bluuebunny/crossref_metadata_2025 huggingface dataset:
Lean Construction Concept Used to Develop Infrastructure Facilities for Tourism Clusters
Authors: Orlov Alexandr K. , Kankhva Vadim S.
Published: December 2021

The relevance of the article is conditioned on tourist infrastructure problems and underdevelopment when creating and developing territorial clusters, for which there is not enough research materials in the context of tourism cluster facilities construction, despite the fact that the issues of lean construction (LC) are widely covered. Based on the relevance, the main hypothesis of the study was determined. It consists of the fact that the use of lean construction can increase the efficiency of construction megaprojects in the field of tourism clusters. The objective of this study is to develop a mechanism for the development of tourism clusters based on the lean construction concept that will be aimed at increasing the efficiency of construction projects taking into account the accumulated world experience. Within the framework of the tasks set, the analysis of the lean construction methodological base was carried out, methodological recommendations aimed at increasing the efficiency of construction megaprojects of tourism clusters based on the lean construction concept were developed, a model for the implementation of lean construction in infrastructure projects of tourism clusters, as well as a checklist of the analysis technology were elaborated. The proposed methodological approach to the implementation of tourism cluster megaprojects based on the lean construction concept is the basis for organizing and planning development activities at the tactical and operational levels. To assess the effectiveness of lean construction tool introduction to implement infrastructure projects of tourism clusters, a comparative analysis was carried out and the construction time and lifecycle cost of a typical guest house were calculated without taking into account the lean construction methodology and after its introduction. The results obtained, namely, the duration of the project and costs at life cycle stages made it possible to conclude that the proposed methodological approach is effective.
The Carcinogenic Effects of Formaldehyde Occupational Exposure: A Systematic Review
Authors: Protano Carmela , Buomprisco Giuseppe , Cammalleri Vittoria , Pocino Roberta Noemi , Marotta Daniela , Simonazzi Stefano , Cardoni Francesca , Petyx Marta , Iavicoli Sergio , Vitali Matteo
Published: December 2021

Background: Formaldehyde, classified as a carcinogen in 2004, as of today is widely used in many work activities. From its classification, further studies were performed to evaluate its carcinogenicity. The aim of the systematic review is to update the evidence on occupational exposure to formaldehyde and cancer onset. Methods: The review, in accordance with the PRISMA statement, includes articles in English reporting original results of studies conducted on workers exposed to formaldehyde, considering all types of cancer, published from 1 January 2000 to 30 July 2021 and selected from the Pubmed and Scopus databases. The studies’ quality was assessed by the Newcastle–Ottawa Scale. Results: A total of 21 articles were included, conducted in different European, American, and Asian countries. The most investigated occupational areas are those characterized by a deliberate use of formaldehyde. Some studies evaluated all types of cancer, whereas others focused on specific sites such as thyroid and respiratory, lymphohematopoietic, or central nervous systems. The results showed weak associations with lung cancer, nasopharyngeal cancer, leukemia, and non-Hodgkin’s lymphoma. Conclusions: The results demonstrate the need for further original studies carried out on representative samples of workers exposed to measured levels of FA. These studies should be designed to reduce the bias due to co-exposure to other carcinogens.
Ubiquitin Activating Enzyme UBA6 Regulates Th1 and Tc1 Cell Differentiation
Authors: Lee Ji Yeon , An Eun-Koung , Hwang Juyoung , Jin Jun-O. , Lee Peter C. W.
Published: December 2021

Ubiquitination is a crucial mechanism in regulating the immune response, setting the balance between immunity and tolerance. Here, we investigated the function of a poorly understood alternative branch of the ubiquitin-activating E1 enzyme UBA6 in activating immune cells. UBA6 expression levels were elevated in T cells by toll-like receptor agonists and anti-CD3/28 antibody stimulation, but not in dendritic cells, macrophages, B cells, and natural killer cells. Additionally, we generated T cell-specific UBA6-deficient mice and found that UBA6-deficient CD4 and CD8 T cells elevated the production of interferon-gamma (IFN-γ). Moreover, the transfer of UBA6-deficient CD4 and CD8 T cells in RAG1-knockout mice exacerbated the development of multi-organ inflammation compared with control CD4 and CD8 T cell transfer. In human peripheral blood CD4 and CD8 T cells, basal levels of UBA6 in lupus patients presented much lower than those in healthy controls. Moreover, the IFN-γ production efficiency of CD4 and CD8 T cells was negatively correlated to UBA6 levels in patients with lupus. Finally, we found that the function of UBA6 was mediated by destabilization of IκBα degradation, thereby increasing NF-κB p65 activation in the T cells. Our study identifies UBA6 as a critical regulator of IFN-γ production in T cells by modulating the NF-κB p65 activation pathway.
In Silico Design of Dual-Binding Site Anti-Cholinesterase Phytochemical Heterodimers as Treatment Options for Alzheimer’s Disease
Authors: Amat-ur-Rasool Hafsa , Ahmed Mehboob , Hasnain Shahida , Ahmed Abrar , Carter Wayne Grant
Published: December 2021

The number of patients with neurodegenerative diseases, particularly Alzheimer’s disease (AD), continues to grow yearly. Cholinesterase inhibitors (ChEIs) represent the first-line symptomatic drug treatment for mild-to-moderate AD; however, there is an unmet need to produce ChEIs with improved efficacy and reduced side effects. Herein, phytochemicals with reported anti-acetylcholinesterase (AChE) activity were ranked in silico for their anti-AChE potential. Ligands with a similar or higher binding affinity to AChE than galantamine were then selected for the design of novel dual-binding site heterodimeric drugs. In silico molecular docking of heterodimers with the target enzymes, AChE and butyrylcholinesterase (BuChE), were performed, and anti-cholinesterase binding affinities were compared with donepezil. Drug-likeliness properties and toxicity of the heterodimers were assessed using the SwissADME and ProTox-II webservers. Nine phytochemicals displayed similar or higher binding affinities to AChE than galantamine: sanguinarine > huperzine A > chelerythrine > yohimbine > berberine > berberastine > naringenin > akuammicine > carvone. Eleven heterodimeric ligands were designed with phytochemicals separated by four- or five-carbon alkyl-linkers. All heterodimers were theoretically potent AChE and BuChE dual-binding site inhibitors, with the highest affinity achieved with huperzine-4C-naringenin, which displayed 34% and 26% improved affinity to AChE and BuChE, respectively, then the potent ChEI drug, donepezil. Computational pharmacokinetic and pharmacodynamic screening suggested that phytochemical heterodimers would display useful gastrointestinal absorption and with relatively low predicted toxicity. Collectively, the present study suggests that phytochemicals could be garnered for the provision of novel ChEIs with enhanced drug efficacy and low toxicity.
Recovery Signals of Rhodoliths Beds since Bottom Trawling Ban in the SCI Menorca Channel (Western Mediterranean)
Authors: Farriols Maria Teresa , Irlinger Camille , Ordines Francesc , Palomino Desirée , Marco-Herrero Elena , Soto-Navarro Javier , Jordà Gabriel , Mallol Sandra , Díaz David , Martínez-Carreño Natalia , Díaz Julio A. , Fernandez-Arcaya Ulla , Joher Sergi , Ramírez-Amaro Sergio , R. de la Ballina Nuria , Vázquez Juan-Tomás , Massutí Enric
Published: December 2021

One of the objectives of the LIFE IP INTEMARES project is to assess the impact of bottom trawling on the vulnerable benthic habitats of the circalittoral bottoms of the Menorca Channel (western Mediterranean), designated a Site of Community Importance (SCI) within the Natura 2000 network. The present study compares the epibenthic communities of four areas, subjected to different bottom trawl fishing intensity levels. The assignment of fishing effort levels was based on the fishing effort distribution in the area calculated from Vessel Monitoring System (VMS) data and the existence of two Fishing Protected Zones in the Menorca Channel. Biological samples were collected from 39 beam trawl stations, sampled during a scientific survey on April 2019. We compare the diversity, composition, and density of the epibenthic flora and fauna, together with the rhodoliths coverage and the morphology of the main species of rhodoliths of four areas subjected to different levels of bottom trawl fishing effort, including one that has never been impacted by trawling. Our results have shown negative impacts of bottom trawling on rhodoliths beds and the first signals of their recovery in areas recently closed to this fishery, which indicate that this is an effective measure for the conservation of this habitat of special interest and must be included in the management plan required to declare the Menorca Channel as a Special Area of Conservation.
High Diversity and Abundance of Foraminifera Associated with Mediterranean Benthic Red Algae Mats
Authors: Rossbach Felix Ivo , Merk Benedikt , Wild Christian
Published: December 2021

The Mediterranean Sea comprises habitats such as Posidonia oceanica seagrass meadows that exhibit high associated biodiversity of sessile organisms. Recent pilot research indicates that benthic mats formed by the scarcely investigated fleshy red alga Phyllophora crispa also host a high diversity of benthic fauna. Among the key taxa found in these mats in the recent pilot studies are benthic foraminifera that live as epiphytes on the red algae thalli. Knowledge about their abundance and species richness associated with this habitat in relation to reference habitats is missing. We thus carried out a comparative assessment focusing on foraminifera within samples from P. crispa mats and neighboring P. oceanica meadows on five different sampling sites around Giglio Island in the Tuscan Archipelago (Tyrrhenian Sea, Italy). A total of 104 different foraminiferal taxa were identified, of which a total of 85 taxa were found in P. crispa samples (46 exclusively in this habitat). This biodiversity was higher compared to other studies on phytal habitats in the Mediterranean Sea. The number of foraminiferal taxa associated with P. crispa was significantly higher (average 27.5 ± 8.1 taxa) compared to P. oceanica (leaves average 7.0 ± 3.6, shoots average 7.9 ± 3.4 taxa). The abundance of foraminifera (12,000 individuals m−2 surface area of P. crispa mat) was also higher than in the neighboring P. oceanica meadows (7792 individuals m−2 leaf and 8171 individuals m−2 shoot surface area). The most frequently found taxa across habitats were Miniacina miniacea, Lobatula lobatula, and Sejunctella sp. (24%, 20%, and 6% of the total population, respectively). Our results imply that P. crispa mats host an exceptional diversity of associated foraminifera that is even higher than those associated with seagrass meadows. Red algae mats built by P. crispa may thus be considered as potential refuge habitats and biodiversity reservoirs in management and conservation.
Switching to a Bictegravir Single Tablet Regimen in Elderly People Living with HIV-1: Data Analysis from the BICTEL Cohort
Authors: Lazzaro Alessandro , Cacciola Elio Gentilini , Borrazzo Cristian , Innocenti Giuseppe Pietro , Cavallari Eugenio Nelson , Mezzaroma Ivano , Falciano Mario , Fimiani Caterina , Mastroianni Claudio Maria , Ceccarelli Giancarlo , d’Ettorre Gabriella
Published: December 2021

Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single tablet regimen for the treatment of people living with HIV-1 (PLWH). We aimed to assess efficacy, safety and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Thus, we recruited an observational retrospective real-life cohort including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the provenience treatment regimen. After 48 weeks of follow-up, 147 PLWH were included and 93 were older than 55 years. PLWH with HIV-RNA < 37 copies/mL increased from 140 to 146 (p < 0.033). Among the overall population, we observed an increase in CD4+ T cells count by 30.1% (p-value < 0.001), in CD8+ T cells count by 7.1% (p-value = 0.004) and in CD4+/CD8+ ratio by 21.5% (p-value < 0.001). Lipidic profile was characterized by decreasing total cholesterol/HDL ratio by 8% (p-value < 0.001) and LDL by 6.8% (p-value = 0.007). Total body weight increased by 1.8% (p-value = 0.014) and BMI by 4.2% (p-value < 0.001), even remaining within the healthy range. Hepatic and renal profile were not altered by the switch, nor were adverse events and/or discontinuations events detected. In conclusion, BIC/FTC/TAF is effective, safe and well tolerated in real life and among PLWH older than 55.
Implementation of a DPU-Based Intelligent Thermal Imaging Hardware Accelerator on FPGA
Authors: Hussein Abdelrahman S. , Anwar Ahmed , Fahmy Yasmine , Mostafa Hassan , Salama Khaled Nabil , Kafafy Mai
Published: December 2021

Thermal imaging has many applications that all leverage from the heat map that can be constructed using this type of imaging. It can be used in Internet of Things (IoT) applications to detect the features of surroundings. In such a case, Deep Neural Networks (DNNs) can be used to carry out many visual analysis tasks which can provide the system with the capacity to make decisions. However, due to their huge computational cost, such networks are recommended to exploit custom hardware platforms to accelerate their inference as well as reduce the overall energy consumption of the system. In this work, an energy adaptive system is proposed, which can intelligently configure itself based on the battery energy level. Besides achieving a maximum speed increase that equals 6.38×, the proposed system achieves significant energy that is reduced by 97.81% compared to a conventional general-purpose CPU.
Travel Time Prediction and Explanation with Spatio-Temporal Features: A Comparative Study
Authors: Ahmed Irfan , Kumara Indika , Reshadat Vahideh , Kayes A. S. M. , van den Heuvel Willem-Jan , Tamburri Damian A.
Published: December 2021

Travel time information is used as input or auxiliary data for tasks such as dynamic navigation, infrastructure planning, congestion control, and accident detection. Various data-driven Travel Time Prediction (TTP) methods have been proposed in recent years. One of the most challenging tasks in TTP is developing and selecting the most appropriate prediction algorithm. The existing studies that empirically compare different TTP models only use a few models with specific features. Moreover, there is a lack of research on explaining TTPs made by black-box models. Such explanations can help to tune and apply TTP methods successfully. To fill these gaps in the current TTP literature, using three data sets, we compare three types of TTP methods (ensemble tree-based learning, deep neural networks, and hybrid models) and ten different prediction algorithms overall. Furthermore, we apply XAI (Explainable Artificial Intelligence) methods (SHAP and LIME) to understand and interpret models’ predictions. The prediction accuracy and reliability for all models are evaluated and compared. We observed that the ensemble learning methods, i.e., XGBoost and LightGBM, are the best performing models over the three data sets, and XAI methods can adequately explain how various spatial and temporal features influence travel time.
DuckCore: A Fault-Tolerant Processor Core Architecture Based on the RISC-V ISA
Authors: Li Jiemin , Zhang Shancong , Bao Chong
Published: December 2021

With the development of large-scale CMOS-integrated circuit manufacturing technology, microprocessor chips are more vulnerable to soft errors and radiation interference, resulting in reduced reliability. Core reliability is an important element of the microprocessor’s ability to resist soft errors. This paper proposes DuckCore, a fault-tolerant processor core architecture based on the free and open instruction set architecture (ISA) RISC-V. This architecture uses improved SECDED (single error correction, double error detection) code between pipelines, detects processor operating errors in real-time through the Supervision unit, and takes instruction rollbacks for different error types, which not only saves resources but also improves the reliability of the processor core. In the implementation process, all error injection tests are passed to verify the completeness of the function. In order to better verify the performance of the processor under different error intensity injections, the software is used to inject errors, the running program is run on the FPGA (Field Programmable Gate Array), and the impact of the actual radiation environment on the architecture is evaluated through the results. The architecture is applied to three–five-stage open-source processor cores and the results show that this method consumes fewer resources and its discrete design makes it more portable.
Studies on the Impact of Hydrogen on the Results of THT Measurement Devices
Authors: Huszal Anna , Jaworski Jacek
Published: December 2021

An essential prerequisite for safe transport and use of natural gas is their appropriate odorization. This enables the detection of uncontrolled gas leaks. Proper and systematic odorization inspection ensures both safe use of gas and continuity of the process itself. In practice, it is conducted through, among others, measuring odorant concentrations in gas. Control devices for rapid gas odorization measurements that are currently used on a large scale in the gas industry are equipped with electrochemical detectors selective for sulfur compounds like tetrahydrothiophene (THT). Because the selectivity of electrochemical detector response to one compound (e.g., THT), the available declarations of manufacturers show that detector sensitivity (indirectly also the quality of the measurement result) is influenced by the presence of increased e.g., sulfur or hydrogen compound content in the gas. Because of the lack of sufficient source literature data in this field, it was necessary to experimentally verify this impact. The results of studies on experimental verification of suspected influence of increased amounts of hydrogen in gas on the response of electrochemical detector was carried out at the Oil and Gas Institute—National Research Institute (INiG—PIB). They are presented in this article. The data gathered in the course of researching the dependence between THT concentration measurement result quality and hydrogen content in gas composition enabled a preliminary assessment of the threat to the safety of end users of gaseous fuels caused by the introduction of this gas into the distribution network. Noticing the scope of necessary changes in the area of odorization is necessary to guarantee this safety.
Analysis of the Influence of Motors Installed in Passenger Car Wheels on the Torsion Beam of the Rear Axle Suspension
Authors: Dukalski Piotr , Będkowski Bartłomiej , Parczewski Krzysztof , Wnęk Henryk , Urbaś Andrzej , Augustynek Krzysztof
Published: December 2021

The influence of mounting motors in wheels’ hubs and flexibility of the twist beam rear suspension on their dynamics and strength is presented in the paper. The international roughness indicator (IRI) is applied to assess the overcoming of road unevenness. This indicator is a combination of a shape of the road unevenness and of overcoming velocity. The movement of a wheel’s axis during obstacles overcoming is described. For the needs of the dynamics analysis, the mathematical model of the rear suspension system with embedded motors is developed using the MSC.Adams-ANSYS interface. The discrete model of the twist beam is prepared in the ANSYS software, which is used in the next step to construct the dynamics model of the rear suspension system using the MSC.Adams program. The vertical components of displacement and acceleration of the wheel’s centre, forces in the suspension’s springs and dampers, as well as forces in the joints are analyzed. The analysis of the suspension beam’s stress during the road unevenness overcoming is also carried out.
Electrothermal Model of Coupled Inductors with Nanocrystalline Cores
Authors: Detka Kalina , Górecki Krzysztof
Published: December 2021

The paper proposes a new electrothermal model of a coupled inductor containing a nanocrystalline core dedicated to the analysis of electrical energy conversion systems. The formulated model has a form of a subcircuit for SPICE. The model takes into account the influence of direct current, frequency, skin effect, temperature, self-heating, and mutual thermal couplings on the parameters and characteristics of the coupled inductors. The form of the developed model and the method of model parameter estimation are presented. The applied measuring system is presented. The results of measurements and calculations made with the use of the proposed model are presented and commented on.
Parks and Recreational Areas as Sinks of Plastic Debris in Urban Sites: The Case of Light-Density Microplastics in the City of Amsterdam, The Netherlands
Authors: Cohen Quirine M. , Glaese Mae , Meng Ke , Geissen Violette , Huerta-Lwanga Esperanza
Published: December 2021

Soils of parks and recreational areas are potential sinks of microplastics because they are under multifunctional use. The aims of this research were to quantify and determine the types and abundance of light-density microplastics in one of the most cosmopolitan cities of the world: Amsterdam, The Netherlands. Therefore, potential differences between the city districts were explored through the assessment of light-density microplastics’ concentrations in soils together with the soil properties. Microplastics were extracted from 74 soil samples. Predictions of microplastic concentrations and soil characteristics were made for the entire city by using ordinary kriging; 97% of the samples contained microplastic particles (MPPs), and on average, there were 4825.31 ± 6513.85 MPP/kg soil. A total of 21 hotspot samples were identified, and all of them contained LDPE, which represented 40.82% of the plastic types, in addition to 35.06% PAC and 15.58% natural polyamide. Other types of plastics were PP (0.19%), PS (1.30%), bioplastic (0.19%), PA (0.37%), PU (0.56), PVC (0.19%), and unidentified plastics (0.19%). There were no significant differences in MPP concentration between city districts. Our results showed that MPPs are abundant in urban soils, which represents a high risk for soil life. Further studies are required for identifying the sources of this pollution.
Degradation of White Birch Shelterbelts by the Attack of White-Spotted Longicorn Beetles in Central Hokkaido, Northern Japan
Authors: Masaka Kazuhiko , Wakita Yohichi , Iwasaki Kenta , Hayamizu Masato
Published: December 2021

A widespread decline of white birch (Betula platyphylla var. japonica) shelterbelts was observed in central Hokkaido, Japan. Many exit holes bored by white-spotted longicorn beetles (Anoplophora malasiaca) were found at the base of the trunks of trees in these stands. The present study aims to evaluate the effects of infestation on the degradation, and demonstrates whether the number of exit holes (Nholes) can be used as an index of the decline of trees. We selected 35 healthy appearing stands and 16 degraded stands in the study area. A generalized linear mixed model with zero inflation revealed that Nholes of standing dead trees tended to be greater than that of living trees, and the tree vigor decreased with increasing Nholes. These results implied that the degradation of the shelterbelts was caused by the beetle. We also found size-dependent mortality, i.e., only a few larvae can cause the death of smaller trees, but not larger trees. Furthermore, evaluation of the degradation at the stand level (Nholes) using a logistic regression analysis revealed that the degradation at the stand level could be predicted by Nholes. Our findings can be used as a useful index marker for diagnosing white birch shelterbelts.
A Framework of Runge–Kutta, Discontinuous Galerkin, Level Set and Direct Ghost Fluid Methods for the Multi-Dimensional Simulation of Underwater Explosions
Authors: Si Nan , Brown Alan
Published: December 2021

This work describes the development of a hybrid framework of Runge–Kutta (RK), discontinuous Galerkin (DG), level set (LS) and direct ghost fluid (DGFM) methods for the simulation of near-field and early-time underwater explosions (UNDEX) in early-stage ship design. UNDEX problems provide a series of challenging issues to be solved. The multi-dimensional, multi-phase, compressible and inviscid fluid-governing equations must be solved numerically. The shock front in the solution field must be captured accurately while maintaining the total variation diminishing (TVD) properties. The interface between the explosive gas and water must be tracked without letting the numerical diffusion across the material interface lead to spurious pressure oscillations and thus the failure of the simulation. The non-reflecting boundary condition (NRBC) must effectively absorb the wave and prevent it from reflecting back into the fluid. Furthermore, the CFD solver must have the capability of dealing with fluid–structure interactions (FSI) where both the fluid and structural domains respond with significant deformation. These issues necessitate a hybrid model. In-house CFD solvers (UNDEXVT) are developed to test the applicability of this framework. In this development, code verification and validation are performed. Different methods of implementing non-reflecting boundary conditions (NRBCs) are compared. The simulation results of single and multi-dimensional cases that possess near-field and early-time UNDEX features—such as shock and rarefaction waves in the fluid, the explosion bubble, and the variation of its radius over time—are presented. Continuing research on two-way coupled FSI with large deformation is introduced, and together with a more complete description of the direct ghost fluid method (DGFM) in this framework will be described in subsequent papers.
Implementation of an Advance Care Planning Inventory and Its Possible Effect on Quality of Dying: A Nationwide Cross-Sectional Study in Group Homes for Persons with Dementia in Japan
Authors: Takada Seira , Ogata Yasuko , Yumoto Yoshie , Ikeda Masaomi
Published: December 2021

This study aimed to develop an inventory for advance care planning implementation for persons with dementia in group homes and to examine the association between inventory implementation and residents’ quality of dying. A nationwide cross-sectional study was conducted via questionnaires mailed from 2000 group homes in Japan, selected through stratified random sampling. Participants were managers and care planners who had provided end-of-life care for recently deceased residents. The newly developed inventory was used to assess advance care planning implementation for persons with dementia, and the Quality of Dying in Long-term Care Scale was used to evaluate quality of dying. The valid response rate was 28.5% (n = 569). The factor structure of the newly developed Advance Care Planning Practice Inventory and the association between its implementation and quality of dying were verified using factor analysis and internal consistency, and logistic regression, respectively. The composite score and the factor score of the newly developed inventory were significantly associated with quality of dying (p < 0.05). The implementation of advance care planning improves the quality of dying. These findings can be used in development of educational programs, as well as research on advance care planning for care providers.
An Integration Method for Regional PM2.5 Pollution Control Optimization Based on Meta-Analysis and Systematic Review
Authors: Qiu Bingkui , Zhou Min , Qiu Yang , Ma Yuxiang , Ma Chaonan , Tu Jiating , Li Siqi
Published: December 2021

PM2.5 pollution in China is becoming increasingly severe, threatening public health. The major goal of this study is to evaluate the mortality rate attributed to PM2.5 pollution and design pollution mitigation schemes in a southern district of China through a two-objective optimization model. The mortality rate is estimated by health effect evaluation model. Subjected to limited data information, it is assumed that the meta-analysis method, through summarizing and combining the research results on the same subject, was suitable to estimate the percentage of deaths caused by PM2.5 pollution. The critical parameters, such as the total number of deaths and the background concentration of PM2.5, were obtained through on-site survey, data collection, literature search, policy analysis, and expert consultation. The equations for estimating the number of deaths caused by PM2.5 pollution were established by incorporating the relationship coefficient of exposure to reaction, calculated residual PM2.5 concentration of affected region, and statistical total base number of deaths into a general framework. To balance the cost from air quality improvement and human health risks, a two-objective optimization model was developed. The first objective is to minimize the mortality rate attributable to PM2.5 pollution, and the second objective is to minimize the total system cost over three periods. The optimization results demonstrated that the combination of weights assigned to the two objectives significantly influenced the model output. For example, a high weight value assigned to minimizing the number of deaths results in the increased use of treatment techniques with higher efficiencies and a dramatic decrease in pollutant concentrations. In contrast, a model weighted more toward minimizing economic loss may lead to an increase in the death toll due to exposure to higher air pollution levels. The effective application of this model in the Nanshan District of Shenzhen City, China, is expected to serve as a basis for similar work in other parts of the world in the future.
An Open-Source Workflow for Spatiotemporal Studies with COVID-19 as an Example
Authors: Malarvizhi Anusha Srirenganathan , Liu Qian , Sha Dexuan , Lan Hai , Yang Chaowei
Published: December 2021

Many previous studies have shown that open-source technologies help democratize information and foster collaborations to enable addressing global physical and societal challenges. The outbreak of the novel coronavirus has imposed unprecedented challenges to human society. It affects every aspect of livelihood, including health, environment, transportation, and economy. Open-source technologies provide a new ray of hope to collaboratively tackle the pandemic. The role of open source is not limited to sharing a source code. Rather open-source projects can be adopted as a software development approach to encourage collaboration among researchers. Open collaboration creates a positive impact in society and helps combat the pandemic effectively. Open-source technology integrated with geospatial information allows decision-makers to make strategic and informed decisions. It also assists them in determining the type of intervention needed based on geospatial information. The novelty of this paper is to standardize the open-source workflow for spatiotemporal research. The highlights of the open-source workflow include sharing data, analytical tools, spatiotemporal applications, and results and formalizing open-source software development. The workflow includes (i) developing open-source spatiotemporal applications, (ii) opening and sharing the spatiotemporal resources, and (iii) replicating the research in a plug and play fashion. Open data, open analytical tools and source code, and publicly accessible results form the foundation for this workflow. This paper also presents a case study with the open-source spatiotemporal application development for air quality analysis in California, USA. In addition to the application development, we shared the spatiotemporal data, source code, and research findings through the GitHub repository.
Inhibition of Bruton Tyrosine Kinase Reduces Neuroimmune Cascade and Promotes Recovery after Spinal Cord Injury
Authors: Yu Chen Guang , Bondada Vimala , Iqbal Hina , Moore Kate L. , Gensel John C. , Bondada Subbarao , Geddes James W.
Published: December 2021

Microglia/astrocyte and B cell neuroimmune responses are major contributors to the neurological deficits after traumatic spinal cord injury (SCI). Bruton tyrosine kinase (BTK) activation mechanistically links these neuroimmune mechanisms. Our objective is to use Ibrutinib, an FDA-approved BTK inhibitor, to inhibit the neuroimmune cascade thereby improving locomotor recovery after SCI. Rat models of contusive SCI, Western blot, immunofluorescence staining imaging, flow cytometry analysis, histological staining, and behavioral assessment were used to evaluate BTK activity, neuroimmune cascades, and functional outcomes. Both BTK expression and phosphorylation were increased at the lesion site at 2, 7, 14, and 28 days after SCI. Ibrutinib treatment (6 mg/kg/day, IP, starting 3 h post-injury for 7 or 14 days) reduced BTK activation and total BTK levels, attenuated the injury-induced elevations in Iba1, GFAP, CD138, and IgG at 7 or 14 days post-injury without reduction in CD45RA B cells, improved locomotor function (BBB scores), and resulted in a significant reduction in lesion volume and significant improvement in tissue-sparing 11 weeks post-injury. These results indicate that Ibrutinib exhibits neuroprotective effects by blocking excessive neuroimmune responses through BTK-mediated microglia/astroglial activation and B cell/antibody response in rat models of SCI. These data identify BTK as a potential therapeutic target for SCI.
Dual-Functional Peroxidase-Copper Phosphate Hybrid Nanoflowers for Sensitive Detection of Biological Thiols
Authors: Le Xuan Ai , Le Thao Nguyen , Kim Moon Il
Published: December 2021

An effective strategy to detect biological thiols (biothiols), including glutathione (GSH), cysteine (Cys), and homocysteine (Hcy), holds significant incentive since they play vital roles in many cellular processes and are closely related to many diseases. Here, we demonstrated that hybrid nanoflowers composed of crystalline copper phosphate and horseradish peroxidase (HRP) served as a functional unit exhibiting dual catalytic activities of biothiol oxidase and HRP, yielding a cascade reaction system for a sensitive one-pot fluorescent detection of biothiols. The nanoflowers were synthesized through the anisotropic growth of copper phosphate petals coordinated with the amine/amide moieties of HRP, by simply incubating HRP and copper(II) sulfate for three days at room temperature. Copper phosphates within the nanoflowers oxidized target biothiols to generate H2O2, which activated the entrapped HRP to oxidize the employed Amplex UltraRed substrate to produce intense fluorescence. Using this strategy, biothiols were selectively and sensitively detected by monitoring the respective fluorescence intensity. This nanoflower-based strategy was also successfully employed for reliable quantification of biothiols present in human serum, demonstrating its great potential for clinical diagnostics.
DUSP-1 Induced by PGE2 and PGE1 Attenuates IL-1β-Activated MAPK Signaling, Leading to Suppression of NGF Expression in Human Intervertebral Disc Cells
Authors: Kusakabe Takuya , Sawaji Yasunobu , Endo Kenji , Suzuki Hidekazu , Konishi Takamitsu , Maekawa Asato , Murata Kazuma , Yamamoto Kengo
Published: December 2021

The molecular mechanism of discogenic low back pain (LBP) involves nonphysiological nerve invasion into a degenerated intervertebral disc (IVD), induced by nerve growth factor (NGF). Selective cyclooxygenase (COX)-2 inhibitors are mainly used in the treatment of LBP, and act by suppressing the inflammatory mediator prostaglandin E2 (PGE2), which is induced by inflammatory stimuli, such as interleukin-1β (IL-1β). However, in our previous in vitro study using cultured human IVD cells, we demonstrated that the induction of NGF by IL-1β is augmented by a selective COX-2 inhibitor, and that PGE2 and PGE1 suppress NGF expression. Therefore, in this study, to elucidate the mechanism of NGF suppression by PGE2 and PGE1, we focused on mitogen-activated protein kinases (MAPKs) and its phosphatase, dual-specificity phosphatase (DUSP)-1. IL-1β-induced NGF expression was altered in human IVD cells by MAPK pathway inhibitors. PGE2 and PGE1 enhanced IL-1β-induced DUSP-1 expression, and suppressed the phosphorylation of MAPKs in human IVD cells. In DUSP-1 knockdown cells established using small interfering RNA, IL-1β-induced phosphorylation of MAPKs was enhanced and prolonged, and NGF expression was significantly enhanced. These results suggest that PGE2 and PGE1 suppress IL-1β-induced NGF expression by suppression of the MAPK signaling pathway, accompanied by increased DUSP-1 expression.
CCN2 Increases TGF-β Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF-β Pathway Regulation
Authors: Tejera-Muñoz Antonio , Marquez-Exposito Laura , Tejedor-Santamaría Lucía , Rayego-Mateos Sandra , Orejudo Macarena , Suarez-Álvarez Beatriz , López-Larrea Carlos , Ruíz-Ortega Marta , Rodrigues-Díez Raúl R.
Published: December 2021

The cellular communication network factor 2 (CCN2/CTGF) has been traditionally described as a mediator of the fibrotic responses induced by other factors including the transforming growth factor β (TGF-β). However, several studies have defined a direct role of CCN2 acting as a growth factor inducing oxidative and proinflammatory responses. The presence of CCN2 and TGF-β together in the cellular context has been described as a requisite to induce a persistent fibrotic response, but the precise mechanisms implicated in this relation are not described yet. Considering the main role of TGF-β receptors (TβR) in the TGF-β pathway activation, our aim was to investigate the effects of CCN2 in the regulation of TβRI and TβRII levels in vascular smooth muscle cells (VSMCs). While no differences were observed in TβRI levels, an increase in TβRII expression at both gene and protein level were found 48 h after stimulation with the C-terminal fragment of CCN2 (CCN2(IV)). Cell pretreatment with a TβRI inhibitor did not modify TβRII increment induced by CCN2(VI), demonstrating a TGF-β-independent response. Secondly, CCN2(IV) rapidly activated the SMAD pathway in VSMCs, this being crucial in the upregulation of TβRII since the preincubation with an SMAD3 inhibitor prevented it. Similarly, pretreatment with the epidermal growth factor receptor (EGFR) inhibitor erlotinib abolished TβRII upregulation, indicating the participation of this receptor in the observed responses. Our findings suggest a direct role of CCN2 maintaining the TGF-β pathway activation by increasing TβRII expression in an EGFR-SMAD dependent manner activation.
Iron-Chelation Treatment by Novel Thiosemicarbazone Targets Major Signaling Pathways in Neuroblastoma
Authors: Macsek Peter , Skoda Jan , Krchniakova Maria , Neradil Jakub , Veselska Renata
Published: December 2021

Despite constant advances in the field of pediatric oncology, the survival rate of high-risk neuroblastoma patients remains poor. The molecular and genetic features of neuroblastoma, such as MYCN amplification and stemness status, have established themselves not only as potent prognostic and predictive factors but also as intriguing targets for personalized therapy. Novel thiosemicarbazones target both total level and activity of a number of proteins involved in some of the most important signaling pathways in neuroblastoma. In this study, we found that di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) potently decreases N-MYC in MYCN-amplified and c-MYC in MYCN-nonamplified neuroblastoma cell lines. Furthermore, DpC succeeded in downregulating total EGFR and phosphorylation of its most prominent tyrosine residues through the involvement of NDRG1, a positive prognostic marker in neuroblastoma, which was markedly upregulated after thiosemicarbazone treatment. These findings could provide useful knowledge for the treatment of MYC-driven neuroblastomas that are unresponsive to conventional therapies.
New Insights into Pulmonary Hypertension: A Role for Connexin-Mediated Signalling
Authors: Htet Myo , Nally Jane. E. , Martin Patricia. E. , Dempsie Yvonne
Published: December 2021

Pulmonary hypertension is a serious clinical condition characterised by increased pulmonary arterial pressure. This can lead to right ventricular failure which can be fatal. Connexins are gap junction-forming membrane proteins which serve to exchange small molecules of less than 1 kD between cells. Connexins can also form hemi-channels connecting the intracellular and extracellular environments. Hemi-channels can mediate adenosine triphosphate release and are involved in autocrine and paracrine signalling. Recently, our group and others have identified evidence that connexin-mediated signalling may be involved in the pathogenesis of pulmonary hypertension. In this review, we discuss the evidence that dysregulated connexin-mediated signalling is associated with pulmonary hypertension.
Citrus Naringenin Increases Neuron Survival in Optic Nerve Crush Injury Model by Inhibiting JNK-JUN Pathway
Authors: Chen Jie , Li Hui , Yang Changming , He Yinjia , Arai Tatsuo , Huang Qiang , Liu Xiaodong , Miao Linqing
Published: December 2021

Traumatic nerve injury activates cell stress pathways, resulting in neuronal death and loss of vital neural functions. To date, there are no available neuroprotectants for the treatment of traumatic neural injuries. Here, we studied three important flavanones of citrus components, in vitro and in vivo, to reveal their roles in inhibiting the JNK (c-Jun N-terminal kinase)-JUN pathway and their neuroprotective effects in the optic nerve crush injury model, a kind of traumatic nerve injury in the central nervous system. Results showed that both neural injury in vivo and cell stress in vitro activated the JNK-JUN pathway and increased JUN phosphorylation. We also demonstrated that naringenin treatment completely inhibited stress-induced JUN phosphorylation in cultured cells, whereas nobiletin and hesperidin only partially inhibited JUN phosphorylation. Neuroprotection studies in optic nerve crush injury mouse models revealed that naringenin treatment increased the survival of retinal ganglion cells after traumatic optic nerve injury, while the other two components had no neuroprotective effect. The neuroprotection effect of naringenin was due to the inhibition of JUN phosphorylation in crush-injured retinal ganglion cells. Therefore, the citrus component naringenin provides neuroprotection through the inhibition of the JNK-JUN pathway by inhibiting JUN phosphorylation, indicating the potential application of citrus chemical components in the clinical therapy of traumatic optic nerve injuries.
Power to the Teachers: An Exploratory Review on Artificial Intelligence in Education
Authors: Lameras Petros , Arnab Sylvester
Published: December 2021

This exploratory review attempted to gather evidence from the literature by shedding light on the emerging phenomenon of conceptualising the impact of artificial intelligence in education. The review utilised the PRISMA framework to review the analysis and synthesis process encompassing the search, screening, coding, and data analysis strategy of 141 items included in the corpus. Key findings extracted from the review incorporate a taxonomy of artificial intelligence applications with associated teaching and learning practice and a framework for helping teachers to develop and self-reflect on the skills and capabilities envisioned for employing artificial intelligence in education. Implications for ethical use and a set of propositions for enacting teaching and learning using artificial intelligence are demarcated. The findings of this review contribute to developing a better understanding of how artificial intelligence may enhance teachers’ roles as catalysts in designing, visualising, and orchestrating AI-enabled teaching and learning, and this will, in turn, help to proliferate AI-systems that render computational representations based on meaningful data-driven inferences of the pedagogy, domain, and learner models.
First Evidence of Feeding-Induced RNAi in Banana Weevil via Exogenous Application of dsRNA
Authors: Mwaka Henry Shaykins , Christiaens Olivier , Bwesigye Priver Namanya , Kubiriba Jerome , Tushemereirwe Wilberforce Kateera , Gheysen Godelieve , Smagghe Guy
Published: December 2021

Banana weevil (Cosmopolites sordidus) is the most devastating pest of banana and plantain worldwide, yet current control measures are neither effective, sustainable, nor environmentally sound, and no resistant farmer-preferred cultivars are known to date. In this paper, we examined the ability to induce RNA interference (RNAi) in the banana weevil via feeding. We first developed an agar- and banana corm (rhizome) flour-based artificial diet in a multi-well plate setup that allowed the banana weevils to complete their life cycle from egg through the larval instars to the pupal stage in an average period of 53 days. Adults emerged about 20 days later. The artificial diet allowed the tunneling and burrowing habits of the larvae and successful metamorphosis up to adult eclosion. Adding dsRNA for laccase2 to the artificial diet resulted in albino phenotypes, confirming gene-silencing. Finally, C. sordidus was fed with dsRNA against a selection of essential target genes: snf7, rps13, mad1, vha-a, vha-d, and lgl for a period of 45 days. 100% mortality within 9–16 days was realized with dssnf7, dsrps13, and dsmad1 at 200 ng/mL artificial diet, and this corresponded to a strong reduction in gene expression. Feeding the dsRNA targeting the two vha genes resulted in 100% mortality after about 3–4 weeks, while treatment with dslgl resulted in no mortality above the dsgfp-control and the water-control. Our results have implications for the development of RNAi approaches for managing important crop pests, in that banana weevils can be controlled based on the silencing of essential target genes as snf7, rps13, and mad1. They also highlight the need for research into the development of RNAi for banana protection, eventually the engineering of host-induced gene-silencing (HIGS) cultivars, given the high RNAi efficacy and its species-specific mode of action, adding the RNAi approach to the armory of integrated pest management (IPM).