bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Large Educational Institutes Become Free from Grid Systems? Determination of Hybrid Renewable Energy Systems in Thailand
Authors: Park Eunil , Kwon Sang Jib , del Pobil Angel P.
Published: June 2019

In some countries, renewable energy resources have become one of the mainstreams of energy savings and sustainable development. Thailand is one of the major countries to use renewable energy generation facilities in public buildings. In particular, public educational institutes consume large amounts of electricity from the grid. To reduce the electricity dependency on the national grid connection and greenhouse gas emissions, this paper introduces potential optimized solutions of renewable energy generation systems for a public university in Thailand, Chiang Mai University. Based on the simulation results from HOMER software, the potential configuration organized by PV panels, batteries and converters is proposed. The suggested configuration achieves 100% of the renewable fraction with $0.728 of the cost of energy for per electricity. Moreover, the greenhouse gas emissions are significantly reduced. Both the implications and limitations are presented based on simulation results.
Determination of the Area Affected by Agricultural Burning
Authors: Prato Daniel F. , Huertas Jose I.
Published: June 2019

Agricultural burning is still a common practice around the world. It is associated with the high emission of air pollutants, including short-term climate change forcing pollutants such as black carbon and PM2.5. The legal requirements to start any regulatory actions to control them is the identification of its area of influence. However, this task is challenging from the experimental and modeling point of view, since it is a short-term event with a moving area source of pollutants. In this work, we assessed this agricultural burning influence-area using the US Environmental authorities recommended air dispersion model (AERMOD). We considered different sizes and geometries of burning areas located on flat terrains, and several crops burning under the worst-case scenario of meteorological conditions. The influence area was determined as the largest area where the short-term concentrations of pollutants (1 h or one day) exceed the local air quality standards. We found that this area is a band around the burning area whose size increases with the burning rate but not with its size. Finally, we suggested alternatives of public policy to regulate this activity, which is based on limiting the burning-rate in the way that no existing households remain inside the resulting influence-area. However, this policy should be understood as a transition towards a policy that forbids agricultural burning.
Recent Advances on the Results for Nonunique Fixed in Various Spaces
Authors: Karapınar Erdal
Published: June 2019

In this short survey, we aim to underline the importance of the non-unique fixed point results in various abstract spaces. We recall a brief background on the topic and we combine, collect and unify several existing non-unique fixed points in the literature. Some interesting examples are considered.
Role of the COP9 Signalosome (CSN) in Cardiovascular Diseases
Authors: Milic Jelena , Tian Yuan , Bernhagen Jürgen
Published: June 2019

The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is an evolutionarily conserved multi-protein complex, consisting of eight subunits termed CSN1-CSN8. The main biochemical function of the CSN is the control of protein degradation via the ubiquitin-proteasome-system through regulation of cullin-RING E3-ligase (CRL) activity by deNEDDylation of cullins, but the CSN also serves as a docking platform for signaling proteins. The catalytic deNEDDylase (isopeptidase) activity of the complex is executed by CSN5, but only efficiently occurs in the three-dimensional architectural context of the complex. Due to its positioning in a central cellular pathway connected to cell responses such as cell-cycle, proliferation, and signaling, the CSN has been implicated in several human diseases, with most evidence available for a role in cancer. However, emerging evidence also suggests that the CSN is involved in inflammation and cardiovascular diseases. This is both due to its role in controlling CRLs, regulating components of key inflammatory pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and complex-independent interactions of subunits such as CSN5 with inflammatory proteins. In this case, we summarize and discuss studies suggesting that the CSN may have a key role in cardiovascular diseases such as atherosclerosis and heart failure. We discuss the implicated molecular mechanisms ranging from inflammatory NF-κB signaling to proteotoxicity and necrosis, covering disease-relevant cell types such as myeloid and endothelial cells or cardiomyocytes. While the CSN is considered to be disease-exacerbating in most cancer entities, the cardiovascular studies suggest potent protective activities in the vasculature and heart. The underlying mechanisms and potential therapeutic avenues will be critically discussed.
Towards CMOS Integrated Microfluidics Using Dielectrophoretic Immobilization
Authors: Matbaechi Ettehad Honeyeh , Yadav Rahul Kumar , Guha Subhajit , Wenger Christian
Published: June 2019

Dielectrophoresis (DEP) is a nondestructive and noninvasive method which is favorable for point-of-care medical diagnostic tests. This technique exhibits prominent relevance in a wide range of medical applications wherein the miniaturized platform for manipulation (immobilization, separation or rotation), and detection of biological particles (cells or molecules) can be conducted. DEP can be performed using advanced planar technologies, such as complementary metal-oxide-semiconductor (CMOS) through interdigitated capacitive biosensors. The dielectrophoretically immobilization of micron and submicron size particles using interdigitated electrode (IDE) arrays is studied by finite element simulations. The CMOS compatible IDEs have been placed into the silicon microfluidic channel. A rigorous study of the DEP force actuation, the IDE’s geometrical structure, and the fluid dynamics are crucial for enabling the complete platform for CMOS integrated microfluidics and detection of micron and submicron-sized particle ranges. The design of the IDEs is performed by robust finite element analyses to avoid time-consuming and costly fabrication processes. To analyze the preliminary microfluidic test vehicle, simulations were first performed with non-biological particles. To produce DEP force, an AC field in the range of 1 to 5 V (peak-to-peak) is applied to the IDE. The impact of the effective external and internal properties, such as actuating DEP frequency and voltage, fluid flow velocity, and IDE’s geometrical parameters are investigated. The IDE based system will be used to immobilize and sense particles simultaneously while flowing through the microfluidic channel. The sensed particles will be detected using the capacitive sensing feature of the biosensor. The sensing and detecting of the particles are not in the scope of this paper and will be described in details elsewhere. However, to provide a complete overview of this system, the working principles of the sensor, the readout detection circuit, and the integration process of the silicon microfluidic channel are briefly discussed.
HOTAIR as a Prognostic Predictor for Diverse Human Cancers: A Meta- and Bioinformatics Analysis
Authors: Toy Halil Ibrahim , Okmen Didem , Kontou Panagiota I. , Georgakilas Alexandros G. , Pavlopoulou Athanasia
Published: June 2019

Several studies suggest that upregulated expression of the long non-coding RNA HOX transcript antisense RNA (HOTAIR) is a negative predictive biomarker for numerous cancers. Herein, we performed a meta-analysis to further investigate the prognostic value of HOTAIR expression in diverse human cancers. To this end, a systematic literature review was conducted in order to select scientific studies relevant to the association between HOTAIR expression and clinical outcomes, including overall survival (OS), recurrence-free survival (RFS)/disease-free survival (DFS), and progression-free survival (PFS)/metastasis-free survival (MFS) of cancer patients. Collectively, 53 eligible studies including a total of 4873 patients were enrolled in the current meta-analysis. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were calculated to assess the relationship between HOTAIR and cancer patients’ survival. Elevated HOTAIR expression was found to be significantly associated with OS, RFS/DFS and PFS/MFS in diverse types of cancers. These findings were also corroborated by the results of bioinformatics analysis on overall survival. Therefore, based on our findings, HOTAIR could serve as a potential biomarker for the prediction of cancer patient survival in many different types of human cancers.
Extracellular Nanovesicles Secreted by Human Osteosarcoma Cells Promote Angiogenesis
Authors: Perut Francesca , Roncuzzi Laura , Zini Nicoletta , Massa Annamaria , Baldini Nicola
Published: June 2019

Angiogenesis involves a number of different players among which extracellular nanovesicles (EVs) have recently been proposed as an efficient cargo of pro-angiogenic mediators. Angiogenesis plays a key role in osteosarcoma (OS) development and progression. Acidity is a hallmark of malignancy in a variety of cancers, including sarcomas, as a result of an increased energetic metabolism. The aim of this study was to investigate the role of EVs derived from osteosarcoma cells on angiogenesis and whether extracellular acidity, generated by tumor metabolism, could influence EVs activity. For this purpose, we purified and characterized EVs from OS cells maintained at either acidic or neutral pH. The ability of EVs to induce angiogenesis was assessed in vitro by endothelial cell tube formation and in vivo using chicken chorioallantoic membrane. Our findings demonstrated that EVs derived from osteosarcoma cells maintained either in acidic or neutral conditions induced angiogenesis. The results showed that miRNA and protein content of EVs cargo are correlated with pro-angiogenic activity and this activity is increased by the acidity of tumor microenvironment. This study provides evidence that EVs released by human osteosarcoma cells act as carriers of active angiogenic stimuli that are able to promote endothelial cell functions relevant to angiogenesis.
Gold as a Possible Alternative to Platinum-Based Chemotherapy for Colon Cancer Treatment
Authors: Mármol Inés , Quero Javier , Rodríguez-Yoldi María Jesús , Cerrada Elena
Published: June 2019

Due to the increasing incidence and high mortality associated with colorectal cancer (CRC), novel therapeutic strategies are urgently needed. Classic chemotherapy against CRC is based on oxaliplatin and other cisplatin analogues; however, platinum-based therapy lacks selectivity to cancer cells and leads to deleterious side effects. In addition, tumor resistance to oxaliplatin is related to chemotherapy failure. Gold(I) derivatives are a promising alternative to platinum complexes, since instead of interacting with DNA, they target proteins overexpressed on tumor cells, thus leading to less side effects than, but a comparable antitumor effect to, platinum derivatives. Moreover, given the huge potential of gold nanoparticles, the role of gold in CRC chemotherapy is not limited to gold(I) complexes. Gold nanoparticles have been found to be able to overcome multidrug resistance along with reduced side effects due to a more efficient uptake of classic drugs. Moreover, the use of gold nanoparticles has enhanced the effect of traditional therapies such as radiotherapy, photothermal therapy, or photodynamic therapy, and has displayed a potential role in diagnosis as a consequence of their optic properties. Herein, we have reviewed the most recent advances in the use of gold(I) derivatives and gold nanoparticles in CRC therapy.
Influence of Chemical Modifications of Polyhydroxyalkanoate-Derived Fatty Acids on Their Antimicrobial Properties
Authors: Snoch Wojciech , Stępień Karolina , Prajsnar Justyna , Staroń Jakub , Szaleniec Maciej , Guzik Maciej
Published: June 2019

Sugar esters are bioactive compounds derived from renewable resources. They consist of a sugar moiety with attached non-polar part – usually a fatty acid. These compounds find uses in cosmetic, food and pharmaceutical industries as surfactants due to their physicochemical and antimicrobial activities. In this study we have produced fatty acids for sugar ester synthesis from bacterially derived polyesters, namely polyhydroxyalkanoates (PHAs). We have developed methodology to decorate PHA monomers with a fluorinated moiety. With aid of biocatalysis a series of glucose esters was created with unmodified and modified PHA monomers. All synthesised compounds showed moderate antimicrobial activity.
A Numerical Method for Flexural Vibration Band Gaps in A Phononic Crystal Beam with Locally Resonant Oscillators
Authors: Liang Xu , Wang Titao , Jiang Xue , Liu Zhen , Ruan Yongdu , Deng Yu
Published: June 2019

The differential quadrature method has been developed to calculate the elastic band gaps from the Bragg reflection mechanism in periodic structures efficiently and accurately. However, there have been no reports that this method has been successfully used to calculate the band gaps of locally resonant structures. This is because, in the process of using this method to calculate the band gaps of locally resonant structures, the non-linear term of frequency exists in the matrix equation, which makes it impossible to solve the dispersion relationship by using the conventional matrix-partitioning method. Hence, an accurate and efficient numerical method is proposed to calculate the flexural band gap of a locally resonant beam, with the aim of improving the calculation accuracy and computational efficiency. The proposed method is based on the differential quadrature method, an unconventional matrix-partitioning method, and a variable substitution method. A convergence study and validation indicate that the method has a fast convergence rate and good accuracy. In addition, compared with the plane wave expansion method and the finite element method, the present method demonstrates high accuracy and computational efficiency. Moreover, the parametric analysis shows that the width of the 1st band gap can be widened by increasing the mass ratio or the stiffness ratio or decreasing the lattice constant. One can decrease the lower edge of the 1st band gap by increasing the mass ratio or decreasing the stiffness ratio. The band gap frequency range calculated by the Timoshenko beam theory is lower than that calculated by the Euler-Bernoulli beam theory. The research results in this paper may provide a reference for the vibration reduction of beams in mechanical or civil engineering fields.
Red Grouper (Epinephelus morio) Shape Faunal Communities via Multiple Ecological Pathways
Authors: Ellis Robert D.
Published: June 2019

Organisms that modify the availability of abiotic resources for other species can alter the structure and function of ecological communities through multiple pathways. In Florida Bay, red grouper (Epinephelus morio) engineer habitats by excavating sediment and detritus from karst solution holes and are also predators that consume a variety of benthic crustaceans and fish, some of which colonize engineered habitats. The effect of red grouper on these communities is complex as colonizing species interact with red grouper in different ways, including both direct (e.g., predator–prey) and indirect interactions. Here, I present the results of an experiment designed to test the direct effects of red grouper on faunal communities associated with Florida Bay solution holes by excluding red grouper from solution holes for four weeks. Red grouper presence generally had positive effects on the abundance, richness, and diversity of faunal communities associated with engineered habitats. Few strong interactions were observed between red grouper and colonizing species, mainly juvenile coral reef fishes. These results suggest that by acting as both a predator and habitat engineer, red grouper shape unique communities, distinct from those of surrounding areas, and influence the composition of communities associated with manipulated habitats.
Invasive Plant Species Establishment and Range Dynamics in Sri Lanka under Climate Change
Authors: Kariyawasam Champika S. , Kumar Lalit , Ratnayake Sujith S.
Published: June 2019

Plant invasion has been widely recognized as an agent of global change that has the potential to have severe impacts under climate change. The challenges posed by invasive alien plant species (IAPS) on biodiversity and ecosystem stability is growing and not adequately studied, especially in developing countries. Defining climate suitability for multiple invasive plants establishment is important for early and strategic interventions to control and manage plant invasions. We modeled priority IAPS in Sri Lanka to identify the areas of greatest climatic suitability for their establishment and observed how these areas could be altered under projected climate change. We used Maximum Entropy method to model 14 nationally significant IAPS under representative concentration pathways 4.5 and 8.5 for 2050 and 2070. The combined climate suitability map produced by summing up climatic suitability of 14 IAPS was further classified into five classes in ArcMap as very high, high, moderate, low, and very low. South and west parts of Sri Lanka are projected to have potentially higher climatic suitability for a larger number of IAPS. We observed suitable area changes (gains and losses) in all five classes of which two were significant enough to make an overall negative impact i.e., (i) contraction of the very low class and (ii) expansion of the moderate class. Both these changes trigger the potential risk from IAPS in Sri Lanka in the future.
An Information Theory Approach for the Analysis of Individual and Combined Evaluation Parameters of Multiple Age-Related Diseases
Authors: Blokh David , Stambler Ilia , Lubart Emilia , Mizrahi Eliyahu H.
Published: June 2019

In view of the frequent presence of several aging-related diseases in geriatric patients, there is a need to develop analytical methodologies that would be able to perform diagnostic evaluation of several diseases at once by individual or combined evaluation parameters and select the most informative parameters or parameter combinations. So far there have been no established formal methods to enable such capabilities. We develop a new formal method for the evaluation of multiple age-related diseases by calculating the informative values (normalized mutual information) of particular parameters or parameter combinations on particular diseases, and then combine the ranks of informative values to provide an overall estimation (or correlation) on several diseases at once. Using this methodology, we evaluate a geriatric cohort, with several common age-related diseases, including cognitive and physical impairments (dementia, chronic obstructive pulmonary disease—COPD and ischemic heart disease), utilizing a set of evaluation parameters (such as demographic data and blood biomarkers) routinely available in geriatric clinical practice. This method permitted us to establish the most informative parameters and parameter combinations for several diseases at once. Combinations of evaluation parameters were shown to be more informative than individual parameters. This method, with additional clinical data, may help establish the most informative parameters and parameter combinations for the diagnostic evaluation of multiple age-related diseases and enhance specific assessment for older multi-morbid patients and treatments against old-age multimorbidity.
Parallel Implementation on FPGA of Support Vector Machines Using Stochastic Gradient Descent
Authors: Lopes Felipe F. , Ferreira João Canas , Fernandes Marcelo A. C.
Published: June 2019

Sequential Minimal Optimization (SMO) is the traditional training algorithm for Support Vector Machines (SVMs). However, SMO does not scale well with the size of the training set. For that reason, Stochastic Gradient Descent (SGD) algorithms, which have better scalability, are a better option for massive data mining applications. Furthermore, even with the use of SGD, training times can become extremely large depending on the data set. For this reason, accelerators such as Field-programmable Gate Arrays (FPGAs) are used. This work describes an implementation in hardware, using FPGA, of a fully parallel SVM using Stochastic Gradient Descent. The proposed FPGA implementation of an SVM with SGD presents speedups of more than 10,000× relative to software implementations running on a quad-core processor and up to 319× compared to state-of-the-art FPGA implementations while requiring fewer hardware resources. The results show that the proposed architecture is a viable solution for highly demanding problems such as those present in big data analysis.
Multi-Model Reliable Control for Variable Fault Systems under LQG Framework
Authors: Liu Lei , Qian Fucai , Xie Guo , Wang Min
Published: June 2019

The problem of reliable control for variable fault systems under linear quadratic Gaussian (LQG) framework is studied in this paper. Firstly, a cluster of models is used to cover the dynamic behaviors of different fault modes of a system and, for each model, LQG control is implemented. By using the a posteriori probability of model innovation as the weight information, a multi-model reliable control (MMRC) is proposed. Secondly, it is proved that MMRC can enable the controller to learn the real operating mode of the system. When the controller is in a deadlock state, a deadlock avoidance strategy is given and its convergence of the a posteriori probability is proved. Finally, the validity of MMRC is verified by an example simulation of the lateral-directional control system of an aircraft. Simulation results show that MMRC guarantees an acceptable performance of the closed-loop system. In addition, since the controller fuses the control law of each model according to the weight information, when the system model is switched, the controller implements a soft switching, which avoids the jitter caused by frequent hard switching to the system.
A Control Strategy of Modular Multilevel Converter with Integrated Battery Energy Storage System Based on Battery Side Capacitor Voltage Control
Authors: Wang Zhe , Lin Hua , Ma Yajun
Published: June 2019

A modular multilevel converter with an integrated battery energy storage system (MMC-BESS) has been proposed for high-voltage applications for large-scale renewable energy resources. As capacitor voltage balance is key to the normal operation of the system, the conventional control strategy for the MMC can be significantly simplified by controlling the individual capacitor voltage through a battery side converter in the MMC-BESS. However, the control strategy of the MMC-BESS under rectifier mode operation has not yet been addressed, where the conventional control strategy cannot be directly employed due to the additional power flow of batteries. For this defect, the rectifier mode operation of the MMC-BESS based on a battery side capacitor voltage control was analyzed in this paper, proposing a control strategy for this application scenario according to the equivalent circuit of MMC-BESS, avoiding passive impact on the state-of-charge (SOC) equalization of batteries. Furthermore, the implementation of a battery side converter control is proposed by simplifying the capacitor voltage filter scheme within phase arm, which enhances its performance and facilitates the realization of control strategy. Finally, simulation and experimental results validate the feasibility and effectiveness of the proposed control strategy.
Genome-Wide Analysis of the miRNA–mRNAs Network Involved in Cold Tolerance in Populus simonii × P. nigra
Authors: Zhou Bo , Kang Yutong , Leng Jingtong , Xu Qijiang
Published: June 2019

Background: Cold tolerance is important for plants’ geographical distribution and survival in extreme seasonal variations of climate. However, Populus simonii × P. nigra shows wide adaptability and strong cold resistance. Transcriptional and post-transcriptional regulation of cold-responsive genes is crucial for cold tolerance in plants. To understand the roles of regulatory RNAs under cold induction in Populus simonii × P. nigra, we constructed cDNA and small RNA libraries from leaf buds treated or not with −4 °C for 8 h for analysis. Results: Through high-throughput sequencing and differential expression analysis, 61 miRNAs and 1229 DEGs were identified under cold induction condition in Populus simonii × P. nigra. The result showed that miR167a, miR1450, miR319a, miR395b, miR393a-5p, miR408-5p, and miR168a-5p were downregulated, whereas transcription level of miR172a increased under the cold treatment. Thirty-one phased-siRNA were also obtained (reads ≥ 4) and some of them proceeded from TAS3 loci. Analysis of the differentially expressed genes (DEGs) showed that transcription factor genes such as Cluster-15451.2 (putative MYB), Cluster-16493.29872 (putative bZIP), Cluster-16493.29175 (putative SBP), and Cluster-1378.1 (putative ARF) were differentially expressed in cold treated and untreated plantlets of Populus simonii × P. nigra. Integrated analysis of miRNAs and transcriptome showed miR319, miR159, miR167, miR395, miR390, and miR172 and their target genes, including MYB, SBP, bZIP, ARF, LHW, and ATL, were predicted to be involved in ARF pathway, SPL pathway, DnaJ related photosystem II, and LRR receptor kinase, and many of them are known to resist chilling injury. Particularly, a sophisticated regulatory model including miRNAs, phasiRNAs, and targets of them was set up. Conclusions: Integrated analysis of miRNAs and transcriptome uncovered the complicated regulation of the tolerance of cold in Populus simonii × P. nigra. MiRNAs, phasiRNAs, and gene-encoded transcription factors were characterized at a whole genome level and their expression patterns were proved to be complementary. This work lays a foundation for further research of the pathway of sRNAs and regulatory factors involved in cold tolerance.
Telemonitoring and Quality of Life in Patients after 12 Months Following a Pacemaker Implant: the Nordland Study, a Randomised Trial
Authors: López-Liria Remedios , López-Villegas Antonio , Enebakk Terje , Thunhaug Hilde , Lappegård Knut Tore , Catalán-Matamoros Daniel
Published: June 2019

The purpose of this study was to analyse the health-related quality of life (HRQoL) of patients followed up using a remote device-monitoring system (TM) compared to patients followed up through standard outpatient visits (HM), 12 months after the implantation of a pacemaker. This was a trial design that used the EuroQol-5D Questionnaire and the Minnesota Living with Heart Failure Questionnaire (MLHF). The HRQoL of a cohort of 50 consecutive patients randomly allocated to one of the two follow-up modalities was measured at baseline and then during follow-up, 12 months after the pacemaker implantation. Eventually, 23 patients were followed-up through standard outpatient visits, while 23 used a remote monitoring system. Results: The baseline clinical characteristics and health-related quality of life of the patients from both groups were observed to be statistically similar. Twelve months after the pacemaker implantation, both groups showed statistically significant improvements in the baseline parameters based on the MLHF. The patients followed up through hospital visits showed a greater increase in MLHF-HRQoL after 12 months, although the increase was not significantly greater than that of the TM group. Furthermore, the frequencies of emergency visits and re-hospitalisations did not differ between the groups.
On Unbalanced Sampling in Bankruptcy Prediction
Authors: Gruszczyński Marek
Published: June 2019

The paper discusses methodological topics of bankruptcy prediction modelling—unbalanced sampling, sample bias, and unbiased predictions of bankruptcy. Bankruptcy models are typically estimated with the use of non-random samples, which creates sample choice biases. We consider two types of unbalanced samples: (a) when bankrupt and non-bankrupt companies enter the sample in unequal numbers; and (b) when sample composition allows for different ratios of bankrupt and non-bankrupt companies than those in the population. An imbalance of type (b), being more general, is examined in several sections of the paper. We offer an extended view of the relationship between the biased and unbiased estimated probabilities of bankruptcy—probability of default (PD). A common error in applications is neglecting the possibility of calibrating the PD obtained from a bankruptcy model to the unbiased PD that is population adjusted. We show that Skogsviks’ formula of 2013 coincides with prior correction known for the logit model. This, together with solutions for other binomial models, serves as practical advice for obtaining the calibration of unbiased PDs from popular bankruptcy models. In the final section, we explore sample bias effects on classification.
The Role of Nitric Oxide, ADMA, and Homocysteine in The Etiopathogenesis of Preeclampsia—Review
Authors: Dymara-Konopka Weronika , Laskowska Marzena
Published: June 2019

Preeclampsia is a serious, pregnancy-specific, multi-organ disease process of compound aetiology. It affects 3–6% of expecting mothers worldwide and it persists as a leading cause of maternal and foetal morbidity and mortality. In fact, hallmark features of preeclampsia (PE) result from vessel involvement and demonstrate maternal endothelium as a target tissue. Growing evidence suggests that chronic placental hypoperfusion triggers the production and release of certain agents that are responsible for endothelial activation and injury. In this review, we will present the latest findings on the role of nitric oxide, asymmetric dimethylarginine (ADMA), and homocysteine in the etiopathogenesis of preeclampsia and their possible clinical implications.
The Role of Extracellular Vesicles in Cutaneous Remodeling and Hair Follicle Dynamics
Authors: Carrasco Elisa , Soto-Heredero Gonzalo , Mittelbrunn María
Published: June 2019

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are cell-derived membranous structures that were originally catalogued as a way of releasing cellular waste products. Since the discovery of their function in intercellular communication as carriers of proteins, lipids, and DNA and RNA molecules, numerous therapeutic approaches have focused on the use of EVs, in part because of their minimized risk compared to cell-based therapies. The skin is the organ with the largest surface in the body. Besides the importance of its body barrier function, much attention has been paid to the skin in regenerative medicine because of its cosmetic aspect, which is closely related to disorders affecting pigmentation and the presence or absence of hair follicles. The use of exosomes in therapeutic approaches for cutaneous wound healing has been reported and is briefly reviewed here. However, less attention has been paid to emerging interest in the potential capacity of EVs as modulators of hair follicle dynamics. Hair follicles are skin appendices that mainly comprise an epidermal and a mesenchymal component, with the former including a major reservoir of epithelial stem cells but also melanocytes and other cell types. Hair follicles continuously cycle, undergoing consecutive phases of resting, growing, and regression. Many biomolecules carried by EVs have been involved in the control of the hair follicle cycle and stem cell function. Thus, investigating the role of either naturally produced or therapeutically delivered EVs as signaling vehicles potentially involved in skin homeostasis and hair cycling may be an important step in the attempt to design future strategies towards the efficient treatment of several skin disorders.
TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis
Authors: Hao Yang , Baker David , ten Dijke Peter
Published: June 2019

Transforming growth factor β (TGF-β) is a secreted cytokine that regulates cell proliferation, migration, and the differentiation of a plethora of different cell types. Consistent with these findings, TGF-β plays a key role in controlling embryogenic development, inflammation, and tissue repair, as well as in maintaining adult tissue homeostasis. TGF-β elicits a broad range of context-dependent cellular responses, and consequently, alterations in TGF-β signaling have been implicated in many diseases, including cancer. During the early stages of tumorigenesis, TGF-β acts as a tumor suppressor by inducing cytostasis and the apoptosis of normal and premalignant cells. However, at later stages, when cancer cells have acquired oncogenic mutations and/or have lost tumor suppressor gene function, cells are resistant to TGF-β-induced growth arrest, and TGF-β functions as a tumor promotor by stimulating tumor cells to undergo the so-called epithelial-mesenchymal transition (EMT). The latter leads to metastasis and chemotherapy resistance. TGF-β further supports cancer growth and progression by activating tumor angiogenesis and cancer-associated fibroblasts and enabling the tumor to evade inhibitory immune responses. In this review, we will consider the role of TGF-β signaling in cell cycle arrest, apoptosis, EMT and cancer cell metastasis. In particular, we will highlight recent insights into the multistep and dynamically controlled process of TGF-β-induced EMT and the functions of miRNAs and long noncoding RNAs in this process. Finally, we will discuss how these new mechanistic insights might be exploited to develop novel therapeutic interventions.
Dietary Fatty Acids Affect Red Blood Cell Membrane Composition and Red Blood Cell ATP Release in Dairy Cows
Authors: Revskij Denis , Haubold Susanne , Viergutz Torsten , Kröger-Koch Claudia , Tuchscherer Armin , Kienberger Hermine , Rychlik Michael , Tröscher Arnulf , Hammon Harald M. , Schuberth Hans-Joachim , Mielenz Manfred
Published: June 2019

Diets of dairy cows are often based on maize silage (MS), delivering lower amounts of n-3 fatty acids (FA) compared to grass silage-based diets. The fatty acid composition of the cell membrane can affect the cell function. We evaluated the effects of an MS-based diet on bovine red blood cell (RBC) membrane FA composition and dietary effects on controlled ATP release of RBC. In trial 1, German Holstein cows were fed an MS-based total mixed ration for 24 weeks. The FA composition of RBC membranes from repeatedly taken blood samples was analysed in addition to the abundance of the RBC membrane protein flotillin-1, which is involved in, for example, cell signalling. In trial 2, four rumen fistulated MS-fed cows were abomasally infused in a 4 × 4 Latin square model with three successively increasing lipid dosages (coconut oil, linseed–safflower oil mix (EFA; rich in n-3 FA), Lutalin®, providing conjugated linoleic acids (CLA) or the combination of the supplements, EFA + CLA) for six weeks, followed by a three-week washout period. In trial 2, we analysed RBC ATP release, flotillin-1, and the membrane protein abundance of pannexin-1, which is involved in ATP release as the last part of a signalling cascade. In trial 1, the total amount of n-3 FA in RBC membranes decreased and the flotillin-1 abundance increased over time. In trial 2, the RBC n-3 FA amount was higher after the six-week infusion period of EFA or EFA + CLA. Furthermore, depending on the dosage of FA, the ATP release from RBC increased. The abundance of flotillin-1 and pannexin-1 was not affected in trial 2. It is concluded that changes of the membrane FA composition influence the RBC function, leading to altered ATP release from intact bovine RBC.
A Critical Review of Electroporation as A Plasmid Delivery System in Mouse Skeletal Muscle
Authors: Sokołowska Emilia , Błachnio-Zabielska Agnieszka Urszula
Published: June 2019

The gene delivery to skeletal muscles is a promising strategy for the treatment of both muscular disorders (by silencing or overexpression of specific gene) and systemic secretion of therapeutic proteins. The use of a physical method like electroporation with plate or needle electrodes facilitates long-lasting gene silencing in situ. It has been reported that electroporation enhances the expression of the naked DNA gene in the skeletal muscle up to 100 times and decreases the changeability of the intramuscular expression. Coelectransfer of reporter genes such as green fluorescent protein (GFP), luciferase or beta-galactosidase allows the observation of correctly performed silencing in the muscles. Appropriate selection of plasmid injection volume and concentration, as well as electrotransfer parameters, such as the voltage, the length and the number of electrical pulses do not cause long-term damage to myocytes. In this review, we summarized the electroporation methodology as well as the procedure of electrotransfer to the gastrocnemius, tibialis, soleus and foot muscles and compare their advantages and disadvantages.
Frame-Based Elicitation of Mid-Air Gestures for a Smart Home Device Ecosystem
Authors: Vogiatzidakis Panagiotis , Koutsabasis Panayiotis
Published: June 2019

If mid-air interaction is to be implemented in smart home environments, then the user would have to exercise in-air gestures to address and manipulate multiple devices. This paper investigates a user-defined gesture vocabulary for basic control of a smart home device ecosystem, consisting of 7 devices and a total of 55 referents (commands for device) that can be grouped to 14 commands (that refer to more than one device). The elicitation study was conducted in a frame (general scenario) of use of all devices to support contextual relevance; also, the referents were presented with minimal affordances to minimize widget-specific proposals. In addition to computing agreement rates for all referents, we also computed the internal consistency of user proposals (single-user agreement for multiple commands). In all, 1047 gestures from 18 participants were recorded, analyzed, and paired with think-aloud data. The study reached to a mid-air gesture vocabulary for a smart-device ecosystem, which includes several gestures with very high, high and medium agreement rates. Furthermore, there was high consistency within most of the single-user gesture proposals, which reveals that each user developed and applied her/his own mental model about the whole set of interactions with the device ecosystem. Thus, we suggest that mid-air interaction support for smart homes should not only offer a built-in gesture set but also provide for functions of identification and definition of personalized gesture assignments to basic user commands.
Long-Term Hydroxychloroquine Therapy and Risk of Coronary Artery Disease in Patients with Systemic Lupus Erythematosus
Authors: Yang Deng-Ho , Leong Pui-Ying , Sia Sung-Kien , Wang Yu-Hsun , Wei James Cheng-Chung
Published: June 2019

Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory disease associated with a high prevalence of cardiovascular disease (CVD). Hydroxychloroquine (HCQ) is commonly used to control disease activity in patients with SLE. We evaluated its potential additional therapeutic effect for reducing CVD in SLE patients. We conducted a retrospective cohort study, in which one million participants were sampled from 23 million beneficiaries and data were collected from 2000 to 2013. In total, 826 SLE patients receiving HCQ medication were included after exclusion for previous CVD. The total number of SLE patients was 795 after follow-up for more than one year. After adjusting for chronic comorbidity, a significantly decreased hazard ratio (HR) for coronary artery disease (CAD) was found among SLE patients with a high usage of HCQ for at least 318 days (HR = 0.31, 95% confidence interval, CI: 0.12–0.76). A low HR for CAD was observed in SLE patients with a high cumulative dose of at least 100,267 mg HCQ (HR = 0.25, 95% CI: 0.09–0.66). However, there was no significant lowering of the HR for stroke. Long-term HCQ therapy decreases the HR of CVD in SLE patients. The cardiovascular protective effect of HCQ therapy was associated with decrease in CAD, but not stroke.
Does Emotional Intelligence Matter in Tough Times? A Moderated Mediation Model for Explaining Health and Suicide Risk amongst Short- and Long-Term Unemployed Adults
Authors: Mérida-López Sergio , Extremera Natalio , Quintana-Orts Cirenia , Rey Lourdes
Published: June 2019

This study contributes to knowledge on psychosomatic research by examining a moderated mediation model in which emotional intelligence (EI) is related to mental health, physical health and suicide risk through perceived stress, in samples of short-term (n = 364) and long-term (n = 594) unemployed individuals. The moderating effect of emotional intelligence on the relationships between perceived stress and mental and physical health and suicide risk was tested. The results showed that emotional intelligence was positively associated with mental and physical health and negatively associated with perceived stress and suicide risk. The proposed model only predicted mental health and suicide risk in the long-term unemployed sample. This suggests that emotional intelligence may act as a buffer against the negative impact of unemployment-related stress on mental health and suicide risk when unemployment is prolonged. Therefore, interventions targeting both the promotion of mental health and the prevention of suicide risk via the promotion of emotional abilities may consider length of unemployment.
Metabolomic Investigation of β-Thalassemia in Chorionic Villi Samples
Authors: Monni Giovanni , Murgia Federica , Corda Valentina , Peddes Cristina , Iuculano Ambra , Tronci Laura , Balsamo Antonella , Atzori Luigi
Published: June 2019

Background: Beta-thalassemias are blood disorders characterized by poorly understood clinical phenotypes ranging from asymptomatic to severe anemia. Metabolic composition of the human placenta could be affected by the presence of pathological states such as β-thalassemia. The aim of our study was to describe metabolic changes in chorionic villi samples of fetuses affected by β-thalassemia compared to a control group by applying a metabolomics approach. Methods: Chorionic villi samples were differentiated according to the genetic diagnosis of β-thalassemia: control (Group 1, n = 27); heterozygous (Group 2, n = 7); homozygous (Group 3, n = 7). Gas chromatography–mass spectrometry was used to detect the metabolic composition of the samples. Subsequently, multivariate and univariate statistical analysis was performed. The discriminant metabolites were used to identify the altered pathways. Results: Supervised multivariate models were devised to compare the groups. The model resulting from the comparison between Group 1 and Group 3 was the most significant. Discriminant metabolites were identified, and the most altered pathways were as follows: pentose phosphate pathway (PPP), arachidonic acid metabolism, glycolysis, and gluconeogenesis, suggesting the presence of an energetic shift toward the PPP and the presence of oxidative stress in β-thalassemia chorionic villi samples. Conclusions: The metabolomics approach identified a specific metabolic fingerprint in chorionic villi of fetuses affected by β-thalassemia.
Machine Learning Models of Survival Prediction in Trauma Patients
Authors: Rau Cheng-Shyuan , Wu Shao-Chun , Chuang Jung-Fang , Huang Chun-Ying , Liu Hang-Tsung , Chien Peng-Chen , Hsieh Ching-Hua
Published: June 2019

Background: We aimed to build a model using machine learning for the prediction of survival in trauma patients and compared these model predictions to those predicted by the most commonly used algorithm, the Trauma and Injury Severity Score (TRISS). Methods: Enrolled hospitalized trauma patients from 2009 to 2016 were divided into a training dataset (70% of the original data set) for generation of a plausible model under supervised classification, and a test dataset (30% of the original data set) to test the performance of the model. The training and test datasets comprised 13,208 (12,871 survival and 337 mortality) and 5603 (5473 survival and 130 mortality) patients, respectively. With the provision of additional information such as pre-existing comorbidity status or laboratory data, logistic regression (LR), support vector machine (SVM), and neural network (NN) (with the Stuttgart Neural Network Simulator (RSNNS)) were used to build models of survival prediction and compared to the predictive performance of TRISS. Predictive performance was evaluated by accuracy, sensitivity, and specificity, as well as by area under the curve (AUC) measures of receiver operating characteristic curves. Results: In the validation dataset, NN and the TRISS presented the highest score (82.0%) for balanced accuracy, followed by SVM (75.2%) and LR (71.8%) models. In the test dataset, NN had the highest balanced accuracy (75.1%), followed by the TRISS (70.2%), SVM (70.6%), and LR (68.9%) models. All four models (LR, SVM, NN, and TRISS) exhibited a high accuracy of more than 97.5% and a sensitivity of more than 98.6%. However, NN exhibited the highest specificity (51.5%), followed by the TRISS (41.5%), SVM (40.8%), and LR (38.5%) models. Conclusions: These four models (LR, SVM, NN, and TRISS) exhibited a similar high accuracy and sensitivity in predicting the survival of the trauma patients. In the test dataset, the NN model had the highest balanced accuracy and predictive specificity.
Stability of Psychiatric Diagnoses in Candidates to Liver Transplantation Referred to a Consultation-Liaison Psychiatry Service
Authors: Mattei Giorgio , Moscara Maria , Balducci Jessica , Cavana Silvia , Cherubini Melissa , Piemonte Chiara , Ferrari Silvia , Galeazzi Gian
Published: June 2019

Objective: To investigate the stability over time of the psychiatric diagnoses among candidates to liver transplantation referred to a consultation-liaison psychiatric service. Method: Descriptive study, carried out at the Consultation-Liaison Psychiatry Service (CLPS) placed at the Modena (Italy) General University Hospital. All patients waiting for liver transplantation and repeatedly referred to the CLPS were enrolled. The observation period was from 1 January 2008 to 31 December 2013. Pearson’s coefficients were calculated to measure diagnostic stability (index referral vs. last referral). Results: One hundred patients were assessed (males 67%; mean age 53 ± 7 years old). The mean number of referrals for patients was 3 ± 2. The stability rate of psychiatric diagnosis was 64%. The following diagnoses or conditions were all significantly stable (i.e., all featured by r > 0.5 and p < 0.05): Adjustment disorder, depressive disorder, comorbid anxiety/depressive disorder, substance use disorder (including alcohol), absence of any disorder, and presence of any disorder. Conclusions: The good level of diagnostic stability displayed in the sample may be a function of the clinical and organizational “style” of the CLPS, namely the focus on identifying the prevailing personality traits, defensive mechanisms, and relational patterns.