bluuebunny/crossref_metadata_2025 huggingface dataset:
Taxonomy, Saving Potentials and Key Performance Indicators for Energy End-Use and Greenhouse Gas Emissions in the Aluminium Industry and Aluminium Casting Foundries
Authors: Haraldsson Joakim , Johnsson Simon , Thollander Patrik , Wallén Magnus
Published: June 2021

Increasing energy efficiency within the industrial sector is one of the main approaches in order to reduce global greenhouse gas emissions. The production and processing of aluminium is energy and greenhouse gas intensive. To make well-founded decisions regarding energy efficiency and greenhouse gas mitigating investments, it is necessary to have relevant key performance indicators and information about energy end-use. This paper develops a taxonomy and key performance indicators for energy end-use and greenhouse gas emissions in the aluminium industry and aluminium casting foundries. This taxonomy is applied to the Swedish aluminium industry and two foundries. Potentials for energy saving and greenhouse gas mitigation are estimated regarding static facility operation. Electrolysis in primary production is by far the largest energy using and greenhouse gas emitting process within the Swedish aluminium industry. Notably, almost half of the total greenhouse gas emissions from electrolysis comes from process-related emissions, while the other half comes from the use of electricity. In total, about 236 GWh/year (or 9.2% of the total energy use) and 5588–202,475 tonnes CO2eq/year can be saved in the Swedish aluminium industry and two aluminium casting foundries. The most important key performance indicators identified for energy end-use and greenhouse gas emissions are MWh/tonne product and tonne CO2-eq/tonne product. The most beneficial option would be to allocate energy use and greenhouse gas emissions to both the process or machine level and the product level, as this would give a more detailed picture of the company’s energy use and greenhouse gas emissions.
Effect of Mainstream Velocity on the Optimization of a Fan-Shaped Film-Cooling Hole on a Flat Plate
Authors: Lee Soo In , Jung Jin Young , Song Yu Jin , Kwak Jae Su
Published: June 2021

In this study, the effect of mainstream velocity on the optimization of a fan-shaped hole on a flat plate was experimentally investigated. The experiment was conducted by changing the forward expansion angle (βfwd), lateral expansion angle (βlat), and metering length ratio (Lm/D) of the film-cooling hole. A total of 13 cases extracted using the Box–Behnken method were considered to examine the effect of the shape parameters of the film-cooling hole under a 90 m/s mainstream velocity condition, and the results were compared with the results derived under a mainstream velocity of 20 m/s. One density ratio (DR = 2.0) and a blowing ratio (M) ranging from 1.0 to 2.5 were considered, and the pressure-sensitive paint (PSP) technique was applied for the film-cooling effectiveness (FCE). As a result of the experiment, the optimized hole showed a 49.3% improvement in the overall averaged FCE compared to the reference hole with DR = 2.0 and M = 2.0. As the blowing ratio increased, the hole exit area tended to increase, and this tendency was the same as that in the 20 m/s mainstream condition.
The Steady Wake of a Wall-Mounted Rectangular Prism with a Large-Depth-Ratio at Low Reynolds Numbers
Authors: Zargar Arash , Tarokh Ali , Hemmati Arman
Published: June 2021

The wakes of wall-mounted small (square) and large (long) depth-ratio rectangular prisms are numerically studied at Reynolds numbers of 50–250. The large depth-ratio significantly alters the dominance of lateral secondary flow (upwash and downwash) in the wake due to the reattachment of leading-edge separated flow on the surfaces of the prism. This changes the wake topology by varying the entrained flow in the wake region and changing the distribution of vorticity. Thus, the magnitude of vorticity significantly decreases by increasing the prism depth-ratio. Furthermore, the length of the recirculation region and the orientation of near wake flow structures are altered for the larger depth-ratio prism compared to the square prism. Drag and lift coefficients are also affected due to the change of pressure distributions on the rear face of the prism and surface friction force. This behavior is consistently observed for the entire range of Reynolds numbers considered here. The wake size is scaled with Re1/2, whereas drag coefficient scaled with Re−0.3.
Fatigue Analysis Design Approach, Manufacturing and Implementation of a 500 kW Wind Turbine Main Load Frame
Authors: Pehlivan Ahmet Selim , Aksit Mahmut Faruk , Erbatur Kemalettin
Published: June 2021

The main load frame of a wind turbine is the primary mount for all nacelle equipment and is used as the principal load transmitter. This frame should have a reliable fatigue safety rating because it is a load-bearing component. In this work, the fatigue life design, manufacturing and implementation process for the main load frame of a 500 kW wind turbine are studied. The weight of the main load frame and static safety factors are preserved while the cyclic life of the bedplate is kept infinite. Modified Goodman theory is applied to achieve an effective fatigue design using a commercial finite element software package. Analytical calculations are carried out to obtain the safety factors of the bedplate and dynamic strength of the materials. A finite element approach is employed to perform stress analysis. Stress oscillations are established for both welded and cast parts of the hybrid bedplate, and the maximum and minimum stress values are established. Fatigue safety factors are calculated via fatigue analysis iterations. The obtained safety factors are adequate from the perspective of commonly accepted fatigue safety standards. Welding and casting techniques are applied together for manufacturing of the frame. On-site testing indicates that the wind turbine does not show any signs of fatigue. Rupture, cracks, and abrupt accelerometer reading variations are not observed.
Development of Solid Biomass Production in Poland, Especially Pellet, in the Context of the World’s and the European Union’s Climate and Energy Policies
Authors: Bełdycka-Bórawska Aneta , Bórawski Piotr , Borychowski Michał , Wyszomierski Rafał , Bórawski Marek Bartłomiej , Rokicki Tomasz , Ochnio Luiza , Jankowski Krzysztof , Mickiewicz Bartosz , Dunn James W.
Published: June 2021

The aim of this research was to present the changes in biomass production, especially pellets in Poland, in the context of world’s and European Union’s (EU) climate and energy policy, compared to other renewable energy sources. We also analyzed the law concerning the biomass production in the EU. Finally, we have elaborated the prognosis of the pellet production on the world scale. We have used different methods to achieve the goals, among which the most important are the Generalized Autoregressive Conditional Heteroscedasticity (GARCH model) and prognosis. We also compared the results of pellet production in different countries in the European Union. The results were presented in tabular and graphic form. We have received the data from Eurostat and the Main Statistical Office (MSO) in Poland. Our research proves the increase of biomass and pellet production on the global scale. Moreover, global wood pellet production increased by 972% in the years 2005–2018. We can conclude that this increase was the result of increasing demand for renewable energy sources. The first research hypothesis assumed that the changes in the European Union Policy have impacted the increase of biomass production in the world. Our prognosis confirmed the second hypothesis that the development of pellets will increase as the result of increasing global demand. The use of more renewable energy sources is necessary to decrease the degradation of the environment.
Experimental Study of Thermal Performance of Different Fruit Packaging Box Designs
Authors: Leitão Fábio , Silva Pedro D. , Gaspar Pedro D. , Pires Luís C. , Duarte Diana
Published: June 2021

Packaging was recently identified as an essential element in addressing the key challenge of sustainable food supply and is gaining interest among researchers. It is a central element in food quality preservation due to its role in heat and mass exchange with the external atmosphere, contributing to the preservation of food quality during storage and extending food shelf life. This work proposes three new packaging configurations with the same size but different geometry and ventilation hole sizes and geometry, that change the conditions in which the heat and mass exchange occurs, during either the cooling period of fruits, inside the cooling chamber, or during the period when the packaging is exposed to ambient conditions, outside the cooling chamber. For this purpose, packages with fruit models that replicate the properties of real fruit were subjected to a cooling process inside a cooling chamber for 8 h. Subsequently, during the heating phase, the packages were exposed to ambient conditions for 10 h. Thermal conditions were also monitored, both inside and outside the chamber. Additionally, for comparative purposes, the thermal behavior of commercial packaging was also evaluated for the same operating conditions in the cooling and heating phases. The results show that the new packages do not substantially promote the preservation of fruits in the cooling phase, but in the heating phase, they ensure an extension of the period with proper thermal conditions of up to 50% in relation to the conventional packaging. This result is particularly important since the heating phase, in which fruits are outside the storage chamber, is the period with the greatest impact on the fruits’ useful life.
Elevated LNG Vapour Dispersion—Effects of Topography, Obstruction and Phase Change
Authors: Tan Felicia , Tam Vincent , Savvides Chris
Published: June 2021

The dispersion of vapour of liquefied natural gas (LNG) is generally assumed to be from a liquid spill on the ground in hazard and risk analysis. However, this cold vapour could be discharged at height through cold venting. While there is similarity to the situation where a heavier-than-air gas, e.g., CO2, is discharged through tall vent stacks, LNG vapour is cold and induces phase change of ambient moisture leading to changes in the thermodynamics as the vapour disperses. A recent unplanned cold venting of LNG vapour event due to failure of a pilot, provided valuable data for further analysis. This event was studied using CFD under steady-state conditions and incorporating the effect of thermodynamics due to phase change of atmospheric moisture. As the vast majority of processing plants do not reside on flat planes, the effect of surrounding topography was also investigated. This case study highlighted that integral dispersion model was not applicable as key assumptions used to derive the models were violated and suggested guidance and methodologies appropriate for modelling cold vent and flame out situations for elevated vents.
Effects of Three Types of Polymeric Proanthocyanidins on Physicochemical and In Vitro Digestive Properties of Potato Starch
Authors: Xu Jiahui , Dai Taotao , Chen Jun , He Xuemei , Shuai Xixiang , Liu Chengmei , Li Ti
Published: June 2021

The effects of three types of polymeric proanthocyanidins (PPC) with different degrees of polymerization (DP), namely PPC1 (DP = 6.39 ± 0.13), PPC2 (DP = 8.21 ± 0.76), and PPC3 (DP = 9.92 ± 0.21), on the physicochemical characteristics and in vitro starch digestibility of potato starch were studied. PPC addition (5%, w/w) increased the gelatinization temperature and decreased some viscosity indices of potato starch, including the peak, trough, breakdown, and setback viscosities. Starch-PPC pastes showed reduced thixotropy and improved stability and gelling properties compared to starch paste. The three types of proanthocyanidins all showed evident inhibitory effects on the digestion and retrogradation of potato starch, including short-term and long-term retrogradation. Among the three, PPC with a lower DP had stronger effects on the starch short-term retrogradation and gelling performance, whereas larger PPC molecules exhibited a greater impact on starch recrystallization and digestive characteristics. The research consequences were conducive to explore the application of functional PPC in starch-based food processing.
From Stem Cells to Populations—Using hiPSC, Next-Generation Sequencing, and GWAS to Explore the Genetic and Molecular Mechanisms of Congenital Heart Defects
Authors: Broberg Martin , Hästbacka Johanna , Helle Emmi
Published: June 2021

Congenital heart defects (CHD) are developmental malformations affecting the heart and the great vessels. Early heart development requires temporally regulated crosstalk between multiple cell types, signaling pathways, and mechanical forces of early blood flow. While both genetic and environmental factors have been recognized to be involved, identifying causal genes in non-syndromic CHD has been difficult. While variants following Mendelian inheritance have been identified by linkage analysis in a few families with multiple affected members, the inheritance pattern in most familial cases is complex, with reduced penetrance and variable expressivity. Furthermore, most non-syndromic CHD are sporadic. Improved sequencing technologies and large biobank collections have enabled genome-wide association studies (GWAS) in non-syndromic CHD. The ability to generate human to create human induced pluripotent stem cells (hiPSC) and further differentiate them to organotypic cells enables further exploration of genotype–phenotype correlations in patient-derived cells. Here we review how these technologies can be used in unraveling the genetics and molecular mechanisms of heart development.
“I Could Not Manage This Long-Term, Absolutely Not.” Aging in Place, Informal Care, COVID-19, and the Neighborhood in Flanders (Belgium)
Authors: D’herde Jakob , Gruijthuijsen Wesley , Vanneste Dominique , Draulans Veerle , Heynen Hilde
Published: June 2021

Public health and care policies across OECD (Organisation for Economic Co-operation and Development) countries increasingly encourage aging in place, enabled by both formal care networks, and informal (family) care and social solidarity in the neighborhood. However, little is known about how a person’s neighborhood might affect their aging in place. The COVID-19 crisis unintendedly offered a good opportunity to observe the neighborhood’s role in the provision of care. Since formal care services were often limited during the lockdown, informal caregiving may have increased. However, intergenerational contacts in and outside of the household were strongly discouraged by governments worldwide, adding another layer of complexity to caregiving. The aim of this qualitative study was to assess how informal caregivers in Flanders managed to provide care to their care receivers, and what role the neighborhood played in this provision of care. Sixteen qualitative Skype and telephone interviews with informal caregivers were conducted between June and December 2020 to understand their experiences and coping strategies. Overall, most respondents increased their frequency of caregiving during the first lockdown. They took on the extra care needs during the lockdown themselves, and did not actively invoke any kind of neighborhood support. The significance of the neighborhood seemingly remained limited. This was often not because no help was offered, but rather due to a sense of pride or the fear of infection, and an increased effort by family caregivers.
Work Climate Scale in Emergency Services: Abridged Version
Authors: Lozano-Lozano José Antonio , Chacón-Moscoso Salvador , Sanduvete-Chaves Susana , Holgado-Tello Francisco Pablo
Published: June 2021

This study is based on a 40-item work climate scale in hospital emergency services (WCSHES). Teams working in these emergency services experience a heavy workload and have a limited amount of time with each patient. COVID-19 has further complicated these existing issues. Therefore, we believed it would be helpful to draft an abridged version of the 40-item WCSHES, considering both validity and reliability criteria, but giving greater weight to validity. One hundred and twenty-six workers between the ages of 20 to 64 (M = 32.45; standard deviation (SD = 9.73)) years old participated voluntarily in the study. The validity, reliability, and fit model were evaluated in an iterative process. The confirmatory factor analysis yielded appropriate global fit indices in the abridged 24-item version (Χ2(248) = 367.84; p < 0.01, RMSEA = 0.06 with an interval of 90% from 0.05 to 0.07, SRMR = 0.08, GFI = 0.9, AGFI = 0.96, CFI = 0.98, NFI = 0.95, and NNFI = 0.98), along with test criteria validity (ρXY = 0.68, p < 0.001) and excellent reliability (α = 0.94 and ω = 0.94), maintaining the same conceptualization and usefulness of the original scale. The abridged 24-item version was used to measure four work climate factors (work satisfaction, productivity/achievement of aims, interpersonal relations, and performance at work). Evidence of the usefulness of the new abridged scale is provided along with a description of our study limitations and future areas for development.
The Association between Health and Culture: The Perspective of Older Adult Hospital In-Patients in Israel
Authors: Even-Zohar Ahuva , Shtanger Varda , Israeli Anat , Averbuch Emma , Segal Gad , Mayan Haim , Steinlauf Shmuel , Galper Alex , Zimlichman Eyal
Published: June 2021

People from different cultures are often hospitalized while the staff treating them do not have sufficient knowledge about the attitudes and feelings of the patients regarding culture and health. To fill this gap, the aim of this study was to examine the perspective of Israeli older adult hospital in-patients regarding the association between health and culture and to understand the meaning of the participants’ experiences with regards to the medical staff’s attitude towards them. This study was carried out using qualitative methodology that followed the interpretive interactionism approach. The research participants were 493 (mean age 70.81, S.D.: 15.88) in-patients at internal care departments at a hospital in Israel who answered an open-ended question included in the questionnaire as part of a wide study held during 2017 to 2018. Two main themes were found: (1) a humane attitude of respect and the right to privacy and (2) beliefs, values, and traditional medicine that are passed down through generations. The findings highlighted the issue of the patients’ cultural heritage and ageist attitudes they ascribed to the professional staff. This study provided recommendations for training the in-patient hospital workforce on the topic of cultural competence, beginning from the stage of diagnosis through treatment and to discharge from the hospital, in order to improve the service.
Public Response on Social Media to a Social Marketing Campaign for Influencing Attitudes towards Boating Safety
Authors: Smith Jennifer , Clemens Tessa , Macpherson Alison , Pike Ian
Published: June 2021

The purpose of this research paper is to assess the response on Facebook to a social marketing campaign for recreational boating safety. The campaign ran for the 2018 and 2019 boating seasons in British Columbia, Canada. Messages related to boating safety were delivered in multi-media formats, including ten Facebook posts. All public comments on the campaign Facebook page in response to the ads were included in the analysis. Comments were reviewed for tone and subject; those that related directly to the campaign or boating safety-related topics, such as alcohol use or enforcement, were labeled positive, negative or neutral in tone. Metrics such as likes and shares were also noted. The overall engagement rate (defined as engagements over people reached) was 4.1%. The posts were liked >7000 times and received 901 shares. A total of 219 comments were analysed. Almost half of the comments were positive (n = 106, 48.4%). Fifty comments were off-topic (22.8%), 45 were neutral (20.5%) and 18 were negative (8.2%). The majority of comments were positive, indicating that the campaign performed as planned and was generally well received by the people for whom it was intended. Comments illuminated prevailing attitudes towards risks, injuries and safety practices related to recreational boating. Positive comments valued safety as an aspect of having a pleasant experience, rather than a barrier. Negative comments were about perceiving reduced fun of boating, rather than objecting to the campaign itself. As a component of a multi-media social marketing strategy, Facebook can be a source of instant feedback from the campaign audience.
The Impact of and Government Planning and Responses to Pandemics for People with Disability: A Rapid Review
Authors: Gupta Adyya , Kavanagh Anne , Disney George
Published: June 2021

Objective—To collate evidence on (1) the risk of infection for people with disability during infectious disease outbreaks and/or pandemics and (2) government responses and pandemic plans for people with disability. Methods—Through two rapid reviews, relevant peer-reviewed studies and grey literature published from 2002 onwards in the English language were identified. Data were synthesised narratively. Results—Aim 1: Of the 680 studies, two studies were included in the review. No grey literature was eligible for inclusion. The evidence regarding risk was inconclusive. Aim 2: Of the 50 studies, three peer-review studies, along with four government reports were included. The literature largely reported on measures being taken to maximise the prevention of transmission of COVID-19 for the general population, with only a few programs including people with disability. Conclusion—Overall, there is inconclusive evidence on the risk of infection for people with disability during infectious disease outbreaks and/or pandemics and the government preparedness and planning for disease outbreaks and/or pandemics largely exclude people with disability. From a population health perspective, during disease outbreaks and pandemics, including the COVID-19 pandemic, along with the general population, it is important for governments to include people with disability in their pandemic planning and response.
Identifying Interactive Factors That May Increase Crash Risk between Young Drivers and Trucks: A Narrative Review
Authors: Freire Melissa R. , Gauld Cassandra , McKerral Angus , Pammer Kristen
Published: June 2021

Sharing the road with trucks is associated with increased risk of serious injury and death for passenger vehicle drivers. However, the onus for minimising risk lies not just with truck drivers; other drivers must understand the unique performance limitations of trucks associated with stopping distances, blind spots, and turning manoeuverability, so they can suitably act and react around trucks. Given the paucity of research aimed at understanding the specific crash risk vulnerability of young drivers around trucks, the authors employ a narrative review methodology that brings together evidence from both truck and young driver road safety research domains, as well as data regarding known crash risks for each driving cohort, to gain a comprehensive understanding of what young drivers are likely to know about heavy vehicle performance limitations, where there may be gaps in their understanding, and how this could potentially increase crash risk. We then review literature regarding the human factors affecting young drivers to understand how perceptual immaturity and engagement in risky driving behaviours are likely to compound risk regarding both the frequency and severity of collision between trucks and young drivers. Finally, we review current targeted educational initiatives and suggest that simply raising awareness of truck limitations is insufficient. We propose that further research is needed to ensure initiatives aimed at increasing young driver awareness of trucks and truck safety are evidence-based, undergo rigorous evaluation, and are delivered in a way that aims to (i) increase young driver risk perception skills, and (ii) reduce risky driving behaviour around trucks.
Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells
Authors: Lee Hanon , Lee Dong Hun , Oh Jang-Hee , Chung Jin Ho
Published: June 2021

Skullcapflavone II (SFII), a flavonoid derived from Scutellaria baicalensis, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-α/IFN-γ-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-α/IFN-γ in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-α/IFN-γ-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-κB, and p38 MAPK mediate TNF-α/IFN-γ-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-α/IFN-γ-induced phosphorylation of STAT1, NF-κB, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-α/IFN-γ-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-κB, and p38 MAPK signaling pathways.
Superoxide Dismutase 3-Transduced Mesenchymal Stem Cells Preserve Epithelial Tight Junction Barrier in Murine Colitis and Attenuate Inflammatory Damage in Epithelial Organoids
Authors: Tak Lee-Jung , Kim Hae-Young , Ham Won-Kook , Agrahari Gaurav , Seo Yoojin , Yang Ji Won , An Eun-Joo , Bang Chul Hwan , Lee Min Jung , Kim Hyung-Sik , Kim Tae-Yoon
Published: June 2021

Superoxide dismutase 3 (SOD3), also known as extracellular superoxide dismutase, is an enzyme that scavenges reactive oxygen species (ROS). It has been reported that SOD3 exerts anti-inflammatory abilities in several immune disorders. However, the effect of SOD3 and the underlying mechanism in inflammatory bowel disease (IBD) have not been uncovered. Therefore, in the present study, we investigated whether SOD3 can protect intestinal cells or organoids from inflammation-mediated epithelial damage. Cells or mice were treated with SOD3 protein or SOD3-transduced mesenchymal stem cells (MSCs). Caco-2 cells or intestinal organoids stimulated with pro-inflammatory cytokines were used to evaluate the protective effect of SOD3 on epithelial junctional integrity. Dextran sulfate sodium (DSS)-induced colitis mice received SOD3 or SOD3-transduced MSCs (SOD3-MSCs), and were assessed for severity of disease and junctional protein expression. The activation of the mitogen-activated protein kinase (MAPK) pathway and elevated expression of cytokine-encoding genes decreased in TNF-α-treated Caco-2 cells or DSS-induced colitis mice when treated with SOD3 or SOD3-MSCs. Moreover, the SOD3 supply preserved the expression of tight junction (ZO-1, occludin) or adherence junction (E-cadherin) proteins when inflammation was induced. SOD3 also exerted a protective effect against cytokine- or ROS-mediated damage to intestinal organoids. These results indicate that SOD3 can effectively alleviate enteritis symptoms by maintaining the integrity of epithelial junctions and regulating inflammatory- and oxidative stress.
BrPP5.2 Overexpression Confers Heat Shock Tolerance in Transgenic Brassica rapa through Inherent Chaperone Activity, Induced Glucosinolate Biosynthesis, and Differential Regulation of Abiotic Stress Response Genes
Authors: Muthusamy Muthusamy , Kim Jong Hee , Kim Suk Hee , Park So Young , Lee Soo In
Published: June 2021

Plant phosphoprotein phosphatases are ubiquitous and multifarious enzymes that respond to developmental requirements and stress signals through reversible dephosphorylation of target proteins. In this study, we investigated the hitherto unknown functions of Brassica rapa protein phosphatase 5.2 (BrPP5.2) by transgenic overexpression of B. rapa lines. The overexpression of BrPP5.2 in transgenic lines conferred heat shock tolerance in 65–89% of the young transgenic seedlings exposed to 46 °C for 25 min. The examination of purified recombinant BrPP5.2 at different molar ratios efficiently prevented the thermal aggregation of malate dehydrogenase at 42 °C, thus suggesting that BrPP5.2 has inherent chaperone activities. The transcriptomic dynamics of transgenic lines, as determined using RNA-seq, revealed that 997 and 1206 (FDR < 0.05, logFC ≥ 2) genes were up- and down-regulated, as compared to non-transgenic controls. Statistical enrichment analyses revealed abiotic stress response genes, including heat stress response (HSR), showed reduced expression in transgenic lines under optimal growth conditions. However, most of the HSR DEGs were upregulated under high temperature stress (37 °C/1 h) conditions. In addition, the glucosinolate biosynthesis gene expression and total glucosinolate content increased in the transgenic lines. These findings provide a new avenue related to BrPP5.2 downstream genes and their crucial metabolic and heat stress responses in plants.
Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives
Authors: Kouhi Aida , Pachipulusu Vyshnavi , Kapenstein Talya , Hu Peisheng , Epstein Alan L. , Khawli Leslie A.
Published: June 2021

Due to their high specificity, monoclonal antibodies have been widely investigated for their application in drug delivery to the central nervous system (CNS) for the treatment of neurological diseases such as stroke, Alzheimer’s, and Parkinson’s disease. Research in the past few decades has revealed that one of the biggest challenges in the development of antibodies for drug delivery to the CNS is the presence of blood–brain barrier (BBB), which acts to restrict drug delivery and contributes to the limited uptake (0.1–0.2% of injected dose) of circulating antibodies into the brain. This article reviews the various methods currently used for antibody delivery to the CNS at the preclinical stage of development and the underlying mechanisms of BBB penetration. It also describes efforts to improve or modulate the physicochemical and biochemical properties of antibodies (e.g., charge, Fc receptor binding affinity, and target affinity), to adapt their pharmacokinetics (PK), and to influence their distribution and disposition into the brain. Finally, a distinction is made between approaches that seek to modify BBB permeability and those that use a physiological approach or antibody engineering to increase uptake in the CNS. Although there are currently inherent difficulties in developing safe and efficacious antibodies that will cross the BBB, the future prospects of brain-targeted delivery of antibody-based agents are believed to be excellent.
Pulmonary Stretch and Lung Mechanotransduction: Implications for Progression in the Fibrotic Lung
Authors: Marchioni Alessandro , Tonelli Roberto , Cerri Stefania , Castaniere Ivana , Andrisani Dario , Gozzi Filippo , Bruzzi Giulia , Manicardi Linda , Moretti Antonio , Demurtas Jacopo , Baroncini Serena , Andreani Alessandro , Cappiello Gaia Francesca , Busani Stefano , Fantini Riccardo , Tabbì Luca , Samarelli Anna Valeria , Clini Enrico
Published: June 2021

Lung fibrosis results from the synergic interplay between regenerative deficits of the alveolar epithelium and dysregulated mechanisms of repair in response to alveolar and vascular damage, which is followed by progressive fibroblast and myofibroblast proliferation and excessive deposition of the extracellular matrix. The increased parenchymal stiffness of fibrotic lungs significantly affects respiratory mechanics, making the lung more fragile and prone to non-physiological stress during spontaneous breathing and mechanical ventilation. Given their parenchymal inhomogeneity, fibrotic lungs may display an anisotropic response to mechanical stresses with different regional deformations (micro-strain). This behavior is not described by the standard stress–strain curve but follows the mechano-elastic models of “squishy balls”, where the elastic limit can be reached due to the excessive deformation of parenchymal areas with normal elasticity that are surrounded by inelastic fibrous tissue or collapsed induration areas, which tend to protrude outside the fibrous ring. Increasing evidence has shown that non-physiological mechanical forces applied to fibrotic lungs with associated abnormal mechanotransduction could favor the progression of pulmonary fibrosis. With this review, we aim to summarize the state of the art on the relation between mechanical forces acting on the lung and biological response in pulmonary fibrosis, with a focus on the progression of damage in the fibrotic lung during spontaneous breathing and assisted ventilatory support.
Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?
Authors: Gabryanczyk Anna , Klimczak Sylwia , Szymczak-Pajor Izabela , Śliwińska Agnieszka
Published: June 2021

There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor β (TGFβ), insulin-like growth factor (IGF) and Wnt-β-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes.
Impaired Leptin Signalling in Obesity: Is Leptin a New Thermolipokine?
Authors: Genchi Valentina Annamaria , D’Oria Rossella , Palma Giuseppe , Caccioppoli Cristina , Cignarelli Angelo , Natalicchio Annalisa , Laviola Luigi , Giorgino Francesco , Perrini Sebastio
Published: June 2021

Leptin is a principal adipose-derived hormone mostly implicated in the regulation of energy balance through the activation of anorexigenic neuronal pathways. Comprehensive studies have established that the maintenance of certain concentrations of circulating leptin is essential to avoid an imbalance in nutrient intake. Indeed, genetic modifications of the leptin/leptin receptor axis and the obesogenic environment may induce changes in leptin levels or action in a manner that accelerates metabolic dysfunctions, resulting in a hyperphagic status and adipose tissue expansion. As a result, a vicious cycle begins wherein hyperleptinaemia and leptin resistance occur, in turn leading to increased food intake and fat enlargement, which is followed by leptin overproduction. In addition, in the context of obesity, a defective thermoregulatory response is associated with impaired leptin signalling overall within the ventromedial nucleus of the hypothalamus. These recent findings highlight the role of leptin in the regulation of adaptive thermogenesis, thus suggesting leptin to be potentially considered as a new thermolipokine. This review provides new insight into the link between obesity, hyperleptinaemia, leptin resistance and leptin deficiency, focusing on the ability to restore leptin sensitiveness by way of enhanced thermogenic responses and highlighting novel anti-obesity therapeutic strategies.
Microelectromechanical System Measurement of Platelet Contraction: Direct Interrogation of Myosin Light Chain Phosphorylation
Authors: George Mitchell J. , Litvinov Julia , Aroom Kevin , Spangler Leland J. , Caplan Henry , Wade Charles E. , Cox Charles S. , Gill Brijesh S.
Published: June 2021

Myosin Light Chain (MLC) regulates platelet contraction through its phosphorylation by Myosin Light Chain Kinase (MLCK) or dephosphorylation by Myosin Light Chain Phosphatase (MLCP). The correlation between platelet contraction force and levels of MLC phosphorylation is unknown. We investigate the relationship between platelet contraction force and MLC phosphorylation using a novel microelectromechanical (MEMS) based clot contraction sensor (CCS). The MLCK and MLCP pair were interrogated by inhibitors and activators of platelet function. The CCS was fabricated from silicon using photolithography techniques and force was validated over a range of deflection for different chip spring constants. The force of platelet contraction measured by the clot contraction sensor (CCS) was compared to the degree of MLC phosphorylation by Western Blotting (WB) and ELISA. Stimulators of MLC phosphorylation produced higher contraction force, higher phosphorylated MLC signal in ELISA and higher intensity bands in WB. Inhibitors of MLC phosphorylation produced the opposite. Contraction force is linearly related to levels of phosphorylated MLC. Direct measurements of clot contractile force are possible using a MEMS sensor platform and correlate linearly with the degree of MLC phosphorylation during coagulation. Measured force represents the mechanical output of the actin/myosin motor in platelets regulated by myosin light chain phosphorylation.
Emulsion-Based Multicompartment Vaginal Drug Carriers: From Nanoemulsions to Nanoemulgels
Authors: Smoleński Michał , Karolewicz Bożena , Gołkowska Anna M. , Nartowski Karol P. , Małolepsza-Jarmołowska Katarzyna
Published: June 2021

In order to overcome the limitations associated with vaginal administration of drugs, e.g., the short contact time of the drug form with the mucosa or continuous carrier wash-out, the development of new carriers for gynecological use is necessary. Furthermore, high individual anatomical and physiological variability resulting in unsatisfactory therapeutic efficacy of lipophilic active substances requires application of multicompartment drug delivery systems. This manuscript provides an up-to-date comprehensive review of the literature on emulsion-based vaginal dosage forms (EVDF) including macroemulsions, microemulsions, nanoemulsions, multiple emulsions and self-emulsifying drug delivery systems. The first part of the paper discusses (i) the influence of anatomical-physiological conditions on therapeutic efficacy of drug forms after local and systemic administration, (ii) characterization of EVDF components and the manufacturing techniques of these dosage forms and (iii) methods used to evaluate the physicochemical and pharmaceutical properties of emulsion-based vaginal dosage forms. The second part of the paper presents (iv) the results of biological and in vivo studies as well as (v) clinical evaluation of EVDF safety and therapeutic efficacy across different indications.
Potentiating Hemorrhage in a Periadolescent Rat Model of Closed-Head Traumatic Brain Injury Worsens Hyperexcitability but Not Behavioral Deficits
Authors: Jalloul Dounya , Hajjar Helene , Asdikian Rita , Maawie Mariam , Nasrallah Leila , Medlej Yasser , Darwich Mouhamad , Karnib Nabil , Lawand Nada , Abdel Rassoul Ronza , Wang Kevin K. W. , Kobeissy Firas , Darwish Hala , Obeid Makram
Published: June 2021

Post-traumatic epilepsy (PTE) and neurocognitive deficits are devastating sequelae of head injuries that are common in adolescents. Investigating desperately needed treatments is hindered by the difficulties in inducing PTE in rodents and the lack of established immature rat models of pediatric PTE. Hemorrhage is a significant risk factor for PTE, but compared to humans, rats are less prone to bleeding because of their rapid blood coagulation system. In this study, we promoted bleeding in the controlled cortical impact (CCI) closed-head injury model with a 20 min pre-impact 600 IU/kg intraperitoneal heparin injection in postnatal day 35 (P35) periadolescent rats, given the preponderance of such injuries in this age group. Temporo-parietal CCI was performed post-heparin (HTBI group) or post-saline (TBI group). Controls were subjected to sham procedures following heparin or saline administration. Continuous long-term EEG monitoring was performed for 3 months post-CCI. Sensorimotor testing, the Morris water maze, and a modified active avoidance test were conducted between P80 and P100. Glial fibrillary acidic protein (GFAP) levels and neuronal damage were also assessed. Compared to TBI rats, HTBI rats had persistently higher EEG spiking and increased hippocampal GFAP levels (p < 0.05). No sensorimotor deficits were detected in any group. Compared to controls, both HTBI and TBI groups had a long-term hippocampal neuronal loss (p < 0.05), as well as contextual and visuospatial learning deficits (p < 0.05). The hippocampal astrogliosis and EEG spiking detected in all rats subjected to our hemorrhage-promoting procedure suggest the emergence of hyperexcitable networks and pave the way to a periadolescent PTE rat model.
Mismatch Intolerance of 5′-Truncated sgRNAs in CRISPR/Cas9 Enables Efficient Microbial Single-Base Genome Editing
Authors: Lee Ho Joung , Kim Hyun Ju , Lee Sang Jun
Published: June 2021

The CRISPR/Cas9 system has recently emerged as a useful gene-specific editing tool. However, this approach occasionally results in the digestion of both the DNA target and similar DNA sequences due to mismatch tolerance, which remains a significant drawback of current genome editing technologies. However, our study determined that even single-base mismatches between the target DNA and 5′-truncated sgRNAs inhibited target recognition. These results suggest that a 5′-truncated sgRNA/Cas9 complex could be used to negatively select single-base-edited targets in microbial genomes. Moreover, we demonstrated that the 5′-truncated sgRNA method can be used for simple and effective single-base editing, as it enables the modification of individual bases in the DNA target, near and far from the 5′ end of truncated sgRNAs. Further, 5′-truncated sgRNAs also allowed for efficient single-base editing when using an engineered Cas9 nuclease with an expanded protospacer adjacent motif (PAM; 5′-NG), which may enable whole-genome single-base editing.
Immunofluorescence Analysis of NF-kB and iNOS Expression in Different Cell Populations during Early and Advanced Knee Osteoarthritis
Authors: Ostojic Marko , Zevrnja Ante , Vukojevic Katarina , Soljic Violeta
Published: June 2021

Synovitis of the knee synovium is proven to be a precursor of knee osteoarthritis (OA), leading to a radiologically advanced stage of the disease. This study was conducted to elucidate the expression pattern of different inflammatory factors—NF-kB, iNOS, and MMP-9 in a subpopulation of synovial cells. Thirty synovial membrane intra-operative biopsies of patients (ten controls, ten with early OA, and ten with advanced OA, according to the Kellgren–Lawrence radiological score) were immunohistochemically stained for NF-kB, iNOS, and MMP9, and for different cell markers for macrophages, fibroblasts, leukocytes, lymphocytes, blood vessel endothelial cells, and blood vessel smooth muscle cells. The total number of CD68+/NF-kB+ cells/mm2 in the intima of early OA patients (median = 2359) was significantly higher compared to the total number of vimentin+/Nf-kB+ cells/mm2 (median = 1321) and LCA+/NF-kB+ cells/mm2 (median = 64) (p < 0.001 and p < 0.0001, respectively). The total number of LCA+/NF-kB+ cells/mm2 in the subintima of advanced OA patients (median = 2123) was significantly higher compared to the total number of vimentin+/NF-kB+ cells/mm2 (median = 14) and CD68+/NF-kB+ cells/mm2 (median = 29) (p < 0.0001). The total number of CD68+/iNOS+ cells/mm2 in the intima of both early and advanced OA patients was significantly higher compared to the total number of vimentin+/iNOS+ cells/mm2 and LCA+/iNOS+ cells/mm2 (p < 0.0001 and p < 0.001, respectively). The total number of CD68+/MMP-9+ cells/mm2 in the intima of both early and advanced OA patients was significantly higher compared to the total number of vimentin+/MMP-9+ cells/mm2 and CD5+/MMP-9+ cells/mm2 (p < 0.0001). Macrophages may have a leading role in OA progression through the NF-kB production of inflammatory factors (iNOS and MMP-9) in the intima, except in advanced OA, where leukocytes could have a dominant role through NF-kB production in subintima. The blocking of macrophageal and leukocyte NF-kB expression is a possible therapeutic target as a disease modifying drug.
Continuous Adjoint-Based Optimization of an Internally Cooled Turbine Blade—Mathematical Development and Application
Authors: Trompoukis Xenofon , Tsiakas Konstantinos , Asouti Varvara , Kontou Marina , Giannakoglou Kyriakos
Published: June 2021

This paper presents an adjoint-based shape optimization framework and its demonstration in a conjugate heat transfer problem in a turbine blading. The gradient of the objective function is computed based on the continuous adjoint method, which also includes the adjoint to the turbulence model. Differences in the gradient resulting from making the frozen turbulence assumption are discussed. The developed software was used to optimize both the blade shape of the internally cooled linear C3X turbine blade and the position of cooling channels aiming at (a) minimum total pressure drop of the hot gas flow and (b) minimum highest temperature within the blade. A two-step optimization procedure was used. A free-form parameterization tool, based on volumetric NURBS, controls the blade airfoil contour, while the cooling channels are free to move following changes in the coordinates of their centers. Geometric and flow constraints are included in the performed optimizations, keeping the cooling channels away from the airfoil sides and retaining the turbine inlet capacity and flow turning.
Stock Trend Prediction Using Deep Learning Approach on Technical Indicator and Industrial Specific Information
Authors: Prachyachuwong Kittisak , Vateekul Peerapon
Published: June 2021

A stock trend prediction has been in the spotlight from the past to the present. Fortunately, there is an enormous amount of information available nowadays. There were prior attempts that have tried to forecast the trend using textual information; however, it can be further improved since they relied on fixed word embedding, and it depends on the sentiment of the whole market. In this paper, we propose a deep learning model to predict the Thailand Futures Exchange (TFEX) with the ability to analyze both numerical and textual information. We have used Thai economic news headlines from various online sources. To obtain better news sentiment, we have divided the headlines into industry-specific indexes (also called “sectors”) to reflect the movement of securities of the same fundamental. The proposed method consists of Long Short-Term Memory Network (LSTM) and Bidirectional Encoder Representations from Transformers (BERT) architectures to predict daily stock market activity. We have evaluated model performance by considering predictive accuracy and the returns obtained from the simulation of buying and selling. The experimental results demonstrate that enhancing both numerical and textual information of each sector can improve prediction performance and outperform all baselines.