bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Verification of Real-Time Flow-Rate Estimations in a Tilting-Ladle-Type Automatic Pouring Machine
Authors: Sueki Yuta , Noda Yoshiyuki
Published: July 2021

This paper discusses a real-time flow-rate estimation method for a tilting-ladle-type automatic pouring machine used in the casting industry. In most pouring machines, molten metal is poured into a mold by tilting the ladle. Precise pouring is required to improve productivity and ensure a safe pouring process. To achieve precise pouring, it is important to control the flow rate of the liquid outflow from the ladle. However, due to the high temperature of molten metal, directly measuring the flow rate to devise flow-rate feedback control is difficult. To solve this problem, specific flow-rate estimation methods have been developed. In the previous study by present authors, a simplified flow-rate estimation method was proposed, in which Kalman filters were decentralized to motor systems and the pouring process for implementing into the industrial controller of an automatic pouring machine used a complicatedly shaped ladle. The effectiveness of this flow rate estimation was verified in the experiment with the ideal condition. In the present study, the appropriateness of the real-time flow-rate estimation by decentralization of Kalman filters is verified by comparing it with two other types of existing real-time flow-rate estimations, i.e., time derivatives of the weight of the outflow liquid measured by the load cell and the liquid volume in the ladle measured by a visible camera. We especially confirmed the estimation errors of the candidate real-time flow-rate estimations in the experiments with the uncertainty of the model parameters. These flow-rate estimation methods were applied to a laboratory-type automatic pouring machine to verify their performance.
Invisalign® vs. Spark™ Template: Which Is the Most Effective in the Attachment Bonding Procedure? A Randomized Controlled Trial
Authors: Bruno Giovanni , Gracco Antonio , Barone Martina , Mutinelli Sabrina , De Stefani Alberto
Published: July 2021

Aim: The primary aim of this randomized clinical trial was to evaluate the percentage of attachments’ debonding at the template’s removal both in Invisalign® and Spark™ systems. The secondary aim was to define the percentage of patients who did not show attachments’ debonding at the template’s removal. Materials and methods: Eighty patients who needed an orthodontic treatment were included in the study and randomly assigned to a treatment to be performed with Spark™ or Invisalign® clear aligners system. The patients were equally divided into two groups: Spark group (n = 40) and Invisalign group (n = 40). At the template removal by the teeth surface after the attachment bonding procedure, in each patient of both groups, it was assessed if some attachment debonding occurred and the number of attachments detached. Results: The Spark group showed, in general, a lower frequency in debonding in comparison with the Invisalign group, as 87.5% of patients in the Spark group did not show any bonding failure versus 27.5% in those of the Invisalign group. Conclusions: At template removal, the Spark™ template showed less attachment debonding compared to the Invisalign® template. The Spark™ template can be considered more effective in attachments’ transferring to the tooth surface than the Invisalign® one.
Developing a Long Short-Term Memory-Based Model for Forecasting the Daily Energy Consumption of Heating, Ventilation, and Air Conditioning Systems in Buildings
Authors: Mendoza-Pittí Luis , Calderón-Gómez Huriviades , Gómez-Pulido José Manuel , Vargas-Lombardo Miguel , Castillo-Sequera José Luis , de Blas Clara Simon
Published: July 2021

Forecasting the energy consumption of heating, ventilating, and air conditioning systems is important for the energy efficiency and sustainability of buildings. In fact, conventional models present limitations in these systems due to their complexity and unpredictability. To overcome this, the long short-term memory-based model is employed in this work. Our objective is to develop and evaluate a model to forecast the daily energy consumption of heating, ventilating, and air conditioning systems in buildings. For this purpose, we apply a comprehensive methodology that allows us to obtain a robust, generalizable, and reliable model by tuning different parameters. The results show that the proposed model achieves a significant improvement in the coefficient of variation of root mean square error of 9.5% compared to that proposed by international agencies. We conclude that these results provide an encouraging outlook for its implementation as an intelligent service for decision making, capable of overcoming the problems of other noise-sensitive models affected by data variations and disturbances without the need for expert knowledge in the domain.
Comparative Study of the Field Performances of Pressure-Grouted Micropiles Using Gravity and Packers
Authors: Heo Ong , Yoon Yeowon , Do Jinung
Published: July 2021

When underground space requires excavation in areas below the water table, the foundation system suffers from buoyancy, which leads to the uplifting of the superstructure. A deep foundation system can be used; however, in cases where a hard layer is encountered, high driving forces and corresponding noises cause civil complaints in urban areas. Micropiles can be an effective alternative option, due to their high performance despite a short installation depth. Pressurized grouting is used with a packer to induce higher interfacial properties between micropile and soil. In this study, the field performance of micropiles installed using gravitational grouting or pressure-grouted using either a geotextile packer or rubber packer was comparatively evaluated by tension and creep tests. Micropiles were installed using pressure grouting in weak and fractured zones. As results, the pressure-grouted micropiles showed more stable and stronger behaviors than ones installed using the gravitational grouting. Moreover, the pressure-grouted micropile installed using the rubber packer showed better performance than the one using the geotextile packer.
Fluorescence Correlation Spectroscopy Measurement Based on Fiber Optics for Biological Materials
Authors: Yamamoto Johtaro , Sasaki Akira
Published: July 2021

A robust fluorescence correlation spectroscopy system called fiber-optic based fluorescence correlation spectroscopy (FB-FCS) was developed; this system enables the measurement of diffusion dynamics and concentration of fluorescent molecules based on the principle of fluorescence correlation spectroscopy without any mechanical adjustment of the experimental setup. The system consisted of fiber optics and a water-immersion objective lens. The hydrodynamic diameters and concentrations of organic fluorescent dyes and fluorescently labeled proteins were successfully measured. Because of the fiber-optic-based setup, the FB-FCS system is compact and inexpensive. We expect FB-FCS to be suitable for use in laboratories, medical diagnosis, and environmental measurements.
An Economical and Precise Cooling Model and Its Application in a Single-Cylinder Diesel Engine
Authors: Xie Zhifeng , Wang Ao , Liu Zhuoran
Published: July 2021

The cooling system is an important subsystem of an internal combustion engine, which plays a vital role in the engine’s dynamical characteristic, the fuel economy, and emission output performance at each speed and load. This paper proposes an economical and precise model for an electric cooling system, including the modeling of engine heat rejection, water jacket temperature, and other parts of the cooling system. This model ensures that the engine operates precisely at the designated temperature and the total power consumption of the cooling system takes the minimum value at some power proportion of fan and pump. Speed maps for the cooling fan and pump at different speeds and loads of engine are predicted, which can be stored in the electronic control unit (ECU). This model was validated on a single-cylinder diesel engine, called the DK32. Furthermore, it was used to tune the temperature of the water jacket precisely. The results show that in the common use case, the electric cooling system can save the power of 255 W in contrast with the mechanical cooling system, which is about 1.9% of the engine’s power output. In addition, the validation results of the DK32 engine meet the non-road mobile machinery China-IV emission standards.
Effects of Visual Active Deceleration Devices on Controlling Vehicle Speeds in a Long Downhill Tunnel of an Expressway
Authors: Wang Fu , Gu Dengjun , Li Yuanyuan , Liu Wei , Wang Guoyun , Ding Naikan
Published: July 2021

Because the inside of a road tunnel is a closed strip, the driving environment changes suddenly at the tunnel entrance and exit, which is why accidents occur more frequently in tunnels than elsewhere. Based on visual psychology, reverse-perspective-illusion deceleration lines (RPIDLs) and visual-intervention deceleration devices (VIDDs) were designed to control vehicle speeds near the entrance and in the middle of a tunnel, respectively. Then, to assess the speed-controlling performance of the RPIDLs and VIDDs for vehicles in a long downhill tunnel, laser velocimeters were used to measure the vehicle speeds at different observation points in the tunnel before and after implementing the RPIDLs and VIDDs. The results show that the RPIDLs and VIDDs decreased the average vehicle speed and controlled its dispersion effectively. The 60 m RPIDLs improved the traffic safety in the tunnel without lessening the passing ability therein. The slash-line VIDD had no obvious effect on the maximum vehicle speeds in the middle of the tunnel. Both the 90° fold-line VIDD and the four-yellow–four-white VIDD decreased the maximum vehicle speeds significantly. The 60 m RPIDLs and the 90° fold-line VIDD gave the best deceleration effect on vehicles near the entrance and in the middle of the tunnel, respectively, and controlled the average speed and its dispersion effectively.
Axial Compressive Performance of a Composite Concrete-Filled GFRP Tube Square Column
Authors: Lu Jiancheng , Qi Yujun , Li Yifei , Wang Xuxu
Published: July 2021

A composite concrete-filled glass fiber reinforced polymer (GFRP) tube square column is a new type of composite column, where GFRP is externally wrapped over several GFRP square tubes to form a multicavity GFRP tube, and then concrete is poured inside. External GFRP wrapping methods can be divided into two types: entirely wrapped and strip-type wrapped methods. The former is superior to the latter in terms of performance under stress. However, difficulties are introduced in the construction process of the former, and substantial materials are required to wrap the entire structure. To examine the axial compressive performance for this new type of composite column and the impact of the wrapping method, we designed and fabricated one type of entirely wrapped composite column and two types of strip-type wrapped composite columns with clear spacings of 85 mm and 40 mm, respectively, and performed static axial compression tests. Through tests and numerical simulations, we obtained the failure mode, load–displacement curve, and load–strain curve of the specimen, and analyzed the impact of the externally wrapped GFRP on the mechanical behavior of the composite column. The results show that the composite column reached the peak load before the fracture of the GFRP tube fiber occurred, and the bearing capacity declined sharply to approximately 75% of the peak load after the fiber fractured, then entered a platform section, thereby displaying ductile failure. As the wrapped layers of GFRP strips increased, the load capacity of the specimen exhibited a linear growth tendency. Compared with the performance of the entirely wrapped method, the load capacity of the specimens in the W5040 group declined 9.8% on average, and the peak efficiency of the GFRP strips increased by 50%, thereby indicating that the use of appropriate GFRP layers and strip distance intervals can ensure the appropriate bearing capacity of composite columns and full utilization of GFRP material properties.
Microbiological Changes during Orthodontic Aligner Therapy: A Prospective Clinical Trial
Authors: Sfondrini Maria Francesca , Butera Andrea , Di Michele Pietro , Luccisano Claudia , Ottini Beatrice , Sangalli Enrico , Gallo Simone , Pascadopoli Maurizio , Gandini Paola , Scribante Andrea
Published: July 2021

The purpose of this study is to assess the variations induced by Clear Aligner Treatment (CAT) on the periodontal status and microbiological composition of oral microbiota. A total of 20 orthodontic patients were submitted to professional oral hygiene and, subsequently, underwent CAT (Group one, trials). A total of 20 non orthodontic patients (Group two, controls) remained untreated after oral hygiene. At T0 (baseline) and T1 (after 2 months), the participants were clinically examined for Probing Pocket Depth (PPD), Bleeding on Probing (BOP) and Plaque Index (PI), and microbiological tests were performed to detect bacteria of the red and orange complexes as well as the presence of Aggregatibacter actinomycetemcomitans. No significant inter- or intra-group differences were shown neither for PPD, PI and BOP (p > 0.05), nor for bacteria expressed in copies/microlitre or in percentages (p > 0.05). The only significant difference was assessed from T0 (baseline) to T1 (2 months) in both groups and is related to the total bacteria count increase. However, this parameter encompasses all the bacteria of the common oral microbiota, thus, not representing a significant result from a clinical point of view. Despite the limitations of this study, CAT does not significantly affect periodontal and microbiological parameters with respect to untreated patients for the first two months of therapy.
Development of a Steel Plant Rescheduling Algorithm Based on Batch Decisions
Authors: García-Menéndez David , Morán-Palacios Henar , Vergara-González Eliseo P. , Rodríguez-Montequín Vicente
Published: July 2021

During the steelmaking and continuous casting process in the steel plant, it is common to encounter delays that affect initial planning. Furthermore, continuous casting machines themselves can lose much of their performance in the event of closure of one or more of their casting strands. The situation that is generated, far from being a planning problem, forces consideration of a vision of cost analysis when deciding changes in the planned sequences. This study presents a detailed analysis of the different circumstances that can cause strands closures or sequence breaks, their consequences and the different options available to minimize losses. Finally, an algorithm capable of analyzing the workshop situation and making the most favorable decision to optimize production is proposed, analyzed and compared with the efficiency of the original scheduling method in a real steel plant. The new algorithm proves its efficiency in all situations, with a time-saving average of 26.41 min per decision taken.
A Novel Hybrid Path Planning Method Based on Q-Learning and Neural Network for Robot Arm
Authors: Abdi Ali , Adhikari Dibash , Park Ju Hong
Published: July 2021

Path planning for robot arms to reach a target and avoid obstacles has had a crucial role in manufacturing automation. Although many path planning algorithms, including RRT, APF, PRM, and RL-based, have been presented, they have many problems: a time-consuming process, high computational costs, slowness, non-optimal paths, irregular paths, failure to find a path, and complexity. Scholars have tried to address some of these issues. However, those methods still suffer from slowness and complexity. In order to address these two limitations, this paper presents a new hybrid path planning method that contains two separate parts: action-finding (active approach) and angle-finding (passive approach). In the active phase, the Q-learning algorithm is used to find a sequence of simple actions, including up, down, left, and right, to reach the target cell in a gridded workspace. In the passive phase, the joints angles of the robot arm, with respect to the found actions, are obtained by the trained neural network. The simulation and test results show that this hybrid approach significantly improves the slowness and complexity due to using the simplified agent-environment interaction in the active phase and simple computing the joints angles in the passive phase.
Spatial Distribution of Black Carbon Concentrations in the Atmosphere of the North Atlantic and the European Sector of the Arctic Ocean
Authors: Sakerin Sergey M. , Kabanov Dmitry M. , Kopeikin Vladimir M. , Kruglinsky Ivan A. , Novigatsky Alexander N. , Pol’kin Viktor V. , Shevchenko Vladimir P. , Turchinovich Yuri S.
Published: July 2021

We discuss the measurements of black carbon concentrations in the composition of atmospheric aerosol over the seas of the North Atlantic and European sector of the Arctic Ocean (21 expeditions in 2007–2020). The black carbon concentrations were measured by an aethalometer and filter method. The comparison of the two variants of the measurements of the black carbon concentrations showed that the data acceptably agreed and can be used jointly. It is noted that the spatial distribution of black carbon over the ocean is formed under the influence of outflows of air masses from the direction of continents, where the main sources of emission of absorbing aerosol are concentrated. We analyzed the statistical characteristics of black carbon concentrations in five marine regions, differing by the outflows of continental aerosol. The largest black carbon content is a salient feature of the atmosphere of the North and Baltic Seas, surrounded by land: average values of concentrations are 210 ng/m3, and modal values are 75 ng/m3. In other regions (except in the south of the Barents Sea), the average black carbon concentrations are 37–44 ng/m3 (modal concentrations are 18–26 ng/m3). We discuss the specific features of the spatial (latitude-longitude) distributions of black carbon concentrations, relying on ship-based measurements and model calculations (MERRA-2 reanalysis data). A common regularity of the experimental and model spatial distributions of black carbon is that the concentrations decrease in the northern direction and with the growing distance from the continent: from several hundred ng/m3 in the southern part of the North Sea to values below 50 ng/m3 in polar regions of the ocean.
Induction of the CD24 Surface Antigen in Primary Undifferentiated Human Adipose Progenitor Cells by the Hedgehog Signaling Pathway
Authors: Muoio Francesco , Panella Stefano , Harder Yves , Tallone Tiziano
Published: July 2021

In the murine model system of adipogenesis, the CD24 cell surface protein represents a valuable marker to label undifferentiated adipose progenitor cells. Indeed, when injected into the residual fat pads of lipodystrophic mice, these CD24 positive cells reconstitute a normal white adipose tissue (WAT) depot. Unluckily, similar studies in humans are rare and incomplete. This is because it is impossible to obtain large numbers of primary CD24 positive human adipose stem cells (hASCs). This study shows that primary hASCs start to express the glycosylphosphatidylinositol (GPI)-anchored CD24 protein when cultured with a chemically defined medium supplemented with molecules that activate the Hedgehog (Hh) signaling pathway. Therefore, this in vitro system may help understand the biology and role in adipogenesis of the CD24-positive hASCs. The induced cells’ phenotype was studied by flow cytometry, Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) techniques, and their secretion profile. The results show that CD24 positive cells are early undifferentiated progenitors expressing molecules related to the angiogenic pathway.
Biological Impact of Photoperiod on Fairy Shrimp (Branchinecta orientalis): Life History and Biochemical Composition
Authors: Farhadi Sara , Atashbar Kangarloei Behrooz , Imani Ahmad , Sarvi Moghanlou Kourosh
Published: July 2021

B. orientalis, fairy shrimp, is often among the most conspicuous invertebrates inhabiting temporary aquatic habitats with a typical variation in environmental conditions. Its life history characteristics and biochemical composition were studied under four different photoperiodic regimes (24L:0D, 0L:24D, 16L:8D, and 12L:12D). The significantly highest cumulative and initial hatching rates (48 h) were obtained at 24L:0D (p < 0.05). Cultivating the larvae under different photoperiods did not significantly affect specific growth rate (SGR) (p > 0.05). However, higher final total body length and daily growth rate were recorded under constant darkness. Higher lipid content was found at 24L:0D to the extent that it was more than two times higher than that at 16L:8D and 12L:12D (p < 0.05). There was also a remarkable increase in body crude protein content at 24L:0D (p < 0.05). Body fatty-acid profiles of the fairy shrimps were also affected by culture condition (p < 0.05). Extension of lighting period resulted in a subtle increase in body contents of arginine, lysine, histidine, isoleucine, leucine, valine, methionine, and phenylalanine, especially in the group kept under a 16L:8D regime. The highest and lowest digestive enzyme activity was observed at 0L:24D and 24L:0D, respectively (p < 0.05). In contrast, the highest and lowest soluble protein content was recorded at 24L:0D and 0L:24D, respectively (p < 0.05). Similarly, antioxidant status was significantly higher at 0L:24D (p < 0.05). In conclusion, a 16L:8D light–dark cycle might be an optimal condition in terms of growth performance and physio-biochemical characteristics. These findings could be helpful in optimizing the rearing conditions for upscaling B. orientalis production.
Vitamin D Is Necessary for Murine Gastric Epithelial Homeostasis
Authors: Ali Ifrah Ismail , Shah Iltaf , Marzouk Sayed , Karam Sherif M. , Al Menhali Asma
Published: July 2021

Unlike other organs, the importance of VD in a normal stomach is unknown. This study focuses on understanding the physiological role of vitamin D in gastric epithelial homeostasis. C57BL/6J mice were divided into three groups that were either fed a standard diet and kept in normal light/dark cycles (SDL), fed a standard diet but kept in the dark (SDD) or fed a vitamin D-deficient diet and kept in the dark (VDD). After 3 months, sera were collected to measure vitamin D levels by LC-MS/MS, gastric tissues were collected for immunohistochemical and gene expression analyses and gastric contents were collected to measure acid levels. The VDD group showed a significant decrease in the acid-secreting parietal cell-specific genes Atp4a and Atp4b when compared with the controls. This reduction was associated with an increased expression of an antral gastrin hormone. VDD gastric tissues also showed a high proliferation rate compared with SDL and SDD using an anti-BrdU antibody. This study indicates the requirement for normal vitamin D levels for proper parietal cell functions.
New Approach for Detection of Normal Alternative Splicing Events and Aberrant Spliceogenic Transcripts with Long-Range PCR and Deep RNA Sequencing
Authors: Dragoš Vita Šetrajčič , Stegel Vida , Blatnik Ana , Klančar Gašper , Krajc Mateja , Novaković Srdjan
Published: July 2021

RNA sequencing is a promising technique for detecting normal and aberrant RNA isoforms. Here, we present a new single-gene, straightforward 1-day hands-on protocol for detection of splicing alterations with deep RNA sequencing from blood. We have validated our method’s accuracy by detecting previously published normal splicing isoforms of STK11 gene. Additionally, the same technique was used to provide the first comprehensive catalogue of naturally occurring alternative splicing events of the NBN gene in blood. Furthermore, we demonstrate that our approach can be used for detection of splicing impairment caused by genetic variants. Therefore, we were able to reclassify three variants of uncertain significance: NBN:c.584G>A, STK11:c.863-5_863-3delCTC and STK11:c.615G>A. Due to the simplicity of our approach, it can be incorporated into any molecular diagnostics laboratory for determination of variant’s impact on splicing.
A Runner’s High for New Neurons? Potential Role for Endorphins in Exercise Effects on Adult Neurogenesis
Authors: Schoenfeld Timothy J. , Swanson Chance
Published: July 2021

Physical exercise has wide-ranging benefits to cognitive functioning and mental state, effects very closely resembling enhancements to hippocampal functioning. Hippocampal neurogenesis has been implicated in many of these mental benefits of exercise. However, precise mechanisms behind these effects are not well known. Released peripherally during exercise, beta-endorphins are an intriguing candidate for moderating increases in neurogenesis and the related behavioral benefits of exercise. Although historically ignored due to their peripheral release and status as a peptide hormone, this review highlights reasons for further exploring beta-endorphin as a key mediator of hippocampal neurogenesis. This includes possible routes for beta-endorphin signaling into the hippocampus during exercise, direct effects of beta-endorphin on cell proliferation and neurogenesis, and behavioral effects of manipulating endogenous opioid signaling. Together, beta-endorphin appears to be a promising mechanism for understanding the specific ways that exercise promotes adult neurogenesis specifically and brain health broadly.
Epigenetic Alterations in Pancreatic Cancer Metastasis
Authors: Wang Sarah S. , Xu Jihao , Ji Keely Y. , Hwang Chang-Il
Published: July 2021

Pancreatic cancer is the third leading cause of cancer-related deaths in the United States. Pancreatic ductal adenocarcinoma (PDA) is the most common (90%) and aggressive type of pancreatic cancer. Genomic analyses of PDA specimens have identified the recurrent genetic mutations that drive PDA initiation and progression. However, the underlying mechanisms that further drive PDA metastasis remain elusive. Despite many attempts, no recurrent genetic mutation driving PDA metastasis has been found, suggesting that PDA metastasis is driven by epigenetic fluctuations rather than genetic factors. Therefore, establishing epigenetic mechanisms of PDA metastasis would facilitate the development of successful therapeutic interventions. In this review, we provide a comprehensive overview on the role of epigenetic mechanisms in PDA as a critical contributor on PDA progression and metastasis. In particular, we explore the recent advancements elucidating the role of nucleosome remodeling, histone modification, and DNA methylation in the process of cancer metastasis.
The Right-Handed Parallel β-Helix Topology of Erwinia chrysanthemi Pectin Methylesterase Is Intimately Associated with Both Sequential Folding and Resistance to High Pressure
Authors: Guillerm Jessica , Frère Jean-Marie , Meersman Filip , Matagne André
Published: July 2021

The complex topologies of large multi-domain globular proteins make the study of their folding and assembly particularly demanding. It is often characterized by complex kinetics and undesired side reactions, such as aggregation. The structural simplicity of tandem-repeat proteins, which are characterized by the repetition of a basic structural motif and are stabilized exclusively by sequentially localized contacts, has provided opportunities for dissecting their folding landscapes. In this study, we focus on the Erwinia chrysanthemi pectin methylesterase (342 residues), an all-β pectinolytic enzyme with a right-handed parallel β-helix structure. Chemicals and pressure were chosen as denaturants and a variety of optical techniques were used in conjunction with stopped-flow equipment to investigate the folding mechanism of the enzyme at 25 °C. Under equilibrium conditions, both chemical- and pressure-induced unfolding show two-state transitions, with average conformational stability (ΔG° = 35 ± 5 kJ·mol−1) but exceptionally high resistance to pressure (Pm = 800 ± 7 MPa). Stopped-flow kinetic experiments revealed a very rapid (τ < 1 ms) hydrophobic collapse accompanied by the formation of an extended secondary structure but did not reveal stable tertiary contacts. This is followed by three distinct cooperative phases and the significant population of two intermediate species. The kinetics followed by intrinsic fluorescence shows a lag phase, strongly indicating that these intermediates are productive species on a sequential folding pathway, for which we propose a plausible model. These combined data demonstrate that even a large repeat protein can fold in a highly cooperative manner.
Transcriptome Analysis Identifies Doublesex and Mab-3 Related Transcription Factor (DMRT3) in Nasal Polyp Epithelial Cells of Patients Suffering from Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease (AERD)
Authors: Priyadharshini V.S. , Jiménez-Chobillon Marcos Alejandro , de Graaf Jos , Porras Gutiérrez de Velasco Raúl , Gratziou Christina , Ramírez-Jiménez Fernando , Teran Luis M.
Published: July 2021

Background: Aspirin-exacerbated respiratory disease (AERD) is a syndrome characterised by chronic rhinosinusitis, nasal polyps, asthma and aspirin intolerance. An imbalance of eicosanoid metabolism with anover-production of cysteinyl leukotrienes (CysLTs) has been associated with AERD. However, the precise mechanisms underlying AERD are unknown. Objective: To establish the transcriptome of the nasal polyp airway epithelial cells derived from AERD patients to discover gene expression patterns in this disease. Methods: Nasal airway epithelial cells were isolated from 12 AERD polyps and 8 AERD non-polyp nasal mucosa samples as controls from the same subjects. Utilising the Illumina HiSeq 2500 platform, RNA samples were sequenced. Potential gene candidate DMRT3 was selected from the differentially-expressed genes for validation. Results: Comparative transcriptome profiling of nasal epithelial cells was accomplished in AERD. A total of 20 genes had twofold mean regulation expression differences or greater. In addition, 8 genes were upregulated, including doublesex and mab-3 related transcription factor 3 (DMRT3), and 12 genes were downregulated. Differentially regulated genes comprised roles in inflammation, defence and immunity. Metabolic process and embryonic development pathways were significantly enriched. Enzyme-linked immune sorbent assay (ELISA) results of DMRT3 in AERD patients were significantly upregulated compared to controls (p = 0.03). Immunohistochemistry (IHC) of AERD nasal polyps localised DMRT3 and was predominantly released in the airway epithelia. Conclusion: Findings suggest that DMRT3 could be potentially involved in nasal polyp development in AERD patients. Furthermore, several genes are downregulated, hinting at the dedifferentiation phenomenon in AERD polyps. However, further studies are imperative to confirm the exact mechanism of polyp formation in AERD patients.
Local Inhibition of Indoleamine 2,3-Dioxygenase Mitigates Renal Fibrosis
Authors: Jensen Camilla Grønkjær , Jensen Michael Schou , Tingskov Stine Julie , Olinga Peter , Nørregaard Rikke , Mutsaers Henricus A. M.
Published: July 2021

Chronic kidney disease (CKD) is a major global health concern and renal fibrosis is an integral part of the pathophysiological mechanism underlying disease progression. In CKD patients, the majority of metabolic pathways are in disarray and perturbations in enzyme activity most likely contribute to the wide variety of comorbidities observed in these patients. To illustrate, catabolism of tryptophan by indoleamine 2,3-dioxygenase (IDO) gives rise to numerous biologically active metabolites implicated in CKD progression. Here, we evaluated the effect of antagonizing IDO on renal fibrogenesis. To this end, we antagonized IDO using 1-methyl-D-tryptophan (1-MT) and BMS-98620 in TGF-β-treated murine precision-cut kidney slices (mPCKS) and in mice subjected to unilateral ureteral obstruction (UUO). The fibrotic response was evaluated on both the gene and protein level using qPCR and western blotting. Our results demonstrated that treatment with 1-MT or BMS-985205 markedly reduced TGF-β-mediated fibrosis in mPCKS, as seen by a decreased expression of collagen type 1, fibronectin, and α-smooth muscle actin. Moreover, IDO protein expression clearly increased following UUO, however, treatment of UUO mice with either 1-MT or BMS-986205 did not significantly affect the gene and protein expression of the tested fibrosis markers. However, both inhibitors significantly reduced the renal deposition of collagen in UUO mice as shown by Sirius red and trichrome staining. In conclusion, this study demonstrates that IDO antagonism effectively mitigates fibrogenesis in mPCKS and reduces renal collagen accumulation in UUO mice. These findings warrant further research into the clinical application of IDO inhibitors for the treatment of renal fibrosis.
Immune Assessment of BNT162b2 m-RNA-Spike Based Vaccine Response in Adults
Authors: San Segundo David , Comins-Boo Alejandra , Irure-Ventura Juan , Renuncio-García Mónica , Roa-Bautista Adriel , González-López Elena , Merino-Fernández David , Lamadrid-Perojo Patricia , Alonso-Peña Marta , Ocejo-Vinyals Javier Gonzalo , Gutiérrez-Larrañaga Maria , Guiral-Foz Sandra , López-Hoyos Marcos
Published: July 2021

Vaccine efficacy is based on clinical data. Currently, the assessment of immune response after SARS-CoV-2 vaccination is scarce. A total of 52 healthcare workers were immunized with the same lot of BNT162b2 vaccine. The immunological response against the vaccine was tested using a T-specific assay based on the expression of CD25 and CD134 after stimulation with anti-N, -S, and -M specific peptides of SARS-CoV-2. Moreover, IgG anti-S2 and -RBD antibodies were detected using ELISA. Furthermore, the cell subsets involved in the response to the vaccine were measured in peripheral blood by flow cytometry. Humoral-specific responses against the vaccine were detected in 94% and 100% after the first and second doses, respectively. Therefore, anti-S T-specific responses were observed in 57% and 90% of the subjects after the first and second doses of the vaccine, respectively. Thirty days after the second dose, significant increases in T helper 1 memory cells (p < 0.001), peripheral memory T follicular helper (pTFH) cells (p < 0.032), and switched memory (p = 0.005) were observed. This study describes the specific humoral and cellular immune responses after vaccination with the new mRNA-based BNT162b2 vaccine. A mobilization of TFH into the circulation occurs, reflecting a specific activation of the immune system.
Platelet-Therapeutics to Improve Tissue Regeneration and Wound Healing—Physiological Background and Methods of Preparation
Authors: Jansen Ellen E. , Braun Andreas , Jansen Patrick , Hartmann Matthias
Published: July 2021

Besides their function in primary hemostasis, platelets are critically involved in the physiological steps leading to wound healing and tissue repair. For this purpose, platelets have a complex set of receptors allowing the recognition, binding, and manipulation of extracellular structures and the detection of pathogens and tissue damage. Intracellular vesicles contain a huge set of mediators that can be released to the extracellular space to coordinate the action of platelets as other cell types for tissue repair. Therapeutically, the most frequent use of platelets is the intravenous application of platelet concentrates in case of thrombocytopenia or thrombocytopathy. However, there is increasing evidence that the local application of platelet-rich concentrates and platelet-rich fibrin can improve wound healing and tissue repair in various settings in medicine and dentistry. For the therapeutic use of platelets in wound healing, several preparations are available in clinical practice. In the present study we discuss the physiology and the cellular mechanisms of platelets in hemostasis and wound repair, the methods used for the preparation of platelet-rich concentrates and platelet-rich fibrin, and highlight some examples of the therapeutic use in medicine and dentistry.
Au2phen and Auoxo6, Two Dinuclear Oxo-Bridged Gold(III) Compounds, Induce Apoptotic Signaling in Human Ovarian A2780 Cancer Cells
Authors: Gorini Giulia , Magherini Francesca , Fiaschi Tania , Massai Lara , Becatti Matteo , Modesti Alessandra , Messori Luigi , Gamberi Tania
Published: July 2021

Au2phen ((2,9-dimethyl-1,10-phenanthroline)2Au2(µ-O)2)(PF6)2 and Auoxo6 ((6,6′-dimethyl-2,2′-bipyridine)2Au2(µ-O)2)(PF6)2 are two structurally related gold(III) complexes that were previously reported to display relevant and promising anticancer properties in vitro toward a large number of human cancer cell lines. To expand the knowledge on the molecular mechanisms through which these gold(III) complexes trigger apoptosis in cancer cells, further studies have been performed using A2780 ovarian cancer cells as reference models. For comparative purposes, parallel studies were carried out on the gold(III) complex AuL12 (dibromo(ethylsarcosinedithiocarbamate)gold(III)), whose proapoptotic profile had been earlier characterized in several cancer cell lines. Our results pointed out that all these gold(III) compounds manifest a significant degree of similarity in their cellular and proapoptotic effects; the main observed perturbations consist of potent thioredoxin reductase inhibition, disruption of the cell redox balance, impairment of the mitochondrial membrane potential, and induction of associated metabolic changes. In addition, evidence was gained of the remarkable contribution of ASK1 (apoptosis-signal-regulating kinase-1) and AKT pathways to gold(III)-induced apoptotic signaling. Overall, the observed effects may be traced back to gold(III) reduction and subsequent formation and release of gold(I) species that are able to bind and inhibit several enzymes responsible for the intracellular redox homeostasis, in particular the selenoenzyme thioredoxin reductase.
Systemic Corticosteroids and the Risk of Venous Thromboembolism in Patients with Severe COPD: A Nationwide Study of 30,473 Outpatients
Authors: Rastoder Ema , Sivapalan Pradeesh , Eklöf Josefin , Saeed Mohamad Isam , Jordan Alexander Svorre , Meteran Howraman , Tønnesen Louise , Biering-Sørensen Tor , Løkke Anders , Seersholm Niels , Lynghøj Nielsen Thyge , Carlsen Jørn , Janner Julie , Godtfredsen Nina , Bodtger Uffe , Laursen Christian B. , Hilberg Ole , Knop Filip K. , Priemé Helene , Ingebrigtsen Truls Sylvan , Gottlieb Vibeke , Wilcke Jon Torgny , Stæhr Jensen Jens Ulrik
Published: July 2021

Due to frequent exacerbations, many patients with chronic obstructive pulmonary disease (COPD) are exposed to oral corticosteroids (OCS), which may be thrombogenic. We evaluated the risk of hospitalisation with venous thromboembolism (VTE) and death in patients with acute exacerbation of COPD (AECOPD) treated with long and short OCS regimens. In this nationwide cohort study of 30,473 COPD outpatients treated for AECOPD, we compared the risk of VTE hospitalisation and all-cause mortality within 6 months in OCS dose of >250 mg vs. ≤250 mg. A multivariable Cox proportional hazard regression was used to estimate the risk. The incidence of VTE hospitalisations was 0.23%. A long OCS treatment course was associated with an increased risk of VTE compared to a short course (hazard ratio (HR) 1.69, [95% confidence interval (CI) 1.05 to 2.72], p < 0.031). A higher risk of all-cause mortality was seen in the group of COPD patients treated with a long OCS course (HR 1.71, [95% CI 1.63 to 1.79], p < 0.0001). The risk of reported VTE hospitalisation was higher among AECOPD patients treated with long courses of OCS, but the absolute risk was low, suggesting under-reporting of the condition.
Is It Possible to Shift from Down to Top Rank? A Focus on the Mesolimbic Dopaminergic System and Cocaine Abuse
Authors: Amaral Inês M. , Hofer Alex , El Rawas Rana
Published: July 2021

Impaired social behavior is a common feature of many psychiatric disorders, in particular with substance abuse disorders. Switching the preference of the substance-dependent individual toward social interaction activities remains one of the major challenges in drug dependence therapy. However, social interactions yield to the emergence of social ranking. In this review, we provide an overview of the studies that examined how social status can influence the dopaminergic mesolimbic system and how drug-seeking behavior is affected. Generally, social dominance is associated with an increase in dopamine D2/3 receptor binding in the striatum and a reduced behavioral response to drugs of abuse. However, it is not clear whether higher D2 receptor availability is a result of increased D2 receptor density and/or reduced dopamine release in the striatum. Here, we discuss the possibility of a potential shift from down to top rank via manipulation of the mesolimbic system. Identifying the neurobiology underlying a potential rank switch to a resilient phenotype is of particular interest in order to promote a positive coping behavior toward long-term abstinence from drugs of abuse and a protection against relapse to drugs. Such a shift may contribute to a more successful therapeutic approach to cocaine addiction.
Wearable Biosensors for Non-Invasive Sweat Diagnostics
Authors: Xu Jing , Fang Yunsheng , Chen Jun
Published: July 2021

Recent advances in microfluidics, microelectronics, and electrochemical sensing methods have steered the way for the development of novel and potential wearable biosensors for healthcare monitoring. Wearable bioelectronics has received tremendous attention worldwide due to its great a potential for predictive medical modeling and allowing for personalized point-of-care-testing (POCT). They possess many appealing characteristics, for example, lightweight, flexibility, good stretchability, conformability, and low cost. These characteristics make wearable bioelectronics a promising platform for personalized devices. In this paper, we review recent progress in flexible and wearable sensors for non-invasive biomonitoring using sweat as the bio-fluid. Real-time and molecular-level monitoring of personal health states can be achieved with sweat-based or perspiration-based wearable biosensors. The suitability of sweat and its potential in healthcare monitoring, sweat extraction, and the challenges encountered in sweat-based analysis are summarized. The paper also discusses challenges that still hinder the full-fledged development of sweat-based wearables and presents the areas of future research.
Impact of a Carbohydrate Mouth Rinse on Corticomotor Excitability after Mental Fatigue in Healthy College-Aged Subjects
Authors: Bailey Stephen P. , Harris G. Keith , Lewis Kaitlin , Llewellyn Tracy A. , Watkins Ruth , Weaver Mark A. , Roelands Bart , Van Cutsem Jeroen , Folger Stephen F.
Published: July 2021

Mental Fatigue (MF) has been associated with reduced physical performance but the mechanisms underlying this result are unclear. A reduction in excitability of the corticomotor system is a way mental fatigue could negatively impact physical performance. Carbohydrate (CHO) mouth rinse (MR) has been shown to increase corticomotor excitability. PURPOSE: The purpose of this study was to determine if CHO MR impacts corticomotor excitability after MF. METHODS: Fifteen subjects (nine females, six males; age = 23 ± 1 years; height = 171 ± 2 cm; body mass = 69 ± 3 kg; BMI = 23.8 ± 0.7) completed two sessions under different MR conditions (Placebo (PLAC), 6.4% glucose (CHO)) separated by at least 48 h and applied in a double-blinded randomized fashion. Motor-evoked potential (MEP) of the left first dorsal interosseous (FDI) was determined by transcranial magnetic stimulation (TMS) before and after MF. Perceived MF was recorded before and after the MF task using a 100 mm visual analog scale (VAS). RESULTS: MF was greater following PLAC (+30.4 ± 4.0 mm) than CHO (+19.4 ± 3.9 mm) (p = 0.005). MEP was reduced more following PLAC (−16.6 ± 4.4%) than CHO (−3.7 ± 4.7%) (p < 0.001). CONCLUSIONS: CHO MR was successful at attenuating the reduction in corticomotor excitability after MF. Carbohydrate mouth rinse may be a valuable tool at combating the negative consequences of mental fatigue.
Reduction of Device Operating Temperatures with Graphene-Filled Thermal Interface Materials
Authors: Lewis Jacob S.
Published: July 2021

The majority of research into few layer graphene (FLG) thermal interface materials (TIM) concerns the direct quantification of innate composite properties with much less direct analysis of these materials in realistic applications. In this study, equilibrium temperatures of engineered device substitutes fixed to passive heat sink solutions with varying FLG concentration TIMs are experimentally measured at varying heat dissipation rates. A custom, precisely-controlled heat source’s temperature is continually measured to determine equilibrium temperature at a particular heat dissipation. It is found that altering the used FLG TIM concentrations from 0 vol.% to as little as 7.3 vol.% resulted in a decrease of combined TIM and passively-cooled heat sink thermal resistance from 4.23∘C/W to 2.93∘C/W, amounting to a reduction in operating temperature of ≈108∘C down to ≈85∘C at a heat dissipation rate of 20 W. The results confirm FLG TIMs’ promising use in the application of device heat dissipation in a novel, controllable experimental technique.
Photocatalytic-Fenton Process under Simulated Solar Radiation Promoted by a Suitable Catalyst Selection
Authors: Díez Aida M. , Valencia Helen E. , Meledina Maria , Mayer Joachim , Kolen'ko Yury V.
Published: July 2021

Considering water scarcity, photo-based processes have been presented as a depollution technique, which should be optimized in order to be applied in the future. For that, the addition of an active photocatalyst and the usage of solar radiation are mandatory steps. Thus, Fe3O4–SiO2–TiO2 was synthesized, and its performance was evaluated using simulated solar radiation and methylene blue as a model pollutant. Under optimal conditions, 86% degradation was attained in 1 h. These results were compared to recent published data, and the better performance can be attributed to both the operational conditions selection and the higher photocatalyst activity. Indeed, Fe3O4–SiO2–TiO2 was physico-chemically characterized with techniques such as XRD, N2 isotherms, spectrophotometry, FTIR, electrochemical assays and TEM.
Low-Temperature Synthesis and Catalytic Activity of Cobalt Ferrite in Nitrous Oxide (N2O) Decomposition Reaction
Authors: Denisova Kristina , Ilyin Alexander A. , Rumyantsev Ruslan , Sakharova Julia , Ilyin Alexander P. , Gordina Natalya
Published: July 2021

Cobalt ferrite (CoFe2O4) nanoparticles were synthesized and investigated as a catalyst in the reaction of nitrous oxide (N2O) decomposition. Cobalt ferrite was synthesized by solid–phase interaction at 1100 °C and by preliminary mechanochemical activation in a roller-ring vibrating mill at 400 °C. The nanoparticles were characterized by X-ray diffraction (XRD), synchronous thermal analysis (TG and DSC) and scanning electron microscopy (SEM). A low-temperature nitrogen adsorption/desorption test was used to evaluate the catalytic activity of the cobalt ferrite nanoparticles. Correlations between the structure and catalytic properties of the catalysts are reported. The highest catalytic activity of CoFe2O4 in the reaction of nitrous oxide decomposition was 98.1% at 475 °C for cobalt ferrite obtained by mechanochemical activation.