bluuebunny/crossref_metadata_2025 huggingface dataset:
PEEK/diatomite composites byin situpolymerization: Synthesis, characterization and fundamental properties
Authors: Liu Yifan , Huang Sa , Tan Jie , Wang Zhaoyang , Jiang Zilong , Zhang Haibo
Published: September 2018

In this study, poly (ether ether ketone)/diatomite composites (PEEK/diatomite composites) were prepared by in situ polymerization. In contrast to the direct melt‐compounding method, particles are produced with up to 25 wt % higher filler content by the in situ polymerization method. We found that filling with diatomite improved the mechanical properties of PEEK by about 15%. Scanning electron microscopy revealed that the diatomite particles are uniformly dispersed in the PEEK matrix. Furthermore, the PEEK resin penetrates into the diatomite channels to form interpenetrating organic–inorganic network structures. The thermal stabilities of the composites were studied by thermogravimetric analysis, which revealed that they possess excellent thermal stabilities; these PEEK/diatomite composites exhibit higher decomposition‐onset temperatures than virgin PEEK and lower rates of decomposition. This is attributable to interactions between the diatomite and the matrix, with the diatomite acting as a physical barrier between the polymer and the superficial zone where polymer combustion takes place. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2019,136, 46983.
Fetal and Infancy Growth Pattern, Cord and Early Childhood Plasma Leptin, and Development of Autism Spectrum Disorder in the Boston Birth Cohort
Authors: Raghavan Ramkripa , Zuckerman Barry , Hong Xiumei , Wang Guoying , Ji Yuelong , Paige David , DiBari Jessica , Zhang Cuilin , Fallin M. Daniele , Wang Xiaobin
Published: September 2018

Leptin is a proinflammatory cytokine that plays an important role in energy homeostasis. Emerging evidence suggests that leptin levels are altered in children with autism spectrum disorder (ASD); however, this has not been studied prospectively. Rapid growth during infancy and early childhood has been implicated in ASD, but the evidence is inconsistent. As leptin is involved in growth and is a potential risk factor for ASD, we explored the associations between (a) cord, early childhood leptin and ASD; and (b) birth weight for gestational age, early childhood weight gain, and ASD. We also assessed the mediating role of leptin in the relationship between weight gain during infancy and ASD. This study was conducted in a sample of 822 subjects from the Boston Birth Cohort. ASD was defined from diagnostic codes in electronic medical records. Extremely rapid weight gain during infancy was associated with a greater ASD risk and this persisted after adjusting for potential confounders (aOR: 3.11; 95% CI: 1.37, 7.07). Similarly, children that had higher plasma leptin levels, prior to ASD diagnosis, had an increased ASD risk in both unadjusted and adjusted models (aOR: 7.87; 95% CI: 2.06, 30.04). Further, early childhood leptin indirectly mediated the relationship between rapid weight gain and ASD. No associations were found between birth weight for gestational age, cord leptin and risk of ASD. Our findings provide a basis to further explore whether the combination of early life growth pattern and a biomarker such as leptin can predict ASD earlier. Autism Res 2018, 11: 1416–1431. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Is early life growth and a biomarker leptin related to ASD risk? To answer this question, we followed 822 children from birth and found that those who gained weight very quickly in infancy, had higher leptin levels in early childhood, had a greater chance of later ASD diagnosis. More research is needed to see if infant's weight gain pattern along with a biomarker (such as leptin) can be used to identify children with ASD sooner.
Residual detection of naproxen, methyltestosterone and 17α‐hydroxyprogesterone caproate in aquatic products by simple liquid–liquid extraction method coupled with liquid chromatography–tandem mass spectrometry
Authors: Zheng Weijia , Yoo Kyung‐Hee , Choi Jeong‐Min , Park Da‐Hee , Kim Seong‐Kwan , Kang Young‐Sun , Abd El‐Aty A. M. , Hacımüftüoğlu Ahmet , Wang Jing , Shim Jae‐Han , Shin Ho‐Chul
Published: September 2018

In the present study, we aimed to develop a reliable screening method based on liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) for the detection and quantification of naproxen, methyltestosterone and 17α‐hydroxyprogesterone caproate residues. The target analytes were extracted from samples of eel, flatfish and shrimp using acetonitrile with 1% acetic acid, followed by liquid–liquid purification with n‐hexane. Chromatographic separation was achieved on a reversed‐phase analytical column using 0.1% formic acid containing 10 mm ammonium formate in distilled water (A) and methanol (B) as mobile phases. All the matrix‐matched calibration curves were linear (R2 ≥ 0.99) over the concentration range of the tested analytes. Recovery at three spiking levels (0.005, 0.01 and 0.02 mg/kg) ranged from 68 to 117% with intra‐ and inter‐day precisions <10%. Five market samples for each matrix (eel, flatfish and shrimp) were collected and tested for method application. In summary, the proposed method is feasible to screen and quantify the analytes with high selectivity in aquatic food products meant for human consumption.
Optimization and validation of an SBSE–HPLC–FD method using laboratory‐made stir bars for fluoxetine determination in human plasma
Authors: Marques Letícia Aparecida , Nakahara Thaís Tiemi , Bervelieri Madeira Tiago , Bortholazzi Almeida Mariana , Maffei Monteiro Alessandra , de Almeida Silva Maria , Carrilho Emanuel , Piccoli de Melo Luiz Gustavo , Nixdorf Suzana Lucy
Published: September 2018

Depression is the largest cause of disability worldwide, affecting 350 million people. Notwithstanding that clinical trials demonstrate antidepressants efficacy, the efficient response can vary individually concerning therapeutic dosage. Although important, plasma levels monitoring remains an analytical challenge whereas clean‐up and pre‐concentration represent critical steps. Therefore, this study aims to develop, optimize and validate a method for fluoxetine determination in human plasma, employing a laboratory‐made device consisting of a PDMS stir bar sorptive for extraction, coupled with high‐performance liquid chromatography–fluorescence detection (SBSE–HPLC–FD). Optimization involved sorption–desorption steps. For sorption, temperature and time were assessed by factorial and central composite design approaches, taking into account the desirability and the response surface results, with stirring speed also examined. For desorption kinetics and ultrasonic and magnetic stirring mode were evaluated. The proposed method after validation was robust, linear (25.00–1000.00 ng mL−1, R2 > 0.98) and presented good intra‐ (RSD 4.18%) and inter‐day‐assay (RSD 11.60%) precision and accuracy (recovery 109.60%), allowing reliable quantitation without interference. The method was successfully applied to real samples. SBSE–HPLC–FD could represent a feasible alternative with good cost–benefit for low‐volume samples and therapeutic drug monitoring, as well as contributing to correlation studies between plasma fluoxetine levels and clinical response, which is still little studied.
Prediction of recombinant protein production by Escherichia coli derived online from indicators of metabolic burden
Authors: Mühlmann Martina Julia , Forsten Eva , Noack Saskia , Büchs Jochen
Published: September 2018

Background: The oxygen transfer rate (OTR) and the biomass concentration are two important parameters describing a microbial fermentation. It has been shown before that from the course of these parameters over time information on metabolic burden during heterologous protein production can be obtained. While online monitoring in large fermenters is ubiquitously established, it is still not a common practice in small‐scale cultures. Nevertheless, several techniques like the Respiration Activity MOnitoring System (RAMOS) device for online monitoring of the OTR in shake flasks and the BioLector device for measuring scattered light (ScL) representing biomass in microtiter plates have been developed. Results: A new microtiter plate‐based method is presented that reveals how online derived ScL signals can be transformed into signals that are proportional to the courses of OTR over time for Escherichia coli. The transformed signal is obtained by simply taking the first derivative of ScL (dScL/dt). The proportionality of both parameters is successfully validated for the strains E. coli BL21(DE3) and Tuner(DE3) expressing cellulases and the fluorescent protein FbFP, respectively. Relative amounts of produced heterologous proteins are predicted exclusively based on the course of the transformed ScL signal. A variety of induction conditions with varying inducer concentration and induction time were investigated with this method. Conclusion: The presented method based on ScL measurement allows for high‐throughput online determination of signals proportional to OTR courses. They enable the interpretation of physiological states and offer the possibility to predict the recombinant protein production in E. coli. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1543–1552, 2018
N‐Heterocyclic Carbene‐Modified Au–Pd Alloy Nanoparticles and Their Application as Biomimetic and Heterogeneous Catalysts
Authors: Tegeder Patricia , Freitag Matthias , Chepiga Kathryn M. , Muratsugu Satoshi , Möller Nadja , Lamping Sebastian , Tada Mizuki , Glorius Frank , Ravoo Bart Jan
Published: September 2018

The preparation of water‐soluble, N‐heterocyclic‐carbene‐stabilized Au–Pd alloy nanoparticles by a straightforward ligand exchange process is presented. Extensive analysis revealed excellent size retention and stability over years in water. The alloy nanoparticles were applied as biomimetic catalysts for aerobic oxidation of d‐glucose, for which monometallic Au and Pd nanoparticles showed no or negligible activity. The alloy nanoparticles were further applied as titania‐supported heterogeneous catalysts for the mild hydrogenation of nitroarenes and the semihydrogenation of 1,2‐diphenylacetylene with a solvent‐dependent selectivity switch between E‐ and Z‐stilbene.
A Gold Carbene Manifold to Prepare Fused γ‐Lactams by Oxidative Cyclisation of Ynamides
Authors: Sánchez‐Cantalejo Fernando , Priest Joshua D. , Davies Paul W.
Published: September 2018

Gold‐catalysed oxidative cyclisation reactions of ynamides offer great promise in γ‐lactam synthesis but are limited by preferential over‐oxidation to form α‐keto imides. Evaluating the factors that might limit N‐cyclisation pathways led to effective gold‐catalysed conditions that allow access to different fused γ‐lactams on changing the ynamide N‐substituent and accommodate previously incompatible substitution patterns. New and efficient methods for the synthesis of functionalised 3‐aryl indoles and cyclohepta[c]pyrrol‐1‐one derivatives are presented. These conditions illustrate the complementarity of gold catalysis to other metals.
90 Years CIT – 90 Years Development in Biotechnology and Bioprocess Engineering
Authors: Akermann Alexander , Bold Manfred , Mehring Alexander , Ulber Roland , van Waveren Leo , Weiermüller Jens
Published: September 2018

90 Jahre Chemie Ingenieur Technik (CIT) spiegeln wesentliche Meilensteine der Entwicklung der Biotechnologie und Bioprozesstechnik wider. In diesem Artikel werden einige der wichtigsten Entwicklungen vorgestellt und die Ausbildung von Trends in der Bioverfahrenstechnik nachgezeichnet. Beim Lesen der älteren Artikel lässt sich feststellen, dass einige der aktuellen Forschungsgebiete durchaus nicht ganz so neu sind, sondern vielversprechende Ansätze auch früher schon bearbeitet wurden.
Metabolic Studies of Tumor Cells Using [1‐13C] Pyruvate Hyperpolarized by Means of PHIP‐Side Arm Hydrogenation
Authors: Cavallari Eleonora , Carrera Carla , Aime Silvio , Reineri Francesca
Published: September 2018

The kinetics of metabolic processes can be assessed, in real time by means of MR hyperpolarized (HP) metabolites. [1‐13C]pyruvate, hyperpolarized by means of d‐DNP, is, by far, the substrate most widely applied to the investigation of several pathologies characterized by deregulated glycolytic metabolic networks, including cancer. Hyperpolarization of [1‐13C]pyruvate by means of the cost effective, fast and easy to handle PHIP‐SAH (para‐hydrogen induced polarization‐side arm hydrogenation) method opens‐up a pathway for the application of HP metabolites to a wide range of cancer‐related studies. Herein, we report the first application of PHIP‐SAH hyperpolarized [1‐13C]pyruvate in the investigation of upregulated glycolysis in two murine breast cancer cell lines (168FARN and 4T1). The results obtained using HP pyruvate have been validated with a conventional biochemical assay and are coherent with previously‐reported lactate dehydrogenase activity measured in those cells.
Presenilin Regulates Retinotectal Synapse Formation through EphB2 Receptor Processing
Authors: Liu Zhenyu , Thakar Amit , Santoro Stephen W. , Pratt Kara G.
Published: September 2018

As the catalytic component of γ‐secretase, presenilin (PS) has long been studied in the context of Alzheimer’s disease through cleaving the amyloid precursor protein. PS/γ‐secretase, however, also cleaves a multitude of single‐pass transmembrane proteins that are important during development, including Notch, the netrin receptor DCC, cadherins, drebrin‐A, and the EphB2 receptor. Because transgenic PS‐KO mice do not survive to birth, studies of this molecule during later embryonic or early postnatal stages of development have been carried out using cell cultures or conditional knock‐out mice, respectively. As a result, the function of PS in synapse formation had not been well‐addressed. Here, we study the role of PS in the developing Xenopus tadpole retinotectal circuit, an in‐vivo model that allows for protein expression to be manipulated specifically during the peak of synapse formation between retinal ganglion cells and tectal neurons. We found that inhibiting PS in the postsynaptic tectal neurons impaired tadpole visual avoidance behavior. Whole cell recordings indicated weaker retinotectal synaptic transmission which was characterized by significant reductions in both NMDA receptor (NMDAR)‐ and AMPA receptor (AMPAR)‐mediated currents. We also found that expression of the C‐tail fragment of the EphB2 receptor, which is normally cleaved by PS/γ‐secretase and which has been shown to upregulate NMDARs at the synapse, rescued the reduced NMDAR‐mediated responses. Our data determine that normal PS function is important for proper formation and strengthening of retinotectal synapses through cleaving the EphB2 receptor.
Decreased Neurogenesis Increases Spatial Reversal Errors in Chickadees (Poecile atricapillus)
Authors: Guitar Nicole A. , Sherry David F.
Published: September 2018

Adult hippocampal neurogenesis has been proposed to both aid memory formation and disrupt memory. We examined the role of adult hippocampal neurogenesis in spatial working and reference memory in black‐capped chickadees (Poecile atricapillus), a passerine bird that relies on spatial memory for cache retrieval and foraging. We tested spatial working and spatial reference memory in birds that had received methylazoxymethanol acetate (MAM), a neurotoxin that decreases hippocampal neurogenesis. MAM treatment significantly reduced neurogenesis in the hippocampus quantified by doublecortin (DCX) labeling of newly divided and migrating neurons. MAM treatment had little effect on the working or reference memory but caused an increase in errors on the reference memory task following reversal. Working memory for recently visited spatial locations and reference memory for familiar spatial locations were thus unaffected by a reduction in neurogenesis. An increase in errors following reference memory reversal may indicate that adult hippocampal neurogenesis aids in pattern separation, the differentiation of similar memories at the time of encoding.
Density‐dependent positive feedbacks buffer aquatic plants from interactive effects of eutrophication and predator loss
Authors: Donadi S. , Austin Å. N. , Svartgren E. , Eriksson B. K. , Hansen J. P. , Eklöf J. S.
Published: September 2018

Self‐facilitation allows populations to persist under disturbance by ameliorating experienced stress. In coastal ecosystems, eutrophication and declines of large predatory fish are two common disturbances that can synergistically impact habitat‐forming plants by benefitting ephemeral algae. In theory, density‐dependent intraspecific plant facilitation could weaken such effects by ameliorating the amount of experienced stress. Here, we tested whether and how shoot density of a common aquatic plant (Myriophyllum spicatum) alters the response of individual plants to eutrophication and exclusion of large predatory fish, using a 12‐week cage experiment in the field. Results showed that high plant density benefitted individual plant performance, but only when the two stressors were combined. Epiphytic algal biomass per plant more than doubled in cages that excluded large predatory fish, indicative of a trophic cascade. Moreover, in this treatment, individual shoot biomass, as well as number of branches, increased with density when nutrients were added, but decreased with density at ambient nutrient levels. In contrast, in open cages that large predatory fish could access, epiphytic algal biomass was low and individual plant biomass and number of branches were unaffected by plant density and eutrophication. Plant performance generally decreased under fertilization, suggesting stressful conditions. Together, these results suggest that intraspecific plant facilitation occurred only when large fish exclusion (causing high epiphyte load) was accompanied by fertilization, and that intraspecific competition instead prevailed when no nutrients were added. As coastal ecosystems are increasingly exposed to multiple and often interacting stressors such as eutrophication and declines of large predatory fish, maintaining high plant density is important for ecosystem‐based management.
Finite element analysis of multi‐turn magnetoplated coils using homogenization method
Authors: Fujita Shogo , Igarashi Hajime
Published: September 2018

Magnetoplated wires (MPW) are effective to reduce eddy current losses in power devices such as converters and contactless power transfer systems. In the conventional finite element analysis (FEA) of MPW, elements must be sufficiently smaller than the skin depth. This results in large number of unknowns. This article proposes a homogenization method using complex permeability for FEA of magnetoplated coils so as to circumvent this problem. The coil impedances obtained by the proposed method with coarse elements are shown to agree well with those computed in the conventional FEA with fine elements.
Biphenyl Sulfonic and Disulfonic Acids with Perfluorinated Alkyl Residues
Authors: Kahrs Christoph , Wickleder Mathias S. , Christoffers Jens
Published: September 2018

Sulfonic acids serve as interesting, yet not intensively studied alternatives to carboxylic acids as linker units in coordination polymers. In this study, we present the synthesis of hybrid sulfonic acids with polar, rigid biphenyl moieties and disordered highly fluorinated alkyl chains. Consequently, eight biphenyl sulfonic and disulfonic acids with one or two perfluoroalkyl chains were prepared. The key steps within the synthesis include two palladium catalyzed C–C bond formations: The perfluoroalkyl residue is installed by Heck reaction (up to 91 %) using 1H,1H,2H‐perfluorinated alkenes (C6 and C8) and the biphenyl unit is established by a Suzuki coupling (up to 88 %) of boronic acids bearing one or two protected thiol groups. Finally, these thiol groups are converted into the sulfonic acids by N‐chlorosuccinimide mediated oxidation followed by hydrolysis of the respective sulfonyl chloride.
Glutarimide Alkaloids Through Multicomponent Reaction Chemistry
Authors: Konstantinidou Markella , Kurpiewska Katarzyna , Kalinowska‐Tłuscik Justyna , Dömling Alexander
Published: September 2018

A concise four step synthetic route for glutarimide alkaloids of high biological interest is presented. The scaffold is accessed via an Ugi four component reaction, hereby introducing two points of variation. This is followed by a hydrolysis, a cyclization under mild conditions, and an amine deprotection. The diastereomers of the cyclized intermediate can be easily separated, thus leading to optically pure alkaloids. By this route, four natural products and ten derivatives were synthesized. The scope and limitations of the synthetic methodology were investigated.
Modified Electrodes for Selective Voltammetric Detection of Biomolecules
Authors: Baig Nadeem , Rana Azeem , Kawde Abdel‐Nasser
Published: September 2018

Electrochemical sensors for selective analysis of biomolecules got tremendous attention due to their better sensitivity and construction possibility of the portable cost‐effective devices. The individual or simultaneous sensing of ascorbic acid (AA), dopamine (DA), and uric acid (UA) is challenging due to their close electrooxidation and co‐existing. Recent years, substantial progress is made to develop electrode with smart materials to overcome the issue related to simultaneous sensing. This review is comparatively consolidating the work was done in fabrication of electrochemical sensors for the simultaneous sensing of AA, DA and UA. The various modification materials such as graphene, CNTs, conductive polymers and the ionic liquids characteristics are concisely described with their figure of merits. In the end, the critical analysis, future prospects, and challenges in commercialization are described.
Seismic isolation: Early history
Authors: Makris Nicos
Published: September 2018

Seismic isolation or “aseismic base isolation” is an earthquake protection strategy that aims to uncouple the motion of a structure from the ground shaking and thereby reduce structural forces. A most effective and successful seismic protection technology, seismic isolation, is by now a mature and viable alternative to traditional capacity design and has been implemented in numerous bridges, buildings, and other special structures worldwide. This paper records the origins and early developments (up to the early 1990s) of seismic isolation.
Approximate solutions for the ignition of a solid as a function of the Biot number
Authors: Quintiere James G.
Published: September 2018

The ignition of a finite planar 1‐dimensional solid is addressed for constant applied radiant heat flux. An ignition temperature criterion is used, with constant properties, and linearized reradiation. An approximate integral analysis leads to analytic formulas to predict the ignition time in terms of Biot (Bi) number and heat flux. The accuracy of the integral solution is found to be good compared to the exact infinite series solution for the conduction equation. The integral model is then used to assess the accuracy of common ideal thick and thin formulas for ignition. There is a domain of heat flux and Bi where the ideal formulas are not accurate. An example is given where the integral model is accurately applied to ignition data to illustrate the range where the ideal formula is not accurate.
Dementia in older people admitted to hospital: An analysis of length of stay and associated costs
Authors: Ahern Susan , Cronin Jodi , Woods Noel , Brady Noeleen M. , O'Regan Niamh A. , Trawley Steven , Timmons Suzanne
Published: September 2018

Objectives

Patients with dementia in the acute setting are generally considered to impose higher costs on the health system compared to those without the disease largely due to longer length of stay (LOS). Many studies exploring the economic impact of the disease extrapolate estimates based on the costs of patients diagnosed using routinely collected hospital discharge data only. However, much dementia is undiagnosed, and therefore in limiting the analysis to this cohort, we believe that LOS and the associated costs of dementia may be overestimated. We examined LOS and associated costs in a cohort of patients specifically screened for dementia in the hospital setting.

Methods

Using primary data collected from a prospective observational study of patients aged ≥70 years, we conducted a comparative analysis of LOS and associated hospital costs for patients with and without a diagnosis of dementia.

Results

There was no significant difference in overall length of stay and total costs between those with (μ = 9.9 days, μ = € 8246) and without (μ = 8.25 days, μ = € 6855) dementia. Categorical data analysis of LOS and costs between the two groups provided mixed results.

Conclusions

The results challenge the basis for estimating the costs of dementia in the acute setting using LOS data from only those patients with a formal dementia diagnosis identified by routinely collected hospital discharge data. Accurate disease prevalence data, encompassing all stages of disease severity, are required to enable an estimation of the true costs of dementia in the acute setting based on LOS.
Liver Disease Monitoring Practices After Hepatitis C Cure in the Underserved Population
Authors: Kim Nicole J. , Magee Catherine , Cummings Cassie , Park Helen , Khalili Mandana
Published: September 2018

Recent hepatitis C virus (HCV) guidelines recommend disease monitoring and hepatocellular carcinoma (HCC) screening in patients with advanced fibrosis after a sustained virologic response (SVR) with direct‐acting antiviral (DAA) therapy. However, data on practice patterns in this setting is lacking. We aimed to characterize disease monitoring and HCC screening practices post‐SVR in an underserved HCV‐infected cohort. Records of 192 patients who received DAA therapy at the San Francisco safety‐net health care system between January 2014 and January 2016 with ≥12 months of follow‐up post‐SVR were reviewed. Patient characteristics were median age 58 years, 61.5% men, 39.1% White (23.4% Black, 16.7% Latino, 16.2% Asian), 78.1% English proficient, 48.9% intravenous drug use, 53.2% alcohol use, and 41% advanced (F3 and F4) fibrosis (26.6% with decompensation, 11.4% with HCC). Median post‐SVR follow‐up time was 22 months. A higher proportion of patients with advanced fibrosis attended liver clinic visits (mean, 1.94 ± 2.03 versus 1.12 ± 1.09 visits; P = 0.014) and had liver imaging (41.4% versus 9.73%; P < 0.001) post‐SVR, but there was no difference in alanine aminotransferase (ALT) testing (72.2% versus 66.4%; P = 0.40) compared to those without advanced fibrosis. However, 20% with advanced fibrosis had no HCC screening while 35% with no advanced fibrosis had liver imaging. Three patients with cirrhosis developed new HCC. Conclusion: Although the majority of patients with advanced fibrosis in this underserved cohort received post‐SVR monitoring, gaps in HCC screening were identified and new cases of HCC occurred during a short follow‐up. This highlights the importance of incorporating recently enhanced guidelines to optimize post‐SVR monitoring, especially in difficult to engage populations.
Evaluating the ecosystem services and benefits of wetland restoration by use of the rapid benefit indicators approach
Authors: Mazzotta Marisa , Bousquin Justin , Berry Walter , Ojo Claudette , McKinney Rick , Hyckha Kristen , Druschke Caroline Gottschalk
Published: September 2018

Wetlands in urban and urbanizing areas are often smaller, more degraded, and subject to more stressors than those in undeveloped locations. Their restored level of functioning may never equal that of a site in an undisturbed landscape. Yet, the social benefits from restoring these wetlands may be significant because of the relative scarcity of wetlands and natural areas in urban settings and also the large number of people who may benefit. In this study, we have outlined a systematic approach to compiling nonmonetary indicators of wetlands restoration benefits: The Rapid Benefit Indicators (RBI) Approach. The RBI approach is grounded in economic theory and compatible with methods used by environmental economists to value ecosystem services. We illustrate the RBI approach with a comparison of 2 sites within the Woonasquatucket River Watershed in Rhode Island. As an urbanizing watershed, the Woonasquatucket illustrates how decisions may differ when based primarily on evaluations of ecological functioning versus those that incorporate benefits to people. It demonstrates how small urban sites with relatively low ecological function can provide large social benefits. Integr Environ Assess Manag 2019;15:148–159. Published 2018. This article is a US Government work and is in the public domain in the USA.
Expression of LAG‐3 and efficacy of combination treatment with anti‐LAG‐3 and anti‐PD‐1 monoclonal antibodies in glioblastoma
Authors: Harris‐Bookman Sarah , Mathios Dimitrios , Martin Allison M. , Xia Yuanxuan , Kim Eileen , Xu Haiying , Belcaid Zineb , Polanczyk Magdalena , Barberi Theresa , Theodros Debebe , Kim Jennifer , Taube Janis M. , Burger Peter C. , Selby Mark , Taitt Corina , Korman Alan , Ye Xiaobu , Drake Charles G. , Brem Henry , Pardoll Drew M. , Lim Michael
Published: September 2018

Like in many tumor types, immunotherapy is currently under investigation to assess its potential efficacy in glioblastoma patients. Trials are under way to assess the efficacy of new immune checkpoint inhibitors including anti‐PD‐1 or CTLA4. We here investigate the expression and efficacy of a novel immune‐checkpoint inhibitor, called LAG‐3. We show that LAG‐3 is expressed in human glioblastoma samples and in a mouse glioblastoma model we show that knock out or LAG‐3 inhibition with a blocking antibody is efficacious against glioblastoma and can be used in combination with other immune checkpoint inhibitors toward complete eradication of the model glioblastoma tumors. From a mechanistic standpoint we show that LAG‐3 expression is an early marker of T cell exhaustion and therefore early treatment with LAG‐3 blocking antibody is more efficacious than later treatment. These data provide insight and support the design of trials that incorporate LAG‐3 in the treatment of glioblastoma.
KDM5 demethylases and their role in cancer cell chemoresistance
Authors: Plch Johana , Hrabeta Jan , Eckschlager Tomas
Published: September 2018

Histone methylation is important in the regulation of genes expression, and thus its dysregulation has been observed in various cancers. KDM5 enzymes are capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4) which makes them potential players in the downregulation of tumor suppressors, but could also suggest that their activity repress oncogenes. Depending on the methylation site, their effect on transcription can be either activating or repressing. There is emerging evidence for deregulation of KDM5A/B/C/D and important phenotypic consequences in various types of cancer. It has been suggested that the KDM5 family of demethylases plays a role in the appearance of drug tolerance. Drug resistance remains a challenge to successful cancer treatment. This review summarizes recent advances in understanding the functions of KDM5 histone demethylases in cancer chemoresistance and potential therapeutic targeting of these enzymes, which seems to prevent the emergence of a drug‐resistant population.
Identifying micro‐level generative mechanisms of ICT‐enabled performance improvement in resource‐constrained healthcare organisations: A critical realist perspective
Authors: Buchana Yasser , Garbutt Malcolm , Seymour Lisa F.
Published: September 2018

Healthcare studies in the information and communication technology for development (ICT4D) domain have attempted to understand how technology can be used to support healthcare organisations in developing countries; organisations whose performance is negatively impacted by resource constraints. Current studies – predominantly informed by positivist and interpretivist paradigms – produce analyses and prescriptions designed without an in‐depth understanding of the underlying mechanisms influencing performance. The result is limited ability to explain how organisational performance is enabled by ICT.

Critical realism as a philosophy of science provides a deeper ontological and broader epistemological approach that makes it possible to theorise the micro‐level mechanisms that hold potential for explaining observed outcomes. The study reported here, informed by the critical realism paradigm, uses interviews, observation and organisational data collected from a single case study to identify the resource optimisation micro‐level generative mechanisms that have improved emergency medical services. The study integrates the technological affordances lens to explain ICT‐enabled organisational performance. Additionally, the paper proposes and tests an understanding of the Bygstad, Munkvold, and Volkoff stepwise framework as a methodology for doing critical realist research using affordances.
Evaluation on the effect of hydrogen sulfide on the NLRP3 signaling pathway and its involvement in the pathogenesis of atherosclerosis
Authors: Yue Li‐Ming , Gao Ya‐Mei , Han Bao‐Hua
Published: September 2018

Background

As a common disease, the incidence of atherosclerosis (AS) in the world is high. Therefore, we aimed to evaluate the involvement of hydrogen sulfide (H
2S)/cystathionine γ‐lyase (CSE) in the pathogenesis of AS as well as their possible signaling pathways.

Methods

Enzyme‐linked immunosorbent assay, real‐time polymerase chain reaction, and Western blot analysis were used to detect the effect of CSE on the expression of inflammatory cytokines, ie, H
2S, thioredoxin‐interacting protein (TXNIP), NLRP3, apoptosis‐associated speck‐like protein (ASC), caspase‐1, and interleukin (IL)‐1β. In addition, immunohistochemistry and Western blot analysis were performed to detect the levels of TXNIP, NLRP3, ASC, caspase‐1, IL‐1β, and IL‐18 among different groups.

Result

Knockdown of CSE by the transfection of CSE small interfering RNA upregulated the levels of two inflammatory cytokines, ie, IL‐1β and IL‐18. In addition, the downregulation of CSE promoted the expression of TXNIP, NLRP3, ASC, caspase‐1, and IL‐1β in THP‐1 cells. Meanwhile, treating the cells with sodium hydrosulfide (NaHS) inhibited the productions of IL‐1β and IL‐18. Furthermore, upregulation of H
2S synthesis by treating the cells with NaHS also reduced the protein levels of TXNIP, NLRP3, ASC, caspase‐1, and IL‐1β. Finally, the protein levels of TXNIP and NLRP3 in the AS group were much higher than those in the AS + H
2S group, which in turn was higher than the sham group. In addition, the AS group displayed the highest protein levels of TXNIP, NLRP3, ASC, caspase‐1, IL‐1β, and IL‐18, while the levels of these proteins in the AS + H
2S group were higher than those in the sham group.

Conclusion

In summary, the present finding suggested a possible linkage between H
2S metabolism and AS through the H
2S/CSE‐TXNIP‐NLRP3‐IL‐18/IL‐1β‐nitric oxide (NO) signaling pathway.
Recent advances in endotoxin tolerance
Authors: Liu Dan , Cao Shousong , Zhou Yejiang , Xiong Yuxia
Published: September 2018

Endotoxin tolerance is defined as a reduced capacity of a cell to respond endotoxin (lipopolysaccharide, LPS) challenge after an initial encounter with endotoxin in advance. The body becomes tolerant to subsequent challenge with a lethal dose of endotoxin and cytokines release and cell/tissue damage induced by inflammatory reaction are significantly reduced in the state of endotoxin tolerance. The main characteristics of endotoxin tolerance are downregulation of inflammatory mediators such as tumor necrosis factor α (TNF‐α), interleukin‐1β (IL‐1β), and C‐X‐C motif chemokine 10 (CXCL10) and upregulation of anti‐inflammatory cytokines such as IL‐10 and transforming growth factor β (TGF‐β). Therefore, endotoxin tolerance is often regarded as the regulatory mechanism of the host against excessive inflammation. Endotoxin tolerance is a complex pathophysiological process and involved in multiple cellular signal pathways, receptor alterations, and biological molecules. However, the exact mechanism remains elusive up to date. To better understand the underlying cellular and molecular mechanisms of endotoxin tolerance, it is crucial to investigate the comprehensive cellular signal pathways, signaling proteins, cell surface molecules, proinflammatory and anti‐inflammatory cytokines, and other mediators. Endotoxin tolerance plays an important role in reducing the mortality of sepsis, endotoxin shock, and other endotoxin‐related diseases. Recent reports indicated that endotoxin tolerance is also related to other diseases such as cystic fibrosis, acute coronary syndrome, liver ischemia‐reperfusion injury, and cancer. The aim of this review is to discuss the recent advances in endotoxin tolerance mainly based on the cellular and molecular mechanisms by outline the current state of the knowledge of the involvement of the toll‐like receptor 4 (TLR4) signaling pathways, negative regulate factor, microRNAs, apoptosis, chromatin modification, and gene reprogramming of immune cells in endotoxin tolerance. We hope to provide a new idea and scientific basis for the rational treatment of endotoxin‐related diseases such as endotoxemia, sepsis, and endotoxin shock clinically.
Identification, characterization, and functional investigation of circular RNAs in subventricular zone of adult rat brain
Authors: Xie Fang , Zhao Yun , Wang Shi‐Da , Ma Jing , Wang Xue , Qian Ling‐Jia
Published: September 2018

Adult neural stem cells (NSCs) are able to self‐renew and generate new neural cells. Identifying regulators of NSCs is significant for the development of NSC‐based therapies for neurodegenerative diseases and brain injuries. Recently, circular RNAs (circRNAs) have been characterized in various cell lines and brain tissues, and found to participate in multiple biological processes. However, the expression pattern of circRNAs in adult NSCs is still unknown. Here, the subventricular zone (SVZ) of the lateral ventricle was isolated as the niche of NSCs in adult rat brain for RNA sequencing and the characteristics of circRNAs profiling in both SVZ and cerebral cortex were also investigated. As a result, 29 049 and 31 975 circRNAs were identified in SVZ and cortex, respectively. Among them, 41 were SVZ‐specific and 48 were cortex‐specific. 467 circRNAs were also found to express predominately in SVZ, while the cortex had other 423 circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the SVZ‐specific circRNAs have close relationship with the regulation of NSC expansion and NSC‐niche interaction, while the other differentially expressed circRNAs might be involved in neural cellular construction and nerve system function. Furthermore, the interactions between circRNAs and microRNAs were also explored, and the result showed that one SVZ‐specific circRNA was capable to competitively bind miR‐138‐5p as a potential derepressive regulator in NSCs proliferation. Hence, our work has laid the foundations to decipher regulation mechanisms of circRNAs in adult NSCs and to develop circRNAs as novel biomarkers for adult NSCs.
Metastasis suppressor protein 1 regulated by PTEN suppresses invasion, migration, and EMT of gastric carcinoma by inactivating PI3K/AKT signaling
Authors: Wang Honglei , Zhao Yongjie , Cao Lei , Zhang Judong , Wang Yu , Xu Min
Published: September 2018

Epithelial‐mesenchymal transition (EMT) is a crucial event for cancer progression and metastasis. Metastasis suppressor protein 1 (MTSS1) is a metastasis suppressor in several cancers. In this study, we elucidated the potential physiological function of MTSS1 in the invasion and migration of gastric cancer (GC), and its distinct role in EMT and subsequently determined the potential molecular mechanism. We observed that MTSS1 expression was downregulated in GC tissues and several GC cell lines (SGC‐7901, MGC‐803, MKN‐28, MKN‐45, and BGC‐823). Importantly, forced expression of MTSS1 drastically diminished the cell viability in both SGC‐7901 and MKN‐45 cells. Moreover, overexpression of MTSS1 attenuated the invasion ability of these two cell lines. In addition to the invasive capability, introduction of MTSS1 led to a loss of migratory potential. Furthermore, augmentation of MTSS1 exhibited the typical EMT phenotype switch, accompanied by enhanced the expression of vimentin and N‐cadherin and reduced E‐cadherin expression. Interestingly, MTSS1 also repressed transforming growth factor beta 1 (TGF‐β1)‐induced EMT. Our mechanistic investigations revealed that MTSS1 was positively regulated by the phosphatase and tensin homolog (PTEN), and it functioned as a tumor suppressor, possibly by inactivating the phosphoinositide 3‐kinase (PI3K)/v‐akt murine thymoma viral oncogene (AKT) pathway in GC cells. Collectively, our data provide insight into an important role for MTSS1 in suppressing tumor cell invasion, migration and EMT, which indicates that MTSS1 may act as a prospective prognostic biological marker and a promising therapeutic target for GC.
MicroRNA‐21 as a predictor and prognostic factor for trastuzumab therapy in human epidermal growth factor receptor 2‐positive metastatic breast cancer
Authors: Badr Marwa , Said Hebatallah , Louka Manal L. , Elghazaly Hesham A. , Gaballah Ahmed , Atef Abd El Mageed Mai
Published: September 2018

Breast cancer is the second most common cancer diagnosed worldwide. Human epidermal growth factor receptor 2 (HER2)‐positive breast cancer represents about 20% to 30% of all breast cancers. Trastuzumab is used in the treatment of HER2‐positive breast cancer. MicroRNA‐21 (miR‐21) is an oncomiR that acts by inhibiting many tumor‐suppressor genes. We analyzed the relative expression levels of serum miR‐21 in 20 HER2‐positive metastatic breast cancer patients before and after 3 months of treatment with trastuzumab. miR‐21 levels decreased with a high significant difference after trastuzumab therapy (P = 0.001). Although miR‐21 expression levels were lower in responders than in nonresponders, the difference was not statistically significant (
P = 0.6). Our results demonstrated a significant negative correlation between its basal expression, expression levels after treatment, and time to progression (
P = 0.03 and 0.01, respectively). These results make miR‐21 a potential prognostic factor for HER2‐positive metastatic breast cancer patients. Additionally, it can be an interesting potential target in therapy using antisense oligonucleotides for miR‐21.
Halogen in materials design: Chloroammonium lead triiodide perovskite (ClNH3PbI3) a dynamical bandgap semiconductor in 3D for photovoltaics
Authors: Varadwaj Pradeep R. , Varadwaj Arpita , Marques Helder M. , Yamashita Koichi
Published: September 2018

Methylammonium lead trihalides and their derivatives are photovoltaic materials. CH3NH3PbI3 is the most efficient light harvester among all the known halide perovskites (PSCs). It is regarded as unsuitable for long‐term stable solar cells, thus it is necessary to develop other types of PSC materials to achieve stable PSCs (Wang et al., Nat. Energy 2016, 2, 16195). Because of this, various research efforts are on‐going to discover novel lead‐based or lead‐free single/double PSCs, which can be stable, synthesizable, transportable, abundant and efficient in solar energy conversion. Keeping these factors in mind, we report here the electronic structures, energetic stabilities and some materials properties (viz. band structures, density of states spectra and photo‐carrier masses) of the PSC chloroammonium lead triiodide (ClNH3PbI3). This emerges through compositional engineering that often focuses on B‐ and Y‐site substitutions within the domain of the BMY3 PSC stoichiometry. ClNH3PbI3 is found to be stable as orthorhombic and pseudocubic polymorphs, which are analogous with the low and high temperature polymorphs of CH3NH3PbI3. The bandgap of ClNH3PbI3 (values between 1.28 and 1.60 eV) is found to be comparable with that of CH3NH3PbI3, (1.58 eV), both obtained with periodic DFT at the PBE level of theory. Spin orbit coupling is shown to have a pronounced effect on both the magnitude and character of the bandgap. The computed results show that ClNH3PbI3 may act as a competitor for CH3NH3PbI3 for photovoltaics. © 2018 Wiley Periodicals, Inc.
stk: A python toolkit for supramolecular assembly
Authors: Turcani Lukas , Berardo Enrico , Jelfs Kim E.
Published: September 2018

A tool for the automated assembly, molecular optimization and property calculation of supramolecular materials is presented. stk is a modular, extensible and open‐source Python library that provides a simple Python API and integration with third party computational codes. stk currently supports the construction of linear polymers, small linear oligomers, organic cages in multiple topologies and covalent organic frameworks (COFs) in multiple framework topologies, but is designed to be easy to extend to new, unrelated, supramolecules or new topologies. Extension to metal–organic frameworks (MOFs), metallocycles or supramolecules, such as catenanes, would be straightforward. Through integration with third party codes, stk offers the user the opportunity to explore the potential energy landscape of the assembled supramolecule and then calculate the supramolecule's structural features and properties. stk provides support for high‐throughput screening of large batches of supramolecules at a time. The source code of the program can be found at https://github.com/supramolecular-toolkit/stk. © 2018 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc.
Trastuzumab‐monomethyl auristatin E conjugate exhibits potent cytotoxic activity in vitro against HER2‐positive human breast cancer
Authors: Abdollahpour‐Alitappeh Meghdad , Lotfinia Majid , Bagheri Nader , Sineh Sepehr Koushan , Habibi‐Anbouhi Mahdi , Kobarfard Farzad , Balalaie Saeed , Foroumadi Alireza , Abbaszadeh‐Goudarzi Ghasem , Abbaszadeh‐Goudarzi Kazem , Abolhassani Mohsen
Published: September 2018

Targeted therapy using specific monoclonal antibodies (mAbs) conjugated to chemotherapeutic agents or toxins has become one of the top priorities in cancer therapy. Antibody–drug conjugates (ADCs) are emerging as a promising strategy for cancer‐targeted therapy. In this study, trastuzumab, a humanized monoclonal anti‐HER2 antibody, was reduced by dithiothreitol and conjugated to the microtubule‐disrupting agent monomethyl auristatin E (MMAE) through a valine‐citrulline peptide linker (trastuzumab‐MC‐Val‐Cit‐PABC‐MMAE [trastuzumab‐vcMMAE]). After conjugation, ADCs were characterized by using UV–vis, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE), and flow cytometry. The antitumor activity of the ADC was evaluated in breast cancer cells in vitro. In addition, ADCs were further characterized using purification by the protein A chromatography, followed by assessment using apoptosis and MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide) assays. Hydrophobic interaction chromatography was used to determine drug‐to‐antibody ratio species of ADCs produced. Our finding showed that approximately 5.12 drug molecules were conjugated to each mAb. H2L2, H2L, HL, H2, H, and L forms of ADCs were detected in nonreducing SDS‐PAGE. The binding of trastuzumab‐vcMMAE to HER2‐positive cells was comparable with that of the parental mAb. The MTT assay showed that our ADCs induced significant cell death in HER2‐positive cells, but not in HER2‐negative cells. The ADCs produced was a mixture of species, unconjugated trastuzumab (14.147%), as well as trastuzumab conjugated with two (44.868%), four (16.886%), six (13.238%), and eight (10.861%) molecules of MMAE. These results indicated that MMAE‐conjugated trastuzumab significantly increases the cytotoxic activity of trastuzumab, demonstrating high affinity, specificity, and antitumor activity in vitro. Trastuzumab‐vcMMAE is an effective and selective agent for the treatment of HER2‐positive breast tumors.