bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Design of a Novel ‘S-shape’ Impeller Blade for a Microbubble Pump
Authors: Jeon Seok-Yun , Yoon Joon-Yong , Jang Choon-Man
Published: May 2019

The newly designed impeller blade, a so-called novel ‘S-shape’ blade, used for microbubble pumps has been introduced to enhance pump performance. Unlike a conventional blade having separated blades, like cantilever-shape blades, the newly designed impeller has a continuous blade, thus having a relatively robust structure as compared to a conventional impeller. The optimal blade design of the ‘S-shape’ blade has been demonstrated to obtain a higher pump efficiency. To analyze the three-dimensional flow field inside the pump by numerical simulation, a general analysis code, ANSYS CFX, is employed in the present work. The computed pump efficiency has a maximum error of 4 percent compared to the experimental data. The optimal design of the pump impeller blade is based on geometric constraints considering blade manufacturing, and uses three design variables: the number of blades, the blade thickness and the radius of the blade rib. The response surface method, a global optimization method, is employed to optimize the pump impeller blade. Throughout the blade optimization of the ‘S-shape’ blade, it is found that the chief influence on the pump efficiency is the number of the impeller blades. Pump efficiency, an object function, is increased by up to 35.3 percent, which corresponds to a 3.7 percent increase compared to the reference one. It is no use to say that the ‘S-shape’ blade having a continuously connected blade has more rigid characteristics. The larger pressure increases of the optimized pump along with the volute casing wall is observed from the middle position of the rotational direction, which comes from the increase of momentum energy due to larger circulating flow inside each blade passage as compared to the reference one. The detailed flow field inside the pump blades is also analyzed and compared.
Configuration Optimization and Performance Comparison of STHX-DDB and STHX-SB by A Multi-Objective Genetic Algorithm
Authors: Xu Zhe , Guo Yingqing , Mao Haotian , Yang Fuqiang
Published: May 2019

Based on the thermohydraulic calculation model verified in this study and Non-dominated Sorted Genetic Algorithm-II (NSGA-II), a multi-objective configuration optimization method is proposed, and the performances of shell-and-tube heat exchanger with disc-and-doughnut baffles (STHX-DDB) and shell-and-tube heat exchanger with segmental baffles (STHX-SB) are compared after optimization. The results show that, except in the high range of heat transfer capacity of 16.5–17 kW, the thermohydraulic performance of STHX-DDB is better. Tube bundle diameter, inside tube bundle diameter, number of baffles of STHX-DDB and tube bundle diameter, baffle cut, number of baffles of STHX-SB are chosen as design parameters, and heat transfer capacity maximization and shell-side pressure drop minimization are considered as common optimization objectives. Three optimal configurations are obtained for STHX-DDB and another three are obtained for STHX-SB. The optimal results show that all the six selected optimal configurations are better than the original configurations. For STHX-DDB and STHX-SB, compared with the original configurations, the heat transfer capacity of optimal configurations increases by 6.26% on average and 5.16%, respectively, while the shell-side pressure drop decreases by 44.33% and 19.16% on average, respectively. It indicates that the optimization method is valid and feasible and can provide a significant reference for shell-and-tube heat exchanger design.
A High-Performance Stochastic Fractal Search Algorithm for Optimal Generation Dispatch Problem
Authors: Pham Ly Huu , Duong Minh Quan , Phan Van-Duc , Nguyen Thang Trung , Nguyen Hoang-Nam
Published: May 2019

This paper proposes applications of a modified stochastic fractal search algorithm (MSFS) to solve the economic load dispatch problem (ELD) in which valve-point effects, prohibited operating zones, power losses in all conductors, multi-fuel sources and other constraints of power system are taken into consideration. The proposed method is first developed in the study by performing two modifications on two procedures of new solution generation from conventional stochastic fractal search (SFS). The first modification is used to change the strategy of producing new solutions of the first and the second update procedures while the second one is to newly update the worst solutions in the first update process and the best solutions in the second update process. These modifications have major influence on the solution search performance of the proposed method. All improvements of the proposed method can be illustrated by solving and analyzing results from various test systems with different system scales including 3-unit, 6-unit, 10-unit, and 20-unit systems. Comparison of results obtained by MSFS, SFS, and other existing methods indicates that the proposed MSFS method is more effective and robust than compared methods in terms of solution quality, high-quality solution search stability and convergence process. Consequently, the proposed method should be used as a very favorable optimization method for the ELD problem and it should be tried for other optimization problems in electrical engineering.
The Impact of Biodiesel Fuel on Ethanol/Diesel Blends
Authors: Al-Esawi Nawar , Al Qubeissi Mansour , Kolodnytska Ruslana
Published: May 2019

The interest in biofuels was stimulated by the fossil fuel depletion and global warming. This work focuses on the impact of biodiesel fuel on ethanol/diesel (ED) fuel blends. The soybean methyl ester was used as a representative composition of typical biodiesel fuels. The heating and evaporation of ethanol–biodiesel–diesel (EBD) blends were investigated using the Discrete–Component (DC) model. The Cetane Number (CN) of the EBD blends was predicted based on the individual hydrocarbon contributions in the mixture. The mixture viscosity was predicted using the Universal Quasi-Chemical Functional group Activity Coefficients and Viscosity (UNIFAC–VISCO) method, and the lower heating value of the mixture was predicted based on the volume fractions and density of species and blends. Results revealed that a mixture of up to 15% biodiesel, 5% ethanol, and 80% diesel fuels had led to small variations in droplet lifetime, CN, viscosity, and heating value of pure diesel, with less than 1.2%, 0.2%, 2%, and 2.2% reduction in those values, respectively.
Modified Power Curves for Prediction of Power Output of Wind Farms
Authors: Vahidzadeh Mohsen , Markfort Corey D.
Published: May 2019

Power curves are used to model power generation of wind turbines, which in turn is used for wind energy assessment and forecasting total wind farm power output of operating wind farms. Power curves are based on ideal uniform inflow conditions, however, as wind turbines are installed in regions of heterogeneous and complex terrain, the effect of non-ideal operating conditions resulting in variability of the inflow must be considered. We propose an approach to include turbulence, yaw error, air density, wind veer and shear in the prediction of turbine power by using high resolution wind measurements. In this study, two modified power curves using standard ten-minute wind speed and high resolution one-second data along with a derived power surface were tested and compared to the standard operating curve for a 2.5 MW horizontal axis wind turbine. Data from supervisory control and data acquisition (SCADA) system along with wind speed measurements from a nacelle-mounted sonic anemometer and wind speed measurements from a nearby meteorological tower are used in the models. The results show that all of the proposed models perform better than the standard power curve while the power surface results in the most accurate power prediction.
Proposal of a Novel Semi-Submersible Floating Wind Turbine Platform Composed of Inclined Columns and Multi-Segmented Mooring Lines
Authors: Liu Zhenqing , Zhou Qingsong , Tu Yuangang , Wang Wei , Hua Xugang
Published: May 2019

The semi-submersible floating offshore wind turbine has been studied in detail due to its good stability. However, the occurrence of typhoons are very frequent in China’s offshore area, putting forward a higher requirement for the stability of the floating wind turbine system. By changing the connection mode of the mooring line as well as the structural form of the platform based on the original OC4 model, two groups of models were examined by an in-house developed code named as the Analysis Tool of Floating Wind Turbine (AFWT). The influence of the arrangement of the mooring lines and the inclination angle of the upper columns on the motion response were clarified. It was found that the surge motion of the platform would be obviously decreased by decreasing the length of the upper segments of the mooring lines, while the heave motion of the platform would be significantly decreased as increasing the inclined angle of the columns. Therefore, a new model integrating the optimized multi-segmented mooring lines and the optimized inclined columns was proposed. The examinations showed that compared with the response motions of the original OC4 semi-submersible model, the proposed model could reduce both the surge and heave motions of the platform effectively.
Energy Storage Sizing Strategy for Grid-Tied PV Plants under Power Clipping Limitations
Authors: Müller Nicolás , Kouro Samir , Zanchetta Pericle , Wheeler Patrick , Bittner Gustavo , Girardi Francesco
Published: May 2019

This paper presents an analyses of an Energy Storage System (ESS) for grid-tied photovoltaic (PV) systems, in order to harness the energy usually lost due to PV array oversizing. A real case of annual PV power generation analysis is presented to illustrate the existing problem and future solutions. Three PV modeling techniques have been applied to estimate non-measured non-harnessed PV power to provide an ESS energy and power sizing strategy. Moreover, a control strategy to store or release power from the DC-link, without modifying the Maximum Power Point Tracking (MPPT) strategy, is presented. The results show an estimation of the annual power loss caused by oversizing the PV array. The ESS sizing strategy gives insight into not only the energy requirements, but also the power requirements of the system. Simulation results show that the proposed ESS control strategy is capable of harnessing the extra power without modifying the existing power converter of the PV plant nor its control strategy.
An Alterable Structure Power Router with General AC and DC Port for Microgrid Applications
Authors: Yao Gang , Zhang Tao , Zhou Lidan , Li Qiang , Jin Nan
Published: May 2019

This paper proposes an alterable structure power router (PR) topology which shares the ability of general Alternating Current (AC) and Direct Current (DC) port. This alterable structure PR aims to better implement the interconnections among micro-grids, renewable energy, and traditional grids. The PR’s converter structure is alterable according to the system power. Based on the operation analysis of the PR, the mathematic model of the power router is established and the relationship between switch states and port voltage is analyzed. According to the PR mathematical model, the control method is designed to realize current control in both AC and DC mode. With the proposed power router topology, the PR’s port can be used in both AC and DC situations, which saves the cost of traditional PRs and increases economic efficiency. The simulation and experimental results prove the good steady-state and dynamic performance of the proposed power router topology.
Quantitative Analysis of Consumer Preferences of Windows Set in South Korea: The Role of Energy Efficiency Levels
Authors: Maeng Kwan Byum , Jung Jiyeon , Koo Yoonmo
Published: May 2019

The building sector is considered to be important for Korean energy issues as it accounts for approximately 20% of Korea’s final energy consumption. As one of Korea’s passive strategies in its emission reduction plan is reducing energy consumption through improvements in energy efficiency because the energy loss mostly occurs from window sets, this study aims to examine the preferences and role of the energy efficiency level of window sets in South Korea. Given that the lifespan of a building exceeds 20 years, a building’s energy efficiency significantly impacts accumulated energy savings. However, window sets affect not only energy efficiency, but also the interior appearance of the building; therefore, it is important to understand consumer preferences and to examine their effect on building energy reduction accordingly. Using a mixed logit model, this study analyzes window set preferences and energy savings. As a result, this study determines that consumers consider the energy efficiency level to be the second most important factor in determining window preference, following the cost of the window. In addition, this study found that the marginal willingness to pay for efficiency level 2 window sets compared to level 3 window sets is USD 1256. For level 1 window sets, this figure increases to USD 3140. Further, a scenario analysis is conducted to analyze the government incentive program’s effectiveness in encouraging consumers to purchasing higher energy efficiency more efficient products, and thus in promoting the eco-friendly consumption of in households. Taking into consideration of households’ willingness to pay and cost saving amount for using energy efficient window sets, the optimal value of government incentives of is found to be approximately USD 700 is found to be optimal.
Terrestrial Cosmopolitanism, Posthumanism, and Multispecies Modes of Being in Cereus Blooms at Night
Authors: Press Sara V.
Published: May 2019

Cosmopolitanism has generally been used to describe a philosophy that imagines all humans as citizens of a single “human” community. This article explores a terrestrial cosmopolitanism that challenges the colonial discourse of human exceptionalism by extending the democratization of people to include environmental bodies within their global context, replacing hierarchies with collectivities to reveal humanism’s underrepresented others. Examining interspecies alliances in Shani Mootoo’s Cereus Blooms at Night, I look towards terrestrial cosmopolitanism as an alternative to anthropocentric forms of cosmopolitanism that continue to reinscribe colonialist aspirations and ontologically exclusionary practices. Mootoo’s work decenters how we think about humans and the environment and offers a nuanced depiction of a positive interspecies community that resists harmful humanist taxonomies. Reading the novel’s protagonist, Mala, as a posthuman figure, I argue that her rejection of human language, in conjunction with her nonhuman interactions, positions her as a keeper of collectivity, as she creates a third space of subjectivity in her garden that blurs the boundaries between humans and nonhumans.
Sickle Cell Anaemia Prevalence among Newborns in the Brazilian Amazon-Savanna Transition Region
Authors: Souza Rayane Cristina , Miranda Neto Pedro Agnel Dias , Santos Jessflan Rafael Nascimento , Monteiro Sílvio Gomes , Gonçalves Maria Cláudia , Silva Fabrício Brito , Holanda Rodrigo Assuncao , Santos Julliana Ribeiro Alves
Published: May 2019

Sickle cell anaemia is one of the most common hemoglobinopathies worldwide and an important public health problem in Brazil. This study evaluated the prevalence of sickle cell anaemia and its traits in newborns from the Amazon-Savanna Transition Region in the state of Maranhão, Brazil. A cross-sectional study was carried out, based on data from neonatal screening tests performed in 2013–2015 in Maranhão. The Hardy-Weinberg theorem was applied to analyse the frequency of expected homozygotes based on HbSS phenotype. A spatial-temporal distribution analysis was performed to delimit the regions with the greatest number of newborn cases with sickle cell anaemia. Of 283,003 newborns, 162 were found to have sickle cell anaemia, while 10,794 had a sickle cell trait, with a prevalence of 0.05% and 3.8%, respectively. The prevalence of expected homozygotes was higher in the North Region and in the state capital of Maranhão. This study may contribute to existing social and public health actions or the creation of new strategies for sickle cell disease in endemic areas in Brazil to improve the quality of life.
Community-Based Participatory Research and Drug Utilization Research to Improve Childhood Diarrhea Case Management in Ujjain, India: A Cross-Sectional Survey
Authors: Mathur Aditya , Baghel Devendra , Jaat Jitendra , Diwan Vishal , Pathak Ashish
Published: May 2019

Childhood diarrhea continues to be a major cause of under-five (U-5) mortality globally and in India. In this study, 1571 U-5 children residing in nine rural villages and four urban slums in Ujjain, India were included with the objective to use community participation and drug utilization research to improve diarrheal case management. The mean age was 2.08 years, with 297 (19%), children living in high diarrheal index households. Most mothers (70%) considered stale food, teething (62%), and hot weather (55%) as causes of diarrhea. Water, sanitation, and hygiene (WASH)-related characteristics revealed that most (93%) households had toilets, but only 23% of the children used them. The study identified ineffective household water treatment by filtration through cloth by most (93%) households and dumping of household waste on the streets (89%). The results revealed low community awareness of correct causes of diarrhea (poor hand hygiene, 21%; littering around the household, 15%) and of correct diarrhea treatment (oral rehydration solution (ORS) and zinc use, 29% and 11%, respectively) and a high antibiotic prescription rate by healthcare providers (83%). Based on the results of the present study, context-specific house-to-house interventions will be designed and implemented.
Microplastic Pollution in Surface Water of Urban Lakes in Changsha, China
Authors: Yin Lingshi , Jiang Changbo , Wen Xiaofeng , Du Chunyan , Zhong Wei , Feng Zhiqiao , Long Yuannan , Ma Yuan
Published: May 2019

As emerging pollutants, microplastics have attracted the attention of scholars from all over the world. However, there is a lack of research on freshwater areas, even in densely populated urban areas. This study investigated eight urban lakes in Changsha, China. It was found that microplastic concentrations ranged from 2425 ± 247.5 items/m3 to 7050 ± 1060.66 items/m3 in the surface water of research areas and the maximum concentration was found in Yuejin Lake, a tourist spot in the center of the city. Anthropogenic factors are an important reason for microplastic abundance in urban lakes. The major shape of microplastics was linear and most of the microplastics were transparent. More than 89.5% of the microplastics had a size of less than 2 mm. Polypropylene was the dominant type in the studied waters. This study can provide a valuable reference for a better understanding of microplastic pollution in urban areas of China.
Coping and Anxiety in Caregivers of Dependent Older Adult Relatives
Authors: Pérez-Cruz Margarita , Parra-Anguita Laura , López-Martínez Catalina , Moreno-Cámara Sara , del-Pino-Casado Rafael
Published: May 2019

The aim of this study was to analyze the relationship between coping and anxiety in caregivers of dependent older adult relatives. A cross-sectional study was carried out in the province of Jaén (Andalusia, Spain). The convenience sample consisted of 198 family caregivers of dependent older adults. The main measurements were anxiety (Hamilton scale), coping (Brief COPE), subjective burden (Caregiver Strain Index), objective burden and sex of the caregiver. The main analyses were bivariate analysis using the Pearson correlation coefficient, and multivariate analysis using multiple linear regression. An independent regression model was developed for anxiety and each type of coping, adjusting for sex, subjective burden and objective burden. Our results demonstrate that anxiety was negatively associated with planning (partial r = −0.18), acceptance (partial r = −0.22) and humor (partial r = −0.20), and it was positively associated with self-distraction (partial r = 0.19), venting (partial r = 0.22), denial (partial r = 0.27) and self-blame (partial r = 0.25). Planning, acceptance and humor coping strategies may be protective factors of anxiety. Strategies such self-management, relief, denial and self-blame may be risk factors for anxiety.
Oxidative Stress Effects of Soluble Sulfide on Human Hepatocyte Cell Line LO2
Authors: Shao Ying , Chen Zhongli , Wu Lingling
Published: May 2019

Soluble sulfide is well known for its toxicity and corrosion for hundreds of years. However, recent studies have demonstrated that hydrogen sulfide (H2S)—a novel gasotransmitter—supports a critical role during neuromodulation, cell proliferation, and cardioprotection for organisms. In particular, soluble sulfide plays multifaceted signaling functions in mammals during oxidative stress processes. However, the specific molecular regulation of soluble sulfide during oxidative stress remains unclear. In this study, Na2S was implemented as a soluble sulfide donor to expose LO2 cells. The 3-(4,5-dimethylthiazolyl-2),-2,5-diphenyltetrazolium bromide (MTT) assay, hydroxyl radical assay, superoxide dismutase (SOD) assay, and glutathione peroxidase (GSH-PX) assay were applied to analyze cytotoxicity, hydroxyl radical levels, SOD and GSH-Px activities, respectively. Soluble sulfide at a concentration 0.01–1.0 mM/L resulted in a marked and concentration-dependent reduction of LO2 cell viability. At low concentrations, sulfide solutions increased SOD activity and GSH-Px activity of LO2 after 24 h exposure, exhibiting a clear hormesis-effect and indicating the protective ability of soluble sulfide against oxidative stress. The decline in SOD and GSH-Px and the increase in hydroxyl radical (0.08–1.0 mM/L) suggested that oxidative damage could be a possible mechanism for sulfide-induced cytotoxicity.
Is the Whole More Than the Sum of Its Parts? Health Effects of Different Types of Traffic Noise Combined
Authors: Seidler Andreas , Hegewald Janice , Seidler Anna Lene , Schubert Melanie , Zeeb Hajo
Published: May 2019

Many epidemiological studies find that people exposed to aircraft, road or railway traffic noise are at increased risk of illness, including cardiovascular disease (CVD) and depression. It is unclear how the combined exposure to these different types of traffic noise affects disease risks. This study addresses this question with a large secondary data-based case-control study (“NORAH disease risk study”). The Akaike information criterion (AIC) is used to compare two different models estimating the disease risks of combined traffic noise. In comparison with the conventional energetic addition of noise levels, the multiplication of CVD risks as well as depression risks reveals a considerably better model fit as expressed by much lower AIC values. This is also the case when risk differences between different types of traffic noise are taken into account by applying supplements or reductions to the single traffic noise pressure levels in order to identify the best fitting energetic addition model. As a consequence, the conventionally performed energetic addition of noise levels might considerably underestimate the health risks of combined traffic noise. Based on the NORAH disease risk study, “epidemiological risk multiplication” seems to provide a better estimate of the health risks of combined traffic noise exposures compared to energetic addition. If confirmed in further studies, these results should imply consequences for noise protection measures as well as for traffic planning.
Structure-Based Approach for the Prediction of Mu-opioid Binding Affinity of Unclassified Designer Fentanyl-Like Molecules
Authors: Floresta Giuseppe , Rescifina Antonio , Abbate Vincenzo
Published: May 2019

Three quantitative structure-activity relationship (QSAR) models for predicting the affinity of mu-opioid receptor (OR) ligands have been developed. The resulted models, exploiting the accessibility of the QSAR modeling, generate a useful tool for the investigation and identification of unclassified fentanyl-like structures. The models have been built using a set of 115 molecules using Forge as a software, and the quality was confirmed by statistical analysis, resulting in being effective for their predictive and descriptive capabilities. The three different approaches were then combined to produce a consensus model and were exploited to explore the chemical landscape of 3000 fentanyl-like structures, generated by a theoretical scaffold-hopping approach. The findings of this study should facilitate the identification and classification of new OR ligands with fentanyl-like structures.
Natural Compounds for Alzheimer’s Disease Therapy: A Systematic Review of Preclinical and Clinical Studies
Authors: Andrade Stephanie , Ramalho Maria João , Loureiro Joana Angélica , Pereira Maria do Carmo
Published: May 2019

Alzheimer’s Disease (AD) is a neurodegenerative disorder related with the increase of age and it is the main cause of dementia in the world. AD affects cognitive functions, such as memory, with an intensity that leads to several functional losses. The continuous increase of AD incidence demands for an urgent development of effective therapeutic strategies. Despite the extensive research on this disease, only a few drugs able to delay the progression of the disease are currently available. In the last years, several compounds with pharmacological activities isolated from plants, animals and microorganisms, revealed to have beneficial effects for the treatment of AD, targeting different pathological mechanisms. Thus, a wide range of natural compounds may play a relevant role in the prevention of AD and have proven to be efficient in different preclinical and clinical studies. This work aims to review the natural compounds that until this date were described as having significant benefits for this neurological disease, focusing on studies that present clinical trials.
Menaquinone-4 Suppresses Lipopolysaccharide-Induced Inflammation in MG6 Mouse Microglia-Derived Cells by Inhibiting the NF-κB Signaling Pathway
Authors: Saputra Wahyu Dwi , Aoyama Nao , Komai Michio , Shirakawa Hitoshi
Published: May 2019

The overactivation of microglia is known to trigger inflammatory reactions in the central nervous system, which ultimately induce neuroinflammatory disorders including Alzheimer’s disease. However, increasing evidence has shown that menaquinone-4 (MK-4), a subtype of vitamin K2, can attenuate inflammation in the peripheral system. Whereas it was also observed at high levels within the brain, its function in this organ has not been well characterized. Therefore, we investigated the effect of MK-4 on microglial activation and clarified the underlying mechanism. Mouse microglia-derived MG6 cells were exposed to lipopolysaccharide (LPS) either with or without MK-4 pretreatment. Cell responses with respect to inflammatory cytokines (Il-1β, Tnf-α, and Il-6) were measured by qRT-PCR. We further analyzed the phosphorylation of TAK1, IKKα/β, and p65 of the NF-κB subunit by Western blotting. We observed that in LPS-induced MG6 cells, MK-4 dose-dependently suppressed the upregulation of inflammatory cytokines at the mRNA level. It also significantly decreased the phosphorylation of p65, but did not affect that TAK1 and IKKα/β. Furthermore, the nuclear translocation of NF-κB in LPS-induced MG6 cells was inhibited by MK-4. These results indicate that MK-4 attenuates microglial inflammation by inhibiting NF-κB signaling.
Geranylgeraniol Suppresses the Expression of IRAK1 and TRAF6 to Inhibit NFκB Activation in Lipopolysaccharide-Induced Inflammatory Responses in Human Macrophage-Like Cells
Authors: Giriwono Puspo E. , Shirakawa Hitoshi , Ohsaki Yusuke , Sato Shoko , Aoyama Yukihide , Ho Hsin-Jung , Goto Tomoko , Komai Michio
Published: May 2019

Geranylgeraniol (GGOH), a natural isoprenoid found in plants, has anti-inflammatory effects via inhibiting the activation of nuclear factor-kappa B (NFκB). However, its detailed mechanism has not yet been elucidated. Recent studies have revealed that isoprenoids can modulate signaling molecules in innate immune responses. We found that GGOH decreased the expression of lipopolysaccharide (LPS)-induced inflammatory genes in human macrophage-like THP-1 cells. Furthermore, we observed that the suppression of NFκB signaling proteins, in particular interleukin-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), occurred in GGOH-treated cells prior to LPS stimulation, suggesting an immunomodulatory effect. These results indicate that GGOH may modulate and help prevent excessive NFκB activation that can lead to numerous diseases.
Review of Therapeutic Applications of Radiolabeled Functional Nanomaterials
Authors: Jeon Jongho
Published: May 2019

In the last two decades, various nanomaterials have attracted increasing attention in medical science owing to their unique physical and chemical characteristics. Incorporating radionuclides into conventionally used nanomaterials can confer useful additional properties compared to the original material. Therefore, various radionuclides have been used to synthesize functional nanomaterials for biomedical applications. In particular, several α- or β-emitter-labeled organic and inorganic nanoparticles have been extensively investigated for efficient and targeted cancer treatment. This article reviews recent progress in cancer therapy using radiolabeled nanomaterials including inorganic, polymeric, and carbon-based materials and liposomes. We first provide an overview of radiolabeling methods for preparing anticancer agents that have been investigated recently in preclinical studies. Next, we discuss the therapeutic applications and effectiveness of α- or β-emitter-incorporated nanomaterials in animal models and the emerging possibilities of these nanomaterials in cancer therapy.
Signal Transduction Pathways in Plants for Resistance against Pathogens
Authors: Liu Jian-Zhong , Lam Hon-Ming
Published: May 2019

Plants are constantly exposed to a diverse group of pathogens and have evolved sophisticated immune systems to combat pathogen attacks [...]
Flavivirus Replication Organelle Biogenesis in the Endoplasmic Reticulum: Comparison with Other Single-Stranded Positive-Sense RNA Viruses
Authors: Arakawa Masashi , Morita Eiji
Published: May 2019

Some single-stranded positive-sense RNA [ssRNA(+)] viruses, including Flavivirus, generate specific organelle-like structures in the host endoplasmic reticulum (ER). These structures are called virus replication organelles and consist of two distinct subdomains, the vesicle packets (VPs) and the convoluted membranes (CMs). The VPs are clusters of small vesicle compartments and are considered to be the site of viral genome replication. The CMs are electron-dense amorphous structures observed in proximity to the VPs, but the exact roles of CMs are mostly unknown. Several recent studies have revealed that flaviviruses recruit several host factors that are usually used for the biogenesis of other conventional organelles and usurp their function to generate virus replication organelles. In the current review, we summarize recent studies focusing on the role of host factors in the formation of virus replication organelles and discuss how these intricate membrane structures are organized.
Involvement of BIG5 and BIG3 in BRI1 Trafficking Reveals Diverse Functions of BIG-subfamily ARF-GEFs in Plant Growth and Gravitropism
Authors: Xue Shan , Zou Junjie , Liu Yangfan , Wang Ming , Zhang Chunxia , Le Jie
Published: May 2019

ADP-ribosylation factor-guanine nucleotide exchange factors (ARF-GEFs) act as key regulators of vesicle trafficking in all eukaryotes. In Arabidopsis, there are eight ARF-GEFs, including three members of the GBF1 subfamily and five members of the BIG subfamily. These ARF-GEFs have different subcellular localizations and regulate different trafficking pathways. Until now, the roles of these BIG-subfamily ARF-GEFs have not been fully revealed. Here, analysis of the BIGs expression patterns showed that BIG3 and BIG5 have similar expression patterns. big5-1 displayed a dwarf growth and big3-1 big5-1 double mutant showed more severe defects, indicating functional redundancy between BIG3 and BIG5. Moreover, both big5-1 and big3-1 big5-1 exhibited a reduced sensitivity to Brassinosteroid (BR) treatment. Brefeldin A (BFA)-induced BR receptor Brassinosteroid insensitive 1 (BRI1) aggregation was reduced in big5-1 mutant, indicating that the action of BIG5 is required for BRI1 recycling. Furthermore, BR-induced dephosphorylation of transcription factor BZR1 was decreased in big3-1 big5-1 double mutants. The introduction of the gain-of-function of BZR1 mutant BZR1-1D in big3-1 big5-1 mutants can partially rescue the big3-1 big5-1 growth defects. Our findings revealed that BIG5 functions redundantly with BIG3 in plant growth and gravitropism, and BIG5 participates in BR signal transduction pathway through regulating BRI1 trafficking.
The Cross-Talk Between the TNF-α and RASSF-Hippo Signalling Pathways
Authors: Oceandy Delvac , Amanda Bella , Ashari Faisal , Faizah Zakiyatul , Aziz M , Stafford Nicholas
Published: May 2019

The regulation of cell death through apoptosis is essential to a number of physiological processes. Defective apoptosis regulation is associated with many abnormalities including anomalies in organ development, altered immune response and the development of cancer. Several signalling pathways are known to regulate apoptosis including the Tumour Necrosis Factor-α (TNF-α) and Hippo signalling pathways. In this paper we review the cross-talk between the TNF-α pathway and the Hippo signalling pathway. Several molecules that tightly regulate the Hippo pathway, such as members of the Ras-association domain family member (RASSF) family proteins, interact and modulate some key proteins within the TNF-α pathway. Meanwhile, TNF-α stimulation also affects the expression and activation of core components of the Hippo pathway. This implies the crucial role of signal integration between these two major pathways in regulating apoptosis.
Liver Zonation in Health and Disease: Hypoxia and Hypoxia-Inducible Transcription Factors as Concert Masters
Authors: Kietzmann Thomas
Published: May 2019

The liver and its zonation contribute to whole body homeostasis. Acute and chronic, not always liver, diseases impair proper metabolic zonation. Various underlying pathways, such as β-catenin, hedgehog signaling, and the Hippo pathway, along with the physiologically occurring oxygen gradient, appear to be contributors. Interestingly, hypoxia and hypoxia-inducible transcription factors can orchestrate those pathways. In the current review, we connect novel findings of liver zonation in health and disease and provide a view about the dynamic interplay between these different pathways and cell-types to drive liver zonation and systemic homeostasis.
An Integrated Analysis of the Rice Transcriptome and Metabolome Reveals Differential Regulation of Carbon and Nitrogen Metabolism in Response to Nitrogen Availability
Authors: Xin Wei , Zhang Lina , Zhang Wenzhong , Gao Jiping , Yi Jun , Zhen Xiaoxi , Li Ziang , Zhao Ying , Peng Chengcheng , Zhao Chen
Published: May 2019

Nitrogen (N) is an extremely important macronutrient for plant growth and development. It is the main limiting factor in most agricultural production. However, it is well known that the nitrogen use efficiency (NUE) of rice gradually decreases with the increase of the nitrogen application rate. In order to clarify the underlying metabolic and molecular mechanisms of this phenomenon, we performed an integrated analysis of the rice transcriptome and metabolome. Both differentially expressed genes (DEGs) and metabolite Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that carbon and nitrogen metabolism is significantly affected by nitrogen availability. Further analysis of carbon and nitrogen metabolism changes in rice under different nitrogen availability showed that high N inhibits nitrogen assimilation and aromatic metabolism pathways by regulating carbon metabolism pathways such as the tricarboxylic acid (TCA) cycle and the pentose phosphate pathway (PPP). Under low nitrogen, the TCA cycle is promoted to produce more energy and α-ketoglutarate, thereby enhancing nitrogen transport and assimilation. PPP is also inhibited by low N, which may be consistent with the lower NADPH demand under low nitrogen. Additionally, we performed a co-expression network analysis of genes and metabolites related to carbon and nitrogen metabolism. In total, 15 genes were identified as hub genes. In summary, this study reveals the influence of nitrogen levels on the regulation mechanisms for carbon and nitrogen metabolism in rice and provides new insights into coordinating carbon and nitrogen metabolism and improving nitrogen use efficiency in rice.
Self-Assembled Benznidazole-Loaded Cationic Nanoparticles Containing Cholesterol/Sialic Acid: Physicochemical Properties, In Vitro Drug Release and In Vitro Anticancer Efficacy
Authors: dos Santos-Silva Alaine Maria , de Caland Lilia Basílio , do Nascimento Ednaldo Gomes , Oliveira Ana Luiza C. de S.L. , de Araújo-Júnior Raimundo F. , Cornélio Alianda Maira , Fernandes-Pedrosa Matheus F. , da Silva-Júnior Arnóbio Antônio
Published: May 2019

Cationic polymeric nanoparticles (NPs) have the ability to overcome biological membranes, leading to improved efficacy of anticancer drugs. The modulation of the particle-cell interaction is desired to control this effect and avoid toxicity to normal cells. In this study, we explored the surface functionalization of cationic polymethylmethacrylate (PMMA) NPs with two natural compounds, sialic acid (SA) and cholesterol (Chol). The performance of benznidazole (BNZ) was assessed in vitro in the normal renal cell line (HEK-293) and three human cancer cell lines, as follows: human colorectal cancer (HT-29), human cervical carcinoma (HeLa), and human hepatocyte carcinoma (HepG2). The structural properties and feasibility of NPs were evaluated and the changes induced by SA and Chol were determined by using multiple analytical approaches. Small (<200 nm) spherical NPs, with a narrow size distribution and high drug-loading efficiency were prepared by using a simple and reproducible emulsification solvent evaporation method. The drug interactions in the different self-assembled NPs were assessed by using Fourier transform-infrared spectroscopy. All formulations exhibited a slow drug-release profile and physical stability for more than 6 weeks. Both SA and Chol changed the kinetic properties of NPs and the anticancer efficacy. The feasibility and potential of SA/Chol-functionalized NPs has been demonstrated in vitro in the HEK-293, HepG2, HeLa, and HT-29 cell lines as a promising system for the delivery of BNZ.
mTOR in Human Diseases
Authors: Dormond Olivier
Published: May 2019

The human body regenerates constantly in part under the control of signaling pathways that regulate cell growth [...]
Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications
Authors: Longo Michele , Zatterale Federica , Naderi Jamal , Parrillo Luca , Formisano Pietro , Raciti Gregory Alexander , Beguinot Francesco , Miele Claudia
Published: May 2019

Obesity is a critical risk factor for the development of type 2 diabetes (T2D), and its prevalence is rising worldwide. White adipose tissue (WAT) has a crucial role in regulating systemic energy homeostasis. Adipose tissue expands by a combination of an increase in adipocyte size (hypertrophy) and number (hyperplasia). The recruitment and differentiation of adipose precursor cells in the subcutaneous adipose tissue (SAT), rather than merely inflating the cells, would be protective from the obesity-associated metabolic complications. In metabolically unhealthy obesity, the storage capacity of SAT, the largest WAT depot, is limited, and further caloric overload leads to the fat accumulation in ectopic tissues (e.g., liver, skeletal muscle, and heart) and in the visceral adipose depots, an event commonly defined as “lipotoxicity.” Excessive ectopic lipid accumulation leads to local inflammation and insulin resistance (IR). Indeed, overnutrition triggers uncontrolled inflammatory responses in WAT, leading to chronic low-grade inflammation, therefore fostering the progression of IR. This review summarizes the current knowledge on WAT dysfunction in obesity and its associated metabolic abnormalities, such as IR. A better understanding of the mechanisms regulating adipose tissue expansion in obesity is required for the development of future therapeutic approaches in obesity-associated metabolic complications.
OsbZIP81, A Homologue of Arabidopsis VIP1, May Positively Regulate JA Levels by Directly Targetting the Genes in JA Signaling and Metabolism Pathway in Rice
Authors: Liu Defang , Shi Shaopeng , Hao Zhijun , Xiong Wentao , Luo Meizhong
Published: May 2019

Rice (Oryza sativa L.) is one of the most important food crops in the world. In plants, jasmonic acid (JA) plays essential roles in response to biotic and abiotic stresses. As one of the largest transcription factors (TFs), basic region/leucine zipper motif (bZIP) TFs play pivotal roles through the whole life of plant growth. However, the relationship between JA and bZIP TFs were rarely reported, especially in rice. In this study, we found two rice homologues of Arabidopsis VIP1 (VirE2-interacting protein 1), OsbZIP81, and OsbZIP84. OsbZIP81 has at least two alternative transcripts, OsbZIP81.1 and OsbZIP81.2. OsbZIP81.1 and OsbZIP84 are typical bZIP TFs, while OsbZIP81.2 is not. OsbZIP81.1 can directly bind OsPIOX and activate its expression. In OsbZIP81.1 overexpression transgenic rice plant, JA (Jasmonic Acid) and SA (Salicylic acid) were up-regulated, while ABA (Abscisic acid) was down-regulated. Moreover, Agrobacterium, Methyl Jasmonic Acid (MeJA), and PEG6000 can largely induce OsbZIP81. Based on ChIP-Seq and Random DNA Binding Selection Assay (RDSA), we identified a novel cis-element OVRE (Oryza VIP1 response element). Combining ChIP-Seq and RNA-Seq, we obtained 1332 targeted genes that were categorized in biotic and abiotic responses, including α-linolenic acid metabolism and fatty acid degradation. Together, these results suggest that OsbZIP81 may positively regulate JA levels by directly targeting the genes in JA signaling and metabolism pathway in rice.
A Symphony of Signals: Intercellular and Intracellular Signaling Mechanisms Underlying Circadian Timekeeping in Mice and Flies
Authors: Hegazi Sara , Lowden Christopher , Rios Garcia Julian , Cheng Arthur H. , Obrietan Karl , Levine Joel D. , Cheng Hai-Ying Mary
Published: May 2019

The central pacemakers of circadian timekeeping systems are highly robust yet adaptable, providing the temporal coordination of rhythms in behavior and physiological processes in accordance with the demands imposed by environmental cycles. These features of the central pacemaker are achieved by a multi-oscillator network in which individual cellular oscillators are tightly coupled to the environmental day-night cycle, and to one another via intercellular coupling. In this review, we will summarize the roles of various neurotransmitters and neuropeptides in the regulation of circadian entrainment and synchrony within the mammalian and Drosophila central pacemakers. We will also describe the diverse functions of protein kinases in the relay of input signals to the core oscillator or the direct regulation of the molecular clock machinery.
Calcium-Binding Proteins in the Nervous System during Hibernation: Neuroprotective Strategies in Hypometabolic Conditions?
Authors: Gattoni Giacomo , Bernocchi Graziella
Published: May 2019

Calcium-binding proteins (CBPs) can influence and react to Ca2+ transients and modulate the activity of proteins involved in both maintaining homeostatic conditions and protecting cells in harsh environmental conditions. Hibernation is a strategy that evolved in vertebrate and invertebrate species to survive in cold environments; it relies on molecular, cellular, and behavioral adaptations guided by the neuroendocrine system that together ensure unmatched tolerance to hypothermia, hypometabolism, and hypoxia. Therefore, hibernation is a useful model to study molecular neuroprotective adaptations to extreme conditions, and can reveal useful applications to human pathological conditions. In this review, we describe the known changes in Ca2+-signaling and the detection and activity of CBPs in the nervous system of vertebrate and invertebrate models during hibernation, focusing on cytosolic Ca2+ buffers and calmodulin. Then, we discuss these findings in the context of the neuroprotective and neural plasticity mechanisms in the central nervous system: in particular, those associated with cytoskeletal proteins. Finally, we compare the expression of CBPs in the hibernating nervous system with two different conditions of neurodegeneration, i.e., platinum-induced neurotoxicity and Alzheimer’s disease, to highlight the similarities and differences and demonstrate the potential of hibernation to shed light into part of the molecular mechanisms behind neurodegenerative diseases.
A Robust Model for Circadian Redox Oscillations
Authors: del Olmo Marta , Kramer Achim , Herzel Hanspeter
Published: May 2019

The circadian clock is an endogenous oscillator that controls daily rhythms in metabolism, physiology, and behavior. Although the timekeeping components differ among species, a common design principle is a transcription-translation negative feedback loop. However, it is becoming clear that other mechanisms can contribute to the generation of 24 h rhythms. Peroxiredoxins (Prxs) exhibit 24 h rhythms in their redox state in all kingdoms of life. In mammalian adrenal gland, heart and brown adipose tissue, such rhythms are generated as a result of an inactivating hyperoxidation reaction that is reduced by coordinated import of sulfiredoxin (Srx) into the mitochondria. However, a quantitative description of the Prx/Srx oscillating system is still missing. We investigate the basic principles that generate mitochondrial Prx/Srx rhythms using computational modeling. We observe that the previously described delay in mitochondrial Srx import, in combination with an appropriate separation of fast and slow reactions, is sufficient to generate robust self-sustained relaxation-like oscillations. We find that our conceptual model can be regarded as a series of three consecutive phases and two temporal switches, highlighting the importance of delayed negative feedback and switches in the generation of oscillations.