bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipocalin-2 (Lcn-2) Attenuates Polymicrobial Sepsis with LPS Preconditioning (LPS Tolerance) in FcGRIIb Deficient Lupus Mice
Authors: Ondee Thunnicha , Gillen Joseph , Visitchanakun Peerapat , Somparn Poorichaya , Issara-Amphorn Jiraphorn , Dang Phi Cong , Chancharoenthana Wiwat , Gurusamy Devikala , Nita-Lazar Aleksandra , Leelahavanichkul Asada
Published: September 2019

In patients with active lupus, spontaneous endotoxemia and possibly tolerance to lipopolysaccharide (LPS) is a potentially adverse complication. Similarly, previous reports have demonstrated that FcGRIIb deficient mice (FcGRIIb-/-; a lupus mouse model) are susceptible to LPS tolerance-induced decreased cytokine responses that inadequate for the organismal control. Thus, understanding the relationship between FcGRIIb and LPS tolerance could improve the therapeutic strategy for lupus. LPS tolerance can be induced through sequential LPS stimulations in either cells or a model organism. In RAW264.7 (a mouse macrophage cell-line), sequential LPS stimulation induced the secretion of Lipocalin-2 (Lcn-2) despite reduced cytokine secretion and severe energy depletion, as measured by the extracellular flux analysis, typical of LPS tolerance. In contrast, treatment with recombinant Lcn-2 (rLcn-2) attenuated LPS tolerance, as shown by an increase in secreted cytokines and altered macrophage polarization toward M1 (increased iNOS and TNF-α) in RAW264.7 cells. These results suggest a role of Lcn-2 in LPS tolerance attenuation. In bone marrow derived macrophages, Lcn-2 level was similar in LPS tolerant FcGRIIb-/- and wild-type (WT) cells despite the increased LPS tolerance of FcGRIIb-/- cells, suggesting relatively low basal levels of Lcn-2 produced in FcGRIIb-/- cells. In addition, attenuation of LPS tolerance effectuated by granulocyte-monocyte colony stimulating factor (GM-CSF) reduced Lcn-2 in both cell types, implying an inverse correlation between Lcn-2 and the severity of LPS tolerance. Consequently, rLcn-2 improved LPS tolerance only in FcGRIIb-/- macrophages and attenuated disease severity of cecal ligation and puncture (CLP) sepsis pre-conditioning with sequential LPS injection (LPS-CLP model) only in FcGRIIb-/- mice, but not in WT mice. To summarize, inadequate Lcn-2 production in FcGRIIb-/- macrophage might, at least in part, be responsible for the inordinate LPS tolerance compared with WT cells. Additionally, supplementation of rLcn-2 attenuates LPS tolerance in FcGRIIb-/- macrophages in vitro, and in FcGRIIb-/- mice with LPS-CLP sepsis in vivo. In conclusion, Lcn-2 secreted by macrophages is possibly an autocrine signal to counter the reduced cytokine secretion in LPS tolerance.
Overcoming Immunological Resistance Enhances the Efficacy of a Novel Anti-tMUC1-CAR T Cell Treatment against Pancreatic Ductal Adenocarcinoma
Authors: Yazdanifar Mahboubeh , Zhou Ru , Grover Priyanka , Williams Chandra , Bose Mukulika , Moore Laura J. , Wu Shu-ta , Maher John , Dreau Didier , Mukherjee Pinku
Published: September 2019

Chimeric antigen receptor (CAR) T cells have shown remarkable success in treating hematologic cancers. However, this efficacy has yet to translate to treatment in solid tumors. Pancreatic ductal adenocarcinoma (PDA) is a fatal malignancy with poor prognosis and limited treatment options. We have developed a second generation CAR T cell using the variable fragments of a novel monoclonal antibody, TAB004, which specifically binds the tumor-associated-MUC1 (tMUC1). tMUC1 is overexpressed on ~85% of all human PDA. We present data showing that TAB004-derived CAR T cells specifically bind to tMUC1 on PDA cells and show robust killing activity; however, they do not bind or kill normal epithelial cells. We further demonstrated that the tMUC1-CAR T cells control the growth of orthotopic pancreatic tumors in vivo. We witnessed that some PDA cells (HPAFII and CFPAC) were refractory to CAR T cell treatment. qPCR analysis of several genes revealed overexpression of indoleamine 2, 3-dioxygenases-1 (IDO1), cyclooxygenase 1 and 2 (COX1/2), and galectin-9 (Gal-9) in resistant PDA cells. We showed that combination of CAR T cells and biological inhibitors of IDO1, COX1/2, and Gal-9 resulted in significant enhancement of CAR T cell cytotoxicity against PDA cells. Overcoming PDA resistance is a significant advancement in the field.
Biologic Treatment Options for Pediatric Psoriasis and Atopic Dermatitis
Authors: Cline Abigail , Bartos Gregory J. , Strowd Lindsay C. , Feldman Steven R.
Published: September 2019

Background and Objectives: Severe, recalcitrant cases of pediatric psoriasis or atopic dermatitis may necessitate treatment with biological agents; however, this may be difficult due to lack of treatment options and standardized treatment guidelines. This review evaluates the biological treatment options available, including off-label uses, and provides a basic therapeutic guideline for pediatric psoriasis and atopic dermatitis. Materials and Methods: A PubMed review of biological treatments for pediatric psoriasis and atopic dermatitis with information regarding age, efficacy, dosing, contra-indications, adverse events, and off-label treatments. Results: Currently there are three European Medicines Agency (EMA)-approved biological treatment options for pediatric psoriasis: etanercept, ustekinumab, and adalimumab. While dupilumab was recently Food and Drug Administration (FDA)- and EMA-approved for adult atopic dermatitis, it is still not yet approved for pediatric atopic dermatitis. Conclusions: Given the high morbidity associated with pediatric atopic dermatitis and psoriasis, there is a need for more treatment options. Further research and post-marketing registries are needed to extend the use of biologics into pediatric patients.
Large-Area Coating of Previtamin D3 Based on Roll-to-Roll Processing
Authors: Park Janghoon , Min Yoonki , Lee Jongsu , Jeong Hakyung , Noh Youngwook , Shin Kee-Hyun , Lee Dongjin
Published: September 2019

We propose a roll-to-roll process for vitamin D3 patch production. A solution of 7-dehydrocholesterol is applied to a plastic film by roll-to-roll slot-die coating and dried by a far-infrared lamp. Upon exposure to ultraviolet B irradiation, these films are converted to previtamin D3 films. After heat-treating the previtamin D3 film, high-performance liquid chromatography measurements are performed using commercial vitamin D3 as a standard sample. The results confirm that vitamin D3 can be produced by large-area coating and post-treatment processes. Specifically, 3.16 ± 0.746 mg of vitamin D3 is obtained through ultraviolet B irradiation and heat-treatment of 24.8 ± 1.44 mg of coated 7-dehydrocholesterol.
Pragmatic Hypotheses in the Evolution of Science
Authors: Esteves Luis Gustavo , Izbicki Rafael , Stern Julio Michael , Stern Rafael Bassi
Published: September 2019

This paper introduces pragmatic hypotheses and relates this concept to the spiral of scientific evolution. Previous works determined a characterization of logically consistent statistical hypothesis tests and showed that the modal operators obtained from this test can be represented in the hexagon of oppositions. However, despite the importance of precise hypothesis in science, they cannot be accepted by logically consistent tests. Here, we show that this dilemma can be overcome by the use of pragmatic versions of precise hypotheses. These pragmatic versions allow a level of imprecision in the hypothesis that is small relative to other experimental conditions. The introduction of pragmatic hypotheses allows the evolution of scientific theories based on statistical hypothesis testing to be interpreted using the narratological structure of hexagonal spirals, as defined by Pierre Gallais.
Hour-Ahead Energy Trading Management with Demand Forecasting in Microgrid Considering Power Flow Constraints
Authors: Feng Kuo , Liu Chunhua , Song Zaixin
Published: September 2019

Multiple small-scale low-voltage distribution networks with distributed generators can be connected in a radial pattern to form a multi-bus medium voltage microgrid. Additionally, each bus has an independent operator that can manage its power supply and demand. Since the microgrid operates in the market-oriented mode, the bus operators aim to maximize their own benefits and expect to protect their privacy. Accordingly, in this paper, a distributed hour-ahead energy trading management is proposed. First, the benefit optimization problem of the microgrid is solved, which is decomposed into the local benefit optimization sub problems of buses. Then, the local sub problems can be solved by the negotiation of operators with their neighbors. Additionally, the reference demand before negotiation is forecasted by the neural network rather than given in advance. Furthermore, the power flow constraints are considered to guarantee the operational stability. Meanwhile, the power loss minimization is considered in the objective function. Finally, the demonstration and simulation cases are given to validate the effectiveness of the proposed hour-ahead energy trading management.
Sensorless PMSM Drive Implementation by Introduction of Maximum Efficiency Characteristics in Reference Current Generation
Authors: Plantić Željko , Marčič Tine , Beković Miloš , Štumberger Gorazd
Published: September 2019

This paper presents the efficiency improvement in a speed closed-loop controlled permanent magnet synchronous machine (PMSM) sensorless drive. The drive efficiency can be improved by minimizing the inverter and the PMSM losses. These can be influenced by proper selection of DC-bus voltage and switching frequency of the inverter. The direct (d-) and quadrature (q-) axis current references generation methods, discussed in this paper, further improve the efficiency of the drive. Besides zero d-axis current reference control, the maximum torque per ampere (MTPA) characteristic is normally applied to generate the d- and q-axis current references in vector controlled PMSM drives. It assures control with maximum torque per unit of current but cannot assure maximum efficiency. In order to improve efficiency of the PMSM drive, this paper proposes the generation of d- and q-axis current references based on maximum efficiency (ME) characteristic. In the case study, the MTPA and ME characteristics are theoretically evaluated and determined experimentally by measurements on discussed PMSM drive. The obtained characteristics are applied for the d- and q-axis current references generation in the speed closed-loop vector controlled PMSM drive. The measured drive efficiency clearly shows that the use of ME characteristic instead of MTPA characteristic or zero d-axis current in the current references generation improves the efficiency of PMSM drive realizations with position sensor and without it—sensorless control.
Additive Aerodynamic and Thermal Effects of a Central Guide Post and Baffle Installed in a Solar Updraft Tower
Authors: Lee Seungjin , Kim Saerom , Chae Jonghyun , Park Joong Yull
Published: September 2019

The solar updraft tower (SUT) is a renewable power generation system that uses natural air convection from the ground that is heated by solar radiation. Placing flow-guide structures within the collector of the SUT can enhance aerodynamic performance, and hence, increase the kinetic power. Here, we propose a central guide post (CGP) structure in the SUT that controls updraft flow. The effect of the CGP geometry on aerodynamic performance was investigated using computational fluid dynamics modeling (ANSYS Fluent 19.2) to show that a CGP can play a positive role by preventing stagnation of the airflow at the center of the collector, resulting in increased kinetic power output (up to ~2%). However, excessively long CGPs retarded airflow, resulting in a dramatic decrease in kinetic power output. We also investigated a system with both a CGP (to improve aerodynamic performance and minimize energy loss) and a heat-exchange baffle (to maximize thermal energy transfer). When installed with a proper distance between components, the CGP and baffle showed a combined effect of increasing the kinetic power output by up to 10%. We expect that our proposed method using the CGP and baffle system will contribute to the development of better future SUT technology.
Individual Rubber Tree Segmentation Based on Ground-Based LiDAR Data and Faster R-CNN of Deep Learning
Authors: Wang Jiamin , Chen Xinxin , Cao Lin , An Feng , Chen Bangqian , Xue Lianfeng , Yun Ting
Published: September 2019

Rubber trees in southern China are often impacted by natural disturbances that can result in a tilted tree body. Accurate crown segmentation for individual rubber trees from scanned point clouds is an essential prerequisite for accurate tree parameter retrieval. In this paper, three plots of different rubber tree clones, PR107, CATAS 7-20-59, and CATAS 8-7-9, were taken as the study subjects. Through data collection using ground-based mobile light detection and ranging (LiDAR), a voxelisation method based on the scanned tree trunk data was proposed, and deep images (i.e., images normally used for deep learning) were generated through frontal and lateral projection transform of point clouds in each voxel with a length of 8 m and a width of 3 m. These images provided the training and testing samples for the faster region-based convolutional neural network (Faster R-CNN) of deep learning. Consequently, the Faster R-CNN combined with the generated training samples comprising 802 deep images with pre-marked trunk locations was trained to automatically recognize the trunk locations in the testing samples, which comprised 359 deep images. Finally, the point clouds for the lower parts of each trunk were extracted through back-projection transform from the recognized trunk locations in the testing samples and used as the seed points for the region’s growing algorithm to accomplish individual rubber tree crown segmentation. Compared with the visual inspection results, the recognition rate of our method reached 100% for the deep images of the testing samples when the images contained one or two trunks or the trunk information was slightly occluded by leaves. For the complicated cases, i.e., multiple trunks or overlapping trunks in one deep image or a trunk appearing in two adjacent deep images, the recognition accuracy of our method was greater than 90%. Our work represents a new method that combines a deep learning framework with point cloud processing for individual rubber tree crown segmentation based on ground-based mobile LiDAR scanned data.
Evaluating the Degree of Uncertainty of Research Activities in Industry 4.0
Authors: Cividino Sirio , Egidi Gianluca , Zambon Ilaria , Colantoni Andrea
Published: September 2019

Research and development (R&D) are always oriented towards new discoveries, based on original terms or hypotheses, and their concluding outcomes are often uncertain. The present work focused on the degree of uncertainty for R&D activities. In fact, uncertainty makes it difficult to quantify the time and resources needed to achieve a final outcome, create a work plan and budget, and finalize the resulting “innovative” products or services that could be transferred or exchanged in a specific market. The present work attempts to indicate the degree of uncertainty of the research activities developed by a set of firms. The method used aimed to quantify the five criteria defined by the Manual of Frascati. Through the creation of an uncertainty cloud, a cone of uncertainty was defined following an approach based on project management. The evaluation grid was characterized by the decomposition of the different variables divided into quartiles, which allowed for the detection of the evolution of the project and each of its component. The ancillary objective aim was to also observe the development degree of these industries towards a framework of Industry 4.0.
A Comparative Transcriptome Analysis Reveals Physiological Maturation Properties of Mycelia in Pleurotus tuoliensis
Authors: Du Fang , Ya Li mai mai ti Nu Er zi ya , Hu Qingxiu , Zou Yajie , Ye Dou , Zhang Haijun
Published: September 2019

Pleurotus tuoliensis is a precious edible fungus with extremely high nutritive and medicinal value. The cultivation period of P. tuoliensis is longer than those of other Pleurotus species, which is mainly due to a longer mycelium physiological maturation period (30–60 days). Currently, the molecular processes underlying physiological maturation of the mycelium remain unclear. We performed a comparative transcriptomic analysis of immature and mature mycelia using RNA-seq. De novo transcriptome assembly resulted in identification of 17,030 unigenes. 451 differentially expressed genes—including those encoding nucleoside diphosphate kinase (NDPK), glycoside hydrolase family proteins, exopolygalacturonase, and versatile peroxidases—were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that nucleotide synthesis and energy metabolism are highly active during the physiological maturation of mycelia, and genes related to these pathways were significantly upregulated in mature mycelia. NDPK is predicted to be essential for mycelia maturation. Our findings contribute to a comprehensive understanding of mycelia maturation in a commercially important fungal species. Future efforts will focus on the function of NDPK and the mechanism by which it regulates mycelia maturation.
Assessment of Delirium Using the Confusion Assessment Method in Older Adult Inpatients in Malaysia
Authors: Khor Hui Min , Ong Hwee Chin , Tan Bee Kuan , Low Chung Min , Saedon Nor’Izzati , Tan Kit Mun , Chin Ai Vyrn , Kamaruzzaman Shahrul B. , Tan Maw Pin
Published: September 2019

The detection of delirium in acutely ill older patients is challenging with the lack of informants and the necessity to identify subtle and fluctuating signs. We conducted a cross-sectional study among older patients admitted to a university hospital in Malaysia to determine the presence, characteristics, and mortality outcomes of delirium. Consecutive patients aged ≥65years admitted to acute medical wards were recruited from August to September 2016. Cognitive screening was performed using the mini-mental test examination (MMSE) and the Confusion Assessment Method (CAM). The CAM-Severity (CAM-S) score was also performed in all patients. Of 161 patients recruited, 43 (26.7%) had delirium. At least one feature of delirium from the CAM-S short and long severity scores were present in 48.4% and 67.1%, respectively. Older age (OR: 1.07, 95% CI: 1.01–1.14), immobility (OR: 3.16, 95% CI: 1.18–8.50), cognitive impairment (OR: 5.04, 95% CI: 2.07–12.24), and malnutrition (OR: 3.37; 95% CI: 1.15–9.85) were significantly associated with delirium. Older patients with delirium had a higher risk of mortality (OR: 7.87, 95% CI: 2.42–25.57). Delirium is common among older patients in our setting. A large proportion of patients had altered mental status on admission to hospital although they did not fulfill the CAM criteria of delirium. This should prompt further studies on strategies to identify delirium and the use of newer, more appropriate assessment tools in this group of vulnerable individuals.
Modeling Group Behavior to Study Innovation Diffusion Based on Cognition and Network: An Analysis for Garbage Classification System in Shanghai, China
Authors: Zheng Junjun , Xu Mingyuan , Cai Ming , Wang Zhichao , Yang Mingmiao
Published: September 2019

In real life, garbage has caused great pollution to the environment. A garbage classification system is an effective way to manage this issue, and is an innovation in Shanghai, China. Innovation diffusion is the topic of this paper. This study uses a mathematical statistics method to formulate individual bounded rationality, and uses the specific graph structure of a scale-free network to characterize group structure. Then, a model of group behavior is constructed and the simulation experiment is run on the Python platform. The results show that: (1) In the case of general cognitive ability and high value innovation, most individuals in the group will accept the innovation in the process of innovation dissemination in a garbage classification system after several rounds of the game; (2) it is more helpful to improve the cognitive ability of individuals and the true value of innovation for the diffusion of innovation; and (3) the larger a group, the greater the scope of innovation diffusion and the more time is needed. It is helpful to expand the scope and reduce the time of innovation diffusion by increasing connections among individuals. The innovation of this study is the characterization of individual bounded rationality, which has a certain theoretical value. Meanwhile, the research results of this paper have important practical significance for the promotion of garbage classification, which can be used to popularize the concept of garbage classification.
Effect of Endogenous Selenium on Arsenic Uptake and Antioxidative Enzymes in As-Exposed Rice Seedlings
Authors: Camara Aboubacar Younoussa , Wan Yanan , Yu Yao , Wang Qi , Wang Kang , Li Huafen
Published: September 2019

Arsenic (As) and selenium (Se) are two metalloids found in the environment. As it poses a significant threat to human health and plant growth due to its prevalence and toxicity, however Se is a required micronutrient for human health. In this study hydroponic experiments were performed to investigate whether endogenous Se can mitigate As toxicity in rice (Oryza sativa L.). We found that As uptake by rice roots increased by pretreatment with selenateSe(VI) or selenite Se(IV). However, co-application of arsenate As(V) or arsenite As(III) with selenate markedly reduced the uptake of As by roots. Co- or pretreatment with Se with five µM of As(V) or one µM of As(III) significantly decreased shoot As content. Conversely, Se pretreatment before the addition of five µM of As(III) or one µM of As(V) resulted in As accumulation in the shoot compared to As and Se co-application. As translocation to the shoot was lower whereas the transfer factor was higher upon the simultaneous application of Se and As compared to Se pretreatment. Se supplementation with As(III) or pretreatment increased antioxidant enzymes: Superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) increased in the root and shoot, but decreased glutathione (GSH) and malondialdehyde (MDA) contents in the shoot. Plants under As(V) treatment showed the same trend except that CAT content decreased in the root and shoot, while MDA content increased in the shoot. These results suggest that cultivating rice in the presence of Se can reduce the accumulation of toxic As in seedlings, thus ensuring the safety of this important crop for human consumption.
Influence of PM2.5 Exposure Level on the Association between Alzheimer’s Disease and Allergic Rhinitis: A National Population-Based Cohort Study
Authors: Li Ruo-Ling , Ho Yung-Chyuan , Luo Ci-Wen , Lee Shiuan-Shinn , Kuan Yu-Hsiang
Published: September 2019

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease that leads to dementia, health impairment, and high economic cost. Allergic rhinitis (AR) is a chronic inflammatory and allergic disease of the respiratory system that leads to health problems and has major effects on the daily lives of patients and their caregivers. Particulate matter (PM) refers to air pollutants 2.5 μm or less in diameter that are a source of concern because of their role in numerous diseases, including AR and other neurodegenerative diseases. To date, no study has demonstrated how PM2.5 exacerbates AR and results in AD. We conducted a national population-based cohort study by obtaining patient data from the National Health Insurance Research Database of Taiwan for the 2008–2013 period. PM2.5 concentration data were obtained from the ambient air quality monitoring network established by the Environmental Protection Administration of Taiwan. Monthly PM2.5 exposure levels were categorized into quartiles from Q1–Q4. The Cox proportional hazards analysis, after adjusting for age, sex, low income, and urbanization level, revealed that patients with AR had an elevated risk of developing AD (hazard ratio (HR): 2.008). In addition, the cumulative incidence of AD in the AR group was significantly higher than in the comparison group. The PM2.5 levels at Q2–Q4 (crude HR: 1.663–8.315; adjusted HR: 1.812–8.981) were stratified on the basis of the PM2.5 exposure group and revealed that AR patients exposed to PM2.5 are significantly prone to develop AD. In addition, the logistic regression analyses, after adjustment, demonstrated that an increase in the PM2.5 exposure level at Q2–Q4 (adjusted odds ratio (OR): 2.656–5.604) increased the risk of AR in AD patients. In conclusion, an increased PM2.5 exposure level could be correlated with AR, which could in turn cause AD. AR increased the risk of AD, in which exposure to PM2.5 increases the higher probability of AD.
Leisure-Time Physical Activity and Metabolic Syndrome in Older Adults
Authors: Gallardo-Alfaro Laura , Bibiloni Maria del Mar , Mateos David , Ugarriza Lucía , Tur Josep A.
Published: September 2019

Background: Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease, atherosclerosis and diabetes mellitus type 2 which may be reduced by practicing regular physical activity. Objective: To assess the leisure-time physical activity (LTPA) of older adults with MetS and without MetS. Methods: Cross-sectional study of older adults (55–80 years old) from Balearic Islands (Spain) with MetS (n = 333; 55% men) and without MetS (n = 144; 43.8% men). LTPA was assessed with the validated Spanish version of the Minnesota LTPA Questionnaire. Two criteria of physically active were used: >150 min/week of moderate physical activity or >75 min/week of vigorous physical activity or a combination of both, and total leisure-time energy expenditure of >300 MET·min/day. Sociodemographic and lifestyle characteristics, anthropometric variables, MetS components, and adherence to the Mediterranean diet (MD) were also measured. Results: MetS subjects showed lower energy expenditure in LTPA, lower adherence to the MD, higher obesity and waist circumference, and were less active than non-MetS peers. LTPA increased as participants got older and there was higher LTPA intensity as educational level increased. Adherence to MD was as high as LTPA was. Conclusions: MetS is associated with physical inactivity and unhealthy diet. To increase LTPA recommendations and raise awareness in the population about the health benefits of PA and high adherence to MD is highly recommended.
Pathways and Associations between Women’s Land Ownership and Child Food and Nutrition Security in Pakistan
Authors: Rehman Azka , Ping Qing , Razzaq Amar
Published: September 2019

Women’s land ownership plays a noteworthy role in improving various development indicators, including her own wellbeing and children’s food and nutrition security. However, the literature linking women’s access to land rights to the nutritional security of children in Pakistan is limited, even though it is a country facing enormous challenges of childhood malnutrition and gender discrimination. This paper contributes to the existing literature on the benefits of empowering women by studying the association and pathways between women’s land rights and child nutrition, using the 2012–2013 Pakistan Demographic and Health Survey. The ordinary least squares (OLS) regression results indicate that women’s individual land ownership and women’s autonomy in large-scale family purchases have a positive impact on children’s food and nutrition security (FNS). The results of quantile regression (QR) show that these effects are more pronounced in cases of children with severe stunted growth. In addition, a structural equation model shows that the positive relationship between women’s land ownership and child nutrition is partially mediated by women’s increased decision-making power in large-scale household purchases. Our research concludes that ensuring women’s land rights can improve women’s autonomy, which can be an effective policy tool that not only improves women’s welfare but also improves their children’s nutritional security.
The Association between Air Pollution and Sleep Duration: A Cohort Study of Freshmen at a University in Beijing, China
Authors: Yu Hongjun , Chen Panpan , Paige Gordon Shelby , Yu Miao , Wang Yangyang
Published: September 2019

Background: Rising levels of air pollution in Beijing, China have become a serious environmental issue affecting human health, and young adults are experiencing high rates of insufficient sleep duration or a lack of sleep. Gaps in previous research remain regarding the relationship between air pollution and sleep duration among young adults. The purpose of this study is to assess the associations between air pollution and sleep duration among college students living in Beijing, China. Methods: We conducted follow-up health surveys on 16,889 freshman students enrolled at Tsinghua University over a five-year study period (2013–2018). Sleep duration was measured using the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), which has been validated in China to measure sleep duration. Corresponding levels of the average hourly air quality index (AQI), PM2.5 (µg/m3), PM10 (µg/m3), and NO2 (µg/m3) were gathered from data provided by the Beijing Municipal Ecological Environment Bureau in a closed site at Tsinghua University. Multilevel mixed-effects linear regression models were used to analyze the data. Results: One standard deviation increase in air pollution concentration in AQI, PM2.5, PM10, and NO2 was associated with a reduction in daily hours of sleep by 0.68 (95% confidence interval (CI) = 0.63, 0.73), 0.55 (95% CI = 0.51, 0.59), 0.70 (95% CI = 0.64, 0.76), and 0.51 (95% CI = 0.47, 0.54), respectively. Conclusions: Air pollution was associated with a reduction in sleep duration among freshman students living in Beijing, China. Replication of this study is warranted among various populations within China.
Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection
Authors: Feria-Garzón Manuel G. , Rugeles María T. , Hernandez Juan C. , Lujan Jorge A. , Taborda Natalia A.
Published: September 2019

Background: HIV-1 induces an uncontrolled inflammatory response of several immune components, such as inflammasomes. These molecular complexes, associated with Toll-like receptor (TLR) activity, induce the maturation and release of IL-1β and IL-18 and eventually induce pyroptosis. It has been previously demonstrated that HIV induces inflammasome activation, which is significantly lower in the gastrointestinal tissue and blood from people living with HIV-1 with spontaneous control of viral replication. Therefore, immunomodulatory agents could be useful in improving HIV prognosis. Objective: To evaluate the potential inhibitory effect of sulfasalazine (SSZ) on inflammasomes and TLRs in peripheral blood mononuclear cells (PBMCs) from people living with HIV and healthy donors. Methods: PBMCs were obtained from 15 people living with HIV and 15 healthy donors. Cells were stimulated with agonists of TLRs and inflammasomes and subsequently treated with SSZ. The concentration of IL-1β and the relative expression of NLRP3, NLRC4, NLRP1, AIM2, ASC, Caspase-1, IL-1β, and IL-18 were quantified. Results: Cells treated with SSZ exhibited a decreased IL-1β production after inflammasome and TLR stimulation, as well as regulation of inflammasome-related genes, in both people with HIV and healthy individuals. The concentration of IL-1β was positively correlated with the CD4+ T-cell count and negatively with the viral load. Conclusion: Our results suggest that SSZ has an immunomodulatory effect on inflammasome and TLR activation that depends on the clinical HIV status.
Mast Cells as Potential Accelerators of Human Atherosclerosis—From Early to Late Lesions
Authors: Kovanen Petri T.
Published: September 2019

Mast cells are present in atherosclerotic lesions throughout their progression. The process of atherogenesis itself is characterized by infiltration and retention of cholesterol-containing blood-derived low-density lipoprotein (LDL) particles in the intimal layer of the arterial wall, where the particles become modified and ingested by macrophages, resulting in the formation of cholesterol-filled foam cells. Provided the blood-derived high-density lipoproteins (HDL) particles are able to efficiently carry cholesterol from the foam cells back to the circulation, the early lesions may stay stable or even disappear. However, the modified LDL particles also trigger a permanent local inflammatory reaction characterized by the presence of activated macrophages, T cells, and mast cells, which drive lesion progression. Then, the HDL particles become modified and unable to remove cholesterol from the foam cells. Ultimately, the aging foam cells die and form a necrotic lipid core. In such advanced lesions, the lipid core is separated from the circulating blood by a collagenous cap, which may become thin and fragile and susceptible to rupture, so causing an acute atherothrombotic event. Regarding the potential contribution of mast cells in the initiation and progression of atherosclerotic lesions, immunohistochemical studies in autopsied human subjects and studies in cell culture systems and in atherosclerotic mouse models have collectively provided evidence that the compounds released by activated mast cells may promote atherogenesis at various steps along the path of lesion development. This review focuses on the presence of activated mast cells in human atherosclerotic lesions. Moreover, some of the molecular mechanisms potentially governing activation and effector functions of mast cells in such lesions are presented and discussed.
Long and Very-Long-Chain Ceramides Correlate with A More Aggressive Behavior in Skull Base Chordoma Patients
Authors: La Corte Emanuele , Dei Cas Michele , Raggi Alberto , Patanè Monica , Broggi Morgan , Schiavolin Silvia , Calatozzolo Chiara , Pollo Bianca , Pipolo Carlotta , Bruzzone Maria Grazia , Campisi Giuseppe , Paroni Rita , Ghidoni Riccardo , Ferroli Paolo
Published: September 2019

Background: Skull base chordomas are rare tumors arising from notochord. Sphingolipids analysis is a promising approach in molecular oncology, and it has never been applied in chordomas. Our aim is to investigate chordoma behavior and the role of ceramides. Methods: Ceramides were extracted and evaluated by liquid chromatography and mass spectrometry in a cohort of patients with a skull base chordoma. Clinical data were also collected and correlated with ceramide levels. Linear regression and correlation analyses were conducted. Results: Analyzing the association between ceramides level and MIB-1, total ceramides and dihydroceramides showed a strong association (r = 0.7257 and r = 0.6733, respectively) with MIB-1 staining (p = 0.0033 and p = 0.0083, respectively). Among the single ceramide species, Cer C24:1 (r = 0.8814, p ≤ 0.0001), DHCer C24:1 (r = 0.8429, p = 0.0002) and DHCer C18:0 (r = 0.9426, p ≤ 0.0001) showed a significant correlation with MIB-1. Conclusion: Our lipid analysis showed ceramides to be promising tumoral biomarkers in skull base chordomas. Long- and very-long-chain ceramides, such as Cer C24:1 and DHCer C24:1, may be related to a prolonged tumor survival and aggressiveness, and the understanding of their effective biological role will hopefully shed light on the mechanisms of chordoma radio-resistance, tendency to recur, and use of agents targeting ceramide metabolism.
Long-Term Vemurafenib Exposure Induced Alterations of Cell Phenotypes in Melanoma: Increased Cell Migration and Its Association with EGFR Expression
Authors: Molnár Eszter , Garay Tamás , Donia Marco , Baranyi Marcell , Rittler Dominika , Berger Walter , Tímár József , Grusch Michael , Hegedűs Balázs
Published: September 2019

Acquired resistance during BRAF inhibitor therapy remains a major challenge for melanoma treatment. Accordingly, we evaluated the phenotypical and molecular changes of isogeneic human V600E BRAF-mutant melanoma cell line pairs pre- and post-treatment with vemurafenib. Three treatment naïve lines were subjected to in vitro long-term vemurafenib treatment while three pairs were pre- and post-treatment patient-derived lines. Molecular and phenotypical changes were assessed by Sulforhodamine-B (SRB) assay, quantitative RT-PCR (q-RT-PCR), immunoblot, and time-lapse microscopy. We found that five out of six post-treatment cells had higher migration activity than pretreatment cells. However, no unequivocal correlation between increased migration and classic epithelial–mesenchymal transition (EMT) markers could be identified. In fast migrating cells, the microphthalmia-associated transcription factor (MITF) and epidermal growth factor receptor (EGFR) mRNA levels were considerably lower and significantly higher, respectively. Interestingly, high EGFR expression was associated with elevated migration but not with proliferation. Cells with high EGFR expression showed significantly decreased sensitivity to vemurafenib treatment, and had higher Erk activation and FRA-1 expression. Importantly, melanoma cells with higher EGFR expression were more resistant to the EGFR inhibitor erlotinib treatment than cells with lower expression, with respect to both proliferation and migration inhibition. Finally, EGFR-high melanoma cells were characterized by higher PD-L1 expression, which might in turn indicate that immunotherapy may be an effective approach in these cases.
Combined Effects of Gold Nanoparticles and Ionizing Radiation on Human Prostate and Lung Cancer Cell Migration
Authors: Shahhoseini Elham , Feltis Bryce N. , Nakayama Masao , Piva Terrence J. , Pouniotis Dodie , Alghamdi Salem S. , Geso Moshi
Published: September 2019

The effect of 15 nm-sized gold nanoparticles (AuNPs) and/or ionizing radiation (IR) on the migration and adhesion of human prostate (DU145) and lung (A549) cancer cell lines was investigated. Cell migration was measured by observing the closing of a gap created by a pipette tip on cell monolayers grown in 6-well plates. The ratio of the gap areas at 0 h and 24 h were used to calculate the relative migration. The relative migration of cells irradiated with 5 Gy was found to be 89% and 86% for DU145 and A549 cells respectively. When the cells were treated with 1 mM AuNPs this fell to ~75% for both cell lines. However, when the cells were treated with both AuNPs and IR an additive effect was seen, as the relative migration rate fell to ~60%. Of interest was that when the cells were exposed to either 2 or 5 Gy IR, their ability to adhere to the surface of a polystyrene culture plate was significantly enhanced, unlike that seen for AuNPs. The delays in gap filling (cell migration) in cells treated with IR and/or AuNPs can be attributed to cellular changes which also may have altered cell motility. In addition, changes in the cytoskeleton of the cancer cells may have also affected adhesiveness and thus the cancer cell’s motility response to IR.
Potential of the NKG2D/NKG2DL Axis in NK Cell-Mediated Clearance of the HIV-1 Reservoir
Authors: Desimio Maria G. , Covino Daniela A. , Doria Margherita
Published: September 2019

Viral persistency in latently infected CD4+ T cells despite antiretroviral therapy (ART) represents a major drawback in the fight against HIV-1. Efforts to purge latent HIV-1 have been attempted using latency reversing agents (LRAs) that activate expression of the quiescent virus. However, initial trials have shown that immune responses of ART-treated patients are ineffective at clearing LRA-reactivated HIV-1 reservoirs, suggesting that an adjuvant immunotherapy is needed. Here we overview multiple lines of evidence indicating that natural killer (NK) cells have the potential to induce anti-HIV-1 responses relevant for virus eradication. In particular, we focus on the role of the NKG2D activating receptor that crucially enables NK cell-mediated killing of HIV-1-infected cells. We describe recent data indicating that LRAs can synergize with HIV-1 at upregulating ligands for NKG2D (NKG2DLs), hence sensitizing T cells that exit from viral latency for recognition and lysis by NK cells; in addition, we report in vivo and ex vivo data showing the potential benefits and drawbacks that LRAs may have on NKG2D expression and, more in general, on the cytotoxicity of NK cells. Finally, we discuss how the NKG2D/NKG2DLs axis can be exploited for the development of effective HIV-1 eradication strategies combining LRA-induced virus reactivation with recently optimized NK cell-based immunotherapies.
Investigation into Early Steps of Actin Recognition by the Intrinsically Disordered N-WASP Domain V
Authors: Chan-Yao-Chong Maud , Durand Dominique , Ha-Duong Tâp
Published: September 2019

Cellular regulation or signaling processes are mediated by many proteins which often have one or several intrinsically disordered regions (IDRs). These IDRs generally serve as binders to different proteins with high specificity. In many cases, IDRs undergo a disorder-to-order transition upon binding, following a mechanism between two possible pathways, the induced fit or the conformational selection. Since these mechanisms contribute differently to the kinetics of IDR associations, it is important to investigate them in order to gain insight into the physical factors that determine the biomolecular recognition process. The verprolin homology domain (V) of the Neural Wiskott–Aldrich Syndrome Protein (N-WASP), involved in the regulation of actin polymerization, is a typical example of IDR. It is composed of two WH2 motifs, each being able to bind one actin molecule. In this study, we investigated the early steps of the recognition process of actin by the WH2 motifs of N-WASP domain V. Using docking calculations and molecular dynamics simulations, our study shows that actin is first recognized by the N-WASP domain V regions which have the highest propensity to form transient α -helices. The WH2 motif consensus sequences “LKKV” subsequently bind to actin through large conformational changes of the disordered domain V.
MicroRNA Networks Modulate Oxidative Stress in Cancer
Authors: Lin Yang-Hsiang
Published: September 2019

Imbalanced regulation of reactive oxygen species (ROS) and antioxidant factors in cells is known as “oxidative stress (OS)”. OS regulates key cellular physiological responses through signal transduction, transcription factors and noncoding RNAs (ncRNAs). Increasing evidence indicates that continued OS can cause chronic inflammation, which in turn contributes to cardiovascular and neurological diseases and cancer development. MicroRNAs (miRNAs) are small ncRNAs that produce functional 18-25-nucleotide RNA molecules that play critical roles in the regulation of target gene expression by binding to complementary regions of the mRNA and regulating mRNA degradation or inhibiting translation. Furthermore, miRNAs function as either tumor suppressors or oncogenes in cancer. Dysregulated miRNAs reportedly modulate cancer hallmarks such as metastasis, angiogenesis, apoptosis and tumor growth. Notably, miRNAs are involved in ROS production or ROS-mediated function. Accordingly, investigating the interaction between ROS and miRNAs has become an important endeavor that is expected to aid in the development of effective treatment/prevention strategies for cancer. This review provides a summary of the essential properties and functional roles of known miRNAs associated with OS in cancers.
Modelling and Resolution of Dynamic Reliability Problems by the Coupling of Simulink and the Stochastic Hybrid Fault Tree Object Oriented (SHyFTOO) Library
Authors: Chiacchio Ferdinando , Aizpurua Jose Ignacio , Compagno Lucio , Khodayee Soheyl Moheb , D’Urso Diego
Published: September 2019

Dependability assessment is one of the most important activities for the analysis of complex systems. Classical analysis techniques of safety, risk, and dependability, like Fault Tree Analysis or Reliability Block Diagrams, are easy to implement, but they estimate inaccurate dependability results due to their simplified hypotheses that assume the components’ malfunctions to be independent from each other and from the system working conditions. Recent contributions within the umbrella of Dynamic Probabilistic Risk Assessment have shown the potential to improve the accuracy of classical dependability analysis methods. Among them, Stochastic Hybrid Fault Tree Automaton (SHyFTA) is a promising methodology because it can combine a Dynamic Fault Tree model with the physics-based deterministic model of a system process, and it can generate dependability metrics along with performance indicators of the physical variables. This paper presents the Stochastic Hybrid Fault Tree Object Oriented (SHyFTOO), a Matlab® software library for the modelling and the resolution of a SHyFTA model. One of the novel features discussed in this contribution is the ease of coupling with a Matlab® Simulink model that facilitates the design of complex system dynamics. To demonstrate the utilization of this software library and the augmented capability of generating further dependability indicators, three different case studies are discussed and solved with a thorough description for the implementation of the corresponding SHyFTA models.
Genomic and Mitochondrial Data Identify Different Species Boundaries in Aposematically Polymorphic Eniclases Net-Winged Beetles (Coleoptera: Lycidae)
Authors: Bocek Matej , Motyka Michal , Kusy Dominik , Bocak Ladislav
Published: September 2019

Species delineation is essential for any evolutionary and biodiversity research, and recent advances in genomic sequencing have made it possible to robustly define species boundaries and detect hidden diversity. Here, we studied 14 species of aposematically colored New Guinean Eniclases (Coleoptera: Lycidae) whose conventional morphology- and single-locus mtDNA-based taxonomy has been contentious. We analyzed mitochondrial and restriction site associated DNA fragments to obtain a phylogenetic hypothesis and compared relationships recovered by the RAD analysis with species limits based on other information. The results show the presence of cryptic diversity and common mitonuclear discordance when over 30% of individuals were incorrectly assigned to species if only mitogenomic markers were considered. Nuclear data falsified the species rank of one species and identified one earlier unrecognized lineage deserving species rank. Further, our analyses demonstrate a highly variable phenotypic differentiation, with several pairs of cryptic species standing in contrast with genetically close but phenotypically highly divergent lineages. We show that morphological and mitogenomic analyses produce reliable information for taxonomy in most cases. Nevertheless, the species boundaries among closely related species should be based on all lines of evidence, including nuclear markers.
BriXs Ultra High Flux Inverse Compton Source Based on Modified Push-Pull Energy Recovery Linacs
Authors: Drebot Illya , Bacci Alberto , Bosotti Angelo , Broggi Francesco , Canella Francesco , Cardarelli Paolo , Cialdi Simone , Faillace Luigi , Galzerano Gianluca , Gambaccini Mauro , Giannotti Dario , Giove Dario , Mettivier Giovanni , Michelato Paolo , Monaco Laura , Paparella Rocco , Paternó Gianfranco , Petrillo Vittoria , Prelz Francesco , Rossetti Conti Marcello , Rossi Andrea Renato , Russo Paolo , Sarno Antonio , Suerra Edoardo , Taibi Angelo , Serafini Luca
Published: September 2019

We present a conceptual design for a compact X-ray Source BriXS (Bright and compact X-ray Source). BriXS, the first stage of the Marix project, is an Inverse Compton Source (ICS) of X-ray based on superconducting cavities technology for the electron beam with energy recirculation and on a laser system in Fabry-Pérot cavity at a repetition rate of 100 MHz, producing 20–180 keV monochromatic X-Rays devoted mainly to medical applications. An energy recovery scheme based on a modified folded push-pull CW-SC twin Energy Recovery Linac (ERL) ensemble allows us to sustain an MW-class beam power with almost one hundred kW active power dissipation/consumption.