bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility-Centric Service Provisioning in Multi-Access Edge Computing
Authors: Pham Xuan-Qui , Nguyen Tien-Dung , Nguyen VanDung , Huh Eui-Nam
Published: September 2019

Recently, multi-access edge computing (MEC) is a promising paradigm to offer resource-intensive and latency-sensitive services for IoT devices by pushing computing functionalities away from the core cloud to the edge of networks. Most existing research has focused on effectively improving the use of computing resources for computation offloading while neglecting non-trivial amounts of data, which need to be pre-stored to enable service execution (e.g., virtual/augmented reality, video analytics, etc.). In this paper, we, therefore, investigate service provisioning in MEC consisting of two sub-problems: (i) service placement determining services to be placed in each MEC node under its storage capacity constraint, and (ii) request scheduling determining where to schedule each request considering network delay and computation limitation of each MEC node. The main objective is proposed to ensure the quality of experience (QoE) of users, which is also yet to be studied extensively. A utility function modeling user perception of service latency is used to evaluate QoE. We formulate the problem of service provisioning in MEC as an Integer Nonlinear Programming (INLP), aiming at maximizing the total utility of all users. We then propose a Nested-Genetic Algorithm (Nested-GA) consisting of two genetic algorithms, each of whom solves a sub-problem regarding service placement or request scheduling decisions. Finally, simulation results demonstrate that our proposal outperforms conventional methods in terms of the total utility and achieves close-to-optimal solutions.
Preparation of Selenium-Enriched Yeast by Re-Using Discarded Saccharomyces cerevisiae from the Beer Industry for Se-Supplemented Fodder Applications
Authors: Wu Guojie , Liu Fei , Sun Xiaowen , Lin Xuegui , Zhan Feng , Fu Zhihuan
Published: September 2019

Both inorganic and organic selenium (Se) can prevent and treat various diseases caused by Se deficiency. However, organic Se has less toxicity and a higher absorption rate than inorganic Se. In this study, inorganic Se (Na2SeO3) was bio-transformed into Se-enriched discarded beer yeast (Se-enriched DB-yeast) through fermentation accumulation by re-using discarded Saccharomyces cerevisiae from the beer industry for Se-enriched fodder application. Through a single-factor experiment and L9(34)-orthogonal test for optimization of fermentation conditions, the Se content and biomass of Se-enriched DB-yeast were calculated as 14.95 mg/L and 7.3 g/L, respectively, under the optimized condition. The total amino-acid content of Se-enriched DB-yeast was increased by 9.9% compared with that from DB yeast. Additionally, alkaline amino-acid content was increased, whereas acidic amino-acid and sulfur-containing amino-acid contents were decreased. Reducing capacity, hydroxyl radical removal capacity, and sulfhydryl content after treatment with H2O2 of the Se-enriched DB-yeast extracted protein were obviously increased compared with those of the DB-yeast extracted protein. Mouse and genetically improved farmed tilapia (Oreochromis niloticus) (GIFT) bioassays showed that the Se sedimentation of organs and serum indexes after feeding Se-enriched DB-yeast-containing fodder were higher than those of DB-yeast-containing fodder. The half lethal dose (LD50) of Se-enriched DB-yeast (9260.0 mg/kg body weight (BW), 18.97 mg/kg of Se content, non-toxic level) was considerably higher than that of Na2SeO3 (20.0 mg/kg BW, 5.08 mg/kg of Se content, highly toxic level) against mouse. Therefore, Se-enriched yeast prepared by re-using discarded S. cerevisiae from beer industry fermentation accumulation has the potential to be a safe and effective Se-enriched fodder additive.
Model Tests of Soil Reinforcement Inside the Bucket Foundation with Vacuum Electroosmosis Method
Authors: Zhai Hanbo , Ding Hongyan , Zhang Puyang , Le Conghuan
Published: September 2019

Offshore wind turbine foundations are commonly subjected to large horizontal, vertical, and bending moment loads. Marine soils have high moisture content, high compressibility, high sensitivity, and low strength, resulting in insufficient foundation bearing capacity. In order to improve the bearing capacity of wind turbine foundations and reduce foundation settlement, an internal vacuum preloading method combined with electroosmosis reinforcement is used to reinforce the soil within bucket foundations. The pore water pressure, vertical settlement, pumping quality of the soil during the reinforcement process, soil moisture content before and after the reinforcement, and undrained shear strength were analyzed. Horizontal and vertical bearing capacity model tests were carried out on the reinforced and nonreinforced soil inside the bucket foundation. Results show that vacuum preloading combined with electroosmosis reinforcement reduces soil moisture content inside the bucket foundation by approximately 20%, and the undrained shear strength of the internal soil increases by approximately 20 times. Soil reinforcement has high spatial uniformity. Results of the bucket foundation bearing capacity model show that when the soil inside the bucket foundation is strengthened, horizontal bearing capacity increased by 2.9 times and vertical bearing capacity increased by 2.1 times. Vacuum preloading combined with electroosmosis reinforcement can effectively improve the shear strength of soft soil and enhance the bearing capacity and stability of bucket foundations.
Pushing Digital Automation of Configure-to-Order Services in Small and Medium Enterprises of the Construction Equipment Industry: A Design Science Research Approach
Authors: Schimanski Christoph Paul , Pasetti Monizza Gabriele , Marcher Carmen , Matt Dominik T.
Published: September 2019

In order to efficiently transform business processes (such as product design, product engineering, production, logistics, sales, deliveries, etc.) into digitally automated processes, new concepts have been introduced in both the manufacturing and construction industries. Under the term Industry 4.0, promising possibilities for high-performance production processes are emerging based on e.g., digital twins and cyber-physical systems. However, the construction industry lags behind in adapting these ideas, and is still facing severe productivity deficits. This paper addresses these deficits by assessing the hypothesis of Building Information Modeling—as the digital twinning methodology in construction—representing a key driver for digital automation and thus enabling more productive processes. To this end, we apply a design science research approach to develop artefacts using computational methods for the automation of business processes in a configure-to-order industry partner. The evaluation is done in the context of a pilot project together with this industry partner. The findings obtained in the pilot project revealed time savings in the phases of bid estimation and work preparation. Based on the findings, the applicability and utility of the suggested approach are discussed and allow for the conclusion that Building Information Model data can usefully streamline and automate many processes at the interface between design and production, if structured and preprocessed purposefully.
Olfactory Characterization of Typical Odorous Pollutants Part I: Relationship Between the Hedonic Tone and Odor Concentration
Authors: Li Jiayin , Zou Kehua , Li Weifang , Wang Gen , Yang Weihua
Published: September 2019

The hedonic tone is a suitable evaluation index which can truly reflect the psychological impact of an odor. To find out the relationship between the odor concentration (OC) and hedonic tone (H), dimethyl disulfide, limonene and butyl acetate were presented as typical odorants with different characters. A panel of 16 persons was engaged to rate the hedonic tone of a series sample with various concentrations according to the nine-point scale. The relationship between the hedonic tone and OC was established based on a multivariate logistic regression analysis. The research results demonstrated that the smell of dimethyl disulfide is unpleasant at various concentration levels, and its perceived unpleasantness is increased with OC, and at the critical point (H = −0.5), the odor index of dimethyl disulfide is 0.5 (OC = 3 OUE·m−3). For limonene, its smell is pleasant when the odor index is between 1.4 and 3.3 (OC = 25~1995 OUE·m−3). For butyl acetate, the average results showed an unpleasant character with the corresponding odor index of 1.87 (OC = 74 OUE·m−3). Each odorant has a unique hedonic behavior curve from which the annoyance potential of different odorants can be clearly discriminated, with the order of dimethyl disulfide > butyl acetate > limonene. The regression equations showed a quadratic nonlinear function between the hedonic tone and OC.
Seasonal Forecasting of the Onset of the Rainy Season in West Africa
Authors: Rauch Manuel , Bliefernicht Jan , Laux Patrick , Salack Seyni , Waongo Moussa , Kunstmann Harald
Published: September 2019

Seasonal forecasts for monsoonal rainfall characteristics like the onset of the rainy seasons (ORS) are crucial for national weather services in semi-arid regions to better support decision-making in rain-fed agriculture. In this study an approach for seasonal forecasting of the ORS is proposed using precipitation information from a global seasonal ensemble prediction system. It consists of a quantile–quantile-transformation for eliminating systematic differences between ensemble forecasts and observations, a fuzzy-rule based method for estimating the ORS date and graphical methods for an improved visualization of probabilistic ORS forecasts. The performance of the approach is tested for several climate zones (the Sahel, Sudan and Guinean zone) in West Africa for a period of eleven years (2000 to 2010), using hindcasts from the Seasonal Forecasting System 4 of ECMWF. We indicated that seasonal ORS forecasts can be skillful for individual years and specific regions (e.g., the Guinean coasts), but also associated with large uncertainties. A spatial verification of the ORS fields emphasizes the importance of selecting appropriate performance measures (e.g., the anomaly correlation coefficient) to avoid an overestimation of the forecast skill. The graphical methods consist of several common formats used in seasonal forecasting and a new index-based method for a quicker interpretation of probabilistic ORS forecast. The new index can also be applied to other seasonal forecast variables, providing an important alternative to the common forecast formats used in seasonal forecasting. Moreover, the forecasting approach proposed in this study is not computationally intensive and is therefore operational applicable for forecasting centers in tropical and subtropical regions where computing power and bandwidth are often limited.
Gravity Waves in Planetary Atmospheres: Their Effects and Parameterization in Global Circulation Models
Authors: Medvedev Alexander S. , Yiğit Erdal
Published: September 2019

The dynamical and thermodynamical importance of gravity waves was initially recognized in the atmosphere of Earth. Extensive studies over recent decades demonstrated that gravity waves exist in atmospheres of other planets, similarly play a significant role in the vertical coupling of atmospheric layers and, thus, must be included in numerical general circulation models. Since the spatial scales of gravity waves are smaller than the typical spatial resolution of most models, atmospheric forcing produced by them must be parameterized. This paper presents a review of gravity waves in planetary atmospheres, outlines their main characteristics and forcing mechanisms, and summarizes approaches to capturing gravity wave effects in numerical models. The main goal of this review is to bridge research communities studying atmospheres of Earth and other planets.
Improved Cordycepin Production by Cordyceps militaris KYL05 Using Casein Hydrolysate in Submerged Conditions
Authors: Lee Soo Kweon , Lee Ju Hun , Kim Hyeong Ryeol , Chun Youngsang , Lee Ja Hyun , Yoo Hah Young , Park Chulhwan , Kim Seung Wook
Published: September 2019

Cordycepin, a beneficial bioactive product specifically found in Cordyceps, has received attention in various bioindustrial applications such as in pharmaceuticals, functional foods, and cosmetics, due to its significant functions. However, low productivity of cordycepin is a barrier to commercialization. In this study, Cordyceps militaris was mutated by UV irradiation to improve the cordycepin production. The highest producer KYL05 strain was finally selected and its cordycepin production was increased about 1.5-fold compared to wild type. In addition, the effects of culture conditions were fundamentally investigated. Optimal conditions were as follows: pH 6, temperature of 25 °C, shaking speed of 150 rpm, and culture time of 6 days. Effects of medium component on cordycepin production were also investigated by using various carbon and nitrogen sources. It was found that glucose and casein hydrolysate (CH) were most effective as carbon and nitrogen sources in cordycepin production (2.3-fold improvement) with maximum cordycepin production of about 445 mg/L. In particular, production was significantly affected by CH. These results should be of value in improving the efficiency of mass production of cordycepin.
Structure of Salmonella Flagellar Hook Reveals Intermolecular Domain Interactions for the Universal Joint Function
Authors: Horváth Péter , Kato Takayuki , Miyata Tomoko , Namba Keiichi
Published: September 2019

The bacterial flagellum is a motility organelle consisting of a rotary motor and a long helical filament as a propeller. The flagellar hook is a flexible universal joint that transmits motor torque to the filament in its various orientations that change dynamically between swimming and tumbling of the cell upon switching the motor rotation for chemotaxis. Although the structures of the hook and hook protein FlgE from different bacterial species have been studied, the structure of Salmonella hook, which has been studied most over the years, has not been solved at a high enough resolution to allow building an atomic model of entire FlgE for understanding the mechanisms of self-assembly, stability and the universal joint function. Here we report the structure of Salmonella polyhook at 4.1 Å resolution by electron cryomicroscopy and helical image analysis. The density map clearly revealed folding of the entire FlgE chain forming the three domains D0, D1 and D2 and allowed us to build an atomic model. The model includes domain Dc with a long β-hairpin structure that connects domains D0 and D1 and contributes to the structural stability of the hook while allowing the flexible bending of the hook as a molecular universal joint.
Real-World Outcomes and Prognostic Factors in Patients Receiving Nivolumab Therapy for Recurrent or Metastatic Head and Neck Carcinoma
Authors: Hori Ryusuke , Shinohara Shogo , Kojima Tsuyoshi , Kagoshima Hiroki , Kitamura Morimasa , Tateya Ichiro , Tamaki Hisanobu , Kumabe Yohei , Asato Ryo , Harada Hiroyuki , Kitani Yoshiharu , Tsujimura Takashi , Honda Keigo , Ichimaru Kazuyuki , Omori Koichi
Published: September 2019

Recently, a global phase III study demonstrated that nivolumab markedly improved patient outcomes in recurrent or metastatic head and neck carcinoma (RMHNC). However, the efficacy of nivolumab in patients who are ineligible for clinical trials is unknown. We investigated nivolumab efficacy in real-world patients and prognostic factors associated with the response to nivolumab. This study was conducted at 11 institutes associated with Kyoto University and its Affiliated Hospitals-Head and Neck Oncology Group. In total, 93 patients with RMHNC who received nivolumab between May 2017 and May 2018 were retrospectively reviewed. Objective response rate (ORR), overall survival, and progression-free survival (PFS) were evaluated. Univariate and multivariate analyses were performed to identify prognostic factors. The ORRs in patients with squamous cell carcinoma (SCC) and non-SCC were 21.8% and 0%, respectively. In patients with SCC and non-SCC, the 1-year PFS rates were 28.7% and 8.9%, respectively. The hazard ratio (HR) for risk of PFS events (SCC versus non-SCC) was 2.28 (95% confidence interval: 1.21–4.1; log-rank p = 0.007). Univariate and multivariate analyses revealed radiotherapy history, platinum-refractory carcinoma, and treatment-related adverse events (TRAEs) as important prognostic factors associated with PFS in patients with SCC. In a real-world setting, non-SCC and platinum-refractory carcinoma were associated with a poorer prognosis, and a history of radiotherapy to the primary tumor, and the occurrence of TRAEs were associated with a better prognosis. These findings could be useful for clinicians and patients when selecting a treatment strategy.
Everything in Moderation: Lessons Learned by Exploiting Moderate Replication Stress in Cancer
Authors: Nazareth Deborah , Jones Mathew J. K. , Gabrielli Brian
Published: September 2019

The poor selectivity of standard cytotoxic chemotherapy regimens causes severe side-effects in patients and reduces the quality of life during treatment. Targeting cancer-specific vulnerabilities can improve response rates, increase overall survival and limit toxic side effects in patients. Oncogene-induced replication stress serves as a tumour specific vulnerability and rationale for the clinical development of inhibitors targeting the DNA damage response (DDR) kinases (CHK1, ATR, ATM and WEE1). CHK1 inhibitors (CHK1i) have served as the pilot compounds in this class and their efficacy in clinical trials as single agents has been disappointing. Initial attempts to combine CHK1i with chemotherapies agents that enhance replication stress (such as gemcitabine) were reported to be excessively toxic. More recently, it has emerged that combining CHK1i with subclinical doses of replication stress inducers is more effective, better tolerated and more compatible with immunotherapies. Here we focus on the lessons learned during the clinical development of CHK1i with the goal of improving the design of future clinical trials utilizing DDR inhibitors to target replication stress in cancer.
Current and Future Horizons of Patient-Derived Xenograft Models in Colorectal Cancer Translational Research
Authors: Inoue Akira , Deem Angela K. , Kopetz Scott , Heffernan Timothy P. , Draetta Giulio F. , Carugo Alessandro
Published: September 2019

Our poor understanding of the intricate biology of cancer and the limited availability of preclinical models that faithfully recapitulate the complexity of tumors are primary contributors to the high failure rate of novel therapeutics in oncology clinical studies. To address this need, patient-derived xenograft (PDX) platforms have been widely deployed and have reached a point of development where we can critically review their utility to model and interrogate relevant clinical scenarios, including tumor heterogeneity and clonal evolution, contributions of the tumor microenvironment, identification of novel drugs and biomarkers, and mechanisms of drug resistance. Colorectal cancer (CRC) constitutes a unique case to illustrate clinical perspectives revealed by PDX studies, as they overcome limitations intrinsic to conventional ex vivo models. Furthermore, the success of molecularly annotated "Avatar" models for co-clinical trials in other diseases suggests that this approach may provide an additional opportunity to improve clinical decisions, including opportunities for precision targeted therapeutics, for patients with CRC in real time. Although critical weaknesses have been identified with regard to the ability of PDX models to predict clinical outcomes, for now, they are certainly the model of choice for preclinical studies in CRC. Ongoing multi-institutional efforts to develop and share large-scale, well-annotated PDX resources aim to maximize their translational potential. This review comprehensively surveys the current status of PDX models in translational CRC research and discusses the opportunities and considerations for future PDX development.
Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients
Authors: Balázs Katalin , Kis Enikő , Badie Christophe , Bogdándi Enikő Noémi , Candéias Serge , Cruz Garcia Lourdes , Dominczyk Iwona , Frey Benjamin , Gaipl Udo , Jurányi Zsolt , Kocsis Zsuzsa S. , Rutten Eric Andreas , Sáfrány Géza , Widlak Piotr , Lumniczky Katalin
Published: September 2019

Though radiotherapy is a local therapy, it has systemic effects mainly influencing immune and inflammation processes. This has important consequences in the long-term prognosis and therapy individualization. Our objective was to investigate immune and inflammation-related changes in the peripheral blood of head and neck cancer patients treated with radiotherapy. Peripheral blood cells, plasma and blood cell-derived RNA were isolated from 23 patients before and at two time points after radiotherapy and cellular immune parameters, plasma protein changes and gene expression alterations were studied. Increased regulatory T cells and increased CTLA4 and PD-1 expression on CD4 cells indicated an immune suppression induced by the malignant condition, which was accentuated by radiotherapy. Circulating dendritic cells were strongly elevated before treatment and were not affected by radiotherapy. Decreased endoglin levels in the plasma of patients before treatment were further decreased by radiotherapy. Expression of the FXDR, SESN1, GADD45, DDB2 and MDM2 radiation-response genes were altered in the peripheral blood cells of patients after radiotherapy. All changes were long-lasting, detectable one month after radiotherapy. In conclusion we demonstrated radiotherapy-induced changes in systemic immune parameters of head and neck cancer patients and proposed markers suitable for patient stratification worth investigating in larger patient cohorts.
Panoptic View of Prognostic Models for Personalized Breast Cancer Management
Authors: Saini Geetanjali , Mittal Karuna , Rida Padmashree , Janssen Emiel A. M. , Gogineni Keerthi , Aneja Ritu
Published: September 2019

The efforts to personalize treatment for patients with breast cancer have led to a focus on the deeper characterization of genotypic and phenotypic heterogeneity among breast cancers. Traditional pathology utilizes microscopy to profile the morphologic features and organizational architecture of tumor tissue for predicting the course of disease, and is the first-line set of guiding tools for customizing treatment decision-making. Currently, clinicians use this information, combined with the disease stage, to predict patient prognosis to some extent. However, tumoral heterogeneity stubbornly persists among patient subgroups delineated by these clinicopathologic characteristics, as currently used methodologies in diagnostic pathology lack the capability to discern deeper genotypic and subtler phenotypic differences among individual patients. Recent advancements in molecular pathology, however, are poised to change this by joining forces with multiple-omics technologies (genomics, transcriptomics, epigenomics, proteomics, and metabolomics) that provide a wealth of data about the precise molecular complement of each patient’s tumor. In addition, these technologies inform the drivers of disease aggressiveness, the determinants of therapeutic response, and new treatment targets in the individual patient. The tumor architecture information can be integrated with the knowledge of the detailed mutational, transcriptional, and proteomic phenotypes of cancer cells within individual tumors to derive a new level of biologic insight that enables powerful, data-driven patient stratification and customization of treatment for each patient, at each stage of the disease. This review summarizes the prognostic and predictive insights provided by commercially available gene expression-based tests and other multivariate or clinical -omics-based prognostic/predictive models currently under development, and proposes a more inclusive multiplatform approach to tackling the challenging heterogeneity of breast cancer to individualize its management. “The future is already here—it’s just not very evenly distributed.”-William Ford Gibson
Elimination of SOX2/OCT4-Associated Prostate Cancer Stem Cells Blocks Tumor Development and Enhances Therapeutic Response
Authors: Vaddi Prasanna Kumar , Stamnes Mark A. , Cao Huojun , Chen Songhai
Published: September 2019

SOX2 and OCT4 are key regulators of embryonic stem cell pluripotency. They are overexpressed in prostate cancers and have been associated with cancer stem cell (CSC) properties. However, reliable tools for detecting and targeting SOX2/OCT4-overexpressing cells are lacking, limiting our understanding of their roles in prostate cancer initiation, progression, and therapeutic resistance. Here, we show that a fluorescent reporter called SORE6 can identify SOX2/OCT4-overexpressing prostate cancer cells. Among tumor cells, the SORE6 reporter identified a small fraction with CSC hallmarks: rapid self-renewal, the capability to form tumors and metastasize, and resistance to chemotherapies. Transcriptome and biochemical analyses identified PI3K/AKT signaling as critical for maintaining the SORE6+ population. Moreover, a SORE6-driven herpes simplex virus thymidine kinase (TK) expression construct could selectively ablate SORE6+ cells in tumors, blocking tumor initiation and progression, and sensitizing tumors to chemotherapy. This study demonstrates a key role of SOX2/OCT4-associated prostate cancer stem cells in tumor development and therapeutic resistance, and identifies the SORE6 reporter system as a useful tool for characterizing CSCs functions in a native tumor microenvironment.
Prediction of Potential miRNA–Disease Associations Through a Novel Unsupervised Deep Learning Framework with Variational Autoencoder
Authors: Zhang Li , Chen Xing , Yin Jun
Published: September 2019

The important role of microRNAs (miRNAs) in the formation, development, diagnosis, and treatment of diseases has attracted much attention among researchers recently. In this study, we present an unsupervised deep learning model of the variational autoencoder for MiRNA–disease association prediction (VAEMDA). Through combining the integrated miRNA similarity and the integrated disease similarity with known miRNA–disease associations, respectively, we constructed two spliced matrices. These matrices were applied to train the variational autoencoder (VAE), respectively. The final predicted association scores between miRNAs and diseases were obtained by integrating the scores from the two trained VAE models. Unlike previous models, VAEMDA can avoid noise introduced by the random selection of negative samples and reveal associations between miRNAs and diseases from the perspective of data distribution. Compared with previous methods, VAEMDA obtained higher area under the receiver operating characteristics curves (AUCs) of 0.9118, 0.8652, and 0.9091 ± 0.0065 in global leave-one-out cross validation (LOOCV), local LOOCV, and five-fold cross validation, respectively. Further, the AUCs of VAEMDA were 0.8250 and 0.8237 in global leave-one-disease-out cross validation (LODOCV), and local LODOCV, respectively. In three different types of case studies on three important diseases, the results showed that most of the top 50 potentially associated miRNAs were verified by databases and the literature.
Melatonin Supplementation Attenuates the Pro-Inflammatory Adipokines Expression in Visceral Fat from Obese Mice Induced by A High-Fat Diet
Authors: Farias Talita , Paixao Regislane , Cruz Maysa , de Sa Roberta , Simão Jussara , Antraco Vitor , Alonso-Vale Maria
Published: September 2019

Obesity is defined as a condition of abnormal or excessive fat accumulation in white adipose tissue that results from the exacerbated consumption of calories associated with low energy expenditure. Fat accumulation in both adipose tissue and other organs contributes to a systemic inflammation leading to the development of metabolic disorders such as type 2 diabetes, hypertension, and dyslipidemia. Melatonin is a potent antioxidant and improves inflammatory processes and energy metabolism. Using male mice fed a high-fat diet (HFD—59% fat from lard and soybean oil; 9:1) as an obesity model, we investigated the effects of melatonin supplementation on the prevention of obesity-associated complications through an analysis of plasma biochemical profile, body and fat depots mass, adipocytes size and inflammatory cytokines expression in epididymal (EPI) adipose depot. Melatonin prevented a gain of body weight and fat depot mass as well as adipocyte hypertrophy. Melatonin also reversed the increase of total cholesterol, triglycerides and LDL-cholesterol. In addition, this neurohormone was effective in completely decreasing the inflammatory cytokines leptin and resistin in plasma. In the EPI depot, melatonin reversed the increase of leptin, Il-6, Mcp-1 and Tnf-α triggered by obesity. These data allow us to infer that melatonin presents an anti-obesity effect since it acts to prevent the progression of pro-inflammatory markers in the epididymal adipose tissue together with a reduction in adiposity.
Plasma Fibrinogen-Like 1 as a Potential Biomarker for Radiation-Induced Liver Injury
Authors: Han Na-Kyung , Jung Myung Gu , Jeong Ye Ji , Son Yeonghoon , Han Su Chul , Park Seungwoo , Lim Young-Bin , Lee Yoon-Jin , Kim Sung-Ho , Park Su Cheol , Lee Hae-June
Published: September 2019

Liver damage upon exposure to ionizing radiation, whether accidental or because of therapy can contribute to liver dysfunction. Currently, radiation therapy is used for various cancers including hepatocellular carcinoma; however, the treatment dose is limited by poor liver tolerance to radiation. Furthermore, reliable biomarkers to predict liver damage and associated side-effects are unavailable. Here, we investigated fibrinogen-like 1 (FGL1)-expression in the liver and plasma after radiation exposure. We found that 30 Gy of liver irradiation (IR) induced cell death including apoptosis, necrosis, and autophagy, with fibrotic changes in the liver occurring during the acute and subacute phase in mice. Moreover, FGL1 expression pattern in the liver following IR was associated with liver damage represented by injury-related proteins and oxidative stress markers. We confirmed the association between FGL1 expression and hepatocellular injury by exposing human hepatocytes to radiation. To determine its suitability, as a potential biomarker for radiation-induced liver injury, we measured FGL1 in the liver tissue and the plasma of mice following total body irradiation (TBI) or liver IR. In TBI, FGL1 showed the highest elevation in the liver compared to other major internal organs including the heart, lung, kidney, and intestine. Notably, plasma FGL1 showed good correlation with radiation dose by liver IR. Our data revealed that FGL1 upregulation indicates hepatocellular injury in response to IR. These results suggest that plasma FGL1 may represent a potential biomarker for acute and subacute radiation exposure to the liver.
mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells
Authors: Kang Phil Jun , Son Daryeon , Ko Tae Hee , Hong Wonjun , Yun Wonjin , Jang Jihoon , Choi Jong-Il , Song Gwonhwa , Lee Jangbo , Kim In Yong , You Seungkwon
Published: September 2019

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, efficient, and patient-specific manner.
Viscosity of Plasma as a Key Factor in Assessment of Extracellular Vesicles by Light Scattering
Authors: Božič Darja , Sitar Simona , Junkar Ita , Štukelj Roman , Pajnič Manca , Žagar Ema , Kralj-Iglič Veronika , Kogej Ksenija
Published: September 2019

Extracellular vesicles (EVs) isolated from biological samples are a promising material for use in medicine and technology. However, the assessment methods that would yield repeatable concentrations, sizes and compositions of the harvested material are missing. A plausible model for the description of EV isolates has not been developed. Furthermore, the identity and genesis of EVs are still obscure and the relevant parameters have not yet been identified. The purpose of this work is to better understand the mechanisms taking place during harvesting of EVs, in particular the role of viscosity of EV suspension. The EVs were harvested from blood plasma by repeated centrifugation and washing of samples. Their size and shape were assessed by using a combination of static and dynamic light scattering. The average shape parameter of the assessed particles was found to be ρ ~ 1 (0.94–1.1 in exosome standards and 0.7–1.2 in blood plasma and EV isolates), pertaining to spherical shells (spherical vesicles). This study has estimated the value of the viscosity coefficient of the medium in blood plasma to be 1.2 mPa/s. It can be concluded that light scattering could be a plausible method for the assessment of EVs upon considering that EVs are a dynamic material with a transient identity.
How to Avoid a No-Deal ER Exit
Authors: Anelli Tiziana , Panina-Bordignon Paola
Published: September 2019

Efficiency and fidelity of protein secretion are achieved thanks to the presence of different steps, located sequentially in time and space along the secretory compartment, controlling protein folding and maturation. After entering into the endoplasmic reticulum (ER), secretory proteins attain their native structure thanks to specific chaperones and enzymes. Only correctly folded molecules are allowed by quality control (QC) mechanisms to leave the ER and proceed to downstream compartments. Proteins that cannot fold properly are instead retained in the ER to be finally destined to proteasomal degradation. Exiting from the ER requires, in most cases, the use of coated vesicles, departing at the ER exit sites, which will fuse with the Golgi compartment, thus releasing their cargoes. Protein accumulation in the ER can be caused by a too stringent QC or by ineffective transport: these situations could be deleterious for the organism, due to the loss of the secreted protein, and to the cell itself, because of abnormal increase of protein concentration in the ER. In both cases, diseases can arise. In this review, we will describe the pathophysiology of protein folding and transport between the ER and the Golgi compartment.
Melatonin Effects on Non-Alcoholic Fatty Liver Disease Are Related to MicroRNA-34a-5p/Sirt1 Axis and Autophagy
Authors: Stacchiotti Alessandra , Grossi Ilaria , García-Gómez Raquel , Patel Gaurangkumar , Salvi Alessandro , Lavazza Antonio , De Petro Giuseppina , Monsalve Maria , Rezzani Rita
Published: September 2019

Melatonin, an indole produced by pineal and extrapineal tissues, but also taken with a vegetarian diet, has strong anti-oxidant, anti-inflammatory and anti-obesogenic potentials. Non-alcoholic fatty liver disease (NAFLD) is the hepatic side of the metabolic syndrome. NAFLD is a still reversible phase but may evolve into steatohepatitis (NASH), cirrhosis and carcinoma. Currently, an effective therapy for blocking NAFLD staging is lacking. Silent information regulator 1 (SIRT1), a NAD+ dependent histone deacetylase, modulates the energetic metabolism in the liver. Micro-RNA-34a-5p, a direct inhibitor of SIRT1, is an emerging indicator of NAFLD grading. Thus, here we analyzed the effects of oral melatonin against NAFLD and underlying molecular mechanisms, focusing on steatosis, ER stress, mitochondrial shape and autophagy. Male C57BL/6J (WT) and SIRT1 heterozygous (HET) mice were placed either on a high-fat diet (58.4% energy from lard) (HFD) or on a standard maintenance diet (8.4% energy from lipids) for 16 weeks, drinking melatonin (10 mg/kg) or not. Indirect calorimetry, glucose tolerance, steatosis, inflammation, ER stress, mitochondrial changes, autophagy and microRNA-34a-5p expression were estimated. Melatonin improved hepatic metabolism and steatosis, influenced ER stress and mitochondrial shape, and promoted autophagy in WT HFD mice. Conversely, melatonin was ineffective in HET HFD mice, maintaining NASH changes. Indeed, autophagy was inconsistent in HET HFD or starved mice, as indicated by LC3II/LC3I ratio, p62/SQSTM1 and autophagosomes estimation. The beneficial role of melatonin in dietary induced NAFLD/NASH in mice was related to reduced expression of microRNA-34a-5p and sterol regulatory element-binding protein (SREBP1) but only in the presence of full SIRT1 availability.
Morphology and Characterisation of Novolac–LDPE-Based Mixtures as Matrix for Injection Moulded Green Bodies for Bio-Based SiC Ceramics
Authors: Mihalic Matthias , Soares de Sousa Fernanda , Burzic Ivana , Hinterreiter Andreas , Stifter David , Fürst Christian
Published: September 2019

This work focuses on the influence of the composition of novolac–LDPE-based mixtures, which serve as a matrix for the green bodies for bio-based silicon carbide (C/Si/SiC) ceramics, on the morphology and the mechanical properties of the green bodies and the ceramics produced thereof. The green bodies were obtained through compounding and injection moulding, and were characterised by scanning electron microscopy (SEM) and mechanical testing. Selected formulations were reinforced with natural fibres, pyrolysed to yield porous carbon templates, and converted into C/Si/SiC ceramics via liquid silicon infiltration. The carbon and ceramic specimens were characterised by light optical microscopy (LOM) and mechanical testing. Without further additives, very coarse morphologies of the novolac–LDPE-based mixtures were obtained, but the miscibility could be improved by the addition of a coupling agent and a lubricant. The pore structure of the carbon specimens was dependent on the phase distribution in the green bodies, and in turn determined the morphology of the C/Si/SiC ceramics. In all steps of the process chain, the morphology had a very strong influence on the mechanical properties. From green bodies with a homogeneous phase distribution, ceramic specimens with a SiC content of up to 75 vol% could be obtained.
One-Step Polylactic Acid Screen-Printing Microfluidic Paper-Based Analytical Device: Application for Simultaneous Detection of Nitrite and Nitrate in Food Samples
Authors: Teepoo Siriwan , Arsawiset Supattra , Chanayota Pitchayatida
Published: September 2019

In this work, we report a one-step approach for fabricating screened-printed microfluidic paper-based analytical devices (μPADs) using polylactic acid as a new hydrophobic material. A polylactic acid solution was screen printed onto chromatography papers to create hydrophobic patterns for fluidic channels. The optimal polylactic acid concentration for successful device fabrication is 9% w/v. The μPADs were fabricated within 2 min and provided high reproducibility and stability. The utility of polylactic acid screen-printing was demonstrated for the simultaneous detection of nitrite and nitrate using colorimetric detection. Under optimized experimental conditions, the detection limits and the linear ranges, respectively, were 1.2 mg L−1 and 2–10 mg L−1 for nitrite and 3.6 mg L−1 and 10–50 mg L−1 for nitrate. The detection times for both ions were found to be within 12 min. The developed μPAD was applied for the simultaneous determination of these ions in food samples, and no significant differences in the analytical results were observed compared to those of the reference method. The polylactic acid screen-printing approach presented here provides a simple, rapid, and cost-effective alternative fabrication method for fabricating μPADs.
Curcumin-Containing Orthopedic Implant Coatings Deposited on Poly-Ether-Ether-Ketone/Bioactive Glass/Hexagonal Boron Nitride Layers by Electrophoretic Deposition
Authors: Virk Ranjot Singh , Rehman Muhammad Atiq Ur , Munawar Muhammad Azeem , Schubert Dirk W. , Goldmann Wolfgang H. , Dusza Ján , Boccaccini Aldo R.
Published: September 2019

Electrophoretic deposition (EPD) was used to produce a multilayer coatings system based on chitosan/curcumin coatings on poly-ether-ether-ketone (PEEK)/bioactive glass (BG)/hexagonal boron nitride (h-BN) layers (previously deposited by EPD on 316L stainless steel) to yield bioactive and antibacterial coatings intended for orthopedic implants. Initially, PEEK/BG/h-BN coatings developed on 316L stainless steel (SS) substrates were analyzed for wear studies. Then, the EPD of chitosan/curcumin was optimized on 316L SS for suspension stability, thickness, and homogeneity of the coatings. Subsequently, the optimized EPD parameters were applied to produce chitosan/curcumin coatings on the PEEK/BG/h-BN layers. The multilayered coatings produced by EPD were characterized in terms of composition, microstructure, drug release kinetics, antibacterial activity, and in vitro bioactivity. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) confirmed the deposition of chitosan/curcumin on the multilayer coating system. The release of curcumin upon immersion of multilayer coatings in phosphate-buffered saline (PBS) was confirmed by ultraviolet/visible (UV/VIS) spectroscopic analysis. The antibacterial effect of chitosan/curcumin as the top coating was determined by turbidity tests (optical density measurements). Moreover, the multilayer coating system formed an apatite-like layer upon immersion in simulated body fluid (SBF), which is similar in composition to the hydroxyapatite component of bone, confirming the possibility of achieving close bonding between bone and the coating surface.
Numerical Study on the Optimization of Roll-to-Roll Ultraviolet Imprint Lithography
Authors: Tahir Usama , Kamran Muhammad Ahmad , Jeong Myung Yung
Published: September 2019

Roll-to-roll ultraviolet (R2R-UV) imprinting is a low-cost and high-throughput method that includes the manufacturing of large-area functional films. However, the quality of the final product is obstructed by the bubble entrapment during the imprinting process. In this study, a multi-phase volume of fluid (VOF) numerical model was used to remove bubble entrapment during the R2R imprinting process, which covered all parameters. This new modified numerical model with open-channel boundary conditions was based on the single zone that contains the direct contact of UV resin with the imprinting mold during the filling process. In addition, this model simulated the UV resin filling into microcavities at the preceding and succeeding ends of the imprinting mold. Different patterns of imprinting mold were considered to enhance the fidelity of R2R-UV imprinting for the comprehensive analysis. The experimental results validated through numerical simulations revealed that the bubble entrapment can be controlled by varying various parameters such as speed of the imprinting system, viscosity, contact angles, and pattern shape. The proposed model may be useful for a continuous bubble-free R2R imprinting process in industrial applications that includes flexible displays and micro/nano-optics.
Magnetite-Accelerated Corrosion of SA508 Tubesheet Material and Its Effect on Steam Generator Tube Denting
Authors: Song Geun Dong , Han Jeoh , Jeon Soon-Hyeok , Hur Do Haeng
Published: September 2019

The objective of this work is to investigate the magnetite-accelerated corrosion phenomenon of SA508 used as tubesheet material in simulated secondary side environments of pressurized water reactors through immersion and electrochemical tests. The presence of sulfate ions induced the fast growth of a corrosion product layer on SA508, and this phenomenon was accelerated when the SA508 was coupled to magnetite. From the perspective of electrochemical behavior, it was found that SA508 behaves as an anodic member in the coupling system with magnetite, resulting in an increased corrosion rate.
Ferroelectric Liquid Crystals: Physics and Applications
Authors: Guo Qi , Yan Kexin , Chigrinov Vladimir , Zhao Huijie , Tribelsky Michael
Published: September 2019

Electrooptic modes with fast response and high contrast ratio are highly desirable in modern photonics and displays. Ferroelectric liquid crystals (FLCs) are especially promising for fulfilling these demands by employing photoalignment technology in FLC cells. Three electrooptic modes including surface stabilized FLC (SSFLC), deformed helix ferroelectric (DHF) mode, and electrically suppressed helix (ESH) mode are reviewed with the corresponding electrooptic effects like bi- and multi-stable switching, continuous modulation of grayscale or phase, and high contrast switching. The general operation principles FLC electrooptic modes are described, and then the characteristics of each modes for potential applications are summarized. With the advantages of controllable anchoring energy, the photoalignment provides FLC samples with uniform alignment and high contrast ratio. The fast FLCs with a high resolution and high contrast can be used in the next generation display including field sequential color FLC microdisplays, as well as switchable 2D/3D televisions.
Inventory and Historical Changes in the Marine Flora of Tomioka Peninsula (Amakusa Island), Japan
Authors: Titlyanov Eduard A. , Titlyanova Tamara V. , Tokeshi Mutsunori , Li Xiubao
Published: September 2019

Intensive algal sampling was conducted from 2012 to 2017 in the Tomioka Peninsula, Amakusa-Shimoshima Island (the East China Sea, Japan), yielding a total of 293 benthic macroalgal taxa, of which 63% were red algae, 16% were brown algae, and 19% were green algae. The majority (69%) of species were previously recorded only for the tropics and/or subtropics, whereas 31% of species were recorded for temperate latitudes. Among all species of algae found from 2012 to 2017 in the Tomioka Peninsula, 163 species (56%) were newly identified species for Amakusa-Shimoshima Island, including six taxa, which were recorded in Japan for the first time. Comparison of the current data from the Amakusa-Shimoshima Island with those of nearby tropical regions suggested that the recent marine flora of the Amakusa-Shimoshima Island was more closely affiliated with the flora of a warm-temperate region. Moreover, we found that the benthic flora of the Tomioka Peninsula was significantly changed between the 1950s (Segawa & Yoshida 1961) and 2012–2017. For example, the species diversity was increased by two times, mainly at the expense of red and green algae, and the biogeographic status of the benthic flora was changed from the flora of a cold-temperate region to the flora of a warm-temperate region, which could be attributed to an introduction of red algae from the tropics of South East Asia and widespread opportunistic green algae, as well as the disappearance of cold-water brown algae. Collectively, our data suggested that these changes were driven by the global warming effect on the ocean.