bluuebunny/crossref_metadata_2025 huggingface dataset:
Indoor Positioning Integrating PDR/Geomagnetic Positioning Based on the Genetic-Particle Filter
Authors: Sun Meng , Wang Yunjia , Xu Shenglei , Cao Hongji , Si Minghao
Published: January 2020

This paper proposes a fusion indoor positioning method that integrates the pedestrian dead-reckoning (PDR) and geomagnetic positioning by using the genetic-particle filter (GPF) algorithm. In the PDR module, the Mahony complementary filter (MCF) algorithm is adopted to estimate the heading angles. To improve geomagnetic positioning accuracy and geomagnetic fingerprint specificity, the geomagnetic multi-features positioning algorithm is devised and five geomagnetic features are extracted as the single-point fingerprint by transforming the magnetic field data into the geographic coordinate system (GCS). Then, an optimization mechanism is designed by using gene mutation and the method of reconstructing a particle set to ameliorate the particle degradation problem in the GPF algorithm, which is used for fusion positioning. Several experiments are conducted to evaluate the performance of the proposed methods. The experiment results show that the average positioning error of the proposed method is 1.72 m and the root mean square error (RMSE) is 1.89 m. The positioning precision and stability are improved compared with the PDR method, geomagnetic positioning, and the fusion-positioning method based on the classic particle filter (PF).
A Simplified Mathematical Model for the Analysis of Varying Compliance Vibrations of a Rolling Bearing
Authors: Tomović Radoslav
Published: January 2020

In this paper, a simplified approach in the analysis of the varying compliance vibrations of a rolling bearing is presented. This approach analyses the generation of vibrations in relation to two boundary positions of the inner ring support on an even and an odd number of the rolling element of a bearing. In this paper, a mathematical model for the calculation of amplitude and frequency of vibrations of a rigid rotor in a rolling bearing is presented. The model is characterized by a big simplicity which makes it very convenient for a practical application. Based on the presented mathematical model a parametric analysis of the influence of the internal radial clearance, external radial load and the total number of rolling elements on the varying compliance vibrations of rolling bearing was conducted. These parameters are the most influential factors for generating varying compliance vibrations. The results of the parametric analysis demonstrate that with the proper choice of the size of the internal radial clearance and external radial load, the level of the varying compliance vibrations in a rolling bearing can be theoretically reduced to zero. This result opposes the opinion that varying compliance vibrations of rolling bearing cannot be avoided, even for geometrically ideally produced bearing.
Determining the Effect of Extreme Weather Events on Human Participation in Recreation and Tourism: A Case Study of the Toronto Zoo
Authors: Hewer Micah
Published: January 2020

This study devises a novel approach for defining extreme weather events and assessing their effects on human participation in recreation and tourism, based on a case study of attendance at the Toronto Zoo (Toronto, ON, Canada). Daily zoo attendance data from 1999 to 2018 was obtained and analyzed in connection with daily weather data from local weather stations for the maximum temperature, minimum temperature, total precipitation, and maximum wind speed. The “climatic distance” method, used for evaluating representative weather stations for case studies in applied climatology, was employed to rank and select surrounding weather stations that most accurately captured daily weather observations recorded at the Toronto Zoo from 1990 to 1992. Extreme weather events can be defined as lying in the outermost (most unusual) 10 percent of a place’s history. Using this definition as the foundation, a percentile approach was developed to identify and assess the effects of extreme weather events across the following thresholds: the 99th percentile, the 95th percentile, and the 90th percentile, as well as less than the 1st percentile, less than the 5th percentile, and less than the 10th percentile. Additionally, revealed, theoretical, and binary thresholds were also assessed to verify their merit and determine their effects, and were compared to the extreme weather events defined by the percentiles approach. Overall, extreme daily weather events had statistically significant negative effects on zoo attendance in Toronto, apart from a few cases, such as the positive effect of usually warm daytime temperatures in the winter and usually cool nighttime temperatures in the summer. The most influential weather event across all seasons was extremely hot temperatures, which has important implications for climate change impact assessments.
Computational Study of the Dissociation Reactions of Secondary Ozonide
Authors: Almatarneh Mansour H. , Alrebei Shefa’ F. , Altarawneh Mohammednoor , Zhao Yuming , Abu-Saleh Abd Al-Aziz
Published: January 2020

This contribution presents a comprehensive computational study on the reactions of secondary ozonide (SOZ) with ammonia and water molecules. The mechanisms were studied in both a vacuum and the aqueous medium. All the molecular geometries were optimized using the B3LYP functional in conjunction with several basis sets. M06-2X, APFD, and ωB97XD functionals with the full basis set were also used. In addition, single-point energy calculations were performed with the G4MP2 and G3MP2 methods. Five different mechanistic pathways were studied for the reaction of SOZ with ammonia and water molecules. The most plausible mechanism for the reaction of SOZ with ammonia yields HC(O)OH, NH3, and HCHO as products, with ammonia herein acting as a mediator. This pathway is exothermic and exergonic, with an overall barrier height of only 157 kJ mol−1 using the G3MP2 method. All the reaction pathways between SOZ and water molecules are endothermic and endergonic reactions. The most likely reaction pathway for the reaction of SOZ with water involves a water dimer, in which the second water molecule acts as a mediator, with an overall barrier height of only 135 kJ mol−1 using the G3MP2 method. Solvent effects were found to incur a significant reduction in activation energies. When the second H2O molecule acts as a mediator in the reaction of SOZ with water, the barrier height of the rate-determining step state decreases significantly.
Fine-Scale Columnar and Surface NOx Concentrations over South Korea: Comparison of Surface Monitors, TROPOMI, CMAQ and CAPSS Inventory
Authors: Kim Hyun Cheol , Kim Soontae , Lee Sang-Hyun , Kim Byeong-Uk , Lee Pius
Published: January 2020

Fine-scale nitrogen oxide (NOx) concentrations over South Korea are examined using surface observations, satellite data and high-resolution model simulations based on the latest emission inventory. While accurate information on NOx emissions in South Korea is crucial to understanding regional air quality in the region, consensus on the validation of NOx emissions is lacking. We investigate the spatial and temporal variation in fine-scale NOx emission sources over South Korea. Surface observations and newly available fine-scale satellite data (TROPOspheric Monitoring Instrument; TROPOMI; 3.5 × 7 km2) are compared with the community multiscale air quality (CMAQ) model based on the clean air policy support system (CAPSS) 2016 emission inventory. The results show that the TROPOMI NO2 column densities agree well with the CMAQ simulations based on CAPSS emissions (e.g., R = 0.96 for June 2018). The surface observations, satellite data and model are consistent in terms of their spatial distribution, the overestimation over the Seoul Metropolitan Area and major point sources; however, the model tends to underestimate the surface concentrations during the cold season.
Heavy Rainfall Events and Mass Movements in the Funchal Area (Madeira, Portugal): Spatial Analysis and Susceptibility Assessment
Authors: Lopes Sérgio , Fragoso Marcelo , Lopes António
Published: January 2020

The article presents new information on the spatial distribution of intense rainfall and a new map of susceptibility to the formation of mass movements in the mountainous streams of the municipality of Funchal, the capital of the Autonomous Region of Madeira, an archipelago of Portugal. The methodology that was adopted is based on the spatial analysis of weighted overlap of variables, with influence in the occurrence of hydro-geomorphological processes that are at the origin of catastrophic events, marked by the mobilization of solid material towards and along the fluvial channels. Intense precipitations are effectively the main triggering factor of mass movements, which is why their statistical characteristics and local contrasts are analyzed, to integrate this layer of information into the new susceptibility assessment model of mass movements produced in this article. This type of spatialized information is of strategic importance to support the planning of urban expansion, which requires a land use management practice in accordance with the existing risk in the Madeira Island.
Hybrid Ventilation System and Soft-Sensors for Maintaining Indoor Air Quality and Thermal Comfort in Buildings
Authors: Vadamalraj Nivetha , Zingre Kishor , Seshadhri Subathra , Arjunan Pandarasamy , Srinivasan Seshadhri
Published: January 2020

Maintaining both indoor air quality (IAQ) and thermal comfort in buildings along with optimized energy consumption is a challenging problem. This investigation presents a novel design for hybrid ventilation system enabled by predictive control and soft-sensors to achieve both IAQ and thermal comfort by combining predictive control with demand controlled ventilation (DCV). First, we show that the problem of maintaining IAQ, thermal comfort and optimal energy is a multi-objective optimization problem with competing objectives, and a predictive control approach is required to smartly control the system. This leads to many implementation challenges which are addressed by designing a hybrid ventilation scheme supported by predictive control and soft-sensors. The main idea of the hybrid ventilation system is to achieve thermal comfort by varying the ON/OFF times of the air conditioners to maintain the temperature within user-defined bands using a predictive control and IAQ is maintained using Healthbox 3.0, a DCV device. Furthermore, this study also designs soft-sensors by combining the Internet of Things (IoT)-based sensors with deep-learning tools. The hardware realization of the control and IoT prototype is also discussed. The proposed novel hybrid ventilation system and the soft-sensors are demonstrated in a real research laboratory, i.e., Center for Research in Automatic Control Engineering (C-RACE) located at Kalasalingam University, India. Our results show the perceived benefits of hybrid ventilation, predictive control, and soft-sensors.
Viscosity Approximation Methods for

*

−Nonexpansive Multi-Valued Mappings in Convex Metric Spaces
Authors: Ghanifard Azadeh , Masiha Hashem Parvaneh , De La Sen Manuel , Ramezani Maryam
Published: January 2020

In this paper, we prove convergence theorems for viscosity approximation processes involving * −nonexpansive multi-valued mappings in complete convex metric spaces. We also consider finite and infinite families of such mappings and prove convergence of the proposed iteration schemes to common fixed points of them. Our results improve and extend some corresponding results.
Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?
Authors: Wang Fei-Xuan , Li Hong-Yan , Li Yun-Qian , Kong Ling-Dong
Published: January 2020

The toxic reactive aldehyde 4-hydroxynonenal (4-HNE) belongs to the advanced lipid peroxidation end products. Accumulation of 4-HNE and formation of 4-HNE adducts induced by redox imbalance participate in several cytotoxic processes, which contribute to the pathogenesis and progression of oxidative stress-related human disorders. Medicinal plants and bioactive natural compounds are suggested to be attractive sources of potential agents to mitigate oxidative stress, but little is known about the therapeutic potentials especially on combating 4-HNE-induced deleterious effects. Of note, some investigations clarify the attenuation of medicinal plants and bioactive compounds on 4-HNE-induced disturbances, but strong evidence is needed that these plants and compounds serve as potent agents in the prevention and treatment of disorders driven by 4-HNE. Therefore, this review highlights the pharmacological basis of these medicinal plants and bioactive compounds to combat 4-HNE-induced deleterious effects in oxidative stress-related disorders, such as neurotoxicity and neurological disorder, eye damage, cardiovascular injury, liver injury, and energy metabolism disorder. In addition, this review briefly discusses with special attention to the strategies for developing potential therapies by future applications of these medicinal plants and bioactive compounds, which will help biological and pharmacological scientists to explore the new vistas of medicinal plants in combating 4-HNE-induced deleterious effects.
Combined Kinetin and Spermidine Treatments Ameliorate Growth and Photosynthetic Inhibition in Vigna angularis by Up-Regulating Antioxidant and Nitrogen Metabolism under Cadmium Stress
Authors: Ahanger Mohammad Abass , Aziz Usman , Alsahli Abdulaziz , Alyemeni Mohammed Nasser , Ahmad Parvaiz
Published: January 2020

Pot experiments were conducted to investigate the probable beneficial role of the individual as well as combined application of kinetin (50 μM Kn) and spermidine (200 μM Spd) on Vigna angularis under cadmium (Cd) stress. Cd treatment reduced growth by declining the content of chlorophylls and carotenoids, photosynthesis, and gas exchange parameters. Exogenously, Kn and Spd application enhanced the photosynthetic parameters and up-regulated the antioxidant system by improving the activities of antioxidant enzymes and the content of non-enzymatic components. In addition, the application of Kn and Spd resulted in significant improvement in the content of sugars, proline, and glycine betaine, ameliorating the decline in relative water content. Oxidative stress parameters including hydrogen peroxide, superoxide, lipid peroxidation, lipoxygenase activity, and electrolyte leakage increased due to Cd stress; however, the application of Kn and Spd imparted a significant decline in all these parameters. Further, reduced Cd uptake was also observed due to Kn and Spd application. Total phenols and flavonoids also increased due to Kn and Spd treatments under normal as well as Cd stress conditions, which may have further helped with the elimination of reactive oxygen species. Reduction in the activity of nitrate reductase and the content of nitrogen was ameliorated due to the exogenous application of Kn and Spd. Therefore, the exogenous application of Kn and Spd benefited Vigna angularis counteracting the damaging effects of Cd stress by up-regulating the tolerance mechanisms, including antioxidant and osmolyte metabolism.
Retinoic Acid: A Key Regulator of Lung Development
Authors: Fernandes-Silva Hugo , Araújo-Silva Henrique , Correia-Pinto Jorge , Moura Rute S
Published: January 2020

Retinoic acid (RA) is a key molecular player in embryogenesis and adult tissue homeostasis. In embryo development, RA plays a crucial role in the formation of different organ systems, namely, the respiratory system. During lung development, there is a spatiotemporal regulation of RA levels that assures the formation of a fully functional organ. RA signaling influences lung specification, branching morphogenesis, and alveolarization by regulating the expression of particular target genes. Moreover, cooperation with other developmental pathways is essential to shape lung organogenesis. This review focuses on the events regulated by retinoic acid during lung developmental phases and pulmonary vascular development; also, it aims to provide a snapshot of RA interplay with other well-known regulators of lung development.
Valorization of Flaxseed Oil Cake Residual from Cold-Press Oil Production as a Material for Preparation of Spray-Dried Functional Powders for Food Applications as Emulsion Stabilizers
Authors: Drozłowska Emilia , Łopusiewicz Łukasz , Mężyńska Monika , Bartkowiak Artur
Published: January 2020

Flaxseed oil cake extract (residual from cold-press oil production and rich in proteins and polysaccharides) was evaluated as a potential substrate for the preparation of spray-dried powders with emulsifying activity. Three variants of powders were obtained using different spray-drying process inlet temperatures: 160 °C, 180 °C, and 200 °C. The influence of temperature on physicochemical features (water holding capacity, oil binding capacity, water activity, solubility, color, chemical composition, antioxidant activity, and surface morphology) of the powders was estimated. Additionally, the emulsifying activity of the powders and the stability of oil-in-water emulsions prepared with their various content (0.5%, 1%, and 3%) were determined. Results showed that inlet temperature had significant influence on all physicochemical and functional properties of the powders. Increased inlet temperature decreased solubility and antioxidant activity but increased water-holding capacity, oil-binding capacity, and emulsifying activity. The emulsions prepared with the powder obtained at 200 °C showed the highest stability. SEM images showed the production of relatively spherical particles which were folded or wrinkled with a lot of dentures. This study could open a promising pathway for producing natural and plant-based spray-dried powders for food applications as emulsion stabilizers.
Comparative Evaluation of the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes and Platelet-Rich Plasma: An In Vitro Analysis
Authors: Moog Philipp , Kirchhoff Katharina , Bekeran Sanjar , Bauer Anna-Theresa , von Isenburg Sarah , Dornseifer Ulf , Machens Hans-Günther , Schilling Arndt F. , Hadjipanayi Ektoras
Published: January 2020

Blood-derived factor preparations are being clinically employed as tools for promoting tissue repair and regeneration. Here we set out to characterize the in vitro angiogenic potential of two types of frequently used autologous blood-derived secretomes: platelet-rich plasma (PRP) and hypoxia preconditioned plasma (HPP)/serum (HPS). The concentration of key pro-angiogenic (VEGF) and anti-angiogenic (TSP-1, PF-4) protein factors in these secretomes was analyzed via ELISA, while their ability to induce microvessel formation and sprouting was examined in endothelial cell and aortic ring cultures, respectively. We found higher concentrations of VEGF in PRP and HPP/HPS compared to normal plasma and serum. This correlated with improved induction of microvessel formation by PRP and HPP/HPS. HPP had a significantly lower TSP-1 and PF-4 concentration than PRP and HPS. PRP and HPP/HPS appeared to induce similar levels of microvessel sprouting; however, the length of these sprouts was greater in HPP/HPS than in PRP cultures. A bell-shaped angiogenic response profile was observed with increasing HPP/HPS dilutions, with peak values significantly exceeding the PRP response. Our findings demonstrate that optimization of peripheral blood cell-derived angiogenic factor signalling through hypoxic preconditioning offers an improved alternative to simple platelet concentration and release of growth factors pre-stored in platelets.
High-Yield Production of Aqueous Graphene for Electrohydrodynamic Drop-on-Demand Printing of Biocompatible Conductive Patterns
Authors: Niaraki Asli Amir Ehsan , Guo Jingshuai , Lai Pei Lun , Montazami Reza , Hashemi Nicole N.
Published: January 2020

Presented here is a scalable and aqueous phase exfoliation of graphite to high yield and quality of few layer graphene (FLG) using Bovine Serum Albomine (BSA) and wet ball milling. The produced graphene ink is tailored for printable and flexible electronics, having shown promising results in terms of electrical conductivity and temporal stability. Shear force generated by steel balls which resulted in 2–3 layer defect-free graphene platelets with an average size of hundreds of nm, and with a concentration of about 5.1 mg/mL characterized by Raman spectroscopy, atomic force microscopy (AFM), transmittance electron microscopy (TEM) and UV-vis spectroscopy. Further, a conductive ink was prepared and printed on flexible substrate (Polyimide) with controlled resolution. Scanning electron microscopy (SEM) and Profilometry revealed the effect of thermal annealing on the prints to concede consistent morphological characteristics. The resulted sheet resistance was measured to be R s   =   36.75   Ω / sqr for prints as long as 100 mm. Printable inks were produced in volumes ranging from 20 mL to 1 L, with potential to facilitate large scale production of graphene for applications in biosensors, as well as flexible and printable electronics.
Polypharmacy Is Associated with Lower Memory Function in African American Older Adults
Authors: Assari Shervin , Wisseh Cheryl , Saqib Mohammed , Bazargan Mohsen
Published: January 2020

Although previous research has linked polypharmacy to lower cognitive function in the general population, we know little about this association among economically challenged African American (AA) older adults. This study explored the link between polypharmacy and memory function among AA older adults. This community-based study recruited 399 AA older adults who were 65+ years old and living in economically disadvantaged areas of South Los Angeles. Polypharmacy (taking 5+ medications) was the independent variable, memory function was the outcome variable (continuous variable), and gender, age, living arrangement, socioeconomic status (educational attainment and financial strain), health behaviors (current smoking and any binge drinking), and multimorbidity (number of chronic diseases) were the covariates. Linear regression was used for data analyses. Polypharmacy was associated with lower scores on memory function, above and beyond covariates. Among AA older adults, polypharmacy may be linked to worse cognitive function. Future research should test the mechanisms by which polypharmacy is associated with lower levels of cognitive decline. There is a need for screening for memory problems in AA older adults who are exposed to polypharmacy.
Dubious Claims about Simplicity and Likelihood: Comment on Pinna and Conti (2019)
Authors: van der Helm Peter A.
Published: January 2020

Pinna and Conti (Brain Sci., 2019, 9, 149, doi:10.3390/brainsci9060149) presented phenomena concerning the salience and role of contrast polarity in human visual perception, particularly in amodal completion. These phenomena are indeed illustrative thereof, but here, the focus is on their claims (1) that neither simplicity nor likelihood approaches can account for these phenomena; and (2) that simplicity and likelihood are equivalent. I argue that their first claim is based on incorrect assumptions, whereas their second claim is simply untrue.
Metformin as Potential Therapy for High-Grade Glioma
Authors: Mazurek Marek , Litak Jakub , Kamieniak Piotr , Kulesza Bartłomiej , Jonak Katarzyna , Baj Jacek , Grochowski Cezary
Published: January 2020

Metformin (MET), 1,1-dimethylbiguanide hydrochloride, is a biguanide drug used as the first-line medication in the treatment of type 2 diabetes. The recent years have brought many observations showing metformin in its new role. The drug, commonly used in the therapy of diabetes, may also find application in the therapy of a vast variety of tumors. Its effectiveness has been demonstrated in colon, breast, prostate, pancreatic cancer, leukemia, melanoma, lung and endometrial carcinoma, as well as in gliomas. This is especially important in light of the poor options offered to patients in the case of high-grade gliomas, which include glioblastoma (GBM). A thorough understanding of the mechanism of action of metformin can make it possible to discover new drugs that could be used in neoplasm therapy.
Sphingosine 1-Phosphate Receptor 2 Induces Otoprotective Responses to Cisplatin Treatment
Authors: Wang Wei , Shanmugam Muthu K. , Xiang Ping , Yam Ting Yu Amelia , Kumar Vineet , Chew Wee Siong , Chang Jing Kai , Ali Muhammad Zulfaqar Bin , Reolo Marie J. Y. , Peh Yee Xin , Abdul Karim Siti Nasuha Binte , Tan Andrew Y.Y. , Sanda Takaomi , Sethi Gautam , Herr Deron R.
Published: January 2020

Ototoxicity is a major adverse effect of platinum-based chemotherapeutics and currently, there remains a lack of United States Food and Drug Administration-approved therapies to prevent or treat this problem. In our study, we examined the role of the sphingosine 1-phosphate receptor 2 (S1P2) in attenuating cisplatin-induced ototoxicity in several different animal models and cell lines. We found that ototoxicity in S1P2 knockout mice is dependent on reactive oxygen species (ROS) production and that S1P2 receptor activation with a specific agonist, CYM-5478, significantly attenuates cisplatin-induced defects, including hair cell degeneration in zebrafish and prolonged auditory brainstem response latency in rats. We also evaluated the cytoprotective effect of CYM-5478 across different cell lines and showed that CYM-5478 protects neural-derived cell lines but not breast cancer cells against cisplatin toxicity. We show that this selective protection of CYM-5478 is due to its differential effects on key regulators of apoptosis between neural cells and breast cancer cells. Overall, our study suggests that targeting the S1P2 receptor represents a promising therapeutic approach for the treatment of cisplatin-induced ototoxicity in cancer patients.
Aptamer-Conjugated Superparamagnetic Ferroarabinogalactan Nanoparticles for Targeted Magnetodynamic Therapy of Cancer
Authors: Kolovskaya Olga S. , Zamay Tatiana N. , Zamay Galina S. , Babkin Vasily A. , Medvedeva Elena N. , Neverova Nadezhda A. , Kirichenko Andrey K. , Zamay Sergey S. , Lapin Ivan N. , Morozov Evgeny V. , Sokolov Alexey E. , Narodov Andrey A. , Fedorov Dmitri G. , Tomilin Felix N. , Zabluda Vladimir N. , Alekhina Yulia , Lukyanenko Kirill A. , Glazyrin Yury E. , Svetlichnyi Valery A. , Berezovski Maxim V. , Kichkailo Anna S.
Published: January 2020

Nanotechnologies involving physical methods of tumor destruction using functional oligonucleotides are promising for targeted cancer therapy. Our study presents magnetodynamic therapy for selective elimination of tumor cells in vivo using DNA aptamer-functionalized magnetic nanoparticles exposed to a low frequency alternating magnetic field. We developed an enhanced targeting approach of cancer cells with aptamers and arabinogalactan. Aptamers to fibronectin (AS-14) and heat shock cognate 71 kDa protein (AS-42) facilitated the delivery of the nanoparticles to Ehrlich carcinoma cells, and arabinogalactan (AG) promoted internalization through asialoglycoprotein receptors. Specific delivery of the aptamer-modified FeAG nanoparticles to the tumor site was confirmed by magnetic resonance imaging (MRI). After the following treatment with a low frequency alternating magnetic field, AS-FeAG caused cancer cell death in vitro and tumor reduction in vivo. Histological analyses showed mechanical disruption of tumor tissues, total necrosis, cell lysis, and disruption of the extracellular matrix. The enhanced targeted magnetic theranostics with the aptamer conjugated superparamagnetic ferroarabinogalactans opens up a new venue for making biocompatible contrasting agents for MRI imaging and performing non-invasive anti-cancer therapies with a deep penetrated magnetic field.
L1 Cell Adhesion Molecule Confers Radioresistance to Ovarian Cancer and Defines a New Cancer Stem Cell Population
Authors: Terraneo Nastassja , Jacob Francis , Peitzsch Claudia , Dubrovska Anna , Krudewig Christiane , Huang Yen-Lin , Heinzelmann-Schwarz Viola , Schibli Roger , Béhé Martin , Grünberg Jürgen
Published: January 2020

Many solid tumors, including ovarian cancer, contain small populations of cancer stem cells (CSCs). These cells are usually resistant against conventional cancer therapies and play a role in disease recurrence. We demonstrated that the L1 cell adhesion molecule (L1CAM) is a new CSC target in ovarian cancer, triggering radioresistance. Using fluorescence-activated cell sorting, specific cell populations expressing L1CAM alone or in combination with the established CSC marker CD133 were isolated from three ovarian cancer cell lines. Double-positive L1CAM+/CD133+ cells displayed higher spherogenic and clonogenic properties in comparison to L1CAM−/CD133− cells. Furthermore, L1CAM+/CD133+ cells retained highest clonogenic capacity after irradiation and exhibited up-regulation of some CSC-specific genes, enhanced tumor-initiating capacity, self-renewal and higher tumor take rate in nude mice when compared with other cell populations. Superior radioresistance by L1CAM expression was confirmed by deletion of L1CAM using CRISPR-Cas9 technology. Moreover, we found expression signatures associated with epithelial-to-mesenchymal transition phenotype in L1CAM deleted cells. These results indicate that L1CAM in combination with CD133 defines a new cancer cell population of ovarian tumor-initiating cells with the implication of targeting L1CAM as a novel therapeutic approach for ovarian CSCs.
Plasma Membrane Ca2+ ATPase Isoform 4 (PMCA4) Has an Important Role in Numerous Hallmarks of Pancreatic Cancer
Authors: Sritangos Pishyaporn , Pena Alarcon Eduardo , James Andrew D. , Sultan Ahlam , Richardson Daniel A. , Bruce Jason I. E.
Published: January 2020

Pancreatic ductal adenocarcinoma (PDAC) is largely resistant to standard treatments leading to poor patient survival. The expression of plasma membrane calcium ATPase-4 (PMCA4) is reported to modulate key cancer hallmarks including cell migration, growth, and apoptotic resistance. Data-mining revealed that PMCA4 was over-expressed in pancreatic ductal adenocarcinoma (PDAC) tumors which correlated with poor patient survival. Western blot and RT-qPCR revealed that MIA PaCa-2 cells almost exclusively express PMCA4 making these a suitable cellular model of PDAC with poor patient survival. Knockdown of PMCA4 in MIA PaCa-2 cells (using siRNA) reduced cytosolic Ca2+ ([Ca2+]i) clearance, cell migration, and sensitized cells to apoptosis, without affecting cell growth. Knocking down PMCA4 had minimal effects on numerous metabolic parameters (as assessed using the Seahorse XF analyzer). In summary, this study provides the first evidence that PMCA4 is over-expressed in PDAC and plays a role in cell migration and apoptotic resistance in MIA PaCa-2 cells. This suggests that PMCA4 may offer an attractive novel therapeutic target in PDAC.
Combined Effects of Eicosapentaenoic Acid and Adipocyte Renin–Angiotensin System Inhibition on Breast Cancer Cell Inflammation and Migration
Authors: Rasha Fahmida , Kahathuduwa Chanaka , Ramalingam Latha , Hernandez Arelys , Moussa Hanna , Moustaid-Moussa Naima
Published: January 2020

Obesity is a major risk factor for breast cancer (BC). Obesity-related metabolic alterations such as inflammation and overactivation of the adipose renin–angiotensin system (RAS) may contribute to the progression of BC. Clinically used antihypertensive drugs such as angiotensin-converting enzyme inhibitors (ACE-I) and dietary bioactive components such as eicosapentaenoic acid (EPA) are known for their anti-inflammatory and adipose RAS blocking properties. However, whether EPA enhances the protective effects of ACE-I in lessening adipocyte inflammation on BC cells has not been studied. We hypothesized that combined EPA and ACE-I would attenuate BC cell inflammation and migration possibly via adipose RAS inhibition. To test our hypothesis, we examined the (i) direct effects of an ACE-I (captopril (CAP)) or EPA, individually and combined, on MCF-7 and MDA-MB-231 human BC cells, and the (ii) effects of conditioned medium (CM) from human adipocytes pretreated with the abovementioned agents on BC cells. We demonstrated that CM from adipocytes pretreated with EPA with or without captopril (but not direct treatments of BC cells) significantly reduced proinflammatory cytokines expression in both BC cell lines. Additionally, cell migration was reduced in MDA-MB-231 cells in response to both direct and CM-mediated CAP and/or EPA treatments. In summary, our study provides a significant insight into added benefits of combining anti-inflammatory EPA and antihypertensive ACE-I to attenuate the effects of adipocytes on breast cancer cell migration and inflammation.
Precision Medicine in Soft Tissue Sarcoma Treatment
Authors: Nakano Kenji , Takahashi Shunji
Published: January 2020

Soft tissue sarcoma (STS) is a rare component of malignant diseases. STS includes various histological subtypes, and there are some important differences among the different histological subtypes regarding the mutation profile and sensitivity to antitumor agents. Many clinical trials of STS incorporating many different histological subtypes in various populations have been conducted; it is difficult to compare the findings and make conclusions about clinical efficacy. Targeted therapies focusing on specific histological subtypes and precision therapy focusing on the specific genetic mutation(s) of each STS patient are being investigated. Since STS patients are a small population, new clinical trial designs are required to evaluate and establish new targeted therapies for each histological subtype that has a limited number of patients, and preclinical investigations are needed to detect targetable mutations. Now that cancer genome profiling is used in clinical practice, it is urgently necessary to connect the genome profiling data obtained in clinical settings to the optimal clinical treatment strategies. Herein we review the development and challenges of precision therapy in the management of STS patients.
Mutation Status and Epithelial Differentiation Stratify Recurrence Risk in Chordoid Meningioma—A Multicenter Study with High Prognostic Relevance
Authors: Georgescu Maria-Magdalena , Nanda Anil , Li Yan , Mobley Bret C. , Faust Phyllis L. , Raisanen Jack M. , Olar Adriana
Published: January 2020

Chordoid meningioma is a rare WHO grade II histologic variant. Its molecular alterations or their impact on patient risk stratification have not been fully explored. We performed a multicenter, clinical, histological, and genomic analysis of chordoid meningiomas from 30 patients (34 tumors), representing the largest integrated study to date. By NHERF1 microlumen immunohistochemical detection, three epithelial differentiation (ED) groups emerged: #1/fibroblastic-like, #2/epithelial-poorly-differentiated and #3/epithelial-well-differentiated. These ED groups correlated with tumor location and genetic profiling, with NF2 and chromatin remodeling gene mutations clustering in ED group #2, and TRAF7 mutations segregating in ED group #3. Mutations in LRP1B were found in the largest number of cases (36%) across ED groups #2 and #3. Pathogenic ATM and VHL germline mutations occurred in ED group #3 patients, conferring an aggressive or benign course, respectively. The recurrence rate significantly correlated with mutations in NF2, as single gene, and with mutations in chromatin remodeling and DNA damage response genes, as groups. The recurrence rate was very high in ED group #2, moderate in ED group #3, and absent in ED group #1. This study proposes guidelines for tumor recurrence risk stratification and practical considerations for patient management.
Engineering and Characterization of Oncolytic Vaccinia Virus Expressing Truncated Herpes Simplex Virus Thymidine Kinase
Authors: Islam S. M. Bakhtiar Ul , Lee Bora , Jiang Fen , Kim Eung-Kyun , Ahn Soon Cheol , Hwang Tae-Ho
Published: January 2020

Oncolytic viruses are a promising class of anti-tumor agents; however, concerns regarding uncontrolled viral replication have led to the development of a replication-controllable oncolytic vaccinia virus (OVV). The engineering involves replacing the native thymidine kinase (VV-tk) gene, in a Wyeth strain vaccinia backbone, with the herpes simplex virus thymidine kinase (HSV-tk) gene, which allows for viral replication control via ganciclovir (GCV, an antiviral/cytotoxic pro-drug). Adding the wild-type HSV-tk gene might disrupt the tumor selectivity of VV-tk deleted OVVs; therefore, only engineered viruses that lacked tk activity were selected as candidates. Ultimately, OTS-412, which is an OVV containing a mutant HSV-tk, was chosen for characterization regarding tumor selectivity, sensitivity to GCV, and the influence of GCV on OTS-412 anti-tumor effects. OTS-412 demonstrated comparable replication and cytotoxicity to VVtk- (control, a VV-tk deleted OVV) in multiple cancer cell lines. In HCT 116 mouse models, OTS-412 replication in tumors was reduced by >50% by GCV (p = 0.004); additionally, combination use of GCV did not compromise the anti-tumor effects of OTS-412. This is the first report of OTS-412, a VV-tk deleted OVV containing a mutant HSV-tk transgene, which demonstrates tumor selectivity and sensitivity to GCV. The HSV-tk/GCV combination provides a safety mechanism for future clinical applications of OTS-412.
RASSF1A Tumour Suppressor: Target the Network for Effective Cancer Therapy
Authors: García-Gutiérrez Lucía , McKenna Stephanie , Kolch Walter , Matallanas David
Published: January 2020

The RASSF1A tumour suppressor is a scaffold protein that is involved in cell signalling. Increasing evidence shows that this protein sits at the crossroad of a complex signalling network, which includes key regulators of cellular homeostasis, such as Ras, MST2/Hippo, p53, and death receptor pathways. The loss of expression of RASSF1A is one of the most common events in solid tumours and is usually caused by gene silencing through DNA methylation. Thus, re-expression of RASSF1A or therapeutic targeting of effector modules of its complex signalling network, is a promising avenue for treating several tumour types. Here, we review the main modules of the RASSF1A signalling network and the evidence for the effects of network deregulation in different cancer types. In particular, we summarise the epigenetic mechanism that mediates RASSF1A promoter methylation and the Hippo and RAF1 signalling modules. Finally, we discuss different strategies that are described for re-establishing RASSF1A function and how a multitargeting pathway approach selecting druggable nodes in this network could lead to new cancer treatments.
Ex-Vivo Treatment of Tumor Tissue Slices as a Predictive Preclinical Method to Evaluate Targeted Therapies for Patients with Renal Carcinoma
Authors: Roelants Caroline , Pillet Catherine , Franquet Quentin , Sarrazin Clément , Peilleron Nicolas , Giacosa Sofia , Guyon Laurent , Fontanell Amina , Fiard Gaëlle , Long Jean-Alexandre , Descotes Jean-Luc , Cochet Claude , Filhol Odile
Published: January 2020

Clear cell renal cell carcinoma (ccRCC) is the third type of urologic cancer. At time of diagnosis, 30% of cases are metastatic with no effect of chemotherapy or radiotherapy. Current targeted therapies lead to a high rate of relapse and resistance after a short-term response. Thus, a major hurdle in the development and use of new treatments for ccRCC is the lack of good pre-clinical models that can accurately predict the efficacy of new drugs and allow the stratification of patients into the correct treatment regime. Here, we describe different 3D cultures models of ccRCC, emphasizing the feasibility and the advantage of ex-vivo treatment of fresh, surgically resected human tumor slice cultures of ccRCC as a robust preclinical model for identifying patient response to specific therapeutics. Moreover, this model based on precision-cut tissue slices enables histopathology measurements as tumor architecture is retained, including the spatial relationship between the tumor and tumor-infiltrating lymphocytes and the stromal components. Our data suggest that acute treatment of tumor tissue slices could represent a benchmark of further exploration as a companion diagnostic tool in ccRCC treatment and a model to develop new therapeutic drugs.
Kinetic Model of the Action of 17α-Ethynylestradiol on the Capacitation of Mouse Sperm, Monitored by HPLC-MS/MS
Authors: Bosakova Tereza , Tockstein Antonin , Sebkova Natasa , Cabala Radomir , Komrskova Katerina
Published: January 2020

17α-Ethynylestradiol (EE2), a synthetic estrogen used in contraceptive pills, is resistant to hepatic degradation and is excreted in the urine. It is chemically stable and has a negative impact on the endocrine system. The aim of this work was to mathematically describe the possible interaction of EE2 (200, 20, and 2 μg/L) with sperm estrogen receptors during sperm maturation, which is called capacitation. The concentrations of the unbound EE2 remaining in capacitating medium during 180 min of sperm capacitation were determined at 30 min intervals by high performance liquid chromatography with tandem mass spectrometric detection (HPLC-MS/MS) and the data obtained (relative concentrations Bt) were subjected to kinetic analysis. The suggested kinetic schema was described by the system of differential equations with the optimization of rate constants used to calculate the theoretical Bt values. Optimal parameters (overall rate constants K1–K5 and molar ratio n) were determined by searching the minimum of absolute values of the difference between theoretical and experimental Bt values. These values were used for the design of the theoretical B(t) curves which fit to experimental points. The proposed kinetic model assumes the formation of an unstable adduct between EE2 and the receptor in cytoplasm, which acts as an autocatalytic agent and gradually decomposes.
Selective Hydration of Nitriles to Corresponding Amides in Air with Rh(I)-N-Heterocyclic Complex Catalysts
Authors: Czégéni Csilla Enikő , De Sourav , Udvardy Antal , Derzsi Nóra Judit , Papp Gergely , Papp Gábor , Joó Ferenc
Published: January 2020

A new synthetic method for obtaining [RhCl(cod)(NHC)] complexes (1–4) (cod = η4-1,5-cyclooctadiene, NHC = N-heterocyclic carbene: IMes, SIMes, IPr, and SIPr, respectively) is reported together with the catalytic properties of 1–4 in nitrile hydration. In addition to the characterization of 1–4 in solution by 13C NMR spectroscopy, the structures of complexes 3, and 4 have been established also in the solid state with single-crystal X-ray diffraction analysis. The Rh(I)-NHC complexes displayed excellent catalytic activity in hydration of aromatic nitriles (up to TOF = 276 h−1) in water/2-propanol (1/1 v/v) mixtures in air.
Recent Advances in Niobium-Based Materials for Photocatalytic Solar Fuel Production
Authors: Nunes Barbara Nascimento , Lopes Osmando Ferreira , Patrocinio Antonio Otavio T. , Bahnemann Detlef W.
Published: January 2020

The search for renewable and clean energy sources is a key aspect for sustainable development as energy consumption has continuously increased over the years concomitantly with environmental concerns caused by the use of fossil fuels. Semiconductor materials have great potential for acting as photocatalysts for solar fuel production, a potential energy source able to solve both energy and environmental concerns. Among the studied semiconductor materials, those based on niobium pentacation are still shallowly explored, although the number of publications and patents on Nb(V)-based photocatalysts has increased in the last years. A large variety of Nb(V)-based materials exhibit suitable electronic/morphological properties for light-driving reactions. Not only the extensive group of Nb2O5 polymorphs is explored, but also many types of layered niobates, mixed oxides, and Nb(V)-doped semiconductors. Therefore, the aim of this manuscript is to provide a review of the latest developments of niobium based photocatalysts for energy conversion into fuels, more specifically, CO2 reduction to hydrocarbons or H2 evolution from water. Additionally, the main strategies for improving the photocatalytic performance of niobium-based materials are discussed.
Additive-Free Baeyer–Villiger Oxidation of Cyclic Ketone Catalyzed by Carboxylic-Functionalized Poly(Ionic Liquids) and Polyoxometalate Ionic Self-Assemblies
Authors: Li Xinzhong , Xue Hanyu , Lin Qi , Yu Aimin
Published: January 2020

Two carboxylic functionalized poly(ionic liquids) and polyoxometalate ionic self-assemblies with tunable amphiphilic and oxidative activity and porous structure were designed and synthesized. They were used as efficient heterogeneous catalysts exhibiting excellent catalytic activity and quite stable reusability in additive–free Baeyer-Villiger oxidation of cyclic ketones, directly using 30% H2O2 solution in liquids–phase. Under optimum conditions, the corresponding lactones were obtained with yields ranging from 59.6 to 90.5%. The unique combination of carboxylic group with polyoxometalate anion, amphiphilic property, and porous structure is revealed to be responsible for their excellent catalytic performances in oxidation.
Characterization of Mesenchymal Stem Cells Derived from Patients with Cerebellar Ataxia: Downregulation of the Anti-Inflammatory Secretome Profile
Authors: Kim Jong-Heon , Han Jin , Seo Donggun , Yoon Jong Hyuk , Yoon Dongyeong , Hong Jungwan , Kim Sang Ryong , Kim Min Sung , Lee Tae Yong , Kim Kyung Suk , Ko Pan-Woo , Lee Ho-Won , Suk Kyoungho
Published: January 2020

Mesenchymal stem cell (MSC) therapy is a promising alternative approach for the treatment of neurodegenerative diseases, according to its neuroprotective and immunomodulatory potential. Despite numerous clinical trials involving autologous MSCs, their outcomes have often been unsuccessful. Several reports have indicated that MSCs from patients have low capacities in terms of the secretion of neurotrophic or anti-inflammatory factors, which might be associated with cell senescence or disease severity. Therefore, a new strategy to improve their capacities is required for optimal efficacy of autologous MSC therapy. In this study, we compared the secretory potential of MSCs among cerebellar ataxia patients (CA-MSCs) and healthy individuals (H-MSCs). Our results, including secretome analysis findings, revealed that CA-MSCs have lower capacities in terms of proliferation, oxidative stress response, motility, and immunomodulatory functions when compared with H-MSCs. The functional differences were validated in a scratch wound healing assay and neuron-glia co-cultures. In addition, the neuroprotective and immunoregulatory protein follistatin-like 1 (FSTL1) was identified as one of the downregulated proteins in the CA-MSC secretome, with suppressive effects on proinflammatory microglial activation. Our study findings suggest that targeting aspects of the downregulated anti-inflammatory secretome, such as FSTL1, might improve the efficacy of autologous MSC therapy for CA.