bluuebunny/crossref_metadata_2025 huggingface dataset:
The Novel Role of SOX2 as an Early Predictor of Cancer Risk in Patients with Laryngeal Precancerous Lesions
Authors: Granda-Díaz Rocío , Menéndez Sofía T. , Pedregal Mallo Daniel , Hermida-Prado Francisco , Rodríguez René , Suárez-Fernández Laura , Vallina Aitana , Sánchez-Canteli Mario , Rodríguez Aida , Fernández-García M. Soledad , Rodrigo Juan P. , García-Pedrero Juana M.
Published: March 2019

The SOX2 gene located at 3q26 is frequently amplified and overexpressed in multiple cancers, including head and neck squamous cell carcinomas (HNSCC). The tumor-promoting activity and involvement of SOX2 in tumor progression has been extensively demonstrated, thereby emerging as a promising therapeutic target. However, the role of SOX2 in early stages of tumorigenesis and its possible contribution to malignant transformation remain unexplored. This study investigates for the first time SOX2 protein expression by immunohistochemistry and gene amplification by real-time PCR using a large series of 94 laryngeal precancerous lesions. Correlations with the histopathological classification and the risk of progression to invasive carcinoma were established. Nuclear SOX2 expression was frequently detected in 38 (40%) laryngeal dysplasias, whereas stromal cells and normal adjacent epithelia showed negative expression. SOX2 gene amplification was detected in 18 (33%) of 55 laryngeal dysplasias. Univariate Cox analysis showed that SOX2 gene amplification (p = 0.046) and protein expression (p < 0.001) but not histological grading (p = 0.432) were significantly associated with laryngeal cancer risk. In multivariate stepwise analysis including age, tobacco, histology, SOX2 gene amplification and SOX2 expression, SOX2 expression (HR = 3.531, 95% CI 1.144 to 10.904; p = 0.028) was the only significant independent predictor of laryngeal cancer development. These findings underscore the relevant role of SOX2 in early tumorigenesis and a novel clinical application of SOX2 expression as independent predictor of laryngeal cancer risk in patients with precancerous lesions beyond current WHO histological grading. Therefore, targeting SOX2 could lead to effective strategies for both cancer prevention and treatment.
Facets of Communication: Gap Junction Ultrastructure and Function in Cancer Stem Cells and Tumor Cells
Authors: Beckmann Anja , Hainz Nadine , Tschernig Thomas , Meier Carola
Published: March 2019

Gap junction proteins are expressed in cancer stem cells and non-stem cancer cells of many tumors. As the morphology and assembly of gap junction channels are crucial for their function in intercellular communication, one focus of our review is to outline the data on gap junction plaque morphology available for cancer cells. Electron microscopic studies and freeze-fracture analyses on gap junction ultrastructure in cancer are summarized. As the presence of gap junctions is relevant in solid tumors, we exemplarily outline their role in glioblastomas and in breast cancer. These were also shown to contain cancer stem cells, which are an essential cause of tumor onset and of tumor transmission into metastases. For these processes, gap junctional communication was shown to be important and thus we summarize, how the expression of gap junction proteins and the resulting communication between cancer stem cells and their surrounding cells contributes to the dissemination of cancer stem cells via blood or lymphatic vessels. Based on their importance for tumors and metastases, future cancer-specific therapies are expected to address gap junction proteins. In turn, gap junctions also seem to contribute to the unattainability of cancer stem cells by certain treatments and might thus contribute to therapeutic resistance.
Cancer-Associated Fibroblasts’ Functional Heterogeneity in Pancreatic Ductal Adenocarcinoma
Authors: Awaji Mohammad , Singh Rakesh K.
Published: March 2019

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths in the USA. Desmoplasia and inflammation are two major hallmarks of PDAC. Desmoplasia, composed of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), and infiltrating immune and endothelial cells, acts as a biophysical barrier to hinder chemotherapy and actively contributes to tumor progression and metastasis. CAFs represent a multifunctional subset of PDAC microenvironment and contribute to tumor initiation and progression through ECM deposition and remodeling, as well as the secretion of paracrine factors. Attempts to resolve desmoplasia by targeting CAFs can render an adverse outcome, which is likely due to CAFs heterogeneity. Recent reports describe subsets of CAFs that assume more secretory functions, in addition to the typical myofibroblast phenotype. Here, we review the literature and describe the relationship between CAFs and inflammation and the role of the secretory-CAFs in PDAC.
Role of Calcium Signaling in GA101-Induced Cell Death in Malignant Human B Cells
Authors: Latour Simon , Zanese Marion , Le Morvan Valérie , Vacher Anne-Marie , Menard Nelly , Bijou Fontanet , Durrieu Francoise , Soubeyran Pierre , Savina Ariel , Vacher Pierre , Bresson-Bepoldin Laurence
Published: March 2019

GA101/obinutuzumab is a novel type II anti-CD20 monoclonal antibody (mAb), which is more effective than rituximab (RTX) in preclinical and clinical studies when used in combination with chemotherapy. Ca2+ signaling was shown to play a role in RTX-induced cell death. This report concerns the effect of GA101 on Ca2+ signaling and its involvement in the direct cell death induced by GA101. We reveal that GA101 triggered an intracellular Ca2+ increase by mobilizing intracellular Ca2+ stores and activating Orai1-dependent Ca2+ influx in non-Hodgkin lymphoma cell lines and primary B-Cell Chronic Lymphocytic Leukemia (B-CLL) cells. According to the cell type, Ca2+ was mobilized from two distinct intracellular compartments. In Raji, BL2, and B-CLL cells, GA101 induced a Ca2+ release from lysosomes, leading to the subsequent lysosomal membrane permeabilization and cell death. Inhibition of this calcium signaling reduced GA101-induced cell death in these cells. In SU-DHL-4 cells, GA101 mobilized Ca2+ from the endoplasmic reticulum (ER). Inhibition of ER replenishment, by blocking Orai1-dependent Ca2+ influx, led to an ER stress and unfolded protein response (UPR) which sensitized these cells to GA101-induced cell death. These results revealed the central role of Ca2+ signaling in GA101’s action mechanism, which may contribute to designing new rational drug combinations improving its clinical efficacy.
Quantitative Measurement of Functional Activity of the PI3K Signaling Pathway in Cancer
Authors: van de Stolpe Anja
Published: March 2019

The phosphoinositide 3-kinase (PI3K) growth factor signaling pathway plays an important role in embryonic development and in many physiological processes, for example the generation of an immune response. The pathway is frequently activated in cancer, driving cell division and influencing the activity of other signaling pathways, such as the MAPK, JAK-STAT and TGFβ pathways, to enhance tumor growth, metastasis, and therapy resistance. Drugs that inhibit the pathway at various locations, e.g., receptor tyrosine kinase (RTK), PI3K, AKT and mTOR inhibitors, are clinically available. To predict drug response versus resistance, tests that measure PI3K pathway activity in a patient sample, preferably in combination with measuring the activity of other signaling pathways to identify potential resistance pathways, are needed. However, tests for signaling pathway activity are lacking, hampering optimal clinical application of these drugs. We recently reported the development and biological validation of a test that provides a quantitative PI3K pathway activity score for individual cell and tissue samples across cancer types, based on measuring Forkhead Box O (FOXO) transcription factor target gene mRNA levels in combination with a Bayesian computational interpretation model. A similar approach has been used to develop tests for other signaling pathways (e.g., estrogen and androgen receptor, Hedgehog, TGFβ, Wnt and NFκB pathways). The potential utility of the test is discussed, e.g., to predict response and resistance to targeted drugs, immunotherapy, radiation and chemotherapy, as well as (pre-) clinical research and drug development.
Macrophage Origin, Metabolic Reprogramming and IL-1β Signaling: Promises and Pitfalls in Lung Cancer
Authors: Guilbaud Emma , Gautier Emmanuel L. , Yvan-Charvet Laurent
Published: March 2019

Macrophages are tissue-resident cells that act as immune sentinels to maintain tissue integrity, preserve self-tolerance and protect against invading pathogens. Lung macrophages within the distal airways face around 8000–9000 L of air every day and for that reason are continuously exposed to a variety of inhaled particles, allergens or airborne microbes. Chronic exposure to irritant particles can prime macrophages to mediate a smoldering inflammatory response creating a mutagenic environment and favoring cancer initiation. Tumor-associated macrophages (TAMs) represent the majority of the tumor stroma and maintain intricate interactions with malignant cells within the tumor microenvironment (TME) largely influencing the outcome of cancer growth and metastasis. A number of macrophage-centered approaches have been investigated as potential cancer therapy and include strategies to limit their infiltration or exploit their antitumor effector functions. Recently, strategies aimed at targeting IL-1β signaling pathway using a blocking antibody have unexpectedly shown great promise on incident lung cancer. Here, we review the current understanding of the bridge between TAM metabolism, IL-1β signaling, and effector functions in lung adenocarcinoma and address the challenges to successfully incorporating these pathways into current anticancer regimens.
The Novel Mnk1/2 Degrader and Apoptosis Inducer VNLG-152 Potently Inhibits TNBC Tumor Growth and Metastasis
Authors: Ramalingam Senthilmurugan , Ramamurthy Vidya P. , Gediya Lalji K. , Murigi Francis N. , Purushottamachar Puranik , Huang Weiliang , Choi Eun Yong , Zhang Yuji , Vasaitis Tadas S , Kane Maureen A. , Lapidus Rena G. , Njar Vincent C. O.
Published: March 2019

Currently, there are no effective therapies for patients with triple-negative breast cancer (TNBC), an aggressive and highly metastatic disease. Activation of eukaryotic initiation factor 4E (eIF4E) by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (Mnk1/2) play a critical role in the development, progression and metastasis of TNBC. Herein, we undertook a comprehensive study to evaluate the activity of a first-in-class Mnk1/2 protein degraders, racemic VNLG-152R and its two enantiomers (VNLG-152E1 and VNLG-152E2) in in vitro and in vivo models of TNBC. These studies enabled us to identify racemic VNLG-152R as the most efficacious Mnk1/2 degrader, superior to its pure enantiomers. By targeting Mnk1/2 protein degradation (activity), VNLG-152R potently inhibited both Mnk-eIF4E and mTORC1 signaling pathways and strongly regulated downstream factors involved in cell cycle regulation, apoptosis, pro-inflammatory cytokines/chemokines secretion, epithelial-mesenchymal transition (EMT) and metastasis. Most importantly, orally bioavailable VNLG-152R exhibited remarkable antitumor (91 to 100% growth inhibition) and antimetastatic (~80% inhibition) activities against cell line and patient-derived TNBC xenograft models, with no apparent host toxicity. Collectively, these studies demonstrate that targeting Mnk-eIF4E/mTORC1 signaling with a potent Mnk1/2 degrader, VNLG-152R, is a novel therapeutic strategy that can be developed as monotherapy for the effective treatment of patients with primary/metastatic TNBC.
Association of miR-34a Expression with Quality of Life of Glioblastoma Patients: A Prospective Study
Authors: Vaitkiene Paulina , Pranckeviciene Aiste , Stakaitis Rytis , Steponaitis Giedrius , Tamasauskas Arimantas , Bunevicius Adomas
Published: March 2019

MiR-34a acts as tumor-suppressor by targeting many oncogenes related to proliferation, apoptosis, and invasion of gliomas. We studied the relationships between health-related quality of life (HRQOL), depression, and miR-34a expression status in patients with newly diagnosed glioblastoma (GBM). A comprehensive HRQOL assessment was completed by 38 patients with glioblastoma prior to surgical resection and included the European Organization for Research and Treatment of Cancer (EORTC) questionnaire for cancer patients (QLQ-C30) and the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20), the Patient Health Questionnaire-9 (PHQ-9), the Karnofsky performance index (KPS), and The Glasgow Outcome Scale (GOS). The miR-34a expression in glioblastoma tissue was measured using quantitative reverse transcription PCR. Our findings show that lower miR-34a expression is significantly associated with higher tumor volume, worse physical functioning, lower KPS, and greater depressive symptom severity of GBM patients. Moreover, analysis reveals that miR-34a effects might be gender specific, as stronger relationships between miR-34a and patient functioning measures were observed in males when compared to females. Despite the fact that, due to small sample size, our results should be considered as preliminary, our study suggests that miR-34a is associated with tumor burden and can be important for health-related quality of life, functional status, and mood symptoms of glioblastoma patients.
Immobilised Cerium-Doped Zinc Oxide as a Photocatalyst for the Degradation of Antibiotics and the Inactivation of Antibiotic-Resistant Bacteria
Authors: Zammit Ian , Vaiano Vincenzo , Ribeiro Ana R. , Silva Adrián M. T. , Manaia Célia M. , Rizzo Luigi
Published: March 2019

The threat of antibiotic resistance to the wellbeing of societies is well established. Urban wastewater treatment plants (UWTPs) are recognised sources for antibiotic resistance dissemination in the environment. Herein a novel cerium-doped zinc oxide (Ce-ZnO) photocatalyst is compared to ZnO and the benchmark TiO2-P25 in the immobilised form on a metallic support, to evaluate a photocatalytic process as a possible tertiary treatment in UWTPs. The catalysts were compared for the removal of two antibiotics, trimethoprim (TMP) and sulfamethoxazole (SMX), and for the inactivation of Escherichia coli (E. coli) strain DH5-Alpha in isotonic sodium chloride solution and of autochthonous bacteria in real secondary wastewater. In real wastewater, E. coli and other coliforms were monitored, as well as the respective fractions resistant to ofloxacin and azithromycin. In parallel, Pseudomonas aeruginosa and the respective sub-population resistant to ofloxacin or ciprofloxacin were also monitored. Photocatalysis with both ZnO and Ce-ZnO was faster than using TiO2-P25 at degrading the antibiotics, with Ce-ZnO the fastest against SMX but slower than undoped ZnO in the removal of TMP. Ce-ZnO catalyst reuse in the immobilised form produced somewhat slower kinetics maintained >50% of the initial activity, even after five cycles of use. Approximately 3 log10 inactivation of E. coli in isotonic sodium chloride water was recorded with reproducible results. In the removal of autochthonous bacteria in real wastewater, Ce-ZnO performed better (more than 2 log values higher) than TiO2-P25. In all cases, E. coli and other coliforms, including their resistant subpopulations, were inactivated at a higher rate than P. aeruginosa. With short reaction times no evidence for enrichment of resistance was observed, yet with extended reaction times low levels of bacterial loads were not further inactivated. Overall, Ce-ZnO is an easy and cheap photocatalyst to produce and immobilise and the one that showed higher activity than the industry standard TiO2-P25 against the tested antibiotics and bacteria, including antibiotic-resistant bacteria.
An Innovative Biocatalyst for Continuous 2G Ethanol Production from Xylo-Oligomers by Saccharomyces cerevisiae through Simultaneous Hydrolysis, Isomerization, and Fermentation (SHIF)
Authors: Milessi-Esteves Thais S. , Corradini Felipe A.S. , Kopp Willian , Zangirolami Teresa C. , Tardioli Paulo W. , Giordano Roberto C. , Giordano Raquel L.C.
Published: March 2019

Many approaches have been considered aimed at ethanol production from the hemicellulosic fraction of biomass. However, the industrial implementation of this process has been hindered by some bottlenecks, one of the most important being the ease of contamination of the bioreactor by bacteria that metabolize xylose. This work focuses on overcoming this problem through the fermentation of xylulose (the xylose isomer) by native Saccharomyces cerevisiae using xylo-oligomers as substrate. A new concept of biocatalyst is proposed, containing xylanases and xylose isomerase (XI) covalently immobilized on chitosan, and co-encapsulated with industrial baker’s yeast in Ca-alginate gel spherical particles. Xylo-oligomers are hydrolyzed, xylose is isomerized, and finally xylulose is fermented to ethanol, all taking place simultaneously, in a process called simultaneous hydrolysis, isomerization, and fermentation (SHIF). Among several tested xylanases, Multifect CX XL A03139 was selected to compose the biocatalyst bead. Influences of pH, Ca2+, and Mg2+ concentrations on the isomerization step were assessed. Experiments of SHIF using birchwood xylan resulted in an ethanol yield of 0.39 g/g, (76% of the theoretical), selectivity of 3.12 gethanol/gxylitol, and ethanol productivity of 0.26 g/L/h.
The Effect of Citric Acid Concentration on the Properties of LaMnO3 as a Catalyst for Hydrocarbon Oxidation
Authors: Sihaib Zakaria , Puleo Fabrizio , Pantaleo Giuseppe , La Parola Valeria , Valverde José Luis , Gil Sonia , Liotta Leonarda Francesca , Giroir-Fendler Anne
Published: March 2019

LaMnO3 (LM) catalysts with a molar ratio of citric acid (CA) to metal (La3+ + Mn2+) nitrates ranging from 0.5 to 2 (LM0.5 to LM2) were synthesized by the citrate sol–gel method with the aim of studying the effect of the citric acid ratio on the physicochemical properties and the catalytic performance in hydrocarbon oxidation. Structural and morphological properties of these catalysts were characterized by X-ray diffraction (XRD) and specific surface area (N2 adsorption) measurements, while the chemical composition was determined by inductively coupled plasma atomic emission spectroscopy (ICP-OES). In the selected samples, additional characterizations were carried out by thermogravimetric and differential thermal analysis (TGA/DTA), Fourier Transform Infrared Spectroscopy (FT-IR), temperature-programmed reduction by hydrogen (H2-TPR), and X-ray photoelectron spectroscopy (XPS). The results showed that the amount of citric acid used significantly influenced the TGA/DTA profile of gels along with the physicochemical properties of the catalysts. The XRD patterns are consistent with the perovskite formation as the main phase. The segregation of a small amount of Mn3O4, detected for molar ratios ranging between 0.5 and 1.5, suggested the formation of a slightly nonstoichiometric LaMn1−xO3 phase with a relatively high content of Mn4+. The catalytic performance was evaluated in the total oxidation of two selected hydrocarbons, toluene and propene, which represent typical volatile organic compounds (VOCs). Typically, three consecutive catalytic cycles were performed in order to reach steady-state performance in toluene and propene oxidation. Moreover, the stability of the catalysts under reaction conditions was investigated through 24-h experiments at 17% of toluene conversion. The catalysts LM1.2, LM1.3, and LM1.5 showed the best catalytic performance in both hydrocarbon oxidations, well comparing with the Pd/Al2O3 used as a reference.
Perovskites as Catalysts in Advanced Oxidation Processes for Wastewater Treatment
Authors: Rojas-Cervantes María Luisa , Castillejos Eva
Published: March 2019

Advanced oxidation processes (AOPs), based on the formation of highly reactive radicals are able to degrade many organic contaminants present in effluent water. In the heterogeneous AOPS the presence of a solid which acts as catalyst in combination with other systems (O3, H2O2, light) is required. Among the different materials that can catalyse these processes, perovskites are found to be very promising, because they are highly stable and exhibit a high mobility of network oxygen with the possibility of forming vacancies and to stabilize unusual oxidation states of metals. In this review, we show the fundaments of different kinds of AOPs and the application of perovskite type oxides in them, classified attending to the oxidant used, ozone, H2O2 or peroxymonosulfate, alone or in combination with other systems. The photocatalytic oxidation, consisting in the activation of the perovskite by irradiation with ultraviolet or visible light is also revised.
Mechanism Analysis and Kinetic Modelling of Cu NPs Catalysed Glycerol Conversion into Lactic Acid
Authors: Zavrazhnov Sergey A. , Esipovich Anton L. , Zlobin Sergey Yu. , Belousov Artem S. , Vorotyntsev Andrey V.
Published: March 2019

Mechanism analysis and kinetic modeling of glycerol conversion into lactic acid in the alkaline media with and without heterogeneous catalyst Cu NPs are reported. The reaction pathways were determined in agreement with the experimental results and comprise several types of reactions, namely dehydrogenation, hydrogenolysis, dehydration and C–C cleavage. Experimental concentration-time profiles were obtained in a slurry batch reactor at different glycerol, NaOH and Cu NPs concentrations in a temperature range of 483–518 K. Power law, Langmuir–Hinshelwood (LH) and Eley–Rideal (ER) models were chosen to fit the experimental data. The proposed reaction pathways and obtained kinetic model adequately describe the experimental data. The reaction over Cu NPs catalyst in the presence of NaOH proceeds with a significantly lower activation barrier (Ea = 81.4 kJ∙mol−1) compared with the only homogeneous catalytic conversion (Ea = 104.0 kJ∙mol−1). The activation energy for glycerol hydrogenolysis into 1,2-propanediol on the catalyst surface without adding hydrogen is estimated of 102.0 kJ∙mol−1. The model parameters obtained in this study would be used to scale an industrial unit in a reactor modeling.
Dye-sensitized Photocatalyst of Sepiolite for Organic Dye Degradation
Authors: Chuaicham Chitiphon , Pawar Radheshyam , Sasaki Keiko
Published: March 2019

The photocatalytic activity of sepiolite was examined for degradation of several dye compounds under visible light irradiation. Higher adsorption capacities and greater photocatalytic performance of cationic dyes (rhodamine B and methylene blue) were observed on sepiolite, in comparison with anionic dyes (orange II and trypan blue). Superiority in the photocatalytic activity of cationic dyes is attributed to the strong electrostatic attraction and photosensitization properties of cationic dye molecules. Sepiolite has degraded 45.3% rhodamine B within 120 min, which is the greatest photocatalytic degradation efficiency when compared with other dyes. Subsequently, the reusability of spent sepiolite after adsorption of rhodamine B was evaluated by the degradation of trypan blue under the visible light irradiation. The photocatalytic degradation performance of trypan blue by spent sepiolite after adsorption of rhodamine B increased about twice as much as with pristine sepiolite, indicating that the dye-sensitized photocatalytic process could enhance the photocatalytic degradation ability of sepiolite. Through radical scavenger tests, it was found that a superoxide radical is mainly responsible for rhodamine B degradation. The possible mechanism of rhodamine B degradation under visible light irradiation was proposed. The sepiolite could be a potential catalyst for the degradation of organic pollutants in wastewater under solar light.
ROR1 Expression and Its Functional Significance in Hepatocellular Carcinoma Cells
Authors: Cetin Metin , Odabas Gorkem , Douglas Leon R. , Duriez Patrick J. , Balcik-Ercin Pelin , Yalim-Camci Irem , Sayan Abdulkadir Emre , Yagci Tamer
Published: March 2019

Background: Hepatocellular carcinoma (HCC) is a common and deadly cancer; however, very little improvement has been made towards its diagnosis and prognosis. The expression and functional contribution of the receptor tyrosine kinase ROR1 have not been investigated in HCC before. Hence, we investigated the expression of ROR1 in HCC cells and assessed its involvement in hepatocarcinogenesis. Methods: Recombinant bacterial ROR1 protein was used as an immunogen to generate ROR1 monoclonal antibodies. ROR1 transcript levels were detected by RT-qPCR and the protein expression of ROR1 in HCC was assessed by Western blotting by using homemade anti-ROR1 monoclonal antibodies. Apoptosis, cell cycle, trans-well migration, and drug efflux assays were performed in shRNA-ROR1 HCC cell clones to uncover the functional contribution of ROR1 to hepatocarcinogenesis. Results: New ROR1 antibodies specifically detected endogenous ROR1 protein in human and mouse HCC cell lines. ROR1-knockdown resulted in decreased proliferation and migration but enhanced resistance to apoptosis and anoikis. The observed chemotherapy-resistant phenotype of ROR1-knockdown cells was due to enhanced drug efflux and increased expression of multi-drug resistance genes. Conclusions: ROR1 is expressed in HCC and contributes to disease development by interfering with multiple pathways. Acquired ROR1 expression may have diagnostic and prognostic value in HCC.
Hypoxia-Inducible Factors and the Regulation of Lipid Metabolism
Authors: Mylonis Ilias , Simos George , Paraskeva Efrosyni
Published: March 2019

Oxygen deprivation or hypoxia characterizes a number of serious pathological conditions and elicits a number of adaptive changes that are mainly mediated at the transcriptional level by the family of hypoxia-inducible factors (HIFs). The HIF target gene repertoire includes genes responsible for the regulation of metabolism, oxygen delivery and cell survival. Although the involvement of HIFs in the regulation of carbohydrate metabolism and the switch to anaerobic glycolysis under hypoxia is well established, their role in the control of lipid anabolism and catabolism remains still relatively obscure. Recent evidence indicates that many aspects of lipid metabolism are modified during hypoxia or in tumor cells in a HIF-dependent manner, contributing significantly to the pathogenesis and/or progression of cancer and metabolic disorders. However, direct transcriptional regulation by HIFs has been only demonstrated in relatively few cases, leaving open the exact and isoform-specific mechanisms that underlie HIF-dependency. This review summarizes the evidence for both direct and indirect roles of HIFs in the regulation of genes involved in lipid metabolism as well as the involvement of HIFs in various diseases as demonstrated by studies with transgenic animal models.
Nuclear Progestin Receptor Phosphorylation by Cdk9 Is Required for the Expression of Mmp15, a Protease Indispensable for Ovulation in Medaka
Authors: Ogiwara Katsueki , Takahashi Takayuki
Published: March 2019

Ovulation denotes the discharge of fertilizable oocytes from ovarian follicles. Follicle rupture during ovulation requires extracellular matrix (ECM) degradation at the apex of the follicle. In the teleost medaka, an excellent model for vertebrate ovulation studies, LH-inducible matrix metalloproteinase 15 (Mmp15) plays a critical role during rupture. In this study, we found that follicle ovulation was inhibited not only by roscovitine, the cyclin-dependent protein kinase (CDK) inhibitor, but also by CDK9-inhibitor II, a specific CDK9 inhibitor. Inhibition of follicle ovulation by the inhibitors was accompanied by the suppression of Mmp15 expression in the follicle. In follicles treated with the inhibitors, the formation of the phosphorylated nuclear progestin receptor (Pgr) was inhibited. Roscovitine treatment caused a reduction in the binding of Pgr to the promoter region of mmp15. The expression of Cdk9 and cyclin I (Ccni), and their association in the follicle was demonstrated, suggesting that Cdk9 and Ccni may be involved in the phosphorylation of Pgr in vivo. LH-induced follicular expression of ccni/Ccni was also shown. This study is the first to report the involvement of CDK in ECM degradation during ovulation in a vertebrate species.
A Comparison of the Performance of Two Kinds of Waterborne Coatings on Bamboo and Bamboo Scrimber
Authors: Xu Jianfeng , Liu Ru , Wu Huagui , Qiu Hongyun , Yu Yanglun , Long Ling , Ni Yonghao
Published: March 2019

For this paper, two kinds of waterborne coatings, polyurethane acrylate (PUA) and epoxy resin, were synthesized and then coated onto neat bamboo and bamboo scrimber (BS), respectively. The coating performance of the samples was investigated. The results showed that, for the two kinds of coatings, there was a chemical reaction occurring between both coatings and the substrates. The permeability with respect to bamboo was higher than that of BS, while that of the epoxy resin coating was better than PUA. However, the PUA film was smoother than epoxy resin. The epoxy resin coating on bamboo had the best adhesion, which was at a 1 level. The abrasion values of the four samples varied in the same substrate. A higher hardness of the coating film was obtained when coated with PUA. In general, the coating performance of bamboo scrimber was poorer than that of bamboo, either coated with PUA or epoxy resin. The epoxy resin had a better coating performance than PUA.
Thermochromic Behavior of VO2/Polymer Nanocomposites for Energy Saving Coatings
Authors: Xygkis Michalis , Gagaoudakis Emmanouil , Zouridi Leila , Markaki Olga , Aperathitis Elias , Chrissopoulou Kyriaki , Kiriakidis George , Binas Vassilios
Published: March 2019

Vanadium dioxide (VO2) is a well-known thermochromic material that can potentially be used as a smart coating on glazing systems in order to regulate the internal temperature of buildings. Most growth techniques for VO2 demand high temperatures (>250 °C), making it impossible to comply with flexible (polymeric) substrates. To overcome this problem, hydrothermally synthesized VO2 particles may be dispersed in an appropriate matrix, leading to a thermochromic coating that can be applied on a substrate at a low temperature (<100 °C). In this work, we reported on the thermochromic properties of a VO2/Poly-Vinyl-Pyrrolidone (PVP) nanocomposite. More specifically, a fixed amount of VO2 particles was dispersed in different PVP quantities forming hybrids of various VO2/PVP molar ratios which were deposited as films on fused silica glass substrates by utilizing the drop-casting method. The crystallite size was calculated and found to be 35 nm, almost independent of the PVP concentration. As far as the thermochromic characteristics are concerned, the molar ratio of the VO2/PVP nanocomposite producing VO2 films with the optimum thermochromic properties was 0.8. These films exhibited integral solar transmittance modulation (overall wavelengths) ΔTrsol = 0.35%–1.7%, infrared (IR) switching at 2000 nm ΔTrIR = 10%, visible transmittance at 550 nm TrVis = 38%, critical transition temperature TC = 66.8 °C, and width of transmittance hysteresis loop ΔTC = 6.8 °C. Moreover, the critical transition temperature was observed to slightly shift depending on the VO2/PVP molar ratio.
Polydopamine-Inspired Surface Modification of Polypropylene Hernia Mesh Devices via Cold Oxygen Plasma: Antibacterial and Drug Release Properties
Authors: Saitaer Xiakeer , Sanbhal Noor , Qiao Yansha , Li Yan , Gao Jing , Brochu Gaetan , Guidoin Robert , Khatri Awais , Wang Lu
Published: March 2019

Mesh infection is a major complication of hernia surgery after polypropylene (PP) mesh implantation. Modifying the PP mesh with antibacterial drugs is an effective way to reduce the chance of infection, but the hydrophobic characteristic of PP fibers has obstructed the drug adhesion. Therefore, to prepare antimicrobial PP mesh with a stable drug coating layer and to slow the drug release property during the hernia repair process has a great practical meaning. In this work, PP meshes were coated by bio-inspired polydopamine (PDA), which can load and release levofloxacin. PP meshes were activated with cold oxygen plasma and then plasma activated PP fibers were coated with PDA. The PDA coated meshes were further soaked in levofloxacin. The levofloxacin loaded PP meshes demonstrate excellent antimicrobial properties for 6 days and the drug release has lasted for at least 24 h. Moreover, a control PP mesh sample without plasma treatment was also prepared, after coating with PDA and loading levofloxacin. The antimicrobial property was sustained only for two days. The maximum inhibition zone of PDA coated meshes with and without plasma treatment was 12.5 and 9 mm, respectively. On all accounts, the modification strategy can facilely lead to long-term property of infection prevention.
Electronic Structure of Boron Flat Holeless Sheet
Authors: Chkhartishvili Levan , Murusidze Ivane , Becker Rick
Published: March 2019

The electronic band structure, namely energy band surfaces and densities-of-states (DoS), of a hypothetical flat and ideally perfect, i.e., without any type of holes, boron sheet with a triangular network is calculated within a quasi-classical approach. It is shown to have metallic properties as is expected for most of the possible structural modifications of boron sheets. The Fermi curve of the boron flat sheet is found to be consisted of 6 parts of 3 closed curves, which can be approximated by ellipses representing the quadric energy-dispersion of the conduction electrons. The effective mass of electrons at the Fermi level in a boron flat sheet is found to be too small compared with the free electron mass m 0 and to be highly anisotropic. Its values distinctly differ in directions Γ–K and Γ–M: m Γ – K / m 0 ≈ 0.480 and m Γ – M / m 0 ≈ 0.052 , respectively. The low effective mass of conduction electrons, m σ / m 0 ≈ 0.094 , indicates their high mobility and, hence, high conductivity of the boron sheet. The effects of buckling/puckering and the presence of hexagonal or other type of holes expected in real boron sheets can be considered as perturbations of the obtained electronic structure and theoretically taken into account as effects of higher order.
pH and Redox Induced Color Changes in Protein Crystals Suffused with Dyes
Authors: McPherson Alexander
Published: March 2019

Protein crystals, otherwise usually colorless, can be stained a variety of hues by saturating them with dyes, by diffusion from the mother liquor or co-crystallization. The colors assumed by dyes are a function of chemical factors, particularly pH and redox potential. Protein crystals saturated with a pH sensitive dye, initially at one pH, can be exposed to the mother liquor at a second pH and the crystal will change color over time as H3O+ ions diffuse through the crystal. This allows diffusion rates of H3O+ through the crystal to be measured. Diffusion fronts are often clearly delineated. Similar experiments can be carried out with redox sensitive dyes by adding reductants, such as ascorbic acid or dithionite, or oxidants such as H2O2, to the crystal’s mother liquor. Presented here are a number of experiments using pH or redox sensitive dye-saturated protein crystals, and some experiments using double dye, sequential redox–pH changes.
Analysis of the Transmission Characteristic and Stress-Induced Birefringence of Hollow-Core Circular Photonic Crystal Fiber
Authors: Yang Jingxuan , Zhang Hu , Zhang Xiaoguang , Li Hui , Xi Lixia
Published: March 2019

Orbital angular momentum modes in optical fibers have polarization mode dispersion. The relationship between polarization mode dispersion and the birefringence vector can be deduced using an optical fiber dynamic equation. First, a mathematical model was established to formulate mode dispersion caused by stress-induced birefringence. Second, in the stress-induced birefringence simulation model, the finite element method was used to analyze the transmission characteristics of the hollow-core circular photonic crystal fiber. Finally, mode dispersion caused by stress-induced birefringence was obtained using theoretical derivation and simulation analyses. The results showed that the new fiber type has good transmission characteristics and strong stress sensitivity, which provide key theoretical support for optimizing the structural parameters of optical fiber and designing stress sensors.
Acquisition of Quasi-Monochromatic Dual-Energy in a Microfocus X-ray Generator and Development of Applied Technology
Authors: Hasegawa Hiroaki , Sato Masanori
Published: March 2019

In regenerative medicine, evaluation of bone mineral density using a microfocus X-ray generator could eventually be used to determine the degree of bone tissue regeneration. To evaluate bone mineral density against regenerated bone material, two low-energy X-rays are necessary. Herein, the acquisition of quasi-monochromatic, dual-energy soft X-ray and the subsequent medical application were examined using the K-absorption edges of two types of metal filters (i.e., zirconium and tin) in a microfocus X-ray generator. Investigation of the optimal tube voltage and filter thickness to form a quasi-monochromatic energy spectrum with a single filter revealed that a filter thickness of 0.3 mm results in an optimal monochromatization state. When a dual filter was used, the required filter thickness was 0.3 mm for tin and 0.2 mm for zirconium at a tube voltage of 35 kV. For the medical application, we measured quasi-monochromatic, dual-energy X-rays to evaluate the measurement accuracy of bone mineral density. Using aluminum as a simulated bone sample, a relative error of ≤5% was consistent within the aluminum thickness range of 1–3 mm. These data suggest that a bone mineral density indicator of recycled bone material can be easily obtained with the quasi-monochromatic X-ray technique using a microfocus X-ray generator.
Accurate Modeling of Conductor Rough Surfaces in Waveguide Devices
Authors: Huang Binke , Jia Qi
Published: March 2019

To address the effects of surface roughness on wave propagation in the microwave and millimeter-wave bands, this paper studies electromagnetic wave propagation and focuses on the propagation loss within an inner environment featuring surface roughness of the metallic waveguide structures. The conductivity gradient model is first developed to treat surface roughness with inhomogeneous conductivity, and then the concept of a frequency-dependent effective conductivity is introduced to model the effects of surface roughness in waveguide structures. With the effective conductivity used in the commercial 3D field solver, High Frequency Structure Simulator (HFSS™), a surface impedance boundary condition strategy is applied on ideally smooth surfaces to model the actual behavior of rough metallic waveguide surfaces. Finally, the propagation performance is predicted by comparing the effects of surface roughness in metallic waveguide structures and the results from the models with ideally smooth surfaces, using rectangular waveguide, cylindrical resonator and coupling cavity filters models. Overall, this effective conductive concept can be applied using various commercial field solvers to handle surface roughness effects accurately and efficiently in any work involving conducting microwave structures.
A Compact Output Power Combiner for Broadband Doherty Power Amplifiers
Authors: McKnight Ken , Darwish Ali , Zaghloul Mona
Published: March 2019

A novel compact output power combiner for broadband Doherty Power Amplifiers is proposed in this paper. The proposed output power combiner avoids the use of quarter-wave impedance transformers as they are sizable and work over narrow bandwidths. Instead, the proposed combiner utilizes a distributed Brune Section to implement a compact broadband impedance inverter. The final area of the proposed output combiner is λ2/48. When compared to the conventional broadband Doherty structure, which has an approximate area of λ2/16, this structure offers an approximate size reduction of 67%. The proposed combiner is verified by using it in the design of a broadband Doherty power amplifier with an operating bandwidth of 1.7 GHz to 3.4 GHz. The saturated output power varies from 39.2 to 40.4 dBm with a peak power drain efficiency ranging from 58% to 66%. The drain efficiency at 6 dB Output Power Back-Off (OPBO) varies from 37.4% to 45% over an octave.
Performance Analysis of Bandwidth Allocation Based on Dynamic User Priority for Indoor Visible Light Communication Ultra-Dense Networks
Authors: Bai Xiang-Wei , Li Qing , Tao Si-Yu
Published: March 2019

Focusing on the high user density in visible light communication ultra-dense networks (VLC-UDNs), this paper proposes a resource allocation method based on dynamic user priority (DUP). Firstly, this paper establishes the DUP model, which realizes a multi-dimensional measurement for differences of users. Considering the variety of network environments, we dynamically select multiple features of users and achieve the calculation of DUP by fuzzy logic (FL). Secondly, the throughput-maximizing resource allocation (TMRA) scheme with user priority guarantee is proposed. Thirdly, the lower bound of the proposed DUP-TMRA is derived. Simulation results show that the proposed multi-dimensional DUP model outperforms the conventional one-dimensional DUP model and fixed priority model. In addition, the proposed TMRA scheme outperforms the conventional proportion allocation scheme. Finally, in comparisons of system throughput, the proposed DUP-TMRA achieves 4% performance improvement against the conventional required data rate proportion allocation (RPA) method. In comparisons of fairness, DUP achieves the modest performance. In comparisons of satisfaction, when the average blocking probability is higher than 0.45, the proposed DUP-TMRA improves the proportion of satisfied users against the conventional RPA method by up to 17.5%.
A Multispectral Backscattered Light Recorder of Insects’ Wingbeats
Authors: Rigakis Iraklis , Potamitis Ilyas , Tatlas Nicolaos-Alexandros , Livadaras Ioannis , Ntalampiras Stavros
Published: March 2019

Most reported optical recorders of the wingbeat of insects are based on the so-called extinction light, which is the variation of light in the receiver due to the cast shadow of the insect’s wings and main body. In this type of recording devices, the emitter uses light and is placed opposite to the receiver, which is usually a single (or multiple) photodiode. In this work, we present a different kind of wingbeat sensor and its associated recorder that aims to extract a deeper representational signal of the wingbeat event and color characterization of the main body of the insect, namely: a) we record the backscattered light that is richer in harmonics than the extinction light, b) we use three different spectral bands, i.e., a multispectral approach that aims to grasp the melanization and microstructural and color features of the wing and body of the insects, and c) we average at the receiver’s level the backscattered signal from many LEDs that illuminate the wingbeating insect from multiple orientations and thus offer a smoother and more complete signal than one based on a single snapshot. We present all the necessary details to reproduce the device and we analyze many insects of interest like the bee Apis mellifera, the wasp Polistes gallicus, and some insects whose wingbeating characteristics are pending in the current literature, like Drosophila suzukii and Zaprionus, another member of the drosophilidae family.
Experimental Study on the Reliability of PBGA Electronic Packaging under Shock Loading
Authors: Shao Jiang , Zhang Hongjian , Chen Bo
Published: March 2019

Plastic Ball Grid Array (PBGA) one of the most important electronic packaging methods, is widely used in aeronautical industry field. According to the JEDEC standard, shock tests of PBGA assemblies are conducted under different loading conditions. Several important parameters, such as the fatigue life of PBGA assemblies, the relationship between solder joint positions and fatigue life, the relationship between strain energy density and fatigue life, are analyzed based on experiment results. The failure modes of PBGA assemblies are studied by optical microscope (OM). The results show that during the shock tests, the strains of the solder joints near the center of the specimen are larger than other positions, and these solder joints are prone to form micro cracks. With the increase of the shock times, these micro cracks extend rapidly which will eventually cause the failure of the PBGA electronic packaging.
An FPGA-Based CNN Accelerator Integrating Depthwise Separable Convolution
Authors: Liu Bing , Zou Danyin , Feng Lei , Feng Shou , Fu Ping , Li Junbao
Published: March 2019

The Convolutional Neural Network (CNN) has been used in many fields and has achieved remarkable results, such as image classification, face detection, and speech recognition. Compared to GPU (graphics processing unit) and ASIC, a FPGA (field programmable gate array)-based CNN accelerator has great advantages due to its low power consumption and reconfigurable property. However, FPGA’s extremely limited resources and CNN’s huge amount of parameters and computational complexity pose great challenges to the design. Based on the ZYNQ heterogeneous platform and the coordination of resource and bandwidth issues with the roofline model, the CNN accelerator we designed can accelerate both standard convolution and depthwise separable convolution with a high hardware resource rate. The accelerator can handle network layers of different scales through parameter configuration and maximizes bandwidth and achieves full pipelined by using a data stream interface and ping-pong on-chip cache. The experimental results show that the accelerator designed in this paper can achieve 17.11GOPS for 32bit floating point when it can also accelerate depthwise separable convolution, which has obvious advantages compared with other designs.
Extension of Zero Voltage Switching Capability for CLLC Resonant Converter
Authors: Park HwaPyeong , Kim DoKyoung , Baek SeungHo , Jung JeeHoon
Published: March 2019

TheCLLC resonant converter has been widely used to obtaina high power conversion efficiency with sinusoidal current waveforms and a soft switching capability. However, it has a limited voltage gain range according to the input voltage variation. The current-fed structure canbe one solution to extend the voltage gain range for the wide input voltage variation, butit has a limited zero voltage switching (ZVS) range. In this paper, the current-fed CLLC resonant converter with additional inductance is proposed to extend the ZVS range. The operational principle is analyzed to design the additional inductance for obtaining the extended ZVS range. The design methodology of the additional inductance is proposed to maximize the ZVS capability for the entire load range. The performance of the proposed method is verified with a 20 W prototype converter.