bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Supplementation with Ultramicronized Palmitoylethanolamide for Joint Disease and Lameness Management in Four Jumping Horses: A Case Report
Authors: Gugliandolo Enrico , Barbagallo Alfio , Peritore Alessio Filippo , Cuzzocrea Salvatore , Crupi Rosalia
Published: August 2020

Background: Four show jumping horses were evaluated for non-responsive lameness, which caused their withdrawal from show jumping competitions. The clinical evaluation was performed by radiographic examination, flexion tests, diagnostic anesthesia and lameness evaluation using the American Association of Equine Practitioners (AAEP) scale. The diagnoses were a case of navicular syndrome, a complicated case of chronic navicular syndrome and arthrosis of the distal interphalangeal joint of the right anterior limb and two cases of distal intertarsal joint arthritis. Nutraceuticals are often an important management strategy or coadjutant of pharmacological therapies in joint disease. Ultramicronized Palmitoylethanolamide (PEA-um) is an endogenous fatty acid amide that is well-known for its anti-inflammatory and analgesic proprieties widely used in human medicine and small animal veterinary medicine. Although it includes a small number of cases, our study describes for the first time the efficacy of the use of PEA-um in horses. The four horses with non-responsive lameness and significant impairment in athletic performance were daily treated with PEA-um into their normal diet. After four months of PEA-um supplementation, all horses showed remissions of lameness that led to their reintroduction into showjumping competitions without disease recurrence. Therefore, despite the small number of cases included in this study, these observations suggest a good prospective for developing a controlled experiment to test PEA in a larger cohort of horses.
Sheep in Species-Rich Temperate Grassland: Combining Behavioral Observations with Vegetation Characterization
Authors: Hall Stephen J.G. , Bunce Robert G.H. , Arney David R. , Vollmer Elis
Published: August 2020

Foraging behavior of livestock in species-rich, less intensively managed grassland communities will require different methodologies from those appropriate in floristically simple environments. In this pilot study on sheep in species-rich grassland in northern Estonia, foraging behavior and the plant species of the immediate area grazed by the sheep were registered by continually-recording Go-Pro cameras. From three days of observation of five sheep (706 animal-minutes), foraging behavior was documented. Five hundred and thirty-six still images were sampled, and a plant species list was compiled for each. Each plant species was assigned a score indicating its location, in the ecophysiological sense, on the main environmental gradient. The scores of the plant species present were averaged for each image. Thus, the fine structure of foraging behavior could be studied in parallel with the vegetation of the precise area being grazed. As expected, there was considerable individual variation, and we characterized foraging behavior by quantifying the patterns of interspersion of grazing and non-grazing behaviors. This combination of behavior recording and vegetation classification could enable a numerical analysis of the responses of grazing livestock to vegetation conditions.
Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation
Authors: Nistri Silvia , Fiorillo Claudia , Becatti Matteo , Bani Daniele
Published: August 2020

Serelaxin (RLX) designates the pharmaceutical form of the human natural hormone relaxin-2 that has been shown to markedly reduce tissue and cell damage induced by hypoxia and reoxygenation (HR). The evidence that RLX exerts similar protective effects on different organs and cells at relatively low, nanomolar concentrations suggests that it specifically targets a common pathogenic mechanism of HR-induced damage, namely oxidative stress. In this study we offer experimental evidence that RLX (17 nmol L-1), added to the medium of HR-exposed H9c2 rat cardiac muscle cells, significantly reduces cell oxidative damage, mitochondrial dysfunction and apoptosis. These effects appear to rely on the up-regulation of the cellular availability of reduced glutathione (GSH), a ubiquitous endogenous antioxidant metabolite. Conversely, superoxide dismutase activity was not influenced by RLX, which, however, was not endowed with chemical antioxidant properties. Taken together, these findings verify the major pharmacological role of RLX in the protection against HR-induced oxidative stress, and shed first light on its mechanisms of action.
Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and its Inhibition by Antioxidants
Authors: Martinez-Gil Natalia , Vidal-Gil Lorena , Flores-Bellver Miguel , Maisto Rosa , Sancho-Pelluz Javier , Diaz-Llopis Manuel , M. Barcia Jorge , Romero Francisco J.
Published: August 2020

The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations. Despite the increase in the levels of ROS, measured by fluorescence probes, the RPE cells exposed to the lowest EtOH concentrations were able to maintain cell survival, measured by the Cell Proliferation Kit II (XTT). However, EtOH-induced oxidative stress modified inflammation and angiogenesis biomarkers, analyzed by proteome array, ELISA, qPCR and Western blot. The highest EtOH concentration used stimulated a large increase in ROS levels, upregulating the cytochrome P450-2E1 (CYP2E1) and promoting cell death. The use of antioxidants such as N-acetylcysteine (NAC) and diallyl sulfide (DAS), which is also a CYP2E1 inhibitor, reverted cell death and oxidative stress, modulating also the upstream angiogenesis and inflammation regulators. Because oxidative stress plays a central role in most frequent ocular diseases, the results herein support the proposal that CYP2E1 upregulation could aggravate retinal degeneration, especially in those patients with high baseline oxidative stress levels due to their ocular pathology and should be considered as a risk factor.
Redox Status, Dose and Antioxidant Intake in Healthcare Workers Occupationally Exposed to Ionizing Radiation
Authors: Sebastià Natividad , Olivares-González Lorena , Montoro Alegría , Barquinero Joan-Francesc , Canyada-Martinez Antonio José , Hervás David , Gras Pilar , Villaescusa Juan Ignacio , Martí-Bonmatí Luis , Muresan Bianca Tabita , Soriano José Miguel , Campayo Juan Manuel , Andani Joaquin , Alonso Oscar , Rodrigo Regina
Published: August 2020

The purpose of this study was to evaluate the relationship between blood redox status, dose and antioxidant dietary intake of different hospital staff groups exposed to low doses of ionizing radiation (LDIR) (Interventional Radiology and Cardiology, Radiation Oncology, and Nuclear Medicine) and non-exposed. Personal dose equivalent (from last year and cumulative), plasma antioxidant markers (total antioxidant capacity, extracellular superoxide dismutase activity, and glutathione/oxidized glutathione ratio), oxidative stress markers (nitrites and nitrates, and lipid peroxidation) and dietary intake (antioxidant capacity using ORAC values) were collected and analyzed from 28 non-exposed healthcare workers and 42 healthcare workers exposed to LDIR. Hospital staff exposed to LDIR presented a redox imbalance in blood that seems to correlate with dose. Workers from the Nuclear Medicine Unit were the most affected group with the lowest value of plasma antioxidant response and the highest value of plasma thiobarbituric acid reactive substances, TBARS (indicator of lipid peroxidation) of all four groups. Cumulative personal dose equivalent positively correlated with nitrites and negatively correlated with total antioxidant capacity in blood. The diet of healthcare workers from Nuclear Medicine Unit had higher ORAC values than the diet of non-exposed. Therefore, occupational exposure to LDIR, especially for the Nuclear Medicine Unit, seems to produce an imbalanced redox status in blood that would correlate with cumulative personal dose equivalent.
Study on Self-Parallel GaN-Based Terahertz Hetero-Structural Gunn Diode
Authors: Wang Ying , Li Liu-An , Yang Lin-An , Ao Jin-Ping , Hao Yue
Published: August 2020

In this paper, we propose a novel gallium nitride-based multi-two-dimensional-electron-gas (2DEG)-channel self-parallel Gunn diode (SPD) for the first time. In the SPD, a trench anode is etched through at least the bottommost 2DEG channels, which splits all 2DEG channels into two shorter channels with lengths of L1 and L2. Therefore, one SPD is just equal to several shorter diodes in parallel; as a result, we call it a self-parallel Gunn diode. In the symmetrical SPD, the component of fundamental frequency is nearly multiplied as compared with the regular Gunn diode. In the asymmetrical SPD (L2 = nL1, n is a positive integer), the harmonic components are greatly enhanced, specially the nth harmonic. Our work demonstrates that the GaN-based terahertz SPD not only offers an easy transfer between two different frequencies, but also realizes the simultaneous enhancement of oscillation power and frequency.
An Aircraft Object Detection Algorithm Based on Small Samples in Optical Remote Sensing Image
Authors: Wang Ting , Cao Changqing , Zeng Xiaodong , Feng Zhejun , Shen Jingshi , Li Weiming , Wang Bo , Zhou Yuedong , Yan Xu
Published: August 2020

In recent years, remote sensing technology has developed rapidly, and the ground resolution of spaceborne optical remote sensing images has reached the sub-meter range, providing a new technical means for aircraft object detection. Research on aircraft object detection based on optical remote sensing images is of great significance for military object detection and recognition. However, spaceborne optical remote sensing images are difficult to obtain and costly. Therefore, this paper proposes the aircraft detection algorithm, itcan detect aircraft objects with small samples. Firstly, this paper establishes an aircraft object dataset containing weak and small aircraft objects. Secondly, the detection algorithm has been proposed to detect weak and small aircraft objects. Thirdly, the aircraft detection algorithm has been proposed to detect multiple aircraft objects of varying sizes. There are 13,324 aircraft in the test set. According to the method proposed in this paper, the f1 score can achieve 90.44%. Therefore, the aircraft objects can be detected simply and efficiently by using the method proposed. It can effectively detect aircraft objects and improve early warning capabilities.
Quantifying the Biophysical Impact of Budding Cell Division on the Spatial Organization of Growing Yeast Colonies
Authors: Banwarth-Kuhn Mikahl , Collignon Jordan , Sindi Suzanne
Published: August 2020

Spatial patterns in microbial colonies are the consequence of cell-division dynamics coupled with cell-cell interactions on a physical media. Agent-based models (ABMs) are a powerful tool for understanding the emergence of large scale structure from these individual cell processes. However, most ABMs have focused on fission, a process by which cells split symmetrically into two daughters. The yeast, Saccharomyces cerevisiae, is a model eukaryote which commonly undergoes an asymmetric division process called budding. The resulting mother and daughter cells have unequal sizes and the daughter cell does not inherit the replicative age of the mother. In this work, we develop and analyze an ABM to study the impact of budding cell division and nutrient limitation on yeast colony structure. We find that while budding division does not impact large-scale properties of the colony (such as shape and size), local spatial organization of cells with respect to spatial layout of mother-daughter cell pairs and connectivity of subcolonies is greatly impacted. In addition, we find that nutrient limitation further promotes local spatial organization of cells and changes global colony organization by driving variation in subcolony sizes. Moreover, resulting differences in spatial organization, coupled with differential growth rates from nutrient limitation, create distinct sectoring patterns within growing yeast colonies. Our findings offer novel insights into mechanisms driving experimentally observed sectored yeast colony phenotypes. Furthermore, our work illustrates the need to include relevant biophysical mechanisms when using ABMs to compare to experimental studies.
Object Semantic Grid Mapping with 2D LiDAR and RGB-D Camera for Domestic Robot Navigation
Authors: Qi Xianyu , Wang Wei , Liao Ziwei , Zhang Xiaoyu , Yang Dongsheng , Wei Ran
Published: August 2020

Occupied grid maps are sufficient for mobile robots to complete metric navigation tasks in domestic environments. However, they lack semantic information to endow the robots with the ability of social goal selection and human-friendly operation modes. In this paper, we propose an object semantic grid mapping system with 2D Light Detection and Ranging (LiDAR) and RGB-D sensors to solve this problem. At first, we use a laser-based Simultaneous Localization and Mapping (SLAM) to generate an occupied grid map and obtain a robot trajectory. Then, we employ object detection to get an object’s semantics of color images and use joint interpolation to refine camera poses. Based on object detection, depth images, and interpolated poses, we build a point cloud with object instances. To generate object-oriented minimum bounding rectangles, we propose a method for extracting the dominant directions of the room. Furthermore, we build object goal spaces to help the robots select navigation goals conveniently and socially. We have used the Robot@Home dataset to verify the system; the verification results show that our system is effective.
Improvement of Light Extraction in Deep Ultraviolet GaN Light Emitting Diodes with Mesh P-Contacts
Authors: Kuo Shiou-Yi , Chang Chia-Jui , Huang Zhen-Ting , Lu Tien-Chang
Published: August 2020

One of the main reasons that the emission efficiency of GaN-based light-emitting diodes (LEDs) decreases significantly as the emission wavelength shorter than 300 nm is the low light extraction efficiency (LEE). Especially in deep ultra-violet (DUV) LEDs, light propagating outside the escape cone and being reflected back to the semiconductor or substrate layer is absorbed not only by active layers but also by p-type layers with narrower bandgaps and electrodes that are neither transparent nor reflective of the DUV wavelength. In this report, we propose a DUV LED structure with mesh p-GaN/indium-tin-oxide (ITO) contacts and a Ti/Al/Ni/Au layer as a reflective layer to improve LEE. The mesh p-GaN/ITO DUV LED showed an output power of 12% higher than that from the conventional DUV LED due to the lower light absorption at 280 nm.
Pansharpening by Complementing Compressed Sensing with Spectral Correction
Authors: Tsukamoto Naoko , Sugaya Yoshihiro , Omachi Shinichiro
Published: August 2020

Pansharpening (PS) is a process used to generate high-resolution multispectral (MS) images from high-spatial-resolution panchromatic (PAN) and high-spectral-resolution multispectral images. In this paper, we propose a method for pansharpening by focusing on a compressed sensing (CS) technique. The spectral reproducibility of the CS technique is high due to its image reproducibility, but the reproduced image is blurry. Although methods of complementing this incomplete reproduction have been proposed, it is known that the existing method may cause ringing artifacts. On the other hand, component substitution is another technique used for pansharpening. It is expected that the spatial resolution of the images generated by this technique will be as high as that of the high-resolution PAN image, because the technique uses the corrected intensity calculated from the PAN image. Based on these facts, the proposed method fuses the intensity obtained by the component substitution method and the intensity obtained by the CS technique to move the spatial resolution of the reproduced image close to that of the PAN image while reducing the spectral distortion. Experimental results showed that the proposed method can reduce spectral distortion and maintain spatial resolution better than the existing methods.
Climatic Indices over the Mediterranean Sea: A Review
Authors: Criado-Aldeanueva Francisco , Soto-Navarro Javier
Published: August 2020

The Mediterranean Sea, strategically situated across a dynamic frontier line that separates two regions with different climates (Europe and North Africa), has been the focus of attention of many studies dealing with its thermohaline circulation, deep water formation processes or heat and freshwater budgets. Large-scale atmospheric forcing has been found to play an important role in these topics and attention has been renewed in climatic indices that can be used as a proxy for atmospheric variability. Among them, the North Atlantic oscillation, the East Atlantic or the East Atlantic–West Russia patterns have been widely addressed but much less attention has been devoted to a Mediterranean mode, the Mediterranean oscillation. This overview summarizes the recent advances that have been achieved in the understanding of these climatic indices and their influence on the functioning of the Mediterranean from a physical point of view. The important role of the Mediterranean oscillation is emphasized and the most relevant aspects of the other indices are revisited and discussed.
A New “Doctor and Patient” Optimization Algorithm: An Application to Energy Commitment Problem
Authors: Dehghani Mohammad , Mardaneh Mohammad , Guerrero Josep M. , Malik Om Parkash , Ramirez-Mendoza Ricardo A. , Matas José , Vasquez Juan C. , Parra-Arroyo Lizeth
Published: August 2020

Regular assessments of events taking place around the globe can be a conduit for the development of new ideas, contributing to the research world. In this study, the authors present a new optimization algorithm named doctor and patient optimization (DPO). DPO is designed by simulating the process of treating patients by a physician. The treatment process has three phases, including vaccination, drug administration, and surgery. The efficiency of the proposed algorithm in solving optimization problems compared to eight other optimization algorithms on a benchmark standard test function with 23 objective functions is been evaluated. The results obtained from this comparison indicate the superiority and quality of DPO in solving optimization problems in various sciences. The proposed algorithm is successfully applied to solve the energy commitment problem for a power system supplied by a multiple energy carriers system.
Quantitative Evaluation of the Spatial Variation of Surface Soil Properties in a Typical Alluvial Plain of the Lower Yellow River Using Classical Statistics, Geostatistics and Single Fractal and Multifractal Methods
Authors: Zhan Jiang , He Yujiang , Zhao Guizhang , Li Zhiping , Yuan Qiaoling , Liu Lili
Published: August 2020

The spatial variability of soil properties has always been a significant research field in geoscience. The types of soil properties cover a wide range, but most studies have focused on the spatial variability of soil physicochemical properties over the past decades. Studies on soil hydraulic characteristics are limited, and most of them are limited to the farmland scale. However, the spatial variability of regional soil properties (soil texture and hydraulic properties) is valuable for the study of sedimentation processes and soil water transport. Therefore, here, the spatial variation of six soil properties (sand, silt, clay content, bulk density, saturated water content and saturated hydraulic conductivity) in the typical alluvial plain area of the lower Yellow River is quantitatively studied, by using classical statistics, geostatistics and single fractal and multifractal methods. This study mainly quantitatively analysed the spatial variability of different soil properties and compared four research methods. Although the coefficient of variation, nugget coefficient, single fractal dimension and multifractal spectral width can reflect spatial variability, diverse conclusions are drawn (on variability) if different methods are used, and the different soil properties show large disparities. These four methods show a different variation order of soil properties, but there are some common conclusions based on analysis and judgment. In general, the silt content in the study area is stable, mainly originating from loess transported by Yellow River erosion, which is also reflected in the Kriging interpolation maps under the geostatistical models. The variation in bulk density and saturated water content is weak, and the spatial variability of sand and clay content is moderate. In addition, the saturated hydraulic conductivity fluctuates violently. This may be related to the differences in local topography, human activity and the content of sand and clay, each of which significantly affects the saturated hydraulic conductivity. Classical statistics has a limitation because it fails to corelate with spatial location. Due to the small sample capacity and calculation error of lag distance, the accuracy of geostatistics and single fractal dimensions needs to be improved. Multifractal spectral analysis does not need to consider the normality of data and can quantitatively represent local characteristics; therefore, its results have high reliability.
From Monolithic Systems to Microservices: A Comparative Study of Performance
Authors: Tapia Freddy , Mora Miguel Ángel , Fuertes Walter , Aules Hernán , Flores Edwin , Toulkeridis Theofilos
Published: August 2020

Currently, organizations face the need to create scalable applications in an agile way that impacts new forms of production and business organization. The traditional monolithic architecture no longer meets the needs of scalability and rapid development. The efficiency and optimization of human and technological resources prevail; this is why companies must adopt new technologies and business strategies. However, the implementation of microservices still encounters several challenges, such as the consumption of time and computational resources, scalability, orchestration, organization problems, and several further technical complications. Although there are procedures that facilitate the migration from a monolithic architecture to micro-services, none of them accurately quantifies performance differences. The current study aims primarily to analyze some related work that evaluated both architectures. Furthermore, we assess the performance and relationship between different variables of an application that runs in a monolithic structure compared to one of the micro-services. With this, the state-of-the-art review was initially conducted, which confirms the interest of the industry. Subsequently, two different scenarios were evaluated: the first one comprises a web application based on a monolithic architecture that operates on a virtual server with KVM, and the second one demonstrates the same web application based on a microservice architecture, but it runs in containers. Both situations were exposed to stress tests of similar characteristics and with the same hardware resources. For their validation, we applied the non-parametric regression mathematical model to explain the dependency relationship between the performance variables. The results provided a quantitative technical interpretation with precision and reliability, which can be applied to similar issues.
Machine Learning in High-Alert Medication Treatment: A Study on the Cardiovascular Drug
Authors: Tai Chun-Tien , Sue Kuen-Liang , Hu Ya-Han
Published: August 2020

The safety of high-alert medication treatment is still a challenge all over the world. Approximately one-half of adverse drug events (ADEs) are related to high-alert medications, which motivates us to improve the predicament faced in clinical practice. The purpose of this study is to use machine-learning techniques to predict the risk of high-alert medication treatment. Taking the cardiovascular drug digoxin as an example, we collected the records of 513 patients who received the pertinent therapy during hospitalization at a tertiary medical center in Taiwan. Considering serum digoxin concentration (SDC) is the primary indicator for assessing the risk of digoxin therapy, patients with SDC being controlled at the recommended range before their discharge were defined as a low-risk population; otherwise, patients were defined as the high-risk population. Weka 3.9.4—an open source machine learning software—was adopted to develop binary classification models to predict the risk of digoxin therapy by a number of machine-learning techniques, including k-nearest neighbors (kNN), decision tree (C4.5), support vector machine (SVM), random forest (RF), artificial neural network (ANN) and logistic regression (LGR). The results showed that the performance of RF was the best, followed by C4.5 and ANN; the remaining classifiers performed poorly. This study confirmed that machine-learning techniques can yield favorable prediction effectiveness for high-alert medication treatment, thereby decreasing the risk of ADEs and improving medication safety.
An Automatic Shadow Compensation Method via a New Model Combined Wallis Filter with LCC Model in High Resolution Remote Sensing Images
Authors: Yang Yuanwei , Ran Shuhao , Gao Xianjun , Wang Mingwei , Li Xi
Published: August 2020

Current automatic shadow compensation methods often suffer because their contrast improvement processes are not self-adaptive and, consequently, the results they produce do not adequately represent the real objects. The study presented in this paper designed a new automatic shadow compensation framework based on improvements to the Wallis principle, which included an intensity coefficient and a stretching coefficient to enhance contrast and brightness more efficiently. An automatic parameter calculation strategy also is a part of this framework, which is based on searching for and matching similar feature points around shadow boundaries. Finally, a final compensation combination strategy combines the regional compensation with the local window compensation of the pixels in each shadow to improve the shaded information in a balanced way. All these strategies in our method work together to provide a better measurement for customizing suitable compensation depending on the condition of each region and pixel. The intensity component I also is automatically strengthened through the customized compensation model. Color correction is executed in a way that avoids the color bias caused by over-compensated component values, thereby better reflecting shaded information. Images with clouds shadows and ground objects shadows were utilized to test our method and six other state-of-the-art methods. The comparison results indicate that our method compensated for shaded information more effectively, accurately, and evenly than the other methods for customizing suitable models for each shadow and pixel with reasonable time-cost. Its brightness, contrast, and object color in shaded areas were approximately equalized with non-shaded regions to present a shadow-free image.
Study of Biomolecular Interactions of Mitochondrial Proteins Related to Alzheimer’s Disease: Toward Multi-Interaction Biomolecular Processes
Authors: Hemmerová Erika , Špringer Tomáš , Krištofiková Zdeňka , Homola Jiří
Published: August 2020

Progressive mitochondrial dysfunction due to the accumulation of amyloid beta (Aβ) peptide within the mitochondrial matrix represents one of the key characteristics of Alzheimer’s disease (AD) and appears already in its early stages. Inside the mitochondria, Aβ interacts with a number of biomolecules, including cyclophilin D (cypD) and 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10), and affects their physiological functions. However, despite intensive ongoing research, the exact mechanisms through which Aβ impairs mitochondrial functions remain to be explained. In this work, we studied the interactions of Aβ with cypD and 17β-HSD10 in vitro using the surface plasmon resonance (SPR) method and determined the kinetic parameters (association and dissociation rates) of these interactions. This is the first work which determines all these parameters under the same conditions, thus, enabling direct comparison of relative affinities of Aβ to its mitochondrial binding partners. Moreover, we used the determined characteristics of the individual interactions to simulate the concurrent interactions of Aβ with cypD and 17β-HSD10 in different model situations associated with the progression of AD. This study not only advances the understanding of Aβ-induced processes in mitochondria during AD, but it also provides a new perspective on research into complex multi-interaction biomolecular processes in general.
Peucedanum ostruthium Inhibits E-Selectin and VCAM-1 Expression in Endothelial Cells through Interference with NF-κB Signaling
Authors: Lammel Christoph , Zwirchmayr Julia , Seigner Jaqueline , Rollinger Judith M. , de Martin Rainer
Published: August 2020

Twenty natural remedies traditionally used against different inflammatory diseases were probed for their potential to suppress the expression of the inflammatory markers E-selectin and VCAM-1 in a model system of IL-1 stimulated human umbilical vein endothelial cells (HUVEC). One third of the tested extracts showed in vitro inhibitory effects comparable to the positive control oxozeaenol, an inhibitor of TAK1. Among them, the extract derived from the roots and rhizomes of Peucedanum ostruthium (i.e., Radix Imperatoriae), also known as masterwort, showed a pronounced and dose-dependent inhibitory effect. Reporter gene analysis demonstrated that inhibition takes place on the transcriptional level and involves the transcription factor NF-κB. A more detailed analysis revealed that the P. ostruthium extract (PO) affected the phosphorylation, degradation, and resynthesis of IκBα, the activation of IKKs, and the nuclear translocation of the NF-κB subunit RelA. Strikingly, early effects on this pathway were less affected as compared to later ones, suggesting that PO may act on mechanism(s) that are downstream of nuclear translocation. As the majority of cognate NF-κB inhibitors affect upstream events such as IKK2, these findings could indicate the existence of targetable signaling events at later stages of NF-κB activation.
Caveolae and Lipid Rafts in Endothelium: Valuable Organelles for Multiple Functions
Authors: Filippini Antonio , D’Alessio Alessio
Published: August 2020

Caveolae are flask-shaped invaginations of the plasma membrane found in numerous cell types and are particularly abundant in endothelial cells and adipocytes. The lipid composition of caveolae largely matches that of lipid rafts microdomains that are particularly enriched in cholesterol, sphingomyelin, glycosphingolipids, and saturated fatty acids. Unlike lipid rafts, whose existence remains quite elusive in living cells, caveolae can be clearly distinguished by electron microscope. Despite their similar composition and the sharing of some functions, lipid rafts appear more heterogeneous in terms of size and are more dynamic than caveolae. Following the discovery of caveolin-1, the first molecular marker as well as the unique scaffolding protein of caveolae, we have witnessed a remarkable increase in studies aimed at investigating the role of these organelles in cell functions and human disease. The goal of this review is to discuss the most recent studies related to the role of caveolae and caveolins in endothelial cells. We first recapitulate the major embryological processes leading to the formation of the vascular tree. We next discuss the contribution of caveolins and cavins to membrane biogenesis and cell response to extracellular stimuli. We also address how caveolae and caveolins control endothelial cell metabolism, a central mechanism involved in migration proliferation and angiogenesis. Finally, as regards the emergency caused by COVID-19, we propose to study the caveolar platform as a potential target to block virus entry into endothelial cells.
Applications of Compounds from Coffee Processing By-Products
Authors: Iriondo-DeHond Amaia , Iriondo-DeHond Maite , del Castillo María Dolores
Published: August 2020

To obtain the coffee beverage, approximately 90% of the edible parts of the coffee cherry are discarded as agricultural waste or by-products (cascara or husk, parchment, mucilage, silverskin and spent coffee grounds). These by-products are a potential source of nutrients and non-nutrient health-promoting compounds, which can be used as a whole ingredient or as an enriched extract of a specific compound. The chemical composition of by-products also determines food safety of the novel ingredients. To ensure the food safety of coffee by-products to be used as novel ingredients for the general consumer population, pesticides, mycotoxins, acrylamide and gluten must be analyzed. According with the priorities proposed by the Food Agriculture Organization of the United Nations (FAO) to maximize the benefit for the environment, society and economy, food waste generation should be avoided in the first place. In this context, the valorization of food waste can be carried out through an integrated bio-refinery approach to produce nutrients and bioactive molecules for pharmaceutical, cosmetic, food and non-food applications. The present research is an updated literature review of the definition of coffee by-products, their composition, safety and those food applications which have been proposed or made commercially available to date based on their chemical composition.
A French–Greek Cross-Site Comparison Study of the Use of Automatic Video Analyses for the Assessment of Autonomy in Dementia Patients
Authors: Karakostas Anastasios , König Alexandra , Crispim-Junior Carlos Fernando , Bremond François , Derreumaux Alexandre , Lazarou Ioulietta , Kompatsiaris Ioannis , Tsolaki Magda , Robert Philippe
Published: August 2020

Background: At present, the assessment of autonomy in daily living activities, one of the key symptoms in Alzheimer’s disease (AD), involves clinical rating scales. Methods: In total, 109 participants were included. In particular, 11 participants during a pre-test in Nice, France, and 98 participants (27 AD, 38 mild cognitive impairment—MCI—and 33 healthy controls—HC) in Thessaloniki, Greece, carried out a standardized scenario consisting of several instrumental activities of daily living (IADLs), such as making a phone call or preparing a pillbox while being recorded. Data were processed by a platform of video signal analysis in order to extract kinematic parameters, detecting activities undertaken by the participant. Results: The video analysis data can be used to assess IADL task quality and provide clinicians with objective measurements of the patients’ performance. Furthermore, it reveals that the HC statistically significantly outperformed the MCI, which had better performance compared to the AD participants. Conclusions: Accurate activity recognition data for the analyses of the performance on IADL activities were obtained.
Investigation of the Effective Use of Photovoltaic Modules in Architecture
Authors: Celadyn Waclaw , Filipek Pawel
Published: August 2020

The application of photovoltaic systems is becoming a dominant feature in contemporary buildings. They allow for the achievement of zero-energy constructions. However, the principles of this strategy are not yet sufficiently known among architects. The purpose of this study is to enhance their expertise, which cannot be widened due to the shortage of targeted publications. The issue presentation was structured in a way that follows the typical design stages, beginning with large-scale urban problems up to the scale of building forms and components. Different types of photovoltaic (PV) systems are considered, based on their efficiency, relations with building fabrics, potential for thermally protecting buildings and their impact on esthetic values. The focus was mainly on the most popular PV modules. The application of these systems requires in-depth analyses which should be carried out by designers at the initial stage and through the next stages of the design. A method to analyze zoning plan regulations and site planning in view of PV modules’ efficiency is novel. This paper also contains considerations with regard to some other untypical applications of these systems. There is need for changing attitudes in architects and investors regarding the issue of promoting the systems through further elucidations.
The Influence of Crystalline Admixtures on the Properties and Microstructure of Mortar Containing By-Products
Authors: Hodul Jakub , Žižková Nikol , Borg Ruben Paul
Published: August 2020

Crystalline admixtures and industrial by-products can be used in cement-based materials in order to improve their mechanical properties. The research examined long-term curing and the exposure to environmental actions of polymer–cement mortars with crystalline admixture (CA) and different by-products, including Bengħisa fly ash and Globigerina limestone waste filler. The by-products were introduced as a percentage replacement of the cement. A crystallization additive was also added to the mixtures in order to monitor the improvement in durability properties. The mechanical properties of the mortar were assessed, with 20% replacement of cement with fly ash resulting in the highest compressive strength after 540 days. The performance was analyzed with respect to various properties including permeable porosity, capillary suction, rapid chloride ion penetration and chloride migration coefficient. It was noted that the addition of fly ash and crystalline admixture significantly reduced the chloride ion penetration into the structure of the polymer cement mortar, resulting in improved durability. A microstructure investigation was conducted on the samples through Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy (SEM-EDS). Crystals forming through the crystalline admixture in the porous structure of the material were clearly observed, contributing to the improved properties of the cement-based polymer mortar.
Carbon Membranes Prepared from Poly (Furfuryl Alcohol–Furfural) Precursors: Effect of FeCl3 Additive
Authors: Zaharopoulou Areti , Yannopoulos Spyros N. , Ioannides Theophilos
Published: August 2020

Thermosetting resins, such as poly (furfuryl alcohol), are efficient precursors for preparation of carbon membranes with molecular sieving properties. Polymerization of furfuryl alcohol is catalyzed by Bronsted or Lewis acids. FeCl3, showing Lewis-acid behavior, is an interesting polymerization catalyst, because it gets reduced into metallic iron during pyrolysis of the resin, promoting transformation of amorphous carbon into graphitic domains. The goal of the present work was to examine whether use of FeCl3 as a polymerization catalyst of furfuryl alcohol–furfural mixtures could lead to preparation of carbon membranes with improved gas separation performance compared to those prepared with use of p-toluenesulfonic acid. The resins were deposited onto tubular porous ceramic supports and pyrolyzed at temperatures in the range of 500–1000 °C. Material characterization was carried out by X-Ray Diffraction, N2 physisorption, Raman spectroscopy and Scanning Electron Microscopy. The membrane performance was examined using H2, CO2 and CH4 as probe molecules. It was found that the membranes operate mainly via the molecular sieving mechanism and the use of FeCl3 instead of p-toluenesulfonic acid does not lead to an improvement in the permeation characteristics of the respective membranes.
Distinct Mutation Patterns Reveal Melanoma Subtypes and Influence Immunotherapy Response in Advanced Melanoma Patients
Authors: Hilke Franz J. , Sinnberg Tobias , Gschwind Axel , Niessner Heike , Demidov German , Amaral Teresa , Ossowski Stephan , Bonzheim Irina , Röcken Martin , Riess Olaf , Garbe Claus , Schroeder Christopher , Forschner Andrea
Published: August 2020

The detection of somatic driver mutations by next-generation sequencing (NGS) is becoming increasingly important in the care of advanced melanoma patients. In our study, we evaluated the NGS results of 82 melanoma patients from clinical routine in 2017. Besides determining the tumor mutational burden (TMB) and annotation of all genetic driver alterations, we investigated their potential as a predictor for resistance to immune checkpoint inhibitors (ICI) and as a distinguishing feature between melanoma subtypes. Melanomas of unknown primary had a similar mutation pattern and TMB to cutaneous melanoma, which hints at its cutaneous origin. Besides the typical hotspot mutation in BRAF and NRAS, we frequently observed CDKN2A deletions. Acral and mucosal melanomas were dominated by CNV alterations affecting PDGFRA, KIT, CDK4, RICTOR, CCND2 and CHEK2. Uveal melanoma often had somatic SNVs in GNA11/Q and amplification of MYC in all cases. A significantly higher incidence of BRAF V600 mutations and EGFR amplifications, PTEN and TP53 deletions was found in patients with disease progression while on ICI. Thus, NGS might help to characterize melanoma subtypes more precisely and to identify possible resistance mechanisms to ICI therapy. Nevertheless, NGS based studies, including larger cohorts, are needed to support potential genetic ICI resistance mechanisms.
Circulating Tumor Cells: From the Laboratory to the Cancer Clinic
Authors: Agashe Ruchi , Kurzrock Razelle
Published: August 2020

Circulating tumor cells (CTCs) are cells that are shed from tumors into the bloodstream. Cell enrichment and isolation technology as well as molecular profiling via next-generation sequencing have allowed for a greater understanding of tumor cancer biology via the interrogation of CTCs. CTC detection can be used to predict cancer relapse, progression, and survival; evaluate treatment effectiveness; and explore the ex vivo functional impact of agents. Detection methods can be by either immunoaffinity (positive or negative enrichment strategies) or biophysical strategies. CTC characterization, which is performed by DNA, RNA, and/or protein techniques, can predict metastatic potential. Currently, CTC-derived explant models may mimic patient response to chemotherapy and help with studying druggable targets and testing treatments. The Food and Drug Administration has cleared a CTC blood test to enumerate CTCs derived from breast, prostate, and colorectal cancers. In conclusion, liquid biopsies via CTCs provide a non-invasive way to obtain important diagnostic, prognostic, and predictive information in patients with cancer.
Uncommon Subtypes of Malignant Melanomas: A Review Based on Clinical and Molecular Perspectives
Authors: Chacón Matías , Pfluger Yanina , Angel Martín , Waisberg Federico , Enrico Diego
Published: August 2020

Malignant melanoma represents the most aggressive type of skin cancer. Modern therapies, including targeted agents and immune checkpoint inhibitors, have changed the dismal prognosis that characterized this disease. However, most evidence was obtained by studying patients with frequent subtypes of cutaneous melanoma (CM). Consequently, there is an emerging need to understand the molecular basis and treatment approaches for unusual melanoma subtypes. Even a standardized definition of infrequent or rare melanoma is not clearly established. For that reason, we reviewed this challenging topic considering clinical and molecular perspectives, including uncommon CMs—not associated with classical V600E/K BRAF mutations—malignant mucosal and uveal melanomas, and some unusual independent entities, such as amelanotic, desmoplastic, or spitzoid melanomas. Finally, we collected information regarding melanomas from non-traditional primary sites, which emerge from locations as unique as meninges, dermis, lymph nodes, the esophagus, and breasts. The aim of this review is to summarize and highlight the main scientific evidence regarding rare melanomas, with a particular focus on treatment perspectives.
Upregulation of DR5 and Downregulation of Survivin by IITZ-01, Lysosomotropic Autophagy Inhibitor, Potentiates TRAIL-Mediated Apoptosis in Renal Cancer Cells via Ubiquitin-Proteasome Pathway
Authors: Shahriyar Sk Abrar , Seo Seung Un , Min Kyoung-jin , Kubatka Peter , Min Do Sik , Chang Jong-Soo , Kim Dong Eun , Woo Seon Min , Kwon Taeg Kyu
Published: August 2020

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively is able to increase apoptosis in cancer cells as agent with minimum toxicity to noncancerous cells. However, all cancer cells are not sensitive to TRAIL-induced apoptosis. In this study, we showed the sub-lethal concentrations of a lysosomotropic autophagy inhibitor, IITZ-01, sensitizes cancer cells (renal, lung, and breast carcinoma) to TRAIL-induced apoptosis through DR5 upregulation and survivin downregulation through ubiquitin-proteasome pathway. Knockdown of DR5 or overexpression of survivin inhibited combined treatment with IITZ-01 and TRAIL-induced apoptosis. IITZ-01 downregulated protein expression of Cbl, ubiquitin E3 ligase, and decreased expression level of Cbl markedly led to increase DR5 protein expression and TRAIL sensitivity. Moreover, IITZ-01 decreased expression level of survivin protein via downregulation of deubiquitinase ubiquitin-specific protease 9X (USP9X) expression. Taken together, these results provide the first evidence that IITZ-01 enhances TRAIL-mediated apoptosis through DR5 stabilization by downregulation of Cbl and USP9X-dependent survivin ubiquitination and degradation in renal carcinoma cells.
TILs Immunophenotype in Breast Cancer Predicts Local Failure and Overall Survival: Analysis in a Large Radiotherapy Trial with Long-Term Follow-Up
Authors: Millar Ewan , Browne Lois , Slapetova Iveta , Shang Fei , Ren Yuqi , Bradshaw Rachel , Ann Brauer Heather , O’Toole Sandra , Beretov Julia , Whan Renee , Graham Peter H.
Published: August 2020

Aim: To determine the prognostic significance of the immunophenotype of tumour-infiltrating lymphocytes (TILs) within a cohort of breast cancer patients with long-term follow-up. Methods: Multiplexed immunofluorescence and automated image analysis were used to assess the expression of CD3, CD8, CD20, CD68, Fox P3, PD-1 and PD-L1 in a clinical trial of local excision and radiotherapy randomised to a cavity boost or not (n = 485, median follow-up 16 years). Kaplan–Meier and Cox multivariate analysis (MVA) methodology were used to ascertain relationships with local recurrence (LR), overall survival (OS) and disease-free survival (DFS). NanoString BC360 gene expression panel was applied to a subset of luminal patients to identify pathways associated with LR. Results: LR was predicted by low CD8 in MVA in the whole cohort (HR 2.34, CI 1.4–4.02, p = 0.002) and luminal tumours (HR 2.19, CI 1.23–3.92, p = 0.008) with associations with increased stromal components, decreased Tregs (FoxP3), inflammatory chemokines and SOX2. Poor OS was associated with low CD20 in the whole cohort (HR 1.73, CI 1.2–2.4, p = 0.002) and luminal tumours on MVA and low PD-L1 in triple-negative cancer (HR 3.44, CI 1.5–7, p = 0.003). Conclusions: Immunophenotype adds further prognostic data to help further stratify risk of LR and OS even in TILs low-luminal tumours.