bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts of Increasing Private Charging Piles on Electric Vehicles’ Charging Profiles: A Case Study in Hefei City, China
Authors: Chen Jian , Li Fangyi , Yang Ranran , Ma Dawei
Published: August 2020

Electric vehicles (EVs) and charging piles have been growing rapidly in China in the last five years. Private charging piles are widely adopted in major cities and have partly changed the charging behaviors of EV users. Based on the charging data of EVs in Hefei, China, this study aims to assess the impacts of increasing private charging piles and smart charging application on EVs’ charging load profiles. The charging load profiles of three types of charging piles which are public, employee-shared, and private ones, are simulated in three different scenarios. The results of scenario simulation indicate that the increase in EVs will reinforce the peak value of the total power load, while increasing private charging piles and the participation rate of smart charging piles will have peak-load shifting effects on the power load on weekdays. Specifically, 12% of the charging load will be shifted from public piles to private ones if the ratio of EVs and private piles increases from 5:3 to 5:4. The adoption of smart charging in private piles will transfer 18% of the charging load from the daytime to the night to achieve peak-load shifting. In summary, promoting the adoption of private piles and smart charging technology will reshape the charging load profile of the city, but the change will possibly reduce the utilization rate of public charging piles. The results suggest that urban governments should consider the growth potential of private piles and promote smart charging in charging infrastructure planning.
Formation Kinetics of the Mixed Cyclopentane—Carbon Dioxide Hydrates in Aqueous Sodium Chloride Solutions
Authors: Zhou Xuebing , Zhang Ye , Zang Xiaoya , Liang Deqing
Published: August 2020

Hydrate formation from cyclopentane (CP) and carbon dioxide was measured at 281 K by powder X-ray diffraction (PXRD) and macroscopic methods. The effect of initial pressure and CP mass fraction in liquid phase was analyzed. The results showed that hydrate formation was assumed to start with the nucleation of the mixed CP-CO2 hydrate with small fraction of CO2 followed by a large continuous CO2 adsorption. Initial pressure was found to have a positive correlation with the total CO2 consumptions when the initial pressure was below 2.5 MPa. However, the total CO2 consumptions dropped by over a half as the initial pressure was 3.0 MPa. PXRD revealed that all the hydrate samples formed at different initial pressures were structure II. The CO2 consumptions were assumed to be inhibited by the competitive occupation of 51264 cages between CP and CO2 molecules when the initial pressure was above 2.5 MPa. The CO2 consumptions were also found to be reduced as the CP mass fraction was above 0.25. An excess of CP molecules was not assumed to strengthen the formation of the mixed CP-CO2 hydrates at the initial stage, but increased the thickness of liquid CP film at aqueous brine and hydrate particles, which increased the diffusion resistance of CO2 molecules. Therefore, the suitable initial pressure and the CP mass fraction for the mixed CP-CO2 hydrate formation should be around 2.5 MPa and 0.2, respectively.
Practical Performance Analysis of a Bifacial PV Module and System
Authors: Jang Juhee , Lee Kyungsoo
Published: August 2020

Bifacial photovoltaic (PV) modules can take advantage of rear-surface irradiance, enabling them to produce more energy compared with monofacial PV modules. However, the performance of bifacial PV modules depends on the irradiance at the rear side, which is strongly affected by the installation setup and environmental conditions. In this study, we experiment with a bifacial PV module and a bifacial PV system by varying the size of the reflective material, vertical installation, temperature mismatch, and concentration of particulate matter (PM), using three testbeds. From our analyses, we found that the specific yield increased by 1.6% when the reflective material size doubled. When the PV module was installed vertically, the reduction of power due to the shadow effect occurred, and thus the maximum current was 14.3% lower than the short-circuit current. We also observed a maximum average surface temperature mismatch of 2.19 °C depending on the position of the modules when they were composed in a row. Finally, in clear sky conditions, when the concentration of PM 10 changed by 100 µg/m3, the bifacial gain increased by 4%. In overcast conditions, when the concentration of PM 10 changed by 100 µg/m3, the bifacial gain decreased by 0.9%.
An Integration Optimization Strategy of Line Voltage Cascaded Quasi-Z-Source Inverter Parameters Based on GRA-FA
Authors: Li Zhiyong , Pu Shiping , Chen Yougen , Wei Renyong
Published: August 2020

Setting reasonable circuit parameters is an important way to improve the quality of inverters, including waveform quality and power loss. In this paper, a circuit system of line voltage cascaded quasi-Z-source inverter (LVC-qZSI) is built. On this basis, the double frequency voltage ripple ratio and power loss ratio are selected as optimization targets to establish a multi-objective optimization model of LVC-qZSI parameters. To simplify the calculation, an integration optimization strategy of LVC-qZSI parameters based on GRA-FA is proposed. Where, the grey relation analysis (GRA) is used to simplify the multi-objective optimization model. In GRA, the main influence factors are selected as optimization variables by considering the preference coefficient. Then, firefly algorithm (FA) is used to obtain the optimal solution of the multi-objective optimization model. In FA, the weights of objective functions are assigned based on the principle of information entropy. The analysis results are verified by simulation. Research results indicate that the optimization strategy can effectively reduce the double frequency voltage ripple ratio and power loss ratio. Therefore, the strategy proposed in this paper has a superior ability to optimize the parameters of LVC-qZSI, which is of great significance to the initial values setting.
Study on the Collapse Process of Cavitation Bubbles Near the Concave Wall by Lattice Boltzmann Method Pseudo-Potential Model
Authors: Liu Yang , Peng Yong
Published: August 2020

In this paper, the lattice Boltzmann pseudo-potential model coupled the Carnahan–Starling (C-S) equation of state and Li’s force scheme are used to study the collapse process of cavitation bubbles near the concave wall. It mainly includes the collapse process of the single and double cavitation bubbles in the near-wall region. Studies have shown that the collapse velocity of a single cavitation bubble becomes slower as the additional pressure reduces, and the velocity of the micro-jet also decreases accordingly. Moreover, the second collapse of the cavitation bubble cannot be found if the additional pressure reduces further. When the cavitation bubble is located in different angles with vertical direction, its collapse direction is always perpendicular to the wall. If the double cavitation bubbles are arranged vertically, the collapse process of the upper bubble will be quicker, as the relative distance increases. When the relative distance between the bubbles is large enough, no second collapse can be found for the upper bubble. On the other hand, when two cavitation bubbles are in the horizontal arrangement, the suppression effect between cavitation bubbles decreases as the relative distance between the bubbles increases and the collapse position of cavitation bubbles moves from the lower part to the upper part.
Hybrid Microencapsulated Phase-Change Material and Carbon Nanotube Suspensions toward Solar Energy Conversion and Storage
Authors: Li Jun , Jia Lisi , Li Longjian , Huang Zehang , Chen Ying
Published: August 2020

In this study, a new type of functional hybrid suspension for solar energy conversion and thermal energy storage was prepared by adding carbon nanotube (CNT) and microencapsulated phase-change material (MEPCM) into deionized water. MEPCM with octadecane as the core material and titania (TiO2) as the shell material was synthesized by the sol–gel method. The MEPCMs were spherical particles with diameters of 2–4 μm, and the thickness of the shell was about 100 nm. The MEPCM achieved better thermal stability and thermal conductivity than the pure octadecane due to the TiO2 shell. The melting and solidification latent heats of the MEPCM were about 154.24 and 154.26 J/g, respectively. The encapsulation efficiency of octadecane was calculated to be 65.84%. Most of all, the novel hybrid CNT and MEPCM suspensions exhibited remarkable dispersion stability owing to the stable reticular structure composed of CNT in the suspension. Compared with pure water, the thermal conductivity, specific heat of the MEPCM/CNT suspension improved by 34.48 and 43.57%, respectively and the photo-thermal conversion efficiency reached a high value of 86.0%. This work provided a new type of hybrid functional suspension towards direct absorption solar collector for solar energy conversion and storage.
Automatically Creating HVAC Control Strategies Based on Building Information Modeling (BIM): Heat Provisioning and Distribution
Authors: Sporr Andreas , Zucker Gerhard , Hofmann René
Published: August 2020

Building Information Modeling (BIM) data are typically exchanged using the Industrial Foundation Classes (IFC) standard. An IFC-based BIM model is a container for data that is created during the design and planning phase and is therefore a rich source of information for the commissioning phase, in which building services are brought to operation. This paper examines the use of BIM data for automated generation of control strategies for energy systems, thus simplifying and accelerating the commissioning phase. We present a methodology to create control strategies of a building heating system with several variations of renewable energy systems and include both heat provisioning and a distribution system. The control goals include favoring the use of non-fossil energy, which is provided by a combination of photovoltaic system (PV), heat pump (HP) and industrial excess-heat source. Thermal energy storages are integrated for load shifting purposes and the control of the heat distribution system is designed towards the requirements of building physics, occupancy and outside climate conditions. A validation of the approach is presented in a combined SIMULINK and TRNSYS simulation environment.
Short-Term Electricity Price Forecasting Based on Similar Day-Based Neural Network
Authors: Lee Chun-Yao , Wu Chang-En
Published: August 2020

This paper presents four refined distance models to the application of forecasting short-term electricity price namely Euclidean norm, Manhattan distance, cosine coefficient, and Pearson correlation coefficient. The four refined models were constructed and used to select the days, which are like a reference day in electricity prices and loads, called similar days in this study. Using the similar days, the electricity prices of a forecast day were further obtained by similar day regression (SDR) and similar day based artificial neural network (SDANN). The simulation results of the case of the PJM (Pennsylvania, New Jersey and Maryland) interchange energy market indicate the superiority and availability of the selection 45 framework days and three similar days based on Pearson correlation coefficient model.
The Simultaneous Impact of EV Charging and PV Inverter Reactive Power on the Hosting Distribution System’s Performance: A Case Study in Kuwait
Authors: Abdullah Heba M. , Kamel Rashad M. , Tahir Anas , Sleit Azzam , Gastli Adel
Published: August 2020

Recently, electric vehicles (EVs) have become an increasingly important topic in the field of sustainable transportation research, alongside distributed generation, reactive power compensation, charging optimization, and control. The process of loading on existing power system infrastructures with increasing demand requires appropriate impact indices to be analyzed. This paper studies the impact of integrating electric vehicle charging stations (EVCSs) into a residential distribution network. An actual case study is modeled to acquire nodal voltages and feeder currents. The model obtains the optimal integration of solar photovoltaic (PV) panels with charging stations while considering reactive power compensation. The impact of EV integration for the case study results in two peaks, which show a 6.4% and 17% increase. Varying the inverter to the PV ratio from 1.1 to 2 decreases system losses by 34% to 41%. The type of charging is dependent on the maximum penetration of EVCSs that the network can install without system upgrades. Increasing the number of EVCSs can cause an increase in power system losses, which is dependent on the network architecture. Installing PV reduces the load peak by 21%, and the installation of PV with consideration of reactive power control increases system efficiency and power delivery.
Assessing the Impacts of Land-Use Zoning Decisions on the Supply of Forest Ecosystem Services
Authors: Kärkkäinen Leena , Haakana Helena , Hirvelä Hannu , Lempinen Reetta , Packalen Tuula
Published: August 2020

Research Highlights: The informed decisions on land use require assessment of the impacts of these decisions on the supply of different ecosystem services. Background and Objectives: Scenario modeling can be used to provide harmonized and quantitative information on the impacts of various zoning decisions on the provision of various ecosystem services. In this study, we explored the effects of land-use zoning decisions on the provision of roundwood and energy wood, carbon stock of living tree components, berry yields, scenic beauty and recreation. Materials and Methods: Three alternative forest scenarios were formulated in terms of restrictions on forest management for already established land-use zones by the provinces in Finland. These data were integrated with the National Forest Inventory (NFI) plot data for forest dynamics modeling. Results: In Finland, 9% of the forest land was protected and 9% was under restricted forest management due to legislative decisions, forest owners’ decisions, or regional land use plans in 2016. These established zoning decisions resulted in an estimated 17% smaller roundwood and energy wood removals per year in 2016–2025 compared to the estimated wood removals in the scenario without any restrictions. The decrease in annual gross stumpage earnings was EUR 775 million per year. The carbon stock of living tree components in 2025 was 12% larger than in the scenario without any restrictions. Bilberry yield increased due to the restrictions considered in our study, while the restrictions had only a slight effect on cowberry yield at province and country levels. The restrictions increased the recreation value, particularly in Lapland, but only slightly affected scenic beauty at province and country levels. Conclusions: Scenario analyses support informed decision making and the balancing of different forest uses. Harmonized translation of restrictions and the use of standard indicators to model the impacts also support comparisons between the regions.
Transcriptome Analysis Reveals Inhibitory Effects of Lentogenic Newcastle Disease Virus on Cell Survival and Immune Function in Spleen of Commercial Layer Chicks
Authors: Zhang Jibin , Kaiser Michael G. , Gallardo Rodrigo A. , Kelly Terra R. , Dekkers Jack C. M. , Zhou Huaijun , Lamont Susan J.
Published: August 2020

As a major infectious disease in chickens, Newcastle disease virus (NDV) causes considerable economic losses in the poultry industry, especially in developing countries where there is limited access to effective vaccination. Therefore, enhancing resistance to the virus in commercial chickens through breeding is a promising way to promote poultry production. In this study, we investigated gene expression changes at 2 and 6 days post inoculation (dpi) at day 21 with a lentogenic NDV in a commercial egg-laying chicken hybrid using RNA sequencing analysis. By comparing NDV-challenged and non-challenged groups, 526 differentially expressed genes (DEGs) (false discovery rate (FDR) < 0.05) were identified at 2 dpi, and only 36 at 6 dpi. For the DEGs at 2 dpi, Ingenuity Pathway Analysis predicted inhibition of multiple signaling pathways in response to NDV that regulate immune cell development and activity, neurogenesis, and angiogenesis. Up-regulation of interferon induced protein with tetratricopeptide repeats 5 (IFIT5) in response to NDV was consistent between the current and most previous studies. Sprouty RTK signaling antagonist 1 (SPRY1), a DEG in the current study, is in a significant quantitative trait locus associated with virus load at 6 dpi in the same population. These identified pathways and DEGs provide potential targets to further study breeding strategy to enhance NDV resistance in chickens.
Mobilization of IMEs Integrated in the oriT of ICEs Involves Their Own Relaxase Belonging to the Rep-Trans Family of Proteins
Authors: Libante Virginie , Sarica Nazim , Mohamad Ali Abbas , Gapp Chloé , Oussalah Anissa , Guédon Gérard , Leblond-Bourget Nathalie , Payot Sophie
Published: August 2020

Integrative mobilizable elements (IMEs) are widespread but very poorly studied integrated elements that can excise and hijack the transfer apparatus of co-resident conjugative elements to promote their own spreading. Sixty-four putative IMEs, harboring closely related mobilization and recombination modules, were found in 14 Streptococcus species and in Staphylococcus aureus. Fifty-three are integrated into the origin of transfer (oriT) of a host integrative conjugative element (ICE), encoding a MobT relaxase and belonging to three distant families: ICESt3, Tn916, and ICE6013. The others are integrated into an unrelated IME or in chromosomal sites. After labeling by an antibiotic resistance gene, the conjugative transfer of one of these IMEs (named IME_oriTs) and its host ICE was measured. Although the IME is integrated in an ICE, it does not transfer as a part of the host ICE (no cis-mobilization). The IME excises and transfers separately from the ICE (without impacting its transfer rate) using its own relaxase, distantly related to all known MobT relaxases, and integrates in the oriT of the ICE after transfer. Overall, IME_oriTs use MobT-encoding ICEs both as hosts and as helpers for conjugative transfer. As half of them carry lsa(C), they actively participate in the dissemination of lincosamide–streptogramin A–pleuromutilin resistance among Firmicutes.
Periodontal Disease and Grip Strength among Older Adults
Authors: Aravindakshan Vinish , Hakeem Faisal F. , Sabbah Wael
Published: August 2020

Objective: The aim of this research was to assess the association between periodontitis and grip strength among older American adults. Methods: Data from the National Health and Nutrition Examination Survey 2011/2012 and 2013/2014 were used. Oral health status and hand grip strength were clinically assessed. Three outcome variables were used: (1) handgrip strength <30 kg for men, <20 kg for women; (2) handgrip strength <26 kg for men, <16 kg for women; and (3) mean maximum grip strength. The main exposure was the case definition of periodontitis. Logistic and linear regression models were constructed for grip strength definitions and the mean grip strength, respectively, adjusting for covariates. Results: The study included 1953 participants. The mean age was 68.5 years, and 47.2% were males. The prevalence of low grip strength (<30 kg for men, <20 kg for women) was 7.4% in men and 13.6% in women. Periodontitis was significantly associated with grip strength (OR 1.53, 95% CI: 1.03, 2.27) in the unadjusted model. Periodontitis was also significantly associated with maximum grip strength (Coefficient 1.05, 95% CI −1.99, −0.09) in a model adjusted for age and gender. However, in all the fully adjusted models there was no statistically significant association between periodontitis and grip strength. Conclusion: Low grip strength appeared to be more common among persons with moderate/severe periodontitis. The observed association is probably attributed to older age and common risk factors for periodontitis and frailty.
Traffic Noise and Mental Health: A Systematic Review and Meta-Analysis
Authors: Hegewald Janice , Schubert Melanie , Freiberg Alice , Romero Starke Karla , Augustin Franziska , Riedel-Heller Steffi G. , Zeeb Hajo , Seidler Andreas
Published: August 2020

Recent evidence suggests that traffic noise may negatively impact mental health. However, existing systematic reviews provide an incomplete overview of the effects of all traffic noise sources on mental health. We conducted a systematic literature search and summarized the evidence for road, railway, or aircraft noise-related risks of depression, anxiety, cognitive decline, and dementia among adults. We included 31 studies (26 on depression and/or anxiety disorders, 5 on dementia). The meta-analysis of five aircraft noise studies found that depression risk increased significantly by 12% per 10 dB LDEN (Effect Size = 1.12, 95% CI 1.02–1.23). The meta-analyses of road (11 studies) and railway traffic noise (3 studies) indicated 2–3% (not statistically significant) increases in depression risk per 10 dB LDEN. Results for road traffic noise related anxiety were similar. We did not find enough studies to meta-analyze anxiety and railway or aircraft noise, and dementia/ cognitive impairment and any traffic noise. In conclusion, aircraft noise exposure increases the risk for depression. Otherwise, we did not detect statistically significant risk increases due to road and railway traffic noise or for anxiety. More research on the association of cognitive disorders and traffic noise is required. Public policies to reduce environmental traffic noise might not only increase wellness (by reducing noise-induced annoyance), but might contribute to the prevention of depression and anxiety disorders.
Parental Optimism and Perceived Control over Children’s Initiation of Tobacco, Cannabis, and Opioid Use
Authors: Chadi Nicholas , Winickoff Jonathan P. , Drouin Olivier
Published: August 2020

Families play an important role in helping teenagers avoid using tobacco, cannabis, and opioids, but some parents may underestimate the risk of their children using those substances. This study aimed to determine parents’ perceived likelihood of their child initiating tobacco, cannabis, and opioid use, as well as the control they have in preventing their child from using those substances. We surveyed 427 parents of children aged 0–18 years old using the online Amazon Mechanical Turk platform in the spring of 2019. We measured participants’ perceived likelihood of their child initiating tobacco, cannabis, or opioid use before the age of 18 compared to other children, using a five-point Likert scale. This perceived likelihood was dichotomized between optimistic (less likely than average) and non-optimistic (average or more likely than average). Independent variables included parental tobacco use, perceived parental control, and perceived severity of the behavior. Participants with missing data and participants with children who had already initiated substance use were excluded from statistical analyses. Mean age of participants was 38.1 years (Standard Deviation 8.4); 67% were female. Level of parental optimism was 59% for cannabis, 77% for tobacco, and 82% for opioids. Perceived severity was significantly lower for cannabis use (71/100) than tobacco (90/100) and opioid use (92/100) (p < 0.001). Current smokers were less likely than never smokers to be optimistic about their child’s risk of initiating using tobacco (Adjusted Odds Ratio (AOR): 0.18 [95% Confidence Interval (CI) 0.10–0.34]) or cannabis (AOR: 0.21 [95% CI 0.12–0.38]). Parental perceived likelihood of a child initiating substance use represents an understudied and potential target for substance use prevention.
Effects of Point-Of-Care Testing in General Practice for Type 2 Diabetes Patients on Ambulatory Visits and Hospitalizations
Authors: Kristensen Troels , Rose-Olsen Kim , Volmar Skovsgaard Christian
Published: August 2020

Point-of-care testing (POCT) of HbA1c means instant test results and more coherent counseling that is expected to improve diabetes management and affect ambulatory visits and hospitalizations. From late 2008, POCT has been implemented and adopted by a segment of the general practices in the capital region of Denmark. The aim of this study is to assess whether the introduction of POCT of HbA1c in general practice (GP) has affected patient outcomes for T2 diabetes patients in terms of hospital activity. We apply difference-in-differences models at the GP clinic level to assess the casual effects of POCT on the following hospital outcomes: (1) admissions for diabetes, (2) admissions for ambulatory care sensitive diabetes conditions (ACSCs), (3) ambulatory visits for diabetes. The use of POCT is remunerated by a fee, and registration of this fee is used to measure the GP’s use of POCT. The control group includes clinics from the same region that did not use POCT. The sensitivity of our results is assessed by an event study approach and a range of robustness tests. The panel data set includes 553 GP clinics and approximately 30,000 diabetes patients from the capital region of Denmark, observed in the years 2004–2012. We find that voluntary adoption of POCT of HbA1c in GP has no effect on hospital admissions and diabetes-related hospital ambulatory visits. Event study analysis and different treatment definitions confirm the robustness of these results. If implementation of POCT of HbA1c improves other parts of diabetes management as indicated in the literature, it seems worthwhile to implement POCT of HbA1c in the capital region of Denmark. However, doubts around the quality of POCT of HbA1c testing and a desire to capture data at central labs may prevent implementation of more value based HbA1c testing.
Design and Validation of the Scale to Measure Aquatic Competence in Children (SMACC)
Authors: Moreno-Murcia Juan Antonio , de Paula Borges Luciane , Huéscar Hernández Elisa
Published: August 2020

(1) Background: The aim of this study was to design and analyze the validity of the SMACC (Scale to Measure Aquatic Competence in Children) to evaluate aquatic competence in three- to six-year-old children. In addition, the relation between real competence obtained with the SMACC and perceived aquatic competence was verified as well as its differences according to sex and age. (2) Methods: Content validation was performed through the consensus of nine experts using the Delphi technique, and comprehension validity was determined through a pilot study on a sample of 122 children. An exploratory and confirmatory factor analysis was performed with two independent samples of 384 and 444 school children between three and six years old, respectively. (3) Results: After the pertinent adjustments, the final questionnaire comprised 17 items, which showed a good fit for both comprehension and content validity. The results of the exploratory and confirmatory analyses support the use of three dimensions in aquatic competence: motor, socio-affective, and cognitive. The correlations support construct validity showing a positive relation with perceived aquatic competence. (4) Conclusions: These promising validity data are discussed from a global and integrative perspective in relation to the improvement of children’s development in the aquatic environment during the early stages of their lives.
Myocardial Injury and Overload among Amateur Marathoners as Indicated by Changes in Concentrations of Cardiovascular Biomarkers
Authors: Kaleta-Duss Anna Maria , Lewicka-Potocka Zuzanna , Dąbrowska-Kugacka Alicja , Raczak Grzegorz , Lewicka Ewa
Published: August 2020

Marathons continue to grow in popularity among amateurs. However, the impact of intensive exercise on the amateur’s cardiovascular system has not yet been studied. Analysis of the influence of the marathon on kinetics of biomarkers reflecting cardiac injury and overload may bring new insights into this issue. We investigated the effect of running a marathon on the concentrations of high sensitivity cardiac troponin I (hs-cTnI), heart-type fatty acid binding protein (H-FABP), N-terminal proatrial natriuretic peptide (NT-proANP), B-type natriuretic peptide (BNP), growth differentiation factor 15 (GDF-15) and galectin 3 (Gal-3) in the population of male amateur runners. The study included 35 amateur marathoners and followed 3 stages: S1—two weeks prior to the marathon, S2—at the finish line and S3—two weeks after. Blood samples were collected at each stage and analyzed for biomarkers and laboratory parameters. Concentrations of all studied biomarkers were significantly higher at S2, whereas at S3 did not differ significantly compared to S1. Running a marathon by an amateur causes an acute rise in biomarkers of cardiac injury and stress. Whether repetitive bouts of intensive exercise elicit long-term adverse cardiovascular effects in amateur marathoners needs further research.
Tuberculosis–Cancer Parallels in Immune Response Regulation
Authors: Bickett Thomas E. , Karam Sana D.
Published: August 2020

Mycobacterium tuberculosis and cancer are two diseases with proclivity for the development of resistance to the host immune system. Mechanisms behind resistance can be host derived or disease mediated, but they usually depend on the balance of pro-inflammatory to anti-inflammatory immune signals. Immunotherapies have been the focus of efforts to shift that balance and drive the response required for diseases eradication. The immune response to tuberculosis has widely been thought to be T cell dependent, with the majority of research focused on T cell responses. However, the past decade has seen greater recognition of the importance of the innate immune response, highlighting factors such as trained innate immunity and macrophage polarization to mycobacterial clearance. At the same time, there has been a renaissance of immunotherapy treatments for cancer since the first checkpoint inhibitor passed clinical trials, in addition to work highlighting the importance of innate immune responses to cancer. However, there is still much to learn about host-derived responses and the development of resistance to new cancer therapies. This review examines the similarities between the immune responses to cancer and tuberculosis with the hope that their commonalities will facilitate research collaboration and discovery.
Novel Insights into the Regulatory Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 in Oxidative Stress and Inflammation of Human Fetal Membranes
Authors: Menon Ramkumar , Peltier Morgan R
Published: August 2020

Fetal membrane dysfunction in response to oxidative stress (OS) is associated with adverse pregnancy outcomes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is one of the regulators of innate OS response. This study evaluated changes in Nrf2 expression and its downstream targets heme oxygenase (HO-1) and peroxisome proliferator-activated receptor gamma (PPARγ) in fetal membranes during OS and infection in vitro. Furthermore, we tested the roles of sulforaphane (SFN; an extract from cruciferous vegetables) and trigonelline (TRN; an aromatic compound in coffee) in regulating Nrf2 and its targets. Fetal membranes (n = 6) collected at term were placed in an organ explant system were treated with water-soluble cigarette smoke extract (CSE), an OS inducer (1:10), and lipopolysaccharide (LPS; 100 ng/mL). Nrf2 expression, expression, its enhancement by sulforaphane (SFN, 10 µM/mL) and down regulation by TRN (10uM/mL) was determined by western blots. Expression of Nrf2 response elements PPARγ (western) heme oxygenase (HO-1), and IL-6 were quantified by ELISA. CSE and LPS treatment of fetal membranes increased nrf2, but reduced HO-1 and PPARγ and increased IL-6. Co-treatment of SFN, but not with TRN, with CSE and LPS increased Nrf2 substantially, as well as increased HO-1 and PPARγ and reduced IL-6 expression. Risk factor-induced Nrf2 increase is insufficient to generate an antioxidant response in fetal membranes. Sulforaphane may enhance innate antioxidant and anti-inflammatory capacity by increasing NRF-2 expression.
Conventional Co-Housing Modulates Murine Gut Microbiota and Hematopoietic Gene Expression
Authors: Chen Jichun , Zhang Shuling , Feng Xingmin , Wu Zhijie , Dubois Wendy , Thovarai Vishal , Ahluwalia Sonia , Gao Shouguo , Chen Jinguo , Peat Tyler , Sen Shurjo K. , Trinchieri Giorgio , Young Neal S. , Mock Beverly A.
Published: August 2020

Specific-pathogen-free (SPF) mice have improved hematopoietic characteristics relative to germ-free mice, however, it is not clear whether improvements in hematopoietic traits will continue when the level of microorganism exposure is further increased. We co-housed SPF C57BL/6 mice in a conventional facility (CVT) and found a significant increase in gut microbiota diversity along with increased levels of myeloid cells and T cells, especially effector memory T cells. Through single cell RNA sequencing of sorted KL (c-Kit+Lin−) cells, we imputed a decline in long-term hematopoietic stem cells and an increase in granulocyte-monocyte progenitors in CVT mice with up-regulation of genes associated with cell survival. Bone marrow transplantation through competitive repopulation revealed a significant increase in KSL (c-Kit+Sca-1+Lin−) cell reconstitution in recipients of CVT donor cells which occurred when donors were co-housed for both one and twelve months. However, there was minimal to no gain in mature blood cell engraftment in recipients of CVT donor cells relative to those receiving SPF donor cells. We conclude that co-housing SPF mice with mice born in a conventional facility increased gut microbiota diversity, augmented myeloid cell production and T cell activation, stimulated KSL cell reconstitution, and altered hematopoietic gene expression.
Redox Signaling and Regional Heterogeneity of Endothelial Dysfunction in db/db Mice
Authors: Sallam Nada A. , Laher Ismail
Published: August 2020

The variable nature of vascular dysfunction in diabetes is not well understood. We explored the functional adaptation of different arteries in db/db mice in relation to increased severity and duration of diabetes. We compared endothelium-dependent and -independent vasodilation in the aortae, as well as the carotid and femoral arteries, of db/db mice at three ages in parallel with increased body weight, oxidative stress, and deterioration of glycemic control. Vascular responses to in vitro generation of reactive oxygen species (ROS) and expression of superoxide dismutase (SOD) isoforms were assessed. There was a progressive impairment of endothelium-dependent and -independent vasorelaxation in the aortae of db/db mice. The carotid artery was resistant to the effects of in vivo and in vitro induced oxidative stress, and it maintained unaltered vasodilatory responses, likely because the carotid artery relaxed in response to ROS. The femoral artery was more reliant on dilation mediated by endothelium-dependent hyperpolarizing factor(s), which was reduced in db/db mice at the earliest age examined and did not deteriorate with age. Substantial heterogeneity exists between the three arteries in signaling pathways and protein expression of SODs under physiological and diabetic conditions. A better understanding of vascular heterogeneity will help develop novel therapeutic approaches for targeted vascular treatments, including blood vessel replacement.
Zinc Deficiency Disturbs Mucin Expression, O-Glycosylation and Secretion by Intestinal Goblet Cells
Authors: Maares Maria , Keil Claudia , Straubing Sophia , Robbe-Masselot Catherine , Haase Hajo
Published: August 2020

Approximately 1 billion people worldwide suffer from zinc deficiency, with severe consequences for their well-being, such as critically impaired intestinal health. In addition to an extreme degeneration of the intestinal epithelium, the intestinal mucus is seriously disturbed in zinc-deficient (ZD) animals. The underlying cellular processes as well as the relevance of zinc for the mucin-producing goblet cells, however, remain unknown. To this end, this study examines the impact of zinc deficiency on the synthesis, production, and secretion of intestinal mucins as well as on the zinc homeostasis of goblet cells using the in vitro goblet cell model HT-29-MTX. Zinc deprivation reduced their cellular zinc content, changed expression of the intestinal zinc transporters ZIP-4, ZIP-5, and ZnT1 and increased their zinc absorption ability, outlining the regulatory mechanisms of zinc homeostasis in goblet cells. Synthesis and secretion of mucins were severely disturbed during zinc deficiency, affecting both MUC2 and MUC5AC mRNA expression with ongoing cell differentiation. A lack of zinc perturbed mucin synthesis predominantly on the post-translational level, as ZD cells produced shorter O-glycans and the main O-glycan pattern was shifted in favor of core-3-based mucins. The expression of glycosyltransferases that determine the formation of core 1-4 O-glycans was altered in zinc deficiency. In particular, B3GNT6 mRNA catalyzing core 3 formation was elevated and C2GNT1 and C2GNT3 elongating core 1 were downregulated in ZD cells. These novel insights into the molecular mechanisms impairing intestinal mucus stability during zinc deficiency demonstrate the essentiality of zinc for the formation and maintenance of this physical barrier.
Revisiting Platelets and Toll-Like Receptors (TLRs): At the Interface of Vascular Immunity and Thrombosis
Authors: Hally Kathryn , Fauteux-Daniel Sebastien , Hamzeh-Cognasse Hind , Larsen Peter , Cognasse Fabrice
Published: August 2020

While platelet function has traditionally been described in the context of maintaining vascular integrity, recent evidence suggests that platelets can modulate inflammation in a much more sophisticated and nuanced manner than previously thought. Some aspects of this expanded repertoire of platelet function are mediated via expression of Toll-like receptors (TLRs). TLRs are a family of pattern recognition receptors that recognize pathogen-associated and damage-associated molecular patterns. Activation of these receptors is crucial for orchestrating and sustaining the inflammatory response to both types of danger signals. The TLR family consists of 10 known receptors, and there is at least some evidence that each of these are expressed on or within human platelets. This review presents the literature on TLR-mediated platelet activation for each of these receptors, and the existing understanding of platelet-TLR immune modulation. This review also highlights unresolved methodological issues that potentially contribute to some of the discrepancies within the literature, and we also suggest several recommendations to overcome these issues. Current understanding of TLR-mediated platelet responses in influenza, sepsis, transfusion-related injury and cardiovascular disease are discussed, and key outstanding research questions are highlighted. In summary, we provide a resource—a “researcher’s toolkit”—for undertaking further research in the field of platelet-TLR biology.
Hydride Abstraction as the Rate-Limiting Step of the Irreversible Inhibition of Monoamine Oxidase B by Rasagiline and Selegiline: A Computational Empirical Valence Bond Study
Authors: Tandarić Tana , Prah Alja , Stare Jernej , Mavri Janez , Vianello Robert
Published: August 2020

Monoamine oxidases (MAOs) catalyze the degradation of a very broad range of biogenic and dietary amines including many neurotransmitters in the brain, whose imbalance is extensively linked with the biochemical pathology of various neurological disorders, and are, accordingly, used as primary pharmacological targets to treat these debilitating cognitive diseases. Still, despite this practical significance, the precise molecular mechanism underlying the irreversible MAO inhibition with clinically used propargylamine inhibitors rasagiline and selegiline is still not unambiguously determined, which hinders the rational design of improved inhibitors devoid of side effects current drugs are experiencing. To address this challenge, we present empirical valence bond QM/MM simulations of the rate-limiting step of the MAO inhibition involving the hydride anion transfer from the inhibitor α-carbon onto the N5 atom of the flavin adenin dinucleotide (FAD) cofactor. The proposed mechanism is strongly supported by the obtained free energy profiles, which confirm a higher reactivity of selegiline over rasagiline, while the calculated difference in the activation Gibbs energies of ΔΔG‡ = 3.1 kcal mol−1 is found to be in very good agreement with that from the measured literature kinact values that predict a 1.7 kcal mol−1 higher selegiline reactivity. Given the similarity with the hydride transfer mechanism during the MAO catalytic activity, these results verify that both rasagiline and selegiline are mechanism-based irreversible inhibitors and offer guidelines in designing new and improved inhibitors, which are all clinically employed in treating a variety of neuropsychiatric and neurodegenerative conditions.
Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite
Authors: Drapala Adrian , Szudzik Mateusz , Chabowski Dawid , Mogilnicka Izabella , Jaworska Kinga , Kraszewska Katarzyna , Samborowska Emilia , Ufnal Marcin
Published: August 2020

Trimethylamine (TMA) is a gut bacteria product oxidized by the liver to trimethylamine-N-oxide (TMAO). Clinical evidence suggests that cardiovascular disease is associated with increased plasma TMAO. However, little headway has been made in understanding this relationship on a mechanistic and molecular level. We investigated the mechanisms affecting plasma levels of TMAO in Spontaneously Hypertensive Heart Failure (SHHF) rats. Healthy Wistar Kyoto (WKY) and SHHF rats underwent metabolic, hemodynamic, histopathological and biochemical measurements, including tight junction proteins analysis. Stool, plasma and urine samples were evaluated for TMA and TMAO using ultra performance liquid chromatography-mass spectrometry. SHHF presented disturbances of the gut–blood barrier including reduced intestinal blood flow, decreased thickness of the colonic mucosa and alterations in tight junctions, such as claudin 1 and 3, and zonula occludens-1. This was associated with significantly higher plasma levels of TMA and TMAO and increased gut-to-blood penetration of TMA in SHHF compared to WKY. There was no difference in kidney function or liver oxidation of TMA to TMAO between WKY and SHHF. In conclusion, increased plasma TMAO in heart failure rats results from a perturbed gut–blood barrier and increased gut-to-blood passage of TMAO precursor, i.e., TMA. Increased gut-to-blood penetration of bacterial metabolites may be a marker and a mediator of cardiovascular pathology.
Metabolic Engineering of the Native Monoterpene Pathway in Spearmint for Production of Heterologous Monoterpenes Reveals Complex Metabolism and Pathway Interactions
Authors: Li Chunhong , Sarangapani Sreelatha , Wang Qian , Nadimuthu Kumar , Sarojam Rajani
Published: August 2020

Spearmint produces and stores large amounts of monoterpenes, mainly limonene and carvone, in glandular trichomes and is the major natural source of these compounds. Towards producing heterologous monoterpenes in spearmint, we first reduced the flux into the native limonene pathway by knocking down the expression of limonene synthase (MsLS) by RNAi method. The MsLS RNAi lines exhibited a huge reduction in the synthesis of limonene and carvone. Detailed GC-MS and LC-MS analysis revealed that MsLS RNAi plants also showed an increase in sesquiterpene, phytosterols, fatty acids, flavonoids, and phenolic metabolites, suggesting an interaction between the MEP, MVA shikimate and fatty acid pathways in spearmint. Three different heterologous monoterpene synthases namely, linalool synthase and myrcene synthase from Picea abies and geraniol synthase from Cananga odorata were cloned and introduced independently into the MsLS RNAi mutant background. The expression of these heterologous terpene synthases resulted mainly in production of monoterpene derivatives. Of all the introduced monoterpenes geraniol showed the maximum number of derivatives. Our results provide new insights into MEP pathway interactions and regulation and reveals the existence of mechanisms for complex metabolism of monoterpenes in spearmint.
Evaluation of Multiple Methods for Quantification of Glycosaminoglycan Biomarkers in Newborn Dried Blood Spots from Patients with Severe and Attenuated Mucopolysaccharidosis-I
Authors: Herbst Zackary M. , Urdaneta Leslie , Klein Terri , Fuller Maria , Gelb Michael H.
Published: August 2020

All newborn screening (NBS) for mucopolysaccharidosis-I (MPS-I) is carried out by the measurement of α-iduronidase (IDUA) enzymatic activity in dried blood spots (DBS). The majority of low enzyme results are due to pseudodeficiencies, and studies from the Mayo Clinic have shown that the false positive rate can be greatly reduced by including a second-tier analysis of glycosaminoglycans (GAGs) in DBS as part of NBS. In the present study, we obtained newborn DBS from 13 patients with severe MPS-I and 2 with attenuated phenotypes. These samples were submitted to four different GAG mass spectrometry analyses in a comparative study: (1) internal disaccharide; (2) endogenous disaccharide; (3) Sensi-Pro; (4) Sensi-Pro Lite (a variation of Sensi-Pro with a simplified workflow). Patients with attenuated MPS-I show less GAG elevation than those with severe disease, and all MPS-I patients were separated from the reference range using all four methods. The minimal differential factor (lowest GAG marker level in MPS-I samples divided by highest level in the reference range of 30 random newborns) was about two for internal disaccharide, Sensi-Pro, and Sensi-Pro Lite methods. The endogenous disaccharide was clearly the best method with a minimal differential of 16-fold. This study supports use of second-tier GAG analysis of newborn DBS, especially the endogenous disaccharide method, as part of NBS to reduce the false positive rate.
Effect of Immune Inducers on Nosema ceranae Multiplication and Their Impact on Honey Bee (Apis mellifera L.) Survivorship and Behaviors
Authors: Valizadeh Pegah , Guzman-Novoa Ernesto , Goodwin Paul H.
Published: August 2020

Nosema disease is a major disease of honey bees caused by two species of microsporidia, Nosema apis and N. ceranae. Current control involves using antibiotics, which is undesirable because of possible antibiotic resistance and contamination. In this study, flagellin, zymosan, chitosan, and peptidoglycan were investigated as alternatives for controlling N. ceranae infections and for their effect on bee survivorship and behaviors. Chitosan and peptidoglycan significantly reduced the infection, and significantly increased survivorship of infected bees, with chitosan being more effective. However, neither compound altered the bees’ hygienic behavior, which was also not affected by the infection. Chitosan significantly increased pollen foraging and both compounds significantly increased non-pollen foraging compared to healthy and infected bees. Memory retention, evaluated with the proboscis extension reflex assay, was temporarily impaired by chitosan but was not affected by peptidoglycan, nor was it affected by N. ceranae infection compared to the non-infected bees. This study indicates that chitosan and peptidoglycan provide benefits by partially reducing N. ceranae spore numbers while increasing survivorship compared to N. ceranae infected bees. Also, chitosan and peptidoglycan improved aspects of foraging behavior even more than in healthy bees, showing that they may act as stimulators of important honey bee behaviors.