bluuebunny/crossref_metadata_2025 huggingface dataset:
Updated geochronology and isotope geochemistry of the Vila de Cruces Ophiolite: a case study of a peri-Gondwanan back-arc ophiolite
Authors: Sánchez Martínez Sonia , Arenas Ricardo , Albert Richard , Gerdes Axel , Fernández-Suárez Javier
Published: April 2020

In the Variscan Orogen, the NW Iberian Massif exposes a variety of ophiolites formed at
c.
500 and
c.
400 Ma that provide constraints on the Paleozoic evolution of the NNW African margin of Gondwana which culminated in the assembly of Pangaea. New U–Pb ages obtained in zircon from one of these ophiolites, the Vila de Cruces Ophiolite, confirm the previous U–Pb age of
c.
500 Ma (thermal ionization mass spectrometry (TIMS)) obtained in zircon from a tonalitic orthogneiss. New samples of the same orthogneiss and related gabbros provided ages (laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)) in the range 498–492 Ma, with the metagabbros being the youngest. Moreover, two different gabbro samples contain a scattered population of inherited zircon grains with an average age of
c.
1150 Ma. These zircons probably represent xenolitic material included in the gabbros during their ascent and intrusion along the margin of Gondwana. Taking into account the architecture of the Vila de Cruces Ophiolite and its geochemical composition, this ophiolite is interpreted as a section of oceanic or transitional lithosphere formed in a back-arc basin opened in the peri-Gondwanan realm. The presence of inherited Mesoproterozoic zircons is likely to suggest the existence of a hidden unexposed Mesoproterozoic basement in the Gondwana margin during Paleozoic times.
A Deep Learning Approach for Identifying User Communities Based on Geographical Preferences and Its Applications to Urban and Environmental Planning
Authors: Ferreira Danielle L. , Nunes Bruno A. A. , Campos Carlos Alberto V. , Obraczka Katia
Published: April 2020

Understanding human mobility plays a vital role in urban and environmental planning as cities continue to grow. Ubiquitous geo-location, localization technology, and availability of big-data-ready computing infrastructure have enabled the development of more sophisticated models to characterize human mobility in urban areas. In this work, our main goal is to extract spatio-temporal features that characterize user mobility and, based on the similarity of these features, identify user
communities
. To this end, we propose a novel approach that leverages image processing techniques to represent user geographical preferences as images and then apply deep convolutional autoencoders to extract latent spatio-temporal mobility features from these images. These features are then fed to a clustering algorithm that identifies the underlying community structures. We use a diverse urban mobility dataset to validate the proposed framework. Our results show that the proposed framework is able to significantly increase the similarity between intra-community nodes (by up to 107%) as well as dissimilarity between inter-community nodes (up to 54%) when compared against no pre-processing of the datasets, i.e without pre-processing the datasets through any feature fusion method. Moreover, it was also able to reach up to 100% improvement when compared against community identification using Principal Component Analysis (PCA). Our results also show that the proposed approach yields significant increase in contact time amongst users belonging to the same community, by up to 80% when compared to the average contact time when not considering community structures, and by up to 150% when compared to the baseline. To the best of our knowledge, our proposal is the first to consider deep convolutional autoencoding to perform automatic extraction of non-linear spatio-temporal mobility features characterizing individual users from raw mobility datasets with the goal of identifying user communities.
SARDINE
Authors: Das Monidipa , Pratama Mahardhika , Ghosh Soumya K.
Published: April 2020

The timely and accurate prediction of remote sensing data is of utmost importance especially in a situation where the predicted data is utilized to provide insights into emerging issues, like environmental nowcasting. Significant research progress can be found to date in devising variants of neural network (NN) models to fulfil this requirement by improving feature extraction and dynamic process representation power. Nevertheless, all these existing NN models are built upon rigid structures that often fail to maintain tradeoff between bias and variance, and consequently, need to spend a lot of time to empirically determine the most appropriate network configuration. This article proposes a self-adaptive recurrent deep incremental network model (SARDINE) which is a novel variant of the deep recurrent neural network with intrinsic capability of self-constructing the network structure in a dynamic and incremental fashion while learning from observed data samples. Moreover, the proposed SARDINE is able to model the spatial feature evolution while scanning the data in a single pass manner, and this further saves significant time when dealing with remote sensing imagery containing millions of pixels. Subsequently, we employ SARDINE in combination with a spatial influence mapping unit to accomplish the prediction. The effectiveness of the proposed model is evaluated in terms of predicting a time series of normalized difference vegetation index (NDVI) data derived from Landsat Thematic Mapper (TM)-5 and Moderate Resolution Imaging Spectroradiometer (MODIS) Terra satellite imagery. The experimental result demonstrates that the SARDINE-based prediction is able to achieve state-of-the-art accuracy with significantly reduced computational cost.
MapLUR
Authors: Steininger Michael , Kobs Konstantin , Zehe Albin , Lautenschlager Florian , Becker Martin , Hotho Andreas
Published: April 2020

Land-use regression (LUR) models are important for the assessment of air pollution concentrations in areas without measurement stations. While many such models exist, they often use manually constructed features based on restricted, locally available data. Thus, they are typically hard to reproduce and challenging to adapt to areas beyond those they have been developed for.

In this article, we advocate a paradigm shift for LUR models: We propose the
D
ata-driven,
O
pen,
G
lobal (DOG) paradigm that entails models based on purely data-driven approaches using only openly and globally available data. Progress within this paradigm will alleviate the need for experts to adapt models to the local characteristics of the available data sources and thus facilitate the generalizability of air pollution models to new areas on a global scale.

To illustrate the feasibility of the DOG paradigm for LUR, we introduce a deep-learning model called MapLUR. It is based on a convolutional neural network architecture and is trained exclusively on globally and openly available map data without requiring manual feature engineering. We compare our model to state-of-the-art baselines like linear regression, random forests and multi-layer perceptrons using a large data set of modeled NO
2
concentrations in Central London. Our results show that MapLUR significantly outperforms these approaches even though they are provided with manually tailored features.

Furthermore, we illustrate that the automatic feature extraction inherent to models based on the DOG paradigm can learn features that are readily interpretable and closely resemble those commonly used in traditional LUR approaches.
Deep Learning for Enrichment of Vector Spatial Databases
Authors: Touya Guillaume , Lokhat Imran
Published: April 2020

Spatial analysis and pattern recognition with vector spatial data is particularly useful to enrich raw data. In road networks, for instance, there are many patterns and structures that are implicit with only road line features, among which highway interchange appeared very complex to recognize with vector-based techniques. The goal is to find the roads that belong to an interchange, such as the slip roads and the highway roads connected to the slip roads. To go further than state-of-the-art vector-based techniques, this article proposes to use raster-based deep learning techniques to recognize highway interchanges. The contribution of this work is to study how to optimally convert vector data into small images suitable for state-of-the-art deep learning models. Image classification with a convolutional neural network (i.e., is there an interchange in this image or not?) and image segmentation with a u-net (i.e., find the pixels that cover the interchange) are experimented and give better results than existing vector-based techniques in this specific use case (99.5% against 74%).
Epithelial transport in digestive diseases: mice, monolayers, and mechanisms
Authors: Barrett Kim E.
Published: April 2020

The transport of electrolytes and fluid by the intestinal epithelium is critical in health to maintain appropriate levels of fluidity of the intestinal contents. The transport mechanisms that underlie this physiological process are also subject to derangement in various digestive disease states, such as diarrheal illnesses. This article summarizes the 2019 Hans Ussing Lecture of the Epithelial Transport Group of the American Physiological Society and discusses some pathways by which intestinal transport is dysregulated, particularly in the setting of infection with the diarrheal pathogen, Salmonella, and in patients treated with small-molecule inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor (EGFr-TKI). The burdensome diarrhea in patients infected with Salmonella may be attributable to decreased expression of the chloride-bicarbonate exchanger downregulated in adenoma (DRA) that participates in electroneutral NaCl absorption. This outcome is possibly secondary to increased epithelial proliferation and/or decreased epithelial differentiation that occurs following infection. Conversely, the diarrheal side effects of cancer treatment with EGFr-TKI may be related to the known ability of EGFr-associated signaling to reduce calcium-dependent chloride secretion. Overall, the findings described may suggest targets for therapeutic intervention in a variety of diarrheal disease states.
Gas exchange calculation may estimate changes in pulmonary blood flow during veno-arterial extracorporeal membrane oxygenation in a porcine model
Authors: Bachmann Kaspar F. , Haenggi Matthias , Jakob Stephan M. , Takala Jukka , Gattinoni Luciano , Berger David
Published: April 2020

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is used as rescue therapy for severe cardiopulmonary failure. We tested whether the ratio of CO2 elimination at the lung and the V-A ECMO (V˙co2ECMO/V˙co2Lung) would reflect the ratio of respective blood flows and could be used to estimate changes in pulmonary blood flow (Q˙Lung), i.e., native cardiac output. Four healthy pigs were centrally cannulated for V-A ECMO. We measured blood flows with an ultrasonic flow probe. V˙co2ECMO and V˙co2Lung were calculated from sidestream capnographs under constant pulmonary ventilation during V-A ECMO weaning with changing sweep gas and/or V-A ECMO blood flow. If ventilation-to-perfusion ratio (V˙/Q˙) of V-A ECMO was not 1, the V˙co2ECMO was normalized to V˙/Q˙ = 1 (V˙co2ECMONorm). Changes in pulmonary blood flow were calculated using the relationship between changes in CO2 elimination and V-A ECMO blood flow (Q˙ECMO). Q˙ECMO correlated strongly with V˙co2ECMONorm ( r2 0.95–0.99). Q˙Lung correlated well with V˙co2Lung ( r2 0.65–0.89, P < = 0.002). Absolute Q˙Lung could not be calculated in a nonsteady state. Calculated pulmonary blood flow changes had a bias of 76 (−266 to 418) mL/min and correlated with measured Q˙Lung ( r2 0.974–1.000, P = 0.1 to 0.006) for cumulative ECMO flow reductions. In conclusion, V˙co2 of the lung correlated strongly with pulmonary blood flow. Our model could predict pulmonary blood flow changes within clinically acceptable margins of error. The prediction is made possible with normalization to a V˙/Q˙ of 1 for ECMO. This approach depends on measurements readily available and may allow immediate assessment of the cardiac output response.
Peroxiredoxin 1 plays a primary role in protecting pancreatic β-cells from hydrogen peroxide and peroxynitrite
Authors: Stancill Jennifer S. , Happ John T. , Broniowska Katarzyna A. , Hogg Neil , Corbett John A.
Published: April 2020

Both reactive nitrogen and oxygen species (RNS and ROS), such as nitric oxide, peroxynitrite, and hydrogen peroxide, have been implicated as mediators of pancreatic β-cell damage during the pathogenesis of autoimmune diabetes. While β-cells are thought to be vulnerable to oxidative damage due to reportedly low levels of antioxidant enzymes, such as catalase and glutathione peroxidase, we have shown that they use thioredoxin reductase to detoxify hydrogen peroxide. Thioredoxin reductase is an enzyme that participates in the peroxiredoxin antioxidant cycle. Peroxiredoxins are expressed in β-cells and, when overexpressed, protect against oxidative stress, but the endogenous roles of peroxiredoxins in the protection of β-cells from oxidative damage are unclear. Here, using either glucose oxidase or menadione to continuously deliver hydrogen peroxide, or the combination of dipropylenetriamine NONOate and menadione to continuously deliver peroxynitrite, we tested the hypothesis that β-cells use peroxiredoxins to detoxify both of these reactive species. Either pharmacological peroxiredoxin inhibition with conoidin A or specific depletion of cytoplasmic peroxiredoxin 1 ( Prdx1) using siRNAs sensitizes INS 832/13 cells and rat islets to DNA damage and death induced by hydrogen peroxide or peroxynitrite. Interestingly, depletion of peroxiredoxin 2 ( Prdx2) had no effect. Together, these results suggest that β-cells use cytoplasmic Prdx1 as a primary defense mechanism against both ROS and RNS.
A novel regulator of thirst behavior: phoenixin
Authors: Haddock Christopher J. , Almeida-Pereira Gislaine , Stein Lauren M. , Yosten Gina L. C. , Samson Willis K.
Published: April 2020

There are examples of physiological conditions under which thirst is inappropriately exaggerated, and the mechanisms for these paradoxical ingestive behaviors remain unknown. We are interested in thirst mechanisms across the female life cycle and have identified a novel mechanism through which ingestive behavior may be activated. We discovered a previously unrecognized endogenous hypothalamic peptide, phoenixin (PNX), identified physiologically relevant actions of the peptide in brain and pituitary gland to control reproductive hormone secretion in female rodents, and in the process identified the previously orphaned G protein-coupled receptor Gpr173 to be a potential receptor for the peptide. Labeled PNX binding distribution in brain parallels areas known to be important in ingestive behaviors as well in areas where gonadal steroids feedback to control estrous cyclicity (Stein LM, Tullock CW, Mathews SK, Garcia-Galiano D, Elias CF, Samson WK, Yosten GLC, Am J Physiol Regul Integr Comp Physiol 311: R489–R496, 2016). We have demonstrated upregulation of Gpr173 during puberty, fluctuations across the estrous cycle, and, importantly, upregulation during the last third of gestation. It is during this hypervolemic, hyponatremic state that both vasopressin secretion and thirst are inappropriately elevated in humans. Here, we show that central administration of PNX stimulated water drinking in both males and females under ad libitum conditions, increased water drinking after overnight fluid deprivation, and increased both water and 1.5% NaCl ingestion under fed and hydrated conditions. Importantly, losartan pretreatment blocked the effect of PNX on water drinking, and knockdown of Gpr173 by use of short interfering RNA constructs significantly attenuated water drinking in response to overnight fluid deprivation. These actions, together with the stimulatory action of PNX on vasopressin secretion, suggest that this recently discovered neuropeptide may impact the recruitment of critically important neural circuits through which ingestive behaviors and endocrine mechanisms that maintain fluid and electrolyte homeostasis are regulated.
Ghrelin signaling contributes to fasting-induced attenuation of hindbrain neural activation and hypophagic responses to systemic cholecystokinin in rats
Authors: Maniscalco James W. , Edwards Caitlyn M. , Rinaman Linda
Published: April 2020

In rats, overnight fasting reduces the ability of systemic cholecystokinin-8 (CCK) to suppress food intake and to activate cFos in the caudal nucleus of the solitary tract (cNTS), specifically within glucagon-like peptide-1 (GLP-1) and noradrenergic (NA) neurons of the A2 cell group. Systemic CCK increases vagal sensory signaling to the cNTS, an effect that is amplified by leptin and reduced by ghrelin. Since fasting reduces plasma leptin and increases plasma ghrelin levels, we hypothesized that peripheral leptin administration and/or antagonism of ghrelin receptors in fasted rats would rescue the ability of CCK to activate GLP-1 neurons and a caudal subset of A2 neurons that coexpress prolactin-releasing peptide (PrRP). To test this, cFos expression was examined in ad libitum-fed and overnight food-deprived (DEP) rats after intraperitoneal CCK, after coadministration of leptin and CCK, or after intraperitoneal injection of a ghrelin receptor antagonist (GRA) before CCK. In fed rats, CCK activated cFos in ~60% of GLP-1 and PrRP neurons. Few or no GLP-1 or PrRP neurons expressed cFos in DEP rats treated with CCK alone, CCK combined with leptin, or GRA alone. However, GRA pretreatment increased the ability of CCK to activate GLP-1 and PrRP neurons and also enhanced the hypophagic effect of CCK in DEP rats. Considered together, these new findings suggest that reduced behavioral sensitivity to CCK in fasted rats is at least partially due to ghrelin-mediated suppression of hindbrain GLP-1 and PrRP neural responsiveness to CCK.
Sex Differences in Human Thermoregulation: Relevance for 2020 and Beyond
Authors: Yanovich R. , Ketko I. , Charkoudian N.
Published: April 2020

The participation of women in physically strenuous athletic and occupational tasks has increased substantially in the past decade. Female sex steroids have influences on thermoregulatory processes that could impact physical performance in the heat. Here, we summarize and evaluate the current literature regarding sex differences in thermoregulation and provide recommendations for heat-illness risk-mitigation strategies.
Fault Mechanism of Fiber Optical Current Transformer Based on Signal Processing Method
Authors: Pang Fubin , Huang Qiang , Liu Yu , Li Peng , Kong Xiangping , Song Liangliang
Published: April 2020

The fiber optical current transformer (FOCT) with sine wave modulation has been widely used in the DC transmission project, while its fault rate is much higher than that of an electromagnetic current transformer, which seriously threatens the safe operation of power grid. In order to investigate the fault mechanism of FOCT, the output signal model of the FOCT photodetector is established, and its basic methods of modulation and demodulation are analyzed to explore the influencing factors of the signal processing method used in the calculation of measured current. It is found that the reduction of the second harmonic component in the photodetector output is the root cause of FOCT fault, and the optical path, modulation signal amplitude, and measured current are important factors affecting the second harmonic component. The influencing law of three factors on the second harmonic component is calculated by simulation and the characteristic differences between them are given. Finally, the fault simulation test of FOCT light intensity and a modulation circuit were carried out in the laboratory, and the results verify the correctness of theoretical analysis. The research in this paper provides reference for fault analysis and reliability improvement of FOCT.
Role of Resveratrol in Regulating Cutaneous Functions
Authors: Wen Si , Zhang Jiechen , Yang Bin , Elias Peter M. , Man Mao-Qiang
Published: April 2020

Protective role of the skin is against external insults and maintenance of electrolyte homeostasis of the body. Cutaneous dysfunction can account for the development of both cutaneous and systemic disorders. Thus, improvements in cutaneous functions can benefit a number of extracutaneous and cutaneous functions. Resveratrol, a natural ingredient, displays multiple benefits for various systems/organs, including the skin. The benefits of resveratrol for cutaneous functions include stimulation of keratinocyte differentiation and antimicrobial peptide expression, inhibition of keratinocyte proliferation and cutaneous inflammation, UV protection, anticancer, antiaging, and inhibition of melanogenesis. The mechanisms of action of resveratrol include activation of sirtuin 1 and nuclear factor erythroid 2‐related factor 2, and inhibition of mitogen‐activated protein kinase signaling. Evidence suggests that topical resveratrol could be a valuable alternative not only for daily skin care, but also for the prevention and treatment of various cutaneous disorders. This review summarizes the benefits of resveratrol for cutaneous functions.
Disturbance Evolution Behavior of Loess Soil under Triaxial Compression
Authors: Xu Yali , Guo Panpan
Published: April 2020

This paper presents an investigation into the evolution law of the structural effects of Xi’an loess soil, based on the disturbed state concept. First, a series of consolidated and drained triaxial compression tests were performed on undisturbed and remoulded loess samples prepared at five different moisture contents and tested at four different confining pressures. Second, two disturbance functions with different parameters were proposed to quantify mathematically the structural effects of loess. Finally, the proposed disturbance functions were validated against documented test results by other researchers. The results indicated that the single‐parameter disturbance function, with the deformation modulus as its parameter, provides convenience for application but takes no account of the respective contributions of deviatoric stress and mean stress to the disturbance evolution behavior of loess. The double‐parameter disturbance function, with the shear and bulk moduli as its parameters, is capable of distinguishing these respective contributions and reflects well the disturbance evolution behavior of loess under various moisture contents and confining pressures. The effects of moisture content and confining pressure on the parameters of the disturbance functions were found to be unsteady. The proposed disturbance functions lay the foundation for establishing a constitutive model for loess accounting for the structural effect.
NLRP3 Inflammasome and Its Central Role in the Cardiovascular Diseases
Authors: Tong Yeqing , Wang Zhihong , Cai Li , Lin Liangqiang , Liu Jiafa , Cheng Jinquan
Published: April 2020

Background/Aims. NLRP3 inflammasome, an inflammasome which consists of nucleotide-binding oligomerization domain- (Nod-) like receptor3 (NLRP3) scaffold, apoptosis-associated speck-like protein (ASC) containing a CARD adaptor, and pro-caspase-1, is assembled after the cytoplasmic leucine-rich repeats (LRRs) of NLRP3 sense pathogens or danger signals. In recent years, the role of inflammasome in cardiovascular diseases has attracted mounting attention, and the in-depth study of its mechanism is gradually clear. Materials. The NLRP3 inflammasome controls the activation of the proteolytic enzyme caspase-1. Caspase-1 in turn regulates the maturation of the proinflammasome cytokines IL-1β and IL-18, which leads to an inflammatory response. We made a mini-review on the association of regulatory mechanisms of NLRP3 inflammasome with the development of cardiovascular diseases systematically based on the recent research studies. Discussion. The inflammasome plays an indispensable role in the development of atherosclerosis, coronary heart diseases (CHD), and heart ischemia-reperfusion (I/R) injury, and NLRP3 inflammasome may become a new target for the prevention and treatment of cardiovascular diseases. Effective regulation of NLRP3 may help prevent or even treat cardiovascular diseases. Conclusion. This mini-review focuses on the association of regulatory mechanisms of NLRP3 inflammasome with the development of cardiovascular diseases, which may supply some important clues for future therapies and novel drug targets for cardiovascular diseases.
Circulating CD14+HLA‐DR−/low Myeloid‐Derived Suppressor Cells as Potential Biomarkers for the Identification of Psoriasis TCM Blood‐Heat Syndrome and Blood‐Stasis Syndrome
Authors: Sun Shipeng , Wei Yali , Zeng Xue , Yuan Yuliang , Wang Na , An Cheng , Duan Jinlong , Pang Bo , Hong Zifu , Liu Guijian
Published: April 2020

Psoriasis is a chronic autoimmune disease. Identification of the biomarkers responsible for Traditional Chinese Medicine (TCM) syndromes of psoriasis can help researchers recognize the different aspects of psoriasis and find novel therapeutic targets for the treatment of psoriasis. The current study investigated the levels of circulating Mo‐MDSCs and Mo‐MDSC‐associated immune factors in the peripheral blood of psoriasis patients with different TCM syndromes. We found that the frequency of Mo‐MDSCs (CD14+HLA‐DR−/low cells) among CD14+ cells from plaque psoriasis patients with blood‐stasis (BS) syndrome was significantly increased when compared with healthy controls (p < 0.001) and blood‐heat (BH) syndrome group (p < 0.001), respectively. However, serum IL‐2, IL‐4, IL‐6, IL‐10, IL‐17A, TNF‐α, IFN‐γ, iNOS, Arg‐1, and NO concentration showed no statistically significant difference between healthy controls and psoriasis patients as well as no significant difference between the BH and BS syndrome groups. Compared with healthy controls, the mRNA expression of Arg‐1, TNF‐α, ROR‐γ, and PD‐L1 was increased, while the mRNA expression of PD‐1 and IL‐10 was decreased in PBMCs from psoriasis patients. Moreover, the mRNA expression of TNF‐α and FOXP3 in PBMCs showed a pronounced statistical difference between the psoriatic BH syndrome group and the BS syndrome group. Therefore, we provide evidence that the percentage of CD14+HLA‐DR−/low MDSC/ CD14+ cells and TNF‐α and Foxp3 mRNA expression levels in PBMCs are potential biomarkers for distinguishing TCM BH syndrome and BS syndrome.
An Analytical Investigation of Fractional-Order Biological Model Using an Innovative Technique
Authors: Khan Hassan , Khan Adnan , Al Qurashi Maysaa , Baleanu Dumitru , Shah Rasool
Published: April 2020

In this paper, a new so-called iterative Laplace transform method is implemented to investigate the solution of certain important population models of noninteger order. The iterative procedure is combined effectively with Laplace transformation to develop the suggested methodology. The Caputo operator is applied to express the noninteger derivative of fractional order. The series form solution is obtained having components of convergent behavior toward the exact solution. For justification and verification of the present method, some illustrative examples are discussed. The closed contact is observed between the obtained and exact solutions. Moreover, the suggested method has a small volume of calculations; therefore, it can be applied to handle the solutions of various problems with fractional-order derivatives.
Neuroprotection of Tropical Fruit Juice Mixture via the Reduction of iNOS Expression and CRH Level in β‐Amyloid‐Induced Rats Model of Alzheimer’s Disease
Authors: Ooi Theng Choon , Ahmad Munawar Munirah , Mohd Rosli Nur Hasnieza , Abdul Malek Siti Nur Aqilah , Rosli Hanisah , Ibrahim Farah Wahida , Azmi Norazrina , Haron Hasnah , Sharif Razinah , Shahar Suzana , Rajab Nor Fadilah
Published: April 2020

This study aimed to determine the effects of tropical fruit juice mixture (pomegranate, white guava, and Roselle) on biochemical, behavioral, and histopathological changes of β‐amyloid‐ (Aβ‐) induced rats. Formulation 8 (F8) of tropical fruit juice mixture was chosen for this present study due to its high phenolic content and antioxidant capacity. Forty Wistar male rats were divided into five groups: dPBS (sham‐operated control), dAβ (Aβ control), JPBS (F8 and PBS), JAβ (F8 and Aβ), and IBFAβ (ibuprofen and Aβ). F8 (5 ml/kg BW), and ibuprofen (10 ml/kg BW) was given orally daily for four weeks before the intracerebroventricular infusion of Aβ for two weeks. Histological analysis and neuronal count of hippocampus tissue in the Cornu Ammonis (CA1) region showed that supplementation with F8 was able to prevent Aβ‐induced tissue damage and neuronal shrinkage. However, no significant difference in locomotor activity and novel object recognition (NOR) percentage was detected among different groups at day 7 and day 14 following Aβ infusion. Only effect of time differences (main effect of day) was observed at day 7 as compared to day 14, where reduction in locomotor activity and NOR percentage was observed in all groups, with F (1, 7) = 6.940, p < 0.05 and F (1, 7) = 7.152, p < 0.05, respectively. Besides, the MDA level of the JAβ group was significantly lower (p < 0.01) than that of the dPBS group. However, no significant changes in SOD activity were detected among different groups. Significant reduction in plasma CRH level (p < 0.05) and iNOS expression (p < 0.01) in the brain was detected in the JAβ group as compared to the dAβ group. Hence, our current findings suggest that the tropical fruit juice mixture (F8) has the potential to protect the rats from Aβ‐induced neurotoxicity in brain hippocampus tissue possibly via its antioxidant properties and the suppression of iNOS expression and CRH production.
Fuel-Efficient on-Orbit Service Vehicle Allocation Based on an Improved Discrete Particle Swarm Optimization Algorithm
Authors: Jian Wu , Qingguo Liu , Xinxue Liu , Yaxiong Li
Published: April 2020

Given the limited fuel capacity of an on-orbit service vehicle (OSV), proper OSV allocation to satellites during each service mission is critical for economic fuel consumption. This allocation problem can be formulated as an optimization problem with many continuous and discrete design variables of wide domains. This problem can be effectively handled through the proposed approach that combines the tabu search with the discrete particle swarm optimization algorithm (DPSO-TS). First of all, Pontryagin’s minimum principle and genetic algorithm (GA) are exploited to find the most fuel-efficient transfer trajectory. This fuel efficiency maximization can then serve as the performance index of the OSV allocation optimization model problem. In particular, the maximization of the minimum residual fuel over individual OSVs is proposed as a performance index for OSV allocation optimization. The optimization problem is numerically solved through the proposed DPSO-TS algorithm. Finally, the simulation results demonstrate that the DPSO-TS algorithm has a higher accuracy compared to the DPSO, the DPSO-PDM and the DPSO-CSA algorithms in the premise that these four algorithms have the basically same computational time. The DPSO-TS algorithm can effectively solve the OSV allocation optimization problem.
Scattering Theory for 2NParameter Models of Finitely Many Relativisticδ-Sphere andδ-Sphere plus Coulomb Interactions Supported by Concentric Spheres in Quantum Mechanics
Authors: Vyabandi A. , Shabani J.
Published: April 2020

We study scattering theory for2Nparameter models of finitely many relativisticδ-sphere andδ-sphere plus Coulomb interactions. We provide the mathematical definitions of the Hamiltonians, solve the resolvent equations, and compute the nonrelativistic limits for both models. We obtain new results related to spectral properties and scattering data.
Monitoring Bioaccumulation (in Gills and Muscle Tissues), Hematology, and Genotoxic Alteration in Ctenopharyngodon idella Exposed to Selected Heavy Metals
Authors: Shah Nazish , Khan Ahsan , Ali Riaz , Marimuthu Kasi , Uddin Muhammad Nazir , Rizwan Muhammad , Rahman Khaliq Ur , Alam Mukhtar , Adnan Muhammad , Muhammad  , Jawad Shahibzada Muhammad , Hussain Saddam , Khisroon Muhammad
Published: April 2020

Health and environmental problems arising from metals present in the aquatic ecosystem are very well known. The present study investigated toxicological effects of LC15 of metals such as copper, chromium, and lead for 24, 48, 72, and 96 h on hematological indices, RBC nucleus and cell morphology, and gill and muscle tissues of grass carp (Ctenopharyngodon idella). Experimental dose concentrations of copper were 1.5, 1.4, 1.2, and 1 mgL−1. Similarly, dose concentrations of chromium were 25.5, 22.5, 20, and 18 mgL−1 while those of lead were 250, 235, 225, and 216 mgL−1, respectively. Maximum decrease in the concentration of Hb, RBCs, and monocytes was observed against chromium, while maximum increase in the concentration of lymphocytes was reported against lead. Abnormalities such as single and double micronuclei, deformed nucleus, nuclear shift, irregular nucleus, deformed cells, microcyte cells, and vacuolated and swollen cells were observed. Gill tissues absorbed maximum concentration of lead followed by chromium and copper. Muscle tissues also absorbed maximum concentration of lead followed by chromium and copper, respectively. Histological alterations such as epithelial lifting, interlamellar spaces, club gill filaments, gill bridging, curling filaments, swelling and fusion of cells, irregular cells, destruction of epithelial cells, cellular necrosis, and inflammatory cells were observed in gill tissues while inflammation and necrosis of muscle fibers, degeneration of muscle fibers, edema of muscle bundles, zig‐zag of muscle fibers, and lesions were observed in muscle tissues of fish exposed with different doses of these heavy metals, indicating the toxicity of metals to aquatic fauna as well as to human being via food chain.
Prevalence of Hepatitis C Virus Infection in a Surgical Population of Southeast China: A Large-Scale Multicenter Study
Authors: Chen Ping , Zheng Yang , Cai Yubo , Zou Pengfei , Li Nan , Peng Conggao , Gao Hainv , Liu Jimin , Chen Yongping , Tong Zhaowei , Li Lanjuan
Published: April 2020

Background. Chronic HCV infection affects 80 million people globally and may progress to advanced liver disease. The present study aims to investigate the present epidemiology of HCV infection in a southeastern Chinese surgical patient cohort. Methods. Blood samples obtained from 78,484 surgical patients from 18 different city and county hospitals were enrolled. The incidence of serum HCV antibody positivity, HCV RNA load, and HCV genotyping, as well as demographics and relevant clinical history, were investigated. Data were stratified using the multistage cluster random sampling method and further analyzed using the SPSS-20 package. Results. HCV antibody positivity was detected in 0.15% of the population (95% confidence interval (CI): 0.12%–0.18%). Genotype 1b (55.74%) was the dominant type. The HCV infection peaked in the age groups of 16–20, 41–50, and 61–65 years, and it was higher in males than in females (0.19% vs. 0.13%, P<0.05). The geographical distribution of infection rates differed: 0.19% (95% CI: 0.14%–0.24%), 0.18% (95% CI: 0.13%–0.23%), and 0.06% (95% CI: 0.03–0.09%) in plain areas, islands, and valley regions, respectively. Patients with transfusion history and urban residence were associated with high HCV RNA levels (adjusted odds ratio = 11.24 and 6.20, P<0.05). Conclusion. The prevalence of HCV infection in this cohort from southeast China was 0.17%, which is lower than the reported 0.43% infection rate in China in 2006. This result can be (partially) explained by the improvement of blood donor screening and the successful campaign for the use of disposable syringes and needles.
Alarmins HMGB1, IL-33, S100A7, and S100A12 in Psoriasis Vulgaris
Authors: Borsky Pavel , Fiala Zdenek , Andrys Ctirad , Beranek Martin , Hamakova Kvetoslava , Malkova Andrea , Svadlakova Tereza , Krejsek Jan , Palicka Vladimir , Borska Lenka , Rehacek Vit
Published: April 2020

Background. Psoriasis vulgaris is a chronic autoimmune disease associated with systemic inflammation. Increased levels of numerous cytokines, chemokines, growth factors, and other molecules were found in the skin and in the circulation of psoriatic patients. Alarmins, also known as danger signals, are intracellular proteins, which are released to an extracellular space after infection or damage. They are the markers of cell destructive processes. Objective. The aim of the present study was to evaluate the suitability of selected alarmins (HMGB1, IL-33, S100A7, and S100A12) as potential biomarkers of severity of psoriasis and to explore possible relationships between these proteins for the purpose of better understanding their roles in the immunopathology of psoriasis. Methods. The serum levels of selected alarmins were measured in 63 psoriatic patients and 95 control individuals. The levels were assessed by the ELISA technique using commercial kits. The data were statistically processed with MedCalc version 19.0.5. Results. In psoriatic patients, we found significantly increased levels of HMGB1 (p<0.05), IL-33 (p<0.01), S100A7 (p<0.0001), and S100A12 (p<0.0001). In addition, we found a significant relationship between HMGB1 and S100A7 (Spearman’s rho=0.276, p<0.05) in the patients and significant relationship between HMGB1 and IL-33 in the controls (Spearman’s rho=0.416, p<0.05). We did not find any relationship between observed alarmins and the disease severity. Conclusions. The alarmins HMGB1, IL-33, S100A7, and S100A12 were significantly elevated in the serum of patients, which states the hypothesis that they play specific roles in the immunopathology of psoriasis. However, we have not yet found a relationship between observed alarmins and the disease severity. The discovery of the relationship between HMGB1 and S100A7 is a novelty that should be studied in the future to further clarify its role and importance.
Diallyl Disulfide Suppresses Inflammatory and Oxidative Machineries following Carrageenan Injection-Induced Paw Edema in Mice
Authors: Zhang Hongxing , Shang Chi , Tian Zhao , Amin Hatem K. , Kassab Rami B. , Abdel Moneim Ahmed E. , Zhang Yingang
Published: April 2020

Diallyl disulfide (DADS) is the major organosulfur constituent in garlic, with a variety of pharmacological activities including antioxidant and anti-inflammatory. Here, we examined the potential antiedematous impact of DADS- versus carrageenan-mediated paw edema in mice. Carrageenan injection potentiated an inflammatory reaction as presented by the elevated serological C-reactive protein (CRP) levels and transcription of tumor necrosis factor-alpha (TNF-α, Tnfα), interleukin-1 beta (IL-1β, Il1b), interleukin-2 (IL-2, Il2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2, Ptgs2), prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1, Ccl1), nuclear factor kappa B (NF-κB), and myeloperoxidase (MPO) activity, while interleukin-10 (IL-10) was declined in the injured paw tissue. Additionally, carrageenan elevated lipid peroxidation in terms of malondialdehyde (MDA) and decreased glutathione content (GSH). Remarkably, DADS was found to inhibit the inflammatory signaling, suppressed the developed oxidative damage, and protected the histopathological alterations in the inflamed paw tissue in response to carrageenan injection. Our findings suggest that DADS could be used as an alternative therapy used to alleviate the pathophysiological changes associated with the genesis of paw edema through its potent anti-inflammatory and antioxidant impacts.
Synthesis of 2‐(2‐Hydroxyethoxy)‐3‐hydroxysqualene and Characterization of Its Anti‐Inflammatory Effects
Authors: Sasaki Kazunori , Inami Yuri , Tominaga Kenichi , Kigoshi Hideo , Arimura Takashi , Isoda Hiroko
Published: April 2020

Squalene (SQ), a natural precursor of many steroids, can inhibit tumor progression and decrease serum cholesterol levels. However, it is difficult to discern the effect of highly active molecules in the treatment of diseases because not enough active compounds reach the site of pathology in crowded biosystems. Therefore, it is necessary to design artificial probes that work effectively within crowded systems. In this study, to facilitate cell penetration, the ethylene glycol moiety (used as a probe) was chemically added to SQ to form 2‐(2‐hydroxyethoxy)‐3‐hydroxysqualene (HEHSQ). HEHSQ was prepared from 2,3‐epoxysqualene and characterized by Rf, FT‐IR, 1H NMR, 13C NMR, and high‐resolution mass spectrometry. We then evaluated the anti‐inflammatory effects of SQ and HEHSQ on lipopolysaccharide‐ (LPS‐) stimulated RAW264.7 murine macrophages. To determine the effect of SQ and HEHSQ on the viability of RAW264.7 cells, an MTT assay was performed. To quantify the anti‐inflammatory effect of SQ and HEHSQ, we measured nitric oxide (NO) production, gene expression, and secretion of the proinflammatory cytokine tumor necrosis factor α (TNF‐α) and chemokine C‐C motif chemokine 2 (CCL2) in LPS‐stimulated RAW264.7 cells using an in vitro inflammatory model. 2,3‐Epoxysqualene was prepared according to a reported methodology. The reaction of 2,3‐epoxysqualene and ethylene glycol in 2‐propanol produced 49% HEHSQ. MTT results showed that 10 and 100 µg/mL HEHSQ treatment decreased cell viability, whereas SQ treatment (1–100 µg/mL) did not have any effect on viability. SQ (100 µg/mL) and HEHSQ (1 µg/mL) treatment significantly reduced the production of LPS‐stimulated NO and decreased the expression and secretion of proinflammatory TNF‐α and CCL2. Therefore, our results suggested that the anti‐inflammatory effects of HEHSQ are 100 times higher than that of unmodified SQ. To the best of our knowledge, this study has demonstrated for the first time that HEHSQ can be potentially used as a safe alternative treatment to anti‐inflammatory drugs.
Ultrasonic Characteristics of Cardiovascular Changes in Children with Hutchinson–Gilford Progeria Syndrome: A Comparative Study with Normal Children and Aging People
Authors: Zhao Xiao-Ni , Song Hong-Ping , Yang Fan , Wu Dang-Jie , Gong Wen-Qing , Zhang Ying , Sun Xin , Zheng Min-Juan
Published: April 2020

Background. The cardiovascular characteristics of children with Hutchinson‐Gilford progeria syndrome (HGPS) remain unclear. The present study is aimed at evaluating the cardiovascular changes with ultrasound examination in children with HGPS and compared these with those in normal children and older people. Methods. Seven HGPS children, 21 age‐matched healthy children, and 14 older healthy volunteers were evaluated by three‐dimensional echocardiography (including strain analysis) and carotid elasticity examination with the echo‐tracking technique. Results. Children with HGPS had higher left ventricular ejection fraction (LVEF) and global longitudinal strain, when compared to older healthy volunteers (P < 0.05). However, these parameters were not significantly different, when compared to those in healthy children. Furthermore, children with HGPS had lower average peak times in the left ventricle, when compared with the other two groups. For the structure of the carotid artery detected by ultrasound, the abnormality rates were similar between children with HGPS and older healthy volunteers (83.3% vs. 71.4%). The elastic parameters, elastic modulus, stiffness parameter, and pulsed wave transmittal velocity of children with HGPS were lower, when compared to those in older healthy volunteers (P < 0.05), while they were higher with arterial compliance (P > 0.05). Furthermore, no significant difference existed among the vascular elastic parameters between HGPS and normal children. Conclusion. HGPS children had impaired left ventricular (LV) synchrony, when compared to normal children, although the difference in LVEF was not statistically significant. Furthermore, the structural abnormality of the carotid artery in HGPS children was similar to that in older people, although the index of elasticity appears to be more favorable. These results suggest that the cardiovascular system in HGPS children differs from natural aging.
Protective Effects of Ligularia fischeri and Aronia melanocarpa Extracts on Alcoholic Liver Disease (In Vitro and In Vivo Study)
Authors: Pyun Chang-Won , Seo Tae-Su , Kim Dae-Jung , Kim Tae-Woo , Bae Jung-Shik
Published: April 2020

Hepatic protective effects of Ligularia fischeri (LF) and Aronia melanocarpa (AM) against alcohol were investigated in vitro and in vivo test. LF, AM, and those composed mixing material (LF+AM) were treated in HepG2 cell. Alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities were significantly increased in each singleness extract and mixed composite. The protective effect on alcoholic liver damage was investigated by animal models. Serum alcohol level and acetaldehyde level were significantly decreased by LF+AM treatment in acute experimental model. In the chronic mouse model study, we had found that the increased plasma liver damage index (alkaline phosphatase) by alcohol treatment was declined by oral administration of LF+AM extraction composite. As well as, it was identified that the protection effect was induced by increasing catalase activity and suppressing COX‐2, TNF‐α, MCP‐1, and IL‐6 mRNA expressions. CYP2E1 mRNA expression was also increased. These results suggest that oral ingestion of LF and AM mixed composite is able to protect liver against alcohol‐induced injury by increasing alcohol metabolism activity and antioxidant system along with decreasing inflammatory responses.
FDA Approval Summary: Pembrolizumab plus Lenvatinib for Endometrial Carcinoma, a Collaborative International Review under Project Orbis
Authors: Arora Shaily , Balasubramaniam Sanjeeve , Zhang Wei , Zhang Lijun , Sridhara Rajeshwari , Spillman Dianne , Mathai Jaigi P. , Scott Bradley , Golding Sarah J. , Coory Michael , Pazdur Richard , Beaver Julia A.
Published: April 2020

On September 17, 2019, FDA granted accelerated approval to pembrolizumab plus lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. The submission and review of this application was conducted through an FDA Oncology Center of Excellence initiative named Project Orbis whereby the FDA, the Australian Therapeutic Goods Administration, and Health Canada were able to simultaneously review and collaborate, rendering simultaneous approval decisions in all countries. Accelerated approval of the pembrolizumab plus lenvatinib combination was based on a single-arm trial of 94 patients, with previously treated metastatic endometrial cancer whose tumors were not MSI-H/dMMR. Efficacy was demonstrated on the basis of an objective response rate of 38.3% (95% confidence interval, 28.5%–48.9%) with 10 complete responses (10.6%) accompanied by supportive durations of response. Trials to confirm clinical benefit of this combination are ongoing. Here, we summarize the benefit–risk analysis supporting accelerated approval of the pembrolizumab plus lenvatinib combination and describe the methodology for the first Project Orbis review.