bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation Principles of Power Flow Gradients to Multiple Characteristic Independent Variables in UPFC Embedded Power System
Authors: Liu Jinlian , Yang Jian , Xu Zheng , Zhang Zheren , Song Pengcheng
Published: March 2020

The power flows in the unified power flow controller (UPFC) embedded system is mainly regulated by the two variables containing the magnitude and the phase angle of the output series inserted voltage (OSIV) of UPFC. Different value combinations of the two variables can form multiple regulation modes of OSIV, and the regulation principles and efficiencies for power flows are distinct by different regulation modes. This paper dedicates to research the regulation principles of active and reactive power flow gradients (PFG) to multiple characteristic independent variables (CIVs) at several selected critical points (SCP) of the system in different operation conditions. The CIVs contains the magnitude of OSIV, the phase angle of OSIV, and the phase difference of the system. First, multiple power flow regulation modes of OSIV are designed, the mathematical models of the PFG to each CIV at each SCP are established, and the theoretical principles for the PFG to each CIV at each SCP are analyzed and compared. Next, four typical operation conditions of the system and four regulation scenarios are assumed and case studies for the PFG to each CIV at different SCP are carried out. The test results at each SCP are analyzed both in the two-dimensional planes and three-dimensional spaces. The regulation principles and efficiencies of PFG to each CIV at different SCP are compared with each other and summarized, which can offer useful references for practical engineering and applications of UPFC.
Re-Defining, Analyzing and Predicting Persistence Using Student Events in Online Learning
Authors: Moreno-Marcos Pedro Manuel , Muñoz-Merino Pedro J. , Alario-Hoyos Carlos , Delgado Kloos Carlos
Published: March 2020

In education, several studies have tried to track student persistence (i.e., students’ ability to keep on working on the assigned tasks) using different definitions and self-reported data. However, self-reported metrics may be limited, and currently, online courses allow collecting many low-level events to analyze student behaviors based on logs and using learning analytics. These analyses can be used to provide personalized and adaptative feedback in Smart Learning Environments. In this line, this work proposes the analysis and measurement of two types of persistence based on students’ interactions in online courses: (1) local persistence (based on the attempts used to solve an exercise when the student answers it incorrectly), and (2) global persistence (based on overall course activity/completion). Results show that there are different students’ profiles based on local persistence, although medium local persistence stands out. Moreover, local persistence is highly affected by course context and it can vary throughout the course. Furthermore, local persistence does not necessarily relate to global persistence or engagement with videos, although it is related to students’ average grade. Finally, predictive analysis shows that local persistence is not a strong predictor of global persistence and performance, although it can add some value to the predictive models.
A Low Torque Ripple Direct Torque Control Method for Interior Permanent Magnet Motor
Authors: Hsieh Min-Fu , Weng Yun-Chung
Published: March 2020

This paper proposes a simple method to generate stable voltage commands for permanent magnet synchronous motors to achieve low torque ripple based on space vector modulation direct torque control (SVM-DTC). The relationship between applied voltage and electromagnetic torque is first analyzed and the effect of the voltage and flux linkage on torque ripple is discussed. Then, the new method is developed to reduce torque ripple by giving low-fluctuation voltage commands to the voltage source inverter. The magnitude of the voltage command is calculated by avoiding the effect of flux linkage angle that can be estimated inaccurately during motor operation. Therefore, the fluctuation of the voltage command can be significantly reduced. In order to validate the proposed method, Simulink is first used for simulation and the performance of the proposed method is evaluated. It is found that the torque ripple can be substantially reduced while keeping a low switching frequency and improving system response. Then, a hardware-in-the-loop (HIL) technique is applied to test the developed algorithm that is written into a Texas Instruments microcontroller. This validates the simulation results and the proposed method.
Nannochloropsis oceanica Cultivation in Pilot-Scale Raceway Ponds—From Design to Cultivation
Authors: Cunha Pedro , Pereira Hugo , Costa Margarida , Pereira João , Silva Joana T. , Fernandes Nuno , Varela João , Silva Joana , Simões Manuel
Published: March 2020

Raceways ponds are the microalgal production systems most commonly used at industrial scale. In this work, two different raceway configurations were tested under the same processing conditions to compare their performance on the production of Nannochloropsis oceanica. Biomass productivity, biochemical composition of the produced biomass, and power requirements to operate those reactors were evaluated. Water depths of 0.20 and 0.13 m, and culture circulation velocities of 0.30 and 0.15 m s−1 were tested. A standard configuration, which had a full channel width paddlewheel, proved to be the most energy efficient, consuming less than half of the energy required by a modified configuration (had a half channel width paddlewheel). The later showed to have slightly higher productivity, not enough to offset the large difference in energetic consumption. Higher flow velocity (0.30 m s−1) led to a 1.7 g m−2 d−1 improvement of biomass productivity of the system, but it increased the energy consumption twice as compared to the 0.15 m s−1 flow velocity. The latter velocity showed to be the most productive in lipids. A water depth of 0.20 m was the most suitable option tested to cultivate microalgae, since it allowed a 54% energy saving. Therefore, a standard raceway pond using a flow velocity of 0.3 m s−1 with a 0.20 m water depth was the most efficient system for microalgal cultivation. Conversely, a flow velocity of 0.15 m s−1 was the most suitable to produce lipids.
Design of a Robust H2 State Feedback Temperature Controller for a Steel Slab Reheating Furnace
Authors: Salcedo-Hernández José , Rivas-Perez Raul , Sotomayor-Moriano Javier
Published: March 2020

This article addresses the design of a robust H2 state feedback controller (H2-SFC) for the effective temperature control in the heating zone of the steel slab reheating furnace. Based on the available field data and system identification procedures, a mathematical model of the heating zone is derived, which presents autoregressive-moving average with exogenous input (ARMAX) structure and fourth order. The design of an H2-SFC controller for the effective control of the heating zone temperature of the slab reheating furnace under study is developed. The simulation results of the designed control system showed its high effectiveness compared to the conventional PID control.
Antijamming Improvement for Frequency Hopping Using Noise-Jammer Power Estimator
Authors: Lee Hojun , Ahn Jongmin , Kim Yongcheol , Chung Jaehak
Published: March 2020

In frequency-hopping spread-spectrum (FHSS) systems, jammer detection and mitigation are important but difficult. Each slot of the FHSS experiences frequency-selective fading and unequal transceiver-frequency gains that hinder the detection of jammed slots and result in a poor bit-error rate (BER). To increase BER performance, we first propose a noise-jammer power estimator (NJPE) that estimates noise and jammer powers regardless of different channel gains, and derived its normalized Cramér–Rao bound (NCRB). Second, we developed a jammer detector based on gamma distribution, and designed a restoration method combining all nonjammed slots. Computer simulations verified the derived NCRB of the proposed NJPE by normalized mean squared error (NMSE), and showed that the jammer-detection probability of the proposed jammer detector was better than that of conventional detectors. The BER performance of the proposed method was also shown to be better than that of conventional methods.
Thin CdTe Layers Deposited by a Chamberless Inline Process using MOCVD, Simulation and Experiment
Authors: Monir Shafiul , Kartopu Giray , Barrioz Vincent , Lamb Dan , Irvine Stuart J. C. , Yang Xiaogang , Vagapov Yuriy
Published: March 2020

The deposition of thin Cadmium Telluride (CdTe) layers was performed by a chamberless metalorganic chemical vapour deposition process, and trends in growth rates were compared with computational fluid dynamics numerical modelling. Dimethylcadmium and diisopropyltelluride were used as the reactants, released from a recently developed coating head orientated above the glass substrate (of area 15 × 15 cm2). Depositions were performed in static mode and dynamic mode (i.e., over a moving substrate). The deposited CdTe film weights were compared against the calculated theoretical value of the molar supply of the precursors, in order to estimate material utilisation. The numerical simulation gave insight into the effect that the exhaust’s restricted flow orifice configuration had on the deposition uniformity observed in the static experiments. It was shown that > 59% of material utilisation could be achieved under favourable deposition conditions. The activation energy determined from the Arrhenius plot of growth rate was ~ 60 kJ/mol and was in good agreement with previously reported CdTe growth using metalorganic chemical vapour deposition (MOCVD). Process requirements for using a chamberless environment for the inline deposition of compound semiconductor layers were presented.
Combination of the Experimental and Theoretical Approaches for the Estimation of the C1–C4 Alkane Permeability Parameters in Poly (4-Methyl-2-Pentyne) and Poly (4-Methyl-1-Pentene)
Authors: Markova Svetlana , Zhmakin Vyacheslav , Gries Thomas , Teplyakov Vladimir
Published: March 2020

Poly (4-methyl-2-pentyne) (PMPentyne) and poly (4-methyl-1-pentene) (PMPentene) as membrane gas-separating media were studied with a combination of experimental and theoretical approaches. Experimental approaches included the permeability measurements for C1–C4 alkanes in linear heating mode (for PMPentyne) and under isothermal conditions (for PMPentene), and diffusivity evaluation by a differential method for PMPentene. Theoretical approaches included the ‘hard-spheres’ theory for calculation of gas solubility in PMPentyne and gas transport theory for two-phase systems for the estimation of the amorphous and crystalline phases contribution in PMPentene. Correlation analysis was used for any type of gas transfer parameter calculation where experimental data were lacking. These combinations of methods allowed obtaining the whole set of parameters for any gas–polymer pairing and explained the butane-selective properties revealed in PMPentyne (C1 < C2 < C3 < C4) and methane-selective properties of PMPentene (C1 > C2 > C3 > C4).
Motion-Based Design of Passive Damping Systems to Reduce Wind-Induced Vibrations of Stay Cables under Uncertainty Conditions
Authors: Naranjo-Pérez Javier , Jiménez-Alonso Javier F. , M. Díaz Iván , Quaranta Giuseppe , Sáez Andrés
Published: March 2020

Stay cables exhibit both great slenderness and low damping, which make them sensitive to resonant phenomena induced by the dynamic character of external actions. Furthermore, for these same reasons, their modal properties may vary significantly while in service due to the modification of the operational and environmental conditions. In order to cope with these two limitations, passive damping devices are usually installed at these structural systems. Robust design methods are thus mandatory in order to ensure the adequate behavior of the stay cables without compromising the budget of the passive control systems. To this end, a motion-based design method under uncertainty conditions is proposed and further implemented in this paper. In particular, the proposal focuses on the robust design of different passive damping devices when they are employed to control the response of stay cables under wind-induced vibrations. The proposed method transforms the design problem into a constrained multi-objective optimization problem, where the objective function is defined in terms of the characteristic parameters of the passive damping device, together with an inequality constraint aimed at guaranteeing the serviceability limit state of the structure. The performance of the proposed method was validated via its application to a benchmark structure with vibratory problems: The longest stay cable of the Alamillo bridge (Seville, Spain) was adopted for this purpose. Three different passive damping devices are considered herein, namely: (i) viscous; (ii) elastomeric; and (iii) frictions dampers. The results obtained by the proposed approach are analyzed and further compared with those provided by a conventional method adopted in the Standards. This comparison illustrates how the newly proposed method allows reduction of the cost of the three types of passive damping devices considered in this study without compromising the performance of the structure.
Spatial Characteristics of Heat Extremes in South Korea from the Climatological Mean Perspective
Authors: Park Doo-Sun R. , Yang Suyeon , Cho Hyung Wook , Park Tae-Won
Published: March 2020

We investigated the spatial characteristics of heat extremes in South Korea from the climatological mean perspective. A heat extreme was defined as a day when the daily maximum temperature was higher than 33 °C. According to our analyses, the eastern area of the Sobaek and Taebaek mountain ranges (hereafter called the eastern district) is significantly more exposed to heat extremes compared to other areas. The onset date and total number of days of annual heat extremes in the eastern district are approximately 13 days earlier and 3 days higher than those in the western district on average, respectively. Likewise, the annual mean of daily maximum temperatures during heat extreme days are approximately 0.25 °C higher. This larger exposure to heat extremes in the eastern district appears to be attributable to the Föhn phenomenon, which is likely induced by the dominant southwesterly monsoon during the early-to-peak summer. In contrast, differences in the ending dates of annual heat extremes are not noticeable between the eastern and western districts, when the southerly winds are dominant. Our analyses suggest that heat extremes in South Korea cannot be understood by a simple function of latitude, but in conjunction with atmospheric physical processes.
Characteristics of Air Pollution and Their Relationship with Meteorological Parameters: Northern Versus Southern Cities of China
Authors: Zhou Haitao , Yu Yueming , Gu Xuan , Wu Yun , Wang Mei , Yue Hao , Gao Jiale , Lei Ruoyuan , Ge Xinlei
Published: March 2020

Air pollution shows a generally decreasing trend from the north to the south in China since 2013 (GB3095-2012, the current standard for monitoring). However, an opposite observation was recorded in 2017, especially in winter. In this study, we collected monitoring data of six air pollutants in 2016 and 2017, from a northern city (Beijing) and a southern city (Nanjing) for comparison. As air pollution was highly dependent upon meteorological conditions, we further analyzed their relationships to explain this abnormal phenomenon. Seasonal averaged PM2.5, PM10, SO2, CO, and NO2 were negatively correlated with wind scale (WS) while 8-h O3 exhibited an opposite relationship. Relative humidity (RH) has opposite effects on the concentrations of different pollutants in Beijing and Nanjing. The 8-h O3 showed the closest positive correlation with temperature (T), which is due to its formation mechanism. In Beijing, decreased RH, together with more wind from northwest in winter, resulted in an improved air quality in 2017. In Nanjing, WS, RH, T, and wind direction fluctuated within a narrow range in each season, leading to relatively stable pollutant concentrations. These results suggest that meteorological conditions are important factors to evaluate the air quality and implement control measures.
Effect of Tillage System and Cover Crop on Maize Mycorrhization and Presence of Magnaporthiopsis maydis
Authors: Patanita Mariana , Campos Maria Doroteia , Félix Maria do Rosário , Carvalho Mário , Brito Isabel
Published: March 2020

The sustainability of agriculture requires the adoption of agricultural soil conservation practices with positive impacts on soil quality, which can promote beneficial soil microbiota like arbuscular mycorrhizal fungi (AMF) and its diversity. This study aims to assess the influence of the presence of intact extraradical mycelium as a preferential source of inoculum of the native AMF in order to guarantee a better colonization as well as its possible bioprotective effect against Magnaporthiopsis maydis. In order to vary the available extraradical mycelium, two experiments, with and without cover crop, were carried out, in which two tillage systems and two maize varieties were studied. The capitalization of the benefits, in terms of grain production and M. maydis presence, associated to the cover crop were only achieved with minimum tillage. Therefore, both cultural practices are necessary to reduce the fungus presence, coupling the effect of mycorrhization together with other benefits associated with the cover crop. Although in the absence of a cover crop and using conventional tillage, yields and lower levels of M. maydis are possibly achieved, this system is more dependent on the variety used, does not benefit from the advantages associated with the cover crop, is more expensive, and environmentally unsustainable.
Haematoxylon campechianum Extract Ameliorates Neuropathic Pain via Inhibition of NF-κB/TNF-α/NOX/iNOS Signalling Pathway in a Rat Model of Chronic Constriction Injury
Authors: Sobeh Mansour , Mahmoud Mona , Rezq Samar , Abdelfattah Mohamed , Mostafa Islam , Alsemeh Amira , El-Shazly Assem , Yasri Aziz , Wink Michael
Published: March 2020

In this study, the phytochemical composition and the possible prophylactic effects of an aqueous ethanol extract of Haematoxylon campechianum flowers (HCF) on peripheral neuropathic pain in a chronic constriction injury (CCI) rat model are investigated. Rats with induced CCI were subjected to neuropathic pain behaviour tests and evaluated by chemical, thermal, and mechanical sensation tests and functional recovery of the brain stem and sciatic nerve at 7- and 14-day intervals. The effect of the extract on acute pain and inflammation is also investigated. The extract exerted both peripheral and central analgesic and anti-inflammatory properties in addition to antipyretic effects that are clear from targeting COX, LOX and PGE. It was found that CCI produced significant thermal and mechanical hyperalgesia, cold allodynia and deleterious structural changes in both sciatic nerve and brain stem. Treatments with HCF extract significantly improved cold and thermal withdrawal latency, mechanical sensibility and ameliorated deleterious changes of sciatic nerve and brain stem at different dose levels. The extract also ameliorated oxidative stress and inflammatory markers in brain stem and sciatic nerve. It suppressed the apoptotic marker, p53, and restored myelin sheath integrity. The effects of HCF extract were more potent than pregabalin. Fifteen secondary metabolites, mainly gallotannins and flavonoids, were characterized in the extract based on their retention times and MS/MS data. The identified phenolic constituents from the extract could be promising candidates to treat neuropathic pain due to their diverse biological activities, including antioxidant, anti-inflammatory and neuroprotective properties.
Homocysteine Induces Inflammation in Retina and Brain
Authors: Elsherbiny Nehal M. , Sharma Isha , Kira Dina , Alhusban Suhib , Samra Yara A. , Jadeja Ravirajsinh , Martin Pamela , Al-Shabrawey Mohamed , Tawfik Amany
Published: March 2020

Homocysteine (Hcy) is an amino acid that requires vitamins B12 and folic acid for its metabolism. Vitamins B12 and folic acid deficiencies lead to hyperhomocysteinemia (HHcy, elevated Hcy), which is linked to the development of diabetic retinopathy (DR), age-related macular degeneration (AMD), and Alzheimer’s disease (AD). The goal of the current study was to explore inflammation as an underlying mechanism of HHcy-induced pathology in age related diseases such as AMD, DR, and AD. Mice with HHcy due to a lack of the enzyme cystathionine-β-synthase (CBS) and wild-type mice were evaluated for microglia activation and inflammatory markers using immuno-fluorescence (IF). Tissue lysates isolated from the brain hippocampal area from mice with HHcy were evaluated for inflammatory cytokines using the multiplex assay. Human retinal endothelial cells, retinal pigment epithelial cells, and monocyte cell lines treated with/without Hcy were evaluated for inflammatory cytokines and NFκB activation using the multiplex assay, western blot analysis, and IF. HHcy induced inflammatory responses in mouse brain, retina, cultured retinal, and microglial cells. NFκB was activated and cytokine array analysis showed marked increase in pro-inflammatory cytokines and downregulation of anti-inflammatory cytokines. Therefore, elimination of excess Hcy or reduction of inflammation is a promising intervention for mitigating damage associated with HHcy in aging diseases such as DR, AMD, and AD.
Surface Probe Linker with Tandem Anti-Fouling Properties for Application in Biosensor Technology
Authors: Spagnolo Sandro , De La Franier Brian , Hianik Tibor , Thompson Michael
Published: March 2020

This paper describes the anti-fouling capability of the novel monolayer-forming surface linker 3-(3-(trichlorosilylpropyloxy) propanoyl chloride (MEG-Cl). This compound was successfully attached to quartz crystal surfaces which are employed in an electromagnetic piezoelectric acoustic sensor (EMPAS) configuration. The MEG-Cl coated surface was both employed with Ni-NTA for the binding of recombinant proteins and for the tandem property of the avoidance of fouling from serum and milk. The MEG-Cl coated surfaces were found to provide a large degree of anti-fouling on the EMPAS device, and were comparable to previously studied MEG-OH surfaces. Importantly, the monolayer continued to provide anti-fouling capability to the biosensor following extension with Ni-NTA in place. Accordingly, this surface linker provides an attractive system for use in biosensor technology in terms of both its anti-fouling and linking properties.
The Growing Interest in Development of Innovative Optical Aptasensors for the Detection of Antimicrobial Residues in Food Products
Authors: Gaudin Valérie
Published: March 2020

The presence of antimicrobial residues in food-producing animals can lead to harmful effects on the consumer (e.g., allergies, antimicrobial resistance, toxicological effects) and cause issues in food transformation (i.e., cheese, yogurts production). Therefore, to control antimicrobial residues in food products of animal origin, screening methods are of utmost importance. Microbiological and immunological methods (e.g., ELISA, dipsticks) are conventional screening methods. Biosensors are an innovative solution for the development of more performant screening methods. Among the different kinds of biosensing elements (e.g., antibodies, aptamers, molecularly imprinted polymers (MIP), enzymes), aptamers for targeting antimicrobial residues are in continuous development since 2000. Therefore, this review has highlighted recent advances in the development of aptasensors, which present multiple advantages over immunosensors. Most of the aptasensors described in the literature for the detection of antimicrobial residues in animal-derived food products are either optical or electrochemical sensors. In this review, I have focused on optical aptasensors and showed how nanotechnologies (nanomaterials, micro/nanofluidics, and signal amplification techniques) largely contribute to the improvement of their performance (sensitivity, specificity, miniaturization, portability). Finally, I have explored different techniques to develop multiplex screening methods. Multiplex screening methods are necessary for the wide spectrum detection of antimicrobials authorized for animal treatment (i.e., having maximum residue limits).
Exploring the Baseline Knowledge and Experience of Healthcare Professionals in the United Kingdom on Novel Psychoactive Substances
Authors: Ramos Camille , Guirguis Amira , Smeeton Nigel , Zaman Hadar , Felice Anna-Marie , Bancroft Stephanie , Gittins Rosalind , Hawksworth Gill , Corkery John Martin , Schifano Fabrizio
Published: March 2020

Objective: This survey aimed to explore knowledge and experience on novel psychoactive substances (NPS) of healthcare professionals (HCPs). The study also aimed to assess how HCPs would like to improve their knowledge of NPS. Methods: Seventy paper questionnaires were disseminated in 2017 within continuing education events to pharmacists, nurses and general practitioners (GPs). Additionally, 127 online surveys were completed using the Qualtrics platform by other HCPs and mental health nurses in six United Kingdom (UK) independent mental health hospitals long-stay in-patient rehabilitation services. Two educational sessions involving pharmacists and GPs were also held in late 2017 and mid-2018. Knowledge of NPS by HCPs was evaluated prior to the start of the educational events. Evaluation forms were handed out post-sessions to garner feedback, especially on areas for improvement for future sessions. Statistical analysis of data was undertaken using SPSS (V.25). Results: Most HCPs reported only ‘basic’ to ‘intermediate’ NPS knowledge. Substance misuse service staff felt more informed, were more often consulted and had greater confidence regarding NPS compared to hospital and primary care professionals. A negative association was found between the age of the HCP and knowledge of NPS. Most participants expressed a need for regular training and updates as insufficient NPS-related information is currently received. Conclusions: An improvement within the self-reported knowledge of HCPs on NPS is evident in comparison to previous studies. Continued education of HCPs on NPS is fundamental for the provision of improved harm reduction services, which can enhance overall care for NPS service users.
Welds Assessment in K-Type Joints of Hollow Section Trusses with I or H Section Chords
Authors: Broniewicz Miroslaw , Broniewicz Filip
Published: March 2020

The use of hollow section structures has received considerable attention in recent years. Since the first publication of CIDECT (International Committee for the Development and Study of Tubular Structures), additional research results became available, especially concerning the design of welds between members of trusses joints. To assess the capacity of welded joints of trusses between braces made of hollow sections and I-beam chords, the effective lengths of the welds should be estimated and their location around the braces and the forces acting on individual weld’s sections. The objective of this paper is to present the most up-to-date information to designers, teachers, and researchers according to the design of welds for certain K and N overlapped joints between rectangular hollow section (RHS) braces and I- or H-section chord.
Exploring the Influence of an Urban Water System on Housing Prices: Case Study of Zhengzhou
Authors: Li Junjie , Hu Yaduo , Liu Chunlu
Published: March 2020

A good living environment is the foundation of sustainable housing. Exploring the external influence of environmental factors on housing prices is one of the key issues in the field of real estate research; however, the current study of the urban water landscape on the spillover effect of housing prices is not sufficient. Taking the Zhengzhou residential market as an example, this paper analyzes the effect of an urban water system on residential prices by constructing the traditional Hedonic price model, spatial lag model (SLM) and geographically weighted regression model (GWR) by selecting the main water system and 678 points of residential data in the main urban area. The results show that the accessibility of rivers and lakes and the width and water quality of rivers have a significant effect on residential prices, and the impact of lakes is greater than that of rivers. The spatial heterogeneity of the water system effect is further revealed by adopting spatial lag model and geographically weighted regression model, and the effect of the water system is gradually reduced from the eastern urban area to the western urban area. The results of this study are of great practical significance to the government’s municipal planning, water environment management and housing market management.
Development and Radiation Response Assessment in A Novel Syngeneic Mouse Model of Tongue Cancer: 2D Culture, 3D Organoids and Orthotopic Allografts
Authors: Vincent-Chong Vui King , Seshadri Mukund
Published: March 2020

Oral squamous cell carcinoma (OSCC) are aggressive cancers that contribute to significant morbidity and mortality in humans. Although numerous human xenograft models of OSCC have been developed, only a few syngeneic models of OSCC exist. Here, we report on a novel murine model of OSCC, RP-MOC1, derived from a tongue tumor in a C57Bl/6 mouse exposed to the carcinogen 4-nitroquinoline-1-oxide. Phenotypic characterization and credentialing (STR profiling, exome sequencing) of RP-MOC1 cells was performed in vitro. Radiosensitivity was evaluated in 2D culture, 3D organoids, and in vivo using orthotopic allografts. RP-MOC1 cells exhibited a stable epithelial phenotype with proliferative, migratory and invasive properties. Exome sequencing identified several mutations commonly found in OSCC patients. The LD50 for RP-MOC1 cells in 2D culture and 3D organoids was found to be 2.4 Gy and 12.6 Gy, respectively. Orthotopic RP-MOC1 tumors were pan-cytokeratin+ and Ki-67+. Magnetic resonance imaging of orthotopic RP-MOC1 tumors established in immunocompetent mice revealed marked growth inhibition following 10 Gy and 15 Gy fractionated radiation regimens. This radiation response was completely abolished in tumors established in immunodeficient mice. This novel syngeneic model of OSCC can serve as a valuable platform for the evaluation of combination strategies to enhance radiation response against this deadly disease.
Impact of the Monocarboxylate Transporter-1 (MCT1)-Mediated Cellular Import of Lactate on Stemness Properties of Human Pancreatic Adenocarcinoma Cells
Authors: Sandforth Leontine , Ammar Nourhane , Dinges Lisa Antonia , Röcken Christoph , Arlt Alexander , Sebens Susanne , Schäfer Heiner
Published: March 2020

Metabolite exchange between stromal and tumor cells or among tumor cells themselves accompanies metabolic reprogramming in cancer including pancreatic adenocarcinoma (PDAC). Some tumor cells import and utilize lactate for oxidative energy production (reverse Warburg-metabolism) and the presence of these “reverse Warburg“ cells associates with a more aggressive phenotype and worse prognosis, though the underlying mechanisms are poorly understood. We now show that PDAC cells (BxPc3, A818-6, T3M4) expressing the lactate-importer monocarboxylate transporter-1 (MCT1) are protected by lactate against gemcitabine-induced apoptosis in a MCT1-dependent fashion, contrary to MCT1-negative PDAC cells (Panc1, Capan2). Moreover, lactate administration under glucose starvation, resembling reverse Warburg co a phenotype of BxPc3 and T3M4 cells that confers greater potential of clonal growth upon re-exposure to glucose, along with drug resistance and elevated expression of the stemness marker Nestin and reprogramming factors (Oct4, KLF4, Nanog). These lactate dependent effects on stemness properties are abrogated by the MCT1/lactate-uptake inhibitor 7ACC2 or MCT1 knock-down. Furthermore, the clinical relevance of these observations was supported by detecting co-expression of MCT1 and reprogramming factors in human PDAC tissues. In conclusion, the MCT1-dependent import of lactate supplies “reverse Warburg “PDAC cells with an efficient driver of metabostemness. This condition may essentially contribute to malignant traits including therapy resistance.
Photochemical Study of a New Bimolecular Photoinitiating System for Vat Photopolymerization 3D Printing Techniques under Visible Light
Authors: Fiedor Paweł , Pilch Maciej , Szymaszek Patryk , Chachaj-Brekiesz Anna , Galek Mariusz , Ortyl Joanna
Published: March 2020

In this work, we presented a new bimolecular photoinitiating system based on 2-amino-4,6-diphenylpyridine-3-carbonitrile derivatives as visible photosensitizers of diphenyliodonium salt. Real-time FTIR and photo-DSC photopolymerization experiments with a cycloaliphatic epoxide and vinyl monomers showed surprisingly good reactivity of the bimolecular photoinitiating systems under UV-A, as well as under visible light sources. Steady-state photolysis, fluorescence experiments, theoretical calculations of molecular orbitals, and electrochemical analysis demonstrated photo-redox behavior as well as the ability to form initiating species via photo-reduction or photo-oxidation pathways, respectively. Therefore, the 2-amino-4,6-diphenylpyridine-3-carbonitrile derivatives were also investigated as a type II free-radical photoinitiator with amine. It was confirmed that the 2-amino-4,6-diphenylpyridine-3-carbonitrile derivatives, in combination with different types of additives, e.g., amine as a co-initiator or the presence of onium salt, can act as bimolecular photoinitiating systems for cationic, free-radical, and thiol-ene photopolymerization processes by hydrogen abstraction and/or electron transfer reactions stimulated by either near-UV or visible light irradiation. Finally, the 2-amino-4,6-diphenylpyridine-3-carbonitrile derivatives were selected for 3D printing rapid prototyping experiments. Test objects were successfully printed using purely cationic photosensitive resin, created on a 3D printer with a visible LED light source.
Manganese Catalysts with Tetradentate N-donor Pyridine-Appended Bipiperidine Ligands for Olefin Epoxidation Reactions: Ligand Electronic Effect and Mechanism
Authors: Zhu Fengfan , Yang Guang , Zoll Adam J. , Rybak-Akimova Elena V. , Zhu Xinbao
Published: March 2020

In this work, we described an electron-rich manganese mesoPYBP catalyst, Mn-SR-mesoPYBP(ClO4)2, by introducing electron-donating substituents on the mesoPYBP ligand. We optimized the catalytic performance in olefin epoxidation with H2O2 in the presence of acetic acid. The electron paramagnetic resonance (EPR) and cyclic voltammetry (CV) studies supported that an electronic effect could stabilize the high-valent intermediates in the catalytic cycles of the catalyst, which largely improved the catalytic performance and the reactivity of olefin epoxidation.
Ceria-Based Catalysts Studied by Near Ambient Pressure X-ray Photoelectron Spectroscopy: A Review
Authors: Garcia Xènia , Soler Lluís , Divins Núria J. , Vendrell Xavier , Serrano Isabel , Lucentini Ilaria , Prat Jordi , Solano Eduardo , Tallarida Massimo , Escudero Carlos , Llorca Jordi
Published: March 2020

The development of better catalysts is a passionate topic at the forefront of modern science, where operando techniques are necessary to identify the nature of the active sites. The surface of a solid catalyst is dynamic and dependent on the reaction environment and, therefore, the catalytic active sites may only be formed under specific reaction conditions and may not be stable either in air or under high vacuum conditions. The identification of the active sites and the understanding of their behaviour are essential information towards a rational catalyst design. One of the most powerful operando techniques for the study of active sites is near ambient pressure X-ray photoelectron spectroscopy (NAP-XPS), which is particularly sensitive to the surface and sub-surface of solids. Here we review the use of NAP-XPS for the study of ceria-based catalysts, widely used in a large number of industrial processes due to their excellent oxygen storage capacity and well-established redox properties.
Hepatocyte Injury and Hepatic Stem Cell Niche in the Progression of Non-Alcoholic Steatohepatitis
Authors: Overi Diletta , Carpino Guido , Franchitto Antonio , Onori Paolo , Gaudio Eugenio
Published: March 2020

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by lipid accumulation in hepatocytes in the absence of excessive alcohol consumption. The global prevalence of NAFLD is constantly increasing. NAFLD is a disease spectrum comprising distinct stages with different prognoses. Non-alcoholic steatohepatitis (NASH) is a progressive condition, characterized by liver inflammation and hepatocyte ballooning, with or without fibrosis. The natural history of NAFLD is negatively influenced by NASH onset and by the progression towards advanced fibrosis. Pathogenetic mechanisms and cellular interactions leading to NASH and fibrosis involve hepatocytes, liver macrophages, myofibroblast cell subpopulations, and the resident progenitor cell niche. These cells are implied in the regenerative trajectories following liver injury, and impairment or perturbation of these mechanisms could lead to NASH and fibrosis. Recent evidence underlines the contribution of extra-hepatic organs/tissues (e.g., gut, adipose tissue) in influencing NASH development by interacting with hepatic cells through various molecular pathways. The present review aims to summarize the role of hepatic parenchymal and non-parenchymal cells, their mutual influence, and the possible interactions with extra-hepatic tissues and organs in the pathogenesis of NAFLD.
The Quest for Cellular Prion Protein Functions in the Aged and Neurodegenerating Brain
Authors: Gavín Rosalina , Lidón Laia , Ferrer Isidre , del Río José Antonio
Published: March 2020

Cellular (also termed ‘natural’) prion protein has been extensively studied for many years for its pathogenic role in prionopathies after misfolding. However, neuroprotective properties of the protein have been demonstrated under various scenarios. In this line, the involvement of the cellular prion protein in neurodegenerative diseases other than prionopathies continues to be widely debated by the scientific community. In fact, studies on knock-out mice show a vast range of physiological functions for the protein that can be supported by its ability as a cell surface scaffold protein. In this review, we first summarize the most commonly described roles of cellular prion protein in neuroprotection, including antioxidant and antiapoptotic activities and modulation of glutamate receptors. Second, in light of recently described interaction between cellular prion protein and some amyloid misfolded proteins, we will also discuss the molecular mechanisms potentially involved in protection against neurodegeneration in pathologies such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.
Exosomes: From Potential Culprits to New Therapeutic Promise in the Setting of Cardiac Fibrosis
Authors: Tikhomirov Roman , Reilly-O’Donnell Benedict , Catapano Francesco , Faggian Giuseppe , Gorelik Julia , Martelli Fabio , Emanueli Costanza
Published: March 2020

Fibrosis is a significant global health problem associated with many inflammatory and degenerative diseases affecting multiple organs, individually or simultaneously. Fibrosis develops when extracellular matrix (ECM) remodeling becomes excessive or uncontrolled and is associated with nearly all forms of heart disease. Cardiac fibroblasts and myofibroblasts are the main effectors of ECM deposition and scar formation. The heart is a complex multicellular organ, where the various resident cell types communicate between themselves and with cells of the blood and immune systems. Exosomes, which are small extracellular vesicles, (EVs), contribute to cell-to-cell communication and their pathophysiological relevance and therapeutic potential is emerging. Here, we will critically review the role of endogenous exosomes as possible fibrosis mediators and discuss the possibility of using stem cell-derived and/or engineered exosomes as anti-fibrotic agents.
C. quinoa and S. hispanica L. Seeds Provide Immunonutritional Agonists to Selectively Polarize Macrophages
Authors: Srdić Maša , Ovčina Ivana , Fotschki Bartosz , Haros Claudia Monika , Laparra Llopis Jose Moises
Published: March 2020

Diet-related immunometabolic-based diseases are associated with chronic inflammation in metabolic tissues, and infiltrated macrophages have been suggested as mediators for tissue- damaging inflammation. Growing evidence implicates Chenopodium quinoa and Salvia hispanica L. as important contributors to immunonutritional health. However, the functional roles of the immunonutritional protease inhibitors (PPIs) found in these crops on the macrophages’ metabolic and phenotypic adaptation remain to be elucidated. The salt soluble fraction of proteins was extracted and analyzed confirming the presence of 11S and 2S albumin. The <30 kDa fraction of the extract from both crops was subjected to simulated gastrointestinal digestion, where (RP-LC-MS/MS analyses) polypeptides from 2S-type of proteins were found, along with the 2S albumin (13 kDa) for S. hispanica in the bioaccessible fraction (BAF). Using human-like macrophage cells to deepen our understanding of the modulatory effects of this BAF, FACS analyses revealed their potential as TLR4 agonists, favoring increased phenotypic CD68/CD206 ratios. The results of mitochondrial stress tests showed that cells increased oxygen consumption rates and non-mitochondrial respiration, confirming negligible deleterious effects on mitochondrial function. At molecular-level, adaptation responses shed light on changes showing biological correlation with TLR4 signaling. The resulting immunometabolic effects triggered by PPIs can be a part of a tailored nutritional intervention strategy in immunometabolic-based diseases.
3,4-Dihydroxybenzalacetone (DBL) Prevents Aging-Induced Myocardial Changes in Senescence-Accelerated Mouse-Prone 8 (SAMP8) Mice
Authors: Giridharan Vijayasree V. , Karupppagounder Vengadeshprabhu , Arumugam Somasundaram , Nakamura Yutaka , Guha Ashrith , Barichello Tatiana , Quevedo Joao , Watanabe Kenichi , Konishi Tetsuya , Thandavarayan Rajarajan A.
Published: March 2020

Aging is a predominant risk factor for the development and progression of cardiovascular complications. Physiologically and anatomically, the heart undergoes numerous changes that result in poor cardiac function in the elderly population. Recently, several studies have provided promising results, confirming the ability of the senescence-accelerated mouse-prone 8 (SAMP8) model to accurately model age-related cardiovascular alterations. In this study, using a murine model of senescence, SAMP8, we aimed to investigate the effect of 3,4-dihydroxybenzalacetone (DBL), a catechol-containing phenylpropanoid derivative isolated from Inonotus obliquus (Chaga), on cardiac aging. DBL was administered at the doses of 10 mg/kg and 20 mg/kg by oral gavage to SAMP8 mice to examine aging-mediated cardiac changes, such as oxidative DNA damage, oxygen radical antioxidant capacity (ORAC) value, fibrosis, inflammation, and apoptosis. The treatment with DBL at both doses significantly reduced aging-mediated oxidative DNA damage, and simultaneously increased the ORAC value in the SAMP8 assay. Cardiac fibrosis was assessed with Azan-Mallory staining, and the number of cardiac remodeling markers was found to be significantly reduced after the treatment with DBL. We also observed a decrease in cardiomyocyte apoptosis as measured by the terminal transferase-mediated dUTP nick end labeling (TUNEL) staining method and the caspase-3 levels in SAMP8 mice compared with senescence-resistant control (SAMR1) mice. The findings from this study suggest that DBL has a potentially beneficial effect on aging-mediated myocardial alterations. Further studies are warranted to confirm the promising potential of this catechol compound against aging-associated myocardial dysfunction.
Immunotherapy in Multiple Myeloma
Authors: Soekojo Cinnie Yentia , Ooi Melissa , de Mel Sanjay , Chng Wee Joo
Published: March 2020

Multiple myeloma is a complex disease and immune dysfunction has been known to play an important role in the disease pathogenesis, progression, and drug resistance. Recent efforts in drug development have been focused on immunotherapies to modify the MM disease process. Here, we summarize the emerging immunotherapies in the MM treatment landscape.
PPE51 Is Involved in the Uptake of Disaccharides by Mycobacterium tuberculosis
Authors: Korycka-Machała Małgorzata , Pawełczyk Jakub , Borówka Paulina , Dziadek Bożena , Brzostek Anna , Kawka Malwina , Bekier Adrian , Rykowski Sebastian , Olejniczak Agnieszka B. , Strapagiel Dominik , Witczak Zbigniew , Dziadek Jarosław
Published: March 2020

We have recently found that selected thio-disaccharides possess bactericidal effects against Mycobacterium tuberculosis but not against Escherichia coli or Staphylococcus aureus. Here, we selected spontaneous mutants displaying resistance against the investigated thio-glycoside. According to next-generation sequencing, four of six analyzed mutants which were resistant to high concentrations of the tested chemical carried nonsynonymous mutations in the gene encoding the PPE51 protein. The complementation of these mutants with an intact ppe51 gene returned their sensitivity to the wild-type level. The uptake of tritiated thio-glycoside was significantly more abundant in wild-type Mycobacterium tuberculosis compared to the strain carrying the mutated ppe51 gene. The ppe51 mutations or CRISPR-Cas9-mediated downregulation of PPE51 expression affected the growth of mutant strains on minimal media supplemented with disaccharides (maltose or lactose) but not with glycerol or glucose as the sole carbon and energy source. Taking the above into account, we postulate that PPE51 participates in the uptake of disaccharides by tubercle bacilli.
The Winner Takes It All: Auxin—The Main Player during Plant Embryogenesis
Authors: Winnicki Konrad
Published: March 2020

In plants, the first asymmetrical division of a zygote leads to the formation of two cells with different developmental fates. The establishment of various patterns relies on spatial and temporal gene expression, however the precise mechanism responsible for embryonic patterning still needs elucidation. Auxin seems to be the main player which regulates embryo development and controls expression of various genes in a dose-dependent manner. Thus, local auxin maxima and minima which are provided by polar auxin transport underlie cell fate specification. Diverse auxin concentrations in various regions of an embryo would easily explain distinct cell identities, however the question about the mechanism of cellular patterning in cells exposed to similar auxin concentrations still remains open. Thus, specification of cell fate might result not only from the cell position within an embryo but also from events occurring before and during mitosis. This review presents the impact of auxin on the orientation of the cell division plane and discusses the mechanism of auxin-dependent cytoskeleton alignment. Furthermore, close attention is paid to auxin-induced calcium fluxes, which regulate the activity of MAPKs during postembryonic development and which possibly might also underlie cellular patterning during embryogenesis.