bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous Carbon Monoxide Signaling Modulates Mitochondrial Function and Intracellular Glucose Utilization: Impact of the Heme Oxygenase Substrate Hemin
Authors: Stucki David , Steinhausen Julia , Westhoff Philipp , Krahl Heide , Brilhaus Dominik , Massenberg Annika , Weber Andreas P. M. , Reichert Andreas S. , Brenneisen Peter , Stahl Wilhelm
Published: July 2020

Stress-inducible heme oxygenase-1 (HO-1) catalyzes the oxidative cleavage of heme yielding biliverdin, ferrous iron, and carbon monoxide (CO). Heme oxygenase activity has been attributed to antioxidant defense via the redox cycling system of biliverdin and bilirubin. There is increasing evidence that CO is a gaseous signaling molecule and plays a role in the regulation of energy metabolism. Inhibitory effects of CO on the respiratory chain are well established, but the implication of such a process on the cellular stress response is not well understood. By means of extracellular flux analyses and isotopic tracing, we studied the effects of CO, either released from the CO donor CORM-401 or endogenously produced by heme oxygenases, on the respiratory chain and glucose metabolism. CORM-401 was thereby used as a tool to mimic endogenous CO production by heme oxygenases. In the long term (>60 min), CORM-401-derived CO exposure inhibited mitochondrial respiration, which was compensated by increased glycolysis accompanied by a loss of the ATP production rate and an increase in proton leakage. This effect pattern was likewise observed after endogenous CO production by heme oxygenases. However, in the present setting, these effects were only observed when sufficient substrate for heme oxygenases (hemin) was provided. Modulation of the HO-1 protein level was less important. The long-term influence of CO on glucose metabolism via glycolysis was preceded by a short-term response (<30 min) of the cells to CO. Stable isotope-labeling experiments and metabolic flux analysis revealed a short-term shift of glucose consumption from glycolysis to the pentose phosphate pathway (PPP) along with an increase in reactive oxygen species (ROS) generation. Overall, we suggest that signaling by endogenous CO stimulates the rapid formation of reduction equivalents (NADPH) via the PPP, and plays an additional role in antioxidant defense, e.g., via feed-forward stimulation of the bilirubin/biliverdin redox cycling system.
Oxidative Stress and Obesity- and Type 2 Diabetes-Induced Heart Failure
Authors: Demaison Luc
Published: July 2020

Obesity is a risk factor for the development of type 2 diabetes (T2D), which is associated with cardiovascular diseases [...]
Molecular Assessment of Epiretinal Membrane: Activated Microglia, Oxidative Stress and Inflammation
Authors: Vishwakarma Sushma , Gupta Rishikesh Kumar , Jakati Saumya , Tyagi Mudit , Pappuru Rajeev Reddy , Reddig Keith , Hendricks Gregory , Volkert Michael R. , Khanna Hemant , Chhablani Jay , Kaur Inderjeet
Published: July 2020

Fibrocellular membrane or epiretinal membrane (ERM) forms on the surface of the inner limiting membrane (ILM) in the inner retina and alters the structure and function of the retina. ERM formation is frequently observed in ocular inflammatory conditions, such as proliferative diabetic retinopathy (PDR) and retinal detachment (RD). Although peeling of the ERM is used as a surgical intervention, it can inadvertently distort the retina. Our goal is to design alternative strategies to tackle ERMs. As a first step, we sought to determine the composition of the ERMs by identifying the constituent cell-types and gene expression signature in patient samples. Using ultrastructural microscopy and immunofluorescence analyses, we found activated microglia, astrocytes, and Müller glia in the ERMs from PDR and RD patients. Moreover, oxidative stress and inflammation associated gene expression was significantly higher in the RD and PDR membranes as compared to the macular hole samples, which are not associated with inflammation. We specifically detected differential expression of hypoxia inducible factor 1-α (HIF1-α), proinflammatory cytokines, and Notch, Wnt, and ERK signaling pathway-associated genes in the RD and PDR samples. Taken together, our results provide new information to potentially develop methods to tackle ERM formation.
On the Procedure of Draught Rate Assessment in Indoor Spaces
Authors: Markov Detelin , Ivanov Nikolay , Pichurov George , Zasimova Marina , Stankov Peter , Smirnov Evgueni , Simova Iskra , Ris Vladimir , A. Angelova Radostina , Velichkova Rositsa
Published: July 2020

The objective of the paper is to demonstrate the importance of the unsteady Computational Fluid Dynamics (CFD) simulations and long-term measurements for the reliable assessment of thermal comfort indoors, for proper categorization of the indoor thermal environment and for identifying the reasons for complaints due to draught discomfort. Numerical simulations and experimental measurements were applied in combination to study ventilation in a field laboratory, a university classroom with a controlled indoor environment. Strong unsteadiness of the airflow was registered both in the unsteady RANS results and the real-scale long-term velocity data measured with thermo anemometer. Low-frequency high-amplitude velocity fluctuations observed lead to substantial time variation of the draught rate. In case of categorization of a thermal environment, the point measurements or steady-state RANS computations would lead to wrong conclusions as well as they cannot be used for identification of the reasons for people’s complaints due to draught discomfort if strong unsteadiness of the airflow exists. It is demonstrated that the length of the time interval for draught rate (DR) assessment may not be universal if low-frequency high-amplitude pulsations are present in the room airflow.
Economic Effects of Individual Heating System and District Heating System in South Korea: An Input-Output Analysis
Authors: Kim Ju-Hee , Kim Sin-Young , Yoo Seung-Hoon
Published: July 2020

When South Korea develops a new city, the government has made a preliminary decision on one of two heating systems, an individual heating system (IHS) or a district heating system (DHS). However, it is still unclear which system is desirable in terms of maximizing the national economic effect. Thus, this article aims to derive quantitative information about the economic effects of the same amount of production or investment in the two systems through an input-output (IO) analysis using the recently published 2017 IO table. More specifically, the production-inducing effects, value-added creation effects, and wage-inducing effects are systematically analyzed focusing on the IHS and DHS sectors. The results show that one dollar of production or investment in IHS or DHS causes about 1.073 and 1.388 dollars of production, about 0.228 and 0.658 dollars of value-added, and about 0.051 and 0.108 dollars in wages, respectively, throughout the national economy. Overall, the economic effects of the DHS sector are greater than those of the IHS sector. That is, when the same amount of investment or production is made in the two sectors, DHS produces more economic effects than IHS.
Optimal F-Number of Ritchey–Chrétien Telescope Based on Tolerance Analysis of Mirror Components
Authors: Lin Sheng-Feng , Chen Cheng-Huan , Huang Yi-Kai
Published: July 2020

The Ritchey–Chrétien telescope has been the key optical module for remote sensing instruments (RSI), in which the root mean square (RMS) random surface wavefront error and the alignment error of the primary and the secondary mirror takes the highest weighting in the tolerance analysis for the fabrication and assembly of the telescope. Therefore, the higher tolerance of those items becomes preferable for higher efficiency of RSI manufacturing. In this paper, the correlation between those tolerance items and the f-number of the telescope has been investigated. Although the f-number is normally a system parameter well specified in the beginning of the design process, it is not very rigid in practice and has a certain amount of allowable range. The optimal f-number can then be chosen based on the consideration of those key tolerance items. The proposed concept can be generalized as a novel methodology of design for tolerance.
Experimental Study of Tool Wear in Electrochemical Discharge Machining
Authors: Bian Jianxiao , Ma Baoji , Liu Xiaofeng , Qi Lijun
Published: July 2020

Electrochemical discharge machining (ECDM) is an emerging special processing technology for non-conductive hard and brittle materials, but it may encounter the problem of tool wear due to its process characteristics, which affects the processing accuracy. In this study, in the non-machining state, the tungsten carbide spiral cathode with a diameter of 400 μm was selected to analyze the influencing mechanism of the process parameters on tool wear, and a suitable voltage range for the processing was obtained. The influence of the cathode’s loss behavior on the film formation time and the average current of spark discharge was discussed based on the current signal. The results show that the tool wear mainly appears from the bottom to the end and edge tip of the protrusion. Loss is mainly in the form of local material melting or gasification at high temperature. In addition, the loss may shorten the film formation time, but the effect on the average current of spark discharge is small.
A CNN CADx System for Multimodal Classification of Colorectal Polyps Combining WL, BLI, and LCI Modalities
Authors: Fonollà Roger , E. W. van der Zander Quirine , Schreuder Ramon M. , Masclee Ad A. M. , Schoon Erik J. , van der Sommen Fons , de With Peter H. N.
Published: July 2020

Colorectal polyps are critical indicators of colorectal cancer (CRC). Blue Laser Imaging and Linked Color Imaging are two modalities that allow improved visualization of the colon. In conjunction with the Blue Laser Imaging (BLI) Adenoma Serrated International Classification (BASIC) classification, endoscopists are capable of distinguishing benign and pre-malignant polyps. Despite these advancements, this classification still prevails a high misclassification rate for pre-malignant colorectal polyps. This work proposes a computer aided diagnosis (CADx) system that exploits the additional information contained in two novel imaging modalities, enabling more informative decision-making during colonoscopy. We train and benchmark six commonly used CNN architectures and compare the results with 19 endoscopists that employed the standard clinical classification model (BASIC). The proposed CADx system for classifying colorectal polyps achieves an area under the curve (AUC) of 0.97. Furthermore, we incorporate visual explanatory information together with a probability score, jointly computed from White Light, Blue Laser Imaging, and Linked Color Imaging. Our CADx system for automatic polyp malignancy classification facilitates future advances towards patient safety and may reduce time-consuming and costly histology assessment.
Effect of Alkaline Artificial Seawater Environment on the Corrosion Behaviour of Duplex Stainless Steel 2205
Authors: Tran Thi Thuy Tien , Kannoorpatti Krishnan , Padovan Anna , Thennadil Suresh
Published: July 2020

Sulphate reducing bacteria (SRB) can be found in alkaline environments. Due to their metabolite products such as hydrogen sulphide, the corrosion behaviour of materials in alkaline environments may be affected by the presence of SRB. This study focuses on the investigation of corrosion behaviour of duplex stainless steel DSS 2205 in nutrient rich artificial seawater containing SRB species, Desulfovibrio vulgaris, at different alkaline conditions with pH range from 7 to 10. The open circuit potential value (OCP), sulphide level and pH were recorded daily. Confocal laser scanning microscopy (CLSM) was used to study the adhesion of SRB on the DSS 2205 surface. Electrochemical impedance spectroscopy (EIS) was used to study the properties of the biofilm. Potentiodynamic polarization was used to study the corrosion behaviour of material. Inductively coupled plasma mass was used to measure the concentration of cations Fe, Ni, Mo, Mn in the experimental solution after 28 days. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) were used for surface analysis. The results showed that D. vulgaris are active in an alkaline environment with pH 7–9. However, at pH 10, D. vulgaris activity exhibited an 8-day lag. The corrosion rate of DSS 2205 at pH 9 was higher than at other pH environments due to a higher dissolved concentration of hydrogen sulphide.
Green Synthesized ZnO Nanoparticles Mediated by Mentha Spicata Extract Induce Plant Systemic Resistance against Tobacco Mosaic Virus
Authors: Abdelkhalek Ahmed , Al-Askar Abdulaziz A.
Published: July 2020

Globally, plant viral infection is one of the most difficult challenges of food security, where considerable losses in crop production occur. Nanoparticles are an effective control agent against numerous plant pathogens. However, there is limited knowledge concerning their effects against viral infection. In the present study, the green synthesis of zinc oxide nanoparticles (ZnO NPs) using aqueous leaf extract of Mentha spicata was achieved. X-ray diffraction patterns confirmed the crystalline nature of the prepared ZnO NPs. Dynamic light scattering and scanning electron microscopy analyses revealed that the resultant ZnO NPs were spherical in shape with a particle size ranged from 11 to 88 nm. Fourier transmission infrared spectroscopy detected different functional groups, capping and stability agents, and showed Zn-O bond within wavenumber of 487 cm−1. Under greenhouse conditions, the antiviral activity of biological synthesized ZnO NPs (100 µg/mL) against Tobacco mosaic virus (TMV) was evaluated. The double foliar application of the prepared ZnO NPs, 24 h before and 24 h after TMV-inoculation, was the most effective treatment that showed a 90.21% reduction of viral accumulation level and disease severity. Additionally, the transcriptional levels of PAL, PR-1 (salicylic acid marker gene), CHS, and POD genes were induced and up-regulated in all ZnO NPs treated plants. Notably, the results exhibited that aqueous extract of Mentha spicata was an effective reducing agent for the green synthesis of ZnO NPs, which showed significant antiviral activity. Finally, the detected protective and curative activity of ZnO NPs against TMV can encourage us to recommend its application for plant viral disease management. To our knowledge, this is the first study describing the antiviral activity of the green synthesized ZnO NPs.
The Influence of Immersive Virtual Reality Systems on Online Social Application
Authors: Yan Zuohao , Lv Zhihan
Published: July 2020

This study presents a face-to-face simulation of social interaction based on scene roaming, real-time voice capture, and action capture. This paper aimed to compare the difference between social and traditional plane social communication, analyzing its advantages and shortcomings. In particular, we designed an experiment to study the performance of face-to-face simulation based on virtual reality technology, observing the adaptability of the user to the system and the accuracy of body language recognition. We developed an immersive virtual reality social application (IVRSA), which has a basic social function. As an experimental platform, IVRSA uses Unity3D as its engine, and HTC VIVE as an external input/output device, with voice communication, immersive virtual tour, and head and hand movement simulation functions. We recruited 30 volunteers for the test. The test consisted of two parts. The first part was to provide a news topic for volunteers to freely communicate in IVRSA and WeChat. After communication, we used questionnaires to obtain feedback results of the test and compared the two social applications. In the second part, some volunteers were given a list of actions, which they were asked to describe to the rest of volunteers in the form of body expression, letting them guess the action they were performing. After the end of test, the accuracy rate and the time used were analyzed. Results showed that user’s intention expression efficiency was very high in the immersive virtual reality social system. Body tracking devices with more tracking points can provide better body expression effect.
A Review of Emerging Technologies for an Assessment of Safety and Seismic Vulnerability and Damage Detection of Existing Masonry Structures
Authors: Stepinac Mislav , Gašparović Mateo
Published: July 2020

The construction sector has proven to be one of the slowest sectors to embrace technology—a problem that must be addressed. This problem can be quickly and efficiently addressed in certain aspects of seismic engineering: from seismic risk assessment to damage detection, as well as condition assessments existing structures before or after an earthquake. In this paper, the literature review of assessment methods and damage detection technologies for existing (mainly) masonry structures is presented. Traditional methods are briefly explained, and modern are critically discussed. Special focus is given to unmanned aerial vehicles, as well as, photogrammetry and close-range remote sensing as a technology that can complement traditional ways of assessment and give us data about a structure that is often different to obtain. Graphical interpretation of one post-earthquake case study is provided. Open challenges and opportunities of emerging technologies for faster and easier assessment of seismic safety and vulnerability are presented.
Piezoelectric Sensor with a Helical Structure on the Thread Core
Authors: Park Cheoleon , Kim Hojoon , Cha Youngsu
Published: July 2020

In this paper, we introduce a piezoelectric sensor curled on a thread core in a helical structure. In particular, a polyvinylidene fluoride film was curled and fixed on a thread core. A series of experiments were designed to deliver flexural loading to the piezoelectric sensor, to study its sensing characteristics. The experimental results show that the sensing output of the sensor is in phase with the applied flexural loading. In addition, the output voltage of the textile-based piezoelectric sensor was measured according to various flexural loadings. The flexural bending angle applied to the piezoelectric sensor is expected to be a power function of the voltage output. In addition, we demonstrate a smart textile by weaving the piezoelectric sensor.
Humulus lupulus L. as a Natural Source of Functional Biomolecules
Authors: Astray Gonzalo , Gullón Patricia , Gullón Beatriz , Munekata Paulo E. S. , Lorenzo José M.
Published: July 2020

Hops (Humulus lupulus L.) are used traditionally in the brewing industry to confer bitterness, aroma, and flavor to beer. However, in recent years, it has been reported that female inflorescences contain a huge variety of bioactive compounds. Due to the growing interest of the consumers by natural ingredients, intense research has been carried out in the last years to find new sources of functional molecules. This review collects the works about the bioactive potential of hops with applications in the food, pharmaceutical, or cosmetic industries. Moreover, an overview of the main extraction technologies to recover biomolecules from hops is shown. Bioactivities of hop extracts such as antibacterial, antifungal, cardioprotective, antioxidant, anti-inflammatory, anticarcinogenic, and antiviral are also summarized. It can be concluded that hops present a high potential of bioactive ingredients with high quality that can be used as preservative agents in fresh foods, extending their shelf life, and they can be incorporated in cosmetic formulation for skincare as well.
Application Research of a New Adaptive Noise Reduction Method in Fault Diagnosis
Authors: Guo Wenxiao , Li Ruiqin , Kou Yanfei , Zhang Jianwei
Published: July 2020

The feature extraction of composite fault of gearbox in mining machinery has always been a difficulty in the field of fault diagnosis. Especially in strong background noise, the frequency of each fault feature is different, so an adaptive time-frequency analysis method is urgently needed to extract different types of faults. Considering that the signal after complementary ensemble empirical mode decomposition (CEEMD) contains a lot of pseudo components, which further leads to misdiagnosis. The article proposes a new method for actively removing noise components. Firstly, the best scale factor of multi-scale sample entropy (MSE) is determined by signals with different signal to noise ratios (SNRs); secondly, the minimum value of a large number of random noise MSE is extracted and used as the threshold of CEEMD; then, the effective Intrinsic mode functions(IMFs) component is reconstructed, and the reconstructed signal is CEEMD decomposed again; finally, after multiple iterations, the MSE values of the component signal that are less than the threshold are obtained, and the iteration is terminated. The proposed method is applied to the composite fault simulation signal and mining machinery vibration signal, and the composite fault feature is accurately extracted.
Development Cycle Modeling: Process Risk
Authors: Denard Samuel , Ertas Atila , Mengel Susan , Ekwaro-Osire Stephen
Published: July 2020

The first part of this paper outlined the Statistical Agent-based Model of Development and Evaluation (SAbMDE) and demonstrated the model’s ability to estimate development cycle resource utilization. This second part of the paper explores the model’s ability to compute development cycle information content and process risk. Risk managers focus mostly on outcome risk, i.e., the likelihood that a running system will behave in an undesirable manner. SAbMDE assumes that a subset of outcome risks are not inherent and immutable but are, instead, the result of defects and vulnerabilities introduced during the system’s development process. The likelihood of defect and vulnerability introduction is a process risk. SAbMDE further assumes that measuring process risk is a prerequisite for minimizing defects and vulnerabilities and, therefore, outcome risk. The model implements the measurement with Shannon’s information–probability relationship similar to its use in Axiomatic Design Theory (ADT). This paper details the SAbMDE’s information and risk calculations and demonstrates those calculations with examples. The process risk calculation is consistent with and offers a mechanism for the ADT Information Axiom.
Mineral Carbonation of CO2 in Mafic Plutonic Rocks, II—Laboratory Experiments on Early-Phase Supercritical CO2‒Brine‒Rock Interactions
Authors: Moita Patrícia , Berrezueta Edgar , Abdoulghafour Halidi , Beltrame Massimo , Pedro Jorge , Mirão José , Miguel Catarina , Galacho Cristina , Sitzia Fabio , Barrulas Pedro , Carneiro Júlio
Published: July 2020

The potential for mineral carbonation of CO2 in plutonic mafic rocks is addressed through a set of laboratory experiments on cumulate gabbro and gabbro-diorite specimens from the Sines Massif (Portugal). The experiments were conducted in an autoclave, for a maximum of 64 days, using a CO2 supersaturated brine under pressure and temperature conditions similar to those expected around an injection well during early-phase CO2 injection. Multiple techniques for mineralogical and geochemical characterization were applied ante- and post-carbonation experiments. New mineralogical phases (smectite, halite and gypsum), roughness increase and material loss were observed after exposure to the CO2 supersaturated brine. The chemical analysis shows consistent changes in the brine and rock specimens: (i) increases in iron (Fe) and magnesium (Mg) in the aqueous phase and decreases in Fe2O3 and MgO in the specimens; (ii) a decrease in aqueous calcium (Ca) and an increase in CaO in the cumulate gabbro, whereas in the gabbro-diorite aqueous Ca increased and afterwards remained constant, whereas CaO decreased. The geochemical model using the CrunchFlow code was able to reproduce the experimental observations and simulate the chemical behavior for longer times. Overall, the study indicates that the early-stage CO2 injection conditions adopted induce mainly a dissolution phase with mineralogical/textural readjustments on the external area of the samples studied.
A Method for Retrieving Stratospheric Aerosol Extinction and Particle Size from Ground-Based Rayleigh-Mie-Raman Lidar Observations
Authors: Zalach Jacob , von Savigny Christian , Langenbach Arvid , Baumgarten Gerd , Lübken Franz-Josef , Bourassa Adam
Published: July 2020

We report on the retrieval of stratospheric aerosol particle size and extinction coefficient profiles from multi-color backscatter measurements with the Rayleigh–Mie–Raman lidar operated at the Arctic Lidar Observatory for Middle Atmosphere Research (ALOMAR) in northern Norway. The retrievals are based on a two-step approach. In a first step, the median radius of an assumed monomodal log-normal particle size distribution with fixed width is retrieved based on a color index formed from the measured backscatter ratios at the wavelengths of 1064 nm and 532 nm. An intrinsic ambiguity of the retrieved aerosol size information is discussed. In a second step, this particle size information is used to convert the measured lidar backscatter ratio to aerosol extinction coefficients. The retrieval is currently based on monthly-averaged lidar measurements and the results for March 2013 are discussed. A sensitivity study is presented that allows for establishing an error budget for the aerosol retrievals. Assuming a monomodal log-normal aerosol particle size distribution with a geometric width of S = 1.5, median radii on the order of below 100 nm are retrieved. The median radii are found to generally decrease with increasing altitude. The retrieved aerosol extinction profiles are compared to observations with the OSIRIS (Optical Spectrograph and InfraRed Imager System) and the OMPS-LP (Ozone Mapping Profiling Suite Limb Profiler) satellite instruments in the 60∘ N to 80∘ N latitude band. The extinction profiles that were retrieved from the lidar measurements show good agreement with the observations of the two satellite instruments when taking the different wavelengths of the instruments into account.
A Weighting Scheme in A Multi-Model Ensemble for Bias-Corrected Climate Simulation
Authors: Shin Yonggwan , Lee Youngsaeng , Park Jeong-Soo
Published: July 2020

A model weighting scheme is important in multi-model climate ensembles for projecting future changes. The climate model output typically needs to be bias corrected before it can be used. When a bias-correction (BC) is applied, equal model weights are usually derived because some BC methods cause the observations and historical simulation to match perfectly. This equal weighting is sometimes criticized because it does not take into account the model performance. Unequal weights reflecting model performance may be obtained from raw data before BC is applied. However, we have observed that certain models produce excessively high weights, while the weights generated in all other models are extremely low. This phenomenon may be partly due to the fact that some models are more fit or calibrated to the observations for a given applications. To address these problems, we consider, in this study, a hybrid weighting scheme including both equal and unequal weights. The proposed approach applies an “imperfect” correction to the historical data in computing their weights, while it applies ordinary BC to the future data in computing the ensemble prediction. We employ a quantile mapping method for the BC and a Bayesian model averaging for performance-based weighting. Furthermore, techniques for selecting the optimal correction rate based on the chi-square test statistic and the continuous ranked probability score are examined. Comparisons with ordinary ensembles are provided using a perfect model test. The usefulness of the proposed method is illustrated using the annual maximum daily precipitation as observed in the Korean peninsula and simulated by 21 models from the Coupled Model Intercomparison Project Phase 6.
Local Climate Zone Classification Scheme Can Also Indicate Local-Scale Urban Ventilation Performance: An Evidence-Based Study
Authors: Zhao Ziqi , Shen Lidu , Li Liguang , Wang Hongbo , He Bao-Jie
Published: July 2020

Studies on urban ventilation indicate that urban ventilation performance is highly dependent on urban morphology. Some studies have linked local-scale urban ventilation performance with the local climate zone (LCZ) that is proposed for surface temperature studies. However, there is a lack of evidence-based studies showing LCZ ventilation performance and affirming the reliability of using the LCZ classification scheme to demonstrate local-scale urban ventilation performance. Therefore, this study aims to analyse LCZ ventilation performances in order to understand the suitability of using the LCZ classification scheme to indicate local-scale urban ventilation performance. This study was conducted in Shenyang, China, with wind information at 16 weather stations in 2018. The results indicate that the Shenyang weather station had an annual mean wind speed of 2.07 m/s, while the mean wind speed of the overall 16 stations was much lower, only 1.44 m/s in value. The mean wind speed at Shenyang weather station and the 16 stations varied with seasons, day and night and precipitation conditions. The spring diurnal mean wind was strong with the speeds of 3.56 m/s and 2.21 m/s at Shenyang weather station and the 16 stations, respectively. The wind speed (2.21 m/s at Shenyang weather station) under precipitation conditions was higher than that (1.75 m/s at Shenyang weather station) under no precipitation conditions. Downtown ventilation performance was weaker than the approaching wind background, where the relative mean wind speed in the downtown area was only 0.53, much less than 1.0. The downtown ventilation performance also varied with seasons, day and night and precipitation conditions, where spring diurnal downtown ventilation performance was the weakest and the winter nocturnal downtown ventilation performance was the strongest. Moreover, the annual mean wind speed of the 16 zones decreased from the sparse, open low-rise zones to the compact midrise zones, indicating the suitability of using LCZ classification scheme to indicate local-scale urban ventilation performance. The high spatial correlation coefficients under different seasons, day and night and precipitation conditions, ranging between 0.68 and 0.99, further affirmed that LCZ classification scheme is also suitable to indicate local-scale urban ventilation performance, despite without the consideration of street structure like precinct ventilation zone scheme.
The Relationship of Energy and CO2 Emissions with GDP per Capita in Colombia
Authors: Patiño Lourdes Isabel , Padilla Emilio , Alcántara Vicent , Raymond Josep Lluís
Published: July 2020

We analyze the relationship of CO2 emissions per capita and primary energy per capita with gross domestic product (GDP) per capita and other relevant variables in Colombia for the period 1971–2017. Two partial adjustment models are estimated through the seemingly unrelated regression equations method. There is a decrease in these environmental pressures during some years of the period. However, the results reject the environmental Kuznets curve hypothesis and indicate that economic growth is still linked to an increase in these environmental pressures in Colombia. Moreover, a linear relationship between both indicators and GDP per capita is not rejected. Several factors explain the changes in energy consumption and emissions over time, the policies applied being crucial. Some determinants that helped to control these environmental pressures are the change in primary energy source composition, which entailed primary energy savings and a reduction in CO2 emissions, as well as the regulations aimed at controlling CO2 emissions from the transport and industrial sectors.
Glutenin and Gliadin, a Piece in the Puzzle of their Structural Properties in the Cell Described through Monte Carlo Simulations
Authors: Markgren Joel , Hedenqvist Mikael , Rasheed Faiza , Skepö Marie , Johansson Eva
Published: July 2020

Gluten protein crosslinking is a predetermined process where specific intra- and intermolecular disulfide bonds differ depending on the protein and cysteine motif. In this article, all-atom Monte Carlo simulations were used to understand the formation of disulfide bonds in gliadins and low molecular weight glutenin subunits (LMW-GS). The two intrinsically disordered proteins appeared to contain mostly turns and loops and showed “self-avoiding walk” behavior in water. Cysteine residues involved in intramolecular disulfide bonds were located next to hydrophobic peptide sections in the primary sequence. Hydrophobicity of neighboring peptide sections, synthesis chronology, and amino acid chain flexibility were identified as important factors in securing the specificity of intramolecular disulfide bonds formed directly after synthesis. The two LMW-GS cysteine residues that form intermolecular disulfide bonds were positioned next to peptide sections of lower hydrophobicity, and these cysteine residues are more exposed to the cytosolic conditions, which influence the crosslinking behavior. In addition, coarse-grained Monte Carlo simulations revealed that the protein folding is independent of ionic strength. The potential molecular behavior associated with disulfide bonds, as reported here, increases the biological understanding of seed storage protein function and provides opportunities to tailor their functional properties for different applications.
Targeting NF-κB Signaling by Calebin A, a Compound of Turmeric, in Multicellular Tumor Microenvironment: Potential Role of Apoptosis Induction in CRC Cells
Authors: Buhrmann Constanze , Shayan Parviz , Banik Kishore , Kunnumakkara Ajaikumar B. , Kubatka Peter , Koklesova Lenka , Shakibaei Mehdi
Published: July 2020

Increasing lines of evidence suggest that chronic inflammation mediates most chronic diseases, including cancer. The transcription factor, NF-κB, has been shown to be a major regulator of inflammation and metastasis in tumor cells. Therefore, compounds or any natural agents that can inhibit NF-κB activation have the potential to prevent and treat cancer. However, the mechanism by which Calebin A, a component of turmeric, regulates inflammation and disrupts the interaction between HCT116 colorectal cancer (CRC) cells and multicellular tumor microenvironment (TME) is still poorly understood. The 3D-alginate HCT116 cell cultures in TME were treated with Calebin A, BMS-345541, and dithiothreitol (DTT) and examined for invasiveness, proliferation, and apoptosis. The mechanism of TME-induced malignancy of cancer cells was confirmed by phase contrast, Western blotting, immunofluorescence, and DNA-binding assay. We found through DNA binding assay, that Calebin A inhibited TME-induced NF-κB activation in a dose-dependent manner. As a result of this inhibition, NF-κB phosphorylation and NF-κB nuclear translocation were down-modulated. Calebin A, or IκB-kinase (IKK) inhibitor (BMS-345541) significantly inhibited the direct interaction of nuclear p65 to DNA, and interestingly this interaction was reversed by DTT. Calebin A also suppressed the expression of NF-κB-promoted anti-apoptotic (Bcl-2, Bcl-xL, survivin), proliferation (Cyclin D1), invasion (MMP-9), metastasis (CXCR4), and down-regulated apoptosis (Caspase-3) gene biomarkers, leading to apoptosis in HCT116 cells. These results suggest that Calebin A can suppress multicellular TME-promoted CRC cell invasion and malignancy by inhibiting the NF-κB-promoting inflammatory pathway associated with carcinogenesis, underlining the potential of Calebin A for CRC treatment.
Evidence-Based Medicine in Oncology: Commercial Versus Patient Benefit
Authors: Schirrmacher Volker , Sprenger Tobias , Stuecker Wilfried , Van Gool Stefaan W.
Published: July 2020

At times of personalized and individualized medicine the concept of randomized- controlled clinical trials (RCTs) is being questioned. This review article explains principles of evidence-based medicine in oncology and shows an example of how evidence can be generated independently from RCTs. Personalized medicine involves molecular analysis of tumor properties and targeted therapy with small molecule inhibitors. Individualized medicine involves the whole patient (tumor and host) in the context of immunotherapy. The example is called Individualized Multimodal Immunotherapy (IMI). It is based on the individuality of immunological tumor–host interactions and on the concept of immunogenic tumor cell death (ICD) induced by an oncolytic virus. The evidence is generated by systematic data collection and analysis. The outcome is then shared with the scientific and medical community. The priority of big pharma studies is commercial benefit. Methods used to achieve this are described and have damaged the image of RCT studies in general. A critical discussion is recommended between all partners of the medical health system with regard to the conduct of RCTs by big pharma companies. Several clinics and institutions in Europe try to become more independent from pharma industry and to develop their own modern cancer therapeutics. Medical associations should include references to such studies from personalized and individualized medicine in their guidelines.
Towards Bacteria Counting in DI Water of Several Microliters or Growing Suspension Using Impedance Biochips
Authors: Kiani Mahdi , Tannert Astrid , Du Nan , Hübner Uwe , Skorupa Ilona , Bürger Danilo , Zhao Xianyue , Blaschke Daniel , Rebohle Lars , Cherkouk Charaf , Neugebauer Ute , Schmidt Oliver G. , Schmidt Heidemarie
Published: July 2020

We counted bacterial cells of E. coli strain K12 in several-microliter DI water or in several-microliter PBS in the low optical density (OD) range (OD = 0.05–1.08) in contact with the surface of Si-based impedance biochips with ring electrodes by impedance measurements. The multiparameter fit of the impedance data allowed calibration of the impedance data with the concentration cb of the E. coli cells in the range of cb = 0.06 to 1.26 × 109 cells/mL. The results showed that for E. coli in DI water and in PBS, the modelled impedance parameters depend linearly on the concentration of cells in the range of cb = 0.06 to 1.26 × 109 cells/mL, whereas the OD, which was independently measured with a spectrophotometer, was only linearly dependent on the concentration of the E. coli cells in the range of cb = 0.06 to 0.50 × 109 cells/mL.
Individual Differences in Infants’ Temperament Affect Face Processing
Authors: Rennels Jennifer L. , Kayl Andrea J. , Kulhanek Kirsty M.
Published: July 2020

Infants show an advantage in processing female and familiar race faces, but the effect sizes are often small, suggesting individual differences in their discrimination abilities. This research assessed whether differences in 6–10-month-olds’ temperament (surgency and orienting) predicted how they scanned individual faces varying in race and gender during familiarization and whether and how long it took them to locate the face during a visual search task. This study also examined whether infants viewing faces posing pleasant relative to neutral expressions would facilitate their discrimination of male and unfamiliar race faces. Results showed that infants’ surgency on its own or in conjunction with their orienting regularly interacted with facial characteristics to predict their scanning and location of faces. Furthermore, infants’ scanning patterns (dwell times and internal–external fixation shifts) correlated with their ability and time to locate a familiarized face. Moreover, infants who viewed faces with pleasant expressions showed better discrimination of unfamiliar race and male faces compared with infants who viewed neutral faces. Including temperament in the analyses consistently demonstrated its significance for understanding infant face processing. Findings suggest that positive interactions with other-race individuals and men might reduce processing disadvantages for those face types. Locating familiar adults in a timely manner is a crucial skill for infants to develop and these data elucidate factors influencing this ability.
Ex Vivo Models Simulating the Bone Marrow Environment and Predicting Response to Therapy in Multiple Myeloma
Authors: Papadimitriou Konstantinos , Kostopoulos Ioannis V. , Tsopanidou Anastasia , Orologas-Stavrou Nikolaos , Kastritis Efstathios , Tsitsilonis Ourania E. , Dimopoulos Meletios A. , Terpos Evangelos
Published: July 2020

Multiple myeloma (MM) remains incurable despite the abundance of novel drugs. As it has been previously shown, preclinical 2D models fail to predict disease progression due to their inability to simulate the microenvironment of the bone marrow. In this review, we focus on 3D models and present all currently available ex vivo MM models that fulfil certain criteria, such as development of complex 3D environments using patients’ cells and ability to test different drugs in order to assess personalized MM treatment efficacy of various regimens and combinations. We selected models representing the top-notch ex vivo platforms and evaluated them in terms of cost, time-span, and feasibility of the method. Finally, we propose where such a model can be more informative in a patient’s treatment timeline. Overall, advanced 3D preclinical models are very promising as they may eventually offer the opportunity to precisely select the optimal personalized treatment for each MM patient.
Hypopigmented Mycosis Fungoides: Loss of Pigmentation Reflects Antitumor Immune Response in Young Patients
Authors: Martínez Villarreal Amelia , Gantchev Jennifer , Lagacé François , Barolet Augustin , Sasseville Denis , Ødum Niels , Charli-Joseph Yann Vincent , Hernández Salazar Amparo , Litvinov Ivan V.
Published: July 2020

Hypopigmented mycosis fungoides (HMF) is a form of cutaneous T-cell lymphoma (CTCL), a heterogeneous group of extranodal non-Hodgkin’s lymphomas. HMF has a unique set of defining features that include light colored to achromic lesions, a predilection for darker skin phototypes, an early onset of disease, and predominance of CD8+ T-cells, among others. In the current review, we detail the known pathways of molecular pathogenesis for this lymphoma and posit that an active Th1/cytotoxic antitumor immune response in part explains why this variant is primarily seen in children/adolescents and young adults, who do not exhibit signs of immunosenescence. As a result of this potent cytotoxic response, HMF patients experience mostly favorable overall prognosis, while hypopigmentation may in fact represent a useful surrogate marker of cytotoxic immunity targeting the malignant cells. Understanding the molecular processes behind the specific features that define HMF may lead to improved diagnostic accuracy, personalized prognosis by risk stratification, and improved management of HMF. Moreover, improving our knowledge of HMF may aid our further understanding of other cutaneous lymphomas.
Chemically Induced Hypoxia Enhances miRNA Functions in Breast Cancer
Authors: Gervin Emma , Shin Bonita , Opperman Reid , Cullen Mackenzie , Feser Riley , Maiti Sujit , Majumder Mousumi
Published: July 2020

In aggressively growing tumors, hypoxia induces HIF-1α expression promoting angiogenesis. Previously, we have shown that overexpression of oncogenic microRNAs (miRNAs, miRs) miR526b/miR655 in poorly metastatic breast cancer cell lines promotes aggressive cancer phenotypes in vitro and in vivo. Additionally, miR526b/miR655 expression is significantly higher in human breast tumors, and high miR526b/miR655 expression is associated with poor prognosis. However, the roles of miR526b/miR655 in hypoxia are unknown. To test the relationship between miR526b/miR655 and hypoxia, we used various in vitro, in silico, and in situ assays. In normoxia, miRNA-high aggressive breast cancer cell lines show higher HIF-1α expression than miRNA-low poorly metastatic breast cancer cell lines. To test direct involvement of miR526b/miR655 in hypoxia, we analyzed miRNA-high cell lines (MCF7-miR526b, MCF7-miR655, MCF7-COX2, and SKBR3-miR526b) compared to controls (MCF7 and SKBR3). CoCl2-induced hypoxia in breast cancer further promotes HIF-1α mRNA and protein expression while reducing VHL expression (a negative HIF-1α regulator), especially in miRNA-high cell lines. Hypoxia enhances oxidative stress, epithelial to mesenchymal transition, cell migration, and vascular mimicry more prominently in MCF7-miR526b/MCF7-miR655 cell lines compared to MCF7 cells. Hypoxia promotes inflammatory and angiogenesis marker (COX-2, EP4, NFκB1, VEGFA) expression in all miRNA-high cells. Hypoxia upregulates miR526b/miR655 expression in MCF7 cells, thus observed enhancement of hypoxia-induced functions in MCF7 could be attributed to miR526b/miR655 upregulation. In silico bioinformatics analysis shows miR526b/miR655 regulate PTEN (a negative regulator of HIF-1α) and NFκB1 (positive regulator of COX-2 and EP4) expression by downregulation of transcription factors NR2C2, SALL4, and ZNF207. Hypoxia-enhanced functions in miRNA-high cells are inhibited by COX-2 inhibitor (Celecoxib), EP4 antagonist (ONO-AE3-208), and irreversible PI3K/Akt inhibitor (Wortmannin). This establishes that hypoxia enhances miRNA functions following the COX-2/EP4/PI3K/Akt pathways and this pathway can serve as a therapeutic target to abrogate hypoxia and miRNA induced functions in breast cancer. In situ, HIF-1α expression is significantly higher in human breast tumors (n = 96) compared to non-cancerous control tissues (n = 20) and is positively correlated with miR526b/miR655 expression. In stratified tumor samples, HIF-1α expression was significantly higher in ER-positive, PR-positive, and HER2-negative breast tumors. Data extracted from the TCGA database also show a strong correlation between HIF-1α and miRNA-cluster expression in breast tumors. This study, for the first time, establishes the dynamic roles of miR526b/miR655 in hypoxia.
A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer
Authors: Fiore Michele , Taralli Silvia , Trecca Pasquale , Scolozzi Valentina , Marinelli Luca , Triumbari Elizabeth K. A. , Caputo Damiano , Angeletti Silvia , Ciccozzi Massimo , Coppola Alessandro , Greco Carlo , Ippolito Edy , Calcagni Maria Lucia , Coppola Roberto , Ramella Sara
Published: July 2020

Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level > 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66–19.47; p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64–57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9–10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (>90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients.