bluuebunny/crossref_metadata_2025 huggingface dataset:
Ring‐Opening Lithiation–Borylation of 2‐Trifluoromethyl Oxirane: A Route to Versatile Tertiary Trifluoromethyl Boronic Esters
Authors: Nandakumar Meganathan , Rubial Belén , Noble Adam , Myers Eddie L. , Aggarwal Varinder K.
Published: November 2019

Stereogenic trifluoromethyl‐substituted carbon centers are highly sought‐after moieties in pharmaceutical and agrochemical discovery. Here, we show that lithiation–borylation reactions of 2‐trifluoromethyl oxirane give densely functionalized and highly versatile trifluoromethyl‐substituted α‐tertiary boronic esters. The intermediate boronate complexes undergo the desired 1,2‐rearrangement of the carbon‐based group with complete retentive stereospecificity, a process that was only observed in non‐polar solvents in the presence of TESOTf. Although the trifluoromethyl group adversely affects subsequent transformations of the α‐boryl group, Zweifel olefinations provide trifluoromethyl‐bearing quaternary stereocenters substituted with alkenes, alkynes and ketones.
Compressive behavior of rigid polyurethane foams nanostructured with bacterial nanocellulose at low and intermediate strain rates
Authors: Chiacchiarelli Leonel Matías , Cerrutti Patricia , Flores‐Johnson Emmanuel A.
Published: November 2019

Nanocellulose reinforced foams are lightweight with improved mechanical properties; however, the strain‐rate effect on their mechanical response is not yet fully understood. In this work, rigid polyurethane foams (PUFs) nanostructured with bacterial nanocellulose at 0.2 wt % (BNCF) and without it (PUF) are synthesized and subjected to compression tests at different strain rates. The BNC acts as a nucleation agent, reducing the cell size but maintaining a similar apparent density of 40.4 ± 3.3 kg m−3. Both BNCF and PUF exhibit strain‐rate effect on yield stress and densification strain. The BNCF exhibits localized progressive crushing and reduced friability, causing a remarkable recovery in the transverse direction. Numerical simulations show that functionally graded foams subjected to impact could be designed using different layers of PUF and BNCF to vary energy absorption and acceleration rate. The results presented herein warrant further research of the mechanical properties of nanostructured foams for impact applications. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48701.
New aryloxy‐quinone derivatives with promising activity on Trypanosoma cruzi
Authors: Espinosa‐Bustos Christian , Vázquez Karina , Varela Javier , Cerecetto Hugo , Paulino Margot , Segura Rodrigo , Pizarro Jaime , Vera Brenda , González Mercedes , Zarate Ana M. , Salas Cristian O.
Published: November 2019

Continuing with a program to develop new quinone derivatives as biologically active compounds, we designed and synthesized a new series of aryloxy‐quinones, which were evaluated in vitro against Trypanosoma cruzi in epimastigote form. Chemical modifications in three specific moieties on the aryloxy‐quinone core were considered for developing new anti‐T. cruzi agents. The majority of our new quinones showed higher potency (IC50 values of <0.70 µM) than nifurtimox, a known pharmaceutical used as a baseline drug (IC50 values of 7.00 µM); however, only two of them elicited higher selectivity than nifurtimox against Vero cells. A structure–activity relationship analysis provided information about the stereoelectronic features of these compounds, which are responsible for an increase in trypanosomicidal activity. Using a pharmacophore model, we mapped the substitution patterns of the five pharmacophoric features of trypanosomicidal activity. We chose the Epc1 compounds and found no relationship with the trypanosomicidal effects. These results provided useful information about the structural characteristics for developing new aryloxy‐quinones with higher potency against the protozoan parasite T. cruzi.
“Trim”ming PolyQ proteins with engineered PML
Authors: Dhar Neha , Arsiwala Ammar , Murali Shruthi , Kane Ravi S.
Published: November 2019

Protein abnormalities are the major cause of neurodegenerative diseases such as spinocerebellar ataxia (SCA). Protein misfolding and impaired degradation leads to the build‐up of protein aggregates inside the cell, which may further cause cellular degeneration. Reducing levels of either the soluble misfolded form of the protein or its precipitated aggregate, even marginally, could significantly improve cellular health. Despite numerous pre‐existing strategies to target these protein aggregates, there is considerable room to improve their specificity and efficiency. In this study, we demonstrated the enhanced intracellular degradation of both monomers and aggregates of mutant ataxin1 (Atxn1 82Q) by engineering an E3 ubiquitin ligase enzyme, promyelocytic leukemia protein (PML). Specifically, we showed enhanced degradation of both soluble and aggregated Atxn1 82Q in mammalian cells by targeting this protein using PML fused to single chain variable fragments (scFvs) specific for monomers and aggregates of the target protein. The ability to solubilize Atxn1 82Q aggregates was due to the PML‐mediated enhanced SUMOylation of the target protein. This ability to reduce the intracellular levels of both misfolded forms of Atxn1 82Q may not only be useful for treating SCA, but also applicable for the treatment of other PolyQ disorders.
Efficient butanol production under aerobic conditions by coculture of Clostridium acetobutylicum and Nesterenkonia sp. strain F
Authors: Ebrahimi Ehsan , Amiri Hamid , Asadollahi Mohammad A. , Shojaosadati Seyed A.
Published: November 2019

Clostridium acetobutylicum is widely used for the microbial production of butanol in a process known as acetone–butanol–ethanol (ABE) fermentation. However, this process suffers from several disadvantages including high oxygen sensitivity of the bacterium which makes the process complicated and necessitate oxygen elimination in the culture medium. Nesterenkonia sp. strain F has attracted interests as the only known non‐Clostridia microorganism with inherent capability of butanol production even in the presence of oxygen. This bacterium is not delimited by oxygen sensitivity, a challenge in butanol biosynthesis, but the butanol titer was far below Clostridia. In this study, Nesterenkonia sp. strain F was cocultivated with C. acetobutylicum to form a powerful “coculture” for butanol production thereby eliminating the need for oxygen removal before fermentation. The response surface method was used for obtaining optimal inoculation amount/time and media formulation. The highest yield, 0.31 g/g ABE (13.6 g/L butanol), was obtained by a coculture initiated with 1.5 mg/L Nesterenkonia sp. strain F and inoculated with 15 mg/L C. acetobutylicum after 1.5 hr in a medium containing 67 g/L glucose, 2.2 g/L yeast extract, 4 g/L peptone, and 1.4% (vol/vol) P2 solution. After butanol toxicity assessment, where Nesterenkonia sp. strain F showed no butanol toxicity, the coculture was implemented in a 2 L fermenter with continual aeration leading to 20 g/L ABE.
Leveraging flow mechanics to determine critical process and scaling parameters in a continuous viral inactivation reactor
Authors: Brown Matthew R. , Orozco Raquel , Coffman Jon
Published: November 2019

A continuous viral inactivation (CVI) chamber has been designed to operate with acceptable residence time distribution (RTD) characteristics. However, altering the CVI's geometry and operation to accommodate the scale was not obvious. In this work, we elucidate the influence of Dean vortices and leverage the transition into the weak turbulent regime to establish relationships between input variables and process outputs. This study was targeted to understand and quantify the impact of viscosity, Dean number, internal diameter, and path length on the RTD. When the Dean number exceeds 70, radial mixing generated by the Dean vortices began to consistently alter the axial dispersive effects experienced by the pulse injection. Increasing to a Dean number of >100, the axial dispersive effects were dominated by the Dean vortices which allowed the calculation of the minimum and maximum residence time to be generated. This work provides a method to calculate operational solutions for a tubular incubation reactor in terms of path length, internal diameter, flow rate, and target minimum and maximum residence time specifications that assures both viral residence times while also establishing criteria to maximize product quality during continuous operation.
Effects of early postnatal exposure to fine particulate matter on emotional and cognitive development and structural synaptic plasticity in immature and mature rats
Authors: Liu Jie , Yang Chen , Yang Jing , Song Xiaojie , Han Wei , Xie Mingdan , Cheng Li , Xie Lingling , Chen Hengsheng , Jiang Li
Published: November 2019

Introduction

Fine particulate matter (PM2.5) is closely associated with many neurological disorders including neurodegenerative disease, stroke, and brain tumors. However, the toxic effects of PM2.5 on neurodevelopment remain unclear. In this study, we aimed to determine the neurotoxic effects of early postnatal exposure to PM2.5 in immature and mature rats.

Methods

We exposed neonatal rats to PM2.5 (2 or 10 mg/kg body weight) through intranasal instillation from postnatal day (PND) 3–15, once a day. Emotional and cognitive development were evaluated using the elevated plus maze, forced swimming, and Morris water maze tests. Hippocampal tissue was collected and subjected to transmission electron microscopy observation and western blot analysis.

Results

Rats had lower body weight after exposure to high dose of PM2.5. The behavioral test results indicated that high‐dose PM2.5 exposure led to increased anxiety‐like symptoms in immature and mature rats, apparent depressive‐like behaviors in mature rats, and impaired spatial learning and memory abilities in immature rats, and low‐dose PM2.5 exposure increased anxiety‐like behaviors in immature rats. Further, high‐dose PM2.5 exposure contributed to fewer synapses, thinner postsynaptic density, and shorter active zone in immature and mature rats, and also decreased expressions of synaptophysin (SYP), growth associated protein‐43 (GAP43), and postsynaptic density‐95 (PSD95) in immature rats, SYP and PSD95 in mature rats. Moreover, low‐dose PM2.5 exposure diminished the expression of PSD95 in immature rats. In addition, high‐dose PM2.5 exposure reduced brain‐derived neurotrophic factor (BDNF) expression and cAMP response element binding protein (CREB) phosphorylation in both immature and mature rats, and low‐dose PM2.5 exposure lessened BDNF expression and CREB phosphorylation in immature rats.

Conclusions

Our findings indicate that PM2.5 impairs emotional and cognitive development by disrupting structural synaptic plasticity, possibly via the CREB/BDNF signaling pathway.
New Vocabulary for Bacterial Communication
Authors: Tobias Nicholas J. , Brehm Jannis , Kresovic Darko , Brameyer Sophie , Bode Helge B. , Heermann Ralf
Published: November 2019

Quorum sensing (QS) is widely accepted as a procedure that bacteria use to converse. However, prevailing thinking places acyl homoserine lactones (AHLs) at the forefront of this communication pathway in Gram‐negative bacteria. With the advent of high‐throughput genomics and the subsequent influx of bacterial genomes, bioinformatics analysis has determined that the genes encoding AHL biosynthesis, originally discovered to be indispensable for QS (LuxI‐like proteins and homologues), are often absent in QS‐capable bacteria. Instead, the sensing protein (LuxR‐like proteins) is present with an apparent inability to produce any outgoing AHL signal. Recently, several signals for these LuxR solos have been identified. Herein, advances in the field of QS are discussed, with a particular focus on recent research in the field of bacterial cell–cell communication.
Spontaneous pneumomediastinum and subcutaneous emphysema in avian influenza A (H5N6) human pneumonia
Authors: Zhang Xiang , Wang Jiwen , Zeng Qiaojun , Wu Xiaoyan , Jiang Shanping , Shen Jun
Published: November 2019

The pneumomediastinum and subcutaneous emphysema can repetitively occur in human H5N6 virus pneumonia. Prompt treatment of this uncommon complication is important for successful rescue of patients with H5N6 virus pneumonia.
Rational De Novo Design of a Cu Metalloenzyme for Superoxide Dismutation
Authors: Mathieu Emilie , Tolbert Audrey E. , Koebke Karl J. , Tard Cédric , Iranzo Olga , Penner‐Hahn James E. , Policar Clotilde , Pecoraro Vincent
Published: November 2019

Superoxide dismutases (SODs) are highly efficient enzymes for superoxide dismutation and the first line of defense against oxidative stress. These metalloproteins contain a redox‐active metal ion in their active site (Mn, Cu, Fe, Ni) with a tightly controlled reduction potential found in a close range around the optimal value of 0.36 V versus the normal hydrogen electrode (NHE). Rationally designed proteins with well‐defined three‐dimensional structures offer new opportunities for obtaining functional SOD mimics. Here, we explore four different copper‐binding scaffolds: H3(His3), H4(His4), H2DH (His3Asp with two His and one Asp in the same plane) and H3D (His3Asp with three His in the same plane) by using the scaffold of the de novo protein GRα3D. EPR and XAS analysis of the resulting copper complexes demonstrates that they are good CuII‐bound structural mimics of Cu‐only SODs. Furthermore, all the complexes exhibit SOD activity, though three orders of magnitude slower than the native enzyme, making them the first de novo copper SOD mimics.
Racemisation in Chemistry and Biology
Authors: Ballard Andrew , Narduolo Stefania , Ahmed Hiwa O. , Keymer Nathaniel I. , Asaad Nabil , Cosgrove David A. , Buurma Niklaas J. , Leach Andrew G.
Published: November 2019

The two enantiomers of a compound often have profoundly different biological properties and thus their liability to racemisation in aqueous solutions is an important piece of information. The authors reviewed the available data concerning the process of racemisation in vivo, in the presence of biological molecules (e.g., racemase enzymes, serum albumin, cofactors and derivatives) and under purely chemical but aqueous conditions (acid, base and other aqueous systems). Mechanistic studies are described critically in light of reported kinetic data. The types of experimental measurement that can be used to effectively determine rate constants of racemisation in various conditions are discussed and the data they provide is summarised. The proposed origins of enzymatic racemisation are presented and suggest ways to promote the process that are different from processes taking place in bulk water. Experimental and computational studies that provide understanding and quantitative predictions of racemisation risk are also presented.
Fabrication of a Hierarchical Ni(OH)2@Ni3S2/Ni Foam Electrode from a Prussian Blue Analogue‐Based Composite with Enhanced Electrochemical Capacitive and Electrocatalytic Properties
Authors: Chen Xiaojuan , Yang Longkun , Huang Yunxia , Ge Shuaipeng , Zhang Hao , Cui Yimin , Huang Anping , Xiao Zhisong
Published: November 2019

Developing high‐efficiency, cost‐effective, and durable electrodes is significant for electrochemical capacitors and electrocatalysis. Herein, a 3D bifunctional electrode consisting of nickel hydroxide nanosheets@nickel sulfide nanocubes arrays on Ni foam (Ni(OH)2@Ni3S2/NF) obtained from a Prussian blue analogue‐based precursor is reported. The 3D higher‐order porous structure and synergistic effect of different compositions endow the electrode with large specific surface area, facile ion/electron transport path, and improved conductivity. As a result, the Ni(OH)2@Ni3S2/NF electrode exhibits a high specific capacity of 211 mA h g−1 at a current density of 1 A g−1 and 73 % capacity retention after 5000 cycles at 5 A g−1. Moreover, the Ni(OH)2@Ni3S2/NF electrode has superior electrocatalytic activity for the hydrogen evolution reaction with low overpotentials of 140 and 210 mV at current densities of 10 and 100 mA cm−2, respectively. The synthetic strategy for the unique higher‐order porous structure can be extended to fabricate other composite materials for energy storage and conversion.
Fighting Deactivation: Classical and Emerging Strategies for Efficient Stabilization of Molecular Electrocatalysts
Authors: Bairagya Monojit Das , Bujol Ryan J. , Elgrishi Noémie
Published: November 2019

Development of highly active molecular electrocatalysts for fuel‐forming reactions has relied heavily on understanding mechanistic aspects of the electrochemical transformations. Careful fine‐tuning of the ligand environment oriented mechanistic pathways towards higher activity and optimal product distribution for several catalysts. Unfortunately, many catalysts deactivate in bulk electrolysis conditions, diminishing the impact of the plethora of highly tuned molecular electrocatalytic systems. This Minireview covers classical and emerging methods developed to circumvent catalyst deactivation and degradation, with an emphasis on successes with molecular electrocatalysts.
A Double‐Band Emitter with Ultranarrow‐Band Blue and Narrow‐Band Green Luminescence
Authors: Ruegenberg Freia , Seibald Markus , Baumann Dominik , Peschke Simon , Schmid Philipp C. , Huppertz Hubert
Published: November 2019

Understanding the origin and mechanisms of luminescence is a crucial point when it comes to the development of new phosphors with targeted luminescence properties. Herein, a new phosphor belonging to the substance class of alkali metal lithosilicates with the generalized sum formula Cs4−x−y−zRbxNayLiz[Li3SiO4]4:Eu2+is reported. Single crystals of the cyan‐emitting UCr4C4‐type phosphor show a peculiar double‐band luminescence with one ultranarrow emission band at 473 nm and a narrow emission band at 531 nm under excitation with UV light (λexc=408 nm). Regarding occupation of the channels by the light metal ions, investigations of single‐crystal XRD data led to the assumption that domain formation with distinct lithium‐ and sodium‐filled channels occurs. Depending on which of these channels hosts the activator ion Eu2+, a green or blue emission results. The herein‐presented results shed new light on the luminescence process in the well‐studied UCr4C4‐type alkali metal lithosilicate phosphors.
Charge Distribution and Stability of SiO2 Nanoarray Electret
Authors: Liang Fei , Li Hua Yang , Wang Ying , Kuang Shuang Yang , Fan You Jun , Wang Zhong Lin , Zhu Guang
Published: November 2019

The devices based on SiO2 electret have significant applications in various MEMS sensors. However, the charge stability of SiO2 electret suffered from the water percolation, which seriously restricts its application. In this work, the long‐term charge stability of the SiO2 nanoarray electret (SiO2 NAE) without any water repellent treatment is demonstrated. When the oxidation time is 1.5 h, the potential decay of the SiO2 NAE is less than 46% during 60 days with an original potential of −120 V. The long‐term charge stability of the SiO2 NAE is attributed to its unique charge decay process and the large H2O diffusion barrier in the SiO2 NAE: firstly, the charge trapped in the planar part of the SiO2 NAE decays rapidly. Then, residual charge stored in the SiO2 nanoarray. Eventually, the large H2O diffusion barrier in the interface of Si/SiO2 effectively hinders the charge decay. In addition, we demonstrate the unique charge stability of nanoelectret, which has a promising application in developing high performance electret‐based devices.
Benchmarking the first generation of production quality Arm‐based supercomputers
Authors: McIntosh‐Smith Simon , Price James , Poenaru Andrei , Deakin Tom
Published: November 2019

In this paper, we present scaling results from two production quality supercomputers that use the first generation of Arm‐based CPUs that have been optimized for scientific workloads. Both systems use Marvell ThunderX2 CPUs, which deliver high core counts and class‐leading memory bandwidth. The first system is Isambard, a Cray XC50 “Scout” system operated by the GW4 Alliance and the UK Met Office as a Tier‐2 national HPC service. The second system is one of three Arm‐based HPE Apollo 70 systems delivered as part of the Catalyst UK project, running at the University of Bristol. We compare scaling results from these two systems with three Cray XC50 systems based on Intel Skylake and Broadwell CPUs. We focus on a range of applications and mini‐apps that are important to the UK national HPC service, ARCHER, and to our project partners. We also compare the performance and maturity of the state‐of‐the‐art toolchains available on Arm‐based HPC systems.
Graded diacylglycerol kinases α and ζ activities ensure mucosal‐associated invariant T‐cell development in mice
Authors: Pan Yun , Deng Wenhai , Xie Jinhai , Zhang Shimeng , Wan Edwin C.K. , Li Lei , Tao Huishan , Hu Zhiming , Chen Yongping , Ma Li , Gao Jimin , Zhong Xiao‐Ping
Published: November 2019

Mucosal‐associated invariant T (MAIT) cells participate in both protective immunity and pathogenesis of diseases. Most murine MAIT cells express an invariant TCRVα19‐Jα33 (iVα19) TCR, which triggers signals crucial for their development. However, signal pathways downstream of the iVα19TCR and their regulation in MAIT cells are unknown. Diacylglycerol (DAG) is a critical second messenger that relays the TCR signal to multiple downstream signaling cascades. DAG is terminated by DAG kinase (DGK)‐mediated phosphorylation and conversion to phosphatidic acid. We have demonstrated here that downregulation of DAG caused by enhanced DGK activity impairs late‐stage MAIT cell maturation in both thymus and spleen. Moreover, deficiency of DGKζ but not DGKα by itself causes modest decreases in MAIT cells, and deficiency of both DGKα and ζ results in severe reductions of MAIT cells in an autonomous manner. Our studies have revealed that DAG signaling is not only critical but also must be tightly regulated by DGKs for MAIT cell development and that both DGKα and, more prominently, DGKζ contribute to the overall DGK activity for MAIT cell development.
TBN‐Catalyzed Dehydrative N‐Alkylation of Anilines with 4‐Hydroxybutan‐2‐one
Authors: Cheng Wenchen , Deng Shue , Jiang Liya , Ren Lanhui , Wang Zicheng , Zhang Jian , Song Weiguo
Published: November 2019

Until now, the substitution of alcohols by N‐nucleophiles via TBN‐catalyzed dehydrogenation was not known. Herein, we reported a TBN catalyzed dehydrative N‐alkylation of anilines with 4‐hydroxybutan‐2‐one in the presence of TEMPO, which was different from the TEMPO/TBN catalyzed oxidation reactions. A range of anilines reacted successfully with 4‐hydroxybutan‐2‐one to generate the N‐monoalkylation products in good yields. Mechanistic studies revealed that this reaction most possibly proceeded through aza‐Michael addition. Water was the only by‐product, making it more environmentally friendly. The gram‐scale reactions verified the synthetic practicality of this protocol.
Utility of a next generation framework for assessment of genomic damage: A case study using the industrial chemical benzene
Authors: Luijten Mirjam , Ball Nicholas S. , Dearfield Kerry L. , Gollapudi B. Bhaskar , Johnson George E. , Madia Federica , Peel Lauren , Pfuhler Stefan , Settivari Raja S. , ter Burg Wouter , White Paul A. , van Benthem Jan
Published: November 2019

We recently published a next generation framework for assessing the risk of genomic damage via exposure to chemical substances. The framework entails a systematic approach with the aim to quantify risk levels for substances that induce genomic damage contributing to human adverse health outcomes. Here, we evaluated the utility of the framework for assessing the risk for industrial chemicals, using the case of benzene. Benzene is a well‐studied substance that is generally considered a genotoxic carcinogen and is known to cause leukemia. The case study limits its focus on occupational and general population health as it relates to benzene exposure. Using the framework as guidance, available data on benzene considered relevant for assessment of genetic damage were collected. Based on these data, we were able to conduct quantitative analyses for relevant data sets to estimate acceptable exposure levels and to characterize the risk of genetic damage. Key observations include the need for robust exposure assessments, the importance of information on toxicokinetic properties, and the benefits of cheminformatics. The framework points to the need for further improvement on understanding of the mechanism(s) of action involved, which would also provide support for the use of targeted tests rather than a prescribed set of assays. Overall, this case study demonstrates the utility of the next generation framework to quantitatively model human risk on the basis of genetic damage, thereby enabling a new, innovative risk assessment concept. Environ. Mol. Mutagen. 61:94–113, 2020. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.
Identification of Optimal Calcium and Temperature Conditions for Quagga Mussel Filtration Rates as a Potential Predictor of Invasion
Authors: Gopalakrishnan Kishore K. , Kashian Donna R.
Published: November 2019

Quagga mussels (Dreissena rostriformis burgensis) are a highly invasive aquatic species to North America, capable of filtering large volumes of water and causing severe ecological and economic impacts. Their range has been expanding since they first invaded the Great Lakes in the 1980s. To predict their spread, it is crucial to understand environmental parameters, which facilitate their range expansion. Two factors likely to influence their distribution include calcium and temperature, because the former is vital for shell development and the latter for metabolic activity. When these factors are optimal for mussels' fitness, the filtration rate has the potential to be maximized if other environmental conditions are also favorable, thus enabling mussels to exploit their growth potential. Deviations from optimal conditions likely result in filtration-rate decline. We identify calcium concentrations and temperatures that maximize the mussel filtration rate for 2 phytoplankton species: Ankistrodesmus facaltus, a common food source for quagga mussels, and a less palatable Microcystis icthyoblabe. In laboratory experiments, filtration rates were measured through cell counts after 24 h of filtration when exposed to a range of temperatures between 2 and 30 °C, and calcium concentrations between 0 and 180 mg/L. Response surface methodology was used to identify a maximum filtration rate, which occurred at 22 mL/mg/h at 137 mg/L of calcium carbonate and 26 °C when fed Ankistrodesmus. To establish a quagga mussel population in a new water source, optimum conditions are required; thus, this information can be used to rank the relative susceptibility of water bodies to invasion by quagga mussels. Environ Toxicol Chem 2020;39:410–418. © 2019 SETAC

Abstract

Investigating the effect of the parameters of temperature and calcium concentration on the mussel filtration rate when fed with 2 different types of algae and determining the optimum parameters for the maximum filtration rate.
Pricing VIX derivatives with infinite‐activity jumps
Authors: Cao Jiling , Ruan Xinfeng , Su Shu , Zhang Wenjun
Published: November 2019

In this paper, we investigate a two‐factor VIX model with infinite‐activity jumps, which is a more realistic way to reduce errors in pricing VIX derivatives, compared with Mencía and Sentana (2013), J Financ Econ, 108, 367–391. Our two‐factor model features central tendency, stochastic volatility and infinite‐activity pure jump Lévy processes which include the variance gamma (VG) and the normal inverse Gaussian (NIG) processes as special cases. We find empirical evidence that the model with infinite‐activity jumps is superior to the models with finite‐activity jumps, particularly in pricing VIX options. As a result, infinite‐activity jumps should not be ignored in pricing VIX derivatives.
Patterns of protein expression in human head and neck cancer cell lines differ after proton vs photon radiotherapy
Authors: Wang Li , Yang Liuqing , Han Shichao , Zhu Jinming , Li Yuting , Wang Zeming , Fan You‐Hong , Lin Eric , Zhang Ruiping , Sahoo Narayan , Li Yupeng , Zhang Xiaodong , Wang Xiaochun , Li Tengfei , Zhu Xiaorong R. , Zhu Hongtu , Heymach John V. , Myers Jeffrey N. , Frank Steven J.
Published: November 2019

Background

Proton radiotherapy (PRT) may be a less toxic alternative to photon radiotherapy (XRT) for patients with head and neck squamous cell carcinoma (HNSCC). However, the molecular responses of HNSCC cells to PRT vs XRT are unclear.

Methods

Proteomics analyses of protein expression profiles by reverse‐phase protein arrays were done for two human papillomavirus [HPV]‐negative and two HPV+ cell lines. Expression patterns of 175 proteins involved in several signaling pathways were tested.

Results

Compared with PRT, XRT tended to induce lower expression of DNA damage repair—and cell cycle arrest‐related proteins and higher expression of cell survival‐ and proliferation‐related proteins.

Conclusions

Under these experimental conditions, PRT and XRT induced different protein expression and activation profiles. Further preclinical verification is needed, as are studies of tumor pathway mutations as biomarkers for choice of treatment or as radiosensitization targets to improve the response of HNSCC to PRT or XRT.
Japan's health care system faces a perfect storm
Authors: Kido Kaori , Tsukamoto Katsura
Published: November 2019

Although Japan has implemented a universal health care system that is universal in terms of free access to health care services, it is managed by fragmented and financially insecure insurance societies that have cumulative deficits even with government subsidies. In terms of insurance premiums, the system is regressive to low‐income and unstable workers, and the social benefit scheme only captures 1.6% of this population. The Japanese government is continuously instituting new health care policies to reduce growing health care expenditures. Recent health care reforms may improve economic efficiency, but the changes remain limited to controlling access to health services and pricing measures.
The impact of climate change on U. K. river flows: A preliminary comparison of two generations of probabilistic climate projections
Authors: Kay Alison Lindsey , Watts Glenn , Wells Steven C. , Allen Stuart
Published: November 2019

The impacts of climate change on future river flows are a growing concern. Typically, impacts are simulated by driving hydrological models with climate model ensemble data. The U.K. Climate Projections 2009 (UKCP09) provided probabilistic projections, enabling a risk‐based approach to decision‐making under climate change. Recently, an update was released—UKCP18—so there is a need for information on how impacts may differ. The probabilistic projections from UKCP18 and UKCP09 are here applied using the change factor method with catchment‐based hydrological modelling for 10 catchments across England. Projections of changes in median, mean, high, and low flows are made for the 2050s, using the A1B emissions scenario from UKCP09 and UKCP18 as well as the RCP4.5 and RCP8.5 emissions scenarios from UCKP18. The results show that, in all catchments for all flow measures, the central estimate of change under UKCP18 is similar to that from UKCP09 (A1B emissions). However, the probabilistic uncertainty ranges from UKCP18 are, in all cases, greater than from UKCP09, despite UKCP18 having a smaller ensemble size than UKCP09. Although there are differences between the central estimates of change using UKCP18 RCP4.5, RCP8.5 and A1B emissions, there is considerable overlap in the uncertainty ranges. The results suggest that existing assessments of hydrological impacts remain relevant, though it will be necessary to evaluate sensitive decisions using the latest projections. The analysis will aid development of advice to users of current guidance based on UKCP09 and help make decisions about the prioritization of further hydrological impacts work using UKCP18, which should also apply other products from UKCP18 like the 12‐km regional data.
Celebrating the 25th anniversary of the International Conference on Population and Development: A perspective from Turkey
Authors: Akin Ayşe , Ali Moazzam
Published: November 2019

On the eve of the 25th anniversary of the International Conference on Population and Development (ICPD) in November 2019, continuous collaborations with different stakeholders and raising public awareness through consistent advocacy efforts are still essential in promoting reproductive rights.
Insulin resistance is improved in high‐fat fed mice by photobiomodulation therapy at 630 nm
Authors: Silva Gabriela , Ferraresi Cleber , de Almeida Rodrigo T. , Motta Mariana L. , Paixão Thiago , Ottone Vinicius O. , Fonseca Ivana A. , Oliveira Murilo X. , Rocha‐Vieira Etel , Dias‐Peixoto Marco F. , Esteves Elizabethe A. , Coimbra Cândido C. , Amorim Fabiano T. , Magalhães Flávio de Castro
Published: November 2019

Photobiomodulation therapy (PBMT) in the infrared spectrum exerts positive effects on glucose metabolism, but the use of PBMT at the red spectrum has not been assessed. Male Swiss albino mice were divided into low‐fat control and high‐fat diet (HFD) for 12 weeks and were treated with red (630 nm) PBMT or no treatment (Sham) during weeks 9 to 12. PBMT was delivered at 31.19 J/cm2, 60 J total dose per day for 20 days. In HFD‐fed mice, PBMT improved glucose tolerance, insulin resistance and fasting hyperinsulinemia. PBMT also reduced adiposity and inflammatory infiltrate in adipose tissue. Phosphorylation of Akt in epididymal adipose tissue and rectus femoralis muscle was improved by PBMT. In epididymal fat PBMT reversed the reduced phosphorylation of AS160 and the reduced Glut4 content. In addition, PBMT reversed the alterations caused by HFD in rectus femoralis muscle on proteins involved in mitochondrial dynamics and β‐oxidation. In conclusion, PBMT at red spectrum improved insulin resistance and glucose metabolism in HFD‐fed mice.
Functional comparison of beating cardiomyocytes differentiated from umbilical cord‐derived mesenchymal/stromal stem cells and human foreskin‐derived induced pluripotent stem cells
Authors: Pushp Pallavi , Sahoo Bijayalaxmi , Ferreira Frederico C. , Sampaio Cabral Joaquim M. , Fernandes‐Platzgummer Ana , Gupta Mukesh K.
Published: November 2019

In recent years, stem cell‐based therapies shown to have promising effects on the clinical management of ischemic heart disease. Moreover, stem cells differentiation into cardiomyocytes (CMs) can overcome the cell source limitations. The current research involves the isolation and expansion of mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs), their differentiation into CMs and subsequent construction of tissue‐engineered myocardium supported by random and aligned polycaprolactone (PCL) nanofibrous matrices (av. dia: 350–850 nm). Umbilical cord matrix (UCM)‐derived MSCs were isolated successfully by routine enzymatic digestion and a nonenzymatic explant culture method and characterized by their morphology, differentiation into different lineages, and surface marker expression. Treatment of UCM‐derived MSCs with 5‐azacytidine (5 μM) induced their differentiation into putative cardiac cells, as revealed by the expression of cardiac‐specific troponin T (cTnT), smooth muscles actin, myogenin (MYOG), smoothelin, cardiac α‐actin genes and cTnT, α‐actinin proteins by RT‐PCR and immunocytochemistry, respectively. However, no beating cells were observed in differentiated MSCs. On the other hand, adult human foreskin‐derived iPSCs cultured on Matrigel™—coated aligned PCL nanofibrous matrices showed anisotropic behavior along the PCL nanofibers and, upon differentiation, expressed cardiac‐specific cTnT (23.34 vs. 32.55%) proteins and showed more synchronized beating than those differentiated on Matrigel™—coated tissue culture coated polystyrene surfaces. Moreover, aligned PCL nanofibers are able to promote cells orientation parallel to the fibers, thus providing an effective way to control anisotropic nature under in vitro condition.
Peroxisome proliferator activated receptor γ promotes mineralization and differentiation in cementoblasts via inhibiting Wnt/β‐catenin signaling pathway
Authors: Hu Yingying , Wang Changning , Ha Shanshan , Zhu Ningjing , Cao Zhengguo , Song Yaling
Published: November 2019

Peroxisome proliferator activated receptor γ (PPARγ) is a member of the nuclear receptor family of transcription factors, which involved in inflammation regulating and bone remodeling. Rare studies explored the effects of PPARγ on mineralization and differentiation in cementoblasts. To explore the potential approaches to repair the damaged periodontal tissues especially for cementum, the present study aims to investigate the effects and the regulating mechanism of PPARγ on mineralization and differentiation in cementoblasts. Murine cementoblast cell lines (OCCM‐30) were cultured in basic medium for 24 hours/48 hours or in mineralization medium for 3/7/10 days, respectively at addition of dimethyl sulphoxide, rosiglitazone (PPARγ agonist), GW9662 (PPARγ antagonist), lithium chloride (LiCl), tumor necrosis factor‐α (TNF‐α), or respective combination. Expression of mineralization genes alkaline phosphatase (ALP), runt related transcription factors 2 (RUNX2), and osteocalcin (OCN) were detected by quantitative real‐time polymerase chain reaction or/and Western blot. ALP staining and alizarin red staining were used to evaluate the mineralization in OCCM‐30 cells. The change of β‐catenin expression and translocation in cytoplasm/nucleus was analyzed by Western blot and immunofluorescence. The results showed that PPARγ agonist rosiglitazone improved the expression of ALP, RUNX2, and OCN, deepened ALP staining, increased mineralized nodules formation, and decreased β‐catenin expression in the nucleus. LiCl, an activator of the Wnt signaling pathway, inhibited the expression of mineralization genes and reversed the upregulated expression of mineralization genes resulted from rosiglitazone. Under inflammatory microenvironment, rosiglitazone not only suppressed the expression of interleukin‐1β caused by TNF‐α, but improved the expression of mineralization genes in OCCM‐30 cells. In conclusion, PPARγ could promote mineralization and differentiation in cementoblasts via inhibiting the Wnt/β‐catenin signaling pathway, which would shed new light on the treatment of periodontitis and periodontal tissue regeneration.
miR‐760 exerts an antioncogenic effect in esophageal squamous cell carcinoma by negatively driving fat metabolism via targeting c‐Myc
Authors: Yang Xuetao , Zhang Cheng , Tie Hongtao , Luo Jun , Wang Yiyang , Wu Qingchen
Published: November 2019

miR‐760 is downregulated in various human tumors, and fat metabolism disorder correlates with tumor progression, especially anomalism of key fat metabolic enzymes that are positively modulated by c‐Myc. The aim of our study is to elucidate the presumptive molecular mechanisms of miR‐760‐mediated esophageal squamous cell carcinoma (ESCC) cell function and to assess the therapeutic significance of miR‐760 in ESCC patients. Quantitative real‐time PCR (RT‐qPCR) analysis indicated that miR‐760 was significantly downexpressed in ESCC tissues and cell lines. Cell counting kit‐8 (CCK‐8) assay, colony formation assay, transwell assay, and flow cytometry denoted that induced ectopic overexpression of miR‐760 dramatically inhibited ESCC cells proliferation, attenuated migration, and invasion facilitated apoptosis in vitro. Mechanistically, c‐Myc predicted using bioinformatics was identified as a potential target gene of miR‐760 by luciferase reporter assay. Furthermore, mRNA and protein expression levels of c‐Myc and key fat metabolic enzymes were downregulated with miR‐760 mimics. The above investigation results, responsible for the antineoplastic properties of miR‐760 in ESCC, preliminarily highlighted that the hypothetical signal amongst miR‐760, c‐Myc, and key fat metabolic enzymes may develop a novel diagnostic marker, therapeutic target, and independent prognostic indicator.
An overview about DNA methylation in childhood obesity: Characteristics of the studies and main findings
Authors: Lima Rafael Silva , de Assis Silva Gomes Juliana , Moreira Paula Rocha
Published: November 2019

Childhood obesity is a global burden affecting millions of children worldwide. It is well‐known that the adiposity profile in children is critical for future occurrence of diseases. As a multifactorial disease, obesity is associated with genetic and environmental factors. Epigenetic mechanisms link the plethora of environmental clues to a given phenotype. DNA methylation is the most studied epigenetic mark and its importance in several diseases was acknowledged. In childhood obesity, specifically, the studies show a consistent association between adiposity and methylation at the gene and genome‐wide scales. The relationship between DNA methylation and childhood obesity has been proved strong for some genes and pathways. However, the studies are heterogeneous in their design, methodologies, and results. The aim of this review is to discuss this heterogeneity and point out some aspects that should be considered in future studies to clarify the role of DNA methylation in childhood obesity.
miR‐146b Reverses epithelial‐mesenchymal transition via targeting PTP1B in cisplatin‐resistance human lung adenocarcinoma cells
Authors: Han Qian , Cheng Peng , Yang Hongjie , Liang Hengpo , Lin Fengchun
Published: November 2019

Epithelial‐mesenchymal transformation (EMT) is associated with drug resistance in human lung adenocarcinoma cells, but its specific mechanism has not been clarified. In this study, we investigated the effect of miRNA‐146b on EMT in cisplatin (DDP) resistant human lung adenocarcinoma cells and the corresponding mechanism. Cisplatin resistant (CR) human lung adenocarcinoma cells (A549/DDP and H1299/DDP) were established, and the EMT characteristics and invasion and metastasis ability of CR cells were determined by tumor cell‐related biological behavior experiments. The role of miR‐146b in EMT of CR cells was determined by in vitro functional test. The targeted binding of miR‐146b to protein tyrosine phosphatase 1B (PTP1B) was verified by biological information and double luciferin gene reporting experiments. The effect of miR‐146b on tumor growth and EMT phenotype in vivo was investigated by establishing the xenotransplantation mouse model. Compared with the control group, H1299/DDP and A549/DDP cells showed the enhanced EMT phenotypes, invasion and migration ability. Besides, miR‐146b was lowly expressed in H1299/DDP and A549/DDP cells. More importantly, overexpressed miR‐146b could specifically bind to PTP1B, thus inhibiting the EMT process and ultimately reducing CR in H1299/DDP and A549/DDP cells. Finally, overexpressed miR‐146b observably inhibited tumor growth in xenograft model mice and inhibited the EMT phenotype of A549/DDP cells in vivo by regulating the expressions of EMT‐related proteins. Overexpressed miR‐146b could reverse the EMT phenotype of CR lung adenocarcinoma cells by targeting PTP1B, providing new therapeutic directions for CR of lung adenocarcinoma cells.
Ginsenoside Rg1 attenuates cardiomyocyte apoptosis and inflammation via the TLR4/NF‐kB/NLRP3 pathway
Authors: Luo Man , Yan Dongsheng , Sun Qingsong , Tao Jiali , Xu Liang , Sun Hong , Zhao Hongmei
Published: November 2019

Sepsis‐induced myocardial dysfunction (SIMD) causes high mortality in seriously ill patients. Ginsenoside Rg1 has been proven to have effective anti‐inflammatory and antiapoptotic properties. However, the specific role of Rg1 in SIMD and the molecular mechanism remain unclear. Hence, we aimed to investigate the latent effects of ginsenoside Rg1 against SIMD and explore its underlying mechanisms. Male C57BL/6J mice and neonatal rat cardiomyocytes (NRCMs) were used as in vivo and in vitro models, respectively. Western blot analysis was used to detect the level of protein expression, and reverse transcription polymerase chain reaction was conducted to determine the messenger RNA expression of inflammatory factors. The terminal deoxynucleotidyl transferase‐mediated nick end labeling assay and flow cytometry were used to determine the apoptosis rate. Echocardiography was performed to assess cardiac function. The results showed that Rg1 improved cardiac function and attenuated lipopolysaccharide (LPS)‐induced apoptosis and inflammation in mice. In addition, in NRCMs, Rg1 downregulated the expression of LPS‐induced inflammatory cytokines and reversed the increased expression of Toll‐like receptor 4 (TLR4), nuclear factor‐κB (NF‐κB), and NOD‐like receptor 3 (NLRP3). In addition, treatment with TLR4 small interfering RNA (siRNA), a p‐NF‐κB inhibitor, or NLRP3 siRNA suppressed LPS‐induced apoptosis and inflammation. In conclusion, Rg1 can attenuate LPS‐induced inflammation and apoptosis both in NRCMs and septic mice and restore impaired cardiac function. Moreover, Rg1 may exert its effect via blocking the TLR4/NF‐κB/NLRP3 pathway.
Study on amniotic fluid metabolism in the second trimester of Trisomy 21
Authors: Liu Xiaoting , Quan Sheng , Fu Yurong , Wang Weiwei , Zhang Wenling , Wang Xiaofei , Zhang Chenxi , Xiang Daijun , Zhang Liwen , Wang Chengbin
Published: November 2019

Background

Trisomy 21 is a common aneuploid condition in humans and accounts for approximately one quarter of all aneuploid live births. To date, early diagnosis of Trisomy 21 remains a challenging task. Metabolomics may prove an innovative tool to study the early pathophysiology of Trisomy 21 at a functional level.

Methods

Ultra‐performance liquid chromatography coupled with mass spectrometer (UPLC‐MS) was used for untargeted metabolomic analysis of amniotic fluid samples from women having normal and trisomy 21 fetuses.

Results

Many significantly changed metabolites were identified between amniotic fluid samples from Trisomy 21 pregnancies and normal euploid pregnancies, such as generally lower levels of several steroid hormones and their derivatives, higher levels of glutathione catabolites coupled with lower levels of gamma‐glutamyl amino acids, and increased levels of phospholipid catabolites, sugars, and dicarboxylic acids. The identification of a human milk oligosaccharide in amniotic fluid may worth further investigation, since confirmation of this observation may have significant implications for regulation of fetal development.

Conclusions

The metabolisms in amniotic fluid from Trisomy 21 and normal pregnancies are quite different, and some of the significantly changed metabolites may be considered as candidates of early diagnostic biomarkers for Trisomy 21.