bluuebunny/crossref_metadata_2025 huggingface dataset:
The modified extended Kalman filter based recursive estimation for Wiener nonlinear systems with process noise and measurement noise
Authors: Wang Xuehai , Zhu Fang , Ding Feng
Published: July 2020

This article develops the modified extended Kalman filter based recursive estimation algorithms for Wiener nonlinear systems with process noise and measurement noise. The prior estimate of the linear block output is computed based on the auxiliary model, and the posterior estimate is updated by designing a modified extended Kalman filter. A multi‐innovation gradient algorithm and a recursive least squares algorithm are derived to estimate the parameters of the linear subsystem, respectively. The simulation examples are provided to demonstrate the effectiveness of the proposed algorithms.
A Biomimetic, Stem Cell‐Derived In Vitro Ocular Outflow Model
Authors: Tian Yangzi Isabel , Zhang Xulang , Torrejon Karen , Danias John , Du Yiqin , Xie Yubing
Published: July 2020

Age‐related human trabecular meshwork (HTM) cell loss is suggested to affect its ability to regulate aqueous humor outflow in the eye. In addition, disease‐related HTM cell loss is suggested to lead to elevated intraocular pressure in glaucoma. Induced pluripotent stem cell (iPSC)‐derived trabecular meshwork (TM) cells are promising autologous cell sources that can be used to restore the declining TM cell population and function. Previously, an in vitro HTM model is bioengineered for understanding HTM cell biology and screening of pharmacological or biological agents that affect trabecular outflow facility. In this study, it is demonstrated that human iPSC‐derived TM cells cultured on SU‐8 scaffolds exhibit HTM‐like cell morphology, extracellular matrix deposition, and drug responsiveness to dexamethasone treatment. These findings suggest that iPSC‐derived TM cells behave like primary HTM cells and can thus serve as reproducible and scalable cell sources when using this in vitro system for glaucoma drug screening and further understanding of outflow pathway physiology, leading to personalized medicine.
The Effect of Equal Channel Angular Pressing on Coarsening Kinetics of AZ80–0.2Y–0.15Ca Alloy in Semisolid State
Authors: Fan Lingling , Zhou Mingyang , Ren Lingbao , Li Houyi , Zhang Hongtao , Lu Tianhui , Liu Chongliang , Quan Gaofeng
Published: July 2020

Semisolid samples of the AZ80–0.2Y–0.15Ca wt% (AZ80M) magnesium alloy are fabricated using equal channel angular pressing (ECAP) followed by semisolid isothermal heating treatment. The effect of the number of ECAP passes on the coarsening dynamics of the alloy at different semisolid temperatures is investigated. The results show that as the number of ECAP passes increases, the coarsening rate constant (K) shows a similar trend downward and then upward at different temperatures. And the K value of the sample after three passes of ECAP processing (3P) is the lowest, which is primarily attributed to the maximum proportion of high‐angle grain boundaries (HAGBs) and the most uniform grain size in the 3P sample. At high solid fractions, a high proportion of HAGBs hinders the coalescence of the adjacent solid grains. At low solid fractions, uniform and fine grains result in insufficient driving force for the Ostwald ripening process. These lead to the lowest K value in the 3P sample.
Black‐Phosphorus‐Incorporated Hydrogel as a Conductive and Biodegradable Platform for Enhancement of the Neural Differentiation of Mesenchymal Stem Cells
Authors: Xu Chao , Xu Yin , Yang Ming , Chang Yukai , Nie Anmin , Liu Zhongyuan , Wang Jianglin , Luo Zhiqiang
Published: July 2020

Conductive hydrogel scaffolds have important applications for electroactive tissue repairs. However, the development of conductive hydrogel scaffolds tends to incorporate nonbiodegradable conductive nanomaterials that will remain in the human body as foreign matters. Herein, a biodegradable conductive hybrid hydrogel is demonstrated based on the integration of black phosphorus (BP) nanosheets into the hydrogel matrix. To address the challenge of applying BP nanosheets in tissue engineering due to its intrinsic instability, a polydopamine (PDA) modification method is developed to improve the stability. Moreover, PDA modification also enhances interfacial bonding between pristine BP nanosheets and the hydrogel matrix. The incorporation of polydopamine‐modified black phosphorous (BP@PDA) nanosheets into the gelatin methacryloyl (GelMA) hydrogels significantly enhances the electrical conductivity of the hydrogels and improves the cell migration of mesenchymal stem cells (MSCs) within the 3D scaffolds. On the basis of the gene expression and protein level assessments, the BP@PDA‐incorporated GelMA scaffold can significantly promote the differentiation of MSCs into neural‐like cells under the synergistic electrical stimulation. This strategy of integrating biodegradable conductive BP nanomaterials within a biocompatible hydrogel provides a new insight into the design of biomaterials for broad applications in tissue engineering of electroactive tissues, such as neural, cardiac, and skeletal muscle tissues.
An Energy‐Dense Solvent‐Free Dual‐Ion Battery
Authors: Chen Chih‐Yao , Matsumoto Kazuhiko , Kubota Keigo , Hagiwara Rika , Xu Qiang
Published: July 2020

Ever‐increasing energy demands call for alternative energy storage technologies with balanced performance and cost characteristics to meet current and emerging applications. Dual‐ion batteries (DIBs) are considered particularly attractive owing to the potentially high specific energy, a rich variety of charge carrier combinations, and the applicability of metal‐free cathode and earth‐abundant anode materials. However, their performance falls far below expectations because of a large excess of solvent needed to dissolve electroactive species that induces side reactions and contributes parasitic weight, which penalizes the reversible capacity and cell‐level energy density. Herein, a solvent‐free DIB utilizing a binary alkali metal molten salt based on bis(fluorosulfonyl)amide as the electrolyte to solve these issues is demonstrated. The cell (NaK‐DIB) operates in a temperature range of 90–120 °C and exhibits high theoretical energy densities of 246 Wh kg−1 and 533 Wh L−1 based on active materials and capacity‐matched electrolyte, far surpassing those of reported DIBs. Further improvements could realize affordable grid‐scale energy storage.
Biomaterial Based Strategies for Engineering New Lymphatic Vasculature
Authors: Campbell Kevin T. , Silva Eduardo A.
Published: July 2020

The lymphatic system is essential for tissue regeneration and repair due to its pivotal role in resolving inflammation, immune cell surveillance, lipid transport, and maintaining tissue homeostasis. Loss of functional lymphatic vasculature is directly implicated in a variety of diseases, including lymphedema, obesity, and the progression of cardiovascular diseases. Strategies that stimulate the formation of new lymphatic vessels (lymphangiogenesis) could provide an appealing new approach to reverse the progression of these diseases. However, lymphangiogenesis is relatively understudied and stimulating therapeutic lymphangiogenesis faces challenges in precise control of lymphatic vessel formation. Biomaterial delivery systems could be used to unleash the therapeutic potential of lymphangiogenesis for a variety of tissue regenerative applications due to their ability to achieve precise spatial and temporal control of multiple therapeutics, direct tissue regeneration, and improve the survival of delivered cells. In this review, the authors begin by introducing therapeutic lymphangiogenesis as a target for tissue regeneration, then an overview of lymphatic vasculature will be presented followed by a description of the mechanisms responsible for promoting new lymphatic vessels. Importantly, this work will review and discuss current biomaterial applications for stimulating lymphangiogenesis. Finally, challenges and future directions for utilizing biomaterials for lymphangiogenic based treatments are considered.
Four Aspects about Solid‐State Nanopores for Protein Sensing: Fabrication, Sensitivity, Selectivity, and Durability
Authors: Hu Rui , Tong Xin , Zhao Qing
Published: July 2020

Solid‐state nanopores are a mimic of innate biological nanopores embedded on lipid membranes. They are fabricated on thin suspended layers of synthetic materials that provide superior thermal, mechanical, chemical stability, and geometry flexibility. As their counterpart biological nanopores reach the goal of DNA sequencing and become commercial, solid‐state nanopores thrive in aspects of protein sensing and have become an important research component for clinical diagnostic technologies. This review focuses on resistive pulse sensing modes, which are versatile for low‐cost, portable sensing devices and summarizes four main aspects toward commercially available resistive pulse‐based protein sensing techniques using solid‐state nanopores. In each aspect of fabrication, sensitivity, selectivity, and durability, brief fundamentals are introduced and the challenges and improvements are discussed. The rapid advance of a practical technique requires greater multidisciplinary cooperation. The review aims at clarifying existing obstacles in solid‐state nanopore based protein sensing, intriguing readers with existing solutions and finally encouraging multidisciplinary researchers to advance the development of this promising protein sensing methodology.
Charge‐Balancing Redox Mediators for High Color Contrast Electrochromism on Polyoxometalates
Authors: Wang Shi‐Ming , Wang Yuhao , Wang Tao , Han Zhengbo , Cho Cheolhyun , Kim Eunkyoung
Published: July 2020

A nonaqueous charge‐balancing electrolyte with a redox couple (I−/I3−) is investigated to improve the electrochromic (EC) performance of polyoxometalate (POM)‐based electrochromic devices (ECDs). PW12O403− (PW12)‐coated porous TiO2 nanoparticle films (PWTNF) with different thicknesses are used as the working electrode. The optical contrast (ΔT) of the optimized PW12‐ECDs reached 59.4% with the electrolyte containing the I−/I3− redox couple. PW12‐ECDs also show a fast response time for bleaching (tb,90% = 1.9 s) and coloration (tc,90% = 3.1 s). On the contrary, without the I−/I3− redox couple, PW12‐ECDs show a poor ΔT of 4.0% and slow response times (>9.0 s). The role of the I−/I3− couple is identified as a charge‐balancing redox mediator between PW12 and the counter electrode. Li+ is the effective intercalating/deintercalating cation required for the EC reaction of PW12. Thus, by simply introducing the I−/I3− redox couple into the electrolyte significantly boosts the EC performance of POMs.
Organic Field‐Effect Transistors as Flexible, Tissue‐Equivalent Radiation Dosimeters in Medical Applications
Authors: Zeidell Andrew M. , Ren Tong , Filston David S. , Iqbal Hamna F. , Holland Emma , Bourland J. Daniel , Anthony John E. , Jurchescu Oana D.
Published: July 2020

Radiation therapy is one of the most prevalent procedures for cancer treatment, but the risks of malignancies induced by peripheral beam in healthy tissues surrounding the target is high. Therefore, being able to accurately measure the exposure dose is a critical aspect of patient care. Here a radiation detector based on an organic field‐effect transistor (RAD‐OFET) is introduced, an in vivo dosimeter that can be placed directly on a patient's skin to validate in real time the dose being delivered and ensure that for nearby regions an acceptable level of low dose is being received. This device reduces the errors faced by current technologies in approximating the dose profile in a patient's body, is sensitive for doses relevant to radiation treatment procedures, and robust when incorporated into conformal large‐area electronics. A model is proposed to describe the operation of RAD‐OFETs, based on the interplay between charge photogeneration and trapping.
All‐Polymer Solar Cells with over 12% Efficiency and a Small Voltage Loss Enabled by a Polymer Acceptor Based on an Extended Fused Ring Core
Authors: Yao Huatong , Ma Lik‐Kuen , Yu Han , Yu Jianwei , Chow Philip C. Y. , Xue Wenyue , Zou Xinhui , Chen Yuzhong , Liang Jiaen , Arunagiri Lingeswaran , Gao Feng , Sun Huiliang , Zhang Guangye , Ma Wei , Yan He
Published: July 2020

Although the field of all‐polymer solar cells (all‐PSCs) has seen rapid progress in device efficiencies during the past few years, there are limited choices of polymer acceptors that exhibit strong absorption in the near‐IR region and achieve high open‐circuit voltage (VOC) at the same time. In this paper, an all‐PSC device is demonstrated with a 12.06% efficiency based on a new polymer acceptor (named PT‐IDTTIC) that exhibits strong absorption (maximum absorption coefficient: 2.41 × 105 cm−1) and a narrow optical bandgap (1.49 eV). Compared to previously reported polymer acceptors such as those based on the indacenodithiophene (IDT) core, the indacenodithienothiophene (IDTT) core has further extended fused ring, providing the polymer with extended absorption into the near‐IR region and also increases the electron mobility of the polymer. By blending PT‐IDTTIC with the donor polymer, PM6, a high‐efficiency all‐PSC is achieved with a small voltage loss of 0.52 V, without sacrificing JSC and FF, which demonstrates the great potential of high‐performance all‐PSCs.
Humic substances and distribution in Mollisols affected by six‐year organic amendments
Authors: Zhou Meng , Wang Chunyu , Xie Zhihuang , Li Yansheng , Zhang Xingyi , Wang Guanghua , Jin Jian , Ding Guangwei , Liu Xiaobing
Published: July 2020

Organic amendments under crop rotation influence soil organic matter (SOM) content, while the distribution and structural changes of humic substances have not been thoroughly examined. Three‐dimensional excitation‐emission matrix (3DEEM) fluorescence spectroscopy with parallel factor analysis (PARAFAC) and fluorescence regional integration (FRI), and projection procedure regression (PPR) were used to comprehensively evaluate the structural characteristics and distribution of fulvic acids (FA). The fertilization regimes were: CNoF‐SNoF (corn and soybean without fertilizer), CCF‐SNoF (corn with chemical fertilizer and soybean without fertilizer), CCR‐SNoF (corn and soybean stovers with chemical fertilizer and soybean without fertilizer), CCF‐SCF (corn and soybean with chemical fertilizer), and CCF‐SFM (corn with chemical fertilizer and soybean with dairy manure). Six‐year organic amendments mainly increased SOM, FA and humic acids (HA) contents, and the ratio of HA to FA (HA/FA), the ratio of percent fluorescence response in the ultraviolet to visible region (PV,n/PIII,n) and projection values in topsoil. Six‐year stover return enhanced labile fractions of SOM in 20–30 cm soil depth, while dairy manure application increased labile fractions of SOM in 0–10 cm and 20–30 cm soil depths. The organic amendments had higher Fmax of component C1 (bioavailable aliphatic compounds) and component C2 (high molecular structure compounds), which could potentially enhance the supply of nutrients while reducing the impact of agriculture on the environment. The increase of fulvic acid‐like substances in the visible region was a major cause of the increase in humification degree. EEM‐PARAFAC, EEM‐FRI, and PPR analyses were all suitable for evaluating humification degree of FA.
AD risk score for the early phases of disease based on unsupervised machine learning
Authors: Wang Zheyu , Tang Zhuojun , Zhu Yuxin , Pettigrew Corinne , Soldan Anja , Gross Alden , Albert Marilyn
Published: July 2020

Introduction

Identifying cognitively normal individuals at high risk for progression to symptomatic Alzheimer's disease (AD) is critical for early intervention.

Methods

An AD risk score was derived using unsupervised machine learning. The score was developed using data from 226 cognitively normal individuals and included cerebrospinal fluid, magnetic resonance imaging, and cognitive measures, and validated in an independent cohort.

Results

Higher baseline AD progression risk scores (hazard ratio = 2.70,P< 0.001) were associated with greater risks of progression to clinical symptoms of mild cognitive impairment (MCI). Baseline scores had an area under the curve of 0.83 (95% confidence interval: 0.75 to 0.91) for identifying subjects who progressed to MCI/dementia within 5 years. The validation procedure, using data from the Alzheimer's Disease Neuroimaging Initiative, demonstrated accuracy of prediction across the AD spectrum.

Discussion

The derived risk score provides high predictive accuracy for identifying which individuals with normal cognition are likely to show clinical decline due to AD within 5 years.
FtsZ Reorganization Facilitates Deformation of Giant Vesicles in Microfluidic Traps**
Authors: Ganzinger Kristina A. , Merino‐Salomón Adrián , García‐Soriano Daniela A. , Butterfield A. Nelson , Litschel Thomas , Siedler Frank , Schwille Petra
Published: July 2020

The geometry of reaction compartments can affect the local outcome of interface‐restricted reactions. Giant unilamellar vesicles (GUVs) are commonly used to generate cell‐sized, membrane‐bound reaction compartments, which are, however, always spherical. Herein, we report the development of a microfluidic chip to trap and reversibly deform GUVs into cigar‐like shapes. When trapping and elongating GUVs that contain the primary protein of the bacterial Z ring, FtsZ, we find that membrane‐bound FtsZ filaments align preferentially with the short GUV axis. When GUVs are released from this confinement and membrane tension is relaxed, FtsZ reorganizes reversibly from filaments into dynamic rings that stabilize membrane protrusions; a process that allows reversible GUV deformation. We conclude that microfluidic traps are useful for manipulating both geometry and tension of GUVs, and for investigating how both affect the outcome of spatially‐sensitive reactions inside them, such as that of protein self‐organization.
A Prelude to Biogermylene Chemistry**
Authors: Mahawar Pritam , Wasson Mishi Kaushal , Sharma Mahendra Kumar , Jha Chandan Kumar , Mukherjee Goutam , Vivekanandan Perumal , Nagendran Selvarajan
Published: July 2020

The biological applications of germylenes remain unrealised owing to their unstable nature. We report the isolation of air‐, water‐, and culture‐medium‐stable germylene DPMGeOH (3; DPM=dipyrromethene ligand) and its potential biological application. Compound 3 exhibits antiproliferative effects comparable to that of cisplatin in human cancer cells. The cytotoxicity of compound 3 on normal epithelial cells is minimal and is similar to that of the currently used anticancer drugs. These findings provide a framework for a plethora of biological studies using germylenes and have important implications for low‐valent main‐group chemistry.
Reversible Hydride Migration from C5Me5 to RhI Revealed by a Cooperative Bimetallic Approach
Authors: Alférez Macarena G. , Moreno Juan J. , Hidalgo Nereida , Campos Jesús
Published: July 2020

The use of cyclopentadienyl ligands in organometallic chemistry and catalysis is ubiquitous, mostly due to their robust spectator role. Nonetheless, increasing examples of non‐innocent behaviour are being documented. Here, we provide evidence for reversible intramolecular C−H activation at one methyl terminus of C5Me5 in [(η‐C5Me5)Rh(PMe3)2] to form a new Rh−H bond, a process so far restricted to early transition metals. Experimental evidence was acquired from bimetallic rhodium/gold structures in which the gold center binds either to the rhodium atom or to the activated Cp* ring. Reversibility of the C−H activation event regenerates the RhI and AuI monometallic precursors, whose cooperative reactivity towards polar E−H bonds (E=O, N), including the N−H bonds in ammonia, can be understood in terms of bimetallic frustration.
Monitoring the Interaction of α‐Synuclein with Calcium Ions through Exclusively Heteronuclear Nuclear Magnetic Resonance Experiments
Authors: Pontoriero Letizia , Schiavina Marco , Murrali Maria Grazia , Pierattelli Roberta , Felli Isabella C.
Published: July 2020

Many properties of intrinsically disordered proteins (IDPs), or protein regions (IDRs), are modulated by the nature of amino acid side chains as well as by local solvent exposure. We propose a set of exclusively heteronuclear NMR experiments to investigate these features in different experimental conditions that are relevant for physiological function. The proposed approach is generally applicable to many IDPs/IDRs whose assignment is available in the Biological Magnetic Resonance Bank (BMRB) to investigate how their properties are modulated by different, physiologically relevant conditions. The experiments, tested on α‐synuclein, are then used to investigate how α‐synuclein senses Ca2+ concentration jumps associated with the transmission of nerve signals. Novel modules in the primary sequence of α‐synuclein optimized for calcium sensing in highly flexible, disordered protein segments are identified.
Quantifying the Covalent Functionalization of Black Phosphorus
Authors: Wild Stefan , Dinh Xuan Thong , Maid Harald , Hauke Frank , Abellán Gonzalo , Hirsch Andreas
Published: July 2020

A straightforward quantification method to consistently determine the overall functionalization degree of covalently modified two‐dimensional (2D) black phosphorus (BP) by Raman spectroscopy has been carried out. Indeed, the successful reductive methylation of the BP lattice using sodium intercalation compounds and exhibiting different functionalization degrees has been demonstrated by31P‐magic angle spinning (MAS) NMR spectroscopy. Furthermore, the correlation of31P‐MAS NMR spectroscopy and statistical Raman spectroscopy (SRS) revealed the first method to determine the functionalization degree of BP solely by evaluating the intensities of distinct peaks in the Raman spectra of the covalently modified material, in a similar way to the widely employedID/IGratio of graphene research.
In vitro CRISPR/Cas9 system for genome editing of Aspergillus niger based on removable bidirectional selection marker AmdS
Authors: Nan Yilin , Ouyang Liming , Chu Ju
Published: July 2020

We established an in vitro clustered regularly interspaced short palindromic repeats (CRISPR)‐associated RNA‐guided DNA endonucleases (Cas9) system to efficiently produce specific genome editing in Aspergillus niger, using a novel recyclable, bidirectional selection marker gene amdS without the need of prior production of an amdS mutant. The donor DNA plasmid consisted of amdS open reading frame, promoter, terminator, and directional repeats (DRs) flanking sequences. It was cotransformed with recombinant nuclease Cas9 and the sgRNA, which targets to the pigment gene olvA of A. niger strain CBS513.88. The positive olive transformants, other than the wild‐type strain, were able to grow on the media containing acetamide as the sole nitrogen source and cesium chloride. Furthermore, culturing the transformants on media with fluoroacetamide and urea allowed a loop‐out of the amdS expression cassette by recombining the flanking DRs. This study confirmed the facts that the endogenous amdS can be used as a dominant marker and that it can be removed by counter‐selection in gene editing of A. niger. The proposed in vitro CRISPR/Cas9 method offers a powerful tool for marker‐free genetic manipulation of filamentous fungi industrial‐specific strains.
Trends in prevalence and spatiotemporal distribution of gastroschisis in Arkansas, 1998–2015
Authors: ELHassan Nahed O. , Young Sean G. , Gokun Yevgeniya , Wan Fei , Nembhard Wendy N.
Published: July 2020

Background

Arkansas (AR) had the highest prevalence of gastroschisis in a recent study including 15 U.S. states. Our objective was to evaluate trends in prevalence and the spatiotemporal distribution of gastroschisis in AR.

Methods

Infants with gastroschisis, born 1998–2015, were identified from the Arkansas Reproductive Health Monitoring System. Birth record data were used as denominators for calculations. Maternal residence at delivery was geocoded for spatial analyses. Annual prevalence rates (PRs) were calculated. Joinpoint regression analysis was performed to examine trends in gastroschisis and report the annual percent changes (APCs) in PRs. Spatiotemporal analyses identified counties with unusually high PRs of gastroschisis. Poisson regression, including county, year, and county*year indicators, was fit to evaluate the PRs of gastroschisis, while adjusting for county‐level maternal variables.

Results

We identified 401 cases of gastroschisis among 694,459 live births. The overall PR of gastroschisis was 5.8/10,000 live births. The prevalence of gastroschisis had a significant APC of +5.3% (p < .0001) between 1998 and 2012, followed by a nonsignificant yearly average decrease of −17% through 2015 (p = 0.2). The Emerging Hot Spot Analysis and SaTScan identified an overlapping five‐county cluster from 2006 to 2013. Poisson regression model, including county (inside vs. outside cluster), time (before vs. after 2006), and county*time indicators, was fit to evaluate the PRs of gastroschisis. The model did not confirm the presence of a spatiotemporal cluster, once it adjusted for county‐level maternal characteristics (p = .549).

Conclusion

Close monitoring of rates of gastroschisis is warranted to determine if the PRs of gastroschisis continue to decline in AR.
Obscenity and fabrication in equity and widening participation methodologies
Authors: Lumb Matt , Jane Burke Penny , Bennett Anna
Published: July 2020

Equity and widening participation (EWP) initiatives in Australia are increasingly reimagined in policy as sites where participants are constructed as competitor‐individuals, with education considered only in terms of employability, social mobility and nation‐state market competition. In the context of EWP outreach, and with school students in particular, this can transpire into demands for narrow forms of ‘legitimate’ aspirations. Goffman defines obscenity as when (1) the very intimate is forced into the public sphere, while (2) the humanising dimensions or contexts are stripped away, with an example being pornography—where intimate encounters are reproduced as de‐contextualised acts while being made public. This article argues that dominant approaches to practicing and evaluating EWP risk obscene consequences if they force community members to present static future‐oriented valuations of intimate, fluid aspirations and experiences of education against a backdrop of increasingly individuated, competitive and standardised educational institutions. In this article, firstly we detail the context to establish a foundation for theorising consequences of particular socio‐educational discursive practices. Secondly, we engage with notions of frame, keying and fabrication as a toolbox to reveal some of the unintended (obscene) dynamics risked via certain approaches to programmatic practice and evaluation. Thirdly, we review the diversity of approaches to evaluation (and their attendant debates), highlighting the importance of these debates and diversities, making a case against methodological imperialism.
Regulation of adipose tissue inflammation and systemic metabolism in murine obesity by polymer implants loaded with lentiviral vectors encoding human interleukin‐4
Authors: Youngblood Richard , Flesher Carmen G. , Delproposto Jennifer , Baker Nicki A. , Neeley Christopher K. , Li Fanghua , Lumeng Carey N. , Shea Lonnie D. , O'Rourke Robert W.
Published: July 2020

Dysfunctional adipose tissue plays a central role in the pathogenesis of the obesity‐related metabolic disease, including type 2 diabetes. Targeting adipose tissue using biopolymer implants is a novel therapeutic approach for metabolic disease. We transplanted porous poly(lactide‐co‐glycolide) (PLG) implants coated with human interleukin‐4 (hIL‐4)‐expressing lentivirus into epididymal white adipose tissue (eWAT) of mice fed a high‐fat diet. Tissue and systemic inflammation and metabolism were studied with flow cytometry, immunohistochemistry, quantitative real‐time polymerase chain reaction, adipose tissue histology, and in vivo glucose tolerance testing at 2 and 10 weeks of a high‐fat diet. PLG implants carrying hIL‐4‐expressing lentivirus implanted into epididymal white adipose tissue of mice‐regulated adipose tissue inflammation, including increased CD3+CD4+T‐cell frequency, increased eWAT adipocyte hypertrophy, and decreased FASN and ATGL expression, along with reduced fasting blood glucose levels. These effects were observed in early obesity but were not maintained in established obesity. Local delivery of bioimplants loaded with cytokine‐expressing lentivirus vectors to adipose tissue influences tissue inflammation and systemic metabolism in early obesity. Further study will be required to show more durable metabolic effects. These data demonstrate that polymer biomaterials implanted into adipose tissue have the potential to modulate local tissue and systemic inflammation and metabolism.
Mechanistic insights into viral clearance during the chromatography steps in antibody processes by using virus surrogates
Authors: Dyer Rachel , Song Yuanli , Chen Jie , Bigelow Elizabeth , McGinnis Jennifer , Jenkins Lauren , Ghose Sanchayita , Li Zheng Jian
Published: July 2020

Viral safety is required for biological products to treat human diseases, and the burden of inactivation and or virus removal lies on the downstream purification process. Minute virus of mice (MVM) is a nonenveloped parvovirus commonly used as the worst‐case model virus in validation studies because of its small size and high chemical stability. In this study, we investigated the use of MVM‐mock virus particle (MVP) and bacteriophage ΦX174 as surrogates for MVM to mimic viral clearance studies, with a focus on chromatography operations. Based on structural models and comparison of log reduction value among MVM, MVP, and ΦX174, it was demonstrated that MVP can be used as a noninfectious surrogate to assess viral clearance during process development in multiple chromatography systems in a biosafety level one (BSL‐1) laboratory. Protein A (ProA) chromatography was investigated to strategically assess the impact of the resin, impurities, and the monoclonal antibody product on virus removal.
Recent Advances in the Tissue Culture of American Ginseng (Panax quinquefolius)
Authors: Qiang Baobao , Miao Jianhua , Phillips Nate , Wei Kunhua , Gao Ying
Published: July 2020

The in vitro tissue culture of medicinal plants is considered as a potential source for plant‐derived bioactive secondary metabolites. The in vitro tissue culture of American ginseng has wide commercial applications in pharmaceutical, nutraceutical, food, and cosmetic fields with regard to the production of bioactive compounds such as ginsenosides and polysaccharides. This review highlights the recent progress made on different types of tissue culture practices with American ginseng, including callus culture, somatic embryo culture, cell suspension culture, hairy root culture, and adventitious root culture. The tissue culture conditions for inducing ginseng callus, somatic embryos, cell suspension, hairy roots, and adventitious roots were analyzed. In addition, the optimized conditions for increasing the production of ginsenosides and polysaccharides were discussed. This review provides references for the use of modern biotechnology to improve the production of bioactive compounds from American ginseng, as well as references for the development and sustainable utilization of American ginseng resources.
Whole‐exome sequencing identified mutational profile of a case with T‐cell chronic lymphocytic leukemia
Authors: Nozaki Kenji , Yokota Takafumi , Itotagawa Eri , Tsutsumi Kazuhito , Kusakabe Shinsuke , Morikawa Yoichiro , Fujita Jiro , Fukushima Kentaro , Maeda Tetsuo , Shibayama Hirohiko , Hosen Naoki , Kumanogo Atsushi , Kanakura Yuzuru
Published: July 2020

We believe that our report and further case reports on T‐cell chronic lymphocytic leukemia with genetic profile will contribute to the molecular classification of this rare but distinct disease.
Nitrate Radical Facilitates Indirect Benzyl Alcohol Oxidation on Bismuth(III) Vanadate Photoelectrodes
Authors: Terry Bradley D. , DiMeglio John L. , Cousineau John P. , Bartlett Bart M.
Published: July 2020

Bismuth(III) vanadate (BiVO4) films show activity for direct benzyl alcohol (PhCH2OH) oxidation to benzaldehyde (PhCHO) in acetonitrile solvent. Introducing tetrabutylammonium nitrate (Bu4NNO3) drastically reduces the overpotential required to generate the PhCHO product while maintaining a high faradaic efficiency (FE) >90 %. BiVO4 corrosion accompanies PhCH2OH oxidation. However, the presence of nitrate ions (NO3−) results in significantly less bismuth‐ and vanadium‐ion leaching (determined by ICP‐MS analysis), as well as reduced surface roughening (determined by SEM imaging). In this reaction, it is proposed that rate‐determining NO3− oxidation generates a highly reactive nitrate radical (NO3⋅) that reacts with PhCH2OH by hydrogen‐atom abstraction (HAT). NO3− is stoichiometrically consumed by the irreversible formation of electrochemically inert HNO3, characterized by an ECi mechanism, rather than a catalytic EC′ mechanism. In the presence of PhCH2OH, NO3− oxidation on BiVO4 becomes more facile; every order of magnitude increase in PhCH2OH concentration shifts the NO3−/ NO3⋅ equilibrium potential negatively by 200 mV. The shift results from the introduction of a consumption pathway for the nitrate radical intermediate via a coupled chemical step with benzyl alcohol. This report is the first example of photoelectrochemical NO3⋅ generation to initiate indirect PhCH2OH oxidation.
Ru‐Doping Enhanced Electrocatalysis of Metal–Organic Framework Nanosheets toward Overall Water Splitting
Authors: Zhao Ming , Li Huilin , Li Wei , Li Junying , Yi Lingya , Hu Weihua , Li Chang Ming
Published: July 2020

An Ru‐doping strategy is reported to substantially improve both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) electrocatalytic activity of Ni/Fe‐based metal–organic framework (MOF) for overall water splitting. As‐synthesized Ru‐doped Ni/Fe MIL‐53 MOF nanosheets grown on nickel foam (MIL‐53(Ru‐NiFe)@NF) afford HER and OER current density of 50 mA cm−2 at an overpotential of 62 and 210 mV, respectively, in alkaline solution with a nominal Ru loading of ≈110 μg cm−2. When using as both anodic and cathodic (pre‐)catalyst, MIL‐53(Ru‐NiFe)@NF enables overall water splitting at a current density of 50 mA cm−2 for a cell voltage of 1.6 V without iR compensation, which is much superior to state‐of‐the‐art RuO2‐Pt/C‐based electrolyzer. It is discovered that the Ru‐doping considerably modulates the growth of MOF to form thin nanosheets, and enhances the intrinsic HER electrocatalytic activity by accelerating the sluggish Volmer step and improving the intermediate oxygen adsorption for increased OER catalytic activity.
Aryl Triflates in On‐Surface Chemistry
Authors: Ren Jindong , Klaasen Henning , Witteler Melanie C. , Viergutz Lena , Neugebauer Johannes , Gao Hong‐Ying , Studer Armido , Fuchs Harald
Published: July 2020

The reactivity of aryl triflates in on‐surface C−C coupling is reported. It is shown that the triflate group in aryl triflates enables regioselective homo coupling with preceding or concomitant hydrodetriflation on Cu(111). Three different symmetrical π‐systems with two and three triflate functionalities were used as monomers leading to oligomeric conjugated π‐systems. The cascade, comprising different intermediates at different reaction temperatures as observed for one of the molecules, proceeds via initial removal of the trifluoromethyl sulfonyl group to give an aryloxy radical which in turn is deoxygenated to the corresponding aryl radical. Thermodynamically driven regioselective 1,2‐hydrogen atom transfer leads to a translocated aryl radical which in turn undergoes coupling. For a sterically more hindered bistriflate, where one ortho position was blocked, dehydrogenative coupling occurred at remote position with good regioselectivity. Starting materials, intermediates as well as products were analyzed by scanning tunneling microscopy. Structures and suggested mechanism were further supported by DFT calculations.
Synthesis of New Donor‐Substituted Biphenyls: Pre‐ligands for Highly Luminescent (C^C^D) Gold(III) Pincer Complexes
Authors: Feuerstein Wolfram , Holzer Christof , Gui Xin , Neumeier Lilly , Klopper Wim , Breher Frank
Published: July 2020

We herein report on new synthetic strategies for the preparation of pyridine and imidazole substituted 2,2’‐dihalo biphenyls. These structures are pre‐ligands suitable for the preparation of respective stannoles. The latter can successfully be transmetalated to K[AuCl4] forming non‐palindromic [(C^C^D)AuIII] pincer complexes featuring a lateral pyridine (D=N) or N‐heterocyclic carbene (NHC, D=C’) donor. The latter is the first report on a pincer complex with two formally anionic sp2and one carbenic carbon donor. The [(C^C^D)AuIII] complexes show intense phosphorescence in solution at room temperature. We discuss the developed multistep strategy and touch upon synthetic challenges. The prepared complexes have been fully characterized including X‐ray diffraction analysis. The gold(III) complexes’ photophysical properties have been investigated by absorption and emission spectroscopy as well as quantum chemical calculations on the quasi‐relativistic two‐component TD‐DFT andGW/Bethe–Salpeter level including spin–orbit coupling. Thus, we shed light on the electronic influence of the non‐palindromic pincer ligand and reveal non‐radiative relaxation pathways of the different ligands employed.
Concise Synthesis of 1,4‐Benzoquinone‐Based Natural Products as Mitochondrial Complex I Substrates and Substrate‐Based Inhibitors
Authors: Han Zhenyu , Angerer Heike , Bischoff Iris , Qin Yihan , Stegmann Dennis , Tuz Karina , Fritz Günter , Juarez Oscar , Fürst Robert , Lashley Dana , Nasiri Hamid R.
Published: July 2020

A short, efficient one‐step synthesis of 2‐methyl‐5‐(3‐methyl‐2‐butenyl)‐1,4‐benzoquinone, a natural product from Pyrola media is described. The synthesis is based on a direct late C−H functionalization of the quinone scaffold. The formation of the natural product was confirmed by means of 2D‐NMR spectroscopy. Additional derivatives were synthesized and tested alongside the natural product as potential substrate and substrate‐based inhibitors of mitochondrial complex I (MCI). The structure‐activity relationship study led to the discovery of 3‐methylbuteneoxide‐1,4‐anthraquinone (1 i), an inhibitor with an IC50 of 5 μM against MCI. The identified molecule showed high selectivity for MCI when tested against other quinone‐converting enzymes, including succinate dehydrogenase, and the Na (+)‐translocating NADH:quinone oxidoreductase. Moreover, the identified inhibitor was also active in cell‐based proliferation assays. Therefore, 1 i can be considered as a novel chemical probe for MCI.
MS Binding Assays for Glycine Transporter 2 (GlyT2) Employing Org25543 as Reporter Ligand
Authors: Ackermann Thomas M. , Allmendinger Lars , Höfner Georg , Wanner Klaus T.
Published: July 2020

This study describes the first binding assay for glycine transporter 2 (GlyT2) following the concept of MS Binding Assays. The selective GlyT2 inhibitor Org25543 was employed as a reporter ligand and it was quantified with a highly sensitive and rapid LC‐ESI‐MS/MS method. Binding of Org25543 at GlyT2 was characterized in kinetic and saturation experiments with an off‐rate of 7.07×10−3 s−1, an on‐rate of 1.01×106 M−1 s−1, and an equilibrium dissociation constant of 7.45 nM. Furthermore, the inhibitory constants of 19 GlyT ligands were determined in competition experiments. The validity of the GlyT2 affinities determined with the binding assay was examined by a comparison with published inhibitory potencies from various functional assays. With the capability for affinity determination towards GlyT2 the developed MS Binding Assays provide the first tool for affinity profiling of potential ligands and it represents a valuable new alternative to functional assays addressing GlyT2.
Self‐Assembled Quaternary Ammonium‐Containing Comb‐Like Polyelectrolytes for the Hydrolysis of Organophosphorous Esters: Effect of Head Groups and Counter‐Ions
Authors: Pashirova Tatiana N. , Fetin Petr A. , Lezov Alexey A. , Kadnikov Matvey V. , Valeeva Farida G. , Burilova Evgenia A. , Bilibin Alexander Yu. , Zorin Ivan M.
Published: July 2020

The aim of this work was to increase the efficiency of catalytic systems for the hydrolytic cleavage of 4‐nitrophenyl esters of phosphonic acids. Quaternary ammonium‐containing comb‐like polyelectrolytes («polymerized micelles») with ester cleavable fragments and a low aggregation threshold were used as catalysts. The synthesis of poly(11‐acryloyloxyundecylammonium) surfactants with different counterions (Br−, NO3−, CH3C6H4SO3−) and head groups was realized by micellar free‐radical polymerization. Molecular weight, critical association concentration, particle sizes and solubilization properties toward Orange OT were determined. Self‐assemblies organized by poly(11‐acryloyloxyundecyltrimethyl ammonium) bromide successfully catalyze the hydrolysis of 4‐nitrophenyl butylchloromethylphosphonate up to two orders of magnitude compared to aqueous alkaline hydrolysis. The development of these catalysts is promising for industrial applications and organophosphorus compound detoxification.
Isomer‐Tailored Carbon Molecular Sieve Membranes with High Gas Separation Performance
Authors: Qiu Wulin , Li Fuyue Stephanie , Fu Shilu , Koros William J.
Published: July 2020

Partial substitution of the asymmetric 3,3′,4,4′‐biphenyl dianhydride monomer (aBPDA) into the backbone of a 6FDA‐BPDA‐DAM (6FDA=4,4′‐hexafluoroisopropylidene, DAM=diaminomesitylene) diphthalic anhydride‐based copolyimide based on symmetrical BPDA (sBPDA) was used to study membrane structure‐processing‐property relationships for gas separation. Properties of the polymer membrane as well as derived carbon molecular sieves (CMS) membranes were compared with copolyimides without the asymmetric monomer structure. CMS membranes derived from the copolyimides are very attractive for CO2/CH4 separation. aBPDA provides the copolyimide with additional packing‐inhibited structures compared with the symmetric ones and yields a corresponding CMS membrane with very high CO2 permeability and good CO2/CH4 selectivity. This work, therefore, outlines a new strategy for tuning CMS membrane structure to meet separation performance needs.
FGF20‐FGFR1 signaling through MAPK and PI3K controls sensory progenitor differentiation in the organ of Corti
Authors: Su Yutao , Yang Lu M. , Ornitz David M.
Published: July 2020

Background

Fibroblast Growth Factor 20 (FGF20)‐FGF receptor 1 (FGFR1) signaling is essential for cochlear hair cell (HC) and supporting cell (SC) differentiation. In other organ systems, FGFR1 signals through several intracellular pathways including MAPK (ERK), PI3K, phospholipase C ɣ (PLCɣ), and p38. Previous studies implicated MAPK and PI3K pathways in HC and SC development. We hypothesized that one or both would be important downstream mediators of FGF20‐FGFR1 signaling for HC differentiation.

Results

By inhibiting pathways downstream of FGFR1 in cochlea explant cultures, we established that both MAPK and PI3K pathways are required for HC differentiation while PLCɣ and p38 pathways are not. Examining the canonical PI3K pathway, we found that while AKT is necessary for HC differentiation, it is not sufficient to rescue the Fgf20−/− phenotype. To determine whether PI3K functions downstream of FGF20, we inhibited Phosphatase and Tensin Homolog (PTEN) in Fgf20−/− explants. Overactivation of PI3K resulted in a partial rescue of the Fgf20−/− phenotype, demonstrating a requirement for PI3K downstream of FGF20. Consistent with a requirement for the MAPK pathway for FGF20‐regulated HC differentiation, we show that treating Fgf20−/− explants with FGF9 increased levels of dpERK.

Conclusions

Together, these data provide evidence that both MAPK and PI3K are important downstream mediators of FGF20‐FGFR1 signaling during HC and SC differentiation.
Declines in plant productivity drive loss of soil elevation in a tidal freshwater marsh exposed to saltwater intrusion
Authors: Solohin Elena , Widney Sarah E. , Craft Christopher B.
Published: July 2020

We experimentally increased salinities in a tidal freshwater marsh on the Altamaha River (Georgia, USA) by exposing the organic rich soils to 3.5 yr of continuous (press) and episodic (pulse) treatments with dilute seawater to simulate the effects of climate change such as sea level rise (press) and drought (pulse). We quantified changes in root production and decomposition, soil elevation, and soil C stocks in replicated (n = 6) 2.5 × 2.5 m field plots. Elevated salinity had no effect on root decomposition, but it caused a significant reduction in root production and belowground biomass that is needed to build and maintain soil elevation capital. The lack of carbon inputs from root production resulted in reduced belowground biomass of 1631 ± 308 vs. 2964 ± 204 g/m2in control plots and an overall 2.8 ± 0.9 cm decline in soil surface elevation in the press plots in the first 3.5 yr, whereas the control (no brackish water additions) and the fresh (river water only) treatments gained 1.2 ± 0.4 and 1.7 ± 0.3 cm, respectively, in a 3.5‐yr period. There was no change in elevation of pulse plots after 3.5 yr. Based on measurements of bulk density and soil C, the decline of 2.8 cm of surface elevation resulted in a loss of 0.77 ± 0.5 kg C/m2in press plots. In contrast, the control and the fresh treatment plots gained 0.25 ± 0.04 and 0.36 ± 0.03 kg C/m2, respectively, which represents a net change in C storage of more than 1 kg C/m2. We conclude that, when continuously exposed to saltwater intrusion, the tidal freshwater marsh’s net primary productivity, especially root production, and not decomposition, are the main drivers of soil organic matter (SOM) accumulation. Reduced productivity leads to loss of soil elevation and soil C, which has important implications for tidal freshwater marsh persistence in the face of rising sea level.
Exploring the Versatility of 7‐Alkynylcycloheptatriene Scaffolds Under π‐Acid Catalysis
Authors: Vayer Marie , Bour Christophe , Gandon Vincent
Published: July 2020

The reactivity of 7‐alkynycycloheptatrienes tethered to an aryl group under π‐acid catalysis has been studied. A variety of useful cyclic products were synthesized via Au(I)‐catalyzed skeletal reorganization, Cu(II)‐catalyzed hydroarylation, or Brønsted acid‐catalyzed tandem hydroarylation/Friedel‐Crafts reaction. We also report a rare type of skeletal reorganization involving the 1,3‐acetonide tether in the presence of a univalent cationic Ga(I)+ complex.
Azetidiniums: Ring‐Expansion to Pyrrolidines, Piperidines, Azepanes, and Azocanes
Authors: Masson Guillaume , Gomez Pardo Domingo , Cossy Janine
Published: July 2020

The 4‐membered ring in bicyclic azetidiniums, e.g. 1‐azabicyclo[2.n.0]alkanes (n = 1–4), can be efficiently transformed to larger rings. This minireview focuses on the ring‐expansion of these azetidiniums to five‐ and eight‐membered nitrogen containing heterocycles (pyrrolidines, piperidines, azepanes and azocanes). The ring‐expansion is induced by nucleophiles which can be internal nucleophiles (leaving groups), or external nucleophiles.