bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease
Authors: Rysz Jacek , Gluba-Brzózka Anna , Rysz-Górzyńska Magdalena , Franczyk Beata
Published: January 2020

Chronic kidney disease (CKD) is a worldwide health problem with steadily increasing occurrence. Significantly elevated cardiovascular morbidity and mortality have been observed in CKD. Cardiovascular diseases are the most important and frequent cause of death of CKD patients globally. The presence of CKD is related to disturbances in lipoprotein metabolism whose consequences are dyslipidemia and the accumulation of atherogenic particles. CKD not only fuels the reduction of high-density lipoprotein (HDL) cholesterol concentration, but also it modifies the composition of this lipoprotein. The key role of HDL is the participation in reverse cholesterol transport from peripheral tissues to the liver. Moreover, HDL prevents the oxidation of low-density lipoprotein (LDL) cholesterol by reactive oxygen species (ROS) and protects against the adverse effects of oxidized LDL (ox-LDL) on the endothelium. Numerous studies have demonstrated the ability of HDL to promote the production of nitric oxide (NO) by endothelial cells (ECs) and to exert antiapoptotic and anti-inflammatory effects. Increasing evidence suggests that in patients with chronic inflammatory disorders, HDLs may lose important antiatherosclerotic properties and become dysfunctional. So far, no therapeutic strategy to raise HDL, or alter the ratio of HDL subfractions, has been successful in slowing the progression of CKD or reducing cardiovascular disease in patients either with or without CKD.
Mechanisms of Tumor-Lymphatic Interactions in Invasive Breast and Prostate Carcinoma
Authors: Oliveira-Ferrer Leticia , Milde-Langosch Karin , Eylmann Kathrin , Rossberg Maila , Müller Volkmar , Schmalfeldt Barbara , Witzel Isabell , Wellbrock Jasmin , Fiedler Walter
Published: January 2020

During the last few years, diverse studies have shown that tumors can actively interact with the lymphatic system and promote metastases development. In order to examine the molecular mechanisms involved in this interaction, we co-cultured tumor and lymphatic endothelial cells (LEC) and subsequently analyzed the molecular alterations of LECs. Therefore, LECs were co-cultivated with either a highly or weakly metastatic breast cancer cell line using contact (mixture) and non-contact (transwell) co-cultures. mRNA profiles from LECs were subsequently analyzed for genes specifically induced by highly metastatic tumor cells (“metastatic specific”). Among the up-regulated “metastatic specific” genes, we found candidates involved in cell cycle, cell adhesion and motility (BST2, E-selectin, and HMMR), cytokines (CCL7, CXCL6, CXCL1, and CSF2) and factors of the complement system (C1R, C3, and CFB). Among the down-regulated genes, we detected the hyaluronan receptor STAB2, angiogenic factor apelin receptor (APLNR), and the glycosylation enzyme MAN1A1. In an additional prostate cancer co-culture model, we could confirm a “metastatic specific” upregulation of E-selectin and CCL7 in LECs after interaction with the prostate cancer cell lines LNCAP (highly metastatic) and DU145 (weakly metastatic). These data allowed us to identify a set of genes regulated in LECs during in vitro communication with cancer cells, which might subsequently facilitate lymphatic metastasis.
The Role of CYP450 Drug Metabolism in Precision Cardio-Oncology
Authors: Fatunde Olubadewa A. , Brown Sherry-Ann
Published: January 2020

As many novel cancer therapies continue to emerge, the field of Cardio-Oncology (or onco-cardiology) has become crucial to prevent, monitor and treat cancer therapy-related cardiovascular toxicity. Furthermore, given the narrow therapeutic window of most cancer therapies, drug-drug interactions are prevalent in the cancer population. Consequently, there is an increased risk of affecting drug efficacy or predisposing individual patients to adverse side effects. Here we review the role of cytochrome P450 (CYP450) enzymes in the field of Cardio-Oncology. We highlight the importance of cardiac medications in preventive Cardio-Oncology for high-risk patients or in the management of cardiotoxicities during or following cancer treatment. Common interactions between Oncology and Cardiology drugs are catalogued, emphasizing the impact of differential metabolism of each substrate drug on unpredictable drug bioavailability and consequent inter-individual variability in treatment response or development of cardiovascular toxicity. This inter-individual variability in bioavailability and subsequent response can be further enhanced by genomic variants in CYP450, or by modifications of CYP450 gene, RNA or protein expression or function in various ‘omics’ related to precision medicine. Thus, we advocate for an individualized approach to each patient by a multidisciplinary team with clinical pharmacists evaluating a treatment plan tailored to a practice of precision Cardio-Oncology. This review may increase awareness of these key concepts in the rapidly evolving field of Cardio-Oncology.
The Effects of TiO2 Nanoparticles on Cisplatin Cytotoxicity in Cancer Cell Lines
Authors: Salama Basma , El-Sherbini El-Said , El-Sayed Gehad , El-Adl Mohamed , Kanehira Koki , Taniguchi Akiyoshi
Published: January 2020

There have been many studies on improving the efficacy of cisplatin and on identifying safe compounds that can overcome multi-drug resistance (MDR) acquired by cancer cells. Our previous research showed that polyethylene glycol-modified titanium dioxide nanoparticles (TiO2 PEG NPs) affect cell membrane receptors, resulting in their aggregation, altered localization and downregulation. TiO2 PEG NPs may affect P-glycoprotein (P-gp), a membrane efflux channel involved in MDR. In this study, we investigated the effect of TiO2 PEG NPs on cisplatin cytotoxicity. We used HepG2 cells, which highly express P-gp and A431 cells, which show low expression of P-gp. The results showed that 10 µg/mL 100 nm TiO2 PEG NPs increased intracellular cisplatin levels and cytotoxicity in HepG2 cells but not in A431 cells. TiO2 PEG NPs treatment decreased the expression level of P-gp in HepG2 cells. Our findings indicate that TiO2 PEG NPs enhance cisplatin cytotoxicity by down regulating P-gp and that TiO2 PEG NPs are promising candidates for inhibiting P-gp and reversing drug resistance acquired by cancer cells.
Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area
Authors: Sanchez-Bezanilla Sonia , Åberg N. David , Crock Patricia , Walker Frederick R. , Nilsson Michael , Isgaard Jörgen , Ong Lin Kooi
Published: January 2020

Motor impairment is the most common and widely recognised clinical outcome after stroke. Current clinical practice in stroke rehabilitation focuses mainly on physical therapy, with no pharmacological intervention approved to facilitate functional recovery. Several studies have documented positive effects of growth hormone (GH) on cognitive function after stroke, but surprisingly, the effects on motor function remain unclear. In this study, photothrombotic occlusion targeting the motor and sensory cortex was induced in adult male mice. Two days post-stroke, mice were administered with recombinant human GH or saline, continuing for 28 days, followed by evaluation of motor function. Three days after initiation of the treatment, bromodeoxyuridine was administered for subsequent assessment of cell proliferation. Known neurorestorative processes within the peri-infarct area were evaluated by histological and biochemical analyses at 30 days post-stroke. This study demonstrated that GH treatment improves motor function after stroke by 50%–60%, as assessed using the cylinder and grid walk tests. Furthermore, the observed functional improvements occurred in parallel with a reduction in brain tissue loss, as well as increased cell proliferation, neurogenesis, increased synaptic plasticity and angiogenesis within the peri-infarct area. These findings provide new evidence about the potential therapeutic effects of GH in stroke recovery.
Glioblastoma Exhibits Inter-Individual Heterogeneity of TSPO and LAT1 Expression in Neoplastic and Parenchymal Cells
Authors: Cai Linzhi , Kirchleitner Sabrina V. , Zhao Dongxu , Li Min , Tonn Jörg-Christian , Glass Rainer , Kälin Roland E.
Published: January 2020

Molecular imaging is essential for diagnosis and treatment planning for glioblastoma patients. Positron emission tomography (PET) with tracers for the detection of the solute carrier family 7 member 5 (SLC7A5; also known as the amino acid transporter light chain L system, LAT1) and for the mitochondrial translocator protein (TSPO) is successfully used to provide additional information on tumor volume and prognosis. The current approaches for TSPO-PET and the visualization of tracer ([18F] Fluoroethyltyrosine, FET) uptake by LAT1 (FET-PET) do not yet exploit the full diagnostic potential of these molecular imaging techniques. Therefore, we investigated the expression of TSPO and LAT1 in patient glioblastoma (GBM) samples, as well as in various GBM mouse models representing patient GBMs of different genetic subtypes. By immunohistochemistry, we found that TSPO and LAT1 are upregulated in human GBM samples compared to normal brain tissue. Next, we orthotopically implanted patient-derived GBM cells, as well as genetically engineered murine GBM cells, representing different genetic subtypes of the disease. To determine TSPO and LAT1 expression, we performed immunofluorescence staining. We found that both TSPO and LAT1 expression was increased in tumor regions of the implanted human or murine GBM cells when compared to the neighboring mouse brain tissue. While LAT1 was largely restricted to tumor cells, we found that TSPO was also expressed by microglia, tumor-associated macrophages, endothelial cells, and pericytes. The Cancer Genome Atlas (TCGA)-data analysis corroborates the upregulation of TSPO in a bigger cohort of GBM patient samples compared to tumor-free brain tissue. In addition, AIF1 (the gene encoding for the myeloid cell marker Iba1) was also upregulated in GBM compared to the control. Interestingly, TSPO, as well as AIF1, showed significantly different expression levels depending on the GBM genetic subtype, with the highest expression being exhibited in the mesenchymal subtype. High TSPO and AIF1 expression also correlated with a significant decrease in patient survival compared to low expression. In line with this finding, the expression levels for TSPO and AIF1 were also significantly higher in (isocitrate-dehydrogenase wild-type) IDHWT compared to IDH mutant (IDHMUT) GBM. LAT1 expression, on the other hand, was not different among the individual GBM subtypes. Therefore, we could conclude that FET- and TSPO-PET confer different information on pathological features based on different genetic GBM subtypes and may thus help in planning individualized strategies for brain tumor therapy in the future. A combination of TSPO-PET and FET-PET could be a promising way to visualize tumor-associated myeloid cells and select patients for treatment strategies targeting the myeloid compartment.
The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model
Authors: Gorska-Ponikowska Magdalena , Kuban-Jankowska Alicja , Marino Gammazza Antonella , Daca Agnieszka , Wierzbicka Justyna M. , Zmijewski Michal A. , Luu Hue H. , Wozniak Michal , Cappello Francesco
Published: January 2020

2-Methoxyestradiol is one of the natural 17β-estradiol derivatives and a potential novel anticancer agent currently being under evaluation in advanced phases of clinical trials. However, the mechanism of anticancer action of 2-methoxyestradiol has not been yet fully established. In our previous studies we have demonstrated that 2-methoxyestradiol selectively induces the expression and nuclear translocation of neuronal nitric oxide synthase in osteosarcoma 143B cells. Heat shock proteins (Hsps) are factors involved in the regulation of expression and activity of nitric oxide synthases. Herein, we chose osteosarcoma cell lines differed in metastatic potential, metastatic 143B and highly metastatic MG63.2 cells, in order to further investigate the anticancer mechanism of 2-methoxyestradiol. The current study aimed to determine the role of major heat shock proteins, Hsp90 and Hsp70 in 2-methoxyestradiol-induced osteosarcoma cell death. We focused on the implication of Hsp90 and Hsp70 in control under expression of neuronal nitric oxide synthase, localization of the enzyme, and further generation of nitro-oxidative stress. To give the insight into the role of Hsp90 in regulation of anticancer efficacy of 2-methoxyestradiol, we used geldanamycin as a potent Hsp90 inhibitor. Herein, we evidenced that inhibition of Hsp90 controls the protein expression of 2-methoxyestradiol-induced neuronal nitric oxide synthase and inhibits enzyme nuclear translocation. We propose that decreased level of neuronal nitric oxide synthase protein after a combined treatment with 2-methoxyestradiol and geldanamycin is directly associated with the accompanying upregulation of Hsp70 and downregulation of Hsp90. This interaction resulted in abrogation of anticancer efficacy of 2-methoxyestradiol by geldanamycin.
High-Fidelity Router Emulation Technologies Based on Multi-Scale Virtualization
Authors: Song He , Wang Xiaofeng , Zhai Mengdong , Zhang Guangjie
Published: January 2020

Virtualization has the advantages of strong scalability and high fidelity in host node emulation. It can effectively meet the requirements of network emulation, including large scale, high fidelity, and flexible construction. However, for router emulation, virtual routers built with virtualization and routing software use Linux Traffic Control to emulate bandwidth, delay, and packet loss rates, which results in serious distortions in congestion scenarios. Motivated by this deficiency, we propose a novel router emulation method that consists of virtualization plane, routing plane, and a traffic control method. We designed and implemented our traffic control module in multi-scale virtualization, including the kernel space of a KVM-based virtual router and the user space of a Docker-based virtual router. Experiments show not only that the proposed method achieves high-fidelity router emulation, but also that its performance is consistent with that of a physical router in congestion scenarios. These findings provide good support for network research into congestion scenarios on virtualization-based emulation platforms.
MANNWARE: A Malware Classification Approach with a Few Samples Using a Memory Augmented Neural Network
Authors: Tran Kien , Sato Hiroshi , Kubo Masao
Published: January 2020

The ability to stop malware as soon as they start spreading will always play an important role in defending computer systems. It must be a huge benefit for organizations as well as society if intelligent defense systems could themselves detect and prevent new types of malware as soon as they reveal only a tiny amount of samples. An approach introduced in this paper takes advantage of One-shot/Few-shot learning algorithms to solve the malware classification problems using a Memory Augmented Neural Network in combination with the Natural Language Processing techniques such as word2vec, n-gram. We embed the malware’s API calls, which are very valuable sources of information for identifying malware’s behaviors, in the different feature spaces, and then feed them to the one-shot/few-shot learning models. Evaluating the model on the two datasets (FFRI 2017 and APIMDS) shows that the models with different parameters could yield high accuracy on malware classification with only a few samples. For example, on the APIMDS dataset, it was able to guess 78.85% correctly after seeing only nine malware samples and 89.59% after fine-tuning with a few other samples. The results confirmed very good accuracies compared to the other traditional methods, and point to a new area of malware research.
Using Nutritional Geometry to Explore How Social Insects Navigate Nutritional Landscapes
Authors: Crumière Antonin J. J. , Stephenson Calum J. , Nagel Manuel , Shik Jonathan Z.
Published: January 2020

Insects face many cognitive challenges as they navigate nutritional landscapes that comprise their foraging environments with potential food items. The emerging field of nutritional geometry (NG) can help visualize these challenges, as well as the foraging solutions exhibited by insects. Social insect species must also make these decisions while integrating social information (e.g., provisioning kin) and/or offsetting nutrients provisioned to, or received from unrelated mutualists. In this review, we extend the logic of NG to make predictions about how cognitive challenges ramify across these social dimensions. Focusing on ants, we outline NG predictions in terms of fundamental and realized nutritional niches, considering when ants interact with related nestmates and unrelated bacterial, fungal, plant, and insect mutualists. The nutritional landscape framework we propose provides new avenues for hypothesis testing and for integrating cognition research with broader eco-evolutionary principles.
Towards a Realistic Estimation of the Powering Performance of a Ship with a Gate Rudder System
Authors: Sasaki Noriyuki , Kuribayashi S. , Fukazawa M. , Atlar Mehmet
Published: January 2020

This paper presents an investigation on the scale effects associated with the powering performance of a Gate Rudder System (GRS) which was recently introduced as a novel energy-saving propulsion and maneuvring device. This new system was applied for the first time on a 2400 GT domestic container ship, and full-scale sea trials were conducted successfully in Japan, in 2017. The trials confirmed the superior powering and maneuvring performance of this novel system. However, a significant discrepancy was also noticed between the model test-based performance predictions and the full-scale measurements. The discrepancy was in the power-speed data and also in the maneuvring test data when these data were compared with the data of her sister container ship which was equipped with a conventional flap rudder. Twelve months after the delivery of the vessel with the gate rudder system, the voyage data revealed a surprisingly more significant difference in the powering performance based on the voyage data. The aim of this paper, therefore, is to take a further step towards an improved estimation of the powering performance of ships with a GRS with a specific emphasis on the scale effect issues associated with a GRS. More specifically, this study investigated the scale effects on the powering performance of a gate rudder system based on the analyses of the data from two tank tests and full-scale trials with the above-mentioned sister ships. The study focused on the corrections for the scale effects, which were believed to be associated with the drag and lift characteristics of the gate rudder blades due to the low Reynolds number experienced in model tests combined with the unique arrangement of this rudder and propulsion system. Based on the appropriate semi-empirical approaches that support model test and full-scale data, this study verified the scale effect phenomenon and presented the associated correction procedure. Also, this study presented an enhanced methodology for the powering performance prediction of a ship driven by a GRS implementing the proposed scale effect correction. The predicted powering performance of the subject container vessel with the GRS presented an excellent agreement with the full-scale trials data justifying the claimed scale effect and associated correction procedure, as well as the proposed enhanced methodology for the practical way of predicting the powering performance of a ship with the GRS.
Unraveling How Candida albicans Forms Sexual Biofilms
Authors: Perry Austin M. , Hernday Aaron D. , Nobile Clarissa J.
Published: January 2020

Biofilms, structured and densely packed communities of microbial cells attached to surfaces, are considered to be the natural growth state for a vast majority of microorganisms. The ability to form biofilms is an important virulence factor for most pathogens, including the opportunistic human fungal pathogen Candida albicans. C. albicans is one of the most prevalent fungal species of the human microbiota that asymptomatically colonizes healthy individuals. However, C. albicans can also cause severe and life-threatening infections when host conditions permit (e.g., through alterations in the host immune system, pH, and resident microbiota). Like many other pathogens, this ability to cause infections depends, in part, on the ability to form biofilms. Once formed, C. albicans biofilms are often resistant to antifungal agents and the host immune response, and can act as reservoirs to maintain persistent infections as well as to seed new infections in a host. The majority of C. albicans clinical isolates are heterozygous (a/α) at the mating type-like (MTL) locus, which defines Candida mating types, and are capable of forming robust biofilms when cultured in vitro. These “conventional” biofilms, formed by MTL-heterozygous (a/α) cells, have been the primary focus of C. albicans biofilm research to date. Recent work in the field, however, has uncovered novel mechanisms through which biofilms are generated by C. albicans cells that are homozygous or hemizygous (a/a, a/Δ, α/α, or α/Δ) at the MTL locus. In these studies, the addition of pheromones of the opposite mating type can induce the formation of specialized “sexual” biofilms, either through the addition of synthetic peptide pheromones to the culture, or in response to co-culturing of cells of the opposite mating types. Although sexual biofilms are generally less robust than conventional biofilms, they could serve as a protective niche to support genetic exchange between mating-competent cells, and thus may represent an adaptive mechanism to increase population diversity in dynamic environments. Although conventional and sexual biofilms appear functionally distinct, both types of biofilms are structurally similar, containing yeast, pseudohyphal, and hyphal cells surrounded by an extracellular matrix. Despite their structural similarities, conventional and sexual biofilms appear to be governed by distinct transcriptional networks and signaling pathways, suggesting that they may be adapted for, and responsive to, distinct environmental conditions. Here we review sexual biofilms and compare and contrast them to conventional biofilms of C. albicans.
Assessment of Shaft Surface Structures on the Tribological Behavior of Journal Bearings by Physical and Virtual Simulation
Authors: Pusterhofer Michael , Summer Florian , Maier Michael , Grün Florian
Published: January 2020

Optimizing the surface topography of cast iron crankshafts offers the opportunity to use this material as an alternative to steel in high-performance combustion engines. In the past, this was not possible due to the higher wear on bearing shells and the higher friction losses in relation to forged steel shafts. In order to find an optimized shaft micro topography, the friction and wear behavior of steel and cast iron shafts with different surface treatments were compared to each other, using a combined physical (experimental) and a virtual (computational) simulation approach. The experiments were carried out with a rotary tribometer using a journal bearing test configuration with the possibility to test real-life bearing shells and shaft specimens, manufactured from real-life crankshafts. In the experiments, a polished steel shaft with low bearing wear was effective. The optimization of cast iron crankshafts by a novel surface treatment showed a significant reduction of bearing wear in relation to the classical surface finishing procedures of cast iron shafts. A computational simulation approach, considering the real-life micro topography by using the Navier–Stokes equations for the calculation of micro hydrodynamics, supports the assessment of fluid friction. The virtual simulation shows, in accordance to the experimental results, only a minor influence of the investigated shaft topographies on the fluid friction. Further optimization of shaft surfaces for journal bearing systems seems possible only by the usage of patterned micro topographies.
Characterization of 1-3 Piezoelectric Composite with a 3-Tier Polymer Structure
Authors: Sun Ruiqing , Wang Likun , Zhang Yanjun , Zhong Chao
Published: January 2020

In order to boost the electromechanical coupling factor and decrease the characteristic impedance, a 1-3 piezoelectric composite with a 3-tier polymer structure was designed and fabricated, in which epoxy resin constitutes the middle layer and silicone rubber is used to clamp the epoxy. The effective parameters of the composite, such as resonant frequency, electromechanical coupling factor, and characteristic impedance, were studied by the finite element method and experiment. The experimental results indicate that the electromechanical coupling factor of the composite is enhanced by 8.4% and the characteristic impedance is decreased by 52.8%, compared with the traditional 1-3 ceramic/epoxy composite.
In Situ Doping of Nitrogen in <110>-Oriented Bulk 3C-SiC by Halide Laser Chemical Vapour Deposition
Authors: Lai Youfeng , Xia Lixue , Xu Qingfang , Li Qizhong , Liu Kai , Yang Meijun , Zhang Song , Han Mingxu , Goto Takashi , Zhang Lianmeng , Tu Rong
Published: January 2020

Doping of nitrogen is a promising approach to improve the electrical conductivity of 3C-SiC and allow its application in various fields. N-doped, <110>-oriented 3C-SiC bulks with different doping concentrations were prepared via halide laser chemical vapour deposition (HLCVD) using tetrachlorosilane (SiCl4) and methane (CH4) as precursors, along with nitrogen (N2) as a dopant. We investigated the effect of the volume fraction of nitrogen (ϕN2) on the preferred orientation, microstructure, electrical conductivity (σ), deposition rate (Rdep), and optical transmittance. The preference of 3C-SiC for the <110> orientation increased with increasing ϕN2. The σ value of the N-doped 3C-SiC bulk substrates first increased and then decreased with increasing ϕN2, reaching a maximum value of 7.4 × 102 S/m at ϕN2 = 20%. Rdep showed its highest value (3000 μm/h) for the undoped sample and decreased with increasing ϕN2, reaching 1437 μm/h at ϕN2 = 30%. The transmittance of the N-doped 3C-SiC bulks decreased with ϕN2 and showed a declining trend at wavelengths longer than 1000 nm. Compared with the previously prepared <111>-oriented N-doped 3C-SiC, the high-speed preparation of <110>-oriented N-doped 3C-SiC bulks further broadens its application field.
Hardware-In-The-Loop Simulations of Hole/Crack Identification in a Composite Plate
Authors: Liang Yen-Chu , Sun Yun-Ping
Published: January 2020

The technology of hardware-in-the-loop simulations (HILS) plays an important role in the design of complex systems, for example, the structural health monitoring (SHM) of aircrafts. Due to the high performance of personal computers, HILS can provide practical solutions to many problems in engineering and sciences, especially in the huge systems, giant dams for civil engineering, and aircraft system. This study addresses the HILS in hole/crack identification in composite laminates. The multiple loading modes method is used for hole/crack identification. The signals of strains measured from the data-acquisition (DAQ) devices are accomplished by the graphical software LabVIEW. The results represent the actual responses of multiple loading mode tests of real specimens. A personal computer is employed to execute the identification work according to the strain data from DAQ devices by using a nonlinear optimization approach. When all the criteria are satisfied, the final identification results will be obtained. HILS will achieve real time identification of hole/crack in the composite plate by using the actual response measured from the sensors. Not only the size, but also the location and orientation of the crack/hole in a composite plate are successfully identified herein.
Spun Carbon Nanotube Fibres and Films as an Alternative to Printed Electronic Components
Authors: Taborowska Patrycja , Giżewski Tomasz , Patmore Jeff , Janczak Daniel , Jakubowska Małgorzata , Lekawa-Raus Agnieszka
Published: January 2020

Current studies of carbon nanotubes have enabled both new electronic applications and improvements to the performance of existing ones. Manufacturing of macroscopic electronic components with this material generally involves the use of printed electronic methods, which must use carbon nanotube (CNT) powders. However, in recent years, it has been shown that the use of ready-made self-standing macroscopic CNT assemblies could have considerable potential in the future development of electronic components. Two examples of these are spun carbon nanotube fibers and CNT films. The following paper considers whether these spun materials may replace printed electronic CNT elements in all applications. To enable the investigation of this question some practical experiments were undertaken. They included the formation of smart textile elements, flexible and transparent components, and structural electronic devices. By taking this approach it has been possible to show that CNT fibres and films are highly versatile materials that may improve the electrical and mechanical performance of many currently produced printed electronic elements. Additionally, the use of these spun materials may enable many new applications and functionalities particularly in the area of e-textiles. However, as with every new technology, it has its limitations, and these are also considered.
Morphological Analysis of KDP-Crystal Workpiece Surfaces Machined by Ultra-Precision Fly Cutting
Authors: Chen Dongju , Zhang Shiwei , Liu Jingfang , Zha Chunqing , Pan Ri
Published: January 2020

Potassium dihydrogen phosphate crystals exhibit excellent nonlinear optical properties that are significantly affected by the surface morphology of the crystal. To comprehensively examine and characterize the morphological features of these crystals, the machined surfaces of workpieces are analyzed using wavelet, fractal, and power spectral density (PSD) methods. First, the fractal method is employed to analyze the features of the machined surfaces of different materials and examine the relationship between the surface roughness and fractal dimension of different materials. Then, the morphological anisotropy of the machined surfaces is analyzed using the two-dimensional PSD method. Based on the orientation of the machined surfaces of the workpieces, the tangential waves on the surfaces are analyzed using wavelet-transform and PSD methods. From a frequency-domain perspective, the scales of various influencing factor signals are identified. Additionally, the frequency range of the spindle vibration is determined based on the machining experiment. On this basis, the cause of the machined surface waviness errors is revealed.
Influence of Annealing Atmosphere on the Characteristics of Ga2O3/4H-SiC n-n Heterojunction Diodes
Authors: Lee Young-Jae , Schweitz Michael A. , Oh Jong-Min , Koo Sang-Mo
Published: January 2020

Ga2O3/4H-SiC n-n isotype heterojunction diodes were fabricated by depositing Ga2O3 thin films by RF magnetron sputtering. The influence of annealing atmosphere on the film quality and electrical properties of Ga2O3 layers was investigated. X-ray diffraction (XRD) analysis showed a significant increase in the peak intensities of different faces of β-Ga2O3 {(−201), (−401) and (002)}. X-ray photoelectron spectroscopy (XPS) measurement showed that the atomic ratio of oxygen increases under high-temperature annealing. Moreover, an N2-annealed diode exhibited a greater rectifying ratio and a lower thermal activation energy owing to the decrease in oxygen-related traps and vacancies on the Ga2O3 film and Ga2O3–metal interface.
Engineering Gels with Time-Evolving Viscoelasticity
Authors: Mattei Giorgio , Cacopardo Ludovica , Ahluwalia Arti
Published: January 2020

From a mechanical point of view, a native extracellular matrix (ECM) is viscoelastic. It also possesses time-evolving or dynamic behaviour, since pathophysiological processes such as ageing alter their mechanical properties over time. On the other hand, biomaterial research on mechanobiology has focused mainly on the development of substrates with varying stiffness, with a few recent contributions on time- or space-dependent substrate mechanics. This work reports on a new method for engineering dynamic viscoelastic substrates, i.e., substrates in which viscoelastic parameters can change or evolve with time, providing a tool for investigating cell response to the mechanical microenvironment. In particular, a two-step (chemical and enzymatic) crosslinking strategy was implemented to modulate the viscoelastic properties of gelatin hydrogels. First, gels with different glutaraldehyde concentrations were developed to mimic a wide range of soft tissue viscoelastic behaviours. Then their mechanical behaviour was modulated over time using microbial transglutaminase. Typically, enzymatically induced mechanical alterations occurred within the first 24 h of reaction and then the characteristic time constant decreased although the elastic properties were maintained almost constant for up to seven days. Preliminary cell culture tests showed that cells adhered to the gels, and their viability was similar to that of controls. Thus, the strategy proposed in this work is suitable for studying cell response and adaptation to temporal variations of substrate mechanics during culture.
Liquid Regions of Lanthanum-Bearing Aluminosilicates
Authors: Li Yandong , Zhang Tongsheng , Feng Yefeng , Liu Chengjun , Jiang Maofa
Published: January 2020

The Al2O3-SiO2, La2O3-Al2O3, and La2O3-SiO2 binary phase diagrams were estimated by Redlich–Kister expression. La4.67Si3O13 (=La4.67(SiO4)3O) was introduced to improve the existing phase diagrams. The Al2O3-SiO2-La2O3 ternary phase diagram extrapolated by Kohler method was optimized. Then, the liquidus of Al2O3-SiO2-La2O3 system at 1600 °C was compared with Al2O3-SiO2-RE2O3 (RE = Rare Earth Elements) systems and experimental results in other literature. The high temperature experiments were conducted in the tube furnace at 1500 °C. Then the field emission scanning electron microscope (FE-SEM), energy dispersive spectrometer (EDS), and X-ray diffraction (XRD) were employed to verify the calculated liquid region and precipitates phase at 1500 °C. Moreover, the liquidus of binary systems were compared with FactSage results and experiments. The optimized ternary phase diagram shows the relatively reliable region of liquid phase, and it is significant to the seal glass of solid oxide fuel cells and other fields being related to RE containing silicates.
Marine Natural Products from the Yucatan Peninsula
Authors: Pech-Puch Dawrin , Pérez-Povedano Mar , Lenis-Rojas Oscar A. , Rodríguez Jaime , Jiménez Carlos
Published: January 2020

Mexico is one of the three areas of the world with the greatest terrestrial and cultural biological diversity. The diversity of Mexican medicinal flora has been studied for a long time and several bioactive compounds have been isolated. The investigation of marine resources, and particularly the potential of Mexican marine resources, has not been intensively investigated, even though the Yucatan Peninsula occupies 17.4% of the total of the Mexican coast, with great biological diversity in its coasts and the ocean. There are very few studies on the chemistry of natural products from marine organisms that were collected along the coasts of the Yucatan Peninsula and most of them are limited to the evaluation of the biological activity of their organic extracts. The investigations carried out on marine species from the Yucatan Peninsula resulted in the identification of a wide structural variety of natural products that include polyketides, terpenoids, nitrogen compounds, and biopolymers with cytotoxic, antibacterial, antifouling, and neurotoxic activities. This review describes the literature of bioprospecting and the exploration of the natural product diversity of marine organisms from the coasts of the Yucatan Peninsula up to mid-2019.
Novel Reporter System Monitoring IL-18 Specific Signaling Can Be Applied to High-Throughput Screening
Authors: Kurata Riho , Shimizu Kenji , Cui Xiaofeng , Harada Masamitsu , Isagawa Takayuki , Semba Hiroaki , Ishihara Jun , Yamada Koji , Nagai Jun , Yoshida Yasuhiro , Takeda Norihiko , Maemura Koji , Yonezawa Tomo
Published: January 2020

Very recently, the immunotherapies against cancer, autoimmune diseases, and infection have been feasible and promising. Thus, we have examined the possibility whether or not human gamma delta T cells can be applied for the novel immunotherapies. We previously established the cells stably maintaining NFkB-driven human secreted embryonic alkaline phosphatase (SEAP) expression. The cells can be used to determine the transcription activity of NFkB with high-standard dynamic range and accuracy. Because IL-18 is a kind of cytokines that enhances cytotoxicity and activity of human gamma delta T cells through NFkB activation, we have focused on the activity and signaling of IL-18. In this study, we modified the previous reporter cell that can determine the transcription activity of NFkB to express two subunits consisted of human IL-18 receptor. The modified cells secreted SEAP in response to treatment with human recombinant IL-18 in a concentration-dependent manner. We also observed the concentration-dependently enhancement of NFkB activity in the cells treated with mouse recombinant IL-18 although the affinity was lower compared to human recombinant IL-18. We also previously established the cells stably expressing and secreting human recombinant IL-18 and then validated whether or not the conditioned medium from the cells activate NFkB transcription activity using this assay. Our university has kept collecting many extracts from over 18,000 marine bacteria in our local sea around Omura bay—fungi, plants for Chinese herbal medicine, and so on—and also have kept gathering synthetic compounds from many Japanese chemists as drug libraries. Finally, in order to identify drugs mimicking IL-18 biological activity or possessing inhibitory effects on IL-18-induced NFkB, we demonstrated drug screening using number of extracts derived from marine bacteria and synthetic compounds.
Total Exenteration En Bloc with a Nephrectomy for Locally Advanced Cervical Cancer Invading a Pelvic Kidney—A Case Report and Literature Review
Authors: Bacalbasa Nicolae , Balescu Irina , Vilcu Mihaela , Dima Simona , Diaconu Camelia , Iliescu Laura , Filipescu Alexandru , Brezean Iulian
Published: January 2020

Introduction: Extended pelvic resection might be the option of choice in patients presenting locally advanced cervical cancer. However, the possibility of a co-existence of an ectopic, pelvic kidney that is invaded by such a tumor is extremely rare. Case Presentation: A 54-year-old female patient, diagnosed with locally advanced cervical cancer in the presence of a pelvic kidney, was submitted to surgery with curative intent. A large, abscessed cervical tumor invading the urinary bladder and the rectum was found, so a total exenteration was planned. Intraoperatively, tumor invasion of the left kidney, which was found in an ectopic, pelvic position was also encountered; therefore, total pelvic exenteration in association with a left nephrectomy was successfully performed. Conclusions: The presence of an ectopic, pelvic disposition of the kidney makes it susceptible to be invaded by locally advanced pelvic tumors; in such cases, a nephrectomy might also be needed.
Fibroblast Growth Factor 23-Producing Phosphaturic Mesenchymal Tumor with Extraordinary Morphology Causing Oncogenic Osteomalacia
Authors: Then Cornelia , Asbach Evelyn , Bartsch Harald , Thon Niklas , Betz Christian , Reincke Martin , Schmidmaier Ralf
Published: January 2020

A possible cause of hypophosphatemia is paraneoplastic secretion of fibroblast growth factor 23 (FGF-23). Tumors secreting FGF-23 are rare, mostly of mesenchymal origin, usually benign, and may be located anywhere in the body, including hands and feet, which are often not represented in conventional imaging. A 50-year-old woman presented with diffuse musculoskeletal pain and several fractures. Secondary causes of osteoporosis were excluded. Laboratory analysis revealed hypophosphatemia and elevated alkaline phosphatase, parathyroid hormone, and FGF-23. Thus, oncogenic osteomalacia due to neoplastic FGF-23 secretion was suspected. FDG-PET-CT and DOTATATE-PET-CT imaging demonstrated no tumor. Cranial MRI revealed a tumorous mass in the left cellulae ethmoidales. The tumor was resected and histopathological examination showed a cell-rich tumor with round to ovoid nuclei, sparse cytoplasm, and sparse matrix, resembling an olfactory neuroblastoma. Immunohistochemical analysis first led to diagnosis of olfactory neuroblastoma, which was later revised to phosphaturic mesenchymal tumor. Following the resection, FGF-23 and phosphate levels normalized. In conclusion, we here describe a patient with an FGF-23-secreting phosphaturic mesenchymal tumor with an unusual morphology. Furthermore, we emphasize diagnostic pitfalls when dealing with FGF-23-induced hypophosphatemia.
Metabolomics in the Context of Plant Natural Products Research: From Sample Preparation to Metabolite Analysis
Authors: Salem Mohamed A. , Perez de Souza Leonardo , Serag Ahmed , Fernie Alisdair R. , Farag Mohamed A. , Ezzat Shahira M. , Alseekh Saleh
Published: January 2020

Plant-derived natural products have long been considered a valuable source of lead compounds for drug development. Natural extracts are usually composed of hundreds to thousands of metabolites, whereby the bioactivity of natural extracts can be represented by synergism between several metabolites. However, isolating every single compound from a natural extract is not always possible due to the complex chemistry and presence of most secondary metabolites at very low levels. Metabolomics has emerged in recent years as an indispensable tool for the analysis of thousands of metabolites from crude natural extracts, leading to a paradigm shift in natural products drug research. Analytical methods such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) are used to comprehensively annotate the constituents of plant natural products for screening, drug discovery as well as for quality control purposes such as those required for phytomedicine. In this review, the current advancements in plant sample preparation, sample measurements, and data analysis are presented alongside a few case studies of the successful applications of these processes in plant natural product drug discovery.
Organic Contaminant Biodegradation by Oxidoreductase Enzymes in Wastewater Treatment
Authors: Barber Edward A. , Liu Ziyi , Smith Stephen R.
Published: January 2020

Organic contaminants (OCs), such as pharmaceuticals, personal care products, flame retardants, and plasticisers, are societally ubiquitous, environmentally hazardous, and structurally diverse chemical compounds whose recalcitrance to conventional wastewater treatment necessitates the development of more effective remedial alternatives. The engineered application of ligninolytic oxidoreductase fungal enzymes, principally white-rot laccase, lignin peroxidase, and manganese peroxidase, has been identified as a particularly promising approach for OC remediation due to their strong oxidative power, broad substrate specificity, low energy consumption, environmental benignity, and cultivability from lignocellulosic waste. By applying an understanding of the mechanisms by which substrate properties influence enzyme activity, a set of semi-quantitative physicochemical criteria (redox potential, hydrophobicity, steric bulk and pKa) was formulated, against which the oxidoreductase degradation susceptibility of twenty-five representative OCs was assessed. Ionisable, compact, and electron donating group (EDG) rich pharmaceuticals and antibiotics were judged the most susceptible, whilst hydrophilic, bulky, and electron withdrawing group (EWG) rich polyhalogenated compounds were judged the least susceptible. OC susceptibility scores were in general agreement with the removal rates reported for experimental oxidoreductase treatments (R2 = 0.60). Based on this fundamental knowledge, and recent developments in enzyme immobilisation techniques, microbiological enzymic treatment strategies are proposed to formulate a new generation of biological wastewater treatment processes for the biodegradation of environmentally challenging OC compounds.
Androgen Receptor in Breast Cancer—Clinical and Preclinical Research Insights
Authors: Anestis Aristomenis , Zoi Ilianna , Papavassiliou Athanasios G. , Karamouzis Michalis V.
Published: January 2020

The Androgen Receptor (AR) is emerging as an important factor in the pathogenesis of breast cancer (BC), which is the most common malignancy among females worldwide. The concordance of more than 70% of AR expression in primary and metastatic breast tumors implies that AR may be a new marker and a potential therapeutic target among AR-positive breast cancer patients. Biological insight into AR-positive breast cancer reveals that AR may cross-talk with several vital signaling pathways, including key molecules and receptors. AR exhibits different behavior depending on the breast cancer subtype. Preliminary clinical research using AR-targeted drugs, which have already been FDA-approved for prostate cancer (PC), has given promising results for AR-positive breast cancer patients. However, since the prognostic and predictive value of AR positivity remains uncertain, it is difficult to identify and stratify patients that would benefit from AR-targeted therapies. Herein, through a review of preclinical studies, clinical studies, and clinical trials, we summarize the biology of AR, its prognostic and predictive value, as well as its therapeutic implications by breast cancer molecular subtype.
Synthesis of Elaborate Benzofuran-2-Carboxamide Derivatives through a Combination of 8-Aminoquinoline Directed C–H Arylation and Transamidation Chemistry
Authors: Oschmann Michael , Johansson Holm Linus , Pourghasemi-Lati Monireh , Verho Oscar
Published: January 2020

Herein, we present a short and highly modular synthetic route that involves 8-aminoquinoline directed C–H arylation and transamidation chemistry, and which enables access to a wide range of elaborate benzofuran-2-carboxamides. For the directed C–H arylation reactions, Pd catalysis was used to install a wide range of aryl and heteroaryl substituents at the C3 position of the benzofuran scaffold in high efficiency. Directing group cleavage and further diversification of the C3-arylated benzofuran products were then achieved in a single synthetic operation through the utilization of a one-pot, two-step transamidation procedure, which proceeded via the intermediate N-acyl-Boc-carbamates. Given the high efficiency and modularity of this synthetic strategy, it constitutes a very attractive method for generating structurally diverse collections of benzofuran derivatives for small molecule screening campaigns.