bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating Multimedia Teaching Methods and Computational Thinking into the Baking Dessert Course
Authors: Chen Yen-Cheng , Tsui Pei-Ling , Lee Ching-Sung , Chiang Ming-Chen , Lan Bo-Kai
Published: November 2022

Rapid developments in motion media technology have prompted the dessert industry to incorporate both motion multimedia and social media into their marketing strategies. Modern consumption patterns have shifted dramatically toward motion multimedia, with data searching and cost-related decision-making gradually becoming a new type of consumption experience. As a result, the effective application of motion multimedia and computational thinking has become a critical skill in culinary education, as it improves students’ learning outcomes and enables them to enter the workforce with a practical modern skill. This study examines the learning outcomes of Chinese Culture University students enrolled in a dessert-making course that experimentally incorporated motion media and computational thinking into its curriculum. The results show that this approach significantly enhances students’ learning outcomes, especially in terms of creativity and teamwork, both of which are critical in dessert-making. This study makes a strong contribution to the literature by demonstrating that motion multimedia-based teaching methods and computational thinking boost learning outcomes in dessert-making education.
Investigation on C and ESR Estimation of DC-Link Capacitor in Maglev Choppers Using Artificial Neural Network
Authors: Chen Xiaoyu , Yang Xin , Zhang Yue
Published: November 2022

The reliability of capacitors is one of the most important issues in power electronics. The health status of capacitors can be evaluated through the comparison of estimated C/ESR values with their original values. In this paper, a two-input artificial neural network (ANN) is proposed for C and ESR estimation of DC-link capacitors in Maglev choppers; combined with the existing voltage and current sensors that are used for protection and control, it provides a promising solution for the health condition monitoring of the Maglev chopper in the Maglev train. Compared with prior-art research, the actual capacitor degradation progress where both C and ESR degrade is considered in training. Moreover, ANN’s advantage of fitting nonlinear and complex relationships is explored by building an aggressive mapping between the voltage ripple at 5 kHz to C/ESR at 120 Hz, which cannot be described or analyzed by linear circuit equations. Thus, cross validation must be implemented to avoid an occasional poor fitting, and ensure the stability of ANN. Experimental results show that the proposed ANN outperforms the support vector regression in both ESR and C estimation. While C estimation suffered from over-fitting and instability, ESR estimation by the ANN is accurate and stable with a low average prediction error within 1%, showing great potential for condition monitoring of DC-link capacitors in Maglev choppers.
A New Method for Modeling and Parameter Identification of Positively Charged Downward Lightning Leader Based on Remote Lightning Electric Field Signatures Recorded in the ELF/MF Range and 3D Doppler Radar Scanning Data
Authors: Karnas Grzegorz , Barański Piotr , Masłowski Grzegorz
Published: November 2022

The aim of this paper is modeling and parameter identification of the leader stage preceding the positive stroke of natural cloud-to-ground lightning. This research is based on electric field and 3D Doppler radar data recorded during thunderstorms in Poland, as supplied by database information from long range lightning location systems. The numerical simulation performed in the MATLAB platform showed that a high number of assumed model parameters, such as non-uniform leader tip speed and lightning channel charge density, allowed us to obtain greater compliance between simulated and measured electric field signatures than in the classical approach. The proposed model can be implemented in lightning location systems and forest fire warning systems, operating globally to reduce the risk of damages caused by positive cloud-to-ground flashes being one of the most dangerous type of lightning events. An alternative application of the model can be for research, including ground-based lightning data supplementation for the corresponding satellite and airborne registrations.
High-Efficiency Power Cycles for Particle-Based Concentrating Solar Power Plants: Thermodynamic Optimization and Critical Comparison
Authors: Reyes-Belmonte Miguel Angel , Rovense Francesco
Published: November 2022

This paper investigates and compares several highly efficient thermodynamic cycles that are suitable for coupling with particle-in-tube fluidized-bed solar receiver technology. In such a receiver, high-temperature particles are used as both a heat transfer fluid and a storage medium. A dense particle suspension (DPS) is created through an upward bubbling fluidized-bed (UBFB) flow inside the receiver tubes, which constitutes the “particle-in-tube” solar receiver concept. Reaching higher temperatures is seen as a key factor for future cost reductions in the solar plant, as this leads to both higher power conversion efficiency and increased energy storage density. Three advanced thermodynamic cycles are analyzed in this work: the supercritical steam Rankine cycle (s-steam), supercritical carbon dioxide cycle (s-CO2) and integrated solar combined cycle (ISCC). For each one, 100% solar contribution, which is considered the total thermal input to the power cycle, can be satisfied by the solar particle receiver. The main findings show that the s-CO2 cycle is the most suitable thermodynamic cycle for the DPS solar plant, exhibiting a net cycle efficiency above 50% for a moderate temperature range (680–730 °C). For the other advanced power cycles, 45.35% net efficiency can be achieved for the s-steam case, while the efficiency of the ISCC configuration is limited to 45.23% for the solar-only operation mode.
Assessment of the Operation of an SI Engine Fueled with Ammonia
Authors: Lanni Davide , Galloni Enzo , Fontana Gustavo , D’Antuono Gabriele
Published: November 2022

Recently, the research interest regarding ammonia applications in energy systems has been increasing. Ammonia is an important hydrogen carrier that can also be obtained starting from renewable energy sources. Furthermore, ammonia can be used as a carbon-free fuel in combustion systems. In particular, the behavior of internal combustion engines (ICEs), fueled by ammonia, needs to be further investigated. The main disadvantage of this kind of fuel is its low laminar flame speed when it is oxidized with air. On the other hand, considering a spark-ignition (SI) engine, the absence of knock phenomena could allow a performance improvement. In this work, a 1D numerical approach was used in order to assess the performance and the operating limits of a downsized PFI SI engine fueled with pure ammonia. Furthermore, the reliability of the 1D model was verified by means of a 3D approach. Both throttled and unthrottled engine operation was investigated. In particular, different boost levels were analyzed under WOT (wide-open throttle) conditions. The potential of the 1D approach was also exploited to evaluate the effect of different geometrical compression ratio on the ammonia engine behavior. The results show that the low laminar flame speed of ammonia–air mixtures leads to increased combustion durations and optimal spark timings more advanced than the typical ones of SI engines. On the other hand, knock phenomena are always avoided. Due to the engine operating limits, the maximum rotational speed guaranteeing proper engine operation is 3000 rpm, except for at the highest boost level. At this regime, the load regulation can be critical in terms of unburned fuel emissions. Considering increased compression ratios and no boost conditions, even the 4000 rpm operating point guarantees proper engine operation.
Free-Standing Li4Ti5O12/Carbon Nanotube Electrodes for Flexible Lithium-Ion Batteries
Authors: Lee Jun-Seok , Yun Sang-Du , Nyamaa Oyunbayar , Yang Jeong-Hyeon , Huh Sun-Chul , Jeong Hyo-Min , Nam Tae-Hyun , Ryu Yeon-Ju , Noh Jung-Pil
Published: November 2022

Lithium-ion batteries (LIBs) have been used in many fields, such as consumer electronics and automotive and grid storage, and its applications continue to expand. Several studies have attempted to improve the performance of LIBs. In particular, the use of high-capacity silicon and tin as anodes has been widely studied. Although anodes composed of silicone and tin have high theoretical capacities, poor electrical conductivity and considerable volume expansion of such anodes deteriorate the LIB performance. Thus, Li4Ti5O12 (LTO), a zero-strain material, has attracted much attention with high cycle stability and rate capability through improved electrical conductivity. However, LTO has the disadvantages of a low electrical conductivity (10−8 to 10−13 S cm−1) and moderate Li+ ion diffusion coefficient (10−9 to 10−16 cm2 s−1). In this study, the flexible and free-standing composite films were fabricated using only LTO and multi-walled carbon nanotube(CNT) with high electrical conductivity and ion diffusivity. The prepared LTO/CNT films showed a higher charge/discharge capacity than the theoretical capacity of the LTO electrode.
In Search of Industry 4.0 and Logistics 4.0 in Small-Medium Enterprises—A State of the Art Review
Authors: Tubis Agnieszka A. , Grzybowska Katarzyna
Published: November 2022

The implementation of Industry 4.0 currently concerns mainly large enterprises. However, the economy of most European countries is based on the activities of small and medium-sized enterprises (SMEs). For this reason, the further development of the I4.0 concept and the technology of Logistics 4.0 depends on adjusting its assumptions to the needs of SMEs. The article aims to identify research areas regarding the adaptation of Industry 4.0 and Logistics 4.0 solutions to the needs of the SME sector, based on a review of the literature. The PRISMA method, one of the popular analytical methods used in a literature review, was used for the research. The selection of publications for the analysis was based on the Web of Science database, an important interdisciplinary research platform. Ninety-five publications were accepted for the final analysis, which concerned only the application of Industry 4.0 in SMEs and 10 publications on Logistics 4.0. The conducted studies of the literature allowed to identify the scope of research on the implementation of the concept of Industry 4.0 and Logistics 4.0 in the SME sector. The research allowed us to distinguish five thematic groups in total, which have been characterized. One of the identified groups concerns the adaptation of Logistics 4.0 systems to the needs of SMEs. The number of publications on this group of studies is minimal, therefore this area has been recognized as the currently existing research gap.
Fuel Cells in Road Vehicles
Authors: Piatkowski Piotr , Michalska-Pozoga Iwona , Szczepanek Marcin
Published: November 2022

Issues related to the reduction of the environmental impact of means of road transport by the use of electric motors powered by Proton Exchange Membrane (PEM) fuel cells are presented in this article. The overall functional characteristics of electric vehicles are presented, as well as the essence of the operation of a fuel cell. On the basis of analyzing the energy conversion process, significant advantages of electric drive are demonstrated, especially in vehicles for urban and suburban applications. Moreover, the analyzed literature indicated problems of controlling and maintaining fuel cell power caused by its highest dynamic and possible efficiency. This control was related to the variable load conditions of the fuel cell vehicle (FCV) engine. The relationship with the conventional dependencies in the field of vehicle dynamics is demonstrated. The final part of the study is related to the historical outline and examples of already operating fuel cell systems using hydrogen as an energy source for energy conversion to power propulsion vehicle’s engines. In conclusion, the necessity to conduct research in the field of methods for controlling the power of fuel cells that enable their effective adaptation to the temporary load resulting from the conditions of vehicle motion is indicated.
Grid Connection Circuits for Powerful Regenerative Electric Drives of Rolling Mills: Review
Authors: Maklakov Alexander S. , Jing Tao , Nikolaev Alexander A. , Gasiyarov Vadim R.
Published: November 2022

AC regenerative electric drives (AC REDs) are widely used in metallurgical rolling due to their reliability, efficiency, and power sufficient to maintain the process. This paper reviews the latest achievements in building the grid connection circuits for the main AC REDs of rolling mills. The paper discusses multipulse connection circuits formed by various transformer types and algorithms for preprogrammed pulse-width modulation with selective harmonic elimination technique (PPWM with SHE) of three-level active front ends (AFE), provides the theoretical and practical measurement results, and gives recommendations for improving existing systems. For 6-, 12-, and 18-pulse grid connection circuits, switching patterns of AFE semiconductor modules with a smooth downward trend within the modulation index range from 0.7 to 1.15 are provided. A simulation was performed under comparable conditions on simulation models in the Matlab/Simulink to objectively evaluate the performance and opportunities of 6-, 12-, and 18-pulse grid connection circuits, including the three-level AFE and transformer specifications. The waveforms and spectra of the grid currents and transformer secondary winding phase currents are shown; total harmonic distortion (THD) factors have been calculated up to the 60th harmonic for various PPWM with SHE patterns. The results of simulation and experimental measurement on operating equipment have been compared. The paper is expected to provide a broad overview of multipulse connection circuits of the rolling mill’s main AC REDs, in particular, identify the latest solutions capable of significantly improving their electromagnetic compatibility with the grid. The results obtained are of high genericity and can be used by researchers and engineers to provide the electromagnetic compatibility of non-linear consumers in similar circuits, as well as design them.
Modelling of a Large Solar PV Facility: England’s Mallard Solar Farm Case Study
Authors: Muneer Tariq , Gul Mehreen Saleem , Alam Marzia
Published: November 2022

With reference to energy generation, the global society has to urgently address three factors that are now critical: sustainability in terms of climate change, security in terms of the war that is currently raging in Europe with consequences that are being felt around the globe and the steep incline of fossil-fuel based energy costs. Around the world, large-scale solar farms are being constructed with tracking systems to improve the efficiency of photovoltaic (PV) modules. This article presents a comparison of energy generation of fixed-slope versus tracking PV modules. The analysis was based on a twenty-year dataset for two locations, namely, Lincoln (England) and Bhavnagar (India), which differ in terms of latitude, sky clarity and ambient temperature. It was demonstrated that a fixed-slope system facing the equator provides a healthy energy receipt that is a high fraction of the energy receipt of a tracking system. Furthermore, analysis was also carried out for a PV facility that will host the largest solar farm in England to conclude that regardless of the solar farm installation location, the use of bifacial PV is beneficial.
Hierarchical Porous Activated Carbon-Supported Ruthenium Catalysts for Catalytic Cleavage of Lignin Model Compounds
Authors: Pham Xuan-Tien , Tran Vy Anh , Tran Lan-Trinh Thi , Nguyen Tram Ngoc P. , Le Thong Hoang , Hoang Huy , Nguyen Thi-Hiep , Vu Khanh B. , Phung Thanh Khoa
Published: November 2022

The catalytic conversion of lignin model compounds was performed using Ru/C catalysts and an autoclave reactor. The Ru/C catalysts were prepared by the impregnation method using highly porous homemade activated carbon and characterized by XRD, SEM, and specific surface area. The catalytic reactions were performed in a high pressure/temperature reactor at different temperatures and with different solvents. The results showed that the novel Ru/C catalysts prepared from carbon supports activated by the KOH agent showed higher catalytic activity than the commercial catalyst. Ethanol and 2-propanol were suitable solvents for the cleavage of the β–O–4 ether bond of 2-phenoxy-1-phenyl ethanol (~65–70% conversion) over a Ru/C-KOH-2 catalyst at 220 °C in comparison to tert-butanol and 1-propanol solvents (~43–47% conversion of 2-phenoxy-1-phenyl ethanol). Also, the increase in reaction temperature from 200 °C to 240 °C enhanced the cleavage of the ether bond with an increase in phenol selectivity from 9.4% to 19.5% and improved the catalytic conversion of 2-phenoxy-1-phenyl ethanol from 46.6% to 98.5% over the Ru/C-KOH-2 catalyst and ethanol solvent. The Ru/C-KOH-2 catalyst showed outstanding conversion (98.5%) of 2-phenoxy-1-phenylethanol at 240 °C, 1 h, ethanol solvent. This novel hierarchical porous activated carbon-supported ruthenium catalyst (Ru/C-KOH-2) can be applied for the further conversion of the lignin compound.
Sustainability and Gender Perspective in Food Innovation: Foods and Food Processing Coproducts as Source of Macro- and Micro-Nutrients for Woman-Fortified Foods
Authors: Sayas-Barberá Estrella , Pérez-Álvarez Jose Angel , Navarro-Rodríguez de Vera Casilda , Fernández-López Manuela , Viuda-Martos Manuel , Fernández-López Juana
Published: November 2022

Micro- and macro-nutrient deficiencies among women are considered a global issue that the food industry has not adequately considered until recently. The industry must provide and guarantee a diversity of food products worldwide that allow women to get a correct and balanced diet according their life stage. The food industry must focus on this challenge within a framework of sustainable production, minimizing the use of natural resources and avoiding the emission of waste and pollutants throughout the life cycle of food. Food coproducts are presented as potential bioactive functional compounds which can be useful for technological purposes, due to the fact that they can serve as non-chemical, natural and health-improving food ingredients. In this review, we focus on the potential use of food processing coproducts which must be part of a strategy to promote and improve women’s health and well-being. This knowledge will make it possible to select potential ingredients from coproducts to be used in the fortification of foods intended for consumption by females and to introduce sustainability and gender perspectives into food innovation. The attainment of fortifications for foods for women has to be linked to the use of sustainable sources from food coproducts in order to be economically viable and competitive.
Is a Food Shortage Coming to the Western Balkans?
Authors: Brankov Tatjana , Matkovski Bojan
Published: November 2022

In the wake of the international food crisis, many countries are paying more attention to food self-sufficiency to protect themselves from instability in the global food markets. Western Balkan region and the rest of the world are facing an array of challenges, including inflation and rising food prices. Recognizing the importance of producing sufficient food to cover a country’s needs in circumstances of increasing risk of trade disruptions due to war or political tensions, this article aims to find the level of food self-sufficiency in the Western Balkan countries. The self-sufficiency ratio is calculated for different food groups and individual products over a 14-year period (2006–2019) based on the FAO data and calculation method. Also, using panel data, the impact of different factors—arable land, rural population, fertilizers efficiency, temperature change, precipitation, and GDP per capita change—on cereals self-sufficiency is estimated. Results showed that in the covered pre-crisis period, the Western Balkans achieved a satisfactory level of food self-sufficiency, suggesting that the region is ready to respond to future challenges. Four indicators positively and significantly affect cereal self-sufficiency: arable land, rural population, fertilizers efficiency and GDP per capita change, while one indicator—temperature change—had a negative and significant effect. This article can serve as a basis for post-crisis research on the topic.
Corporate Cash Holdings and Exposure to Macroeconomic Conditions
Authors: Ki YoungHa , Adhikari Ramesh
Published: November 2022

Determinants of a firm’s cash holdings have been a popular topic of research in finance, especially after the rapid surge in cash holdings for U.S. firms since the 1980s. The wide array of research has focused primarily on firm-specific factors to explain the cross-sectional variations but has found insufficient explanatory power for the variations in cash holdings. We incorporate variables for macroeconomic conditions and uncertainty with firm-specific variables. Using 19,223 firms with 213,663 firm-year observations from 1971 to 2019 and introducing five variables for macroeconomic conditions of the Aruoba–Diebold–Scotti index and three variables for macroeconomic and financial uncertainty, we find that a firm’s sensitivity to macroeconomic conditions and uncertainty plays important role in determining the level of cash holdings. We find supportive evidence from the robustness test with the firm’s age that variables for macroeconomic variables have an impact on the level of cash holdings irrespective of the firm’s age.
Evaluating BFASTMonitor Algorithm in Monitoring Deforestation Dynamics in Coniferous and Deciduous Forests with LANDSAT Time Series: A Case Study on Marmara Region, Turkey
Authors: Mashhadi Nooshin , Alganci Ugur
Published: November 2022

Time series analysis combined with remote sensing data allows for the study of abrupt changes in the environment due to significant and severe disturbances such as deforestation, agricultural activities, fires, and urban expansion, as well as gradual changes such as climate variability and forest degradation in the ecosystem. The precision of any change detection analysis is highly dependent upon its ability to separate actual changes and fluctuations on a seasonal scale. One of the efficient methods in this context is using the Breaks for Additive Seasonal and Trend (BFAST) set of algorithms. This study aims to perform a comprehensive and comparative evaluation of different Vis’ performance in forest degradation with the Landsat 8 images and BFASTMonitor approach. Through evaluation, the study also considers the potential effects of different forest types and deforestation scales in the Marmara region of Turkey. For this purpose, the Normalized Difference Vegetation Index (NDVI), Enhanced Vegetation Index (EVI), Normalized Difference Moisture Index (NDMI), and Normalized Burn Ratio (NBR) vegetation indices (VI) were selected for a comparative evaluation. The overall accuracy of VIs in deciduous forests was around 85% for NDVI, NDMI, and NBR, and 78.80% for EVI, while in coniferous forests, the overall accuracy demonstrated higher values of about 88% for NDVI, NDMI, and EVI, and 87.28% for NBR. Consequently, water-sensitive VIs that utilize shortwave infrared bands proved to be slightly more sensitive in detecting forest disturbances while chlorophyll-sensitive VIs represented lower accuracy for both forest types. Overall, all VIs faced an underestimation error in deforested area detection that was observable through negative BIAS. The results illuminate that BFASTMonitor can be considered as a tool in monitoring forest environments due to its acceptable deforestation determination capability in deciduous and coniferous forests, with slightly higher performance for small-scale deforestation patterned regions.
Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 Receptors in the Head Twitch Response Induced by 5-Hydroxytryptophan and Psilocybin: Translational Implications
Authors: Shahar Orr , Botvinnik Alexander , Esh-Zuntz Noam , Brownstien Michal , Wolf Rachel , Lotan Amit , Wolf Gilly , Lerer Bernard , Lifschytz Tzuri
Published: November 2022

There is increasing interest in the therapeutic potential of psilocybin. In rodents, the serotonin precursor, 5-hydroxytryptophan (5-HTP) and psilocybin induce a characteristic 5-HT2A receptor (5-HT2AR)-mediated head twitch response (HTR), which is correlated with the human psychedelic trip. We examined the role of other serotonergic receptors and the trace amine -associated receptor 1 (TAAR1) in modulating 5-HTP- and psilocybin-induced HTR. Male C57BL/6J mice (11 weeks, ~30 g) were administered 5-HTP, 50–250 mg/kg i.p., 200 mg/kg i.p. after pretreatment with 5-HT/TAAR1 receptor modulators, psilocybin 0.1–25.6 mg/kg i.p. or 4.4 mg/kg i.p., immediately preceded by 5-HT/TAAR1 receptor modulators. HTR was assessed in a custom-built magnetometer. 5-HTP and psilocybin induced a dose-dependent increase in the frequency of HTR over 20 min with attenuation by the 5-HT2AR antagonist, M100907, and the 5-HT1AR agonist, 8-OH-DPAT. The 5-HT2CR antagonist, RS-102221, enhanced HTR at lower doses but reduced it at higher doses. The TAAR1 antagonist, EPPTB, reduced 5-HTP- but not psilocybin-induced HTR. We have confirmed the key role of 5-HT2AR in HTR, an inhibitory effect of 5-HT1AR, a bimodal contribution of 5-HT2CR and a role of TAAR1 in modulating HTR induced by 5-HTP. Compounds that modulate psychedelic-induced HTR have important potential in the emerging therapeutic use of these compounds.
Activity and Synergy of Cu-ATCUN Antimicrobial Peptides
Authors: Greve Jenna M. , Cowan J. A.
Published: November 2022

Antibiotic resistance demands innovative strategies and therapies. The pairs of antimicrobial peptides tested in this work show broad-spectrum synergy and are capable of interacting with diverse bacterial membranes. In most cases, the ATCUN motif enhanced the activity of peptides tested in combination. Our studies also show CP10A to be a multifaceted peptide, displaying both cell membrane and intracellular activity and acting as a chameleon, improving the activity of other peptides as needed. The results of the synergy experiments demonstrate the importance of varied modes of action and how these changes can affect the ability to combat pathogens, while also illustrating the value of the metal-binding domain in enhancing the activity of antimicrobial peptides in combination.
Phytochemical Targeting of Mitochondria for Breast Cancer Chemoprevention, Therapy, and Sensitization
Authors: Zunica Elizabeth R. M. , Axelrod Christopher L. , Kirwan John P.
Published: November 2022

Breast cancer is a common and deadly disease that causes tremendous physical, emotional, and financial burden on patients and society. Early-stage breast cancer and less aggressive subtypes have promising prognosis for patients, but in aggressive subtypes, and as cancers progress, treatment options and responses diminish, dramatically decreasing survival. Plants are nutritionally rich and biologically diverse organisms containing thousands of metabolites, some of which have chemopreventive, therapeutic, and sensitizing properties, providing a rich source for drug discovery. In this study we review the current landscape of breast cancer with a central focus on the potential role of phytochemicals for treatment, management, and disease prevention. We discuss the relevance of phytochemical targeting of mitochondria for improved anti-breast cancer efficacy. We highlight current applications of phytochemicals and derivative structures that display anti-cancer properties and modulate cancer mitochondria, while describing future applicability and identifying areas of promise.
Genome-Wide Identification and Characterization of the SBP Gene Family in Passion Fruit (Passiflora edulis Sims)
Authors: Liu Yanhui , Yuan Jieyu , Zhang Dan , Deng Kao , Chai Gaifeng , Huang Youmei , Ma Suzhuo , Qin Yuan , Wang Lulu
Published: November 2022

The SQUAMOSA promoter binding proteins (SBPs) gene family plays important roles in plant growth and development. The SBP gene family has been identified and reported in many species, but it has not been well studied in passion fruit. In this study, a total of 14 SBP genes were identified in passion fruit and named from PeSBP1 to PeSBP14 based on their chromosomal distribution. The phylogenetic tree, gene structure, conserved motifs, collinearity analysis, and expression patterns of the identified SBP members were analyzed. We classified the PeSBP genes into eight groups (I to VIII) according to the phylogenetic tree, gene structure, and conserved motifs. Synteny analysis found that 5 homologous gene pairs existed in PeSBP genes and 11 orthologous gene pairs existed between passion fruit and Arabidopsis. Synonymous nucleotide substitution analysis showed that the PeSBP genes were under strong negative selection. The expression pattern of PeSBP genes in seed, root, leaf, and flower showed that nine of the PeSBP genes displayed high expression in the leaf and the flower. The expression patterns of PeSBP3/6/8/9/10 were further detected by qRT-PCR. In addition, differences in the expression levels occurred for each gene in the different flower organs and at the different developmental stages. There were large differences among SBPs based on transcriptional levels under cold, heat, salt, and osmotic stress conditions. Altogether, this study provides an overview of SBP genes in passion fruit and lays the foundation for further functional analysis.
Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment
Authors: Brett Elizabeth , Duscher Dominik , Pagani Andrea , Daigeler Adrien , Kolbenschlag Jonas , Hahn Markus
Published: November 2022

Breast cancer represents the most common malignancy among women in the world. Although immuno-, chemo- and radiation therapy are widely recognized as the therapeutic trifecta, new strategies in the fight against breast cancer are continually explored. The local microenvironment around the tumor plays a great role in cancer progression and invasion, representing a promising therapeutic target. CCL5 is a potent chemokine with a physiological role of immune cell attraction and has gained particular attention in R&D for breast cancer treatment. Its receptor, CCR5, is a well-known co-factor for HIV entry through the cell membrane. Interestingly, biology research is unusually unified in describing CCL5 as a pro-oncogenic factor, especially in breast cancer. In silico, in vitro and in vivo studies blocking the CCL5/CCR5 axis show cancer cells become less invasive and less malignant, and the extracellular matrices produced are less oncogenic. At present, CCR5 blocking is a mainstay of HIV treatment, but despite its promising role in cancer treatment, CCR5 blocking in breast cancer remains unperformed. This review presents the role of the CCL5/CCR5 axis and its effector mechanisms, and names the most prominent hurdles for the clinical adoption of anti-CCR5 drugs in cancer.
Moderator Effect of Hypoalbuminemia in Volume Resuscitation and Plasma Expansion with Intravenous Albumin Solution
Authors: Wiedermann Christian J.
Published: November 2022

Intravenous administration of crystalloid or colloid solutions is the most common intervention for correcting hypovolemia in intensive care unit patients. In critical illness, especially sepsis and severe trauma, vascular wall permeability increases, and trans-endothelial escape of serum albumin, the major oncotic plasma constituent, contributes to the development of hypoalbuminemia and edema formation. The volume effects of intravenous human albumin solution exceed those of crystalloid solutions. If hypoalbuminemia is an effect moderator, the crystalloid-to-albumin ratio of fluid resuscitation volumes is not well characterized. Randomized controlled trials have confirmed that intravenous administration of human albumin solutions for volume resuscitation results in a lower net fluid balance compared with crystalloids, and smaller infusion volumes may be sufficient for hemodynamic stabilization when human albumin solutions are used. This narrative review summarizes the current evidence and conclusions drawn regarding the role of hypoalbuminemia in volume resuscitation. In the ‘Saline versus Albumin Fluid Evaluation’ study using 4% human albumin solution or saline, the saline-to-albumin ratio of study fluids was significantly higher in patients with baseline serum albumin concentrations of 25 g/L or less as compared to patients with baseline serum albumin concentrations of more than 25 g/L. In patients receiving renal replacement therapy, intravenous administration of 20–25% human albumin solution reduces intradialytic hypotension and improves fluid removal better than saline if serum albumin levels are similarly reduced. These data suggest that hypoalbuminemia acts as an effect moderator in volume resuscitation and plasma expansion with albumin solution. The volume effectiveness of intravenous human albumin solution in resuscitation appears to be greater when the serum albumin levels are low. In clinical situations, serum albumin concentrations per se may inform when and how to include intravenous albumin in fluid resuscitation if large amounts of crystalloids are needed, which requires further studies.
Design and Evaluation of Novel HIV-1 Protease Inhibitors Containing Phenols or Polyphenols as P2 Ligands with High Activity against DRV-Resistant HIV-1 Variants
Authors: Ma Ling , Wen Jiajia , Dong Biao , Zhou Jinming , Hu Shangjiu , Wang Juxian , Wang Yucheng , Zhu Mei , Cen Shan
Published: November 2022

With the increasing prevalence of drug-resistant variants, novel potent HIV-1 protease inhibitors with broad-spectrum antiviral activity against multidrug-resistant causative viruses are urgently needed. Herein, we designed and synthesized a new series of HIV-1 protease inhibitors with phenols or polyphenols as the P2 ligands and a variety of sulfonamide analogs as the P2′ ligands. A number of these new inhibitors showed superb enzymatic inhibitory activity and antiviral activity. In particular, inhibitors 15d and 15f exhibited potent enzymatic inhibitory activity in the low picomolar range, and the latter showed excellent activity against the Darunavir-resistant HIV-1 variant. Furthermore, the molecular modeling studies provided insight into the ligand-binding site interactions between inhibitors and the enzyme cavity, and they sparked inspiration for the further optimization of potent inhibitors.
Subclinical Acute Kidney Injury in COVID-19: Possible Mechanisms and Future Perspectives
Authors: Silva-Aguiar Rodrigo P. , Teixeira Douglas E. , Peres Rodrigo A. S. , Peruchetti Diogo B. , Gomes Carlos P. , Schmaier Alvin H. , Rocco Patricia R. M. , Pinheiro Ana Acacia S. , Caruso-Neves Celso
Published: November 2022

Since the outbreak of COVID-19 disease, a bidirectional interaction between kidney disease and the progression of COVID-19 has been demonstrated. Kidney disease is an independent risk factor for mortality of patients with COVID-19 as well as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to the development of acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with COVID-19. However, the detection of kidney damage in patients with COVID-19 may not occur until an advanced stage based on the current clinical blood and urinary examinations. Some studies have pointed out the development of subclinical acute kidney injury (subAKI) syndrome with COVID-19. This syndrome is characterized by significant tubule interstitial injury without changes in the estimated glomerular filtration rate. Despite the complexity of the mechanism(s) underlying the development of subAKI, the involvement of changes in the protein endocytosis machinery in proximal tubule (PT) epithelial cells (PTECs) has been proposed. This paper focuses on the data relating to subAKI and COVID-19 and the role of PTECs and their protein endocytosis machinery in its pathogenesis.
3K3A-Activated Protein C Prevents Microglia Activation, Inhibits NLRP3 Inflammasome and Limits Ocular Inflammation
Authors: Palevski Dahlia , Ben-David Gil , Weinberger Yehonatan , Haj Daood Rabeei , Fernández José A. , Budnik Ivan , Levy-Mendelovich Sarina , Kenet Gili , Nisgav Yael , Weinberger Dov , Griffin John H. , Livnat Tami
Published: November 2022

3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with pleiotropic cytoprotective properties albeit without the bleeding risks. The anti-inflammatory activities of 3K3A-APC were demonstrated in multiple preclinical injury models, including various neurological disorders. We determined the ability of 3K3A-APC to inhibit ocular inflammation in a murine model of lipopolysaccharide (LPS)-induced uveitis. Leukocyte recruitment, microglia activation, NLRP3 inflammasome and IL-1β levels were assessed using flow cytometry, retinal cryosection histology, retinal flatmount immunohistochemistry and vascular imaging, with and without 3K3A-APC treatment. LPS triggered robust inflammatory cell recruitment in the posterior chamber. The 3K3A-APC treatment significantly decreased leukocyte numbers and inhibited leukocyte extravasation from blood vessels into the retinal parenchyma to a level similar to controls. Resident microglia, which underwent an inflammatory transition following LPS injection, remained quiescent in eyes treated with 3K3A-APC. An inflammation-associated increase in retinal thickness, observed in LPS-injected eyes, was diminished by 3K3A-APC treatment, suggesting its clinical relevancy. Finally, 3K3A-APC treatment inhibited inflammasome activation, determined by lower levels of NLRP3 and its downstream effector IL-1β. Our results highlight the anti-inflammatory properties of 3K3A-APC in ocular inflammation and suggest its potential use as a novel treatment for retinal diseases associated with inflammation.
Modifier Factors of Cystic Fibrosis Phenotypes: A Focus on Modifier Genes
Authors: Mésinèle Julie , Ruffin Manon , Guillot Loïc , Corvol Harriet
Published: November 2022

Although cystic fibrosis (CF) is recognized as a monogenic disease, due to variants within the CFTR (Cystic Fibrosis Transmembrane Regulator) gene, an extreme clinical heterogeneity is described among people with CF (pwCF). Apart from the exocrine pancreatic status, most studies agree that there is little association between CFTR variants and disease phenotypes. Environmental factors have been shown to contribute to this heterogeneity, accounting for almost 50% of the variability of the lung function of pwCF. Nevertheless, pwCF with similar CFTR variants and sharing the same environment (such as in siblings) may have highly variable clinical manifestations not explained by CFTR variants, and only partly explained by environmental factors. It is recognized that genetic variants located outside the CFTR locus, named “modifier genes”, influence the clinical expression of the disease. This short review discusses the latest studies that have described modifier factors associated with the various CF phenotypes as well as the response to the recent CFTR modulator therapies.
Impact of Siponimod on Enteric and Central Nervous System Pathology in Late-Stage Experimental Autoimmune Encephalomyelitis
Authors: Weier Alicia , Enders Michael , Kirchner Philipp , Ekici Arif , Bigaud Marc , Kapitza Christopher , Wörl Jürgen , Kuerten Stefanie
Published: November 2022

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Although immune modulation and suppression are effective during relapsing-remitting MS, secondary progressive MS (SPMS) requires neuroregenerative therapeutic options that act on the CNS. The sphingosine-1-phosphate receptor modulator siponimod is the only approved drug for SPMS. In the pivotal trial, siponimod reduced disease progression and brain atrophy compared with placebo. The enteric nervous system (ENS) was recently identified as an additional autoimmune target in MS. We investigated the effects of siponimod on the ENS and CNS in the experimental autoimmune encephalomyelitis model of MS. Mice with late-stage disease were treated with siponimod, fingolimod, or sham. The clinical disease was monitored daily, and treatment success was verified using mass spectrometry and flow cytometry, which revealed peripheral lymphopenia in siponimod- and fingolimod-treated mice. We evaluated the mRNA expression, ultrastructure, and histopathology of the ENS and CNS. Single-cell RNA sequencing revealed an upregulation of proinflammatory genes in spinal cord astrocytes and ependymal cells in siponimod-treated mice. However, differences in CNS and ENS histopathology and ultrastructural pathology between the treatment groups were absent. Thus, our data suggest that siponimod and fingolimod act on the peripheral immune system and do not have pronounced direct neuroprotective effects.
Energy and CO2 Impact of the Eco-Design Regulation for Fans on the European Market
Authors: Händel Claus
Published: November 2022

Fans are components in many different products and have been regulated since 2011 by the Eco-Design Regulation. A fan is typically not a final product but is used as a component in different applications, systems, and products. This study shows that it is helpful to target and regulate a component (possibly additionally) such a fan and that the Eco-Design Regulation of fans is an important driver of energy efficiency and has a significant impact. Regulating fans as a component stimulates the availability of efficient fans at reasonable prices and drives efficiency, also in cases where fans are implemented in other products where a fan’s efficiency does not dominate its performance. Since it was first implemented in 2013, the following savings in electrical energy were achieved: 12 GW electrical power, 150 TWh electrical energy, and 12 MT CO2. This is significant and a good example for regulation.
The Prevalence, Characteristics and Risk Factors of Persistent Symptoms in Non-Hospitalized and Hospitalized Children with SARS-CoV-2 Infection Followed-Up for up to 12 Months: A Prospective, Cohort Study in Rome, Italy
Authors: Buonsenso Danilo , Pazukhina Ekaterina , Gentili Carolina , Vetrugno Luigi , Morello Rosa , Zona Margherita , De Matteis Alessia , D’Ilario Federico , Lanni Roberta , Rongai Teresa , del Balzo Patrizia , Fonte Maria Teresa , Valente Michele , De Rose Cristina , Munblit Daniel , Sigfrid Louise , Valentini Piero
Published: November 2022

Previous studies assessing the prevalence of COVID-19 sequelae in children have included either a small number of children or a short follow-up period, or have only focused on hospitalized children. We investigated the prevalence of persistent symptoms amongst children and assessed the risk factors, including the impact of variants. A prospective cohort study included children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection. The participants were assessed via telephone and face-to-face visits at 1–5, 6–9 and 12 or more months post-SARS-CoV-2 diagnosis using the ISARIC COVID-19 follow-up survey. Of the 679 children enrolled, 51% were female; 488 were infected during the wild virus wave, and 29 were infected with the Alpha, 42 with the Delta and 120 with the Omicron variants. Fatigue (19%), headache (12%), insomnia (7.5%), muscle pain (6.9%) and confusion with concentration issues (6.8%) were the most common persistent symptoms. Families reported an overall improvement over time, with 0.7% of parents interviewed at 12 months or more of the follow-up period reporting a poor recovery. Patients that had not recovered by 6–9 months had a lower probability of recovering during the next follow-up period. Children infected with a variant or the wild virus had an overall similar rate of persistent symptoms (although the pattern of reported symptoms differed significantly) and recovery rates. Conclusions: Recovery rates after SARS-CoV-2 infection improved as time passed from the initial infection, ranging from 4% of children having poor recovery at 1–5 months’ follow-up to 1.3% at 6–9 months and 0.7% at 12 months. The patterns of persistence changed according to the variants involved at the time of infection. This study reinforces that a subgroup of children develop long-lasting persistent symptoms and highlights the need for further studies investigating the reasons behind the development of PCC.
Megakaryocyte- and Platelet-Derived Microparticles as Novel Diagnostic and Prognostic Biomarkers for Immune Thrombocytopenia
Authors: Wang Wen , Zuo Bin , Wang Yao , Li Xinyu , Weng Zhen , Zhai Juping , Wu Qingyu , He Yang
Published: November 2022

Altered cell-derived microparticles (MPs) have been reported in multiple autoimmune diseases. However, the roles of megakaryocyte- and platelet-derived MPs (MKMPs and PMPs) in immune thrombocytopenia (ITP) have not been investigated. In this study, we examined plasma MKMP and PMP levels in patients with ITP and evaluated their potential diagnostic values. Plasma MKMP and PMP levels were analyzed by flow cytometry in a discovery set of ITP patients (n = 78), non-immune thrombocytopenia (TP) patients (n = 69), and age- and gender-matched healthy controls (n = 88). Samples from a therapy set of ITP patients (n = 21) were used to assess the response to thrombopoietin receptor agonist (TPO-RA) treatment. Spearman correlation analysis was performed between MP levels and disease parameters. Receiver operator characteristic (ROC) curves were generated to evaluate the diagnostic values of the MPs. We found that plasma MKMP and PMP levels were significantly lower in ITP patients than those in healthy controls (p values < 0.0001) but higher than in those in TP patients (p < 0.002 and p < 0.0002, respectively). After normalization to platelet counts, PMP/Platelet ratios in ITP patients were higher than those in TP patients and healthy controls (p values < 0.001). PMP/Platelet ratios had a diagnostic value for ITP (area under the curve = 0.808, p < 0.0001) with 73.1% sensitivity and 77.3% specificity. MKMP levels can be used to discriminate ITP from TP with a cut-off value of 112.5 MPs/μL and a sensitivity of 74.4%. Moreover, both MKMP and PMP levels were elevated in ITP patients who responded to TPO-RA treatment. Plasma PMP levels positively correlated with platelet counts in the responders (r = 0.558, p < 0.01). Our results indicate that plasma MKMP and PMP levels are decreased in ITP patients and that plasma MKMP and PMP levels may serve as biomarkers for ITP diagnosis and prediction of TPO-RA treatment response.