bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment with 6‐Gingerol Regulates Dendritic Cell Activity and Ameliorates the Severity of Experimental Autoimmune Encephalomyelitis
Authors: Han Juan‐Juan , Li Xing , Ye Ze‐Qing , Lu Xin‐Yu , Yang Ting , Tian Jing , Wang Yu‐Qian , Zhu Lin , Wang Zhe‐Zhi , Zhang Yuan
Published: July 2019

Scope

Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder, with increasing incidence worldwide but unknown etiology. 6‐Gingerol (6‐GIN), a major dietary compound found in ginger rhizome, has immunomodulatory activity. However, its role in autoimmune diseases, as well as the underlying mechanisms, are unclear. In this study, it is evaluated if 6‐GIN can effectively ameliorate the clinical disease severity of experimental autoimmune encephalomyelitis, an animal model of MS.

Methods and results

Clinical scores of experimental autoimmune encephalomyelitis (EAE) mice are recorded daily. Inflammation of periphery and neuroinflammation of EAE mice are determined by flow cytometry analysis, ELISA, and histopathological analysis, and results show that 6‐GIN significantly inhibits inflammatory cell infiltration from the periphery into the central nervous system and reduces neuroinflammation and demyelination. Flow cytometry analysis, ELISA, and quantitative PCR show that 6‐GIN could suppress lipolysaccharide‐induced dendritic cell (DC) activation and induce the tolerogenic DCs. Immunoblot analysis reveals that the phosphorylation of nuclear factor‐κB and mitogen‐activated protein kinase, two critical regulators of inflammatory signaling, are significantly inhibited in 6‐GIN‐treated DCs.

Conclusion

The results of this study demonstrate that 6‐GIN has significant potential as a novel anti‐inflammatory agent for the treatment of autoimmune diseases such as MS via direct modulatory effects on DCs.
An improved dual‐band shared aperture waveguide slot array antenna
Authors: Zong Yao , Ding Jun , Guo Chenjiang
Published: July 2019

In this article, an improved C/X band shared aperture waveguide slot array antenna with orthogonal polarizations is designed. The waveguide narrow‐edged inclined slots are used to realize the X‐band antenna array located in the upper layer. The waveguide wide‐edged longitudinal slots are used to realize the C‐band array located in the lower layer. A novel T‐shaped transition cavity is placed in the middle of two antennas to reduce the shadowing effect of X‐band on C‐band antenna. To verify the design method, a 3 × 3 C‐band array integrated with a 16 × 30 X‐band array is discussed in detail. The measured −10 dB return loss bandwidth of C‐band antenna is 300 MHz. The maximum gain is 17.6 dB at 5.5 GHz with the aperture efficiency of 85%. The good agreements between simulations and experiments demonstrate that the proposed C/X band shared aperture array antenna is a novel and effective method for dual‐frequency waveguide slot array. It presents an excellent candidate for dual frequency antenna with large frequency ratio and high power capacity.
Hyper‐reflective foci segmentation in SD‐OCT retinal images with diabetic retinopathy using deep convolutional neural networks
Authors: Yu Chenchen , Xie Sha , Niu Sijie , Ji Zexuan , Fan Wen , Yuan Songtao , Liu Qinghuai , Chen Qiang
Published: July 2019

Purpose

The purpose of this study was to automatically and accurately segment hyper‐reflective foci (HRF) in spectral domain optical coherence tomography (SD‐OCT) images with diabetic retinopathy (DR) using deep convolutional neural networks.

Methods

An automatic HRF segmentation model for SD‐OCT images based on deep networks was constructed. The model segmented small lesions through pixel‐wise predictions based on small image patches. We used an approach for discriminative features extraction for small patches by introducing small kernels and strides in convolutional and pooling layers, which was applied on the state‐of‐the‐art deep classification networks (GoogLeNet and ResNet). The features extracted by the adapted deep networks were fed into a softmax layer to produce the probabilities of HRF. We trained different models on a dataset with 16 HRF eyes by using different sizes of patches, and then, we fused these models to generate optimal results.

Results

Experimental results on 18 eyes demonstrated that our method is effective for the HRF segmentation. The dice similarity coefficient (DSC) for the foci area in B‐scan, projection images, and foci amount in B‐scan images reaches 67.81%, 74.09%, and 72.45%, respectively.

Conclusions

The proposed segmentation model can accurately segment HRF in SD‐OCT images with DR and outperforms traditional methods. Our model may provide reliable segmentations for small lesions in SD‐OCT images and may be helpful in the clinical diagnosis of diseases.
Solid‐state NMR studies of the acidity of functionalized metal–organic framework UiO‐66 materials
Authors: Tang Jing , Li Shenhui , Chu Yueying , Xiao Yuqing , Xu Jun , Deng Feng
Published: July 2019

The acid strength of metal–organic frameworks plays a key role in their catalytic performance such as activity and selectivity during catalytic reactions. Solid‐state nuclear magnetic resonance in combination with probe molecules including 2‐13C‐acetone and pyridine‐d5 was employed to characterize the acid strength of UiO‐66‐X (X = ‐H, ‐2COOH, ‐SO3H). It was found that after introduction of the functional groups, the acid strength of UiO‐66‐2COOH and UiO‐66‐SO3H is considerably enhanced compared with that of parent UiO‐66, with that of the former being similar to that of zeolite H‐ZSM‐5, and with that of the latter being slightly stronger than that of the former. Even though the acid density can efficiently be modified through changing the relative ratio in multivariate functionalized UiO‐66‐X, no significant alternation for the acid strength could be discerned in the MTV‐UiO‐66‐X compared with acidic same‐link counterpart. Theoretical calculations were employed to further confirm the acid strength of UiO‐66‐SO3H and UiO‐66‐2COOH.
Bayesian model selection for sand with generalization ability evaluation
Authors: Jin Yin‐Fu , Yin Zhen‐Yu , Zhou Wan‐Huan , Shao Jian‐Fu
Published: July 2019

Current studies have focused on selecting constitutive models using optimization methods or selecting simple formulas or models using Bayesian methods. In contrast, this paper deals with the challenge to propose an effective Bayesian‐based selection method for advanced soil models accounting for the soil uncertainty. Four representative critical state‐based advanced sand models are chosen as database of constitutive model. Triaxial tests on Hostun sand are selected as training and testing data. The Bayesian method is enhanced based on transitional Markov chain Monte Carlo method, whereby the generalization ability for each model is simultaneously evaluated, for the model selection. The most plausible/suitable model in terms of predictive ability, generalization ability, and model complexity is selected using training data. The performance of the method is then validated by testing data. Finally, a series of drained triaxial tests on Karlsruhe sand is used for further evaluating the performance.
A hybrid adaptive finite element phase‐field method for quasi‐static and dynamic brittle fracture
Authors: Tian Fucheng , Tang Xiaoliang , Xu Tingyu , Yang Junsheng , Li Liangbin
Published: July 2019

The phase‐field approach has unique advantages in describing fracture phenomena, which has received extensive attention in the past decade. Nevertheless, the phase‐field modeling of fracture is computationally demanding, due to the high temporal‐spatial resolution required for crack tracking. In this contribution, a novel hybrid adaptive finite element phase‐field method (ha‐PFM) is developed to solve brittle fracture problems under quasi‐static and dynamic loading. ha‐PFM can dynamically track the propagation of the cracks and adaptively refine the meshes based on a novel crack tip identification strategy. Afterward, the refined meshes in the noncrack progression region are reconverted into coarse meshes. This scheme prominently reduces the computational cost, eg, CPU time and memory usage. Unlike the previous adaptive phase‐field method, multilevel hybrid triangular and quadrilateral elements were developed to discretize the computational domain, which eliminates hanging nodes and ensures that the meshes in the vicinity of the crack tip are highly isotropic. Several representative benchmarks containing quasi‐static and dynamic fracture were reinvestigated with ha‐PFM, and its excellent performance is substantiated by comparison with the standard phase‐field method and literature results.
External commercial borrowings by the corporate sector in India
Authors: Pradhan Ashis Kumar , Hiremath Gourishankar S.
Published: July 2019

The growing levels of external commercial borrowings (ECBs) among the emerging and developing economies have raised the fears that ECBs would lead to widespread crisis and threaten financial stability in India. Against this backdrop, the current study seeks to examine the trends and critically evaluate the policy pertaining to ECBs. In order to immune the economy from potential exchange rate shocks, we suggest to having specific policy focus on the domestic bond market, hedging mechanisms, and appropriate decisions on the cap and level of ECBs by the regulator.
Flame retardancy of epoxy resin nanocomposite with a novel polymeric nanoflame retardant
Authors: Zhai Congcong , Xin Fei , Chen Yu , Cai Liyun , Qian Lijun
Published: July 2019

A wrapped nanoflame retardant, designated as polyhedral oligomeric silsesquioxane (POSS)‐poly(4‐bromostyrene) (PBS)‐carbon nanotubes (CNTs), was synthesized via π‐π stacking interactions between the walls of multiwalled carbon nanotubes and the silicon‐bromine containing hybrid copolymer (designated as POSS‐PBS) that was copolymerized by 4‐bromostyrene and acryloyloxyisobutyl polyhedral oligomeric silsesquioxane. The POSS‐PBS‐CNTs exhibited good dispersibility in epoxy resin (EP) without obvious aggregation. Furthermore, the fire behaviors of this flame‐retardant EP (FR‐EP) nanocomposites were examined via limited oxygen index (LOI) and cone calorimeter (CONE) tests. The FR‐EP had an ideal LOI value of 35.3% and its residual char yield obtained from CONE test was significantly enhanced from 5.9% to 15.3% with the incorporation of 4 wt% POSS‐PBS‐CNTs and 1.33 wt% Sb2O3 into EP matrix. Additionally, the addition of 4 wt% POSS‐PBS‐CNTs or POSS‐PBS can efficiently decrease the peak heat release rate (PHRR) of EP matrix by 41.0% or 45.6%, respectively.
Rapid identification of dragon blood samples from Daemonorops draco, Dracaena cinnabari and Dracaena cochinchinensis by MALDI‐TOF mass spectrometry
Authors: Wu Chunhung , Cai Xin‐Qi , Chang Yu , Chen Chueh‐Hsuan , Ho Tsung‐Jung , Lai Shang‐Chih , Chen Hao‐Ping
Published: July 2019

Introduction

Dragon blood is a deep‐red plant resin which has been used as folk medicine for more than a thousand years. It can be produced from at least four entirely different plant families: Asparagaceae, Arecaceae, Chamaesyce, and Fabaceae. Current pharmacopeia states that the only “authentic” source of dragon blood is the palm tree, Daemonorops draco.

Objective

The present study aims to find a high‐throughput method to screen and identify the plant sources of commercial dragon blood products.

Methodology

A matrix‐assisted laser desorption ionisation time‐of‐flight mass spectrometry (MALDI‐TOF MS) based method for rapid screening of dracorhodin in commercial dragon blood samples was established in this study.

Results

Well‐resolved peaks of dracorhodin in spectra were observed in the crude extracts of samples. Dragon blood samples from two other plant species, Dracaena cinnabari and Dracaena cochinchinensis, were also examined. Their indicator compounds, loureirin A and B, were detected in these plants.

Conclusion

A MALDI‐TOF based method for preliminarily examination of commercial dragon blood samples is reported here. In contrast to MALDI‐TOF, liquid chromatography mass spectrometry (LC‐MS) is a time‐consuming and costly method, not ideal for routine and large‐scale screening of commercial samples.
Green extraction of oil from Carum carvi seeds using bio‐based solvent and supercritical fluid: Evaluation of its antioxidant and anti‐inflammatory activities
Authors: Bourgou Soumaya , Bettaieb Rebey Iness , Dakhlaoui Sarra , Msaada Kamel , Saidani Tounsi Moufida , Ksouri Riadh , Fauconnier Marie‐Laure , Hamrouni‐Sellami Ibtissem
Published: July 2019

Introduction

The consumption of health‐promoting products such as oil seeds may improve human health and prevent certain diseases. Carvi seeds have the potential to produce oil with nutritional and functional properties rich in active compounds.

Objective

To extract bioactive lipids from Carum carvi seeds using green methodologies.

Material and methods

Supercritical‐carbon dioxide (Sc‐CO2) and ethanol as co‐solvent and bio‐based solvent 2‐methyltetrahydrofuran (MeTHF) were used to extract the oil from Carum carvi. The yield, the chemical composition, as well as antioxidant and anti‐inflammatory activities of green extracted oils were investigated and compared to those obtained with conventional methods (hexane and Folch system).

Results

MeTHF extraction gave higher oil yield than that obtained by hexane. Fatty acids composition of the two obtained green extracted oils was similar to conventional extracted ones where petroselinic (39–43%), linoleic (29–31%) and oleic (19–21%) acids were the major compounds. Furthermore, MeTHF and Sc‐CO2 green extracted oils were enriched of bioactive compounds including sterols (5.4 and 7.3 mg/g oil) and total polyphenols (9.3 and 7.6 mg GAE/g oil) which were correlated to enhanced antiradical capacity. Moreover, the green extracted oils exhibited high anti‐inflammatory capacity inhibiting nitric oxide (NO) release in lipopolysaccharide (LPS)‐induced RAW 264.7 macrophages with IC50 values of 28 and 24 μg/mL.

Conclusion

Green solvents are a good alternative to petroleum solvents to recover oil from carvi seeds with high amount of nutritionally important fatty acids, along with significant antioxidant and anti‐inflammatory potential.
Rheological behavior of polypropylene nanocomposites with tailored polymer/multiwall carbon nanotubes interface
Authors: Wang Po‐Hsiang , Gulgunje Prabhakar , Ghoshal Sushanta , Verghese Nikhil , Kumar Satish
Published: July 2019

Maleic anhydride grafted polypropylene (MA‐g‐PP) or polypropylene (PP) was noncovalently coated onto acid functionalized multiwall carbon nanotube (f‐MWNT) through solution mixing. These coated f‐MWNTs and pristine MWNT (p‐MWNT) were melt microcompounded with neat PP to form PP/f‐MWNT and PP/p‐MWNT nanocomposites at 0.1–1 wt% MWNT concentration. Complex viscosity and tan δ (ratio of loss modulus to storage modulus) behavior of these systems were studied using dynamic frequency sweep test, while relaxation time, activation energy, and melt homogeneity were also calculated and compared. Among the three types of samples, PP/f‐MWNT masterbatch‐based nanocomposite demonstrated not only the presence of interphase but also good processability. As a consequence, increase of both the crystallization rate in the presence of shear and the melt elasticity during annealing were found only in the masterbatch‐based samples but not in the PP/p‐MWNT. The mechanism of such increased melt elasticity was attributed to the formation of the space‐spanning network, which is consistent with the Cole–Cole plot showing similar behavior to the branched polymers in the literature. This has implications in polymer processing due to suggested changes in the balance between melt strength and polymer flow. Nanocomposite rheological behavior has also been correlated with the mechanical properties. POLYM. ENG. SCI., 59:1763–1777, 2019. © 2019 Society of Plastics Engineers
High residual mechanical properties at elevated temperatures of bamboo/glass reinforced‐polybenzoxazine hybrid composite
Authors: Zhang Kai , Wang Fangxin , Pang Yuezhao , Liang Wenyan , Wang Zhenqing
Published: July 2019

We successfully added bamboo and glass fibers into bisphenol A‐aniline based benzoxazine (BA‐a) resin by hot‐pressing method. In order to improve the interfacial adhesion between bamboo fibers and the matrix, bamboo fibers were pretreated in 6 wt% NaOH solutions for 12 h. The results showed alkali‐treatment had a positive effect on mechanical properties of the composites at both room and elevated temperatures (60°C, 110°C, 160°C, and 210°C). Due to the incorporation of glass fibers, the bamboo/glass reinforced‐polybenzoxazine hybrid composites exhibited highest strength and modulus among all samples and had high residual mechanical properties at elevated temperatures (residual mechanical properties refers to the ratio of strength and modulus of the composites at elevated temperatures to that measured at room temperature). The fractured surface morphologies of the composites were observed by scanning electron microscope. The results showed with the increase of temperature, the debonding and fiber pull‐out became apparent, and the matrix softening could be clearly observed at 210°C. In addition, thermal and thermomechanical properties of neat benzoxazine and the composites were also investigated through thermogravimetric analysis and dynamic mechanical analyzer, respectively. POLYM. ENG. SCI., 59:1818–1829, 2019. © 2019 Society of Plastics Engineers
Short self‐assembling cationic antimicrobial peptide mimetics based on a 3,5‐diaminobenzoic acid scaffold
Authors: Thota Chaitanya K. , Berger Allison A. , Harms Björn , Seidel Maria , Böttcher Christoph , von Berlepsch Hans , Xie Chaunxiong , Süssmuth Roderich , Roth Christian , Koksch Beate
Published: July 2019

Infections caused by Staphylococcal and Micrococcal species represent a major public health burden. Although treatments do exist, these tend to be associated with cytotoxic effects; furthermore, the emergence of antimicrobial resistance presents an immediate challenge. New classes of active compounds are required to address these threats to human health. Here we present a de novo peptidomimetic strategy that produces self‐assembling cationic antimicrobials. To identify a candidate compound with bactericidal activity, a small library of 8 peptidomimetics comprising ultrashort peptide sequences attached to a 3,5‐diaminobenzoic acid scaffold was generated and tested against Micrococcus luteus and Staphylococcus aureus. Self‐assembly appears to be the driving force for increased potency, likely by contributing to increased local surface charge density and peptide mass and producing a multivalent effect that enhances electrostatic interactions with negatively charged bacterial membranes, causing membrane disruption. The most active library member C7 forms patched micellar nanoparticles and has an activity higher than that of known natural antimicrobial peptides against M luteus. C7 also shows activity comparable to that of gramicidin S and the standard antibiotic vancomycin used in antibacterial therapy, but with a greater selectivity index. Importantly, C7 is also nontoxic and nonhemolytic, unlike the currently administered vancomycin, which can cause acute renal failure, and gramicidin S, which is highly hemolytic in nature. The short sequence length, ease of design, convenient synthesis strategy, and presence of a substitutable hydrophobic residue that enables self‐assembly into different nanostructures make this model compound highly attractive for generating cost‐effective, rapid‐acting peptide‐based antimicrobials.
PEGylated polylysine derived copolymers with reduction‐responsive side chains for anticancer drug delivery
Authors: Yao Jiuxu , He Pan , Zhang Yu , Zhang Hongyu , Zhang Peng , Deng Mingxiao , Xiao Chunsheng
Published: July 2019

Reduction‐responsive drug delivery systems have recently gained intense attention in intracellular delivery of anticancer drugs. In this study, we developed a PEGylated polypeptide, poly(ethylene glycol)‐block‐poly(ϵ‐propargyloxycarbonyl‐l‐lysine) (PEG113‐b‐PPAL), as a novel clickable substrate for conjugation of reduction‐responsive side chains for antineoplastic drug delivery. PEG113‐b‐PPAL was synthesized through ring‐opening polymerization of alkyne‐containing N‐carboxyanhydride monomers. A designed disulfide‐containing side chain was introduced onto the PEGylated polypeptide by click reaction. The obtained copolymer PEG113‐b‐P(Lys‐DSA) formed micelles by self‐assembly, which exhibited reduction‐responsive behavior under the stimulus of 10 mmol L–1 glutathione (GSH) in water. A small molecule intermediate, compound 2, was used as a model to investigate the thiol reduction mechanism of PEG113‐b‐P(Lys‐DSA) copolymers. The anticancer drug doxorubicin (DOX) was then loaded into the micelles with a drug loading content of 6.73 wt% and a loading efficiency of 40.3%. Both the blank and the drug‐loaded micelles (DOX‐loaded polylysine derived polymeric micelles (LMs/DOX)) adopted a spherical morphology, with average diameters of 48.0 ± 13.1 and 63.8 ± 20.0 nm, respectively. The in vitro drug release results indicated that DOX could be released faster from the micelles by the trigger of GSH in phosphate buffered saline. Confocal laser scanning microscopy and flow cytometer analysis further proved the intracellular delivery of DOX by LMs/DOX and their GSH‐sensitive release behavior. A 3‐(4,5‐dimethyl‐thiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay showed that the polymers exhibited negligible cytotoxicity towards normal L929 cells or cancer MCF‐7 cells with a treated concentration up to 1.0 mg mL–1. In conclusion, our synthesized biocompatible and biodegradable PEGylated polypeptides hold great promise for intracellular antineoplastic drug delivery. © 2019 Society of Chemical Industry
Physiological instability after respiratory pauses in preterm infants
Authors: Marshall Andrew P. , Lim Kathleen , Ali Sanoj K. , Gale Timothy J. , Dargaville Peter A.
Published: July 2019

Background

The factors influencing the severity of apnea‐related hypoxemia and bradycardia are incompletely characterized, especially in infants receiving noninvasive respiratory support.

Objectives

To identify the frequency and predictors of physiological instability (hypoxemia—oxygen saturation (SpO2) <80%, or bradycardia—heart rate (HR) < 100 bpm) following respiratory pauses in infants receiving noninvasive respiratory support.

Methods

Respiratory pause duration, derived from capsule pneumography, was measured in 30 preterm infants of gestation 30 (24‐32) weeks [median (interquartile range)] receiving noninvasive respiratory support and supplemental oxygen. For identified pauses of 5 to 29 seconds duration, we measured the magnitude and duration of SpO2 and HR reductions over a period starting at the pause onset and ending 60 seconds after resumption of breathing. Temporally clustered pauses (<60 seconds separation) were analyzed separately. The relative contribution of respiratory pauses to overall physiological instability was determined, and predictors of instability were sought in regression analysis, including demographic, clinical and situational variables as inputs.

Results

In total, 17 105 isolated and 9180 clustered pauses were identified. Hypoxemia and bradycardia were more likely after longer duration and temporally‐clustered pauses. However, the majority of such episodes occurred after 5 to 9 second pauses given their numerical preponderance, and short‐lived pauses made a substantial contribution to physiological instability overall. Birth gestation, hemoglobin concentration, form of respiratory support, caffeine treatment, respiratory pause duration and temporal clustering were identified as predictors of instability.

Conclusions

Brief respiratory pauses, especially when clustered, contribute substantially to hypoxemia and bradycardia in preterm infants.
Ethnicity and neighbourhood attainment in England and Wales: A study of second generations' spatial integration
Authors: Zuccotti Carolina V.
Published: July 2019

Ethnic minorities' spatial concentration and their predominance in deprived areas are two well‐known patterns that characterise Britain's social landscape. However, little is known about ethnic minorities' opportunities for spatial integration, especially those of the second generations. Using a large‐scale longitudinal data set of England and Wales covering a 40‐year period (1971–2011), in combination with aggregated census data, the article examines ethnic inequalities in access to neighbourhoods with varying levels of ethnic concentration and deprivation. On equality of individual, social origin, and childhood neighbourhood characteristics, second generation ethnic minorities are less likely than White British individuals to reside in “whiter” and less deprived neighbourhoods. For most minorities, these differences reduce among those with higher education and a higher social class, in line with weak place stratification/ethnic enclave. Growing up in areas with high ethnic concentration and high deprivation has a particularly strong “retention effect” among second generation Asians. The study shows that ethnic spatial segregation is, in part, the product of time‐persisting ethnic inequalities in the access to neighbourhoods and that these inequalities are conditioned both by childhood and by adult resources.
Herbal medicine: Who cares? The changing views on medicinal plants and their roles in British lifestyle
Authors: Lazarou Rebecca , Heinrich Michael
Published: July 2019

Herbal medicines are not only widely used but also contentious health care products. Currently, little is known about the products' place in people's health care strategies and their views about such products. The aims of the study are to gain insight into the public's perception of herbal medicine/general use of herbs for health, as well as on the growing of plants for medicine. Core to the research was a survey that covered participants' views about herbal medicines. Data were collected online and from visitors at the Eden Project, as well as some other garden events. Survey responses were categorized and analysed using Qualtrics. Overall, 408 participants participated though numbers varied across questions. Results show that herbal medicines are popular, particularly amongst the 36‐ to 55‐year‐old age group. Participants mostly used herbal medicines for minor self‐limiting conditions. Popular reasons for use included that plant medicines are natural and have fewer side effects, as well as for a few changing relationship with conventional medicines. Around a third of participants grew their own plants for health care. This is the first larger U.K.‐based survey indicating a wide use of such products, and it is therefore recommended that there is an increase in quality control and wider regulation. Access to high‐quality products should be prioritized.
Neuronal Stem Cell and Drug Interactions: A Systematic Review and Meta-Analysis: Concise Review
Authors: Ikhsan Maulana , Palumbo Alex , Rose Dorothee , Zille Marietta , Boltze Johannes
Published: July 2019

Stem cell therapy is a promising treatment option for neurodegenerative diseases that mostly affect geriatric patients who often suffer from comorbidities requiring multiple medications. However, not much is known about the interactions between stem cells and drugs. Here, we focus on the potential interactions between drugs used to treat the comorbidities or sequelae of neurodegenerative diseases and neuronal stem cells to reveal potential effects on drug safety and efficacy. To determine the potential effects of drugs frequently used in geriatric patients (analgesic, antibiotic, antidepressant, antidiabetic, antihyperlipidemic, and antihypertensive drugs) on neuronal stem cell differentiation and proliferation, we systematically searched PubMed to identify nonreview articles published in English in peer-reviewed journals between January 1, 1991, and June 7, 2018. We identified 5,954 publications, of which 214 were included. Only 62 publications provided the complete data sets required for meta-analysis. We found that antidepressants stimulated neuronal stem cell proliferation but not differentiation under physiologic conditions and increased the proliferation of stem cells in the context of stress. Several other potential interactions were identified, but the limited number of available data sets precludes robust conclusions. Although available data were in most cases insufficient to perform robust meta-analysis, a clear interaction between antidepressants and neuronal stem cells was identified. We reveal other potential interactions requiring further experimental investigation. We recommend that future research addresses such interactions and investigates the best combination of pharmacological interventions and neuronal stem cell treatments for more efficient and safer patient care. Stem Cells Translational Medicine  2019;8:1202–1211
Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review
Authors: Mastrolia Ilenia , Foppiani Elisabetta Manuela , Murgia Alba , Candini Olivia , Samarelli Anna Valeria , Grisendi Giulia , Veronesi Elena , Horwitz Edwin M. , Dominici Massimo
Published: July 2019

Identified 50 years ago, mesenchymal stromal/stem cells (MSCs) immediately generated a substantial interest among the scientific community because of their differentiation plasticity and hematopoietic supportive function. Early investigations provided evidence of a relatively low engraftment rate and a transient benefit for challenging congenital and acquired diseases. The reasons for these poor therapeutic benefits forced the entire field to reconsider MSC mechanisms of action together with their ex vivo manipulation procedures. This phase resulted in advances in MSCs processing and the hypothesis that MSC-tissue supportive functions may be prevailing their differentiation plasticity, broadening the spectrum of MSCs therapeutic potential far beyond their lineage-restricted commitments. Consequently, an increasing number of studies have been conducted for a variety of clinical indications, revealing additional challenges and suggesting that MSCs are still lagging behind for a solid clinical translation. For this reason, our aim was to dissect the current challenges in the development of still promising cell types that, after more than half a century, still need to reach their maturity. Stem Cells Translational Medicine  2019;8:1135–1148
Exposure density sampling: Dynamic matching with respect to a time‐dependent exposure
Authors: Ohneberg Kristin , Beyersmann Jan , Schumacher Martin
Published: July 2019

Estimating the potential risk associated with an exposure occurring over time requires complex statistical techniques, since ignoring the time from study entry until the exposure leads to potentially seriously biased effect estimates. A prominent example is estimating the effect of hospital‐acquired infections on adverse outcomes in patients admitted to the intensive care unit. Exposure density sampling has been proposed as an approach to dynamic matching with respect to a time‐dependent exposure. Firstly, exposure density sampling can be useful to reduce the workload of study follow up, as it includes all exposed but only a subset of the not yet exposed individuals. Secondly, it can help to obtain a comparable control group by including propensity score matching. In the present article, we provide the theoretical justification that data obtained by exposure density sampling can be analyzed as a left‐truncated cohort. It is shown that exposure density sampling allows estimation of the effect of a time‐dependent exposure as well as further baseline covariates on a subsequent event, with only minor loss in precision as compared with a full cohort analysis. The sampling is applied to a real data example (hospital‐acquired infections in intensive care units) and in a simulation study. We also provide an estimate of the loss in precision in terms of an increased standard error in the reduced data set after exposure density sampling as compared with the full cohort.
Accounting for established predictors with the multistep elastic net
Authors: Chase Elizabeth C. , Boonstra Philip S.
Published: July 2019

Multivariable models for prediction or estimating associations with an outcome are rarely built in isolation. Instead, they are based upon a mixture of covariates that have been evaluated in earlier studies (eg, age, sex, or common biomarkers) and covariates that were collected specifically for the current study (eg, a panel of novel biomarkers or other hypothesized risk factors). For that context, we present the multistep elastic net (MSN), which considers penalized regression with variables that can be qualitatively grouped based upon their degree of prior research support: established predictors vs unestablished predictors. The MSN chooses between uniform penalization of all predictors (the standard elastic net) and weaker penalization of the established predictors in a cross‐validated framework and includes the option to impose zero penalty on the established predictors. In simulation studies that reflect the motivating context, we show the comparability or superiority of the MSN over the standard elastic net, the Integrative LASSO with Penalty Factors, the sparse group lasso, and the group lasso, and we investigate the importance of not penalizing the established predictors at all. We demonstrate the MSN to update a prediction model for pediatric ECMO patient mortality.
Highly Active and Easily Fabricated NiCo2O4 Nanoflowers for Enhanced Methanol Oxidation
Authors: Faid Alaa Y. , Ismail Hadeer
Published: July 2019

Metal oxides with tailored nanomorphology represent a powerful tool to improve the electrocatalytic activity. Herein NiCo2O4 nanoflowers were synthesized via facile microwave method. NiCo2O4 nanoflowers were characterized by scanning and transmission electron microscopy, X‐ray diffraction (XRD), Raman spectroscopy, N2 gas adsorption/desorption, and X‐ray photoelectron spectroscopy (XPS). Through comparing NiCo2O4 nanoparticle vs nanoflowers morphology, NiCo2O4 nanoflowers have a superior mass and specific electroactivity towards oxygen evolution reaction (OER) by achieving a current density of 10 mA/cm2 at an overpotential of only 280 mV in 1M KOH electrolyte. Moreover, NiCo2O4 nanoflowers display superior performance for methanol electrooxidation in fuel cells by achieving 200 A/g and recovers 92.3 % of the original activity through the addition of new (1M KOH + 0.5M methanol) electrolyte after 500 cycles.
Engineering cyber‐physical systems through performance‐based modelling and analysis: A case study experience report
Authors: Pagliari Lorenzo , Mirandola Raffaela , Trubiani Catia
Published: July 2019

The process of engineering cyber‐physical systems (CPS) is inevitably challenging because of the intrinsic problem of merging the specification of different ensembles that indicate hardware, software, and physical aspects of such systems. This intrinsic complexity is exacerbated when modelling and analysing the performance characteristics of CPS since multiple models need to coexist in order to get meaningful performance indicators. In this paper, we present a case study, a delivery robots system, whose experience is exploited towards building a guided process for engineering CPS through performance‐based modelling and analysis. Model‐based performance results are provided while analysing different design alternatives, thus to support architects in the process of better understanding the performance characteristics of CPS under development.
Tackling complexity and problem formulation in rural electrification through conceptual modelling in system dynamics
Authors: Hartvigsson Elias , Ahlgren Erik Oscar , Molander Sverker
Published: July 2019

Mini‐grids are considered important in order to improve access to electricity in developing countries. Their technical and organizational independence from the large national grids and their interactions with local social, economic, and environmental factors suggests that system dynamics is a useful method of analysis. However, the successful implementation of mini‐grids in rural electrification has partly been prevented due to complexity issues, making problem formulation difficult. Most problem‐solving methods, such as system dynamics, require well‐defined problems. Previous work on the problem formulation process in system dynamics is limited. This work presents a conceptual framework for tackling complexity and uncertainties in rural electrification. The conceptual framework is general and draws on research in conceptual modelling and system dynamics. The focus is on the learning that can be achieved from a system description and how it can be used to tackle complexity by reducing uncertainties and improving knowledge.
A multiattribute cumulative sum‐np chart
Authors: Chong Nger Ling , Khoo Michael B.C. , Haridy Salah , Shamsuzzaman Mohammad
Published: July 2019

Multiattribute charts can be adopted in various processes as there are numerous quality characteristics that cannot be represented quantitatively or are not easily expressed on a numerical scale. However, only a limited amount of research has been done on multiattribute charts. The multiattribute np (Mnp) chart has been developed to monitor attribute data with multiple quality characteristics. In this paper, a binomial multiattribute cumulative sum (MCUSUM) chart is developed. For a better detection effectiveness, the multiattribute cumulative sum‐np (MCUSUM‐np) chart that merges the binomial MCUSUM and Mnp charts to monitor upward shifts in fraction nonconforming is further proposed. A comprehensive comparison of the MCUSUM‐np chart with its individual counterparts, in terms of the average number of nonconforming units and average time to signal criteria, shows that the MCUSUM‐np chart has a better or at least equal performance compared with its basic charts. The implementation of the proposed charts is illustrated with a real‐life application on the cold rolling process. The findings of this paper will improve the detection of shifts in fraction nonconforming so that practitioners can take swift corrective actions to return an out‐of‐control process to its in‐control condition.
Persistent organic pollutants (POPs) increase rage signaling to promote downstream cardiovascular remodeling
Authors: Coole Jackson B. , Burr Stephanie S. , Kay Amber M. , Singh Jaime A. , Kondakala Sandeep , Yang Eun‐Ju , Kaplan Barbara L. F. , Howell George E. , Stewart James A.
Published: July 2019

Exposure to environmental contaminants and consumption of a high, saturated fatty diet has been demonstrated to promote precursors for metabolic syndrome (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this study was to determine if exposure to the most prevalent environmental persistent organic pollutants (POPs) would act as causative agents to promote metabolic syndrome independent of dietary intake. We hypothesized that POPs will activate the advanced glycated end‐product (AGE)‐and receptor for AGE (RAGE) signaling cascade to promote downstream signaling modulators of cardiovascular remodeling and oxidative stress in the heart. At 5‐weeks of age nondiabetic (WT) and diabetic (ob/ob) mice were exposed POPs mixtures by oral gavage twice a week for 6‐weeks. At the end of 6‐weeks, animals were sacrificed and the hearts were taken for biochemical analysis. Increased activation of the AGE‐RAGE signaling cascade via POPs exposure resulted in elevated levels of fibroblast differentiation (α‐smooth muscle actin) and RAGE expression indicated maladaptive cardiac remodeling. Conversely, the observed decreased superoxide dismutase‐1 and ‐2 (SOD‐1 and SOD‐2) expression may exacerbate the adverse changes occurring as a result of POPs treatment to reduce innate cardioprotective mechanisms. In comparison, ventricular collagen levels were decreased in mice exposed to POPs. In conclusion, exposure to organic environmental pollutants may intensify oxidative and inflammatory stressors to overwhelm protective mechanisms allowing for adverse cardiac remodeling.
NLRP3 inflammasome activation is associated with PM2.5‐induced cardiac functional and pathological injury in mice
Authors: Duan Shuyin , Wang Na , Huang Li , Zhao Ying , Shao Hua , Jin Yuefei , Zhang Ruiqin , Li Chunyang , Wu Weidong , Wang Jing , Feng Feifei
Published: July 2019

Growing evidences indicate that inflammation induced by PM2.5 exposure has been considered as a major driving force for the development of cardiovascular diseases. However, the mechanisms underlying PM2.5‐induced cardiac injury remain unclear. This study aims to investigate the role of NLRP3 inflammasome in PM2.5‐induced cardiac functional and pathological injury in mice. In this study, BALB/c mice were intratracheally instilled with PM2.5 suspension (4.0 mg/kg BW) for 5 days to set up a cardiac injury model, which was evaluated by electrocardiogram monitoring, HE and Masson staining. Then, the effects of PM2.5 on the expression of α‐SMA, NLRP3, IL‐1β, and IL‐18 proteins and the activation of caspase‐1 and IL‐1β were investigated. The results showed that PM2.5 exposure induced characteristic abnormal ECG changes such as the abnormality of heart rhythm, tachycardia, and T‐wave reduction. Inflammatory cell infiltration and fibrosis were observed in the heart tissues of PM2.5‐exposed mice. Meanwhile, PM2.5 exposure increased the expression of α‐SMA. And, NLRP3 activation‐associated proteins of NLRP3, IL‐1β, IL‐18, Cleaved caspase‐1 p10, and Cleaved IL‐1β were upregulated in heart tissue of PM2.5‐induced mice. In summary, PM2.5 exposure could induce cardiac functional and pathological injury, which may be associated with the activation of NLRP3 inflammasome.
Critical infrastructure and flood resilience: Cascading effects beyond water
Authors: Fekete Alexander
Published: July 2019

Critical infrastructure and cascading effects are analyzed in this article as cross‐cutting topics in flood risk and resilience. A concept is developed for integrating aspects of disaster risk, hazard, vulnerability and resilience with critical infrastructure analytic components such as redundancy, rapidity or resourcefulness. These components are expressed for each phase of an unfolding flood event and cascading effects are indicated, too. This contribution discusses the implications of such a conceptual frame for the advancement of existing flood risk management concepts. Current international guiding strategies such as the United Nations Sendai Framework for Disaster Risk Reduction, the “Making Cities Resilient” campaigns in field of urban disaster resilience, Climate Change Adaptation processes such as the Paris Agreement of the IPCC process, or urban planning in the field of UN HABITAT are all interconnected to the topic of (critical) infrastructure. The article shows how flood risk management can connect to such wider international developments by the conceptual frame discussion presented.

This article is categorized under:

Engineering Water > Planning Water

Science of Water > Water Extremes

Human Water > Water Governance
Coal and climate change
Authors: Edwards Gareth A. S.
Published: July 2019

This overview adopts a critical social science perspective to examine the state of play and potential futures for coal in the context of climate change. It introduces key trends in coal consumption, production and trade, before reviewing the relevant literature. Finding surprisingly little literature directly focused on coal and climate change, it appraises existing work and highlights key areas for future research. In addition to established literatures on the situated politics of coal and the political economy of coal, new work calling for demand side policies to be supplemented with supply side policies highlights the increasing importance of normative contestations in driving debates over coal. This suggests that scholars must engage much more directly with climate change as an issue, and particularly with the place of coal in a just transition. Because of coal's mammoth contribution to climate change and the complex political economy which drives its production and consumption, it is likely that coal will remain at the center of difficult questions about the relationship between climate action and development for quite some time.

This article is categorized under:

Climate and Development > Decoupling Emissions from Development
Hybrid modeling frameworks of tumor development and treatment
Authors: Chamseddine Ibrahim M. , Rejniak Katarzyna A.
Published: July 2019

Tumors are complex multicellular heterogeneous systems comprised of components that interact with and modify one another. Tumor development depends on multiple factors: intrinsic, such as genetic mutations, altered signaling pathways, or variable receptor expression; and extrinsic, such as differences in nutrient supply, crosstalk with stromal or immune cells, or variable composition of the surrounding extracellular matrix. Tumors are also characterized by high cellular heterogeneity and dynamically changing tumor microenvironments. The complexity increases when this multiscale, multicomponent system is perturbed by anticancer treatments. Modeling such complex systems and predicting how tumors will respond to therapies require mathematical models that can handle various types of information and combine diverse theoretical methods on multiple temporal and spatial scales, that is, hybrid models. In this update, we discuss the progress that has been achieved during the last 10 years in the area of the hybrid modeling of tumors. The classical definition of hybrid models refers to the coupling of discrete descriptions of cells with continuous descriptions of microenvironmental factors. To reflect on the direction that the modeling field has taken, we propose extending the definition of hybrid models to include of coupling two or more different mathematical frameworks. Thus, in addition to discussing recent advances in discrete/continuous modeling, we also discuss how these two mathematical descriptions can be coupled with theoretical frameworks of optimal control, optimization, fluid dynamics, game theory, and machine learning. All these methods will be illustrated with applications to tumor development and various anticancer treatments.

This article is characterized under:

Analytical and Computational Methods > Computational Methods

Translational, Genomic, and Systems Medicine > Therapeutic Methods

Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
A magnetic spectrometer for electron‐positron pair spectroscopy in storage rings
Authors: Hagmann Siegbert , Hillenbrand Pierre‐Michel , Litvinov Yuri A. , Spillmann Uwe , Stöhlker Thomas
Published: July 2019

We report an analysis of electron‐optical properties of a toroidal magnetic sector spectrometer and examine parameters for its implementation in a relativistic heavy‐ion storage ring, for example the High Energy Storage ring (HESR) at the future Facility for Antiproton and Ion Research (FAIR) facility. For studies of free–free pair production in heavy‐ion atom collisions, this spectrometer exhibits very high efficiencies for coincident e+–e− pair spectroscopy over a wide range of momenta of emitted lepton pairs. The high coincidence efficiency of the spectrometer is the key for stringent tests of theoretical predictions for the phase space correlation of lepton vector momenta in free–free pair production.
Correction to: Pathways and Consequences of Legal Irregularity
Authors: Vickstrom Erik R.
Published: July 2019

This book was inadvertently published without the inclusion of an Acknowledgement. It has now been updated.