bluuebunny/crossref_metadata_2025 huggingface dataset:
Titanium Dioxide in Chromogenic Devices: Synthesis, Toxicological Issues, and Fabrication Methods
Authors: De Matteis Valeria , Cannavale Alessandro , Ayr Ubaldo
Published: December 2020

The use of titanium dioxide (TiO2) within two specific classes of devices, namely electrochromic and photoelectrochromic, is described hereafter, with respect to its inherent properties and chromogenic features within architectures that have appeared so far, in this field. The new research trends, involving the applications of TiO2 in chromogenic materials are reported, with particular attention paid to the techniques used for film deposition as well as the synthesis of nanoparticles. Furthermore, the main studies concerning its chemical-physical properties and approaches to its chemical syntheses and fabrication are reviewed, with special regard to “green” routes. In addition, the main aspects relating to toxicological profiles are exposed, with reference to nanoparticles and thin films.
Floating Offshore Wind Farms in Italy beyond 2030 and beyond 2060: Preliminary Results of a Techno-Economic Assessment
Authors: Serri Laura , Colle Lisa , Vitali Bruno , Bonomi Tullia
Published: December 2020

At the end of 2019, 10.5 GW of wind capacity was installed in Italy, all onshore. The National Integrated Climate and Energy Plan sets a target of 18.4 GW of onshore wind capacity and 0.9 GW of offshore wind capacity by 2030. Significant exploitation of offshore wind resources in Italy is expected after 2030, using floating wind turbines, suitable for water depths greater than 50 m. This technology is at the demonstration phase at present. Results of a preliminary techno-economic assessment of floating wind plants in Italian marine areas in a medium (2030) and long-term (2060) scenario are presented. In 2030, a reference park with 10 MW wind turbines will be defined, and parametric costs, depending on distance from shore, were assessed. In 2060, possible wind resource variations due to climate change, and cost reductions due to large diffusion of the technology were considered in three case studies. The economic model used was the simple Levelized Cost of Energy (sLCoE). Different values of Weighted Average Cost of Capital (WACC) were considered too. The results show LCoEs comparable to the ones expected for the sector in 2030. In 2060, even in the more pessimistic scenario, wind resource decreases will be abundantly compensated by expected cost reductions.
Retained Austenite Destabilization during Tempering of Low-Temperature Bainite
Authors: Ruiz-Jimenez Victor , Kuntz Matthias , Sourmail Thomas , Caballero Francisca G. , Jimenez Jose A. , Garcia-Mateo Carlos
Published: December 2020

The thermal stability of nanostructured microstructures consisting of a mixture of bainitic ferrite and carbon-enriched retained austenite has been studied in two steels containing 0.6 C (wt %) by tempering cycles of 1 h at temperatures ranging from 450 to 650 °C. Volume changes due to microstructural transformations during thermal treatments were measured by high-resolution dilatometry. The correlation of these results with the detailed microstructural characterization performed by X-ray diffraction and scanning electron microscope examination showed a sequence of different decomposition events beginning with the precipitation of very fine cementite particles. This precipitation, which starts in the austenite thin films and then continues in retained austenite blocks, decreases the carbon content in this phase so that fresh martensite can form from the low-carbon austenite on cooling to room temperature. In a subsequent tempering stage, the remaining austenite decomposes into ferrite and cementite, and due to carbide precipitation, the bainitic ferrite loses its tetragonality, its dislocation density is reduced, and the bainitic laths coarsen.
An Approach Based on Fog Computing for Providing Reliability in IoT Data Collection: A Case Study in a Colombian Coffee Smart Farm
Authors: Montoya-Munoz Ana Isabel , Rendon Oscar Mauricio Caicedo
Published: December 2020

The reliability in data collection is essential in Smart Farming supported by the Internet of Things (IoT). Several IoT and Fog-based works consider the reliability concept, but they fall short in providing a network’s edge mechanisms for detecting and replacing outliers. Making decisions based on inaccurate data can diminish the quality of crops and, consequently, lose money. This paper proposes an approach for providing reliable data collection, which focuses on outlier detection and treatment in IoT-based Smart Farming. Our proposal includes an architecture based on the continuum IoT-Fog-Cloud, which incorporates a mechanism based on Machine Learning to detect outliers and another based on interpolation for inferring data intended to replace outliers. We located the data cleaning at the Fog to Smart Farming applications functioning in the farm operate with reliable data. We evaluate our approach by carrying out a case study in a network based on the proposed architecture and deployed at a Colombian Coffee Smart Farm. Results show our mechanisms achieve high Accuracy, Precision, and Recall as well as low False Alarm Rate and Root Mean Squared Error when detecting and replacing outliers with inferred data. Considering the obtained results, we conclude that our approach provides reliable data collection in Smart Farming.
Chemometric Study of the Correlation between Human Exposure to Benzene and PAHs and Urinary Excretion of Oxidative Stress Biomarkers
Authors: Buonaurio Flavia , Paci Enrico , Pigini Daniela , Marini Federico , Bauleo Lisa , Ancona Carla , Tranfo Giovanna
Published: December 2020

Urban air contains benzene and polycyclic aromatic hydrocarbons (PAHs) which have carcinogenic properties. The objective of this paper is to study the correlation of exposure biomarkers with biomarkers of nucleic acid oxidation also considering smoking. In 322 subjects, seven urinary dose biomarkers were analyzed for benzene, pyrene, nitropyrene, benzo[a]pyrene, and naphthalene exposure, and four effect biomarkers for nucleic acid and protein oxidative stress. Chemometrics was applied in order to investigate the existence of a synergistic effect for the exposure to the mixture and the contribution of active smoking. There is a significant difference between nicotine, benzene and PAH exposure biomarker concentrations of smokers and non-smokers, but the difference is not statistically significant for oxidative stress biomarkers. The PAH biomarkers are those which best correlate with all the oxidative stress biomarkers. Results suggest that 8-Oxo-7,8-dihydroguanine and protein nitro-oxidation 3-nitrotyrosine are the most sensitive biomarkers for the exposure to the urban pollutant mixtures and that a synergic effect of the mixtures exists. All the oxidative stress biomarkers studied drive the increase in the oxidative stress biomarkers in the subjects having higher exposures. Chemometrics proved to be a powerful method for the interpretation of human biomonitoring data.
Impact of Lidar Data Assimilation on Low-Level Wind Shear Simulation at Lanzhou Zhongchuan International Airport, China: A Case Study
Authors: Li Lanqian , Xie Ningjing , Fu Longyan , Zhang Kaijun , Shao Aimei , Yang Yi , Ren Xuwei
Published: December 2020

Doppler wind lidar has played an important role in alerting low-level wind shear (LLW). However, these high-resolution observations are underused in the model-based analysis and forecasting of LLW. In this regard, we employed the Weather Research and Forecasting (WRF) model and its three-dimensional variational (3D-VAR) system to investigate the impact of lidar data assimilation (DA) on LLW simulations. Eight experiments (including six assimilation experiments) were designed for an LLW process as reported by pilots, in which different assimilation intervals, assimilation timespans, and model vertical resolutions were examined. Verified against observations from Doppler wind lidar and an automated weather observing system (AWOS), the introduction of lidar data is helpful for describing the LLW event, which can represent the temporal and spatial features of LLW, whereas experiments without lidar DA have no ability to capture LLW. While lidar DA has an obviously positive role in simulating LLW in the 10–20 min after the assimilation time, this advantage cannot be maintained over a longer time. Therefore, a smaller assimilation interval is favorable for improving the simulated effect of LLW. In addition, increasing the vertical resolution does not evidently improve the experimental results, either with or without assimilation.
Pressure-Gradient Forcing Methods for Large-Eddy Simulations of Flows in the Lower Atmospheric Boundary Layer
Authors: Pimont François , Dupuy Jean-Luc , Linn Rodman R. , Sauer Jeremy A. , Muñoz-Esparza Domingo
Published: December 2020

Turbulent flows over forest canopies have been successfully modeled using Large-Eddy Simulations (LES). Simulated winds result from the balance between a simplified pressure gradient forcing (e.g., a constant pressure-gradient or a canonical Ekman balance) and the dissipation of momentum, due to vegetation drag. Little attention has been paid to the impacts of these forcing methods on flow features, despite practical challenges and unrealistic features, such as establishing stationary velocity or streak locking. This study presents a technique for capturing the effects of a pressure-gradient force (PGF), associated with atmospheric patterns much larger than the computational domain for idealized simulations of near-surface phenomena. Four variants of this new PGF are compared to existing forcings, for turbulence statistics, spectra, and temporal averages of flow fields. Results demonstrate that most features of the turbulent flow are captured. The variants can either enable modelers to prescribe a wind speed and direction at a reference height close to the ground as required in wildfire simulations, and/or mitigate streaks locking by reproducing the stability of the Ekman balance. Conditions of use, benefits, and drawbacks are discussed. PGF approaches, therefore, provide a viable solution for precursor inflows, including for the specific domains used in fire simulations.
The Microscale Urban Surface Energy (MUSE) Model for Real Urban Application
Authors: Lee Doo-Il , Lee Sang-Hyun
Published: December 2020

Urban atmospheric environmental issues are commonly associated with the physical processes of urban surfaces. Much progress has been made on the building-resolving microscale atmospheric models, but a realistic representation of the physical processes of urban surfaces on those models is still lacking. This study presents a new microscale urban surface energy (MUSE) model for real urban meteorological and environmental applications that is capable of representing the urban radiative, convective, and conductive energy transfer processes along with their interactions, and that is directly compatible with the Cartesian grid microscale atmospheric models. The physical processes of shadow casting and radiative transfers were validated on an analytical accuracy level. The full capability of the model in simulating the three-dimensional surface heterogeneities in a real urban environment was tested for a hot summer day in August 2016 using the field measurements obtained from the Kongju National University campus, South Korea. The validation against the measurements showed that the model is capable of predicting surface temperatures and energy balance fluxes in a patch scale at the heterogeneous urban surfaces by virtue of the interactive representation of the urban physical processes. The excellent performance and flexible grid design emphasize the potential capabilities of the MUSE model for use in urban meteorological and environmental applications through the building-resolving microscale atmospheric models, such as computational fluid dynamics (CFD) and large-eddy simulations (LES).
Impact of Urban Canopy Parameters on a Megacity’s Modelled Thermal Environment
Authors: Varentsov Mikhail , Samsonov Timofey , Demuzere Matthias
Published: December 2020

Urban canopy parameters (UCPs) are essential in order to accurately model the complex interplay between urban areas and their environment. This study compares three different approaches to define the UCPs for Moscow (Russia), using the COSMO numerical weather prediction and climate model coupled to TERRA_URB urban parameterization. In addition to the default urban description based on the global datasets and hard-coded constants (1), we present a protocol to define the required UCPs based on Local Climate Zones (LCZs) (2) and further compare it with a reference UCP dataset, assembled from OpenStreetMap data, recent global land cover data and other satellite imagery (3). The test simulations are conducted for contrasting summer and winter conditions and are evaluated against a dense network of in-situ observations. For the summer period, advanced approaches (2) and (3) show almost similar performance and provide noticeable improvements with respect to default urban description (1). Additional improvements are obtained when using spatially varying urban thermal parameters instead of the hard-coded constants. The LCZ-based approach worsens model performance for winter however, due to the underestimation of the anthropogenic heat flux (AHF). These results confirm the potential of LCZs in providing internationally consistent urban data for weather and climate modelling applications, as well as supplementing more comprehensive approaches. Yet our results also underline the continued need to improve the description of built-up and impervious areas and the AHF in urban parameterizations.
Can Technological Development Compensate for the Unfavorable Impacts of Climate Change? Conclusions from 50 Years of Maize (Zea mays L.) Production in Hungary
Authors: Huzsvai László , Zsembeli József , Kovács Elza , Juhász Csaba
Published: December 2020

The goals of our study were to evaluate the historical aspects of maize (Zea mays L.) production in Hungary, and to provide a prognosis for the yield for 2050 based on the trends of temperature, precipitation, and climatic water balance changes. Different climate zones for the period of 1970–2019 were investigated by means of correlation analyses, normality tests, time series analysis, and multiple linear regression analysis. Two well-distinguishable linear trends in the yields were found, the first representing large-scale farming, and the second starting with the change of the socio-economic system in 1989. The annual amount of precipitation showed high variations both spatially and temporally, although no significant change was identified for the last five decades. In the period 1990–2019, not only were higher temperatures characteristic, but the frequency of extreme high temperature values (Tmax > 30 °C) also increased. We quantified the heat stress, expressing it in heat stress units (HSU, °C) derived from the heat-sum of the daily maximum air temperature values above 30 °C. By 2050, the average increase in HSUs may reach 35 °C. Increasing HSU causes yield depression; according to our estimations, a 1 °C increase in HSU results in a 23 kg ha−1 yield depression of maize. Taking the unfavorable effect of heat stress and technological development into consideration, the average domestic yield of maize will be 8.2 t ha−1. Our study revealed that without taking technological development into consideration, prediction models may overestimate the adverse effect of climate change on crop production.
Thermal Inversion and Particulate Matter Concentration in Wrocław in Winter Season
Authors: Nidzgorska-Lencewicz Jadwiga , Czarnecka Małgorzata
Published: December 2020

Studies on air quality frequently adopt clustering, in particular the k-means technique, owing to its simplicity, ease of implementation and efficiency. The aim of the present paper was the assessment of air quality in a winter season (December–February) in the conditions of temperature inversion using the k-means method, representing a non-hierarchical algorithm of cluster analysis. The air quality was assessed on the basis of the concentrations of particulate matter (PM10, PM2.5). The studies were conducted in four winter seasons (2015/16, 2016/17, 2017/18, 2019/20) in Wrocław (Poland). As a result of the application of the v-fold cross test, six clusters for each fraction of PM were identified. Even though the analysis covers only four winter seasons, the applied method has unequivocally revealed that the characteristics of surface-based (SBI) and elevated inversions (ELI) affect the concentration level of both fractions of particulate matter. In the case of PM10, the average lowest daily concentration (15.5 µg·m−3) was recorded in the conditions of approx. 205 m in thickness, 0.5 °C intensity of the SBI and at the height of the base of the ELI at approx. 1700 m a.g.l., a thickness of 148 m and an intensity of 1.2 °C. In turn, the average highest concentration (136 µg·m−3) was recorded at a thickness of SBI of approx. 400 m and an intensity of 1.4 °C. Such high concentration occurred when the lowest location of ELI formed at 764 m a.g.l. with a thickness of 308 m and an intensity of 0.96 °C. A marked role of the thickness of the SBI and ELI as well as the height of the base of the lowest location of ELI was also manifested with respect to PM2.5 concentrations.
Farming Practices for Reducing Ammonia Emissions in Polish Agriculture
Authors: Piwowar Arkadiusz
Published: December 2020

The main source of ammonia emissions in Poland is agriculture. In 2017, approximately 94% of the total ammonia emissions in Poland came from agriculture, of which the largest part (78%) was related to livestock manure and 22% to nitrogen fertilization. This study presents the results of representative research on the implementation of technologies and techniques that reduce ammonia emissions on farms in Poland. The research methodology, including statistical data analysis (multiple correspondence analysis), allowed comparisons to be made of the applied low-carbon practices, taking into account farmers’ characteristics (e.g., age and education) and farm attributes (area size, location, etc.). According to the research, both in the case of mineral fertilization and animal production, farmers in Poland relatively rarely undertake pro-ecological practices aimed at reducing ammonia emissions. The most frequently undertaken activities include dividing the doses of nitrogen fertilizers (in terms of plant production) and the use of feed additives (in terms of livestock production). Empirical studies, supported by correspondence analyses, confirmed a significant differentiation of coexistence and strength of the relationship between the studied variables. The use of correspondence analysis made it possible to precisely recognize the differentiation and co-occurrence of variable categories. In the course of analytical work, a relatively strong correlation was found between the use of divided doses of nitrogen fertilizers and the economic size of farms (φ2 = 0.11571). In turn, the use of feed additives was most strongly determined by the economic size of farms (φ2 = 0.072614) and the location of farms (φ2 = 0.072223).
Depletion of Boric Acid and Cobalt from Cultivation Media: Impact on Recombinant Protein Production with Komagataella phaffii
Authors: Pekarsky Alexander , Mihalyi Sophia , Weiss Maximilian , Limbeck Andreas , Spadiut Oliver
Published: December 2020

The REACH regulation stands for “Registration, Evaluation, Authorization and Restriction of Chemicals” and defines certain substances as harmful to human health and the environment. This urges manufacturers to adapt production processes. Boric acid and cobalt dichloride represent such harmful ingredients, but are commonly used in yeast cultivation media. The yeast Komagataella phaffii (Pichia pastoris) is an important host for heterologous protein production and compliance with the REACH regulation is desirable. Boric acid and cobalt dichloride are used as boron and cobalt sources, respectively. Boron and cobalt support growth and productivity and a number of cobalt-containing enzymes exist. Therefore, depletion of boric acid and cobalt dichloride could have various negative effects, but knowledge is currently scarce. Herein, we provide an insight into the impact of boric acid and cobalt depletion on recombinant protein production with K. phaffii and additionally show how different vessel materials affect cultivation media compositions through leaking elements. We found that boric acid could be substituted through boron leakiness from borosilicate glassware. Furthermore, depletion of boric acid and cobalt dichloride neither affected high cell density cultivation nor cell morphology and viability on methanol. However, final protein quality of three different industrially relevant enzymes was affected in various ways.
Dual Role of the PTPN13 Tyrosine Phosphatase in Cancer
Authors: Mcheik Soha , Aptecar Leticia , Coopman Peter , D’Hondt Véronique , Freiss Gilles
Published: December 2020

In this review article, we present the current knowledge on PTPN13, a class I non-receptor protein tyrosine phosphatase identified in 1994. We focus particularly on its role in cancer, where PTPN13 acts as an oncogenic protein and also a tumor suppressor. To try to understand these apparent contradictory functions, we discuss PTPN13 implication in the FAS and oncogenic tyrosine kinase signaling pathways and in the associated biological activities, as well as its post-transcriptional and epigenetic regulation. Then, we describe PTPN13 clinical significance as a prognostic marker in different cancer types and its impact on anti-cancer treatment sensitivity. Finally, we present future research axes following recent findings on its role in cell junction regulation that implicate PTPN13 in cell death and cell migration, two major hallmarks of tumor formation and progression.
Oncolytic Adenovirus CD55-Smad4 Suppresses Cell Proliferation, Metastasis, and Tumor Stemness in Colorectal Cancer by Regulating Wnt/β-Catenin Signaling Pathway
Authors: Xiao Boduan , Zhang Leilei , Liu Huihui , Fang Huiling , Wang Chunming , Huang Biao , Liu Xinyuan , Zhou Xiumei , Wang Yigang
Published: December 2020

During the past few decades, colorectal cancer (CRC) incidence and mortality have significantly increased, and CRC has become the leading cause of cancer-related death worldwide. Thus, exploring novel effective therapies for CRC is imperative. In this study, we investigated the effect of oncolytic adenovirus CD55-Smad4 on CRC cell growth. Cell viability assay, animal experiments, flow cytometric analysis, cell migration, and invasion assays, and Western blotting were used to detect the proliferation, apoptosis, migration, and invasion of CRC cells. The oncolytic adenovirus CD55-Smad4 was successfully constructed and effectively suppressed CRC cell proliferation in vivo and in vitro. Notably, CD55-Smad4 activated the caspase signaling pathway, inducing the apoptosis of CRC cells. Additionally, the generated oncolytic adenovirus significantly suppressed migration and invasion of CRC cells by overexpressing Smad4 and inhibiting Wnt/β-catenin/epithelial-mesenchymal transition (EMT) signaling pathway. Moreover, CRC cells treated with CD55-Smad4 formed less and smaller spheroid colonies in serum-free culture than cells in control groups, suggesting that CD55-Smad4 suppressed the stemness of CRC cells by inhibiting the Wnt/β-catenin pathway. Together, the results of this study provide valuable information for the development of a novel strategy for cancer-targeting gene-virotherapy and provide a deeper understanding of the critical significance of Smad4 in gene therapy of CRC.
Haloperidol Induced Cell Cycle Arrest and Apoptosis in Glioblastoma Cells
Authors: Papadopoulos Fotios , Isihou Rafaela , Alexiou George A. , Tsalios Thomas , Vartholomatos Evrysthenis , Markopoulos Georgios S. , Sioka Chrissa , Tsekeris Pericles , Kyritsis Athanasios P. , Galani Vasiliki
Published: December 2020

Although several antipsychotic drugs have been shown to possess anticancer activities, haloperidol, a “first-generation” antipsychotic drug, has not been extensively evaluated for potential antineoplastic properties. The aim of this study was to investigate the antitumoral effects of haloperidol in glioblastoma (GBM) U87, U251 and T98 cell lines, and the effects of combined treatment with temozolomide (TMZ) and/or radiotherapy, using 4 Gy of irradiation. The viability and proliferation of the cells were evaluated with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis, using the annexin-propidium iodide (PI), and cell cycle, cluster of differentiation (CD) expression and caspase-8 activation were measured using flow cytometry. Treatment with haloperidol significantly reduced cell viability in U87, U251 and T98 GBM cell lines. Haloperidol induced apoptosis in a dose-dependent manner, inhibited cell migration and produced an alteration in the expression of CD24/CD44. The additional effect of haloperidol, combined with temozolomide and radiation therapy, increased tumor cell death. Haloperidol was observed to induce apoptosis and to increase caspase-8 activation. In conclusion, haloperidol may represent an innovative strategy for the treatment of GBM and further studies are warranted in glioma xenograft models and other malignancies.
Regulation of Oncogenic Targets by the Tumor-Suppressive miR-139 Duplex (miR-139-5p and miR-139-3p) in Renal Cell Carcinoma
Authors: Okada Reona , Goto Yusuke , Yamada Yasutaka , Kato Mayuko , Asai Shunichi , Moriya Shogo , Ichikawa Tomohiko , Seki Naohiko
Published: December 2020

We previously found that both the guide and passenger strands of the miR-139 duplex (miR-139-5p and miR-139-3p, respectively) were downregulated in cancer tissues. Analysis of TCGA datasets revealed that low expression of miR-139-5p (p < 0.0001) and miR-139-3p (p < 0.0001) was closely associated with 5-year survival rates of patients with renal cell carcinoma (RCC). Ectopic expression assays showed that miR-139-5p and miR-139-3p acted as tumor-suppressive miRNAs in RCC cells. Here, 19 and 22 genes were identified as putative targets of miR-139-5p and miR-139-3p in RCC cells, respectively. Among these genes, high expression of PLXDC1, TET3, PXN, ARHGEF19, ELK1, DCBLD1, IKBKB, and CSF1 significantly predicted shorter survival in RCC patients according to TCGA analyses (p < 0.05). Importantly, the expression levels of four of these genes, PXN, ARHGEF19, ELK1, and IKBKB, were independent prognostic factors for patient survival (p < 0.05). We focused on PXN (paxillin) and investigated its potential oncogenic role in RCC cells. PXN knockdown significantly inhibited cancer cell migration and invasion, possibly by regulating epithelial–mesenchymal transition. Involvement of the miR-139-3p passenger strand in RCC molecular pathogenesis is a new concept. Analyses of tumor-suppressive-miRNA-mediated molecular networks provide important insights into the molecular pathogenesis of RCC.
The Specificity of Downstream Signaling for A1 and A2AR Does Not Depend on the C-Terminus, Despite the Importance of This Domain in Downstream Signaling Strength
Authors: Jain Abhinav R. , McGraw Claire , Robinson Anne S.
Published: December 2020

Recent efforts to determine the high-resolution crystal structures for the adenosine receptors (A1R and A2AR) have utilized modifications to the native receptors in order to facilitate receptor crystallization and structure determination. One common modification is a truncation of the unstructured C-terminus, which has been utilized for all the adenosine receptor crystal structures obtained to date. Ligand binding for this truncated receptor has been shown to be similar to full-length receptor for A2AR. However, the C-terminus has been identified as a location for protein-protein interactions that may be critical for the physiological function of these important drug targets. We show that variants with A2AR C-terminal truncations lacked cAMP-linked signaling compared to the full-length receptor constructs transfected into mammalian cells (HEK-293). In addition, we show that in a humanized yeast system, the absence of the full-length C-terminus affected downstream signaling using a yeast MAPK response-based fluorescence assay, though full-length receptors showed native-like G-protein coupling. To further study the G protein coupling, we used this humanized yeast platform to explore coupling to human-yeast G-protein chimeras in a cellular context. Although the C-terminus was essential for Gα protein-associated signaling, chimeras of A1R with a C-terminus of A2AR coupled to the A1R-specific Gα (i.e., Gαi1 versus Gαs). This surprising result suggests that the C-terminus is important in the signaling strength, but not specificity, of the Gα protein interaction. This result has further implications in drug discovery, both in enabling the experimental use of chimeras for ligand design, and in the cautious interpretation of structure-based drug design using truncated receptors.
Development of a Biomarker Panel to Distinguish Risk of Progressive Chronic Kidney Disease
Authors: Owens Evan , Tan Ken-Soon , Ellis Robert , Del Vecchio Sharon , Humphries Tyrone , Lennan Erica , Vesey David , Healy Helen , Hoy Wendy , Gobe Glenda
Published: December 2020

Chronic kidney disease (CKD) patients typically progress to kidney failure, but the rate of progression differs per patient or may not occur at all. Current CKD screening methods are sub-optimal at predicting progressive kidney function decline. This investigation develops a model for predicting progressive CKD based on a panel of biomarkers representing the pathophysiological processes of CKD, kidney function, and common CKD comorbidities. Two patient cohorts are utilised: The CKD Queensland Registry (n = 418), termed the Biomarker Discovery cohort; and the CKD Biobank (n = 62), termed the Predictive Model cohort. Progression status is assigned with a composite outcome of a ≥30% decline in eGFR from baseline, initiation of dialysis, or kidney transplantation. Baseline biomarker measurements are compared between progressive and non-progressive patients via logistic regression. In the Biomarker Discovery cohort, 13 biomarkers differed significantly between progressive and non-progressive patients, while 10 differed in the Predictive Model cohort. From this, a predictive model, based on a biomarker panel of serum creatinine, osteopontin, tryptase, urea, and eGFR, was calculated via linear discriminant analysis. This model has an accuracy of 84.3% when predicting future progressive CKD at baseline, greater than eGFR (66.1%), sCr (67.7%), albuminuria (53.2%), or albumin-creatinine ratio (53.2%).
Prevalence of Cognitive Frailty, Do Psychosocial-Related Factors Matter?
Authors: Navarro-Pardo Esperanza , Facal David , Campos-Magdaleno María , Pereiro Arturo , Juncos-Rabadán Onésimo
Published: December 2020

Cognitive frailty (CF) is a topic of growing interest with implications for the study of preventive interventions in aging. Nevertheless, little research has been done to assess the influence of psychosocial variables on the risk of CF. Our objectives were to estimate the prevalence of CF in a Spanish sample and to explore the influence of psychosocial variables in this prevalence. Physical frailty and cognitive, functional, psychosocial, and socio-demographic aspects were assessed in a sample of 285 participants over 60 years. Univariate and multivariate logistic regression models were carried out. A prevalence of 21.8% (95% CI 17.4–26.9) was established when both frail and pre-frail conditions were included, and a prevalence of 3.2% (95% CI 1.7–5.9) if only frail individuals were considered. Age, educational level, profession and psychological well-being variables significantly predicted CF. Frailty and pre-frailty are high-prevalence health conditions in older adults influenced by socio-demographic, socio-educative and affective factors.
Brain Connectivity Changes after Osteopathic Manipulative Treatment: A Randomized Manual Placebo-Controlled Trial
Authors: Tramontano Marco , Cerritelli Francesco , Piras Federica , Spanò Barbara , Tamburella Federica , Piras Fabrizio , Caltagirone Carlo , Gili Tommaso
Published: December 2020

The effects of osteopathic manipulative treatment (OMT) on functional brain connectivity in healthy adults is missing in the literature. To make up for this lack, we applied advanced network analysis methods to analyze resting state functional magnetic resonance imaging (fMRI) data, after OMT and Placebo treatment (P) in 30 healthy asymptomatic young participants randomized into OMT and placebo groups (OMTg; Pg). fMRI brain activity measures, performed before (T0), immediately after (T1) and three days after (T2) OMT or P were used for inferring treatment effects on brain circuit functional organization. Repeated measures ANOVA and post-hoc analysis demonstrated that Right Precentral Gyrus (F (2, 32) = 5.995, p < 0.005) was more influential over the information flow immediately after the OMT, while decreased betweenness centrality in Left Caudate (F (2, 32) = 6.496, p < 0.005) was observable three days after. Clustering coefficient showed a distinct time-point and group effect. At T1, reduced neighborhood connectivity was observed after OMT in the Left Amygdala (L-Amyg) (F (2, 32) = 7.269, p < 0.005) and Left Middle Temporal Gyrus (F (2, 32) = 6.452, p < 0.005), whereas at T2 the L-Amyg and Vermis-III (F (2, 32) = 6.772, p < 0.005) increased functional interactions. Data demonstrated functional connectivity re-arrangement after OMT.
The Significance of Tau Aggregates in the Human Brain
Authors: Castellani Rudy J.
Published: December 2020

Neurofibrillary degeneration has attracted the attention of neuroscientists as both a hallmark of the disease and a subject for experimentation for more than a century. Recent studies implicate phosphorylated tau (p-tau) directly in neurodegenerative disease pathogenesis, although the human data continue to raise questions. P-tau accumulates with age in a roughly hierarchical manner, but avoids abundance in the neocortex unless co-occurring with amyloid-β. Neurodegenerative tauopathies tend to have p-tau morphologies that differ from aging and Alzheimer’s disease. Tau isoforms (3R vs. 4R) have a tendency to vary with tauopathy phenotype for unknown reasons. Selective vulnerability to p-tau and spatial-temporal disconnect from amyloid-β are evident in aging. P-tau assessment at autopsy involves tissue decomposition, which may skew microanatomical observations toward limited biological meaning. Two major consensus guidelines for interpreting p-tau at autopsy emphasize the challenges of clinicopathologic correlation, and reinforce the observation that regional neurodegeneration is a better correlate of clinical signs than is proteinopathy. Despite the proliferation of interesting and novel theories related to tau-mediated pathogenesis, the weight of the human observations suggests that neurofibrillary degeneration is an epiphenomenal hallmark of aging and disease rather than an epicenter of neurotoxicity. This is consistent with numerous tau-targeted therapeutic strategies that have been unsuccessful to date.
DLK1 Expressed in Mouse Orexin Neurons Modulates Anxio-Depressive Behavior but Not Energy Balance
Authors: Harris Tatiyana , Bugescu Raluca , Kelly Jaylyn , Makela Anna , Sotzen Morgan , Sisk Cheryl , Atkin Graham , Pratt Rebecca , Crockett Elahé , Leinninger Gina
Published: December 2020

Lateral hypothalamic area (LHA) neurons expressing the neuropeptide orexin (OX) are implicated in obesity and anxio-depression. However, these neurons release OX as well as a host of other proteins that might contribute to normal physiology and disease states. We hypothesized that delta-like homolog 1 (DLK1), a protein reported to be co-expressed by all OX neurons, contributes to the regulation of energy balance and/or anxio-depression. Consistent with previous reports, we found that all rat OX neurons co-express DLK1. Yet, in mice and humans only a subset of OX neurons co-expressed DLK1. Since human OX-DLK1 distribution is more similar to mice than rats, mice are a comparable model to assess the human physiologic role of DLK1. We therefore used a viral lesion strategy to selectively delete DLK1 within the LHA of adult mice (DLK1Null) to reveal its role in body weight and behavior. Adult-onset DLK1 deletion had no impact on body weight or ingestive behavior. However, DLK1Null mice engaged in more locomotor activity than control mice and had decreased anxiety and depression measured via the elevated plus maze and forced swim tests. These data suggest that DLK1 expression via DLK1-expressing OX neurons primarily contributes to anxio-depression behaviors without impacting body weight.
Feasibility of Using Foot–Ground Clearance Biofeedback Training in Treadmill Walking for Post-Stroke Gait Rehabilitation
Authors: Nagano Hanatsu , Said Catherine M. , James Lisa , Begg Rezaul K.
Published: December 2020

Hemiplegic stroke often impairs gait and increases falls risk during rehabilitation. Tripping is the leading cause of falls, but the risk can be reduced by increasing vertical swing foot clearance, particularly at the mid-swing phase event, minimum foot clearance (MFC). Based on previous reports, real-time biofeedback training may increase MFC. Six post-stroke individuals undertook eight biofeedback training sessions over a month, in which an infrared marker attached to the front part of the shoe was tracked in real-time, showing vertical swing foot motion on a monitor installed in front of the subject during treadmill walking. A target increased MFC range was determined, and participants were instructed to control their MFC within the safe range. Gait assessment was conducted three times: Baseline, Post-training and one month from the final biofeedback training session. In addition to MFC, step length, step width, double support time and foot contact angle were measured. After biofeedback training, increased MFC with a trend of reduced step-to-step variability was observed. Correlation analysis revealed that MFC height of the unaffected limb had interlinks with step length and ankle angle. In contrast, for the affected limb, step width variability and MFC height were positively correlated. The current pilot-study suggested that biofeedback gait training may reduce tripping falls for post-stroke individuals.
Outdoor Thermal Comfort: Coupling Microclimatic Parameters with Subjective Thermal Assessment to Design Urban Performative Spaces
Authors: Elnabawi Mohamed , Hamza Neveen
Published: December 2020

Thermal comfort plays a main role in encouraging people to use outdoor spaces, specifically in hot arid and humid climates. The reconciliation of climatic aspects during the urban design phase is limited in implementation, due to the need for multidisciplinary collaboration between desperate scientific fields of climatology, urban planning, and urban environmental modelling. This paper aims to create an integrated interface between the microclimate, outdoor thermal comfort, and design guidelines. The investigation combines subjective and objective approaches, including on-site field measurements, a structured questionnaire using the seven-point American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE 55) thermal sensation votes, and a correlation study of these votes and the microclimatic parameters. Pedestrian thermal comfort was then examined under six shading scenarios, addressing the form and opening of shading devices using computational fluid dynamics. Modelling is based on four dependent variables: wind velocity, ventilation flow rate, air temperature, and the physiological equivalent temperature (PET) index. Findings indicate that the form and location of apertures of the shading devices were the dominant factors in achieving thermal comfort on the urban scale, and led to a reduction in air temperature and a physiological equivalent temperature of 2.3–2.4 °C. Subjective votes indicate that people who live in hot arid climates have a wider range of adaptation and tolerance to local climatic conditions Accordingly, a psychometric chart, for the case study outdoor thermal comfort was developed.
Critical Value Management Activities in Building Projects: A Case of Egypt
Authors: Kineber Ahmed , Othman Idris , Oke Ayodeji , Chileshe Nicholas , Alsolami Badr
Published: December 2020

Value management (VM) is one of the principles adopted by stakeholders to manage issues in the building industry. This paper aims to examine VM diffusion between residential building entities in the Egyptian residential building industry. This research was confined to the Cairo and Giza regions, with enough residential building experience from clients, consultants, and contractors. A quantitative questionnaire survey was generated to find answers from those active in the residential building industry. The results show that although VM’s most widely practiced activities in the Egyptian construction industry are only information phase activities, professionals in Egyptian building projects agreed that all VM activities are important. The results also demonstrated that there is a significant positive correlation among VM phases. The results constitute activities for the adoption of VMs in Egypt. Its guidelines will dramatically enhance the implementation of VMs both in Egypt and in other developing countries where similar projects are conducted. Finally, this research strengthens the residential building industry’s present management by enhancing VM tools and elements to generate value for money.
Differential Effects of IGF-1R Small Molecule Tyrosine Kinase Inhibitors BMS-754807 and OSI-906 on Human Cancer Cell Lines
Authors: Fuentes-Baile María , Ventero María P. , Encinar José A. , García-Morales Pilar , Poveda-Deltell María , Pérez-Valenciano Elizabeth , Barberá Víctor M. , Gallego-Plazas Javier , Rodríguez-Lescure Álvaro , Martín-Nieto José , Saceda Miguel
Published: December 2020

We have determined the effects of the IGF-1R tyrosine kinase inhibitors BMS-754807 (BMS) and OSI-906 (OSI) on cell proliferation and cell-cycle phase distribution in human colon, pancreatic carcinoma, and glioblastoma cell lines and primary cultures. IGF-1R signaling was blocked by BMS and OSI at equivalent doses, although both inhibitors exhibited differential antiproliferative effects. In all pancreatic carcinoma cell lines tested, BMS exerted a strong antiproliferative effect, whereas OSI had a minimal effect. Similar results were obtained on glioblastoma primary cultures, where HGUE-GB-15, -16 and -17 displayed resistance to OSI effects, whereas they were inhibited in their proliferation by BMS. Differential effects of BMS and OSI were also observed in colon carcinoma cell lines. Both inhibitors also showed different effects on cell cycle phase distribution, BMS induced G2/M arrest followed by cell death, while OSI induced G1 arrest with no cell death. Both inhibitors also showed different effects on other protein kinases activities. Taken together, our results are indicative that BMS mainly acts through off-target effects exerted on other protein kinases. Given that BMS exhibits a potent antiproliferative effect, we believe that this compound could be useful for the treatment of different types of tumors independently of their IGF-1R activation status.
The Suitability of Glioblastoma Cell Lines as Models for Primary Glioblastoma Cell Metabolism
Authors: Arthurs Anya L. , Keating Damien J. , Stringer Brett W. , Conn Simon J.
Published: December 2020

In contrast to most non-malignant tissue, cells comprising the brain tumour glioblastoma (GBM) preferentially utilise glycolysis for metabolism via “the Warburg effect”. Research into therapeutics targeting the disease’s highly glycolytic state offer a promising avenue to improve patient survival. These studies often employ GBM cell lines for in vitro studies which translate poorly to the in vivo patient context. The metabolic traits of five of the most used GBM cell lines were assessed and compared to primary GBM and matched, healthy brain tissue. In patient-derived GBM cell lines, the basal mitochondrial rate (p = 0.043) and ATP-linked respiration (p < 0.001) were lower than primary adjacent normal cells from the same patient, while reserve capacity (p = 0.037) and Krebs cycle capacity (p = 0.002) were higher. Three cell lines, U251MG, U373MG and D54, replicate the mitochondrial metabolism of primary GBM cells. Surprisingly, glycolytic capacity is not different between healthy and GBM tissue. The T98G cell line recapitulated glycolysis-related metabolic parameters of the primary GBM cells and is recommended for research relating to glycolysis. These findings can guide preclinical research into the development of novel therapeutics targeting metabolic pathways in GBM.
The CCR2/MCP-1 Chemokine Pathway and Lung Adenocarcinoma
Authors: Mittal Payal , Wang Liqing , Akimova Tatiana , Leach Craig A. , Clemente Jose C. , Sender Matthew R. , Chen Yao , Turunen Brandon J. , Hancock Wayne W.
Published: December 2020

Host anti-tumor immunity can be hindered by various mechanisms present within the tumor microenvironment, including the actions of myeloid-derived suppressor cells (MDSCs). We investigated the role of the CCR2/MCP-1 pathway in MDSC-associated tumor progression in murine lung cancer models. Phenotypic profiling revealed maximal expression of CCR2 by tumor-resident MDSCs, and MCP-1 by transplanted TC1 tumor cells, respectively. Use of CCR2-knockout (CCR2-KO) mice showed dependence of tumor growth on CCR2 signaling. Tumors in CCR2-KO mice had fewer CCR2low MDSCs, CD4 T cells and Tregs than WT mice, and increased infiltration by CD8 T cells producing IFN-γ and granzyme-B. Effects were MDSC specific, since WT and CCR2-KO conventional T (Tcon) cells had comparable proliferation and production of inflammatory cytokines, and suppressive functions of WT and CCR2-KO Foxp3+ Treg cells were also similar. We used a thioglycolate-induced peritonitis model to demonstrate a role for CCR2/MCP-1 in trafficking of CCR2+ cells to an inflammatory site, and showed the ability of a CCR2 antagonist to inhibit such trafficking. Use of this CCR2 antagonist promoted anti-tumor immunity and limited tumor growth. In summary, tumor cells are the prime source of MCP-1 that promotes MDSC recruitment, and our genetic and pharmacologic data demonstrate that CCR2 targeting may be an important component of cancer immunotherapy.