bluuebunny/crossref_metadata_2025 huggingface dataset:
O fim de uma aurora: sobre Roberto Franco, bonequeiro
Authors: Mercurio Sergio Adrian
Published: July 2020

Resumo: Este ensaio é o fruto de uma investigação por meio de entrevistas realizadas ao longo de dois anos. Relata a história de Roberto Franco, bonequeiro salvadorenho que desenvolveu seu trabalho durante o conflito armado em seu país. Ele fez parte das Fuerzas Populares de Liberación (FPL), uma organização política e guerrilheira. Em 23 de novembro de 1983 desapareceu, e até os dias de hoje não se sabe nada de seu pa- radeiro. Esta é a história do bonequeiro que criou uma personagem chamada Aurora, uma rã de cor vermelha e cabelo amarelo, com a qual cumpriu a missão de agitar as massas estudantis e operárias, com o objetivo de conscientizá-las.Palavras-chave: Desaparecido. Bonequeiro. El Salvador. Roberto Franco.
El final de la aurora: sobre Roberto Franco, titiritero
Authors: Mercurio Sergio Adrian
Published: July 2020

Durante los años de la guerra civil en El Salvador, vivió Roberto Franco, quien consideró que su forma de acción en esa guerra era la de ser titiritero. El artículo cuenta la historia de su vida. La de un titiritero que murió  siéndolo aun en una de las situaciones más traumáticas que puede vivir una sociedad
Una historia tejida en el hielo: comentarios en torno a la investigación educativa basada en artes visuales, a propósito de una puesta en escena
Authors: Rodríguez-Aguilar Jorge Luis
Published: July 2020

Resumen: La vinculación ineludible entre los distintos géneros de las artes visuales son recursos que posibilitan, cada vez más, el desarrollo de nuevos ejercicios académicos e investigativos. Sin renunciar a sus individualidades, el teatro de títeres y la fotografía, pueden estructurar dinámicas investigativas provechosas para los procesos creativos contemporáneos, en particular, la producción de imágenes simbólico-metafóricas. Hacerlo no resulta difícil; solo se necesita el empeño.Palavras-clave: Teatro de títeres. Fotografía. Investigación educativa basada en artes visuales. Metodología. Didáctica fotográfica.
La empleabilidad a debate: ¿qué sabemos sobre la empleabilidad como estrategia de cambio social?
Authors: Llinares Insa Lucía , Córdoba-Iñesta Ana Isabel , González-Navarro Pilar
Published: July 2020

Los cambios en mundo laboral derivados de la globalización y el neoliberalismo han puesto a la empleabilidad en el centro de atención del desarrollo económico y social. Sin embargo, la falta de consenso en las teorías y las dimensiones que la definen reclaman un análisis de la investigación que permita su uso como estrategia de cambio social. El objetivo de este trabajo es realizar una revisión sistemática de los marcos teóricos sobre empleabilidad. Se ha realizado un análisis de 239 artículos científicos atendiendo a dos áreas temáticas: la historia del concepto y las perspectivas teóricas. Los resultados de esta revisión han permitido sistematizar y comprender las orientaciones teóricas desde las que se ha analizado la empleabilidad, las premisas que toman las diferentes teorías como punto de partida y los indicadores propuestos. A partir de todo ello, se han abierto algunas cuestiones para la reflexión de los agentes sociales vinculados a la educación, la acción social y al empleo.
Virus infection is controlled by hematopoietic and stromal cell sensing of murine cytomegalovirus through STING
Authors: Piersma Sytse J , Poursine-Laurent Jennifer , Yang Liping , Barber Glen N , Parikh Bijal A , Yokoyama Wayne M
Published: July 2020

Recognition of DNA viruses, such as cytomegaloviruses (CMVs), through pattern-recognition receptor (PRR) pathways involving MyD88 or STING constitute a first-line defense against infections mainly through production of type I interferon (IFN-I). However, the role of these pathways in different tissues is incompletely understood, an issue particularly relevant to the CMVs which have broad tissue tropisms. Herein, we contrasted anti-viral effects of MyD88 versus STING in distinct cell types that are infected with murine CMV (MCMV). Bone marrow chimeras revealed STING-mediated MCMV control in hematological cells, similar to MyD88. However, unlike MyD88, STING also contributed to viral control in non-hematological, stromal cells. Infected splenic stromal cells produced IFN-I in a cGAS-STING-dependent and MyD88-independent manner, while we confirmed plasmacytoid dendritic cell IFN-I had inverse requirements. MCMV-induced natural killer cytotoxicity was dependent on MyD88 and STING. Thus, MyD88 and STING contribute to MCMV control in distinct cell types that initiate downstream immune responses.
Notch and TLR signaling coordinate monocyte cell fate and inflammation
Authors: Gamrekelashvili Jaba , Kapanadze Tamar , Sablotny Stefan , Ratiu Corina , Dastagir Khaled , Lochner Matthias , Karbach Susanne , Wenzel Philip , Sitnow Andre , Fleig Susanne , Sparwasser Tim , Kalinke Ulrich , Holzmann Bernhard , Haller Hermann , Limbourg Florian P
Published: July 2020

Conventional Ly6Chi monocytes have developmental plasticity for a spectrum of differentiated phagocytes. Here we show, using conditional deletion strategies in a mouse model of Toll-like receptor (TLR) 7-induced inflammation, that the spectrum of developmental cell fates of Ly6Chi monocytes, and the resultant inflammation, is coordinately regulated by TLR and Notch signaling. Cell-intrinsic Notch2 and TLR7-Myd88 pathways independently and synergistically promote Ly6Clo patrolling monocyte development from Ly6Chi monocytes under inflammatory conditions, while impairment in either signaling axis impairs Ly6Clo monocyte development. At the same time, TLR7 stimulation in the absence of functional Notch2 signaling promotes resident tissue macrophage gene expression signatures in monocytes in the blood and ectopic differentiation of Ly6Chi monocytes into macrophages and dendritic cells, which infiltrate the spleen and major blood vessels and are accompanied by aberrant systemic inflammation. Thus, Notch2 is a master regulator of Ly6Chi monocyte cell fate and inflammation in response to TLR signaling.
Accurate and versatile 3D segmentation of plant tissues at cellular resolution
Authors: Wolny Adrian , Cerrone Lorenzo , Vijayan Athul , Tofanelli Rachele , Barro Amaya Vilches , Louveaux Marion , Wenzl Christian , Strauss Sören , Wilson-Sánchez David , Lymbouridou Rena , Steigleder Susanne S , Pape Constantin , Bailoni Alberto , Duran-Nebreda Salva , Bassel George W , Lohmann Jan U , Tsiantis Miltos , Hamprecht Fred A , Schneitz Kay , Maizel Alexis , Kreshuk Anna
Published: July 2020

Quantitative analysis of plant and animal morphogenesis requires accurate segmentation of individual cells in volumetric images of growing organs. In the last years, deep learning has provided robust automated algorithms that approach human performance, with applications to bio-image analysis now starting to emerge. Here, we present PlantSeg, a pipeline for volumetric segmentation of plant tissues into cells. PlantSeg employs a convolutional neural network to predict cell boundaries and graph partitioning to segment cells based on the neural network predictions. PlantSeg was trained on fixed and live plant organs imaged with confocal and light sheet microscopes. PlantSeg delivers accurate results and generalizes well across different tissues, scales, acquisition settings even on non plant samples. We present results of PlantSeg applications in diverse developmental contexts. PlantSeg is free and open-source, with both a command line and a user-friendly graphical interface.
Lichen mimesis in mid-Mesozoic lacewings
Authors: Fang Hui , Labandeira Conrad C , Ma Yiming , Zheng Bingyu , Ren Dong , Wei Xinli , Liu Jiaxi , Wang Yongjie
Published: July 2020

Animals mimicking other organisms or using camouflage to deceive predators are vital survival strategies. Modern and fossil insects can simulate diverse objects. Lichens are an ancient symbiosis between a fungus and an alga or a cyanobacterium that sometimes have a plant-like appearance and occasionally are mimicked by modern animals. Nevertheless, lichen models are almost absent in fossil record of mimicry. Here, we provide the earliest fossil evidence of a mimetic relationship between the moth lacewing mimic Lichenipolystoechotes gen. nov. and its co-occurring fossil lichen model Daohugouthallus ciliiferus. We corroborate the lichen affinity of D. ciliiferus and document this mimetic relationship by providing structural similarities and detailed measurements of the mimic’s wing and correspondingly the model’s thallus. Our discovery of lichen mimesis predates modern lichen-insect associations by 165 million years, indicating that during the mid-Mesozoic, the lichen-insect mimesis system was well established and provided lacewings with highly honed survival strategies.
A novel curation system to facilitate data integration across regional citizen science survey programs
Authors: Campbell Dana L. , Thessen Anne E. , Ries Leslie
Published: July 2020

Integrative modeling methods can now enable macrosystem-level understandings of biodiversity patterns, such as range changes resulting from shifts in climate or land use, by aggregating species-level data across multiple monitoring sources. This requires ensuring that taxon interpretations match up across different sources. While encouraging checklist standardization is certainly an option, coercing programs to change species lists they have used consistently for decades is rarely successful. Here we demonstrate a novel approach for tracking equivalent names and concepts, applied to a network of 10 regional programs that use the same protocols (so-called “Pollard walks”) to monitor butterflies across America north of Mexico. Our system involves, for each monitoring program, associating the taxonomic authority (in this case one of three North American butterfly fauna treatments: Pelham, 2014; North American Butterfly Association, Inc., 2016; Opler & Warren, 2003) that shares the most similar overall taxonomic interpretation to the program’s working species list. This allows us to define each term on each program’s list in the context of the appropriate authority’s species concept and curate the term alongside its authoritative concept. We then aligned the names representing equivalent taxonomic concepts among the three authorities. These stepping stones allow us to bridge a species concept from one program’s species list to the name of the equivalent in any other program, through the intermediary scaffolding of aligned authoritative taxon concepts. Using a software tool we developed to access our curation system, a user can link equivalent species concepts between data collecting agencies with no specialized knowledge of taxonomic complexities.
Identification of viruses infecting six plum cultivars in Korea by RNA-sequencing
Authors: Jo Yeonhwa , Choi Hoseong , Lian Sen , Cho Jin Kyong , Chu Hyosub , Cho Won Kyong
Published: July 2020

Background

Plums are a kind of stone fruit, a category that includes peaches, cherries, apricots, and almonds. In Korea, Japanese plum trees are usually cultivated as they best suit the climate. To date, there have been few studies in Korea on viruses infecting plum trees compared to those infecting peach trees.

Methods

To identify viruses and viroids infecting plum trees, we collected leaf samples from six different plum cultivars and subjected them to RNA-sequencing (RNA-seq). Six different plum transcriptomes were de novo assembled using the Trinity assembler followed by BLAST searching against a viral reference database.

Results

We identified hop stunt viroid (HSVd) and six viruses, including apple chlorotic leaf spot virus (ACLSV), little cherry virus-1 (LChV-1), peach virus D (PeVD), peach leaf pitting-associated virus (PLPaV), plum bark necrosis stem pitting-associated virus (PBNSPaV), and prunus necrotic ringspot virus (PNRSV), from six plum cultivars by RNA-seq. RT-PCR confirmed the infection of HSVd and three viruses—ACLSV, PBNSPaV, and PNRSV—in plum trees. However, RT-PCR demonstrated that plum trees in this study were not infected by LChV-1, PeVD, or PLPaV. It is likely that the three viruses LChV-1, PeVD, and PLPaV as identified by RNA-seq were contaminants from other peach libraries caused by index misassignment, which suggests that careful confirmation by other methods should be carried out in next-generation sequencing (NGS)-based virus identification. Taken together, we identified a viroid and three viruses infecting plum trees in Korea.
Physiochemical and Microbiological Analysis of Drinking Water in Chattogram City, Bangladesh
Authors: Nishan Kanij Fatema , Yeasmin Nilufa , Devi Urmi Rani , Akter Sumiya , Bakar Md. Abu , Haque Md. Mozibul
Published: July 2020

Chattogram is the second most populated city in Bangladesh. This port city faces a serious threat mainly due to the lack of safe drinking water. This study was conducted for determining drinking water quality of groundwater sources in Chattogram city. The study was performed in the BCSIR laboratory, Chattogram. It was carried out for a period of six months from 1st July, 2018 to 31th December, 2018. Total six water samples were collected from three different locations (Baluchora, C&B colony and Khulshi area). Each sampling location consists of two separate sampling points. Physicochemical parameters of the collected samples like Temperature, pH, Electrical Conductivity (EC), Total dissolved solid (TDS), Hardness, Turbidity and concentration of Cl, As, Mn, Fe, Pb, Cr and Cd were examined. Microbial parameters like Total Coliform (TC) were also measured. All the analyzed parameters compared with BSTI and WHO drinking water quality standards to understand the overall ground water quality status of the study area. The results reveal that water samples in almost all locations were contaminated with microbial contamination and that the range of physico-chemical parameters was not adequate for consumption. Preliminary treatments like boiling, filtering etc are required before using groundwater for drinking and the necessary measures must be taken for a safe alternative source of drinking water.
Política dos diamantes em Angola durante a primeira era colonial: as relações entre o estado e a Diamang 1917-1961
Authors: Alencastro Mathias
Published: July 2020

Este artigo tem como objetivo examinar as origens e a evolução do setor dos diamantes em Angola. Ele começa em 1921 com a criação da companhia Diamantes de Angola (Diamang) e termina em 1961 com o início da luta anticolonial. Ao longo desse período, o Estado colonial e o setor dos diamantes desenvolveram uma relação simbiótica: o Estado atribuía os poderes necessários para a Diamang estabelecer um “estado dentro do estado” e, assim, consolidar a presença territorial das autoridades portugueses. Para explicar a emergência e a consolidação dessa relação, o artigo explora as razões pelas quais o Estado colonial cedeu poderes à Diamang, sublinhando sua fraca capacidade institucional para projetar autoridade no interior da colônia de Angola. Em seguida, o artigo mostra como a Diamang passou a ter um papel essencial nos debates sobre política administrativa e fiscal na colônia e na metrópole.

Palavras-chave: Lunda - setor dos diamantes - história colonial - Angola.

Abstract

This article examines the origins and evolution of the diamond sector in Angola. It begins in 1921 with the creation of DIAMANG and ends in 1961 with the outbreak of the liberation war. It argues that throughout this period (and beyond) the colonial state and the diamond sector shared a complex but ultimately co-constitutive relationship: the state granted DIAMANG the necessary powers, while DIAMANG built a ‘state inside the state’ on the former’s behalf. To explain the emergence – and the persistence – of this relationship, the chapter explores the reasons why the colonial state empowered DIAMANG to perform state functions in Lunda in the first place, highlighting the institutional incapacity of the early colonial state to broadcast its power directly in the hinterland. It then shows how DIAMANG furthered the financial and other interests of Portuguese colonial officials and other influential individuals in the colony as well as in the metropolis, and vice-versa.

Keywords: Lunda - diamond sector - colonial history - Angola
Africanos livres e o estado imperial
Authors: Bertin Enidelce
Published: July 2020

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A linha do horizonte: uma metáfora mal-resolvida dos africanos no filme Chocolat de Claire Denis
Authors: Ashaolu Olubunmi O.
Published: July 2020

No filme Chocolat, de Claire Denis (1989), os colonizadores fazem alusão constante a uma linha do horizonte aparentemente banal; um discurso que corrobora as complexidades do poder paralelo e a singularidade cultural entre os africanos e os colonizadores/ocidentais. Este trabalho argumenta que a inter-relação colonial de europeus e africanos se incorpora na alusão do filme à linha do horizonte, uma metáfora, com o seu fim visível mas restritivo, inacessível e inexistente. Por um lado, a linha do horizonte significa um lamento da apreciação interna de autocondenação do colonizador — uma característica raramente percebida no discurso do colonizador. Por outro, a linha do horizonte simboliza a pouca profundidade dos colonizadores, o que sugere suas limitações e sua incompetência na tentativa de sustentar o poder colonial. Pela sua insensibilidade e seu desinteresse em procurar conhecer os africanos como seres com quem se podia contar, os colonizadores/ocidentais acabaram não descobrindo, nem dominando completamente, os africanos. A nossa tese é a de que a linha do horizonte motiva uma inadequação que representa a inadequação e a incapacidade dos ocidentais para compreender a personalidade dos africanos.

Palavras-chave: colonizador/ocidental - poder - conhecimento - ilusão - africanos.
Creative communication – using poetry and games to generate dialogue between scientists and nonscientists
Authors: Illingworth Sam
Published: July 2020

Science communication is often perceived as an opportunity for scientists to broadcast their expertise and knowledge to a general public, so that this lay audience might better understand a specific field of study. However, in order for science to be made more accessible, science communication initiatives need to move away from this one‐way discourse aimed at an unrealistically homogeneous public. Instead, science communicators need to consider how best to engage multiple audiences in a two‐way communication that can both inform research governance and lead to the cocreation of new knowledge. In this article, I discuss how poetry and tabletop games provide two media through which scientists can engage nonscientists in meaningful dialogue, helping to address a scientist's social responsibility and diversify science in the process.
A systematic mutational analysis identifies a 5‐residue proline tag that enhances the in vivo immunogenicity of a non‐immunogenic model protein
Authors: Rahman Nafsoon , Islam Mohammad Monirul , Kibria Md. Golam , Unzai Satoru , Kuroda Yutaka
Published: July 2020

Poor immunogenicity of small proteins is a major hurdle in developing vaccines or producing antibodies for biopharmaceutical usage. Here, we systematically analyzed the effects of 10 solubility controlling peptide tags (SCP‐tags) on the immunogenicity of a non‐immunogenic model protein, bovine pancreatic trypsin inhibitor (BPTI‐19A; 6 kDa). CD, fluorescence, DLS, SLS, and AUC measurements indicated that the SCP‐tags did not change the secondary structure content nor the tertiary structures of the protein nor its monomeric state. ELISA results indicated that the 5‐proline (C5P) and 5‐arginine (C5R) tags unexpectedly increased the IgG level of BPTI‐19A by 240‐ and 73‐fold, respectively, suggesting that non‐oligomerizing SCP‐tags may provide a novel method for increasing the immunogenicity of a protein in a highly specific manner.
The cerebral tremor circuit in a patient with Holmes tremor
Authors: Nieuwhof Freek , de Bie Rob M.A. , Praamstra Peter , van den Munckhof Pepijn , Helmich Rick C.
Published: July 2020

The cerebral network associated with Holmes tremor has never been determined directly. A previous study reported a brain network that is functionally connected, in healthy individuals, to different lesions that cause Holmes tremor (lesion connectome). We report a 71‐year‐old man with severe left‐sided tremor caused by a microbleed near the right red nucleus. Using accelerometry‐fMRI, we show tremor‐related activity in contralateral sensorimotor cortex and cerebellar vermis. This network was distinct from, but functionally coupled to, the Holmes lesion connectome. We propose that Holmes tremor involves three distinct cerebral mechanisms: a structural lesion, an intermediate lesion connectome, and symptom‐related activity.
Metal Halide Perovskites Functionalized by Patterning Technologies
Authors: Huang Xiongjian , Xiao Xiudi , Dong Guoping
Published: July 2020

Metal halide perovskites (MHPs), as emerging stars, are greatly attracted due to their superior optical and optoelectrical properties. The design and construction of patterned materials have been considered as a powerful tool to improve the performance of optical and optoelectronic devices. Therefore, the marriage of MHPs and patterning technologies is expected to boost the development of perovskite‐based applications with novel functions and optimized properties. Moreover, with the merits of patterning technologies, integrated and small‐sized perovskite‐based optoelectronic devices with compactness are foreseen. In this review, recent progress in this field is summarized, including template‐assisted and template‐free patterning technologies that can endow MHPs with high crystallinity, long‐term stability, and special structures. Besides, the advantages and mechanisms of patterned MHPs toward high‐performance applications are discussed.
Barrier Designs in Perovskite Solar Cells for Long‐Term Stability
Authors: Zhang Shasha , Liu Zonghao , Zhang Wenjun , Jiang Zhaoyi , Chen Weitao , Chen Rui , Huang Yuqian , Yang Zhichun , Zhang Yiqiang , Han Liyuan , Chen Wei
Published: July 2020

Perovskite solar cells (PSCs) have attracted much attention in the past decade and their power conversion efficiency has been rapidly increasing to 25.2%, which is comparable with commercialized solar cells. Currently, the long‐term stability of PSCs remains as a major bottleneck impeding their future commercial applications. Beyond strengthening the perovskite layer itself and developing robust external device encapsulation/packaging technology, integration of effective barriers into PSCs has been recognized to be of equal importance to improve the whole device’s long‐term stability. These barriers can not only shield the critical perovskite layer and other functional layers from external detrimental factors such as heat, light, and H2O/O2, but also prevent the undesired ion/molecular diffusion/volatilization from perovskite. In addition, some delicate barrier designs can simultaneously improve the efficiency and stability. In this review article, the research progress on barrier designs in PSCs for improving their long‐term stability is reviewed in terms of the barrier functions, locations in PSCs, and material characteristics. Regarding specific barriers, their preparation methods, chemical/photoelectronic/mechanical properties, and their role in device stability, are further discussed. On the basis of these accumulative efforts, predictions for the further development of effective barriers in PSCs are provided at the end of this review.
Health and safety in the Maine woods: Assemblage and baseline characteristics of a longitudinal cohort of logging workers
Authors: Scott Erika , Hirabayashi Liane , Graham Judy , Franck Katherine , Krupa Nicole , Jenkins Paul
Published: July 2020

Background

Logging remains one of the most hazardous industries in the United States, despite many safety improvements made in the last decades. Currently, we know little about regional trends in health conditions of logging workers, especially in the Northeast. However, the forest products industry is a critical component of the Northeast's economy, especially in the State of Maine.

Methods

This paper reports on the baseline data of a longitudinal cohort study involving Maine loggers, aimed to assess the health and safety of the industry.

Results

Three hundred twenty‐five are included in these analyses, 246 mechanized loggers, and 79 conventional. On average mechanized loggers worked longer days (11.8 vs 9.7 hours) and had longer commutes from home to the woodlot (72.6 vs 40.7 minutes) than conventional loggers. For health factors, mechanized and conventional loggers had similar responses. Nearly two‐thirds of both mechanized and conventional loggers had an annual physical in the previous year, and 36.3% had seen a health specialist during that same time period. The overall work‐related injury and illness rate is 6.8 of 100 workers for this cohort.

Conclusions

These factors contribute to a need to work with the community on transforming logging into a safer and healthier profession for the current workforce, as well as the workforce of the future. This study provides the basis for an appropriate intervention, in collaboration with the loggers and industry stakeholders, to improve the lives of these vital workers.
Accelerating Electrochemical Reactions in a Voltage‐Controlled Interfacial Microreactor
Authors: Cheng Heyong , Tang Shuli , Yang Tingyuan , Xu Shiqing , Yan Xin
Published: July 2020

Microdroplet chemistry is attracting increasing attention for accelerated reactions at the solution–air interface. We report herein a voltage‐controlled interfacial microreactor that enables acceleration of electrochemical reactions which are not observed in bulk or conventional electrochemical cells. The microreactor is formed at the interface of the Taylor cone in an electrospray emitter with a large orifice, thus allowing continuous contact of the electrode and the reactants at/near the interface. As a proof‐of‐concept, electrooxidative C−H/N−H coupling and electrooxidation of benzyl alcohol were shown to be accelerated by more than an order of magnitude as compared to the corresponding bulk reactions. The new electrochemical microreactor has unique features that allow i) voltage‐controlled acceleration of electrochemical reactions by voltage‐dependent formation of the interfacial microreactor; ii) “reversible” electrochemical derivatization; and iii) in situ mechanistic study and capture of key radical intermediates when coupled with mass spectrometry.
Nickel(II) Bisporphyrin‐Fused Pentacenes Exhibiting Abnormal High Stability
Authors: Hu Yi , Thomas Michael B. , Webre Whitney A. , Moss Austen , Jinadasa R. G. Waruna , Nesterov Vladimir N. , D'Souza Francis , Wang Hong
Published: July 2020

A series of largely π‐extended multichromophoric molecules including cross‐conjugated, half cross‐conjugated, conjugation‐interrupted and linearly conjugated systems were synthesized and characterized. These multichromophoric molecular systems revealed interesting structural‐property relationships. Bisporphyrin‐fused pentacenes Pen‐1 b and Pen‐2 a showed rich redox chemistry with 7 and 8 observable redox states, respectively. The linearly‐conjugated bisporphyrin‐fused pentacenes (Pen‐1 b and Pen‐2 a) possess much narrower HOMO–LUMO gaps (1.65 and 1.42 eV redox, respectively) and higher HOMO energy levels than those of their pentacene analogues (2.23 and 2.01 eV redox, respectively), similar to those of much less stable hexacenes and heptacenes. An estimated half‐life of >945 h was obtained for bisporphyrin‐fused pentacene Pen‐2 a, which is much longer than that of its pentacene analogue (BPE‐P, half‐life, 33 h).
Multiple Site Hydrogen Isotope Labelling of Pharmaceuticals
Authors: Daniel‐Bertrand Marion , Garcia‐Argote Sébastien , Palazzolo Alberto , Mustieles Marin Irene , Fazzini Pier‐Francesco , Tricard Simon , Chaudret Bruno , Derdau Volker , Feuillastre Sophie , Pieters Grégory
Published: July 2020

Radiolabelling is fundamental in drug discovery and development as it is mandatory for preclinical ADME studies and late‐stage human clinical trials. Herein, a general, effective, and easy to implement method for the multiple site incorporation of deuterium and tritium atoms using the commercially available and air‐stable iridium precatalyst [Ir(COD)(OMe)]2 is described. A large scope of pharmaceutically relevant substructures can be labelled using this method including pyridine, pyrazine, indole, carbazole, aniline, oxa‐/thia‐zoles, thiophene, but also electron‐rich phenyl groups. The high functional group tolerance of the reaction is highlighted by the labelling of a wide range of complex pharmaceuticals, containing notably halogen or sulfur atoms and nitrile groups. The multiple site hydrogen isotope incorporation has been explained by the in situ formation of complementary catalytically active species: monometallic iridium complexes and iridium nanoparticles.
A Frequency‐Selective pH‐Responsive paraCEST Agent
Authors: Ratnakar S. James , Chirayil Sara , Funk Alexander M. , Zhang Shanrong , Queiró João F. , Geraldes Carlos F. G. C. , Kovacs Zoltan , Sherry A. Dean
Published: July 2020

Paramagnetic chemical exchange saturation transfer (paraCEST) agents are well‐suited for imaging tissue pH because the basis of CEST, chemical exchange, is inherently sensitive to pH. Several previous pH‐sensitive paraCEST agents were based on an exchanging Ln3+‐bound water molecule as the CEST antenna but this design often added additional line‐broadening to the bulk water signal due to T2 exchange. We report herein a pH‐sensitive paraCEST agent that lacks an inner‐sphere water molecule but contains one Ln‐bound −OH group for CEST activation. The Yb3+ complex, Yb(1), displayed a single, highly shifted CEST peak originating from the exchangeable Yb‐OH proton, the frequency of which changed over the biologically relevant pH range. CEST images of phantoms ranging in pH from 6 to 8 demonstrate the potential of this agent for imaging pH. Initial rodent imaging studies showed that Gd(1) remains in the vascular system much longer than anticipated but is cleared slowly via renal filtration.
Total Synthesis of Malacidin A by β‐Hydroxyaspartic Acid Ligation‐Mediated Cyclization and Absolute Structure Establishment
Authors: Sun Zhenquan , Shang Zhuo , Forelli Nicholas , Po Kathy Hiu Laam , Chen Sheng , Brady Sean F. , Li Xuechen
Published: July 2020

The development of novel antibiotics is critical to combating the growing emergence of drug‐resistant pathogens. Malacidin A is a new member of the calcium‐dependent antibiotic (CDAs) family with activity against antibiotic‐resistant pathogens. Its mode of action is distinct from classical CDAs. However, the absolute structure of malacidin A has not been established. Herein, the total syntheses of malacidin A and its analogues are reported by a combination of Fmoc‐based solid‐phase peptide synthesis (SPPS) and β‐hydroxyaspartic acid ligation‐mediated peptide cyclization. The total synthesis enabled us to establish the absolute configuration of malacidin A, which is in agreement with those for natural malacidin A confirmed by advanced Marfey's analysis in our study.
Arene C−H Activation at Aluminium(I): meta Selectivity Driven by the Electronics of SNAr Chemistry
Authors: Hicks Jamie , Vasko Petra , Heilmann Andreas , Goicoechea Jose M. , Aldridge Simon
Published: July 2020

The reactivity of the electron‐rich anionic AlI aluminyl compound K2[(NON)Al]2 (NON=4,5‐bis(2,6‐diisopropylanilido)‐2,7‐di‐tert‐butyl‐9,9‐dimethylxanthene) towards mono‐ and disubstituted arenes is reported. C−H activation chemistry with n‐butylbenzene gives exclusively the product of activation at the arene meta position. Mechanistically, this transformation proceeds in a single step via a concerted Meisenheimer‐type transition state. Selectivity is therefore based on similar electronic factors to classical SNAr chemistry, which implies the destabilisation of transition states featuring electron‐donating groups in either ortho or para positions. In the cases of toluene and the three isomers of xylene, benzylic C−H activation is also possible, with the product(s) formed reflecting the feasibility (or otherwise) of competing arene C−H activation at a site which is neither ortho nor para to a methyl substituent.
Effect of copper on textural and acidic properties of hierarchical nanocrystalline ZSM‐5
Authors: O. P Farsana , Kumari Prajitha , P Aneesh
Published: July 2020

In this work, hierarchically porous nanocrystalline ZSM‐5 was synthesized hydrothermally. Different concentrations of copper were incorporated into the matrix by ion exchange method. The synthesized samples were characterized by means of X‐ray diffraction (XRD), Fourier‐transform infrared (FTIR), energy‐dispersive X‐ray spectroscopy, scanning electron microscopy, X‐ray photoelectron spectroscopy (XPS), ultraviolet (UV), 27Al magic angle spinning nuclear magnetic resonance spectroscopy, and nitrogen sorption analysis. The acid sites on the surface of Cu‐ZSM‐5 have been systematically investigated using temperature‐programmed desorption of ammonia (NH3‐TPD) and pyridine sorption followed by FTIR. The diffraction pattern obtained from XRD studies confirmed the typical Mobil Five. NH3‐TPD reveals the enhancement of acidity achieved by copper. The FTIR spectra of pyridine desorbed samples show that the intensity of bands corresponding to Lewis acidity increases by modification. The ZSM‐5 zeolite samples exhibit spherical‐shaped MFI crystal structure. The UV spectrum indicates that copper has been doped in the form of cations or in the form of oxides. XPS analysis confirms that the copper exists as Cu(I) and Cu(II). The nitrogen sorption isotherms reveal that the modified samples are mesoporous in nature. The pore volume and diameter were found to be enhanced by the modification. The better textural properties and acidic properties of the Cu‐ZSM‐5 can make it suitable for catalyzing organic reactions.
Effect of gas‐condensed phase synergistic system of 9,10‐dihydro‐9‐oxo‐10‐phosphaphenanthrene‐10‐oxide and polydopamine on flame retardancy of epoxy resin
Authors: Xu Yao , Sun Jinhao , Qian Lijun , Li Juan
Published: July 2020

Polydopamine (PDA) was prepared by using dopamine which has good charring ability. The PDA was used as an environmentally friendly flame retardant and combined with 9,10‐dihydro‐9‐oxo‐10‐phosphaphenanthrene‐10‐oxide (DOPO) to improve the flame retardancy of epoxy (EP) resin. The flame retardancy and thermal stability of EP composites were researched by UL‐94 vertical burning, limiting oxygen index (LOI), cone calorimetry tests, and thermal gravimetric analyzer. Adding DOPO alone requires 6% to make EP obtain the UL‐94 V0. If DOPO and PDA are combined, only 4% is needed to make EP obtain the UL‐94 V0, which suggests that there is good synergistic effect between them. Moreover, the peak of heat release rate of EP/DOPO/PDA composites is less than that of EP/DOPO composites. The reactions among EP, DOPO, and PDA reduce the release of combustible gases at the early stage of degradation; at the same time, DOPO volatilize to the gas phase, quench the free radicals, and the combustion can be stopped. In addition, due to the decrease of the amount of PDA/DOPO, the EP composite can get a higher glass transition temperature, but due to the aggregation of PDA in EP, the tensile property of EP composite decreases.
Cross‐linked Salen‐based polyphosphazenes (Salen‐PZNs) enhancing the fire resistance of epoxy resin composites
Authors: Zhang Yabin , Cui Jinfeng , Wang Lurong , Yu Hailong , Li Fuchong , Yang Baoping , Guo Junhong , Mu Bo , Tian Li
Published: July 2020

In this work, two cross‐linked Salen‐based polyphosphazenes (Salen‐PZNs: Salen‐PZN‐1 microspheres and layered Salen‐PZN‐2), which contains Salen‐Schiff base and phosphazene components, were synthesized. The results showed that the peak heat release rate and total smoke production of 3% Salen‐PZN‐1/epoxy resin (EP) (3 wt% addition) were reduced by 23.8% and 87.3%, respectively. Meanwhile, after introducing the layered Salen‐PZN‐2 into EP, efficient flame resistance was obtained. The results of thermogravimetric analysis/infrared spectrometry proved that the harmful gasses of 5% Salen‐PZN‐1/EP composites were reduced during the combustion. The possible flame retardancy mechanism was considered to be the synergy of phosphate group catalysis, release of nitrogen‐containing noncombustible gasses and gas phase quenching. Therefore, this work provides a method for preparing polymers with highly efficient flame‐retardant properties.
An algorithm for computing robust forward invariant sets of two dimensional nonlinear systems
Authors: Mukhopadhyay Shayok , Zhang Fumin
Published: July 2020

Robustness of nonlinear systems can be analyzed by computing robust forward invariant sets (RFISs). Knowledge of the smallest RFIS of a system, can help analyze system performance under perturbations. A novel algorithm is developed to compute an approximation of the smallest RFIS for two‐dimensional nonlinear systems subjected to a bounded additive disturbance. The problem of computing an RFIS is formulated as a path planning problem, and the algorithm developed plans a path which iteratively converges to the boundary of an RFIS. Rigorous mathematical analysis shows that the proposed algorithm terminates in a finite number of iterations, and that the output of the proposed algorithm is an RFIS. Simulations are presented to illustrate the proposed algorithm, and to support the mathematical results. This work may aid future development, for use with higher dimensional systems.
Comparative Study in Different Filters for Efficient Sterile Filtration
Authors: An Hyun Ho , Moon Byung Seok , Park Hyun Sik , Lee Hong Jin , Lee Sang Ju , Oh Seung Jun , Kim Bom Sahn , Lee Byung Chul , Lee Won Woo , Kim Sang Eun
Published: July 2020

Simple membrane filtration is suitable as a terminal sterilization method for radiopharmaceuticals due to their short half‐life and radiation exposure of process operator. However, it often adheres to the filter membrane and causes a considerable loss of radioactivity. We herein describe the investigation of sterile filtration performance varying individual sterile filters in order to identify the optimal sterile filter on demand for lipophilic radiopharmaceuticals.
Using COVID‐19 as a teaching tool in a time of remote learning: A workflow for bioinformatic approaches to identifying candidates for therapeutic and vaccine development
Authors: Bryce Samantha , Heath Kevin N. , Issi Luca , Ryder Elizabeth F. , P. Rao Reeta
Published: July 2020

The COVID‐19 pandemic has led to an urgent need for engaging computational alternatives to traditional laboratory exercises. Here we introduce a customizable and flexible workflow, designed with the SARS CoV‐2 virus that causes COVID‐19 in mind, as a means of reinforcing fundamental biology concepts using bioinformatics approaches. This workflow is accessible to a wide range of students in life science majors regardless of their prior bioinformatics knowledge, and all software is freely available, thus eliminating potential cost barriers. Using the workflow can thus provide a diverse group of students the opportunity to conduct inquiry‐driven research. Here we demonstrate the utility of this workflow and outline the logical steps involved in the identification of therapeutic or vaccine targets against SARS CoV‐2. We also provide an example of how the workflow may be adapted to other infectious microbes. Overall, our workflow anchors student understanding of viral biology and genomics and allows students to develop valuable bioinformatics expertise as well as to hone critical thinking and problem‐solving skills, while also creating an opportunity to better understand emerging information surrounding the COVID‐19 pandemic.
Quantification of 10 bioactive components of Yazhangsan in rat plasma by LC–MS/MS and its application
Authors: Zhang Qing , Chen Sha , Liu An , Wang Yuesheng
Published: July 2020

Yazhangsan (YZS) is a common prescription for the treatment of cough and asthma caused by wind‐cold. The purpose of this study was to investigate the pharmacokinetic profiles of 10 bioactive components in YZS. A simple, sensitive and reliable high‐performance liquid chromatography coupled with a triple‐quadruple mass spectrometry method (LC–MS/MS) was developed and fully validated in this study for the measurement of these 10 bioactive compounds in rat plasma. One‐step protein precipitation method using methanol was applied to the treatment of rat plasma samples. Chromatographic separation was conducted on a C18 column by gradient elution, and water (containing 0.1% formic acid) and acetonitrile were chosen as the mobile phase. The analytes were quantified by using a mass spectrometer in multiple reaction monitoring scanning mode, and electrospray ionization was performed in positive and negative ion modes. The established method met the requirements for the quantification of these 10 bioactive compounds in biological samples, and it was successfully applied to the pharmacokinetic study of 10 components in rats after the intragastrical administration of YZS. This study will lay a foundation for the investigation of the mechanism of action of YZS and provide useful data for the rational use of YZS in clinical.
A genome‐scale CRISPR knock‐out screen in chronic myeloid leukemia identifies novel drug resistance mechanisms along with intrinsic apoptosis and MAPK signaling
Authors: Lewis Matthieu , Prouzet‐Mauléon Valérie , Lichou Florence , Richard Elodie , Iggo Richard , Turcq Béatrice , Mahon François‐Xavier
Published: July 2020

Understanding resistance mechanisms in cancer is of utmost importance for the discovery of novel “druggable” targets. Efficient genetic screening, now even more possible with CRISPR‐Cas9 gene‐editing technology, next‐generation sequencing and bioinformatics, is an important tool for deciphering novel cellular processes, such as resistance to treatment in cancer. Imatinib specifically eliminates chronic myeloid leukemia (CML) cells by targeting and blocking the kinase activity of BCR‐ABL1; however, resistance to treatment exists. In order to discover BCR‐ABL1 independent mechanisms of imatinib resistance, we utilized the genome‐scale CRISPR knock‐out library to screen for imatinib‐sensitizing genes in vitro on K562 cells. We revealed genes that seem essential for imatinib‐induced cell death, such as proapoptotic genes (BIM, BAX) or MAPK inhibitor SPRED2. Specifically, reestablishing apoptosis in BIM knock‐out (KO) cells with BH3 mimetics, or inhibiting MAPK signaling in SPRED2 KO cells with MEK inhibitors restores sensitivity to imatinib. In this work, we discovered previously identified pathways and novel pathways that modulate response to imatinib in CML cell lines, such as the implication of the Mediator complex, mRNA processing and protein ubiquitinylation. Targeting these specific genetic lesions with combinational therapy can overcome resistance phenotypes and paves the road for the use of precision oncology.
Patient and caregiver benefit‐risk preferences for nonmetastatic castration‐resistant prostate cancer treatment
Authors: Srinivas Sandy , Mohamed Ateesha F. , Appukkuttan Sreevalsa , Botteman Marc , Ng Xinyi , Joshi Namita , Tsai Jui‐Hua , Fang Jarjieh , Waldeck A. Reginald , Simmons Stacey J.
Published: July 2020

Background

Recently approved second‐generation androgen receptor inhibitors (SGARIs) for non‐metastatic castration‐resistant prostate cancer (nmCRPC) have similar efficacy but differ in safety profiles. We used a discrete choice experiment (DCE) to examine how nmCRPC patients and caregivers perceive the benefits versus risks of these new treatments.

Methods

An online DCE survey with 14 treatment choice questions was administered to nmCRPC patients and caregivers. Each choice question compared two hypothetical medication profiles varying in terms of 5 safety attributes (risk or severity of adverse events [AEs]: fatigue, skin rash, cognitive problems, serious fall, and serious fracture) and two efficacy attributes (duration of overall survival [OS] and time to pain progression). Random parameters logit models were used to estimate each attribute's relative importance. We also estimated the amounts of OS that respondents were willing to forego for a reduction in AEs.

Results

In total, 143 nmCRPC patients and 149 caregivers viewed the AEs in following order of importance (most to least): serious fracture, serious fall, cognitive problems, fatigue, and skin rash. On average, patients were willing to trade 5.8 and 4.0 months of OS to reduce the risk of serious fracture and fall, respectively, from 3% to 0%; caregivers were willing to trade 6.6 and 5.4 months of OS.

Conclusions

nmCRPC patients and caregivers preferred treatments with lower AE burdens and were willing to forego OS to reduce the risk and severity of AEs. Our results highlight the importance of carefully balancing risks and benefits when selecting treatments in this relatively asymptomatic population.
In Silico Anticipation of Metabolic Pathways Extended to Organic Chemistry Reactions: A Case Study with Caffeine Alkaline Hydrolysis and The Origin of Camellimidazoles
Authors: Turpin Victor , Beniddir Mehdi A. , Genta‐Jouve Grégory , Skiredj Adam , Gallard Jean‐François , Leblanc Karine , Le Pogam Pierre , Poupon Erwan
Published: July 2020

Camellimidazoles A–C were recently reported as natural substances in Keemun black tea. Although a “biosynthetic” route to these intriguing imidazole dimers was proposed from caffeine by the authors in this seminal report, we envisioned that a artefactual scenario, consisting of alkaline hydrolysis of caffeine and spontaneous cascade reactions with a methylene donor such as formaldehyde or methylene chloride, could also have led to their formation. To capture the diversity of molecules obtained under these conditions (i.e. alkaline treatment of caffeine/formaldehyde), an in silico MetWork‐based pipeline was implemented, highlighting the sought‐after camellimidazoles B and C. A wealth of further compounds were also tagged, notably comprising the herein newly described and unnatural camellimidazoles D–F that were subsequently confirmed as anticipated in silico upon extensive spectroscopic analyses. Likewise, camellimidazoles B and C could also be obtained using methylene chloride as an alternative methylene donor which may also have occurred in the initial phytochemical pipeline that implied this solvent. The current investigation emphasizes the fitness of MetWork tagging to extend the logic of in silico anticipation of metabolic pathways to organic chemistry reactions.
Compressor Cost Optimization Based on Extended Annual Load Duration Curves
Authors: Geitner Christian , Waesker Markus , Doetsch Christian
Published: July 2020

Volatile exhaust gas flows in the steel industry are potential resources to reduce greenhouse gas emissions. The project Carbon2Chem® analyzes possible carbon capture and utilization processes for the gas streams of a steel mill. Therefore, compressors for volatile gas flows are required in all process concepts. The large amount and volatility of the gas as well as inert compounds contained therein make the compressors the pivotal cost block. This approach extends the annual load duration curve to optimize the compressor cost.
Heat on – Calibration of IR Spectroscopy at Process Conditions for Continuous Esterification
Authors: Schnoor Johann‐Kilian , Schulte Lennard D. , Liauw Marcel A.
Published: July 2020

This work tries to close the gap between continuous synthesis, measurement, calibration, and analysis on R&D scale. By introducing new calibration methods, the full potential of inline ATR‐FTIR spectroscopy in continuous reactor setups is unraveled. A fast, fully automated calibration of the reaction mixtures is carried out at process conditions. The use of different compositions underlines the robustness of this calibration method, which was used for the determination of kinetic parameters. The conversion‐based calibration significantly increased the precision of the analysis. In difference, the new method only requires the preparation of two calibration mixtures. By that, this method can also be applied to large‐scale processes and allows the use of a single measurement setup from R&D to industrial scale.