bluuebunny/crossref_metadata_2025 huggingface dataset:
RFID Based Manufacturing Process of Cloud MES
Authors: Wang Chuang , Chen Xu’nan , Soliman Abdel-Hamid Ali , Zhu Zhixiang
Published: October 2018

RFID (radio frequency identification) is widely used in the manufacturing processes of enterprises. At the same time, with the advent of the Industry 4.0 era, Manufacturing Execution System (MES) systems began to evolve into cloud MES systems. In this paper, a RFID-based manufacturing process for cloud MES is proposed and a framework manufacturing process fora cloud MES system centered on machine tools is constructed. The process division of the manufacturing process, RFID configuration and cloud processing are analyzed, and other key technologies involved in implementing the framework are briefly discussed. Finally, the effectiveness of a RFID-based manufacturing process of cloud MES is verified by two different types of case analysis namely photovoltaic slice production and garment outsourcing processing.
A Hybrid Approach for Model Order Reduction of Barotropic Quasi-Geostrophic Turbulence
Authors: Rahman Sk. Mashfiqur , San Omer , Rasheed Adil
Published: October 2018

We put forth a robust reduced-order modeling approach for near real-time prediction of mesoscale flows. In our hybrid-modeling framework, we combine physics-based projection methods with neural network closures to account for truncated modes. We introduce a weighting parameter between the Galerkin projection and extreme learning machine models and explore its effectiveness, accuracy and generalizability. To illustrate the success of the proposed modeling paradigm, we predict both the mean flow pattern and the time series response of a single-layer quasi-geostrophic ocean model, which is a simplified prototype for wind-driven general circulation models. We demonstrate that our approach yields significant improvements over both the standard Galerkin projection and fully non-intrusive neural network methods with a negligible computational overhead.
A Numerical Study of the Sound and Force Production of Flexible Insect Wings
Authors: Geng Biao , Zheng Xudong , Xue Qian , Liu Geng , Dong Haibo
Published: October 2018

We numerically solved the acoustic and flow field around cicada wing models with parametrically varied flexibility using the hydrodynamic/acoustic splitting method. We observed a gradual change of sound directivity with flexibility. We found that flexible wings generally produce lower sound due to reduced aerodynamic forces, which were further found to scale with the dynamic pressure force defined as the integration of dynamic pressure over the wing area. Unlike conventional scaling where the incoming flow velocity is used as the reference to calculate the force coefficients, here only the normal component of the relative velocity of the wing to the flow was used to calculate the dynamic pressure, putting kinematic factors into the dynamic pressure force and leaving the more fundamental physics to the force coefficients. A high correlation was found between the aerodynamic forces and the dynamic pressure. The scaling is also supported by previously reported data of revolving wing experiments.
Aptamer Chimeras for Therapeutic Delivery: The Challenging Perspectives
Authors: Esposito Carla Lucia , Catuogno Silvia , Condorelli Gerolama , Ungaro Paola , De Franciscis Vittorio
Published: October 2018

Nucleic acid-based aptamers have emerged as efficient delivery carriers of therapeutics. Thanks to their unique features, they can be, to date, considered one of the best targeting moieties, allowing the specific recognition of diseased cells and avoiding unwanted off-target effects on healthy tissues. In this review, we revise the most recent contributes on bispecific and multifunctional aptamer therapeutic chimeras. We will discuss key examples of aptamer-mediated delivery of nucleic acid and peptide-based therapeutics underlying their great potentiality and versatility. Achieved objectives and challenges will be highlighted as well.
Correction: Ruiz-Rodríguez et al. Gut Microbiota of Great Spotted Cuckoo Nestlings Is a Mixture of Those of Their Foster Magpie Siblings and of Cuckoo Adults. Genes 2018, 9, 381
Authors: Ruiz-Rodríguez Magdalena , Martín-Vivaldi Manuel , Martínez-Bueno Manuel , Soler Juan
Published: October 2018

The authors wish to make the following changes in their paper [...]
Understanding Weather and Hospital Admissions Patterns to Inform Climate Change Adaptation Strategies in the Healthcare Sector in Uganda
Authors: Bishop-Williams Katherine E. , Berrang-Ford Lea , Sargeant Jan M. , Pearl David L. , Lwasa Shuaib , Namanya Didacus Bambaiha , Edge Victoria L. , Cunsolo Ashlee ,   IHACC Research Team,   Bwindi Community Hospital, Huang Yi , Ford James , Garcia Patricia , Harper Sherilee L.
Published: October 2018

Background: Season and weather are associated with many health outcomes, which can influence hospital admission rates. We examined associations between hospital admissions (all diagnoses) and local meteorological parameters in Southwestern Uganda, with the aim of supporting hospital planning and preparedness in the context of climate change. Methods: Hospital admissions data and meteorological data were collected from Bwindi Community Hospital and a satellite database of weather conditions, respectively (2011 to 2014). Descriptive statistics were used to describe admission patterns. A mixed-effects Poisson regression model was fitted to investigate associations between hospital admissions and season, precipitation, and temperature. Results: Admission counts were highest for acute respiratory infections, malaria, and acute gastrointestinal illness, which are climate-sensitive diseases. Hospital admissions were 1.16 (95% CI: 1.04, 1.31; p = 0.008) times higher during extreme high temperatures (i.e., >95th percentile) on the day of admission. Hospital admissions association with season depended on year; admissions were higher in the dry season than the rainy season every year, except for 2014. Discussion: Effective adaptation strategy characteristics include being low-cost and quick and practical to implement at local scales. Herein, we illustrate how analyzing hospital data alongside meteorological parameters may inform climate-health planning in low-resource contexts.
Smartphone Applications for Encouraging Asthma Self-Management in Adolescents: A Systematic Review
Authors: Alquran Alaa , Lambert Katrina A. , Farouque Ambereen , Holland Anne , Davies Janet , Lampugnani Edwin R. , Erbas Bircan
Published: October 2018

Adolescent asthma is still a major problem with poor adherence to treatment. Globally, adolescents are devoted users of smartphone technologies and app use in asthma self-management may improve adherence. The objective of this systematic review is to assess the feasibility and efficacy of mobile technology in improving asthma outcomes in adolescents. We conducted an extensive review of the peer-review literature of studies with populations consisting of children and adolescents under 18 years in seven bibliographic databases and Google Scholar. All study designs were considered. Quality assessment of included studies were independently assessed and reported. The search identified 291 articles; of the 16 eligible full-text papers, 8 met the review criteria, reporting two interventional, two qualitative and four observational studies. Samples ranged from 12 to 21 participants. Heterogeneity related to study design and the methods of the included studies prevented meta-analysis. Nevertheless, the intervention studies reported a positive effect of smartphone apps on asthma control, medication adherence and self-efficacy. Smartphone apps may be an effective asthma control tool especially among adolescents who are major users of smartphones; however, conclusions are limited by a lack of controlled trials and adequate sample sizes.
Space-Time Statistical Insights about Geographic Variation in Lung Cancer Incidence Rates: Florida, USA, 2000–2011
Authors: Hu Lan , Griffith Daniel A. , Chun Yongwan
Published: October 2018

The geographic distribution of lung cancer rates tends to vary across a geographic landscape, and covariates (e.g., smoking rates, demographic factors, socio-economic indicators) commonly are employed in spatial analysis to explain the spatial heterogeneity of these cancer rates. However, such cancer risk factors often are not available, and conventional statistical models are unable to fully capture hidden spatial effects in cancer rates. Introducing random effects in the model specifications can furnish an efficient approach to account for variations that are unexplained due to omitted variables. Especially, a random effects model can be effective for a phenomenon that is static over time. The goal of this paper is to investigate geographic variation in Florida lung cancer incidence data for the time period 2000–2011 using random effects models. In doing so, a Moran eigenvector spatial filtering technique is utilized, which can allow a decomposition of random effects into spatially structured (SSRE) and spatially unstructured (SURE) components. Analysis results confirm that random effects models capture a substantial amount of variation in the cancer data. Furthermore, the results suggest that spatial pattern in the cancer data displays a mixture of positive and negative spatial autocorrelation, although the global map pattern of the random effects term may appear random.
Exploring the Opportunities and Challenges of the Digital World for Early Childhood Services with Vulnerable Children
Authors: Harris Leona , Davis Niki , Cunningham Una , De Vocht Lia , Macfarlane Sonja , Gregory Nikita , Aukuso Saili , Taleni Tufulasifa’atafatafa Ova , Dobson Jan
Published: October 2018

Potentially addictive behaviours supported by the internet and mobile phones raise concerns in education services for early childhood. Although there is evidence that screen media can distract the attention of young children, there was a massive uptake of digital devices by early childhood centres (ECCs). We investigated practices of families (n = 85) and of six ECCs serving vulnerable children in New Zealand, many of whom are emergent bilinguals. Descriptions of the limited and exemplary choice of screen media of the ECCs include digital portfolios containing children’s learning stories in multiple languages illustrated with digital photos. This was facilitated by increasing partnership with the families and the inclusion of their languages in the physical and digital landscapes of the ECCs. However, these families and the ECCs are seeking additional guidance to face the complex challenges of the digital world. These early findings from our national research programme, A Better Start, E Tipu E Rea, already informed significant changes in the ECCs; we also identified the potential for young children to act as agents of change.
Arsenic and Heavy Metal Accumulation and Risk Assessment in Soils around Mining Areas: The Urad Houqi Area in Arid Northwest China as an Example
Authors: Song Shuai , Li Yuanjie , Li Lin , Liu Maoyong , Li Jing , Wang Liang , Su Chao
Published: October 2018

Mining activities make important contributions to economic growth, but they can also produce massive amounts of solid waste, such as tailings and metal accumulations. Taking the Urad Houqi mining area in Inner Mongolia as the study area, this study systematically assessed the contamination risk of arsenic and heavy metals in the soils of the study area and explored the contamination characteristics in a key polymetallic mining area. For the whole study area, based on the Nemerow comprehensive pollution method, almost half of the investigated sites were contaminated, and the most contaminated site was Urad Houqi Qianzhen Mineral Concentration Co., Ltd. (Bayannaoer, China), a cooperation between the lead and zinc mining industry. The assessment results indicated that Cd and As were the elements of greatest concern, followed by Pb, Cr and Hg. Particularly, for the typical Dongshengmiao mining area, when compared with the GB15618-1995 standard values, As, Zn and Cd posed the most serious contamination threat, while Cr and Ni exhibited clean conditions. In addition, the vertical distribution maps demonstrated that the contents of arsenic and metals in some soil profiles were correlated with sampling depth. Therefore, arsenic and heavy metals pose high threat to soil ecosystems in this area, there is encouragement for some control and remediation measures to be taken into effect.
Trace Metal Pollution in Topsoil Surrounding the Xiangtan Manganese Mine Area (South-Central China): Source Identification, Spatial Distribution and Assessment of Potential Ecological Risks
Authors: Jiang Feng , Ren Bozhi , Hursthouse Andrew S. , Zhou Yingying
Published: October 2018

In this study, we identified the sources of trace metals, investigated their spatial distribution in topsoil and assessed their potential ecological risk in the area surrounding a typical manganese mining area in Xiangtan, Hunan Province, China. The concentrations of Mn, Cu, Pb, Zn, Cd, Ni, Cr and Hg in the topsoil of the study area were measured. Except for Cr and Hg, all trace metals exceeded the corresponding soil background values for Hunan Province. The spatial variation in trace metals was visualized by GIS, and the results show that trace metals in topsoil are enriched mainly around mines and smelters. Two groups of trace metals were identified using the spatial distribution, trend analysis, Pearson’s correlation and principal component analysis: Mn, Cu, Pb, Zn, Cd and Ni can be attributed to industrial and mining activities, whereas Cr and Hg are of natural origin. The results also revealed the extent of the influence of secondary processes such as the prevailing wind direction, erosion of mine tailings and rainwater runoff play significant roles in the wider dispersal and transfer of trace metals. In addition, the environmental risk of metal pollution was evaluated by applying the geoaccumulation index and potential ecological risk index (PERI) to the study area. The accumulated PERI for metals of concern is at highest risk level in the main manganese mine area. This decreases to a moderate risk around the manganese mine area, highlighting locations for further risk management concern. Furthermore, nearly 80% of the potential ecological risk was from Cd across the study area.
Reduced Lung Function among Workers in Primary Coffee Processing Factories in Ethiopia: A Cross Sectional Study
Authors: Abaya Samson Wakuma , Bråtveit Magne , Deressa Wakgari , Kumie Abera , Moen Bente E.
Published: October 2018

Dust exposure is one of the major risk factors for respiratory health in many workplaces, including coffee factories. The aim of this study was to assess the prevalence of respiratory symptoms and lung function reduction among workers in Ethiopian primary coffee processing factories, compared to a control group of workers. A total of 115 coffee workers and 110 water bottling workers were involved in this study, from 12 coffee and 3 water bottling factories in Ethiopia, respectively. The chronic respiratory symptoms were assessed using a structured interview, using a standardized questionnaire adopted from the American Thoracic Society (ATS). The lung function tests were performed according to the ATS recommendation for spirometry. The coffee workers had a significantly higher prevalence of coughing, coughing with sputum, breathlessness, work-related shortness of breath, and wheezing compared with the controls. The prevalence ratio of work-related shortness of breath (PR = 3.7, 95% CI: 1.6–8.7) and wheezing (PR = 3.3, 95% CI: 1.3–8.4) was significantly higher for the coffee workers compared to the controls. The coffee workers in the age groups 28–39 years and ≥40 years, had a significantly lower forced vital capacity and forced expiratory volume in 1 s compared to the controls in the similar age groups. The findings indicated the need for longitudinal studies on the possible effect of coffee dust on respiratory health of coffee production workers.
Removal of Endocrine Disrupting Chemicals from Water: Adsorption of Bisphenol-A by Biobased Hydrophobic Functionalized Cellulose
Authors: Tursi Antonio , Chatzisymeon Efthalia , Chidichimo Francesco , Beneduci Amerigo , Chidichimo Giuseppe
Published: October 2018

The aim of this study is to examine the efficiency of biobased Spanish broom (SB) surface modified cellulose fibers to remove bisphenol A (BPA), a well-known endocrine disruptor, from water. Spanish brooms are flowering plants, which are native and abundant to Mediterranean regions. The functionalized fibers (FF) were found to have the best adsorption efficiency at pH 5, due to the optimal hydrophobic interaction between the FF fiber and BPA. Adsorption kinetics of BPA was found to fit well a pseudo-second order reaction. Equilibrium isotherm data were fitted by Langmuir and Freundlich models. A very fast and simple regeneration method was developed and it was observed that adsorption capacity of the fibers was kept almost unchanged after 3 consecutive uses. Bottled water and synthetic wastewater were also tested to assess the efficiency of the process under more realistic water and wastewater treatment conditions. It was found that BPA removal was slightly decreased from 77% in ultrapure water to 64% in synthetic wastewater matrix, indicating that FF has a high selectivity toward BPA, even in the presence of other organic compounds. Overall, it was observed that SB-modified fibers can be a new promising green biotechnology for water purification.
Evaluation of a Workplace Health and Wellbeing Training Course Delivered Online and Face-To-Face
Authors: Talati Zenobia , Davey Emily , Grapes Carly , Shilton Trevor , Pettigrew Simone
Published: October 2018

Organisations may benefit from training champions to promote healthy workplace environments and initiatives. This study compared the perceived usefulness and relative effectiveness of an employee training course offered via online and face-to-face formats. Individuals who took part in the training course were assessed on their perceived competence and confidence to implement changes pre- and post-training. Repeated measures Analysis of Variance (ANOVA) and a t-test were conducted to test for significant differences between pre- and post-training scores and/or mode of training, respectively. Although the face-to-face training course was rated as slightly more useful, there were no significant differences between the two modes of training for the other dependent variables, and both modes led to significantly greater perceived competence and confidence post-training. These findings demonstrate the potential benefits of training employees to implement changes in their workplaces.
Multidisciplinary Intervention and Acceptance and Commitment Therapy for Return-to-Work and Increased Employability among Patients with Mental Illness and/or Chronic Pain: A Randomized Controlled Trial
Authors: Berglund Erik , Anderzén Ingrid , Andersén Åsa , Carlsson Lars , Gustavsson Catharina , Wallman Thorne , Lytsy Per
Published: October 2018

Background: People on long-term sick leave often have a long-lasting process back to work, where the individuals may be in multiple and recurrent states; i.e., receiving different social security benefits or working, and over time they may shift between these states. The purpose of this study was to evaluate the effects of two vocational rehabilitation programs, compared to a control, on return-to-work (RTW) or increased employability in patients on long-term sick leave due to mental illness and/or chronic pain. Methods: In this randomized controlled study, 427 women and men were allocated to either (1) multidisciplinary team management, i.e., multidisciplinary assessments and individual rehabilitation management, (2) acceptance and commitment therapy (ACT), or (3) control. A positive outcome was defined as RTW or increased employability. The outcome was considered negative if the (part-time) wage was reduced or ceased, or if there was an indication of decreased employability. The outcome was measured one year after entry in the project and analyzed using binary and multinomial logistic regressions. Results: Participants in the multidisciplinary team group reported having RTW odds ratio (OR) 3.31 (95% CI 1.39–7.87) compared to the control group in adjusted models. Participants in the ACT group reported having increased employability OR 3.22 (95% CI 1.13–9.15) compared to the control group in adjusted models. Conclusions: This study of vocational rehabilitation in mainly female patients on long-term sick leave due to mental illness and/or chronic pain suggests that multidisciplinary team assessments and individually adapted rehabilitation interventions increased RTW and employability. Solely receiving the ACT intervention also increased employability.
Design of a Generic Mobile GIS for Professional Users
Authors: Kuper Paul Vincent
Published: October 2018

There are multiple location-based services (LBSs) and mobile GIS available for a wide range of applications. Usually such applications are developed to solve a restricted task within a restricted environment. The focus on a particular task is strong, and therefore, such applications can usually not be used in multiple environments. To overcome this issue, this paper presents a concept of a generic professional mobile GIS with a focus on interoperability. Firstly, common issues of mobile applications are presented, and their impact on the development of mobile GIS is analyzed. Subsequently, a new approach for a generic mobile GIS for professional users is presented. Based on multiple OGC standards, the approach leads to a system that can be used in various applications where the quality of surveyed data and analysis capabilities are improved. To prove the strength of the approach with GeoTechMobile, a prototype is presented and evaluated in a case study.
Assessment of Segmentation Parameters for Object-Based Land Cover Classification Using Color-Infrared Imagery
Authors: Akcay Ozgun , Avsar Emin Ozgur , Inalpulat Melis , Genc Levent , Cam Ahmet
Published: October 2018

Using object-based image analysis (OBIA) techniques for land use-land cover classification (LULC) has become an area of interest due to the availability of high-resolution data and segmentation methods. Multi-resolution segmentation in particular, statistically seen as the most used algorithm, is able to produce non-identical segmentations depending on the required parameters. The total effect of segmentation parameters on the classification accuracy of high-resolution imagery is still an open question, though some studies were implemented to define the optimum segmentation parameters. However, recent studies have not properly considered the parameters and their consequences on LULC accuracy. The main objective of this study is to assess OBIA segmentation and classification accuracy according to the segmentation parameters using different overlap ratios during image object sampling for a predetermined scale. With this aim, we analyzed and compared (a) high-resolution color-infrared aerial images of a newly-developed urban area including different land use types; (b) combinations of multi-resolution segmentation with different shape, color, compactness, bands, and band-weights; and (c) accuracies of classifications based on varied segmentations. The results of various parameters in the study showed an explicit correlation between segmentation accuracies and classification accuracies. The effect of changes in segmentation parameters using different sample selection methods for five main LULC types was studied. Specifically, moderate shape and compactness values provided more consistency than lower and higher values; also, band weighting demonstrated substantial results due to the chosen bands. Differences in the variable importance of the classifications and changes in LULC maps were also explained.
Advances in Understanding the Mechanism of Action of the Auxin Permease AUX1
Authors: Singh Gaurav , Retzer Katarzyna , Vosolsobě Stanislav , Napier Richard
Published: October 2018

In over 40 years of research on the cellular uptake of auxin it is somewhat chastening that we have elaborated so little on the original kinetic descriptions of auxin uptake by plant cells made by Rubery and Sheldrake in 1974. Every aspect of that seminal work has been investigated in detail, and the uptake activity they measured is now known to be attributed to the AUX1/LAX family of permeases. Recent pharmacological studies have defined the substrate specificity of AUX1, biochemical studies have evaluated its permeability to auxin in plant cell membranes, and rigourous kinetic studies have confirmed the affinity of AUX1 for IAA and synthetic auxins. Advances in genome sequencing have provided a rich resource for informatic analysis of the ancestry of AUX1 and the LAX proteins and, along with models of topology, suggest mechanistic links to families of eukaryotic proton co-transporters for which crystal structures have been presented. The insights gained from all the accumulated research reflect the brilliance of Rubery and Sheldrake’s early work, but recent biochemical analyses are starting to advance further our understanding of this vitally important family of auxin transport proteins.
High Catalytic Activity of Lipase from Yarrowia lipolytica Immobilized by Microencapsulation
Authors: Da S. Pereira Adejanildo , L. Fraga Jully , M. Diniz Marianne , C. Fontes-Sant’Ana Gizele , F. F. Amaral Priscilla
Published: October 2018

Microencapsulation of lipase from Yarrowia lipolytica IMUFRJ 50682 was performed by ionotropic gelation with sodium alginate. Sodium alginate, calcium chloride and chitosan concentrations as well as complexation time were evaluated through experimental designs to increase immobilization yield (IY) and immobilized lipase activity (ImLipA) using p-nitrophenyl laurate as substrate. To adjust both parameters (IY and ImLipA), the desirability function showed that microcapsule formation with 3.1%(w/v) sodium alginate, 0.19%(w/v) chitosan, 0.14 M calcium chloride, and 1 min complexation time are ideal for maximal immobilization yield and immobilized lipase activity. A nearly twofold enhancement in Immobilization yield and an increase up to 280 U/g of the lipase activity of the microcapsules were achieved using the experimental design optimization tool. Chitosan was vital for the high activity of this new biocatalyst, which could be reused a second time with about 50% of initial activity and for four more times with about 20% of activity.
HDL-Mediated Lipid Influx to Endothelial Cells Contributes to Regulating Intercellular Adhesion Molecule (ICAM)-1 Expression and eNOS Phosphorylation
Authors: Muñoz-Vega Mónica , Massó Felipe , Páez Araceli , Vargas-Alarcón Gilberto , Coral-Vázquez Ramón , Mas-Oliva Jaime , Carreón-Torres Elizabeth , Pérez-Méndez Óscar
Published: October 2018

Reverse cholesterol transport (RCT) is considered as the most important antiatherogenic role of high-density lipoproteins (HDL), but interventions based on RCT have failed to reduce the risk of coronary heart disease. In contrast to RCT, important evidence suggests that HDL deliver lipids to peripheral cells. Therefore, in this paper, we investigated whether HDL could improve endothelial function by delivering lipids to the cells. Internalization kinetics using cholesterol and apolipoprotein (apo) AI fluorescent double-labeled reconstituted HDL (rHDL), and human dermal microvascular endothelial cells-1 (HMEC-1) showed a fast cholesterol influx (10 min) and a slower HDL protein internalization as determined by confocal microscopy and flow cytometry. Sphingomyelin kinetics overlapped that of apo AI, indicating that only cholesterol became dissociated from rHDL during internalization. rHDL apo AI internalization was scavenger receptor class B type I (SR-BI)-dependent, whereas HDL cholesterol influx was independent of SR-BI and was not completely inhibited by the presence of low-density lipoproteins (LDL). HDL sphingomyelin was fundamental for intercellular adhesion molecule-1 (ICAM-1) downregulation in HMEC-1. However, vascular cell adhesion protein-1 (VCAM-1) was not inhibited by rHDL, suggesting that components such as apolipoproteins other than apo AI participate in HDL’s regulation of this adhesion molecule. rHDL also induced endothelial nitric oxide synthase eNOS S1177 phosphorylation in HMEC-1 but only when the particle contained sphingomyelin. In conclusion, the internalization of HDL implies the dissociation of lipoprotein components and a SR-BI-independent fast delivery of cholesterol to endothelial cells. HDL internalization had functional implications that were mainly dependent on sphingomyelin. These results suggest a new role of HDL as lipid vectors to the cells, which could be congruent with the antiatherogenic properties of these lipoproteins.
mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants
Authors: Eckstein Markus , Wirtz Ralph , Gross-Weege Matthias , Breyer Johannes , Otto Wolfgang , Stoehr Robert , Sikic Danijel , Keck Bastian , Eidt Sebastian , Burger Maximilian , Bolenz Christian , Nitschke Katja , Porubsky Stefan , Hartmann Arndt , Erben Philipp
Published: October 2018

Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan®-based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort (GSE48277 + GSE47993) was performed. High expression of KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for KRT5 high: 58%; 5-year DSS for KRT20 high: 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20+/KRT5−, 5-year DSS 0%, p < 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high: 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20+/KRT− tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested).
Reconstituted HDL (Milano) Treatment Efficaciously Reverses Heart Failure with Preserved Ejection Fraction in Mice
Authors: Mishra Mudit , Muthuramu Ilayaraja , Aboumsallem Joseph Pierre , Kempen Herman , De Geest Bart
Published: October 2018

Heart failure with preserved ejection fraction (HFpEF) represents a major unmet therapeutic need. This study investigated whether feeding coconut oil (CC diet) for 26 weeks in female C57BL/6N mice induces HFpEF and evaluated the effect of reconstituted high-density lipoprotein (HDL)Milano (MDCO-216) administration on established HFpEF. Eight intraperitoneal injections of MDCO-216 (100 mg/kg protein concentration) or of an equivalent volume of control buffer were executed with a 48-h interval starting at 26 weeks after the initiation of the diet. Feeding the CC diet for 26 weeks induced pathological left ventricular hypertrophy characterized by a 17.1% (p < 0.0001) lower myocardial capillary density and markedly (p < 0.0001) increased interstitial fibrosis compared to standard chow (SC) diet mice. Parameters of systolic and diastolic function were significantly impaired in CC diet mice resulting in a reduced stroke volume, decreased cardiac output, and impaired ventriculo-arterial coupling. However, ejection fraction was preserved. Administration of MDCO-216 in CC diet mice reduced cardiac hypertrophy, increased capillary density (p < 0.01), and reduced interstitial fibrosis (p < 0.01). MDCO-216 treatment completely normalized cardiac function, lowered myocardial acetyl-coenzyme A carboxylase levels, and decreased myocardial transforming growth factor-β1 in CC diet mice. In conclusion, the CC diet induced HFpEF. Reconstituted HDLMilano reversed pathological remodeling and functional cardiac abnormalities.
Inhibitory and Inductive Effects of Opuntia ficus indica Extract and Its Flavonoid Constituents on Cytochrome P450s and UDP-Glucuronosyltransferases
Authors: Jeong Hyesoo , Kim Soolin , Kim Mi-yeon , Lee Jimin , An Byoung Ha , Kim Hee-Doo , Jeong Hyunyoung , Song Yun Seon , Chang Minsun
Published: October 2018

Opuntia ficus indica (OFI) is grown abundantly in arid areas and its fruits are regarded as an important food and nutrient source owing to the presence of flavonoids, minerals, and proteins. The previous report that OFI exerts phytoestrogenic activity makes it plausible for OFI-containing supplements to be used as alternative estrogen replacement therapy. In the case of polypharmacy with the consumption of OFI-containing botanicals in post- or peri-menopausal women, it is critical to determine the potential drug-OFI interaction due to the modulation of drug metabolism. In the present study, the modulating effects on the hepatic drug metabolizing enzymes (DMEs) by OFI and its flavonoid constituents (kaempferol, quercetin, isorhamnetin, and their glycosidic forms) were investigated using the liver microsomal fractions prepared from ovariectomized (OVX) rats, human liver microsomes, and human hepatocarcinoma cell line (HepG2). As a result, the oral administration of extracts of OFI (OFIE) in OVX rats induced hepatic CYP2B1, CYP3A1, and UGT2B1. OFIE, hydrolyzed (hdl) OFIE, and several flavonols induced the transcriptional activities of both CYP2B6 and CYP3A4 genes in HepG2 cells. Finally, OFIE did not inhibit activities of cytochrome P450 (CYPs) or uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), whereas hdl OFIE or flavonol treatment inhibited CYP1A2 and CYP3A1/3A4 in rat and human liver microsomes. Our data demonstrate that OFIE may induce or inhibit certain types of DMEs and indicate that drug-OFI interaction may occur when the substrate or inhibitor drugs of specific CYPs or UGTs are taken concomitantly with OFI-containing products.
Targeting Cytokines as Evolving Treatment Strategies in Chronic Inflammatory Airway Diseases
Authors: Garth Jaleesa , Barnes Jarrod W. , Krick Stefanie
Published: October 2018

Cytokines are key players in the initiation and propagation of inflammation in chronic inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD), bronchiectasis and allergic asthma. This makes them attractive targets for specific novel anti-inflammatory treatment strategies. Recently, both interleukin-1 (IL-1) and IL-6 have been associated with negative health outcomes, mortality and a pro-inflammatory phenotype in COPD. IL-6 in COPD was shown to correlate negatively with lung function, and IL-1beta was induced by cigarette smoke in the bronchial epithelium, causing airway inflammation. Furthermore, IL-8 has been shown to be a pro-inflammatory marker in bronchiectasis, COPD and allergic asthma. Clinical trials using specific cytokine blockade therapies are currently emerging and have contributed to reduce exacerbations and steroid use in COPD. Here, we present a review of the current understanding of the roles of cytokines in the pathophysiology of chronic inflammatory airway diseases. Furthermore, outcomes of clinical trials in cytokine blockade as novel treatment strategies for selected patient populations with those diseases will be discussed.
PWCDA: Path Weighted Method for Predicting circRNA-Disease Associations
Authors: Lei Xiujuan , Fang Zengqiang , Chen Luonan , Wu Fang-Xiang
Published: October 2018

CircRNAs have particular biological structure and have proven to play important roles in diseases. It is time-consuming and costly to identify circRNA-disease associations by biological experiments. Therefore, it is appealing to develop computational methods for predicting circRNA-disease associations. In this study, we propose a new computational path weighted method for predicting circRNA-disease associations. Firstly, we calculate the functional similarity scores of diseases based on disease-related gene annotations and the semantic similarity scores of circRNAs based on circRNA-related gene ontology, respectively. To address missing similarity scores of diseases and circRNAs, we calculate the Gaussian Interaction Profile (GIP) kernel similarity scores for diseases and circRNAs, respectively, based on the circRNA-disease associations downloaded from circR2Disease database (http://bioinfo.snnu.edu.cn/CircR2Disease/). Then, we integrate disease functional similarity scores and circRNA semantic similarity scores with their related GIP kernel similarity scores to construct a heterogeneous network made up of three sub-networks: disease similarity network, circRNA similarity network and circRNA-disease association network. Finally, we compute an association score for each circRNA-disease pair based on paths connecting them in the heterogeneous network to determine whether this circRNA-disease pair is associated. We adopt leave one out cross validation (LOOCV) and five-fold cross validations to evaluate the performance of our proposed method. In addition, three common diseases, Breast Cancer, Gastric Cancer and Colorectal Cancer, are used for case studies. Experimental results illustrate the reliability and usefulness of our computational method in terms of different validation measures, which indicates PWCDA can effectively predict potential circRNA-disease associations.
Regulating Apoptosis by Degradation: The N-End Rule-Mediated Regulation of Apoptotic Proteolytic Fragments in Mammalian Cells
Authors: Eldeeb Mohamed A. , Fahlman Richard P. , Esmaili Mansoore , Ragheb Mohamed A.
Published: October 2018

A pivotal hallmark of some cancer cells is the evasion of apoptotic cell death. Importantly, the initiation of apoptosis often results in the activation of caspases, which, in turn, culminates in the generation of proteolytically-activated protein fragments with potentially new or altered roles. Recent investigations have revealed that the activity of a significant number of the protease-generated, activated, pro-apoptotic protein fragments can be curbed via their selective degradation by the N-end rule degradation pathways. Of note, previous work revealed that several proteolytically-generated, pro-apoptotic fragments are unstable in cells, as their destabilizing N-termini target them for proteasomal degradation via the N-end rule degradation pathways. Remarkably, previous studies also showed that the proteolytically-generated anti-apoptotic Lyn kinase protein fragment is targeted for degradation by the UBR1/UBR2 E3 ubiquitin ligases of the N-end rule pathway in chronic myeloid leukemia cells. Crucially, the degradation of cleaved fragment of Lyn by the N-end rule counters imatinib resistance in these cells, implicating a possible linkage between the N-end rule degradation pathway and imatinib resistance. Herein, we highlight recent studies on the role of the N-end rule proteolytic pathways in regulating apoptosis in mammalian cells, and also discuss some possible future directions with respect to apoptotic proteolysis signaling.
Tissue Expression Difference between mRNAs and lncRNAs
Authors: Chen Lei , Zhang Yu-Hang , Pan Xiaoyong , Liu Min , Wang Shaopeng , Huang Tao , Cai Yu-Dong
Published: October 2018

Messenger RNA (mRNA) and long noncoding RNA (lncRNA) are two main subgroups of RNAs participating in transcription regulation. With the development of next generation sequencing, increasing lncRNAs are identified. Many hidden functions of lncRNAs are also revealed. However, the differences in lncRNAs and mRNAs are still unclear. For example, we need to determine whether lncRNAs have stronger tissue specificity than mRNAs and which tissues have more lncRNAs expressed. To investigate such tissue expression difference between mRNAs and lncRNAs, we encoded 9339 lncRNAs and 14,294 mRNAs with 71 expression features, including 69 maximum expression features for 69 types of cells, one feature for the maximum expression in all cells, and one expression specificity feature that was measured as Chao-Shen-corrected Shannon’s entropy. With advanced feature selection methods, such as maximum relevance minimum redundancy, incremental feature selection methods, and random forest algorithm, 13 features presented the dissimilarity of lncRNAs and mRNAs. The 11 cell subtype features indicated which cell types of the lncRNAs and mRNAs had the largest expression difference. Such cell subtypes may be the potential cell models for lncRNA identification and function investigation. The expression specificity feature suggested that the cell types to express mRNAs and lncRNAs were different. The maximum expression feature suggested that the maximum expression levels of mRNAs and lncRNAs were different. In addition, the rule learning algorithm, repeated incremental pruning to produce error reduction algorithm, was also employed to produce effective classification rules for classifying lncRNAs and mRNAs, which gave competitive results compared with random forest and could give a clearer picture of different expression patterns between lncRNAs and mRNAs. Results not only revealed the heterogeneous expression pattern of lncRNA and mRNA, but also gave rise to the development of a new tool to identify the potential biological functions of such RNA subgroups.
Effects of Nitrogen Level during Seed Production on Wheat Seed Vigor and Seedling Establishment at the Transcriptome Level
Authors: Wen Daxing , Xu Haicheng , Xie Liuyong , He Mingrong , Hou Hongcun , Wu Chenglai , Li Yan , Zhang Chunqing
Published: October 2018

Nitrogen fertilizer is a critical determinant of grain yield and seed quality in wheat. However, the mechanism of nitrogen level during seed production affecting wheat seed vigor and seedling establishment at the transcriptome level remains unknown. Here, we report that wheat seeds produced under different nitrogen levels (N0, N168, N240, and N300) showed significant differences in seed vigor and seedling establishment. In grain yield and seed vigor, N0 and N240 treatments showed the minimum and maximum, respectively. Subsequently, we used RNA-seq to analyze the transcriptomes of seeds and seedlings under N0 and N240 at the early stage of seedling establishment. Gene Ontology (GO) term enrichment analysis revealed that dioxygenase-activity-related genes were dramatically upregulated in faster growing seedlings. Among these genes, the top three involved linoleate 9S-lipoxygenase (Traes_2DL_D4BCDAA76, Traes_2DL_CE85DC5C0, and Traes_2DL_B5B62EE11). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that pathways involved in nutrient mobilization and the antioxidant system showed enhanced expression under N240. Moreover, seeds with faster growing seedlings had a higher gene expression level of α-amylase, which was consistent with α-amylase activity. Taken together, we propose a model for seedling establishment and seed vigor in response to nitrogen level during seed production.
Ero1-Mediated Reoxidation of Protein Disulfide Isomerase Accelerates the Folding of Cone Snail Toxins
Authors: O’Brien Henrik , Kanemura Shingo , Okumura Masaki , Baskin Robert P. , Bandyopadhyay Pradip K. , Olivera Baldomero M. , Ellgaard Lars , Inaba Kenji , Safavi-Hemami Helena
Published: October 2018

Disulfide-rich peptides are highly abundant in nature and their study has provided fascinating insight into protein folding, structure and function. Venomous cone snails belong to a group of organisms that express one of the largest sets of disulfide-rich peptides (conotoxins) found in nature. The diversity of structural scaffolds found for conotoxins suggests that specialized molecular adaptations have evolved to ensure their efficient folding and secretion. We recently showed that canonical protein disulfide isomerase (PDI) and a conotoxin-specific PDI (csPDI) are ubiquitously expressed in the venom gland of cone snails and play a major role in conotoxin folding. Here, we identify cone snail endoplasmic reticulum oxidoreductin-1 (Conus Ero1) and investigate its role in the oxidative folding of conotoxins through reoxidation of cone snail PDI and csPDI. We show that Conus Ero1 preferentially reoxidizes PDI over csPDI, suggesting that the reoxidation of csPDI may rely on an Ero1-independent molecular pathway. Despite the preferential reoxidation of PDI over csPDI, the combinatorial effect of Ero1 and csPDI provides higher folding yields than Ero1 and PDI. We further demonstrate that the highest in vitro folding rates of two model conotoxins are achieved when all three enzymes are present, indicating that these enzymes may act synergistically. Our findings provide new insight into the generation of one of the most diverse classes of disulfide-rich peptides and may improve current in vitro approaches for the production of venom peptides for pharmacological studies.
Structural and Functional Dynamics of Dehydrins: A Plant Protector Protein under Abiotic Stress
Authors: Yu Zhengyang , Wang Xin , Zhang Linsheng
Published: October 2018

Abiotic stress affects the growth and development of crops tremendously, worldwide. To avoid adverse environmental effects, plants have evolved various efficient mechanisms to respond and adapt to harsh environmental factors. Stress conditions are associated with coordinated changes in gene expressions at a transcriptional level. Dehydrins have been extensively studied as protectors in plant cells, owing to their vital roles in sustaining the integrity of membranes and lactate dehydrogenase (LDH). Dehydrins are highly hydrophilic and thermostable intrinsically disordered proteins (IDPs), with at least one Lys-rich K-segment. Many dehydrins are induced by multiple stress factors, such as drought, salt, extreme temperatures, etc. This article reviews the role of dehydrins under abiotic stress, regulatory networks of dehydrin genes, and the physiological functions of dehydrins. Advances in our understanding of dehydrin structures, gene regulation and their close relationships with abiotic stresses demonstrates their remarkable ability to enhance stress tolerance in plants.