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Cigarette smoking is positively and robustly associated with cardiovascular disease (CVD), including hypertension, atherosclerosis, cardiac arrhythmias, stroke, thromboembolism, myocardial infarctions, and heart failure. However, after more than a decade of ENDS presence in the U.S. marketplace, uncertainty persists regarding the long-term health consequences of ENDS use for CVD. New approach methods (NAMs) in the field of toxicology are being developed to enhance rapid prediction of human health hazards. Recent technical advances can now consider impact of biological factors such as sex and race/ethnicity, permitting application of NAMs findings to health equity and environmental justice issues. This has been the case for hazard assessments of drugs and environmental chemicals in areas such as cardiovascular, respiratory, and developmental toxicity. Despite these advances, a shortage of widely accepted methodologies to predict the impact of ENDS use on human health slows the application of regulatory oversight and the protection of public health. Minimizing the time between the emergence of risk (e.g., ENDS use) and the administration of well-founded regulatory policy requires thoughtful consideration of the currently available sources of data, their applicability to the prediction of health outcomes, and whether these available data streams are enough to support an actionable decision. This challenge forms the basis of this white paper on how best to reveal potential toxicities of ENDS use in the human cardiovascular system—a primary target of conventional tobacco smoking. We identify current approaches used to evaluate the impacts of tobacco on cardiovascular health, in particular emerging techniques that replace, reduce, and refine slower and more costly animal models with NAMs platforms that can be applied to tobacco regulatory science. The limitations of these emerging platforms are addressed, and systems biology approaches to close the knowledge gap between traditional models and NAMs are proposed. It is hoped that these suggestions and their adoption within the greater scientific community will result in fresh data streams that will support and enhance the scientific evaluation and subsequent decision-making of tobacco regulatory agencies worldwide. Models for Cardiovascular Toxicity Testing E-cigarettes and nicotine delivery systems can be examined using multiple model systems. In silico models might predict adverse cardiovascular effects that can be screened for using 2-D and 3-D models using induced pluripotent stem cell (iPSC) derived cardiac tissue and "omics" profiling such as single-cell RNA sequencing (scRNA-seq) or high-throughput functional analysis with a multiple electrode array (MEA). Biologic plausibility of detected effects can be corroborated using ex vivo or in vivo models, which may also lead to the discovery of new biomarkers or treatments for CVD. [ABSTRACT FROM AUTHOR]

Quick Access Recorders (QARs) provide an important data source for Flight Operation Quality Assurance (FOQA) and flight safety. It is generally characterized by large volume, high-dimensionality and high frequency, and these features result in extreme complexities and uncertainties in its usage and comprehension. In this study, we proposed a Time-Feature Attention (TFA)-based Convolutional Auto-Encoder (TFA-CAE) network model to extract essential flight features from QAR data. As a case study, we used the QAR data landing at the Kunming Changshui International Airport and Lhasa Gonggar International Airport as the experimental data. The results show that (1) the TFA-CAE model performs the best in extracting representative flight features in comparison to some traditional or similar approaches, such as Principal Component Analysis (PCA), Convolutional Auto-Encoder (CAE), Self-Attention-based CAE (SA-CAE), Gate Recurrent Unit based Auto-Encoder (GRU-AE) and TFA-GRU-AE models; (2) flight patterns corresponding to different runways can be recognized; and (3) anomalous flights can effectively deviate from many observations. Overall, the TFA-CAE model provides a well-established technique for further usage of QAR data, such as flight risk detection or FOQA. [ABSTRACT FROM AUTHOR]

Molecular clock REV-ERBα is central to regulating lung injuries, and decreased REV-ERBα abundance mediates sensitivity to pro-fibrotic insults and exacerbates fibrotic progression. In this study, we determine the role of REV-ERBα in fibrogenesis induced by bleomycin and Influenza A virus (IAV). Bleomycin exposure decreases the abundance of REV-ERBα, and mice dosed with bleomycin at night display exacerbated lung fibrogenesis. Rev-erbα agonist (SR9009) treatment prevents bleomycin induced collagen overexpression in mice. Rev-erbα global heterozygous (Rev-erbα Het) mice infected with IAV showed augmented levels of collagens and lysyl oxidases compared with WT-infected mice. Furthermore, Rev-erbα agonist (GSK4112) prevents collagen and lysyl oxidase overexpression induced by TGFβ in human lung fibroblasts, whereas the Rev-erbα antagonist exacerbates it. Overall, these results indicate that loss of REV-ERBα exacerbates the fibrotic responses by promoting collagen and lysyl oxidase expression, whereas Rev-erbα agonist prevents it. This study provides the potential of Rev-erbα agonists in the treatment of pulmonary fibrosis. The molecular clock REV-ERBα regulates lung injury during fibrosis, but the role of REV-ERBα in fibrogenesis remains unknown. Here, the authors show that REV-ERBα interacts with the lysyl oxidase-collagen axis during fibrogenesis and demonstrate the therapeutic potential of Rev-erbα agonist against lung fibrosis. [ABSTRACT FROM AUTHOR]

We study a type of correlated queue in which its inter-arrival and service times are correlated, with their joint distribution being characterized by a copula function. This characterization allows for very generally correlated inter-arrival and service times. For such a queue, we first derive an infinite system of linear equations for the moments of the waiting time, based on which we design an algorithm to calculate the moments of the waiting time. In contrast with traditional methods, our algorithm incorporates a recursive procedure which is computationally much more efficient. Furthermore, we show how the moments and covariances of the inter-departure times of the queue can be obtained based on the moments of the waiting time. Numerical experiments are provided to validate our method. [ABSTRACT FROM AUTHOR]

Malaria is an ancient infectious disease that threatens millions of lives globally even today. The discovery of artemisinin, inspired by traditional Chinese medicine (TCM), has brought in a paradigm shift and been recognized as the "best hope for the treatment of malaria" by World Health Organization. With its high potency and low toxicity, the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries, including China, to eventually eradicate malaria. Here, we will first review the initial discovery of artemisinin, an extraordinary journey that was in stark contrast with many drugs in western medicine. We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer, inflammation, immunoregulation-related diseases, and COVID-19. Finally, we will discuss the implications of the "artemisinin story" and how that can better guide the development of TCM today. We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century. [ABSTRACT FROM AUTHOR]

The rapid and efficient determination of heavy metal content in food crops is essential for human health and environmental protection. The use of hyperspectral data has become a popular way to predict heavy metal content in plants; however, many challenges remain. One challenge is that lab conditions differ from actual agricultural production conditions. Another challenge is that spectral data characteristics are not universally applicable to all situations. Therefore, in this study, the field test method was adopted to conduct experiments during the full growth period of wheat, and the spectrum data of wheat canopy were processed by the first derivative method to screen-sensitive spectral bands as the basis for the prediction model of the copper content in wheat. The results showed that the copper content increased with an increase in the soil copper content, and there were dissimilar subtle differences in the spectral reflectance of wheat canopy under different stressed soil copper concentrations; sensitive spectral indices and wavelengths were screened based on good correlation with the copper content in the wheat canopy. Different optimal predicting models in different periods were built and verified. The established linear regression models, which were based on NDVI/SIPI and W728, were the most suitable predicting models during the tillering stage with R2 = 0.669 and 0.818; Rg, W741, and multiple bands were the most suitable predicting models during the jointing stage with R2 = 0.548, 0.830, and 0.868; the optimal model during the heading stage was based on W480 (R2 = 0.625). This study demonstrated that the constructed models had good potential for estimating the copper content in wheat leaves during full growth periods, and this method had the potential to be applied to the actual agricultural production process. [ABSTRACT FROM AUTHOR]

Considering the effect of physiologic uptake on [ SP 18 sp F]F-FDG PET/CT images, the patient received a [ SP 68 sp Ga]Ga-DOTA-FAPI-04 PET/CT scan the next day. [ SP 68 sp Ga]Ga-DOTA-FAPI-04 PET/CT showed a soft tissue density nodule in front of the middle segment of the rectum, about 2.3 cm × 1.9 cm in size. On [ SP 18 sp F]F-FDG PET/CT, the intestinal glucose metabolism in her abdomen and pelvis was diffusely increased (SUVmax was 21.6). [Extracted from the article]

According to the ideas of risk assessment, the theory of support vector regression is introduced to forecast the ice thickness distribution and achieve the ice extreme value of the wire. Combined with the exponential function of failure rate when the line is under stress, the failure rate model of the line is established in the particular icing condition. The ice strengthening standard is developed by the icing thickness of transmission line, which is used to strengthen lines differentially. Especially, the lines that cross different meteorological conditions are strengthened by the method of segmentation. Finally, the method of economic assessment based on the total life cycle cost is improved, and the comprehensive failure rate is used to calculate differentiated "impairment" benefits. Different lines are made differentiated planning through the simulation example. Various economic indicators are comprehensively compared, in that case, economic assessment results of lines under different strengthening schemes are obtained, which proves the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Four gridding methods for GPS velocities are compared in terms of their precision, applicability and robustness by analyzing simulated data with uncertainties from 0.0 to ±3.0 mm/a. When the input data are 1° × 1° grid sampled and the uncertainty of the additional error is greater than ±1.0 mm/a, the gridding results show that the least-squares collocation method is highly robust while the robustness of the Kriging method is low. In contrast, the spherical harmonics and the multi-surface function are moderately robust, and the regional singular values for the multi-surface function method and the edge effects for the spherical harmonics method become more significant with increasing uncertainty of the input data. When the input data (with additional errors of ±2.0 mm/a) are decimated by 50% from the 1° × 1° grid data and then erased in three 6° × 12° regions, the gridding results in these three regions indicate that the least-squares collocation and the spherical harmonics methods have good performances, while the multi-surface function and the Kriging methods may lead to singular values. The gridding techniques are also applied to GPS horizontal velocities with an average error of ±0.8 mm/a over the Chinese mainland and the surrounding areas, and the results show that the least-squares collocation method has the best performance, followed by the Kriging and multi-surface function methods. Furthermore, the edge effects of the spherical harmonics method are significantly affected by the sparseness and geometric distribution of the input data. In general, the least-squares collocation method is superior in terms of its robustness, edge effect, error distribution and stability, while the other methods have several positive features. [ABSTRACT FROM AUTHOR]

This paper mainly addresses formation control problem of non-holonomic systems in an optimized manner. Instead of using linearization to solve this problem approximately, we designed control laws with guaranteed global convergence by leveraging nonlinear transformations. Under this nonlinear transformation, consensus of non-holonomic robots can be converted into a stabilization problem, to which optimal treatment applies. This concept is then extended to the formation control and tracking problem for a team of robots following leader-follower strategy. A trajectory generator prescribes the feasible motion of virtual reference robot, a decentralized control law is used for each robot to track the reference while maintaining the formation. The asymptotic convergence of follower robots to the position and orientation of the reference robot is ensured using the Lyapunov function which is also generated using chained form differential equations. In order to witness the efficacy of the scheme, simulations results are presented for Unicycle and Car-like robots. [ABSTRACT FROM AUTHOR]

Cephalosporin C acylase (CCA), an important industrial enzyme for the production of 7-aminocephalosporanic acid, has very limited and scattered surface lysine residues. A mutant of cephalosporin C acylase (mCCA) has been designed to fuse a poly-lysine tag to the C-terminal of the β-subunit, which is far away from the active site. The free mCCA showed a near equal specific activity with the wild-type CCA, while a much higher activity recovery was obtained for the mCCA than its wild-type counterpart after immobilization on glyoxyl agarose support (73.3 versus 53.3 %). The mCCA's oriented immobilization enables it to obtain a higher substrate affinity and even a higher thermal stability than the wild-type enzyme. The improvement of stability might be attributed to the multipoint covalent attachment by the oriented enzyme immobilization via the adhered poly-lysine tag, which prevents the dissociation of the β-subunit of CCA from the support. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the clinical efficacy of hydrogen sulfide (HS) treatment on the endothelin-induced cardiac hypertrophy. Sixty-four adult male rats, weighing from 180 to 200 g, were randomly divided into four groups: ten in normal group, ten in sham group, 44 in model group established by inducing the myocardial hypertrophy with endothelin. The myocardial hypertrophy model rats were randomly divided into two groups: 22 in the simple myocardial hypertrophy model group and 22 in the HS treatment group. Rats in normal group were given 2 ml pure water by gavage per day, those in the sham group and simple cardiac hypertrophy model group were given 2 ml of saline by gavage per day, and rats in the pure cardiac hypertrophy with HS treatment were given intraperitoneal injections of 2 ml NaHS saline per day for a period of 4 weeks. Left ventricular mass index, myocyte hypertrophy, volume fraction of myocardial interstitial collagen, myocardial hydroxyproline content and other indicators of cardiac hypertrophy were observed after 4 weeks. (1) There were significant differences on the ventricular mass between the treatment group and the cardiac hypertrophy group: The left ventricular mass decreased 21.4 % and the left ventricular mass index decreased 5.97 % ( P < 0.05; (2) the smallest cardiomyocytes diameter and cardiomyocytes cross-sectional area decreased 12.5 and 10.8 %, respectively ( P < 0.05) in the treatment group compared to the cardiac hypertrophy group; (3) the volume fraction of myocardial interstitial collagen and the myocardial hydroxyproline content decreased 22.3 and 31.3 % in treatment group compared with the cardiac hypertrophy group, respectively ( P < 0.05). HS had a good clinical efficacy in reducing left ventricular mass fraction and myocardial collagen levels, improving myocardial hypertrophy and decrease myocardial fibrosis. It is worthy for further clinical studies. [ABSTRACT FROM AUTHOR]

Most commercial network switches are designed to achieve good average throughput and delay needed for Internet traffic, whereas hard real-time applications demand a bounded delay. Our real-time switch combines clearance-time-optimal switching with clock-based scheduling on a crossbar switching fabric. We use real-time virtual machine tasks to serve both periodic and aperiodic traffic, which simplifies analysis and provides isolation from other system operations. We can then show that any feasible traffic will be switched in two clock periods. This delay bound is enabled by introducing one-shot traffic, which can be constructed at the cost of a fixed delay of one clock period. We carry out simulation to compare our switch with the popular iSLIP crossbar switch scheduler. Our switch has a larger schedulability region, a bounded lower end-to-end switching delay, and a shorter clearance time which is the time required to serve every packet in the system. [ABSTRACT FROM AUTHOR]

Background: Seven patients with chronic hepatitis C virus (HCV) infection were followed up for 10 years in order to analyze the molecular evolution of the HCV nonstructural 5A (NS5A) gene.Methods: Serum samples were obtained from seven patients with anti-HCV who were HCV-RNA positive. The HCV NS5A region, including the interferon sensitivity-determining region (ISDR), protein kinase R binding domain (PKR-BD), and V3 was amplified and cloned, and then sequenced. The nucleotide sequences of the region at the beginning and at the end of the 10 years were aligned with the CLUSTAL W program, version 1.8, and the corresponding amino-acid sequences were deduced.Results: The three serine residues at positions 2197, 2201, and 2204, suggested to be important for hyperphosphorylation of NS5A, were highly conserved in different patients and were within the quasispecies of each patient. The wild-type ISDR or minimally mutated strain was dominant in all the patients and the number of quasispecies decreased over time.Conclusions: Our findings showed that the functional domains of NS5A were generally conserved over an interval of 10 years. Quasispecies distribution was variable and distinctly clustered over time during the natural course of HCV infection. These results may contribute to better understanding of HCV natural infection. [ABSTRACT FROM AUTHOR]

Global Positioning System (GPS) stations installed in and around the epicenter of the Lushan earthquake (Mw 6.7), which occurred almost 5 years after the 2008 Wenchuan earthquake, recorded preseismic deformation corresponding to the Lushan earthquake within the southern Longmenshan thrust belt. A half-space dislocation model is used to simulate the theoretical values of the postseismic displacements caused by the 2008 Wenchuan earthquake, and after transforming the reference frame and filtering the GPS displacement time series, the theoretical and observed GPS values are compared to identify the geodetic anomaly preceding the Lushan earthquake. The abnormal extent of this geodetic anomaly decreases with increasing epicentral distance for each GPS site. This geodetic signal reflects preslip along a locked section of the 2013 seismogenic fault, which caused the accumulation of elastic strain energy until the faulting strength was overcome, thereby generating the Lushan earthquake. Hence, this anomaly might be used as an observable and identifiable precursor to forecast an impending earthquake within a period of less than two and half years before its occurrence. [ABSTRACT FROM AUTHOR]

The Pearl River Delta Economic Zone is one of the fastest growing areas of China's social and economic development. However, the contradiction between people and land, the deterioration of ecological environment and the damage of urban ecological security have become more serious problems. In previous studies there was single land utilization type in small-area and the evaluation method was not suitable to large areas, this study proposes a new method. Firstly, the study implements ecological land zoning from assessing the importance of ecosystem services functional in four aspects: biodiversity, water conservation, soil conservation and coastal protected zone. Then, the suitability evaluation index system of agricultural and construction land is established from the geological environment perspective, and introduces variable weight-analytical hierarchy process-comprehensive index model to evaluate the suitability of agricultural land and construction land. Re-zoning the type of land that has a special effect on the socio-economic, the mining land, protected area of geological relics and groundwater resources, respectively. Finally, considering the actual condition use status and suitability distribution of land, the results of comprehensive zoning of land utilization is got. The results of this study can provide some geological basis for the future land utilization zoning. [ABSTRACT FROM AUTHOR]