bluuebunny/crossref_metadata_2025 huggingface dataset:
Flavokawain B and Doxorubicin Work Synergistically to Impede the Propagation of Gastric Cancer Cells via ROS-Mediated Apoptosis and Autophagy Pathways
Authors: Hseu You-Cheng , Lin Ruei-Wan , Shen Yi-Chun , Lin Kai-Yuan , Liao Jiunn-Wang , Thiyagarajan Varadharajan , Yang Hsin-Ling
Published: September 2020

Chalcone flavokawain B (FKB) possesses a chemopreventive and anti-cancer activity. Doxorubicin is a chemotherapeutic DNA intercalating agent widely used in malignancy treatment. The present study investigated whether synergistic effects exist between the combination of FKB (1.25–5 µg/mL) and doxorubicin (0.5 µg/mL) on the apoptosis and autophagy in human gastric cancer (AGS) cells, and the possible in vitro and in vivo mechanisms. The MTT assay measured cell viability. Various apoptotic-, autophagy-associated protein expression was determined by the Western blot technique. FKB+doxorubicin synergy was estimated by the Chou-Talalay combination index (CI) method. In vivo studies were performed on BALB/c mice. Results showed that compared to FKB/doxorubicin treatments, low doses of FKB+doxorubicin suppressed AGS cell growth. FKB potentiated doxorubicin-induced DNA fragmentation, apoptotic cell death, and enhanced doxorubicin-mediated mitochondrial, death receptor pathways. FKB+doxorubicin activated increased LC3-II accumulation, p62/SQSTM1 expression, and AVO formation as compared to the FKB/doxorubicin alone treatments indicating autophagy in these cells. The death mechanism in FKB+doxorubicin-treated AGS cells is due to the activation of autophagy. FKB+doxorubicin-mediated dysregulated Bax/Bcl-2, Beclin-1/Bcl-2 ratios suggested apoptosis, autophagy induction in AGS cells. FKB+doxorubicin-induced LC3-II/AVOs downregulation was suppressed due to an apoptotic inhibitor Z-VAD-FMK. Whereas, 3-methyladenine/chloroquine weakened FKB+doxorubicin-induced apoptosis (decreased DNA fragmentation/caspase-3). Activation of ERK/JNK may be involved in FKB+doxorubicin-induced apoptosis and autophagy. FKB+doxorubicin-triggered ROS generation, but NAC attenuated FKB+doxorubicin-induced autophagic (LC3 accumulation) and apoptotic (caspase-3 activation and PARP cleavage) cell death. FKB+doxorubicin blocked gastric cancer cell xenografts in nude mice in vivo as compared to FKB/doxorubicin alone treatments. FKB and doxorubicin wielded synergistic anti-tumor effects in gastric cancer cells and is a promising therapeutic approach.
IL-1β and TNF-α Modulation of Proliferated and Committed Myoblasts: IL-6 and COX-2-Derived Prostaglandins as Key Actors in the Mechanisms Involved
Authors: Alvarez Angela M. , DeOcesano-Pereira Carlos , Teixeira Catarina , Moreira Vanessa
Published: September 2020

In this study, we investigated the effects and mechanisms of the pro-inflammatory cytokines IL-1β and TNF-α on the proliferation and commitment phases of myoblast differentiation. C2C12 mouse myoblast cells were cultured to reach a proliferated or committed status and were incubated with these cytokines for the evaluation of cell proliferation, cyclooxygenase 2 (COX-2) expression, release of prostaglandins (PGs) and myokines, and activation of myogenic regulatory factors (MRFs). We found that inhibition of the IL-6 receptor reduced IL-1β- and TNF-α-induced cell proliferation, and that the IL-1β effect also involved COX-2-derived PGs. Both cytokines modulated the release of the myokines myostatin, irisin, osteonectin, and IL-15. TNF-α and IL-6 reduced the activity of Pax7 in proliferated cells and reduced MyoD and myogenin activity at both proliferative and commitment stages. Otherwise, IL-1β increased myogenin activity only in committed cells. Our data reveal a key role of IL-6 and COX-2-derived PGs in IL-1β and TNF-α-induced myoblast proliferation and support the link between TNF-α and IL-6 and the activation of MRFs. We concluded that IL-1β and TNF-α induce similar effects at the initial stages of muscle regeneration but found critical differences between their effects with the progression of the process, bringing new insights into inflammatory signalling in skeletal muscle regeneration.
Senescence Induction by Combined Ionizing Radiation and DNA Damage Response Inhibitors in Head and Neck Squamous Cell Carcinoma Cells
Authors: Dobler Clara , Jost Tina , Hecht Markus , Fietkau Rainer , Distel Luitpold
Published: September 2020

DNA damage response inhibitors (DDRi) may selectively enhance the inactivation of tumor cells in combination with ionizing radiation (IR). The induction of senescence may be the key mechanism of tumor cell inactivation in this combinatorial treatment. In the current study the effect of combined IR with DDRi on the induction of senescence was studied in head and neck squamous cell carcinoma (HNSCC) cells with different human papilloma virus (HPV) status. The integrity of homologous recombination (HR) was assessed in two HPV positive, two HPV negative HNSCC, and two healthy fibroblast cell cultures. Cells were treated with the DDRi CC-115 (DNA-dependent protein kinase, DNA-pK; dual mammalian target of rapamycin, mTor), VE-822 (ATR; ataxia telangiectasia and Rad3-related kinase), and AZD0156 (ATM; ataxia telangiectasia mutated kinase) combined with IR. Effects on senescence, apoptosis, necrosis, and cell cycle were analyzed by flow cytometry. The fibroblast cell lines generally tolerated IR or combined treatment better than the tumor cell lines. The ATM and ATR inhibitors were effectively inducing senescence when combined with IR. The DNA-PK inhibitor was not an important inductor of senescence. HPV status and HR activity had a limited influence on the efficacy of DDRi. Induction of senescence and necrosis varied individually among the cell lines due to molecular heterogeneity and the involvement of DNA damage response pathways in senescence induction.
Angle-Resolved Photoemission Study on the Band Structure of Organic Single Crystals
Authors: Wang Ke , Ecker Ben , Gao Yongli
Published: September 2020

Angle-resolved photoemission spectroscopy (ARPES) is a vital technique, collecting data from both the energy and momentum of photoemitted electrons, and is indispensable for investigating the electronic band structure of solids. This article provides a review on ARPES studies of the electronic band structure of organic single crystals, including organic charge transfer conductors; organic semiconductors; and organo-metallic perovskites. In organic conductors and semiconductors, band dispersions are observed that are highly anisotropic. The Van der Waals crystal nature, the weak electron wavefunction overlap, as well as the strong electron-phonon coupling result in many organic crystals having indiscernible dispersion. In comparison, organo-metallic perovskite halides are characterized by strong s-p orbitals from the metal and halide at the top of the valence bands, with dispersions similar to those in inorganic materials.
Management of an Unsuccessful Regenerative Endodontic Procedure after Tooth Fracture: A Case Report
Authors: Bandeira Lopes Luísa , Paredes Francisco , Pimenta Andreia , Carpinteiro Inês
Published: September 2020

Dental trauma is a very frequent occurrence in children and adolescents, which creates a great impact on the esthetics, functions, and phonetics. Traumatic dental injuries can range from simple enamel fractures to permanent tooth loss. This case report presents an eight-year-old patient with an uncomplicated crown fracture of tooth 21, and 30 days after trauma, it was diagnosed as necrotic pulp. The first treatment choice was a regenerative endodontic procedure (REP), however, the failure led to apexification with Mineral Trioxide Aggregate (MTA). The chosen rehabilitation was a composite veneer. Concerning the available literature and fracture enamel dentin, the treatment approach proposed for the case provided good functional and esthetic outcomes.
Experimental Analysis of an Air Heat Pump for Heating Service Using a “Hardware-In-The-Loop” System
Authors: Conti Paolo , Bartoli Carlo , Franco Alessandro , Testi Daniele
Published: September 2020

Estimating and optimizing the dynamic performance of a heat pump system coupled to a building is a paramount yet complex task, especially under intermittent conditions. This paper presents the “hardware-in-the-loop” experimental campaign of an air-source heat pump serving a typical dwelling in Pisa (Italy). The experimental apparatus uses real pieces of equipment, together with a thermal load emulator controlled by a full energy dynamic simulation of the considered building. Real weather data are continuously collected and used to run the simulation. The experimental campaign was performed from November 2019 to February 2020, measuring the system performances under real climate and load dynamics. With a water set point equal to 40 °C, the average heat pump coefficient of performance was about 3, while the overall building-plant performance was around 2. The deviation between the two performance indexes can be ascribed to the continuous on-off signals given by the zone thermostat due to the oversized capacity of the heat emission system. The overall performance raised to 2.5 thanks to a smoother operation obtained with reduced supply temperature (35 °C) and fan coil speed. The paper demonstrates the relevance of a dynamic analysis of the building-HVAC system and the potential of the “hardware-in-the-loop” approach in assessing actual part-load heat pump performances with respect to the standard stationary methodology.
Real-Time Control Based on a CAN-Bus of Hybrid Electrical Systems
Authors: Agbli Kréhi Serge , Hilairet Mickaël , Gustin Frédéric
Published: September 2020

Power management of a one-converter parallel structure with battery and supercapacitor is addressed in this paper. The controller is implemented on a DSP from a Microchip and uses a Controller Area Network (CAN) bus communication for data exchange. However, the low data transmission rate of the CAN bus data impacts the performances of regular power management strategies. This paper details an initial strategy with a charge sustaining mode for an application coupling a battery with supercapacitors, in which low performances have been witnessed due to the high sampling time of the CAN bus data. Therefore, a new strategy is proposed to tackle the sample time issue based on a depleting mode. Simulation and experimental results with a dsPIC33EP512MU810 DSP based on a 10 kW hybrid system proves the feasibility of the proposed approach.
Ecological and Economic Benefits of the “Medium” Level of the Building Thermo-Modernization: A Case Study in Poland
Authors: Adamczyk Janusz , Dylewski Robert
Published: September 2020

Energy saving is at the heart of sustainable development in the context of climate change. Saving energy is not only the amount of energy that we save, but also reducing emissions of pollutants to the atmosphere, as well as reducing the consumption of energy resources that are used to produce energy. Reducing pollutant emissions and the use of energy resources can be achieved by increasing the use of renewable energy sources, but at present, this method of obtaining energy in the world is not representative. It should be noted that renewable energy devices throughout the life cycle generate environmental impact. Similar to this situation, the building’s thermo-modernization, which is focused on reducing the pressure on the environment of the building’s user, also has an impact on the environment throughout the building’s life cycle. Determining this environmental impact and ecological or economic benefits or costs is the purpose of the following article. Thermo-modernization of the building, for the purposes of the article, is understood as thermal insulation of walls and replacement of the heat source for heating the building and preparation of hot utility water. The need to replace the heat source with a much more ecological one results in Poland from provincial legal regulations announced by virtue of a resolution. In the study, data from the Ecoinvent data library included in the SimaPro computer program was used for the LCA (Life Cycle Assessment) analysis. As a result of thermo-modernization of the representative buildings, large ecological benefits were obtained, while economic costs remain at a high level.
Hydrate Plugging and Flow Remediation during CO2 Injection in Sediments
Authors: Gauteplass Jarand , Almenningen Stian , Barth Tanja , Ersland Geir
Published: September 2020

Successful geological sequestration of carbon depends strongly on reservoir seal integrity and storage capacity, including CO2 injection efficiency. Formation of solid hydrates in the near-wellbore area during CO2 injection can cause permeability impairment and, eventually, injectivity loss. In this study, flow remediation in hydrate-plugged sandstone was assessed as function of hydrate morphology and saturation. CO2 and CH4 hydrates formed consistently at elevated pressures and low temperatures, reflecting gas-invaded zones containing residual brine near the injection well. Flow remediation by methanol injection benefited from miscibility with water; the methanol solution contacted and dissociated CO2 hydrates via liquid water channels. Injection of N2 gas did not result in flow remediation of non-porous CO2 and CH4 hydrates, likely due to insufficient gas permeability. In contrast, N2 as a thermodynamic inhibitor dissociated porous CH4 hydrates at lower hydrate saturations (<0.48 frac.). Core-scale thermal stimulation proved to be the most efficient remediation method for near-zero permeability conditions. However, once thermal stimulation ended and pure CO2 injection recommenced at hydrate-forming conditions, secondary hydrate formation occurred aggressively due to the memory effect. Field-specific remediation methods must be included in the well design to avoid key operational challenges during carbon injection and storage.
The Design and Test for Degradation of Energy Density of a Silica Gel-Based Energy Storage System Using Low Grade Heat for Desorption Phase
Authors: Ayisi Emmanuel Nyarko , Fraňa Karel
Published: September 2020

This paper presents the design and a short cycle repeatability test of a silica gel-based thermal energy storage system using low grade heat for the desorption phase. The system was designed to test the degradation in the energy storage density of the adsorbent material for a 2 h working period in a short number of cycles (5 cycles). Low grade heat of 70 °C is used for regeneration during the desorption phase in each cycle. It was found that a reduction of 1.6 W/kg per each cycle of energy storage was observed, up to 5 cycles. The maximal heat storage density was 292 kJ/kg at the first cycle and reduced to 225 kJ/kg at the fifth cycle. Furthermore, the total amount of water vapor adsorbed in the silica gel was observed as well. The test of energy storage was performed under a short time period (maximal approx. 165 min).
Formic Acid as a Hydrogen Donor for Catalytic Transformations of Tar
Authors: Chesnokov Vladimir V. , Dik Pavel P. , Chichkan Aleksandra S.
Published: September 2020

Specific features of the catalytic tar cracking in the presence of formic acid, BEA zeolite and 8% Ni-2.5% Mo/Sibunit catalyst were studied at 350 °C and 1.0 MPa pressure. The obtained results evidenced that formic acid can be used as a hydrogen donor during catalytic reactions. The formic acid addition made it possible to perform efficient hydrocracking of heavy feed such as tar. It was found that both the tar conversion and selectivity to light (gasoline-diesel) fractions grew in the sequence: tar < (tar - formic acid) < (tar - formic acid - BEA zeolite) < (tar - formic acid - BEA zeolite - 8% Ni-2.5% Mo/Sibunit catalyst). Furthermore, significantly lower concentrations of impurities containing sulfur and nitrogen were observed for the (tar - formic acid - BEA zeolite - 8% Ni-2.5% Mo/Sibunit catalyst) system. For example, the sulfur and nitrogen concentrations in the tar precursor were 1.50% and 0.86%, respectively. Meanwhile, their concentrations in the liquid products after the catalytic cracking were 0.73% and 0.18%, respectively.
Simulations on Design and System Performance of Building Heating Boosted by Thermal Energy Storage (TES) with Magnesium Hydro Carbonates/Silica Gel
Authors: Erlund Rickard , Zevenhoven Ron
Published: September 2020

In this paper, a simulations model of a seasonal thermal energy storage (TES) reactor integrated into a house heating system is presented. The water vapour chemisorbing reactor contains a composite material composed of silica gel and hydrated magnesium carbonate (nesquehonite, MgCO3·3H2O) that can be produced by a carbon capture and storage by mineralisation process. The performance of the TES to supply winter heat instead of electrical resistance heat is analysed. Dividing the reactor into a few units (connected in series) for better heat output and storage capacity as developed by the authors is compared to one unit or parallel unit solutions. The heating system components are an exhaust air heat pump, solar collectors and a heat recovery ventilation unit (HRV). The TES is used as heat source during colder periods, which implies improved efficiency and coefficient of performance (COP). Around 70% of electrical resistance heat, assisting an exhaust air heat pump during cold periods, can be substituted with heat from the TES according to the simulation model. Connecting three units in series will increase the usable storage capacity possibilities with by a 49% higher heat output.
Simulation Study of the Formation of Corrosive Gases in Coal Combustion in an Entrained Flow Reactor
Authors: von Bohnstein Maximilian , Yildiz Coskun , Frigge Lorenz , Ströhle Jochen , Epple Bernd
Published: September 2020

Gaseous sulfur species play a major role in high temperature corrosion of pulverized coal fired furnaces. The prediction of sulfur species concentrations by 3D-Computational Fluid Dynamics (CFD) simulation allows the identification of furnace wall regions that are exposed to corrosive gases, so that countermeasures against corrosion can be applied. In the present work, a model for the release of sulfur and chlorine species during coal combustion is presented. The model is based on the mineral matter transformation of sulfur and chlorine bearing minerals under coal combustion conditions. The model is appended to a detailed reaction mechanism for gaseous sulfur and chlorine species and hydrocarbon related reactions, as well as a global three-step mechanism for coal devolatilization, char combustion, and char gasification. Experiments in an entrained flow were carried out to validate the developed model. Three-dimensional numerical simulations of an entrained flow reactor were performed by CFD using the developed model. Calculated concentrations of SO2, H2S, COS, and HCl showed good agreement with the measurements. Hence, the developed model can be regarded as a reliable method for the prediction of corrosive sulfur and chlorine species in coal fired furnaces. Further improvement is needed in the prediction of some minor trace species.
Analyzing Impact of Distributed PV Generation on Integrated Transmission & Distribution System Voltage Stability—A Graph Trace Analysis Based Approach
Authors: Bhatti Bilal Ahmad , Broadwater Robert , Dilek Murat
Published: September 2020

The use of a Graph Trace Analysis (GTA)-based power flow for analyzing the voltage stability of integrated Transmission and Distribution (T&D) networks is discussed in the context of distributed Photovoltaic (PV) generation. The voltage stability of lines and the load carrying capability of buses is analyzed at various PV penetration levels. It is shown that as the PV generation levels increase, an increase in the steady state voltage stability of the system is observed. Moreover, within certain regions of stability margin changes, changes in voltage stability margins of transmission lines are shown to be linearly related to changes in the loading of the lines. Two case studies are presented, where one case study involves a model with eight voltage levels and 784,000 nodes. In one case study, a voltage-stability heat map is used to demonstrate the identification of weak lines and buses.
Intake of Radionuclides in the Trees of Fukushima Forests 4. Binding of Radioiodine to Xyloglucan
Authors: Nonaka Miki , Yasukawa Chisato , Aoki Shoko , Itakura Masateru , Willför Stefan , Capek Peter , Shoseyov Oded , Tsubokura Masaharu , Baba Kei’ichi , Kaida Rumi , Taji Teruaki , Sakata Yoichi , Hayashi Takahisa
Published: September 2020

The 1,4-linked glucans such as xyloglucan and amylose are known to form a complex with iodine/iodide ions and to also be precipitated with CaCl2 in the presence of iodine. Here, we show that iodine gas could be specifically incorporated into xyloglucan. Furthermore, we show that [125I]I2 gas is, over time, incorporated at high levels into the entire outer surface of poplar seedlings but that spraying seedlings with abscisic acid to close stomata decreases the incorporation of the gas. There was less incorporation of the gas in a transgenic poplar overexpressing xyloglucanase at the early stages when compared with a wild type. This shows that xyloglucan serves as a key absorber of iodine gas into a plant body. After individual leaves of cultured seedlings were exposed to the gas for 30 min, no radioiodine was emitted from those leaves over the following two weeks, indicating that no turnover occurs in radioiodine once it is bound to the polysaccharides in plant tissues. We conclude that forest trees could serve as one of the largest enormous capture systems for the radioiodine fallout following the nuclear power plant accident in Fukushima.
Evaluation of Antimicrobial Coatings on Preservation and Shelf Life of Fresh Chicken Breast Fillets Under Cold Storage
Authors: Garavito Johanna , Moncayo-Martínez Diana , Castellanos Diego A.
Published: September 2020

Fresh poultry products such as chicken breast are very convenient for consumption due to their availability and nutritional and sensory characteristics but they have a short shelf life (3–5 days) due to their high water activity and propensity to microbial contamination and spoilage. In this work, the characteristics of edible coatings (EC) prepared from various formulations of guar gum (GG) and isolated soy protein were evaluated. From this evaluation, and due to the guar gum EC being the most suitable, antimicrobial coatings were prepared with different proportions of GG, nisin, and oregano oil to determine its effect on shelf life and change in physicochemical and microbiological properties of chicken breast fillets under refrigerated conditions. Fresh samples were coated with a coating-forming solution based on GG and stored at 4 °C for 16 days. During this time, the change in color, firmness, acidity, pH, growth of microorganisms was determined, and sensory tests of appearance, taste, and odor were performed. GG-coated samples retained color and firmness during storage. Likewise, a decrease in weight loss was achieved in the treated samples, and the sensory attributes were preserved compared to the uncoated samples. The application of the coating considerably delayed the growth of microorganisms, increasing the product shelf life (9 days) compared to the control samples (6 days).
Physicochemical Fingerprint of “Pera Rocha do Oeste”. A PDO Pear Native from Portugal
Authors: Pedro Soraia I. , Coelho Elisabete , Peres Fátima , Machado Ana , Rodrigues António M. , Wessel Dulcineia F. , Coimbra Manuel A. , Anjos Ofélia
Published: September 2020

“Pera Rocha do Oeste” is a pear (Pyrus communis L.) variety native from Portugal with a Protected Designation of Origin (PDO). To supply the world market for almost all the year, the fruits are kept under controlled storage. This study aims to identify which classical physicochemical parameters (colour, total soluble solids (TSS), pH, acidity, ripening index, firmness, vitamin C, total phenols, protein, lipids, fibre, ash, other compounds including carbohydrates, and energy) could be fingerprint markers of PDO “Pera Rocha do Oeste”. For this purpose, a data set constituting fruits from the same size, harvested from three orchards of the most representative PDO locations and stored in refrigerated conditions for 2 or 5 months at atmospheric conditions or for 5 months under a modified atmosphere, were selected. To validate the fingerprint parameters selected with the first set, an external data set was used with pears from five PDO orchards stored under different refrigerated conditions. Near infrared (NIR) spectroscopy was used as a complementary tool to assess the global variability of the samples. The lightness of the pulp; the b* CIELab coordinate of the pulp and peel; and the pulp TSS, pH, firmness, and total phenols, due to their lower variability, are proposed as fingerprint markers of this pear.
How a Spanish Group of Millennial Generation Perceives the Commercial Novel Smoothies?
Authors: Cano-Lamadrid Marina , Tkacz Karolina , Turkiewicz Igor Piotr , Clemente-Villalba Jesús , Sánchez-Rodríguez Lucía , Lipan Leontina , García-García Elena , Carbonell-Barrachina Ángel A. , Wojdyło Aneta
Published: September 2020

The World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO) constantly emphasize the importance of increasing fruit and vegetable consumption; these natural products help in the prevention of major diseases. Smoothies are a simple and convenient way of doing so; thus, their demand is constantly growing and their market is becoming important for the food industry. Therefore, the objective of this research was to determine Millennial consumer opinion towards novel fruit- and vegetable-smoothies available on the retail market. Napping®, descriptive sensory analysis, and consumer studies were conducted. Napping® results group samples into four clusters of smoothies; the main grouping factor was the type of fruit and the percentage of vegetables. Penalty analysis showed that smoothies need improvement mainly dealing with sweetness, bitterness, and vegetable flavors. Millennial consumers formed a homogeneous sensory group in which the overall liking was negatively correlated with the level of sweetness, and earthy, carrot, beetroot, and pear flavors. The key liking drivers were sourness and notes of mango, banana, and peach flavors. This research is a new insight into the perception of smoothies, provides comprehensive knowledge for the food industry, and can guide the design of new healthy smoothies.
Are There Seasonal Variations in Faecal Contamination of Exposure Pathways? An Assessment in a Low–Income Settlement in Uganda
Authors: Ronoh Patrick , Furlong Claire , Kansiime Frank , Mugambe Richard , Brdjanovic Damir
Published: September 2020

Sanitation infrastructure are not able to cope with the increasing population in low-income countries, which leaves populations exposed to faecal contamination from multiple pathways. This study evaluated public health risk (using SaniPath) in a low-income community during the dry season, to identify the dominant exposure pathways, and compare this data to existing data for the rainy season, questioning the assumption that risk of faecal contamination is higher in the rainy season. SaniPath was used to collect and assess exposure and environmental data, and to generate risk profiles for each pathway. In the dry season the highest exposure frequency was for bathing and street food, exposure frequency generally increased, and seasonal variation was found in five pathways. The highest hazards in the dry season were through contact with drains, soil, and street food. Seasonal variation was found in the contamination of open drains and street food, with higher levels of Escherichia coli (E. coli) in the dry season. Open drains were identified as the most dominant risk pathway in both seasons, but risk was higher in the dry season. This highlights the complex nature of seasonal variation of faecal risk, and questions the assumption that risk is higher in the rainy season.
Heat Stress, Physiological Response, and Heat-Related Symptoms among Thai Sugarcane Workers
Authors: Boonruksa Pongsit , Maturachon Thatkhwan , Kongtip Pornpimol , Woskie Susan
Published: September 2020

Prolonged or intense exposure to heat can lead to a range of health effects. This study investigated heat exposure and heat-related symptoms which sugarcane workers (90 sugarcane cutters and 93 factory workers) experienced during a harvesting season in Thailand. During the hottest month of harvesting season, wet bulb globe temperature was collected in the work environment, and workloads observed, to assess heat stress. Urine samples for dehydration test, blood pressure, heart rate, and body temperature were measured pre- and post-shift to measure heat strain. Fluid intake and heat-related symptoms which subjects had experienced during the harvesting season were gathered via interviews at the end of the season. From the results, sugarcane cutters showed high risk for heat stress and strain, unlike factory workers who had low risk based on the American Conference of Governmental Industrial Hygiene (ACGIH) threshold limit values (TLVs) for heat stress. Dehydration was observed among sugarcane cutters and significant physiological changes including heart rate, body temperature, and systolic blood pressure occurred across the work shift. Significantly more sugarcane cutters reported experiencing heat-related symptoms including weakness/fatigue, heavy sweating, headache, rash, muscle cramp, dry mouth, dizziness, fever, dry/cracking skin, and swelling, compared to sugarcane factory workers. We conclude that the heat stress experienced by sugarcane cutters working in extremely hot environments, with high workloads, is associated with acute health effects. Preventive and control measures for heat stress are needed to reduce the risk of heat strain.
Physical Activity and Physical Competence in Overweight and Obese Children: An Intervention Study
Authors: Morano Milena , Robazza Claudio , Bortoli Laura , Rutigliano Irene , Ruiz Montse C. , Campanozzi Angelo
Published: September 2020

With the current obesity epidemic and the decline of fitness among school-aged children, the importance of obesity interventions to promote physical activity and healthy habits has become indisputable. The purpose of this study was to assess the efficacy of a school-based multicomponent intervention in increasing physical activity (PA) levels, actual physical abilities, and perceived physical abilities in clinical and nonclinical samples of overweight/obese boys and girls aged 10–12 years. The clinical intervention group (n = 35) participated in a 7-month after-school program in addition to curricular physical education lessons, while the nonclinical control group (n = 29) received usual curricular lessons. Measures included levels of PA and fitness and individual’s perceptions of physical ability. After treatment, the intervention group showed improved PA levels, perceived physical ability, and throwing and jumping task performances compared to the control group. Results indicate that a multicomponent program can improve levels of PA, fitness, and perceived competence of overweight participants. Findings highlight the importance of a comprehensive healthy lifestyle program that includes physical, psychosocial, and behavioral factors and suggest practical implications for educators, trainers, and teachers in identifying best practices targeting childhood obesity.
How Health Habits Influence the Physiological Response During a Physical Activity in Extreme Temperatures?
Authors: Martin-Conty José Luis , Martin-Rodríguez Francisco , Criado-Álvarez Juan José , Castillo-Sarmiento Carlos Alberto , Maestre-Miquel Clara , Mohedano-Moriano Alicia , Polonio-López Begoña , Durantez-Fernández Carlos , Castro-Villamor Miguel Ángel , Viñuela Antonio
Published: September 2020

Background: The purpose of the study was to determine to what degree the health habits of university students influence their physiological response during a 10-min high-intensity exercise. Methods: We conducted a cross-sectional cohort study with 59 health science students, in which we analyzed their adherence to a Mediterranean and low-fat diet, as well as their activity levels. We correlated these factors with the physiological response (lactic acid and heart rate) and a series of anthropometric parameters in intense physical activity (cardiopulmonary resuscitation (CPR) for 10 min) in three scenarios: extreme cold, extreme heat and a control situation at room temperature. Results: The results of this study demonstrate that in university students, a greater adherence to the Mediterranean diet was associated with a better response to physical exercise, in this case, 10-min CPR, in hostile environments. Conclusions: Following healthy eating guidelines improves physical performance and delays the appearance of fatigue; both are important aspects for a better performance of CPR.
Novel Missense CACNA1G Mutations Associated with Infantile-Onset Developmental and Epileptic Encephalopathy
Authors: Berecki Géza , Helbig Katherine L. , Ware Tyson L. , Grinton Bronwyn , Skraban Cara M. , Marsh Eric D. , Berkovic Samuel F. , Petrou Steven
Published: September 2020

The CACNA1G gene encodes the low-voltage-activated Cav3.1 channel, which is expressed in various areas of the CNS, including the cerebellum. We studied two missense CACNA1G variants, p.L208P and p.L909F, and evaluated the relationships between the severity of Cav3.1 dysfunction and the clinical phenotype. The presentation was of a developmental and epileptic encephalopathy without evident cerebellar atrophy. Both patients exhibited axial hypotonia, developmental delay, and severe to profound cognitive impairment. The patient with the L909F mutation had initially refractory seizures and cerebellar ataxia, whereas the L208P patient had seizures only transiently but was overall more severely affected. In transfected mammalian cells, we determined the biophysical characteristics of L208P and L909F variants, relative to the wild-type channel and a previously reported gain-of-function Cav3.1 variant. The L208P mutation shifted the activation and inactivation curves to the hyperpolarized direction, slowed the kinetics of inactivation and deactivation, and reduced the availability of Ca2+ current during repetitive stimuli. The L909F mutation impacted channel function less severely, resulting in a hyperpolarizing shift of the activation curve and slower deactivation. These data suggest that L909F results in gain-of-function, whereas L208P exhibits mixed gain-of-function and loss-of-function effects due to opposing changes in the biophysical properties. Our study expands the clinical spectrum associated with CACNA1G mutations, corroborating further the causal association with distinct complex phenotypes.
Molecular Investigation on a Triple Negative Breast Cancer Xenograft Model Exposed to Proton Beams
Authors: Cammarata Francesco P. , Forte Giusi I. , Broggi Giuseppe , Bravatà Valentina , Minafra Luigi , Pisciotta Pietro , Calvaruso Marco , Tringali Roberta , Tomasello Barbara , Torrisi Filippo , Petringa Giada , Cirrone Giuseppe A. P. , Cuttone Giacomo , Acquaviva Rosaria , Caltabiano Rosario , Russo Giorgio
Published: September 2020

Specific breast cancer (BC) subtypes are associated with bad prognoses due to the absence of successful treatment plans. The triple-negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptor status, is a clinical challenge for oncologists, because of its aggressiveness and the absence of effective therapies. In addition, proton therapy (PT) represents an effective treatment against both inaccessible area located or conventional radiotherapy (RT)-resistant cancers, becoming a promising therapeutic choice for TNBC. Our study aimed to analyze the in vivo molecular response to PT and its efficacy in a MDA-MB-231 TNBC xenograft model. TNBC xenograft models were irradiated with 2, 6 and 9 Gy of PT. Gene expression profile (GEP) analyses and immunohistochemical assay (IHC) were performed to highlight specific pathways and key molecules involved in cell response to the radiation. GEP analysis revealed in depth the molecular response to PT, showing a considerable immune response, cell cycle and stem cell process regulation. Only the dose of 9 Gy shifted the balance toward pro-death signaling as a dose escalation which can be easily performed using proton beams, which permit targeting tumors while avoiding damage to the surrounding healthy tissue.
Insights into Disease-Associated Tau Impact on Mitochondria
Authors: Szabo Leonora , Eckert Anne , Grimm Amandine
Published: September 2020

Abnormal tau protein aggregation in the brain is a hallmark of tauopathies, such as frontotemporal lobar degeneration and Alzheimer’s disease. Substantial evidence has been linking tau to neurodegeneration, but the underlying mechanisms have yet to be clearly identified. Mitochondria are paramount organelles in neurons, as they provide the main source of energy (adenosine triphosphate) to these highly energetic cells. Mitochondrial dysfunction was identified as an early event of neurodegenerative diseases occurring even before the cognitive deficits. Tau protein was shown to interact with mitochondrial proteins and to impair mitochondrial bioenergetics and dynamics, leading to neurotoxicity. In this review, we discuss in detail the different impacts of disease-associated tau protein on mitochondrial functions, including mitochondrial transport, network dynamics, mitophagy and bioenergetics. We also give new insights about the effects of abnormal tau protein on mitochondrial neurosteroidogenesis, as well as on the endoplasmic reticulum-mitochondria coupling. A better understanding of the pathomechanisms of abnormal tau-induced mitochondrial failure may help to identify new targets for therapeutic interventions.
Calmodulin Binding to Connexin 35: Specializations to Function as an Electrical Synapse
Authors: Aseervatham Jaya , Li Xiaofan , Mitchell Cheryl K. , Lin Ya-Ping , Heidelberger Ruth , O’Brien John
Published: September 2020

Calmodulin binding is a nearly universal property of gap junction proteins, imparting a calcium-dependent uncoupling behavior that can serve in an emergency to decouple a stressed cell from its neighbors. However, gap junctions that function as electrical synapses within networks of neurons routinely encounter large fluctuations in local cytoplasmic calcium concentration; frequent uncoupling would be impractical and counterproductive. We have studied the properties and functional consequences of calmodulin binding to the electrical synapse protein Connexin 35 (Cx35 or gjd2b), homologous to mammalian Connexin 36 (Cx36 or gjd2). We find that specializations in Cx35 calmodulin binding sites make it relatively impervious to moderately high levels of cytoplasmic calcium. Calmodulin binding to a site in the C-terminus causes uncoupling when calcium reaches low micromolar concentrations, a behavior prevented by mutations that eliminate calmodulin binding. However, milder stimuli promote calcium/calmodulin-dependent protein kinase II activity that potentiates coupling without interference from calmodulin binding. A second calmodulin binding site in the end of the Cx35 cytoplasmic loop, homologous to a calmodulin binding site present in many connexins, binds calmodulin with very low affinity and stoichiometry. Together, the calmodulin binding sites cause Cx35 to uncouple only at extreme levels of intracellular calcium.
The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes
Authors: Kubin Thomas , Cetinkaya Ayse , Kubin Natalia , Bramlage Peter , Sen-Hild Bedriye , Gajawada Praveen , Akintürk Hakan , Schönburg Markus , Schaper Wolfgang , Choi Yeong-Hoon , Barancik Miroslav , Richter Manfred
Published: September 2020

Fetal and hypertrophic remodeling are hallmarks of cardiac restructuring leading chronically to heart failure. Since the Ras/Raf/MEK/ERK cascade (MAPK) is involved in the development of heart failure, we hypothesized, first, that fetal remodeling is different from hypertrophy and, second, that remodeling of the MAPK occurs. To test our hypothesis, we analyzed models of cultured adult rat cardiomyocytes as well as investigated myocytes in the failing human myocardium by western blot and confocal microscopy. Fetal remodeling was induced through endothelial morphogens and monitored by the reexpression of Acta2, Actn1, and Actb. Serum-induced hypertrophy was determined by increased surface size and protein content of cardiomyocytes. Serum and morphogens caused reprogramming of Ras/Raf/MEK/ERK. In both models H-Ras, N-Ras, Rap2, B- and C-Raf, MEK1/2 as well as ERK1/2 increased while K-Ras was downregulated. Atrophy, MAPK-dependent ischemic resistance, loss of A-Raf, and reexpression of Rap1 and Erk3 highlighted fetal remodeling, while A-Raf accumulation marked hypertrophy. The knock-down of B-Raf by siRNA reduced MAPK activation and fetal reprogramming. In conclusion, we demonstrate that fetal and hypertrophic remodeling are independent processes and involve reprogramming of the MAPK.
The Effect of Low Temperatures on Environmental Radiation Damage in Living Systems: Does Hypothermia Show Promise for Space Travel?
Authors: Fukunaga Hisanori
Published: September 2020

Low-temperature treatments (i.e., hypothermia) may be one way of regulating environmental radiation damage in living systems. With this in mind, hibernation under hypothermic conditions has been proposed as a useful approach for long-term human space flight. However, the underlying mechanisms of hypothermia-induced radioresistance are as yet undetermined, and the conventional risk assessment of radiation exposure during hibernation remains insufficient for estimating the effects of chronic exposure to galactic cosmic rays (GCRs). To promote scientific discussions on the application of hibernation in space travel, this literature review provides an overview of the progress to date in the interdisciplinary research field of radiation biology and hypothermia and addresses possible issues related to hypothermic treatments as countermeasures against GCRs. At present, there are concerns about the potential effects of chronic radiation exposure on neurological disorders, carcinogenesis, ischemia heat failures, and infertility in astronauts; these require further study. These concerns may be resolved by comparing and integrating data gleaned from experimental and epidemiological studies.
CDK4/6 Inhibitors in Breast Cancer Treatment: Potential Interactions with Drug, Gene, and Pathophysiological Conditions
Authors: Roncato Rossana , Angelini Jacopo , Pani Arianna , Cecchin Erika , Sartore-Bianchi Andrea , Siena Salvatore , De Mattia Elena , Scaglione Francesco , Toffoli Giuseppe
Published: September 2020

Palbociclib, ribociclib, and abemaciclib belong to the third generation of cyclin-dependent kinases inhibitors (CDKis), an established therapeutic class for advanced and metastatic breast cancer. Interindividual variability in the therapeutic response of CDKis has been reported and some individuals may experience increased and unexpected toxicity. This narrative review aims at identifying the factors potentially concurring at this variability for driving the most appropriate and tailored use of CDKis in the clinic. Specifically, concomitant medications, pharmacogenetic profile, and pathophysiological conditions could influence absorption, distribution, metabolism, and elimination pharmacokinetics. A personalized therapeutic approach taking into consideration all factors potentially contributing to an altered pharmacokinetic/pharmacodynamic profile could better drive safe and effective clinical use.
Arachidonic Acid Metabolites of CYP450 Enzymes and HIF-1α Modulate Endothelium-Dependent Vasorelaxation in Sprague-Dawley Rats under Acute and Intermittent Hyperbaric Oxygenation
Authors: Mihaljević Zrinka , Matić Anita , Stupin Ana , Frkanec Ruža , Tavčar Branka , Kelava Vanja , Tartaro Bujak Ivana , Kolobarić Nikolina , Kibel Aleksandar , Drenjančević Ines
Published: September 2020

Acetylcholine-induced vasorelaxation (AChIR) and responses to reduced pO2 (hypoxia-induced relaxation (HIR), 0% O2) were assessed in vitro in aortic rings of healthy male Sprague-Dawley rats (N = 252) under hyperbaric (HBO2) protocols. The studied groups consisted of the CTRL group (untreated); the A-HBO2 group (single HBO2; 120 min of 100% O2 at 2.0 bars); the 24H-HBO2 group (examined 24 h after single exposure) and the 4D-HBO2 group (four consecutive days of single HBO2). AChIR, sensitivity to ACh and iNOS expression were decreased in the A-HBO2 group. HIR was prostanoid- and epoxyeicosatrienoic acid (EET)-mediated. HIF-1α expression was increased in the 24H-HBO2 and 4D-HBO2 groups. LW6 (HIF-1α inhibitor) decreased HIR in the 24H-HBO2 group. HBO2 affected the expression of COX-1 and COX-2. CYP2c11 expression was elevated in the 24H-HBO2 and 4D-HBO2 groups. Concentrations of arachidonic acid (AA) metabolites 14(15)-DiHET, 11(12)-DiHET and 8(9)-DiHET were increased in A-HBO2 and 24H-HBO2. An increased concentration of 8(9)-EET was observed in the A-HBO2 and 24h-HBO2 groups vs. the CTRL and 4D-HBO2 groups, and an increased concentration of 5(6)-DiHET was observed in the 24H-HBO2 group vs. the 4D-HBO2 group. The 20-HETE concentration was increased in the A-HBO2 group. All were determined by LC-MS/MS of the aorta. The results show that AChIR in all groups is mostly NO-dependent. HIR is undoubtedly mediated by the CYP450 enzymes’ metabolites of AA, whereas HIF-1α contributes to restored HIR. Vasoconstrictor metabolites of CYP450 enzymes contribute to attenuated AChIR and HIR in A-HBO2.
Infrared Thermography Investigation of Heat Transfer on Outlet Guide Vanes in a Turbine Rear Structure
Authors: Jonsson Isak , Chernoray Valery , Dhanasegaran Radheesh
Published: September 2020

Aerothermal heat transfer measurements in fluid dynamics have a relatively high acceptance of uncertainty due to the intricate nature of the experiments. The large velocity and pressure gradients present in turbomachinery application add further complexity to the measurement procedure. Recent method and manufacturing development has addressed some of the primary sources of uncertainty in these heat transfer measurements. However, new methods have so far not been applied in a holistic approach for heat transfer studies. This gap is bridged in the present study where a cost-effective and highly accurate method for heat transfer measurements is implemented, utilising infrared thermography technique (IRT) for surface temperature measurement. Novel heat transfer results are obtained for the turbine rear sturcture (TRS), at engine representative conditions for three different outlet guide vane (OGV) blade loading and at Reynolds Number of 235000. In addition to that, an extensive description of the implementation and error mitigation is presented.
Developing Amaia: A Conversational Agent for Helping Portuguese Entrepreneurs—An Extensive Exploration of Question-Matching Approaches for Portuguese
Authors: Santos José , Duarte Luís , Ferreira João , Alves Ana , Oliveira Hugo Gonçalo
Published: September 2020

This paper describes how we tackled the development of Amaia, a conversational agent for Portuguese entrepreneurs. After introducing the domain corpus used as Amaia’s Knowledge Base (KB), we make an extensive comparison of approaches for automatically matching user requests with Frequently Asked Questions (FAQs) in the KB, covering Information Retrieval (IR), approaches based on static and contextual word embeddings, and a model of Semantic Textual Similarity (STS) trained for Portuguese, which achieved the best performance. We further describe how we decreased the model’s complexity and improved scalability, with minimal impact on performance. In the end, Amaia combines an IR library and an STS model with reduced features. Towards a more human-like behavior, Amaia can also answer out-of-domain questions, based on a second corpus integrated in the KB. Such interactions are identified with a text classifier, also described in the paper.