bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Coated Cysteamine on Oxidative Stress and Inflammation in Weaned Pigs
Authors: Wang Shanshan , Bai Miaomiao , Xu Kang , Shao Yirui , Yang Zhe , Xiong Xia , Huang Ruilin , Li Yao , Liu Hongnan
Published: July 2021

This study aimed to explore the effects of dietary coated cysteamine on oxidative stress and inflammation in diquat-induced weaning pigs. Twenty-four pigs were randomly assigned to three dietary groups with eight replicates: the control (fed base diet), diquat (fed base diet), and coated cysteamine + diquat groups (fed 80 mg/kg cysteamine). The experiment was conducted for 21 d, and consisted of a pre-starter period (14 d) and a starter period (7 d). Coated cysteamine treatment significantly increased (p < 0.05) the final weight and average daily gain (ADG) in pigs. The contents of alkaline phosphatase (ALP), immunoglobulin G (IgG), serine (Ser), and isoleucine (Ile) were elevated (p < 0.05) while the contents of albumin (ALB) and aspartic acid (Asp) were reduced (p < 0.05) in the serum after coated cysteamine supplementation. Coated cysteamine supplementation resulted in greater (p < 0.05) serum superoxide dismutase (SOD) activity, the expression of interleukin-10 (IL-10) mRNA in the colon, and the CuSOD mRNA expression in the jejunum (p < 0.05) and colon (p = 0.073). Coated cysteamine supplementation showed an increasing trend in villus height (p = 0.060), villus height/crypt depth (V/C) (p = 0.056), the expression levels of zonula occludens-1 (ZO-1) mRNA (p = 0.061), and Occludin mRNA (p = 0.074) in the jejunum. In summary, dietary supplementation with coated cysteamine improves the intestinal barrier function of the jejunum by increasing the immunoglobulin content and the relative expression of intestinal immune factor mRNA in pigs while alleviating oxidative stress and inflammatory reactions caused by diquat.
Comparison of Delivery Methods in Phage Therapy against Flavobacterium columnare Infections in Rainbow Trout
Authors: Kunttu Heidi M. T. , Runtuvuori-Salmela Anniina , Middelboe Mathias , Clark Jason , Sundberg Lotta-Riina
Published: July 2021

Viruses of bacteria, bacteriophages, specifically infect their bacterial hosts with minimal effects on the surrounding microbiota. They have the potential to be used in the prevention and treatment of bacterial infections, including in the field of food production. In aquaculture settings, disease-causing bacteria are often transmitted through the water body, providing several applications for phage-based targeting of pathogens, in the rearing environment, and in the fish. We tested delivery of phages by different methods (via baths, in phage-coated material, and via oral delivery in feed) to prevent and treat Flavobacterium columnare infections in rainbow trout fry using three phages (FCOV-S1, FCOV-F2, and FCL-2) and their hosts (FCO-S1, FCO-F2, and B185, respectively). Bath treatments given before bacterial infection and at the onset of the disease symptoms were the most efficient way to prevent F. columnare infections in rainbow trout, possibly due to the external nature of the disease. In a flow-through system, the presence of phage-coated plastic sheets delayed the onset of the disease. The oral administration of phages first increased disease progression, although total mortality was lower at the end of the experiment. When analysed for shelf-life, phage titers remained highest when maintained in bacterial culture media and in sterile lake water. Our results show that successful phage therapy treatment in the aquaculture setting requires optimisation of phage delivery methods in vivo.
Decreasing the Likelihood of Multiple Organ Dysfunction Syndrome in Burn Injury with Early Antioxidant Treatment
Authors: Sterling Jackson P. , Lombardi Vincent C.
Published: July 2021

Major burn trauma initiates a cascade of physiological events that cause profound stress on the body, resulting in significant complications which often lead to death. An understanding of these events may afford earlier and more precise interventions which, in turn, may reduce these complications, thus, improving patient outcomes. Burn trauma is associated with numerous inflammatory events that result in the release of free radicals, which promote oxidative stress and subsequent tissue damage. These mass-inflammatory events affect the body systemically, leading to several detrimental responses including complement activation, excessive histamine release, decrease in blood pressure, release of reactive oxygen species, and ultimately multiple organ dysfunction syndrome (MODS). However, recent studies conducted on the use of antioxidants as a part of a burn treatment protocol have shown promising results. In this review, we will discuss the current research and advancements in the treatment of burn trauma with the use of antioxidants, and how the early administration of antioxidant can possibly reduce the risk of developing MODS.
Potential Use of Annona Genus Plants Leaf Extracts to Produce Bioactive Transdermal Patches by Supercritical Solvent Impregnation
Authors: Fernández Ponce María Teresa , Cejudo Bastante Cristina , Casas Cardoso Lourdes , Mantell Casimiro , Martínez de la Ossa Enrique J. , Pereyra Clara
Published: July 2021

The objective of the present work was to develop a bioactive transdermal patch functionalized with Annona leaf extracts (ALE) by means of supercritical impregnation technique. The potential of six different Annona leaf extracts (ALE) obtained with the enhanced solvent system formed by carbon dioxide + ethanol/acetone was evaluated taking into account the antioxidant activity, total phenol composition and global extraction yields. For the impregnation of ALE, two drug supporting systems were tested: hydrocolloid sodium carboxymethyl cellulose (NaCMC) and polyester dressings (PD). The effect of the impregnation conditions, including pressure (P), temperature (T), percent of co-solvent (ethanol) and ALE/polymer mass ratio, was determined with regard to the loading and the functional activity of the impregnated samples. The optimal impregnation conditions of ALE were established at 55 °C and 300 bar which led to obtained transdermal patches with antioxidant and antimicrobial capacity. In order to understand the behavior of the process, the homogeneity of the samples in the vessels was also evaluated. The best results were obtained at higher proportions of co-solvent in the system.
Nutraceutical Strategy to Counteract Eye Neurodegeneration and Oxidative Stress in Drosophila melanogaster Fed with High-Sugar Diet
Authors: Catalani Elisabetta , Fanelli Giuseppina , Silvestri Federica , Cherubini Agnese , Del Quondam Simona , Bongiorni Silvia , Taddei Anna Rita , Ceci Marcello , De Palma Clara , Perrotta Cristiana , Rinalducci Sara , Prantera Giorgio , Cervia Davide
Published: July 2021

Aberrant production of reactive oxygen species (ROS) is a common feature of damaged retinal neurons in diabetic retinopathy, and antioxidants may exert both preventive and therapeutic action. To evaluate the beneficial and antioxidant properties of food supplementation with Lisosan G, a powder of bran and germ of grain (Triticum aestivum) obtained by fermentation with selected lactobacillus and natural yeast strains, we used an in vivo model of hyperglycemia-induced retinal damage, the fruit fly Drosophila melanogaster fed with high-sucrose diet. Lisosan G positively affected the visual system of hyperglycemic flies at structural/functional level, decreased apoptosis, and reactivated protective autophagy at the retina internal network. Also, in high sucrose-fed Drosophila, Lisosan G reduced the levels of brain ROS and retina peroxynitrite. The analysis of oxidative stress-related metabolites suggested 7,8-dihydrofolate, uric acid, dihydroorotate, γ-L-glutamyl-L-cysteine, allantoin, cysteinyl-glycine, and quinolate as key mediators of Lisosan G-induced inhibition of neuronal ROS, along with the upregulation of glutathione system. Of note, Lisosan G may impact oxidative stress and the ensuing retinal cell death, also independently from autophagy, although the autophagy-ROS cross-talk is critical. This study demonstrated that the continuous supplementation with the alimentary integrator Lisosan G exerts a robust and multifaceted antioxidant effect on retinal neurons, thus providing efficacious neuroprotection of hyperglycemic eye.
New Mechanisms of Action of Natural Antioxidants in Health and Disease II
Authors: Hrelia Silvana , Angeloni Cristina
Published: July 2021

Epidemiological studies have demonstrated an association between natural antioxidants and human health [...]
Intracellular Pathways of Holothuroid Oocyte Maturation Induced by the Thioredoxin Trx-REES
Authors: Delroisse Jérôme , Léonet Aline , Alexandre Henri , Eeckhaut Igor
Published: July 2021

In holothuroids, oocyte maturation is stopped in ovaries at the prophase I stage of meiosis. In natural conditions, the blockage is removed during the spawning by an unknown mechanism. When oocytes are isolated by dissection, the meiotic release can be successfully induced by a natural inducer, the REES (i.e., Rough Extract of Echinoid Spawn) that is used in aquaculture to obtain viable larvae in mass. A thioredoxin has recently been identified in the REES as the molecule responsible for holothuroid oocyte maturation. As a redox-active protein, thioredoxin is thought to reduce target proteins within the oocyte membrane and initiate an intracellular reaction cascade that leads to the unblocking of the oocyte meiosis. Our results allow us to understand additional steps in the intracellular reaction cascade induced by the action of thioredoxin on oocytes. Pharmacological agents known to have activating or inhibiting actions on oocyte maturation have been used (Forskolin, Isobutylmethylxanthine, Hypoxanthine, 6-dimethyaminopurine, Lavendustin, Genistein, Roscovitine, Cycloheximide). The effects of these agents were analysed on oocytes of the holothuroid Holothuria tubulosa incubated with or without REES and were compared to those obtained with another reducing agent, the dithiothreitol. Our results demonstrated that, at the opposite of dithiothreitol-induced oocyte maturation, thioredoxin-induced oocyte maturation is cAMP independent, but dependent of the presence of calcium in the seawater. Both pathways of induction require the activation of protein serine/threonine kinases.
Surface Plasmon Resonance Sensor of CO2 for Indoors and Outdoors
Authors: Pérez-Ocón Francisco , Pozo Antonio M. , Cortina Jorge , Rabaza Ovidio
Published: July 2021

The ability to detect CO2 with the smallest possible devices, equipped with alarms and having great precision, is vital for human life, whether indoors or outdoors. It is essential to know if we are being subjected to this gas to establish the level of ventilation in factories, houses, classrooms, etc., and to be protected against viruses or dangerous gas concentrations. Equally, when we are in the countryside, it is useful to be able to evaluate if the greenhouse effect, caused by this gas, is increasing. We propose a surface plasmon resonance (SPR) sensor for the measurement of CO2 concentrations taking into account that the refractive index of carbon dioxide depends on temperature, humidity, pressure, etc. With our sensor we can measure (in air) in any type of environment and concentration. Our sensor has a resolution of 5.15 × 10−5 RIU and a sensitivity of 19.4 RIU−1 for 400 ppm.
Evaluation of Marblewood Dust’s (Marmaroxylon racemosum) Effect on Ignition Risk
Authors: Vandličkova Miroslava , Markova Iveta , Holla Katarina , Gašpercová Stanislava
Published: July 2021

The paper deals with the selected characteristics, such as moisture, average bulk density, and fraction size, of tropical marblewood dust (Marmaroxylon racemosum) that influence its ignition risk. Research was focused on sieve analysis, granulometric analysis, measurement of moisture level in the dust, and determination of the minimum ignition temperatures of airborne tropical dust and dust layers. Samples were prepared using a Makita 9556CR 1400W grinder and K36 sandpaper for the purpose of selecting the percentages of the various fractions (<63, 63, 71, 100, 200, 315, 500 μm). The samples were sized on an automatic vibratory sieve machine Retsch AS 200. More than 65% of the particles were determined to be under 100 μm. The focus was on microfractions of tropical wood dust (particles with a diameter of ≤100 µm) and on the impact assessment of particle size (particle size < 100 µm) on the minimum ignition temperatures of airborne tropical dust and dust layers. The minimum ignition temperature of airborne marblewood dust decreased with the particle size to the level of 400 °C (particle size 63 μm).
Dynamic Aeroelastic Response of Stall-Controlled Wind Turbine Rotors in Turbulent Wind Conditions
Authors: Jalal Sara , Ponta Fernando , Baruah Apurva , Rajan Anurag
Published: July 2021

With the current global trend of the wind turbines to be commissioned, the next generation of state-of-the-art turbines will have a generating capacity of 20 MW with rotor diameters of 250 m or larger. This systematic increase in rotor size is prompted by economies-of-scale factors, thereby resulting in a continuously decreasing cost per kWh generated. However, such large rotors have larger masses associated with them and necessitate studies in order to better understand their dynamics. The present work regarding the aeroelastic behavior of stall-controlled rotors involves the study of the frequency content and time evolution of their oscillatory behavior. A wide range of experiments were conducted to assess the effects of rapid variations on the rotor’s operational conditions. Various gust conditions were tested at different wind speeds, which are represented by pulses of different intensities, occurring suddenly in an otherwise constant wind regime. This allowed us to observe the pure aero-elasto-inertial dynamics of the rotor’s response. A reduced-order characterization of the rotor’s dynamics as an oscillatory system was obtained on the basis of energy-transfer principles. This is of fundamental interest for researchers and engineers working on developing optimized control strategies for wind turbines. It allows for the critical elements of the rotor’s dynamic behavior to be described as a reduced-order model that can be solved in real time, an essential requirement for determining predictive control actions.
Predicting the Performance of Solar Power Generation Using Deep Learning Methods
Authors: Lee Chung-Hong , Yang Hsin-Chang , Ye Guan-Bo
Published: July 2021

In recent years, many countries have provided promotion policies related to renewable energy in order to take advantage of the environmental factors of sufficient sunlight. However, the application of solar energy in the power grid also has disadvantages. The most obvious is the variability of power output, which will put pressure on the system. As more grid reserves are needed to compensate for fluctuations in power output, the variable nature of solar power may hinder further deployment. Besides, one of the main issues surrounding solar energy is the variability and unpredictability of sunlight. If it is cloudy or covered by clouds during the day, the photovoltaic cell cannot produce satisfactory electricity. How to collect relevant factors (variables) and data to make predictions so that the solar system can increase the power generation of solar power plants is an important topic that every solar supplier is constantly thinking about. The view is taken, therefore, in this work, we utilized the historical monitoring data collected by the ground-connected solar power plants to predict the power generation, using daily characteristics (24 h) to replace the usual seasonal characteristics (365 days) as the experimental basis. Further, we implemented daily numerical prediction of the whole-point power generation. The preliminary experimental evaluations demonstrate that our developed method is sensible, allowing for exploring the performance of solar power prediction.
Maximum Admissible Slip of Tractor Wheels without Disturbing the Soil Structure
Authors: Bulgakov Volodymyr , Aboltins Aivars , Beloev Hristo , Nadykto Volodymyr , Kyurchev Volodymyr , Adamchuk Valerii , Kaminskiy Viktor
Published: July 2021

One of the most important parameters that characterize the traction-coupling properties of a wheeled tractor is its slip. The more tractor’s gross traction exists, the higher its traction-coupling properties are. However, this gross traction should not exceed its maximum possible value, which, in turn out, is to be determined by the maximum permissible slip, δmax. This article provides the equation to calculate this crucial parameter and establishes the dependencies between the tractor’s slip and soil structure coefficient. It was shown that the value of δmax basically depends on such soil characteristics as the bulk deformation coefficient and the coefficient of rolling resistance. Calculations showed that, for the average value of the soil bulk deformation coefficient at 4000 kN·m−3, the average value of rolling resistance coefficient at 0.16, and the ratio value of the maximum permissible soil pressure to the tractor wheel rolling radius at 222 kPa·m−1, the maximum permitted amount slip of the tractor wheels should not exceed 15%. With more slip, the soil structure deteriorates significantly. In this case, its structure coefficient may be less than critical, equal to 0.4.
Three-Dimensional Numerical Investigations of the Flow Pattern and Evolution of the Horseshoe Vortex at a Circular Pier during the Development of a Scour Hole
Authors: Helmi Ahmed M. , Shehata Ahmed H.
Published: July 2021

In the current study, a three-dimensional CFD model is utilized to investigate the variation of the flow structure and bed shear stress at a single cylindrical pier during scour development. The scour development is presented by seven solidified geometries of the scour hole, collected during previous experimental work at different scour stages. Different turbulence models are evaluated and the (k-ω) model is chosen due to its relative accuracy in capturing the flow oscillation and vortex shedding at the pier downstream side with personal computer computational and storage resources. The numerical results are verified against dimensionless parameters from different previous experimental works. This research describes in detail the flow structure and bed shear stress variations through seven stages of the scour hole development. The dimensionless area-averaged circulation coefficient (Ψi) is developed to evaluate the changes in the vortex strength through the scouring process by eliminating the calculation area effect. It was concluded that the circulation in the (Y) direction is the main driving factor in the development of the scour hole more than the circulation in the (X) direction. The ratio between the horseshoe vortex (HV) mean size and the scouring depth (DV/dS) in addition to the location of the maximum bed shear stress are investigated during different stages of the scour development.
Geongangbuja-Tang Decoction and Its Active Ingredient, Aconiti Lateralis Radix Preparata, Exerts Inhibitory Effects on Heat Stress-Induced Inflammation in Mice
Authors: Huh Eugene , Lee Wonil , Choi Yujin , Lee Tae Hee , Oh Myung Sook
Published: July 2021

Heat stress induces the hypothalamic-pituitary-adrenal (HPA) axis activation, influences biological responses, and reduces energy metabolism. Geongangbuja-tang (GBT) and its components, Zingiberis Rhizoma (ZOR) and Aconiti Lateralis Radix Preparata (ALRP) have been used to induce energy metabolism; however, the effects of GBT and its ingredients on heat-induced inflammatory responses have not yet been investigated. In this study, we performed an open-field test to evaluate locomotor activity in mice. To assess the effects of GBT and its ingredients on inflammation, the protein levels of c-fos, pro-inflammatory cytokines, and cortisol were measured in the mouse hypothalamus and serum. The results showed that GBT alleviated locomotive activity and reduced c-fos levels in a dose-dependent manner under the heat exposure. After investigating the active constituent of GBT, we found that compared to GBT and ZOR, ALRP significantly suppressed c-fos expression under heat stress. Subsequently, ALRP decreased the expression of pro-inflammatory cytokines, such as interleukin-9 and -13 and prostaglandin, under the heat stress in the mouse hypothalamus. Moreover, treatment with ALRP inhibited cortisol secretion in the mouse serum following heat exposure. These results indicate that GBT and its active component, ALRP, could be the thermoregulatory agents that regulate the HPA axis.
Effects of Pile Installation on Existing Tunnels Using Model Test and Numerical Analysis with Medium Density Sand
Authors: Kong Suk-Min , Oh Dong-Wook , Lee Seong-Won , Kim Chang-Yong , Lee Yong-Joo
Published: July 2021

Vital underground structures such as sewers, power transmission lines, subways, and underpasses are potentially vulnerable to adverse effects from aboveground construction. In this study, the influence of pile installation on nearby existing tunnels was investigated. Both a laboratory model test and finite-element numerical analysis were conducted. Twelve different combinations of horizontal and vertical offsets between the pile and the tunnel were investigated. Different surcharge loads (allowable and ultimate) were also considered. In this way, the appropriate separation distance between the existing tunnel and the piles was established for sandy, medium-compaction soil. Although this study considers simple ground conditions, it facilitates safe construction by confirming the appropriate separation distance and comparing the areas that cannot be penetrated by the structures of each standard.
Theoretical and Experimental Investigation of Vehicle-Mounted Transient Electromagnetic Method Detection for Internal Defects of Operational Tunnels
Authors: Qian Wangping , Li Honghui , Yu Jun , Gu Zhenyuan
Published: July 2021

With the durable operation of high-speed railway tunnels in China, many tunnel defects successively appeared in the tunnel lining structure and gradually threatened the safe operation of the tunnels. In the limited maintenance time of high-speed railways, it is urgent to find out and maintain tunnel defects, especially internal defects. We propose an applied detection technology called the vehicle-mounted transient electromagnetic method (TEM). The detection technology aims to rapidly detect and locate the internal defects of the lining structure throughout the entire tunnel. Firstly, we investigate tunnel defects in detail and introduce the rapid detection method. Secondly, we analyze the principle and process of vehicle-mounted TEM. Thirdly, the rationality and applicability of vehicle-mounted TEM are verified by three different methods, including theoretical analysis, numerical simulation, and laboratory experiment. Finally, we compare the inversion results of experimental data under the two conditions. The results illustrate that tunnel surface defects are the external manifestations and characteristics of tunnel defects, while the forms of surface defects are directly related to internal defects. This detection method is suitable for the significant resistivity difference between tunnel defects and surrounding rocks, and its rationality is effectively validated. Furthermore, the apparent resistivity results reveal that there is a low resistivity region in front of the transmitter coil, and that the relative position can be preliminarily judged. The research results can provide a potential and significant application technology for the rapid detection of tunnel defects.
Portable Prototypes: Canterbury Badges and the Thomasaltar in Hamburg
Authors: Lee Jennifer
Published: July 2021

Pilgrims’ badges often depicted works of art located at a cult center, and these cheap, small images frequently imitated monumental works. Was this relationship ever reversed? In late medieval Hamburg, a painted altarpiece from a Hanseatic guild narrates the life of Thomas Becket in four scenes, two of which survive. In 1932, Tancred Borenius declared this altarpiece to be the first monumental expression of Becket’s narrative in northern Germany. Since then, little scholarship has investigated the links between this work and the Becket cult elsewhere. With so much visual art from the medieval period lost, it is impossible to trace the transmission of imagery with any certainty. Nevertheless, this discussion considers badges as a means of disseminating imagery for subsequent copying. This altarpiece and the pilgrims’ badges that it closely resembles may provide an example of a major work of art borrowing a composition from an inexpensive pilgrim’s badge and of the monumental imitating the miniature.
Expected Health Effects of Reduced Air Pollution from COVID-19 Social Distancing
Authors: Cicala Steve , Holland Stephen P. , Mansur Erin T. , Muller Nicholas Z. , Yates Andrew J.
Published: July 2021

The COVID-19 pandemic resulted in stay-at-home policies and other social distancing behaviors in the United States in spring of 2020. This paper examines the impact that these actions had on emissions and expected health effects through reduced personal vehicle travel and electricity consumption. Using daily cell phone mobility data for each U.S. county, we find that vehicle travel dropped about 40% by mid-April across the nation. States that imposed stay-at-home policies before March 28 decreased travel slightly more than other states, but travel in all states decreased significantly. Using data on hourly electricity consumption by electricity region (e.g., balancing authority), we find that electricity consumption fell about 6% on average by mid-April with substantial heterogeneity. Given these decreases in travel and electricity use, we estimate the county-level expected improvements in air quality, and, therefore, expected declines in mortality. Overall, we estimate that, for a month of social distancing, the expected premature deaths due to air pollution from personal vehicle travel and electricity consumption declined by approximately 360 deaths, or about 25% of the baseline 1500 deaths. In addition, we estimate that CO2 emissions from these sources fell by 46 million metric tons (a reduction of approximately 19%) over the same time frame.
Characteristics of Dust Events in China from 2015 to 2020
Authors: Yang Lili , Zhang Shuwen , Huang Zhongwei , Yang Yanping , Wang Lina , Han Wenyu , Li Xiaoyun
Published: July 2021

As the main source of dust in Asia, China often suffers from dust events. The temporal and spatial characteristics of dust events change with the variations of geography, climate and human activities. Based on the criteria of selecting dust events proposed recently by the China Environmental Monitoring Station, the hourly concentration of PM10 and PM2.5 of 336 cities in China from 2015 to 2020 were used to study the temporal and spatial characteristics of dust events more accurately and objectively. The results showed that all of the dust events in China clearly decreased, but the strong dust events did not decrease. There were 334 cities that had dust events except Shenzhen and Dongguan, 299 cities were seriously polluted due to dust events, 134 cities encountered dust level III and 56 cities encountered dust level IV. The high frequencies of dust events were mainly distributed in Northern China, especially in Northwest China. The dust contribution of PM10 to the cities in Northwest China was more than 10% and about 5–10% for PM2.5. The most likely month for dust was May. The starting time of dust was bimodally distributed, and the most common starting time was 10:00–11:00 BJT, followed by 22:00–23:00 BJT. According to the PSCF (Potential Source Contribution Function) results, the dust potential source contribution of different cities mainly came from the northwest, and was mainly affected by Mongolia in addition to the local dust in China. In addition, Beijing was obviously affected by dust recirculation. This study is of great significance to the improvement of the forecast of dust weather and the warning of heavy pollution caused by dust events.
Machine Learning Emulation of Spatial Deposition from a Multi-Physics Ensemble of Weather and Atmospheric Transport Models
Authors: Gunawardena Nipun , Pallotta Giuliana , Simpson Matthew , Lucas Donald D.
Published: July 2021

In the event of an accidental or intentional hazardous material release in the atmosphere, researchers often run physics-based atmospheric transport and dispersion models to predict the extent and variation of the contaminant spread. These predictions are imperfect due to propagated uncertainty from atmospheric model physics (or parameterizations) and weather data initial conditions. Ensembles of simulations can be used to estimate uncertainty, but running large ensembles is often very time consuming and resource intensive, even using large supercomputers. In this paper, we present a machine-learning-based method which can be used to quickly emulate spatial deposition patterns from a multi-physics ensemble of dispersion simulations. We use a hybrid linear and logistic regression method that can predict deposition in more than 100,000 grid cells with as few as fifty training examples. Logistic regression provides probabilistic predictions of the presence or absence of hazardous materials, while linear regression predicts the quantity of hazardous materials. The coefficients of the linear regressions also open avenues of exploration regarding interpretability—the presented model can be used to find which physics schemes are most important over different spatial areas. A single regression prediction is on the order of 10,000 times faster than running a weather and dispersion simulation. However, considering the number of weather and dispersion simulations needed to train the regressions, the speed-up achieved when considering the whole ensemble is about 24 times. Ultimately, this work will allow atmospheric researchers to produce potential contamination scenarios with uncertainty estimates faster than previously possible, aiding public servants and first responders.
Sensitivity of Spring Phenology Simulations to the Selection of Model Structure and Driving Meteorological Data
Authors: Dávid Réka Ágnes , Barcza Zoltán , Kern Anikó , Kristóf Erzsébet , Hollós Roland , Kis Anna , Lukac Martin , Fodor Nándor
Published: July 2021

Accurate estimation of the timing of intensive spring leaf growth initiation at mid and high latitudes is crucial for improving the predictive capacity of biogeochemical and Earth system models. In this study, we focus on the modeling of climatological onset of spring leaf growth in Central Europe and use three spring phenology models driven by three meteorological datasets. The MODIS-adjusted NDVI3g dataset was used as a reference for the period between 1982 and 2010, enabling us to study the long-term mean leaf onset timing and its interannual variability (IAV). The performance of all phenology model–meteorology database combinations was evaluated with one another, and against the reference dataset. We found that none of the constructed model–database combinations could reproduce the observed start of season (SOS) climatology within the study region. The models typically overestimated IAV of the leaf onset, where spatial median SOS dates were best simulated by the models based on heat accumulation. When aggregated for the whole study area, the complex, bioclimatic index-based model driven by the CarpatClim database could capture the observed overall SOS trend. Our results indicate that the simulated timing of leaf onset primarily depends on the choice of model structure, with a secondary contribution from the choice of the driving meteorological dataset.
Skewed and Mixture of Gaussian Distributions for Ensemble Postprocessing
Authors: Taillardat Maxime
Published: July 2021

The implementation of statistical postprocessing of ensemble forecasts is increasingly developed among national weather services. The so-called Ensemble Model Output Statistics (EMOS) method, which consists of generating a given distribution whose parameters depend on the raw ensemble, leads to significant improvements in forecast performance for a low computational cost, and so is particularly appealing for reduced performance computing architectures. However, the choice of a parametric distribution has to be sufficiently consistent so as not to lose information on predictability such as multimodalities or asymmetries. Different distributions are applied to the postprocessing of the European Centre for Medium-range Weather Forecast (ECMWF) ensemble forecast of surface temperature. More precisely, a mixture of Gaussian and skewed normal distributions are tried from 3- up to 360-h lead time forecasts, with different estimation methods. For this work, analytical formulas of the continuous ranked probability score have been derived and appropriate link functions are used to prevent overfitting. The mixture models outperform single parametric distributions, especially for the longest lead times. This statement is valid judging both overall performance and tolerance to misspecification.
Comparative Chloroplast Genomes of Four Lycoris Species (Amaryllidaceae) Provides New Insight into Interspecific Relationship and Phylogeny
Authors: Zhang Fengjiao , Wang Ning , Cheng Guanghao , Shu Xiaochun , Wang Tao , Zhuang Weibing , Lu Ruisen , Wang Zhong
Published: July 2021

The genus Lycoris (Amaryllidaceae) consists of about 20 species, which is endemic to East Asia. Although the Lycoris species is of great horticultural and medical importance, challenges in accurate species identification persist due to frequent natural hybridization and large-scale intraspecific variation. In this study, we sequenced chloroplast genomes of four Lycoris species and retrieved seven published chloroplast (cp) genome sequences in this genus for comparative genomic and phylogenetic analyses. The cp genomes of these four newly sequenced species were found to be 158,405–158,498 bp with the same GC content of 37.8%. The structure of the genomes exhibited the typical quadripartite structure with conserved gene order and content. A total of 113 genes (20 duplicated) were identified, including 79 protein-coding genes (PCGs), 30 tRNAs, and 4 rRNAs. Phylogenetic analysis showed that the 11 species were clustered into three main groups, and L. sprengeri locate at the base of Lycoriss. The L. radiata was suggested to be the female donor of the L. incarnata, L. shaanxiensis, and L. squamigera. The L. straminea and L. houdyshelii may be derived from L. anhuiensis, L. chinensis, or L. longituba. These results could not only offer a genome-scale platform for identification and utilization of Lycoris but also provide a phylogenomic framework for future studies in this genus.
OsARP6 Is Involved in Internode Elongation by Regulating Cell-Cycle-Related Genes
Authors: Ikram Aziz , Ding Yong , Su Yanhua
Published: July 2021

The SWR1 complex (SWR1-C) is important for the deposition of histone variant H2A.Z into chromatin to regulate gene expression. Characterization of SWR1-C subunits in Arabidopsis thaliana has revealed their role in variety of developmental processes. Oryza sativa actin related protein 6 (OsARP6) is a subunit of rice SWR1-C. Its role in rice plant development is unknown. Here, we examined the subcellular localization, expression patterns, and loss of function phenotypes for this protein and found that OsARP6 is a nuclear localized protein, and is broadly expressed. OsARP6 interacted with OsPIE1, a central ATPase subunit of rice SWR1-C. The osarp6 knockout mutants displayed pleiotropic phenotypic alterations in vegetative and reproductive traits, including semi-dwarf phenotype, lower tillers number, short leaf length, changes in spikelet morphology, and seed abortion. Microscopic thin sectioning of the top internode revealed that the dwarf phenotype of osarp6 was due to reduced number of cells rather than reduced cell length. The altered transcript level of genes involved in cell division suggested that OsARP6 affects cell cycle regulation. In addition, H2A.Z levels were reduced at the promoters and transcription start sites (TSS) of the regulated genes in osarp6 plants. Together, these results suggest that OsARP6 is involved in rice plant development, and H2A.Z deposition.
LRRK2 Targeting Strategies as Potential Treatment of Parkinson’s Disease
Authors: Wojewska Dominika Natalia , Kortholt Arjan
Published: July 2021

Parkinson’s Disease (PD) affects millions of people worldwide with no cure to halt the progress of the disease. Leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of PD and, as such, LRRK2 inhibitors are promising therapeutic agents. In the last decade, great progress in the LRRK2 field has been made. This review provides a comprehensive overview of the current state of the art, presenting recent developments and challenges in developing LRRK2 inhibitors, and discussing extensively the potential targeting strategies from the protein perspective. As currently there are three LRRK2-targeting agents in clinical trials, more developments are predicted in the upcoming years.
Against the Resilience of High-Grade Gliomas: Gene Therapies (Part II)
Authors: Giotta Lucifero Alice , Luzzi Sabino
Published: July 2021

Introduction: High-grade gliomas (HGGs) still have a high rate of recurrence and lethality. Gene therapies were projected to overcome the therapeutic resilience of HGGs, due to the intrinsic genetic heterogenicity and immune evasion pathways. The present literature review strives to provide an updated overview of the novel gene therapies for HGGs treatment, highlighting evidence from clinical trials, molecular mechanisms, and future perspectives. Methods: An extensive literature review was conducted through PubMed/Medline and ClinicalTrials.gov databases, using the keywords “high-grade glioma,” “glioblastoma,” and “malignant brain tumor”, combined with “gene therapy,” “oncolytic viruses,” “suicide gene therapies,” “tumor suppressor genes,” “immunomodulatory genes,” and “gene target therapies”. Only articles in English and published in the last 15 years were chosen, further screened based on best relevance. Data were analyzed and described according to the PRISMA guidelines. Results: Viruses were the most vehicles employed for their feasibility and transduction efficiency. Apart from liposomes, other viral vehicles remain largely still experimental. Oncolytic viruses and suicide gene therapies proved great results in phase I, II preclinical, and clinical trials. Tumor suppressor, immunomodulatory, and target genes were widely tested, showing encouraging results especially for recurrent HGGs. Conclusions: Oncolytic virotherapy and suicide genes strategies are valuable second-line treatment options for relapsing HGGs. Immunomodulatory approaches, tumor suppressor, and target genes therapies may implement and upgrade standard chemoradiotherapy. Future research aims to improve safety profile and prolonging therapeutic effectiveness. Further clinical trials are needed to assess the efficacy of gene-based therapies.
Neural Interruption by Unilateral Labyrinthectomy Biases the Directional Preference of Otolith-Related Vestibular Neurons
Authors: Nguyen Nguyen , Kim Kyu-Sung , Kim Gyutae
Published: July 2021

Background: The directional preference of otolith-related vestibular neurons elucidates the neuroanatomical link of labyrinths, but few direct experimental data have been provided. Methods: The directional preference of otolith-related vestibular neurons was measured in the vestibular nucleus using chemically induced unilateral labyrinthectomy (UL). For the model evaluation, static and dynamic behavioral tests as well as a histological test were performed. Extracellular neural activity was recorded for the neuronal responses to the horizontal head rotation and the linear head translation. Results: Seventy-seven neuronal activities were recorded, and the total population was divided into three groups: left UL (20), sham (35), and right UL (22). Based on directional preference, two sub-groups were again classified as contra- and ipsi-preferred neurons. There was no significance in the number of those sub-groups (contra-, 15/35, 43%; ipsi-, 20/35, 57%) in the sham (p = 0.155). However, more ipsi-preferred neurons (19/22, 86%) were observed after right UL (p = 6.056 × 10−5), while left UL caused more contra-preferred neurons (13/20, 65%) (p = 0.058). In particular, the convergent neurons mainly led this biased difference (ipsi-, 100% after right UL and contra-, 89% after left UL) (p < 0.002). Conclusions: The directional preference of the neurons depended on the side of the lesion, and its dominance was mainly led by the convergent neurons.
Factor VIIa Regulates the Level of Cell-Surface Tissue Factor through Separate but Cooperative Mechanisms
Authors: Madkhali Yahya , Rondon Araci M. R. , Featherby Sophie , Maraveyas Anthony , Greenman John , Ettelaie Camille
Published: July 2021

Procoagulant activity of tissue factor (TF) in response to injury or inflammation is accompanied with cellular signals which determine the fate of cells. However, to prevent excessive signalling, TF is rapidly dissipated through release into microvesicles, and/or endocytosis. To elucidate the mechanism by which TF signalling may become moderated on the surface of cells, the associations of TF, fVII/fVIIa, PAR2 and caveolin-1 on MDA-MB-231, BxPC-3 and 786-O cells were examined and compared to that in cells lacking either fVII/fVIIa or TF. Furthermore, the localisation of labelled-recombinant TF with cholesterol-rich lipid rafts was explored on the surface of primary human blood dermal endothelial cells (HDBEC). Finally, by disrupting the caveolae on the surface of HDBEC, the outcome on TF-mediated signalling was examined. The association between TF and PAR2 was found to be dependent on the presence of fVIIa. Interestingly, the presence of TF was not pre-requisite for the association between fVII/fVIIa and PAR2 but was significantly enhanced by TF, which was also essential for the proliferative signal. Supplementation of HDBEC with exogenous TF resulted in early release of fVII/fVIIa from caveolae, followed by re-sequestration of TF-fVIIa. Addition of labelled-TF resulted in the accumulation within caveolin-1-containing cholesterol-rich regions and was also accompanied with the increased assimilation of cell-surface fVIIa. Disruption of the caveolae/rafts in HDBEC using MβCD enhanced the TF-mediated cellular signalling. Our data supports a hypothesis that cells respond to the exposure to TF by moderating the signalling activities as well as the procoagulant activity of TF, through incorporation into the caveolae/lipid rafts.
Endogenous and Therapeutic Estrogens: Maestro Conductors of the Microenvironment of ER+ Breast Cancers
Authors: Schuler Linda A. , Murdoch Fern E.
Published: July 2021

Estrogen receptor alpha (ERα) marks heterogeneous breast cancers which display a repertoire of somatic genomic mutations and an immune environment that differs from other breast cancer subtypes. These cancers also exhibit distinct biological behaviors; despite an overall better prognosis than HER2+ or triple negative breast cancers, disseminated dormant cells can lead to disease recurrence decades after the initial diagnosis and treatment. Estrogen is the best studied driver of these cancers, and antagonism or reduction of estrogen activity is the cornerstone of therapeutic approaches. In addition to reducing proliferation of ERα+ cancer cells, these treatments also alter signals to multiple other target cells in the environment, including immune cell subpopulations, cancer-associated fibroblasts, and endothelial cells via several distinct estrogen receptors. In this review, we update progress in our understanding of the stromal cells populating the microenvironments of primary and metastatic ER+ tumors, the effects of estrogen on tumor and stromal cells to modulate immune activity and the extracellular matrix, and net outcomes in experimental and clinical studies. We highlight new approaches that will illuminate the unique biology of these cancers, provide the foundation for developing new treatment and prevention strategies, and reduce mortality of this disease.
The Treatment Effect of Liver Transplantation versus Liver Resection for HCC: A Review and Future Perspectives
Authors: Beumer Berend R. , de Wilde Roeland F. , Metselaar Herold J. , de Man Robert A. , Polak Wojciech G. , Ijzermans Jan N. M.
Published: July 2021

For patients presenting with hepatocellular carcinoma within the Milan criteria, either liver resection or liver transplantation can be performed. However, to what extent either of these treatment options is superior in terms of long-term survival is unknown. Obviously, the comparison of these treatments is complicated by several selection processes. In this article, we comprehensively review the current literature with a focus on factors accounting for selection bias. Thus far, studies that did not perform an intention-to-treat analysis conclude that liver transplantation is superior to liver resection for early-stage hepatocellular carcinoma. In contrast, studies performing an intention-to-treat analysis state that survival is comparable between both modalities. Furthermore, all studies demonstrate that disease-free survival is longer after liver transplantation compared to liver resection. With respect to the latter, implications of recurrences for survival are rarely discussed. Heterogeneous treatment effects and logical inconsistencies indicate that studies with a higher level of evidence are needed to determine if liver transplantation offers a survival benefit over liver resection. However, randomised controlled trials, as the golden standard, are believed to be infeasible. Therefore, we suggest an alternative research design from the causal inference literature. The rationale for a regression discontinuity design that exploits the natural experiment created by the widely adopted Milan criteria will be discussed. In this type of study, the analysis is focused on liver transplantation patients just within the Milan criteria and liver resection patients just outside, hereby ensuring equal distribution of confounders.
Development and Implementation of Proton Therapy for Hodgkin Lymphoma: Challenges and Perspectives
Authors: Loap Pierre , De Marzi Ludovic , Mirandola Alfredo , Dendale Remi , Iannalfi Alberto , Vitolo Viviana , Barcellini Amelia , Filippi Andrea Riccardo , Jereczek-Fossa Barbara Alicja , Kirova Youlia , Orlandi Ester
Published: July 2021

Consolidative radiation therapy for early-stage Hodgkin lymphoma (HL) improves progression-free survival. Unfortunately, first-generation techniques, relying on large irradiation fields, were associated with an increased risk of secondary cancers, and of cardiac and lung toxicity. Fortunately, the use of smaller target volumes combined with technological advances in treatment techniques currently allows efficient organs-at-risk sparing without altering tumoral control. Recently, proton therapy has been evaluated for mediastinal HL treatment due to its potential to significantly reduce the dose to organs-at-risk, such as cardiac substructures. This is expected to limit late radiation-induced toxicity and possibly, second-neoplasm risk, compared with last-generation intensity-modulated radiation therapy. However, the democratization of this new technique faces multiple issues. Determination of which patient may benefit the most from proton therapy is subject to intense debate. The development of new effective systemic chemotherapy and organizational, societal, and political considerations might represent impediments to the larger-scale implementation of HL proton therapy. Based on the current literature, this critical review aims to discuss current challenges and controversies that may impede the larger-scale implementation of mediastinal HL proton therapy.