD patients. TargetScan database and luciferase reporter gene assay indicated that gasdermin D (GSDMD) was the target gene of miRNA‐22. miRNA‐22 mimic was transfected into microglia, followed by administration of LPS and Nigericin to induce pyroptosis.

Results

In this study, we found that the expression level of miRNA‐22 in peripheral blood was lower in AD patients than that in healthy population. The expression of inflammatory factors was higher in AD patients than that in healthy people, which was negatively correlated with miRNA‐22. miRNA‐22 mimic could significantly inhibit pyroptosis, the expression of GSDMD and p30‐GSDMD was down‐regulated, the release of inflammatory factor was decreased, and the expression of NLRP3 inflammasome was down‐regulated as feedback. In the APP/PS1 double transgenic mouse model, the injection of miRNA‐22 mimic significantly improved the memory ability and behavior of mice. In addition, the expression of the vital protein of pyroptosis in mouse brain tissue, including GSDMD and p30‐GSDMD, was down‐regulated, and the expression of inflammatory factors was also decreased.

Conclusion

miRNA‐22 was negatively correlated with the expression of inflammatory factors in AD patients, and miRNA‐22 could inhibit the release of inflammatory cytokines by regulating the inflammatory pyroptosis of glial cells via targeting GSDMD, thereby improving cognitive ability in AD mice. miRNA‐22 and pyroptosis are potential novel therapeutic targets in the treatment of AD.