bluuebunny/crossref_metadata_2025 huggingface dataset:
The Infographic
Authors: Dick Murray
Published: April 2020

An exploration of infographics and data visualization as a cultural phenomenon, from eighteenth-century print culture to today's data journalism.

Infographics and data visualization are ubiquitous in our everyday media diet, particularly in news—in print newspapers, on television news, and online. It has been argued that infographics are changing what it means to be literate in the twenty-first century—and even that they harmonize uniquely with human cognition. In this first serious exploration of the subject, Murray Dick traces the cultural evolution of the infographic, examining its use in news—and resistance to its use—from eighteenth-century print culture to today's data journalism. He identifies six historical phases of infographics in popular culture: the proto-infographic, the classical, the improving, the commercial, the ideological, and the professional.

Dick describes the emergence of infographic forms within a wider history of journalism, culture, and communications, focusing his analysis on the UK. He considers their use in the partisan British journalism of late eighteenth and early nineteenth-century print media; their later deployment as a vehicle for reform and improvement; their mass-market debut in the twentieth century as a means of explanation (and sometimes propaganda); and their use for both ideological and professional purposes in the post–World War II marketized newspaper culture. Finally, he proposes best practices for news infographics and defends infographics and data visualization against a range of criticism. Dick offers not only a history of how the public has experienced and understood the infographic, but also an account of what data visualization can tell us about the past.
CSF1R blockade induces macrophage ablation and results in mouse choroidal vascular atrophy and RPE disorganization
Authors: Yang Xiao , Zhao Lian , Campos Maria M , Abu-Asab Mones , Ortolan Davide , Hotaling Nathan , Bharti Kapil , Wong Wai T
Published: April 2020

The choroid, which provides vascular supply to the outer retina, demonstrates progressive degeneration in aging and age-related macular degeneration (AMD). However mechanisms that maintain or compromise choroidal homeostasis are obscure. We discovered that the ablation of choroidal macrophages via CSF1R blockade was associated with choroidal vascular atrophy and retinal pigment epithelial (RPE) changes including structural disruption, downregulation of visual cycle genes, and altered angiogenic factor expression. Suspending CSF1R blockade following ablation enabled spontaneous macrophage regeneration, which fully restored original macrophage distributions and morphologies. Macrophage regeneration was accompanied by arrested vascular degeneration and ameliorated pathological RPE alterations. These findings suggest that choroidal macrophages play a previously unappreciated trophic role in maintaining choroidal vasculature and RPE cells, implicating insufficiency in choroidal macrophage function as a factor in aging- and AMD-associated pathology. Modulating macrophage function may constitute a strategy for the therapeutic preservation of the choroid and RPE in age-related retinal disorders.
Delta glutamate receptor conductance drives excitation of mouse dorsal raphe neurons
Authors: Gantz Stephanie C , Moussawi Khaled , Hake Holly S
Published: April 2020

The dorsal raphe nucleus is the predominant source of central serotonin, where neuronal activity regulates complex emotional behaviors. Action potential firing of serotonin dorsal raphe neurons is driven via α1-adrenergic receptors (α1-AR) activation. Despite this crucial role, the ion channels responsible for α1-AR-mediated depolarization are unknown. Here, we show in mouse brain slices that α1-AR-mediated excitatory synaptic transmission is mediated by the ionotropic glutamate receptor homolog cation channel, delta glutamate receptor 1 (GluD1). GluD1R-channels are constitutively active under basal conditions carrying tonic inward current and synaptic activation of α1-ARs augments tonic GluD1R-channel current. Further, loss of dorsal raphe GluD1R-channels produces an anxiogenic phenotype. Thus, GluD1R-channels are responsible for α1-AR-dependent induction of persistent pacemaker-type firing of dorsal raphe neurons and regulate dorsal raphe-related behavior. Given the widespread distribution of these channels, ion channel function of GluD1R as a regulator of neuronal excitability is proposed to be widespread in the nervous system.
Changes in the Eradication Efficacy of Fluoroquinolone-containing Triple Therapy for Helicobacter pylori Infection in Korea
Authors: Lee Jung Won , Kim Nayoung , Kim Geun , Kim Siho , Nam Hwawon , Lee Siwon , Shin Cheol Min , Park Young Soo , Lee Dong Ho
Published: April 2020

Background/Aims: Fluoroquinolone-containing triple eradication therapy could be considered an alternative regimen for the second- line treatment of Helicobacter pylori infection. This study aimed to investigate the changes in the eradication efficacy of fluoroquinolone- containing triple therapy from 2003 to 2018 in Korea.Materials and Methods: Patients with a history of first-line eradication therapy failure were consecutively enrolled at Seoul National University Bundang Hospital from 2003 to 2018. All patients took moxifloxacin-containing triple therapy as the second-line eradication therapy. The treatment regimen comprised a three-drug combination comprising a proton pump inhibitor, amoxicillin, and moxifloxacin. Data on age, sex, endoscopic diagnosis, eradication results, compliance, and adverse outcomes were acquired and analyzed.Results: In total, 824 participants were enrolled during the study period, of whom, 46 were lost to follow-up. Finally, 778 participants were included in the per-protocol (PP) analysis, of whom, 72.1% received moxifloxacin-containing triple therapy for 14 days. The eradication rate of moxifloxacin-containing triple therapy was 72.1% (594/824) in the intention-to-treat analysis and 76.3% (594/778) in the PP analysis. A decline in eradication efficacy was observed, especially in the PP analysis (P=0.046). Diarrhea was the most commonly observed adverse event, accounting for 19.6% (41/209) of recorded adverse events.Conclusions: Moxifloxacin-containing triple therapy has shown suboptimal eradication efficacy as the second-line eradication therapy. In addition, there is a concern that eradication rate will decrease due to increase in antimicrobial resistance.
Helicobacter pylori Eradication in Patients Undergoing Gastrectomy: Diagnosis and Therapy
Authors: Choi Youn I , Chung Jun-Won
Published: April 2020

The role of Helicobacter pylori (H. pylori) eradication in patients undergoing gastrectomy for gastric cancer is unclear. Although European and Asian guidelines strongly recommend H. pylori eradication in patients who undergo endoscopic resection for early gastric cancer, these guidelines do not specify the tests useful for diagnosing H. pylori infection, the optimal timing and appropriate eradication regimens, and follow-up strategies in patients undergoing gastrectomy for gastric cancer. This review aims to update the guidelines for the diagnosis and management of H. pylori infection in patients undergoing gastrectomy for gastric cancer. We have focused on the following issues: 1) diagnostic tests for H. pylori infection in the remnant stomach, 2) optimal timing and regimen for H. pylori eradication, and 3) role of H. pylori eradication in reducing the risk of metachronous gastric cancer in the remnant stomach.
New anatomical information onDsungaripterus weiiYoung, 1964 with focus on the palatal region
Authors: Chen He , Jiang Shunxing , Kellner Alexander W.A. , Cheng Xin , Zhang Xinjun , Qiu Rui , Li Yang , Wang Xiaolin
Published: April 2020

Pterosaur specimens with complete and well-preserved palatal region are rare. Here we describe new and previously collected specimens of the pterodactyloid pterosaurDsungaripterus weiithat are three-dimensionally preserved and provide new anatomical information for this species. Among the unique features is a lateral process of the pterygoid divided into two parts: an anterior thin, parabolic arc shaped element that separates the secondary subtemporal and the subtemporal fenestrae, followed by a dorsoventrally flattened portion that is directed inside the subtemporal fenestrae. The interpterygoid fenestrae join forming an irregular oval shape with two symmetrical posterior notches and a smooth anterior margin. Among all pterosaurs where the palate is known, the posterior configuration of the palate ofD. weiiis similar to some azhdarchoids, which is consistent with the suggested phylogenetic position of the Dsungaripteridae as closely related to the Azhdarchoidea. Furthermore, we identify symmetrical grooves on the lateral surface of the upper and lower jaws, that likely represent the impression of the edge of a keratinous sheath that would cover the upturned toothless rostrum during foraging activity, most likely consisting of hard elements, as has been previously assumed. Wear facets on the teeth also support this feeding mode.
Modelagem orientada a objetivo como suporte à gestão estratégica de TI nos Institutos Federais de Educação
Authors: Gonçalves Dayene Mendes Silva , Leal André Leal Luiz de Castro , Castro Maria Cristina Drumond e , Macêdo Fábio Carlos
Published: April 2020

Em uma organização, a área de Tecnologia da Informação deve dar suporte às demais, possibilitando o alinhamento entre as decisões e as ações, a fim de atender aos objetivos almejados. A proposta deste trabalho é investigar a realidade da Gestão Estratégica de TI nos Institutos Federais de Educação, através da verificação de como os gestores dessa área elaboram e mantém um planejamento estratégico, partindo do pressuposto de que eles enfrentam dificuldades devido à falta de alinhamento e planejamento da área com os objetivos estratégicos institucionais.  Em termos metodológicos, trata-se de uma pesquisa descritiva, de abordagem qualitativa no que concerne às características e ao modo de investigação. A base desse estudo foi feita pelo levantamento de dados de pesquisas realizados pelo Tribunal de Contas da União, pela percepção dos gestores de TI e por documentos disponibilizados pelos Institutos Federais. Os dados analisados permitiram que os autores confirmassem seus pressupostos, mas que esse já é um tema de importância reconhecida entre os gestores que procuram meios de propiciar o fortalecimento da gestão estratégica e da governança de TI.
A teoria de Schumacher vista sobre o ângulo da confiança organizacional
Authors: Vasconcelos César Ricardo Maia de , Araújo Iriane Teresa de
Published: April 2020

As mudanças dos mercados ao longo da história trouxeram transformações para a ciência administrativa afetando as companhias como um todo. A organização, preocupada com a subjetividade do indivíduo motivou a discussão sobre a socialização da confiança, objetivo deste estudo, buscando estabelecer uma sinergia com a proposta teórica de Ernst Friedrich Schumacher.De natureza quantitativa e qualitativa, foi aplicado um questionário referente a Escala de confiança organizacional com 237 indivíduos respondentes, significativo a 95% de confiança. Os resultados apontaram que os padrões éticos, a solidez organizacional, o reconhecimento financeiro organizacional, as normas relativas a demissão de empregados e a promoção do crescimento do empregado são fatores determinantes que potencializam a confiança na organização. A conclusão demonstra que as empresas podem estimular a esperança institucional utilizando-se dos princípios propostos por Schumacher.
As mudanças que o marco regulatório trouxe para as organizações alternativas
Authors: Starosky Filho Loriberto
Published: April 2020

A consolidação de uma democracia e de um Estado de Direito passa pelo desenvolvimento de uma sociedade civil organizada, com forte atuação e autonomia em relação ao Estado, permitindo a construção de um ambiente favorável ao desenvolvimento de organizações da sociedade civil (OSC). O estudo busca identificar quais adaptações as OSCs precisam promover para estarem aderentes ao marco regulatório do terceiro setor (MROSC), e estarem elegíveis a transacionar com o poder público. Sob característica qualitativa, abordagem dedutiva e com emprego de levantamento em fontes secundárias, observou-se que quesitos que não partem da decisão da coletividade da OSC tolhem sua vontade e sua participação na tomada das decisões. Apesar de se verificar aspectos aderentes ao MROSC, o estabelecimento de regras precisa emanar da coletividade. Caso isto ocorra vindo de organismo externo, a OSC que aceitar tal condição, perderá uma de suas características essenciais.
Efecto del gobierno corporativo en la carga tributaria efectiva diante del desempeño en empresas brasileras
Authors: Lima Lauro Vinício de Almeida , Martins Orleans Silva , Machado Márcia Reis , Bocanegra Mariano Vieira
Published: April 2020

La investigación tuvo como objetivo verificar la influencia de la adopción de prácticas de Gobierno Corporativo en las empresas que cotizan en la Bolsa de Valores del Brasil denominado “Brasil Bolsa Balcão (B3)”,en la relación entre la carga tributaria efectiva incidente sobre las ganancias obtenidas e la rentabilidad sobre el patrimonio neto. La muestra abarcó los años 2010 al 2015, se excluyeron las empresas del sector financiero, de seguros y las que presentaron patrimonio neto negativo en el período de estudio, quedando un total de 246 empresas y 1456 observaciones estudiadas. Los resultados obtenidos indican que en el sector denominado “Novo Mercado”, en las empresas que cotizaron en el B3, presenta una relación inversa entre la carga tributaria efectiva e la rentabilidad sobre el patrimonio neto, como consecuencia probable de prácticas de planeamiento tributário, en razón de la adopción plena de las prácticas de Gobierno Corporativo em aquel sector. Los resultados muestran indícios que las empresas que poseen Gobierno Corporativo en el mercado de capitales brasilero utilizan la inteligencia fiscal para atender las necesidades demandadas por la responsabilidad corporativa. De este modo, la investigación contribuye científicamente a encontrar evidencias de la utilización de instrumentos de gestión fiscal para la reducción de la carga tributaria, en el ámbito del Gobierno Corporativo, como un medio de proteger los intereses de los inversionistas.
Firm Characteristics and Dividend Policy of Quoted Manufacturing Firms in Sub-Sahara Africa
Authors: Temitope Ajibade, Ayodeji , Kysburn Agi, Mayflowers
Published: April 2020

The study examined the effect of firm characteristics on dividend policy in quoted manufacturing firms in Sub-Sahara Africa. Panel data were obtained from twenty (20) quoted manufacturing firms from the Nigerian Stock Exchange, Ghana Stock Exchange, Lusaka Stock Exchange, Johannesburg Stock Exchange and Nairobi Stock Exchange over a period of ten (10) years (2008-2017). The data were analyzed using both descriptive and inferential statistics. Dividend payout ratio was used as a proxy for dividend policy, while liquidity, ownership structure, firm size and leverage were used as proxies for firm characteristics. The study found liquidity to have a positive insignificant impact on dividend payout ratio; a positive insignificant impact of ownership structure on dividend payout ratio; a positive insignificant impact of firm size on dividend payout ratio; a positive significant impact of leverage on dividend payout ratio and jointly, a positive significant impact. It was therefore recommended that manufacturing firms should practice optimum working capital management in order to increase its liquidity level and diminish any likelihood of financial distress. An efficient use of its resources in order to improve performance, profitability as well as its ability to pay dividends. Investors should look out for trends in dividend payments before making investments.
Present
LIB
Chemistries
Authors: Ogumi Zempachi , Arai Hajime , Abe Takeshi , Morita Masayuki
Published: April 2020

Typical materials used in commercial lithium‐ion batteries and their chemistries are focused in this article. Materials for positive and negative electrodes and electrolytes are separately discussed, paying attention on reactions between them. Selected new trends of these materials are also shortly added.

Several lithium‐containing (lithiated) compounds are introduced as the positive‐electrode active materials for present lithium‐ion batteries (LIBs), such as LiCoO
2
, LiNiO
2
, LiMn
2
O
4
, LiFePO
4
, and their derivatives. The properties of these materials are presented, including crystal structures, potential, capacity, rate capability, safety, and cost. Technologies applied to these materials for various applications are also shown.

Carbonaceous materials, lithium titanate, and silicon‐based materials have been employed as negative electrodes for LIBs. In particular, graphite has played a main role as a negative‐electrode material for 25 years. This is principally because of its high capacity, low potential, low cost, etc. Recently, small amounts of silicon‐based materials are mixed with graphite to enhance the volumetric energy density of LIBs. In addition, high‐potential negative electrode of lithium titanate has also been used since little electrolyte decomposition takes place, resulting in the long cycle lives of LIBs. These commercialized negative electrodes are discussed.

Electrolyte systems that have been proposed for and practically used in LIBs are surveyed. Those are categorized into several groups and their compositions and physicochemical properties are separately described. Each electrolyte system group has its own advantages and disadvantages as the LIB electrolytes. Contributions of the electrolyte composition to the battery performances are briefly discussed.
Mistakes on display: Incorrect examples refine equation solving and algebraic feature knowledge
Authors: Barbieri Christina Areizaga , Booth Julie L.
Published: April 2020

Although findings from cognitive science have suggested learning benefits of confronting errors (Metcalfe, 2017), they are not often capitalized on in many mathematics classrooms (Tulis, 2013). The current study assessed the effects of examples focused on either common mathematical misconceptions and errors or correct concepts and procedures on algebraic feature knowledge and solving quadratic equations. Middle school algebra students (N = 206) were randomly assigned to four conditions. Two errorful conditions either displayed errors and asked students to explain or displayed correct solutions and primed students to reflect on potential errors by problem type. A correct example condition and problem‐solving control group were also included. Studying and explaining common errors displayed in incorrect examples improved equation‐solving ability. An aptitude‐by‐treatment interaction revealed that learners with limited understandings of algebraic features demonstrated greater benefits. Theoretical implications about using examples to promote learning from errors are considered in addition to suggestions for educational practice.
Architecture and Increased Adhesive Strength of Vacuum‐Plasma Coating on Ultrafine‐Grained Titanium Alloy
Authors: Valiev Roman R. , Selivanov Konstantin S. , Modina Iuliia M. , Dyblenko Yuriy M. , Semenova Irina P. , Valiev Ruslan Z.
Published: April 2020

Herein, the research conducted in the field of vacuum‐plasma coating TiVN deposited on the substrate of VT8M‐1 titanium alloy (Ti–5.7Al–3.8 Mo–1.2Zr–1.3Sn) with an ultrafine‐grained (UFG) structure processed by severe plastic deformation (SPD) is explained. The strength characteristics of deposited coating, layer thickness, chemical composition and adhesive properties on substrates with the initial coarse‐grained (CG) and UFG structures are studied. The influence of substrate UFG structure on increasing the hardness of deposited coating and its adhesive characteristics is established. The nature of enhancing the adhesion strength of the coating depending on the substrate microstructure is discussed.
Effect of Selective Laser Melting on Microstructure, Mechanical, and Corrosion Properties of Biodegradable FeMnCS for Implant Applications
Authors: Hufenbach Julia , Sander Jan , Kochta Fabian , Pilz Stefan , Voss Andrea , Kühn Uta , Gebert Annett
Published: April 2020

Selective laser melting (SLM) of biodegradable metallic materials offers a great potential for manufacturing customized implants. Herein, SLM processing of a novel Fe–30Mn–1C–0.02S twinning‐induced plasticity (TWIP) alloy and the resulting structural, mechanical, and corrosion properties are presented. The occurring rapid solidification results in a fine‐grained austenitic microstructure with mainly homogeneous element distribution, which is investigated by scanning electron microscopy (SEM) combined with energy‐dispersive X‐ray spectroscopy (EDX) and electron backscatter diffraction (EBSD) as well as X‐ray diffraction (XRD). By processing the alloy via SLM, significantly higher strengths under tensile and compressive load in comparison with those for the as‐cast counterpart and a 316L reference steel are achieved. Electrochemical corrosion tests in a simulated body fluid (SBF) indicate a moderate corrosion activity, and a beneficial uniform degradation is shown in immersion tests in SBF. Regarding the envisaged application for vascular implants, SLM‐processed stent prototypes out of the novel alloy are presented and a first functionality test is shown.
Diastereoisomer‐Induced Morphology Tunable Self‐Assembled Organic Microcrystals of Conjugated Molecules for Ultraviolet Laser
Authors: Liu Yuyu , Bo Yifan , Xie Xinmiao , Yan Yong , Xu Man , Ou Changjin , Zhang He , Xiao Chao , Yang Cheng , Yu Mengna , Xu Weifeng , Wang Shasha , Xie Linghai , Liu Wei , Xu Chunxiang , Lin Jinyi , Huang Wei
Published: April 2020

Precisely controlling self‐assembly behavior and micro/nanostructure morphology of conjugated materials is significant for constructing optoelectronic devices. Inspired by natural functional materials, molecular stereoisomerism strategy (MSS) is an effective and convenient means to tune their molecular arrangement and macroscopic property of conjugated materials. Herein, a supramolecular chiral difluorenols, 9,9′‐diphenyl‐9H,9′H‐[2,2′‐bifluorene]‐9,9′‐diol (DPFOH), is set as a desirable model to reveal the diastereomeric effects of conjugated molecules toward controlling the micro/nanostructure morphology and optoelectronic behavior for deep‐blue organic laser. Two diastereomers, raceme (rac)‐ and mesomer (meso)‐DPFOH, are obtained and unambiguously elucidated by X‐ray crystallography. It is common sense to observe the slight diastereomeric effects on photophysical properties and electrochemical characteristics in solution or pristine film state for the isotropic phase. Interestingly, as a consequent of the disparate multi‐dimensional intermolecular interaction, rac‐DPFOH molecule can self‐assemble into 1D rod‐shaped but rectangular plate‐shaped microcrystals for meso‐DPFOH. Impressively, rac‐DPFOH microrod presents a well‐defined emission with an excellent ultraviolet microlasing behavior at 398 nm, whereas the 2D microplate of meso‐DPFOH show a broad emission centered at 420 nm without gain processing. Therefore, MSS provides a new approach to design conjugated molecules and tune superstructure morphology for optoelectronic applications.
Molecular and Topographical Organization: Influence on Cicada Wing Wettability and Bactericidal Properties
Authors: Román‐Kustas Jessica , Hoffman Jacob B. , Reed Julian H. , Gonsalves Andrew E. , Oh Junho , Li Longnan , Hong Sungmin , Jo Kyoo D. , Dana Catherine E. , Miljkovic Nenad , Cropek Donald M. , Alleyne Marianne
Published: April 2020

Numerous natural surfaces have micro/nanostructures that result in extraordinary functionality, such as superhydrophobicity, self‐cleaning, antifogging, and antimicrobial properties. One such example is the cicada wing, where differences in nanopillar geometry and composition among species can impact and influence the degree of exhibited properties. To understand the relationships between surface topography and chemical composition with multifunctionality, the wing properties of Neotibicen pruinosus (superhydrophobic) and Magicicada cassinii (hydrophobic) cicadas are investigated at time points after microwave‐assisted extraction of surface molecules to characterize the chemical contribution to nanopillar functionality. Electron microscopy of the wings throughout the extraction process illustrates nanoscale topographical changes, while concomitant changes in hydrophobicity, bacterial fouling, and bactericidal properties are also measured. Extract analysis reveals the major components of the nanostructures to be fatty acids and saturated hydrocarbons ranging from C17 to C44. Effects on the antimicrobial character of a wing surface with respect to the extracted chemicals suggest that the molecular composition of the nanopillars plays both a direct and an indirect role in concert with nanopillar geometry. The data presented not only correlates the nanopillar molecular organization to macroscale functional properties, but it also presents design guidelines to consider during the replication of natural nanostructures onto engineered substrates to induce desired properties.
Investigation of pressure drop in a cocurrent downflow three‐phase moving bed
Authors: Li Shaoshuo , Wang Chao , Yang Yao , Huang Zhengliang , Sun Jingyuan , Liao Zuwei , Wang Jingdai , Yang Yongrong , Du Bing , Behkish Arsam
Published: April 2020

Based on a self‐established cold‐flow experimental device, the pressure drop in a cocurrent downflow three‐phase moving bed was investigated under a wide range of gas, liquid, and solid flow rates during dynamic and steady‐state operation. The results showed that for the startup of the bed, since the first bed layer packed by fall‐falling of particles had lower voidage, it would take at least one bed volume time to make the voidage in the bed reach the steady‐state. Under steady‐state conditions, the pressure drop increased with the increase of gas and liquid mass flow rates, liquid viscosity, and decreased with the increase of solid flow rate. Furthermore, it was found that the liquid distribution became more uniform due to particle movement. The experimental data obtained in this study was used to develop a correlation to predict the pressure drop in a three‐phase moving bed with an average relative error of 9.32%.
Viscoelastic surfactant fluids filtration in porous media: A pore‐scale study
Authors: Li Yuan , Dai Caili , Wu Yining , Xu Ke , Zhao Mingwei , Wang Yuhe
Published: April 2020

We investigated the flow of viscoelastic surfactant (VES) solutions, an important type of fracturing fluids for unconventional hydrocarbon recovery, through a diverging–converging microfluidic channel that mimics realistic unit in porous media. Newtonian fluid and viscoelastic hydrolyzed polyacrylamide (HPAM) solution were used as control groups. We vary Deborah numbers (De) up to 61.2, and found that the flow patterns of HPAM and VES solutions become very different once De ≥ 6.12. This is attributed to different generation mechanisms of viscoelasticity, thus different responses to extensional rates at pore‐throats, for HPAM and VES solutions. It results in significantly smaller pressure drop of VES solutions through the microchannel compared to HPAM solution. It interprets higher filtration loss of VES solution than HPAM in core experiments and in field observations. The set‐up can be generalized as a prototype to effectively evaluate the filtration of fracturing fluids.
Rapid and Scalable Access to Sequence‐Controlled DHDM Multiblock Copolymers by FLP Polymerization
Authors: Bai Yun , Wang Huaiyu , He Jianghua , Zhang Yuetao
Published: April 2020

An immortalN‐(diphenylphosphanyl)‐1,3‐diisopropyl‐4,5‐dimethyl‐1,3‐dihydro‐2H‐imidazol‐2‐imine/diisobutyl (2,6‐di‐tert‐butyl‐4‐methylphenoxy) aluminum (P(NIiPr)Ph2/(BHT)AliBu2)‐based frustrated Lewis pair (FLP) polymerization strategy is presented for rapid and scalable synthesis of the sequence‐controlled multiblock copolymers at room temperature. Without addition of extra initiator or catalyst and complex synthetic procedure, this method enabled a tripentacontablock copolymer (n=53,k=4,dpn=50) to be achieved with the highest reported block number (n=53) and molecular weight (Mn=310 kg mol−1) within 30 min. More importantly, this FLP polymerization strategy provided access to the multiblock copolymers with tailored properties by precisely adjusting the monomer sequence and block numbers.
Rhodium‐Catalyzed Highly Diastereo‐ and Enantioselective Synthesis of a Configurationally Stable S‐Shaped Double Helicene‐Like Molecule
Authors: Kinoshita Suzuka , Yamano Ryota , Shibata Yu , Tanaka Yusuke , Hanada Kyoichi , Matsumoto Takashi , Miyamoto Kazunori , Muranaka Atsuya , Uchiyama Masanobu , Tanaka Ken
Published: April 2020

An S‐shaped double helicene‐like molecule (>99 % ee), possessing stable helical chirality, has been synthesized by the rhodium(I)/difluorphos complex‐catalyzed highly diastereo‐ and enantioselective intramolecular double [2+2+2] cycloaddition of a 2‐naphthol‐ and benzene‐linked hexayne. The collision between two terminal naphthalene rings destabilizes the helical chirality of the S‐shaped double helicene‐like molecule, but the introduction of two additional fused benzene rings significantly increases the configurational stability. Thus, no epimerization and racemization were observed even at 100 °C. The enantiopure S‐shaped double helicene‐like molecule forms a trimer through the multiple C−H⋅⋅⋅π and C−H⋅⋅⋅O interactions in the solid‐state. The trimers stack to form columnar packing structures, in which neighboring stacks have opposite dipole directions. The accumulation of helical structures in the same direction in the S‐shaped double helicene‐like molecule enhanced the chiroptical properties.
2D ZnO/Fe3O4 nanocomposites as a novel catalyst‐promoted green synthesis of novel quinazoline phosphonate derivatives
Authors: Ezzatzadeh Elham , Hossaini Zinatossadat
Published: April 2020

In this research a novel and efficient procedure for the preparation of phosphonate derivatives using the reaction of 2,4‐dihydroxyacetophenone, isopropenylacetylene, 2‐amino‐N‐alkyl benzamide, dialkyl acetylenedicarboxylates and trimethyl phosphite or triphenyl phosphite in the presence of reusable 2D ZnO/Fe3O4 nanocomposites in water at room temperature was investigated. The 2D ZnO/Fe3O4 nanocomposites were synthesized using ionic liquid [OMIM]Br as a stabilizer and soft template. In addition, the power of antioxidant for some prepared compounds was studied using trapping of radicals by DPPH and a ferric reduction activity potential experiment. As a result, compound 6f displayed a noteworthy power for trapping of free radicals and 6b exhibited excellent reducing power compared with standards (BHT and TBHQ). Moreover, the antimicrobial power of some prepared quinazolinone phosphonates was proved by employing the disk diffusion experiment on two kinds of bacteria, Gram‐positive and ‐negative bacteria. The obtained outcomes of disk diffusion test showed that these compounds prevented bacterial growth. Some advantages of this procedure are: short time of reaction, high yields of product and easy separation of catalyst and products.
Influence of overflow port selection on the gas desulfurization of gas cyclone–liquid jet absorption separator
Authors: Ma Liang , Peng Lv , Zhang Zheng‐Wei , Tian Cheng‐Cheng
Published: April 2020

The purification of industrial sulfur‐containing tail gas mainly adopts the wet flue gas desulfurization of gas–liquid mass transfer, and a new separator utilizes the gas–liquid coupling field to rapidly update the effective phase boundary area in the reaction process to enhance the mass transfer effect. This study used NaOH solution as the reaction liquid phase to determine the effects of the selection of overflow port of gas cyclone–liquid jet absorption separator on gas desulfurization efficiency under the changing rates of gas and absorption liquid flow. Results showed that desulfurization efficiency decreased as the diameter of the overflow port increased but increased as the depth of the overflow port increased. The optimal design ratio Dx/D1 of overflow tube diameter Dx and separator tube diameter D1 is 0.35, and the optimal design ratio S/H1 of overflow tube insertion depth S and separator tube length H1 is 0.62. At constant operating conditions, overflow port selection can increase desulfurization efficiency by up to 20%, which provides optimization guidance for the structural design of a gas cyclone–liquid jet absorption separator.
Stochastic differential equations harvesting policies: Allee effects, logistic‐like growth and profit optimization
Authors: Brites Nuno M. , Braumann Carlos A.
Published: April 2020

In this article, stochastic differential equations are used to model the dynamics of a harvested population in the presence of weak Allee effects. Two optimal harvesting policies are presented, one with variable effort based on optimal control theory, which is for practical reasons inapplicable in a random environment, and the other with constant effort and easily applicable. For a logistic‐like model with weak Allee effects, we show that the optimal policy based on constant effort implies, in a suitable range of effort values, the existence of a steady‐state stochastic equilibrium with a stationary density, obtained explicitly here, for the population size. With this new result, we compare the performance of both policies in terms of the profit obtained over a finite time horizon. Using realistic data from a harvested population and a logistic‐type growth model, we quantify the profit reduction when choosing the optimal policy based on constant effort instead of the optimal policy based on variable effort. We also study the influence of the Allee effects strength.
The protective role of metformin in autophagic status in peripheral blood mononuclear cells of type 2 diabetic patients
Authors: Bhattacharya Debalina , Dutta Moumita , Mukhopadhyay Mainak , Bhattacharyya Maitree , Chowdhury Subhankar , Karmakar Parimal
Published: April 2020

Autophagy plays an important role in the pathophysiology of type 2 diabetes (T2D). Metformin is the most common antidiabetic drug. The main objective of this study was to explore the molecular mechanism of metformin in starvation‐induced autophagy in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic patients. PBMCs were isolated from 10 diabetic patients and 7 non‐diabetic healthy volunteers. The autophagic puncta and markers were measured with the help of monodansylcadaverine staining and western blot. Additionally, transmission electron microscopy was also performed. No significant changes were observed in the initial autophagy marker protein levels in PBMCs of T2D after metformin treatment though diabetic PBMCs showed a high level of phospho‐mammalian target of rapamycin, p62 and reduced expression of phospho‐AMP‐activated protein kinase and lysosomal membrane‐associated protein 2, indicating a defect in autophagy. Also, induction of autophagy by tunicamycin resulted in apoptosis in diabetic PBMCs as observed by caspase‐3 cleavage and reduced expression of Bcl2. Inhibition of autophagy by bafilomycin rendered consistent expression of p62 indicating a defect in the final process of autophagy. Further, electron microscopic studies also confirmed massive vacuole overload and a sign of apoptotic cell death in PBMCs of diabetic patients, whereas metformin treatment reduced the number of autophagic vacuoles perhaps by lysosomal fusion. Thus, our results indicate that defective autophagy in T2D is associated with the fusion process of lysosomes which could be overcome by metformin.
Luminogens for Aggregation‐Induced Emission via Titanium‐Mediated Double Nucleophilic Addition to 2,5‐Dialkynylpyridines: Formation and Transformation of the Emitting Aggregates
Authors: Foschi Francesco , Synnatschke Kevin , Grieger Sebastian , Zhang Wen‐Shan , Wadepohl Hubert , Schröder Rasmus R. , Backes Claudia , Gade Lutz H.
Published: April 2020

Invited for the cover of this issue are Lutz H. Gade, Claudia Backes, and co‐workers at Heidelberg University. The image depicts 2‐(1,2,2‐triarylvinyl)‐pyridines, which are luminogens for aggregation‐induced emission which “light up” upon irradiation. Read the full text of the article at 10.1002/chem.201905611.
Yield—not only Lifetime—of the Photoinduced Charge‐Separated State in Iridium Complex–Polyoxometalate Dyads Impact Their Hydrogen Evolution Reactivity
Authors: Luo Yusen , Maloul Salam , Schönweiz Stefanie , Wächtler Maria , Streb Carsten , Dietzek Benjamin
Published: April 2020

Covalently linked photosensitizer–polyoxometalate (PS‐POM) dyads are promising molecular systems for light‐induced energy conversion processes, such as “solar” hydrogen generation. To date, very little is known of their fundamental photophysical properties which affect the catalytic reactivity and stability of the systems. PS‐POM dyads often feature short‐lived photoinduced charge‐separated states, and the lifetimes of these states are considered crucial for the function of PS‐POM dyads in molecular photocatalysis. Hence, strategies have been developed to extend the lifetimes of the photoinduced charge‐separated states, either by tuning the PS photophysics or by tuning the POM redox properties. Recently, some of us reported PS‐POM dyads based on cyclometalated IrIII complexes covalently linked to Anderson‐type polyoxometalate. Distinct hydrogen evolution reactivity (HER) of the dyads was observed, which was tuned by varying the central metal ion M of the POMM (M=Mn3+, Co3+, Fe3+). In this manuscript, the photoinduced electron‐transfer processes in the three Ir‐POMM dyads are investigated to rationalize the underlying reasons for the differences in HER activity observed. We report that upon excitation of the IrIII complex, ultrafast (sub‐ps) charge separation occurs, leading to different amounts of the charge‐separated states (Ir.+‐POMM.−) generated in the different dyads. However, in all dyads studied, the resulting Ir.+‐POMM.− species are short‐lived (sub‐ns) when compared to reference electron acceptors (e.g. porphyrins or fullerenes) reported in the literature. The reductive quenching of Ir.+‐POMM.− by a sacrificial donor, triethyl amine (1 m), to generate the intermediate Ir‐POMM.− is estimated to be very efficient (70–80 %) for all dyads studied. Based on this analyses, we conclude that the yield instead of the lifetime of the Ir.+‐POMM.− charge‐separated state determines the catalytic capacity of the dyads investigated. This new feature in the PS‐POM photophysics could lead to new design criteria for the development of novel PS‐POM dyads.
A Microfluidic Co‐Flow Route for Human Serum Albumin‐Drug–Nanoparticle Assembly
Authors: Hakala Tuuli A. , Davies Sarah , Toprakcioglu Zenon , Bernardim Barbara , Bernardes Gonçalo J. L. , Knowles Tuomas P. J.
Published: April 2020

Nanoparticles are widely studied as carrier vehicles in biological systems because their size readily allows access through cellular membranes. Moreover, they have the potential to carry cargo molecules and as such, these factors make them especially attractive for intravenous drug delivery purposes. Interest in protein‐based nanoparticles has recently gained attraction due to particle biocompatibility and lack of toxicity. However, the production of homogeneous protein nanoparticles with high encapsulation efficiencies, without the need for additional cross‐linking or further engineering of the molecule, remains challenging. Herein, we present a microfluidic 3D co‐flow device to generate human serum albumin/celastrol nanoparticles by co‐flowing an aqueous protein solution with celastrol in ethanol. This microscale co‐flow method resulted in the formation of nanoparticles with a homogeneous size distribution and an average size, which could be tuned from ≈100 nm to 1 μm by modulating the flow rates used. We show that the high stability of the particles stems from the covalent cross‐linking of the naturally present cysteine residues within the particles formed during the assembly step. By choosing optimal flow rates during synthesis an encapsulation efficiency of 75±24 % was achieved. Finally, we show that this approach achieves significantly enhanced solubility of celastrol in the aqueous phase and, crucially, reduced cellular toxicity.
Computationally Empowered Workflow Identifies Novel Covalent Allosteric Binders for KRASG12C
Authors: Mortier Jérémie , Friberg Anders , Badock Volker , Moosmayer Dieter , Schroeder Jens , Steigemann Patrick , Siegel Franziska , Gradl Stefan , Bauser Marcus , Hillig Roman C. , Briem Hans , Eis Knut , Bader Benjamin , Nguyen Duy , Christ Clara D.
Published: April 2020

Due to its frequent mutations in multiple lethal cancers, KRAS is one of the most‐studied anticancer targets nowadays. Since the discovery of the druggable allosteric binding site containing a G12C mutation, KRASG12C has been the focus of attention in oncology research. We report here a computationally driven approach aimed at identifying novel and selective KRASG12C covalent inhibitors. The workflow involved initial enumeration of virtual molecules tailored for the KRAS allosteric binding site. Tools such as pharmacophore modeling, docking, and free‐energy perturbations were deployed to prioritize the compounds with the best profiles. The synthesized naphthyridinone scaffold showed the ability to react with G12C and inhibit KRASG12C. Analogues were prepared to establish structure‐activity relationships, while molecular dynamics simulations and crystallization of the inhibitor‐KRASG12C complex highlighted an unprecedented binding mode.
Preclinical Anticancer Activity of an Electron‐Deficient Organoruthenium(II) Complex
Authors: Soldevila‐Barreda Joan J. , Azmanova Maria , Pitto‐Barry Anaïs , Cooper Patricia A. , Shnyder Steven D. , Barry Nicolas P. E.
Published: April 2020

Ruthenium compounds have been shown to be promising alternatives to platinum(II) drugs. However, their clinical success depends on achieving mechanisms of action that overcome Pt‐resistance mechanisms. Electron‐deficient organoruthenium complexes are an understudied class of compounds that exhibit unusual reactivity in solution and might offer novel anticancer mechanisms of action. Here, we evaluate the in vitro and in vivo anticancer properties of the electron‐deficient organoruthenium complex [(p‐cymene)Ru(maleonitriledithiolate)]. This compound is found to be highly cytotoxic: 5 to 60 times more potent than cisplatin towards ovarian (A2780 and A2780cisR), colon (HCT116 p53+/+ and HCT116 p53−/−), and non‐small cell lung H460 cancer cell lines. It shows no cross‐resistance and is equally cytotoxic to both A2780 and A2780cisR cell lines. Furthermore, unlike cisplatin, the remarkable in vitro antiproliferative activity of this compound appears to be p53‐independent. In vivo evaluation in the hollow‐fibre assay across a panel of cancer cell types and subcutaneous H460 non‐small cell lung cancer xenograft model hints at the activity of the complex. Although the impressive in vitro data are not fully corroborated by the in vivo follow‐up, this work is the first preclinical study of electron‐deficient half‐sandwich complexes and highlights their promise as anticancer drug candidates.
Exploring the Porosity in Ceramics at the nm Scale: From Understanding Historical Ceramics to Innovative Materials Design
Authors: Mondelli Claudia , Zorzi Sandro , Ricci Giulia , Galvan Victór , Balliana Eleonora , Schweins Ralf , Cattaruzza Elti
Published: April 2020

Ceramics are complex objects and a rich source of information: they constitute a large part of the staple memory of past and present human activities. A deep understanding of traditional ceramics is an essential key to designing new ceramic materials. The demanding synthesis of ceramics with fine‐tuned properties, such as enhanced mechanical, electrical, optical or magnetic characteristics, must be associated with cutting‐edge analysis procedures in order to improve the engineering process. In this context, we describe a neutron‐based non‐destructive approach to investigating the nanoporosity of an historical pottery matrix as an effective investigation technique for exploring both traditional and advanced ceramic materials.
Boolean Logic Networks Mimicked with Chimeric Enzymes Activated/Inhibited by Several Input Signals
Authors: Bollella Paolo , Bellare Madhura , Kadambar Vasantha Krishna , Guo Zhong , Alexandrov Kirill , Melman Artem , Katz Evgeny
Published: April 2020

The front cover artwork is provided by groups of Prof. Evgeny Katz and Prof. Artem Melman (Clarkson University, NY, USA) as well as Prof. Kirill Alexandrov (Queensland University of Technology, Brisbane, Australia). The image shows activation/inhibition of a chimeric enzyme with biomolecular signals and a corresponding logic network – the artistic vision. Read the full text of the Communication at 10.1002/cphc.201901050.
Pharmacogenetic‐Pharmacokinetic Interactions in Drug Marketing Authorization Applications via the European Medicines Agency Between 2014 and 2017
Authors: Maliepaard Marc , Toiviainen Timi , De Bruin Marie L. , Meulendijks Didier
Published: April 2020

This study aimed to determine to which extent data on potential pharmacogenetic‐pharmacokinetic (PG‐PK) interactions are provided to, and assessed by, the European Medicines Agency (EMA) in novel drug marketing authorization applications (MAAs), and whether regulatory assessment of PG‐PK interactions is adequate or could be optimized. For this purpose, we retrospectively analyzed MAAs of small molecule drugs assessed by the EMA between January 2014 and December 2017. As per two key requirements in the EMA’s guideline, we analyzed cases where (i) a single functionally polymorphic drug metabolizing enzyme (DME) metabolizes > 25% of the drug, or (ii) the drug’s PK shows high interindividual variability not explained by other factors than PG. Results showed that, of 113 drugs analyzed, 53 (47%) had ≥ 1 functionally polymorphic DME accounting for > 25% of the drug’s metabolism, yielding 55 gene‐drug pairs. For 36 of 53 (68%) of the products, CYP3A4 was the major DME. Compliance with European Union (EU) guidance on PG‐PK issues in drug development was notably different for CYP3A4 substrates vs. non‐CYP3A4 substrates. Adequate PG‐PK data were provided during registration in 89% (16/18) of cases concerning non‐CYP3A4 substrates, compared with 32% (12/37) of cases concerning CYP3A4 substrates. Concluding, PG‐PK interactions related to non‐CYP3A4 substrate drugs were, in general, addressed adequately in EU MAAs. PG‐PK information on CYP3A4 substrates was available less frequently, despite some available evidence on the functional relevance of CYP3A4 polymorphisms. A more harmonized approach toward assessment of PG‐PK issues in EU MAAs seems warranted, and a discussion on the relevance of CYP3A4 polymorphisms, such as CYP3A4*22, is recommended.