bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexible, Wearable Organic Light‐Emitting Fibers Based on PEDOT:PSS/Ag‐Fiber Embedded Hybrid Electrodes for Large‐Area Textile Lighting
Authors: Ko Keum‐Jin , Lee Hock Beng , Kang Jae‐Wook
Published: April 2020

Organic light emitting diodes (OLEDs), which possess wonderful device performance and mechanical robustness have been extensively explored in textile lighting applications. In this work, an ITO‐free, PEDOT:PSS/Ag‐fiber hybrid transparent conducting electrode (TCE) embedded in polymeric substrate (denoted as hybrid‐fiber TCE henceforth) for the fabrication of large‐area OLEDs is designed. The optimum hybrid‐fiber TCE with a pitch of 150 µm shows extraordinarily low sheet resistance (Rsheet = 1.3 Ω ▫−1) and exceptional mechanical flexibility, exhibiting ≈100% Rsheet retention at a bending radius of up to ≈0.5 mm. The device performance of the resulting OLEDs based on hybrid‐fiber TCEs (fiber‐OLEDs) is on‐par with that of ITO‐based OLED analogues. More fascinatingly, organic light emitting fibers (OLEFs), obtained via slitting the fiber‐OLEDs, display a maximum luminance efficiency of ≈38.2 cd A−1 and a maximum external quantum efficiency of ≈10.9%, which surpasses all previously reported results. In addition, the OLEFs are mechanically robust and able to withstand a high degree of deformation, thus can be woven into fabric matrix for smart textile application. The vacuum‐free, scalable fabrication of the high performance OLEFs demonstrated herein is significant for the development of extremely large‐area smart textile applications.
The Role of Electrostatic Interaction between Free Charge Carriers and Counterions in Thermoelectric Power Factor of Conducting Polymers: From Crystalline to Polycrystalline Domains
Authors: Shi Wen , Yildirim Erol , Wu Gang , Wong Zicong Marvin , Deng Tianqi , Wang Jian‐Sheng , Xu Jianwei , Yang Shuo‐Wang
Published: April 2020

One of the most burning problems in organic thermoelectrics is the lack of deep understanding on the key limiting factors of thermoelectric efficiency at different length scales for conducting polymers. Here, by examining a prototypical π‐conjugated polymer, poly(3‐hexylthiophene) from molecular level to crystalline and polycrystalline domains, and on the basis of first‐principles calculations, new insights are presented into the thermoelectric transport in conducting polymers, and new material design guidelines are provided. It is proved that in the crystalline domains of conducting polymers, due to the strong electrostatic interactions between free charge carriers and counterions, the power factor within a wide range of doping level is governed by the counterion‐induced electronic scattering. It is corroborated that in the polycrystalline domains, although the short mean free path prevents the holes undergoing grain‐boundary scatterings, the crystallite orientations relative to the conduction path and the grain sizes strongly affect the power factor, leading to the modulation of the power factor by at least two orders of magnitude.
Methane Adsorption Properties of Mn‐Modified Graphene: A First‐Principles Study
Authors: Zhao Yingjie , Chen Yuhong , Song Mingxia , Liu Xiaocong , Xu Wenhui , Zhang Meiling , Zhang Cairong
Published: April 2020

Graphene (GR), as a 2D carbon nanomaterial with high specific surface area, is one of the primary candidates for energy‐storage applications. In this work, the adsorption properties of graphene and Mn‐modified graphene (Mn‐GR) systems for CH4 molecules are investigated, based on first‐principles density functional theory. It is found that intrinsic graphene adsorbs CH4 molecules weakly. The single side can adsorb up to 4 CH4 molecules, and the average adsorption energy is −0.220 eV per CH4. Mn atom modification can significantly improve the adsorption performance of GR system on CH4. The structure with the largest methane storage capacity is that the GR modified by two Mn atoms that are located in the spacer holes on the opposite sides. The system can adsorb 10 CH4 molecules on both sides, the CH4 adsorption amount can reach 32.93 wt%, and the average adsorption energy is −0.402 eV per CH4. The interaction between the Mn atom and graphene is mainly between the d orbital of the Mn atom and the p orbital of the C atom. After the CH4 molecule is adsorbed, charge transfer occurs between Mn atoms and CH4, which results in a Coulomb attraction and enhances the adsorption performance of CH4 molecules.
Adiponectin attenuates the premature senescence of vascular smooth muscle cells induced by high glucose through mTOR signaling pathway
Authors: Cui Xing‐Jun , Lin Xiao , Zhong Jia‐Yu , Li Shuang , He Jie‐Yu , Ni Yu‐Qing , Zhan Jun‐Kun , Liu You‐Shuo
Published: April 2020

Objective

Cardiovascular diseases and vascular aging are common in patients with diabetes. High glucose is a major cause of vascular aging and cardiovascular diseases. Premature senescence of vascular smooth muscle cells (VSMCs) is one of the main contributors to vascular aging. Adiponectin has been demonstrated to have an anti‐aging effect. The present study explored the mechanisms by which adiponectin protects VSMCs against high‐glucose‐induced senescence.

Methods

Senescence‐associated β‐galactosidase (SA‐β‐gal) staining was used to detect senescence cells. Western blot was used for measuring protein levels. Flow cytometry was carried out to detect the cell cycle and telomeric repeat amplification protocol (TRAP)–polymerase chain reaction (PCR) silver staining was selected to measure the telomerase activity.

Results

Premature senescence of VSMCs was induced by high glucose (30 mM) in a time‐dependent manner, which was verified by an increased number of senescence cells, p21 and p53 expression, as well as the decreased proliferation index. High glucose reduced telomerase activity of VSMCs via inhibition of the AMPK/TSC2/mTOR/S6K1 pathway and activation of the PI3K/Akt/mTOR/S6K1 pathway, while adiponectin treatment significantly increased telomerase activity of VSMCs through activation of AMPK/TSC2/mTOR/S6K1 signaling and inhibition of PI3K/Akt/mTOR/S6K1 signaling.

Conclusion

Adiponectin attenuated the high‐glucose‐induced premature senescence of VSMCs via increasing telomerase activity of VSMCs, which was achieved by activation of AMPK/TSC2/mTOR/S6K1 signaling and inhibition of PI3K/Akt/mTOR/S6K1 signaling.
Topological Phase Transition of Non‐Hermitian Crosslinked Chain
Authors: Zhao X. L. , Chen L. B. , Fu L. B. , Yi X. X.
Published: April 2020

The contents of topological classification of matter are enriched by non‐Hermiticity, such as exceptional points, bulk‐edge correspondence, and skin effects. Physically, gain and loss can be introduced by imaginary on‐site potentials of lattice Hamiltonians, and the topological phase transition for a cross‐linked chain in the presence of such non‐Hermiticity is investigated. The topological phase diagram in terms of a winding number is obtained analytically with phase boundaries coinciding with the surfaces of exceptional points. The topologically original edge states with distribution mainly at the joints between domains of different phases are protected even
for long chains. The non‐Hermitian topological feature can also be reflected by vortex structures in the vector fields of complex eigenenergies, expected values of Pauli matrices, and trajectories of these quantities. This model may be implemented in coupled photonic crystals, fermions trapped in optical lattice, or non‐Hermitian electrical‐circuit lattices, and the edge states are immune to various kinds of disorders until topological phase transition occurs. This work gives insight into the influence of non‐Hermiticity on topological phase of matter.
Transition‐Metal‐Free Carbon Isotope Exchange of Phenyl Acetic Acids
Authors: Destro Gianluca , Horkka Kaisa , Loreau Olivier , Buisson David‐Alexandre , Kingston Lee , Del Vecchio Antonio , Schou Magnus , Elmore Charles S. , Taran Frédéric , Cantat Thibault , Audisio Davide
Published: April 2020

A transition‐metal‐free carbon isotope exchange procedure on phenyl acetic acids is described. Utilizing the universal precursor CO2, this protocol allows the carbon isotope to be inserted into the carboxylic acid position, with no need of precursor synthesis. This procedure enabled the labeling of 15 pharmaceuticals and was compatible with carbon isotopes [14C] and [13C]. A proof of concept with [11C] was also obtained with low molar activity valuable for distribution studies.
Molecular Expansion for Constructing Porous Organic Polymers with High Surface Areas and Well‐Defined Nanopores
Authors: Liu Yuchuan , Wang Shun , Meng Xianyu , Ye Yu , Song Xiaowei , Liang Zhiqiang , Zhao Yanli
Published: April 2020

Construction of porous organic polymers (POPs) with high surface areas, well‐defined nanopores, and excellent stability remains extremely challenging because of the unmanageable reaction process. Until now, only a few reported POPs have Brunauer‐Emmett‐Teller (BET) surface areas (SBET) exceeding 3000 m2 g−1. Herein, we demonstrate a molecular expansion strategy to integrate high surface areas, large nanopore sizes, and outstanding stability into POPs. A series of hyper‐crosslinked conjugated polymers (HCCPs) with exceptional porosity are synthesized through this strategy. Specially, HCCP‐6 and HCCP‐11 exhibit the highest surface areas (SBET >3000 m2 g−1) and excellent total pore volumes (up to 3.98 cm3 g−1) among these HCCPs. They present decent total CH4 storage capacities of 491 and 421 mg g−1 at 80 bar and 298 K, respectively. Meanwhile, they are highly stable in harsh environments. The facile and general molecular expansion strategy would lead to improved synthetic routes of POPs for desired functions.
Aufbau‐ und Abbaureaktionen von weißem Phosphor induziert durch N‐heterocyclische Carbenkomplexe von Nickel(0)
Authors: Hierlmeier Gabriele , Coburger Peter , van Leest Nicolaas P. , de Bruin Bas , Wolf Robert
Published: April 2020

Die Reaktion von Nickel(0)‐Verbindungen mit weißem Phosphor (P4) ist eine kaum erforschte Syntheseroute für binäre Nickelphosphidcluster. Wir zeigen, dass die Reaktion von P4 mit koordinativ und elektronisch ungesättigten N‐heterocyclischen Carbenkomplexen von Nickel(0) die Darstellung ungewöhnlicher Clusterverbindungen mit P1‐, P3‐, P5‐ und P8‐Einheiten ermöglicht. Die Verwendung von [Ni(IMes)2] [IMes=1,3‐Bis(2,4,6‐trimethylphenyl)imidazolin‐2‐yliden] führt zu Spezies mit Ni3P4‐ und Ni3P6 Gerüst, die als superhypercloso‐ bzw. hypercloso‐Cluster beschrieben werden können. Komplexe mit sterisch anspruchsvolleren Carbenliganden [Ni(IPr)2] bzw. [(IPr)Ni(η6‐Toluol) [IPr=1,3‐Bis(2,6‐diisopropylphenyl)imidazolin‐2‐yliden] führen hingegen zur Synthese eines closo‐Ni3P8‐Clusters. Die inversen Sandwichkomplexe [(NHC)2Ni2P5] (NHC=IMes, IPr) mit einem aromatischen cyclo‐P5−‐Liganden wurden als weitere Reaktionsprodukte identifiziert.
Synthesis of All‐Carbon Disubstituted Bicyclo[1.1.1]pentanes by Iron‐Catalyzed Kumada Cross‐Coupling
Authors: Nugent Jeremy , Shire Bethany R. , Caputo Dimitri F. J. , Pickford Helena D. , Nightingale Frank , Houlsby Ian T. T. , Mousseau James J. , Anderson Edward A.
Published: April 2020

1,3‐Disubstituted bicyclo[1.1.1]pentanes (BCPs) are important motifs in drug design as surrogates for p‐substituted arenes and alkynes. Access to all‐carbon disubstituted BCPs via cross‐coupling has to date been limited to use of the BCP as the organometallic component, which restricts scope due to the harsh conditions typically required for the synthesis of metallated BCPs. Here we report a general method to access 1,3‐C‐disubstituted BCPs from 1‐iodo‐bicyclo[1.1.1]pentanes (iodo‐BCPs) by direct iron‐catalyzed cross‐coupling with aryl and heteroaryl Grignard reagents. This chemistry represents the first general use of iodo‐BCPs as electrophiles in cross‐coupling, and the first Kumada coupling of tertiary iodides. Benefiting from short reaction times, mild conditions, and broad scope of the coupling partners, it enables the synthesis of a wide range of 1,3‐C‐disubstituted BCPs including various drug analogues.
Experimental Determination of Magnetic Anisotropy in Exchange‐Bias Dysprosium Metallocene Single‐Molecule Magnets
Authors: Meng Yin‐Shan , Xiong Jin , Yang Mu‐Wen , Qiao Yu‐Sen , Zhong Zhi‐Qiang , Sun Hao‐Ling , Han Jun‐Bo , Liu Tao , Wang Bing‐Wu , Gao Song
Published: April 2020

We investigate a family of dinuclear dysprosium metallocene single‐molecule magnets (SMMs) bridged by methyl and halogen groups [Cp′2Dy(μ‐X)]2 (Cp′=cyclopentadienyltrimethylsilane anion; 1: X=CH3−; 2: X=Cl−; 3: X=Br−; 4: X=I−). For the first time, the magnetic easy axes of dysprosium metallocene SMMs are experimentally determined, confirming that the orientation of them are perpendicular to the equatorial plane which is made up of dysprosium and bridging atoms. The orientation of the magnetic easy axis for 1 deviates from the normal direction (by 10.3°) due to the stronger equatorial interactions between DyIII and methyl groups. Moreover, its magnetic axes show a temperature‐dependent shifting, which is caused by the competition between exchange interactions and Zeeman interactions. Studies of fluorescence and specific heat as well as ab initio calculations reveal the significant influences of the bridging ligands on their low‐lying exchange‐based energy levels and, consequently, low‐temperature magnetic properties.
Formation of Hierarchical FeCoS2–CoS2 Double‐Shelled Nanotubes with Enhanced Performance for Photocatalytic Reduction of CO2
Authors: Wang Yan , Wang Sibo , Zhang Song Lin , Lou Xiong Wen (David)
Published: April 2020

Hierarchical FeCoS2–CoS2 double‐shelled nanotubes have been rationally designed and constructed for efficient photocatalytic CO2 reduction under visible light. The synthetic strategy, engaging the two‐step cation‐exchange reactions, precisely integrates two metal sulfides into a double‐shelled tubular heterostructure with both of the shells assembled from ultrathin two‐dimensional (2D) nanosheets. Benefiting from the distinctive structure and composition, the FeCoS2–CoS2 hybrid can reduce bulk‐to‐surface diffusion length of photoexcited charge carriers to facilitate their separation. Furthermore, this hybrid structure can expose abundant active sites for enhancing CO2 adsorption and surface‐dependent redox reactions, and harvest incident solar irradiation more efficiently by light scattering in the complex interior. As a result, these hierarchical FeCoS2–CoS2 double‐shelled nanotubes exhibit superior activity and high stability for photosensitized deoxygenative CO2 reduction, affording a high CO‐generating rate of 28.1 μmol h−1 (per 0.5 mg of catalyst).
Fast Hydrocarbon Oxidation by a High‐Valent Nickel–Fluoride Complex
Authors: Mondal Prasenjit , Lovisari Marta , Twamley Brendan , McDonald Aidan R.
Published: April 2020

In the search for highly reactive oxidants we have identified high‐valent metal–fluorides as a potential potent oxidant. The high‐valent Ni–F complex [NiIII(F)(L)] (2, L=N,N′‐(2,6‐dimethylphenyl)‐2,6‐pyridinedicarboxamidate) was prepared from [NiII(F)(L)]− (1) by oxidation with selectfluor. Complexes 1 and 2 were characterized by using 1H/19F NMR, UV‐vis, and EPR spectroscopies, mass spectrometry, and X‐ray crystallography. Complex 2 was found to be a highly reactive oxidant in the oxidation of hydrocarbons. Kinetic data and products analysis demonstrate a hydrogen atom transfer mechanism of oxidation. The rate constant determined for the oxidation of 9,10‐dihydroanthracene (k2=29 m−1 s−1) compared favorably with the most reactive high‐valent metallo‐oxidants. Complex 2 displayed reaction rates 2000–4500‐fold enhanced with respect to [NiIII(Cl)(L)] and also displayed high kinetic isotope effect values. Oxidative hydrocarbon and phosphine fluorination was achieved. Our results provide an interesting direction in designing catalysts for hydrocarbon oxidation and fluorination
Enhanced Multiple Anchoring and Catalytic Conversion of Polysulfides by Amorphous MoS3 Nanoboxes for High‐Performance Li‐S Batteries
Authors: Yu Jian , Xiao Jiewen , Li Anran , Yang Zhao , Zeng Liang , Zhang Qianfan , Zhu Yujie , Guo Lin
Published: April 2020

The practical implementation of lithium–sulfur batteries is obstructed by poor conductivity, sluggish redox kinetics, the shuttle effect, large volume variation, and low areal loading of sulfur electrodes. Now, amorphous N‐doped carbon/MoS3 (NC/MoS3) nanoboxes with hollow porous architectures have been meticulously designed as an advanced sulfur host. Benefiting from the enhanced conductivity by the N‐doped carbon, reduced shuttle effect by the strong chemical interaction between unsaturated Mo and lithium polysulfides, improved redox reaction kinetics by the catalytic effect of MoS3, great tolerance of volume variation and high sulfur loading arising from flexible amorphous materials with hollow‐porous structures, the amorphous NC/MoS3 nanoboxes enabled sulfur electrodes to deliver a high areal capacity with superior rate capacity and decent cycling stability. The synthetic strategy can be generalized to fabricate other amorphous metal sulfide nanoboxes.
Rhodiumkatalysierte elektrooxidative C‐H‐Olefinierung von Benzamiden
Authors: Zhang Yan , Struwe Julia , Ackermann Lutz
Published: April 2020

Metallkatalysierte, Chelat‐unterstützte C‐H‐Olefinierungen haben sich zu einem leistungsstarken Werkzeug für die Herstellung von funktionalisierten Alkenen entwickelt. Nun beschreiben wir die rhodaelektrokatalysierte C‐H‐Aktivierung/Alkenylierung von Arenen. Die Olefinierung von herausfordernden, elektronenarmen Benzamiden verläuft unter elektrochemischen Bedingungen ausschließlich nach einem dehydrierenden Mechanismus und vermeidet den Einsatz eines chemischen Oxidationsmittels in stöchiometrischer Menge, sodass H2 als einziges Koppelprodukt gebildet wird. Die vielfältige Alkenylierungsreaktion mit elektrischen Strom als “grünem” Oxidationsmittel weist ein breites Anwendungsspektrum auf.
Enantioselective Synthesis of 3‐Fluorochromanes via Iodine(I)/Iodine(III) Catalysis
Authors: Sarie Jérôme C. , Thiehoff Christian , Neufeld Jessica , Daniliuc Constantin G. , Gilmour Ryan
Published: April 2020

The chromane nucleus is common to a plenum of bioactive small molecules where it is frequently oxidized at position 3. Motivated by the importance of this position in conferring efficacy, and the prominence of bioisosterism in drug discovery, an iodine(I)/iodine(III) catalysis strategy to access enantioenriched 3‐fluorochromanes is disclosed (up to 7:93 e.r.). In situ generation of ArIF2 enables the direct fluorocyclization of allyl phenyl ethers to generate novel scaffolds that manifest the stereoelectronic gauche effect. Mechanistic interrogation using deuterated probes confirms a stereospecific process consistent with a type IIinv pathway.
Rhodium‐Catalyzed Electrooxidative C−H Olefination of Benzamides
Authors: Zhang Yan , Struwe Julia , Ackermann Lutz
Published: April 2020

Metal‐catalyzed chelation‐assisted C−H olefinations have emerged as powerful tools for the construction of functionalized alkenes. Herein, we describe the rhoda‐electrocatalyzed C−H activation/alkenylation of arenes. The olefinations of challenging electron‐poor benzamides were thus accomplished in a fully dehydrogenative fashion under electrochemical conditions, avoiding stoichiometric chemical oxidants, and with H2 as the only byproduct. This versatile alkenylation reaction also features broad substrate scope and used electricity as a green oxidant.
CeO2/CuO@N‐GQDs@NH2 nanocomposite as a high‐performance catalyst for the synthesis of benzo[g]chromenes
Authors: Safaei‐Ghomi Javad , Bateni Fatemeh‐Sadat , Babaei Pouria
Published: April 2020

A three‐component reaction of aromatic aldehydes, malononitrile or ethyl cyanoacetate and 2‐hydroxy‐1,4‐naphthaquinone has been achieved in the presence of an amino‐functionalized CeO2/CuO@ nitrogen graphene quantum dot nanocomposite as a highly effective heterogeneous catalyst to produce benzo[g]chromenes. The catalyst has been characterized by X‐ray diffraction, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared, energy‐dispersive X‐ray spectroscopy, thermogravimetric analysis, X‐ray photoelectron spectroscopy, Brunauer‐Emmett‐Teller (BET) and vibrating sample magnetometry. This new catalyst has been demonstrated to be highly effective in the preparation of benzo[g]chromenes.
Forward‐backward doubly stochastic differential equations with random jumps and related games
Authors: Zhu Qingfeng , Shi Yufeng , Teng Bin
Published: April 2020

A type of forward‐backward doubly stochastic differential equations driven by Brownian motions and the Poisson process (FBDSDEP) is studied. Under some monotonicity assumptions, the existence and uniqueness results for measurable solutions of FBDSDEP are established via a method of continuation. Then the continuity and differentiability of the solutions to FBDSDEP depending on parameters is discussed. Furthermore, these results were applied to backward doubly stochastic linear quadratic (LQ) nonzero sum differential games with random jumps to get the explicit form of the open‐loop Nash equilibrium point by the solution of the FBDSDEP.
Ganzglaskonstruktion für das Dach des Pützerturms der TU Darmstadt
Authors: Schula Sebastian , Schneider Jens
Published: April 2020

Vor über 75 Jahren wurde die Pützerturmhaube des Uhrturms der Technischen Universität Darmstadt in der Brandnacht vom 11. September 1944 zerstört. Seitdem präsentiert sich der ehemalige Uhrturm als Stumpf am zentralen Standort der Universität. Dem Entwurf von Walter & Sichau Architekten folgend erhielt der Turm nun einen neuen Turmabschluss in moderner Formsprache. Die als absturzsichernde Ganzglaskonstruktion ausgeführte Konstruktion greift die Anpassungen an die baulichen Veränderungen der Nachkriegszeit auf und fügt sich so in das Gebäudeensemble ein. Die aus lediglich vier großformatigen und etwa jeweils 2 t schweren Glaselementen bestehende Konstruktion folgt dem Trend immer größerer Ganzglasanwendungen. Im vorliegenden Beitrag werden die Konstruktionseigenschaften beschrieben und an diesem Beispiel die objektspezifischen Abweichungen zu den technischen Baubestimmungen und die hiermit wesentlich verbundenen erforderlichen Nachweise aufgezeigt, welche schlussendlich eine vorhabenbezogene Bauartgenehmigung (vBG) ermöglichten.
Effects of Inferred Gender on Patterns of Co‐Authorship in Ecology and Evolutionary Biology Publications
Authors: Frances Dachin N. , Fitzpatrick Connor R. , Koprivnikar Janet , McCauley Shannon J.
Published: April 2020

Senior positions in academia such as tenured faculty and editorial positions often exhibit large gender imbalances across a broad range of research disciplines. The forces driving these imbalances have been the subject of extensive speculation and a more modest body of research. Given the central role publications play in determining individual outcomes and progress in academic settings, unequal patterns of authorship across gender could be a potent driver of observed gender imbalance in academia. Here, we investigate patterns of co‐authorship across four journals in ecology and evolutionary biology at four time‐points spanning four decades. Co‐authorship patterns are of interest because collaborations are important in scientific research, affecting individual researcher productivity, and increasingly, funding opportunities. Based on inferred gender from set criteria, we found significant differences between male and female researchers in their tendency to publish with female co‐authors. Specifically, compared to women, male researchers in the last author position were more likely to co‐author papers with other males. While we did find that the proportion of female co‐authors has increased modestly over the last thirty years, this is strongly correlated with an increase in the average number of authors per paper over time. Additionally, the proportion of female co‐authors on papers remains well below the proportion of PhDs awarded to females in biology.
The Vertebrate Tooth Row: Is It Initiated by a Single Organizing Tooth?
Authors: Sadier Alexa , Jackman William R. , Laudet Vincent , Gibert Yann
Published: April 2020

Teeth are one of the most fascinating innovations of vertebrates. Their diversity of shape, size, location, and number in vertebrates is astonishing. If the molecular mechanisms underlying the morphogenesis of individual teeth are now relatively well understood, thanks to the detailed experimental work that has been performed in model organisms (mainly mouse and zebrafish), the mechanisms that control the organization of the dentition are still a mystery. Mammals display simplified dentitions when compared to other vertebrates with only a single tooth row positioned in the anterior part of the mouth, whereas other vertebrates exhibit tooth rows in many locations. As proposed 60 years ago, tooth rows can be formed sequentially from an initiator tooth. Recent results in zebrafish have now largely confirmed this hypothesis. Here this observation is generalized upon and it is suggested that in most vertebrates tooth rows could form sequentially from a single initiator tooth.
The area between ROC curves, a non‐parametric method to evaluate a biomarker for patient treatment selection
Authors: Blangero Yoann , Rabilloud Muriel , Laurent‐Puig Pierre , Le Malicot Karine , Lepage Côme , Ecochard René , Taieb Julien , Subtil Fabien
Published: April 2020

Treatment selection markers are generally sought for when the benefit of an innovative treatment in comparison with a reference treatment is considered, and this benefit is suspected to vary according to the characteristics of the patients. Classically, such quantitative markers are detected through testing a marker‐by‐treatment interaction in a parametric regression model. Most alternative methods rely on modeling the risk of event occurrence in each treatment arm or the benefit of the innovative treatment over the marker values, but with assumptions that may be difficult to verify. Herein, a simple non‐parametric approach is proposed to detect and assess the general capacity of a quantitative marker for treatment selection when no overall difference in efficacy could be demonstrated between two treatments in a clinical trial. This graphical method relies on the area between treatment‐arm‐specific receiver operating characteristic curves (ABC), which reflects the treatment selection capacity of the marker. A simulation study assessed the inference properties of the ABC estimator and compared them with other parametric and non‐parametric indicators. The simulations showed that the estimate of the ABC had low bias, power comparable to parametric indicators, and that its confidence interval had a good coverage probability (better than the other non‐parametric indicator in some cases). Thus, the ABC is a good alternative to parametric indicators. The ABC method was applied to data of the PETACC‐8 trial that investigated FOLFOX4 versus FOLFOX4 + cetuximab in stage III colon adenocarcinoma. It enabled the detection of a treatment selection marker: theDDR2 gene.
A doubly auxotrophic CHO‐K1 cell line for the production of recombinant monoclonal antibodies
Authors: Zhang Qinghao , Jiang Bo , Du Zhimei , Chasin Lawrence A.
Published: April 2020

Chinese hamster ovary (CHO) cells are the most widely used mammalian hosts for recombinant protein production due to their hardiness, ease of transfection, and production of glycan structures similar to those in natural human monoclonal antibodies. To enhance the usefulness of CHO‐K1 cells we developed a new selection system based on double auxotrophy. We used CRISPR‐Cas9 to knockout the genes that encode the bifunctional enzymes catalyzing the last two steps in the de novo synthesis of pyrimidines and purines (uridine monophosphate synthase and 5‐aminoimidazole‐4‐carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase [ATIC], respectively). Survival of these doubly auxotrophic cells depends on the provision of sources of purines and pyrimidines or on the transfection and integration of open reading frames encoding these two enzymes. We successfully used one such double auxotroph (UA10) to select for stable transfectants carrying (a) the recombinant tumor necrosis factor‐α receptor fusion protein etanercept and (b) the heavy and light chains of the anti‐Her2 monoclonal antibody trastuzumab. Transfectant clones produced these recombinant proteins in a stable manner and in substantial amounts. The availability of this double auxotroph provides a rapid and efficient selection method for the serial or simultaneous transfer of genes for multiple polypeptides of choice into CHO cells using readily available purine‐ and pyrimidine‐free commercial media.
Tangential flow filtration of haptoglobin
Authors: Pires Ivan S. , Palmer Andre F.
Published: April 2020

Haptoglobin (Hp) is a plasma glycoprotein that scavenges cell‐free hemoglobin (Hb). Hp has various potential therapeutic applications, but it has been mainly studied for treatment of acute hemolytic conditions that can arise from situations such as massive blood transfusion, infusion of stored red blood cells, severe burns, trauma, sepsis, radiation injury, and others. Therefore, Hp may also be beneficial during chronic hemolytic disease states such as hereditary spherocytosis, nocturnal hemoglobinuria, sickle‐cell anemia, and malaria. Various methods have been developed to purify Hp from plasma or plasma fractions. However, none of these methods have exploited the large molecular weight (MW) range distribution of Hp polymers to easily isolate Hp from other plasma proteins. The present study used tangential flow filtration (TFF) to isolate polymeric Hp from plasma proteins using human Fraction IV (FIV) as the starting material. After removal of insoluble material from a suspension of FIV paste, the protein mixture was clarified on a 0.2 μm hollow fiber (HF) TFF filter. The clarified protein solution was then bracketed based on protein MW using HF filters with MW cut‐offs (MWCOs) of 750, 500, and 100 kDa. Using untreated FIV, the Hp purity of the main bracket was ~75% with a total Hb binding capacity (HbBC) yield of 1.2 g starting from 500 g of FIV paste. However, pretreatment of FIV with fumed silica to remove lipoproteins increased Hp purity to >95% with a HbBC yield of 1.7 g per 500 g of FIV. Taken together this study provides a novel and scalable method to purify Hp from plasma or plasma fractions.
Computer‐aided 3D analysis of anatomy and radiographic parameters of the distal radius
Authors: Suojärvi Nora , Tampio Juha , Lindfors Nina , Waris Eero
Published: April 2020

Introduction

This study applied mathematical modeling to examine the anatomy of the distal radius; to define the radiographic parameters in a 3D imaging modality; and to report their normal ranges in the uninjured radius.

Materials and methods

A series of 50 cone‐beam computed tomography (CBCT) scans of uninjured radii were analyzed using computer‐aided image processing. The radius shape model was used to determine the optimal location for measuring the longitudinal axis. With the axis determined, the volar tilt and radial inclination angles and the areas of the articular facets and their reference points were analyzed.

Results

The optimal location for determining the longitudinal axis was between 28.8 and 53.3 mm proximally from the articular surface. The mean radial inclination angle was 21.8°. The mean volar tilt angle via the most distal tips of the volar and dorsal rims was 13.0°; along the lunate and scaphoid facets it was 9.1° and 11.2°, respectively. The scaphoid facet was larger than the lunate facet and 25% of it was convex.

Conclusions

Computer‐aided CBCT image processing offers an advanced tool to record 3D geometry and the radiographic parameters of the osseous structures of the wrist. Analysis of the distal radius' anatomy showed that the longitudinal axis was affected by its measurement location and subsequently also affected the determination of the angular parameters. We also report the variation of the volar tilt along the articular surface and the shapes and sizes of the articular facets.
The underlying mechanisms of lorlatinib penetration across the blood‐brain barrier and the distribution characteristics of lorlatinib in the brain
Authors: Chen Wei , Jin Dujia , Shi Yafei , Zhang Yujun , Zhou Haiyan , Li Guohui
Published: April 2020

Objective

To clarify the distribution of lorlatinib in the brain and elucidate the molecular mechanisms of lorlatinib penetration across the blood‐brain barrier (BBB).

Methods

Cytological experiments were performed to investigate the growth inhibitory effect of lorlatinib on different cells (endothelial cells HUVEC, HMEC‐1, and HCMEC/D3) and to investigate the protective effect of lorlatinib on neuronal cells after SH‐SY5Y hypoxia/reoxygenation injury. Furthermore, rat brain tissue was sequenced, and the differentially expressed genes (secreted phosphoprotein 1 (SPP1), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF‐β), Claudin, ZO‐1 and P‐gp) in several different drug treatment groups were verified by Real‐Time PCR. Lorlatinib brain distribution was predicted by physiologically based pharmacokinetics (PBPK).

Results

Lorlatinib and crizotinib both had inhibitory effects on endothelial cells, however lorlatinib inhibited the growth of HCMEC/D3 more efficaciously than crizotinib. In the SH‐SY5Y hypoxia model, lorlatinib had a greater protective effect on nerve cell damage caused by hypoxia and reoxygenation than crizotinib. The expression of SPP1, VEGF, TGF‐β, and Claudin in brain tissue was significantly downregulated after lorlatinib administration, and the expression level of early growth transcription factor 1 (Egr‐1) was significantly increased. The PBPK model successfully described lorlatinib concentrations in blood and brain tissue in the mouse model and gave a brain tissue partition coefficient of 0.7.

Conclusion

Lorlatinib can increase the permeability of the blood‐brain barrier whereby we suggest its underlying working mechanism is related to downregulating SPP1, inhibiting VEGF, TGF‐β, and Claudin subsequently reducing the number of tight junctions between BBB cells. Lorlatinib plays a protective role on injured nerve cells and does not change the amount of P‐gp expression in brain tissue, which may be important for its ability to be efficacious across the BBB with a low incidence of resistance.
MiR‐646 suppresses proliferation and metastasis of non‐small cell lung cancer by repressing FGF2 and CCND2
Authors: Wang Jing , Shu Huizhen , Guo Shuigen
Published: April 2020

MicroRNA‐646 (miR‐646) has been implicated in several other cancers; however, its functional mechanism in non‐small cell lung cancer (NSCLC) remains unclear. In this study, we observed the downregulation of miR‐646 expression in NSCLC tissues and cell lines. Low‐level expression of miR‐646 was associated with metastasis and stage of NSCLCs. Functional assays showed that overexpression of miR‐646 could suppress NSCLC cell proliferation, clonogenicity, invasion, and inhibit epithelial‐mesenchymal transition (EMT), whereas decreased miR‐646 expression showed the opposite effects. Importantly, miR‐646 overexpression attenuated in vivo tumor growth and metastasis in nude mice models. Mechanically, miR‐646 directly targeted and suppressed fibroblast growth factor 2 (FGF2) and cyclin D2 (CCND2) expression. Reintroduction of FGF2 and CCND2 attenuated miR‐646‐mediated suppression of proliferation and invasion in NSCLC. Collectively, these results demonstrate that miR‐646 acts as a tumor suppressor in NSCLC by targeting FGF2 and CCND2, and may serve as a therapeutic target for patients with NSCLC.
Ammonium‐Charged Sterically Hindered Phenols with Antioxidant and Selective Anti‐Gram‐Positive Bacterial Activity
Authors: Bogdanov Andrei V. , Iskhakova Kamilla R. , Voloshina Alexandra D. , Sapunova Anastasia S. , Kulik Natalia V. , Terekhova Natalia V. , Arsenyev Maxim V. , Ziyatdinova Guzel K. , Bukharov Sergey V.
Published: April 2020

The increase in the resistance of pathogens, in particular Staphylococcus aureus, to the action of antibiotics necessitates the search for new readily available and non‐toxic drugs. In solving this problem, phenolic acylhydrazones have high potential. In this communication, the synthesis of quaternary ammonium compounds containing a differently substituted phenolic moiety has been performed. An initial study of antimicrobial activity showed that these compounds are highly selective against S. aureus and B. cereus. The highest activity (MIC 2.0 μm) was shown by hydrazones containing a catechol fragment. These compounds are more than 3‐fold more active against S. aureus and 3–10‐fold more active against B. cereus than norfloxacin. Low hemolytic and high antioxidant activities of all new compounds were also established.
The experience of treating patients with acute myocardial infarction under the COVID‐19 epidemic
Authors: Xiao Zhichao , Xu Chang , Wang Daowen , Zeng Hesong
Published: April 2020

Worldwide Coronavirus Disease 2019 (COVID‐19) epidemic makes the management of acute myocardial infarction (AMI) more complicated, effective treatment without further dissemination is thus quite challenging. Recently, we successfully treated three representative AMI cases, by sharing these detailed procedures, we summarized some important issues including patient screening, reperfusion strategy selecting, personnel/catheter lab protection principle, as well as operation tactics, which may lend precious experience on AMI treating during the ongoing COVID‐19 pandemic situation.
Breast cancer patient advocacy: A qualitative study of the challenges and opportunities for civil society organizations in low‐income and middle‐income countries
Authors: Dvaladze Allison , Kizub Darya A. , Cabanes Anna , Nakigudde Gertrude , Aguilar Bertha , Zujewski Jo Anne , Duggan Catherine , Anderson Benjamin O. , Pritam Singh R. K. , Gralow Julie R.
Published: April 2020

Background

Breast cancer advocacy movements, driven by advocate‐led civil society organizations (CSOs), have proven to be a powerful force for the advancement of cancer control in high‐income countries (HICs). However, although patient advocacy movements are growing in low‐income and middle‐income countries (LMICs) in response to an increasing cancer burden, the experiences and needs of advocate‐led breast cancer CSOs in LMICs is understudied.

Methods

The authors conducted a qualitative study using in‐depth interviews and focus group discussions with 98 participants representing 23 LMICs in Eastern Europe, Central Asia, East and Southern Africa, and Latin America.

Results

Despite geographic, cultural, and socioeconomic differences, the common themes that emerged from the data across the 3 regions are strikingly similar: trust, knowledge gaps, stigma, sharing experiences, and sustainability. The authors identified common facilitators (training/education, relationship building/networking, third‐party facilitators, and communication) and barriers (mistrust, stigma, organizational fragility, difficulty translating HIC strategies) to establishing trust, collaboration, and advancing cancer advocacy efforts. To the authors' knowledge, the current study is the first to describe the role that coalitions and regional networks play in advancing breast cancer advocacy in LMICs across multiple regions.

Conclusions

The findings of the current study corroborate the importance of investing in 3‐way partnerships between CSOs, political leaders, and health experts. When provided with information that is evidence‐based and resource appropriate, as well as opportunities to network, advocates are better equipped to achieve their goals. The authors propose that support for CSOs focuses on building trust through increasing opportunities for engagement, disseminating best practices and evidence‐based information, and fostering the creation of platforms for partnerships and networks.
Can pathology diagnostic services for cancer be stratified and serve global health?
Authors: Anglade Fabienne , Milner Danny A. , Brock Jane E.
Published: April 2020

Background

Before initiating cancer therapy, a diagnostic tumor tissue sample evaluated within a pathology laboratory by a pathologist is essential to confirm the malignancy type and provide key prognostic factors that direct the treatment offered.

Methods

Pathology evaluation includes multiple expensive reagents, complex equipment, and both laboratory and pathologist technical skills. By using breast cancer as an example, at a minimum, key tumor prognostic information required before the initiation of treatment includes subtype, tumor grade, tumor size, lymph node status when possible, and biomarker expression determined by immunohistochemistry for estrogen receptor. The additional determination of biomarker expression of progesterone receptor and human epidermal growth factor receptor (HER2) is the standard of care in high‐resource settings, but assays may not be affordable in low‐income and middle‐income countries.

Results

With positive tests, patients are eligible for either tamoxifen (for estrogen receptor‐positive/progesterone receptor‐positive cancers) or monoclonal antibody therapy (for HER2‐positive cancers). For settings in which endocrine therapy and/or HER2‐targeted therapy is unavailable, biomarker studies have no utility, and high‐resource setting standards for pathology evaluation and reporting are unachievable. Resource‐stratified pathology evaluation guidelines in cancer diagnosis have not been developed, in contrast to excellent comprehensive, resource‐stratified clinical guidelines for use in low‐income and middle‐income countries, and these are long overdue.

Conclusions

The challenges of pathology evaluation in the context of global health are being met by innovative solutions, which may change the face of pathology practice.
Situational analysis of breast health care systems: Why context matters
Authors: Duggan Catherine , Dvaladze Allison , Scheel John R. , Stevens Lisa M. , Anderson Benjamin O.
Published: April 2020

Background

Implementation of evidence‐based, resource‐appropriate guidelines for breast cancer control should be preceded by a baseline assessment or situational analysis to assess breast health infrastructure, workforce capacity, patient pathways, existing practices, accessibility, and costs.

Methods

To support the assessment of breast health care systems within the broader context in which they exist, the Breast Health Global Initiative (BHGI) developed, tested, and refined a set of situational analysis tools with which to guide the assessment of breast health care capacity, identify the relative strengths and weaknesses of the health system, and support stakeholders in prioritizing actionable items to advance breast cancer care using evidence‐based strategies tailored to their setting. The tools address 6 domains of breast health care delivery: 1) breast cancer early detection practices; 2) breast cancer awareness programs; 3) the availability of breast cancer surgery; 4) the availability of pathology; 5) the availability of radiotherapy, and 6) the availability of systemic therapy services. The current study also describes the more comprehensive International Atomic Energy Agency Programme of Action for Cancer Therapy (PACT) integrated missions for PACT (imPACT) review.

Results

As of 2020, 5 formal BHGI situational analyses have been performed in India, Brazil, Panama, Tanzania, and Uganda. As of August 2019, a total of 100 imPACT reviews have been conducted in 91 countries. These assessments can contribute to more informed policymaking.

Conclusions

Situational analyses are a prerequisite for the development of resource‐appropriate strategies with which to advance breast cancer control in any setting and should assess services across the entire breast health care continuum as well as the broader structural, sociocultural, personal, and financial contexts within which they operate.
Distributed service‐level agreement management with smart contracts and blockchain
Authors: Uriarte Rafael Brundo , Zhou Huan , Kritikos Kyriakos , Shi Zeshun , Zhao Zhiming , De Nicola Rocco
Published: April 2020

The current cloud market is dominated by a few providers, which offer cloud services in a take‐it‐or‐leave‐it manner. However, the dynamism and uncertainty of cloud environments may require the change over time of both application requirements and service capabilities. The current service‐level agreement (SLA) management solutions cannot easily guarantee a trustworthy, distributed SLA adaptation due to the centralized authority of the cloud provider who could also misbehave to pursue individual goals. To address the above issues, we propose a novel SLA management framework, which facilitates the specification and enforcement of dynamic SLAs that enable one to describe how, and under which conditions, the offered service level can change over time. The proposed framework relies on a two‐level blockchain architecture. At the first level, the smart SLA is transformed into a smart contract that dynamically guides service provisioning. At the second level, a permissioned blockchain is built through a federation of monitoring entities to generate objective measurements for the smart SLA/contract assessment. The scalability of this permissioned blockchain is also thoroughly evaluated. The proposed framework enables creating open distributed clouds, which offer manageable and dynamic services, and facilitates cost reduction for cloud consumers, while it increases flexibility in resource management and trust in the offered cloud services.
Development of sex‐linked SSR marker in the genus Phoenix and validation in P. dactylifera
Authors: Wang Yong , Ihase Leonard O. , Htwe Yin M. , Shi Peng , Zhang Dapeng , Li Dongxia , Emoghene Beatrice O. , Iserhienrhien Anthony
Published: April 2020

Species in the genus Phoenix are dioecious, requiring 5–10 yr for sex determination of individuals raised from seeds. Date palm (Phoenix dactylifera L.), an important member of the genus, is grown for food in Middle East, whereas Khejur palm [Phoenix sylvestris (L.) Roxb.] is widely used as a source of sugar in India and also as an ornamental plant in China. Availability of an accurate method for sex determination of male and female individuals at the nursery stage is highly desirable. We designed polymerase chain reaction (PCR) primers flanking simple sequence repeats (SSRs) found on the whole‐genome shotgun sequences of Phoenix. Also, three previously reported sex‐linked markers were included. Markers mPdIRDP52 and DPM4 proved to be sex linked, as they were 100% accurate and efficient for sex determination. Marker DPM4, unlike the previous markers, showed distinct bands for both “X” and “Y” alleles and proved to be very efficient in sex determination. Validation of the marker using F1 population (192 palms) revealed accurate conformity with phenotype data. The predicted protein sequence of the amplification product of primer DPM4 revealed four open reading frames (ORFs). Basic local alignment search tool (BLAST) analyses showed similarity with some regions in organisms known to exhibit gender genes. Male palms showed a single melt peak in quantitative PCR (qPCR), as opposed to the female palms that showed two closely related melt peaks. Marker DPM4 has been validated with 192 full‐sib palms of known phenotype for the sex gene and proven efficient for marker‐assisted selection of male and female palms in seedling propagation and popularization in Phoenix spp.