bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Progress in the Drug Development Targeting SARS-CoV-2 Main Protease as Treatment for COVID-19
Authors: Cui Wen , Yang Kailin , Yang Haitao
Published: December 2020

The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) rapidly turned into an unprecedented pandemic of coronavirus disease 2019 (COVID-19). This global healthcare emergency marked the third occurrence of a deadly coronavirus (CoV) into the human society after entering the new millennium, which overwhelmed the worldwide healthcare system and affected the global economy. However, therapeutic options for COVID-19 are still very limited. Developing drugs targeting vital proteins in viral life cycle is a feasible approach to overcome this dilemma. Main protease (Mpro) plays a dominant role in processing CoV-encoded polyproteins which mediate the assembly of replication-transcription machinery and is thus recognized as an ideal antiviral target. Here we summarize the recent progress in the discovery of anti-SARS-CoV-2 agents against Mpro. Combining structural study, virtual screen, and experimental screen, numerous therapeutic candidates including repurposed drugs and ab initio designed compounds have been proposed. Such collaborative effort from the scientific community would accelerate the pace of developing efficacious treatment for COVID-19.
A Potential Mechanism of Sodium Channel Mediating the General Anesthesia Induced by Propofol
Authors: Xiao Jinglei , Chen Zhengguo , Yu Buwei
Published: December 2020

General anesthesia has revolutionized healthcare over the past 200 years and continues to show advancements. However, many phenomena induced by general anesthetics including paradoxical excitation are still poorly understood. Voltage-gated sodium channels (NaV) were believed to be one of the proteins targeted during general anesthesia. Based on electrophysiological measurements before and after propofol treatments of different concentrations, we mathematically modified the Hodgkin–Huxley sodium channel formulations and constructed a thalamocortical model to investigate the potential roles of NaV. The ion channels of individual neurons were modeled using the Hodgkin–Huxley type equations. The enhancement of propofol-induced GABAa current was simulated by increasing the maximal conductance and the time-constant of decay. Electroencephalogram (EEG) was evaluated as the post-synaptic potential from pyramidal (PY) cells. We found that a left shift in activation of NaV was induced primarily by a low concentration of propofol (0.3–10 μM), while a left shift in inactivation of NaV was induced by an increasing concentration (0.3–30 μM). Mathematical simulation indicated that a left shift of NaV activation produced a Hopf bifurcation, leading to cell oscillations. Left shift of NaV activation around a value of 5.5 mV in the thalamocortical models suppressed normal bursting of thalamocortical (TC) cells by triggering its chaotic oscillations. This led to irregular spiking of PY cells and an increased frequency in EEG readings. This observation suggests a mechanism leading to paradoxical excitation during general anesthesia. While a left shift in inactivation led to light hyperpolarization in individual cells, it inhibited the activity of the thalamocortical model after a certain depth of anesthesia. This finding implies that high doses of propofol inhibit the network partly by accelerating NaV toward inactivation. Additionally, this result explains why the application of sodium channel blockers decreases the requirement for general anesthetics. Our study provides an insight into the roles that NaV plays in the mechanism of general anesthesia. Since the activation and inactivation of NaV are structurally independent, it should be possible to avoid side effects by state-dependent binding to the NaV to achieve precision medicine in the future.
Lactic Acidosis Interferes With Toxicity of Perifosine to Colorectal Cancer Spheroids: Multimodal Imaging Analysis
Authors: Pavlatovská Barbora , Machálková Markéta , Brisudová Petra , Pruška Adam , Štěpka Karel , Michálek Jan , Nečasová Tereza , Beneš Petr , Šmarda Jan , Preisler Jan , Kozubek Michal , Navrátilová Jarmila
Published: December 2020

Colorectal cancer (CRC) is a disease with constantly increasing incidence and high mortality. The treatment efficacy could be curtailed by drug resistance resulting from poor drug penetration into tumor tissue and the tumor-specific microenvironment, such as hypoxia and acidosis. Furthermore, CRC tumors can be exposed to different pH depending on the position in the intestinal tract. CRC tumors often share upregulation of the Akt signaling pathway. In this study, we investigated the role of external pH in control of cytotoxicity of perifosine, the Akt signaling pathway inhibitor, to CRC cells using 2D and 3D tumor models. In 3D settings, we employed an innovative strategy for simultaneous detection of spatial drug distribution and biological markers of proliferation/apoptosis using a combination of mass spectrometry imaging and immunohistochemistry. In 3D conditions, low and heterogeneous penetration of perifosine into the inner parts of the spheroids was observed. The depth of penetration depended on the treatment duration but not on the external pH. However, pH alteration in the tumor microenvironment affected the distribution of proliferation- and apoptosis-specific markers in the perifosine-treated spheroid. Accurate co-registration of perifosine distribution and biological response in the same spheroid section revealed dynamic changes in apoptotic and proliferative markers occurring not only in the perifosine-exposed cells, but also in the perifosine-free regions. Cytotoxicity of perifosine to both 2D and 3D cultures decreased in an acidic environment below pH 6.7. External pH affects cytotoxicity of the other Akt inhibitor, MK-2206, in a similar way. Our innovative approach for accurate determination of drug efficiency in 3D tumor tissue revealed that cytotoxicity of Akt inhibitors to CRC cells is strongly dependent on pH of the tumor microenvironment. Therefore, the effect of pH should be considered during the design and pre-clinical/clinical testing of the Akt-targeted cancer therapy.
Intratumor Heterogeneity Correlates With Reduced Immune Activity and Worse Survival in Melanoma Patients
Authors: Lin Zhen , Meng Xianyi , Wen Jinming , Corral José María , Andreev Darja , Kachler Katerina , Schett Georg , Chen Xiaoxiang , Bozec Aline
Published: December 2020

Background

Human malignant melanoma is a highly aggressive, heterogeneous and drug-resistant cancer. Due to a high number of clones, harboring various mutations that affect key pathways, there is an exceptional level of phenotypic variation and intratumor heterogeneity (ITH) in melanoma. This poses a significant challenge to personalized cancer medicine. Hitherto, it remains unclear to what extent the heterogeneity of melanoma affects the immune microenvironment. Herein, we explore the interaction between the tumor heterogeneity and the host immune response in a melanoma cohort utilizing The Cancer Genome Atlas (TCGA).

Methods

Clonal Heterogeneity Analysis Tool (CHAT) was used to estimate intratumor heterogeneity, and immune cell composition was estimated using CIBERSORT. The Overall Survival (OS) among groups was analyzed using Kaplan–Meier curves with the log-rank test and multivariate cox regression. RNA-seq data were evaluated to identify differentially expressed immunomodulatory genes. The reverse phase protein array (RPPA) data platform was used to validate immune responses at protein level.

Results

Tumors with high heterogeneity were associated with decreased overall survival (p = 0.027). High CHAT tumors were correlated with less infiltration by anti-tumor CD8 T cells (p = 0.0049), T follicular cells (p = 0.00091), and M1 macrophages (p = 0.0028), whereas tumor-promoting M2 macrophages were increased (p = 0.02). High CHAT tumors correlated with a reduced expression of immunomodulatory genes, particularly Programmed Cell Death 1 (PD1) and its ligand PD-L1. In addition, high CHAT tumors exhibited lower immune Cytotoxic T lymphocytes (CTLs)-mediated toxicity pathway score (p = 2.9E−07) and cytotoxic pathway score (p = 2.9E−08). High CHAT tumors were also associated with a lower protein level of immune-regulatory kinases, such as lymphocyte-specific protein tyrosine kinase (LCK) (p = 3.4e−5) and spleen tyrosine kinase (SYK) (p = 0.0011).

Conclusions

Highly heterogeneous melanoma tumors are associated with reduced immune cell infiltration and immune response activation as well as decreased survival. Our results reveal that intratumor heterogeneity is an indicative factor for patient survival due to its impact on anti-tumor immune response.
Wilms Tumor in Sub-Saharan Africa: Molecular and Social Determinants of a Global Pediatric Health Disparity
Authors: Apple Annie , Lovvorn Harold N.
Published: December 2020

Wilms tumor (WT) is the most common renal malignancy of childhood. Global disparities in WT have been reported with the highest incidence and lowest overall survival occurring in sub-Saharan African nations. After a detailed search of PubMed, we reviewed available literature on WT in sub-Saharan Africa and summarized findings that explore biologic and social factors contributing to this alarming cancer health disparity. Access to care and treatment abandonment are the most frequently reported factors associated with decreased outcomes. Implementation of multidisciplinary teams, collaborative networks, and financial support has improved overall survival in some nations. However, treatment abandonment remains a challenge. In high-income countries globally, WT therapy now is risk-stratified according to biology and histology. To a significantly lesser extent, biologic features have been studied only recently in sub-Saharan African WT, yet unique molecular and genetic signatures, including congenital anomaly-associated syndromes and biomarkers associated with treatment-resistance and poor prognosis have been identified. Together, challenges with access to and delivery of health care in addition to adverse biologic features likely contribute to increased burden of disease in sub-Saharan African children having WT. Publications on biologic features of WT that inform treatment stratification and personalized therapy in resource-limited regions of sub-Saharan Africa have lagged in comparison to publications that discuss social determinants of health. Further efforts to understand both WT biology and social factors relevant to appropriate treatment delivery should be prioritized in order to reduce health disparities for children residing in resource-limited areas of sub-Saharan Africa battling this lethal childhood cancer.
Effects of Emotional Valence and Concreteness on Children’s Recognition Memory
Authors: Kim Julia M. , Sidhu David M. , Pexman Penny M.
Published: December 2020

There are considerable gaps in our knowledge of how children develop abstract language. In this paper, we tested the Affective Embodiment Account, which proposes that emotional information is more essential for abstract than concrete conceptual development. We tested the recognition memory of 7- and 8-year-old children, as well as a group of adults, for abstract and concrete words which differed categorically in valence (negative, neutral, and positive). Word valence significantly interacted with concreteness in hit rates of both children and adults, such that effects of valence were only found in memory for abstract words. The pattern of valence effects differed for children and adults: children remembered negative words more accurately than neutral and positive words (a negativity effect), whereas adults remembered negative and positive words more accurately than neutral words (a negativity effect and a positivity effect). In addition, signal detection analysis revealed that children were better able to discriminate negative than positive words, regardless of concreteness. The findings suggest that the memory accuracy of 7- and 8-year-old children is influenced by emotional information, particularly for abstract words. The results are in agreement with the Affective Embodiment Account and with multimodal accounts of children’s lexical development.
Synchronization Stability Model of Complex Brain Networks: An EEG Study
Authors: Yin Guimei , Li Haifang , Tan Shuping , Yao Rong , Cui Xiaohong , Zhao Lun
Published: December 2020

In this paper, from the perspective of complex network dynamics we investigated the formation of the synchronization state of the brain networks. Based on the Lyapunov stability theory of complex networks, a synchronous steady-state model suitable for application to complex dynamic brain networks was proposed. The synchronization stability problem of brain network state equation was transformed into a convex optimization problem with Block Coordinate Descent (BCD) method. By using Random Apollo Network (RAN) method as a node selection rule, the brain network constructs its subnet work dynamically. We also analyzes the change of the synchronous stable state of the subnet work constructed by this method with the increase of the size of the network. Simulation EEG data from alcohol addicts patients and Real experiment EEG data from schizophrenia patients were used to verify the robustness and validity of the proposed model. Differences in the synchronization characteristics of the brain networks between normal and alcoholic patients were analyzed, so as differences between normal and schizophrenia patients. The experimental results indicated that the establishment of a synchronous steady state model in this paper could be used to verify the synchronization of complex dynamic brain networks and potentially be of great value in the further study of the pathogenic mechanisms of mental illness.
Suicide in Chinese Graduate Students: A Review From 2000 to 2019
Authors: Cheng Yun , Zhang Xiao Meng , Ye Shui Ying , Jin Hui Min , Yang Xiu Hong
Published: December 2020

Suicide is an important public problem in China. The characteristics of Chinese graduate students' suicides and the reasons they occur have never been reported systematically. We conducted a systematic search of public reports on local media and medical websites in this review to gain a basic understanding of these questions. A total of 150 cases of graduate students' suicides were reported from 2000 to 2019. Among the 150 students, 65.8% were male, nearly half between 26 and 30 years old, most (83.3%) never married, and 43.4% of graduation students committed suicide in graduation year and postponed years. The top three suicide methods were jumping, hanging, and drowning. Graduation pressure, depression, and academic pressure were the three leading suicidal causes. There is an urgent need for the Chinese government and universities to pay more attention to prevent suicides among graduate students.
Network Governance for Collective Action in Implementing United Nations Sustainable Development Goals
Authors: Kapucu Naim , Beaudet Sean
Published: December 2020

As the number of complex transnational problems have continued to grow, so too has the desire to combat them through global partnerships and collective action. In response, the United Nations (U.N.) and member states created the Sustainable Development Goals (SDGs) in 2015. This study provides a background on international organizations and efforts in collectively moving towards sustainable development goals. It examines the SDGs (specific emphasis on Food–Energy–Water (FEW) Nexus) and means of governance and implementation at the global level. It also seeks to describe and visualize partnerships and collective action using network analysis tools and techniques. The network visualization demonstrates the organizations working together and towards the SDGs, which provides the type of structure and key actors and arrangements for implementation at the global stage.
Study of Non-Periodic Pinhole Array Filter for Decreasing High-Order Noise for Compact Holographic Display
Authors: Kim Yoo Kwang , Ryu Won Jong , Lee Jin Su
Published: December 2020

The non-periodic pinhole array filtering of a spatial light modulator (SLM) is proposed for filtering the high-order noise and DC noise of a holographic display. Conventionally, DC and high-order noise sources are filtered by a 4f filtering system. Because the 4f filtering system requires a long optical path length, noise filtering is a stumbling block when attempting to realize a compact holographic display. By contrast, the proposed method simply uses a thin filter fabricated by photolithography. In order to verify this concept, we confirmed the feasibility of the filter with a numerical simulation and with a custom-made non-periodic pinhole array filter used in a practical experiment. The proposed method was shown to have the potential to be used in applications ranging from compact wearable devices to table-top holographic displays.
Correlation of Biomechanical Alterations under Gonarthritis between Overlying Menisci and Articular Cartilage
Authors: Pordzik Johannes , Bernstein Anke , Watrinet Julius , Mayr Hermann O. , Latorre Sergio H. , Schmal Hagen , Seidenstuecker Michael
Published: December 2020

Just like menisci, articular cartilage is exposed to constant and varying stresses. Injuries to the meniscus are associated with the development of gonarthritis. Both the articular cartilage and the menisci are subject to structural changes under gonarthritis. The aim of this study was to investigate biomechanical alterations in articular cartilage and the menisci under gonarthritis by applying an indentation method. The study assessed 11 menisci from body donors as controls and 21 menisci from patients with severe gonarthritis. For the simultaneous examination of the articular cartilage and the menisci, we only tested the joint surfaces of the tibial plateau covered by the corresponding menisci. Over the posterior horn of the meniscus, the maximum applied load—the highest load registered by the load cell—of the arthritic samples of 0.02 ± 0.02 N was significantly greater (p = 0.04) than the maximum applied load of the arthritis-free samples of 0.01 ± 0.01 N. The instantaneous modulus (IM) at the center of the arthritic cartilage covered by the meniscus with 3.5 ± 2.02 MPa was significantly smaller than the IM of the arthritis-free samples with 5.17 ± 1.88 MPa (p = 0.04). No significant difference was found in the thickness of the meniscus-covered articular cartilage between the arthritic and arthritis-free samples. Significant correlations between the articular cartilage and the corresponding menisci were not observed at any point. In this study, the biomechanical changes associated with gonarthritis affected the posterior horn of the meniscus and the mid region of the meniscus-covered articular cartilage. The assessment of cartilage thickness as a structural characteristic of osteoarthritis may be misleading with regard to the interpretation of articular cartilage’s biomechanical properties.
In Search of Lightweight Deployable Tensegrity Columns
Authors: Zawadzki Adam , Al Sabouni-Zawadzka Anna
Published: December 2020

In civil engineering, there is an occasional need to assure an additional support for a structure due to the loss of the load carrying capacity (e.g., as a result of natural disasters or aging) or for a lightweight structure to support temporary objects (e.g., tents, big advertisement banners, temporary antenna masts). In the present study, the authors propose deployable tensegrity columns to be used in such cases. This paper is aimed at answering the question: Which tensegrity column would be the best for the specified application? Four tensegrity columns are analyzed in various deployment configurations to find the answer to this question. Computer simulations are performed in the finite element (FE) and multibody dynamics (MBD) software to provide quantitative and qualitative results. The applied methods are validated by comparing self-stress states at various steps of the analysis. The most important part of the article is the comparative table, which contains quantitative results obtained from the performed analyses, which can be used to indicate the structures that are most appropriate for certain applications. The results may also be used as a starting point for research in other fields of science like robotics or mechatronics. This paper is focused on obtaining full data for building scaled models for laboratory tests in the future.
Development of an NT-ProBNP Assay Reagent Based on High Specific Activity Alkaline Phosphatase CmAP and an Improved Coupling Method
Authors: Li Hai-Chao , He Xin , Qiao Shan-Peng , Liu Zhen-Ni , Gao Yu-Zhou
Published: December 2020

(1) Background: Chemiluminescent enzyme immunoassay (CLEIA) is an efficient analytical method. Alkaline phosphatase (ALP) with high specific activity is the basis for CLEIA to achieve high sensitivity. In this study, a high specific activity Cobetia marina ALP (CmAP) and an improved coupling method were used to develop an N-terminal pro-B-type natriuretic peptide (NT-proBNP) diagnostic reagent. (2) Methods: The purification method of CmAP was improved and the related enzyme activities were assessed. The enzyme and magnetic beads were coupled only to the Fc region of the detection antibody and the capture antibody, respectively, by using a specially improved method. The NT-proBNP in human serum was assessed. (3) Results: The specific activity of the purified CmAP was found to be 13,133 U/mg. No loss in the enzyme activity was observed after its storage at room temperature for 4 months. The sensitivity of the in vitro diagnostic reagents was found to be 0.58 ng/L. (4) Conclusions: CmAP can be applied as a substitute for the commercial ALP. Analytical parameters indicated that the chemiluminescence diagnostic reagent for NT-proBNP is adequately sensitive and reliable for detecting the serum NT-proBNP, which suggests that both the enzyme and coupling method are suitable for the CLEIA.
PickupSimulo–Prototype of Intelligent Software to Support Warehouse Managers Decisions for Product Allocation Problem
Authors: Lorenc Augustyn , Lerher Tone
Published: December 2020

In this paper, a new model supporting decisions about product allocation in an order-picking shelf warehouse is presented. Industry 4.0 pays attention to inciting the processes, self-analysis and self-optimization of the short response time to market changes, and the maximum use of related data. Methods for solving the product allocation problem (PAP) are not enough to meet the requirements of Industry 4.0. The authors present a new approach for solving PAP. The novelty introduced in the model is based on correlated data—products parameters, clients’ orders and warehouse layout. The proposed model contains elements of intelligence. The model, after product classification and allocation, analyzes its effectiveness by a simulation of the order-picking process. The application of artificial neural networks (ANN) as a part of the computing model enables the analysis of large data sets in a short time. The presented study has proved the proposed model, both for practical and scientific purposes. Relying on the research results, the total warehouse cost could be reduced by 10 to 16 per cent. With the use of the proposed model, it is possible to predict the effect of future actions before their execution. The model can be implemented in most conventional warehouses to raise the throughput performance of the order-picking process.
Dynamic and Static Investigation of Ground Heat Exchangers Equipped with Internal and External Fins
Authors: Maleki Zanjani Atefeh , Gharali Kobra , Al-Haq Armughan , Nathwani Jatin
Published: December 2020

Using fins on the inner and outer surfaces of pipes is one method to improve the heat transfer rate of ground heat exchangers (GHEs), thereby reducing the borehole depth and construction and operation costs. Results of 3D numerical studies of simple and finned U-tubes with outer and inner fins are evaluated for GHEs under similar physical conditions. Dynamic and static simulations show the effects of longitudinal fins on the thermal performance of borehole heat exchangers (BHEs) and heat transfer rate between circulating fluid and soil around pipes, while the dynamic tests include short timescale and frequency response tests. The results indicate that the maximum fluid temperature change is about 2.9% in the external finned pipe and 11.3% in the internal finned pipe compared to the finless pipe. The effects of the inlet velocity on temperature profiles, the patterns of the velocity and temperature contours due to the borehole curvature and the response times of the systems under various frequencies are also investigated in detail.
The ATP-Binding Cassette (ABC) Transport Systems in Mycobacterium tuberculosis: Structure, Function, and Possible Targets for Therapeutics
Authors: Cassio Barreto de Oliveira Marcelo , Balan Andrea
Published: December 2020

Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), a disease that affects millions of people in the world and that is associated with several human diseases. The bacillus is highly adapted to infect and survive inside the host, mainly because of its cellular envelope plasticity, which can be modulated to adapt to an unfriendly host environment; to manipulate the host immune response; and to resist therapeutic treatment, increasing in this way the drug resistance of TB. The superfamily of ATP-Binding Cassette (ABC) transporters are integral membrane proteins that include both importers and exporters. Both types share a similar structural organization, yet only importers have a periplasmic substrate-binding domain, which is essential for substrate uptake and transport. ABC transporter-type importers play an important role in the bacillus physiology through the transport of several substrates that will interfere with nutrition, pathogenesis, and virulence. Equally relevant, exporters have been involved in cell detoxification, nutrient recycling, and antibiotics and drug efflux, largely affecting the survival and development of multiple drug-resistant strains. Here, we review known ABC transporters from M. tuberculosis, with particular focus on the diversity of their structural features and relevance in infection and drug resistance.
Optimization of Polyhydroxybutyrate Production by Amazonian Microalga Stigeoclonium sp. B23
Authors: Mourão Murilo Moraes , Gradíssimo Diana Gomes , Santos Agenor Valadares , Schneider Maria Paula Cruz , Faustino Silvia Maria Mathes , Vasconcelos Vitor , Xavier Luciana Pereira
Published: December 2020

The present work established the optimization and production of biodegradable thermoplastic polyhydroxybutyrate (PHB) from Amazonian microalga Stigeoclonium sp. B23. The optimization was performed in eight different growth media conditions of Stigeoclonium sp. B23, supplemented with sodium acetate and sodium bicarbonate and total deprivation of sodium nitrate. B23 was stained with Nile Red, and PHB was extracted and quantified by correlating the amount of fluorescence and biopolymer concentration through spectrofluorimetry and spectrophotometry, respectively. Our results detected the production of PHB in Stigeoclonium sp. B23 and in all modified media. Treatment with increased acetate and bicarbonate and without nitrate gave the highest concentration of PHB, while the treatment with only acetate gave the lowest among supplemented media. Our results showed a great potential of Stigeoclonium sp. B23, the first Amazonian microalga reported on PHB production. The microalga was isolated from a poorly explored and investigated region and proved to be productive when compared to other cyanobacterial and bacterial species. Additionally, microalga biomass changes due to the nutritional conditions and, reversely, biopolymer is well-synthetized. This great potential could lead to the pursuit of new Amazonian microalgae species in the search for alternative polyesters.
Alginate–Halloysite Nanocomposite Aerogel: Preparation, Structure, and Oil/Water Separation Applications
Authors: Bhagyaraj Sneha , Krupa Igor
Published: December 2020

Environmental remediation using green approaches for addressing various pollution-related issues, especially water pollution, is in high demand. Here, we designed an environmentally friendly, low-cost, and stable sodium alginate–halloysite clay composite aerogel (SAHA) for oil/water separation via a two-step synthesis procedure, including ionic crosslinking and freeze-drying. The as-prepared SAHA aerogels were characterized in detail by scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and Fourier transformation infrared (FT-IR) spectroscopy. Characterization of the SAHA aerogels revealed a three-dimensional porous microstructure with uniformly dispersed halloysite nanotubes (HA) within the alginate matrix. The elemental composition of the hydrogels investigated using energy dispersive X-ray spectrometry (EDX) revealed the presence of minerals, such as magnesium, sodium, aluminum, and silicon in the SAHA aerogels. The presence of a hydrophilic alginate matrix combined with these unique morphological characteristics resulted in SAHA aerogels with underwater oleophobicity and excellent oil/water separation efficiency (up to 99.7%). The ease of fabrication, excellent oil/water separation, and multiple performances make the SAHA aerogel an interesting candidate for practical applications in water recycling.
Response of an Existing Two-Storey RC Frame Designed for Gravity Loads: In Situ Pushover Tests and Numerical Analyses
Authors: Peloso Simone , Casarotti Chiara , Dacarro Filippo , Sinopoli Giuseppe
Published: December 2020

The purpose of the research was to study the response of existing constructions, designed for gravity loads only in the South of Italy, more precisely in the Sicily Region. The building is an existing two-story reinforced concrete structure, built in the ‘80s. In order to design the test, numerical study on the structure has been conducted, using information reported on original design drawings or derived by in situ geometric and material investigation. A number of numerical models and pushover analyses of the structure have been carried out, in order to account for the uncertainties related to possible different responses. The numerical analyses aimed at estimating the capacity of the structure in terms of both force and displacement, the ductility reserve, and the most likely sequence of formation of plastic hinges. The pseudo-static cyclic test was designed to push and pull the building in one direction at increasing displacement levels, up to a drift of about 2%. At the end of the test, the infill panels were completely collapsed. Beams, columns, and joints showed plastic hinges and shear failures in different parts of the structure, with spread spalling of the concrete. Numerical and experimental results were found in fair agreement.
Simple Electrochemical Synthesis of Polyethylenimine-Encapsulated Ag Nanoparticles from Solid AgCl Applied in Catalytic Reduction of H2O2
Authors: Kim Kyung Tae , Park Deog-Su
Published: December 2020

We report a simple and environmentally friendly synthesis of polyethylenimine (PEI)-encapsulated Ag nanoparticles (AgNPs) by a direct electroreduction of solid AgCl. The AgNPs, characterized by field-emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), and energy dispersive X-ray spectroscopy (EDS), revealed that AgNPs diameters (100–500 nm) depended on the loading of the AgCl precursor. Using cyclic voltammetry (CV), it was confirmed that the AgNPs had a catalytic effect on the electrochemical reduction of H2O2. The obtained AgNPs were subsequently used to construct an electrochemical H2O2 sensor exhibiting a low detection limit (1.66 μM) and a wide linear response range, with real-life tests indicating an insensitivity to common interferents and confirming the potential use of the developed technique in diverse applications.
The Interplay among Subunit Composition, Cardiolipin Content, and Aggregation State of Bovine Heart Cytochrome c Oxidase
Authors: Sedlák Erik , Kožár Tibor , Musatov Andrey
Published: December 2020

Mitochondrial cytochrome c oxidase (CcO) is a multisubunit integral membrane complex consisting of 13 dissimilar subunits, as well as three to four tightly bound molecules of cardiolipin (CL). The monomeric unit of CcO is able to form a dimer and participate in the formation of supercomplexes in the inner mitochondrial membrane. The structural and functional integrity of the enzyme is crucially dependent on the full subunit complement and the presence of unperturbed bound CL. A direct consequence of subunit loss, CL removal, or its oxidative modification is the destabilization of the quaternary structure, loss of the activity, and the inability to dimerize. Thus, the intimate interplay between individual components of the complex is imperative for regulation of the CcO aggregation state. While it appears that the aggregation state of CcO might affect its conformational stability, the functional role of the aggregation remains unclear as both monomeric and dimeric forms of CcO seem to be fully active. Here, we review the current status of our knowledge with regard to the role of dimerization in the function and stability of CcO and factors, such as subunit composition, amphiphilic environment represented by phospholipids/detergents, and posttranslational modifications that play a role in the regulation of the CcO aggregation state.
Comparative Study of Senescent Th Biomarkers in Healthy Donors and Early Arthritis Patients. Analysis of VPAC Receptors and Their Influence
Authors: Villanueva-Romero Raúl , Lamana Amalia , Flores-Santamaría Marissa , Carrión Mar , Pérez-García Selene , Triguero-Martínez Ana , Tomero Eva , Criado Gabriel , Pablos José L. , González-Álvaro Isidoro , Martínez Carmen , Juarranz Yasmina , Gomariz Rosa P. , Gutiérrez-Cañas Irene
Published: December 2020

Pro-inflammatory CD4+CD28− T cells are characteristic of immunosenescence, but also of several autoimmune/inflammatory diseases. Vasoactive intestinal peptide (VIP) acts as an anti-inflammatory and immunomodulatory mediator on these cells. Our objective was to study the mutual influence between senescent Th cells and VIP axis in early arthritis (EA), comparing with non-EA donors. We characterized the correlation between senescent Th cells and clinic parameters of EA as well as the behavior of senescent Th biomarkers by real-time PCR. Clinical data were systematically recorded at baseline and after 6 months of follow-up. The number of CD4+CD28− T cells measured by sorting is higher in patients who initially meet ACR classification criteria for rheumatoid arthritis (RA) compared to those who were classified as undifferentiated arthritis (UA). A slight positive correlation between EA CD4+CD28− T cells and CRP or ESR and a negative correlation with bone mineral density were found. Th senescent biomarkers in EA CD4+CD28− T cells were similar to donors, however some of them increased after 6 months of follow-up. VPAC receptors were analyzed by real-time PCR and immunofluorescence, and CD4+CD28− T cells showed higher expression of VPAC2 and lower of VPAC1, VPAC2 showing a significant increased expression in EA cells. Sorted CD4+CD28− T cells were in vitro expanded in presence of VIP, wherein VIP increased senescent biomarker CD27, while it diminished CD57 or NKG2 senescent biomarkers. Our study demonstrates for the first time the existence of a link between senescent Th cells and the VIP axis.
Sex Hormone-Binding Globulin Is Associated with Obesity and Dyslipidemia in Prepubertal Children
Authors: Park Gihong , Song Kyungchul , Choi Youngha , Oh Jun Suk , Choi Han Saem , Suh Junghwan , Kwon Ahreum , Kim Ho-Seong , Chae Hyun Wook
Published: December 2020

Sex hormone-binding globulin (SHBG) is associated with age, sex, and puberty. The association of SHBG with various diseases has been suggested nowadays, however, the relationships in prepubertal children have not been sufficiently investigated. This study analyzed the relationship of SHBG with body mass index (BMI) and plasma lipid levels in prepubertal children. We evaluated the association of SHBG with BMI among the 693 prepubertal children subdivided into normal, overweight, and obese groups, with plasma lipid levels among the children subdivided into normal and dyslipidemia groups. The obese and overweight group had lower SHBG levels than the normal BMI group in both sexes. The dyslipidemia group included subjects with low high-density lipoprotein cholesterol (HDL-C), high triglycerides (TG), or a high atherogenic index of plasma (AIP); this group had lower SHBG than the normal lipid group. SHBG was positively correlated with HDL-C, and negatively correlated with TG and AIP. After adjusting for BMI, SHBG was positively correlated with HDL-C and negatively correlated with TG and AIP in all groups. In conclusion, SHBG levels are closely correlated with BMI in prepubertal children. SHBG may play a meaningful role in the decrease in HDL-C and increase in TG during prepubertal age.
Executive Functioning in Adolescents with Chronic Musculoskeletal Pain
Authors: Jastrowski Mano Kristen E. , Beckmann Emily A. , Fussner Lauren M. , Kashikar-Zuck Susmita
Published: December 2020

Adolescents with chronic pain often suffer significant impairment in physical, emotional, and social domains. Surprisingly little is known about executive functioning (EF) in youth with chronic pain or how EF deficits may contribute to functional impairment. Study participants included 60 adolescents between the ages of 12 and 17 years (M = 14.57). Thirty participants with chronic musculoskeletal pain and 30 age- and gender-matched healthy controls were recruited from a large Midwestern children’s hospital in the United States. Participants completed the Behavior Rating Inventory of Executive Functioning (BRIEF-2) as well as multiple measures of functional impairment across key domains: school, social, emotional (anxiety, depression), and physical. Adolescents with chronic musculoskeletal pain reported significantly greater EF impairment compared to healthy age- and gender-matched peers. Clinically elevated risk levels of impairment were reported across all aspects of EF, with many adolescents in the chronic pain group scoring above the clinical risk cut off for working memory (52%), inhibition (45%), and cognitive flexibility (38%). EF was also significantly related to functional impairment across all domains. Findings suggest that EF may have an impact across several critical domains of functioning for youth with chronic pain.
Studies on the Oxidation Behavior of a Designed Nanocrystalline Coating on K38 Alloy at 1050 °C
Authors: Wang Jinlong , Meng Bo , Sun Wenyao , Yang Lanlan , Chen Minghui , Wang Fuhui
Published: December 2020

A new framework for a nanocrystalline coating system is established and prepared to study the oxidation behavior with a significant difference in elemental composition. K38 superalloy is selected as a substrate alloy and the composition of the 2nd-generation single-crystal superalloy Rene N5 is used as the sputtered nanocrystalline coating. The oxidation behavior of the newly designed nanocrystalline coating is comparatively studied with the original K38 coating and its substrate alloy at 1050 °C for 500 h. Moreover, microstructure evolution on the interface is used for studying the influence of element interdiffusion behavior on the substrate alloy. Results show that the nanocrystalline coatings increase the oxidation performance of alloys at 1050 °C for 100 h. The sputtered SN-N5 nanocrystalline coating exhibits the best oxidation resistance among the three groups of specimens for 500 h. Interdiffusion occurred and is observed on the SN-N5 coating after long-term oxidation. However, no topologically close-packed phases participated in the substrate alloy.
How Can Flipped Classroom Approach Support the Development of University Students’ Working Life Skills?—University Teachers’ Viewpoint
Authors: Väisänen Sanna , Hirsto Laura
Published: December 2020

Higher education students need both generic skills and field-specific knowledge in order to cope with the diverse demands of working life. The aim of this study was to gain a better understanding of the development of university students’ working life skills and of how these skills can be developed in learning environments utilizing the flipped classroom approach. The focus was on the experiences and thoughts of higher education teachers concerning which learning environment features support the development of working life skills. Altogether, 22 higher education teachers from a Finnish university were interviewed with semistructured interviews, and the data was subjected to content analysis. The results indicated that teachers identified several generic and field-specific working life skills, the most important of which were collaboration, communication, information literacy, and skills related to career and responsibilities. The flipped classroom appeared to support students’ active role and facilitate versatile ways of learning. Especially, cooperative and active learning were identified to be the key means to support the development of students’ working life skills in flipped classroom environments. Facilitating students’ opportunities to develop their working life skills can be seen as an integral part of flipped classroom environments in many ways. However, it is important that the opportunities are actively promoted, and conceptual and practical tools are provided for the student through university studies.
Traffic Steering for eMBB in Multi-Connectivity Scenarios
Authors: Burgueño Jesús , de-la-Bandera Isabel , Palacios David , Barco Raquel
Published: December 2020

Multi-connectivity (MC) is one of the most important features to be introduced in 5G networks, allowing User Equipment (UE) to simultaneously aggregate radio resources from several network nodes to enhance both data rates and reliability. Thus, this feature enables a further flexibility in the allocation of resources to the UEs in order to fulfil the users’ requirements in more complex 5G scenarios. This paper takes advantage of this wide flexibility to present a traffic steering approach that determines the amount of traffic to be held by each of the serving nodes in a multi-connectivity scenario. In this sense, the proposed technique is based on network and UE performance metrics in order to maximize the users’ perceived quality of experience (QoE) for enhanced Mobile Broadband (eMBB) services. It is then compared with a homogeneous traffic split among the serving nodes, with a single-connectivity approach and with state-of-the-art solutions. The benefits are analysed in terms of throughput and Mean Opinion Score (MOS), which is the main QoE metric. The analysis shows that a noticeable UE throughput improvement is reached when the proposed traffic steering method is applied. Consequently, this enhancement is noticed in the users’ QoE, which can lead to a reduction of operating expenses (OPEX) of the network.
FPGA-Based Reliable Fault Secure Design for Protection against Single and Multiple Soft Errors
Authors: Shaker Manar N. , Hussien Ahmed , Alkady Gehad I. , Amer Hassanein H. , Adly Ihab
Published: December 2020

Field programmable gate arrays (FPGAs) are increasingly used in industry (e.g., biomedical, space, and automotive industries). FPGAs are subjected to single, as well as multiple event upsets (SEUs and MEUs), due to the continuous shrinking of transistor dimensions. These upsets inevitably decrease system lifetime. Fault-tolerant techniques are often used to mitigate these problems. In this research, penta and hexa modular redundancy, as well as dynamic partial reconfiguration (DPR), are used to increase system reliability. We show, depending on the relative rates of the SEUs and MEUs, that penta modular redundancy has a higher reliability than hexa modular redundancy, which is a counter-intuitive result in some cases since increasing redundancy is expected to increase reliability. Focusing on penta modular redundancy, an error detection and recovery mechanism (voter) is designed. This mechanism uses the internal configuration access port (ICAP) and its associated controller, as well as DPR to mitigate SEUs and MEUs. Then, it is implemented on Xilinx Vivado tools targeting the Kintex7 7k410tfbg676 device. Finally, we show how to render this design fault secure in the event that SEUs or MEUs affect the voter itself. This fault secure voter either produces the correct output or gives an indication that the output is incorrect.
Case Studies Demonstrate That Common Carp Can Be Sustainably Reduced by Exploiting Source-Sink Dynamics in Midwestern Lakes
Authors: Sorensen Peter W. , Bajer Przemyslaw G.
Published: December 2020

The common carp has been highly problematic in North American ecosystems since its introduction over a century ago. In many watersheds, its abundance appears to be driven by source-sink dynamics in which carp reproduce successfully in peripheral ponds that lack egg/larva micro-predators which then serve as sources of recruits for deeper lakes. This manuscript describes how carp were sustainably reduced in two chains of lakes by disrupting source-sink dynamics in three steps. First, we ascertained whether lakes had problematic densities of carp that could be explained by source-sink dynamics. Second, ways to control recruitment were developed and implemented including: (i) aerating source ponds to reduce hypoxia and increase micro-predator abundance, (ii) blocking carp migration, and (iii) locating and removing adults from sinks using targeted netting guided by Judas fish. Third, we monitored and adapted. Using this strategy, the density of carp in 3 lakes in one chain was reduced from 177 kg/ha to ~100 kg/ha in 3 years and held constant for a decade. Similarly, adult density was reduced from 300 kg carp/ha in 2 lakes in the other chain to 25 kg/ha. Once carp densities were low, aluminum sulfate treatments became reasonable and once conducted, water quality improved.
The Impact of COVID-19 on Women’s Physical Activity Behavior and Mental Well-Being
Authors: Nienhuis Carl P. , Lesser Iris A.
Published: December 2020

Background: A global pandemic caused by COVID-19 resulted in restrictions to daily living for Canadians, including social distancing and closure of recreation facilities and provincial parks. Methods: The objective of this study was to assess whether sex differences exist in physical activity and well-being since COVID-19 and to explore how barriers or facilitators to physical activity may explain these differences. Chi-square tests, independent t-tests and one-way ANOVAs were conducted to evaluate data provided by 1098 Canadians—215 men and 871 women. Results: Women were significantly less physically active than men and reported more barriers and fewer facilitators to physical activity and experienced significantly more generalized anxiety than men. Women who were engaged in less physical activity due to COVID-19 reported significantly lower mental health scores, lower social, emotional and psychological well-being, and significantly higher generalized anxiety, while women who engaged in more physical activity had improved mental health scores. Conclusions: Given the challenges that women uniquely face due to restrictions, it is imperative to advocate and provide environmental opportunity and support for physical activity to reduce the mental duress women may be experiencing. Specific physical activity programming that is inclusive of lifestyle physical activity and can engage children is encouraged.