bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Characterization of an Endo-β-1,4-Glucanase, CelAJ93, from the Recently Isolated Marine Bacterium, Cellulophaga sp. J9-3
Authors: Kim Da Som , Chi Won-Jae , Hong Soon-Kwang
Published: September 2019

A novel cellulase was characterized from a newly isolated marine bacterium, strain J9-3. Phylogenetic analysis based on the 16S rRNA gene revealed that strain J9-3 belonged to the genus Cellulophaga, and thus, it was named Cellulophaga sp. J9-3. An extracellular cellulase was purified from cell-free culture broth of J9-3 cultured in Marine Broth containing 0.2% carboxymethylcellulose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the protein revealed a single band with an apparent molecular weight (Mw) of 35 kDa. Based on the NH2-terminal amino acid sequence (N-N-T-E-Q-T-V-V-D-A-Y-G), the gene (named celAJ93) encoding the protein was identified from J9-3 genomic sequencing data. CelAJ93 was expected to be translated into a premature protein (359 amino acids) and then processed to a mature protein (307 amino acids, Mw = 34,951 Da), which is consistent with our results. CelAJ93 had high homology with many uncharacterized putative glycosyl hydrolases of the genus Cellulophaga and it was highly specific for carboxymethylcellulose and cellooligosaccharides under optimum conditions (pH 7.5, 60 °C). Co2+ completely recovered CelAJ93 activity that was severely inhibited by ethylenediaminetetraacetic acid (EDTA), indicating that CelAJ93 required Co2+ as a cofactor. Thus, CelAJ93 is a Co2+-dependent endo-β-1,4-glucanase that can hydrolyze carboxymethylcellulose and cellooligosaccharides into cellobiose at a relatively high temperature.
Air Quality Index and Air Pollutant Concentration Prediction Based on Machine Learning Algorithms
Authors: Liu Huixiang , Li Qing , Yu Dongbing , Gu Yu
Published: September 2019

Air pollution has become an important environmental issue in recent decades. Forecasts of air quality play an important role in warning people about and controlling air pollution. We used support vector regression (SVR) and random forest regression (RFR) to build regression models for predicting the Air Quality Index (AQI) in Beijing and the nitrogen oxides (NOX) concentration in an Italian city, based on two publicly available datasets. The root-mean-square error (RMSE), correlation coefficient (r), and coefficient of determination (R2) were used to evaluate the performance of the regression models. Experimental results showed that the SVR-based model performed better in the prediction of the AQI (RMSE = 7.666, R2 = 0.9776, and r = 0.9887), and the RFR-based model performed better in the prediction of the NOX concentration (RMSE = 83.6716, R2 = 0.8401, and r = 0.9180). This work also illustrates that combining machine learning with air quality prediction is an efficient and convenient way to solve some related environment problems.
Patent Keyword Analysis Using Time Series and Copula Models
Authors: Kim Jong-Min , Yoon Jaeeun , Hwang Sun Young , Jun Sunghae
Published: September 2019

The technological keywords extracted from patent documents have much information about a developed technology. We can understand the technological structure of a product by examining the results of patent analysis. So far, much research has been done on patent data analysis. The technological keywords of patent documents contain representative information on the developed technology. As such, the patent keyword is one of the most important factors in patent data analysis. In this paper, we propose a patent data analysis model combining a integer valued time series model and copula direction dependence for integer valued patent keyword analysis over time. Most patent keywords are frequency values and keywords often change over time. However, the existing patent keywords analysis works do not account for two major factors: integer value and time. For modeling integer valued keyword data with time factor, we use a copula directional dependence model based on marginal regression with a beta logit function and integer valued generalized autoregressive conditional heteroskedasticity model. Using the proposed model, we find technological trends and relations in the target technological domain. To illustrate the performance and implication of our paper, we carry out experiments using the patent documents applied and registered by Apple company. This study contributes to the effective planning for the research and development of technologies by utilizing the evolution of technology over time.
A Two-Stage Building Information Modeling Based Building Design Method to Improve Lighting Environment and Increase Energy Efficiency
Authors: Liu Sha , Ning Xin
Published: September 2019

Buildings are one of the largest energy consumers in the world, and have great energy saving potential. Thermal systems and lighting systems take most of the energy in a building. Comparing with the optimization solutions developed for a thermal system, the research of improving the lighting system is insufficient. This study aims to improve the lighting environment and reduce the energy by optimizing the building design, which has the largest potential for cutting energy economically compared with the other stages in the life cycle of a building. Although many approaches have been developed for building design optimization, there is still one big problem obstructing their successful practices, in that the designers who take the responsibility of making building designs are not experts in building physics, thus they are not capable of calculating the most appropriate parameters and operating the professional software to optimize their designs. Therefore, this study proposes a user-friendly method for designers to improve building designs. Firstly, Building Information Modeling (BIM) and particle swarm optimization algorithm are applied to build an intelligent optimal design search system. The optimized design from this system can largely use daylighting for internal illumination and save energy. Secondly, different types of lighting control systems are compared and the one which can save maximal energy is added to the selected optimal design. A case study demonstrates that optimized designs generated by the proposed design method can save large amounts of life cycle energy and costs, and is effective and efficient.
Analysis Regarding the Risk of Injuries of Soldiers Inside a Vehicle during Accidents Caused by Improvised Explosive Devices
Authors: Sławiński Grzegorz , Malesa Piotr , Świerczewski Marek
Published: September 2019

This article presents the description of the mechanism of selected dysfunctions of the human skeletal system and internal organs. The problem is wide and requires extensive experimental and numerical research. This article presents the outline of the problem regarding the creation of personal injuries of soldiers inside armored vehicles. The explanation of the mechanism of injuries caused as a result of strong effects of pulse forces, resulting from both the consequences of the wave of pressure created during an explosion, as well as high accelerations of the vehicle’s hull, is presented herein. Examples of the results of numerical analyses of the pressure wave impact from an explosion are presented in the Article. LS-Dyna software was used to perform the numerical calculations. The analyses were carried out using the Conwep algorithm implemented in the calculation code. The significance of calculation methods, thanks to which it is possible to recreate a simulation in which there is a risk of injuries of soldiers without posing a threat to their health and life, should be noted here. The main parts of the human body, such as the bottom limb, the pelvic belt, the cervical spine and the abdomen, have been considered. Mechanisms causing typical injuries of soldiers inside vehicles under which explosives are detonated have been analyzed for particular body parts through multiple numerical simulations. The analysis of the process of injury creation has been conducted on the basis of the statistical data regarding the most common injuries of soldiers. The validation process of numerical analyses was carried out using the results of experimental research.
Investigation and Improvement of Thermal Stability of a Chromatic Confocal Probe with a Mode-Locked Femtosecond Laser Source
Authors: Sato Ryo , Shimizu Yuki , Chen Chong , Matsukuma Hiraku , Gao Wei
Published: September 2019

An intentional investigation on the thermal stability of a mode-locked femtosecond laser chromatic confocal probe, which is a critical issue for the probe to be applied for long-term displacement measurement or surface profile measurement requiring long-time scanning, is carried out. At first, the thermal instability of the first prototype measurement setup is evaluated in experiments where the existence of a considerably large thermal instability is confirmed. Then the possible reasons for the thermal instability of the measurement setup are analyzed quantitatively, such as the thermal instability of the refractive index of the confocal lens and the thermal expansion of mechanical jigs employed in the probe. It is verified that most of the thermal instability of the measurement setup is caused by the thermal expansion of mechanical jigs in the probe. For the improvement of the thermal stability of the probe, it is necessary to employ a low thermal expansion material for the mechanical jigs in the measurement setup and to shorten the optical path length of the laser beam. Based on the analysis result, a second prototype probe is newly designed and constructed. The improved thermal stability of the second prototype probe is verified through theoretical calculations and experiments.
Instruction2vec: Efficient Preprocessor of Assembly Code to Detect Software Weakness with CNN
Authors: Lee Yongjun , Kwon Hyun , Choi Sang-Hoon , Lim Seung-Ho , Baek Sung Hoon , Park Ki-Woong
Published: September 2019

Potential software weakness, which can lead to exploitable security vulnerabilities, continues to pose a risk to computer systems. According to Common Vulnerability and Exposures, 14,714 vulnerabilities were reported in 2017, more than twice the number reported in 2016. Automated vulnerability detection was recommended to efficiently detect vulnerabilities. Among detection techniques, static binary analysis detects software weakness based on existing patterns. In addition, it is based on existing patterns or rules, making it difficult to add and patch new rules whenever an unknown vulnerability is encountered. To overcome this limitation, we propose a new method—Instruction2vec—an improved static binary analysis technique using machine. Our framework consists of two steps: (1) it models assembly code efficiently using Instruction2vec, based on Word2vec; and (2) it learns the features of software weakness code using the feature extraction of Text-CNN without creating patterns or rules and detects new software weakness. We compared the preprocessing performance of three frameworks—Instruction2vec, Word2vec, and Binary2img—to assess the efficiency of Instruction2vec. We used the Juliet Test Suite, particularly the part related to Common Weakness Enumeration(CWE)-121, for training and Securely Taking On New Executable Software of Uncertain Provenance (STONESOUP) for testing. Experimental results show that the proposed scheme can detect software vulnerabilities with an accuracy of 91% of the assembly code.
Dependence-Analysis-Based Data-Refinement in Optical Scatterometry for Fast Nanostructure Reconstruction
Authors: Dong Zhengqiong , Chen Xiuguo , Wang Xuanze , Shi Yating , Jiang Hao , Liu Shiyuan
Published: September 2019

Optical scatterometry is known as a powerful tool for nanostructure reconstruction due to its advantages of being non-contact, non-destructive, low cost, and easy to integrate. As a typical model-based method, it usually makes use of abundant measured data for structural profile reconstruction, on the other hand, too much redundant information significantly degrades the efficiency in profile reconstruction. We propose a method based on dependence analysis to identify and then eliminate the measurement configurations with redundant information. Our experiments demonstrated the capability of the proposed method in an optimized selection of a subset of measurement wavelengths that contained sufficient information for profile reconstruction and strikingly improved the profile reconstruction efficiency without sacrificing accuracy, compared with the primitive approach, by making use of the whole spectrum.
Orbit Determination of Resident Space Objects Using the P-Band Mono-Beam Receiver of the Sardinia Radio Telescope
Authors: Losacco Matteo , Schirru Luca
Published: September 2019

The population of space debris in near-Earth space is continuously growing and it represents a serious problem for active satellites and spacecraft. A performant ground-based and space-based network of sensors is necessary for space surveillance and consequently to prevent new collisions and monitoring atmospheric reentry of these objects. This paper illustrates the possible role of the Italian ground-based novel bi-static radar sensor, named BIRALET, for space monitoring and resident space objects tracking. The main characteristics of the receiver system, the Sardinia Radio Telescope with its P-band mono-beam receiver, are described in detail. Then, a preliminary analysis of the performance of the sensor is presented, and the results of numerical simulations are shown, providing a general overview on both observation capabilities and orbit determination accuracy achievable with the Sardinia Radio Telescope.
Singing to Emmanuel: The Wall Paintings of Sant Miquel in Terrassa and the 6th Century Artistic Reception of Byzantium in the Western Mediterranean
Authors: Sánchez Márquez Carles
Published: September 2019

Since the late 19th century the wall paintings of Sant Miquel in Terrassa have drawn attention due to their singularity. From the early studies of Josep Puig i Cadafalch (1867–1956) to the present, both the iconographic program and the chronology of the paintings have fueled controversy among scholars. In particular, chronological estimates range from the time of Early Christian Art to the Carolingian period. However, a recent technical study of the paintings seems to confirm an early date around the 6th century. This new data allows us to reassess the question in other terms and explore a new possible context for the paintings. First, it is very likely that the choice of iconographic topics was related to the debates on the Arian heresy that took place in Visigothic Spain during the 5th and 6th centuries. Secondly, the paintings of Sant Miquel should be reconsidered as a possible reception of a larger 6th-century pictorial tradition linked to the Eastern Mediterranean, which is used in a very particular way. However, thus far we ignore which were the means for this artistic transmission as well as the reasons which led the “doers” of Terrassa to select such a peculiar and unique repertoire of topics, motifs, and inscriptions. My paper addresses all these questions in order to propose a new Mediterranean framework for the making of this singular set of paintings.
NMDA Receptor Opening and Closing—Transitions of a Molecular Machine Revealed by Molecular Dynamics
Authors: Černý Jiří , Božíková Paulína , Balík Aleš , Marques Sérgio M. , Vyklický Ladislav
Published: September 2019

We report the first complete description of the molecular mechanisms behind the transition of the N-methyl-d-aspartate (NMDA) receptor from the state where the transmembrane domain (TMD) and the ion channel are in the open configuration to the relaxed unliganded state where the channel is closed. Using an aggregate of nearly 1 µs of unbiased all-atom implicit membrane and solvent molecular dynamics (MD) simulations we identified distinct structural states of the NMDA receptor and revealed functionally important residues (GluN1/Glu522, GluN1/Arg695, and GluN2B/Asp786). The role of the “clamshell” motion of the ligand binding domain (LBD) lobes in the structural transition is supplemented by the observed structural similarity at the level of protein domains during the structural transition, combined with the overall large rearrangement necessary for the opening and closing of the receptor. The activated and open states of the receptor are structurally similar to the liganded crystal structure, while in the unliganded receptor the extracellular domains perform rearrangements leading to a clockwise rotation of up to 45 degrees around the longitudinal axis of the receptor, which closes the ion channel. The ligand-induced rotation of extracellular domains transferred by LBD–TMD linkers to the membrane-anchored ion channel is responsible for the opening and closing of the transmembrane ion channel, revealing the properties of NMDA receptor as a finely tuned molecular machine.
The Effect of Dimethyl Sulfoxide on the Lysozyme Unfolding Kinetics, Thermodynamics, and Mechanism
Authors: Magsumov Timur , Fatkhutdinova Alisa , Mukhametzyanov Timur , Sedov Igor
Published: September 2019

The thermal stability of proteins in the presence of organic solvents and the search for ways to increase this stability are important topics in industrial biocatalysis and protein engineering. The denaturation of hen egg-white lysozyme in mixtures of water with dimethyl sulfoxide (DMSO) with a broad range of compositions was studied using a combination of differential scanning calorimetry (DSC), circular dichroism (CD), and spectrofluorimetry techniques. In this study, for the first time, the kinetics of unfolding of lysozyme in DMSO–water mixtures was characterized. In the presence of DMSO, a sharp decrease in near-UV CD and an increase in the fluorescence signal were observed at lower temperatures than the DSC denaturation peak. It was found that differences in the temperatures of the CD and DSC signal changes increase as the content of DMSO increases. Changes in CD and fluorescence are triggered by a break of the tertiary contacts, leading to an intermediate state, while the DSC peak corresponds to a subsequent complete loss of the native structure. In this way, the commonly used two-state model was proven to be unsuitable to describe the unfolding of lysozyme in the presence of DMSO. In kinetic studies, it was found that even high concentrations of DMSO do not drastically change the activation energy of the initial stage of unfolding associated with a disruption of the tertiary structure, while the enthalpy of denaturation shows a significant dependence on DMSO content. This observation suggests that the structure of the transition state upon unfolding remains similar to the structure of the native state.
Analyzing Fluctuation Properties in Protein Elastic Networks with Sequence-Specific and Distance-Dependent Interactions
Authors: Amyot Romain , Togashi Yuichi , Flechsig Holger
Published: September 2019

Simple protein elastic networks which neglect amino-acid information often yield reasonable predictions of conformational dynamics and are broadly used. Recently, model variants which incorporate sequence-specific and distance-dependent interactions of residue pairs have been constructed and demonstrated to improve agreement with experimental data. We have applied the new variants in a systematic study of protein fluctuation properties and compared their predictions with those of conventional anisotropic network models. We find that the quality of predictions is frequently linked to poor estimations in highly flexible protein regions. An analysis of a large set of protein structures shows that fluctuations of very weakly connected network residues are intrinsically prone to be significantly overestimated by all models. This problem persists in the new models and is not resolved by taking into account sequence information. The effect becomes even enhanced in the model variant which takes into account very soft long-ranged residue interactions. Beyond these shortcomings, we find that model predictions are largely insensitive to the integration of chemical information, at least regarding the fluctuation properties of individual residues. One can furthermore conclude that the inherent drawbacks may present a serious hindrance when improvement of elastic network models are attempted.
Antidiabetic Potential of Medicinal Plants and Their Active Components
Authors: Salehi Bahare , Ata Athar , V. Anil Kumar Nanjangud , Sharopov Farukh , Ramírez-Alarcón Karina , Ruiz-Ortega Ana , Abdulmajid Ayatollahi Seyed , Valere Tsouh Fokou Patrick , Kobarfard Farzad , Amiruddin Zakaria Zainul , Iriti Marcello , Taheri Yasaman , Martorell Miquel , Sureda Antoni , N. Setzer William , Durazzo Alessandra , Lucarini Massimo , Santini Antonello , Capasso Raffaele , Adrian Ostrander Elise , -ur-Rahman Atta , Iqbal Choudhary Muhammad , C. Cho William , Sharifi-Rad Javad
Published: September 2019

Diabetes mellitus is one of the major health problems in the world, the incidence and associated mortality are increasing. Inadequate regulation of the blood sugar imposes serious consequences for health. Conventional antidiabetic drugs are effective, however, also with unavoidable side effects. On the other hand, medicinal plants may act as an alternative source of antidiabetic agents. Examples of medicinal plants with antidiabetic potential are described, with focuses on preclinical and clinical studies. The beneficial potential of each plant matrix is given by the combined and concerted action of their profile of biologically active compounds.
Triple Immunochromatographic System for Simultaneous Serodiagnosis of Bovine Brucellosis, Tuberculosis, and Leukemia
Authors: Barshevskaya Lyubov V. , Sotnikov Dmitriy V. , Zherdev Anatoly V. , Khassenov Bekbolat B. , Baltin Kayrat K. , Eskendirova Saule Z. , Mukanov Kassym K. , Mukantayev Kanatbek K. , Dzantiev Boris B.
Published: September 2019

An immunochromatographic test system has been developed for the simultaneous rapid multiplex serodiagnostics of bovine brucellosis, tuberculosis, and leukemia. The test system is based on the use of a conjugate of gold nanoparticles with the chimeric protein Cysteine-A/G and three analytical zones with immobilized pathogen antigens: Brucella abortus lipolysaccharide, recombinant proteins MPB64 and MPB83-MPB63 of Mycobacterium bovis, and recombinant protein p24 of the bovine leukemia virus. Prototypes of the test system were tested on 98 samples of sera from healthy and infected animals. The diagnostic sensitivity of the developed test system was 92% for brucellosis, 92% for tuberculosis, and 96% for leukemia. False positive test results were not observed.
Comparative Volumetric Analysis of the Brain and Cerebrospinal Fluid in Chiari Type I Malformation Patients: A Morphological Study
Authors: Aydin Seckin , Ozoner Baris
Published: September 2019

Background: Chiari Type I malformation (CM-I) is defined as the migration of cerebellar tonsils from the foramen magnum in the caudal direction and is characterized by the disproportion of the neural structures. The aim of this study was to investigate the brain volume differences between CM-I patients and normal population using a comparative volumetric analysis. Methods: 140 patients with CM-I and 140 age- and sex-matched healthy controls were included in this study. The magnetic resonance imaging (MRI) data of both groups were analyzed with an automated MRI brain morphometry system. Total intracranial, cerebrum, cerebellum, brainstem, cerebrospinal fluid (CSF), and lateral ventricle volumes as well as cerebrum and cerebellum gray/white matter (GM/WM) volumes were measured. Statistical analysis was performed. Results: Both total CSF and lateral ventricle volumes and volume percentages (Pct) were found significantly higher in CM-I patients compared to the control group. However, there were significant decreases in cerebrum and cerebellum volume Pct in CM-I patients. Although there were no significant differences in cerebrum WM volumes and volume Pct, cerebrum GM volume Pct were found to be significantly lower in CM-I patients. Conclusions: Revealing the increased CSF and lateral ventricle volume, and volume Pct supported concomitant ventricular enlargement and hydrocephalus in some CM-I patients. Decreased cerebrum GM volume Pct compared to the control group might be the underlying factor of some cortical dysfunctions in CM-I patients.
Field Study on Nationality Differences in Thermal Comfort of University Students in Dormitories during Winter in Japan
Authors: Draganova Vanya , Tsuzuki Kazuyo , Nabeshima Yuki
Published: September 2019

Comfort in university dormitory buildings in Japan is under-investigated as compared to offices and residences. A winter field survey conducted in two university dormitories in Central Japan aimed at investigating the differences in thermal responses of occupants relative to nationality and; to estimate their neutral and comfortable temperature under identical climatic conditions. Acceptability of the indoor environment was invariably high. While evaluation and preference votes depended on nationality; thermal sensation vote did not. Both Japanese and non-Japanese subjects voted neutral at a mean indoor temperature of 22 °C. The estimated probability of voting neutral for Japanese subjects was highest (65%) from 19 °C to 22 °C, while for non-Japanese subjects it was highest (75%) at a wider range: From 19 °C to 24 °C. Japanese students were more sensitive of and more critical about their indoor environment as opposed to the internationals (adjusted regression coefficients 0.55/K and 0.20/K). Griffiths’ model estimated the comfortable temperature for non-Japanese subjects at a 2 °C wider range and at a 2 °C higher average than for Japanese subject. Neutral and comfortable temperatures observed and estimated in the study were split above and below the recommended temperature threshold of 20 °C for Japan in winter.
A Functional Analysis of the Unclassified Pro2767Ser BRCA2 Variant Reveals Its Potential Pathogenicity that Acts by Hampering DNA Binding and Homology-Mediated DNA Repair
Authors: Esposito Maria Valeria , Minopoli Giuseppina , Esposito Luciana , D’Argenio Valeria , Di Maggio Federica , Sasso Emanuele , D’Aiuto Massimiliano , Zambrano Nicola , Salvatore Francesco
Published: September 2019

BRCA1 and BRCA2 are the genes most frequently associated with hereditary breast and ovarian cancer (HBOC). They are crucial for the maintenance of genome stability, particularly in the homologous recombination-mediated repair pathway of DNA double-strand breaks (HR-DSBR). Widespread BRCA1/2 next-generation sequencing (NGS) screening has revealed numerous variants of uncertain significance. Assessing the clinical significance of these variants is challenging, particularly regarding the clinical management of patients. Here, we report the functional characterization of the unclassified BRCA2 c.8299C > T variant, identified in a young breast cancer patient during BRCA1/2 NGS screening. This variant causes the change of Proline 2767 to Serine in the DNA binding domain (DBD) of the BRCA2 protein, necessary for the loading of RAD51 on ssDNA during the HR-DSBR. Our in silico analysis and 3D-structure modeling predicted that the p.Pro2767Ser substitution is likely to alter the BRCA2 DBD structure and function. Therefore, to evaluate the functional impact of the p.Pro2767Ser variant, we used a minigene encoding a truncated protein that contains the BRCA2 DBD and the nearby nuclear localization sequence. We found that the ectopically expressed truncated protein carrying the normal DBD, which retains the DNA binding function and lacks the central RAD51 binding domain, interferes with endogenous wild-type BRCA2 mediator functions in the HR-DSBR. We also demonstrated that the BRCA2 Pro2767Ser DBD is unable to compete with endogenous BRCA2 DNA binding, thereby suggesting that the p.Pro2767Ser substitution in the full-length protein causes the functional loss of BRCA2. Consequently, our data suggest that the p.Pro2767Ser variant should be considered pathogenic, thus supporting a revision of the ClinVar interpretation. Moreover, our experimental strategy could be a valid method with which to preliminarily evaluate the pathogenicity of the unclassified BRCA2 germline variants in the DBD and their risk of predisposing to HBOC.
Replication Stress Response Links RAD52 to Protecting Common Fragile Sites
Authors: Wu Xiaohua
Published: September 2019

Rad52 in yeast is a key player in homologous recombination (HR), but mammalian RAD52 is dispensable for HR as shown by the lack of a strong HR phenotype in RAD52-deficient cells and in RAD52 knockout mice. RAD52 function in mammalian cells first emerged with the discovery of its important backup role to BRCA (breast cancer genes) in HR. Recent new evidence further demonstrates that RAD52 possesses multiple activities to cope with replication stress. For example, replication stress-induced DNA repair synthesis in mitosis (MiDAS) and oncogene overexpression-induced DNA replication are dependent on RAD52. RAD52 becomes essential in HR to repair DSBs containing secondary structures, which often arise at collapsed replication forks. RAD52 is also implicated in break-induced replication (BIR) and is found to inhibit excessive fork reversal at stalled replication forks. These various functions of RAD52 to deal with replication stress have been linked to the protection of genome stability at common fragile sites, which are often associated with the DNA breakpoints in cancer. Therefore, RAD52 has important recombination roles under special stress conditions in mammalian cells, and presents as a promising anti-cancer therapy target.
Current Perspectives in Cancer Immunotherapy
Authors: Christofi Theodoulakis , Baritaki Stavroula , Falzone Luca , Libra Massimo , Zaravinos Apostolos
Published: September 2019

Different immunotherapeutic approaches have proved to be of significant clinical value to many patients with different types of advanced cancer. However, we need more precise immunotherapies and predictive biomarkers to increase the successful response rates. The advent of next generation sequencing technologies and their applications in immuno-oncology has helped us tremendously towards this aim. We are now moving towards the realization of personalized medicine, thus, significantly increasing our expectations for a more successful management of the disease. Here, we discuss the current immunotherapeutic approaches against cancer, including immune checkpoint blockade with an emphasis on anti-PD-L1 and anti-CTLA-4 monoclonal antibodies. We also analyze a growing list of other co-inhibitory and co-stimulatory markers and emphasize the mechanism of action of the principal pathway for each of these, as well as on drugs that either have been FDA-approved or are under clinical investigation. We further discuss recent advances in other immunotherapies, including cytokine therapy, adoptive cell transfer therapy and therapeutic vaccines. We finally discuss the modulation of gut microbiota composition and response to immunotherapy, as well as how tumor-intrinsic factors and immunological processes influence the mutational and epigenetic landscape of progressing tumors and response to immunotherapy but also how immunotherapeutic intervention influences the landscape of cancer neoepitopes and tumor immunoediting.
Photodynamic Therapy Activity of New Porphyrin-Xylan-Coated Silica Nanoparticles in Human Colorectal Cancer
Authors: Bretin Ludovic , Pinon Aline , Bouramtane Soukaina , Ouk Catherine , Richard Laurence , Perrin Marie-Laure , Chaunavel Alain , Carrion Claire , Bregier Frédérique , Sol Vincent , Chaleix Vincent , Leger David Yannick , Liagre Bertrand
Published: September 2019

Photodynamic therapy (PDT) using porphyrins has been approved for treatment of several solid tumors due to the generation of cytotoxic reactive oxygen species (ROS). However, low physiological solubility and lack of selectivity towards tumor sites are the main limitations of their clinical use. Nanoparticles are able to spontaneously accumulate in solid tumors through an enhanced permeability and retention (EPR) effect due to leaky vasculature, poor lymphatic drainage, and increased vessel permeability. Herein, we proved the added value of nanoparticle vectorization on anticancer efficacy and tumor-targeting by 5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (TPPOH). Using 80 nm silica nanoparticles (SNPs) coated with xylan-TPPOH conjugate (TPPOH-X), we first showed very significant phototoxic effects of TPPOH-X SNPs mediated by post-PDT ROS generation and stronger cell uptake in human colorectal cancer cell lines compared to free TPPOH. Additionally, we demonstrated apoptotic cell death induced by TPPOH-X SNPs-PDT and the interest of autophagy inhibition to increase anticancer efficacy. Finally, we highlighted in vivo, without toxicity, elevated anticancer efficacy of TPPOH-X SNPs through improvement of tumor-targeting compared to a free TPPOH protocol. Our work demonstrated for the first time the strong anticancer efficacy of TPPOH in vitro and in vivo and the merit of SNPs vectorization.
Reactive Fe-O-Ce Sites in Ceria Catalysts for Soot Oxidation
Authors: Li Boyu , Raj Abhishek , Croiset Eric , Wen John Z.
Published: September 2019

This study investigates the role of oxygen vacancy on Fe-doped CeO2 catalyst activity for soot oxidation. The oxygen vacancy was assessed through Ce3+ content. The Fe content was varied between 0 and 30% for two catalyst preparation methods, co-precipitation (CP) and solution combustion synthesis (SCS). X-ray photoelectron spectroscopy indicates that ceria exists as both Ce4+ and Ce3+, while iron is present only as Fe3+. The catalyst’s activity was evaluated by ignition (T10) and combustion (T50) temperatures using thermogravimetric analysis. Optimum Fe contents yielding the highest activity were found to be 10% and 5% for CP and SCS catalysts, respectively. The surface area and morphology showed a moderate effect on catalyst activity, because catalytic soot oxidation involves solid–solid contact. More importantly, regardless of the fabrication method, it was found that Ce3+ content, which is closely related to oxygen vacancies, plays the most important role in affecting the catalyst activity.
Highly Active CuFeAl-containing Catalysts for Selective Hydrogenation of Furfural to Furfuryl Alcohol
Authors: Selishcheva Svetlana A. , Smirnov Andrey A. , Fedorov Alexander V. , Bulavchenko Olga A. , Saraev Andrey A. , Lebedev Maksim Yu. , Yakovlev Vadim A.
Published: September 2019

CuFe-containing catalysts with different copper oxide content were prepared by fusion of metal salts. The obtained catalyst showed high activity in the hydrogenation of furfural to furfuryl alcohol (FA) in the batch reactor in the presence of isopropanol as a solvent at a temperature of 100 °C and a hydrogen pressure of 6.0 MPa. The yield of FA and furfural conversion are 97% and 98%, respectively. In the solvent-free reaction in the flow-type reactor; the most active catalyst Cu20Fe66Al14 leads to the 96% formation of FA with 100% conversion of furfural at liquid hourly space velocity (LHSV) = 1 h−1; 160 °C and a hydrogen pressure of 5.0 MPa during 30 h. According to the X-ray diffraction (XRD) method, the active component of the spent and fresh Cu20Fe66Al14 catalyst is the same and is represented by metallic copper and Fe3O4-type spinel. Using different methods, the formation of active sites was investigated.
Patient-Derived Glioma Models: From Patients to Dish to Animals
Authors: da Hora Cintia Carla , Schweiger Markus W. , Wurdinger Thomas , Tannous Bakhos A.
Published: September 2019

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults associated with a poor survival. Current standard of care consists of surgical resection followed by radiation and chemotherapy. GBMs are highly heterogeneous, having a complex interaction among different cells within the tumor as well as the tumor microenvironment. One of the main challenges in the neuro-oncology field in general, and GBM in particular, is to find an optimum culture condition that maintains the molecular genotype and phenotype as well as heterogeneity of the original tumor in vitro and in vivo. Established cell lines were shown to be a poor model of the disease, failing to recapitulate the phenotype and harboring non-parental genotypic mutations. Given the growing understanding of GBM biology, the discovery of glioma cancer stem-like cells (GSCs), and their role in tumor formation and therapeutic resistance, scientists are turning more towards patient-derived cells and xenografts as a more representative model. In this review, we will discuss the current state of patient-derived GSCs and their xenografts; and provide an overview of different established models to study GBM biology and to identify novel therapeutics in the pre-clinical phase.
Exportin-1-Dependent Nuclear Export of DEAD-box Helicase DDX3X is Central to its Role in Antiviral Immunity
Authors: Heaton Steven M. , Atkinson Sarah C. , Sweeney Melissa N. , Yang Sundy N. Y. , Jans David A. , Borg Natalie A.
Published: September 2019

DEAD-box helicase 3, X-linked (DDX3X) regulates the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-mediated antiviral response, but can also be a host factor contributing to the replication of viruses of significance to human health, such as human immunodeficiency virus type 1 (HIV-1). These roles are mediated in part through its ability to actively shuttle between the nucleus and the cytoplasm to modulate gene expression, although the trafficking mechanisms, and impact thereof on immune signaling and viral infection, are incompletely defined. We confirm that DDX3X nuclear export is mediated by the nuclear transporter exportin-1/CRM1, dependent on an N-terminal, leucine-rich nuclear export signal (NES) and the monomeric guanine nucleotide binding protein Ran in activated GTP-bound form. Transcriptome profiling and ELISA show that exportin-1-dependent export of DDX3X to the cytoplasm strongly impacts IFN-β production and the upregulation of immune genes in response to infection. That this is key to DDX3X’s antiviral role was indicated by enhanced infection by human parainfluenza virus-3 (hPIV-3)/elevated virus production when the DDX3X NES was inactivated. Our results highlight a link between nucleocytoplasmic distribution of DDX3X and its role in antiviral immunity, with strong relevance to hPIV-3, as well as other viruses such as HIV-1.
Zileuton, a 5-Lipoxygenase Inhibitor, Exerts Anti-Angiogenic Effect by Inducing Apoptosis of HUVEC via BK Channel Activation
Authors: Lim Hyun-Joung , Park Jinbong , Um Jae-Young , Lee Sang-Seob , Kwak Hyun-Jeong
Published: September 2019

The arachidonic acid metabolism through 5-lipoxygenase (5-LO) pathways is involved in modulating both tumorigenesis and angiogenesis. Although anti-carcinogenic activities of certain 5-LO inhibitors have been reported, the role of zileuton, a well known 5-LO inhibitor, on the endothelial cell proliferation and angiogenesis has not been fully elucidated. Here, we report that zileuton has an anti-angiogenic effect, and the underlying mechanisms involved activation of the large-conductance Ca2+-activated K+ (BK) channel. Our results show that zileuton significantly prevented vascular endothelial growth factor (VEGF)-induced proliferation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as in vivo. However, such anti-angiogenic effect of zileuton was abolished by iberiotoxin (IBTX), a BK channel blocker, suggesting zileuton-induced activation of BK channel was critical for the observed anti-angiogenic effect of zileuton. Furthermore, the anti-angiogenic effect of zileuton was, at least, due to the activation of pro-apoptotic signaling cascades which was also abolished by IBTX. Additionally, zileuton suppressed the expression of VCAM-1, ICAM-1, ETS related gene (Erg) and the production of nitric oxide (NO). Taken together, our results show that zileuton prevents angiogenesis by activating the BK channel dependent-apoptotic pathway, thus highlighting its therapeutic capacity in angiogenesis-related diseases, such as cancer.
The Effect of Cu and Ga Doped ZnIn2S4 under Visible Light on the High Generation of H2 Production
Authors: Tateishi Ikki , Furukawa Mai , Katsumata Hideyuki , Kaneco Satoshi
Published: September 2019

A Cu+ and Ga3+ co-doped ZnIn2S4 photocatalyst (Zn(1−2x)(CuGa)xIn2S4) with controlled band gap was prepared via a simple one-step solvothermal method. Zn(1−2x)(CuGa)xIn2S4 acted as an efficient photocatalyst for H2 evolution under visible light irradiation (λ > 420 nm; 4500 µW/cm2). The effects of the (Cu and Ga)/Zn molar ratios of Zn(1−2x)(CuGa)xIn2S4 on the crystal structure (hexagonal structure), morphology (microsphere-like flower), optical property (light harvesting activity and charge hole separation ability), and photocatalytic activity have been investigated in detail. The maximum H2 evolution rate (1650 µmol·h−1·g−1) was achieved over Zn0.84(CuGa)0.13In2S4, showing a 3.3 times higher rate than that of untreated ZnIn2S4. The bandgap energy of Zn(1−2x)(CuGa)xIn2S4 decreased from 2.67 to 1.90 eV as the amount of doping Cu+ and Ga3+ increased.
Atomic Oxygen Adaptability of Flexible Kapton/Al2O3 Composite Thin Films Prepared by Ion Exchange Method
Authors: Jiang Donghua , Wang Dan , Liu Gang , Wei Qiang
Published: September 2019

Polyimide film (Kapton) is an important polymer material used for the construction of spacecrafts. The performance of Kapton can be degraded for atomic oxygen erosion in space. Commonly used atomic oxygen protective layers have issues such as poor toughness and poor adhesion with the film. In this paper, Kapton/Al2O3 nanocomposite films were prepared via an ion exchange method, and the optical properties, mechanical properties, and mechanisms for the change in the mass and microstructure, before and after atomic oxygen exposure, were analyzed. The results show that the deposition of the Kapton/Al2O3 surface nanocomposite film prepared via the ion exchange method has no obvious effects on the internal structure and optical transmittance of the Kapton film matrix. The tensile strength and elongation of the prepared film were much higher than those of the pure Kapton film, demonstrating its good flexibility. Scanning electron microscope (SEM) analysis showed that the etching pits had a carpet-like morphology on the composite film surface and were relatively small after atomic oxygen erosion. In contrast with the C–C bond rupture in the oxydianiline (ODA) benzene in Kapton films, the Kapton/Al2O3 nanocomposite film mainly destroyed the C=C bond in the pyromellitic dianhydride (PMDA) benzene ring. On exposure to an atomic oxygen environment for a short period, the Kapton/Al2O3 nanocomposite film exhibited improved atomic oxygen erosion resistance because the Al2O3 layer inhibited atomic oxygen diffusion. With increasing atomic oxygen exposure time, the atomic oxygen diffused into the Kapton matrix via the pores of the Al2O3 layer, causing damage to the substrate. This resulted in a detachment of the surface Al2O3 layer and exposure of the Kapton matrix, and thereby the atomic oxygen resistance was decreased. The applicability of the ion exchange mechanism of trivalent Al element on the surface modification of the polyimide is explored in this study. The behavior of the Kapton/Al2O3 composite film under the atomic oxygen environment of space is investigated, which provides the basis for studying the effects of atomic oxygen on the flexible protective Kapton film.
Thermal Boundaries in Cone Calorimetry Testing
Authors: Kang Sungwook , Kwon Minjae , Choi Joung Yoon , Choi Sengkwan
Published: September 2019

Bench-scale cone calorimetry is often used to evaluate the fire performance of intumescent-type coatings. During the tests, the coating geometry inflates. These thick, block-shaped specimens expose their perimeter side surfaces to both the heat source and the surroundings, unlike the typical thin, plate-shaped samples used in flammability tests. We assessed the thermal boundaries of block-shaped specimens using plain steel solids with several thicknesses. The heat transmitted through the exposed boundaries in convection and radiation modes was determined by four sub-defining functions: non-linear irradiance, convective loss, and radiant absorption into and radiant emission from solids. The individual functions were methodically derived and integrated into numerical calculations. The predictions were verified by physical measurements of the metals under different heating conditions. The results demonstrate that (1) considering absorptivity, being differentiated from emissivity, led to accurate predictions of time-temperature relationships for all stages from transient, through steady, and to cooling states; (2) the determined values for the geometric view factor and the fluid dynamic coefficient of convection can be generalized for engineering applications; (3) the proposed process provides a practical solution for the determination of optical radiative properties (absorptivity and emissivity) for use in engineering; and (4) the heat transmitted through the side surfaces of block specimens should be included in energy balance, particularly in the quantification of a heat loss mechanism. This paper outlines a comprehensive heat transfer model for cone calorimetry testing, providing insights into the mechanism of complex heat transmission generated on the test samples and quantifying their individual contributions.
Structural Stabilization of Mullite Films Exposed to Oxygen Potential Gradients at High Temperatures
Authors: Kitaoka Satoshi , Matsudaira Tsuneaki , Kawashima Naoki , Yokoe Daisaku , Kato Takeharu , Takata Masasuke
Published: September 2019

The oxygen shielding properties of polycrystalline Al4+2xSi2−2xO10−x (mullite) films applied as environmental barrier coatings (EBCs) on SiC fiber-reinforced SiC matrix composites (SiC/SiC) are determined by the grain boundary (GB) diffusion of oxide ions in the films, from the higher oxygen partial pressure (PO₂) surface to the lower PO₂ surface, with simultaneous GB diffusion of Al ions in the opposite direction. Herein, strategies to improve the oxygen shielding and phase stability of these films when applied to SiC/SiC substrates through bond coats are proposed, based on oxygen permeation data for mullite at high temperatures. The validity of these strategies is verified using experimental trials at 1673 K with bilayer specimens consisting of mullite films and bond coat substrates, serving as model EBCs. The data show that employing a bond coat made of β’-SiAlON rather than Si provides a source of Al for the overlying mullite film that greatly improves the phase stability of the film in the vicinity of the junction interface. Because the minimum equilibrium PO₂ values required to form SiO2 due to oxidation of the β’-SiAlON on a thermodynamic basis are significantly larger than those for oxidation of Si, the inward GB diffusion of oxide ions is effectively retarded, resulting in excellent oxygen shielding characteristics.
Enzyme Immobilization on Polymer Membranes: A Quantum and Molecular Mechanics Study
Authors: Petrosino Francesco , Curcio Stefano , Chakraborty Sudip , De Luca Giorgio
Published: September 2019

Adsorption of the phosphotriesterase on a polysulfone membrane surface was investigated in this paper through a double-scale computational approach. Surface charges of the enzyme, as well as membrane, were calculated at sub and nanoscale while protein adsorption was simulated at larger scale. Adsorption energies were calculated as a function of the enzyme–surface distance, and for each distance, several protein rotations were tested to find the most stable orientations of the macromolecule. The results of this model were useful in obtaining information about the adhesion of the enzyme and to give indications on the orientations of its binding site. Adsorption energies agreed with the literature data. Furthermore, the binding site of the immobilized phosphotriesterase was less accessible with respect to native enzymes due to the steric hindrance of the polymer surface; thus, a reduction of its efficiency is expected. The proposed methodology made use of fundamental quantities, calculated without resorting to adjustable or empirical parameters, providing basic outputs useful for ascertaining enzymatic catalysis rate.