bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Significance of Timing of Intubation in Critically Ill Patients with COVID-19: A Multi-Center Retrospective Study
Authors: Lee Yong Hoon , Choi Keum-Ju , Choi Sun Ha , Lee Shin Yup , Kim Kyung Chan , Kim Eun Jin , Lee Jaehee
Published: September 2020

The effect of intubation timing on the prognosis of critically ill patients with coronavirus 2019 (COVID-19) is not yet well understood. We investigated whether early intubation is associated with the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS). This multicenter, retrospective, observational study was done on 47 adult COVID-19 patients with ARDS who were admitted to the intensive care unit (ICU) in Daegu, Korea between February 17 and April 23, 2020. Clinical characteristics and in-hospital mortality were compared between the early intubation and initially non-intubated groups, and between the early and late intubation groups, respectively. Of the 47 patients studied, 23 (48.9%) were intubated on the day of meeting ARDS criteria (early intubation), while 24 (51.1%) were not initially intubated. Eight patients were never intubated during the in-hospital course. Median follow-up duration was 46 days, and 21 patients (44.7%) died in the hospital. No significant difference in in-hospital mortality rate was noted between the early group and initially non-intubated groups (56.5% vs. 33.3%, p = 0.110). Furthermore, the risk of in-hospital death in the early intubation group was not significantly different compared to the initially non-intubated group on multivariate adjusted analysis (p = 0.385). Results were similar between early and late intubation in the subgroup analysis of 39 patients treated with mechanical ventilation. In conclusion, in this study of critically ill COVID-19 patients with ARDS, early intubation was not associated with improved survival. This result may help in the efficient allocation of limited medical resources, such as ventilators.
Machine Tool Component Health Identification with Unsupervised Learning
Authors: Gittler Thomas , Scholze Stephan , Rupenyan Alisa , Wegener Konrad
Published: September 2020

Unforeseen machine tool component failures cause considerable losses. This study presents a new approach to unsupervised machine component condition identification. It uses test cycle data of machine components in healthy and various faulty conditions for modelling. The novelty in the approach consists of the time series representation as features, the filtering of the features for statistical significance, and the use of this feature representation to train a clustering model. The benefit in the proposed approach is its small engineering effort, the potential for automation, the small amount of data necessary for training and updating the model, and the potential to distinguish between multiple known and unknown conditions. Online measurements on machines in unknown conditions are performed to predict the component condition with the aid of the trained model. The approach was exemplarily tested and verified on different healthy and faulty states of a grinding machine axis. For the accurate classification of the component condition, different clustering algorithms were evaluated and compared. The proposed solution demonstrated encouraging results as it accurately classified the component condition. It requires little data, is straightforward to implement and update, and is able to precisely differentiate minor differences of faults in test cycle time series.
Remotely-Sensed Surface Temperature and Vegetation Status for the Assessment of Decadal Change in the Irrigated Land Cover of North-Central Victoria, Australia
Authors: Abuzar Mohammad , McAllister Andy , Whitfield Des , Sheffield Kathryn
Published: September 2020

Monitoring of irrigated land cover is important for both resource managers and farmers. An operational approach is presented to use the satellite-derived surface temperature and vegetation cover in order to distinguish between irrigated and non-irrigated land. Using an iterative thresholding procedure to minimize within-class variance, the bilevel segmentation of surface temperature and vegetation cover was achieved for each irrigation period (Spring, Summer and Autumn). The three periodic profiles were used to define irrigation land covers from 2008–2009 to 2018–2019 in a key agricultural region of Australia. The overall accuracy of identifying farms with irrigated land cover amounted to 95.7%. Total irrigated land cover was the lowest (approximately 200,000 ha) in the 2008–2009 crop year which increased more than three-fold in 2012–2013, followed by a gradual decline in the following years. Satellite images from Landsat series (L-5, L-7 and L-8), Sentinel-2 and ASTER were found suitable for land cover classification, which is scalable from farm to regional levels. For this reason, the results are desirable for a range of stakeholders.
Protected Area Governance and Its Influence on Local Perceptions, Attitudes and Collaboration
Authors: Ayivor Jesse Sey , Nyametso Johnie Kodjo , Ayivor Sandra
Published: September 2020

Globally, protected areas are faced with a myriad of threats emanating principally from anthropogenic drivers, which underpins the importance of the human element in protected area management. Delving into the “exclusive” and “inclusive” approaches to nature conservation discourse, this study explored the extent to which local communities collaborate in the management of protected areas and how the governance regime of these areas influences local perceptions and attitudes. Data for the study were collected through stakeholder interviews, focus group discussions as well as a probe into participating groups’ collective perceptions and opinions on certain key issues. A total of 51 focus group discussions were held in 45 communities involving 630 participants. The analysis was done using qualitative methods and simple case counts to explain levels of acceptance or dislike of issues. The results showed that the objectives of state-managed protected areas, by their nature, tend to exclude humans and negatively influence local perceptions and attitudes. This, in addition to human-wildlife conflicts and high handedness by officials on protected area offenders, affects community collaboration. The study concluded that for protected area management to be effective, effort must be made to positively influence local perceptions and attitudes by promoting “win-win-win” partnerships among all stakeholders.
The Impact of Urbanization on Farmland Productivity: Implications for China’s Requisition–Compensation Balance of Farmland Policy
Authors: Deng Zhongqi , Zhao Qianyu , Bao Helen X. H.
Published: September 2020

The rapid growth of China’s economy since the reform in 1978 should be largely attributed to urbanization. Nonetheless, in terms of farmland productivity, urbanization may lead to perverse incentives and thus threaten food security. On the one hand, the requisition–compensation balance of farmland (RCBF) policy could reduce farmland productivity because of a “superior occupation and inferior compensation”; on the other hand, urbanization promotes the transfer of the younger labor force and thus reduces the productivity of the agricultural labor force. To investigate the undesirable effects, based on some stylized facts, this study selects 29,415 county-level samples in a Chinese county from 2000–2014 to construct an empirical model. With a new stochastic frontier analysis method that eliminates the classical econometric issues of endogeneity and heterogeneity, the empirical results show that there is a U-shaped relationship between the farmland use efficiency (productivity) and urbanization rate, indicating that only when the urbanization rate is relatively low would urbanization decrease the farmland use efficiency; in contrast, when the urbanization rate is relatively high, technical progress would obviously be accompanied by urbanization, and thus, the undesirable effects are fully offset. Furthermore, the U-shaped relationship is robust after considering the endogeneity of the urbanization rate and total-factor farmland use efficiency. With these findings, recommendations to implement sustainable management and conservation policies regarding farmland resources are made.
Analytical Elastostatic Contact Mechanics of Highly-Loaded Contacts of Varying Conformity
Authors: Johns-Rahnejat Patricia M. , Dolatabadi Nader , Rahnejat Homer
Published: September 2020

In applications requiring high load carrying capacity, conforming contacting pairs with a relatively large contact footprint are used. These include circular arc, Novikov, and Wildhaber gears found, for example, in helicopter rotors. Closely conforming contacts also occur in many natural endo-articular joints, such as hips, or their replacement arthroplasty. The main determining factors in contact fatigue are the sub-surface shear stresses. For highly loaded contacts, classical Hertzian contact mechanics is used for many gears, bearings, and joints. However, the theory is essentially for concentrated counterforming contacts, where the problem is reduced to a rigid ellipsoidal solid penetrating an equivalent semi-infinite elastic half-space. Applicability is limited though, and the theory is often used inappropriately for contacts of varying degrees of conformity. This paper presents a generic contact mechanics approach for the determination of sub-surface stresses, which is applicable to both highly conforming as well as concentrated counterforming contacts. It is shown that sub-surface shear stresses alter in magnitude and disposition according to contact conformity, and lead to the different modes of fatigue failure noted in practice.
Impact of the Carbon Nanofillers Addition on Rheology and Absorption Ability of Composite Shear Thickening Fluids
Authors: Nakonieczna-Dąbrowska Paulina , Wróblewski Rafał , Płocińska Magdalena , Leonowicz Marcin
Published: September 2020

Synthesis and characterization of composite shear thickening fluids (STFs) containing carbon nanofillers are presented. Shear thickening fluids have attracted particular scientific and technological interest due to their unique ability to abruptly increase viscosity in the case of a sudden impact. The fluids have been developed as a potential component of products with high energy absorbing efficiency. This study reports on the rheological behavior, stability, and microstructure of the STFs modified with the following carbon nanofillers: multi-walled carbon nanotubes, reduced graphene oxide, graphene oxide, and carbon black. In the current experiment, the basic STF was made as a suspension of silica particles with a diameter of 500 nm in polypropylene glycol and with a molar mass of 2000 g/mol. The STF was modified with carbon nanofillers in the following proportions: 0.05, 0.15, and 0.25 vol.%. The addition of the carbon nanofillers modified the rheological behavior and impact absorption ability; for the STF containing 0.25 vol.% of carbon nanotubes, an increase of force absorption up to 12% was observed.
Analysis of the Open Die Forging Process of the AZ91 Magnesium Alloy
Authors: Banaszek Grzegorz , Bajor Teresa , Kawałek Anna , Garstka Tomasz
Published: September 2020

The paper presents the results of numerical modelling of the forging process of magnesium alloy ingots on a hydraulic press with the use of flat and shaped anvils. The use of shaped (rhombic-trapezoid) anvils will affect the uniform distribution of temperature and strain intensity in the entire volume of the forging, causing a number of forging passes, which in consequence will reduce the costs of the blank manufacturing process. However, higher values of the strain intensity were obtained during the deformation of the material in flat anvils. The purpose of the research was to propose assumptions for forging technology of producing a blank from AZ91 alloy with the use of flat and shaped anvils. Numerical examination for AZ91 magnesium alloy was carried out using the Forge®NxT commercial software. The rheological properties of the investigated alloy were determined on the basis of uniaxial compression tests carried out in the Gleeble 3800 metallurgical simulation system. The numerical analysis of the process of forging AZ91 alloy ingots on a press was conducted in the temperature range of 200–400 °C and at several forging passes.
Whey Protein Concentrate/Isolate Biofunctional Films Modified with Melanin from Watermelon (Citrullus lanatus) Seeds
Authors: Łopusiewicz Łukasz , Drozłowska Emilia , Trocer Paulina , Kostek Mateusz , Śliwiński Mariusz , Henriques Marta H. F. , Bartkowiak Artur , Sobolewski Peter
Published: September 2020

Valorization of food industry waste and plant residues represents an attractive path towards obtaining biodegradable materials and achieving “zero waste” goals. Here, melanin was isolated from watermelon (Citrullus lanatus) seeds and used as a modifier for whey protein concentrate and isolate films (WPC and WPI) at two concentrations (0.1% and 0.5%). The modification with melanin enhanced the ultraviolet (UV) blocking, water vapor barrier, swelling, and mechanical properties of the WPC/WPI films, in addition to affecting the apparent color. The modified WPC/WPI films also exhibited high antioxidant activity, but no cytotoxicity. Overall, the effects were melanin concentration-dependent. Thus, melanin from watermelon seeds can be used as a functional modifier to develop bioactive biopolymer films with good potential to be exploited in food packaging and biomedical applications.
Fatigue Prediction of Aluminum Alloys Considering Critical Plane Orientation under Complex Stress States
Authors: Kurek Marta
Published: September 2020

This publication is intended to present a new way of estimating the fatigue life of various construction materials. Carpinteri’s proposal was modified by replacing the fatigue limits ratio with the value of the normal to shear stress ratio for a given number of cycles. In this study, the proposed criterion and calculation model was verified for the selected group of aluminium alloys. The purpose of the analysis of the experimental studies was to check the effectiveness of the proposed method of estimating fatigue life under the applied bending and torsional load conditions. The results of the fatigue calculations are presented in graphical form by means of diagrams showing the comparison of design and experimental strength. Before fatigue life was calculated, the critical plane orientation according to Carpinteri’s model and the proposed model were determined. After analyzing the results of the comparison of design and experimental durability, it can be stated that the proposed fatigue life estimation algorithm gives satisfactory results for multiaxial cyclic loads.
Using Inverse Reinforcement Learning with Real Trajectories to Get More Trustworthy Pedestrian Simulations
Authors: Martinez-Gil Francisco , Lozano Miguel , García-Fernández Ignacio , Romero Pau , Serra Dolors , Sebastián Rafael
Published: September 2020

Reinforcement learning is one of the most promising machine learning techniques to get intelligent behaviors for embodied agents in simulations. The output of the classic Temporal Difference family of Reinforcement Learning algorithms adopts the form of a value function expressed as a numeric table or a function approximator. The learned behavior is then derived using a greedy policy with respect to this value function. Nevertheless, sometimes the learned policy does not meet expectations, and the task of authoring is difficult and unsafe because the modification of one value or parameter in the learned value function has unpredictable consequences in the space of the policies it represents. This invalidates direct manipulation of the learned value function as a method to modify the derived behaviors. In this paper, we propose the use of Inverse Reinforcement Learning to incorporate real behavior traces in the learning process to shape the learned behaviors, thus increasing their trustworthiness (in terms of conformance to reality). To do so, we adapt the Inverse Reinforcement Learning framework to the navigation problem domain. Specifically, we use Soft Q-learning, an algorithm based on the maximum causal entropy principle, with MARL-Ped (a Reinforcement Learning-based pedestrian simulator) to include information from trajectories of real pedestrians in the process of learning how to navigate inside a virtual 3D space that represents the real environment. A comparison with the behaviors learned using a Reinforcement Learning classic algorithm (Sarsa(λ)) shows that the Inverse Reinforcement Learning behaviors adjust significantly better to the real trajectories.
Comparison of Ensemble Machine Learning Methods for Automated Classification of Focal and Non-Focal Epileptic EEG Signals
Authors: Jukic Samed , Saracevic Muzafer , Subasi Abdulhamit , Kevric Jasmin
Published: September 2020

This research presents the epileptic focus region localization during epileptic seizures by applying different signal processing and ensemble machine learning techniques in intracranial recordings of electroencephalogram (EEG). Multi-scale Principal Component Analysis (MSPCA) is used for denoising EEG signals and the autoregressive (AR) algorithm will extract useful features from the EEG signal. The performances of the ensemble machine learning methods are measured with accuracy, F-measure, and the area under the receiver operating characteristic (ROC) curve (AUC). EEG-based focus area localization with the proposed methods reaches 98.9% accuracy using the Rotation Forest classifier. Therefore, our results suggest that ensemble machine learning methods can be applied to differentiate the EEG signals from epileptogenic brain areas and signals recorded from non-epileptogenic brain regions with high accuracy.
Efficient Methods for Parameter Estimation of Ordinary and Partial Differential Equation Models of Viral Hepatitis Kinetics
Authors: Churkin Alexander , Lewkiewicz Stephanie , Reinharz Vladimir , Dahari Harel , Barash Danny
Published: September 2020

Parameter estimation in mathematical models that are based on differential equations is known to be of fundamental importance. For sophisticated models such as age-structured models that simulate biological agents, parameter estimation that addresses all cases of data points available presents a formidable challenge and efficiency considerations need to be employed in order for the method to become practical. In the case of age-structured models of viral hepatitis dynamics under antiviral treatment that deal with partial differential equations, a fully numerical parameter estimation method was developed that does not require an analytical approximation of the solution to the multiscale model equations, avoiding the necessity to derive the long-term approximation for each model. However, the method is considerably slow because of precision problems in estimating derivatives with respect to the parameters near their boundary values, making it almost impractical for general use. In order to overcome this limitation, two steps have been taken that significantly reduce the running time by orders of magnitude and thereby lead to a practical method. First, constrained optimization is used, letting the user add constraints relating to the boundary values of each parameter before the method is executed. Second, optimization is performed by derivative-free methods, eliminating the need to evaluate expensive numerical derivative approximations. The newly efficient methods that were developed as a result of the above approach are described for hepatitis C virus kinetic models during antiviral therapy. Illustrations are provided using a user-friendly simulator that incorporates the efficient methods for both the ordinary and partial differential equation models.
Micellar-Enhanced Ultrafiltration Using a Plant-Derived Surfactant for Dye Separation in Wastewater Treatment
Authors: Aryanti Nita , Nafiunisa Aininu , Kusworo Tutuk Djoko , Wardhani Dyah Hesti
Published: September 2020

Micellar-enhanced ultrafiltration (MEUF) is one of several membrane methods used for the removal of trace organic pollutants from aqueous streams. In this process, a surfactant is added to a polluted aqueous solution at a concentration higher than its critical micelle concentration (CMC). Unlike synthetic surfactants, natural surfactants, from plants such as the saponin, while ecologically adaptable as surfactants in MEUF systems, are also biodegradable, renewable, and environmentally safe. This study applied Sapindus rarak extract as the natural surfactant in MEUF for Remazol dye separation. It was found that the presence of Sapindus rarak extract increased separation of Remazol red and blue dyes by up to 97.02% and 99.42%, respectively. However, the addition of surfactant decreased permeate fluxes due to membrane fouling and concentration polarization. In addition, loading micelle (Lm), representing the performance of the surfactant micelle for dye separation, as well as the blocking mechanism, was investigated. Lm was found to be in the range of 0.002–0.068 mM dyes/mM saponin. Ultrafiltration blocking mechanisms, as confirmed by the Hermia model, were: standard blocking, for cases without the addition of surfactant; cake formation, for cases with surfactant below the CMC; and complete blocking, for cases with surfactant above the CMC.
Electrodialytic Processes: Market Overview, Membrane Phenomena, Recent Developments and Sustainable Strategies
Authors: Bazinet Laurent , Geoffroy Thibaud R.
Published: September 2020

In the context of preserving and improving human health, electrodialytic processes are very promising perspectives. Indeed, they allow the treatment of water, preservation of food products, production of bioactive compounds, extraction of organic acids, and recovery of energy from natural and wastewaters without major environmental impact. Hence, the aim of the present review is to give a global portrait of the most recent developments in electrodialytic membrane phenomena and their uses in sustainable strategies. It has appeared that new knowledge on pulsed electric fields, electroconvective vortices, overlimiting conditions and reversal modes as well as recent demonstrations of their applications are currently boosting the interest for electrodialytic processes. However, the hurdles are still high when dealing with scale-ups and real-life conditions. Furthermore, looking at the recent research trends, potable water and wastewater treatment as well as the production of value-added bioactive products in a circular economy will probably be the main applications to be developed and improved. All these processes, taking into account their principles and specificities, can be used for specific eco-efficient applications. However, to prove the sustainability of such process strategies, more life cycle assessments will be necessary to convince people of the merits of coupling these technologies.
Study on the Effect of Powder-Bed Fusion Process Parameters on the Quality of as-Built IN718 Parts Using Response Surface Methodology
Authors: Ravichander Bharath Bhushan , Amerinatanzi Amirhesam , Shayesteh Moghaddam Narges
Published: September 2020

Inconel 718 (IN718) is a nickel-based superalloy which is widely used in aerospace, oil, and gas industries due to its outstanding mechanical properties at high temperatures, corrosion, fatigue resistance, and excellent weldability. Selective laser melting (SLM), one of the most used powder-bed based methods, is being extensively used to fabricate functional IN718 components with high accuracy. The accuracy and the properties of the SLM fabricated IN718 parts highly depend on the process parameters employed during fabrication. Thus, depending on the desired properties, the process parameters for a given material need to be optimized for improving the overall reliability of the SLM devices. In this study, design of experiment (DOE) was used to evaluate the dimensional accuracy, composition, and hardness corresponding to the interaction between the SLM process parameters such as laser power (P), scan speed (v), and hatch spacing (h). Contour plots were generated by co-relating the determined values for each characteristic and the process parameters to improve the as-built characteristics of the fabricated IN718 parts and reduce the post-processing time. The outcome of this study shows a range of energy density values for the IN718 superalloy needed to attain optimal values for each of the analyzed characteristics. Finally, an optimal processing region for SLM IN718 fabrication was identified which is in accordance with the values for each characteristic mentioned in literature.
Effects of Thermal Simulation on the Creep Fracture of the Mod. 9Cr-1Mo Weld Metal
Authors: Liao Chien-Chun , Wang Chu-Chun , Chen Tai-Cheng , Shiue Ren-Kae , Tsay Leu-Wen
Published: September 2020

The effects of thermal simulation on the short-term creep fracture of modified 91 (mod. 91) weld metal (WM) were evaluated at elevated temperature. The reheated zones in the WM during multiple passes were simulated by an infrared heater. The simulated WM specimens after post-weld tempering at 1023 K/2 h were loaded with dead weight either at 903 K/120 MPa or 933 K/80 MPa. In this work, the simulated WM specimens after tempering were loaded either at 903 and 933 K during the tests. The loss in creep lives of various specimens at elevated temperature was determined accordingly and further compared with the Gr. 91 steel base metals, which were normalized either at 1213 K or 1333 K and then tempered at 1033 K for 2 h. The coarse, solidified structure of the WM had much better creep resistance than the base metal even that of the base metal normalized at 1333 K. However, the imposed welding thermal cycles would cause a significant decrease in creep resistance of the WM. Creep lives were shortened obviously in the simulated WM samples, especially in the simulated sample that underwent partial transformation. The combination of a fine-grained structure and soft ferrite present in the simulated WM was responsible for their huge decline in creep resistance, as compared with the WM in the as-tempered condition.
An 1H NMR- and MS-Based Study of Metabolites Profiling of Garden Snail Helix aspersa Mucus
Authors: Vassilev Nikolay G. , Simova Svetlana D. , Dangalov Miroslav , Velkova Lyudmila , Atanasov Venceslav , Dolashki Aleksandar , Dolashka Pavlinka
Published: September 2020

Metabolic profiling based on 1H nuclear magnetic resonance (NMR) spectroscopy was applied with the aim to investigate the functional role of the metabolites in lyophilized mucus from the garden snail Helix aspersa. Twenty metabolites were unambiguously identified by 1H, 1D TOCSY, 2D J-resolved, 2D COSY, and 2D HSQC NMR spectra with water suppression. The metabolic profiles of two fractions with low molecular weight (Mw < 1 kDa and Mw < 3 kDa) are very similar. Metabolites with known antioxidant, antibacterial, and antimicrobial activity were detected by NMR metabolic analysis of mucus samples from Helix aspersa. Some of them were confirmed by mass spectrometric analysis. The primary structure of several peptides was identified in low molecular weight fractions (Mw < 1 kDa) by tandem mass spectrometry.
Metabolic Responses to Arsenite Exposure Regulated through Histidine Kinases PhoR and AioS in Agrobacterium tumefaciens 5A
Authors: Rawle Rachel A. , Tokmina-Lukaszewska Monika , Shi Zunji , Kang Yoon-Suk , Tripet Brian P. , Dang Fang , Wang Gejiao , McDermott Timothy R. , Copie Valerie , Bothner Brian
Published: September 2020

Arsenite (AsIII) oxidation is a microbially-catalyzed transformation that directly impacts arsenic toxicity, bioaccumulation, and bioavailability in environmental systems. The genes for AsIII oxidation (aio) encode a periplasmic AsIII sensor AioX, transmembrane histidine kinase AioS, and cognate regulatory partner AioR, which control expression of the AsIII oxidase AioBA. The aio genes are under ultimate control of the phosphate stress response via histidine kinase PhoR. To better understand the cell-wide impacts exerted by these key histidine kinases, we employed 1H nuclear magnetic resonance (1H NMR) and liquid chromatography-coupled mass spectrometry (LC-MS) metabolomics to characterize the metabolic profiles of ΔphoR and ΔaioS mutants of Agrobacterium tumefaciens 5A during AsIII oxidation. The data reveals a smaller group of metabolites impacted by the ΔaioS mutation, including hypoxanthine and various maltose derivatives, while a larger impact is observed for the ΔphoR mutation, influencing betaine, glutamate, and different sugars. The metabolomics data were integrated with previously published transcriptomics analyses to detail pathways perturbed during AsIII oxidation and those modulated by PhoR and/or AioS. The results highlight considerable disruptions in central carbon metabolism in the ΔphoR mutant. These data provide a detailed map of the metabolic impacts of AsIII, PhoR, and/or AioS, and inform current paradigms concerning arsenic–microbe interactions and nutrient cycling in contaminated environments.
Recognition of Candida albicans and Role of Innate Type 17 Immunity in Oral Candidiasis
Authors: Pavlova Anna , Sharafutdinov Irshad
Published: September 2020

Candida albicans is an opportunistic pathogenic fungus considered to be a common member of the human microflora. Similar to some other opportunistic microbes, C. albicans can invade and benefit from its host when the immune status of that host is weakened. Most often this happens to immunocompromised individuals, leading to the infection of oral and vaginal mucosae or the systemic spread of the pathogen throughout the entire body. Oropharyngeal candidiasis (OPC) occurs in up to 90 percent of patients with acquired immunodeficiency syndrome (AIDS), making it the most frequent opportunistic infection for this group. Upon first signs of fungal invasion, a range of host signaling activates in order to eliminate the threat. Epithelial and myeloid type cells detect C. albicans mainly through receptor tyrosine kinases and pattern-recognition receptors. This review provides an overview of downstream signaling resulting in an adequate immune response through the activation of various transcription factors. The study discusses recent advances in research of the interleukin-17 (IL-17) producing innate cells, including natural T helper 17 (nTh17) cells, γδ T cells, invariant natural killer T (iNKT) cells and type 3 innate lymphoid cells (ILC3) that are involved in response to oral C. albicans infections.
Influence of Microbial Transglutaminase on Physicochemical and Cross-Linking Characteristics of Individual Caseins
Authors: Chen Chun-Chi , Chen Liang-Yu , Chan Der-Sheng , Chen Bang-Yuan , Tseng Hsien-Wei , Hsieh Jung-Feng
Published: September 2020

The effects of microbial transglutaminase (MTGase) cross-linking on the physicochemical characteristics of individual caseins were investigated. MTGase was used to modify three major individual caseins, namely, κ-casein (κ-CN), αS-casein (αS-CN) and β-casein (β-CN). The SDS-PAGE analysis revealed that MTGase-induced cross-linking occurred during the reaction and that some components with high molecular weights (>130 kDa) were formed from the individual proteins κ-CN, αS-CN and β-CN. Scanning electron microscopy (SEM) and particle size analysis respectively demonstrated that the κ-CN, αS-CN and β-CN particle diameters and protein microstructures were larger and polymerized after MTGase cross-linking. The polymerized κ-CN (~749.9 nm) was smaller than that of β-CN (~7909.3 nm) and αS-CN (~7909.3 nm). The enzyme kinetics results showed KM values of 3.04 × 10−6, 2.37 × 10−4 and 8.90 × 10−3 M for κ-CN, αS-CN and β-CN, respectively, and, furthermore, kcat values of 5.17 × 10−4, 1.92 × 10−3 and 4.76 × 10−2 1/s, for κ-CN, αS-CN and β-CN, respectively. Our results revealed that the cross-linking of β-CN catalyzed by MTGase was faster than that of αS-CN or κ-CN. Overall, the polymers that formed in the individual caseins in the presence of MTGase presented a higher molecular weight and larger particles.
Palladium (II)–Salan Complexes as Catalysts for Suzuki–Miyaura C–C Cross-Coupling in Water and Air. Effect of the Various Bridging Units within the Diamine Moieties on the Catalytic Performance
Authors: Bunda Szilvia , Voronova Krisztina , Kathó Ágnes , Udvardy Antal , Joó Ferenc
Published: September 2020

Water-soluble salan ligands were synthesized by hydrogenation and subsequent sulfonation of salens (N,N’-bis(slicylidene)ethylenediamine and analogues) with various bridging units (linkers) connecting the nitrogen atoms. Pd (II) complexes were obtained in reactions of sulfosalans and [PdCl4]2−. Characterization of the ligands and complexes included extensive X-ray diffraction studies, too. The Pd (II) complexes proved highly active catalysts of the Suzuki–Miyaura reaction of aryl halides and arylboronic acid derivatives at 80 °C in water and air. A comparative study of the Pd (II)–sulfosalan catalysts showed that the catalytic activity largely increased with increasing linker length and with increasing steric congestion around the N donor atoms of the ligands; the highest specific activity was 40,000 (mol substrate) (mol catalyst × h)−1. The substrate scope was explored with the use of the two most active catalysts, containing 1,4-butylene and 1,2-diphenylethylene linkers, respectively.
Wheat Bran Extract Regulates Mast Cell-Mediated Allergic Responses In Vitro and In Vivo
Authors: Lee Jae Yeon , Ahn Eun-Kyung , Park Ju-Hyoung , Oh Joa Sub
Published: September 2020

In the present study the effects and molecular mechanisms of wheat bran (WB), the hard outer layer of the wheat kernel used in food ingredients, on mast cell-mediated allergic responses in vitro and in vivo were investigated. The water extract of WB inhibited degranulation and expression of allergic and inflammatory mediators such as tumor necrosis factor-α, cyclooxygenase-2 and inducible nitric oxide synthase in antigen-stimulated RBL-2H3 cells. These anti-allergic activities of WB were mediated by the inactivation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, which play important roles in degranulation and expression of various allergic and inflammatory molecules. In agreement with its in vitro effects, WB inhibited immunoglobulin E (IgE)/antigen-induced and compound 48/80-induced anaphylactic reactions in vivo. Taken together, these findings suggest the pharmacological potential of WB in the regulation of allergic diseases, including allergic rhinitis, atopic dermatitis, asthma and anaphylaxis.
Alginate-, Carboxymethyl Cellulose-, and κ-Carrageenan-Based Microparticles as Storage Vehicles for Cranberry Extract
Authors: Tsirigotis-Maniecka Marta
Published: September 2020

This study discusses the relationship between the structural properties of the selected polysaccharides (low (ALGLV) and medium viscosity (ALGMV) sodium alginate, 90 kDa (CMC90) and 250 kDa (CMC250) carboxymethyl cellulose, and κ-carrageenan (CARκ)) and their abilities to serve as protective materials of encapsulated large cranberry (Vaccinium macrocarpon Aiton) fruit extract (CE) from losing its health beneficial activities during long-term storage. The microparticles were characterized in terms of their encapsulation efficiency (UV-Vis and FTIR), morphology (SEM) and the physical stability in various environments (gravimetry). The microparticles’ size and encapsulation efficiency were 46–50 µm and 28–58%, respectively, and the microparticles were physically stable. CMC90 and ALGMV most efficiently protected the plant extract from losing its biological activity after 18 months, while the plant extract stored outside the particles had lost its activity. CE was intended for oral administration, thus CE release from the microparticles was monitored in vitro under gastrointestinal conditions. In vitro gastrointestinal release studies revealed that the ALGMV-, CMC90-, and CMC250-based particles exhibited the desired intestinal release pattern. This result supports the suitability of sodium alginate and carboxymethyl cellulose for the safe delivery of CE to the intestines while maintaining its biological properties and improving long-term storage stability.
Phenylalanine Stereoisomers of CJ-15,208 and [d-Trp]CJ-15,208 Exhibit Distinctly Different Opioid Activity Profiles
Authors: Brice-Tutt Ariana C. , Senadheera Sanjeewa N. , Ganno Michelle L. , Eans Shainnel O. , Khaliq Tanvir , Murray Thomas F. , McLaughlin Jay P. , Aldrich Jane V.
Published: September 2020

The macrocyclic tetrapeptide cyclo[Phe-d-Pro-Phe-Trp] (CJ-15,208) and its stereoisomer cyclo[Phe-d-Pro-Phe-d-Trp] exhibit different opioid activity profiles in vivo. The present study evaluated the influence of the Phe residues’ stereochemistry on the peptides’ opioid activity. Five stereoisomers were synthesized by a combination of solid-phase peptide synthesis and cyclization in solution. The analogs were evaluated in vitro for opioid receptor affinity in radioligand competition binding assays, and for opioid activity and selectivity in vivo in the mouse 55 °C warm-water tail-withdrawal assay. Potential liabilities of locomotor impairment, respiratory depression, acute tolerance development, and place conditioning were also assessed in vivo. All of the stereoisomers exhibited antinociception following either intracerebroventricular or oral administration differentially mediated by multiple opioid receptors, with kappa opioid receptor (KOR) activity contributing for all of the peptides. However, unlike the parent peptides, KOR antagonism was exhibited by only one stereoisomer, while another isomer produced DOR antagonism. The stereoisomers of CJ-15,208 lacked significant respiratory effects, while the [d-Trp]CJ-15,208 stereoisomers did not elicit antinociceptive tolerance. Two isomers, cyclo[d-Phe-d-Pro-d-Phe-Trp] (3) and cyclo[Phe-d-Pro-d-Phe-d-Trp] (5), did not elicit either preference or aversion in a conditioned place preference assay. Collectively, these stereoisomers represent new lead compounds for further investigation in the development of safer opioid analgesics.
Milk Authentication: Stable Isotope Composition of Hydrogen and Oxygen in Milks and Their Constituents
Authors: Hamzić Gregorčič Staša , Potočnik Doris , Camin Federica , Ogrinc Nives
Published: September 2020

This paper summarises the isotopic characteristics, i.e., oxygen and hydrogen isotopes, of Slovenian milk and its major constituents: water, casein, and lactose. In parallel, the stable oxygen isotope ratios of cow, sheep, and goat’s milk were compared. Oxygen stable isotope ratios in milk water show seasonal variability and are also 18O enriched in relation to animal drinking water. The δ18Owater values were higher in sheep and goat’s milk when compared to cow milk, reflecting the isotopic composition of drinking water source and the effect of differences in the animal’s thermoregulatory physiologies. The relationship between δ18Omilk and δ18Olactose is an indication that even at lower amounts (>7%) of added water to milk can be determined. This procedure once validated on an international scale could become a reference method for the determination of milk adulteration with water.
Identification and Quantification of a Phytotoxic Metabolite from Alternaria dauci
Authors: Leyte-Lugo Martha , Richomme Pascal , Poupard Pascal , Peña-Rodriguez Luis M.
Published: September 2020

Alternaria dauci is the causal agent of Alternaria leaf blight (ALB) in carrot (Daucus carota) crops around the world. However, to date, A. dauci has received limited attention in its production of phytotoxic metabolites. In this investigation, the bioassay-guided isolation of the extract from liquid cultures of A. dauci resulted in the isolation of two metabolites identified as α-acetylorcinol (1) and p-hydroxybenzoic acid (2), based on their spectroscopic data and results from chemical correlation reactions. Testing of both metabolites in different assays showed an important phytotoxic activity for p-hydroxybenzoic acid (2) when tested in the leaf-spot assay on parsley (Petroselinum crispum), in the leaf infiltration assay on tobacco (Nicotiana alata) and marigold (Tagetes erecta), and in the immersion assay on parsley and parsnip (Pastinaca sativa) leaves. Quantification of the two metabolites in the crude extract of A. dauci kept at different times showed that p-hydroxybenzoic acid (2) is one of the first metabolites to be synthesized by the pathogen, suggesting that this salicylic acid derivative could play an important role in the pathogenicity of the fungus.
Memantine Derivatives as Multitarget Agents in Alzheimer’s Disease
Authors: Marotta Giambattista , Basagni Filippo , Rosini Michela , Minarini Anna
Published: September 2020

Memantine (3,5-dimethyladamantan-1-amine) is an orally active, noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist approved for treatment of moderate-to-severe Alzheimer’s disease (AD), a neurodegenerative condition characterized by a progressive cognitive decline. Unfortunately, memantine as well as the other class of drugs licensed for AD treatment acting as acetylcholinesterase inhibitors (AChEIs), provide only symptomatic relief. Thus, the urgent need in AD drug development is for disease-modifying therapies that may require approaching targets from more than one path at once or multiple targets simultaneously. Indeed, increasing evidence suggests that the modulation of a single neurotransmitter system represents a reductive approach to face the complexity of AD. Memantine is viewed as a privileged NMDAR-directed structure, and therefore, represents the driving motif in the design of a variety of multi-target directed ligands (MTDLs). In this review, we present selected examples of small molecules recently designed as MTDLs to contrast AD, by combining in a single entity the amantadine core of memantine with the pharmacophoric features of known neuroprotectants, such as antioxidant agents, AChEIs and Aβ-aggregation inhibitors.
Synthesis of Potential Haptens with Morphine Skeleton and Determination of Protonation Constants
Authors: Köteles István , Mazák Károly , Tóth Gergő , Tűz Boglárka , Hosztafi Sándor
Published: September 2020

Vaccination could be a promising alternative warfare against drug addiction and abuse. For this purpose, so-called haptens can be used. These molecules alone do not induce the activation of the immune system, this occurs only when they are attached to an immunogenic carrier protein. Hence obtaining a free amino or carboxylic group during the structural transformation is an important part of the synthesis. Namely, these groups can be used to form the requisite peptide bond between the hapten and the carrier protein. Focusing on this basic principle, six nor-morphine compounds were treated with ethyl acrylate and ethyl bromoacetate, while the prepared esters were hydrolyzed to obtain the N-carboxymethyl- and N-carboxyethyl-normorphine derivatives which are considered as potential haptens. The next step was the coupling phase with glycine ethyl ester, but the reactions did not work or the work-up process was not accomplishable. As an alternative route, the normorphine-compounds were N-alkylated with N-(chloroacetyl)glycine ethyl ester. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine side chain. The acid-base properties of these molecules are characterized in detail. In the N-carboxyalkyl derivatives, the basicity of the amino and phenolate site is within an order of magnitude. In the glycine derivatives the basicity of the amino group is significantly decreased compared to the parent compounds (i.e., morphine, oxymorphone) because of the electron withdrawing amide group. The protonation state of the carboxylate group significantly influences the basicity of the amino group. All of the glycine ester and the glycine carboxylic acid derivatives are currently under biological tests.
Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy
Authors: Eychenne Romain , Bouvry Christelle , Bourgeois Mickael , Loyer Pascal , Benoist Eric , Lepareur Nicolas
Published: September 2020

Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand–receptor complex and triggers different cellular signaling pathways. Interestingly, the expression of SSTRs is significantly enhanced in many solid tumors, especially gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). Thus, somatostatin analogs (SSAs) have been developed to improve the stability of the endogenous ligand and so extend its half-life. Radiolabeled analogs have been developed with several radioelements such as indium-111, technetium-99 m, and recently gallium-68, fluorine-18, and copper-64, to visualize the distribution of receptor overexpression in tumors. Internal metabolic radiotherapy is also used as a therapeutic strategy (e.g., using yttrium-90, lutetium-177, and actinium-225). With some radiopharmaceuticals now used in clinical practice, somatostatin analogs developed for imaging and therapy are an example of the concept of personalized medicine with a theranostic approach. Here, we review the development of these analogs, from the well-established and authorized ones to the most recently developed radiotracers, which have better pharmacokinetic properties and demonstrate increased efficacy and safety, as well as the search for new clinical indications.
Free Amino Acids in Three Pleurotus Species Cultivated on Agricultural and Agro-Industrial By-Products
Authors: Tagkouli Dimitra , Kaliora Andriana , Bekiaris Georgios , Koutrotsios Georgios , Christea Margarita , Zervakis Georgios I. , Kalogeropoulos Nick
Published: September 2020

Previous studies have demonstrated the feasibility of employing by-products of the olive and wine sectors for the production of Pleurotus mushrooms with enhanced functionalities. In this work we investigated the influence of endogenous and exogenous factors on free amino acids (FAAs) profile of Pleurotus ostreatus, P. eryngii and P. nebrodensis mushrooms produced on wheat straw (WS), alone or mixed with grape marc (GM), and on by-products of the olive industry (OL). Overall, 22 FAAs were determined in substrates and mushrooms, including all the essential amino acids, the neurotransmitter γ-aminobutyric acid (GABA) and ornithine. On a dry weight (dw) basis, total FAAs ranged from 17.37 mg/g in P. nebrodensis to 130.12 mg/g in P. ostreatus samples, with alanine, leucine, glutamine, valine and serine predominating. Similar distribution patterns were followed by the monosodium glutamate (MSG)-like, sweet and bitter FAAs. Significant differences in FAAs level were observed among the species examined and among the cultivation substrates used. Principal Component Analysis (PCA) performed on the entire FAAs profile of six Pleurotus strains, clearly separated P. ostreatus from P. eryngii and P. nebrodensis, in accordance to their phylogenetic affinity. This is the first report of FAAs in P. nebrodensis.