bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Optimal Power Control for a City Transit Hybrid Bus Equipped with a Partitioned Hydrogen Fuel Cell Stack
Authors: D’Ovidio Gino , Ometto Antonio , Villante Carlo
Published: May 2020

The development of more sustainable and zero-emissions collective transport solutions could play a very important measure in the near future within smart city policies. This paper tries to give a contribution to this aim, proposing a novel approach to fuel cell vehicle design and operation. Traditional difficulties experienced in fuel cell transient operation are, in fact, normally solved in conventional vehicle prototypes, through the hybridization of the propulsion system and with the complete fulfillment of transients in road energy demand through a high-capacity onboard energy storage device. This makes it normally necessary to use Li-ion battery solutions, accepting their restrictions in terms of weight, costs, energy losses, limited lifetime, and environmental constraints. The proposed solution, instead, introduces a partitioning of the hydrogen fuel cell (FC) and novel optimal power control strategy, with the aim of limiting the capacity of the energy storage, still avoiding FC transient operation. The limited capacity of the resulting energy storage systems which, instead, has to answer higher power requests, makes it possible to consider the utilization of a high-speed flywheel energy storage system (FESS) in place of high energy density Li-ion batteries. The proposed control strategy was validated by vehicle simulations based on a modular and parametric model; input data were acquired experimentally on an operating electric bus in real traffic conditions over an urban bus line. Simulation results highlight that the proposed control strategy makes it possible to obtain an overall power output for the FC stacks which better follows road power demands, and a relevant downsizing of the FESS device.
A New Model for Discriminating the Source of Produced Water from Cyclic Steam Stimulation Wells in Edge-Bottom Water Reservoirs
Authors: Zhu Yuanrui , Huang Shijun , Zhao Lun , Yang Menglu , Wu Tong
Published: May 2020

Heavy oil reservoirs with edge-bottom water represent a huge portion of the world’s reserves, and the effective development of such reservoirs with cyclic steam stimulation (CSS) is significant for the petroleum supply. However, the water cut of some CSS wells increases, and production decreases, with the increase of circulation turns. Discerning the source of the produced water is the basis of targeted treatment measures. In this paper, a new model is established for discriminating the source of produced water from CSS wells in edge-bottom water reservoirs. The model combines traditional hydrochemical characteristics analysis and factor analysis, and considers the quality change in injected water. The coefficient of formation water and injected water in produced water can thus be obtained. In addition, the normal distribution method is used to further divide interlayer water and edge-bottom water. The model was applied to a field case, and the results showed that one well was severely invaded by edge-bottom water. The results are consistent with field production performance, which further verifies the accuracy of the model. This model is of great significance for not only discriminating the source of produced water in an edge-bottom water reservoir, but also providing a basis for further the provision of further treatment measures.
Non-Salient Brushless Synchronous Generator Main Exciter Design for More Electric Aircraft
Authors: Kutt Filip , Michna Michał , Kostro Grzegorz
Published: May 2020

This paper presents a prototype of high speed brushless synchronous generators (BSG) design for the application in autonomous electric power generation systems (e.g., airplane power grid). Commonly used salient pole field of the main generator part of BSG was replaced with a prototype non-salient pole field. The main objective of the research is an investigation into the advantages and disadvantages of a cylindrical field of the main generator part of BSG over the original salient pole field. The design process of the prototype generator is presented with a focus on the electromagnetic and mechanical finite element method (FEM) analysis. The measurements of prototype and commercial BSG were conducted for the nominal speed of 8 krpm. The advantages and disadvantages of the proposed solution were established based on measurements in load and no-load conditions.
Identification of Suitable Areas for Biomass Power Plant Construction through Environmental Impact Assessment of Forest Harvesting Residues Transportation
Authors: Pergola Maria , Rita Angelo , Tortora Alfonso , Castellaneta Maria , Borghetti Marco , De Franchi Antonio Sergio , Lapolla Antonio , Moretti Nicola , Pecora Giovanni , Pierangeli Domenico , Todaro Luigi , Ripullone Francesco
Published: May 2020

In accordance with European objectives, the Basilicata region intends to promote the use of energy systems and heat generators powered by lignocellulosic biomass, so the present study aimed to investigate the availability of logging residues and most suitable areas for the construction of bioenergy production plants. The life cycle assessment (LCA) methodology was employed to conduct an environmental impact assessment of the biomass distribution and its transport, and spatial LCA was used to evaluate the impact of regional transport. One cubic meter kilometer (m3 km−1) was used as the functional unit and a small lorry was considered for the transport. The results showed that the available harvesting residues amounted to 36,000 m3 and their loading environmental impact accounted for 349 mPt m−3. The impacts of transport (4.01 mPt m−3) ranged from 3.4 to 144,400 mPt km−1 forest parcel−1, mainly affecting human health (95%) and, second, the ecosystem quality (5%). Three possible sites for bioenergy plant location were identified considering the environmental impact distribution due to feedstock transport. Findings from this research show the importance of considering the LCA of biomass acquisition in site selection and can fill the knowledge gaps in the available literature about spatial LCA.
Modeling and Optimal Dimensioning of a Pumped Hydro Energy Storage System for the Exploitation of the Rejected Wind Energy in the Non-Interconnected Electrical Power System of the Crete Island, Greece
Authors: Nikolaou Triantafyllia , Stavrakakis George S. , Tsamoudalis Konstantinos
Published: May 2020

The aim of the present paper is to investigate the use of the site “Potamon” Dam in the Prefecture of Rethymnon, Crete island, Greece, as a “virtual” renewable electricity supply of a pumped storage plant (PSP) in order to save and exploit the maximum possible part of the rejected wind energy of the autonomous power system of the Crete island. Taking into account the annual time series of the rejected power of the Crete power grid, the present research work targets the optimal configuration of the proposed PSP power station, including the sizing of its individual components as well as the determination of the capacity it could guarantee in order to be economically viable. The rejected electric energy from the actually operating wind farm production, which is not possible to be absorbed by the grid of Crete due to its stable operation limitations, could be absorbed by the here proposed pump storage plant (PSP) and converted to hydraulic energy. This can be achieved by pumping the water from the lower reservoir, which is the existing reservoir of the site “Potamon” Dam, with a storage capacity of about 22.5 million m3, up to the upper reservoir, which must be constructed accordingly. For the proposed PSP’s optimal size determination, established financial indices are used as an evaluation criterion for an investment life cycle of 25 years. The proposed PSP optimization is based on the dynamic mathematical model of the simulation results of the PSP’s hourly operation when incorporated in the Crete power grid for a whole year, performed in the Matlab 2016b computational environment (The MathWorks, Inc., Natick, MA, USA). The results of this research demonstrate the PSP’s technical feasibility and determine the PSP’s optimal CAPEX and the PSP’s whole life-time financial indicators in order that the whole investment be viable. Furthermore, the appropriate selling prices of the electricity produced from the proposed PSP were determined to achieve the PSP’s financial viability. The results comprise the key elements to prove the necessity for the establishment a.s.a.p. of the appropriate legal framework in order to have authorization to exploit the rejected RES (renewable energy sources) electric energy or the major part of it through PSPs, in priority in both the non-interconnected, as well as the interconnected power systems.
Energy Use and Labor Productivity in Ethiopia: The Case of the Manufacturing Industry
Authors: Kebede Selamawit G. , Heshmati Almas
Published: May 2020

This study investigates the effect of energy use on labor productivity in the Ethiopian manufacturing industry. It uses panel data for the manufacturing industry groups to estimate the coefficients using the dynamic panel estimator. The study’s results confirm that energy use increases manufacturing labor productivity. The coefficients for the control variables are in keeping with theoretical predictions. Capital positively augments productivity in the industries. Based on our results, technology induces manufacturing’s labor productivity. Likewise, more labor employment induces labor productivity due to the dominance of labor-intensive manufacturing industries in Ethiopia. Alternative model specifications provide evidence of a robust link between energy and labor productivity in the Ethiopian manufacturing industry. Our results imply that there needs to be more focus on the efficient use of energy, labor, capital, and technology to increase the manufacturing industry’s labor productivity and to overcome the premature deindustrialization patterns being seen in Ethiopia.
Methods for the Separation of Failure Modes in Power-Cycling Tests of High-Power Transistor Modules Using Accurate Voltage Monitoring
Authors: Sarkany Zoltan , Rencz Marta
Published: May 2020

The accurate measurement of on-state device voltage during power-cycling tests can deliver important information about the health of the tested power electronics components. In this article, we present the major aspects of how a power-cycling test can be set up to enable high-resolution device voltage monitoring, during both heating and cooling stages, and discuss the effect of some important parameters on the arising failure modes. The thermal transient of the component can also be captured in these setups. We show how the structure functions calculated from the captured thermal transients can be used to reveal the location of degradation in the module structure. Finally, the method for identification of bond-wire cracking and lift-off using only the measured voltage curves, is shown.
Willingness to Pay for Renovation of Multi-Flat Buildings and to Share the Costs of Renovation
Authors: Streimikiene Dalia , Balezentis Tomas
Published: May 2020

The paper deals with the problems linked to the energy renovation of multi-apartment buildings and developed a case study in Lithuania with the aim to assess the household’s willingness to pay for energy renovation and to define the main barriers preventing the households from making decisions to renovate their apartments in residential buildings. Energy renovation provides huge energy savings and greenhouse gas emissions reduction potential and though policies and measures exist to promote large scale energy renovation, there are still many barriers and the pace of energy renovation is still very slow, especially in new EU member states and former Soviet Union members. These countries have inherited old, energy inefficient residential buildings from their Soviet past, and their inhabitants are locked in energy poverty because of their inability to renovate their apartments. This paper analyzed the current situation in the selected country and presents the results of a case study on willingness to pay (WTP) for energy renovation in Lithuanian residential buildings. The survey of 104 Lithuanian households living in unrenovated multi-flat buildings was conducted. The 39 multiple choice questions were asked in order to define the main barriers and drivers of energy renovation. The main results of this pilot study indicated that there are several important organizational and economic barriers for energy renovation in multi-flat buildings and current policies and support schemes have not addressed them in a proper way. The high heating bills and low heat comfort in apartments were the main drivers of energy renovation decision-making for households, however, inadequate state support, reluctance to take a loan due to low income, and inability to make collective decisions on renovation due to the lack of cooperation and housing association were the main barriers that prevented them from this step. New innovative schemes like the Energy Service Companies ESCO model with consolidated billing can be applied to address the identified barriers.
The Implementation of the UNESCO World Heritage Convention: Continuity and Compatibility as Qualifying Conditions of Integrity
Authors: Khalaf Roha W.
Published: May 2020

This article explores the nexus between integrity, continuity, and compatibility (compatible change) in the implementation of the UNESCO World Heritage Convention. Integrity is a measure by which the Advisory Bodies, namely the International Council on Monuments and Sites (ICOMOS) and the International Union for Conservation of Nature (IUCN), evaluate nominations of cultural and/or natural properties to determine whether they qualify for inscription on the World Heritage List. Yet, its application remains unclear as presently worded in the Operational Guidelines. This article argues that continuity and compatibility should become qualifying conditions of integrity. Together, they can maintain wholeness, maintain intactness, and prevent adverse effects of development and/or neglect (Paragraph 88(a)(b)(c)) to keep properties in a good state of conservation, to sustain their cultural-natural significance including Outstanding Universal Value, and to enable sustainable development. This is an alternative conceptual and operational framework for nomination, evaluation, protection and management that bridges the culture/nature divide. If adopted, the “system of collective protection of the cultural and natural heritage of Outstanding Universal Value” established by the Convention would become more credible, practical, and effective. This article, therefore, contributes to World Heritage policy formulation and to a fruitful international exchange of ideas.
Analyzing the Status of Sustainable Development in the Manufacturing Sector Using Multi-Expert Multi-Criteria Fuzzy Decision-Making and Integrated Triple Bottom Lines
Authors: Hendiani Sepehr , Liao Huchang , Bagherpour Morteza , Tvaronavičienė Manuela , Banaitis Audrius , Antucheviciene Jurgita
Published: May 2020

A sustainable manufacturing company depends on the developments in three aspects in order to minimize harmful impacts on the environment, improve the social relations, and simultaneously maximize the economic benefits. Despite the increasing types of investigations that researchers have carried out in environmental and economic aspects, the minimum attention has been paid to social relations. In response to this deficiency, this paper proposes a new framework to obtain the overall sustainability index in manufacturing companies by encapsulating the sustainability criteria/sub-criteria. This article collected 33 sub-criteria for five pillars of sustainability as social, environment, economic, technological advancement, and performance management. The key contributions of this paper are highlighted as the hierarchical method that obtains the status of sustainability in uncertain conditions, the ability to identify the weak points, and a new framework for gathering the data about sustainability performance in manufacturing companies. The findings of this paper will aid both policymakers and decision-makers to assess the sustainability status of manufacturing systems and improve the performances of them.
Association between Ambient Air Pollution and Hospital Length of Stay among Children with Asthma in South Texas
Authors: Baek Juha , Kash Bita A. , Xu Xiaohui , Benden Mark , Roberts Jon , Carrillo Genny
Published: May 2020

Although hospital length of stay (LOS) has been identified as a proxy measure of healthcare expenditures in the United States, there are limited studies investigating the potentially important association between outdoor air pollution and LOS for pediatric asthma. This study aims to examine the effect of ambient air pollution on LOS among children with asthma in South Texas. It included retrospective data on 711 children aged 5–18 years old admitted for asthma to a pediatric tertiary care hospital in South Texas between 2010 and 2014. Air pollution data including particulate matter (PM2.5) and ozone were collected from the U.S. Centers for Disease Control and Prevention. The multivariate binomial logistic regression analyses were performed to determine the association between each air pollutant and LOS, controlling for confounders. The regression models showed the increased ozone level was significantly associated with prolonged LOS in the single- and two-pollutant models (p < 0.05). Furthermore, in the age-stratified models, PM2.5 was positively associated with LOS among children aged 5–11 years old (p < 0.05). In conclusion, this study revealed a concerning association between ambient air pollution and LOS for pediatric asthma in South Texas.
Occurrence of Halogenated Pollutants in Domestic and Occupational Indoor Dust
Authors: Simonetti Giulia , Di Filippo Patrizia , Riccardi Carmela , Pomata Donatella , Sonego Elisa , Buiarelli Francesca
Published: May 2020

The occurrence of halogenated organic pollutants in indoor dust can be high due to the presence of textile, electronic devices, furniture, and building materials treated with these chemicals. In this explorative study, we focused on emerging organic pollutants, such as novel brominated flame retardants (nBFRs) and some perfluoroalkyl substances, together with legacy polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (BDEs) in settled dust collected in houses and workplaces such as one office and two electrotechnical and mechanical workshops. The total contribution of the investigated pollutants was lower in house and in office dusts except for few nBFRs (such as bis (2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate at a concentration of 464.5 ng/g in a house and hexachlorocyclopentadienyldibromocyclooctane at 40.4 ng/g in the office), whereas in electrotechnical and mechanical workshops a high incidence of PCBs, BDEs, and nBFRs occurred (for example, BDE 209 at a concentration of 2368.0 ng/g and tetrabromobisphenol A at 32,320.1 ng/g in electrotechnical and mechanical workshops). Estimated daily intakes were also calculated, showing that domestic and occupational environments can lead to a similar contribution in terms of human exposure. The higher exposure contribution was associated to nBFRs, whose EDIs were in the range of 3968.2–555,694.2 pg/kg bw/day. To provide a complete view about the indoor contamination, in this investigation, we also included polycyclic aromatic hydrocarbons (PAHs) and their oxygenated and nitrated derivatives. Definitely, dust collection represents a simple, fast, and cost-effective sampling and dust contamination level can be a useful indicator of environment healthiness. Besides, the presented method can be a smart tool to provide a time and money saving technique to characterize 99 pollutants thanks to a single sample treatment.
Uterine Fibroids Increase the Risk of Thyroid Cancer
Authors: Sun Li-Min , Chung Li-Min , Lin Cheng-Li , Kao Chia-Hung
Published: May 2020

Objectives: The formation of uterine fibroids (UF) is potentially linked to the development of thyroid cancer through a common factor: female sex hormones. Methods: We conducted a nationwide population-based cohort study to determine whether Taiwanese women with UF have an increased risk of thyroid cancer. The data of both the UF and control groups were derived from the National Health Insurance Research Database (NHIRD) of Taiwan. Groups were matched by the year of UF diagnosis, age, income, urbanization level, occupation, and comorbidities. A Cox proportional hazard regression model was used to compare the incidence of thyroid cancer between the UF and control groups. In addition, the model was used to determine the hazard ratio of thyroid cancer in the UF group in comparison with the control group. Results: Women with UF had a statistically significantly increased risk of thyroid cancer compared with controls (adjusted hazard ratio (aHR): 1.64, 95% confidence interval (CI): 1.26–2.13). Stratified analyses showed that women with UF who had a significantly increased risk of thyroid cancer were more likely to be middle aged, have middle and higher income levels, and a medium follow-up period (1–5 years) of UF. No other UF patient characteristics and comorbidities showed association with the risk of thyroid cancer. In addition, UF patients had a significantly increased risk of thyroid cancer regardless of whether or not they underwent myomectomy. Conclusions: The results suggest that women with UF have an increased risk of subsequent thyroid cancer. Further research is needed to explore whether surveillance strategies for the early detection of thyroid cancer using ultrasonography should be implemented among patients with UF.
Incidence of Anorexia Nervosa in Women: A Systematic Review and Meta-Analysis
Authors: Martínez-González Leticia , Fernández-Villa Tania , Molina Antonio José , Delgado-Rodríguez Miguel , Martín Vicente
Published: May 2020

Background: Anorexia nervosa (AN) among the general population is a rare but often fatal illness. Objective: To summarize the incidence of AN using a systematic review and meta-analysis. Methods: Four online databases (PubMed, Scopus, WoS and Embase) were consulted. The review was conducted according to with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was limited to women. The methodological quality of the studies was assessed by the Newcastle–Ottawa Scale (NOS). Results: A total of 31 articles were included in the study. The incidence rate of AN ranged from 0.5 to 318.0 cases per 100,000 women–years. The incidence in studies based on outpatient healthcare services (OHS) was higher than those based on hospital admissions (HA) (8.8 95% CI: 7.83–9.80 vs. 5.0 95% CI: 4.87–5.05). In young women, the incidence in OHS was higher than HA (63.7, 95% CI 61.21–66.12 vs. 8.1 95% CI 7.60–8.53). The linear trend in the incidence of AN was increasing in all ages of women and young women, both in studies with hospital admission records, and in those based on outpatient healthcare services. Conclusion: The incidence of AN depends on the methodology, the type of population and the diagnostic criteria used.
Changes in Thyroid and Glycemic Status and Food Intake in Children with Excess Weight Who Were Submitted for a Multi-Component School Intervention for 16 Months
Authors: Martins Vinicius J. B. , Filgueiras Andrea R. , Almeida Viviane B. P. , de Moraes Rúbia C. S. , Sawaya Ana L.
Published: May 2020

We investigated if children with excess weight who submitted to two types of intervention at school for 16 months showed improvements in thyroid and glycemic function and food intake. Children (8–11 years) with a body mass index-for-age (BMI/A) of ≥1 Z score were divided into two groups: Treatment 1 (n = 73) involved motivation to adopt healthier lifestyle; Treatment 2 (n = 103) involved performing weekly nutritional education, motivational, and physical activities at school. A semi-quantitative food frequency questionnaire was used. The delta BMI/A were similar after 16 months; Treatment 1 showed higher decrease in thyroid-stimulating hormone (TSH; median (range)): −0.45 (−3.19 to 2.17) and 0.06 (−4.57 to 1.63) mIU/L, p = 0.001), FreeT3 (−0.46 (−2.92 to 1.54) and −0.15 (−2.46 to 1.38) pmol/L, p = 0.038), and FreeT4 −1.41 (−6.18 to 3.47) and −0.90 (−4.89 to 2.96) pmol/L, p = 0.018), followed by decrease in energy intake (7304 (6806 to 7840) and 8267 (7739 to 8832) kJ, Ptreatment = 0.439, Ptime <0.001, interaction group–time p < 0.001), macronutrients and sugar. A positive correlation between FreeT3 and BMI/A, and a negative correlation with FreeT4 and insulin were found at baseline (r 0.212, p < 0.01; r −0.155, p < 0.01, respectively) and follow-up (r 0.222, p < 0.01; r −0.221, p < 0.01). The decrease in overall diet and particularly sugar intake was accompanied by a greater reduction in TSH and FreeT3 in Treatment 1, demonstrating the impact of dietary intake on thyroid function.
Contribution of Chronic Fatigue to Psychosocial Status and Quality of Life in Spanish Women Diagnosed with Endometriosis
Authors: Mundo-López Antonio , Ocón-Hernández Olga , San-Sebastián Ainhoa P. , Galiano-Castillo Noelia , Rodríguez-Pérez Olga , Arroyo-Luque María S. , Arroyo-Morales Manuel , Cantarero-Villanueva Irene , Fernández-Lao Carolina , Artacho-Cordón Francisco
Published: May 2020

Aim: To analyze the levels of chronic fatigue in Spanish women with endometriosis and its relationship with their psychosocial status and quality of life (QoL). Methods: A total of 230 Spanish women with a clinical diagnosis of endometriosis were recruited. Chronic fatigue (Piper Fatigue Scale) and pelvic pain (Numeric Rating Scale) were evaluated. An on-line battery of validated scales was used to assess psychosocial status [Hospital Anxiety and Depression Scale, Scale for Mood Assessment, Pain Catastrophizing Scale, Pittsburgh Sleep Quality Index, Gastrointestinal Quality of Life Index, Female Sexual Function Index and Medical Outcomes Study-Social Support Survey] and QoL [Endometriosis-Health Profile questionnaire-30]. Associations between fatigue and both psychosocial and QoL outcomes were explored through multivariate regression models. Results: One-third and one-half of women showed moderate and severe fatigue, respectively. Fatigue was associated with higher anxiety and depression, poorer sleep quality, poorer sexual functioning, worse gastrointestinal health, higher catastrophizing thoughts, higher anger/hostility scores and lower QoL (p-values < 0.050). Moreover, fatigue and catastrophizing thoughts showed a mediating effect on the association between pelvic pain and QoL. Conclusion: This work reveals the important role of fatigue in the association between pain, psychosocial status, and QoL of Spanish women with endometriosis.
Effects of Knowing the Task’s Duration on Soccer Players’ Positioning and Pacing Behaviour during Small-Sided Games
Authors: Ferraz Ricardo , Gonçalves Bruno , Coutinho Diogo , Oliveira Rafael , Travassos Bruno , Sampaio Jaime , C. Marques Mário
Published: May 2020

The study aimed to identify how the manipulation of knowledge regarding a training task duration constrains the pacing and tactical behaviour of soccer players when playing small-sided games (SSG). Twenty professional and experienced soccer players participated in a cross-sectional field study using three conditions: not informed on the duration of the SSG, which ended after 20 min (Unknown Condition); briefed about playing the SSG for 10 min, but after they completed the 10-min game, they were requested to complete another 10 min (Partial Condition) and informed before that they would play for 20 min (Known Condition). A global positioning system was used to measure the total distance covered and distances of different exercise training zones (walking to sprinting) and to access the dynamic players positioning through the distance from each player to all the teammates and opponents. Additionally, approximate entropy was measured to identify the regularity pattern of each gathered individual variable. The results indicate that the first 10 min of each scenario presented a higher physical impact independently of the initial information. During this time, the tactical behaviour also revealed higher variability. An increase in the distance of the teammates during the second period of 10-min for the Known scenario was also found, which may result from a lower pacing strategy. This study showed that the prior knowledge of the task duration led to different physical and tactical behaviours of the players. Furthermore, the relationship between the physical impact and the regularity of team game patterns should be well analysed by the coach, because the physical impact may be harmful to the development of the collective organization of the team.
Inhibition of Heparanase Expression Results in Suppression of Invasion, Migration and Adhesion Abilities of Bladder Cancer Cells
Authors: Tatsumi Yoshihiro , Miyake Makito , Shimada Keiji , Fujii Tomomi , Hori Shunta , Morizawa Yosuke , Nakai Yasushi , Anai Satoshi , Tanaka Nobumichi , Konishi Noboru , Fujimoto Kiyohide
Published: May 2020

Heparan sulfate proteoglycan syndecan-1, CD138, is known to be associated with cell proliferation, adhesion, and migration in malignancies. We previously reported that syndecan-1 (CD138) may contribute to urothelial carcinoma cell survival and progression. We investigated the role of heparanase, an enzyme activated by syndecan-1 in human urothelial carcinoma. Using human urothelial cancer cell lines, MGH-U3 and T24, heparanase expression was reduced with siRNA and RK-682, a heparanase inhibitor, to examine changes in cell proliferation activity, induction of apoptosis, invasion ability of cells, and its relationship to autophagy. A bladder cancer development mouse model was treated with RK-682 and the bladder tissues were examined using immunohistochemical analysis for Ki-67, E-cadherin, LC3, and CD31 expressions. Heparanase inhibition suppressed cellular growth by approximately 40% and induced apoptosis. The heparanase inhibitor decreased cell activity in a concentration-dependent manner and suppressed invasion ability by 40%. Inhibition of heparanase was found to suppress autophagy. In N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer mice, treatment with heparanase inhibitor suppressed the progression of cancer by 40%, compared to controls. Immunohistochemistry analysis showed that heparanase inhibitor suppressed cell growth, and autophagy. In conclusion, heparanase suppresses apoptosis and promotes invasion and autophagy in urothelial cancer.
Leptin Signaling Affects Survival and Chemoresistance of Estrogen Receptor Negative Breast Cancer
Authors: Lipsey Crystal C. , Harbuzariu Adriana , Robey Robert W. , Huff Lyn M. , Gottesman Michael M. , Gonzalez-Perez Ruben R.
Published: May 2020

Estrogen-receptor-negative breast cancer (BCER−) is mainly treated with chemotherapeutics. Leptin signaling can influence BCER− progression, but its effects on patient survival and chemoresistance are not well understood. We hypothesize that leptin signaling decreases the survival of BCER− patients by, in part, inducing the expression of chemoresistance-related genes. The correlation of expression of leptin receptor (OBR), leptin-targeted genes (CDK8, NANOG, and RBP-Jk), and breast cancer (BC) patient survival was determined from The Cancer Genome Atlas (TCGA) mRNA data. Leptin-induced expression of proliferation and chemoresistance-related molecules was investigated in triple-negative BC (TNBC) cells that respond differently to chemotherapeutics. Leptin-induced gene expression in TNBC was analyzed by RNA-Seq. The specificity of leptin effects was assessed using OBR inhibitors (shRNA and peptides). The results show that OBR and leptin-targeted gene expression are associated with lower survival of BCER− patients. Importantly, the co-expression of these genes was also associated with chemotherapy failure. Leptin signaling increased the expression of tumorigenesis and chemoresistance-related genes (ABCB1, WNT4, ADHFE1, TBC1D3, LL22NC03, RDH5, and ITGB3) and impaired chemotherapeutic effects in TNBC cells. OBR inhibition re-sensitized TNBC to chemotherapeutics. In conclusion, the co-expression of OBR and leptin-targeted genes may be used as a predictor of survival and drug resistance of BCER− patients. Targeting OBR signaling could improve chemotherapeutic efficacy.
Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy
Authors: Rayego-Mateos Sandra , Morgado-Pascual José Luis , Opazo-Ríos Lucas , Guerrero-Hue Melania , García-Caballero Cristina , Vázquez-Carballo Cristina , Mas Sebastián , Sanz Ana Belén , Herencia Carmen , Mezzano Sergio , Gómez-Guerrero Carmen , Moreno Juan Antonio , Egido Jesús
Published: May 2020

Diabetic nephropathy (DN) is associated with an increased morbidity and mortality, resulting in elevated cost for public health systems. DN is the main cause of chronic kidney disease (CKD) and its incidence increases the number of patients that develop the end-stage renal disease (ESRD). There are growing epidemiological and preclinical evidence about the close relationship between inflammatory response and the occurrence and progression of DN. Several anti-inflammatory strategies targeting specific inflammatory mediators (cell adhesion molecules, chemokines and cytokines) and intracellular signaling pathways have shown beneficial effects in experimental models of DN, decreasing proteinuria and renal lesions. A number of inflammatory molecules have been shown useful to identify diabetic patients at high risk of developing renal complications. In this review, we focus on the key role of inflammation in the genesis and progression of DN, with a special interest in effector molecules and activated intracellular pathways leading to renal damage, as well as a comprehensive update of new therapeutic strategies targeting inflammation to prevent and/or retard renal injury.
Participation of Somatic Stem Cells, Labeled by a Unique Antibody (A3) Recognizing Both N-glycan and Peptide, to Hair Follicle Cycle and Cutaneous Wound Healing in Rats
Authors: Katou-Ichikawa Chisa , Nishina Hironobu , Tanaka Miyuu , Takenaka Shigeo , Izawa Takeshi , Kuwamura Mitsuru , Yamate Jyoji
Published: May 2020

A monoclonal antibody (A3) was generated by using rat malignant fibrous histiocytoma (MFH) cells as the antigen. Generally, MFH is considered to be a sarcoma derived from undifferentiated mesenchymal cells. Molecular biological analyses using the lysate of rat MFH cells revealed that A3 is a conformation specific antibody recognizing both N-glycan and peptide. A3-labeled cells in bone marrow were regarded as somatic stem cells, because the cells partly coexpressed CD90 and CD105 (both immature mesenchymal markers). In the hair follicle cycle, particularly the anagen, the immature epithelial cells (suprabasal cells) near the bulge and some immature mesenchymal cells in the disassembling dermal papilla and regenerating connective tissue sheath/hair papilla reacted to A3. In the cutaneous wound-healing process, A3-labeled epithelial cells participated in re-epithelialization in the wound bed, and apparently, the labeled cells were derived from the hair bulge; in addition, A3-labeled immature mesenchymal cells in the connective tissue sheath of hair follicles at the wound edge showed the expansion of the A3 immunolabeling. A3-labeled immature epithelial and mesenchymal cells contributed to morphogenesis in the hair cycle and tissue repair after a cutaneous wound. A3 could become a unique antibody to identify somatic stem cells capable of differentiating both epithelial and mesenchymal cells in rat tissues.
Exercise Oncology and Immuno-Oncology; A (Future) Dynamic Duo
Authors: Holmen Olofsson Gitte , Jensen Agnete Witness Praest , Idorn Manja , thor Straten Per
Published: May 2020

Recent advances in clinical oncology is based on exploiting the capacity of the immune system to combat cancer: immuno-oncology. Thus, immunotherapy of cancer is now used to treat a variety of malignant diseases. A striking feature is that even patients with late-stage disease may experience curative responses. However, most patients still succumb to disease, and do not benefit from treatment. Exercise has gained attention in clinical oncology and has been used for many years to improve quality of life, as well as to counteract chemotherapy-related complications. However, more recently, exercise has garnered interest, largely due to data from animal studies suggesting a striking therapeutic effect in preclinical cancer models; an effect largely mediated by the immune system. In humans, physical activity is associated with a lower risk for a variety of malignancies, and some data suggest a positive clinical effect for cancer patients. Exercise leads to mobilization of cells of the immune system, resulting in redistribution to different body compartments, and in preclinical models, exercise has been shown to lead to immunological changes in the tumor microenvironment. This suggests that exercise and immunotherapy could have a synergistic effect if combined.
Erythropoietin Mediated Bone Loss in Mice Is Dose-Dependent and Mostly Irreversible
Authors: Kolomansky Albert , Hiram-Bab Sahar , Ben-Califa Nathalie , Liron Tamar , Deshet-Unger Naamit , Mittelman Moshe , Oster Howard , Rauner Martina , Wielockx Ben , Neumann Drorit , Gabet Yankel
Published: May 2020

Recent studies have demonstrated that erythropoietin (EPO) treatment in mice results in trabecular bone loss. Here, we investigated the dose-response relationship between EPO, hemoglobin (Hgb) and bone loss and examined the reversibility of EPO-induced damage. Increasing doses of EPO over two weeks led to a dose-dependent increase in Hgb in young female mice, accompanied by a disproportionate decrease in trabecular bone mass measured by micro-CT (µCT). Namely, increasing EPO from 24 to 540 IU/week produced a modest 12% rise in Hgb (20.2 ± 1.3 mg/dL vs 22.7 ± 1.3 mg/dL), while trabecular bone volume fraction (BV/TV) in the distal femur decreased dramatically (27 ± 8.5% vs 53 ± 10.2% bone loss). To explore the long-term skeletal effects of EPO, we treated mice for two weeks (540 IU/week) and monitored bone mass changes after treatment cessation. Six weeks post-treatment, there was only a partial recovery of the trabecular microarchitecture in the femur and vertebra. EPO-induced bone loss is therefore dose-dependent and mostly irreversible at doses that offer only a minor advantage in the treatment of anemia. Because patients requiring EPO therapy are often prone to osteoporosis, our data advocate for using the lowest effective EPO dose for the shortest period of time to decrease thromboembolic complications and minimize the adverse skeletal outcome.
Molecular Aspects and Treatment of Iron Deficiency in the Elderly
Authors: Romano Antonino Davide , Paglia Annalisa , Bellanti Francesco , Villani Rosanna , Sangineto Moris , Vendemiale Gianluigi , Serviddio Gaetano
Published: May 2020

Iron deficiency (ID) is the most frequent nutritional deficiency in the whole population worldwide, and the second most common cause of anemia in the elderly. The prevalence of anemia is expecting to rise shortly, because of an ageing population. Even though WHO criteria define anemia as a hemoglobin serum concentration <12 g/dL in women and <13 g/dL in men, several authors propose different and specific cut-off values for the elderly. Anemia in aged subjects impacts health and quality of life, and it is associated with several negative outcomes, such as longer time of hospitalization and a higher risk of disability. Furthermore, it is an independent risk factor of increased morbidity and mortality. Even though iron deficiency anemia is a common disorder in older adults, it should be not considered as a normal ageing consequence, but a sign of underlying dysfunction. Relating to the molecular mechanism in Iron Deficiency Anemia (IDA), hepcidin has a key role in iron homeostasis. It downregulates the iron exporter ferroportin, inhibiting both iron absorption and release. IDA is frequently dependent on blood loss, especially caused by gastrointestinal lesions. Thus, a diagnostic algorithm for IDA should include invasive investigation such as endoscopic procedures. The treatment choice is influenced by the severity of anemia, underlying conditions, comorbidities, and the clinical state of the patient. Correction of anemia and iron supplementation should be associated with the treatment of the causal disease.
ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment
Authors: Jeong Jae Woong , Kim Minki , Lee Jiwoo , Lee Hae-Kyung , Ko Younhee , Kim Hyunkyung , Fang Sungsoon
Published: May 2020

Glucagon-like peptide-1 (GLP-1) is a well-known incretin hormone secreted from enteroendocrinal L cells in response to nutrients, such as glucose and dietary fat, and controls glycemic homeostasis. However, the detailed intracellular mechanisms of how L cells control GLP-1 secretion in response to nutrients still remain unclear. Here, we report that bone morphogenetic protein (BMP) signaling pathway plays a pivotal role to control GLP-1 secretion in response to nutrient replenishment in well-established mouse enteroendocrinal L cells (GLUTag cells). Nutrient starvation dramatically reduced cellular respiration and GLP-1 secretion in GLUTag cells. Transcriptome analysis revealed that nutrient starvation remarkably reduced gene expressions involved in BMP signaling pathway, whereas nutrient replenishment rescued BMP signaling to potentiate GLP-1 secretion. Transient knockdown of inhibitor of DNA binding (ID)1, a well-known target gene of BMP signaling, remarkably reduced GLP-1 secretion. Consistently, LDN193189, an inhibitor of BMP signaling, markedly reduced GLP-1 secretion in L cells. In contrast, BMP4 treatment activated BMP signaling pathway and potentiated GLP-1 secretion in response to nutrient replenishment. Altogether, we demonstrated that BMP signaling pathway is a novel molecular mechanism to control GLP-1 secretion in response to cellular nutrient status. Selective activation of BMP signaling would be a potent therapeutic strategy to stimulate GLP-1 secretion in order to restore glycemic homeostasis.
Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy: The Involvement of Macrophage Activation
Authors: Tod Pál , Bukosza Eva Nora , Róka Beáta , Kaucsár Tamás , Fintha Attila , Krenács Tibor , Szénási Gábor , Hamar Péter
Published: May 2020

(1) Background: Successful treatment of acute kidney injury (AKI)-induced chronic kidney disease (CKD) is unresolved. We aimed to characterize the time-course of changes after contralateral nephrectomy (Nx) in a model of unilateral ischemic AKI-induced CKD with good translational utility. (2) Methods: Severe (30 min) left renal ischemia-reperfusion injury (IRI) or sham operation (S) was performed in male Naval Medical Research Institute (NMRI) mice followed by Nx or S one week later. Expression of proinflammatory, oxidative stress, injury and fibrotic markers was evaluated by RT-qPCR. (3) Results: Upon Nx, the injured kidney hardly functioned for three days, but it gradually regained function until day 14 to 21, as demonstrated by the plasma urea. Functional recovery led to a drastic reduction in inflammatory infiltration by macrophages and by decreases in macrophage chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) mRNA and most injury markers. However, without Nx, a marked upregulation of proinflammatory (TNF-α, IL-6, MCP-1 and complement-3 (C3)); oxidative stress (nuclear factor erythroid 2-related factor 2, NRF2) and fibrosis (collagen-1a1 (Col1a1) and fibronectin-1 (FN1)) genes perpetuated, and the injured kidney became completely fibrotic. Contralateral Nx delayed the development of renal failure up to 20 weeks. (4) Conclusion: Our results suggest that macrophage activation is involved in postischemic renal fibrosis, and it is drastically suppressed by contralateral nephrectomy ameliorating progression.
Lipid Raft Destabilization Impairs Mouse TRPA1 Responses to Cold and Bacterial Lipopolysaccharides
Authors: Startek Justyna B. , Talavera Karel
Published: May 2020

The Transient Receptor Potential ankyrin 1 cation channel (TRPA1) is expressed in nociceptive sensory neurons and epithelial cells, where it plays key roles in the detection of noxious stimuli. Recent reports showed that mouse TRPA1 (mTRPA1) localizes in lipid rafts and that its sensitivity to electrophilic and non-electrophilic agonists is reduced by cholesterol depletion from the plasma membrane. Since effects of manipulating membrane cholesterol levels on other TRP channels are known to vary across different stimuli we here tested whether the disruption of lipid rafts also affects mTRPA1 activation by cold or bacterial lipopolysaccharides (LPS). Cooling to 12 °C, E. coli LPS and allyl isothiocyanate (AITC) induced robust Ca2+ responses in CHO-K1 cells stably transfected with mTRPA1. The amplitudes of the responses to these stimuli were significantly lower in cells treated with the cholesterol scavenger methyl β-cyclodextrin (MCD) or with the sphingolipids hydrolyzer sphingomyelinase (SMase). This effect was more prominent with higher concentrations of the raft destabilizers. Our data also indicate that reduction of cholesterol does not alter the expression of mTRPA1 in the plasma membrane in the CHO-K1 stable expression system, and that the most salient effect is that on the channel gating. Our findings further indicate that the function of mTRPA1 is regulated by the local lipid environment and suggest that targeting lipid-TRPA1 interactions may be a strategy for the treatment of pain and neurogenic inflammation.
Adhesive Properties of the Hyaluronan Pericellular Coat in Hyaluronan Synthases Overexpressing Mesenchymal Stem Cells
Authors: Reiprich Sebastian , Hofbauer Eva , Kiderlen Stefanie , Clausen-Schaumann Hauke , Böcker Wolfgang , Aszódi Attila , Schönitzer Veronika
Published: May 2020

Hyaluronan (HA), a natural component of the extracellular matrix, is supposed to have a regulatory function in the stem cell niche. Bone marrow-derived human mesenchymal stem cells (hMSCs) are known to express all three hyaluronan synthases (HASes), which are responsible for HA production. HA is extruded into the extracellular matrix, but also stays bound to the plasma membrane forming a pericellular coat, which plays a key role during early cell adhesion. Since HAS isoenzymes, HAS1, HAS2 and HAS3, produce HA with different molecular weights, a difference in their role for cell adhesion is expected. Here, we transduced the immortalized hMSC cell line SCP1 to constitutively express eGFP-tagged HASes (SCP1-HAS-eGFP) by lentiviral gene transfer. The overexpression of the HAS-eGFP was shown on RNA and protein levels, HA was determined by ELISA and the stained HA-coat was analyzed using confocal microscopy. Time-lapse microscopy, spreading assay and single cell force spectroscopy using atomic force microscopy were applied to characterize adhesion of the different HAS transduced SCP1 cells. We showed in this study that HAS3 overexpressing cells formed the thickest pericellular coat compared with control or HAS1 and HAS2 transduced cells. Furthermore, SCP1-HAS3-eGFP displayed faster and stronger adhesion compared to cells overexpressing the other synthases or control cells. We conclude that overexpression of HASes in hMSCs differentially modulates their initial adhesive interactions with the substrate. This observation might be helpful in regenerative medicine goals.