bluuebunny/crossref_metadata_2025 huggingface dataset:
The multifaceted Foxp3fgfp allele enhances spontaneous and therapeutic immune surveillance of cancer in mice
Authors: Almeida‐Santos José , Bergman Marie‐Louise , Amendoeira Cabral Inês , Correia Vasco , Caramalho Íris , Demengeot Jocelyne
Published: November 2019

It is well established that therapeutic impairment of Foxp3+ Treg in mice and humans favors immune rejection of solid tumors. Less explored is the impact Foxp3 allelic variants may have on tumor incidence, progression and therapy. In this work, we tested and demonstrate that the Foxp3fgfp reporter allele, found previously to either enhance or reduce Treg function in specific autoimmunity settings, confers increased anti‐tumor immunity. Our conclusions stem out of the analysis of three tumor models of different tissue origin, in two murine genetic backgrounds. When compared to wild type animals, mice carrying the Foxp3fgfp allele spontaneously delay, reduce or prevent primary tumor growth, decrease metastasis growth, and potentiate the response to anti‐CTLA4 monotherapy. These findings suggest allelic variances at the Foxp3 locus may serve as predictive indicators for personalized therapy and prognostics, and point at possible new therapeutic targets.
Energy and exergy analyses of the solar assisted multigeneration system with thermal energy storage system
Authors: Ratlamwala Tahir A. H. , Gill Eliezer Z.
Published: November 2019

The following analysis has been conducted to investigate the energy and exergy efficiencies of solar assisted multigeneration system, the system comprises of parabolic trough solar collector, thermal energy storage tank, regenerative power plant, double effect absorption cooling system, and PEM electrolyzer. The variation in energy and exergy efficiencies of the parabolic solar trough collector with respect to solar absorptivity is also shown in the analysis. The heat transfer rate, the resultant outputs, the efficiencies, and the rate of exergy destructions for each component are calculated. The freshwater is used as the primary working fluid for the overall cycle and the net power produced by the low‐pressure turbine is 1.384 MW, additionally, the rate of heat produced by the thermal storage tank is 205.7 kW and the calculated thermal efficiency of the thermal storage tank is 14.33%. The overall analysis has been done by using engineering equation solver and parametric results are shown in order to determine the variations in the system.
Biocontrol of toxigenic Aspergillus strains isolated from baby foods by essential oils
Authors: Yassein Asmaa S. , El‐Said Ahmed H. M. , El‐Dawy Eman G. A.
Published: November 2019

Essential oils are natural antimicrobial agents that can be used to control fungal and mycotoxin contamination. Although there are numerous reports discussing the fungal and mycotoxin contamination of foods, there are few researches on baby food contamination so this work aimed to determine the fungal and mycotoxin contamination in cerelac, cornflakes and milk powder and tried to control the mycotoxigenic strain growth and their production of mycotoxins by using essential oils. Cornflakes were heavily contaminated (24 species including 9 genera), while cerelac and milk powder were less contaminated. Aspergillus and Penicillium were the prevalent genera. The produced aflatoxins and ochratoxins from the tested strains of Aspergillus flavus and A. niger were extracted and estimated by fluorometric method. We used the 18S rRNA sequence technique to identify the genotypes of the three isolates. Two isolates were identified as Aspergillus niger and the third isolate as A. flavus. Omt‐A gene was detected in the A. flavus, while Aopks gene was detected in A. niger isolates. Amongst the five used essential oils, only cumin and peppermint oil depressed the mycotoxigenic strain growth and peppermint oil had the highest result. Its inhibitory effect on aflatoxin and ochratoxin production was evaluated. Aflatoxin production was highly reduced by 52.1%, but ochratoxin inhibition was very low, 4.88% and 3.17% by A. niger obtained from cornflakes and milk powder, respectively. The three tested samples were contaminated by ochratoxins, but cerelac and milk powder samples were free of aflatoxins. Cornflakes sample recorded the highest reading for both toxins.
A mixed least‐squares finite element formulation with explicit consideration of the balance of moment of momentum, a numerical study
Authors: Igelbüscher Maximilian , Schröder Jörg , Schwarz Alexander
Published: November 2019

Important conditions in structural analysis are the fulfillment of the balance of linear momentum (vanishing resultant forces) and the balance of angular momentum (vanishing resultant moment), which is not a priori satisfied for arbitrary element formulations. In this contribution, we analyze a mixed least‐squares (LS) finite element formulation for linear elasticity with explicit consideration of the balance of angular momentum. The considered stress‐displacement (σ − u) formulation is based on the squared L2(ℬ)‐norm minimization of the residuals of a first‐order system of differential equations. The formulation is constructed by means of two residuals, that is, the balance of linear momentum and the constitutive equation. Motivated by the crucial point of weighting factors within LS formulations, a scale independent formulation is constructed. The displacement approximation is performed by standard Lagrange polynomials and the stress approximation with Raviart‐Thomas functions. The latter ansatz functions do not a priori fulfill the symmetry of the Cauchy stress tensor. Therefore, a redundant residual, the balance of angular momentum ((x − x0) × (divσ + f) + axl[σ − σT]), is introduced and the results are discussed from the engineering point of view, especially for coarse mesh discretizations. However, this formulation shows an improvement compared to standard LS σ − u formulations, which is considered here in a numerical study.
What's Your Organization's Carbon Budget?
Authors: Livermore John
Published: November 2019

The urgency to address the existing climate crisis cannot be overstated. The October 2018 Intergovernmental Panel on Climate Change (IPCC) Special Report on Global Warming of 1.5°C clearly indicates our society has just 10 years in which to reduce our carbon emissions in half. If we do not achieve this, society risks passing a global climate tipping point beyond which climate feedback loops take over, causing an irreversible chain reaction beyond human control, and no amount of human mitigation can keep the world's climate from catastrophic disruption. This is a sobering scientific reality that presents an existential emergency not only for each of us individually, but for each organization and business, since all enterprise depends on a stable climate in order to operate.
Electric‐Sector Capabilities Needed to Address Climate Change
Authors: DeCotis Paul A.
Published: November 2019

Climate‐change mitigation strategies and clean energy goals of some 23 states are currently requiring utilities to invest directly or support private‐sector investment in distributed energy resources (DERs), including renewable energy, energy efficiency, load‐modifying demand response, and electricity storage. These technologies include land‐based and offshore wind, rooftop and utility‐scale solar, load‐modification technologies for homes and businesses and for electric vehicle charging, and storage, which can include batteries, pumped‐storage hydro, or other technologies, to name a few.
Studying the effect of radiation on thin‐film sprayed nanofluid flow with heat transfer
Authors: Abdel‐Rahman Rashed Gamal M. , El-Fayez Faiza M. N.
Published: November 2019

In this paper, we discuss thin‐film nanofluid sprayed in non‐Darcian, magnetohydrodynamic, embedding in a porous medium flow and thermal radiation with heat transfer generation on a stretching cylinder. The spray rate is a function of film size. A comparative study is made for the nanoparticles, namely, copper oxide , alumina oxide (), and iron oxide . The governing continuity, momentum, and energy equations of the nanofluid are reduced using similarity transformation and converted into a system of nonlinear ordinary differential equations, which are solved numerically. Numerical solutions are obtained for the velocity and temperature fields as well as for the skin‐friction coefficient and Nusselt number. The pressure distribution and spray rate are also calculated. The results are presented in graphical forms to study the effects of various parameters.
Assessing effects of model complexity and structure on predictions of hydrological responses using serial and parallel model design
Authors: Chien Huicheng , Mackay D. Scott
Published: November 2019

By utilizing functional relationships based on observations at plot or field scales, water quality models first compute surface runoff and then use it as the primary governing variable to estimate sediment and nutrient transport. When these models are applied at watershed scales, this serial model structure, coupling a surface runoff sub‐model with a water quality sub‐model, may be inappropriate because dominant hydrological processes differ among scales. A parallel modeling approach is proposed to evaluate how best to combine dominant hydrological processes for predicting water quality at watershed scales. In the parallel scheme, dominant variables of water quality models are identified based entirely on their statistical significance using time series analysis. Four surface runoff models of different model complexity were assessed using both the serial and parallel approaches to quantify the uncertainty on forcing variables used to predict water quality. The eight alternative model structures were tested against a 25‐year high‐resolution data set of streamflow, suspended sediment discharge, and phosphorous discharge at weekly time steps. Models using the parallel approach consistently performed better than serial‐based models, by having less error in predictions of watershed scale streamflow, sediment and phosphorus, which suggests model structures of water quantity and quality models at watershed scales should be reformulated by incorporating the dominant variables. The implication is that hydrological models should be constructed in a way that avoids stacking one sub‐model with one set of scale assumptions onto the front end of another sub‐model with a different set of scale assumptions.
Liner and nonliner sectoral response of stock markets to oil price movements: The case of Saudi Arabia
Authors: Hamdan Reem Khamis , Hamdan Allam Mohammed
Published: November 2019

With respect to Saudi Arabia for the period 2007–2016, this study employs linear (ordinary least square and causality tests) and nonlinear (Markov switching technique) to determine the long‐run relationship between stock market returns, in aggregate, and oil prices, as independent variable on the one hand, with sectoral returns in stock markets, and as dependent variable on the other. Results suggest that sectors in the Saudi market generally respond asymmetrically to oil prices. Overall, in the long run, the Saudi market, in aggregate, was found to be cointegrated with sectoral returns being affected more by overall stock market returns than by oil returns. When nonlinear Markov switching technique was employed, results were only significant in certain sectors namely cement, petrochemical industries, building and construction, and energy and utilities where regime switching between high and low volatilities was detected around the global financial crisis in 2008. Based on these findings, the study recommends investors to consider investing in sectors that balance between those with returns that vary directly and inversely with oil prices in an effort to create “oil‐neutral” portfolios rather than uniformly investing across all sectors in the Saudi market or consider investing in Saudi market sectors in the case of high oil prices.
Integration of Ontogeny Into a Physiologically Based Pharmacokinetic Model for Monoclonal Antibodies in Premature Infants
Authors: Malik Paul R. V. , Edginton Andrea N.
Published: November 2019

An understanding of pediatric pharmacokinetics (PK) is essential for first‐in‐pediatric dose selection and clinical trial design. At present, there is no reliable way to scale the PK of monoclonal antibodies and immunoglobulin G drug products from adults to young children or to premature infants—a vulnerable population with a rapidly growing drug development pipeline. In this work, pediatric physiologically based PK models are constructed in PK‐Sim and Mobi to explore the PK of pagibaximab, palivizumab, MEDI8897, and intravenous immunoglobulin in preterm infants. In addition to considering ontogeny in pediatric organ volumes, organ composition, blood flow rates, and hematocrit, advanced ontogeny is applied for 3 key parameters: capillary surface area, hematopoietic cell concentration, and lymph flow rate. The role and importance of each parameter for determining pediatric clearance (CL) and volume of distribution at steady state (VSS) are quantitatively assessed with a local sensitivity analysis. In addition, the uncertainty around parameters with limited information in pediatrics is addressed (eg, free neonatal Fc receptor concentration). The full ontogeny parameterization yields pediatric PK predictions that are within 1.5‐fold prediction error >90% of the time for preterm infants, with an absolute average fold error of 1.05. This result suggests that many of the key factors related to ontogeny are appropriately addressed. Overall, this study makes a first step toward developing a platform pediatric physiologically based PK model for monoclonal antibodies and immunoglobulin G drug products by solidifying existing parameterizations, integrating new concepts, and drawing attention to unmet needs for physiologic knowledge in children.
A new NOTCH3 damaging variant in a thrombocytopenia family of Miao ethnic group
Authors: Zhao Yingling , Li Juheng
Published: November 2019

Background

Pediatric inherited thrombocytopenia, also known as a deficiency of platelets in children, is caused by genetic factors and it is hard to obtain an effective treatment. Thus, it is necessary to identify the possible genetic variants that are responsible for thrombocytopenia.

Methods

Whole exome sequencing was used to detect genetic variants in two members of a thrombocytopenia family of Miao ethnic group. Multiple in silico analyses were performed to evaluate the effects of the novel missense variants.

Results

Finally, a novel variant (chr19: g.15170364G>A) in the NOTCH3 gene was found, as confirmed with Sanger sequencing, which could result in a R1694Q substitution in the protein. This variant was consistently suggested to be damaging by sift (Sorting Tolerant From Intolerant; http://sift.jcvi.org), polyphen (Polymorphism Phenotyping, version 2.0; http://genetics.bwh.harvard.edu/pph2) and mutationtaster (http://www.mutationtaster.org) software. By building the 3D model of the key region of NOTCH3 protein and performing the structure simulation, we found that (i) this variant affected the 3D structure model with a root‐mean‐square deviation = 0.46 between wild‐type and mutant type; (ii) this variant caused the protein to reduce the solvent accessible surface area by 421 Å2; and (iii) compared to the wild‐type protein, the mutant protein had two less amino acids to maintain protein stability.

Conclusions

A novel damaging variant in the NOTCH3 gene was identified in a thrombocytopenia family with respect to decreasing the stability of NOTCH3, which may help with the prognosis and therapy of inherited thrombocytopenia.
Bortezomib induces HSV-1 lethality in mice with neutrophil deficiency
Authors: Yao Hui-Wen , Wang Li-Chiu , Tsai Hsien-Yang , Fang Yi-Hsuan , Zheng Chunfu , Chen Shun-Hua , Hsu Sheng-Min
Published: November 2019

Bortezomib suppressing NF-κB activity is an effective therapy for patients with myeloma or lymphoma. However, this drug can cause adverse effects, neutropenia, and recurrent infections of herpes viruses. Among herpes viruses, HSV-1 can reactivate to induce mortality. The important issues regarding how bortezomib diminishes neutrophils, whether bortezomib can induce HSV-1 reactivation, and how bortezomib exacerbates HSV-1 infection, need investigation. Using the murine model, we found that bortezomib induced HSV-1 reactivation. Bortezomib diminished neutrophil numbers in organs of uninfected and HSV-1-infected mice and turned a nonlethal infection to lethal with elevated tissue viral loads. In vitro results showed that bortezomib and HSV-1 collaborated to enhance the death and apoptosis of mouse neutrophils. The leukocyte deficiency induced by chemotherapies is generally believed to be the cause for aggravating virus infections. Here we show the potential of pathogen to exacerbate chemotherapy-induced leukocyte deficiency.
Olefinic reagents tested for peptide derivatization with switchable properties: Stable upon collision induced dissociation and cleavable by in‐source Paternò‐Büchi reactions
Authors: Esch Patrick , Fischer Moritz , Heiles Sven , Schäfer Mathias
Published: November 2019

This contribution is part of our ongoing efforts to develop innovative cross‐linking (XL) reagents and protocols for facilitated peptide mixture analysis and efficient assignment of cross‐linked peptide products. In this report, we combine in‐source Paternò‐Büchi (PB) photo‐chemistry with a tandem mass spectrometry approach to selectively address the fragmentation of a tailor‐made cross‐linking reagent. The PB photochemistry, so far exclusively used for the identification of unsaturation sites in lipids and in lipidomics, is now introduced to the field of chemical cross‐linking. Based on trans‐3‐hexenedioic acid, an olefinic homo bifunctional amine reactive XL reagent was designed and synthesized for this proof‐of‐principle study. Condensation products of the olefinic reagent with a set of exemplary peptides are used to test the feasibility of the concept. Benzophenone is photochemically reacted in the nano‐electrospray ion source and forms oxetane PB reaction products. Subsequent CID‐MS triggered retro‐PB reaction of the respective isobaric oxetane molecular ions and delivers reliably and predictably two sets of characteristic fragment ions of the cross‐linker. Based on these signature ion sets, a straightforward identification of covalently interconnected peptides in complex digests is proposed. Furthermore, CID‐MSn experiments of the retro‐PB reaction products deliver peptide backbone characteristic fragment ions. Additionally, the olefinic XL reagents exhibit a pronounced robustness upon CID‐activation, without previous UV‐excitation. These experiments document that a complete backbone fragmentation is possible, while the linker‐moiety remains intact. This feature renders the new olefinic linkers switchable between a stable, noncleavable cross‐linking mode and an in‐source PB cleavable mode.
Treating Adults With Complex Posttraumatic Stress Disorder Using a Modular Approach to Treatment: Rationale, Evidence, and Directions for Future Research
Authors: Karatzias Thanos , Cloitre Marylene
Published: November 2019

ICD‐11 complex PTSD (CPTSD) is a new condition, and, therefore, there are as yet no clinical trials evaluating interventions for its treatment. In this paper, we provide the rationale for a flexible multimodular approach to the treatment of CPTSD, its feasibility, and some evidence suggesting its potential benefits. The approach highlights flexibility in the selection of empirically supported interventions (or a set of interventions) and the order of delivery based on symptoms that are impairing, severe, and of relevance to the patient. The approach has many potential benefits. It can incorporate the use of interventions for which there is already evidence of efficacy allowing the leveraging of past scientific efforts. It is also consistent with patient‐centered care, which highlights the importance of patient choice in identification of the problems to target, interventions to select, and outcomes to monitor. Researchers on modular treatments of other disorders have found that, compared to disorder‐specific manualized protocols, flexible multimodular treatment programs are superior in resolving identified problems and are associated with greater therapist satisfaction and reduced patient burden. We briefly identify types of interventions that have been successful in treating trauma‐exposed populations as well as emerging interventions that are relevant to the particular problems associated with exposure to complex trauma. We conclude with examples of how such treatments can be organized and tested. Research is now urgently needed on the effectiveness of existing and new intervention approaches to ICD‐11 CPTSD treatment.
Construction and evaluation of an efficient C‐Jun siRNA to downregulate matrix metalloproteinase in human keratinocytes and fibroblasts under UV exposure
Authors: Xiao Hong , Yang Ruinian , Yang Fang , Zhao Yanan , Liu Yin
Published: November 2019

Background

C‐Jun and EGFR have not been explored as targets via the mechanism of RNA silencing. Hence, this study designed an efficient C‐Jun‐h‐825 small interfering RNA (siRNA) and investigated its effect on matrix metalloproteinase (MMP) and collagen expression in human keratinocytes exposed to UV radiation.

Methods

Five C‐Jun siRNAs were designed and screened for their ability to downregulate C‐Jun expression in human fibroblasts. These constructs were used to study changes in skin cancer‐related protein expression. HaCaT cells were grouped into 5‐carboxyfluorescien (FAM‐labeled) C‐Jun‐h‐825 siRNA + 2 hr prior irradiation; mock transfected + 2 hr prior irradiation; normal control; irradiation only for 2 hr; and Blank. Twenty‐four hours posttransfection, mRNA and protein levels of MMP‐I, MMP‐III, collagen‐I and collagen‐III were determined using standard RT‐PCR and ELISA kits.

Results

FAM‐labeled C‐Jun siRNA showed 80%–90% transfection efficiency. There was a significant increase in MMP‐I and MMP‐III and decrease in Col‐I and III mRNA levels when the cells were exposed to UV irradiation without siRNA transfection compared to blank (p < .05). This effect was reversed upon transfection with C‐Jun‐h‐825 (p < .01).

Conclusion

Thus, C‐Jun‐h‐825 siRNA might help restore skin collagen by decreasing MMP expression in cells exposed to UVA. Constructs and vectors designed herein have the potential to be translated into a treatment for photoaging induced skin cancer.
Description of stability for linear time‐invariant systems based on the first curvature
Authors: Wang Yuxin , Sun Huafei , Huang Shoudong , Song Yang
Published: November 2019

This paper focuses on using the first curvature κ(t) of trajectory to describe the stability of linear time‐invariant system. We extend the results for two and three‐dimensional systems (Wang, Sun, Song et al, arXiv:1808.00290) to n‐dimensional systems. We prove that for a system
, (a) if there exists a measurable set whose Lebesgue measure is greater than zero, such that
or
does not exist for any initial value in this set, then the zero solution of the system is stable; (b) if the matrix A is invertible, and there exists a measurable set whose Lebesgue measure is greater than zero, such that
for any initial value in this set, then the zero solution of the system is asymptotically stable.
Orbital analysis in the planar circular Copenhagen problem using polar coordinates
Authors: Zotos Euaggelos E.
Published: November 2019

We examine the orbital dynamics of the planar Copenhagen problem, by classifying sets of starting conditions of orbits, expressed in polar coordinates. Specifically, we examine how the Jacobi constant influences several aspects of the overall dynamics of the test particle, such as its final state, as well as the time of escape/collision. By using modern diagrams with color codes, we manage to present the different types of basins. It is shown that both the character of the orbits and the fractal degree of the system are highly dependent on the Jacobi constant.
Accuracy, uncertainty, and adaptability of automatic myocardial ASL segmentation using deep CNN
Authors: Do Hung P. , Guo Yi , Yoon Andrew J. , Nayak Krishna S.
Published: November 2019

Purpose

To apply deep convolution neural network to the segmentation task in myocardial arterial spin labeled perfusion imaging and to develop methods that measure uncertainty and that adapt the convolution neural network model to a specific false‐positive versus false‐negative tradeoff.

Methods

The Monte Carlo dropout U‐Net was trained on data from 22 subjects and tested on data from 6 heart transplant recipients. Manual segmentation and regional myocardial blood flow were available for comparison. We consider 2 global uncertainty measures, named “Dice uncertainty” and “Monte Carlo dropout uncertainty,” which were calculated with and without the use of manual segmentation, respectively. Tversky loss function with a hyperparameter β was used to adapt the model to a specific false‐positive versus false‐negative tradeoff.

Results

The Monte Carlo dropout U‐Net achieved a Dice coefficient of 0.91 ± 0.04 on the test set. Myocardial blood flow measured using automatic segmentations was highly correlated to that measured using the manual segmentation (R2 = 0.96). Dice uncertainty and Monte Carlo dropout uncertainty were in good agreement (R2 = 0.64). As β increased, the false‐positive rate systematically decreased and false‐negative rate systematically increased.

Conclusion

We demonstrate the feasibility of deep convolution neural network for automatic segmentation of myocardial arterial spin labeling, with good accuracy. We also introduce 2 simple methods for assessing model uncertainty. Finally, we demonstrate the ability to adapt the convolution neural network model to a specific false‐positive versus false‐negative tradeoff. These findings are directly relevant to automatic segmentation in quantitative cardiac MRI and are broadly applicable to automatic segmentation problems in diagnostic imaging.
Changes in Fish Assemblages at the Mirror Lake Complex in the Lower Columbia River Before and After a Culvert Modification
Authors: Sol Sean Y. , Hanson Amanda C. , Marcoe Keith , Johnson Lyndal L.
Published: November 2019

Changes in fish assemblages were examined before and after a culvert was modified to improve the fish passage at the Mirror Lake Complex (MLC), located along the Columbia River Gorge, Oregon. Conditions at the culvert limited water flow between the Columbia River and the MLC during certain portions of the year; thus, the outlet and interior of the culvert were modified to improve fish passage. Prior to the culvert modification, three sites were sampled monthly between April and August 2008, 5.0 km and 0.5 km upstream of the culvert and immediately downstream of the culvert. Following the culvert modification in the late summer of 2008, the same sites were sampled from 2009 to 2012, with two additional sites added in 2010. Prior to the culvert modification, the lower sites (i.e., the sites closest to the Columbia River) supported native and nonnative fish species, while the upper sites were dominated by native species. During the 4 years of monitoring after culvert modification, these distinctions between the upper and lower sites remained. A significant increase in water temperature and species richness was observed at the site just upstream of the culvert, but other changes in fish composition (density, diversity, percent of nonnative species) were not observed. However, at the upper sites, while nonnative species were absent before culvert modification, they were present after modification. Modifications made at the culvert, in combination with seasonal variation in water level and water temperature, may have influenced fish communities in the MLC. Given predicted regional and global climatic changes, our study indicates the importance of long-term monitoring of restoration sites for the presence of nonnative species and the effects of environmental variables, such as water temperature.
Oligopolistic contracting: Channel coordination under competition
Authors: Gallego Guillermo , Talebian Masoud
Published: November 2019

We study contracts between a single retailer and multiple suppliers of two substitutable products, where suppliers have fixed capacities and present the retailer cost contracts for their supplies. After observing the contracts, the retailer decides how much capacity to purchase from each supplier, to maximize profits from the purchased capacity from the suppliers plus his possessed inventory (endowment). This is modeled as a noncooperative, nonzero‐sum game, where suppliers, or principals, move simultaneously as leaders and the retailer, the common agent, is the sole follower. We are interested in the form of the contracts in equilibrium, their effect on the total supply chain profit, and how the profit is split between the suppliers and the retailer. Under mild assumptions, we characterize the set of all equilibrium contracts and discuss all‐unit and marginal‐unit quantity discounts as special cases. We also show that the supply chain is coordinated in equilibrium with a unique profit split between the retailer and the suppliers. Each supplier's profit is equal to the marginal contribution of her capacity to supply chain profits in equilibrium. The retailer's profit is equal to the total revenue collected from the market minus the payments to the suppliers and the associated sales costs.
Metamaterial topology optimization of nonpneumatic tires with stress and buckling constraints
Authors: Maharaj Yeshern , James Kai A.
Published: November 2019

This article presents the design of a metamaterial for the shear layer of a nonpneumatic tire using topology optimization, under stress and buckling constraints. These constraints are implemented for a smooth maximum function using global aggregation. A linear elastic finite element model is used, implementing solid isotropic material with penalization. Design sensitivities are determined by the adjoint method. The method of moving asymptotes is used to solve the numerical optimization problem. Two different optimization statements are used. Each requires a compliance limit and some aspect of continuation. The buckling analysis is linear, considering the generalized eigenvalue problem of the conventional and stress stiffness matrices. Various symmetries, base materials, and starting geometries are considered. This leads to novel topologies that all achieve the target effective shear modulus of 10 MPa, while staying within the stress constraint. The stress‐only designs generally were susceptible to buckling failure. A family of designs (columnar, noninterconnected representative unit cells) that emerge in this study appears to exhibit favorable properties for this application.
Hyperandrogenemia is Common in Asymptomatic Women and is Associated with Increased Metabolic Risk
Authors: Torchen Laura C. , Tsai Joy N. , Jasti Prathima , Macaya Rodrigo , Sisk Ryan , Dapas Matthew L. , Hayes M. Geoffrey , Urbanek Margrit , Dunaif Andrea
Published: November 2019

Objective

Women with metabolic syndrome (MetS) have higher endogenous testosterone (T) levels than unaffected women. This study investigated whether hyperandrogenemia (HA) was a marker for increased cardiometabolic risk in reproductively normal premenopausal women.

Methods

Reproductive hormones and metabolic parameters were assessed in 198 women with regular menses and no clinical hyperandrogenism (eumenorrheic [EM]). Hyperandrogenic EM women were compared with 110 women with NIH criteria polycystic ovary syndrome.

Results

Twenty‐two percent of EM women had HA. Levels of non–sex hormone–binding globulin (SHBG)‐bound T were elevated in 68% of women, total T levels were elevated in 43% of women, and dehydroepiandrosterone sulfate levels were elevated in 30% of women. The prevalence of HA increased with BMI category (P = 0.01): 12% for BMI < 25 kg/m2, 22% for BMI of 25 to 30 kg/m2, and 31% for BMI ≥ 30 kg/m2. MetS (adjusted odds ratio 2.9; 95% CI: 1.2‐6.9) and dysglycemia risks (adjusted odds ratio 2.7; 95% CI: 1.2‐5.8) were increased in hyperandrogenic EM women compared with normoandrogenic EM women, with adjustment for BMI. SHBG levels were independently associated with these metabolic end points (P < 0.001), whereas androgen levels were not. A cluster analysis confirmed that there was a discrete subset of EM women with HA and metabolic abnormalities.

Conclusions

HA is common in EM women and is associated with increased risks for MetS and dysglycemia. However, low SHBG levels rather than elevated androgen levels may be the primary predictor of this relationship with metabolic dysfunction.
Environmental management amidst energy use, urbanization, trade openness, and deforestation: The Nigerian experience
Authors: Nathaniel Solomon Prince , Bekun Festus Victor
Published: November 2019

This study empirically explores the linkage between urbanization and deforestation while controlling for the role of energy consumption, trade openness, and economic growth within recent data from 1971 to 2015. To do this, we employed the vector error correction‐Granger causality approach and Pesaran's autoregressive distributed lag cointegration technique. The Bayer–Hanck cointegration test establishes an equilibrium relationship among the variables. Results reveal that economic growth, energy consumption, and urbanization have a significant impact on deforestation in Nigeria, thereby reducing the quality of the environment. Short‐ and long‐run unidirectional casualty flows from urbanization to deforestation. Therefore, policies for reducing deforestation and enhancing environmental sustainability for growth and development were suggested.
Fabrication of high thermal stable cured novolac/Cloisite 30B nanocomposites by chemical modification of resin structure
Authors: Javanbakht Fatemeh , Razavi Bahareh , Salami‐Kalajahi Mehdi , Roghani‐Mamaqani Hossein , Ommati Masoud
Published: November 2019

Cloisite 30B as a modified kind of nanoclay was utilized for the formation of 3D network based on novolac resin with high thermal stable properties. Two types of phenolic resins including neat novolac (NR) and modified novolac resin were used to create a compatible matrix with nanoclay. For this purpose, NR modified with (3‐chloropropyl)triethoxysilane (CPTES) to form SiNR. For improvement of thermal behaviors, Cloisite 30B was dispersed in matrix via ultrasonic waves and cured with hexamethylenetetramine (HMTA) to form 3D network. X‐ray diffraction (XRD) analysis was used to measure the d‐spacing in intercalated systems and results indicated the optimum amount of clay for appropriate thermal properties. Investigation of the thermal properties of the samples by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) showed that the presence of Cloisite 30B in matrix resulted in much higher thermal stability and char yield with respect to modification of novolac resin originated from formation of 3D Si–O–Si network. Also, cured modified resin and its nanocomposites showed much higher thermal stability than cured NR and its nanocomposites. Such nanocomposite materials with high thermal stability have potential applications in advanced fields such electronic, industrial molds, coatings, adhesives, and aerospace composites.
Effect of Pickering emulsion on the mechanical performances and fracture toughness of epoxy composites
Authors: Li Shuiping
Published: November 2019

The improvement of mechanical properties and toughness of nanoparticles for epoxy composites was mostly dependent on the disperse state of nanoparticles in epoxy matrices. When the content of nanoparticles was higher than a threshold value, it was easy to aggregate and then affect the improvement effect. Pickering emulsion was prepared using SiO2 nanoparticles as emulsifier and functional monomer as oil phase. The influence of Pickering emulsion on the curing process was investigated. The effect of Pickering emulsion on the mechanical properties, toughness, and glass transition temperature (Tg) was studied. Impact and tensile fracture surface were observed by scanning electron microscopy (SEM). Results from differential scanning calorimeter (DSC), tensile, impact, and fracture toughness tests are provided. The results indicated that the introduction of Pickering emulsion can eliminate the residual stress and accelerate curing reaction. Epoxy composites were capable of increasing tensile strength by up to 29.9%, impact strength of three‐fold, fracture toughness of 35%, and Tg of 20.7°C in comparison with the reference sample. SEM images showed that SiO2 nanoparticles exhibit a good dispersion in epoxy matrix. The increases in mechanical properties, toughness, and Tg of epoxy composites were attributed to the “Second Phase Toughness” mechanism.
Synthesis, characterization, and dynamic‐mechanical properties of styrene‐acrylate/nanoclay interpenetrating polymer network
Authors: Fatemi Khadar Parisa , Maghsoud Zahra , Dashti Ali
Published: November 2019

Waterborne styrene/acrylate latex interpenetrating polymer network (LIPN) with core‐shell structure was synthesized via a three‐stage emulsion polymerization method. A natural montmorillonite (MMt) and an organically modified montmorillonite (OMMt) were used to see their effect on the morphology and damping properties of polymer‐clay nanocomposite LIPN. The samples were characterized by dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic mechanical thermal analysis (DMTA), and X‐ray diffraction (XRD). The appearance of a single peak in the particle size distribution curve and nearly monodisperse latex particles observed in the SEM images indicated that all LIPN particles were of nanoscale size, without evidence for new nucleation occurrence. TEM images demonstrated that latex particles had clearly core‐shell structures. It also showed that most of the OMMt clay platelets were encapsulated in the polymer latex particles. According to the tan δ‐temperature curve, addition of 0.5 wt% OMMt to the core layer improved the damping properties of the LIPN, while MMt could not affect the damping curve significantly. The results indicated that the diffusion of polymer chains into the OMMt clay galleries has increased the internal friction and so improved the damping properties.
Epidemiology of multimorbidity in Iran: An investigation of a large pharmacy claims database
Authors: Ebrahimoghli Reza , Janati Ali , Sadeghi‐Bazargani Homayoun , Hamishehkar Hadi , Ghaffari Samad , Sanaat Zohreh , Farahbakhsh Mostafa , Farhoudi Mehdi , Khalili‐Azimi Atefeh
Published: November 2019

Purpose

Multimorbidity (MM) (presence of more than one chronic condition within a same patient) imposes a heavy burden on patients and health care systems. In contrast to high‐income countries, the epidemiology of this phenomenon is unclear in low‐ and middle‐income countries, particularly among Iranian population.

Methods

This was a retrospective cohort study using Iranian Health Insurance Organization claims database. A framework was developed for identifying a set of 18 chronic conditions from the pharmacy claims data in Iran. All 2013 outpatient utilizers (aged 18 years or older) were included. Data were analyzed according to number of chronic conditions, gender, and age. The association between MM and utilizations of health services was examined for 2013 to 2016.

Results

In total, 481 733 people were included. Cardiovascular diseases (including hypertension) (19.1%), depression/anxiety/sleep disorders (13.7%), and acid‐related disorders (10.3%) were the three most prevalent conditions. MM was present in 21.1%. Although prevalence of MM is higher in older age groups and was present in 40% of individuals aged 65 and older, the absolute number of multimorbid patients was higher in those younger than 65 years (66 271 vs 35 386). MM was more prevalent among women (22.1%) compared with men (19.5). After multivariate adjustment for age group and sex, each additional chronic condition was associated with an increase of 2.23 physician visits, 2.86 drugs dispensed, 2.32 laboratory tests, and 1.6 medical imaging.

Conclusions

Our findings challenge the current single‐disease–based assumption implicit in Iranian health care system. To take account of MM, complementary strategies should be designed and implement in health care system.
The role of photovoltaics in a sustainable European energy system under variable CO2emissions targets, transmission capacities, and costs assumptions
Authors: Victoria Marta , Zhu Kun , Brown Tom , Andresen Gorm B. , Greiner Martin
Published: November 2019

PyPSA‐Eur‐Sec‐30 is an open‐source, hourly resolved, networked model of the European energy system that includes one node per country as well as electricity, heating, and transport sectors. The capacity and dispatch of generation and storage technologies in every country can be cost optimized under different CO2emissions constraints. This paper presents an overview of the most relevant results previously obtained with the model, highlighting the influence of solar photovoltaic (PV) generation on them. For 95% CO2emissions reduction, relative to 1990 level, PV generation supplies in average 33% of the electricity demand. Southern European countries install large PV capacities together with electric batteries, while northern countries install onshore and offshore wind capacities and use hydrogen storage and reinforced interconnections to deal with wind fluctuations. The strong daily generation profile of solar PV heavily impacts the dispatch time series of backup generation and storage technologies. The optimal PV and wind capacities are investigated for variable CO2emissions, transmission interconnection among neighbouring countries, and cost assumptions.
Role of glycosylation on the ensemble of conformations in the MUC1 immunodominant epitope
Authors: Singh Jaideep , Her Cheenou , Supekar Nitin , Boons Geert‐Jan , Krishnan Viswanathan V. , Brooks Cory L.
Published: November 2019

MUC1 is a membrane glycoprotein, which in adenocarninomas is overexpressed and exhibits truncated O‐glycosylation. Overexpression and altered glycosylation make MUC1 into a candidate for immunotherapy. Monoclonal antibodies directed against MUC1 frequently bind an immunodominant epitope that contains a single site for O‐glycosylation. Glycosylation with tumor carbohydrate antigens such as the Tn‐antigen (GalNAc‐O‐Ser/Thr) results in antibodies binding with higher affinity. One proposed model to explain the enhanced affinity of antibodies for the glycosylated antigen is that the addition of a carbohydrate alters the conformational properties, favoring a binding‐competent state. The conformational effects associated with Tn glycosylation of the MUC1 antigen was investigated using solution‐state NMR and molecular dynamics. NMR experiments revealed distinct substructures of the glycosylated MUC1 peptides compared with the unglycosylated peptide. Molecular dynamics simulations of the MUC1 glycopeptide and peptide revealed distinguishing differences in their conformational preferences.

Furthermore, the glycopeptide displayed a smaller conformational sampling compared with the peptide, suggesting that the glycopeptide sampled a narrower conformational space and is less dynamic. A comparison of the computed ensemble of conformations assuming random distribution, NMR models, and molecular dynamics simulations indicated that the MUC1 glycopeptide and aglycosylated peptide sampled structurally distinctly ensembles and that these ensembles were different from that of the random coil. Together, these data support the hypothesis that that conformational pre‐selection could be an essential feature of these peptides that dictates the binding affinities to MUC1 specific antibodies.
Cancer immunotherapy trial design with delayed treatment effect
Authors: Wu Jianrong , Wei Jing
Published: November 2019

A challenge arising in cancer immunotherapy trial design is the presence of a delayed treatment effect wherein the proportional hazard assumption no longer holds true. As a result, a traditional survival trial design based on the standard log‐rank test, which ignores the delayed treatment effect, will lead to substantial loss of statistical power. Recently, a piecewise weighted log‐rank test is proposed to incorporate the delayed treatment effect into consideration of the trial design. However, because the sample size formula was derived under a sequence of local alternative hypotheses, it results in an underestimated sample size when the hazard ratio is relatively small for a balanced trial design and an inaccurate sample size estimation for an unbalanced design. In this article, we derived a new sample size formula under a fixed alternative hypothesis for the delayed treatment effect model. Simulation results show that the new formula provides accurate sample size estimation for both balanced and unbalanced designs.
Frontier molecular orbital analysis for determining the equilibrium geometries of atmospheric prenucleation complexes
Authors: Sebastianelli Paolo , Pereyra Rodolfo G.
Published: November 2019

A systematic characterization of the frontier molecular orbitals (FMO) of gas‐phase prenucleation complexes between H2SO4 and other molecules present in the atmosphere (NH3, H2O, (CH3)OH, HF, (CH3)2PH, (CH3)SH) is carried out using the ωB97X‐D/6‐311++(2d,2p) method at the density functional theory level of theory. The FMO theory principles are taken into account to gain insight into the nature of intermolecular interactions. The results show that the highest occupied molecular orbital/lowest unoccupied molecular orbital molecular system characterization can be adopted as a complementary tool of analysis in supporting the study of atmospheric prenucleation processes. It is shown that the stability and the spatial arrangement of molecular systems can be also thought in terms of inter‐ and intra‐molecular energy gaps ΔEHL that play an important role in the development of association processes.
Electronic and vibrational hyperpolarizabilities of alkali‐ and alkaline‐earth‐doped boron nitride nanotubes
Authors: Marques Suélio , Castro Marcos A. , Pontes Renato B. , Leão Salviano A. , Fonseca Tertius L.
Published: November 2019

This work reports the results of the vibrational corrections and frequency dependence to the first hyperpolarizabilities of the alkali‐ and alkaline‐earth‐doped boron nitride nanotubes. The electronic contributions were computed by means of the density functional theory with the M06‐2X functional, and the vibrational corrections were calculated using the perturbation theoretical method and the field‐induced coordinates methodology. The results for the electronic contribution show that such materials exhibit large first hyperpolarizabilities and electride characteristic. We also show that the distribution of the excess electron, which originates from the doping atoms, plays an important role in the large electronic hyperpolarizabilities (βel). Moreover, our findings strongly indicate that the effect of vibrations on the hyperpolarizabilities can be quite important and can even be much larger than the electronic counterpart.