bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Cand1 in Prostate Cancer
Authors: Eigentler Andrea , Tymoszuk Piotr , Zwick Johanna , Schmitz Arndt A. , Pircher Andreas , Kocher Florian , Schlicker Andreas , Lesche Ralf , Schäfer Georg , Theurl Igor , Klocker Helmut , Heidegger Isabel
Published: February 2020

Evidence has accumulated asserting the importance of cullin-RING (really interesting new gene) ubiquitin ligases (CRLs) and their regulator Cullin-associated neural-precursor-cell-expressed developmentally down-regulated 8 (NEDD8) dissociated protein 1 (Cand1) in various cancer entities. However, the role of Cand1 in prostate cancer (PCa) has not been intensively investigated so far. Thus, in the present study, we aimed to assess the relevance of Cand1 in the clinical and preclinical setting. Immunohistochemical analyses of radical prostatectomy specimens of PCa patients showed that Cand1 protein levels are elevated in PCa compared to benign areas. In addition, high Cand1 levels were associated with higher Gleason Scores, as well as higher tumor recurrence and decreased overall survival. In line with clinical findings, in vitro experiments in different PCa cell lines revealed that knockdown of Cand1 reduced cell viability and proliferation and increased apoptosis, therefore underlining its role in tumor progression. We also found that the cyclin-dependent kinase inhibitor p21 is significantly upregulated upon downregulation of Cand1. Using bioinformatic tools, we detected genes encoding for proteins linked to mRNA turnover, protein polyubiquitination, and proteasomal degradation to be significantly upregulated in Cand1high tumors. Next generation sequencing of PCa cell lines resistant to the anti-androgen enzalutamide revealed that Cand1 is mutated in enzalutamide-resistant cells, however, with little functional and clinically relevant impact in the process of resistance development. To summarize the present study, we found that high Cand1 levels correlate with PCa aggressiveness.
Biphasic Mathematical Model of Cell–Drug Interaction That Separates Target-Specific and Off-Target Inhibition and Suggests Potent Targeted Drug Combinations for Multi-Driver Colorectal Cancer Cells
Authors: Shen Jinyan , Li Li , Yang Tao , Cohen Paul S. , Sun Gongqin
Published: February 2020

Quantifying the response of cancer cells to a drug, and understanding the mechanistic basis of the response, are the cornerstones for anti-cancer drug discovery. Classical single target-based IC50 measurements are inadequate at describing cancer cell responses to targeted drugs. In this study, based on an analysis of targeted inhibition of colorectal cancer cell lines, we develop a new biphasic mathematical model that accurately describes the cell–drug response. The model describes the drug response using three kinetic parameters: ratio of target-specific inhibition, F1, potency of target-specific inhibition, Kd1, and potency of off-target toxicity, Kd2. Determination of these kinetic parameters also provides a mechanistic basis for predicting effective combination targeted therapy for multi-driver cancer cells. The experiments confirmed that a combination of inhibitors, each blocking a driver pathway and having a distinct target-specific effect, resulted in a potent and synergistic blockade of cell viability, improving potency over mono-agent treatment by one to two orders of magnitude. We further demonstrate that mono-driver cancer cells represent a special scenario in which F1 becomes nearly 100%, and the drug response becomes monophasic. Application of this model to the responses of >400 cell lines to kinase inhibitor dasatinib revealed that the ratio of biphasic versus monophasic responses is about 4:1. This study develops a new mathematical model of quantifying cancer cell response to targeted therapy, and suggests a new framework for developing rational combination targeted therapy for colorectal and other multi-driver cancers.
Accelerated Partial Breast Irradiation: Macrophage Polarisation Shift Classification Identifies High-Risk Tumours in Early Hormone Receptor-Positive Breast Cancer
Authors: Schnellhardt Sören , Erber Ramona , Büttner-Herold Maike , Rosahl Marie-Charlotte , Ott Oliver J. , Strnad Vratislav , Beckmann Matthias W. , King Lillian , Hartmann Arndt , Fietkau Rainer , Distel Luitpold
Published: February 2020

Studies have demonstrated correlations between accumulations of tumour-associated macrophages (TAMs), especially of M2-like phenotype, and increased mortality in advanced breast cancer. We investigated the prognostic potential of both main macrophage phenotypes in early hormone receptor-positive (HR+) breast cancer. The studied cohort of 136 patients participated in an institutional APBI phase II trial. Patient selection was characterized by HR+, small tumour size and no metastasis. Tissue microarrays from pre-RT resection samples were double stained for CD68/CD163 using immunohistochemistry. CD68+/CD163− cells were considered M1-like macrophages and CD68+/CD163+ was representative of M2-like macrophages. M1 and M2 macrophage densities were analysed semi-automatically in the stromal and intraepithelial tumour compartment. Low M1 and high M2 densities were strongly associated with decreased disease-free survival (DFS). Combined TAM phenotype densities were studied after defining a macrophage shift classification: M1-shifted (M1 high, M2 low) and non-shifted (M1 low, M2 low; M1 high, M2 high) tumours entailed a favourable outcome. In contrast, M2-shifted (M1 low, M2 high) TAM populations were associated with extremely reduced DFS. Thus, the full predictive potential of TAMs was revealed in a combined analysis of both phenotypes. The M2-shifted subgroup of tumours is classified as high-risk and probably not suitable for partial breast irradiation.
The Multifaceted Roles of the Tumor Susceptibility Gene 101 (TSG101) in Normal Development and Disease
Authors: Ferraiuolo Rosa-Maria , Manthey Karoline C. , Stanton Marissa J. , Triplett Aleata A. , Wagner Kay-Uwe
Published: February 2020

The multidomain protein encoded by the Tumor Susceptibility Gene 101 (TSG101) is ubiquitously expressed and is suggested to function in diverse intracellular processes. In this review, we provide a succinct overview of the main structural features of the protein and their suggested roles in molecular and cellular functions. We then summarize, in more detail, key findings from studies using genetically engineered animal models that demonstrate essential functions of TSG101 in cell proliferation and survival, normal tissue homeostasis, and tumorigenesis. Despite studies on cell lines that provide insight into the molecular underpinnings by which TSG101 might function as a negative growth regulator, a biologically significant role of TSG101 as a tumor suppressor has yet to be confirmed using genuine in vivo cancer models. More recent observations from several cancer research teams suggest that TSG101 might function as an oncoprotein. A potential role of post-translational mechanisms that control the expression of the TSG101 protein in cancer is being discussed. In the final section of the review, we summarize critical issues that need to be addressed to gain a better understanding of biologically significant roles of TSG101 in cancer.
Proteome Profiling Uncovers an Autoimmune Response Signature That Reflects Ovarian Cancer Pathogenesis
Authors: Kobayashi Makoto , Katayama Hiroyuki , Irajizad Ehsan , Vykoukal Jody V. , Fahrmann Johannes F. , Kundnani Deepali L. , Yu Chuan-Yih , Cai Yining , Hsiao Fu Chung , Yang Wei-Lei , Lu Zhen , Celestino Joseph , Long James P. , Do Kim-Ann , Lu Karen H. , Ladd Jon J. , Urban Nicole , Bast Jr. Robert C. , Hanash Samir M.
Published: February 2020

Harnessing the immune response to tumor antigens in the form of autoantibodies, which occurs early during tumor development, has relevance to the detection of cancer at early stages. We conducted an initial screen of antigens associated with an autoantibody response in serous ovarian cancer using recombinant protein arrays. The top 25 recombinants that exhibited increased reactivity with cases compared to controls revealed TP53 and MYC, which are ovarian cancer driver genes, as major network nodes. A mass spectrometry based independent analysis of circulating immunoglobulin (Ig)-bound proteins in ovarian cancer and of ovarian cancer cell surface MHC-II bound peptides also revealed a TP53–MYC related network of antigens. Our findings support the occurrence of a humoral immune response to antigens linked to ovarian cancer driver genes that may have utility for early detection applications.
Imaging of Monoclonal Gammapathy of Undetermined Significance and Smoldering Multiple Myeloma
Authors: Jamet Bastien , Bailly Clément , Carlier Thomas , Touzeau Cyrille , Michaud Anne-Victoire , Bourgeois Mickael , Moreau Philippe , Bodet-Milin Caroline , Kraeber-Bodere Françoise
Published: February 2020

Multiple myeloma (MM) is always preceded by an initial monoclonal gammopathy of undetermined significance (MGUS) that then develops into asymptomatic or smoldering multiple myeloma (SMM), which constitutes an intermediate clinical stage between MGUS and MM. According to a recent study, risk factors for faster MGUS to MM progression include an M protein of 1.5 g/dL or more and an abnormal free light chain ratio in patients with non-IgM MGUS. Therefore, the International Myeloma Working Group (IMWG) decided to recommend whole-body computed tomography (WBCT) for patients with high-risk MGUS in order to exclude early bone destruction. Studies evaluating magnetic resonance imaging (MRI) in SMM found an optimal cutoff of two or more focal lesions to be of prognostic significance for fast progression into symptomatic disease and considered this biomarker as a myeloma-defining event (MDE) needing to start therapy with the aim to avoid progression to harmful bone lesions. Moreover, studies assessing positron emission tomography (PET) with computed tomography (CT) using 18F-deoxyglucose (FDG) (FDG-PET/CT) in SMM showed that presence of focal bone lesion without underlying osteolysis is associated with a rapid progression to symptomatic MM. Latest IMWG guidelines recommended to perform WBCT (either CT alone or as part of an FDG-PET/CT protocol) as the first imaging technique at suspected SMM and, if these images are negative or inconclusive, to perform whole-body MRI. The goal of this paper is to clarify the role of different imaging modalities in MGUS and SMM workups.
Circulating Tumor Cells and Metabolic Parameters in NSCLC Patients Treated with Checkpoint Inhibitors
Authors: Castello Angelo , Carbone Francesco Giuseppe , Rossi Sabrina , Monterisi Simona , Federico Davide , Toschi Luca , Lopci Egesta
Published: February 2020

Circulating tumor cells (CTC) count and characterization have been associated with poor prognosis in recent studies. Our aim was to examine CTC count and its association with metabolic parameters and clinical outcomes in non-small cell lung carcinoma (NSCLC) patients treated with immune checkpoint inhibitors (ICI). For this prospective study, data from 35 patients (23 males, 12 females) were collected and analyzed. All patients underwent an 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) scan and CTC detection through Isolation by Size of Tumor/Trophoblastic Cells (ISET) from peripheral blood samples obtained at baseline and 8 weeks after ICI initiation. Association of CTC count with clinical and metabolic characteristics was studied. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and the log-rank test. Median follow-up was 13.2 months (range of 4.9–21.6). CTC were identified in 16 out of 35 patients (45.7%) at baseline and 10 out of 24 patients at 8 weeks (41.7%). Mean CTC numbers before and after 8 weeks were 15 ± 28 and 11 ± 19, respectively. Prior to ICI, the mean CTC number was significantly higher in treatment-naïve patients (34 ± 39 vs. 9 ± 21, p = 0.004). CTC count variation (ΔCTC) was significantly associated with tumor metabolic response set by European Organization for Research and Treatment of Cancer (EORTC) criteria (p = 0.033). At the first restaging, patients with a high tumor burden, that is, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), had a higher CTC count (p = 0.009). The combination of mean CTC and median MTV at 8 weeks was associated with PFS (p < 0.001) and OS (p = 0.024). Multivariate analysis identified CTC count at 8 weeks as an independent predictor for PFS and OS, whereas ΔMTV and maximum standardized uptake value variation (ΔSUVmax) was predictive for PFS and OS, respectively. Our study confirmed that CTC number is modulated by previous treatments and correlates with metabolic response during ICI. Moreover, elevated CTC count, along with metabolic parameters, were found to be prognostic factors for PFS and OS.
Relating Bat Passage Rates to Wind Turbine Fatalities
Authors: Smallwood K. Shawn , Bell Douglas A.
Published: February 2020

Wind energy siting to minimize impacts to bats would benefit from impact predictions following pre-construction surveys, but whether pre- or even post-construction activity patterns can predict fatalities remains unknown. We tested whether bat passage rates through rotor-swept airspace differ between groups of wind turbines where bat fatalities were found and not found during next-morning dog searches for fatalities. Passage rates differed significantly and averaged four times higher where freshly killed bats were found in next-morning fatality searches. Rates of near misses and risky flight behaviors also differed significantly between groups of turbines where bats were found and not found, and rate of near misses averaged eight times higher where bat fatalities were found in next-morning searches. Hours of turbine operation averaged significantly higher, winds averaged more westerly, and the moon averaged more visible among turbines where and when bat fatalities were found. Although dogs found only one of four bats seen colliding with turbine blades, they found many more bat fatalities than did human-only searchers at the same wind projects, and our fatality estimates were considerably higher. Our rates of observed bat collisions, adjusted for the rates of unseen collisions, would predict four to seven times the fresh fatalities we found using dogs between two wind projects. Despite markedly improved carcass detection through use of dogs, best estimates of bat fatalities might still be biased low due to crippling bias and search radius bias.
Entropy Generation Methodology for Defect Analysis of Electronic and Mechanical Components—A Review
Authors: Cai Miao , Cui Peng , Qin Yikang , Geng Daoshuang , Wei Qiqin , Wang Xiyou , Yang Daoguo , Zhang Guoqi
Published: February 2020

Understanding the defect characterization of electronic and mechanical components is a crucial step in diagnosing component lifetime. Technologies for determining reliability, such as thermal modeling, cohesion modeling, statistical distribution, and entropy generation analysis, have been developed widely. Defect analysis based on the irreversibility entropy generation methodology is favorable for electronic and mechanical components because the second law of thermodynamics plays a unique role in the analysis of various damage assessment problems encountered in the engineering field. In recent years, numerical and theoretical studies involving entropy generation methodologies have been carried out to predict and diagnose the lifetime of electronic and mechanical components. This work aimed to review previous defect analysis studies that used entropy generation methodologies for electronic and mechanical components. The methodologies are classified into two categories, namely, damage analysis for electronic devices and defect diagnosis for mechanical components. Entropy generation formulations are also divided into two detailed derivations and are summarized and discussed by combining their applications. This work is expected to clarify the relationship among entropy generation methodologies, and benefit the research and development of reliable engineering components.
Exploring Impact of Age and Gender on Sentiment Analysis Using Machine Learning
Authors: Kumar Sudhanshu , Gahalawat Monika , Roy Partha Pratim , Dogra Debi Prosad , Kim Byung-Gyu
Published: February 2020

Sentiment analysis is a rapidly growing field of research due to the explosive growth in digital information. In the modern world of artificial intelligence, sentiment analysis is one of the essential tools to extract emotion information from massive data. Sentiment analysis is applied to a variety of user data from customer reviews to social network posts. To the best of our knowledge, there is less work on sentiment analysis based on the categorization of users by demographics. Demographics play an important role in deciding the marketing strategies for different products. In this study, we explore the impact of age and gender in sentiment analysis, as this can help e-commerce retailers to market their products based on specific demographics. The dataset is created by collecting reviews on books from Facebook users by asking them to answer a questionnaire containing questions about their preferences in books, along with their age groups and gender information. Next, the paper analyzes the segmented data for sentiments based on each age group and gender. Finally, sentiment analysis is done using different Machine Learning (ML) approaches including maximum entropy, support vector machine, convolutional neural network, and long short term memory to study the impact of age and gender on user reviews. Experiments have been conducted to identify new insights into the effect of age and gender for sentiment analysis.
Comparison of Saturated and Superheated Steam Plants for Waste-Heat Recovery of Dual-Fuel Marine Engines
Authors: Altosole Marco , Benvenuto Giovanni , Zaccone Raphael , Campora Ugo
Published: February 2020

From the working data of a dual-fuel marine engine, in this paper, we optimized and compared two waste-heat-recovery single-pressure steam plants—the first characterized by a saturated-steam Rankine cycle, the other by a superheated-steam cycle–using suitably developed simulation models. The objective was to improve the recovered heat from the considered engine, running with both heavy fuel oil and natural gas. The comparison was carried out on the basis of energetic and exergetic considerations, concerning various aspects such as the thermodynamic performance of the heat-recovery steam generator and the efficiency of the Rankine cycle and of the combined dual-fuel-engine–waste-heat-recovery plant. Other important issues were also considered in the comparison, particularly the dimensions and weights of the steam generator as a whole and of its components (economizer, evaporator, superheater) in relation to the exchanged thermal powers. We present the comparison results for different engine working conditions and fuel typology (heavy fuel oil or natural gas).
Evaluation of Temporal Complexity Reduction Techniques Applied to Storage Expansion Planning in Power System Models
Authors: Raventós Oriol , Bartels Julian
Published: February 2020

The growing share of renewable energy makes the optimization of power flows in power system models computationally more complicated, due to the widely distributed weather-dependent electricity generation. This article evaluates two methods to reduce the temporal complexity of a power transmission grid model with storage expansion planning. The goal of the reduction techniques is to accelerate the computation of the linear optimal power flow of the grid model. This is achieved by choosing a small number of representative time periods to represent one whole year. To select representative time periods, a hierarchical clustering is used to aggregate either adjacent hours chronologically or independently distributed coupling days into clusters of time series. The aggregation efficiency is evaluated by means of the error of the objective value and the computational time reduction. Further, both the influence of the network size and the efficiency of parallel computation in the optimization process are analysed. As a test case, the transmission grid of the northernmost German federal state of Schleswig-Holstein with a scenario corresponding to the year 2035 is considered. The considered scenario is characterized by a high share of installed renewables.
Optimal Inventory Control Strategies for Deteriorating Items with a General Time-Varying Demand under Carbon Emission Regulations
Authors: Xu Chunming , Liu Xiaojie , Wu Chenchen , Yuan Baiyun
Published: February 2020

Climate warming nowadays has caused people to increasingly enhance public awareness about carbon emissions from industries. In the storing industry, inventory management for deteriorating items is crucial in the business competition. To slow down the deterioration and ensure the quality of products, the items are usually stored in certain temperature-controlled environment. However, a lot of carbon emissions of the inventory system are caused by these warehousing activities. In a finite panning period, this paper studies a continuous review inventory system and proposes inventory models to analyze the impacts of carbon emissions on inventory system for deteriorating items with a general time-varying demand, in which shortages are allowed, and the customer demand during shortage period is partially backlogged till the next replenishment. Under carbon emission regulations, the existence and uniqueness of the optimal solution to each model is explored and comparisons of optimality among the proposed models are given. Numerical examples and robust analysis of the models are presented to illustrate the applicability in practice. Some management insights about inventory policies and emission reduction strategies are obtained.
Assessment of the Quality of Life in Patients before and after Coronary Artery Bypass Grafting (CABG): A Prospective Study
Authors: Pačarić Stana , Turk Tajana , Erić Ivan , Orkić Želimir , Petek Erić Anamarija , Milostić-Srb Andrea , Farčić Nikolina , Barać Ivana , Nemčić Ana
Published: February 2020

The aim of this study was to examine the quality of life and to report on the utility and QALY measures in patients before and after coronary artery bypass grafting (CABG); to investigate whether the SF-12 is comparable with the SF-36 for measuring health-related quality of life of patients with CABG; and to determine the impact of individual predictors on poor quality of life assessment after rehabilitation. This prospective study was conducted between January 2017 and December 2018 at the University Hospital Center Osijek, at three time points: pre-operation, 1 month after surgery, and after rehabilitation. The study was conducted with the SF-36 and SF-12 health questionnaires on 47 participants. After rehabilitation, there was a significant improvement in all domains of quality of life. The highest score was given to the change in pain (BP); mean scores were 63.8 (95% CI 56.9 to 70.6) (p = 0.001). The lowest grade (the lowest quality) after rehabilitation was in the domain of limitations due to physical difficulties (RP); arithmetic mean was 48.5 (95% CI 41 to 55.9) (p < 0.001). Quality-adjusted life-year was 0.41 (95% CI 0.38–0.44) after the CABG. The results of this study show that patients with coronary heart disease have poor quality of life before surgery. One month after the surgery, the quality of life improved, but was still inadequate. One year after surgery, satisfactory results were obtained in almost all subscales. The SF-36, SF-12, and its components, can be used effectively in patients with CABG. Age, gender, lifestyle, and risk factors in our sample of participants are not predictors of poor quality of life assessment after rehabilitation.
Risk Factors Associated with Carious Lesions in Permanent First Molars in Children: A Seven-Year Retrospective Cohort Study
Authors: Llena Carmen , Calabuig Elena , Sanz José Luis , Melo Maria
Published: February 2020

The aim of this study was to evaluate the risk factors associated with the occurrence of caries in permanent teeth (PT) and in the permanent first molar (PFM) seven years after their eruption. Children born in 2005 who were enrolled in a Community Dental Program were included. A total of 278 children were enrolled. Evaluated risk factors were parental caries experience, educational level of the mother, routine medications, systemic diseases, dietary habits, toothbrushing frequency, existence of molar incisor hypomineralization (MIH) in the PT, and caries in the temporary teeth (TT). Associations between independent variables and the DMF-T (decayed, missing, and filled teeth in PT) and DMF-M (DMF in PFM) indices, only considering cavitated and non-cavitated carious lesions or cavitated carious lesions as outcomes, were evaluated by Poisson regression with robust variance analysis. A cariogenic diet (sweets and soft drinks), toothbrushing frequency of <1 a day, a presence of df-t (decayed and filled temporary teeth) score of >0, low educational level of the mother, and existence of MIH were associated with high DMF-T or DMF-M values (p < 0.05). We can conclude that the intake of sweets and soft drinks, toothbrushing frequency, the presence of caries in TT, and MIH in PT were the best predictors of the occurrence of caries in PT and PFM.
Relationship between Serum Vitamin D and Leg Strength in Older Adults with Pre-Dialysis Chronic Kidney Disease: A Preliminary Study
Authors: Saito Akira , Hiraki Koji , Otobe Yuhei , P. Izawa Kazuhiro , Sakurada Tsutomu , Shibagaki Yugo
Published: February 2020

Active vitamin D (calcitriol, or 1.25 (OH) 2 D) is associated with muscle weakness, falls, and fracture in community-dwelling older people. This study aimed to investigate the relationship between a serum active vitamin D level and lower extremity muscle strength in elderly patients with pre-dialysis chronic kidney disease (CKD). This cross-sectional study included 231 patients with CKD treated conservatively as outpatients. We analyzed patient background factors, including age, sex, body mass index (BMI), intact parathyroid hormone (PTH), phosphorus, calcium, albumin, serum calcitriol level as an indicator of active vitamin D, and estimated glomerular filtration rate (eGFR) collected from medical records. As an index of lower extremity muscle strength, the isometric knee extension muscle strength-to-weight ratio (kgf/kg) was calculated. The mean patient age was 75.9 ± 6.1 years (68.8% male), and the BMI was 24.1 ± 3.8 kg/m2. A significant correlation was observed between knee extensor muscle strength and serum calcitriol level (r = 0.32, p < 0.01), age (r = –0.30, p < 0.01), BMI (r = −0.31, p < 0.01), intact PTH (r = −0.22, p < 0.01), phosphorus (r = −0.29, p < 0.01), albumin (r = −0.28, p < 0.01), and eGFR (r = 0.25, p < 0.01). Multiple regression analysis showed calcitriol to be significantly associated with knee extensor muscle strength (β: 0.14, 95% confidence interval: 0–0.002, p = 0.04) after adjustment for covariates. These results suggest that the serum active vitamin D level is associated with lower extremity muscle strength in older adults with pre-dialysis CKD. It is necessary to verify whether vitamin D supplementation increases lower extremity muscle strength in pre-dialysis CKD patients.
GALNT14: An Emerging Marker Capable of Predicting Therapeutic Outcomes in Multiple Cancers
Authors: Lin Wey-Ran , Yeh Chau-Ting
Published: February 2020

Members of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family function as the initiating enzymes that catalyze mucin-type O-glycosylation of proteins, and their dysregulated expression can alter cancer cell behaviors such as de novo occurrence, proliferation, migration, metastasis, and drug resistance. Recent studies have demonstrated that one of the family’s members, GALNT14, is aberrantly expressed in multiple cancers and involved in a variety of biological functions. Moreover, the single nucleotide polymorphisms (SNPs) of GALNT14-rs9679162 have been shown to predict therapeutic outcomes in patients with hepatocellular carcinoma as well as several other different types of gastrointestinal cancer. This review summarizes the structural features of GANLT14, its functional roles, and the predictive values of GALNT14 genotypes and enzyme levels in multiple cancers receiving distinct anticancer therapies.
Transcriptome Analysis Reveals Differences in Key Genes and Pathways Regulating Carbon and Nitrogen Metabolism in Cotton Genotypes under N Starvation and Resupply
Authors: Iqbal Asif , Dong Qiang , Wang Xiangru , Gui Huiping , Zhang Hengheng , Zhang Xiling , Song Meizhen
Published: February 2020

Nitrogen (N) is the most important limiting factor for cotton production worldwide. Genotype-dependent ability to cope with N shortage has been only partially explored in cotton, and in this context, the comparison of molecular responses of cotton genotypes with different nitrogen use efficiency (NUE) is of particular interest to dissect the key molecular mechanisms underlying NUE. In this study, we employed Illumina RNA-Sequencing to determine the genotypic difference in transcriptome profile using two cotton genotypes differing in NUE (CCRI-69, N-efficient, and XLZ-30, N-inefficient) under N starvation and resupply treatments. The results showed that a large genetic variation existed in differentially expressed genes (DEGs) related to amino acid, carbon, and nitrogen metabolism between CCRI-69 and XLZ-30. Further analysis of metabolic changes in cotton genotypes under N resupply showed that nitrogen metabolism and aromatic amino acid metabolism pathways were mainly enriched in CCRI-69 by regulating carbon metabolism pathways such as starch and sucrose metabolism, glycolysis/gluconeogenesis, and pentose phosphate pathway. Additionally, we performed an expression network analysis of genes related to amino acid, carbon, and nitrogen metabolism. In total, 75 and 33 genes were identified as hub genes in shoots and roots of cotton genotypes, respectively. In summary, the identified hub genes may provide new insights into coordinating carbon and nitrogen metabolism and improving NUE in cotton.
ERM Proteins at the Crossroad of Leukocyte Polarization, Migration and Intercellular Adhesion
Authors: García-Ortiz Almudena , Serrador Juan Manuel
Published: February 2020

Ezrin, radixin and moesin proteins (ERMs) are plasma membrane (PM) organizers that link the actin cytoskeleton to the cytoplasmic tail of transmembrane proteins, many of which are adhesion receptors, in order to regulate the formation of F-actin-based structures (e.g., microspikes and microvilli). ERMs also effect transmission of signals from the PM into the cell, an action mainly exerted through the compartmentalized activation of the small Rho GTPases Rho, Rac and Cdc42. Ezrin and moesin are the ERMs more highly expressed in leukocytes, and although they do not always share functions, both are mainly regulated through phosphatidylinositol 4,5-bisphosphate (PIP2) binding to the N-terminal band 4.1 protein-ERM (FERM) domain and phosphorylation of a conserved Thr in the C-terminal ERM association domain (C-ERMAD), exerting their functions through a wide assortment of mechanisms. In this review we will discuss some of these mechanisms, focusing on how they regulate polarization and migration in leukocytes, and formation of actin-based cellular structures like the phagocytic cup-endosome and the immune synapse in macrophages/neutrophils and lymphocytes, respectively, which represent essential aspects of the effector immune response.
Influence of Exercise Training on Skeletal Muscle Insulin Resistance in Aging: Spotlight on Muscle Ceramides
Authors: Reidy Paul T. , Mahmassani Ziad S. , McKenzie Alec I. , Petrocelli Jonathan J. , Summers Scott A. , Drummond Micah J.
Published: February 2020

Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.
Oestrogenic Endocrine Disruptors in the Placenta and the Fetus
Authors: Tang Zi-Run , Xu Xue-Ling , Deng Shou-Long , Lian Zheng-Xing , Yu Kun
Published: February 2020

Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with the stability and regulation of the endocrine system of the body or its offspring. These substances are generally stable in chemical properties, not easy to be biodegraded, and can be enriched in organisms. In the past half century, EDCs have gradually entered the food chain, and these substances have been frequently found in maternal blood. Perinatal maternal hormone levels are unstable and vulnerable to EDCs. Some EDCs can affect embryonic development through the blood-fetal barrier and cause damage to the neuroendocrine system, liver function, and genital development. Some also effect cross-generational inheritance through epigenetic mechanisms. This article mainly elaborates the mechanism and detection methods of estrogenic endocrine disruptors, such as bisphenol A (BPA), organochlorine pesticides (OCPs), diethylstilbestrol (DES) and phthalates (PAEs), and their effects on placenta and fetal health in order to raise concerns about the proper use of products containing EDCs during pregnancy and provide a reference for human health.
Serum Levels and Removal by Haemodialysis and Haemodiafiltration of Tryptophan-Derived Uremic Toxins in ESKD Patients
Authors: Paats Joosep , Adoberg Annika , Arund Jürgen , Dhondt Annemieke , Fernström Anders , Fridolin Ivo , Glorieux Griet , Leis Liisi , Luman Merike , Gonzalez-Parra Emilio , Perez-Gomez Vanessa Maria , Pilt Kristjan , Sanchez-Ospina Didier , Segelmark Mårten , Uhlin Fredrik , Arduan Ortiz Alberto
Published: February 2020

Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, −0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (−72%, −39%, −43%, respectively), serum tryptophan levels increased, resulting in negative RR (−8%) towards the end of the dialysis session (p < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses.
Analysis and Identification of Possible Automation Approaches for Embedded Systems Design Flows
Authors: Horita Augusto Y. , Loubach Denis S. , Bonna Ricardo
Published: February 2020

Sophisticated and high performance embedded systems are present in an increasing number of application domains. In this context, formal-based design methods have been studied to make the development process robust and scalable. Models of computation (MoC) allows the modeling of an application at a high abstraction level by using a formal base. This enables analysis before the application moves to the implementation phase. Different tools and frameworks supporting MoCs have been developed. Some of them can simulate the models and also verify their functionality and feasibility before the next design steps. In view of this, we present a novel method for analysis and identification of possible automation approaches applicable to embedded systems design flow supported by formal models of computation. A comprehensive case study shows the potential and applicability of our method.
Experimental Study of an Enhanced Phase Change Material of Paraffin/Expanded Graphite/Nano-Metal Particles for a Personal Cooling System
Authors: Ma Chuyuan , Zhang Ying , Chen Xianfeng , Song Xiande , Tang Kaixuan
Published: February 2020

A composite phase change material (PCM) was prepared by incorporating paraffin (PA) with expanded graphite (EG) and nano-metal particles to improve the thermal conductivity and reduce the leakage performance of PA once it melts and, consequently, develop a more efficient PCM for a personal phase change cooling system. A series of experiments was carried out by a scanning electron microscope, a differential scanning calorimeter, a hot-disk thermal analyzer, and leakage tests on the composite PCM with various mass fractions of EG and metals (i.e., Cu, Al, Ni, and Fe). Through comprehensive consideration of the thermal conductivity, leakage, and homogeneity, a composite PCM with the optimal proportion (PA-EG11%-Cu1.9%) was screened out. Its thermal conductivity was significantly improved nine times, while the phase change enthalpy showed a minimal decrease. In addition, the relationships of the composite PCM with its temperature and density were systematically investigated. The experimental results are important for determining the proper package density of PCM for application into a personal cooling system because its weight is crucial for the system design and benefits the performance comparison of various PCMs prepared under various conditions. Lastly, the heat storage efficiency of the PA–EG–Cu material was investigated using heat storage tests. Cooling performance clearly improved compared to the PCM without nano-particles added.
Friction and Wear Properties of Ni3Si Alloy with Ti Addition at High Temperatures
Authors: Wu Changyin , Niu Muye , Bao Shuai , Sun Yuhang , Zhang Xinghua
Published: February 2020

The tribological properties of Ni3Si alloy were studied at high temperatures. The effect of the addition of Ti was also analyzed. The surface composition was analyzed by Raman spectroscopy. The results showed that the friction coefficient decreased with the increasing temperature, and the wear rate changed slightly from 25 to 400 °C. However, the wear resistance of the alloys decreased sharply at 600 °C, and this was due to the decrease of the high-temperature strength and the severe oxidation of the alloys. Although the oxidation resistance of Ni3Si alloy decreased with Ti addition, the tribological property was improved by the addition of Ti. The Ni3Si alloy with 5% Ti addition had the best wear resistance at high temperatures as compared to pure Ni3Si alloy and with 10% Ti addition, and the wear rates of the alloys were in the order of magnitude of 10−5 mm3/Nm. With the increase of temperature, the wear mechanism of pure Ni3Si alloy transformed from abrasive wear to oxidation wear. As the Ti content increased, the wear mechanisms of the alloys changed from abrasive wear to fatigue wear at low temperature, and oxidation wear and fatigue wear at high temperature.
Microstructure Evolution and Mechanical Properties of Melt Spun Skutterudite-based Thermoelectric Materials
Authors: Geng Huiyuan , Zhang Jialun , He Tianhong , Zhang Lixia , Feng Jicai
Published: February 2020

The rapid solidification of melt spinning has been widely used in the fabrication of high-performance skutterudite thermoelectric materials. However, the microstructure formation mechanism of the spun ribbon and its effects on the mechanical properties are still unclear. Here, we report the microstructure evolution and mechanical properties of La–Fe–Co–Sb skutterudite alloys fabricated by both long-term annealing and melt-spinning, followed by sintering approaches. It was found that the skutterudite phase nucleated directly from the under-cooled melt and grew into submicron dendrites during the melt-spinning process. Upon heating, the spun ribbons started to form nanoscale La-rich and La-poor skutterudite phases through spinodal decomposition at temperatures as low as 473 K. The coexistence of the micron-scale grain size, the submicron-scale dendrite segregation and the nanoscale spinodal decomposition leads to high thermoelectric performance and mechanical strength. The maximum three-point bending strength of the melt spinning sample was about 195 MPa, which was 70% higher than that of the annealed sample.
Processing and Mechanical Properties of Ti2AlC MAX Phase Reinforced AE44 Magnesium Composite
Authors: Pi Xufeng , Yu Wenbo , Ma Chaosheng , Wang Xiaojun , Xiong ShouMei , Guitton Antoine
Published: February 2020

AE44 alloys and nanolaminated Ti2AlC particle-reinforced AE44 magnesium composites were synthesized by stir casting techniques and textured by hot extrusion methods. It was found that lamellar Al11RE3 precipitates spheroidized with the introduction of Ti2AlC into the AE44 matrix. Both transmission electron microscope and planar disregistries calculations reveal a good match for interfacial lattice transition between Mg (0001) and the basal plane (0001) of Ti2AlC. This suggests that Ti2AlC is an efficient potent nucleating substrate for Mg, thus fertilizing the formation of strong interfacial bonds. After hot extrusion treatment, Ti2AlC particles were reoriented in the textured magnesium matrix, as confirmed by X-ray diffraction. This texture effect on the composite’s mechanical properties was carefully studied by tensile and compressive tests.
Orientation and Microstructure Evolution of Al-Al2Cu Regular Eutectic Lamellar Bifurcating in an Abruptly Changing Velocity under Directional Solidification
Authors: Gao Ka , Zhang Zan , Zhao Junliang , Sun Dejian , Wang Fu
Published: February 2020

In an abruptly changing velocity under directional solidification, microstructures and the growth orientation of Al-Al2Cu eutectic lamellar were characterized. The change in solidification rate led to an interfacial instability, which results in a bifurcation of the eutectic lamella into new, refined lamellae. The growth orientation of the eutectic Al2Cu phase was also only in its (001) direction and more strongly oriented to the heat flow direction. The results suggest that the eutectic lamellar Al-Al2Cu bifurcation and the spacing adjustment may be caused by the rate determining lateral diffusion of the solutes after interfacial instability.
Influence of Electroplated CBN Wheel Wear on Grinding Surface Morphology of Powder Metallurgy Superalloy FGH96
Authors: Wang Haining , Li Xun , Wang Ziming , Xu Rufeng
Published: February 2020

The electroplated cubic boron nitride (CBN) wheel has perfect precision retention and high-temperature grinding performance, which is widely used in the field of grinding difficult-to-cut materials, such as nickel-based superalloy. However, the research on the influence law and mechanism of grinding surface morphology affected by the wear state of small-size grinding wheel is insufficient, which limits the further promotion and application of electroplated CBN wheel in the field of precision grinding of superalloy materials. Based on the in-depth analysis of the structure of FGH96 turbine disk, and combined with the actual processing requirements, the electroplated CBN wheel was designed, and the abrasive grains size selection experiments and CBN wheel wear experiments were then carried out for the powder metallurgy superalloy FGH96 in turn. The influence law of the abrasive grain size of CBN grinding wheel and the wear state of grinding wheel on the surface morphology was investigated, respectively. The obtained results showed that under the given processing parameters, the surface roughness Ra using 400# and 600# electroplated CBN wheels are around 0.66 μm and 0.53 μm during the normal wear state of grinding wheels, respectively, which can meet the requirement of surface quality less than Ra 0.8 μm in engineering application of turbine disk, and prove the feasibility of small-size CBN wheel grinding FGH96. In addition, the failure form of electroplated CBN wheel is mainly the accumulation and adhesion of abrasive debris, and the crushing and shedding of abrasive grain are hard to appear.
Mineral Processing and Metallurgical Treatment of Lead Vanadate Ores
Authors: Silin Ivan , Hahn Klaus , Gürsel Devrim , Kremer Dario , Gronen Lars , Stopić Srećko , Friedrich Bernd , Wotruba Hermann
Published: February 2020

Vanadium has been strongly moving into focus in the last decade. Due to its chemical properties, vanadium is vital for applications in the upcoming renewable energy revolution as well as usage in special alloys. The uprising demand forces the industry to consider the exploration of less attractive sources besides vanadiferous titanomagnetite deposits, such as lead vanadate deposits. Mineral processing and metallurgical treatment of lead vanadate deposits stopped in the 1980s, although the deposits contain a noteworthy amount of the desired resource vanadium. There has been a wide variety of research activities in the first half of the last century, including density sorting and flotation to recover concentrates as well as pyro- and hydrometallurgical treatment to produce vanadium oxide. There have been ecological issues and technical restrictions in the past that made these deposits uninteresting. Meanwhile, regarding the development of mineral processing and metallurgy, there are methods and strategies to reconsider lead vanadates as a highly-potential vanadium resource. This review does not merely provide an overview of lead vanadate sources and the challenges in previous mechanical and metallurgical processing activities, but shows opportunities to ensure vanadium production out of primary sources in the future.