bluuebunny/crossref_metadata_2025 huggingface dataset:
ECG-Signal Multi-Classification Model Based on Squeeze-and-Excitation Residual Neural Networks
Authors: Park Junsang , Kim Jin-kook , Jung Sunghoon , Gil Yeongjoon , Choi Jong-Il , Son Ho Sung
Published: September 2020

Accurate electrocardiogram (ECG) interpretation is crucial in the clinical ECG workflow because it is most likely associated with a disease that can cause major problems in the body. In this study, we proposed an ECG-signal multi-classification model using deep learning. We used a squeeze-and-excitation residual network (SE-ResNet), which is a residual network(ResNet) with a squeeze-and-excitation block. Experiments were performed for seven different types of lead-II ECG data obtained from the Korea University Anam Hospital in South Korea. These seven types are normal sinus rhythm, atrial fibrillation, atrial flutter, sinus bradycardia, sinus tachycardia, premature ventricular contraction and first-degree atrioventricular block. We compared the SE-ResNet with a ResNet, as a baseline model, for various depths of layer (18/34/50/101/152). We confirmed that the SE-ResNet had better classification performance than the ResNet, for all layers. The SE-ResNet classifier with 152 layers achieved F1 scores of 97.05% for seven-class classifications. Our model surpassed the baseline model, ResNet, by +1.40% for the seven-class classifications. For ECG-signal multi-classification, considering the F1 scores, the SE-ResNet might be better than the ResNet baseline model.
Wettability Alteration by Carbonated Brine Injection and Its Impact on Pore-Scale Multiphase Flow for Carbon Capture and Storage and Enhanced Oil Recovery in a Carbonate Reservoir
Authors: Drexler Santiago , Hoerlle Fernanda , Godoy William , Boyd Austin , Couto Paulo
Published: September 2020

Carbon capture and storage is key for sustainable economic growth. CO2-enhanced oil recovery (EOR) methods are efficient practices to reduce emissions while increasing oil production. Although it has been successfully implemented in carbonate reservoirs, its effect on wettability and multiphase flow is still a matter of research. This work investigates the wettability alteration by carbonated water injection (CWI) on a coquina carbonate rock analogue of a Pre-salt reservoir, and its consequences in the flow of oil. The rock was characterized by routine petrophysical analysis and nuclear magnetic resonance. Moreover, micro-computed tomography was used to reconstruct the pore volume, capturing the dominant flow structure. Furthermore, wettability was assessed by contact angle measurement (before and after CWI) at reservoir conditions. Finally, pore-scale simulations were performed using the pore network modelling technique. The results showed that CWI altered the wettability of the carbonate rock from neutral to water-wet. In addition, the simulated relative permeability curves presented a shift in the crossover and imbibition endpoint values, indicating an increased flow capacity of oil after CWI. These results suggest that the wettability alteration mechanism contributes to enhancing the production of oil by CWI in this system.
Lightweight Stacked Hourglass Network for Human Pose Estimation
Authors: Kim Seung-Taek , Lee Hyo Jong
Published: September 2020

Human pose estimation is a problem that continues to be one of the greatest challenges in the field of computer vision. While the stacked structure of an hourglass network has enabled substantial progress in human pose estimation and key-point detection areas, it is largely used as a backbone network. However, it also requires a relatively large number of parameters and high computational capacity due to the characteristics of its stacked structure. Accordingly, the present work proposes a more lightweight version of the hourglass network, which also improves the human pose estimation performance. The new hourglass network architecture utilizes several additional skip connections, which improve performance with minimal modifications while still maintaining the number of parameters in the network. Additionally, the size of the convolutional receptive field has a decisive effect in learning to detect features of the full human body. Therefore, we propose a multidilated light residual block, which expands the convolutional receptive field while also reducing the computational load. The proposed residual block is also invariant in scale when using multiple dilations. The well-known MPII and LSP human pose datasets were used to evaluate the performance using the proposed method. A variety of experiments were conducted that confirm that our method is more efficient compared to current state-of-the-art hourglass weight-reduction methods.
Novel Industry 4.0 Technologies and Applications
Authors: Papakostas Nikolaos , Constantinescu Carmen , Mourtzis Dimitris
Published: September 2020

The Industry 4 [...]
Suitability of Wooden Shingles for Ventilated Roofs: An Evaluation of Ventilation Efficiency
Authors: Kain Günther , Idam Friedrich , Federspiel Franz , Réh Roman , Krišťák Ľuboš
Published: September 2020

Wooden shingles are a traditional roofing material on many culturally important building artifacts. Currently, the roof space of many traditional buildings is used for residential purposes and, consequently, cold roof constructions with ventilation layers are applied. In this study, it is evaluated whether the moisture content of wooden shingles is adversely affected by such constructions, compared with unvented shingle roofs over cold attics and whether a temporary closing of the ventilation gaps at the eaves contributes to a lower wood moisture content. Various sensors were installed in and around a building with wooden shingles on a ventilated roof and temperature, air moisture, and air speed in the ventilation layer were measured throughout a year. The findings show that the air speed in the ventilation layer can be adjusted from 0.06 to 0.25 m/s depending on the layout of the eaves. A hygrothermal model was applied to evaluate the effects of different ventilation operation modes and cardinal orientations of the roof on the moisture content of the wooden shingles. The results show that roof ventilation results in a 1% lower shingle moisture content on average than an unventilated roof over a cold attic. Finally, it is shown that the wood moisture content repeatedly reaches dangerous levels above 25% throughout a year, which is worse on north-facing roofs and, hence, measures to increase the dry-out are relevant.
Tripod-Loop Metasurfaces for Terahertz-Sensing Applications: A Comparison
Authors: Jáuregui-López Irati , Orazbayev Bakhtiyar , Pacheco-Peña Victor , Beruete Miguel
Published: September 2020

The high electric field intensity achieved on the surface of sensors based on metasurfaces (metasensors) makes them an excellent alternative for sensing applications where the volume of the sample to be identified is tiny (for instance, thin-film sensing devices). Various shapes and geometries have been proposed recently for the design of these metasensors unit-cells (meta-atoms) such as split ring resonators or hole arrays, among others. In this paper, we propose, design, and evaluate two types of tripod metasurfaces with different complexity in their geometry. An in-depth comparison of their performance is presented when using them as thin-film sensor devices. The meta-atoms of the proposed metasensors consist of a simple tripod and a hollow tripod structure. From numerical calculations, it is shown that the best geometry to perform thin-film sensing is the compact hollow tripod (due to the highest electric field on its surface) with a mean sensitivity of 3.72 × 10−5 nm−1. Different modifications are made to this structure to improve this value, such as introducing arms in the design and rotating the metallic pattern 30 degrees. The best sensitivity achieved for extremely thin film analytes (5–25 nm thick) has an average value of 1.42 × 10−4 nm, which translates into an extremely high improvement of 381% with respect to the initial hollow tripod structure. Finally, a comparison with other designs found in the literature shows that our design is at the top of the ranking, improving the overall performance by more than one order of magnitude. These results highlight the importance of using metastructures with more complex geometries so that a higher electric field intensity distribution and, therefore, designs with better performance can be obtained.
The Ursolic Acid-Rich Extract of Dracocephalum heterophyllum Benth. with Potent Antidiabetic and Cytotoxic Activities
Authors: Numonov Sodik , Sharopov Farukh , Qureshi Muhammad Nasimullah , Gaforzoda Latofat , Gulmurodov Isomiddin , Khalilov Qosimjon , Setzer William N , Habasi Maidina , Aisa Haji Akber
Published: September 2020

Pentacyclic triterpenoids are one of the main functional components in Dracocephalum heterophyllum. In this study the optimal process, the fairly simple and accessible extraction and purification of triterpenoids of D. heterophyllum, was developed by a remaceration method. Remaceration is characterized by minimal loss of biologically active compounds on diffusion, which contributes to the largest depletion of raw materials. The triterpenoid yield was 2.4% under optimal conditions which was enhanced to 98.03% after purification. The triterpenoid profiles and their anticancer and antidiabetic activities were further analyzed. GC-MS analysis of triterpenoidal extract of D. heterophyllum resulted ursolic acid (71.9%) and oleanolic acid (18.1%) as the major components. Additionally, total purified triterpenoid contents of D. heterophyllum and its main components were shown to possess significant cytotoxic activity against three human breast cancer cell lines (SK-Br-3, T47D, and MCF-7). The purification of triterpenoids influenced their biological activity. The antidiabetic effect, as measured by inhibition of protein-tyrosine phosphatase (PTP-1B), of the purified fraction of triterpenoids of D. heterophyllum increased by five-fold against the enzyme. The results provide important guidance for the industrial application of D. heterophyllum confirming the prospect of developing plant extracts into effective drugs and health foods for human applications.
An Easy and Effective Technique for Silicone Facial Implant Insertion and Fixation to Periosteum
Authors: Rauso Raffaele , Lo Giudice Giorgio , Lo Faro Carmelo , Nicoletti Giovanni Francesco , Fragola Romolo , Sesenna Enrico , Tartaro Gianpaolo
Published: September 2020

In this paper, we present a simple way to place the implant into a harvested pocket and to subsequently fix it percutaneously. Eighteen patients (1 male, 13 females, 4 transgender), underwent facial implant placement; a total of 31 implants were placed (1 pair of angles of the mandible implants, 12 pairs of malar/sub-malar implants, and 5 chin implants). The intraoral approach was performed on 15 patients, and on the remaining three patients, the sub-ciliary lower lid approach was preferred. Patients were followed up for at least one year with a maximum follow-up of seven years (mean 1.8 years). In all the cases, except one, patients healed without complications. One case of implant displacement and infection was recorded. No other complication was documented. The technique described is similar to the one suggested by Peled, although some useful tips were added, namely the use of sutures, not only to fix the implant but also to drive it into the harvested pocket. In addition, larger absorbable “left in place” sutures were used, avoiding accidental implant dislocation during their removal. Further studies are required to gain a more complete understanding of the effectiveness and reproducibility of this surgical technique.
Seismic Risk Assessment of a Novel Self-Centering Precast Concrete Frame under Near-Fault Ground Motions
Authors: Geng Fangfang , Ding Youliang , Wu Honglei , Yang Kang
Published: September 2020

The damage to structures caused by the velocity pulse effect of near-fault earthquake waves cannot be ignored, yet there are few studies on the risk assessment of seismic performance for precast concrete frame under near-fault earthquake waves. A novel self-centering precast concrete (SCPC) frame with hysteretic dampers is proposed to obtain great self-recovering and energy consumption characteristics. To accurately assess the seismic behaviors of the novel SCPC frame under the near-fault earthquake waves, a prototype structure is modelled and elastoplastic dynamic analysis is conducted at the design basis earthquake (DBE) and the maximum considered earthquake (MCE) seismic levels. Incremental dynamic analysis and the vulnerability analysis are performed. Annual and 50-year exceeding probabilities of the novel SCPC frame are calculated afterwards. In addition, the reinforced concrete (RC)frame and the traditional SCPC frame are also modelled, whose section sizes, reinforcements arrangement and seismic intensity are consistent with the novel SCPC frame. The dynamic time-history analysis at the two seismic levels are also carried out for two types of frames. The analysis results demonstrate that the novel SCPC frame has great seismic performance and low seismic risk possibility under the near-fault earthquakes loading.
Ingredients Acting as a Physical Barrier for the Prevention and Treatment of the Rhinovirus Infection
Authors: Sittek Lisa-Marie , Schmidts Thomas Michael , Schlupp Peggy
Published: September 2020

Although the common cold, usually caused by human rhinoviruses, is responsible for enormous damage to the economy and health every year, there are hardly any treatment options or prophylaxis for rhinovirus infections. In this work, the potential of a hydrogel complex, based on polymers and an aqueous extract of Icelandic moss in isla® medic lozenges (Engelhard Arzneimittel, Niederdorfelden, Germany), and two other hydrogels (based on solely xanthan gum or sodium hyaluronate) are investigated for the first time in order to prevent and treat rhinovirus infections. By means of rheological investigations, we demonstrate that isla® medic and containing polymers cause artificial saliva to thicken. Additionally, we demonstrate that the thickening results in the formation of a physical diffusion barrier, which leads to a significant reduction in plaques in a preventive plaque assay with rhinovirus 14 (RV-14). Furthermore, it is shown in a curative plaque assay that the hydrogel complex also has a curative effect on rhinovirus infections in that it reduces the spread of the RV-14-infection on H1-HeLa cell monolayers. Overall, polymer-based hydrogels and related products, such as isla® medic, could contribute to the prevention and treatment of rhinovirus infections.
Effects of Dentifrices Containing Nanohydroxyapatite on Dentinal Tubule Occlusion—A Scanning Electron Microscopy and EDX Study
Authors: Bologa Emilia , Stoleriu Simona , Iovan Gianina , Ghiorghe Cristina Angela , Nica Irina , Andrian Sorin , Amza Oana Elena
Published: September 2020

This in vitro study evaluated the effects of dentifrices containing nano-hydroxyapatite (n-HAp) on dentinal tubule occlusion and on mineral deposition. Dentin specimens of ten human teeth were submersed for 30 s in 40% citric acid and then randomly divided into four groups (three study groups and one control group). In the study groups, the dentin samples were exposed to three different n-HAp toothpastes: Karex (Dr. Kurt Wolff GmbH & Co. KG, Bielefeld, Germany), Biorepair Plus Sensitive (Coswell SpA, Bologna, Italy), and Dr. Wolff’s Biorepair (Dr. Kurt Wolff GmbH & Co. KG, Bielefeld, Germany); in the control group no toothpaste was applied. All of the samples were evaluated using scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) analysis. In the control group all of the samples showed a frank and wide opening of the dentinal tubules, whereas in the study groups different degrees of tubule closure by mineral depositions were observed. Toothpastes containing n-HAp determined a significant occlusion of dentinal tubules and a significant increase of mineral deposition on the dentin surface. All three tested toothpastes showed similar results regarding the degree of dentinal tubule closure. Varying degrees of differences in calcium, phosphate, carbon, and oxygen ion concentrations among the three tested toothpastes were obtained.
A Bio-Inspired Manipulator with Claw Prototype for Winged Aerial Robots: Benchmark for Design and Control
Authors: Feliu-Talegon Daniel , Acosta José Ángel , Suarez Alejandro , Ollero Anibal
Published: September 2020

Nature exhibits many examples of birds, insects and flying mammals with flapping wings and limbs offering some functionalities. Although in robotics, there are some examples of flying robots with wings, it has not been yet a goal to add to them some manipulation-like capabilities, similar to ones that are exhibited on birds. The flying robot (ornithopter) that we propose improves the existent aerial manipulators based on multirotor platforms in terms of longer flight duration of missions and safety in proximity to humans. Moreover, the manipulation capabilities allows them to perch in inaccessible places and perform some tasks with the body perched. This work presents a first prototype of lightweight manipulator to be mounted to an ornithopter and a new control methodology to balance them while they are perched and following a desired path with the end effector imitating their beaks. This allows for several possible applications, such as contact inspection following a path with an ultrasonic sensor mounted in the end effector. The manipulator prototype imitates birds with two-link legs and a body link with an actuated limb, where the links are all active except for the first passive one with a grabbing mechanism in its base, imitating a claw. Unlike standard manipulators, the lightweight requirement limits the frame size and makes it necessary to use micro motors. Successful experimental results with this prototype are reported.
Digital Twin and Internet of Things—Current Standards Landscape
Authors: Jacoby Michael , Usländer Thomas
Published: September 2020

Industry 4.0 is revolutionizing industrial production by bridging the physical and the virtual worlds and further improving digitalization. Two essential building blocks in industry 4.0 are digital twins (DT) and the internet of things (IoT). While IoT is about connecting resources and collecting data about the physical world, DTs are the virtual representations of resources organizing and managing information and being tightly integrated with artificial intelligence, machine learning and cognitive services to further optimize and automate production. The concepts of DTs and IoT are overlapping when it comes to describing, discovering and accessing resources. Currently, there are multiple DT and IoT standards covering these overlapping aspects created by different organizations with different backgrounds and perspectives. With regard to interoperability, which is presumably the most important aspect of industry 4.0, this barrier needs to be overcome by consolidation of standards. The objective of this paper is to investigate current DT and IoT standards and provide insights to stimulate this consolidation. Overlapping aspects are identified and a classification scheme is created and applied to the standards. The results are compared, aspects with high similarity or divergence are identified and a proposal for stimulating consolidation is presented. Consensus between standards are found regarding the elements a resource should consist of and which serialization format(s) and network protocols to use. Controversial topics include which query language to use for discovery as well as if geo-spatial, temporal and historical data should be explicitly supported.
Robustness Analysis for Multi-Agent Consensus Systems with Application to DC Motor Synchronization
Authors: Olivares Daniel , Romero Gerardo , Guerrero Jose A. , Lozano Rogelio
Published: September 2020

DC motor speed synchronization is a critical problem in industrial and robotic applications. To tackle this problem, we propose to use a multi-agent consensus-based control scheme that guarantees the convergence of the DC motor speeds to either fixed or time-varying reference. A detailed robustness analysis considering parametric uncertainty and time delay in the multi-agent system is performed to guarantee the consensus on the speed of DC motors in actual practice. The results obtained concerning the robustness analysis allowed us to implement experimental tests on a three-motor system using a wireless communication system to achieve satisfactory performance.
Study of the Healing Properties of Natural Sources of Georgia and Modeling of Their Purification Processes
Authors: Bejanidze Irina , Petrov Oleksandr , Kharebava Tina , Pohrebennyk Volodymyr , Davitadze Nazi , Didmanidze Nato
Published: September 2020

The studies were conducted on the natural waters of Georgia: Gortubani and Naminauri (Adigeni region), Danisparauli, Dandalo and Makhinjauri (Adjara region) which exhibit medicinal properties. The following water indicators were determined: titratable acidity, electrical conductivity, hardness, the content of solids, sulfates, chlorides, hydrocarbonates, nitrates, ammonium salts and metals. These indicators were determined in the source water, as well as in the concentrate and permeate obtained by ultrafiltration. The productivity of the ultrafiltration process was determined, its dependence on the duration of the process, the applied pressure and the location of the spring. The productivity of the Danisparauli water ultrafiltration process decreases with time; the productivity remains unchanged during the filtration of the Makhinjauri and Naminauri waters; during ultrafiltration, the titratable acidity of the Makhinjauri water increases significantly, by 66.5%, that of the water Naminauri by 36.6%, the titratable acidity of the Danisparauli water remains unchanged, the sulfide ion content in the Makhinjauri water increases by 12%, and in the Naminauri water by 35.5%, the chloride content in the process of concentrating practically does not change. It was found that all the investigated waters are contaminated with heavy metals and the population should not use them for treatment. The data obtained can be used to simulate the purification of natural sources.
Mechanical Characterization of Timber-to-Timber Composite (TTC) Joints with Self-Tapping Screws in a Standard Push-Out Setup
Authors: Bedon Chiara , Sciomenta Martina , Fragiacomo Massimo
Published: September 2020

Self-tapping screws (STSs) can be efficiently used in various fastening solutions for timber constructions and are notoriously able to offer high stiffness and load-carrying capacity, compared to other timber-to-timber composite (TTC) joint typologies. The geometrical and mechanical characterization of TTC joints, however, is often hard and uncertain, due to a combination of various influencing parameters and mechanical aspects. Among others, the effects of friction phenomena between the system components and their reciprocal interaction under the imposed design loads can remarkably influence the final estimates on structural capacity, in the same way of possible variations in the boundary conditions. The use of Finite Element (FE) numerical models is well-known to represent a robust tool and a valid alternative to costly and time consuming experiments and allows one to further explore the selected load-bearing components at a more refined level. Based on previous research efforts, this paper presents an extended FE investigation based on full three-dimensional (3D) brick models and surface-based cohesive zone modelling (CZM) techniques. The attention is focused on the mechanical characterization of small-scale TTC specimens with inclined STSs having variable configurations, under a standard push-out (PO) setup. Based on experimental data and analytical models of literature, an extended parametric investigation is presented and correlation formulae are proposed for the analysis of maximum resistance and stiffness variations. The attention is then focused on the load-bearing role of the steel screws, as an active component of TTC joints, based on the analysis of sustained resultant force contributions. The sensitivity of PO numerical estimates to few key input parameters of technical interest, including boundaries, friction and basic damage parameters, is thus discussed in the paper.
Optical Element Surface Defect Size Recognition Based on Decision Regression Tree
Authors: Lou Weimin , Cao Pin , Zhang Danhui , Yang Yongying
Published: September 2020

Defect size recognition is significant to the evaluation of optical element surface quality. Currently, it’s mainly achieved by the conventional image process, such as threshold segmentation. However, as the defect size gradually approaches the diffraction limit of the imaging system, the defect gray distribution changes from bimodal to unimodal, which makes it difficult to be accurately recognized. In this paper, an electromagnetic simulation model of the microscopic scattering dark-field imaging (MSDI) system is built based on the finite-difference time-domain (FDTD) method to research the defect imaging mechanism. The point spread function (PSF) of our MSDI system is measured to revise the far-field simulation light intensity distribution, and the mean value of the distance between three groups of feature points, whose intensity is 0.75, 0.5, and 0.25 of the light intensity distribution peak value, is taken as the feature parameter of the light intensity distribution. To obtain the defect size, the decision regression tree (DRT) is proposed to get the relationship between the feature parameter and the defect size. Besides, some scratches samples are made to verify the validity of the DRT. The results show the relative error of DRT is within 10%, which is better than the threshold segmentation.
Allosteric Inhibition of Adenylyl Cyclase Type 5 by G-Protein: A Molecular Dynamics Study
Authors: Frezza Elisa , Amans Tina-Méryl , Martin Juliette
Published: September 2020

Adenylyl cyclases (ACs) have a crucial role in many signal transduction pathways, in particular in the intricate control of cyclic AMP (cAMP) generation from adenosine triphosphate (ATP). Using homology models developed from existing structural data and docking experiments, we have carried out all-atom, microsecond-scale molecular dynamics simulations on the AC5 isoform of adenylyl cyclase bound to the inhibitory G-protein subunit Gαi in the presence and in the absence of ATP. The results show that Gαi has significant effects on the structure and flexibility of adenylyl cyclase, as observed earlier for the binding of ATP and Gsα. New data on Gαi bound to the C1 domain of AC5 help explain how Gαi inhibits enzyme activity and obtain insight on its regulation. Simulations also suggest a crucial role of ATP in the regulation of the stimulation and inhibition of AC5.
Mulinane- and Azorellane-Type Diterpenoids: A Systematic Review of Their Biosynthesis, Chemistry, and Pharmacology
Authors: Dzul-Beh Angel de Jesús , Uc-Cachón Andrés Humberto , Bórquez Jorge , Loyola Luis A. , Peña-Rodríguez Luis Manuel , Molina-Salinas Gloria María
Published: September 2020

Mulinane- and azorellane-type diterpenoids have unique tricyclic fused five-, six-, and seven-membered systems and a wide range of biological properties, including antimicrobial, antiprotozoal, spermicidal, gastroprotective, and anti-inflammatory, among others. These secondary metabolites are exclusive constituents of medicinal plants belonging to the Azorella, Laretia, and Mulinum genera. In the last 30 years, more than 95 mulinanes and azorellanes have been reported, 49 of them being natural products, 4 synthetics, and the rest semisynthetic and biotransformed derivatives. This systematic review highlights the biosynthetic origin, the chemistry, and the pharmacological activities of this remarkably interesting group of diterpenoids.
Dibenzoylthiamine Has Powerful Antioxidant and Anti-Inflammatory Properties in Cultured Cells and in Mouse Models of Stress and Neurodegeneration
Authors: Sambon Margaux , Gorlova Anna , Demelenne Alice , Alhama-Riba Judit , Coumans Bernard , Lakaye Bernard , Wins Pierre , Fillet Marianne , Anthony Daniel C. , Strekalova Tatyana , Bettendorff Lucien
Published: September 2020

Thiamine precursors, the most studied being benfotiamine (BFT), have protective effects in mouse models of neurodegenerative diseases. BFT decreased oxidative stress and inflammation, two major characteristics of neurodegenerative diseases, in a neuroblastoma cell line (Neuro2a) and an immortalized brain microglial cell line (BV2). Here, we tested the potential antioxidant and anti-inflammatory effects of the hitherto unexplored derivative O,S-dibenzoylthiamine (DBT) in these two cell lines. We show that DBT protects Neuro2a cells against paraquat (PQ) toxicity by counteracting oxidative stress at low concentrations and increases the synthesis of reduced glutathione and NADPH in a Nrf2-independent manner. In BV2 cells activated by lipopolysaccharides (LPS), DBT significantly decreased inflammation by suppressing translocation of NF-κB to the nucleus. Our results also demonstrate the superiority of DBT over thiamine and other thiamine precursors, including BFT, in all of the in vitro models. Finally, we show that the chronic administration of DBT arrested motor dysfunction in FUS transgenic mice, a model of amyotrophic lateral sclerosis, and it reduced depressive-like behavior in a mouse model of ultrasound-induced stress in which it normalized oxidative stress marker levels in the brain. Together, our data suggest that DBT may have therapeutic potential for brain pathology associated with oxidative stress and inflammation by novel, coenzyme-independent mechanisms.
Recent Advances in Portable Biosensors for Biomarker Detection in Body Fluids
Authors: Senf Brian , Yeo Woon-Hong , Kim Jong-Hoon
Published: September 2020

A recent development in portable biosensors allows rapid, accurate, and on-site detection of biomarkers, which helps to prevent disease spread by the control of sources. Less invasive sample collection is necessary to use portable biosensors in remote environments for accurate on-site diagnostics and testing. For non- or minimally invasive sampling, easily accessible body fluids, such as saliva, sweat, blood, or urine, have been utilized. It is also imperative to find accurate biomarkers to provide better clinical intervention and treatment at the onset of disease. At the same time, these reliable biomarkers can be utilized to monitor the progress of the disease. In this review, we summarize the most recent development of portable biosensors to detect various biomarkers accurately. In addition, we discuss ongoing issues and limitations of the existing systems and methods. Lastly, we present the key requirements of portable biosensors and discuss ideas for functional enhancements.
Functional Connectivity Analysis on Resting-State Electroencephalography Signals Following Chiropractic Spinal Manipulation in Stroke Patients
Authors: Steven Waterstone Toby , Niazi Imran Khan , Navid Muhammad Samran , Amjad Imran , Shafique Muhammad , Holt Kelly , Haavik Heidi , Samani Afshin
Published: September 2020

Stroke impairments often present as cognitive and motor deficits, leading to a decline in quality of life. Recovery strategy and mechanisms, such as neuroplasticity, are important factors, as these can help improve the effectiveness of rehabilitation. The present study investigated chiropractic spinal manipulation (SM) and its effects on resting-state functional connectivity in 24 subacute to chronic stroke patients monitored by electroencephalography (EEG). Functional connectivity of both linear and non-linear coupling was estimated by coherence and phase lag index (PLI), respectively. Non-parametric cluster-based permutation tests were used to assess the statistical significance of the changes in functional connectivity following SM. Results showed a significant increase in functional connectivity from the PLI metric in the alpha band within the default mode network (DMN). The functional connectivity between the posterior cingulate cortex and parahippocampal regions increased following SM, t (23) = 10.45, p = 0.005. No significant changes occurred following the sham control procedure. These findings suggest that SM may alter functional connectivity in the brain of stroke patients and highlights the potential of EEG for monitoring neuroplastic changes following SM. Furthermore, the altered connectivity was observed between areas which may be affected by factors such as decreased pain perception, episodic memory, navigation, and space representation in the brain. However, these factors were not directly monitored in this study. Therefore, further research is needed to elucidate the underlying mechanisms and clinical significance of the observed changes.
Signal Transduction Pathway Activity in High-Grade, Serous Ovarian Carcinoma Reveals a More Favorable Prognosis in Tumors with Low PI3K and High NF-κB Pathway Activity: A Novel Approach to a Long-Standing Enigma
Authors: van Lieshout Laura , van de Stolpe Anja , van der Ploeg Phyllis , Bowtell David , de Hullu Joanne , Piek Jurgen
Published: September 2020

We investigated signal transduction pathway (STP) activity in high-grade serous ovarian carcinoma (HGSC) in relation to progression-free survival (PFS) and overall survival (OS). We made use of signal transduction pathway activity analysis (STA analysis), a novel method to quantify functional STP activity. Activity of the following pathways was measured: androgen receptor (AR), estrogen receptor (ER), phosphoinositide 3-kinase (PI3K), Hedgehog (Hh), Notch, nuclear factor-kappa B (NF-κB), transforming growth factor beta (TGF-β), and Wnt. We selected HGSC samples from publicly available datasets of ovarian cancer tissue, and used repeated k-means clustering to identify pathway activity clusters. PFS and OS of the clusters were analyzed. We used a subset of publicly available dataset GSE9891 (n = 140), where repeated k-means clustering based on PI3K and NF-κB pathway activity in HGSC samples resulted in two stable clusters. The cluster with low PI3K and high NF-κB pathway activity (n = 72) had a more favorable prognosis for both PFS (p = 0.004) and OS (p = 0.001) compared to the high-PI3K and low-NF-κB pathway activity cluster (n = 68). The low PI3K and high NF-κB pathway activity of the favorable prognosis cluster may indicate a more active immune response, while the high PI3K and low NF-κB pathway activity of the unfavorable prognosis cluster may indicate high cell division.
EVI1 in Leukemia and Solid Tumors
Authors: Liang Beiyuan , Wang Jing
Published: September 2020

The EVI1 gene encodes for a transcription factor with two zinc finger domains and is transcriptionally activated in a subset of myeloid leukemias. In leukemia, the transcriptional activation of EVI1 usually results from chromosomal rearrangements. Besides leukemia, EVI1 has also been linked to solid tumors including breast cancer, lung cancer, ovarian cancer and colon cancer. The MDS1/EVI1 gene is encoded by the same locus as EVI1. While EVI1 functions as a transcription repressor, MDS1/EVI1 acts as a transcription activator. The fusion protein encoded by the AML1/MDS1/EVI1 chimeric gene, resulting from chromosomal translocations in a subset of chronic myeloid leukemia, exhibits a similar function to EVI1. EVI1 has been shown to regulate cell proliferation, differentiation and apoptosis, whereas the functions of MDS1/EVI1 and AML1/MDS1/EVI1 remain elusive. In this review, we summarize the genetic structures, biochemical properties and biological functions of these proteins in cancer.
Modification of the Histone Landscape with JAK Inhibition in Myeloproliferative Neoplasms
Authors: Greenfield Graeme , McPherson Suzanne , Smith James , Mead Adam , Harrison Claire , Mills Ken , McMullin Mary Frances
Published: September 2020

Dysregulation of epigenetic processes is increasingly understood to play a role in the pathogenesis of myeloproliferative neoplasms (MPNs). Ruxolitinib, a JAK/STAT inhibitor, has proved a useful addition to the therapeutic arsenal for these disorders, but has limited disease modifying activity. We determined the effect of JAK inhibition on the histone landscape of MPN cells in cell line models of MPNs and validated using samples from the MAJIC randomised clinical trial of ruxolitinib in polycythaemia vera and essential thrombocythaemia. We demonstrated an epigenetic modifying effect of ruxolitinib using a histone modification assay. The majority of 21 histone H3 modifications were upregulated, with H3K27me3 and H3K36me2 significant in the combined cell line results. Chromatin immunoprecipitation and sequencing (CHIP-seq) for three marks of interest, H3K4me1, H3K4me3 and H3K27ac, was consistent with the histone modification assay showing a significant increase in H3K4me3 and H3K27ac peaks at promoter regions, both marks of active transcription. In contrast, RNA sequencing demonstrates a coordinated reduction in gene expression in a number of cell pathways including PI3K-AKT signalling, transcriptional misregulation in cancer and JAK-STAT signalling in spite of these histone changes. This highlights the complex mechanisms of transcriptional control within the cells which was reflected in analysis of the histone landscape in patient samples following ruxolitinib treatment.
Reply to Comment on “Jilkova, Z.M.; et al. Predictive Factors for Response to PD-1/PD-L1 Checkpoint Inhibition in the Field of Hepatocellular Carcinoma: Current Status and Challenges” Cancers 2019, 11, 1554
Authors: Macek Jilkova Zuzana , Aspord Caroline , Decaens Thomas
Published: September 2020

We appreciate the comments made on our review paper focused on possible predictive factors for responses to PD-1/PD-L1 checkpoint inhibitors in the field of hepatocellular carcinoma [...]
Molybdenum and Nickel Nanoparticles Synthesis by Laser Ablation towards the Preparation of a Hydrodesulfurization Catalyst
Authors: Londoño-Calderón Viviana , Ospina Rogelio , Rodriguez-Pereira Jhonatan , Rincón-Ortiz Sergio A. , Restrepo-Parra Elisabeth
Published: September 2020

A clean straightforward laser ablation method in deionized (DI) water is reported for the synthesis of Molybdenum (Mo) and Nickel (Ni) nanoparticles (NPs). The structural, morphological, and optical properties of the as-synthesized nanoparticles were investigated. Particle size was estimated to be less than 10 nm, the UV–vis spectra of the samples show the formation of H2MoO4 and NiO. The XRD results for the Ni sample show the presence of two phases, cubic nickel oxide, and an fcc metallic nickel phase, indicating the possible formation of Ni/NiO compound. The nanoparticles synthesized were used as precursors in the production of a NiMo/γ-Al2O3 catalyst. The textural and structural properties, chemical composition, and catalytic performance in a hydrodesulfurization (HDS) reaction are reported. The textural and structural properties results show the lack of pore-blocking due to the small sizes and the distribution of the metallic nanoparticles on the support. Chemical composition measured by XPS shows a ratio Ni/Mo of 1.34. Therefore, possibly Ni was deposited on Mo covering part of its active area, occupying active sites of Mo, removing its effective surface and resulting in a relatively low conversion of DBT (17%). A lower Ni/Mo ratio is required to improve the model system, which could be achieved by changing parameters at the production of the nanoparticles. The model system can also be further tuned by changing the size of the nanoparticles.
Biocatalyzed Reactions towards Functional Food Components 4-Alkylcatechols and Their Analogues
Authors: Martínková Ludmila , Příhodová Romana , Kulik Natalia , Pelantová Helena , Křístková Barbora , Petrásková Lucie , Biedermann David
Published: September 2020

Catechols are antioxidants and radical scavengers with a broad medical potential. 4-Methylcatechol (1b) and 4-ethylcatechol (2b) (occurring in some traditional fermented and smoked foods) activate the cell defense against oxidative stress. We examined the biocatalyzed reactions towards 4-n-alkylcatechols with different side chains length, which is a factor important for the biological activities of catechols. 4-n-Alkylcatechols with methyl through heptyl side chains (1b–7b) were obtained in one pot by (i) oxidation of phenols 1a–7a with tyrosinase from Agaricus bisporus followed by (ii) reduction of ortho-quinones (intermediates) with L-ascorbic acid sodium salt. The conversions decreased with increasing side chain length. The preparative reactions were carried out with substrates 1a–5a. The isolated yields of the purified products decreased from 59% in 2b to 10% in 5b in correlation with logP of the substrates. Homology modeling indicated that the affinities of two tyrosinase isoforms (PPO3 and PPO4) to the substrates with side chains longer than C2 decreased with increasing side chain length. This was probably due to steric limitations and to missing interactions of the extended side chains in the active sites. We envisage using the model to predict further substrates of tyrosinase and testing the products, catechols, for radical-scavenging and biological activities.
Asymmetric Cyanation of Activated Olefins with Ethyl Cyanoformate Catalyzed by Ti(IV)-Catalyst: A Theoretical Study
Authors: Su Zhishan , Hu Changwei , Shahzad Nasir , Kim Chan Kyung
Published: September 2020

The reaction mechanism and origin of asymmetric induction for conjugate addition of cyanide to the C=C bond of olefin were investigated at the B3LYP-D3(BJ)/6-31+G**//B3LYP-D3(BJ)/6-31G**(SMD, toluene) theoretical level. The release of HCN from the reaction of ethyl cyanoformate (CNCOOEt) and isopropanol (HOiPr) was catalyzed by cinchona alkaloid catalyst. The cyanation reaction of olefin proceeded through a two-step mechanism, in which the C-C bond construction was followed by H-transfer to generate a cyanide adduct. For non-catalytic reaction, the activation barrier for the rate-determining C-H bond construction step was 34.2 kcal mol−1, via a four-membered transition state. The self-assembly Ti(IV)-catalyst from tetraisopropyl titanate, (R)-3,3′-disubstituted biphenol, and cinchonidine accelerated the addition of cyanide to the C=C double bond by a dual activation process, in which titanium cation acted as a Lewis acid to activate the olefin and HNC was orientated by hydrogen bonding. The steric repulsion between the 9-phenanthryl at the 3,3′-position in the biphenol ligand and the Ph group in olefin raised the Pauli energy (ΔE≠Pauli) of reacting fragments at the re-face attack transition state, leading to the predominant R-product.
Comparison of Catalytic Properties of Vanadium Centers Introduced into BEA Zeolite and Present on (010) V2O5 Surface–DFT Studies
Authors: Drzewiecka-Matuszek Agnieszka , Tokarz-Sobieraj Renata , Witko Małgorzata , Rutkowska-Zbik Dorota
Published: September 2020

Vanadium-based catalysts, in which vanadium is present either as bulk V2O5 or as isolated species, are active in numerous oxidation reactions. In the present study, vanadium speciation and the possibility of its introduction in various forms (V=O, V–OH, V(=O)(–OH)) into the structurally different crystallographic positions in BEA zeolite was considered by means of Density Functional Theory (DFT). Out of nine nonequivalent positions, T2 and T3 positions are the most preferred. The former may accommodate V=O or V–OH, the latter V–OH or V(=O)(–OH). The structural and electronic properties of all possible centers present in the BEA zeolite are then compared with the characteristics of the same species on the most abundant (010) V2O5 surface. It is demonstrated that they exhibit higher nucleophilic character when introduced into the zeolite, and thus, may be more relevant for catalysis.
A Novel Thermostable Cytochrome P450 from Sequence-Based Metagenomics of Binh Chau Hot Spring as a Promising Catalyst for Testosterone Conversion
Authors: Nguyen Kim-Thoa , Nguyen Ngọc-Lan , Tung Nguyen Van , Nguyen Huy Hoang , Milhim Mohammed , Le Thi-Thanh-Xuan , Lai Thi-Hong-Nhung , Phan Thi-Tuyet-Minh , Bernhardt Rita
Published: September 2020

Biotechnological applications of cytochromes P450 show difficulties, such as low activity, thermal and/or solvent instability, narrow substrate specificity and redox partner dependence. In an attempt to overcome these limitations, an exploitation of novel thermophilic P450 enzymes from nature via uncultured approaches is desirable due to their great advantages that can resolve nearly all mentioned impediments. From the metagenomics library of the Binh Chau hot spring, an open reading frame (ORF) encoding a thermostable cytochrome P450—designated as P450-T3—which shared 66.6% amino acid sequence identity with CYP109C2 of Sorangium cellulosum So ce56 was selected for further identification and characterization. The ORF was synthesized artificially and heterologously expressed in Escherichia coli C43(DE3) using the pET17b system. The purified enzyme had a molecular weight of approximately 43 kDa. The melting temperature of the purified enzyme was 76.2 °C and its apparent half-life at 60 °C was 38.7 min. Redox partner screening revealed that P450-T3 was reduced well by the mammalian AdR-Adx4-108 and the yeast Arh1-Etp1 redox partners. Lauric acid, palmitic acid, embelin, retinoic acid (all-trans) and retinoic acid (13-cis) demonstrated binding to P450-T3. Interestingly, P450-T3 also bound and converted testosterone. Overall, P450-T3 might become a good candidate for biocatalytic applications on a larger scale.
Syntheses of 3,3-Disubstituted Dihydrobenzofurans, Indolines, Indolinones and Isochromanes by Palladium-Catalyzed Tandem Reaction Using Pd(PPh3)2Cl2/(±)-BINAP as a Catalytic System
Authors: Yue Guizhou , Li Sicheng , Jiang Dan , Ding Gang , Feng Juhua , Chen Huabao , Yang Chunping , Yin Zhongqiong , Song Xu , Liang Xiaoxia , Zhang Li , Wang Xianxiang , Lu Cuifen
Published: September 2020

A general procedure for the tandem arylation reaction of arylbromide with heteroaryl compounds was developed by using Pd(PPh3)2Cl2/(±)-BINAP (1,1′-Binaphthalene-2,2′-diylbis (diphenylphosphane)) as catalytic system. Both sulphur- and oxygen-containing heterocycles were also employed as an efficient reagent for arylation, which gave moderate to excellent yields with moderate to good regioselectivities (5:1 to > 20:1 ir (isomer ratio)). Except for dihydrobenzofurans, indolines and indolinones, this type of tandem reaction was also expanded to synthesize isochromanes. The synthesized new compounds were well characterized through different spectroscopic techniques, such as 1H and 13C NMR (nuclear magnetic resonance), and mass spectral analysis.
Analysis of Temperature Change in Uzbekistan and the Regional Atmospheric Circulation of Middle Asia during 1961–2016
Authors: Kholmatjanov Bakhtiyar M. , Petrov Yuriy V. , Khujanazarov Temur , Sulaymonova Nigora N. , Abdikulov Farrukh I. , Tanaka Kenji
Published: September 2020

Climate change and shrinking of the Aral Sea have significantly affected the region’s temperature variations. Observed interannual changes in Uzbekistan’s air temperature compared to the duration of synoptic weather types (SWT) in Middle Asia were analyzed. Nonparametric Mann–Kendall statistical test and climate trends coefficients were used to identify trend characteristics of observed temperature from 1961–2016 to the baseline period of 1961–1990. The results showed increasing temperature trends average to 1 °C in warm and cold half years over Uzbekistan. The 1991–2016 decadal temperature trend ranged from 0.25 °C/decade in the northwest to 0.52 °C/decade in the center, especially pronounced in the oasis and Aral Sea zones. There were also significant changes in the structure of regional SWT. The main difference in the structure of SWT in Middle Asia relative to the baseline period was expressed in a decrease of cold mass invasion duration from 113.4 to 76.1 days and an increase in low-gradient baric field duration from 65.8 to 134.6 days. The process of anthropogenic warming, which began in Uzbekistan in the 1960s of the twentieth century, has accelerated from the mid-1970s with a higher mean annual air temperature than the baseline period’s climate normals (1961–1990) and is associated with changes in the regional SWT over Middle Asia.