bluuebunny/crossref_metadata_2025 huggingface dataset:
Centrosomal and Non-Centrosomal Microtubule-Organizing Centers (MTOCs) in Drosophila melanogaster
Authors: Tillery Marisa M. L. , Blake-Hedges Caitlyn , Zheng Yiming , Buchwalter Rebecca A. , Megraw Timothy L.
Published: August 2018

The centrosome is the best-understood microtubule-organizing center (MTOC) and is essential in particular cell types and at specific stages during Drosophila development. The centrosome is not required zygotically for mitosis or to achieve full animal development. Nevertheless, centrosomes are essential maternally during cleavage cycles in the early embryo, for male meiotic divisions, for efficient division of epithelial cells in the imaginal wing disc, and for cilium/flagellum assembly in sensory neurons and spermatozoa. Importantly, asymmetric and polarized division of stem cells is regulated by centrosomes and by the asymmetric regulation of their microtubule (MT) assembly activity. More recently, the components and functions of a variety of non-centrosomal microtubule-organizing centers (ncMTOCs) have begun to be elucidated. Throughout Drosophila development, a wide variety of unique ncMTOCs form in epithelial and non-epithelial cell types at an assortment of subcellular locations. Some of these cell types also utilize the centrosomal MTOC, while others rely exclusively on ncMTOCs. The impressive variety of ncMTOCs being discovered provides novel insight into the diverse functions of MTOCs in cells and tissues. This review highlights our current knowledge of the composition, assembly, and functional roles of centrosomal and non-centrosomal MTOCs in Drosophila.
Photodegradation of Stearic Acid Adsorbed on Copper Oxide Heterojunction Thin Films Prepared by Magnetron Sputtering
Authors: Montero José , Österlund Lars
Published: August 2018

Nanocrystalline copper oxide thin films were fabricated by reactive DC magnetron sputtering. The structure and optical properties of the films were measured with X-ray diffraction, scanning electron microscopy, and spectrophotometry. Variations of oxygen partial pressure resulted in oxide composition ranging from Cu, Cu-Cu2O, Cu2O-CuO1−x, and CuO. Optical band transitions at 2.06 eV and 2.55 eV were found for Cu2O corresponding to the direct forbidden and direct allowed interband transitions. For CuO an indirect allowed interband transition was found at 1.28 eV. The photocatalytic activity was determined by quantifying the rate constant and quantum yield (destroyed molecules/photons absorbed) under stearic acid degradation. Photocatalytic activity was found to be highest in mixed-phase films with Cu-Cu2O films the highest. Results from post-annealed Cu-Cu2O and CuO films show similar results. We interpret our results as being due to efficient electron-hole charge separation in the heterojunction films. The obtained quantum yields were generally about ten times lower than for comparable dense TiO2 and WO3 binary oxides, which calls for further studies of the spectral dependence of the quantum yield and electron-hole pair life times for oxides with different purity levels.
High-Risk Neuroblastoma Treatment Review
Authors: Smith Valeria , Foster Jennifer
Published: August 2018

Neuroblastoma is the most common extracranial solid tumor in children. One subset, high-risk neuroblastoma, is very difficult to treat and requires multi-modal therapy. Intensification of therapy has vastly improved survival rates, and research is focused on novel treatments to further improve survival rates. The current treatment schema is divided into three stages—induction, consolidation, and maintenance. This review serves as an overview of the current treatment for high-risk neuroblastoma and a glimpse at current research for future therapy.
Improvement of Thin Film Adhesion Due to Bombardment by Fast Argon Atoms
Authors: Grigoriev Sergey , Metel Alexander , Volosova Marina , Melnik Yury
Published: August 2018

A new hollow cathode sputtering system is used for beam-assisted deposition of thin films on dielectric substrates. A copper target placed at the hollow cathode bottom is uniformly sputtered by argon ions from the glow discharge plasma filling the cathode. Through an emissive grid, sputtered copper atoms leave the cathode together with accelerated argon ions. On their way to the substrate, the ions—due to charge exchange collisions—turn into fast argon atoms bombarding the growing film. With increasing argon ion energy, continuous bombardment results in the film adhesion improvement and reduction of the deposition rate down to zero, at an energy of about 2 keV. The pulsed bombardment does not influence the film deposition rate, and results in a monotonic growth of the film adhesion up to 20 MPa when increasing the fast atom energy up to 10 keV.
Influence of Ge Incorporation from GeSe2 Vapor on the Properties of Cu2ZnSn(S,Se)4 Material and Solar Cells
Authors: Gao Chao , Sun Yali , Yu Wei
Published: August 2018

Cu2ZnSn(S,Se)4 (CZTSSe) and Cu2Zn(Sn,Ge)(S,Se)4 (CZTGSSe) thin films were prepared based on a non-vacuum solution method. The CZTSSe films were obtained by annealing the solution-deposited precursor films with Se, while the CZTGSSe films were obtained by annealing the similar precursor films with Se and GeSe2. We found that Ge could be incorporated into the annealed films when GeSe2 was present during the annealing process. The Ge incorporation obviously enlarged the sizes of the crystalline grains in the annealed films. However, the energy dispersive spectrometry (EDS) measurements revealed that the element distribution was not uniform in the CZTGSSe films. We fabricated solar cells based on the CZTSSe and CZTGSSe films. It was found the Ge incorporation decreases the Eu energy of the absorber material. The solar cell efficiency was increased from 5.61% (CZTSSe solar cell) to 7.14% (CZTGSSe solar cell) by the Ge incorporation. Compared to CZTSSe solar cells, the CZTGSSe solar cells exhibited a lower diode ideality factor and lower reverse saturation current density.
Temperature Dependence of the Vacancy Formation Energy in Solid 4He
Authors: Rota Riccardo , Boronat Jordi
Published: August 2018

We studied the thermal effects on the behavior of incommensurate solid 4He at low temperatures using the path integral Monte Carlo method. Below a certain temperature, depending on the density and the structure of the crystal, the vacancies delocalize and a finite condensate fraction appears. We calculated the vacancy formation energy as a function of the temperature and observed a behavior compatible with a two-step structure, with a gap of few K appearing at the onset temperature of off-diagonal long-range order. Estimation of the energy cost of creating two vacancies seems to indicate an effective attractive interaction among the vacancies but the large error inherent to its numerical estimation precludes a definitive statement.
A Simple, Membrane-Free, Direct Glycerol Fuel Cell Utilizing a Precious Metal-Free Cathode and Gold-Plated Anode Surfaces
Authors: Tseng Yi Jie , Scott Daniel
Published: August 2018

As bio-diesel production continues around the world, the amount of low-grade glycerol, a byproduct from the process, in increasing, as is the demand for a simple, easy-to-make, fuel cell capable of running off glycerol and oxygen from the air. Despite the research that has already been done with glycerol fuel cells, the complexity of the fuel cell designs for such a simple fuel appears to be prohibitive toward the actualization of such a cell. Here the simplest of fuel cells, an alkaline, membrane-free, glycerol fuel cell with a non-platinum-containing MnO2 cathode is explored. Glycerol oxidation is catalyzed on various surfaces including carbon felt, platinum, and silver-plated nickel with and without gold plating. The maximum power this glycerol fuel cell generates, with 1.4 M glycerol and 8.0 M KOH, is 1.27 mW cm−2 at 200 mV. It has an open circuit voltage of 704 mV. Additionally, the effects of different, gold-plated anodic surfaces, electrolytes and temperatures are also explored. This work demonstrates the feasibility of this simple, reusable robust cell design using pure and crude glycerol from bio-diesel production and preliminarily explores the products of this reaction.
A Study of the Production and Combustion Characteristics of Pyrolytic Oil from Sewage Sludge Using the Taguchi Method
Authors: Chen Guan-Bang , Li Jia-Wen , Lin Hsien-Tsung , Wu Fang-Hsien , Chao Yei-Chin
Published: August 2018

Sewage sludge is a common form of municipal solid waste, and can be utilized as a renewable energy source. This study examines the effects of different key operational parameters on sewage sludge pyrolysis process for pyrolytic oil production using the Taguchi method. The digested sewage sludge was provided by the urban wastewater treatment plant of Tainan, Taiwan. The experimental results indicate that the maximum pyrolytic oil yield, 10.19% (18.4% on dry ash free (daf) basis) by weight achieved, is obtained under the operation conditions of 450 °C pyrolytic temperature, residence time of 60 min, 10 °C/min heating rate, and 700 mL/min nitrogen flow rate. According to the experimental results, the order of sensitivity of the parameters that affect the yield of sludge pyrolytic oil is the nitrogen flow rate, pyrolytic temperature, heating rate and residence time. The pyrolysis and oxidation reactions of sludge pyrolytic oil are also investigated using thermogravimetric analysis. The combustion performance parameters, such as the ignition temperature, burnout temperature, flammability index and combustion characteristics index are calculated and compared with those of heavy fuel oil. For the blend of sludge pyrolytic oil with heavy fuel oil, a synergistic effect occurs and the results show that sludge pyrolytic oil significantly enhances the ignition and combustion of heavy fuel oil.
An Indicator-Based Approach for Analysing the Resilience of Transitions for Energy Regions. Part II: Empirical Application to the Case of Weiz-Gleisdorf, Austria
Authors: Wyss Romano , Mühlemeier Susan , Binder Claudia R.
Published: August 2018

In this paper, we apply an indicator-based approach to measure the resilience of energy regions in transition to a case study region in Austria. The indicator-based approach allows to determine the resilience of the transition of regional energy systems towards higher shares of renewables and potentially overall higher sustainability. The indicators are based on two core aspects of resilience, diversity and connectivity. Diversity is thereby operationalized by variety, disparity and balance, whereas connectivity is operationalized by average path length, degree centrality and modularity. In order to get a full picture of the resilience of the energy system at stake throughout time, we apply the measures to four distinct moments, situated in the pre-development, take-off, acceleration and stabilization phase of the transition. By contextually and theoretically embedding the insights in the broader transitions context and empirically applying the indicators to a specific case, we derive insights on (1) how to interpret the results in a regional context and (2) how to further develop the indicator-based approach for future applications.
Effective Separation of a Water in Oil Emulsion from a Direct Contact Latent Heat Storage System
Authors: Ammann Sebastian , Ammann Andreas , Ravotti Rebecca , Fischer Ludger J. , Stamatiou Anastasia , Worlitschek Jörg
Published: August 2018

The problem of emulsification between Phase Change Material (PCM) and Heat Transfer Fluid (HTF) in direct contact latent heat storage systems has been reported in various studies. This issue causes the PCM to flow out of the storage tank and crystallize at unwanted locations and thus presents a major limitation for the proper operation of such systems. These anomalies become more pronounced when high HTF flow rates are employed with the aim to achieve fast heat transfer rates. The goal of this paper is to find a method which will enable the fast separation of the formed emulsion and thus the uninterrupted operation of the storage unit. In this study, three separation methods were examined and the use of superhydrophobic filters was chosen as the best candidate for the demulsification of the PCM and HTF mixtures. The filter was produced by processing of a melamine sponge with different superhydrophobic adhesives and was tested with emulsions closely resembling the ones formed in a real direct contact setup. The superhydrophobic filter obtained, was able to separate the emulsions effectively while presenting a very high permeability (up to 1,194,980 kg h−1 m−2 bar−1). This is the first time the use of a superhydrophobic sponge has been investigated in the context of demulsification in direct contact latent heat storage.
Milk Protein Concentration Using Negatively Charged Ultrafiltration Membranes
Authors: Arunkumar Abhiram , Etzel Mark R.
Published: August 2018

In this work, milk protein concentrate (MPC) was made using wide-pore negatively charged ultrafiltration membranes. The charged membranes were used for a six-fold volume concentration of skim milk and subsequent diafiltration to mimic the industrial MPC process. The charged 100 kDa membranes had at least a four-fold higher permeate flux at the same protein recovery as unmodified 30 kDa membranes, which are currently used in the dairy industry to make MPC. By placing a negative charge on the surface of an ultrafiltration membrane, the negatively charged proteins were rejected by electrostatic repulsion and not simply size-based sieving. Mass balance models of concentration and diafiltration were developed and the calculations matched the experimental observations. This is the first study to use wide-pore charged tangential-flow membranes for MPC manufacturing. Additionally, a unique mass balance model was applied, which accurately predicted experimental results.
Groundwater Characterization by Means of Conservative (δ18O and δ2H) and Non-Conservative (87Sr/86Sr) Isotopic Values: The Classical Karst Region Aquifer Case (Italy–Slovenia)
Authors: Calligaris Chiara , Mezga Kim , Slejko Francesca Federica , Urbanc Janko , Zini Luca
Published: August 2018

The study of the different hydrogeological compartments is a prerequisite for understanding and monitoring different fluxes, thereby evaluating the environmental changes in an ecosystem where anthropogenic disturbances are present in order to preserve the most vulnerable groundwaters from contamination and degradation. In many karst domains in the Mediterranean, areas groundwaters and surface waters are a single system, as a result of the features that facilitate the ingression of waters from surface to subsurface. This is also the case for the Classical Karst hydrostructure, which is a carbonate plateau that rises above the northern Adriatic Sea, shared between Italy and Slovenia. The main suppliers to the aquifer are the effective precipitations and the waters from three different rivers: Reka/Timavo, Soča/Isonzo and Vipava/Vipacco. Past and ongoing hydrogeological studies on the area have focused on the connections within the Classical Karst Region aquifer system through the analysis of water caves and springs hydrographs and chemographs. In this paper, the authors present new combined data from major ions, oxygen, hydrogen and strontium stable and radiogenic isotopes which have allowed a more complementary knowledge of the groundwater circulation, provenance and water-rock interactions. All the actions occurred in the framework of the European project HYDROKARST.
Sleep and Mental Health in Truck Drivers: Descriptive Review of the Current Evidence and Proposal of Strategies for Primary Prevention
Authors: Garbarino Sergio , Guglielmi Ottavia , Sannita Walter G , Magnavita Nicola , Lanteri Paola
Published: August 2018

Background: Professional truck drivers (TDs) are exposed to stressful working (and living) conditions and are vulnerable. They report physical and mental health problems and psychological distress more frequently than the general population and their problems can affect safety on the roads. Actions to improve TDs’ health and reduce the risks of (co-)morbidity or unsafe driving are imperative. Methods: The published studies dealing with the TDs’ sleep habits and mental health were reviewed to define the scenario and organize the preventive strategies proposed thus far. Results: Awareness among TDs of the high risk for health and safety due to (often co-existing) untreated sleep and mental health problems is critical. Alcohol and prescribed or illicit drugs are often misused to compensate for depression, anxiety, job strain, fatigue, and social isolation. Polypharmacy and dependence increase the chance of unsafe behaviors on the road. The TDs’ access to healthcare services is scant, and participation in industry-sponsored wellness programs is limited. Conclusions: Primary prevention is a first unavoidable step to deal with sleep and mental health problems. Educational programs, online support and tele-health assessment/monitoring would help improve the well-being, safety and health of professional TDs and increase safety on the road.
Increased Urgent Care Center Visits by Southeast European Migrants: A Retrospective, Controlled Trial from Switzerland
Authors: Klukowska-Röetzler Jolanta , Eracleous Maria , Müller Martin , Srivastava David S. , Krummrey Gert , Keidar Osnat , Exadaktylos Aristomenis K.
Published: August 2018

We investigated whether immigrants from Southeast Europe (SE) and Swiss patients have different reasons for visiting the emergency department (ED). Our retrospective data analysis for the years 2013–2017 describes the pattern of ED consultations for immigrants from SE living in Switzerland (Canton Bern), in comparison with Swiss nationals, with a focus on type of referral and reason for admission. A total of 153,320 Swiss citizens and 12,852 immigrants from SE were included in the study. The mean age was 51.30 (SD = 21.13) years for the Swiss patients and 39.70 (SD = 15.87) years for the SE patients. For some countries of origin (Albania, Bosnia and Herzegovina, and Turkey), there were highly statistically significant differences in sex distribution, with a predominance of males. SE immigrants had a greater proportion of patients in the lower triage level (level 3: SE: 67.3% vs. Swiss: 56.0%) and a greater proportion of patients in the high triage level than the Swiss population (level 1: SE: 3.4% vs. Swiss: 8.8%). SE patients of working age (16–65 years) were six times more often admitted by ambulance than older (≥65 years) SE patients, whereas this ratio was similar in the Swiss population. In both groups, the fast track service was primarily used for patients of working age (<65) and more than three times more often in the SE than the Swiss group (SE: 39.1%, Swiss: 12.6%). We identified some indications for access to primary care in emergency departments for immigrants and highlighted the need for attention to the role of organizational characteristics of primary health care in Switzerland. We highlighted the need for professional support to improve the quality of healthcare for immigrants. In the future, we will need more primary care services and general practitioners with a migrant background.
Truck and Multivehicle Truck Accidents with Injuries Near Colorado Oil and Gas Operations
Authors: Blair Benjamin D. , Hughes John , Allshouse William B. , McKenzie Lisa M. , Adgate John L.
Published: August 2018

Unconventional and conventional oil and gas (O&G) operations raise public health concerns, such as the potential impacts from trucking activity in communities that host these operations. In this work, we used two approaches to evaluate accidents in relation to O&G activities in the State of Colorado. First, we calculated the rate of truck accidents by computing the ratio of accident count and county population. When comparing counties with increased O&G operations to counties with less activity, we found that counties with more activity have greater rates of truck traffic accidents per capita (Rate Ratio = 1.07, p < 0.05, 95% CI: 1.01–1.13). Second, we laid a grid over the eleven counties of interest and counted, for each cell, the number of truck accidents, the number of multivehicle accidents with injuries, the number of homes, and the number of O&G wells. We then applied hurdle count models, using the accident counts as the outcomes and the number of homes and number of wells as independent variables. We found that both independent variables are significant predictors of truck accidents and multivehicle truck accidents. These accidents are of concern since they can have an impact on the people who live near O&G operations.
Space–Time Analysis of Vehicle Theft Patterns in Shanghai, China
Authors: Mao Yuanyuan , Dai Shenzhi , Ding Jiajun , Zhu Wei , Wang Can , Ye Xinyue
Published: August 2018

To identify and compare the space–time patterns of vehicle thefts and the effects of associated environmental factors, this paper conducts a case study of the Pudong New Area (PNA), a major urban district in Shanghai, China’s largest city. Geographic information system (GIS)-based analysis indicated that there was a stable pattern of vehicle theft over time. Hotspots of vehicle theft across different time periods were identified. These data provide clues for how law enforcement can prioritize the deployment of limited patrol and investigative resources. Vehicle thefts, especially those of non-motor vehicles, tend to be concentrated in the central-western portion of the PNA, which experienced a dramatic rate of urbanization and has a high concentration of people and vehicles. Important factors contributing to vehicle thefts include a highly mobile and transitory population, a large population density, and high traffic volume.
Therapeutic Immunization against Glioblastoma
Authors: Schijns Virgil , Pretto Chrystel , Strik Anna , Gloudemans-Rijkers Rianne , Devillers Laurent , Pierre Denis , Chung Jinah , Dandekar Manisha , Carrillo Jose , Kong Xiao-Tang , Fu Beverly , Hsu Frank , Hofman Florence , Chen Thomas , Zidovetzki Raphael , Bota Daniela , Stathopoulos Apostolos
Published: August 2018

Glioblastoma is the most common form of brain cancer in adults that produces severe damage to the brain leading to a very poor survival prognosis. The standard of care for glioblastoma is usually surgery, as well as radiotherapy followed by systemic temozolomide chemotherapy, resulting in a median survival time of about 12 to 15 months. Despite these therapeutic efforts, the tumor returns in the vast majority of patients. When relapsing, statistics suggest an imminent death dependent on the size of the tumor, the Karnofsky Performance Status, and the tumor localization. Following the standard of care, the administration of Bevacizumab, inhibiting the growth of the tumor vasculature, is an approved medicinal treatment option approved in the United States, but not in the European Union, as well as the recently approved alternating electric fields (AEFs) generator NovoTTF/Optune. However, it is clear that regardless of the current treatment regimens, glioma patients continue to have dismal prognosis and novel treatments are urgently needed. Here, we describe different approaches of recently developed therapeutic glioma brain cancer vaccines, which stimulate the patient’s immune system to recognize tumor-associated antigens (TAA) on cancer cells, aiming to instruct the immune system to eventually attack and destroy the brain tumor cells, with minimal bystander damage to normal brain cells. These distinct immunotherapies may target particular glioma TAAs which are molecularly defined, but they may also target broad patient-derived tumor antigen preparations intentionally evoking a very broad polyclonal antitumor immune stimulation.
Development of an Image-Guided Orthotopic Xenograft Mouse Model of Endometrial Cancer with Controllable Estrogen Exposure
Authors: Konings Gonda , Saarinen Niina , Delvoux Bert , Kooreman Loes , Koskimies Pasi , Krakstad Camilla , Fasmer Kristine , Haldorsen Ingfrid , Zaffagnini Amina , Häkkinen Merja , Auriola Seppo , Dubois Ludwig , Lieuwes Natasja , Verhaegen Frank , Schyns Lotte , Kruitwagen Roy ,   ENITEC Consortium, Xanthoulea Sofia , Romano Andrea
Published: August 2018

Endometrial cancer (EC) is the most common gynaecological malignancy in Western society and the majority of cases are estrogen dependent. While endocrine drugs proved to be of insufficient therapeutic value in the past, recent clinical research shows promising results by using combinational regimens and pre-clinical studies and identified potential novel endocrine targets. Relevant pre-clinical models can accelerate research in this area. In the present study we describe an orthotopic and estrogen dependent xenograft mouse model of EC. Tumours were induced in one uterine horn of female athymic nude mice using the well-differentiated human endometrial adenocarcinoma Ishikawa cell line—modified to express the luciferase gene for bioluminescence imaging (BLI). BLI and contrast-enhanced computed-tomograph (CE-CT) were used to measure non-invasive tumour growth. Controlled estrogen exposure was achieved by the use of MedRod implants releasing 1.5 μg/d of 17β-estradiol (E2) in ovariectomized mice. Stable E2 serum concentration was demonstrated by LC-MS/MS. Induced tumours were E2 responsive as increased tumour growth was observed in the presence of E2 but not placebo, assessed by BLI, CE-CT, and tumour weight at sacrifice. Metastatic spread was assessed macroscopically by BLI and histology and was seen in the peritoneal cavity, in the lymphovascular space, and in the thoracic cavity. In conclusion, we developed an orthotopic xenograft mouse model of EC that exhibits the most relevant features of human disease, regarding metastatic spread and estrogen dependency. This model offers an easy to manipulate estrogen dosage (by simply adjusting the MedRod implant length), image-guided monitoring of tumour growth, and objectively measurable endpoints (including tumour weight). This is an excellent in vivo tool to further explore endocrine drug regimens and novel endocrine drug targets for EC.
Synthesis, Evaluation for Cytotoxicity and Molecular Docking Studies of Benzo[c]furan-Chalcones for Potential to Inhibit Tubulin Polymerization and/or EGFR-Tyrosine Kinase Phosphorylation
Authors: Mphahlele Malose J. , Maluleka Marole M. , Parbhoo Nishal , Malindisa Sibusiso T.
Published: August 2018

A series of 2-arylbenzo[c]furan-chalcone hybrids 3a–y have been synthesized and evaluated for antiproliferative effects against the human breast cancer (MCF-7) cell line and for its potential to induce apoptosis and also to inhibit tubulin polymerization and/or epidermal growth factor receptor-tyrosine kinase (EGFR-TK) phosphorylation. Most of these compounds exhibited moderate to significant antigrowth effects in vitro against the MCF-7 cell line when compared to the reference standard actinomycin D. The capabilities of the most cytotoxic benzofuran-chalcone hybrids 3b and 3i, to induce apoptosis, have been evaluated by Annexin V-Cy3 SYTOX staining and caspase-3 activation. The experimental and molecular docking results suggest that the title compounds have the potential to exhibit inhibitory effects against tubulin polymerization and epidermal growth factor receptor tyrosine kinase (EGFR-TK) phosphorylation. The modeled structures of representative compounds displayed hydrophobic interactions as well as hydrogen and/or halogen bonding with the protein residues. These interactions are probably responsible for the observed increased binding affinity for the two receptors and their significant antigrowth effect against the MCF-7 cell line.
DNA Methylation Profiling of Breast Cancer Cell Lines along the Epithelial Mesenchymal Spectrum—Implications for the Choice of Circulating Tumour DNA Methylation Markers
Authors: Le Anh , Szaumkessel Marcin , Tan Tuan , Thiery Jean-Paul , Thompson Erik , Dobrovic Alexander
Published: August 2018

(1) Background: Epithelial–mesenchymal plasticity (EMP) is a dynamic process whereby epithelial carcinoma cells reversibly acquire morphological and invasive characteristics typical of mesenchymal cells. Identifying the methylation differences between epithelial and mesenchymal states may assist in the identification of optimal DNA methylation biomarkers for the blood-based monitoring of cancer. (2) Methods: Methylation-sensitive high-resolution melting (MS-HRM) was used to examine the promoter methylation status of a panel of established and novel markers in a range of breast cancer cell lines spanning the epithelial–mesenchymal spectrum. Pyrosequencing was used to validate the MS-HRM results. (3) Results: VIM, DKK3, and CRABP1 were methylated in the majority of epithelial breast cancer cell lines, while methylation of GRHL2, MIR200C, and CDH1 was restricted to mesenchymal cell lines. Some markers that have been used to assess minimal residual disease such as AKR1B1 and APC methylation proved to be specific for epithelial breast cell lines. However, RASSF1A, RARβ, TWIST1, and SFRP2 methylation was seen in both epithelial and mesenchymal cell lines, supporting their suitability for a multimarker panel. (4) Conclusions: Profiling DNA methylation shows a distinction between epithelial and mesenchymal phenotypes. Understanding how DNA methylation varies between epithelial and mesenchymal phenotypes may lead to more rational selection of methylation-based biomarkers for circulating tumour DNA analysis.
Clinical and Histopathologic Features of Interstitial Lung Disease in Erdheim–Chester Disease
Authors: Haroutunian Sara , O’Brien Kevin , Estrada-Veras Juvianee , Yao Jianhua , Boyd Louisa , Mathur Kavya , Gahl William , Mirmomen S. , Malayeri Ashkan , Kleiner David , Jaffe Elaine , Gochuico Bernadette
Published: August 2018

Limited information is available regarding interstitial lung disease (ILD) in Erdheim–Chester disease (ECD), a rare multisystemic non-Langerhans cell histiocytosis. Sixty-two biopsy-confirmed ECD patients were divided into those with no ILD (19.5%), minimal ILD (32%), mild ILD (29%), and moderate/severe ILD (19.5%), based on computed tomography (CT) findings. Dyspnea affected at least half of the patients with mild or moderate/severe ILD. Diffusion capacity was significantly reduced in ECD patients with minimal ILD. Disease severity was inversely correlated with pulmonary function measurements; no correlation with BRAF V600E mutation status was seen. Reticulations and ground-glass opacities were the predominant findings on CT images. Automated CT scores were significantly higher in patients with moderate/severe ILD, compared to those in other groups. Immunostaining of lung biopsies was consistent with ECD. Histopathology findings included subpleural and septal fibrosis, with areas of interspersed normal lung, diffuse interstitial fibrosis, histiocytes with foamy cytoplasm embedded in fibrosis, lymphoid aggregates, and focal type II alveolar cell hyperplasia. In conclusion, ILD of varying severity may affect a high proportion of ECD patients. Histopathology features of ILD in ECD can mimic interstitial fibrosis patterns observed in idiopathic ILD.
SET Overexpression is Associated with Worse Recurrence-Free Survival in Patients with Primary Breast Cancer Receiving Adjuvant Tamoxifen Treatment
Authors: Huang Yu-Hsiang , Chu Pei-Yi , Chen Ji-Lin , Huang Chun-Teng , Lee Chia-Han , Lau Ka-Yi , Wang Wan-Lun , Wang Yu-Ling , Lien Pei-Ju , Tseng Ling-Ming , Liu Chun-Yu
Published: August 2018

Adjuvant tamoxifen reduces the recurrence rate of estrogen receptor (ER)-positive breast cancer. Previous in vitro studies have suggested that tamoxifen can affect the cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein phosphatase 2A (PP2A)/phosphorylation Akt (pAkt) signaling in ER-negative breast cancer cells. In addition to CIP2A, SET nuclear proto-oncogene (SET) oncoprotein is another intrinsic inhibitor of PP2A, participating in cancer progression. In the current study, we explored the clinical significance of SET, CIP2A, PP2A, and Akt in patients with ER-positive breast cancer receiving adjuvant tamoxifen. A total of 218 primary breast cancer patients receiving adjuvant tamoxifen with a median follow-up of 106 months were analyzed, of which 17 (7.8%) experienced recurrence or metastasis. In an immunohistochemical (IHC) stain, SET overexpression was independently associated with worse recurrence-free survival (RFS) (hazard ratio = 3.72, 95% confidence interval 1.26–10.94, p = 0.017). In silico analysis revealed mRNA expressions of SET, PPP2CA, and AKT1 significantly correlated with worse RFS. In vitro, SET overexpression reduced tamoxifen-induced antitumor effects and drove luciferase activity in an Estrogen receptor element (ERE)-dependent manner. In conclusion, SET is a prognostic biomarker in patients with primary ER-positive breast cancer receiving adjuvant tamoxifen and may contribute to the failure of the tamoxifen treatment by modulating the ER signaling. Our study warrants further investigation into the potential role of SET in ER-positive breast cancer.
Effect of Hangeshashin-To (Japanese Herbal Medicine Tj-14) on Tolerability of Irinotecan: Propensity Score and Instrumental Variable Analyses
Authors: Urushiyama Hirokazu , Jo Taisuke , Yasunaga Hideo , Michihata Nobuaki , Yamana Hayato , Matsui Hiroki , Hasegawa Wakae , Hiraishi Yoshihisa , Mitani Akihisa , Fushimi Kiyohide , Nagase Takahide , Yamauchi Yasuhiro
Published: August 2018

Irinotecan hydrochloride (CPT-11) is used to treat a wide spectrum of malignant tumors. Hangeshashin-to (Japanese herbal medicine TJ-14) is reportedly effective in preventing and controlling diarrhea associated with CPT-11. However, the effect of TJ-14 on tolerability of chemotherapy with CPT-11 has not been fully investigated. We used the Japanese Diagnosis Procedure Combination inpatient database to retrospectively identify patients who had received CPT-11 on their first admission with and without TJ-14. Patients who did receive TJ-14 (N = 7092) received CPT-11 more often and in larger doses than those who did not receive TJ-14 (N = 82,019). The incidence rate ratio of CPT-11 administration was 1.34 for frequency (95% confidence interval [CI], 1.31–1.38; p < 0.001), and 1.16 for total dose (95% CI, 1.14–1.19; p < 0.001) according to stabilized inverse probability treatment weighting using propensity scores. Instrumental variable analysis showed similar trends. In-hospital mortality was significantly lower in patients who received TJ-14 than in those who did not. Odds ratios of in-hospital death in patients receiving TJ-14 was 0.81 (95% CI, 0.71–0.93; p = 0.002) according to stabilized inverse probability treatment weighting using propensity scores and 0.42 (95% CI, 0.22–0.81; p = 0.009) according to instrumental variable analysis. Our findings indicate that TJ-14 improve the tolerability of CPT-11.
Impact Assessment of a Major River Basin in Bangladesh on Storm Surge Simulation
Authors: Mohit Md. Abdul Al , Yamashiro Masaru , Hashimoto Noriaki , Mia Md. Bodruddoza , Ide Yoshihiko , Kodama Mitsuyoshi
Published: August 2018

A two-dimensional bay and river coupled numerical model in Cartesian coordinates was developed to find the impact of the river on the simulated water levels associated with a storm along the coast of Bangladesh. The shallow water models developed for both the bay and river were discretized by the finite difference method with forward in time and central in space. The boundaries for the coast and islands were approximated through proper stair steps representation and solved by a conditionally stable semi-implicit manner on a staggered Arakawa C-grid. A one-way nested scheme technique was used in the bay model to include coastal complexities as well as to save computational costs. A stable tidal condition was made by forcing the sea levels with the most energetic tidal constituent, M2, along with the southern open boundary of the bay model omitting wind stress. The developed model was then applied to foresee the sea-surface elevation associated with the catastrophic cyclone of 1991 and cyclone MORA. A comparative study of the water levels associated with a storm was made through model simulations with and without the inclusion of the river system. We found that the surge height in the bay-river junction area decreased by 20% and the surge height reduced by about 3–8% outside the junction area from this study. The obtained results were found to have a satisfactory similarity with some of the observed data.
Heuristics Algorithms for a Heterogeneous Fleets VRP with Excessive Demand for the Vehicle at the Pickup Points, and the Longest Traveling Time Constraint: A Case Study in Prasitsuksa Songkloe, Ubonratchathani Thailand
Authors: Kaewman Sasitorn , Akararungruangkul Raknoi
Published: August 2018

This paper presents a methodology to solve a special case of the vehicle routing problem (VRP) called the heterogeneous fleets VRP with excessive demand of the vehicle at the pickup points, and the longest time constraint (HFVRP-EXDE-LTC). We developed two metaheuristics—a differential evolution (DE) algorithm and an adaptive large neighborhood search (ALNS)—to solve the problem. These two proposed methods have been designed to effectively solve a special case of VRP. From the computational results, we can see that the proposed heuristics outperformed the best practices that are currently in use. The DE yielded a 9.78% lower cost than that of the current practice (757,250 baht per year), while ALNS generated a 10.89% (906,750 baht per year) lower cost than that of current practice. Comparing the proposed heuristics, ALNS achieved a 1.01% lower cost than that of DE, as ALNS had a better mechanism that was designed to escape from the local optimal.
Advancing Dielectric and Ferroelectric Properties of Piezoelectric Polymers by Combining Graphene and Ferroelectric Ceramic Additives for Energy Storage Applications
Authors: Ishaq Saira , Kanwal Farah , Atiq Shahid , Moussa Mahmoud , Azhar Umar , Imran Muhammad , Losic Dusan
Published: August 2018

To address the limitations of piezoelectric polymers which have a low dielectric constant andto improve their dielectric and ferroelectric efficiency for energy storage applications, we designed and characterized a new hybrid composite that contains polyvinylidene fluoride as a dielectric polymer matrix combined with graphene platelets as a conductive and barium titanite as ceramic ferroelectric fillers. Different graphene/barium titanate/polyvinylidene fluoride nanocomposite films were synthesized by changing the concentration of graphene and barium titanate to explore the impact of each component and their potential synergetic effect on dielectric and ferroelectric properties of the composite. Results showed that with an increase in the barium titanate fraction, dielectric efficiency ofthe nanocomposite was improved. Among all synthesized nanocomposite films, graphene/barium titanate/polyvinylidene fluoride nanocomposite in the weight ratio of 0.15:0.5:1 exhibited thehighest dielectric constant of 199 at 40 Hz, i.e., 15 fold greater than that of neat polyvinylidene fluoride film at the same frequency, and possessed a low loss tangent of 0.6. However, AC conductivity and ferroelectric properties of graphene/barium titanate/polyvinylidene fluoride nanocomposite films were enhanced with an increase in the graphene weight fraction. Graphene/barium titanate/polyvinylidene fluoride nanocomposite films with a weight ratio of 0.2:0.1:1 possessed a high AC conductivity of 1.2 × 10−4 S/m at 40 Hz. While remanent polarization, coercive field, and loop area of the same sample were 0.9 μC/cm2, 9.78 kV/cm, and 24.5 μC/cm2·V, respectively. Our results showed that a combination of graphene and ferroelectric ceramic additives are an excellent approach to significantly advance the performance of dielectric and ferroelectric properties of piezoelectric polymers for broad applications including energy storage.
Chemical Reactivity Properties, pKa Values, AGEs Inhibitor Abilities and Bioactivity Scores of the Mirabamides A–H Peptides of Marine Origin Studied by Means of Conceptual DFT
Authors: Frau Juan , Flores-Holguín Norma , Glossman-Mitnik Daniel
Published: August 2018

The MN12SX density functional, in connection with the Def2TZVP basis set, was assessed, together with the SMD solvation model (Solvation Model based on the Density), for calculation of the molecular properties and structure of a group of peptides of marine origin named Mirabamides A–H. All the chemical reactivity descriptors for the systems were calculated via Conceptual Density Functional Theory (CDFT). The active sites suitable for nucleophilic, electrophilic, and radical attacks were chosen by linking them with the Fukui function indices, nucleophilic and electrophilic Parr functions, and condensed Dual Descriptor Δ f ( r ) , respectively. Additionally, the p K a values for the different peptides are predicted with great accuracy as well as the ability of the studied molecule in acting as an efficient inhibitor of the formation of Advanced Glycation Endproducts (AGEs), which constitutes a useful knowledge for the development of drugs for fighting Diabetes, Alzheimer and Parkinson diseases. Finally, the bioactivity scores for the Mirabamides A–H are predicted through different methodologies.
The Integration of Process and Product Metallurgy in Niobium Bearing Steels
Authors: Jansto Steven G.
Published: August 2018

A review of the technological integration of both the process and physical metallurgical advancements of value-added niobium (Nb) microalloyed thermo-mechanical controlled process (TMCP) steels have evolved into the development of higher quality steels for more demanding end user requirements. The connection of process and physical metallurgy is evolving through the integration of research that is aimed at improving product quality. However, often the connection of the process metallurgical parameters is not reported, especially with industrial data. The importance of this innovative metallurgical connection is validated by the market demand for reduced fuel consumption, improved quality, and CO2 emissions in both the automotive and construction sectors. This situation has further increased the demand for new higher quality Nb-bearing steel grades. This integrative process/physical metallurgical (IP/PM) approach applies to both low and high strength steel grades in numerous applications. Often, the transition from laboratory melted and TMCP to the production scale is challenging. The methodology, process control, and key production steps that are required during the melting, ladle metallurgy, continuous casting, thermal, and hot rolling production conditions often vary significantly from the laboratory conditions. Understanding the reasons and corrective action for these variations is a critical product development success factor. These process metallurgy parameters for the industrial melting, casting, reheating, and hot rolling of Nb grades are connected and correlated to the resultant microstructures, physical metallurgy, and mechanical properties. These advanced high strength steels are microalloyed with Nb, V, Ti and/or other elements, which affect the austenite-ferrite transformation. Niobium enables the achievement of substantial grain refinement when the plate or sheet is rolled with the proper reheat, hot reduction, and thermal schedule. A recently developed key metallurgical transition is in progress applying this integrative approach with the use of MicroNiobium. A reduction of Mn and C levels with the complementary refinement of the microstructural grain size through MicroNiobium additions improves the robustness of the steel to better accommodate some process metallurgy variations. Applications are evolving in lower strength steels with Nb to achieve complementary grain refinement.
Study of Solidification Cracking Susceptibility during Laser Welding in an Advanced High Strength Automotive Steel
Authors: Agarwal Gautam , Gao He , Amirthalingam Murugaiyan , Hermans Marcel
Published: August 2018

Susceptibility to weld solidification cracking in transformation-induced plasticity steel sheets was studied using a modified standard hot cracking test used in the automotive industry. To vary the amount of self-restraint, bead-on-plate laser welding was carried out on a single-sided clamped specimen at increasing distances from the free edge. Solidification cracking was observed when welding was carried out close to the free edge. With increasing amount of restraint, the crack length showed a decreasing trend, and at a certain distance, no cracking was observed. With the aid of a finite element-based model, dynamic thermal and mechanical conditions that prevail along the transverse direction of the mushy zone are used to explain the cracking susceptibility obtained experimentally. The results indicate that the transverse strain close to the fusion boundary can be used as a criterion to predict the cracking behavior. The outcome of the study shows that optimum processing parameters can be used to weld steels closer to the free edge without solidification cracking.
Experimental Determination of Continuous Cooling Transformation (CCT) Diagrams for Dual-Phase Steels from the Intercritical Temperature Range
Authors: Bräutigam–Matus Krishna , Altamirano Gerardo , Salinas Armando , Flores Alfredo , Goodwin Frank
Published: August 2018

The phase transformation kinetics under continuous cooling conditions for intercritical austenite in a cold rolled low carbon steel were investigated over a wide range of cooling rates (0.1–200 ∘ C/s). The start and finish temperatures of the intercritical austenite transformation were determined by quenching dilatometry and a continuous cooling transformation (CCT) diagram was constructed. The resulting experimental CCT diagram was compared with that calculated via JMatPro software, and verified using electron microscopy and hardness tests. In general, the results reveal that the experimental CCT diagram can be helpful in the design of thermal cycles for the production of different grades of dual-phase–advanced high-strengh steels (DP-AHSS) in continuous processing lines. The results suggest that C enrichment of intercritical austenite as a result of heating in the two phases (ferrite–austenite) region and C partitioning during the formation of pro-eutectoid ferrite on cooling significantly alters the character of subsequent austenite phase transformations.
Geometallurgical Flowsheet as a Tool for Designing and Communicating Geometallurgical Programs
Authors: Lang Aleksandra Maria , Ellefmo Steinar Løve , Aasly Kurt
Published: August 2018

This paper introduces the concept of using a geometallurgical flowsheet as a tool to design, visualize and communicate a geometallurgical program. The development of the concept is carried out using a case study of an industrial mineral mining operation. A modified Integration Definition for Function Modeling (IDEF0) technique is proposed as a methodology to develop the geometallurgical flowsheet. The geometallurgical program is defined as a summary of the operations necessary to develop and validate the geometallurgical model. The geometallurgical model is defined as the function that links georeferenced in-situ geological characteristics and a georeferenced measure of performance in a processing plant. The geometallurgical flowsheet in this study is developed both as a general concept as well as a case-specific illustration based on the example of the Verdalskalk AS industrial mineral operation.