bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Correlation of Solar Activity and Troposphere on the GNSS/EGNOS Integrity. Fuzzy Logic Approach
Authors: Krzykowska-Piotrowska Karolina , Dudek Ewa , Wielgosz Paweł , Milanowska Beata , Batalla Jordi Mongay
Published: July 2021

There is a noticeable number of studies carried out on both the operational parameters of Global Navigation Satellite System (GNSS) and the satellite signal itself. Researchers look for, inter alia, proven sources of errors affecting the integrity of the satellite signal because this parameter determines the approval of the system’s operational use. It also seems of key importance that the atmospheric conditions, in any area of satellite signal usage, should not be underestimated due to their extensive impact. As the ionospheric refraction seriously limits the operational use of the satellite navigation signal, in this article, the authors attempted to quantify the effect of solar activity (expressed by sunspots) on the signal integrity using fuzzy logic. Fuzzy reasoning is used when information is inaccurate or incomplete and necessitates making decisions under conditions of uncertainty. Thanks to fuzzy sets, there are no obstacles to characterize the degree of intensity of a given phenomenon. In order to look at the problem more broadly, attention was also paid to the tropospheric conditions, and it was verified whether, against the background of cloudiness, precipitation, humidity, pressure and temperature, solar activity affects the integrity to the greatest extent. The integrity measurements from the EGNOS system (PRN120 and PRN126) collected at the monitoring station in Warsaw, Poland in 2014 were used.
Operating Cost Reduction in Distribution Networks Based on the Optimal Phase-Swapping including the Costs of the Working Groups and Energy Losses
Authors: Montoya Oscar Danilo , Alarcon-Villamil Jorge Alexander , Hernández Jesus C.
Published: July 2021

The problem of optimal phase-balancing in three-phase asymmetric distribution networks is addressed in this research from the point of view of combinatorial optimization using a master–slave optimization approach. The master stage employs an improved sine cosine algorithm (ISCA), which is entrusted with determining the load reconfiguration at each node. The slave stage evaluates the energy losses for each set of load connections provided by the master stage by implementing the triangular-based power flow method. The mathematical model that was solved using the ISCA is designed to minimize the annual operating costs of the three-phase network. These costs include the annual costs of the energy losses, considering daily active and reactive power curves, as well as the costs of the working groups tasked with the implementation of the phase-balancing plan at each node. The peak load scenario was evaluated for a 15-bus test system to demonstrate the effectiveness of the proposed ISCA in reducing the power loss (18.66%) compared with optimization methods such as genetic algorithm (18.64%), the classical sine cosine algorithm (18.42%), black-hole optimizer (18.38%), and vortex search algorithm (18.59%). The IEEE 37-bus system was employed to determine the annual total costs of the network before and after implementing the phase-balancing plan provided by the proposed ISCA. The annual operative costs were reduced by about 13% with respect to the benchmark case, with investments between USD 2100 and USD 2200 in phase-balancing activities developed by the working groups. In addition, the positive effects of implementing the phase-balancing plan were evidenced in the voltage performance of the IEEE 37-bus system by improving the voltage regulation with a maximum of 4% in the whole network from an initial regulation of 6.30%. All numerical validations were performed in the MATLAB programming environment.
Upgrading BRICKS—The Context-Aware Semantic Rule-Based System for Intelligent Building Energy and Security Management
Authors: Santos Gabriel , Pinto Tiago , Vale Zita , Carvalho Rui , Teixeira Brígida , Ramos Carlos
Published: July 2021

Building management systems (BMSs) are being implemented broadly by industries in recent decades. However, BMSs focus on specific domains, and when installed on the same building, they lack interoperability to work on a centralized user interface. On the other hand, BMSs interoperability allows the implementation of complex rules based on multi-domain contexts. The Building’s Reasoning for Intelligent Control Knowledge-based System (BRICKS) is a context-aware semantic rule-based system for the intelligent management of buildings’ energy and security. It uses ontologies and semantic web technologies to interact with different domains, taking advantage of cross-domain knowledge to apply context-based rules. This work upgrades the previously presented version of BRICKS by including services for energy consumption and generation forecast, demand response, a configuration user interface (UI), and a dynamic building monitoring and management UI. The case study demonstrates BRICKS deployed at different aggregation levels in the authors’ laboratory building, managing a demand response event and interacting autonomously with other BRICKS instances. The results validate the correct functioning of the proposed tool, which contributes to the flexibility, efficiency, and security of building energy systems.
Effects of Harvest Maturity, Refrigeration and Blanching Treatments on the Volatile Profiles of Ripe “Tasti-Lee” Tomatoes
Authors: Xi Yu , Li Qing , Yan Jiaqi , Baldwin Elizabeth , Plotto Anne , Rosskopf Erin , Hong Jason C. , Zuo Jinhua , Bai Jinhe , Li Jian
Published: July 2021

The interactive effects of six maturity stages and refrigerated storage (chilling)/blanching (heating) treatments on the volatile profiles of ripe tomatoes were studied. A total of 42 volatiles were identified, of which 19 compounds had odor activity values equal to or greater than 1. Of those, “green” and “leafy” aroma volatiles were most abundant. Chilling and heating treatments both suppressed overall volatile production, with chilling having the greater impact, regardless of harvest maturity. However, fruit harvested at the turning stage had the least volatile suppression by chilling and heating treatments in comparison with fruit harvested earlier or later, mostly in the fatty acid- and phenylalanine-derived volatiles. Volatiles derived from amino acids were promoted by heat treatment for fruit harvested at all maturities, and those derived from carotenoid and phenylalanine pathways and harvested at advanced harvest maturities were stimulated by chilling treatment. Volatile production is generally believed to be improved by delayed harvest, with vine-ripe being optimum. However, opposite results were observed possibly because the later-harvested fruit had longer exposure to open-field weather stress. The best harvest maturity recommendation is the turning stage where fruit developed abundant volatiles and were least impacted by chilling and heating treatments.
Development of Nervilia fordii Extract-Loaded Electrospun PVA/PVP Nanocomposite for Antioxidant Packaging
Authors: Wen Peng , Hu Teng-Gen , Wen Yan , Li Ke-Er , Qiu Wei-Peng , He Zhi-Lin , Wang Hong , Wu Hong
Published: July 2021

An ethyl acetate extract from of Nervilia fordii (NFE) with considerable suppression activity on lipid peroxidation (LPO) was first obtained with total phenolic and flavonoid contents and anti-LPO activity (IC50) of 86.67 ± 2.5 mg GAE/g sample, 334.56 ± 4.7 mg RE/g extract and 0.307 mg/mL, respectively. In order to improve its stability and expand its application in antioxidant packaging, the nano-encapsulation of NFE within poly(vinyl alcohol) (PVA) and polyvinyl(pyrrolidone) (PVP) bio-composite film was then successfully developed using electrospinning. SEM analysis revealed that the NFE-loaded fibers exhibited similar morphology to the neat PVA/PVP fibers with a bead-free and smooth morphology. The encapsulation efficiency of NFE was higher than 90% and the encapsulated NFE still retained its antioxidant capacity. Fourier transform infrared spectroscopy (FTIR) and X-ray powder diffraction (XRD) analysis confirmed the successful encapsulation of NFE into fibers and their compatibility, and the thermal stability of which was also improved due to the intermolecular interaction demonstrated by thermo gravimetric analysis (TGA). The ability to preserve the fish oil’s oxidation and extend its shelf-life was also demonstrated, suggesting the obtained PVA/PVP/NFE fiber mat has the potential as a promising antioxidant food packaging material.
The Provenance of Slovenian Milk Using 87Sr/86Sr Isotope Ratios
Authors: Gregorčič Staša Hamzić , Ogrinc Nives , Frew Russell , Nečemer Marijan , Strojnik Lidija , Zuliani Tea
Published: July 2021

This work presents the first use of Sr isotope ratios for determining the provenance of bovine milk from different regions of Slovenia. The analytical protocol for the determination of 87Sr/86Sr isotope ratio was optimised and applied to authentic milk samples. Considerable variability of 87Sr/86Sr ratios found in Slovenian milk reflects the substantial heterogeneity of the geological background of its origin. The results, although promising, cannot discount possible inter-annual or annual variation of the Sr isotopic composition of milk. The 87Sr/86Sr ratios of groundwater and surface waters are in good correlation with milk, indicating that the Sr isotopic fingerprint in milk is reflective of cow drinking water. The 87Sr/86Sr ratio has the potential to distinguish between different milk production areas as long as these areas are characterised by geo-lithology. Discriminant analysis (DA) incorporating the elemental composition and stable isotopes of light elements showed that 87Sr/86Sr ratio together with δ13Ccas and δ15Ncas values have the main discrimination power to distinguish the Quaternary group (group 6) from the others. Group 1 (Cretaceous: Carbonate Rocks and Flysch) is associated with Br content, 1/Sr and δ18Ow values. The overall prediction ability was found to be 63.5%. Pairwise comparisons using OPLS-DA confirmed that diet and geologic parameters are important for the separation.
Sustainability of the Olive Oil System
Authors: Alamprese Cristina , Caponio Francesco , Chiavaro Emma
Published: July 2021

Sustainability is a widely accepted goal across many sectors of our society and, according to new concepts, it includes resilience and adaptive capacity [...]
Mechanisms Involved in Interspecific Communication between Wine Yeasts
Authors: Mencher Ana , Morales Pilar , Tronchoni Jordi , Gonzalez Ramon
Published: July 2021

In parallel with the development of non-Saccharomyces starter cultures in oenology, a growing interest has developed around the interactions between the microorganisms involved in the transformation of grape must into wine. Nowadays, it is widely accepted that the outcome of a fermentation process involving two or more inoculated yeast species will be different from the weighted average of the corresponding individual cultures. Interspecific interactions between wine yeasts take place on several levels, including interference competition, exploitation competition, exchange of metabolic intermediates, and others. Some interactions could be a simple consequence of each yeast running its own metabolic programme in a context where metabolic intermediates and end products from other yeasts are present. However, there are clear indications, in some cases, of specific recognition between interacting yeasts. In this article we discuss the mechanisms that may be involved in the communication between wine yeasts during alcoholic fermentation.
Encapsulation of Olive Pomace Extract in Rocket Seed Gum and Chia Seed Gum Nanoparticles: Characterization, Antioxidant Activity and Oxidative Stability
Authors: Akcicek Alican , Bozkurt Fatih , Akgül Cansu , Karasu Salih
Published: July 2021

The aim of this study was to determine the potential use of rocket seed and chia seed gum as wall materials, to encapsulate and to prevent degradation of olive pomace extract (OPE) in polymeric nanoparticles, and to characterize olive pomace extract-loaded rocket seed gum nanoparticles (RSGNPs) and chia seed gum nanoparticles (CSGNPs). The phenolic profile of olive pomace extract and physicochemical properties of olive pomace, rocket seed gum (RSG), and chia seed gum (CSG) were determined. The characterization of the nanoparticles was performed using particle size and zeta potential measurement, differential scanning calorimeter (DSC), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), encapsulation efficiency (EE%), in vitro release, and antioxidant activity analyses. Nanoparticles were used to form oil in water Pickering emulsions and were evaluated by oxitest. The RSGNPs and CSGNPs showed spherical shape in irregular form, had an average size 318 ± 3.11 nm and 490 ± 8.67 nm, and zeta potential values of −22.6 ± 1.23 and −29.9 ± 2.57, 25 respectively. The encapsulation efficiency of the RSGNPs and CSGNPs were found to be 67.01 ± 4.29% and 82.86 ± 4.13%, respectively. The OPE-RSGNP and OPE-CSGNP presented peaks at the 1248 cm−1 and 1350 cm−1 which represented that C-O groups and deformation of OH, respectively, shifted compared to the OPE (1252.53 cm−1 and 1394.69 cm−1). The shift in wave numbers showed interactions of a phenolic compound of OPE within the RSG and CSG, respectively. In vitro release study showed that the encapsulation of OPE in RSGNPs and CSGNPs led to a delay of the OPE released in physiological pH. The total phenolic content and antioxidant capacity of RSGNPs and CSGNPs increased when the OPE-loaded RSGNPs and CSGNPs were formed. The encapsulation of OPE in RSGNPs and CSGNPs and the IP values of the oil in water Pickering emulsions containing OPE-RSGNPs and OPE-CSGNPs were higher than OPE, proving that OPE-loaded RSGNPs and CSGNPs significantly increased oxidative stability of Pickering emulsions. These results suggest that the RSG and CSG could have the potential to be utilized as wall materials for nanoencapsulation and prevent degradation of cold-pressed olive pomace phenolic extract.
Signal and Texture Features from T2 Maps for the Prediction of Mild Cognitive Impairment to Alzheimer’s Disease Progression
Authors: Trejo-Castro Alejandro I. , Caballero-Luna Ricardo A. , Garnica-López José A. , Vega-Lara Fernando , Martinez-Torteya Antonio
Published: July 2021

Early detection of Alzheimer’s disease (AD) is crucial to preserve cognitive functions and provide the opportunity for patients to enter clinical trials. In recent years, some studies have reported that features related to the signal and texture of MRI images can be an effective biomarker of AD. To test these claims, a study was conducted using T2 maps, a sequence not previously studied, of 40 patients with mild cognitive impairment (MCI) from the Alzheimer’s Disease Neuroimaging Initiative database, who either progressed to AD (18) or remained stable (22). From these maps, the mean value and absolute difference of 37 signal and texture imaging features for 40 contralateral pairs of regions were measured. We used seven machine learning methods to analyze whether, by adding these imaging features to the neuropsychological studies currently used for diagnosis, we could more accurately identify patients who will progress to AD. The predictive models improved with the addition of signal and texture features. Additionally, features related to the signal and texture of the images were much more relevant than volumetric ones. Our results suggest that contralateral signal and texture features should be further investigated as potential biomarkers for the prediction of AD.
Self-Perception of Quality of Life and Emotional Well-Being among Students Attending Hospital Classrooms during COVID-19 Pandemic
Authors: Riera-Negre Laia , Paz-Lourido Berta , Negre Francisca , Rosselló María Rosa , Verger Sebastià
Published: July 2021

The COVID-19 pandemic caused disruptions in schooling and the closure of schools worldwide, how this has affected children’s and youth’s health and wellbeing is a current area of research. However, those who suffer a chronic or temporary disease may be attending hospital classrooms, and this scenario has received little attention in comparison to regular schools. The objective of this exploratory quantitative study focuses on exploring the quality of life and emotional well-being of students attending hospital classrooms. For this purpose, four Chilean hospital classrooms from different regions of the country were randomly selected. A total number of 248 students participated in the survey, each of whom filled out two online questionnaires. The findings show similar scores in children with mental illness and those with other health conditions. In comparison with one year before, students rate their general health as the same or somewhat better now, as well as manifesting an optimistic view of the future regarding the pandemic.
Determinants of Diabetes Disease Management, 2011–2019
Authors: Fulton Lawrence V. , Adepoju Omolola E. , Dolezel Diane , Ekin Tahir , Gibbs David , Hewitt Barbara , McLeod Alexander , Liaw Winston , Lieneck Cristian , Ramamonjiarivelo Zo , Shanmugam Ram , Woodward Lechauncey D.
Published: July 2021

This study estimated the effects of Medicaid Expansion, demographics, socioeconomic status (SES), and health status on disease management of diabetes over time. The hypothesis was that the introduction of the ACA and particularly Medicaid Expansion would increase the following dependent variables (all proportions): (1) provider checks of HbA1c, (2) provider checks of feet, (3) provider checks of eyes, (4) patient education, (5) annual physician checks for diabetes, (6) patient self-checks of blood sugar. Data were available from the Behavioral Risk Factor Surveillance System for 2011 to 2019. We filtered the data to include only patients with diagnosed non-gestational diabetes of age 45 or older (n = 510,991 cases prior to weighting). Linear splines modeled Medicaid Expansion based on state of residence as well as implementation status. Descriptive time series plots showed no major changes in proportions of the dependent variables over time. Quasibinomial analysis showed that implementation of Medicaid Expansion had a statistically negative effect on patient self-checks of blood sugar (odds ratio = 0.971, p < 0.001), a statistically positive effect on physician checks of HbA1c (odds ratio = 1.048, p < 0.001), a statistically positive effect on feet checks (odds ratio = 1.021, p < 0.001), and no other significant effects. Evidence of demographic, SES, and health status disparities existed for most of the dependent variables. This finding was especially significant for HbA1c checks by providers. Barriers to achieving better diabetic care remain and require innovative policy interventions.
A Nationwide Mystery Caller Evaluation of Oral Emergency Contraception Practices from German Community Pharmacies: An Observational Study Protocol
Authors: Kunow Christian , Bello Moulika Aline , Diedrich Laura , Eutin Laura , Sonnenberg Yanneck , Wachtel Nele , Langer Bernhard
Published: July 2021

To prevent unwanted pregnancies, oral emergency contraception (EC) with the active ingredients levonorgestrel (LNG) and ulipristal acetate (UPA) is recommended by the guidelines of the German Federal Chamber of Pharmacists (BAK). In this respect, community pharmacies (CPs) in Germany have a major responsibility for information gathering, selecting the appropriate medicine, availability and pricing, among other things. Therefore, it would be appropriate to conduct a study with the aim of investigating information gathering, a possible recommendation as well as availability and pricing for oral EC in German CPs. A representative nationwide observational study based on the simulated patient methodology (SPM) in the form of covert mystery calls will be conducted in a random sample of German CPs stratified according to the 16 federal states. Each selected CP will be randomly called once successfully by one of six both female and male trained mystery callers (MCs). The MCs will simulate a product-based scenario using the request for oral EC. For quality assurance of the data collection, a second observer accompanying the MC is planned. After all mystery calls have been made, each CP will receive written, pharmacy-specific performance feedback. The only national SPM study on oral EC to date has identified deficits in the provision of self-medication consultations with the help of visits in the CPs studied. International studies suggest that UPA in particular is not always available. Significant price differences could be found analogous to another German study for a different indication.
Effects of Nursing Simulation Using Mixed Reality: A Scoping Review
Authors: Kim Kyeng-Jin , Choi Moon-Ji , Kim Kyu-Jin
Published: July 2021

Mixed reality (MR) has recently been suggested as a new educational tool for nursing simulation. However, few studies have assessed the use and evaluation of MR nursing simulations. Therefore, this review identified studies of MR nursing simulations through a scoping review using the framework proposed by Arksey and O’Malley. The studies reviewed were found through DBpia, RISS, PubMed, CINAHL, and Google Scholar. Each study was analyzed, and data were abstracted into publication characteristics, simulation program details, device use, and simulation evaluation. A total of 10 studies were reviewed. Senses that were mainly used in MR nursing simulation included audition and haptics via motion, in addition to visual information. Simulations were evaluated using various outcome variables. Knowledge was most commonly evaluated, followed by clinical performance and satisfaction. This study is significant as it analyzed trends in research on MR nursing simulations in Korea and other countries and suggested directions for the use of MR technology in nursing simulations based on the findings. Additional studies are required to develop scenarios for the effective use of MR in nursing education and to evaluate the effects of MR nursing simulations.
Computer Modeling of the Heart for ECG Interpretation—A Review
Authors: Dössel Olaf , Luongo Giorgio , Nagel Claudia , Loewe Axel
Published: July 2021

Computer modeling of the electrophysiology of the heart has undergone significant progress. A healthy heart can be modeled starting from the ion channels via the spread of a depolarization wave on a realistic geometry of the human heart up to the potentials on the body surface and the ECG. Research is advancing regarding modeling diseases of the heart. This article reviews progress in calculating and analyzing the corresponding electrocardiogram (ECG) from simulated depolarization and repolarization waves. First, we describe modeling of the P-wave, the QRS complex and the T-wave of a healthy heart. Then, both the modeling and the corresponding ECGs of several important diseases and arrhythmias are delineated: ischemia and infarction, ectopic beats and extrasystoles, ventricular tachycardia, bundle branch blocks, atrial tachycardia, flutter and fibrillation, genetic diseases and channelopathies, imbalance of electrolytes and drug-induced changes. Finally, we outline the potential impact of computer modeling on ECG interpretation. Computer modeling can contribute to a better comprehension of the relation between features in the ECG and the underlying cardiac condition and disease. It can pave the way for a quantitative analysis of the ECG and can support the cardiologist in identifying events or non-invasively localizing diseased areas. Finally, it can deliver very large databases of reliably labeled ECGs as training data for machine learning.
The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19
Authors: Emanuele Sonia , Celesia Adriana , D’Anneo Antonella , Lauricella Marianna , Carlisi Daniela , De Blasio Anna , Giuliano Michela
Published: July 2021

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 overstimulation often occurs in tumour cells and a complex correlation of Nrf2 with cancer initiation and progression has been widely described. Therefore, if on one hand, Nrf2 has a dual role in cancer, on the other hand, the factor seems to display a univocal function in preventing inflammation and cytokine storm that occur under viral infections, specifically in coronavirus disease 19 (COVID-19). In such a variegate context, the present review aims to dissect the roles of Nrf2 in both cancer and COVID-19, two widespread diseases that represent a cause of major concern today. In particular, the review describes the molecular aspects of Nrf2 signalling in both pathological situations and the most recent findings about the advantages of Nrf2 inhibition or activation as possible strategies for cancer and COVID-19 treatment respectively.
Ultrasound Imaging by Thermally Tunable Phononic Crystal Lens
Authors: Jin Yuqi , Neogi Arup
Published: July 2021

This work demonstrates the detections and mappings of a solid object using a thermally tunable solid-state phononic crystal lens at low frequency for potential use in future long-distance detection. The phononic crystal lens is infiltrated with a polyvinyl alcohol-based poly n-isopropyl acrylamide (PVA-PNIPAm) bulk hydrogel polymer. The hydrogel undergoes a volumetric phase transition due to a temperature change leading to a temperature-dependent sound velocity and density. The temperature variation from 20 °C to 39 °C changes the focal length of the tunable solid-state lens by 1 cm in the axial direction. This thermo-reversible tunable focal length lens was used in a monostatic setup for one- and two-dimensional mapping scans in both frequency domain echo-intensity and temporal domain time-of-flight modes. The experimental results illustrated 1.03 ± 0.15λ and 2.35 ± 0.28λ on the lateral and axial minimum detectable object size. The experiments using the tunable lens demonstrate the capability to detect objects by changing the temperature in water without translating an object, source, or detector. The time-of-flight mode modality using the tunable solid-state phononic lens increases the signal-to-noise ratio compared to a conventional phononic crystal lens.
Cardioprotection by SGLT2 Inhibitors—Does It All Come Down to Na+?
Authors: Trum Maximilian , Riechel Johannes , Wagner Stefan
Published: July 2021

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are emerging as a new treatment strategy for heart failure with reduced ejection fraction (HFrEF) and—depending on the wistfully awaited results of two clinical trials (DELIVER and EMPEROR-Preserved)—may be the first drug class to improve cardiovascular outcomes in patients suffering from heart failure with preserved ejection fraction (HFpEF). Proposed mechanisms of action of this class of drugs are diverse and include metabolic and hemodynamic effects as well as effects on inflammation, neurohumoral activation, and intracellular ion homeostasis. In this review we focus on the growing body of evidence for SGLT2i-mediated effects on cardiac intracellular Na+ as an upstream mechanism. Therefore, we will first give a short overview of physiological cardiomyocyte Na+ handling and its deterioration in heart failure. On this basis we discuss the salutary effects of SGLT2i on Na+ homeostasis by influencing NHE1 activity, late INa as well as CaMKII activity. Finally, we highlight the potential relevance of these effects for systolic and diastolic dysfunction as well as arrhythmogenesis.
Prenatal Trimethyltin Exposure Induces Long-Term DNA Methylation Changes in the Male Mouse Hippocampus
Authors: Kim Soon-Ae , Chai Jung-Hoon , Jang Eun-Hye
Published: July 2021

Trimethyltin (TMT) is an irreversible neurotoxicant. Because prenatal TMT exposure has been reported to induce behavioral changes, this study was conducted to observe gender differences and epigenetic changes using a mouse model. In behavioral testing of offspring at 5 weeks of age, the total times spent in the center, corner, or border zones in the male prenatal TMT-exposed mice were less than those of control unexposed mice in the open-field test. Female TMT-exposed mice scored lower on total numbers of arm entries and percentages of alternations than controls in the Y-maze test with lower body weight. We found that only TMT-exposed males had fewer copies of mtDNA in the hippocampus and prefrontal cortex region than controls. Additional epigenetic changes, including increased 5-methyl cytosine/5-hydroxymethyl cytosine levels in the male TMT hippocampus, were observed. After methylation binding domain (MBD) sequencing, multiple signaling pathways related to metabolism and neurodevelopment, including FoxO signaling, were identified by pathway analysis for differentially methylated regions (DMRs). Increased FOXO3 and decreased ASCL1 expression were also observed in male TMT hippocampi. This study suggests that sex differences and epigenetics should be more carefully considered in prenatal toxicology studies.
Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery
Authors: Kang Taewook , Huang Honggang , Mandrup-Poulsen Thomas , Larsen Martin R.
Published: July 2021

Pro-inflammatory cytokines promote cellular iron-import through enhanced divalent metal transporter-1 (DMT1) expression in pancreatic β-cells, consequently cell death. Inhibition of β-cell iron-import by DMT1 silencing protects against apoptosis in animal models of diabetes. However, how alterations of signaling networks contribute to the protective action of DMT1 knock-down is unknown. Here, we performed phosphoproteomics using our sequential enrichment strategy of mRNA, protein, and phosphopeptides, which enabled us to explore the concurrent molecular events in the same set of wildtype and DMT1-silenced β-cells during IL-1β exposure. Our findings reveal new phosphosites in the IL-1β-induced proteins that are clearly reverted by DMT1 silencing towards their steady-state levels. We validated the levels of five novel phosphosites of the potential protective proteins using parallel reaction monitoring. We also confirmed the inactivation of autophagic flux that may be relevant for cell survival induced by DMT1 silencing during IL-1β exposure. Additionally, the potential protective proteins induced by DMT1 silencing were related to insulin secretion that may lead to improving β-cell functions upon exposure to IL-1β. This global profiling has shed light on the signal transduction pathways driving the protection against inflammation-induced cell death in β-cells after DMT1 silencing.
Rapamycin Plus Doxycycline Combination Affects Growth Arrest and Selective Autophagy-Dependent Cell Death in Breast Cancer Cells
Authors: Dankó Titanilla , Petővári Gábor , Sztankovics Dániel , Moldvai Dorottya , Raffay Regina , Lőrincz Péter , Visnovitz Tamás , Zsiros Viktória , Barna Gábor , Márk Ágnes , Krencz Ildikó , Sebestyén Anna
Published: July 2021

Metabolic alteration is characteristic during tumour growth and therapy; however, targeting metabolic rewiring could overcome therapy resistance. mTOR hyperactivity, autophagy and other metabolic processes, including mitochondrial functions, could be targeted in breast cancer progression. We investigated the growth inhibitory mechanism of rapamycin + doxycycline treatment in human breast cancer model systems. Cell cycle and cell viability, including apoptotic and necrotic cell death, were analysed using flow cytometry, caspase activity measurements and caspase-3 immunostainings. mTOR-, autophagy-, necroptosis-related proteins and treatment-induced morphological alterations were analysed by WesTM, Western blot, immunostainings and transmission electron microscopy. The rapamycin + doxycycline combination decreased tumour proliferation in about 2/3rd of the investigated cell lines. The continuous treatment reduced tumour growth significantly both in vivo and in vitro. The effect after short-term treatment was reversible; however, autophagic vacuoles and degrading mitochondria were detected simultaneously, and the presence of mitophagy was also observed after the long-term rapamycin + doxycycline combination treatment. The rapamycin + doxycycline combination did not cause apoptosis or necrosis/necroptosis, but the alterations in autophagy- and mitochondria-related protein levels (LC3-B-II/I, p62, MitoTracker, TOM20 and certain co-stainings) were correlated to autophagy induction and mitophagy, without mitochondria repopulation. Based on these results, we suggest considering inducing metabolic stress and targeting mTOR hyperactivity and mitochondrial functions in combined anti-cancer treatments.
Isoform-Specific Properties of Orai Homologues in Activation, Downstream Signaling, Physiology and Pathophysiology
Authors: Tiffner Adéla , Derler Isabella
Published: July 2021

Ca2+ ion channels are critical in a variety of physiological events, including cell growth, differentiation, gene transcription and apoptosis. One such essential entry pathway for calcium into the cell is the Ca2+ release-activated Ca2+ (CRAC) channel. It consists of the Ca2+ sensing protein, stromal interaction molecule 1 (STIM1) located in the endoplasmic reticulum (ER) and a Ca2+ ion channel Orai in the plasma membrane. The Orai channel family includes three homologues Orai1, Orai2 and Orai3. While Orai1 is the “classical” Ca2+ ion channel within the CRAC channel complex and plays a universal role in the human body, there is increasing evidence that Orai2 and Orai3 are important in specific physiological and pathophysiological processes. This makes them an attractive target in drug discovery, but requires a detailed understanding of the three Orai channels and, in particular, their differences. Orai channel activation is initiated via Ca2+ store depletion, which is sensed by STIM1 proteins, and induces their conformational change and oligomerization. Upon STIM1 coupling, Orai channels activate to allow Ca2+ permeation into the cell. While this activation mechanism is comparable among the isoforms, they differ by a number of functional and structural properties due to non-conserved regions in their sequences. In this review, we summarize the knowledge as well as open questions in our current understanding of the three isoforms in terms of their structure/function relationship, downstream signaling and physiology as well as pathophysiology.
Non-Covalent Forces in Naphthazarin—Cooperativity or Competition in the Light of Theoretical Approaches
Authors: Jezierska Aneta , Błaziak Kacper , Klahm Sebastian , Lüchow Arne , Panek Jarosław J.
Published: July 2021

Non-covalent interactions responsible for molecular features and self-assembly in Naphthazarin C polymorph were investigated on the basis of diverse theoretical approaches: Density Functional Theory (DFT), Diffusion Quantum Monte Carlo (DQMC), Symmetry-Adapted Perturbation Theory (SAPT) and Car-Parrinello Molecular Dynamics (CPMD). The proton reaction paths in the intramolecular hydrogen bridges were studied. Two potential energy minima were found indicating that the proton transfer phenomena occur in the electronic ground state. Diffusion Quantum Monte Carlo (DQMC) and other levels of theory including Coupled Cluster (CC) employment enabled an accurate inspection of Potential Energy Surface (PES) and revealed the energy barrier for the proton transfer. The structure and reactivity evolution associated with the proton transfer were investigated using Harmonic Oscillator Model of Aromaticity - HOMA index, Fukui functions and Atoms In Molecules (AIM) theory. The energy partitioning in the studied dimers was carried out based on Symmetry-Adapted Perturbation Theory (SAPT) indicating that dispersive forces are dominant in the structure stabilization. The CPMD simulations were performed at 60 K and 300 K in vacuo and in the crystalline phase. The temperature influence on the bridged protons dynamics was studied and showed that the proton transfer phenomena were not observed at 60 K, but the frequent events were noticed at 300 K in both studied phases. The spectroscopic signatures derived from the CPMD were computed using Fourier transformation of autocorrelation function of atomic velocity for the whole molecule and bridged protons. The computed gas-phase IR spectra showed two regions with OH absorption that covers frequencies from 2500 cm−1 to 2800 cm−1 at 60 K and from 2350 cm−1 to 3250 cm−1 at 300 K for both bridged protons. In comparison, the solid state computed IR spectra revealed the environmental influence on the vibrational features. For each of them absorption regions were found between 2700–3100 cm−1 and 2400–2850 cm−1 at 60 K and 2300–3300 cm−1 and 2300–3200 cm−1 at 300 K respectively. Therefore, the CPMD study results indicated that there is a cooperation of intramolecular hydrogen bonds in Naphthazarin molecule.
Alternative Approach for Cerebral Protection during Complex Aortic Arch and Redo Surgery
Authors: Capoccia Massimo , Nienaber Christoph A. , Mireskandari Maziar , Sabetai Michael , Young Christopher , Cheshire Nicholas J. , Rosendahl Ulrich P.
Published: July 2021

Total arch replacement remains a very demanding surgical procedure. It can be associated with reasonable long-term outcomes but carries serious perioperative complications. Aortic arch surgery has progressed in recent years to a wider adoption of reproducible and reliable techniques. Conventional open, surgical aortic arch replacement is currently offered to the majority of patients, although hybrid and wholly endovascular techniques are gaining popularity. With regards to open arch replacement, the nuances of surgical technique, the mode of cannulation and the optimal cerebral protection protocols remain a matter of debate. We propose an alternative cannulation approach facilitated by the cooperation between cardiac and vascular surgeons. A three-way arterial cannulation including both carotid arteries and the femoral artery (or ascending aorta) is the key feature of this approach. A case series of complex patients is presented to show both the feasibility and relative safety of a standardised new approach with a 100% technical success rate and a 16% 30-day mortality. The three-way cannulation approach may have a role to play for complex and extensive procedures requiring prolonged cerebral protection. We believe that a shared skill set from cardiac and vascular specialists is essential for the safe management and successful outcomes using this adaptive technique.
Difference in Prognosis between Continuation and Discontinuation of A 5-Month Cardiac Rehabilitation Program in Outpatients with Heart Failure with Preserved Ejection Fraction
Authors: Morita Hidetaka , Suematsu Yasunori , Morita Kai , Yano Yuiko , Sakamoto Maaya , Matsuda Takuro , Kaino Kouji , Teshima Reiko , Ura Nobuyuki , Fujita Masaomi , Tazawa Rie , Nakagawa Hironari , Kitajima Ken , Kamada Satoshi , Fujimi Kanta , Miura Shin-ichiro
Published: July 2021

Background: Cardiac rehabilitation (CR) is a requisite component of care for patients with heart failure (HF). We aimed to evaluate the clinical outcomes in outpatients with HF with preserved ejection fraction (HFpEF) compared to those in patients with non-HFpEF who did and did not continue a 5-month CR program. Methods: 173 outpatients with HF who participated in a 5-month CR program were registered. We divided them into two groups: HFpEF (n = 84, EF 63 ± 7%) and non-HFpEF (n = 89, EF 31 ± 11%). We further divided the patients into those who continued the CR program (continued group) and those who did not (discontinued group) in the HFpEF and non-HFpEF groups. The clinical outcomes at 5 months were compared among the groups. Results: There were no significant differences in patient characteristics at baseline between the continued and discontinued groups in the HFpEF and non-HFpEF groups except for % diabetes mellitus in the non-HFpEF group. The rates of all-cause death and hospital admissions in the continued group in both the HFpEF and non-HFpEF groups were significantly lower than those in the discontinued group. The all-cause death and hospital admissions in each group were independently associated with the continuation of the CR program. Conclusions: The continuation of a 5-month CR program was associated with the prevention of all-cause death and hospital admissions in both the HFpEF and non-HFpEF groups.
Implementation of Power-Efficient Class AB Miller Amplifiers Using Resistive Local Common-Mode Feedback
Authors: Paul Anindita , Renteria-Pinon Mario , Ramirez-Angulo Jaime , Bolaños-Pérez Ricardo , Vázquez-Leal Héctor , Huerta-Chua Jesús , Diaz-Sánchez Alejandro
Published: July 2021

An approach to implement single-ended power-efficient static class-AB Miller op-amps with symmetrical and significantly enhanced slew-rate and accurately controlled output quiescent current is introduced. The proposed op-amp can drive a wide range of resistive and capacitive loads. The output positive and negative currents can be much higher than the total op-amp quiescent current. The enhanced performance is achieved by utilizing a simple low-power auxiliary amplifier with resistive local common-mode feedback that increases the quiescent power dissipation by less than 10%. The proposed class AB op-amp is characterized by significantly enhanced large-signal dynamic, static current efficiency, and small-signal figures of merits. The dynamic current efficiency is 15.6 higher, the static current efficiency is 10.6 times higher, and the small-signal figure of merit is 2.3 times higher than the conventional class-A op-amp. A global figure of merit that determines an op-amp’s ultimate speed is 6.33 times higher than the conventional class A op-amp.
An Improved Background Normalization Algorithm for Noise Resilience in Low Frequency
Authors: Zhu Jiahua , Peng Chengyan , Zhang Bingbing , Jia Wentao , Xu Guojun , Wu Yanqun , Hu Zhengliang , Zhu Min
Published: July 2021

Background normalization algorithms attempt to suppress the ambient and self-noise during the measurements of sonar, which enhance the detection performance and the display effect of weak signals. Conventional background normalization methods are usually sensitive to the accuracy of prior set filtering interval and threshold, while significant noise is still detected in low frequency. In this paper, an improved background normalization algorithm is proposed by thresholding the processing interval between several local peak values and local valley values. Compared to the existing scenarios, the proposed approach automatically calculates the filtering interval and threshold, with substantial resilience to the noise level in low frequency. Experimental results illustrate the effectiveness of our algorithm.
Identification and Prediction of Ship Maneuvering Motion Based on a Gaussian Process with Uncertainty Propagation
Authors: Xue Yifan , Liu Yanjun , Xue Gang , Chen Gang
Published: July 2021

Maritime transport plays a vital role in economic development. To establish a vessel scheduling model, accurate ship maneuvering models should be used to optimize the strategy and maximize the economic benefits. The use of nonparametric modeling techniques to identify ship maneuvering systems has attracted considerable attention. The Gaussian process has high precision and strong generalization ability in fitting nonlinear functions and requires less training data, which is suitable for ship dynamic model identification. Compared with other machine learning methods, the most obvious advantage of the Gaussian process is that it can provide the uncertainty of prediction. However, most studies on ship modeling and prediction do not consider the uncertainty propagation in Gaussian processes. In this paper, a moment-matching-based approach is applied to address the problem. The proposed identification scheme for ship maneuvering systems is verified by container ship simulation data and experimental data from the Workshop on Verification and Validation of Ship Maneuvering Simulation Methods (SIMMAN) database. The results indicate that the identified model is accurate and shows good generalization performance. The uncertainty of ship motion prediction is well considered based on the uncertainty propagation technology.
A Multi-AUV Path Planning System Based on the Omni-Directional Sensing Ability
Authors: Ru Jingyu , Yu Shuangjiang , Wu Hao , Li Yuhan , Wu Chengdong , Jia Zixi , Xu Hongli
Published: July 2021

Following the development of autonomous underwater vehicles (AUVs), multiple trajectory-based submarine target information collection constitutes one of the key technologies that significantly influence underwater information collection ability and deployment efficiency. In this paper, we propose an underwater information collection AUV, O-AUV, that can perceive the omnidirectional area and could detect a larger area than the traditional AUV. A 3D sensing model for the O-AUV is proposed to describe the complex underwater information collection spaces. Thereafter, a cube-based environment model involving candidate observation point calculation methods are suggested to adapt the O-AUV model. A voyage cost map is also built according to the multi-AUV path planning for a common submarine mission that must traverse numerous mission targets in complex environments through the R-Dijkstra algorithm. Specifically, the voyage planning problem is solved through a critical algorithm called ANSGA (accelerated NSGA-II algorithm), which in turn, is developed by modifying the non-dominated sorting genetic algorithm (NSGA-II) to accelerate the optimization rate for the Pareto solution. Experiments are carried out in MATLAB, and the results verify the validity of the proposed O-AUV+ANSGA algorithm framework.
Optimization of the Equivalent Source Configuration for the Equivalent Source Method
Authors: Zhang Lanyue , Wang Jia , Yang Desen , Hu Bo , Wu Di
Published: July 2021

The equivalent source method is widely applied to study structural acoustic radiation in an underwater environment. However, there is still uncertainty in arranging the equivalent source, and the current mainstream configuration method needs a large number of equivalent sources, limiting its practical applicability. In this paper, an equivalent source configuration method that is simple, effective, and easy to implement, and which based on a tradeoff between the ill condition of the transfer matrix and the adequacy of the simulated structure’s radiated sound field, is proposed. The optimization method can derive the appropriate positions and quantity of monopole equivalent sources simultaneously. The method does not yield an optimal solution in a strict mathematical sense but provides satisfactory results compared with those obtained by uniformly distributed equivalent sources. Numerical simulation results showed that the optimization method derives accurate sound field calculation results with a relatively small number of equivalent sources, significantly reducing the number of subsequent calculations needed. Finally, the experiments conducted with a cylindrical shell structure verified the validity and practicality of the proposed method.