bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy Stress-Mediated Cytotoxicity in Tuberous Sclerosis Complex 2-Deficient Cells with Nelfinavir and Mefloquine Treatment
Authors: McCann Henry D. , Johnson Charlotte E. , Errington Rachel J. , Davies D. Mark , Dunlop Elaine A. , Tee Andrew R.
Published: October 2018

To find new anti-cancer drug therapies, we wanted to exploit homeostatic vulnerabilities within Tuberous Sclerosis Complex 2 (TSC2)-deficient cells with mechanistic target of rapamycin complex 1 (mTORC1) hyperactivity. We show that nelfinavir and mefloquine synergize to selectively evoke a cytotoxic response in TSC2-deficient cell lines with mTORC1 hyperactivity. We optimize the concentrations of nelfinavir and mefloquine to a clinically viable range that kill cells that lack TSC2, while wild-type cells tolerate treatment. This new clinically viable drug combination causes a significant level of cell death in TSC2-deficient tumor spheroids. Furthermore, no cell recovery was apparent after drug withdrawal, revealing potent cytotoxicity. Transcriptional profiling by RNA sequencing of drug treated TSC2-deficient cells compared to wild-type cells suggested the cytotoxic mechanism of action, involving initial ER stress and an imbalance in energy homeostatic pathways. Further characterization revealed that supplementation with methyl pyruvate alleviated energy stress and reduced the cytotoxic effect, implicating energy deprivation as the trigger of cell death. This work underpins a critical vulnerability with cancer cells with aberrant signaling through the TSC2-mTORC1 pathway that lack flexibility in homeostatic pathways, which could be exploited with combined nelfinavir and mefloquine treatment.
Classification of Cells in CTC-Enriched Samples by Advanced Image Analysis
Authors: De Wit Sanne , Zeune Leonie L. , Hiltermann T. Jeroen N. , Groen Harry J. M. , Dalum Guus van , Terstappen Leon W. M. M.
Published: October 2018

In the CellSearch® system, blood is immunomagnetically enriched for epithelial cell adhesion molecule (EpCAM) expression and cells are stained with the nucleic acid dye 4′6-diamidino-2-phenylindole (DAPI), Cytokeratin-PE (CK), and CD45-APC. Only DAPI+/CK+ objects are presented to the operator to identify circulating tumor cells (CTC) and the identity of all other cells and potential undetected CTC remains unrevealed. Here, we used the open source imaging program Automatic CTC Classification, Enumeration and PhenoTyping (ACCEPT) to analyze all DAPI+ nuclei in EpCAM-enriched blood samples obtained from 192 metastatic non-small cell lung cancer (NSCLC) patients and 162 controls. Significantly larger numbers of nuclei were detected in 300 patient samples with an average and standard deviation of 73,570 ± 74,948, as compared to 359 control samples with an average and standard deviation of 4191 ± 4463 (p < 0.001). In patients, only 18% ± 21% and in controls 23% ± 15% of the nuclei were identified as leukocytes or CTC. Adding CD16-PerCP for granulocyte staining, the use of an LED as the light source for CD45-APC excitation and plasma membrane staining obtained with wheat germ agglutinin significantly improved the classification of EpCAM-enriched cells, resulting in the identification of 94% ± 5% of the cells. However, especially in patients, the origin of the unidentified cells remains unknown. Further studies are needed to determine if undetected EpCAM+/DAPI+/CK-/CD45- CTC is present among these cells.
Frequency Conversion in KTP Crystal and Its Isomorphs
Authors: Gagarskiy Sergey , Grechin Sergey , Druzhinin Pioter , Kato Kiyoshi , Kochiev David , Nikolaev Pavel , Umemura Nobihuro
Published: October 2018

We report the results of an analysis of the functional capabilities of the KTP crystal and its isomorphs for nonlinear-optical frequency conversion of all types of interactions in the transparency range of the crystal. The possibility of implementing angle, wavelength (frequency), and temperature-noncritical phase matching is shown.
Lightning Breakdown Voltage Evaluation of Palm Oil and Coconut Oil as Transformer Oil under Quasi-Uniform Field Conditions
Authors: Katim Nurul Izzatul Akma , Ishak Mohd Taufiq , Mohamad Amin Nur Aqilah , Abdul Hamid Mardhiah Hayati , Amali Ahmad Khairol , Azis Norhafiz
Published: October 2018

This paper presents lightning (1.2/50 µs) breakdown voltages of palm oil (PO), coconut oil (CO) and mineral oil (MO) in a quasi-uniform sphere to sphere electric field at two gap distances. The type of PO used in this study is Refined Bleached Deodorized Palm Oil (RBDPO) Olein type. The effect of voltage polarities (positive and negative) and testing methods (rising voltage, up and down and multiple level) on the lightning breakdown performance were investigated. The results indicated that lightning breakdown voltages of CO and RBDPO are comparable to those of MO under various test conditions. The results indicated that there is no polarity effect for lightning impulse breakdown tests in a quasi-uniform field. The testing methods, including rising voltage method, up and down method and multiple level method have a notable influence on the breakdown voltages. The effect of the 50% breakdown voltage on rising voltage method, up and down method and multiple level method for RBDPO and CO is comparable to MO. The withstand voltage at 1% and 50% breakdown probabilities were obtained using the Normal distribution fitting on the cumulative probability plot of impulse shots. Based on a normal distribution fitting, withstand voltages 1% breakdown probability of POA were close to the MO. Finally, based on statistical studies and simulation using ANSYS software, the prediction formulas for breakdown voltage for larger gap distances for all samples were derived.
Applications of Digital-Physical Hybrid Real-Time Simulation Platform in Power Systems
Authors: Leng Feng , Mao Chengxiong , Wang Dan , An Ranran , Zhang Yuan , Zhao Yanjun , Cai Linglong , Tian Jie
Published: October 2018

Digital-physical hybrid real-time simulation (hybrid simulation) platform integrates the advantages of both digital simulation and physical simulation by combining the physical simulation laboratory and the real-time digital simulator. Based on a 400 V/50 kVA hybrid simulation platform with 500 kVA short-circuit capacity, the hybrid simulation methodology and a Hausdorff distance based accuracy evaluation method are proposed. The case validation of power system fault recurrence is performed through this platform, and the stability and accuracy are further validated by comparing the hybrid simulation waveform and field-recorded waveform and by evaluating the accuracy with the proposed error index. Two typical application scenarios in power systems are studied subsequently. The static var generator testing shows the hybrid simulation platform can provide system-level testing conditions for power electronics equipment conveniently. The low-voltage ride through standard testing of a photovoltaic inverter indicates that the hybrid simulation platform can be also used for voltage standard testing for various power system apparatus with low cost. With this hybrid simulation platform, the power system simulation and equipment testing can be implemented with many advantages, such as short period of modelling, flexible modification of parameter and network, low cost, and low risk. Based on this powerful tool platform, there will be more application scenarios in future power systems.
Schedule-Based Operation Method Using Market Data for an Energy Storage System of a Customer in the Ontario Electricity Market
Authors: Hwang Pyeong-Ik , Kwon Seong-Chul , Yun Sang-Yun
Published: October 2018

A new operation method for an energy storage system (ESS) was proposed to reduce the electricity charges of a customer paying the wholesale price and participating in the industrial conservation initiative (ICI) in the Ontario electricity market of Canada. Electricity charges were overviewed and classified into four components: fixed cost, electricity usage cost, peak demand cost, and Ontario peak contribution cost (OPCC). Additionally, the online market data provided by the independent electricity system operator (IESO), which operates the Ontario electricity market, were reviewed. From the reviews, it was identified that (1) the portion of the OPCC in the electricity charges increased continuously, and (2) large errors can sometimes exist in the forecasted data given by the IESO. In order to reflect these, a new schedule-based operation method for the ESS was proposed in this paper. In the proposed method, the operation schedule for the ESS is determined by solving an optimization problem to minimize the electricity charges, where the OPCC is considered and the online market data provided by the IESO is used. The active power reference for the ESS is then calculated from the scheduled output for the current time interval. To reflect the most recent market data, the operation schedule and the active power reference for the ESS are iteratively determined for every five minutes. In addition, in order to cope with the prediction errors, methods to correct the forecasted data for the current time interval and secure the energy reserve are presented. The results obtained from the case study and actual operation at the Penetanguishene microgrid test bed in Ontario are presented to validate the proposed method.
A Micro Swing Rotor Engine and the Preliminary Study of Its Thermodynamic Characteristics
Authors: Xia Chen , Zhang Zhiguang , Huang Guoping , Zhou Tong , Xu Jianhua
Published: October 2018

The rapid progress in microelectromechanical system technology has facilitated great developments in micro heat engines, however, defects in these engines still need to be overcome. Thus, a novel four-stroke micro swing rotor engine (MSRE) that features the advantages of Wankel engine and the micro swing engine is proposed in this study. Kinematic and thermodynamic analyses of the MSRE were performed, and a preliminary experimental research was conducted. In the MSRE, the driver assembly was used to dominate the movements of the two rotors. By the design guideline adaptable to the engine operation principle, the volume of each chamber will vary in a sine-like waveform, which was validated by kinematic analyses. Then, a prototype in mesoscale was designed and fabricated. In consideration of the leakage effect, the thermodynamic characteristics of this engine were numerically investigated. Results indicate that the engine thermodynamic processes were seriously affected by leakage flow, especially when working at low frequencies. Gap height and operation frequency were the two dominant factors that affected engine performance. Under a certain gap height, the MSRE had to work at a specific frequency range and the corresponding optical values exist for engine efficiency and power. With a 20 μm height, the MSRE reached the maximum efficiency of 23.62% at 55 Hz and the maximum power of 3442 W at 95 Hz. Feasibility of the engine was further verified by an experimental test on the operation characteristics, including the cold state test with pressured air blow and the combustion test for engine operation at thermal state. This research lays a good foundation for future development of MSRE, which is of great practical significance for the progress in micro power systems.
Economic Consequences of Cooling Water Insufficiency in the Thermal Power Sector under Climate Change Scenarios
Authors: Zhou Qian , Hanasaki Naota , Fujimori Shinichiro
Published: October 2018

Currently, thermal power is the largest source of power in the world. Although the impacts of climate change on cooling water sufficiency in thermal power plants have been extensively assessed globally and regionally, their economic consequences have seldom been evaluated. In this study, the Asia-Pacific Integrated Model Computable General Equilibrium model (AIM/CGE) was used to evaluate the economic consequences of projected future cooling water insufficiency on a global basis, which was simulated using the H08 global hydrological model. This approach enabled us to investigate how the physical impacts of climate change on thermal power generation influence economic activities in regions and industrial sectors. To account for the uncertainty of climate change projections, five global climate models and two representative concentration pathways (RCPs 2.6 and 8.5) were used. The ensemble-mean results showed that the global gross domestic product (GDP) loss in 2070–2095 due to cooling water insufficiency in the thermal power sector was −0.21% (−0.12%) in RCP8.5 (RCP2.6). Among the five regions, the largest GDP loss of −0.57% (−0.27%) was observed in the Middle East and Africa. Medium-scale losses of −0.18% (−0.12%) and −0.14% (−0.12%) were found in OECD90 (the member countries of the Organization for Economic Co-operation and Development as of 1990) and Eastern Europe and the Former Soviet Union, respectively. The smallest losses of −0.05% (−0.06%) and −0.09% (−0.08%) were found in Latin America and Asia, respectively. The economic impact of cooling water insufficiency was non-negligible and should be considered as one of the threats induced by climate change.
Vibration Characteristics Analysis of Planetary Gears with a Multi-Clearance Coupling in Space Mechanism
Authors: Zhang Huibo , Qi Chaoqun , Fan Jizhuang , Dai Shijie , You Bindi
Published: October 2018

Multi-clearance is the main cause for the performance and reliability decline of complicated mechanical systems. The increased clearance could induce contacts and impacts in joints, and consequently affect control accuracy. A nonlinear dynamic model of planetary gears with multi-clearance coupling is proposed in the current study to investigate the mechanism of influence of clearance on the dynamic performance. In addition, the coupling relationship between radial clearance and backlash is integrated into the multi-body system dynamics. The vibration characteristics of planetary gears with the changes of rotational velocity, clearance size and inertia load are explored. The numerical simulation results show that there are complex coupling relations in planetary gear systems, due to the multi-clearance coupling. The phenomenon of system resonance may occur with the changes of rotational velocities and clearances’ sizes. Multi-clearance coupling can significantly increase the resonant response of planetary gear systems in empty-load or light-load states.
Building Energy Management Strategy Using an HVAC System and Energy Storage System
Authors: Kim Nam-Kyu , Shim Myung-Hyun , Won Dongjun
Published: October 2018

Recently, a worldwide movement to reduce greenhouse gas emissions has emerged, and includes efforts such as the Paris Agreement in 2015. To reduce greenhouse gas emissions, it is important to reduce unnecessary energy consumption or use environmentally-friendly energy sources and consumer products. Many studies have been performed on building energy management systems and energy storage systems (ESSs), which are aimed at efficient energy management. Herein, a heating, ventilation, and air-conditioning (HVAC) system peak load reduction algorithm and an ESS peak load reduction algorithm are proposed. First, an HVAC system accounts for the largest portion of building energy consumption. An HVAC system operates by considering the time-of-use price. However, because the indoor temperature is constantly changing with time, load shifting can be expected only immediately prior to use. Therefore, the primary objective is to reduce the operating time by changing the indoor temperature constraint at the forecasted peak time. Next, numerous research initiatives on ESSs are ongoing. In this study, we aim to systematically design the peak load reduction algorithm of ESS. The structure is designed such that the algorithm can be applied by distinguishing between the peak and non-peak days. Finally, the optimization scheduling simulation is performed. The result shows that the electricity price is minimized by peak load reduction and electricity usage reduction. The proposed algorithm is verified through MATLAB simulations.
A Novel Step-Up Converter with an Ultrahigh Voltage Conversion Ratio
Authors: Wang Faqiang , Iu Herbert , Li Jing
Published: October 2018

A new step-up converter with an ultrahigh voltage conversion ratio is proposed in this paper. Two power switches of such a converter, which conduct synchronically, and its output voltage, which has common ground and common polarity with its input voltage, lead to the simple control circuit. No abrupt changes in the capacitor voltage and the inductor current of the proposed step-up converter mean that it does not suffer from infinite capacitor current and inductor voltage. Two input inductors with different values can still allow the proposed step-up converter to work appropriately. An averaged model of the proposed step-up converter was built and one could see that it was still fourth-order even with its five storage elements. Some theoretical derivations, theoretical analysis, Saber simulations, and circuit experiments are provided to validate the effectiveness of the proposed step-up converter.
A New Hybrid Fault Identification Method Based on Multiterminals Synchronous Measure Information for All Parallel at Traction Power Supply System
Authors: Wang Shuai , Chen Minwu , Li Qunzhan , Huang Wenxun , Wu Bo
Published: October 2018

The all parallel autotransformer (AT) traction power supply system (TPSS) including several subsections is widely used for high-speed railways. Unfortunately, any fault of catenary and negative feeder will cause all subsections power interruption in the whole system. Moreover, due to the nonlinear relationship between the distance and impedance as well as the symmetry of the system, conventional distance protection schemes fail to identify the fault subsection and the fault types. In this paper, a novel segmental power supply scheme is presented, which can switch the catenary and negative feeder at each AT subsection on and off independently. Based on the theoretical analysis of the electrical characteristics of the traction power network, multiterminals synchronous information is applied and a hybrid fault identification method is proposed, which can accurately identify the fault subsection and fault type. Consequently, only the catenary or negative feeder at the fault subsection will be quickly removed from service without the effect on normal operation of other subsections. Therefore, the reliability of all parallel AT TPSS is improved considerably. This method was verified through simulation and laboratory experiments by the case studies.
Optimization of Hybrid Energy Storage Systems for Vehicles with Dynamic On-Off Power Loads Using a Nested Formulation
Authors: Liu Jiajun , Dong Huachao , Jin Tianxu , Liu Li , Manouchehrinia Babak , Dong Zuomin
Published: October 2018

In this paper, identification of an appropriate hybrid energy storage system (HESS) architecture, introduction of a comprehensive and accurate HESS model, as well as HESS design optimization using a nested, dual-level optimization formulation and suitable optimization algorithms for both levels of searches have been presented. At the bottom level, design optimization focuses on the minimization of power loss in batteries, converter, and ultracapacitors (UCs), as well as the impact of battery depth of discharge (DOD) to its operation life, using a dynamic programming (DP)-based optimal energy management strategy (EMS). At the top level, HESS optimization of component size and battery DOD is carried out to achieve the minimum life-cycle cost (LCC) of the HESS for given power profiles and performance requirements as an outer loop. The complex and challenging optimization problem is solved using an advanced Multi-Start Space Reduction (MSSR) search method developed for computation-intensive, black-box global optimization problems. An example of load-haul-dump (LHD) vehicles is employed to verify the proposed HESS design optimization method and MSSR leads to superior optimization results and dramatically reduces computation time. This research forms the foundation for the design optimization of HESS, hybridization of vehicles with dynamic on-off power loads, and applications of the advanced global optimization method.
Estimating Forest Canopy Cover in Black Locust (Robinia pseudoacacia L.) Plantations on the Loess Plateau Using Random Forest
Authors: Zhao Qingxia , Wang Fei , Zhao Jun , Zhou Jingjing , Yu Shichuan , Zhao Zhong
Published: October 2018

The forest canopy is the medium for energy and mass exchange between forest ecosystems and the atmosphere. Remote sensing techniques are more efficient and appropriate for estimating forest canopy cover (CC) than traditional methods, especially at large scales. In this study, we evaluated the CC of black locust plantations on the Loess Plateau using random forest (RF) regression models. The models were established using the relationships between digital hemispherical photograph (DHP) field data and variables that were calculated from satellite images. Three types of variables were calculated from the satellite data: spectral variables calculated from a multispectral image, textural variables calculated from a panchromatic image (Tpan) with a 15 × 15 window size, and textural variables calculated from spectral variables (TB+VIs) with a 9 × 9 window size. We compared different mtry and ntree values to find the most suitable parameters for the RF models. The results indicated that the RF model of spectral variables explained 57% (root mean square error (RMSE) = 0.06) of the variability in the field CC data. The soil-adjusted vegetation index (SAVI) and enhanced vegetation index (EVI) were more important than other spectral variables. The RF model of Tpan obtained higher accuracy (R2 = 0.69, RMSE = 0.05) than the spectral variables, and the grey level co-occurrence matrix-based texture measure—Correlation (COR) was the most important variable for Tpan. The most accurate model was obtained from the TB+VIs (R2 = 0.79, RMSE = 0.05), which combined spectral and textural information, thus providing a significant improvement in estimating CC. This model provided an effective approach for detecting the CC of black locust plantations on the Loess Plateau.
Approaching Local Perceptions of Forest Governance and Livelihood Challenges with Companion Modeling from a Case Study around Zahamena National Park, Madagascar
Authors: Bodonirina Nathalie , Reibelt Lena M. , Stoudmann Natasha , Chamagne Juliette , Jones Trevor G. , Ravaka Annick , Ranjaharivelo Hoby V. F. , Ravonimanantsoa Tantelinirina , Moser Gabrielle , De Grave Arnaud , Garcia Claude , Ramamonjisoa Bruno S. , Wilmé Lucienne , Waeber Patrick O.
Published: October 2018

Community-based natural resource management (CBNRM) is a widely used approach aimed at involving those utilizing resources in their management. In Madagascar, where forest decentralization has been implemented since the 1990s to spur local resource users’ involvement in management processes, impacts remain unclear. This study aimed to investigate farmers’ perceptions and practices regarding forest use under various forest governance systems, using a participatory gaming approach implemented in the Zahamena region of Madagascar. We report on (i) the conceptual models of the Zahamena socio-ecological system; (ii) the actual research tool in the form of a tabletop role-playing game; and (iii) main outcomes of the gaming workshops and accompanying research. The results allow the linking of game reality with real-world perceptions based on game debriefing discussions and game workshop follow-up surveys, as well as interviews and focus group research with other natural resource users from the study area. Results show that the Zahamena protected area plays the role of buffer zone by slowing down deforestation and degradation. However, this fragile barrier and CBNRM are not long-term solutions in the face of occurring changes. Rather, the solution lies in one of the main causes of the problem: agriculture. Further use of tools such as participatory gaming is recommended to enhance knowledge exchange and the development of common visions for the future of natural resource management to foster resilience of forest governance.
Estimation of Forest Carbon Stocks for National Greenhouse Gas Inventory Reporting in South Korea
Authors: Lee Sun Jeoung , Yim Jong Su , Son Yeong Mo , Son Yowhan , Kim Raehyun
Published: October 2018

The development of country-specific emission factors in relation to the Agriculture, Forestry, and Other Land Use (AFOLU) sector has the potential to improve national greenhouse gas inventory systems. Forests are carbon sinks in the AFOLU that can play an important role in mitigating global climate change. According to the United Nations Framework Convention on Climate Change (UNFCCC), signatory countries must report forest carbon stocks, and the changes within them, using emission factors from the Intergovernmental Panel on Climate Change (IPCC) or from country-specific values. This study was conducted to estimate forests carbon stocks and to complement and improve the accuracy of national greenhouse gas inventory reporting in South Korea. We developed country-specific emissions factors and estimated carbon stocks and their changes using the different approaches and methods described by the IPCC (IPCCEF: IPCC default emission factors, CSFT: country-specific emission factors by forest type, and CSSP: country-specific emission factors by species). CSFT returned a result for carbon stocks that was 1.2 times higher than the value using IPCCEF. Using CSSP, CO2 removal was estimated to be 60,648 Gg CO2 per year with an uncertainty of 22%. Despite a reduction in total forest area, forests continued to store carbon and absorb CO2, owing to differences in the carbon storage capacities of different forest types and tree species. The results of this study will aid estimations of carbon stock changes and CO2 removal by forest type or species, and help to improve the completeness and accuracy of the national greenhouse gas inventory. Furthermore, our results provide important information for developing countries implementing Tier 2, the level national greenhouse gas inventory systems recommended by the IPCC.
Hydrogels as Porogens for Nanoporous Inorganic Materials
Authors: Weinberger Christian , Kuckling Dirk , Tiemann Michael
Published: October 2018

Organic polymer-hydrogels are known to be capable of directing the nucleation and growth of inorganic materials, such as silica, metal oxides, apatite or metal chalcogenides. This approach can be exploited in the synthesis of materials that exhibit defined nanoporosity. When the organic polymer-based hydrogel is incorporated in the inorganic product, a composite is formed from which the organic component may be selectively removed, yielding nanopores in the inorganic product. Such porogenic impact resembles the concept of using soft or hard templates for porous materials. This micro-review provides a survey of select examples from the literature.
Sequence Composition and Evolution of Mammalian B Chromosomes
Authors: Rubtsov Nikolay B. , Borisov Yury M.
Published: October 2018

B chromosomes (Bs) revealed more than a hundred years ago remain to be some of the most mysterious elements of the eukaryotic genome. Their origin and evolution, DNA composition, transcriptional activity, impact on adaptiveness, behavior in meiosis, and transfer to the next generation require intensive investigations using modern methods. Over the past years, new experimental techniques have been applied and helped us gain a deeper insight into the nature of Bs. Here, we consider mammalian Bs, taking into account data on their DNA sequencing, transcriptional activity, positions in nuclei of somatic and meiotic cells, and impact on genome functioning. Comparative cytogenetics of Bs suggests the existence of different mechanisms of their formation and evolution. Due to the long and complicated evolvement of Bs, the similarity of their morphology could be explained by the similar mechanisms involved in their development while the difference between Bs even of the same origin could appear due to their positioning at different stages of their evolution. A complex analysis of their DNA composition and other features is required to clarify the origin and evolutionary history of Bs in the species studied. The intraspecific diversity of Bs makes this analysis a very important element of B chromosome studies.
Chromosome Painting in Neotropical Long- and Short-Tailed Parrots (Aves, Psittaciformes): Phylogeny and Proposal for a Putative Ancestral Karyotype for Tribe Arini
Authors: Furo Ivanete de Oliveira , Kretschmer Rafael , O’Brien Patrícia C. M. , Pereira Jorge C. , Garnero Analía del Valle , Gunski Ricardo J. , Ferguson-Smith Malcolm A. , De Oliveira Edivaldo Herculano Corrêa
Published: October 2018

Most Neotropical Psittacidae have a diploid number of 2n = 70, and a dichotomy in chromosome patterns. Long-tailed species have biarmed macrochromosomes, while short-tailed species have telo/acrocentric macrochromosomes. However, the use of chromosome painting has demonstrated that karyotype evolution in Psittacidae includes a high number of inter/intrachromosomal rearrangements. To determine the phylogeny of long- and short-tailed species, and to propose a putative ancestral karyotype for this group, we constructed homology maps of Pyrrhura frontalis (PFR) and Amazona aestiva (AAE), belonging to the long- and short-tailed groups, respectively. Chromosomes were analyzed by conventional staining and fluorescent in situ hybridization using whole chromosome paints of Gallus gallus and Leucopternis albicollis. Conventional staining showed a karyotype with 2n = 70 in both species, with biarmed macrochromosomes in PFR and telo/acrocentric chromosomes in AAE. Comparison of the results with the putative avian ancestral karyotype (PAK) showed fusions in PFR of PAK1p/PAK4q (PFR1) and PAK6/PAK7 (PFR6) with a paracentric inversion in PFR6. However, in AAE, there was only the fusion between PAK6/7 (AAE7) with a paracentric inversion. Our results indicate that PFR retained a more basal karyotype than long-tailed species previously studied, and AAE a more basal karyotype for Neotropical Psittacidae analyzed so far.
Increasing Environmental Health Literacy through Contextual Learning in Communities at Risk
Authors: Davis Leona F. , Ramirez-Andreotta Mónica D. , McLain Jean E. T. , Kilungo Aminata , Abrell Leif , Buxner Sanlyn
Published: October 2018

Environmental health literacy (EHL) has recently been defined as the continuum of environmental health knowledge and awareness, skills and self-efficacy, and community action. In this study, an interdisciplinary team of university scientists, partnering with local organizations, developed and facilitated EHL trainings with special focus on rainwater harvesting and water contamination, in four communities with known environmental health stressors in Arizona, USA. These participatory trainings incorporated participants’ prior environmental health risk knowledge and personal experiences to co-create training content. Mixed methods evaluation was conducted via pre-post participant surveys in all four trainings (n = 53). Participants who did not demonstrate baseline environmental science knowledge pre-training demonstrated significant knowledge increase post-training, and participants who demonstrated low self-efficacy (SE) pre-training demonstrated a significant increase in SE post-training. Participants overall demonstrated a significant increase in specific environmental health skills described post-training. The interdisciplinary facilitator-scientist team also reported multiple benefits, including learning local knowledge that informed further research, and building trust relationships with community members for future collaboration. We propose contextual EHL education as a valuable strategy for increasing EHL in environmental health risk communities, and for building academia-community partnerships for environmental health research and action.
The Epidemiological Influence of Climatic Factors on Shigellosis Incidence Rates in Korea
Authors: Song Yeong-Jun , Cheong Hae-Kwan , Ki Myung , Shin Ji-Yeon , Hwang Seung-sik , Park Mira , Ki Moran , Lim Jiseun
Published: October 2018

Research has shown the effects of climatic factors on shigellosis; however, no previous study has evaluated climatic effects in regions with a winter seasonality of shigellosis incidence. We examined the effects of temperature and precipitation on shigellosis incidence in Korea from 2002–2010. The incidence of shigellosis was calculated based on data from the Korean Center for Disease Control and Prevention (KCDC, Cheongju, Korea), and a generalized additive model (GAM) was used to analyze the associations between the incidence and climatic factors. The annual incidence rate of shigellosis was 7.9 cases/million persons from 2002–2010. During 2007–2010, high incidence rates and winter seasonality were observed among those aged ≥65 years, but not among lower age groups. Based on the GAM model, the incidence of shigellosis is expected to increase by 13.6% and 2.9% with a temperature increase of 1 °C and a lag of two weeks and with a mean precipitation increase of 1 mm and a lag of five weeks after adjustment for seasonality, respectively. This study suggests that the incidence of shigellosis will increase with global climate change despite the winter seasonality of shigellosis in Korea. Public health action is needed to prevent the increase of shigellosis incidence associated with climate variations.
AMP-Activated Protein (AMPK) in Pathophysiology of Pregnancy Complications
Authors: Kumagai Asako , Itakura Atsuo , Koya Daisuke , Kanasaki Keizo
Published: October 2018

Although the global maternal mortality ratio has been consistently reduced over time, in 2015, there were still 303,000 maternal deaths throughout the world, of which 99% occurred in developing countries. Understanding pathophysiology of pregnancy complications contributes to the proper prenatal care for the reduction of prenatal, perinatal and neonatal mortality and morbidity ratio. In this review, we focus on AMP-activated protein kinase (AMPK) as a regulator of pregnancy complications. AMPK is a serine/threonine kinase that is conserved within eukaryotes. It regulates the cellular and whole-body energy homeostasis under stress condition. The functions of AMPK are diverse, and the dysregulation of AMPK is known to correlate with many disorders such as cardiovascular disease, diabetes, inflammatory disease, and cancer. During pregnancy, AMPK is necessary for the proper placental differentiation, nutrient transportation, maternal and fetal energy homeostasis, and protection of the fetal membrane. Activators of AMPK such as 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR), resveratrol, and metformin restores pregnancy complications such as gestational diabetes mellitus (GDM), preeclampsia, intrauterine growth restriction, and preterm birth preclinically. We also discuss on the relationship between catechol-O-methyltransferase (COMT), an enzyme that metabolizes catechol, and AMPK during pregnancy. It is known that metformin cannot activate AMPK in COMT deficient mice, and that 2-methoxyestradiol (2-ME), a metabolite of COMT, recovers the AMPK activity, suggesting that COMT is a regulator of AMPK. These reports suggest the therapeutic use of AMPK activators for various pregnancy complications, however, careful analysis is required for the safe use of AMPK activators since AMPK activation could cause fetal malformation.
Effects of Streptozotocin-Induced Diabetes on the Pineal Gland in the Domestic Pig
Authors: Lewczuk Bogdan , Prusik Magdalena , Ziółkowska Natalia , Dąbrowski Michał , Martniuk Kamila , Hanuszewska Maria , Zielonka Łukasz
Published: October 2018

Several observations from experiments in rodents and human patients suggest that diabetes affects pineal gland function, including melatonin secretion; however, the accumulated data are not consistent. The aim of the present study was to determine the effects of streptozotocin-induced diabetes on the pineal gland in the domestic pig, a species widely used as a model in various biomedical studies. The study was performed on 10 juvenile pigs, which were divided into two groups: control and diabetic. Diabetes was evoked by administration of streptozotocin (150 mg/kg of body weight). After six weeks, the animals were euthanized between 12.00 and 14.00, and the pineal glands were removed and divided into two equal parts, which were used for biochemical analyses and for preparation of explants for the superfusion culture. The pineal contents (per 100 μg protein) of serotonin, 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid, 5-methoxytryptophol, and 5-methoxytryptamine were significantly lower in diabetic pigs than in control pigs. In contrast, the level of N-acetylserotonin was significantly higher in diabetic animals. No significant differences were found in the level of melatonin between control and experimental pigs. The amounts of 3,4-dihydroxyphenylalanine, dopamine, norepinephrine, and 3,4-dihydroxyphenylacetic acid were significantly lower in the pineal glands of diabetic animals. The level of vanillylmandelic acid was higher in diabetic pigs. No differences were observed in the level of basal and NE-stimulated release of N-acetylserotonin or melatonin between the pineal explants prepared from control and experimental animals. In vitro treatment with insulin was ineffective. In conclusion, streptozotocin-induced diabetes affects both indole metabolism and adrenergic neurotransmission in the pig pineal gland.
Exploring the Remote Ties between Helitron Transposases and Other Rolling-Circle Replication Proteins
Authors: Heringer Pedro , Kuhn Gustavo C. S.
Published: October 2018

Rolling-circle replication (RCR) elements constitute a diverse group that includes viruses, plasmids, and transposons, present in hosts from all domains of life. Eukaryotic RCR transposons, also known as Helitrons, are found in species from all eukaryotic kingdoms, sometimes representing a large portion of their genomes. Despite the impact of Helitrons on their hosts, knowledge about their relationship with other RCR elements is still elusive. Here, we compared the endonuclease domain sequence of Helitron transposases with the corresponding region from RCR proteins found in a wide variety of mobile genetic elements. To do that, we used a stepwise alignment approach followed by phylogenetic and multidimensional scaling analyses. Although it has been suggested that Helitrons might have originated from prokaryotic transposons or eukaryotic viruses, our results indicate that Helitron transposases share more similarities with proteins from prokaryotic viruses and plasmids instead. We also provide evidence for the division of RCR endonucleases into three groups (Y1, Y2, and Yx), covering the whole diversity of this protein family. Together, these results point to prokaryotic elements as the likely closest ancestors of eukaryotic RCR transposons, and further demonstrate the fluidity that characterizes the boundaries separating viruses, plasmids, and transposons.
Neuronal Cell Death Mechanisms in Major Neurodegenerative Diseases
Authors: Chi Hao , Chang Hui-Yun , Sang Tzu-Kang
Published: October 2018

Neuronal cell death in the central nervous system has always been a challenging process to decipher. In normal physiological conditions, neuronal cell death is restricted in the adult brain, even in aged individuals. However, in the pathological conditions of various neurodegenerative diseases, cell death and shrinkage in a specific region of the brain represent a fundamental pathological feature across different neurodegenerative diseases. In this review, we will briefly go through the general pathways of cell death and describe evidence for cell death in the context of individual common neurodegenerative diseases, discussing our current understanding of cell death by connecting with renowned pathogenic proteins, including Tau, amyloid-beta, alpha-synuclein, huntingtin and TDP-43.
Comprehensive Analysis of MicroRNA–Messenger RNA from White Yak Testis Reveals the Differentially Expressed Molecules Involved in Development and Reproduction
Authors: Zhang Quanwei , Wang Qi , Zhang Yong , Cheng Shuru , Hu Junjie , Ma Youji , Zhao Xingxu
Published: October 2018

Testis development is a vital and tightly regulated process in mammals. Understanding the biological mechanisms underlying testis development will benefit the animal reproduction industry. Expression changes in microRNA and messenger RNA in response to dynamic regulation effects have been associated with this process. However, very little is known about the roles of these molecules in yak development. Using whole-genome small RNA and messenger RNA sequencing, we performed a comprehensive analysis of the microRNA–messenger RNA interaction network expression in the testicles of Tianzhu white yaks during three developmental stages. Using Short Time-series Expression Miner analysis we identified 589 differentially expressed microRNAs (DERs) and 3383 differentially expressed messenger RNAs (DEGs) in the three age groups. A total of 93 unique DEGs are primarily involved in reproduction and testis development. Subsequently, four integration networks were constructed according to the DEGs and DERs in three biological processes. Nineteen DEGs were potentially regulated by 60 DERs, of which miR-574 and target gene AURKA played a crucial role in yak testis development and reproduction. The results of this study provide a basis for further exploration of the microRNA–messenger RNA interactions in testis development and reproduction and aid in uncovering the molecular mechanisms of spermatogenesis in male mammals.
Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches
Authors: Soleilhac Emmanuelle , Brillet-Guéguen Loraine , Roussel Véronique , Prudent Renaud , Touquet Bastien , Dass Sheena , Aci-Sèche Samia , Kasam Vinod , Barette Caroline , Imberty Anne , Breton Vincent , Vantard Marylin , Horvath Dragos , Botté Cyrille , Tardieux Isabelle , Roy Sylvaine , Maréchal Eric , Lafanechère Laurence
Published: October 2018

Dinitroanilines are chemical compounds with high selectivity for plant cell α-tubulin in which they promote microtubule depolymerization. They target α-tubulin regions that have diverged over evolution and show no effect on non-photosynthetic eukaryotes. Hence, they have been used as herbicides over decades. Interestingly, dinitroanilines proved active on microtubules of eukaryotes deriving from photosynthetic ancestors such as Toxoplasma gondii and Plasmodium falciparum, which are responsible for toxoplasmosis and malaria, respectively. By combining differential in silico screening of virtual chemical libraries on Arabidopsis thaliana and mammal tubulin structural models together with cell-based screening of chemical libraries, we have identified dinitroaniline related and non-related compounds. They inhibit plant, but not mammalian tubulin assembly in vitro, and accordingly arrest A. thaliana development. In addition, these compounds exhibit a moderate cytotoxic activity towards T. gondii and P. falciparum. These results highlight the potential of novel herbicidal scaffolds in the design of urgently needed anti-parasitic drugs.
Inhibition of NADPH Oxidase Activation by Apocynin Rescues Seizure-Induced Reduction of Adult Hippocampal Neurogenesis
Authors: Lee Song Hee , Choi Bo Young , Kho A Ra , Jeong Jeong Hyun , Hong Dae Ki , Kang Dong Hyeon , Kang Beom Seok , Song Hong Ki , Choi Hui Chul , Suh Sang Won
Published: October 2018

Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. Apocynin is known to be an inhibitor of NADPH (Nicotinamide adenine dinucleotide phosphate) oxidase activity and is highly effective in suppressing the production of superoxide. The neuroprotective effects of apocynin have been investigated in numerous brain injury settings, such as stroke, traumatic brain injury (TBI), and epilepsy. Our lab has demonstrated that TBI or seizure-induced oxidative injury and neuronal death were reduced by apocynin treatment. Several studies have also demonstrated that neuroblast production is transiently increased in the hippocampus after seizures. Here, we provide evidence confirming the hypothesis that long-term treatment with apocynin may enhance newly generated hippocampal neuronal survival by reduction of superoxide production after seizures. A seizure was induced by pilocarpine [(25 mg/kg intraperitoneal (i.p.)] injection. Apocynin was continuously injected for 4 weeks after seizures (once per day) into the intraperitoneal space. We evaluated neuronal nuclear antigen (NeuN), bromodeoxyuridine (BrdU), and doublecortin (DCX) immunostaining to determine whether treatment with apocynin increased neuronal survival and neurogenesis in the hippocampus after seizures. The present study indicates that long-term treatment of apocynin increased the number of NeuN+ and DCX+ cells in the hippocampus after seizures. Therefore, this study suggests that apocynin treatment increased neuronal survival and neuroblast production by reduction of hippocampal oxidative injury after seizures.
ABD-Derived Protein Blockers of Human IL-17 Receptor A as Non-IgG Alternatives for Modulation of IL-17-Dependent Pro-Inflammatory Axis
Authors: Hlavničková Marie , Kuchař Milan , Osička Radim , Vaňková Lucie , Petroková Hana , Malý Michal , Černý Jiří , Arenberger Petr , Malý Petr
Published: October 2018

Interleukin 17 (IL-17) and its cognate receptor A (IL-17RA) play a crucial role in Th17 cells-mediated pro-inflammatory pathway and pathogenesis of several autoimmune disorders including psoriasis. IL-17 is mainly produced by activated Th-17 helper cells upon stimulation by IL-23 and, via binding to its receptors, mediates IL-17-driven cell signaling in keratinocytes. Hyper-proliferation of keratinocytes belongs to major clinical manifestations in psoriasis. To modulate IL-17-mediated inflammatory cascade, we generated a unique collection of IL-17RA-targeting protein binders that prevent from binding of human IL-17A cytokine to its cell-surface receptor. To this goal, we used a highly complex combinatorial library derived from scaffold of albumin-binding domain (ABD) of streptococcal protein G, and ribosome display selection, to yield a collection of ABD-derived high-affinity ligands of human IL-17RA, called ARS binders. From 67 analyzed ABD variants, 7 different sequence families were identified. Representatives of these groups competed with human IL-17A for binding to recombinant IL-17RA receptor as well as to IL-17RA-Immunoglobulin G chimera, as tested in enzyme-linked immunosorbent assay (ELISA). Five ARS variants bound to IL-17RA-expressing THP-1 cells and blocked binding of human IL-17 cytokine to the cell surface, as tested by flow cytometry. Three variants exhibited high-affinity binding with a nanomolar Kd value to human keratinocyte HaCaT cells, as measured using Ligand Tracer Green Line. Upon IL-17-stimulated activation, ARS variants inhibited secretion of Gro-α (CXCL1) by normal human skin fibroblasts in vitro. Thus, we identified a novel class of inhibitory ligands that might serve as immunosuppressive IL-17RA-targeted non-IgG protein antagonists.