bluuebunny/crossref_metadata_2025 huggingface dataset:
Raman Spectroscopy Analysis of Free Fatty Acid in Olive Oil
Authors: Qiu Jin , Hou Hua-Yi , Yang In-Sang , Chen Xiang-Bai
Published: October 2019

Free fatty acid (FFA) is one of the most critical parameters for evaluating the quality of olive oil. In this paper, we present a simple and rapid Raman spectroscopy method for analyzing free fatty acid in olive oil. First, FFA degradation of carotenoids in olive oil is confirmed by analyzing the relative intensity of characteristic vibrational modes and introducing an intensity decrease factor. Second, it is demonstrated that the relative intensity ratio of the two characteristic vibrational modes at 1525 cm−1 and 1655 cm−1 presents a good and rapid analysis of FFA content in olive oil; the relative intensity ratio decreases linearly with FFA content. In addition, resonance Raman scattering of carotenoid is discussed, showing that a green laser should be utilized to study FFA in olive oil.
Estimation of Parameters of Parathyroid Glands Using Particle Swarm Optimization and Multivariate Generalized Gaussian Function Mixture
Authors: Listewnik Maria H. , Piwowarska-Bilska Hanna , Safranow Krzysztof , Iwanowski Jacek , Laszczyńska Maria , Chosia Maria , Ostrowski Marek , Birkenfeld Bożena , Oszutowska-Mazurek Dorota , Mazurek Przemyslaw
Published: October 2019

The paper introduces a fitting method for Single-Photon Emission Computed Tomography (SPECT) images of parathyroid glands using generalized Gaussian function for quantitative assessment of preoperative parathyroid SPECT/CT scintigraphy results in a large patient cohort. Parathyroid glands are very small for SPECT acquisition and the overlapping of 3D distributions was observed. The application of multivariate generalized Gaussian function mixture allows modeling, but results depend on the optimization algorithm. Particle Swarm Optimization (PSO) with global best, ring, and random neighborhood topologies were compared. The obtained results show benefits of random neighborhood topology that gives a smaller error for 3D position and the position estimation was improved by about 3 % voxel size, but the most important is the reduction of processing time to a few minutes, compared to a few hours in relation to the random walk algorithm. Moreover, the frequency of obtaining low MSE values was more than two times higher for this topology. The presented method based on random neighborhood topology allows quantifying activity in a specific voxel in a short time and could be applied it in clinical practice.
Improved Shear Strength Equation for Concrete Wide Beams
Authors: Kim Min Sook , Kang Joowon , Lee Young Hak
Published: October 2019

An improved shear strength equation is proposed that considers transverse reinforcement spacing and support conditions for concrete wide beams. Eighteen specimens were fabricated to examine the influence of transverse reinforcement spacing, the number of transverse shear reinforcement, and support width on shear capacity. From the test results, a shear strength equation is proposed and used to evaluate the shear strength of 23 specimens from previous studies and 18 from this study. For the 41 specimens, the proposed shear strength equation results had a mean of 1.16 and a standard deviation of 0.16. It showed that the proposed shear strength equation can predict shear strength reasonably well for concrete wide beams.
Reuse of Waste Material “Waste Sludge Water” from a Concrete Plant in Cement Composites: A Case Study
Authors: Klus Lukáš , Václavík Vojtěch , Dvorský Tomáš , Svoboda Jakub , Botula Jiří
Published: October 2019

This paper presents the results of research dealing with the use of recycled waste sludge water from a concrete plant (CP) as partial or complete replacement of mixing water in cement mixtures. The need to recycle waste sludge water generated as a by-product (waste sludge water) during the production of fresh concrete in the concrete plant results from the environmental and economic problems associated with the operation of the concrete plant. Mixing water was replaced with recycled waste sludge water in the amount of 25%, 50%, 75%, and 100%. In order to determine the effect of partial or complete replacement of mixing water with waste sludge water from the concrete plant in the production of cement composites, laboratory tests of waste sludge water were carried out to determine whether the waste sludge water complies with the requirements for mixing water defined in CSN EN 1008. The tests also determined the properties of fresh cement mortar and hardened cement composites. These were tests of the beginning and end of cement mortar setting, and the strength characteristics (flexural strength, compressive strength). The results of these tests show that it is possible to replace the mixing water by waste sludge water from the concrete plant in the amount of up to 25% without significantly affecting the tested properties, in comparison with the formula containing pure mixing water.
New Thermal-Conductivity Constitutive Matrix in Fourier’s Law for Heat Transfer Using the Cell Method
Authors: González-Domínguez Pablo Ignacio , Monzón-Verona José Miguel , García-Alonso Santiago
Published: October 2019

In this paper, a new constitutive matrix [ M τ ] for thermal conduction, for tetrahedral meshes, in a steady state thermal regime is developed through a new algebraic methodology, using the Cell Method as a computational method, which is included in the finite formulation. The constitutive matrix defines the behavior of solids when they are under a thermal potential. The results are compared with those obtained for the same problem by means of the constitutive matrix [ M λ ] developed previously, taking in both cases with a 2D axisymmetric model as reference, calculated with the finite element method. The errors obtained with the new matrix [ M τ ] are of the order of 0.0025%, much lower than those obtained with the matrix [ M λ ] .
What is still Limiting the Deployment of Cellulosic Ethanol? Analysis of the Current Status of the Sector
Authors: Padella Monica , O’Connell Adrian , Prussi Matteo
Published: October 2019

Ethanol production from cellulosic material is considered one of the most promising options for future biofuel production contributing to both the energy diversification and decarbonization of the transport sector, especially where electricity is not a viable option (e.g., aviation). Compared to conventional (or first generation) ethanol production from food and feed crops (mainly sugar and starch based crops), cellulosic (or second generation) ethanol provides better performance in terms of greenhouse gas (GHG) emissions savings and low risk of direct and indirect land-use change. However, despite the policy support (in terms of targets) and significant R&D funding in the last decade (both in EU and outside the EU), cellulosic ethanol production appears to be still limited. The paper provides a comprehensive overview of the status of cellulosic ethanol production in EU and outside EU, reviewing available literature and highlighting technical and non-technical barriers that still limit its production at commercial scale. The review shows that the cellulosic ethanol sector appears to be still stagnating, characterized by technical difficulties as well as high production costs. Competitiveness issues, against standard starch based ethanol, are evident considering many commercial scale cellulosic ethanol plants appear to be currently in idle or on-hold states.
AR Graphic Representation of Musical Notes for Self-Learning on Guitar
Authors: Del Rio-Guerra Marta Sylvia , Martin-Gutierrez Jorge , Lopez-Chao Vicente A. , Flores Parra Rodolfo , Ramirez Sosa Mario A.
Published: October 2019

Despite being one of the most commonly self-taught instruments, and despite the ready availability of significant amounts of didactic material, the guitar is a challenging instrument to learn. This paper proposes an application based on augmented reality (AR) that is designed to teach beginner students basic musical chords on the guitar, and provides details of the experimental study performed to determine whether the AR methodology produced faster results than traditional one-on-one training with a music teacher. Participants were divided into two groups of the same size. Group 1 consisted of 32 participants who used the AR app to teach themselves guitar, while Group 2, with a further 32 participants, received formal instruction from a music teacher. Results found no differences in learning times between the two groups based on the variables of method and gender. However, participant feedback suggested that there are advantages to the self-taught approach using AR that are worth considering. A system usability scale (SUS) questionnaire was used to measure the usability of the application, obtaining a score of 82.5, which was higher than the average of 68 that indicates an application to be good from a user experience point of view, and satisfied the purpose for which the application was created.
Adsorption of Ni2+ and Cd2+ from Water by Calcium Alginate/Spent Coffee Grounds Composite Beads
Authors: Torres-Caban Roberto , Vega-Olivencia Carmen A. , Mina-Camilde Nairmen
Published: October 2019

The use of heavy metals in technological applications has led to detrimental effects on human health and the environment. Activated carbon and ion-exchange resins are commonly used to remove pollutants but they are expensive. Therefore, the research of low-cost alternatives derived from natural resources and organic wastes is being considered. The aim of this study considers the use of Calcium Alginate/Spent Coffee Grounds (CA–SCGs) composite beads to adsorb heavy metals from aqueous solutions, particularly, the removal of Ni2+ or Cd2+ at concentrations from 10 ppm to 100 ppm. CA–SCGs beads were made of equal proportions of alginate and spent coffee grounds and compared with calcium alginate beads (CA beads) and spent coffee grounds (SCGs) in terms of capacity and rate of adsorption. Three cycles of adsorption/desorption were done. The beads were characterized by Scanning Electron Microscopy coupled with an energy-dispersive X-ray spectroscopy (SEM–EDX), Fourier-transform infrared spectroscopy (FT–IR), Raman spectroscopy, and point of zero charge. Langmuir, Freundlich, and Sips models, and a pseudo-second-order kinetic equation were used. Sips model showed the best correlation with the adsorption of CA–SCGs beads with capacities of adsorption of 91.18 mg/g for cadmium and 20.96 mg/g for nickel. CA–SCGs beads had a greater adsorption than the CA beads, achieving adsorption percentages close to 100% than alginate alone, showing their effectiveness in heavy metal removal.
Integrated Predictor Based on Decomposition Mechanism for PM2.5 Long-Term Prediction
Authors: Jin Xuebo , Yang Nianxiang , Wang Xiaoyi , Bai Yuting , Su Tingli , Kong Jianlei
Published: October 2019

It is crucial to predict PM2.5 concentration for early warning regarding and the control of air pollution. However, accurate PM2.5 prediction has been challenging, especially in long-term prediction. PM2.5 monitoring data comprise a complex time series that contains multiple components with different characteristics; therefore, it is difficult to obtain an accurate prediction by a single model. In this study, an integrated predictor is proposed, in which the original data are decomposed into three components, that is, trend, period, and residual components, and then different sub-predictors including autoregressive integrated moving average (ARIMA) and two gated recurrent units are used to separately predict the different components. Finally, all the predictions from the sub-predictors are combined in fusion node to obtain the final prediction for the original data. The results of predicting the PM2.5 time series for Beijing, China showed that the proposed predictor can effectively improve prediction accuracy for long-term prediction.
Performance and Loss Analysis of Squirrel Cage Induction Machine Based Flywheel Energy Storage System
Authors: Soomro Abid , Amiryar Mustafa E. , Nankoo Daniel , Pullen Keith R.
Published: October 2019

Flywheel energy storage systems (FESS) are one of the earliest forms of energy storage technologies with several benefits of long service time, high power density, low maintenance, and insensitivity to environmental conditions being important areas of research in recent years. This paper focusses on the electrical machine and power electronics, an important part of a flywheel system, the electrical machine rotating with the flywheel inertia in order to perform charge-discharge cycles. The type of machine used in the electrical drive plays an important role in the characteristics governing electrical losses as well as standby losses. Permanent magnet synchronous machine (PMSM) and induction machines (IM) are the two most common types of electric machines used in FESS applications where the latter has negligible standby losses due to its lower rotor magnetic field until energised by the stator. This paper describes research in which the operational and standby losses of a squirrel-cage induction machine-based flywheel storage system (SCIM-FESS) are modelled as a system developed in MATLAB/Simulink environment inclusive of the control system for the power electronics converters. Using the proposed control algorithm and in-depth analysis of the system losses, a detailed assessment of the dynamic performance of the SCIM-FESS is performed for different states of charging, discharging, and standby modes. The results of the analysis show that, in presence of system losses including aerodynamic and bearing friction losses, the SCIM-FESS has satisfactory characteristics in energy regulation and dynamic response during load torque variations. The compliance of FESS and its conversion between the generating and motoring mode within milliseconds show the responsiveness of the proposed control system.
Correlation between the Morphology of ZnO Layers and the Electroluminescence of Quantum Dot Light-Emitting Diodes
Authors: Oh Seongkeun , Kim Jiwan
Published: October 2019

The present work shows the effect of the ZnO layer morphology on inverted quantum dot light-emitting diodes (QLEDs) using different spin-coating processes. In the inverted structure of ITO/ZnO/QDs/CBP/MoO3/Al, ZnO nanoparticles were used as the electron transport layer. The utilization of a two-step spin-coating process to deposit a ZnO layer on a patterned ITO glass substrate resulted in an increase in the surface roughness of the ZnO layer and a decrease in the luminance of the QLEDs. However, the current efficiency of the device was enhanced by more than two-fold due to the reduced current density. Optimization of the ZnO spin-coating process can efficiently improve the optical and electrical properties of QLEDs.
A Dynamic Programmable Network for Large-Scale Scientific Data Transfer Using AmoebaNet
Authors: Shah Syed Asif Raza , Noh Seo-Young
Published: October 2019

Large scientific experimental facilities currently are generating a tremendous amount of data. In recent years, the significant growth of scientific data analysis has been observed across scientific research centers. Scientific experimental facilities are producing an unprecedented amount of data and facing new challenges to transfer the large data sets across multi continents. In particular, these days the data transfer is playing an important role in new scientific discoveries. The performance of distributed scientific environment is highly dependent on high-performance, adaptive, and robust network service infrastructures. To support large scale data transfer for extreme-scale distributed science, there is the need of high performance, scalable, end-to-end, and programmable networks that enable scientific applications to use the networks efficiently. We worked on the AmoebaNet solution to address the problems of a dynamic programmable network for bulk data transfer in extreme-scale distributed science environments. A major goal of the AmoebaNet project is to apply software-defined networking (SDN) technology to provide “Application-aware” network to facilitate bulk data transfer. We have prototyped AmoebaNet’s SDN-enabled network service that allows application to dynamically program the networks at run-time for bulk data transfers. In this paper, we evaluated AmoebaNet solution with real world test cases and shown that how it efficiently and dynamically can use the networks for bulk data transfer in large-scale scientific environments.
Multilayer Perceptron-Based Phenological and Radiometric Normalization for High-Resolution Satellite Imagery
Authors: Seo Dae Kyo , Eo Yang Dam
Published: October 2019

Radiometric normalization is an essential preprocessing step that must be performed to detect changes in multi-temporal satellite images and, in general, relative radiometric normalization is utilized. However, most relative radiometric normalization methods assume a linear relationship and they cannot take into account nonlinear properties, such as the distribution of the earth’s surface or phenological differences that are caused by the growth of vegetation. Thus, this paper proposes a novel method that assumes a nonlinear relationship and it uses a representative nonlinear regression model—multilayer perceptron (MLP). The proposed method performs radiometric resolution compression while considering both the complexity and time cost, and radiometric control set samples are extracted based on a no-change set method. Subsequently, the spectral index is selected for each band to compensate for the phenological properties, phenological normalization is performed based on MLP, and the global radiometric properties are adjusted through postprocessing. Finally, a performance evaluation is conducted by comparing the results herein with those from conventional relative radiometric normalization algorithms. The experimental results show that the proposed method outperforms conventional methods in terms of both visual inspection and quantitative evaluation. In other words, the applicability of the proposed method to the normalization of multi-temporal images with nonlinear properties is confirmed.
Royal Divine Coronation Iconography. Preliminary Considerations
Authors: Vagnoni Mirko
Published: October 2019

In recent decades, art historians have stressed the benefits of analysing medieval images and their contents within their specific context and, in particular, have underlined the importance of their visual impact on contemporary beholders to determine their functions and specific meanings. In other words, in the analysis of a medieval image, it has become fundamental to verify where it was collocated and whom it was aimed at, and which practical reasons it was made for (its visibility, fruition, and usability). As a result, new perspectives have been opened, creating an active historiographical debate about one of the most fascinating and studied iconographic themes of the Middle Ages: the royal divine coronation. Hence, there has been a complete rethinking of the function and meaning of this iconographic theme. For instance, the divine coronation of the king might not symbolically allude to his earthly power but to the devotional hope of receiving the crown of eternal life in the afterworld. Moreover, in the specific case of some Ottonian and Salian illuminations, historiographers have proposed that their function was not only celebrative (a manifesto of the political ideologies that legitimized power), but also liturgical and religious. This paper places this topic in a historiographical framework and provides some preliminary methodological considerations in order to stimulate new research.
Numerical Solutions of Coupled Burgers’ Equations
Authors: Ahmad Hijaz , Khan Tufail A. , Cesarano Clemente
Published: October 2019

In this article, two new modified variational iteration algorithms are investigated for the numerical solution of coupled Burgers’ equations. These modifications are made with the help of auxiliary parameters to speed up the convergence rate of the series solutions. Three numerical test problems are given to judge the behavior of the modified algorithms, and error norms are used to evaluate the accuracy of the method. Numerical simulations are carried out for different values of parameters. The results are also compared with the existing methods in the literature.
24-Epibrassinolide (EBR) Confers Tolerance against NaCl Stress in Soybean Plants by Up-Regulating Antioxidant System, Ascorbate-Glutathione Cycle, and Glyoxalase System
Authors: Alam Pravej , Albalawi Thamer H. , Altalayan Fahad H. , Bakht Md Afroz , Ahanger Mohammad Abass , Raja Vaseem , Ashraf Muhammad , Ahmad Parvaiz
Published: October 2019

The present research was performed to assess the effect of 24-epibrassinolide (EBR) on salt-stressed soybean plants. Salt stress suppressed growth, biomass yield, gas exchange parameters, pigment content, and chlorophyll fluorescence, but all these parameters were up-regulated by EBR supply. Moreover, salt stress increased hydrogen peroxide, malondialdehyde, and electrolyte leakage. EBR supplementation reduced the accumulation of oxidative stress biomarkers. The activities of superoxide dismutase and catalase, and the accumulation of proline, glycinebetaine, total phenols, and total flavonoids increased with NaCl stress, but these attributes further increased with EBR supplementation. The activities of enzymes and the levels of non-enzymatic antioxidants involved in the Asc-Glu cycle also increased with NaCl stress, and further enhancement in these attributes was recorded by EBR supplementation. Salinity elevated the methylglyoxal content, but it was decreased by the EBR supplementation accompanying with up-regulation of the glyoxalase cycle (GlyI and GlyII). Salinity enhanced the Na+ uptake in root and shoot coupled with a decrease in uptake of Ca2+, K+, and P. However, EBR supplementation declined Na+ accumulation and promoted the uptake of the aforementioned nutrients. Overall, EBR supplementation regulated the salt tolerance mechanism in soybean plants by modulating osmolytes, activities of key enzymes, and the levels of non-enzymatic antioxidants.
The Loop of the TPR1 Subdomain of Phi29 DNA Polymerase Plays a Pivotal Role in Primer-Terminus Stabilization at the Polymerization Active Site
Authors: del Prado Alicia , Santos Eugenia , Lázaro José M. , Salas Margarita , de Vega Miguel
Published: October 2019

Bacteriophage Phi29 DNA polymerase belongs to the protein-primed subgroup of family B DNA polymerases that use a terminal protein (TP) as a primer to initiate genome replication. The resolution of the crystallographic structure showed that it consists of an N-terminal domain with the exonuclease activity and a C-terminal polymerization domain. It also has two subdomains specific of the protein-primed DNA polymerases; the TP Regions 1 (TPR1) that interacts with TP and DNA, and 2 (TPR2), that couples both processivity and strand displacement to the enzyme. The superimposition of the structures of the apo polymerase and the polymerase in the polymerase/TP heterodimer shows that the structural changes are restricted almost to the TPR1 loop (residues 304–314). In order to study the role of this loop in binding the DNA and the TP, we changed the residues Arg306, Arg308, Phe309, Tyr310, and Lys311 into alanine, and also made the deletion mutant Δ6 lacking residues Arg306–Lys311. The results show a defective TP binding capacity in mutants R306A, F309A, Y310A, and Δ6. The additional impaired primer-terminus stabilization at the polymerization active site in mutants Y310A and Δ6 allows us to propose a role for the Phi29 DNA polymerase TPR1 loop in the proper positioning of the DNA and TP-priming 3’-OH termini at the preinsertion site of the polymerase to enable efficient initiation and further elongation steps during Phi29 TP-DNA replication.
Strategies for Developing Functional Secretory Epithelia from Porcine Salivary Gland Explant Outgrowth Culture Models
Authors: Urkasemsin Ganokon , Castillo Phoebe , Rungarunlert Sasitorn , Klincumhom Nuttha , Ferreira Joao N.
Published: October 2019

Research efforts have been made to develop human salivary gland (SG) secretory epithelia for transplantation in patients with SG hypofunction and dry mouth (xerostomia). However, the limited availability of human biopsies hinders the generation of sufficient cell numbers for epithelia formation and regeneration. Porcine SG have several similarities to their human counterparts, hence could replace human cells in SG modelling studies in vitro. Our study aims to establish porcine SG explant outgrowth models to generate functional secretory epithelia for regeneration purposes to rescue hyposalivation. Cells were isolated and expanded from porcine submandibular and parotid gland explants. Flow cytometry, immunocytochemistry, and gene arrays were performed to assess proliferation, standard mesenchymal stem cell, and putative SG epithelial stem/progenitor cell markers. Epithelial differentiation was induced and different SG-specific markers investigated. Functional assays upon neurostimulation determined α-amylase activity, trans-epithelial electrical resistance, and calcium influx. Primary cells exhibited SG epithelial progenitors and proliferation markers. After differentiation, SG markers were abundantly expressed resembling epithelial lineages (E-cadherin, Krt5, Krt14), and myoepithelial (α-smooth muscle actin) and neuronal (β3-tubulin, Chrm3) compartments. Differentiated cells from submandibular gland explant models displayed significantly greater proliferation, number of epithelial progenitors, amylase activity, and epithelial barrier function when compared to parotid gland models. Intracellular calcium was mobilized upon cholinergic and adrenergic neurostimulation. In summary, this study highlights new strategies to develop secretory epithelia from porcine SG explants, suitable for future proof-of-concept SG regeneration studies, as well as for testing novel muscarinic agonists and other biomolecules for dry mouth.
Improvement of Mitochondrial Activity and Fibrosis by Resveratrol Treatment in Mice with Schistosoma japonicum Infection
Authors: Chen Tina Tuwen , Peng Shihyi , Wang Yanjuan , Hu Yuan , Shen Yujuan , Xu Yuxin , Yin Jianhai , Liu Congshan , Cao Jianping
Published: October 2019

Schistosomiasis caused by Schistosoma japonicum is a major parasitic disease in the People’s Republic of China. Liver fibrosis is the main pathological mechanism of schistosomiasis, and it is also the major lesion. The common drug used for its treatment, praziquantel (PZQ), does not have a marked effect on liver fibrosis. Resveratrol (RSV), which is an antioxidant, improves mitochondrial function and also attenuates liver fibrosis. The combination of PZQ and RSV has been found to have a synergistic antischistosomal effect on Schistosoma mansoni; additionally, the activity of PZQ is enhanced in the presence of RSV. Here, we examine the therapeutic effects of RSV on the S. japonicum infection in a mouse model, and we investigate RSV as a novel therapeutic agent for mitochondrial function and schistosomiasis-associated liver fibrosis (SSLF). Mitochondrial membrane potential was examined using flow cytometry analysis. The expression of the mitochondrial biogenesis genes PGC-α and fibrosis-associated genes collagen I, collagen III and α-SMA were examined using western blot analysis. Fibrosis-associated histological changes were examined using Masson trichrome staining. Additionally, the effects of RSV on S. japonicum adult worms were examined using scanning electron microscopy and transmission electron microscopy. RSV treatment improved mitochondrial function by increasing membrane potential and increasing PGC-α expression (mitochondrial biogenesis). Further, RSV attenuated liver injury, including liver scarring, by decreasing collagen deposition and the extent of fibrosis, based on the decrease in expression of the fibrosis-related genes. RSV also decreased the adult worm count and caused considerable physical damage to the worm. These results indicate that RSV upregulates mitochondrial biogenesis and inhibits fibrosis. RSV may have potential as a therapeutic target for the treatment of fibrosis in schistosomiasis.
RAD52 Functions in Homologous Recombination and Its Importance on Genomic Integrity Maintenance and Cancer Therapy
Authors: Nogueira Augusto , Fernandes Mara , Catarino Raquel , Medeiros Rui
Published: October 2019

Genomes are continually subjected to DNA damage whether they are induced from intrinsic physiological processes or extrinsic agents. Double-stranded breaks (DSBs) are the most injurious type of DNA damage, being induced by ionizing radiation (IR) and cytotoxic agents used in cancer treatment. The failure to repair DSBs can result in aberrant chromosomal abnormalities which lead to cancer development. An intricate network of DNA damage signaling pathways is usually activated to eliminate these damages and to restore genomic stability. These signaling pathways include the activation of cell cycle checkpoints, DNA repair mechanisms, and apoptosis induction, also known as DNA damage response (DDR)-mechanisms. Remarkably, the homologous recombination (HR) is the major DSBs repairing pathway, in which RAD52 gene has a crucial repairing role by promoting the annealing of complementary single-stranded DNA and by stimulating RAD51 recombinase activity. Evidence suggests that variations in RAD52 expression can influence HR activity and, subsequently, influence the predisposition and treatment efficacy of cancer. In this review, we present several reports in which the down or upregulation of RAD52 seems to be associated with different carcinogenic processes. In addition, we discuss RAD52 inhibition in DDR-defective cancers as a possible target to improve cancer therapy efficacy.
Adenylyl Cyclase Type 8 Overexpression Impairs Phosphorylation-Dependent Orai1 Inactivation and Promotes Migration in MDA-MB-231 Breast Cancer Cells
Authors: Sanchez-Collado Jose , Lopez Jose J. , Jardin Isaac , Camello Pedro J. , Falcon Debora , Regodon Sergio , Salido Gines M. , Smani Tarik , Rosado Juan A.
Published: October 2019

Orai1 plays a major role in store-operated Ca2+ entry (SOCE) in triple-negative breast cancer (TNBC) cells. This channel is inactivated via different mechanisms, including protein kinase C (PKC) and protein kinase A (PKA)-dependent phosphorylation at Ser-27 and Ser-30 or Ser-34, respectively, which shapes the Ca2+ responses to agonists. The Ca2+ calmodulin-activated adenylyl cyclase type 8 (AC8) was reported to interact directly with Orai1, thus mediating a dynamic interplay between the Ca2+- and cyclic adenosine monophosphate (cAMP)-dependent signaling pathways. Here, we show that the breast cancer cell lines MCF7 and MDA-MB-231 exhibit enhanced expression of Orai1 and AC8 as compared to the non-tumoral breast epithelial MCF10A cell line. In these cells, AC8 interacts with the Orai1α variant in a manner that is not regulated by Orai1 phosphorylation. AC8 knockdown in MDA-MB-231 cells, using two different small interfering RNAs (siRNAs), attenuates thapsigargin (TG)-induced Ca2+ entry and also Ca2+ influx mediated by co-expression of Orai1 and the Orai1-activating small fragment (OASF) of STIM1 (stromal interaction molecule-1). Conversely, AC8 overexpression enhances SOCE, as well as Ca2+ entry, in cells co-expressing Orai1 and OASF. In MDA-MB-231 cells, we found that AC8 overexpression reduces the Orai1 phosphoserine content, thus suggesting that AC8 interferes with Orai1 serine phosphorylation, which takes place at residues located in the AC8-binding site. Consistent with this, the subset of Orai1 associated with AC8 in naïve MDA-MB-231 cells is not phosphorylated in serine residues in contrast to the AC8-independent Orai1 subset. AC8 expression knockdown attenuates migration of MCF7 and MDA-MB-231 cells, while this maneuver has no effect in the MCF10A cell line, which is likely attributed to the low expression of AC8 in these cells. We found that AC8 is required for FAK (focal adhesion kinase) phosphorylation in MDA-MB-231 cells, which might explain its role in cell migration. Finally, we found that AC8 is required for TNBC cell proliferation. These findings indicate that overexpression of AC8 in breast cancer MDA-MB-231 cells impairs the phosphorylation-dependent Orai1 inactivation, a mechanism that might support the enhanced ability of these cells to migrate.
Clinical Challenges and Consequences of Measurable Residual Disease in Non-APL Acute Myeloid Leukemia
Authors: Jentzsch Madlen , Schwind Sebastian , Bach Enrica , Stasik Sebastian , Thiede Christian , Platzbecker Uwe
Published: October 2019

The ability to detect residual levels of leukemic blasts (measurable residual disease, MRD) has already been integrated in the daily routine for treatment of patients with chronic myeloid and acute lymphoblastic leukemia. In acute myeloid leukemia (AML), a variety of mostly retrospective studies have shown that individuals in AML remission who tested positive for MRD at specific time-points or had increasing MRD levels are at significantly higher risk of relapse and death compared to MRD-negative patients. However, these studies differ with respect to the “MRD-target”, time-point of MRD determination, material analyzed, and method applied. How this probably very valuable MRD information in individual patients may be adapted in the daily clinical routine, e.g., to separate patients who need more aggressive therapies from those who may be spared additional—potentially toxic—therapies is still a work-in-progress. With the exception of MRD assessment in acute promyelocytic leukemia (APL), the lack of randomized, prospective trials renders MRD-based decisions and clinical implications in AML a difficult task. As of today, we still do not have proof that early intervention in MRD-positive AML patients would improve outcomes, although this is very likely. In this article, we review the current knowledge on non-APL AML MRD assessment and possible clinical consequences.
Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches
Authors: Thyagarajan Anita , Alshehri Mamdouh Salman A. , Miller Kelly L.R. , Sherwin Catherine M. , Travers Jeffrey B. , Sahu Ravi P.
Published: October 2019

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target MDSCs to limit their effects. Multiple strategies including immune-based approaches have been explored either alone or in combination with therapeutic agents to target MDSCs in preclinical and clinical settings of PDAC. The current review highlights the roles and mechanisms of MDSCs as well as the implications of this immunomodulatory cell type as a potential target to improve the efficacy of therapeutic regimens for PDAC.
Applications of Bioinformatics in Cancer
Authors: Brenner Chad
Published: October 2019

This series of 25 articles (22 original articles, 3 reviews) is presented by international leaders in bioinformatics and biostatistics [...]
Antiplatelet Agents for Cancer Prevention: Current Evidences and Continuing Controversies
Authors: Frere Corinne , Lejeune Manon , Kubicek Pierre , Faille Dorothée , Marjanovic Zora ,   the Groupe Francophone Thrombose et Cancer
Published: October 2019

Over the past two decades, aspirin has emerged as a promising chemoprotective agent to prevent colorectal cancer (CRC). In 2016, the mounting evidence supporting its chemoprotective effect, from both basic science and clinical research, led the US Preventive Services Task Force to recommend regular use of low-dose aspirin in some subgroups of patients for whom the benefits are deemed to outweigh the risks. In contrast, data on the chemoprotective effect of aspirin against other cancers are less clear and remain controversial. Most data come from secondary analyses of cardiovascular prevention trials, with only a limited number reporting cancer outcomes as a prespecified endpoint, and overall unclear findings. Moreover, the potential chemoprotective effect of aspirin against other cancers has been recently questioned with the publication of 3 long-awaited trials of aspirin in the primary prevention of cardiovascular diseases reporting no benefit of aspirin on overall cancer incidence and cancer-related mortality. Data on the chemoprotective effects of other antiplatelet agents remain scarce and inconclusive, and further research to examine their benefit are warranted. In this narrative review, we summarize current clinical evidence and continuing controversies on the potential chemoprotective properties of antiplatelet agents against cancer.
Anti-Proliferative Effects of an Extra-Virgin Olive Oil Extract Enriched in Ligstroside Aglycone and Oleocanthal on Human Liver Cancer Cell Lines
Authors: De Stefanis Daniela , Scimè Salvatore , Accomazzo Simone , Catti Andrea , Occhipinti Andrea , Bertea Cinzia Margherita , Costelli Paola
Published: October 2019

Oleocanthal and ligstroside aglycone are olive oil-derived polyphenols. The former interferes with tumor growth with minor or no cytotoxicity on non-tumorigenic primary cell lines. The information about the bioactivity of ligstroside aglycone are scanty, with the exception of a known antioxidant power. Hepatocellular carcinoma is a malignant tumor with high mortality rates. Systemic chemotherapy is only marginally effective and is frequently complicated by toxicity. Previous observations have shown that hepatocellular carcinoma cell lines become more sensitive to taxol when it is combined with Tumor Necrosis Factor α (TNFα). The present work aimed to assess the effects of a polyphenolic extract containing both oleocanthal and ligstroside aglycone on proliferation and/or death in three liver cancer cell lines (HepG2, Huh7 and Hep3B). The possibility to enhance such effect by the addition of TNFα was also investigated. Both cell proliferation and death were enhanced by the exposure to the polyphenolic extract. Such effect was associated with induction of autophagy and could be potentiated by TNFα. The presence of ligstroside aglycone in the extract lowered the oleocanthal concentration required for cytotoxicity. These results show for the first time that the effects of a polyphenol extract can be potentiated by TNFα and that modulation of autophagy likely account for these effects.
Tumor BRCA Test for Patients with Epithelial Ovarian Cancer: The Role of Molecular Pathology in the Era of PARP Inhibitor Therapy
Authors: Fumagalli Caterina , Tomao Federica , Betella Ilaria , Rappa Alessandra , Calvello Mariarosaria , Bonanni Bernardo , Bernard Loris , Peccatori Fedro , Colombo Nicoletta , Viale Giuseppe , Barberis Massimo , Guerini-Rocco Elena
Published: October 2019

The PARP inhibitor olaparib has been approved in the maintenance setting of platinum-sensitive epithelial ovarian cancer patients with germline or somatic BRCA1/2 mutation. Therefore, the availability of a tumor BRCA test has become a clinical need. We report the results of the clinical implementation of a tumor BRCA test within the frame of an institutional workflow for the management of patients with nonmucinous and nonborderline epithelial ovarian cancer. In total, 223 patients with epithelial ovarian cancer were prospectively analyzed. BRCA1/2 status was evaluated on formalin-fixed, paraffin-embedded tumor specimens using next-generation sequencing technology. The tumor BRCA test had a success rate of 99.1% (221 of 223 successfully analyzed cases) and a median turnaround time of 17 calendar days. Among the 221 cases, BRCA1 or BRCA2 pathogenic/likely pathogenic mutations were found in 62 (28.1%) cases and variants of uncertain significance in 25 (11.3%) cases. The concordance rate between tumor BRCA test results and germline BRCA1/2 status was 87%, with five cases harboring pathogenic/likely pathogenic somatic-only mutations. The next-generation, sequencing-based tumor BRCA test showed a high success rate and a turnaround time compatible with clinical purposes. The tumor BRCA test could be implemented in a molecular diagnostic setting and it may guide the clinical management of patients with epithelial ovarian cancer.
Computerized Cytological Features for Papillary Thyroid Cancer Diagnosis—Preliminary Report
Authors: Shih Shyang-Rong , Jan I-Shiow , Chen Kuen-Yuan , Chuang Wan-Yu , Wang Chih-Yuan , Hsiao Yung-Lien , Chang Tien-Chun , Chen Argon
Published: October 2019

Fine needle aspiration cytology (FNAC) is the final diagnosis of thyroid nodules before surgery. It is important to further improve the indeterminate FNAC diagnosis results using computerized cytological features. This retrospective cross-sectional study included 240 cases, of whom 110 had histologic diagnosis of papillary thyroid cancers (PTC), 100 had nodular/adenomatous goiters/hyperplasia (benign goiters), 10 had follicular/Hurthle cell carcinomas, and 20 had follicular adenomas. Morphological and chromatic features of FNAC were quantified and analyzed. The result showed that six quantified cytological features were found significantly different between patients with a histologic diagnosis of PTC and patients with histologic diagnosis of benign goiters in multivariate analysis. These cytological features were used to estimate the malignancy risk in nodules with indeterminate FNAC results. The Area Under the Receiver Operating Characteristics (AUROC) of the diagnostic accuracy with a benign or malignant nature was 81.3% (p < 0.001), 78.7% (p = 0.014), and 56.8% (p = 0.52) for nodules with FNAC results of atypia, which is suspicious for malignancy and follicular neoplasm, respectively. In conclusion, quantification of cytological features could be used to develop a computer-aided tool for diagnosing PTC in thyroid nodules with indeterminate FNAC results.
Tumor and Cerebrospinal Fluid microRNAs in Primary Central Nervous System Lymphomas
Authors: Zajdel Michalina , Rymkiewicz Grzegorz , Sromek Maria , Cieslikowska Maria , Swoboda Pawel , Kulinczak Mariusz , Goryca Krzysztof , Bystydzienski Zbigniew , Blachnio Katarzyna , Ostrowska Beata , Borysiuk Anita , Druzd-Sitek Agnieszka , Walewski Jan , Chechlinska Magdalena , Siwicki Jan Konrad
Published: October 2019

Primary central nervous system lymphoma (PCNSL) is a rare, highly aggressive, extranodal form of non-Hodgkin lymphoma, predominantly diagnosed as primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL). Fast and precise diagnosis of PCNSL is critical yet challenging. microRNAs, important regulators in physiology and pathology are potential biomarkers. In 131 patients with CNS DLBCL and with non-malignant brain lesions (n-ML), miR-21, miR-19b and miR-92a, miR-155, miR-196b, miR-let-7b, miR-125b, and miR-9 were examined by RT-qPCR in brain biopsy samples (formalin-fixed paraffin-embedded tissues, FFPET; CNS DLBCL, n = 52; n-ML, n = 42) and cerebrospinal fluid samples (CSF; CNS DLBCL, n = 30; n-ML, n = 23) taken for routine diagnosis. FFPET samples were split into study and validation sets. Significantly higher CSF levels of miR-21, miR-19b, and miR-92a were identified in PCNSL but not in n-ML, and differentiated PCNSL from n-ML with 63.33% sensitivity and 80.77% specificity. In FFPETs, miR-155 and miR-196b were significantly overexpressed and miR-let-7b, miR-125b, and miR-9 were downregulated in PCNSL as compared to n-ML. Combined miR-155 and miR-let-7b expression levels in FFPETs discriminated PCNSL and n-ML with a 97% accuracy. In conclusion, tissue miR-155, miR-196b, miR-9, miR-125b, and miR-let-7b expression profiles differentiate PCNSL from n-ML. PCNSL CSFs and the relevant biopsy samples are characterized by specific, different microRNA profiles. A logistic regression model is proposed to discriminate between PCNSL and non-malignant brain lesions. None of the examined microRNAs influenced overall survival of PCNSL patients. Further ongoing developments involve next generation sequencing-based profiling of biopsy and CSF samples.
NPY Gene Methylation as a Universal, Longitudinal Plasma Marker for Evaluating the Clinical Benefit from Last-Line Treatment with Regorafenib in Metastatic Colorectal Cancer
Authors: Jensen Lars Henrik , Olesen René , Petersen Lone Noergaard , Boysen Anders Kindberg , Andersen Rikke Fredslund , Lindebjerg Jan , Nottelmann Lise , Thomsen Caroline Emilie Brenner , Havelund Birgitte Mayland , Jakobsen Anders , Hansen Torben Frøstrup
Published: October 2019

There is a need for biomarkers to improve the clinical benefit from systemic treatment of colorectal cancer. We designed a prospective, clinical study where patients receiving regorafenib as last-line treatment had sequential blood samples drawn. Effect and toxicity was monitored. The primary clinical endpoint was progression free survival (PFS). Cell-free circulating tumor (ct) DNA was measured as either the fraction with Neuropeptide Y (NPY) methylated DNA or KRAS/NRAS/BRAF mutated ctDNA. One hundred patients were included from three Danish centers. Among 95 patients who received regorafenib for at least two weeks, the median PFS was 2.1 months (95% confidence interval (CI) 1.8–3.3) and the median overall survival (OS) was 5.2 months (95% CI 4.3–6.5). Grade 3–4 toxicities were reported 51 times, most frequently hypertension, hand-food syndrome, and skin rash. In the biomarker population of 91 patients, 49 could be monitored using mutated DNA and 90 using methylated DNA. There was a strong correlation between mutated and methylated DNA. The median survival for patients with a level of methylated ctDNA above the median was 4.3 months compared to 7.6 months with ctDNA below the median, p < 0.001. The median time from increasing methylated ctDNA to disease progression was 1.64 months (range 0.46–8.38 months). In conclusion, NPY methylated ctDNA was a universal liquid biopsy marker in colorectal cancer patients treated with regorafenib. High baseline levels correlated with short survival and changes during treatment may predict early effect and later progression. We suggest plasma NPY methylation analysis as an easy and universally applicable method for longitudinal monitoring of ctDNA in metastatic colorectal cancer patients.