bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Ultrasonication Pretreatment on the Production of Polyphenol-Enriched Extracts from Moringa oleifera L. (Drumstick Tree) Using a Novel Bio-Based Deep Eutectic Solvent
Authors: Lakka Achillia , Grigorakis Spyros , Kaltsa Olga , Karageorgou Ioanna , Batra Georgia , Bozinou Eleni , Lalas Stavros , Makris Dimitris P.
Published: December 2019

Moringa oleifera L. leaves are a plant tissue particularly rich in polyphenolic phytochemicals with significant bioactivities, and there has been significant recent interest for the production of extracts enriched in these substances. The current investigation is aimed at establishing a green extraction process, using a novel eco-friendly natural deep eutectic solvent, composed of glycerol and nicotinamide. Furthermore, sample ultrasonication prior to batch stirred-tank extraction was studied to examine its usefulness as a pretreatment step. Optimization of the extraction process through response surface methodology showed that the maximum total polyphenol yield (82.87 ± 4.28 mg gallic acid equivalents g−1 dry mass) could be achieved after a 30 min ultrasonication pretreatment, but the difference with the yield obtained from the non-pretreated sample was statistically non-significant (p < 0.05). Extraction kinetics revealed that the activation energy for the ultrasonication-pretreated samples was more energy-demanding, a fact attributed to phenomena pertaining to washing of the readily extracted polyphenols during pretreatment. Liquid-chromatography-diode array-mass spectrometry showed that ultrasonication pretreatment may have a limited positive effect on polyphenol extractability, but the overall polyphenolic profile was identical for the ultrasonication-pretreated and non-pretreated samples.
An Effective Wide-Bandwidth Channel Access in Next-Generation WLAN-Based V2X Communications
Authors: Hong Hanseul , Kim Young Yong , Kim Ronny Yongho , Ahn Woojin
Published: December 2019

As Intelligent Transport System (ITS) applications are diversified and amount of ITS data increases, high throughput and reliability are required in next-generation V2X communications. In order to meet such increased throughput and reliability requirements, IEEE 802.11bd, the next-generation V2X communication standard, has commenced standard development. One of the main features of IEEE 802.11bd is a 20-MHz bandwidth transmission. In this paper, a novel wide-bandwidth channel access scheme in next-generation Wireless Local Area Network (WLAN)-based vehicular communications is proposed. The proposed scheme is designed to provide fairness with other ITS devices and channel efficiency considering adjacent channel interference. By using the proposed scheme, through extensive simulations, it is verified that, while satisfying the fairness requirement with other ITS devices, the channel access delay of wide-bandwidth packet transmission can be optimized.
Analysis of Flow Characteristics and Pressure Drop for an Impinging Plate Fin Heat Sink with Elliptic Bottom Profiles
Authors: Duan Zhipeng , Lv Xianghui , Ma Hao , Su Liangbin , Zhang Mengqiao
Published: December 2019

The performance of impingement air cooled plate fin heat sinks differs significantly from that of parallel flow plate fin heat sinks. The impinging flow situations at the entrance and the right-angled bends of the plate fin heat sink are quite involved. Flow characteristics of a plate fin heat sink with elliptic bottom profiles cooled by a rectangular impinging jet with different inlet widths are studied by numerical simulations. The results of pressure drop of numerical simulations and experimental results match quite well. The numerical results show that at the same flow rate, the pressure drop decreases with the increase of the impingement inlet width, and the pressure drop increases significantly with the increase of the fin height. The larger the impingement inlet width of air-cooled plate fin heat sink, the milder the pressure drop changes with velocity. Pressure drop for an impinging plate fin heat sink without elliptic bottom profiles is larger than that with elliptic bottom profiles at the same inlet width and velocity. Based on the fundamental developing laminar continuum flow theory, an improved model which is very concise and nice for quick real world approximations is proposed. Furthermore, this paper verifies the effectiveness of this simple impinging pressure drop model.
Carbon Mass Balance in Arthrospira platensis Culture with Medium Recycle and High CO2 Supply
Authors: Kishi Masatoshi , Yamada Yukina , Katayama Tomoyo , Matsuyama Tatsushi , Toda Tatsuki
Published: December 2019

Medium recycling combined with CO2 recovery helps sustainable use of the alkaline medium in Arthrospira culture. However, high CO2 supply may cause inorganic carbon accumulation and pH reduction, which could result in low CO2 recovery and reduced algal growth. This study aimed to elucidate the effect of medium recycling and high CO2 supply through carbon mass balance analysis in Arthrospira culture. In all CO2 supply conditions, carbon supply was higher than Arthrospira carbon assimilation, which accounted for 30–58% of supply. However, CO2 recovery of nearly 100% and 63% for lower (0.20 and 0.39 gC L−1 d−1) and higher (0.59 gC L−1 d−1) CO2 supply rates were achieved, respectively, because of the high concentration of the alkaline agent. The excess carbon accumulated in the medium and ultimately escaped from the system in a form of dissolved inorganic carbon (DIC). Dissolved organic carbon (DOC) contributed to 16–24% of the total photosynthetically assimilated carbon, and the final concentration reached 260–367 mgC L−1, but there was no significant growth reduction caused by DIC and DOC accumulation. This study demonstrated the stability of the medium-recycling process even at high CO2 supply rates although a balanced supply is recommended for longer operations.
Interferometry of Gas-Phase Flows during Selective Laser Melting
Authors: Podrabinnik Pavel A. , Shtanko Alexander E. , Khmyrov Roman S. , Korotkov Andrey D. , Gusarov Andrey V.
Published: December 2019

Gas-phase flows occurring in a plume in a processing zone during selective laser melting (SLM) can significantly affect the quality of the process. To further enhance SLM performance, the characteristics of the flows should be considered. In this article, the vapor-gas jet emerging from the laser processing zone was studied. It was visualized by interferometry to evaluate flow velocity, geometry and changes in refractory index depending on laser power. The velocity and pressure fields of the vapor jet and the entrained ambient gas were estimated by mathematical modeling. It was shown that the increase of laser power led to higher jet velocity and greater change in its refractory index. The latter also was used to evaluate the content of metal vapor in the plume and its influence on the absorption of laser radiation.
Calibration of Polarization Fields and Electro-Optical Response of Group-III Nitride Based c-Plane Quantum-Well Heterostructures by Application of Electro-Modulation Techniques
Authors: Papadimitriou Dimitra N.
Published: December 2019

The polarization fields and electro-optical response of PIN-diodes based on nearly lattice-matched InGaN/GaN and InAlN/GaN double heterostructure quantum wells grown on (0001) sapphire substrates by metalorganic vapor phase epitaxy were experimentally quantified. Dependent on the indium content and the applied voltage, an intense near ultra-violet emission was observed from GaN (with fundamental energy gap Eg = 3.4 eV) in the electroluminescence (EL) spectra of the InGaN/GaN and InAlN/GaN PIN-diodes. In addition, in the electroreflectance (ER) spectra of the GaN barrier structure of InAlN/GaN diodes, the three valence-split bands, Γ9, Γ7+, and Γ7−, could selectively be excited by varying the applied AC voltage, which opens new possibilities for the fine adjustment of UV emission components in deep well/shallow barrier DHS. The internal polarization field Epol = 5.4 ± 1.6 MV/cm extracted from the ER spectra of the In0.21Al0.79N/GaN DHS is in excellent agreement with the literature value of capacitance-voltage measurements (CVM) Epol = 5.1 ± 0.8 MV/cm. The strength and direction of the polarization field Epol = −2.3 ± 0.3 MV/cm of the (0001) In0.055Ga0.945N/GaN DHS determined, under flat-barrier conditions, from the Franz-Keldysh oscillations (FKOs) of the electro-optically modulated field are also in agreement with the CVM results Epol = −1.2 ± 0.4 MV/cm. The (absolute) field strength is accordingly significantly higher than the Epol strength quantified in published literature by FKOs on a semipolar ( 11 2 ¯ 2 ) oriented In0.12Ga0.88N quantum well.
Visual Detection of Surface Defects Based on Self-Feature Comparison in Robot 3-D Printing
Authors: Shen Hongyao , Du Wangzhe , Sun Weijun , Xu Yuetong , Fu Jianzhong
Published: December 2019

Fused Deposition Modeling (FDM) additive manufacturing technology is widely applied in recent years. However, there are many defects that may affect the surface quality, accuracy, or even cause the collapse of the parts in the printing process. In the existing defect detection technology, the characteristics of parts themselves may be misjudged as defects. This paper presents a solution to the problem of distinguishing the defects and their own characteristics in robot 3-D printing. A self-feature extraction method of shape defect detection of 3D printing products is introduced. Discrete point cloud after model slicing is used both for path planning in 3D printing and self-feature extraction at the same time. In 3-D printing, it can generate G-code and control the shooting direction of the camera. Once the current coordinates have been received, the self-feature extraction begins, whose key steps are keeping a visual point cloud of the printed part and projecting the feature points to the picture under the equal mapping condition. After image processing technology, the contours of pictured projected and picture captured will be detected. At last, the final defects can be identified after evaluation of contour similarity based on empirical formula. This work will help to detect the defects online, improve the detection accuracy, and reduce the false detection rate without being affected by its own characteristics.
Coupling of Soil Moisture and Air Temperature from Multiyear Data During 1980–2013 over China
Authors: Yuan Qing , Wang Guojie , Zhu Chenxia , Lou Dan , Hagan Daniel Fiifi Tawia , Ma Xiaowen , Zhan Mingyue
Published: December 2019

Soil moisture is an important parameter in land surface processes, which can control the surface energy and water budgets and thus affect the air temperature. Studying the coupling between soil moisture and air temperature is of vital importance for forecasting climate change. This study evaluates this coupling over China from 1980–2013 by using an energy-based diagnostic method, which represents the momentum, heat, and water conservation equations in the atmosphere, while the contributions of soil moisture are treated as external forcing. The results showed that the soil moisture–temperature coupling is strongest in the transitional climate zones between wet and dry climates, which here includes Northeast China and part of the Tibetan Plateau from a viewpoint of annual average. Furthermore, the soil moisture–temperature coupling was found to be stronger in spring than in the other seasons over China, and over different typical climatic zones, it also varied greatly in different seasons. We conducted two case studies (the heatwaves of 2013 in Southeast China and 2009 in North China) to understand the impact of soil moisture–temperature coupling during heatwaves. The results indicated that over areas with soil moisture deficit and temperature anomalies, the coupling strength intensified. This suggests that soil moisture deficits could lead to enhanced heat anomalies, and thus, result in enhanced soil moisture coupling with temperature. This demonstrates the importance of soil moisture and the need to thoroughly study it and its role within the land–atmosphere interaction and the climate on the whole.
Estimating Sunshine Duration Using Hourly Total Cloud Amount Data from a Geostationary Meteorological Satellite
Authors: Zhu Weiwei , Wu Bingfang , Yan Nana , Ma Zonghan , Wang Linjiang , Liu Wenjun , Xing Qiang , Xu Jiaming
Published: December 2019

Sunshine duration is an important indicator of the amount of solar radiation received in a region and an important input parameter for the study of atmospheric energy balance, climate change, ecosystem evolution, and social sustainability. Currently, extrapolation and interpolation of data from meteorological stations are the most common methods used to calculate sunshine duration on a regional scale. However, it is difficult to obtain high precision sunshine duration in areas lacking ground observation or where sunshine duration is highly heterogeneous on the ground. In this paper, a new method is proposed to estimate sunshine duration with hourly total cloud amount (CTA) data from sunrise to sunset derived from the Fengyun-2G geostationary meteorological satellite (FY-2G). This method constructs a new index known as daytime mean total cloud coverage amount and provides quadratic equations relating daytime mean total cloud coverage amount to relative sunshine duration in different seasons. The method was validated with ground observation data for 2016 from 18 meteorological stations in the Three-River Headwaters Region of Qinghai Province, China. For individual stations, the coefficient of determination (R2) between estimated and measured sunshine was at least 0.894, the RMSE (root mean square error) was 0.977 h/day or less, the MAE (mean absolute error) was 0.824 h/day or less, the RE (relative error) was 0.150 or lower, and the value of d was 0.963 or greater, which validated that the proposed method can effectively predict daily sunshine duration. These equations can also provide higher precision estimates of regional-scale sunshine duration. This was demonstrated by comparing, for the entire study region, the spatial distribution of sunshine duration estimated from season-based equations with results from three different interpolation methods based on ground observations. Overall, the study confirms that total cloud amount measures from a geostationary satellite can be used to successfully estimate sunshine duration.
Concentration Fluctuations and Odor Dispersion in Lagrangian Models
Authors: Ferrero Enrico , Manor Alon , Mortarini Luca , Oettl Dietmar
Published: December 2019

In this paper, a review of the Lagrangian stochastic models developed in the last decades for the simulation of the concentration–fluctuation dispersion is presented. The main approaches available in the literature are described and their ability in reproducing the higher order moments of the probability density function is discussed. Then, the Lagrangian approaches for evaluating of the odor annoyance are presented. It is worth to notice that, while Lagrangian stochastic models for mean concentrations are well-known and their ability in correctly reproducing the observation is well assessed, concerning concentration fluctuations the approaches are often new and unknown for most of the scientific community.
The Effect of Technological Progress, Demand, and Energy Policy on Agricultural and Bioenergy Markets
Authors: Kapilakanchana Montalee , McCarl Bruce A.
Published: December 2019

This study investigates the consequences of agricultural technological progress, biofuel policy, and agricultural demand growth on crop, livestock, and bioenergy markets, as well as resource usage and greenhouse gas (GHG) emissions, over data in the United States. We formed scenarios for future technological progress, demand growth, and biofuel policy and carried out a dynamic simulation. The major findings are: (1) Increasing technological progress reduces cropland for biofuel and cropland pasture for livestock but increases cropland for crop production; (2) Reducing corn ethanol requirements causes more cropland to move from cropping to pasture uses for livestock, however, lowering ethanol from corn residue has minor effects on cropland use; (3) Lowering the requirement of ethanol from corn lowers the price for most of the field crops and meat commodities, especially corn, hay, sorghum, and non-fed beef; (4) Technological progress and biofuel policy have significant effects of on GHG emissions. Increasing technical progress reduces overall GHG emissions. A lower corn ethanol level results in much larger GHG emissions as compared with the control case. This implies producing corn ethanol is effective in reducing emissions; and (5) Technological improvement is a key factor in meeting growing global demand for food and energy and reducing emissions.
Surface Aerosol Properties Studied Using a Near-Horizontal Lidar
Authors: Ong Prane Mariel , Lagrosas Nofel , Shiina Tatsuo , Kuze Hiroaki
Published: December 2019

Studying near-surface aerosol properties is of importance for a better assessment of the aerosol effect on radiative forcing. We employ the data from a near-horizontal lidar to investigate the diurnal behavior of aerosol extinction and single scattering albedo (SSA) at 349 nm. The response of these parameters to ambient relative humidity (RH) is examined for the data from a one-month campaign conducted in Chiba, Japan, during November 2017, a transition period from fall to winter. The Klett method and adaptive slope method are used in deriving the aerosol extinction coefficient from the lidar data, while the SSA values are retrieved using an aethalometer. Also, a visibility-meter is used to examine the aerosol loading inside the atmospheric boundary layer. It is found that the aerosol growth during the deliquescence phase is more readily observed than the contraction in the efflorescence phase. The decrease of SSA before the deliquescence RH is found for approximately 46% of the deliquescence cases, presumably representing the particle shrinkage of soot particles.
On a Common Jungck Type Fixed Point Result in Extended Rectangular b-Metric Spaces
Authors: Aydi Hassen , Mitrović Zoran D. , Radenović Stojan , de la Sen Manuel
Published: December 2019

In this paper, we present a Jungck type common fixed point result in extended rectangular b-metric spaces. We also give some examples and a known common fixed point theorem in extended b-metric spaces.
Measuring Test Bench with Adjustable Thermal Connection of Cells to Their Neighbors and a New Model Approach for Parallel-Connected Cells
Authors: Fill Alexander , Mader Tobias , Schmidt Tobias , Llorente Raphael , Birke Kai Peter
Published: December 2019

This article presents a test bench with variable temperature control of the individual cells connected in parallel. This allows to reconstruct arising temperature gradients in a battery module and to investigate their effects on the current distribution. The influence of additional contact resistances induced by the test bench is determined and minimized. The contact resistances are reduced from R Tab + = 81.18 μ Ω to R Tab + = 55.15 μ Ω at the positive respectively from R Tab − = 35.59 μ Ω to R Tab − = 28.2 μ Ω at the negative tab by mechanical and chemical treating. An increase of the contact resistance at the positive tab is prevented by air seal of the contact. The resistance of the load cable must not be arbitrarily small, as the cable is used as a shunt for current measurement. In order to investigate their impacts, measurements with two parallel-connected cells and different load cables with a resistance of R Cab + = 0.3 m Ω , R Cab + = 1.6 m Ω and R Cab + = 4.35 m Ω are conducted. A shift to lower current differences with decreasing cable resistance but qualitatively the same dynamic of the current distribution is found. An extended dual polarization model is introduced, considering the current distribution within the cells as well as the additional resistances induced by the test bench. The model shows a high correspondence to measurements with two parallel-connected cells, with a Root Mean Square Deviation (RMSD) of ξ RMSD = 0.083 A.
Bioactivities of Geranium wallichianum Leaf Extracts Conjugated with Zinc Oxide Nanoparticles
Authors: Abbasi Banzeer Ahsan , Iqbal Javed , Ahmad Riaz , Zia Layiq , Kanwal Sobia , Mahmood Tariq , Wang Canran , Chen Jen-Tsung
Published: December 2019

This study attempts to obtain and test the bioactivities of leaf extracts from a medicinal plant, Geranium wallichianum (GW), when conjugated with zinc oxide nanoparticles (ZnONPs). The integrity of leaf extract-conjugated ZnONPs (GW-ZnONPs) was confirmed using various techniques, including Ultraviolet–visible spectroscopy, X-Ray Diffraction, Fourier Transform Infrared Spectroscopy, energy-dispersive spectra (EDS), scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy. The size of ZnONPs was approximately 18 nm, which was determined by TEM analysis. Additionally, the energy-dispersive spectra (EDS) revealed that NPs have zinc in its pure form. Bioactivities of GW-ZnONPs including antimicrobial potentials, cytotoxicity, antioxidative capacities, inhibition potentials against α-amylase, and protein kinases, as well as biocompatibility were intensively tested and confirmed. Altogether, the results revealed that GW-ZnONPs are non-toxic, biocompatible, and have considerable potential in biological applications.
Polymorphic Protective Dps–DNA Co-Crystals by Cryo Electron Tomography and Small Angle X-Ray Scattering
Authors: Kamyshinsky Roman , Chesnokov Yury , Dadinova Liubov , Mozhaev Andrey , Orlov Ivan , Petoukhov Maxim , Orekhov Anton , Shtykova Eleonora , Vasiliev Alexander
Published: December 2019

Rapid increase of intracellular synthesis of specific histone-like Dps protein that binds DNA to protect the genome against deleterious factors leads to in cellulo crystallization—one of the most curious processes in the area of life science at the moment. However, the actual structure of the Dps–DNA co-crystals remained uncertain in the details for more than two decades. Cryo-electron tomography and small-angle X-ray scattering revealed polymorphous modifications of the co-crystals depending on the buffer parameters. Two different types of the Dps–DNA co-crystals are formed in vitro: triclinic and cubic. Three-dimensional reconstruction revealed DNA and Dps molecules in cubic co-crystals, and the unit cell parameters of cubic lattice were determined consistently by both methods.
Plant Growth-Promoting Fungi (PGPF) Instigate Plant Growth and Induce Disease Resistance in Capsicum annuum L. upon Infection with Colletotrichum capsici (Syd.) Butler & Bisby
Authors: Naziya Banu , Murali Mahadevamurthy , Amruthesh Kestur Nagaraj
Published: December 2019

In the current study, a total of 70 fungi were isolated from the rhizosphere soil of chilli collected from six different districts of south Karnataka, India. All the rhizospheric fungi were evaluated for its antagonistic nature against Colletotrichum capsici—the causal agent of anthracnose disease—and eight isolates were found positive. The antagonistic fungi were further characterized for the production of plant growth-promoting traits wherein five isolates were recorded positive for all the traits tested and were also positive for root colonization. All five plant growth-promoting fungi (PGPF) were subjected to molecular characterization for identification up to the species level and the accession numbers were obtained from NCBI. The five isolates, namely NBP-08, NBP-45, NBP-61, NBP-66 and NBP-67, were further experimented with on susceptible seeds to evaluate its efficacy on seed and plant growth parameters along with induction of resistance against the anthracnose disease. The evaluated PGPF offered significant enhancement in seed and plant growth parameters with maximum improvement observed in seeds treated with NBP-61. Among the PGPF isolates, NBP-61 showed the maximum protection of 78.75%, while all the other isolates also showed significant protection against anthracnose disease compared to untreated plants. The higher accumulation of lignin and callose deposition along with enhanced defense enzyme activities in the PGPF-treated challenge-inoculated seedlings authenticated the protection offered by PGPF. The study evidenced the immense ability of PGPF in eliciting disease protection and enhancement of plant growth in chilli, which may act as a possible substitute for harmful chemicals.
Influence of Exogenous Salicylic Acid and Nitric Oxide on Growth, Photosynthesis, and Ascorbate-Glutathione Cycle in Salt Stressed Vigna angularis
Authors: Ahanger Mohammad Abass , Aziz Usman , Alsahli Abdulaziz Abdullah , Alyemeni Mohammed Nasser , Ahmad Parvaiz
Published: December 2019

The present study was carried out to investigate the beneficial role of exogenous application of salicylic acid (1 mM SA) and nitric oxide (100 μM NO) in preventing the oxidative damage in Vigna angularis triggered by salinity stress. Salinity (100 mM NaCl) stress reduced growth, biomass accumulation, chlorophyll synthesis, photosynthesis, gas exchange parameters, and photochemical efficiency (Fv/Fm) significantly. Exogenous application of SA and NO was affective in enhancing these growth and photosynthetic parameters. Salinity stress reduced relative water content over control. Further, the application of SA and NO enhanced the synthesis of proline, glycine betaine, and sugars as compared to the control as well as NaCl treated plants contributing to the maintenance of tissue water content. Exogenous application of SA and NO resulted in up-regulation of the antioxidant system. Activities of enzymatic antioxidants including superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), and glutathione reductase (GR), as well as the content of non-enzymatic components, were more in SA + NO treated seedlings as compared to control and salinity stressed counterparts resulting in significant alleviation of the NaCl mediated oxidative damage. Content of nitrogen, potassium, and calcium increased due to SA and NO under normal conditions and NaCl stress conditions while as Na and Cl content reduced significantly.
Identification of the NADP+ Structural Binding Site and Coenzyme Effect on the Fused G6PD::6PGL Protein from Giardia lamblia
Authors: Morales-Luna Laura , González-Valdez Abigail , Sixto-López Yudibeth , Correa-Basurto José , Hernández-Ochoa Beatriz , Cárdenas-Rodríguez Noemí , Castillo-Rodríguez Rosa Angélica , Ortega-Cuellar Daniel , Arreguin-Espinosa Roberto , Pérez de la Cruz Verónica , Serrano-Posada Hugo , Centeno-Leija Sara , Rocha-Ramírez Luz María , Sierra-Palacios Edgar , Montiel-González Alba Mónica , Rufino-González Yadira , Marcial-Quino Jaime , Gómez-Manzo Saúl
Published: December 2019

Giardia lambia is a flagellated protozoan parasite that lives in the small intestine and is the causal agent of giardiasis. It has been reported that G. lamblia exhibits glucose-6-phosphate dehydrogenase (G6PD), the first enzyme in the pentose phosphate pathway (PPP). Our group work demonstrated that the g6pd and 6pgl genes are present in the open frame that gives rise to the fused G6PD::6PGL protein; where the G6PD region is similar to the 3D structure of G6PD in Homo sapiens. The objective of the present work was to show the presence of the structural NADP+ binding site on the fused G6PD::6PGL protein and evaluate the effect of the NADP+ molecule on protein stability using biochemical and computational analysis. A protective effect was observed on the thermal inactivation, thermal stability, and trypsin digestions assays when the protein was incubated with NADP+. By molecular docking, we determined the possible structural-NADP+ binding site, which is located between the Rossmann fold of G6PD and 6PGL. Finally, molecular dynamic (MD) simulation was used to test the stability of this complex; it was determined that the presence of both NADP+ structural and cofactor increased the stability of the enzyme, which is in agreement with our experimental results.
Current Therapeutic Strategies for Glioblastoma
Authors: Rossignol Julien , Srinageshwar Bhairavi , Dunbar Gary L.
Published: December 2019

Glioblastomas (GB) are grade 4 brain tumors, one of the most aggressive forms of brain cancer found in humans. Although current treatments for GB are largely ineffective, new alternate approaches, beyond standard chemo- or radiation therapies have shown promising results in both pre-clinical and clinical settings. Some of these approaches include stem cell therapy, new pharmaceuticals and nutraceuticals, and the use of tumor specific peptides or GB-targeted antibodies and immune-based therapies. A common limitation in the efficacy of these treatments is the inability of these therapeutic agents to readily cross the blood–brain barrier (BBB) to reach the tumor site. Therefore, many strategies are being developed to achieve targeted delivery of drugs across the BBB so that they can kill the cancer cells, while sparing healthy tissue. One of the most promising new approaches involves the use of nanoparticles that can carry therapeutic drugs and genes across the BBB and home in on the GB tumor site.
Temporal Limitations of the Standard Leaky Integrate and Fire Model
Authors: Merzon Liya , Malevich Tatiana , Zhulikov Georgiy , Krasovskaya Sofia , MacInnes W. Joseph
Published: December 2019

Itti and Koch’s Saliency Model has been used extensively to simulate fixation selection in a variety of tasks from visual search to simple reaction times. Although the Saliency Model has been tested for its spatial prediction of fixations in visual salience, it has not been well tested for their temporal accuracy. Visual tasks, like search, invariably result in a positively skewed distribution of saccadic reaction times over large numbers of samples, yet we show that the leaky integrate and fire (LIF) neuronal model included in the classic implementation of the model tends to produce a distribution shifted to shorter fixations (in comparison with human data). Further, while parameter optimization using a genetic algorithm and Nelder–Mead method does improve the fit of the resulting distribution, it is still unable to match temporal distributions of human responses in a visual task. Analysis of times for individual images reveal that the LIF algorithm produces initial fixation durations that are fixed instead of a sample from a distribution (as in the human case). Only by aggregating responses over many input images do they result in a distribution, although the form of this distribution still depends on the input images used to create it and not on internal model variability.
The Relationship between the Conscious Self-Regulation of Schoolchildren’s Learning Activity, Their Test Anxiety Level, and the Final Exam Result in Mathematics
Authors: Morosanova Varvara , Fomina Tatiana , Filippova Elena
Published: December 2019

This article presents the results of a study on the relationship between conscious self-regulation of learning activity, test anxiety and performance in the Unified State Exam in mathematics in a sample of Russian students (N = 231). The Self-Regulation Profile of Learning Activity Questionnaire (SRPLAQ, 2015) and Spielberger’s Test Anxiety Inventory (TAI) (Russian adaptation, 2004) were used to measure self-regulation and anxiety, respectively. The study also took into account the students’ results for the Unified State Exam in mathematics. The study revealed a negative correlation for the test anxiety indicators with both the exam results and regulatory characteristics. The cluster analysis identified groups of students that differed in their level of self-regulation development, anxiety indicators, and the math exam result. It appears that students who have the lowest exam results are characterized not only by high test anxiety rates, but also by lower self-regulation levels. The regression analysis within the groups showed that a higher exam result is largely associated with a person’s regulatory resources. Examination success is based not so much on the ability to cope with adverse functional states, but on the maturity and stability of an integrated system of conscious self-regulation, which determines students’ effectiveness in achieving educational goals.
Angioregulatory microRNAs in Colorectal Cancer
Authors: Soheilifar Mohammad Hasan , Grusch Michael , Neghab Hoda Keshmiri , Amini Razieh , Maadi Hamid , Saidijam Massoud , Wang Zhixiang
Published: December 2019

Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Angiogenesis is a rate-determining step in CRC development and metastasis. The balance of angiogenic and antiangiogenic factors is crucial in this process. Angiogenesis-related genes can be regulated post-transcriptionally by microRNAs (miRNAs) and some miRNAs have been shown to shuttle between tumor cells and the tumor microenvironment (TME). MiRNAs have context-dependent actions and can promote or suppress angiogenesis dependent on the type of cancer. On the one hand, miRNAs downregulate anti-angiogenic targets and lead to angiogenesis induction. Tumor suppressor miRNAs, on the other hand, enhance anti-angiogenic response by targeting pro-angiogenic factors. Understanding the interaction between these miRNAs and their target mRNAs will help to unravel molecular mechanisms involved in CRC progression. The aim of this article is to review the current literature on angioregulatory miRNAs in CRC.
A Phase 1B Clinical Study of Combretastatin A1 Diphosphate (OXi4503) and Cytarabine (ARA-C) in Combination (OXA) for Patients with Relapsed or Refractory Acute Myeloid Leukemia
Authors: Uckun Fatih M. , Cogle Christopher R. , Lin Tara L. , Qazi Sanjive , Trieu Vuong N. , Schiller Gary , Watts Justin M.
Published: December 2019

Combretastatin A1 (OXi4503) is a dual-function drug with vascular disrupting and cytotoxic properties that has exhibited single-agent anti-leukemia activity in murine xenograft models of acute myeloid leukemia (AML) and in a prior Phase 1A clinical study for relapsed/refractory (R/R) AML. The purpose of the present multicenter Phase 1B study was to define the maximum tolerated dose (MTD) and safety profile of OXi4503 and cytarabine (ARA-C) administered in combination (OXA). At four centers, 29 patients with R/R AML or myelodysplastic syndrome (MDS) were treated with OXA. The most common grade 3/4 treatment-emergent adverse events (AEs) were febrile neutropenia (28%), hypertension (17%), thrombocytopenia (17%), and anemia (14%). There were no treatment-emergent grade 5 AEs. Drug-related serious adverse events (SAEs) developed in 4/29 patients (14%) and included febrile neutropenia (N = 2), pneumonia/acute respiratory failure (N = 1), and hypotension (N = 1). 9.76 mg/m2 was defined as the MTD of OXi4503 when administered in combination with 1 g/m2 ARA-C. In 26 evaluable AML patients, there were 2 complete remissions (CR), 2 complete remissions with incomplete count recovery (CRi) and one partial response (PR), for an overall response rate (ORR) of 19%. The median overall survival (OS) time for the four patients who achieved a CR/CRi was 528 days (95% CI: 434–NA), which was significantly longer than the median OS time of 113 days (95% CI: 77–172) for the remaining 22 patients who did not achieve a CR/CRi (Log Rank Chi Square = 11.8, p-value = 0.0006). The safety and early evidence of efficacy of the OXA regimen in R/R AML patients warrant further investigation in a Phase 2 clinical study.
A Case-Control Analysis of the Impact of Venous Thromboembolic Disease on Quality of Life of Patients with Cancer: Quality of Life in Cancer (Qca) Study
Authors: Marin-Barrera Lucia , Muñoz-Martin Andres J. , Rios-Herranz Eduardo , Garcia-Escobar Ignacio , Beato Carmen , Font Carme , Oncala-Sibajas Estefania , Revuelta-Rodriguez Alfonso , Areses Maria Carmen , Rivas-Jimenez Victor , Moreno-Santos Maria Angeles , Ballaz-Quincoces Aitor , Lopez-Saez Juan-Bosco , Gallego Iria , Elias-Hernandez Teresa , Asensio-Cruz Maria Isabel , Chasco-Eguilaz Leyre , Garcia-Gonzalez Gonzalo , Estevez-Garcia Purificacion , Otero Remedios , Lima-Alvarez Jorge , Jara-Palomares Luis
Published: December 2019

Although there is published research on the impact of venous thromboembolism (VTE) on quality of life (QoL), this issue has not been thoroughly investigated in patients with cancer—particularly using specific questionnaires. We aimed to examine the impact of acute symptomatic VTE on QoL of patients with malignancies. This was a multicenter, prospective, case-control study conducted in patients with cancer either with (cases) or without (controls) acute symptomatic VTE. Participants completed the EORTC QLQ-C30, EQ-5D-3L, PEmb-QoL, and VEINES-QOL/Sym questionnaires. Statistically significant and clinically relevant differences in terms of global health status were examined. Between 2015 and 2018, we enrolled 425 patients (128 cases and 297 controls; mean age: 60.2 ± 18.4 years). The most common malignancies were gastrointestinal (23.5%) and lung (19.8%) tumors. We found minimally important differences in global health status on the EQ-5D-3L (cases versus controls: 0.55 versus 0.77; mean difference: −0.22) and EORTC QLQ-C30 (47.7 versus 58.4; mean difference: −10.3) questionnaires. There were minimally important differences on the PEmb-QoL questionnaire (44.4 versus 23; mean difference: −21.4) and a significantly worse QoL on the VEINES-QOL/Sym questionnaire (42.7 versus 51.7; mean difference: −9). In conclusion, we showed that acute symptomatic VTE adversely affects the QoL of patients with malignancies.
Long-Term Outcomes after Use of Perioperative Glucocorticoids in Patients Undergoing Cancer Surgery: A Systematic Review and Meta-Analysis
Authors: Rosenkrantz Hölmich Emma , Petring Hasselager Rune , Tvilling Madsen Michael , Orhan Adile , Gögenur Ismail
Published: December 2019

The surgical stress response can accelerate clinical metastasis formation. Perioperative glucocorticoids might modulate this response and the metastatic process. We aimed to describe associations between perioperative glucocorticoids and long-term outcomes after cancer surgery. We searched four databases for eligible trials and performed meta-analyses on frequency and time-to-event data. We included sixteen studies that evaluated eight different cancer types. No association was found between perioperative glucocorticoids and recurrence in either the frequency meta-analysis, risk ratio (RR) 1.04, 95% confidence interval (CI) (0.87–1.25), or in the time-to-event meta-analysis, hazard ratio (HR) 1.18, 95% CI (0.78–1.79). Increased 1-year overall survival, RR 0.70, 95% (0.51–0.97), and disease-free survival, RR 0.77, 95% CI (0.60–0.97), was found for the glucocorticoid group, but five years after surgery, overall survival was reduced for the glucocorticoid group, RR 1.64, 95% CI (1.00–2.71). An exploratory subgroup analysis revealed decreased overall survival, HR 1.78, 95% CI (1.57–2.03), for patients undergoing colorectal cancer surgery while receiving glucocorticoids. Perioperative glucocorticoids were not associated with recurrence after cancer surgery. We found neither beneficial or deleterious associations between glucocorticoids and overall survival or disease-free survival. The available evidence remains heterogenous; low in quality and amount; and cancer-specific at present.
Immune Therapy for Liver Cancers
Authors: Hilmi Marc , Vienot Angélique , Rousseau Benoît , Neuzillet Cindy
Published: December 2019

Hepatocellular carcinoma (HCC) and biliary tract cancers (BTC) display a poor prognosis with 5-year overall survival rates around 15%, all stages taken together. These primary liver malignancies are often diagnosed at advanced stages where therapeutic options are limited. Recently, immune therapy has opened new opportunities in oncology. Based on their high programmed death-ligand 1 expression and tumor-infiltrating lymphocytes, HCC and BTC are theoretically good candidates for immune checkpoint blockade. However, clinical activity of single agent immunotherapy appears limited to a subset of patients, which is still ill-defined, and combinations are under investigation. In this review, we provide an overview of (i) the biological rationale for immunotherapies in HCC and BTC, (ii) the current state of their clinical development, and (iii) the predictive value of immune signatures for both clinical outcome and response to these therapies.
Editorial: Cobalt and Iron Catalysis
Authors: Shafer Wilson D. , Jacobs Gary
Published: December 2019

Cobalt and iron have long history of importance in the field of catalysis that continues to this day [...]
TDP-43-Mediated Toxicity in HEK293T Cells: A Fast and Reproducible Protocol To Be Employed in the Search of New Therapeutic Options against Amyotrophic Lateral Sclerosis
Authors: Lanznaster Débora , Bourgeais Jérôme , Bruno Clement , Hergesheimer Rudolf C. , Thepault Rose-Anne , Vourc’h Patrick , Corcia Philippe , Andres Christian R. , Herault Olivier , Blasco Hélène
Published: December 2019

Cytoplasmic TDP-43 aggregates are a hallmark of amyotrophic lateral sclerosis (ALS). Today, only two drugs are available for ALS treatment, and their modest effect prompts researchers to search for new therapeutic options. TDP-43 represents one of the most promising targets for therapeutic intervention, but reliable and reproducible in vitro protocols for TDP-43-mediated toxicity are lacking. Here, we used HEK293T cells transfected with increasing concentrations of TDP-43-expressing plasmid to evaluate different parameters of toxicity and alterations in cellular metabolism. Overexpression of TDP-43 induced aggregates occurrence followed by the detection of 25- and 35-kDa forms of TDP-43. TDP-43 overexpression decreased cell viability and increased cells arrested at G2/M phase and nuclear fragmentation. Analysis of the energetic metabolism showed a tendency to decrease oxidative phosphorylation and increase glycolysis, but no statistical differences were observed. Metabolomics revealed alterations in different metabolites (mainly sphingolipids and glycerophospholipids) in cells overexpressing TDP-43. Our data reveal the main role of TDP-43 aggregation in cellular death and highlight novel insight into the mechanism of cellular toxicity induced by TDP-43. Here, we provide a simple, sensitive, and reliable protocol in a human-derived cell line to be used in high-throughput screenings of potential therapeutic molecules for ALS treatment.
Quantitative Predictive Modelling Approaches to Understanding Rheumatoid Arthritis: A Brief Review
Authors: Macfarlane Fiona R. , Chaplain Mark A. J. , Eftimie Raluca
Published: December 2019

Rheumatoid arthritis is a chronic autoimmune disease that is a major public health challenge. The disease is characterised by inflammation of synovial joints and cartilage erosion, which lead to chronic pain, poor life quality and, in some cases, mortality. Understanding the biological mechanisms behind the progression of the disease, as well as developing new methods for quantitative predictions of disease progression in the presence/absence of various therapies is important for the success of therapeutic approaches. The aim of this study is to review various quantitative predictive modelling approaches for understanding rheumatoid arthritis. To this end, we start by briefly discussing the biology of this disease and some current treatment approaches, as well as emphasising some of the open problems in the field. Then, we review various mathematical mechanistic models derived to address some of these open problems. We discuss models that investigate the biological mechanisms behind the progression of the disease, as well as pharmacokinetic and pharmacodynamic models for various drug therapies. Furthermore, we highlight models aimed at optimising the costs of the treatments while taking into consideration the evolution of the disease and potential complications.
Precision Medicine in Neurodegenerative Diseases: Some Promising Tips Coming from the microRNAs’ World
Authors: Nuzziello Nicoletta , Ciaccia Loredana , Liguori Maria
Published: December 2019

Novel insights in the development of a precision medicine approach for treating the neurodegenerative diseases (NDDs) are provided by emerging advances in the field of pharmacoepigenomics. In this context, microRNAs (miRNAs) have been extensively studied because of their implication in several disorders related to the central nervous system, as well as for their potential role as biomarkers of diagnosis, prognosis, and response to treatment. Recent studies in the field of neurodegeneration reported evidence that drug response and efficacy can be modulated by miRNA-mediated mechanisms. In fact, miRNAs seem to regulate the expression of pharmacology target genes, while approved (conventional and non-conventional) therapies can restore altered miRNAs observed in NDDs. The knowledge of miRNA pharmacoepigenomics may offers new clues to develop more effective treatments by providing novel insights into interindividual variability in drug disposition and response. Recently, the therapeutic potential of miRNAs is gaining increasing attention, and miRNA-based drugs (for cancer) have been under observation in clinical trials. However, the effective use of miRNAs as therapeutic target still needs to be investigated. Here, we report a brief review of representative studies in which miRNAs related to therapeutic effects have been investigated in NDDs, providing exciting potential prospects of miRNAs in pharmacoepigenomics and translational medicine.
Sequential Detection of Palladium and Chromium Oxyanion by a Fluorescein Based Chemosensor in Mixed Aqueous Media
Authors: Helal Aasif
Published: December 2019

A new highly selective chemosensor, based on fluorescein-allyloxy benzene conjugate 1, was developed for the sequential detection of palladium and chromium oxyanions in a mixed aqueous media, and was studied by UV-visible and fluorescence spectroscopy. The sensing of palladium ions produces a chemodosimetric and ratiometric change in the emission band of 1 from 450 to 525 nm, followed by the sensing of chromate ions by 2 that quenches the emission band at 525 nm in a buffered H2O: DMF solution (9:1, pH = 7.4). The rate constants of palladium and chromate ions were found to be 8.6 × 105 M−1, 2.1 × 105 M−1, and 5.4 × 104 M−1 respectively. The chemosensor 1 has a palladium detection limit of 49 ppb while the sequential detection limit of chromate ions (CrO42− and Cr2O72−) were 127 and 259 ppb. The ratiometric change in the emission is produced due to the deallylation of 1 by palladium to produce 2 that restores the ESIPT (excited state intramolecular proton transfer) of the phenolic ring and enhances the electron transfer (ET) phenomenon from the phenolic group to fluorescein. The sequential binding of chromate ions to 2 inhibits the ESIPT and causes chelation enhanced quenching (CHEQ) of the fluorescence.