bluuebunny/crossref_metadata_2025 huggingface dataset:
Material Design of Aqueous Redox Flow Batteries: Fundamental Challenges and Mitigation Strategies
Authors: Li Zhejun , Lu Yi‐Chun
Published: October 2020

Redox flow batteries (RFBs) are critical enablers for next‐generation grid‐scale energy‐storage systems, due to their scalability and flexibility in decoupling power and energy. Aqueous RFBs (ARFBs) using nonflammable electrolytes are intrinsically safe. However, their development has been limited by their low energy density and high cost. Developing ARFBs with higher energy density, lower cost, and longer lifespan than the current standard is of significant interest to academic and industrial research communities. Here, a critical review of the latest progress on advanced electrolyte material designs of ARFBs is presented, including a fundamental overview of their physicochemical properties, major challenges, and design strategies. Assessment methodologies and metrics for the evaluation of RFB stability are discussed. Finally, future directions for material design to realize practical applications and achieve the commercialization of ARFB energy‐storage systems are highlighted.
Halide Perovskite Lateral Heterostructures for Energy Routing Based Photonic Applications
Authors: Ren Yinjuan , Wang Ziming , Wang Yue , Wang Weihua , Feng Likuan , Xia Siyang , Zeng Haibo
Published: October 2020

Semiconductor heterostructures hold the promise for developing novel integrated devices with on‐demand photonic and optoelectronic properties. Herein, the perovskite lateral heterostructures in forms of microplates and microwires are fabricated by precise control of two‐step atmospheric pressure chemical vapor deposition course and the unique optical properties are demonstrated for the first time. The comprehensive spectroscopic and elemental mapping characterizations reveal the core‐shell‐like configuration of the individual heterostructure, which features the fascinating energy routing nature. Taking advantage of the effective photon recycling and the energy transfer processes, the record‐low threshold (≈3.5 µJ cm−2) lasing and the indirect pumping induced lasers from the single micro‐heterostructure are demonstrated. Moreover, the distinctive optical waveguides with propagation length independent output spectra from the microwire heterostructure are realized. These findings represent a significant advance in developing novel and functional optoelectronic devices by engineering the perovskite heterostructure.
Efficient Sky‐Blue Organic Light‐Emitting Diodes Using a Highly Horizontally Oriented Thermally Activated Delayed Fluorescence Emitter
Authors: Zhang Zhen , Crovini Ettore , dos Santos Paloma L. , Naqvi Bilal A. , Cordes David B. , Slawin Alexandra M. Z. , Sahay Prakhar , Brütting Wolfgang , Samuel Ifor D. W. , Bräse Stefan , Zysman‐Colman Eli
Published: October 2020

Organic thermally activated delayed fluorescent (TADF) materials can harvest 100% of the electrically generated excitons as a result of their small singlet–triplet energy difference. However, maximizing the external quantum efficiency (EQE) of a device also requires enhancing the light out‐coupling efficiency. This work presents a new acceptor–donor–acceptor (ADA) emitter employing an indolocarbazole donor and diphenyltriazine acceptors that show nearly‐completely horizontal orientation regardless of the host matrix, leading to a sky‐blue organic light‐emitting diode (λEL = 483 nm, CIE coordinates of 0.17, 0.32) with EQEMAX of 22.1%, a maximum luminance of 7800 cd m−2, and blue emission.
Recent Progress on Advanced Optical Structures for Emerging Photovoltaics and Photodetectors
Authors: Chen Chien-Yu , Tan Guang-Hsun , Hsu Hsiang-Lin , Chen Chih-Ping , Lin Hao-Wu
Published: October 2020

Organic‐ and perovskite‐based optoelectronics, which merge excellent optoelectronic properties with potentially large and high‐throughput manufacturing, have attracted attention as emerging revolutionary technologies with considerable practical applications. Herein, the recent progresses in organic‐ and perovskite‐based photovoltaics and photodetectors with integration of judicious optical structure designs are summarized. The characterization and performance metrics of such devices from the perspectives of device architecture, physics, and material science are studied. Research related to devices having dielectric mirrors, diffracted Bragg reflectors/photonic crystals, microcavities, and 2D photonic structures as design elements is discussed. Some suggestions of promising directions for future studies are concluded.
Discordant Monozygotic Parkinson Disease Twins: Role of Mitochondrial Integrity
Authors: Dulovic‐Mahlow Marija , König Inke R. , Trinh Joanne , Diaw Sokhna Haissatou , Urban Peter P. , Knappe Evelyn , Kuhnke Neele , Ingwersen Lena‐Christin , Hinrichs Frauke , Weber Joachim , Kupnicka Patrycja , Balck Alexander , Delcambre Sylvie , Vollbrandt Tillman , Grünewald Anne , Klein Christine , Seibler Philip , Lohmann Katja
Published: October 2020

Objective

Even though genetic predisposition has proven to be an important element in Parkinson's disease (PD) etiology, monozygotic (MZ) twins with PD displayed a concordance rate of only about 20% despite their shared identical genetic background.

Methods

We recruited 5 pairs of MZ twins discordant for idiopathic PD and established skin fibroblast cultures to investigate mitochondrial phenotypes in these cellular models against the background of a presumably identical genome. To test for genetic differences, we performed whole genome sequencing, deep mitochondrial DNA (mtDNA) sequencing, and tested for mitochondrial deletions by multiplex real‐time polymerase chain reaction (PCR) in the fibroblast cultures. Further, the fibroblast cultures were tested for mitochondrial integrity by immunocytochemistry, immunoblotting, flow cytometry, and real‐time PCR to quantify gene expression.

Results

Genome sequencing did not identify any genetic difference. We found decreased mitochondrial functionality with reduced cellular adenosine triphosphate (ATP) levels, altered mitochondrial morphology, elevated protein levels of superoxide dismutase 2 (SOD2), and increased levels of peroxisome proliferator‐activated receptor‐gamma coactivator‐α (PPARGC1A) messenger RNA (mRNA) in skin fibroblast cultures from the affected compared to the unaffected twins. Further, there was a tendency for a higher number of somatic mtDNA variants among the affected twins.

Interpretation

We demonstrate disease‐related differences in mitochondrial integrity in the genetically identical twins. Of note, the clinical expression matches functional alterations of the mitochondria. ANN NEUROL 2021;89:158–164
Protofibril–Fibril Interactions Inhibit Amyloid Fibril Assembly by Obstructing Secondary Nucleation
Authors: Hasecke Filip , Niyangoda Chamani , Borjas Gustavo , Pan Jianjun , Matthews Garrett , Muschol Martin , Hoyer Wolfgang
Published: October 2020

Amyloid‐β peptides (Aβ) assemble into both rigid amyloid fibrils and metastable oligomers termed AβO or protofibrils. In Alzheimer's disease, Aβ fibrils constitute the core of senile plaques, but Aβ protofibrils may represent the main toxic species. Aβ protofibrils accumulate at the exterior of senile plaques, yet the protofibril–fibril interplay is not well understood. Applying chemical kinetics and atomic force microscopy to the assembly of Aβ and lysozyme, protofibrils are observed to bind to the lateral surfaces of amyloid fibrils. When utilizing Aβ variants with different critical oligomer concentrations, the interaction inhibits the autocatalytic proliferation of amyloid fibrils by secondary nucleation on the fibril surface. Thus, metastable oligomers antagonize their replacement by amyloid fibrils both by competing for monomers and blocking secondary nucleation sites. The protofibril—fibril interaction governs their temporal evolution and potential to exert specific toxic activities.
Tag‐Free Internal RNA Labeling and Photocaging Based on mRNA Methyltransferases
Authors: Ovcharenko Anna , Weissenboeck Florian P. , Rentmeister Andrea
Published: October 2020

The mRNA modification N6‐methyladenosine (m6A) is associated with multiple roles in cell function and disease. The methyltransferases METTL3‐METTL14 and METTL16 act as “writers” for different target transcripts and sequence motifs. The modification is perceived by dedicated “reader” and “eraser” proteins, but not by polymerases. We report that METTL3‐14 shows remarkable cosubstrate promiscuity, enabling sequence‐specific internal labeling of RNA without additional guide RNAs. The transfer of ortho‐nitrobenzyl and 6‐nitropiperonyl groups allowed enzymatic photocaging of RNA in the consensus motif, which impaired polymerase‐catalyzed primer extension in a reversible manner. METTL16 was less promiscuous but suitable for chemo‐enzymatic labeling using different types of click chemistry. Since both enzymes act on distinct sequence motifs, their combination allowed orthogonal chemo‐enzymatic modification of different sites in a single RNA.
Decoding Protein Gas‐Phase Stability with Alanine Scanning and Collision‐Induced Unfolding Ion Mobility Mass Spectrometry
Authors: Bellamy‐Carter Jeddidiah , O'Grady Louisa , Passmore Munro , Jenner Matthew , Oldham Neil J.
Published: October 2020

Native mass spectrometry is a widely used tool in structural biology, providing information on protein structure and interactions through preservation of complexes in the gas phase. Herein, the importance of intramolecular non‐covalent interactions in the gas phase has been studied by alanine scanning and collision‐induced unfolding (CIU) ion mobility‐mass spectrometry. Mutation of specific polar and ionic residues on the surface of an acyl carrier protein (ACP) were found to destabilise the compact gas‐phase structure with mutants E31A, D32A, D41A and D65A being particularly destabilised. Molecular dynamics simulations of the ACP 7+ and 8+ ions showed extended intramolecular interactions, resulting from sidechain collapse of polar surface residues, which were confined to the gas phase and consistent with the CIU data. These findings provide evidence for the importance of specific ionic residues, and their interactions, in the maintenance of compact protein gas‐phase structure.
Markovnikov versus anti‐Markovnikov addition and C–H activation: Pd–Cu synergistic catalysis
Authors: Ullah Zakir , Thomas Renjith
Published: October 2020

Copper‐ and palladium‐mediated transmetalation and coupling reactions are the backbone to several synthetic methodologies in organic chemistry for C–C bond formation. Computer‐aided simulations using density functional theory (DFT) (B3LYP‐D3 functional with 6‐31G** and effective core potential (ECP)‐LACVP** for heavy atoms for optimizations and cc‐pVTZ(−f) and ECP‐LACV3P** for single‐point calculations) was used to shed light on the probable mechanism of a novel synergistic Cu/Pd catalysts for the coupling of alkene, (Bpin)2 (where, pin = pinacolate), and vinyl‐ or aryl‐halogenated analogues. Every single conceivable pathway was carefully contemplated, and the base minimum energy pathway was found effectively. The copper‐catalyzed nucleophilic generation yields anti‐Markovnikov product using styrene as an alkene. This study affirms quantitatively and accurately how the reaction proceeds and at which steps of the synergistic catalysis the demand of the transmetalation and nucleophile formation for the C–C coupling using phosphine ligands arise. We conclude that the E and Z selectivity depends on the stereochemistry of the substrates used.
Improved dielectric properties of poly(vinylidene fluoride)–BaTiO3 composites by solvent‐free processing
Authors: Brunengo Elisabetta , Conzatti Lucia , Schizzi Ilaria , Buscaglia Maria Teresa , Canu Giovanna , Curecheriu Lavinia , Costa Chiara , Castellano Maila , Mitoseriu Liliana , Stagnaro Paola , Buscaglia Vincenzo
Published: October 2020

Composites of poly(vinylidene fluoride) (PVDF) and BaTiO3 nanoparticles (average diameter ca. 125 nm) are fabricated by a solvent‐free and industrially scalable technique, that is, melt blending, followed by compression molding. The effect of processing parameters on the spectroscopic, microstructural, thermal, mechanical and dielectric properties are evaluated as a function of composition (loading up to 30 vol%). The presence of nanoparticle inclusions as well as specific compression molding parameters demonstrate both to affect the molecular relaxations of the PVDF matrix, studied by correlating the results of different techniques, and to induce the PVDF crystallization as β phase. Processing parameters also play a key role for optimizing the dielectric properties. An improved dielectric behavior of the composites is obtained in terms of both permittivity, whose value increases up to four times that of neat PVDF, and dielectric losses, lower than 5% between 10 and 3·104 Hz. The obtained performances resulted enhanced compared to analogous composites prepared with the use of solvents.
Liquid crystal behavior of cellulose nanoparticles‐ethyl cellulose composites: Preparation, characterization, and rheology
Authors: Basta Altaf H. , Lotfy Vivian F. , Micky Jehane A. , Salem Aya M.
Published: October 2020

This work deals with assessing the approach for preparation of cellulose nanoparticles (CNPs) to be acted as synergistic component in liquid crystal (LC) ethyl cellulose composite (EC‐CNPs). In this respect different structures of CNPs were prepared by acid and salt agents. These prepared CNPs were characterized by carboxyl content, IR, transmission electron microscope (TEM), and zeta potential, while their composites with EC were characterized by rheological measurements as a key factor for measuring the critical concentration of LC behavior. The results showed that, the crystallinity of CNPs obtained by ammonium persulfate exceeded that prepared by sulfuric acid hydrolysis. TEM images of stained CNPs showed both methods led to produce nanoparticles have rod like shape with aspect ratio (L/W) between 7.69 ± 3 and 31.3 ± 5. For the rheological measurements, it demonstrated the efficient of incorporating the CNPs to EC (EC‐CNPs composites) to decrease the critical concentration of EC from 40 wt% to approximately 34 wt%.
Chondrogenic stimulation in mesenchymal stem cells using scaffold‐based sustained release of platelet‐rich plasma
Authors: Bolandi Behzad , Imani Rana , Bonakdar Shahin , Fakhrzadeh Hossein
Published: October 2020

Developing minimal invasive strategies via injectable hydrogels for effective repairing of cartilage defects is highly desired. Injectable hydrogels, which can simultaneously embed cell and growth factors (GFs), serve as in situ formed scaffolds and could support an accelerated tissue regeneration process. The purpose of this study is to fabricate a composite injectable hydrogel, based on alginate (Alg)/polyvinyl alcohol (PVA) incorporating platelet rich plasma (PRP)‐encapsulated Alg sulfate (AlgS) microbeads, as a localized sustained release system of GFs, for the articular cartilage regeneration. The results show that synthesized AlgS microbeads support the sustained release of PRP GFs during 14 days, where preserve the bioactivity of them more than the free PRP. Rabbit adipose‐derived mesenchymal stem cells in contact with PRP‐loaded AlgS beads show more proliferation (2.7 folds) and have obviously higher deposition of collagen type ΙΙ and GAGs than free PRP treated ones. In addition, cells encapsulated into the hydrogel including PRP sustained release system show upregulated expression of collagen type ΙΙ (61 folds), Aggrecan (294 folds) and SOX9 (71.5 folds), as cartilage‐critical genes, compared to the direct treatment by PRP. To summarize, the developed hybrid Alg/PVA hydrogel embedding with PRP‐encapsulated AlgS microbeads is suggested as a potential in situ formed scaffold for cartilage regeneration.
Hyperbranched poly(glycerol esteramide): A biocompatible drug carrier from glycerol feedstock and dicarboxylic acid
Authors: Muniandy Amala , Lee Choy Sin , Lim Wen Huei , Pichika Mallikarjuna Rao , Mak Kit Kay
Published: October 2020

Polymer carrier with biodegradable, biocompatible as well as solubility enhancing properties are highly looked upon in the pharmaceutical industry to improve the drug delivery systems. A series of hyperbranched poly(glycerol esteramide) (HPGEA) with Mw of 5000–12,000 Da, degree of branching of 57%–62%, and hydroxyl values of 200–280 mg KOH/g sample were synthesized through polycondensation of N,N‐bis(2‐hydroxyethyl)stearamide (diethanolamide) and poly(glycerol ester) (PGE). The HPGEAs were characterized by ATR‐FTIR, GPC, 1H and 13C‐NMR, and DSC. The enthalpy of fusion of HPGEAs (43–84 J g−1) were lower than the commercial polymers (193–391 J g−1), indicating its potential as drug carrier for solid dispersion (SD). HPGEA‐based SDs showed substantial enhancement in solubility and release rate than pure drug, commercial polymer‐based SDs, as well as commercial formulation. The safety of HPGEAs and HPGEA‐based SDs were proven through MTT assay with IC50 of 2400–9800 and 1200–3500 μg ml−1, respectively.
Directed evolution of conformation‐specific antibodies for sensitive detection of polypeptide aggregates in therapeutic drug formulations
Authors: Lou Wenjia , Stimple Samuel D. , Desai Alec A. , Makowski Emily K. , Kalyoncu Sibel , Mogensen Jesper E. , Spang Lotte T. , Asgreen Désirée J. , Staby Arne , Duus Karen , Amstrup Jan , Zhang Yulei , Tessier Peter M.
Published: October 2020

Biologics such as peptides and proteins possess a number of attractive attributes that make them particularly valuable as therapeutics, including their high activity, high specificity, and low toxicity. However, one of the key challenges associated with this class of drugs is their propensity to aggregate. Given the safety and immunogenicity concerns related to polypeptide aggregates, it is particularly important to sensitively detect aggregates in therapeutic drug formulations as part of the quality control process. Here, we report the development of conformation‐specific antibodies that recognize polypeptide aggregates composed of a GLP‐1 receptor agonist (liraglutide) and their integration into a sensitive immunoassay for detecting liraglutide amyloid fibrils. We sorted single‐chain antibody libraries against liraglutide fibrils using yeast surface display and magnetic‐activated cell sorting, and identified several antibodies with high conformational specificity. Interestingly, these antibodies cross‐react with amyloid fibrils formed by several other polypeptides, revealing that they recognize molecular features common to different types of fibrils. Moreover, we find that our immunoassay using these antibodies is >50‐fold more sensitive than the conventional method for detecting liraglutide aggregation (Thioflavin T fluorescence). We expect that our systematic approach for generating a sensitive, aggregate‐specific immunoassay can be readily extended to other biologics to improve the quality and safety of formulated drug products.
The role of MOOCs in engineering education: An exploratory systematic review of peer‐reviewed literature
Authors: Sezgin Sezan , Sevim Cirak Nese
Published: October 2020

The aim of the current study is to explore and evaluate the current status of massive open online courses (MOOCs) in the field of Engineering Education. In line with this aim, the study intends to identify and map the role of “MOOCs in engineering education research” through a review of empirical articles published in peer‐reviewed journals indexed in the “Web of Science,” “IEEE Xplore,” “Scopus,” “Science Direct,” and the “ACM Digital Library” databases. Social network analysis, content analysis, and inferential‐descriptive statistics were applied in the study. The study's findings indicate a growing trend in “MOOCs in engineering education research.” Online virtual labs, social networks, flipped classroom strategy, active learning, small private online courses, and motivation are the key lodestar topics in “MOOCs in engineering education research” and engineering education researchers mostly employ practice‐based and quantitative research approaches. Besides this, it was found that engineering education researchers use MOOCs for three main purposes: designing a domain‐specific MOOC with unique features; developing a system/model for e‐learning and MOOCs, or aiming to improve engineering education using interactive online technologies. The findings of the current study indicate that engineering education researchers primarily give importance to performance outcomes and motivation in learning, and try to increase the quality of engineering education through the use of MOOCs. Finally, the findings imply that the general discourse among the sampled articles is positive, and may be considered useful in the exploration of potential research into “MOOCs in engineering education research.”
Characterization of β‐Cryptoxanthin and Other Carotenoid Derivatives from Rhodotorula taiwanensis, A Novel Yeast Isolated from Traditional Starter Culture of Assam
Authors: Parasar Deep Prakash , Ramakrishnan Elancheran , Kabilan Senthamaraikannan , Kotoky Jibon , Sarma Hridip Kumar
Published: October 2020

The present investigation was intended to characterize pigments for the first time from Rhodotorula taiwanensis (LC011412) yeast isolated from the ethic fermentation starter culture source meant to evaluate its carotenoid contents for beneficial applications. The pigments were extracted by an optimized solvent system, purified by flash chromatography and were identified by TLC and UV/VIS spectroscopy. The absorbance spectra confirmed the presence of β‐carotene, β‐cryptoxanthin, torulene and torularhodin that showed maximum absorbance (λmax) within the ranges. The fractions were further characterized by LC/MS and analyzed through FT‐IR and NMR for structure elucidation. Spectral analyses also confirmed the presence of the compounds mentioned above. These compounds promise great commercial value and could be useful for large scale production anticipated for potential applications in food, nutraceutical, pharmaceutical and cosmetic sectors. It is pertinent that the characterized carotenoid pigments from the isolate have incredible prospects in industrial applications which require profound attention.
Pili Tree (Canarium ovatum) Resin's Antibacterial Essential Oil and Hydrosol as Rich Sources of (S)‐Phellandrenes Derivatives
Authors: Mercier Sylvain , Lorenzo Russell Y. , Pichette André , Côté Héloïse , Legault Jean , St‐Gelais Alexis
Published: October 2020

Five batches of resin from the Pili tree (Canarium ovatum Engl.) were distilled, and their essential oils and hydrosols were analyzed by gas chromatography. The oils, obtained in yields of 13.4–19.7 % v/m, featured α‐phellandrene in high proportions (50–65 %), alongside limonene, β‐phellandrene and para‐cymene. Chiral GC analysis confirmed that both phellandrenes were in fact >95 % (S)‐(+) enantiomers, while the other monoterpenes featured less pronounced enantiomeric excesses. The hydrosols were rich in α‐phellandrene oxidation products including cis‐α‐phellandrene epoxide and a series of para‐menth‐5‐ene‐1,2‐diol isomers. Both essential oils and hydrosols were tested for their antibacterial activity against Escherichia coli and Staphylococcus aureus and exhibited MIC90 of less than 5 and 0.5 mg/mL of total volatiles, respectively. The essential oil features some potential as a source of readily available natural (S)‐(+)‐α‐phellandrene.
Machine Learning Enables Selection of Epistatic Enzyme Mutants for Stability Against Unfolding and Detrimental Aggregation
Authors: Li Guangyue , Qin Youcai , Fontaine Nicolas T. , Ng Fuk Chong Matthieu , Maria‐Solano Miguel A. , Feixas Ferran , Cadet Xavier F. , Pandjaitan Rudy , Garcia‐Borràs Marc , Cadet Frederic , Reetz Manfred T.
Published: October 2020

Machine learning (ML) has pervaded most areas of protein engineering, including stability and stereoselectivity. Using limonene epoxide hydrolase as the model enzyme and innov'SAR as the ML platform, comprising a digital signal process, we achieved high protein robustness that can resist unfolding with concomitant detrimental aggregation. Fourier transform (FT) allows us to take into account the order of the protein sequence and the nonlinear interactions between positions, and thus to grasp epistatic phenomena. The innov'SAR approach is interpolative, extrapolative and makes outside‐the‐box, predictions not found in other state‐of‐the‐art ML or deep learning approaches. Equally significant is the finding that our approach to ML in the present context, flanked by advanced molecular dynamics simulations, uncovers the connection between epistatic mutational interactions and protein robustness.
Disseminated pulmonary emboli caused by mercury: A rare consequence of Munchausen's syndrome
Authors: Shi Wen , Jiao Yang
Published: October 2020

To learn about the imaging characteristics of pulmonary emboli caused by metallic mercury and be aware that an underlying psychiatric condition might exist when mercury poisoning is not caused by occupational exposure.
Continuous Neutralization of NaOH Solution with CO2 in an Internal‐Loop Airlift Reactor
Authors: Pichler Thomas , Stoppacher Bernd , Kaufmann Alexander , Siebenhofer Matthäus , Kienberger Marlene
Published: October 2020

The neutralization of NaOH with CO2 in a continuously operated airlift reactor with gas flow rates up to 10 NL min−1 and gas phase recycle was investigated. Neutralization experiments were performed at 25 °C and the amount of absorbed CO2, as well as the NaOH feed rate, were recorded. The reaction rate was calculated based on the two‐film theory and empirical equations for several parameters. The calculations of the volumetric mass transfer coefficient, the liquid phase circulation velocity, and the gas holdup were experimentally validated. The reaction rate and the process efficiency were modeled with a deviation of 5 %.
Effect of rheology on mass transfer and bubble sizes in a bubble column operated in the heterogeneous regime
Authors: Augier Frédéric , Raimundo Pedro M.
Published: October 2020

A recently developed measurement method has been applied for the first time to the characterization of a bubble column operated in the heterogeneous regime and in presence of non‐Newtonian fluids. The resulting measurements of bubble size are completed with local gas holdup and global mass transfer characterizations. A strong impact of rheology on both bubble size and mass transfer is observed, at any tested superficial gas velocity. A dissociation of the liquid side mass transfer kL and the specific interfacial area (a) is proposed. Results show that the kL model previously validated in stirred tanks filled with complex fluids is satisfyingly extended to bubble columns. The incoming databank will be of great help to develop and validate multiphase hydrodynamic models, especially in the scope of biotechnology and associated systems of complex rheology.
Recent Advances of Catalytic Enantioselective Heck Reactions and Reductive‐Heck Reactions
Authors: Xie Jia‐Qi , Liang Ren‐Xiao , Jia Yi‐Xia
Published: October 2020

Heck reaction is one of the most important carbon‐carbon bond forming reactions with wide applications in organic synthesis. Considerable advances of enantioselective Heck reaction have been achieved in the past decades. This review focuses on recent development of catalytic asymmetric Heck reaction and reductive Heck reaction, which covers intermolecular and intramolecular versions since 2011. The article is organized in terms of the catalysts and olefin substrates.
Optimizing the measurement of health‐related quality of life in adolescents and young adults with cancer
Authors: Salsman John M. , Danhauer Suzanne C. , Moore Justin B. , Canzona Mollie R. , Victorson David E. , Zebrack Bradley J. , Reeve Bryce B.
Published: October 2020

To date, the health‐related quality of life experiences of adolescents and young adults (AYA) with cancer have been inconsistently and incompletely captured by existing patient‐reported outcome (PRO) measures. The National Institutes of Health Patient‐Reported Outcomes Measurement Information System (PROMIS) represents the state of the art for measurement science of PROs and provides an optimal approach for addressing these measurement challenges and catalyzing future patient‐centered research in AYA oncology.
A Gadolinium Metal‐Organic Framework Film as a Converter Layer for Neutron Detection
Authors: Canatelli Axel X. , Pérez Martín , Lipovetzky José , Marín Julio H. , Albornoz Cecilia A. , Tartaglione Aureliano , Roncaroli Federico
Published: October 2020

Metal‐organic frameworks (MOFs) are known for their versatility in terms of their crystalline structure, porosity, resistance to temperature, radiation damage, and luminescence among others. Gadolinium (Gd) is one of the elements with the highest reported cross‐section for low energy neutron capture, producing internal conversion electrons and γ rays as a result of the neutron absorption. The development of Gd‐BTC films (BTC=1,3,5‐benzenetricarboxylate) is shown that were deposited on Si and Al substrates by airbrushing, and characterized by profilometry, Raman, EDX and X‐ray diffraction. Radiation damage, thermal decomposition and neutron absorption of these films were studied as well. Gd‐BTC films were attached to CMOS devices (Complementary Metal‐Oxide‐Semiconductor), which are sensible to the internal conversion electrons, in order to build a neutron detector. The devices Gd‐BTC/CMOS could selectively detect neutrons in the presence of γ rays with a thermal neutron detection efficiency of 3.3±0.1 %, a signal to noise ratio of 6 : 1, and were suitable to obtain images.
Nanocomposite‐Based Matrices in Laser Desorption/Ionization Mass Spectrometry for Small‐Molecule Analysis
Authors: Pei Congcong , Wan Jingjing
Published: October 2020

The efficient detection of small molecules is of significance for environmental monitoring, pharmacology, metabolomics, and lipidomics. The laser desorption/ionization mass spectrometry (LDI MS) platform enables high sensitivity, accuracy, resolution, and throughput in molecular analysis, but its analytical capability with respect to small molecules is limited due to inherent drawbacks arising from conventional organic matrices. The selection of an appropriate matrix is thus a precondition for small molecule detection by LDI MS. To date, various inorganic matrices have been developed, with a growing interest in composite materials displaying synergetic effects. This Minireview highlights the development of nanocomposites as LDI matrices driven by numerous innovations in material science, and their emerging use in small‐molecule analysis.
A validated method for the simultaneous quantification of cannabidiol, Δ9‐tetrahydrocannabinol, and their metabolites in human plasma and application to plasma samples from an oral cannabidiol open‐label trial
Authors: Kevin Richard C. , Vogel Rebecca , Doohan Peter , Berger Maximus , Amminger G. Paul , McGregor Iain S.
Published: October 2020

Cannabidiol (CBD) and Δ9‐tetrahydrocannabinol (THC) are the two best known and most extensively studied phytocannabinoids within Cannabis sativa. An increasing number of preclinical studies and clinical trials have been conducted with one or both compounds, often probing their therapeutic effects in conditions such as paediatric epilepsy, anxiety disorders or chronic pain. Accurate monitoring of THC and CBD and their metabolites is essential for tracking treatment adherence and pharmacokinetics. However, fully validated methods for the comprehensive analysis of major Phase I CBD metabolites are yet to be developed due to a historical lack of commercially available reference material. In the present study, we developed, optimised and validated a method for the simultaneous quantification of CBD, THC and their major Phase I metabolites 6‐hydroxy‐CBD (6‐OH‐CBD), 7‐hydroxy‐CBD (7‐OH‐CBD), 7‐carboxy‐CBD (7‐COOH‐CBD), 11‐hydroxy‐tetrahydrocannabinol (11‐OH‐THC) and 11‐carboxy‐tetrahydrocannabinol (11‐COOH‐THC) as per Food and Drug Administration (FDA) guidelines for bioanalytical method validation. The method is accurate, reproducible, sensitive and can be carried out in high‐throughput 96‐well formats, ideal for larger scale clinical trials. Deuterated internal standards for each analyte were crucial to account for variable matrix effects between plasma lots. The application of the method to plasma samples, taken from people who had been administered oral CBD as part of an open‐label trial of CBD effects in anxiety disorders, demonstrated its immediate utility in ongoing and upcoming clinical trials. The method will prove useful for future studies involving CBD and/or THC and can likely accommodate the inclusion of additional metabolites as analytical reference materials become commercially available.
GDE2 expression in oligodendroglia regulates the pace of oligodendrocyte maturation
Authors: Choi Bo‐Ran , Dobrowolski Mateusz , Sockanathan Shanthini
Published: October 2020

Background

Oligodendrocytes generate specialized lipid‐rich sheaths called myelin that wrap axons and facilitate the rapid, saltatory transmission of action potentials. Extrinsic signals and surface‐mediated pathways coordinate oligodendrocyte development to ensure appropriate axonal myelination, but the mechanisms involved are not fully understood. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a six‐transmembrane enzyme that regulates the activity of surface glycosylphosphatidylinositol (GPI)‐anchored proteins by cleavage of the GPI‐anchor. GDE2 is expressed in neurons where it promotes oligodendrocyte maturation through the release of neuronally‐derived soluble factors. GDE2 is also expressed in oligodendrocytes but the function of oligodendroglial GDE2 is not known.

Results

Using Cre‐lox technology, we generated mice that lack GDE2 expression in oligodendrocytes (O‐Gde2KO). O‐Gde2KOs show normal production and proliferation of oligodendrocyte precursor cells. However, oligodendrocyte maturation is accelerated leading to the robust increase of myelin proteins and increased myelination during development. These in vivo observations are recapitulated in vitro using purified primary oligodendrocytes, supporting cell‐autonomous functions for GDE2 in oligodendrocyte maturation.

Conclusions

These studies reveal that oligodendroglial GDE2 expression is required for controlling the pace of oligodendrocyte maturation. Thus, the cell‐type specific expression of GDE2 is important for the coordination of oligodendrocyte maturation and axonal myelination during neural development.
Cardiopoietic stem cell therapy in ischaemic heart failure: long‐term clinical outcomes
Authors: Bartunek Jozef , Terzic Andre , Davison Beth A. , Behfar Atta , Sanz‐Ruiz Ricardo , Wojakowski Wojciech , Sherman Warren , Heyndrickx Guy R. , Metra Marco , Filippatos Gerasimos S. , Waldman Scott A. , Teerlink John R. , Henry Timothy D. , Gersh Bernard J. , Hajjar Roger , Tendera Michal , Senger Stefanie , Cotter Gad , Povsic Thomas J. , Wijns William ,   for the CHART Program
Published: October 2020

Aims

This study aims to explore long‐term clinical outcomes of cardiopoiesis‐guided stem cell therapy for ischaemic heart failure assessed in the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART‐1) trial.

Methods and results

CHART‐1 is a multinational, randomized, and double‐blind trial conducted in 39 centres in heart failure patients (n = 315) on standard‐of‐care therapy. The ‘active’ group received cardiopoietic stem cells delivered intramyocardially using a retention‐enhanced catheter. The ‘control’ group underwent patient‐level sham procedure. Patients were followed up to 104 weeks. In the entire study population, results of the primary hierarchical composite outcome were maintained neutral at Week 52 [Mann–Whitney estimator 0.52, 95% confidence interval (CI) 0.45–0.59, P = 0.51]. Landmark analyses suggested late clinical benefit in patients with significant left ventricular enlargement receiving adequate dosing. Specifically, beyond 100 days of follow‐up, patients with left ventricular end‐diastolic volume of 200–370 mL treated with ≤19 injections of cardiopoietic stem cells showed reduced risk of death or cardiovascular hospitalization (hazard ratio 0.38, 95% CI 0.16–0.91, P = 0.031) and cardiovascular death or heart failure hospitalization (hazard ratio 0.28, 95% CI 0.09–0.94, P = 0.040). Cardiopoietic stem cell therapy was well tolerated long term with no difference in safety readouts compared with sham at 2 years.

Conclusions

Longitudinal follow‐up documents that cardiopoietic stem cell therapy is overall safe, and post hoc analyses suggest benefit in an ischaemic heart failure subpopulation defined by advanced left ventricular enlargement on tolerable stem cell dosing. The long‐term clinical follow‐up thus offers guidance for future targeted trials.
A simplified transient technique for porosity and permeability determination in tight formations: Numerical simulation and experimental validation
Authors: Li Zequan , Feng Ruimin , Liu Jun , Pandey Rohit
Published: October 2020

A simplified pulse decay method (PDM) with only a single downstream reservoir is proposed to replicate the in situ conditions for reservoir fluid flow, where the pore pressure at any location declines as production continues. The proposed PDM also allows determining the effective porosity and permeability for the core sample under replicated in situ conditions. A mathematical model is firstly established to closely represent the experimental design and verify the feasibility of the method. The analytical solutions of the model are derived to calculate the effective sample porosity and permeability. A series of experiments are then conducted under triaxial stress condition, and a detailed comparison is also made between the PDMs with a single upstream reservoir and a single downstream reservoir. The experimental results showed that accurate measurements on effective sample porosity and permeability can be achieved by the single downstream reservoir PDM due to its capability of better replicating the in situ fluid flow behavior, which extends the application of the transient technique. It is also found that the pore pressure along the sample changes linearly, and its gradient varies with time, indicating the applicability of the single‐reservoir PDMs in permeability determination. This method also lays a foundation for studying flow behavior when a second fluid phase evolves during pressure decline, which occurs in many reservoirs.
Ethanolic extract of okra has a potential gastroprotective effect on acute gastric lesions in Sprague Dawley rats
Authors: Yasin Hafsa , Tariq Farwa , Sameen Aysha , Ahmad Nazir , Manzoor Muhammad Faisal , Yasin Maria , Tariq Tayyaba , Iqbal Muhammad Waheed , Ishfaq Bushra , Mahmood Sana , Siddeeg Azhari
Published: October 2020

Okra (Abelmoschus esculentus) has various bioactive components used for the treatment of different diseases such as gastritis and ulcers. This research aims to examine the anti‐inflammatory and anti‐ulcer attributes of okra extract against gastric lesions. Adult Sprague Dawley male albino rats were divided into five groups. The negative control (G1) received normal feed, positive control (G2) received ulcer‐inducing drug aspirin 150 mg/kg of body weight (b.w), G3 group received reference drug omeprazole 20 mg/kg of b.w, G4 group received okra extract 250 mg/kg of b.w, and G5 group received 500 mg/kg of b.w. Acute gastric damage was induced in G1, G2, G3, and G4 using aspirin 150 mg/kg of b.w, during 14‐day‐long efficacy trials after that all the animals were sacrificed. Anti‐ulcer parameters and histopathological analysis of stomachs were performed to evaluate the degree of recovery against tissue damage by the administration of okra extract. The obtained results indicated that the 500 mg/kg of b.w okra extract exerted a protective effect in aspirin‐induced gastric ulcers by significantly (p < .05) reducing ulcer score, ulcer area, total acidity, and gastric volume, and significantly (p < .05) increasing gastric pH. Moreover, histopathological observation revealed that gastric mucosa was normal in G1, G3, G4, and G5; however, disruptions in the gastric epithelium were observed in G2. Congestion was observed in all groups except G1 and G5. Gastric pits and gastric glands were increased in size in G2 and G4. A higher concentration of okra extract (500 mg/kg of b.w) showed almost similar results when compared to the reference drug omeprazole.
Parental beliefs and willingness to pay for reduction in their child's asthma symptoms: A joint estimation approach
Authors: Mussio Irene , Brandt Sylvia , Hanemann Michael
Published: October 2020

Many aspects of asthma—in particular the relationship between beliefs, averting behaviors, and symptoms—are not directly observable from market data. An approach that combines observable market data with nonmarket valuation to gather data on unobservable aspects of the illness can improve efforts to quantify the burden of asthma if it accounts for the endogeneity in the system. Such approaches are used in the valuation of recreation but have not been widely used to value the burden of a chronic illness. We estimate parents' willingness to pay (WTP) to reduce their child's asthma symptoms using a three‐equation model that combines revealed preference, contingent valuation, and burden of asthma, increasing the efficiency of estimation and correcting for endogeneity. WTP for a device that reduces a child's asthma symptoms by 50% is $125/month (s.d. $20). Parents' valuations are driven by beliefs about asthma and by their degree of worry about asthma between episodes. There is a nonlinear relationship between the number of days with symptoms and WTP per symptom day. The experience of living with asthma affects families' responses to a contingent valuation scenario, because it influences willingness to spend money to manage the illness and their subjective perceptions and beliefs about the illness itself.
All in a day's work: Towards improved understanding of safety leadership during regular safety‐related tasks in mining
Authors: Donovan Sarah‐Louise , Salmon Paul M. , Horberry Tim , Lenné Michael G.
Published: October 2020

This article examines safety leadership during regular safety‐related tasks conducted across a mining work system. Applying a systems‐thinking methodology, a modified version of the critical decision method (CDM) interview technique was used to examine decision‐making and behavior in association with five safety‐related tasks executed across the work system; hazard identification, inspections, standard operating procedure development, task observation and return to work coordination activities. Data were mapped onto Rasmussen's risk management framework to explore the characteristics of safety leadership decision‐making and behavior which occurred across the work system to support successful task execution. Vertical integration was present and was associated with a core set of decision‐making elements and leadership behaviors that facilitated the communication and exchange of information within and across the work system in association with tasks executed. In addition, different profiles of decision‐making characteristics and behavioral engagement were evident at different system levels, which indicated variability in safety leadership was required to support successful task execution across the work system. Task type was found to influence safety leadership, with structured tasks demonstrating less intensive decision‐making and behavioral engagement requirements than unstructured tasks. The findings add to the knowledge base on safety leadership through improved understanding of the concept, its occurrence across tasks and work system levels, and the factors which influence it to support safe system functioning. Future research endeavors and practical implications are discussed.
Preparation and Structural Characterization of [CpRu(1,10‐phenanthroline)(CH3CN)][X] and Precursor Complexes (X=PF6, BArF, TRISPHAT‐N)
Authors: Achard Thierry , Egger Léo , Tortoreto Cecilia , Guénée Laure , Lacour Jérôme
Published: October 2020

Cationic [Ru(η5‐C5H5)(CH3CN)3]+ complex, tris(acetonitrile)(cyclopentadienyl)ruthenium(II), gives rise to a very rich organometallic chemistry. Combined with diimine ligands, and 1,10‐phenanthroline in particular, this system efficiently catalyzes diazo decomposition processes to generate metal‐carbenes which undergo a series of original transformations in the presence of Lewis basic substrates. Herein, syntheses and characterizations of [CpRu(Phen)(L)] complexes with (large) lipophilic non‐coordinating (PF6− and BArF−) and coordinating TRISPHAT‐N− anions are reported. Complex [CpRu(η6‐naphthalene)][BArF] ([1][BArF]) is readily accessible, in high yield, by direct counterion exchange between [1][PF6] and sodium tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate (NaBArF) salts. Ligand exchange of [1][BArF] in acetonitrile generated stable [Ru(η5‐C5H5)(CH3CN)3][BArF] ([2][BArF]) complex in high yield. Then, the desired [CpRu(Phen)(CH3CN)] ([3]) complexes were obtained from either the [1] or [2] complex in the presence of the 1,10‐phenanthroline as ligand. For characterization and comparison purposes, the anionic hemilabile ligand TRISPHAT−N (TTN) was introduced on the ruthenium center, from the complex [3][PF6], to quantitatively generate the desired complex [CpRu(Phen)(TTN)] ([4]) by displacement of the remaining acetonitrile ligand and of the PF6− anion. Solid state structures of complexes [1][BArF], [2][BArF], [3][BArF], [3][PF6] and [4] were determined by X‐ray diffraction studies and are discussed herein.
Effect of dispersion on thermally stable stratified power‐law fluids over the vertical frustum of a cone in a non‐Darcy porous medium: Flow separation
Authors: Chetteti RamReddy , Srivastav Abhinava
Published: October 2020

The present problem shares out the influences of convective heating and thermal dispersion on thermally stable stratified power‐law fluid flow over the vertical frustum of a cone situated in a non‐Darcy porous medium. For the first time, it is considered in both aiding and opposing flow cases as it is readily applicable in realistic, practical situations. The local nonsimilarity approach, along with the spectral local linearization method, is used to analyze the fluid behavior and heat transfer within the boundary layer region. In addition, error analysis and comparison with the existing results are also included to validate the obtained results wherever feasible. It is significant to perceive the existence of flow separation in this study as more gain of the velocity of a power‐law fluid is seen for aiding flow case in comparison with the opposing flow case. Also, it is evident from these results that the separation of flow is less in the presence of thermal stratification, but it is more in the absence of thermal stratification. Finally, thermal stratification significantly affects the heat transfer rate of power‐law fluids besides delaying the boundary layer separation.