bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged Load Carriage Impacts Magnitude and Velocity of Knee Adduction Biomechanics
Authors: Salverda Gaervyn J. , Drew Micah D. , Krammer Samantha M. , Brown Tyler N.
Published: December 2021

Background: This study determined whether prolonged load carriage increased the magnitude and velocity of knee adduction biomechanics and whether increases were related to knee varus thrust or alignment. Methods: Seventeen participants (eight varus thrust and nine control) had knee adduction quantified during 60-min of walking (1.3 m/s) with three body-borne loads (0 kg, 15 kg, and 30 kg). Magnitude, average and maximum velocity, and time to peak of knee adduction biomechanics were submitted to a mixed model ANOVA. Results: With the 0 and 15 kg loads, varus thrust participants exhibited greater magnitude (p ≤ 0.037, 1.9–2.3°), and average (p ≤ 0.027, up to 60%) and maximum velocity (p ≤ 0.030, up to 44%) of varus thrust than control, but differences were not observed with the 30 kg load. The 15 and 30 kg loads led to significant increases in magnitude (p ≤ 0.017, 15–25%) and maximum velocity (p ≤ 0.017, 11–20%) of knee adduction moment, while participants increased magnitude (p ≤ 0.043, up to 0.3°) and maximum velocity (p ≤ 0.022, up to 5.9°/s and 6.7°/s) for knee adduction angle and varus thrust at minutes 30 and 60. Static alignment did not differ between groups (p = 0.412). Conclusion: During prolonged load carriage, all participants increased the magnitude and velocity of knee adduction biomechanics and the potential risk of knee OA.
Mast Cell Tryptase and Implications for SARS-CoV-2 Pathogenesis
Authors: Karimi Negar , Morovati Solmaz , Chan Lily , Napoleoni Christina , Mehrani Yeganeh , Bridle Byram W. , Karimi Khalil
Published: December 2021

Mast cells (MCs) are heterogenous innate leukocytes producing many inflammatory mediators during viral infections that can be protective or damaging to the host, as is seen in the infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for the coronavirus disease that was first identified in 2019 (COVID-19). MCs can sense viruses by diverse mechanisms. They express angiotensin-converting enzyme 2 (ACE2), known as the principal entry receptor for SARS-CoV-2, and tryptase that can promote SARS-CoV-2 infection. Tryptase is one of the most abundant serine proteases released by MCs during degranulation and is reported to have both beneficial and detrimental roles in respiratory diseases. Reviewed here are the potential roles of MC-derived tryptase during COVID-19, the implications it has in the pathogenesis of SARS-CoV-2, and the possibility of treating COVID-19 by targeting tryptase.
Can SARS-CoV-2 Infection Lead to Neurodegeneration and Parkinson’s Disease?
Authors: Krey Lea , Huber Meret Koroni , Höglinger Günter U. , Wegner Florian
Published: December 2021

The SARS-CoV-2 pandemic has affected the daily life of the worldwide population since 2020. Links between the newly discovered viral infection and the pathogenesis of neurodegenerative diseases have been investigated in different studies. This review aims to summarize the literature concerning COVID-19 and Parkinson’s disease (PD) to give an overview on the interface between viral infection and neurodegeneration with regard to this current topic. We will highlight SARS-CoV-2 neurotropism, neuropathology and the suspected pathophysiological links between the infection and neurodegeneration as well as the psychosocial impact of the pandemic on patients with PD. Some evidence discussed in this review suggests that the SARS-CoV-2 pandemic might be followed by a higher incidence of neurodegenerative diseases in the future. However, the data generated so far are not sufficient to confirm that COVID-19 can trigger or accelerate neurodegenerative diseases.
Deterministic Tractography Analysis of Rat Brain Using SIGMA Atlas in 9.4T MRI
Authors: Im Sang-Jin , Suh Ji-Yeon , Shim Jae-Hyuk , Baek Hyeon-Man
Published: December 2021

Preclinical studies using rodents have been the choice for many neuroscience researchers due totheir close reflection of human biology. In particular, research involving rodents has utilized MRI to accurately identify brain regions and characteristics by acquiring high resolution cavity images with different contrasts non-invasively, and this has resulted in high reproducibility and throughput. In addition, tractographic analysis using diffusion tensor imaging to obtain information on the neural structure of white matter has emerged as a major methodology in the field of neuroscience due to its contribution in discovering significant correlations between altered neural connections and various neurological and psychiatric diseases. However, unlike image analysis studies with human subjects where a myriad of human image analysis programs and procedures have been thoroughly developed and validated, methods for analyzing rat image data using MRI in preclinical research settings have seen significantly less developed. Therefore, in this study, we present a deterministic tractographic analysis pipeline using the SIGMA atlas for a detailed structural segmentation and structural connectivity analysis of the rat brain’s structural connectivity. In addition, the structural connectivity analysis pipeline presented in this study was preliminarily tested on normal and stroke rat models for initial observation.
Thermal Comfort Performances of Temporary Shelters Using Experimental and Computational Assessments
Authors: Tan Alex Yong Kwang , Tan Chi-Keong
Published: December 2021

This paper examines the thermal comfort of temporary shelters under Taiwan’s subtropical summer conditions. The temperature within the tent was higher compared to the standard configuration of the temporary shelter, but its relative humidity was lower. During the time period 09:30 to 14:30, temperatures at the center of the tent at positions 0.10 m, 1.10 m and 1.70 m above ground were 3.1 °C, 5.5 °C and 6.0 °C higher, respectively, than the average ambient temperature of 36.3 °C. However, temperatures for the standard configuration at similar central positions of 0.10 m, 1.10 m and 1.70 m above ground were 1.2 °C, 0.5 °C and 0.7 °C lower, respectively, than the same average ambient. In the afternoon, the standard configuration (PMV of 3.14 and PPD of 100) performed better than the tent (PMV of 5.03 and PPD of 100), although neither achieved thermal comfort. Various experimental configurations showed that double layers of roof lowered temperatures, but the thermal comfort (PMV of 3.32 and PPD of 100) remained unchanged. Various computational configurations showed that closing the door and one window and installing a mechanical fan of average speed 2.75 m/s lowered the temperature and increased the air speed to achieve thermal comfort with PMV and PPD values of 1.49 and 50, respectively.
Theoretical Impact of Building Façade Thickness on Daylight Metrics and Lighting Energy Demand in Buildings: A Case Study of the Tropics
Authors: Mangkuto Rizki A. , Atthaillah  , Koerniawan Mochamad Donny , Yuliarto Brian
Published: December 2021

In daylighting design, variation of building façade thickness (f) will result in variation of the daylight opening areas, which in turn will modify the values of daylight metrics within the space. However, studies dedicated to investigating the impact of varying f on indoor daylight metrics are relatively scarce. This study, therefore, aims to assess the theoretical impact of various façade thicknesses on various daylight metrics and lighting energy demands in a reference office space. Analytical calculations are performed using an outdoor diffuse illuminance profile of a tropical city. The building façade thickness values are varied within 0–0.50 m, at window-to-wall ratios (WWR) of 25%, 50%, and 75%. Based on sensitivity analysis, it is found that variation of f yields different impacts on the observed metrics, with sDA300/50% being the least influenced. Among all metrics in the central calculation point, DA300, UDI-a, and UDI-a′ yield relatively small coefficients of variation, and thus, have the lowest uncertainty with respect to f. Among all metrics for the entire room, sDA300/50% and sUDI-a50% have the lowest uncertainty, with interquartile ranges of no more than 0.4%. Overall, the contribution of this study is providing insight into the impact of façade thickness on various daylight metrics in indoor spaces, particularly in the worst-case scenario under the standard CIE overcast sky.
Optimal Planning of Hotel Renovation Projects
Authors: AlOtaibi Mansour , El-Rayes Khaled , Altuwaim Ayman , AlOmani Abdullah
Published: December 2021

This paper presents the development of a novel model for optimizing the planning of hotel renovation projects to maximize hotel revenues during renovation work while minimizing project cost. The model is developed in three main modules: optimization, scheduling, and hotel profit modules. The model integrates an innovative methodology that enables renovation planners to select which hotels to renovate during any fiscal year based on an allocated renovation budget and identify an optimal floor renovation start date, optimal overtime hours usage and number of assigned crews for each renovation activity, and an optimal floor renovation order in each hotel. An application example of three hotels is analyzed to illustrate the use of the model and demonstrate its capabilities. The results of this analysis illustrate the novel contributions of the model and its original capability in generating optimal plans for hotel renovation projects that enable hotel owners to maximize revenues of their hotels during renovation work while minimizing hotel renovation costs.
Working from Home in Italy during COVID-19 Lockdown: A Survey to Assess the Indoor Environmental Quality and Productivity
Authors: Salamone Francesco , Barozzi Benedetta , Bellazzi Alice , Belussi Lorenzo , Danza Ludovico , Devitofrancesco Anna , Ghellere Matteo , Meroni Italo , Scamoni Fabio , Scrosati Chiara
Published: December 2021

Italians were the first European citizens to experience the lockdown due to Sars-Cov-2 in March 2020. Most employees were forced to work from home. People suddenly had to share common living spaces with family members for longer periods of time and convert home spaces into workplaces. This inevitably had a subjective impact on the perception, satisfaction and preference of indoor environmental quality and work productivity. A web-based survey was designed and administered to Italian employees to determine how they perceived the indoor environmental quality of residential spaces when Working From Home (WFH) and to investigate the relationship between different aspects of users’ satisfaction. A total of 330 valid questionnaires were collected and analysed. The article reports the results of the analyses conducted using a descriptive approach and predictive models to quantify comfort in living spaces when WFH, focusing on respondents’ satisfaction. Most of them were satisfied with the indoor environmental conditions (89% as the sum of “very satisfied” and “satisfied” responses for thermal comfort, 74% for visual comfort, 68% for acoustic quality and 81% for indoor air quality), while the layout of the furniture negatively influenced the WFH experience: 45% of the participants expressed an unsatisfactory or neutral opinion. The results of the sentiment analysis confirmed this trend. Among the Indoor Environmental factors that affect productivity, visual comfort is the most relevant variable. As for the predictive approach using machine learning, the Support Vector Machine classifier performed best in predicting overall satisfaction.
Seismic Vulnerability Assessment and Strengthening of Heritage Timber Buildings: A Review
Authors: Shabani Amirhosein , Alinejad Ali , Teymouri Mohammad , Costa André Nascimento , Shabani Mahgol , Kioumarsi Mahdi
Published: December 2021

Recent studies highlight the potential impact of earthquakes on cultural heritage sites and monuments, which in turn yield significant adverse impacts on economies, politics, and societies. Several aspects such as building materials, structural responses, and restoration strategies must be considered in the conservation of heritage structures. Timber is an old organic construction material. Most of the historic timber structures were not designed to withstand seismic forces; therefore, the seismic vulnerability assessment of heritage timber structures in areas with high seismic hazard is essential for their conservation. For this purpose, different strategies for the numerical modeling of heritage timber buildings have been developed and validated against tests results. After performing seismic analysis using detailed analytical methods and predicting the susceptible structural components, strengthening techniques should be utilized to mitigate the risk level. To this aim, various methods using wooden components, composite material, steel components, SMA etc., have been utilized and tested and are reviewed in this study. There are still some gaps, such as full-scale numerical modeling of strengthened buildings and investigating the soil–structure interaction effects on the seismic behavior of buildings that should be investigated.
Theorizing to Improve Mental Health in Multicultural Construction Industries: An Intercultural Coping Model
Authors: Liu Qinjun , Feng Yingbin , London Kerry
Published: December 2021

Construction workers are exposed to a range of stressors that lead to mental ill-health. In a multicultural construction workplace, the interactions between workers with different cultural backgrounds may aggravate mental health issues. Existing studies on coping typically focus on a reactive approach to managing stressors in the absence of cultural-related factors. This approach is inadequate in addressing mental health issues in a culturally diverse construction workplace. This paper presents a critical review that synthesizes and analyses theories and models of stress and coping, proactive coping, occupational stress, acculturative stress, and intercultural competence to develop a conceptual model for managing mental health in a multicultural construction workforce. The proposed model relies upon a positive coping mechanism, i.e., intercultural coping, to manage stressful events during the entire coping process in a multicultural workplace, towards achieving sustained good mental health. The proposed conceptual model contributes to the development of coping theories and positive psychology approaches and provides effective coping strategies to enhance psychological well-being in a multicultural context.
Numerical Simulation and Design Recommendations for Web Crippling Strength of Cold-Formed Steel Channels with Web Holes under Interior-One-Flange Loading at Elevated Temperatures
Authors: Fang Zhiyuan , Roy Krishanu , Liang Hao , Poologanathan Keerthan , Ghosh Kushal , Mohamed Abdeliazim , Lim James
Published: December 2021

This paper investigates the interior-one-flange web crippling strength of cold-formed steel channels at elevated temperatures. The stress-strain curves of G250 and G450 grade cold-formed steel (CFS) channels at ambient and elevated temperatures were taken from the literature and the temperatures were varied from 20 to 700 °C. A detailed parametric analysis comprising 3474 validated finite element models was undertaken to investigate the effects of web holes and bearing length on the web crippling behavior of these channels at elevated temperatures. From the parametric study results, it was found that the web crippling strength reduction factor is sensitive to the changes of the hole size, hole location, and the bearing length, with the parameters of hole size and hole location having the largest effect on the web crippling reduction factor. However, the web crippling strength reduction factor remains stable when the temperature is changed from 20 to 700 °C. Based on the parametric analysis results, the web crippling strength reduction factors for both ambient and elevated temperatures are proposed, which outperformed the equations available in the literature and in the design guidelines of American standard (AISI S100-16) and Australian/New Zealand standard (AS/NZS 4600:2018) for ambient temperatures. Then, a reliability analysis was conducted, the results of which showed that the proposed design equations could closely predict the reduced web crippling strength of CFS channel sections under interior-one-flange loading conditions at elevated temperatures.
Upper Limits of Downstaging for Hepatocellular Carcinoma in Liver Transplantation
Authors: Biolato Marco , Galasso Tiziano , Marrone Giuseppe , Miele Luca , Grieco Antonio
Published: December 2021

In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60–70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to “extended” downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion.
Pan-Genomic Sequencing Reveals Actionable CDKN2A/2B Deletions and Kataegis in Anaplastic Thyroid Carcinoma
Authors: Stenman Adam , Yang Minjun , Paulsson Johan O. , Zedenius Jan , Paulsson Kajsa , Juhlin C. Christofer
Published: December 2021

Anaplastic thyroid carcinoma (ATC) is a lethal malignancy characterized by poor response to conventional therapies. Whole-genome sequencing (WGS) analyses of this tumor type are limited, and we therefore interrogated eight ATCs using WGS and RNA sequencing. Five out of eight cases (63%) displayed cyclin-dependent kinase inhibitor 2A (CDKN2A) abnormalities, either copy number loss (n = 4) or truncating mutations (n = 1). All four cases with loss of the CDKN2A locus (encoding p16 and p14arf) also exhibited loss of the neighboring CDKN2B gene (encoding p15ink4b), and displayed reduced CDKN2A/2B mRNA levels. Mutations in established ATC-related genes were observed, including TP53, BRAF, ARID1A, and RB1, and overrepresentation of mutations were also noted in 13 additional cancer genes. One of the more predominant mutational signatures was intimately coupled to the activity of Apolipoprotein B mRNA-editing enzyme, the catalytic polypeptide-like (APOBEC) family of cytidine deaminases implied in kataegis, a focal hypermutation phenotype, which was observed in 4/8 (50%) cases. We corroborate the roles of CDKN2A/2B in ATC development and identify kataegis as a recurrent phenomenon. Our findings pinpoint clinically relevant alterations, which may indicate response to CDK inhibitors, and focal hypermutational phenotypes that may be coupled to improved responses using immune checkpoint inhibitors.
Synthesis of Mesoporous Zeolites and Their Opportunities in Heterogeneous Catalysis
Authors: Singh Bhupendra Kumar , Kim Yongseok , Kwon Seungdon , Na Kyungsu
Published: December 2021

Currently, zeolites are one of the most important classes of heterogeneous catalysts in chemical industries owing to their unique structural characteristics such as molecular-scale size/shape-selectivity, heterogenized single catalytic sites in the framework, and excellent stability in harsh industrial processes. However, the microporous structure of conventional zeolite materials limits their applications to small-molecule reactions. To alleviate this problem, mesoporous zeolitic frameworks were developed. In the last few decades, several methods have been developed for the synthesis of mesoporous zeolites; these zeolites have demonstrated greater lifetime and better performance than their bulk microporous counterparts in many catalytic processes, which can be explained by the rapid diffusion of reactant species into the zeolite framework and facile accessibility to bulky molecules through the mesopores. Mesoporous zeolites provide versatile opportunities not only in conventional chemical industries but also in emerging catalysis fields. This review presents many state-of-the-art mesoporous zeolites, discusses various strategies for their synthesis, and details their contributions to catalytic reactions including catalytic cracking, isomerization, alkylation and acylation, alternative fuel synthesis via methanol-to-hydrocarbon (MTH) and Fischer–Tropsch synthesis (FTS) routes, and different fine-chemical syntheses.
Effect of Calcination Conditions on the Properties and Photoactivity of TiO2 Modified with Biuret
Authors: Piątkowska Aleksandra , Mozia Sylwia
Published: December 2021

A simple wet impregnation-calcination method was used to obtain a series of novel non-metal doped TiO2 photocatalysts. Biuret was applied as C and N source, while raw titanium dioxide derived from sulfate technology process was used as TiO2 and S source. The influence of the modification with biuret and the effect of the atmosphere (air or argon) and temperature (500–800 °C) of calcination on the physicochemical properties and photocatalytic activity of the photocatalysts towards ketoprofen decomposition under simulated solar light was investigated. Moreover, selected photocatalysts were applied for ketoprofen photodecomposition under visible and UV irradiation. Crucial features affecting the photocatalytic activity were the anatase to rutile phase ratio, anatase crystallites size and non-metals content. The obtained photocatalysts revealed improved activity in the photocatalytic ketoprofen decomposition compared to the crude TiO2. The best photoactivity under all irradiation types exhibited the photocatalyst calcined in the air atmosphere at 600 °C, composed of 96.4% of anatase with 23 nm crystallites, and containing 0.11 wt% of C, 0.05 wt% of N and 0.77 wt% of S.
Cost-Effective 1T-MoS2 Grown on Graphite Cathode Materials for High-Temperature Rechargeable Aluminum Ion Batteries and Hydrogen Evolution in Water Splitting
Authors: Patil Shivaraj B. , An Ji-Yao , Li Zhi-Jie , Wu Yu-Cheng , Gowdru Swathi M. , Hsieh Han-Hsuan , Chen Zhen , Wang Di-Yan
Published: December 2021

The high dependence on and high cost of lithium has led to a search for alternative materials. Aluminum ion batteries (AIBs) have gained interest due to their abundance, low cost, and high capacity. However, the use of the expensive 1-ethyl-3-methylimidazolium chloride (EMIC) electrolyte in AIBs curtails its wide application. Recently, high-temperature batteries have also gained much attention owing to their high demand by industries. Herein, we introduce cost-effective 1T molybdenum sulfide grown on SP-1 graphite powder (1T-MoS2/SP-1) as a cathode material for high-temperature AIBs using the AlCl3-urea eutectic electrolyte (1T-MoS2/SP-1–urea system). The AIB using the 1T-MoS2/SP-1–urea system exhibited a capacity as high as 200 mAh/g with high efficiency of 99% over 100 cycles at 60 °C when cycled at the rate of 100 mA/g. However, the AIB displayed a capacity of 105 mAh/g when cycled at room temperature. The enhanced performance of the 1T-MoS2/SP-1–urea system is attributed to reduced viscosity of the AlCl3-urea eutectic electrolyte at higher temperatures with high compatibility of 1T-MoS2 with SP-1. Moreover, the electrocatalytic lithiation of 1T-MoS2 and its effect on the hydrogen evolution reaction were also investigated. We believe that our work can act as a beacon for finding alternative, cost-effective, and high-temperature batteries.
Thermochemical and Catalytic Conversion Technologies for the Development of Brazilian Biomass Utilization
Authors: Schmitt Caroline Carriel , Fonseca Frederico Gomes , Fraga Mariana M. Campos , Wisniewski Alberto , Karp Susan , Mello José Álvaro Henrique , Rodrigues Rita C. L. B. , Moreira Renata , Hirayama Danilo Eiji , Raffelt Klaus , Dahmen Nicolaus
Published: December 2021

The social, economic, and environmental impacts of climate change have been shown to affect poorer populations throughout the world disproportionally, and the COVID-19 pandemic of 2020–2021 has only exacerbated the use of less sustainable energy, fuel, and chemical sources. The period of economic and social recovery following the pandemic presents an unprecedented opportunity to invest in biorefineries based on the pyrolysis of agricultural residues. These produce a plethora of sustainable resources while also contributing to the economic valorization of first-sector local economies. However, biomass-derived pyrolysis liquid is highly oxygenated, which hinders its long-term stability and usability. Catalytic hydrogenation is a proposed upgrading method to reduce this hindrance, while recent studies on the use of nickel and niobium as low-cost catalysts, both abundant in Brazil, reinforce the potential synergy between different economic sectors within the country. This review gathers state-of-the-art applications of these technologies with the intent to guide the scientific community and lawmakers alike on yet another alternative for energy and commodities production within an environmentally sustainable paradigm.
Investigations of the Effect of H2 in CO Oxidation over Ceria Catalysts
Authors: Davó-Quiñonero Arantxa , López-Rodríguez Sergio , Chaparro-Garnica Cristian , Martín-García Iris , Bailón-García Esther , Lozano-Castelló Dolores , Bueno-López Agustín , García-Melchor Max
Published: December 2021

The preferential CO oxidation (so-called CO-PROX) is the selective CO oxidation amid H2-rich atmospheres, a process where ceria-based materials are consolidated catalysts. This article aims to disentangle the potential CO–H2 synergism under CO-PROX conditions on the low-index ceria surfaces (111), (110) and (100). Polycrystalline ceria, nanorods and ceria nanocubes were prepared to assess the physicochemical features of the targeted surfaces. Diffuse reflectance infrared Fourier-transformed spectroscopy (DRIFTS) shows that ceria surfaces are strongly carbonated even at room temperature by the effect of CO, with their depletion related to the CO oxidation onset. Conversely, formate species formed upon OH + CO interaction appear at temperatures around 60 °C and remain adsorbed regardless the reaction degree, indicating that these species do not take part in the CO oxidation. Density functional theory calculations (DFT) reveal that ceria facets exhibit high OH coverages all along the CO-PROX reaction, whilst CO is only chemisorbed on the (110) termination. A CO oxidation mechanism that explains the early formation of carbonates on ceria and the effect of the OH coverage in the overall catalytic cycle is proposed. In short, hydroxyl groups induce surface defects on ceria that increase the COx–catalyst interaction, revealed by the CO adsorption energies and the stabilization of intermediates and readsorbed products. In addition, high OH coverages are shown to facilitate the hydrogen transfer to form less stable HCOx products, which, in the case of the (110) and (100), is key to prevent surface poisoning. Altogether, this work sheds light on the yet unclear CO–H2 interactions on ceria surfaces during CO-PROX reaction, providing valuable insights to guide the design of more efficient reactors and catalysts for this process.
The Effect of Catalyst Placement on the Stability of a U-Bend Catalytic Heat-Recirculating Micro-Combustor: A Numerical Investigation
Authors: Kaisare Niket S. , Di Sarli Valeria
Published: December 2021

This study investigates the combined effect of catalyst placement and solid thermal conductivity on the stability of a U-bend catalytic heat-recirculating micro-combustor. The CFD code ANSYS Fluent 2020 R1 was used for two-dimensional simulations of lean premixed propane/air combustion by varying the inlet gas velocity, i.e., the input power. Three configurations were compared at low (3 W/(m K)) and high (30 W/(m K)) wall thermal conductivity: (A) the configuration in which both inner and outer walls are catalyst coated; (B) only the inner wall is catalyst coated; and (C) only the outer wall is catalyst coated. Numerical results show that, at low thermal conductivity, configuration (B) exhibits the same resistance to extinction as configuration (A), whereas at high thermal conductivity, configurations (B) and (C) exhibit much lower resistance to blowout than configuration (A). Accordingly, for low-power systems, which typically lose stability via extinction and thus require low-conductive materials, an optimal catalyst placement can be the partial coating of configuration (B). Conversely, for high-power systems, which are prone to blowout and thus require high-conductivity materials, a full coating of both the inner and outer walls is needed to guarantee higher stability. To elucidate these findings, a detailed analysis of the combustion behavior of the three configurations is presented.
Novel CNT Supported Molybdenum Catalyst for Detection of L-Cysteine in Its Natural Environment
Authors: Selçuk Kadir , Kivrak Hilal , Aktaş Nahit
Published: December 2021

In this study, novel carbon nanotube-supported Mo (Mo/CNT) catalysts were prepared with the sodium borohydride reduction method for the detection of L-cysteine (L-Cys, L-C). Mo/CNT catalysts were characterized with scanning electron microscopy with elemental dispersion X-ray (EDX-SEM), X-ray diffraction (XRD), UV-vis diffuse reflectance spectrometry (UV-vis), temperature-programmed reduction (TPR), temperature programmed oxidation (TPO), and temperature-programmed desorption (TPD) techniques. The results of these advanced surface characterization techniques revealed that the catalysts were prepared successfully. Electrochemical measurements were employed to construct a voltammetric L-C sensor based on Mo/CNT catalyst by voltammetric techniques such as cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Further measurements were carried out with electrochemical impedance spectroscopy (EIS). Mo/CNT/GCE exhibited excellent performance for L-C detection with a linear response in the range of 0–150 µM, with a current sensitivity of 200 mA/μM cm2 (0.0142 μA/μM), the lowest detection limit of 0.25 μM, and signal-to-noise ratio (S/N = 3). Interference studies showed that the Mo/CNT/GCE electrode was not affected by D-glucose, uric acid, L-tyrosine, and L-trytophane, commonly interfering organic structures. Natural sample analysis was also accomplished with acetyl L-C. Mo/CNT catalyst is a promising material as a sensor for L-C detection.
EGFR-D770>GY and Other Rare EGFR Exon 20 Insertion Mutations with a G770 Equivalence Are Sensitive to Dacomitinib or Afatinib and Responsive to EGFR Exon 20 Insertion Mutant-Active Inhibitors in Preclinical Models and Clinical Scenarios
Authors: Kobayashi Ikei , Viray Hollis , Rangachari Deepa , Kobayashi Susumu , Costa Daniel
Published: December 2021

Epidermal growth factor receptor (EGFR) exon 20 insertion mutations account for a tenth of all EGFR mutations in lung cancers. An important unmet clinical need is the identification of EGFR exon 20 insertion mutants that can respond to multiple classes of approved EGFR-TKIs. We sought to characterize variants involving EGFR-D770 to EGFR-G770 position equivalence changes that structurally allow for response to irreversible 2nd generation EGFR-TKIs. Our group used preclinical models of EGFR exon 20 insertion mutations to probe representative 1st (erlotinib), 2nd (afatinib, dacomitinib), 3rd generation (osimertinib) and EGFR exon 20 insertion mutant-active (poziotinib, mobocertinib) TKIs; we also queried the available clinical literature plus our institutional database to enumerate clinical outcomes. EGFR-D770>GY and other EGFR insertions with a G770 equivalence were identified at a frequency of 3.96% in separate cohorts of EGFR exon 20 insertion mutated lung cancer (n = 429). Cells driven by EGFR-D770>GY were insensitive to erlotinib and osimertinib, displayed sensitivity to poziotinib and mobocertinib and were uniquely sensitive to afatinib and dacomitinib in comparison with other more typical EGFR exon 20 insertion mutations using proliferation and biochemical assays. Clinical cases with EGFR-G770 equivalence from the literature and our center mirrored the preclinical data, with radiographic responses and clinical benefits restricted to afatinib, dacomitinib, poziotinib and mobocertinib, but not to erlotinib or osimertinib. Although they are rare, at <4% of all exon 20 insertion mutations, EGFR-G770 equivalence exon 20 insertion mutations are sensitive to approved 2nd generation EGFR TKIs and EGFR exon 20 insertion mutant-active TKIs (mobocertinib and poziotinib). EGFR-D770>GY and other insertions with a G770 equivalence join EGFR-A763_Y764insFQEA as exon 20 insertion mutationsresponsive to approved EGFR TKIs beyond mobocertinib; this data should be considered for clinical care, genomic profiling reports and clinical trial elaboration.
Mitophagy in Yeast: Molecular Mechanism and Regulation
Authors: Innokentev Aleksei , Kanki Tomotake
Published: December 2021

Mitophagy is a type of autophagy that selectively degrades mitochondria. Mitochondria, known as the “powerhouse of the cell”, supply the majority of the energy required by cells. During energy production, mitochondria produce reactive oxygen species (ROS) as byproducts. The ROS damage mitochondria, and the damaged mitochondria further produce mitochondrial ROS. The increased mitochondrial ROS damage cellular components, including mitochondria themselves, and leads to diverse pathologies. Accordingly, it is crucial to eliminate excessive or damaged mitochondria to maintain mitochondrial homeostasis, in which mitophagy is believed to play a major role. Recently, the molecular mechanism and physiological role of mitophagy have been vigorously studied in yeast and mammalian cells. In yeast, Atg32 and Atg43, mitochondrial outer membrane proteins, were identified as mitophagy receptors in budding yeast and fission yeast, respectively. Here we summarize the molecular mechanisms of mitophagy in yeast, as revealed by the analysis of Atg32 and Atg43, and review recent progress in our understanding of mitophagy induction and regulation in yeast.
Ionizing Radiation-Induced Brain Cell Aging and the Potential Underlying Molecular Mechanisms
Authors: Wang Qin-Qi , Yin Gang , Huang Jiang-Rong , Xi Shi-Jun , Qian Feng , Lee Rui-Xue , Peng Xiao-Chun , Tang Feng-Ru
Published: December 2021

Population aging is occurring rapidly worldwide, challenging the global economy and healthcare services. Brain aging is a significant contributor to various age-related neurological and neuropsychological disorders, including Alzheimer’s disease and Parkinson’s disease. Several extrinsic factors, such as exposure to ionizing radiation, can accelerate senescence. Multiple human and animal studies have reported that exposure to ionizing radiation can have varied effects on organ aging and lead to the prolongation or shortening of life span depending on the radiation dose or dose rate. This paper reviews the effects of radiation on the aging of different types of brain cells, including neurons, microglia, astrocytes, and cerebral endothelial cells. Further, the relevant molecular mechanisms are discussed. Overall, this review highlights how radiation-induced senescence in different cell types may lead to brain aging, which could result in the development of various neurological and neuropsychological disorders. Therefore, treatment targeting radiation-induced oxidative stress and neuroinflammation may prevent radiation-induced brain aging and the neurological and neuropsychological disorders it may cause.
Effects of Dithiothreitol on Fertilization and Early Development in Sea Urchin
Authors: Limatola Nunzia , Chun Jong Tai , Cherraben Sawsen , Schmitt Jean-Louis , Lehn Jean-Marie , Santella Luigia
Published: December 2021

The vitelline layer (VL) of a sea urchin egg is an intricate meshwork of glycoproteins that intimately ensheathes the plasma membrane. During fertilization, the VL plays important roles. Firstly, the receptors for sperm reside on the VL. Secondly, following cortical granule exocytosis, the VL is elevated and transformed into the fertilization envelope (FE), owing to the assembly and crosslinking of the extruded materials. As these two crucial stages involve the VL, its alteration was expected to affect the fertilization process. In the present study, we addressed this question by mildly treating the eggs with a reducing agent, dithiothreitol (DTT). A brief pretreatment with DTT resulted in partial disruption of the VL, as judged by electron microscopy and by a novel fluorescent polyamine probe that selectively labelled the VL. The DTT-pretreated eggs did not elevate the FE but were mostly monospermic at fertilization. These eggs also manifested certain anomalies at fertilization: (i) compromised Ca2+ signaling, (ii) blocked translocation of cortical actin filaments, and (iii) impaired cleavage. Some of these phenotypic changes were reversed by restoring the DTT-exposed eggs in normal seawater prior to fertilization. Our findings suggest that the FE is not the decisive factor preventing polyspermy and that the integrity of the VL is nonetheless crucial to the egg’s fertilization response.
Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas
Authors: Mueller-Buehl Ana M. , Buehner Torsten , Pfarrer Christiane , Deppe Leonie , Peters Laura , Dick Burkhard H. , Joachim Stephanie C.
Published: December 2021

Considering the fact that many retinal diseases are yet to be cured, the pathomechanisms of these multifactorial diseases need to be investigated in more detail. Among others, oxidative stress and hypoxia are pathomechanisms that take place in retinal diseases, such as glaucoma, age-related macular degeneration, or diabetic retinopathy. In consideration of these diseases, it is also evidenced that the immune system, including the complement system and its activation, plays an important role. Suitable models to investigate neuroretinal diseases are organ cultures of porcine retina. Based on an established model, the role of the complement system was studied after the induction of oxidative stress or hypoxia. Both stressors led to a loss of retinal ganglion cells (RGCs) accompanied by apoptosis. Hypoxia activated the complement system as noted by higher C3+ and MAC+ cell numbers. In this model, activation of the complement cascade occurred via the classical pathway and the number of C1q+ microglia was increased. In oxidative stressed retinas, the complement system had no consideration, but strong inflammation took place, with elevated TNF, IL6, and IL8 mRNA expression levels. Together, this study shows that hypoxia and oxidative stress induce different mechanisms in the porcine retina inducing either the immune response or an inflammation. Our findings support the thesis that the immune system is involved in the development of retinal diseases. Furthermore, this study is evidence that both approaches seem suitable models to investigate undergoing pathomechanisms of several neuroretinal diseases.
Lactobacillus casei and Epidermal Growth Factor Prevent Osmotic Stress-Induced Tight Junction Disruption in Caco-2 Cell Monolayers
Authors: Samak Geetha , Rao Rupa , Rao Radhakrishna
Published: December 2021

Osmotic stress plays a crucial role in the pathogenesis of many gastrointestinal diseases. Lactobacillus casei and epidermal growth factor (EGF) effects on the osmotic stress-induced epithelial junctional disruption and barrier dysfunction were investigated. Caco-2 cell monolayers were exposed to osmotic stress in the presence or absence of L. casei or EGF, and the barrier function was evaluated by measuring inulin permeability. Tight junction (TJ) and adherens junction integrity were assessed by immunofluorescence confocal microscopy. The role of signaling molecules in the L. casei and EGF effects was determined by using selective inhibitors. Data show that pretreatment of cell monolayers with L. casei or EGF attenuates osmotic stress-induced TJ and adherens junction disruption and barrier dysfunction. EGF also blocked osmotic stress-induced actin cytoskeleton remodeling. U0126 (MEK1/2 inhibitor), the MAP kinase inhibitor, blocked EGF-mediated epithelial protection from osmotic stress. In contrast, the L. casei-mediated epithelial protection from osmotic stress was unaffected by U0126, AG1478 (EGFR tyrosine kinase inhibitor), SP600125 (JNK1/2 inhibitor), or SB202190 (P38 MAP kinase inhibitor). On the other hand, Ro-32-0432 (PKC inhibitor) blocked the L. casei-mediated prevention of osmotic stress-induced TJ disruption and barrier dysfunction. The combination of EGF and L. casei is more potent in protecting the barrier function from osmotic stress. These findings suggest that L. casei and EGF ameliorate osmotic stress-induced disruption of apical junctional complexes and barrier dysfunction in the intestinal epithelium by distinct signaling mechanisms.
Adjunctive Thymosin Beta-4 Treatment Influences PMN Effector Cell Function during Pseudomonas aeruginosa-Induced Corneal Infection
Authors: Wang Yuxin , Carion Thomas W. , Ebrahim Abdul Shukkur , Sosne Gabriel , Berger Elizabeth A.
Published: December 2021

Previous work examining the therapeutic efficacy of adjunct thymosin beta 4 (Tβ4) to ciprofloxacin for ocular infectious disease has revealed markedly reduced inflammation (inflammatory mediators and innate immune cells) with increased activation of wound healing pathways. Understanding the therapeutic mechanisms of action have further revealed a synergistic effect with ciprofloxacin to enhance bacterial killing along with a regulatory influence over macrophage effector cell function. As a natural extension of the aforementioned work, the current study uses an experimental model of P. aeruginosa-induced keratitis to examine the influence of Tβ4 regarding polymorphonuclear leukocyte (PMN/neutrophil) cellular function, contributing to improved disease response. Flow cytometry was utilized to phenotypically profile infiltrating PMNs after infection. The generation of reactive oxygen species (ROS), neutrophil extracellular traps (NETs), and PMN apoptosis were investigated to assess the functional activities of PMNs in response to Tβ4 therapy. In vitro work using peritoneal-derived PMNs was similarly carried out to verify and extend our in vivo findings. The results indicate that the numbers of infiltrated PMNs into infected corneas were significantly reduced with adjunctive Tβ4 treatment. This was paired with the downregulated expression of proinflammatory markers on these cells, as well. Data generated from PMN functional studies suggested that the corneas of adjunctive Tβ4 treated B6 mice exhibit a well-regulated production of ROS, NETs, and limited PMN apoptosis. In addition to confirming the in vivo results, the in vitro findings also demonstrated that neutrophil elastase (NE) was unnecessary for NETosis. Collectively, these data provide additional evidence that adjunctive Tβ4 + ciprofloxacin treatment is a promising option for bacterial keratitis that addresses both the infectious pathogen and cellular-mediated immune response, as revealed by the current study.
Direct Current Stimulation in Cell Culture Systems and Brain Slices—New Approaches for Mechanistic Evaluation of Neuronal Plasticity and Neuromodulation: State of the Art
Authors: Euskirchen Nadine , Nitsche Michael A. , van Thriel Christoph
Published: December 2021

Non-invasive direct current stimulation (DCS) of the human brain induces neuronal plasticity and alters plasticity-related cognition and behavior. Numerous basic animal research studies focusing on molecular and cellular targets of DCS have been published. In vivo, ex vivo, and in vitro models enhanced knowledge about mechanistic foundations of DCS effects. Our review identified 451 papers using a PRISMA-based search strategy. Only a minority of these papers used cell culture or brain slice experiments with DCS paradigms comparable to those applied in humans. Most of the studies were performed in brain slices (9 papers), whereas cell culture experiments (2 papers) were only rarely conducted. These ex vivo and in vitro approaches underline the importance of cell and electric field orientation, cell morphology, cell location within populations, stimulation duration (acute, prolonged, chronic), and molecular changes, such as Ca2+-dependent intracellular signaling pathways, for the effects of DC stimulation. The reviewed studies help to clarify and confirm basic mechanisms of this intervention. However, the potential of in vitro studies has not been fully exploited and a more systematic combination of rodent models, ex vivo, and cellular approaches might provide a better insight into the neurophysiological changes caused by tDCS.
Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress
Authors: Groen Nathalie , Leenders Floris , Mahfouz Ahmed , Munoz-Garcia Amadeo , Muraro Mauro J. , de Graaf Natascha , Rabelink Ton. J. , Hoeben Rob , van Oudenaarden Alexander , Zaldumbide Arnaud , Reinders Marcel J. T. , Koning Eelco J. P. de , Carlotti Françoise
Published: December 2021

The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet cells. Using drug-induced ER stress and cytoskeleton modification models, we demonstrate that altering the islet structure triggers an unfolding protein response that causes the downregulation of β-cell maturity genes. Collectively, our findings illustrate the close relationship between endoplasmic reticulum homeostasis and β-cell phenotype, and strengthen the concept of altered β-cell identity as a mechanism underlying the loss of functional β-cell mass.
The Functional and Mechanistic Roles of Immunoproteasome Subunits in Cancer
Authors: Tripathi Satyendra Chandra , Vedpathak Disha , Ostrin Edwin Justin
Published: December 2021

Cell-mediated immunity is driven by antigenic peptide presentation on major histocompatibility complex (MHC) molecules. Specialized proteasome complexes called immunoproteasomes process viral, bacterial, and tumor antigens for presentation on MHC class I molecules, which can induce CD8 T cells to mount effective immune responses. Immunoproteasomes are distinguished by three subunits that alter the catalytic activity of the proteasome and are inducible by inflammatory stimuli such as interferon-γ (IFN-γ). This inducible activity places them in central roles in cancer, autoimmunity, and inflammation. While accelerated proteasomal degradation is an important tumorigenic mechanism deployed by several cancers, there is some ambiguity regarding the role of immunoproteasome induction in neoplastic transformation. Understanding the mechanistic and functional relevance of the immunoproteasome provides essential insights into developing targeted therapies, including overcoming resistance to standard proteasome inhibition and immunomodulation of the tumor microenvironment. In this review, we discuss the roles of the immunoproteasome in different cancers.