bluuebunny/crossref_metadata_2025 huggingface dataset:
A Resource-Based View of Competitiveness in the Wind Energy Sector: The Case of Gran Canaria and Tenerife
Authors: Santana-Sarmiento Francisco , Álamo-Vera Francisca Rosa , De Saá-Pérez Petra
Published: March 2019

This paper proposes a new model to assess the socio-economic potential of two outermost islands of the EU to exploit their resources and capabilities for the sustainable development of the wind energy sector. To that end, a territory competitiveness index is calculated from the resource-based view to assess the socio-economic potential of renewable energy sources in Gran Canaria and Tenerife. We propose a model where local resources and capabilities in the wind energy industry are measured, taking into account different sources of information and methodologies, thus ensuring a rigorous process in the index calculation. In order to quantify the basic resources, for example, a methodology based on a multi-criteria analysis (MCA) with a geographic information system (GIS) is suggested, with the objective of obtaining an indicator called “index of available territorial resources." This index synthesizes the map information through a numerical value that allows integrating the territory resource with other indicators of the model, such as market growth, innovative behavior, firms’ concentration, or investment effort by the government. The results of the study show that capabilities development is a key factor to exploit the islands resource endowment in order to achieve a competitive advantage in wind energy.
The Moisture Sources and Transport Processes for a Sudden Rainstorm Associated with Double Low-Level Jets in the Northeast Sichuan Basin of China
Authors: Zhang Fangli , Li Guoping , Yue Jun
Published: March 2019

A sudden rainstorm that occurred in the northeast Sichuan Basin of China in early May 2017 was associated with a southwest low-level jet (SWLJ) and a mountainous low-level jet (MLLJ). This study investigates the impact of the double low-level jets (LLJs) on rainfall diurnal variation by using the data from ERA5 reanalysis, and explores the characteristics of water vapor transport, including the main paths and sources of moisture, by using the HYSPLIT-driven data of the ERA—interim, GDAS (Global Data Assimilation System), and NCEP/NCAR reanalysis data. The analysis shows that the sudden rainstorm in the mountain terrain was located at the left side of the large-scale SWLJ at 700 hPa, and at the exit region of the meso-scale MLLJ at 850 hPa. The double LLJs provide favorable moisture conditions, and the enhancement (weakening) of the LLJs is ahead of the start (end) of the rainstorm. The capacity of the LLJ at 850 hPa with respect to moisture convergence is superior to that at 700 hPa, especially when the MLLJ and the southerly LLJ at 850 hPa appear at the same time. The HYSPLIT backward trajectory model based on Lagrangian methods has favorable applicability in the event of sudden rainstorms in mountainous terrain, and there is no special path of moisture transport in this precipitation event. The main moisture sources of this process are the East China Sea–South China Sea, the Arabian Sea–Indian Peninsula, the Bay of Bengal, and the Middle East, accounting for 38%, 34%, 17% and 11% of the total moisture transport, respectively. Among them, the moisture transport in the Bay of Bengal and the South China Sea–East China Sea is mainly located in the lower troposphere, which is below 900 hPa, while the moisture transport in the Arabian Sea–Indian Peninsula and the Middle East is mainly in the middle and upper layers of the troposphere. The moisture changes of the transport trajectories are affected by the topography, especially the high mountains around the Sichuan Basin.
Structure and Ligands Interactions of Citrus Tryptophan Decarboxylase by Molecular Modeling and Docking Simulations
Authors: Facchiano Angelo , Pignone Domenico , Servillo Luigi , Castaldo Domenico , De Masi Luigi
Published: March 2019

In a previous work, we in silico annotated protein sequences of Citrus genus plants as putative tryptophan decarboxylase (pTDC). Here, we investigated the structural properties of Citrus pTDCs by using the TDC sequence of Catharanthus roseus as an experimentally annotated reference to carry out comparative modeling and substrate docking analyses. The functional annotation as TDC was verified by combining 3D molecular modeling and docking simulations, evidencing the peculiarities and the structural similarities with C. roseus TDC. Docking with l-tryptophan as a ligand showed specificity of pTDC for this substrate. These combined results confirm our previous in silico annotation of the examined protein sequences of Citrus as TDC and provide support for TDC activity in this plant genus.
Zebrafish Larvae as a Behavioral Model in Neuropharmacology
Authors: Basnet Ram Manohar , Zizioli Daniela , Taweedet Somrat , Finazzi Dario , Memo Maurizio
Published: March 2019

Zebrafish larvae show a clear and distinct pattern of swimming in response to light and dark conditions, following the development of a swim bladder at 4 days post fertilization. This swimming behavior is increasingly employed in the screening of neuroactive drugs. The recent emergence of high-throughput techniques for the automatic tracking of zebrafish larvae has further allowed an objective and efficient way of finding subtle behavioral changes that could go unnoticed during manual observations. This review highlights the use of zebrafish larvae as a high-throughput behavioral model for the screening of neuroactive compounds. We describe, in brief, the behavior repertoire of zebrafish larvae. Then, we focus on the utilization of light-dark locomotion test in identifying and screening of neuroactive compounds.
Parkinsonism Risk Factors in Salt Lake City, Utah: A Community-Based Study
Authors: Shprecher David , Zhang Nan , Halverson Matthew , Savica Rodolfo
Published: March 2019

Background: The prevalence of dream enactment behavior and other risk factors for a parkinsonian disorder is not well documented. Methods: A survey on prevalence of parkinsonism risk factors was designed using two validated instruments (REM behavior disorder single item question, bowel movement frequency for constipation) and three exploratory instruments (for hallucinations, cognitive and olfactory complaints.) It was sent by mail and email to patients aged 50 and over at two University of Utah community clinics in Salt Lake City. A total of 7888 unique patients were sent the survey, and 1607 responses were recorded (response rate 20%). Those whose age was missing (n = 117) or less than 50 years (n = 10) were excluded from the analysis. Results: Of the 1406 without personal diagnosis of neurodegenerative disease 62.7% were female, and median age was 63. Family history (FH) of Parkinson’s disease was endorsed by 9%, constipation (defined as a bowel movement less than once per day) by 19%, mild cognitive complaints (MCI) 15.8%, dream enactment 13.7%, subjective hyposmia or anosmia 18.2%, and at least one potential psychotic symptom in 37.6%. Multivariable logistic regression showed male gender, mild cognitive complaints, hearing voices, and at least one potentially psychotic symptom to be significantly associated with dream enactment. Conclusions: This survey shows that dream enactment, a strong predictor of risk for synucleinopathy, is relatively common in the older population; because such individuals rarely come to medical attention of a sleep clinic, such survey research may be useful to identify and recruit at-risk individuals for trials aimed at preventing neurodegenerative disease.
Editorial for Brain Sciences Special Issue: “Diagnosis of Neurogenetic Disorders: Contribution of Next-Generation Sequencing and Deep Phenotyping”
Authors: McNeill Alisdair
Published: March 2019

In this Special Issue we bring together papers demonstrating the need for both detailed genomic and phenotypic studies to aid our scientific and clinical understanding of neurogenetic disorders [...]
Does the Number of Occupants in an Office Influence Individual Perceptions of Comfort and Productivity?—New Evidence from 5000 Office Workers
Authors: Rasheed Eziaku Onyeizu , Khoshbakht Maryam , Baird George
Published: March 2019

Purpose—The purpose of this article is to present evidence of occupants’ perception of their work environment in five different office types (Solo, Duo, 2–4, 5–8 and 8Plus offices). The study examined the influence of the number of office occupants on individual perception of indoor environment quality (IEQ) in office environments. Design/methodology/approach—A dataset of 5000 respondents in 67 commercial and institutional office buildings was analysed using IBM SPSS v23. The dataset contained user response on the BUS Methodology questionnaire that is designed to retrieve occupants’ perception of their work environments. Analysis of Variance (ANOVA) and multiple regression analysis were conducted to calculate the impact of the office environment on occupants’ perception of comfort and productivity. Findings - This study showed that occupants in Solo and Duo offices perceived higher satisfaction with their environment (except for temperature in summer), better health and productivity; and more control over the office environment than those in 5–8 and 8Plus offices. Occupants in 8Plus offices were most satisfied with the temperature in summer. It was also noted that the IEQ factors that predicted comfort were observed to not predict productivity. Noise was the only IEQ factor that had predictive power for both comfort and productivity in all the office spaces. Originality/value—This article provides intriguing findings on occupants’ perception of various types of office environment that contributes significantly to the debate on open-plan versus cellular office environments.
Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen
Authors: Hussaarts Koen G.A.M. , Hurkmans Daan P. , Oomen-de Hoop Esther , van Harten Leonie J. , Berghuis Stan , van Alphen Robbert J. , Spierings Leontine E.A. , van Rossum-Schornagel Quirine C. , Vastbinder Mijntje B. , van Schaik Ron H.N. , van Gelder Teun , Jager Agnes , van Leeuwen Roelof W.F. , Mathijssen Ron H.J.
Published: March 2019

Tamoxifen is a prodrug that is primarily metabolized into the pharmacologically active metabolite endoxifen and eventually into inactive metabolites. The herb curcumin may increase endoxifen exposure by affecting phase II metabolism. We compared endoxifen and tamoxifen exposure in breast cancer patients with or without curcumin, and with addition of the bio-enhancer piperine. Tamoxifen (20–30mg per day (q.d.)) was either given alone, or combined with curcumin (1200 mg three times daily (t.i.d.)) +/− piperine (10 mg t.i.d.). The primary endpoint of this study was the difference in geometric means for the area under the curve (AUC) of endoxifen. Genotyping was performed to determine CYP2D6 and CYP3A4 phenotypes. The endoxifen AUC0–24h decreased with 7.7% (95%CI: −15.4 to 0.7%; p = 0.07) with curcumin and 12.4% (95%CI: −21.9 to −1.9%; p = 0.02) with curcumin and piperine, compared to tamoxifen alone. Tamoxifen AUC0–24h showed similar results. For patients with an extensive CYP2D6 metabolism phenotype (EM), effects were more pronounced than for intermediate CYP2D6 metabolizers (IMs). In conclusion, the exposure to tamoxifen and endoxifen was significantly decreased by concomitant use of curcumin (+/− piperine). Therefore, co-treatment with curcumin could lower endoxifen concentrations below the threshold for efficacy (potentially 20–40% of the patients), especially in EM patients.
Alpha6-Integrin Regulates FGFR1 Expression through the ZEB1/YAP1 Transcription Complex in Glioblastoma Stem Cells Resulting in Enhanced Proliferation and Stemness
Authors: KOWALSKI-CHAUVEL Aline , GOUAZE-ANDERSSON Valerie , BARICAULT Laurent , MARTIN Elodie , DELMAS Caroline , TOULAS Christine , COHEN-JONATHAN-MOYAL Elizabeth , SEVA Catherine
Published: March 2019

Glioblastoma (GBM) is the most lethal primary brain tumor in adults and is known to be particularly aggressive and resistant to anti-cancer therapies, mainly due to the presence of GBM stem cells (GBMSC). By in vitro approaches supported by analysis from patients’ databases, we determined how α6-integrin and Fibroblast Growth Factor Receptor 1 (FGFR1) work in concert to regulate proliferation and stemness of GBMSC. We showed that α6-integrin regulates the expression of FGFR1 and its target gene Fokhead Box M1 (FOXM1) via the ZEB1/YAP1 transcription complex. These results were in accordance with the positive correlation observed in GBM between α6-integrin expression and its target genes ZEB1/YAP1, FGFR1, and FOXM1 in the databases, TCGA and Rembrandt. In addition, the clinical data demonstrate that GBM patients with high levels of the five genes signature, including α6-integrin, ZEB1/YAP1, FGFR1 and FOXM1, have a significantly shorter overall survival. In vitro, we observed a similar decrease in the expression of stemness-related factors, neurospheres forming capacity, as well as spheroids growth when α6-integrin or FGFR1 was blocked individually with specific siRNA, whereas the combination of both siRNA led to a significantly higher inhibition of spheres formation. These data suggest that co-administration of anti-FGFR1 and anti-α6-integrin could provide an improved therapeutic response in GBMSC.
Safety and Usefulness of Cryobiopsy and Stamp Cytology for the Diagnosis of Peripheral Pulmonary Lesions
Authors: Imabayashi Tatsuya , Uchino Junji , Yoshimura Akihiro , Chihara Yusuke , Tamiya Nobuyo , Kaneko Yoshiko , Yamada Tadaaki , Takayama Koichi
Published: March 2019

Reports on the use of cryobiopsy (CB) for lung cancer diagnosis are limited. The aims of the present study were to evaluate the safety and usefulness of CB using radial endobronchial ultrasonography, without a guide sheath, for the diagnosis of peripheral pulmonary lesions and determine the utility of stamp cytology, an on-site diagnostic technique for determining tumor inclusion in CB samples. We retrospectively analyzed data for 35 patients (36 lesions) with suspected peripheral lung cancer who underwent CB between August 2017 and February 2019 at our medical facility. The diagnostic yield, incidence of complications, and the utility of stamp cytology for diagnosis were investigated. The diagnostic yield of CB was 86.1% (31/36) with histological diagnosis, and 80.5% (29/36) with diagnosis using stamp cytology; the overall yield was 91.6% (33/36). Pneumothorax requiring thoracic drainage occurred in two patients, both of whom had lesions contacting the pleura. Grade 2 and grade 1 bleeding occurred in one and 25 patients, respectively. CB enables the collection of very large, nearly intact tissue samples, thus resulting in an improvement in the true diagnosis rate and facilitating the measurement of multiple biomarkers as well as rapid histological diagnosis.
New Phosphorylation Sites of Rad51 by c-Met Modulates Presynaptic Filament Stability
Authors: Chabot Thomas , Defontaine Alain , Marquis Damien , Renodon-Corniere Axelle , Courtois Emmanuelle , Fleury Fabrice , Cheraud Yvonnick
Published: March 2019

Genomic instability through deregulation of DNA repair pathways can initiate cancer and subsequently result in resistance to chemo and radiotherapy. Understanding these biological mechanisms is therefore essential to overcome cancer. RAD51 is the central protein of the Homologous Recombination (HR) DNA repair pathway, which leads to faithful DNA repair of DSBs. The recombinase activity of RAD51 requires nucleofilament formation and is regulated by post-translational modifications such as phosphorylation. In the last decade, studies have suggested the existence of a relationship between receptor tyrosine kinases (RTK) and Homologous Recombination DNA repair. Among these RTK the c-MET receptor is often overexpressed or constitutively activated in many cancer types and its inhibition induces the decrease of HR. In this study, we show for the first time that c-MET is able to phosphorylate the RAD51 protein. We demonstrate in vitro that c-MET phosphorylates four tyrosine residues localized mainly in the subunit-subunit interface of RAD51. Whereas these post-translational modifications do not affect the presynaptic filament formation, they strengthen its stability against the inhibitor effect of the BRC peptide obtained from BRCA2. Taken together, these results confirm the role of these modifications in the regulation of the BRCA2-RAD51 interaction and underline the importance of c-MET in DNA damage response.
The ‘Ins and Outs’ of Early Preclinical Models for Brain Tumor Research: Are They Valuable and Have We Been Doing It Wrong?
Authors: Rominiyi Ola , Al-Tamimi Yahia , Collis Spencer J.
Published: March 2019

In this perspective, we congratulate the international efforts to highlight critical challenges in brain tumor research through a recent Consensus Statement. We also illustrate the importance of developing more accurate and clinically relevant early translational in vitro brain tumor models—a perspective given limited emphasis in the Consensus Statement, despite in vitro models being widely used to prioritize candidate therapeutic strategies prior to in vivo studies and subsequent clinical trials. We argue that successful translation of effective novel treatments into the clinic will require investment into the development of more predictive early pre-clinical models. It is in the interest of researchers, clinicians, and ultimately, patients that the most promising therapeutic candidates are identified and translated toward use in the clinic. Highlighting the value of early pre-clinical brain tumor models and debating how such models can be improved is of the utmost importance to the neuro-oncology research community and cancer research more broadly.
CO2 Microwave Plasma—Catalytic Reactor for Efficient Reforming of Methane to Syngas
Authors: Chun Se Min , Shin Dong Hun , Ma Suk Hwal , Yang Geon Woo , Hong Yong Cheol
Published: March 2019

CO2 was converted to synthesis gas in a microwave plasma–catalytic reactor by methane reforming at atmospheric pressure. The hybrid system used waste heat from the plasma to heat the catalyst. Conversion degrees were examined as a function of gas temperature, and the reforming efficiency of the plasma-only system was compared with that of the hybrid system. As a result, the hybrid system was shown to be more efficient under catalyst-free conditions. The use of microwave plasma alone resulted in low conversions of CO2 and CH4, which were 32.9% and 42.7%, respectively, at 3 kW microwave power. High CO2 and CH4 conversions of 87.9% and 92.9%, respectively, were achieved in the presence of catalyst at the same microwave power. At constant microwave power, catalyst addition increased the H2 and CO mass yield rates to 0.27 kg/h and 2.012 kg/h, respectively. Additionally, the H2 energy yield were 270 g/h, and 91.2 g/kWh. Thus, the developed hybrid system is well suited for efficient and economically viable CO2 reduction and synthesis gas production, paving the way for next-generation CO2 utilization and zero-emission industrial processes.
Transition Metal Phosphides for the Catalytic Hydrodeoxygenation of Waste Oils into Green Diesel
Authors: Alvarez-Galvan M. , Campos-Martin Jose , Fierro Jose
Published: March 2019

Recently, catalysts based on transition metal phosphides (TMPs) have attracted increasing interest for their use in hydrodeoxygenation (HDO) processes destined to synthesize biofuels (green or renewable diesel) from waste vegetable oils and fats (known as hydrotreated vegetable oils (HVO)), or from bio-oils. This fossil-free diesel product is produced completely from renewable raw materials with exceptional quality. These efficient HDO catalysts present electronic properties similar to noble metals, are cost-efficient, and are more stable and resistant to the presence of water than other classical catalytic formulations used for hydrotreatment reactions based on transition metal sulfides, but they do not require the continuous supply of a sulfide source. TMPs develop a bifunctional character (metallic and acidic) and present tunable catalytic properties related to the metal type, phosphorous-metal ratio, support nature, texture properties, and so on. Here, the recent progress in TMP-based catalysts for HDO of waste oils is reviewed. First, the use of TMPs in catalysis is addressed; then, the general aspects of green diesel (from bio-oils or from waste vegetable oils and fats) production by HDO of nonedible oil compounds are presented; and, finally, we attempt to describe the main advances in the development of catalysts based on TMPs for HDO, with an emphasis on the influence of the nature of active phases and effects of phosphorous, promoters, and preparation methods on reactivity.
Photocatalytic Degradation of Profenofos and Triazophos Residues in the Chinese Cabbage, Brassica chinensis, Using Ce-Doped TiO2
Authors: Liu Xiangying , Zhan You , Zhang Zhongqin , Pan Lang , Hu Lifeng , Liu Kailin , Zhou Xuguo , Bai Lianyang
Published: March 2019

Pesticides have revolutionized the modern day of agriculture and substantially reduced crop losses. Synthetic pesticides pose a potential risk to the ecosystem and to the non-target organisms due to their persistency and bioaccumulation in the environment. In recent years, a light-mediated advanced oxidation processes (AOPs) has been adopted to resolve pesticide residue issues in the field. Among the current available semiconductors, titanium dioxide (TiO2) is one of the most promising photocatalysts. In this study, we investigated the photocatalytic degradation of profenofos and triazophos residues in Chinese cabbage, Brassica chinensis, using a Cerium-doped nano semiconductor TiO2 (TiO2/Ce) under the field conditions. The results showed that the degradation efficiency of these organophosphate pesticides in B. chinensis was significantly enhanced in the presence of TiO2/Ce. Specifically, the reactive oxygen species (ROS) contents were significantly increased in B. chinensis with TiO2/Ce treatment, accelerating the degradation of profenofos and triazophos. Ultra-performance liquid chromatography–mass spectroscopy (UPLC-MS) analysis detected 4-bromo-2-chlorophenol and 1-phenyl-3-hydroxy-1,2,4-triazole, the major photodegradation byproducts of profenofos and triazophos, respectively. To better understand the relationship between photodegradation and the molecular structure of these organophosphate pesticides, we investigated the spatial configuration, the bond length and Mulliken atomic charge using quantum chemistry. Ab initio analysis suggests that the bonds connected by P atom of profenofos/triazophos are the initiation cleavage site for photocatalytic degradation in B. chinensis.
Biodiesel Production (FAEEs) by Heterogeneous Combi-Lipase Biocatalysts Using Wet Extracted Lipids from Microalgae
Authors: Sánchez-Bayo Alejandra , Morales Victoria , Rodríguez Rosalía , Vicente Gemma , Bautista Luis Fernando
Published: March 2019

The production of fatty acids ethyl esters (FAEEs) to be used as biodiesel from oleaginous microalgae shows great opportunities as an attractive source for the production of renewable fuels without competing with human food. To ensure the economic viability and environmental sustainability of the microbial biomass as a raw material, the integration of its production and transformation into the biorefinery concept is required. In the present work, lipids from wet Isochrysis galbana microalga were extracted with ethyl acetate with and without drying the microalgal biomass (dry and wet extraction method, respectively). Then, FAEEs were produced by lipase-catalyzed transesterification and esterification of the extracted lipids with ethanol using lipase B from Candida antarctica (CALB) and Pseudomonas cepacia (PC) lipase supported on SBA-15 mesoporous silica functionalized with amino groups. The conversion to FAEEs with CALB (97 and 85.5 mol% for dry and wet extraction, respectively) and PC (91 and 87 mol%) biocatalysts reached higher values than those obtained with commercial Novozym 435 (75 and 69.5 mol%). Due to the heterogeneous nature of the composition of microalgae lipids, mixtures with different CALB:PC biocatalyst ratio were used to improve conversion of wet-extracted lipids. The results showed that a 25:75 combi-lipase produced a significantly higher conversion to FAEEs (97.2 mol%) than those produced by each biocatalyst independently from wet-extracted lipids and similar ones than those obtained by each lipase from the dry extraction method. Therefore, that optimized combi-lipase biocatalyst, along with achieving the highest conversion to FAEEs, would allow improving viability of a biorefinery since biodiesel production could be performed without the energy-intensive step of biomass drying.
Suzuki–Miyaura Coupling Using Monolithic Pd Reactors and Scaling-Up by Series Connection of the Reactors
Authors: Nagaki Aiichiro , Hirose Katsuyuki , Moriwaki Yuya , Takumi Masahiro , Takahashi Yusuke , Mitamura Koji , Matsukawa Kimihiro , Ishizuka Norio , Yoshida Jun-ichi
Published: March 2019

The space integration of the lithiation of aryl halides, the borylation of aryllithiums, and Suzuki–Miyaura coupling using a Pd catalyst supported by a polymer monolith flow reactor without using an intentionally added base was achieved. To scale up the process, a series connection of the monolith Pd reactor was examined. To suppress the increase in the pressure drop caused by the series connection, a monolith reactor having larger pore sizes was developed by varying the temperature of the monolith preparation. The monolithic Pd reactor having larger pore sizes enabled Suzuki–Miyaura coupling at a higher flow rate because of a lower pressure drop and, therefore, an increase in productivity. The present study indicates that series connection of the reactors with a higher flow rate serves as a good method for increasing the productivity without decreasing the yields.
C-Met as a Key Factor Responsible for Sustaining Undifferentiated Phenotype and Therapy Resistance in Renal Carcinomas
Authors: Marona Paulina , Górka Judyta , Kotlinowski Jerzy , Majka Marcin , Jura Jolanta , Miekus Katarzyna
Published: March 2019

C-Met tyrosine kinase receptor plays an important role under normal and pathological conditions. In tumor cells’ overexpression or incorrect activation of c-Met, this leads to stimulation of proliferation, survival and increase of motile activity. This receptor is also described as a marker of cancer initiating cells. The latest research shows that the c-Met receptor has an influence on the development of resistance to targeted cancer treatment. High c-Met expression and activation in renal cell carcinomas is associated with the progression of the disease and poor survival of patients. C-Met receptor has become a therapeutic target in kidney cancer. However, the therapies used so far using c-Met tyrosine kinase inhibitors demonstrate resistance to treatment. On the other hand, the c-Met pathway may act as an alternative target pathway in tumors that are resistant to other therapies. Combination treatment together with c-Met inhibitor reduces tumor growth, vascularization and pro-metastatic behavior and results in suppressed mesenchymal phenotype and vascular endothelial growth factor (VEGF) secretion. Recently, it has been shown that the acquirement of mesenchymal phenotype or lack of cell differentiation might be related to the presence of the c-Met receptor and is consequently responsible for therapy resistance. This review presents the results from recent studies identifying c-Met as an important factor in renal carcinomas being responsible for tumor growth, progression and metastasis, indicating the role of c-Met in resistance to antitumor therapy and demonstrating the pivotal role of c-Met in supporting mesenchymal cell phenotype.
Mitochondrial Retrograde Signalling and Metabolic Alterations in the Tumour Microenvironment
Authors: Yang Dongki , Kim Jaehong
Published: March 2019

This review explores the molecular mechanisms that may be responsible for mitochondrial retrograde signalling related metabolic reprogramming in cancer and host cells in the tumour microenvironment and provides a summary of recent updates with regard to the functional modulation of diverse cells in the tumour microenvironment.
Novel Flavivirus Antiviral That Targets the Host Nuclear Transport Importin α/β1 Heterodimer
Authors: Yang Sundy , Atkinson Sarah , Fraser Johanna , Wang Chunxiao , Maher Belinda , Roman Noelia , Forwood Jade , Wagstaff Kylie , Borg Natalie , Jans David
Published: March 2019

Dengue virus (DENV) threatens almost 70% of the world’s population, with no effective vaccine or therapeutic currently available. A key contributor to infection is nuclear localisation in the infected cell of DENV nonstructural protein 5 (NS5) through the action of the host importin (IMP) α/β1 proteins. Here, we used a range of microscopic, virological and biochemical/biophysical approaches to show for the first time that the small molecule GW5074 has anti-DENV action through its novel ability to inhibit NS5–IMPα/β1 interaction in vitro as well as NS5 nuclear localisation in infected cells. Strikingly, GW5074 not only inhibits IMPα binding to IMPβ1, but can dissociate preformed IMPα/β1 heterodimer, through targeting the IMPα armadillo (ARM) repeat domain to impact IMPα thermal stability and α-helicity, as shown using analytical ultracentrifugation, thermostability analysis and circular dichroism measurements. Importantly, GW5074 has strong antiviral activity at low µM concentrations against not only DENV-2, but also zika virus and West Nile virus. This work highlights DENV NS5 nuclear targeting as a viable target for anti-flaviviral therapeutics.
Ethanol-Induced Mitochondrial Damage in Sertoli Cells is Associated with Parkin Overexpression and Activation of Mitophagy
Authors: Eid Nabil , Ito Yuko , Horibe Akio , Otsuki Yoshinori , Kondo Yoichi
Published: March 2019

This study was conducted to elucidate the involvement of the PINK1-Parkin pathway in ethanol-induced mitophagy among Sertoli cells (SCs). In the research, adult rats were given intraperitoneal injections of ethanol (5 gm/kg) and sacrificed at various time periods within 24 h. Transmission electron microscopy was applied to reveal enhanced mitochondrial damage in SCs of the ethanol-treated rats (ETRs) in association with a significant increase in numbers of mitophagic vacuoles (mitophagosomes and autolysosomes) in contrast to very low levels in a control group treated with phosphate-buffered saline (PBS). This enhancement was ultra-structurally verified via observation of trapped mitochondria within LC3-labeled membranes, upregulation of LC3 protein levels, colocalization of LC3 and cytochrome c, and reduced expression of mitochondrial proteins. Importantly, Parkin expression was found to be upregulated in ETR SCs, specifically in mitochondria and mitophagosomes in addition to colocalization with PINK1 and pan-cathepsin, indicating augmented mitophagy. Transcription factor EB (TFEB, a transcription factor for autophagy and mitophagy proteins) was also found to be upregulated in nuclei of ETR SCs and associated with enhanced expression of iNOS. Enhanced Parkin-related mitophagy in ETR SCs may be a protective mechanism with therapeutic implications. To the authors’ knowledge, this is the first report demonstrating the ultrastructural characteristics and molecular mechanisms of Parkin-related mitophagy in ETR SCs.
IL-6, IL-12, and IL-23 STAT-Pathway Genetic Risk and Responsiveness of Lymphocytes in Patients with Multiple Sclerosis
Authors: von Essen Marina R. , Søndergaard Helle B. , Petersen Eva R.S. , Sellebjerg Finn
Published: March 2019

Multiple sclerosis (MS) is an immune-mediated demyelinating disease characterized by central nervous system (CNS) lymphocyte infiltration, abundant production of pro-inflammatory cytokines, and inappropriate activation of Th1 and Th17 cells, B cells, and innate immune cells. The etiology of MS is complex, and genetic factors contribute to disease susceptibility. Genome-wide association studies (GWAS) have revealed numerous MS-risk alleles in the IL-6/STAT3, IL-12/STAT4, and IL-23/STAT3-pathways implicated in the differentiation of Th1 and Th17 cells. In this study, we investigated the signaling properties of these pathways in T, B, and NK cells from patients with relapsing-remitting MS (RRMS) and healthy controls, and assessed the genetic contribution to the activity of the pathways. This revealed a great variability in the level of STAT-pathway molecules and STAT activation between the cell types investigated. We also found a strong donor variation in IL-6, IL-12, and IL-23 responsiveness of primed CD4+ T cells. This variation could not be explained by a single MS-risk variant in a pathway component, or by an accumulation of multiple STAT-pathway MS-risk SNPs. The data of this study suggests that other factors in cohesion with the genetic background contribute to the responsiveness of the IL-6/STAT3, IL-12/STAT4, and IL-23/STAT3-pathways.
Philanthrocapitalism: Promoting Global Health but Failing Planetary Health
Authors: Butler Colin D
Published: March 2019

Focusing on the Bill and Melinda Gates Foundation (BMGF) as a case study, this paper explores the relationship between philanthrocapitalism, economic history, and global and planetary health. The Wellcome Trust is also briefly discussed, chiefly in the context of planetary health. The paper argues that in the last 45 years there has been an increased preference for market-based approaches, often called neoliberalism, particularly in the U.S. and its allies. This has generated greater inequality in many high-income settings and weakened the norm of taxation. This has provided a setting in which philanthrocapitalism has flourished, including the BMGF. The latter has in turn become an important actor for global health, partially balancing the adverse consequences of neoliberalism. Planetary health is here defined as the interaction between global health and global environmental change, including to the climate and other elements of the Earth System. Although the Wellcome Trust has recently made funds available for ecological health research, it continues to invest in fossil fuels. The Gates Foundation provide no or minimal grants for ecological or planetary health but appear to have recently substantially divested from fossil fuels, for unclear reasons. The paper concludes that these large philanthrocapitalist organizations partly compensate for the decline in attention to global health driven by market-preferring solutions, but remain insufficiently proactive in the face of the great dangers associated with declining planetary health.
Efficacy of Sweet Potato Starch-Based Coating to Improve Quality and Safety of Hen Eggs during Storage
Authors: Sharaf Eddin Abdulhakim , Tahergorabi Reza
Published: March 2019

Egg deterioration occurs during storage time, which leads to quality loss. Thus, different preservations methods have been used to extend the shelf-life and maintain the safety of eggs. Edible coating materials based on biopolymers, such as starches and other renewable sources, have been used for different food products and been identified as an effective method of food preservation. In this study, eggs were coated with edible coatings prepared from sweet potato starch (SPS) and varying levels of thyme essential oil (TEO), including 0 (control), 2%, 4%, and 6%. The quality and safety of the coated and uncoated eggs during five weeks of storage at 25 °C were studied. The application of 4% TEO in SPS-based coatings maintained the quality and safety of eggs two weeks longer than non-coated eggs. This study showed that the SPS-TEO coating could be useful in extending the shelf life of eggs during storage time, by delaying changes in egg quality.
Electrodeposition of Hydroxyapatite Coatings for Marble Protection: Preliminary Results
Authors: Sassoni Enrico , Masi Giulia , Bignozzi Maria Chiara , Franzoni Elisa
Published: March 2019

Surface coatings made of hydroxyapatite (HAP) have been proposed to protect marble artworks from dissolution in rain, originated by the aqueous solubility of calcite. However, HAP coatings formed by wet chemistry exhibit incomplete coverage of marble surface, which results in limited protective efficacy. In this study, electrodeposition was explored as a new route to possibly form continuous coatings over the marble surface, leaving no bare areas. Electrodeposition was performed by placing marble samples in poultices containing the electrolyte (an aqueous solution with calcium and phosphate precursors) and the electrodes. The influence of several parameters was investigated, namely the role of the working electrode (cathode or anode), the distance between the marble sample and the working electrode, the deposition conditions (potentiostatic or galvanostatic), the electrolyte composition and concentration, the applied voltage, and time. The coating morphology and composition were assessed by SEM/EDS and FT-IR. The protective ability of the most promising formulations was then evaluated, in all cases comparing electrodeposition with traditional wet synthesis methods. The results of the study suggest that electrodeposition is able to accelerate and improve formation of HAP coatings over the marble surface, even though the obtained protective efficacy is not complete yet.
Effect of Surface Roughness and Electroless Ni–P Plating on the Bonding Strength of Bi–Te-based Thermoelectric Modules
Authors: Bae Sung Hwa , Kim Sungsoon , Yi Seong Hoon , Son Injoon , Kim Kyung Tae , Chung Hoyong
Published: March 2019

In this study, electroless-plating of a nickel-phosphor (Ni–P) thin film on surface-controlled thermoelectric elements was developed to significantly increase the bonding strength between Bi–Te materials and copper (Cu) electrodes in thermoelectric modules. Without electroless Ni–P plating, the effect of surface roughness on the bonding strength was negligible. Brittle SnTe intermetallic compounds were formed at the bonding interface of the thermoelectric elements and defects such as pores were generated at the bonding interface owing to poor wettability with the solder. However, defects were not present at the bonding interface of the specimen subjected to electroless Ni–P plating, and the electroless Ni–P plating layer acted as a diffusion barrier toward Sn and Te. The bonding strength was higher when the specimen was subjected to Ni–P plating compared with that without Ni–P plating, and it improved with increasing surface roughness. As electroless Ni–P plating improved the wettability with molten solder, the increase in bonding strength was attributed to the formation of a thicker solder reaction layer below the bonding interface owing to an increase in the bonding interface with the solder at higher surface roughness.
Diode-Pumped Actively Q-Switched Nd:YVO4/RTP Intracavity Raman Laser at 1.49 µm
Authors: Jiao Yue , Liu Zhaojun , Zhang Xingyu , Gao Feilong , Jia Chenyang , Chen Xiaohan , Cong Zhenhua
Published: March 2019

For the first time, a diode-pumped actively Q-switched Nd:YVO4/RbTiOPO4 (RTP) intracavity Raman laser at 1.49 µm was demonstrated to the best of our knowledge. Experimentally, a dual-end diffusion-bonded YVO4–Nd:YVO4–YVO4 crystal was employed as the laser medium to generate 1.34 µm laser radiation, and an RTP crystal as the Raman medium to enable the frequency conversion, by which radiation at 1.49 µm was achieved successfully. With an incident pump power of 10.4 W, an average output power of 502 mW was obtained at a pulse repetition rate of 15 kHz, corresponding to a conversion efficiency of 4.8%.
Optical Characterization and Photovoltaic Performance Evaluation of GaAs p-i-n Solar Cells with Various Metal Grid Spacings
Authors: Wu Jenq-Shinn , Lin Der-Yuh , Li Yun-Guang , Hsu Hung-Pin , Kao Ming-Cheng , Chen Hone-Zern
Published: March 2019

GaAs p-i-n solar cells are studied using electroreflectance (ER) spectroscopy, light beam induced current (LBIC) mapping and photovoltaic characterization. Using ER measurements, the electric field across the pn junction of a wafer can be evaluated, showing 167 kV/cm and 275 kV/cm in the built-in condition and at −3 V reverse bias, respectively. In order to understand the effect of the interval between metal grids on the device’s solar performance, we performed LBIC mapping and solar illumination on samples of different grid spacings. We found that the integrated photocurrent intensity of LBIC mapping shows a consistent trend with the solar performance of the devices with various metal grid spacings. For the wafer used in this study, the optimal grid spacing was found to be around 300 μm. Our results clearly show the importance of the metal grid pattern in achieving high-efficiency solar cells.
Impact of Weak Nanoparticle Induced Disorder on Nematic Ordering
Authors: Črešnar Dejvid , Kyrou Christina , Lelidis Ioannis , Drozd-Rzoska Aleksandra , Starzonek Szymon , Rzoska Sylwester Janusz , Kutnjak Zdravko , Kralj Samo
Published: March 2019

Dilute mixtures of nanoparticles (NPs) and nematic liquid crystals (LCs) are considered. We focus on cases where NPs enforce a relatively weak disorder to the LC host. We use a Lebwohl-Lasher semi-microscopic-type modeling where we assume that NPs effectively act as a spatially-dependent external field on nematic spins. The orientational distribution of locally favoured “easy” orientations is described by a probabilistic distribution function P. By means of a mean field-type approach, we derive a self-consistent equation for the average degree of nematic uniaxial order parameter S as a function of the concentration p of NPs, NP-LC coupling strength and P. Using a simple step-like probability distribution shape, we obtain the S(p) dependence displaying a crossover behaviour between two different regimes which is in line with recent experimental observations. We also discuss a possible origin of commonly observed non-monotonous variations of the nematic-isotropic phase temperature coexistence width on varying p.
Numerical Simulation of Temperature and Fluid Fields in Solidification Process of Ferritic Stainless Steel under Vibration Conditions
Authors: Wang Wenli , Chen Jing , Li Miaomiao , Wang Along , Su Mengyao
Published: March 2019

A three-dimensional model of a circular casting mold with a vibrating nucleus generator was established, and the characteristics of temperature and flow fields during the solidification process of ferritic stainless steel Cr17 in the casting mold were analyzed using finite element and finite difference methods. A standard k-ε turbulent current model was adopted to simulate the temperature field, and a standard k-ε model in Reynolds-averaged Navier–Stokes equations (RANS) was employed to deal with the flow field. The temperature field diffuses outward with a positive temperature gradient. Low degrees of undercooling can prevent solidified shells from forming rapidly on the surface of the nucleus generator. The temperature perpendicular to the direction of vibration is lower than that in the direction of vibration. The flow field exhibits a heart-shaped distribution and spreads gradually outward. The uniform distribution of grains can be achieved at three different frequencies of vibration. The results show that the degree of undercooling affects the distribution of the temperature field while the frequency of vibration affects the flow field significantly. Under the conditions of undercooling of 540 K and vibration frequency of 1000 Hz, the region perpendicular to the vibration direction of the nucleus generator is the optimum area for equiaxed crystal formation.
Synthesis, Structures and Co-Crystallizations of Perfluorophenyl Substituted β-Diketone and Triketone Compounds
Authors: Kusakawa Takumi , Sakai Shunichiro , Nakajima Kyosuke , Yuge Hidetaka , Rzeznicka Izabela I. , Hori Akiko
Published: March 2019

Perfluorophenyl-substituted compounds, 3-hydroxy-1,3-bis(pentafluorophenyl)-2- propen-1-one (H1) and 1,5-dihydroxy-1,5-bis(pentafluorophenyl)-1,4-pentadien-3-one (H22), were prepared in 56 and 30% yields, respectively, and only the enol forms were preferentially obtained among the keto-enol tautomerism. Molecular conformations and tautomerism of the fluorine-substituted compounds were certified based on X-ray crystallographic studies and density functional calculations. The solvent dependency of the absorption spectra was only observed for the fluorinated compounds. The compounds H1 and H22 quantitatively formed co-crystals with the corresponding non-perfluorinated compounds, dibenzoylmethane (H3) and 1,5-dihydroxy-1,5-diphenyl-1,4-pentadien-3-one (H24), respectively, through the arene–perfluoroarene interaction to give the 1:1 co-crystals H1•H3 and H22•H24, which were characterized by X-ray crystallographic and elemental analysis studies.
Active Matrix Metalloproteinase-8 Point-of-Care (PoC)/Chairside Mouthrinse Test vs. Bleeding on Probing in Diagnosing Subclinical Periodontitis in Adolescents
Authors: Räisänen Ismo T. , Sorsa Timo , van der Schoor Gerrit-Jan , Tervahartiala Taina , van der Schoor Peter , Gieselmann Dirk-Rolf , Heikkinen Anna Maria
Published: March 2019

This cross-sectional study compares the effectiveness of an active MMP-8 (aMMP-8) point-of-care (PoC)/chairside mouthrinse test to the conventional bleeding on probing (BOP) (cutoff 20%) test in detecting subclinical periodontitis/pre-periodontitis in Finnish adolescents. The study was carried out at the Kotka Health Center, Finland. A total of 47 adolescents (30 boys/17 girls) aged 15–17 were first tested with the aMMP-8 PoC test, followed by a full-mouth evaluation of clinical parameters of oral health including periodontal, oral mucosal, and caries assessment. A periodontist performed these clinical examinations. The aMMP-8 PoC test result had much stronger association with subclinical periodontitis than the BOP 20% test (2.8–5.3 times stronger in terms of odds ratio). The aMMP-8 PoC test had ≥2 times higher sensitivity than the BOP 20% test with, generally, the same specificity. Further, the aMMP-8 PoC test had generally better accuracy and lower false negative percentages. The aMMP-8 PoC test seemed to be more effective than the conventional BOP test in detecting subclinical periodontitis/pre-periodontitis in adolescents reducing the risk of their undertreatment. However, the sample size may be a limiting factor, and more studies are needed to confirm our results for both adolescents and adults.