bluuebunny/crossref_metadata_2025 huggingface dataset:
The Feasibility of Contrast-to-Noise Ratio on Measurements to Evaluate CT Image Quality in Terms of Low-Contrast Detailed Detectability
Authors: Alsleem Haney A , Almohiy Hussain M
Published: July 2020

Background: To evaluate contrast-to-noise ratio (CNR) measurements in assessing image quality, in the context of the detectability performance of low-contrast detail (LCD), in computed tomography (CT) images, since exposure to elevated ionising-type radiation is considered to present excessive carcinogenic risk, whilst also causing distress in study subjects. Methods: An LCD phantom module (CTP515) was utilised in the study. Three dissimilar contrast items were used to analyse the ramifications of the proportions of an object on the CNR. Three multidetector CT (MDCT) scanners were used, with 16-MDCT, 64-MDCT and 80-MDCT frameworks, respectively. The CT scans were recreated using three dissimilar remaking algorithms—soft, standard and lung. The effects exerted on the CNR by various remodelling algorithms, as well as the contrast of various objects along with the size of the objects, were explored. The Hounsfield units of each chosen object (one unit representing the outer portion of the object) and the background and the standard deviation of the noise parameter were quantified, and algorithms were developed using MATLAB. Results: The CNR information was greatly influenced by changing the image recreation calculations and was very much increased in the soft-tissue recreation images using 16-MDCT and 64-MDCT. The CNR information was also increased more in the optimum recreation images than in the reproduced images from the computational procedure used in the 80-MDCT. The results did not show any remarkable contrasts in the CNR values between the different object sizes. Overall, a higher kVp produced an improved CNR in all the CT scanners. In particular, there were prominent upgrades in the CNR information when the kVp was increased from 80 to 120. Higher mAs levels gave better CNR values overall, especially for greater section thicknesses. Based on the CNR estimations, the 64-MDCT provided the best correlation among the CT scanners. Conclusions: The objective LCD appraisal method, based on CNR measurements, was confirmed as being useful for checking the different impacts of kVp, mAs and section thickness on the nature of the picture. This procedure was similarly viable in assessing the impacts of the different reconstruction calculations and the different differentiation questions on the nature of the image.
Estimation of Heat Source Model’s Parameters for GMAW with Non-linear Global Optimization—Part I: Application of Multi-island Genetic Algorithm
Authors: Pyo Changmin , Kim Jisun , Kim Jaewoong
Published: July 2020

Estimating the thermo-elasto-plastic deformation by arc welding through finite element analysis has been used in various industrial fields. The Goldak heat source model is one of the most important and widely used models in finite element analysis, and its parameters are estimated based on the results of previous studies and tests. Part I of this study focused on the adequate heat source model, and the study for the welding deformation with the moving heat source will be done on the latter research. This study used the parameters of Goldak’s heat source model, weld efficiency, and the location of the heat source as design variables, and defined the Heat Affected Zone (HAZ) boundary line of Bead on Plate (BOP) welding as the target. BOP welding was performed using SS400 plates, the HAZ boundary line was determined based on examining the shape of the cross-section, and the optimization condition was that temperature inside the boundary line exceeded 727 °C while the temperature outside the line did not exceed 727 °C during the welding process. During this process, a multi-island genetic algorithm (non-linear global optimization method) was used to obtain the optimal results out of 1000 candidate groups, in which the HAZ boundary was similar to the experimental results. Applying a global optimization algorithm to determine the parameters of the most important heat source model to analyze welding deformation is significant, and this may be applied in various industrial fields that use welding including shipbuilding, aviation, and machinery industries.
Analysis of the Wall Geometry with Different Strategies for High Deposition Wire Arc Additive Manufacturing of Mild Steel
Authors: Aldalur Eider , Veiga Fernando , Suárez Alfredo , Bilbao Jon , Lamikiz Aitzol
Published: July 2020

Additive manufacturing has gained relevance in recent decades as an alternative to the manufacture of metal parts. Among the additive technologies, those that are classified as Directed Energy Deposition (DED) are characterized by their high deposition rate, noticeably, Wire Arc Additive Manufacturing (WAAM). However, having the inability to produce parts with acceptable final surface quality and high geometric precision is to be considered an important disadvantage in this process. In this paper, different torch trajectory strategies (oscillatory motion and overlap) in the fabrication of low carbon steel walls will be compared using Gas Metal Arc Welding (GMAW)-based WAAM technology. The comparison is done with a study of the mechanical and microstructural characteristics of the produced walls and finally, addressing the productivity obtained utilizing each strategy. The oscillation strategy shows better results, regarding the utilization rate of deposited material and the flatness of the upper surface, this being advantageous for subsequent machining steps.
Review of Intermediate Strain Rate Testing Devices
Authors: Bhujangrao Trunal , Froustey Catherine , Iriondo Edurne , Veiga Fernando , Darnis Philippe , Mata Franck Girot
Published: July 2020

Materials undergo various loading conditions during different manufacturing processes, including varying strain rates and temperatures. Research has shown that the deformation of metals and alloys during manufacturing processes such as metal forming, machining, and friction stir welding (FSW), can reach a strain rate ranging from 10−1 to 106 s−1. Hence, studying the flow behavior of materials at different strain rates is important to understanding the material response during manufacturing processes. Experimental data for a low strain rate of <101 s−1 and a high strain rate of >103 s−1 are readily available by using traditional testing devices such as a servo-hydraulic testing machine and the split Hopkinson pressure bar method, respectively. However, for the intermediate strain rate (101 to 103 s−1), very few testing devices are available. Testing the intermediate strain rate requires a demanding test regime, in which researchers have expanded the use of special instruments. This review paper describes the development and evolution of the existing intermediate strain rate testing devices. They are divided based on the loading mechanism; it includes the high-speed servo-hydraulic testing machines, hybrid testing apparatus, the drop tower, and the flywheel machine. A general description of the testing device is systematically reviewed; which includes the working principles, some critical theories, technological innovation in load measurement techniques, components of the device, basic technical assumption, and measuring techniques. In addition, some research direction on future implementation and development of an intermediate strain rate apparatus is also discussed in detail.
Study on Dissolution of Al2Cu in Al-4.3Cu and A205 Cast Alloys
Authors: Zamani Mohammadreza , Belov Ilia , Sjölander Emma , Bjurenstedt Anton , Ghassemali Ehsan , Seifeddine Salem
Published: July 2020

Evolution of microstructure in a binary Al-Cu system (Al-4.3Cu) and a commercially alloyed Al-Cu system (A205) during solution heat treatment was investigated using optical microscopy (OM), scanning electron microscopy (SEM), wavelength-dispersive X-ray spectroscopy (WDS), and differential scanning calorimetry (DSC). The diversified coarseness of the microstructure was initiated by controlling the solidification rate. Different solution treatment temperatures were applied to identify a proper solutioning temperature. The larger microstructural scale required an increased solutioning temperature and prolonged holding time to obtain homogenized solutes in the α-Al matrix. The diffusion of Cu primarily controlled the solution heat treatment process. A diffusion-based model was applied and calibrated to determine the dissolution rate of an Al2Cu particle in the matrix. The model operates on a similar time scale with the experimental results for the Al-4.3Cu and A205 alloys with various microstructural scales, different chemical compositions, and at different solution treatment temperatures. Three-dimensional (3D) reconstructed images from SEM images and energy dispersive spectroscopy (EDS) map of elements showed that TiB2 particles shield the Cu-rich phases in the boundaries of α-Al grains, presumably acting as a physical barrier to the diffusion of Cu solutes toward α-Al grains. The model also suggests that the effective diffusion coefficient of Cu in Al, in the presence of TiB2 particles, reduced by a factor of 2.0–2.5 in the A205 alloy compared with the binary Al-Cu alloy.
Metabolic Signatures of 10 Processed and Non-processed Meat Products after In Vitro Digestion
Authors: Wedekind Roland , Keski-Rahkonen Pekka , Robinot Nivonirina , Mercier Frederic , Engel Erwan , Huybrechts Inge , Scalbert Augustin
Published: July 2020

The intake of processed meat has been associated with several adverse health outcomes such as type II diabetes and cancer; however, the mechanisms are not fully understood. A better knowledge of the metabolite profiles of different processed and non-processed meat products from this heterogeneous food group could help in elucidating the mechanisms associated with these health effects. Thirty-three different commercial samples of ten processed and non-processed meat products were digested in triplicate with a standardized static in vitro digestion method in order to mimic profiles of small molecules formed in the gut upon digestion. A metabolomics approach based on high-resolution mass spectrometry was used to identify metabolite profiles specific to the various meat products. Processed meat products showed metabolite profiles clearly distinct from those of non-processed meat. Several discriminant features related to either specific ingredients or processing methods were identified. Those were, in particular, syringol compounds deposited in meat during smoking, biogenic amines formed during meat fermentation and piperine and related compounds characteristic of pepper used as an ingredient. These metabolites, characteristic of specific processed meat products, might be used as potential biomarkers of intake for these foods. They may also help in understanding the mechanisms linking processed meat intake and adverse health outcomes such as cancer.
Developing a Novel Miniature 3D-Printed TLBS with High Mechanical Efficiency and Better Controllability
Authors: Lee Chung-Wei , Chou Jung-Hua
Published: July 2020

This paper focuses on the development of a 3D-printed threadless ball screw (TLBS) for the applications that require miniaturization, customization, and accuracy controllability. To enhance the efficiency of the TLBS, a novel model of the TLBS for analyzing the mechanical efficiency is presented to obtain the key affecting factors. From these factors, the design parameters for fabrication are determined. For miniaturization, a novel 3D-printed one-piece preloaded structure of light weight of 0.9 g is implemented as the TLBS nut part. Experimental results show that the measured mechanical efficiency of TLBS is close to that predicted by the theoretical model with a normalized root mean square error of 3.16%. In addition, the mechanical efficiency of the present TLBS (maximum efficiency close to 90%) is better than that of the lead screw and close to the ball screw. The unique characteristic of the present TLBS is that its total torque loss is a weak function of the load, a phenomenon not observed in either the ball screw or the lead screw. This characteristic is advantageous in enhancing the controllability of accuracy at different loads.
Root Herbivory: Grass Species, Epichloë Endophytes and Moisture Status Make a Difference
Authors: Popay Alison J. , Jensen Joanne G. , Mace Wade J.
Published: July 2020

The root-feeding scarab insect Costelytra giveni causes severe damage to pasture ecosystems in New Zealand. Loline alkaloids produced by some Epichloë endophytes deter this insect. In two experiments, tall fescue infected with E. coenophiala, strain AR584, and endophyte-free (Nil) controls were subjected to pulse drought stress (DS) or well-watered conditions (WW). The second experiment also included meadow fescue infected with E. uncinata. After 4–6 weeks exposure to the different conditions, roots were excised and fed to C. giveni larvae for 7 days. Relative root consumption (RC), frass production, and relative weight change (RWC) of larvae were measured and the loline content of roots determined. RC and frass output were higher for larvae feeding on Nil DS tall fescue than WW and reduced by AR584. RWC was also greater on DS than on WW Nil plants but reduced by endophyte only in DS plants. RC, frass output, and RWC of larvae were reduced by endophyte in DS and WW meadow fescue, but the effect was greater for WW plants. Loline alkaloid concentration in roots was significantly higher in DS than WW tall fescue in Experiment I but higher in WW than DS meadow fescue in Experiment II. These experiments have demonstrated that moisture status interacts with endophyte to differentially affect root herbivory in tall fescue and meadow fescue.
Identification of a Novel Yersinia enterocolitica Strain from Bats in Association with a Bat Die-Off That Occurred in Georgia (Caucasus)
Authors: Imnadze Tata , Natradze Ioseb , Zhgenti Ekaterine , Malania Lile , Abazashvili Natalia , Sidamonidze Ketevan , Khmaladze Ekaterine , Zakalashvili Mariam , Imnadze Paata , Arner Ryan J. , Motin Vladimir , Kosoy Michael
Published: July 2020

Yersinia entercolitica is a bacterial species within the genus Yersinia, mostly known as a human enteric pathogen, but also recognized as a zoonotic agent widespread in domestic pigs. Findings of this bacterium in wild animals are very limited. The current report presents results of the identification of cultures of Y. entercolitica from dead bats after a massive bat die-off in a cave in western Georgia. The growth of bacterial colonies morphologically suspected as Yersinia was observed from three intestine tissues of 11 bats belonging to the Miniopterus schreibersii species. These three isolates were identified as Y. enterocolitica based on the API29 assay. No growth of Brucella or Francisella bacteria was observed from tissues of dead bats. Full genomes (a size between 4.6–4.7 Mbp) of the Yersinia strains isolated from bats were analyzed. The phylogenetic sequence analyses of the genomes demonstrated that all strains were nearly identical and formed a distinct cluster with the closest similarity to the environmental isolate O:36/1A. The bat isolates represent low-pathogenicity Biotype 1A strains lacking the genes for the Ail, Yst-a, Ysa, and virulence plasmid pYV, while containing the genes for Inv, YstB, and MyfA. Further characterization of the novel strains cultured from bats can provide a clue for the determination of the pathogenic properties of those strains.
A Genome-Scale Metabolic Model of 2,3-Butanediol Production by Thermophilic Bacteria Geobacillus icigianus
Authors: Kulyashov Mikhail , Peltek Sergey E. , Akberdin Ilya R.
Published: July 2020

The thermophilic strain of the genus Geobacillus, Geobacillus icigianus is a promising bacterial chassis for a wide range of biotechnological applications. In this study, we explored the metabolic potential of Geobacillus icigianus for the production of 2,3-butanediol (2,3-BTD), one of the cost-effective commodity chemicals. Here we present a genome-scale metabolic model iMK1321 for Geobacillus icigianus constructed using an auto-generating pipeline with consequent thorough manual curation. The model contains 1321 genes and includes 1676 reactions and 1589 metabolites, representing the most-complete and publicly available model of the genus Geobacillus. The developed model provides new insights into thermophilic bacterial metabolism and highlights new strategies for biotechnological applications of the strain. Our analysis suggests that Geobacillus icigianus has a potential for 2,3-butanediol production from a variety of utilized carbon sources, including glycerine, a common byproduct of biofuel production. We identified a set of solutions for enhancing 2,3-BTD production, including cultivation under anaerobic or microaerophilic conditions and decreasing the TCA flux to succinate via reducing citrate synthase activity. Both in silico predicted metabolic alternatives have been previously experimentally verified for closely related strains including the genus Bacillus.
Relationship between the Oral and Vaginal Microbiota of South African Adolescents with High Prevalence of Bacterial Vaginosis
Authors: Balle Christina , Esra Rachel , Havyarimana Enock , Jaumdally Shameem Z. , Lennard Katie , Konstantinus Iyaloo N. , Barnabas Shaun L. , Happel Anna-Ursula , Gill Katherine , Pidwell Tanya , Lingappa Jairam R. , Gamieldien Hoyam , Bekker Linda-Gail , Passmore Jo-Ann S. , Jaspan Heather B.
Published: July 2020

Bacterial vaginosis (BV) and periodontal disease (PD) are characterised as bacterial dysbioses. Both are associated with an increased risk of poor pregnancy outcomes, yet it is unknown whether PD and BV are related. We characterised the oral microbiota of young South African females with a high prevalence of BV and investigated the association between oral communities and vaginal microbiota. DNA was extracted from vaginal lateral wall, saliva and supragingival plaque samples from 94 adolescent females (aged 15–19 years). 16S rRNA gene sequencing of the V4 hypervariable region was performed for analysis of the oral and vaginal microbiota and BV status was determined by Nugent scoring. The core oral microbiota was predominately comprised of Firmicutes followed by Proteobacteria and Bacteroidetes. The salivary microbiota of participants with BV was more diverse than those with lactobacillus-dominated communities (p = 0.030). PD-associated bacterial species, including Prevotella intermedia and Porphyromonas endodontalis were enriched in the supragingival microbiota of women with non-optimal vaginal communities compared to those with Lactobacillus-dominant communities, while Pseudomonas aeruginosa and Prevotella intermedia were enriched in the saliva of women with non-optimal vaginal microbiota. These data suggest a relationship between oral and vaginal dysbiosis, warranting further investigation into whether they are casually related.
Notch-1 Signaling Modulates Macrophage Polarization and Immune Defense against Mycobacterium avium paratuberculosis Infection in Inflammatory Diseases
Authors: Keewan Esra’a , Naser Saleh A.
Published: July 2020

Despite the extensive research on Notch signaling involvement in inflammation, its specific role in macrophage response in autoimmune disease and defense mechanisms against bacterial infection, such as Mycobacterium avium paratuberculosis (MAP), remains unknown. In this study, we investigated the molecular role of Notch-1 signaling in the macrophage response during MAP infection. In particular, we measured the in vitro effect of MAP on Notch-1 signaling and downstream influence on interleukin (IL)-6 and myeloid cell leukemia sequence-1 (MCL-1) and consequent cellular apoptosis, MAP viability, and macrophage polarization. Overall, the data show significant upregulation in Notch-1, IL-6, and MCL-1 in MAP-infected macrophages, parallel with a decrease in apoptosis and elevated pro-inflammatory response in these infected cells. On the contrary, blocking Notch signaling with γ-secretase inhibitor (DAPT) decreased MAP survival and burden, increased apoptosis, and diminished the pro-inflammatory response. In particular, the treatment of infected macrophages with DAPT shifted macrophage polarization toward M2 anti-inflammatory phenotypic response. The outcome of this study clearly demonstrates the critical role of Notch signaling in macrophage response during infection. We conclude that MAP infection in macrophages activates Notch-1 signaling and downstream influence on IL-6 which hijack MCL-1 dependent inhibition of apoptosis leading to its chronic persistence, and further inflammation. This study supports Notch-1 signaling as a therapeutic target to combat infection in autoimmune diseases such as Crohn’s disease and Rheumatoid Arthritis.
Tetrahymena Glutathione Peroxidase Family: A Comparative Analysis of These Antioxidant Enzymes and Differential Gene Expression to Metals and Oxidizing Agents
Authors: Cubas-Gaona Liliana L. , de Francisco Patricia , Martín-González Ana , Gutiérrez Juan Carlos
Published: July 2020

In the present work, an extensive analysis of the putative glutathione peroxidases (GPx) of the eukaryotic microorganism model Tetrahymena thermophila is carried out. A comparative analysis with GPx present in other Tetrahymena species and other very taxonomically diverse ciliates is also performed. A majority of ciliate GPx have replaced the selenocysteine (Sec) by Cys in its catalytic center, so they can be considered as phospholipid hydroperoxide glutathione peroxidases (PHGPx). Selenocysteine insertion sequence (SECIS) elements have been detected in several ciliate GPx that do not incorporate Sec in their amino acid sequences, and conversely, in other ciliate GPx with Sec, no SECIS elements are detected. These anomalies are analyzed and discussed. From the phylogenetic analysis using the ciliate GPx amino acid sequences, the existence of extensive intra- and interspecific gene duplications that produced multiple GPx isoforms in each species is inferred. The ancestral character of the selenoproteins is also corroborated. The analysis by qRT-PCR of six selected T. thermophila GPx genes has shown a quantitative differential expression between them, depending on the stressor (oxidizing agents, apoptotic inducer or metals) and the time of exposure.
Identification of Economic Activity in a Bronze Age Settlement in Central Russia Based on the Results of XRF Analysis of Samples of the Cultural Layer
Authors: Voronin Konstantin
Published: July 2020

In central Russia, the examination of characteristics of economic activity of Bronze Age settlements and the determination of functional zones that existed in their territories in the first half of the second millennium BC based on the results of XRF (X-ray Fluorescence) analysis of samples of the cultural layer have never been done before. The data from elemental analysis of the samples of the cultural layer of the Bronze Age settlement Pesochnoe 1 from an excavation area of 126 m2 obtained via the XRF method showed significant content of copper (Cu), zinc (Zn), calcium (Ca) and phosphorus (P), several times exceeding the content of the same chemical elements in the surrounding soils. The discovered Cu can be associated with metalworking, Zn are likely from ash and the biomass of the aquatic environment, and Ca and P can be found in bone remnants. Analysis of the spatial distribution of archaeological objects with quantitative indicators of Cu, Zn, Ca, P made it possible to distinguish two functional areas in the excavation of the Bronze Age settlement. A very high concentration of Cu, Zn, Ca, P recorded in the first functional zone, in the center of which was a hearth, indicates diverse activity that took place in this territory, including the use of different organic materials (plants, bones) as fuel and melting of metal. The second functional area with high concentrations of Zn, Ca and especially P suggests it was a place where biomaterials of animal origin might have been used.
Micro RNA Sensing with Green Emitting Silver Nanoclusters
Authors: Yourston Liam E. , Krasnoslobodtsev Alexey V.
Published: July 2020

Micro RNA (miR) are regulatory non-coding RNA molecules, which contain a small number of nucleotides ~18–28 nt. There are many various miR sequences found in plants and animals that perform important functions in developmental, metabolic, and disease processes. miRs can bind to complementary sequences within mRNA molecules thus silencing mRNA. Other functions include cardiovascular and neural development, stem cell differentiation, apoptosis, and tumors. In tumors, some miRs can function as oncogenes, others as tumor suppressors. Levels of certain miR molecules reflect cellular events, both normal and pathological. Therefore, miR molecules can be used as biomarkers for disease diagnosis and prognosis. One of these promising molecules is miR-21, which can serve as a biomarker with high potential for early diagnosis of various types of cancer. Here, we present a novel design of miR detection and demonstrate its efficacy on miR-21. The design employs emissive properties of DNA-silver nanoclusters (DNA/AgNC). The detection probe is designed as a hairpin DNA structure with one side of the stem complimentary to miR molecule. The binding of target miR-21 opens the hairpin structure, dramatically modulating emissive properties of AgNC hosted by the C12 loop of the hairpin. “Red” fluorescence of the DNA/AgNC probe is diminished in the presence of the target miR. At the same time, “green” fluorescence is activated and its intensity increases several-fold. The increase in intensity of “green” fluorescence is strong enough to detect the presence of miR-21. The intensity change follows the concentration dependence of the target miR present in a sample, which provides the basis of developing a new, simple probe for miR detection. The detection strategy is specific, as demonstrated using the response of the DNA/AgNC probe towards the scrambled miR-21 sequence and miR-25 molecule. Additionally, the design reported here is very sensitive with an estimated detection limit at ~1 picomole of miR-21.
In Vitro Interaction of Organophosphono- and Organophosphorothioates with Human Acetylcholinesterase
Authors: Worek Franz , Thiermann Horst , Koller Marianne , Wille Timo
Published: July 2020

The implementation of the Chemical Weapons Convention (CWC) in 1997 was a milestone in the prohibition of chemical warfare agents (CWA). Yet, the repeated use of CWA underlines the ongoing threat to the population. Organophosphorus (OP) nerve agents still represent the most toxic CWA subgroup. Defensive research on nerve agents is mainly focused on the “classical five”, namely tabun, sarin, soman, cyclosarin and VX, although Schedule 1 of the CWC covers an unforeseeable number of homologues. Likewise, an uncounted number of OP pesticides have been produced in previous decades. Our aim was to determine the in vitro inhibition kinetics of selected organophosphono- and organophosphorothioates with human AChE, as well as hydrolysis of the agents in human plasma and reactivation of inhibited AChE, in order to derive potential structure–activity relationships. The investigation of the interactions of selected OP compounds belonging to schedule 1 (V-agents) and schedule 2 (amiton) of the CWC with human AChE revealed distinct structural effects of the P-alkyl, P-O-alkyl and N,N-dialkyl residues on the inhibitory potency of the agents. Irrespective of structural modifications, all tested V-agents presented as highly potent AChE inhibitors. The high stability of the tested agents in human plasma will most likely result in long-lasting poisoning in vivo, having relevant consequences for the treatment regimen. In conclusion, the results of this study emphasize the need to investigate the biological effects of nerve agent analogues in order to assess the efficacy of available medical countermeasures.
Exploring the Characteristics of an Aroma-Blending Mixture by Investigating the Network of Shared Odors and the Molecular Features of Their Related Odorants
Authors: Tromelin Anne , Koensgen Florian , Audouze Karine , Guichard Elisabeth , Thomas-Danguin Thierry
Published: July 2020

The perception of aroma mixtures is based on interactions beginning at the peripheral olfactory system, but the process remains poorly understood. The perception of a mixture of ethyl isobutyrate (Et-iB, strawberry-like odor) and ethyl maltol (Et-M, caramel-like odor) was investigated previously in both human and animal studies. In those studies, the binary mixture of Et-iB and Et-M was found to be configurally processed. In humans, the mixture was judged as more typical of a pineapple odor, similar to allyl hexanoate (Al-H, pineapple-like odor), than the odors of the individual components. To explore the key features of this aroma blend, we developed an in silico approach based on molecules having at least one of the odors—strawberry, caramel or pineapple. A dataset of 293 molecules and their related odors was built. We applied the notion of a “social network” to describe the network of the odors. Additionally, we explored the structural properties of the molecules in this dataset. The network of the odors revealed peculiar links between odors, while the structural study emphasized key characteristics of the molecules. The association between “strawberry” and “caramel” notes, as well as the structural diversity of the “strawberry” molecules, were notable. Such elements would be key to identifying potential odors/odorants to form aroma blends.
Chemistry and Biological Activities of 1,2,4-Triazolethiones—Antiviral and Anti-Infective Drugs
Authors: Aly Ashraf A. , A. Hassan Alaa , Makhlouf Maysa M. , Bräse Stefan
Published: July 2020

Mercapto-substituted 1,2,4-triazoles are very interesting compounds as they play an important role in chemopreventive and chemotherapeutic effects on cancer. In recent decades, literature has been enriched with sulfur- and nitrogen-containing heterocycles which are used as a basic nucleus of different heterocyclic compounds with various biological applications in medicine and also occupy a huge part of natural products. Therefore, we shed, herein, more light on the synthesis of this interesting class and its application as a biologically active moiety. They might also be suitable as antiviral and anti-infective drugs.
Droplet Rolling and Spinning in V-Shaped Hydrophobic Surfaces for Environmental Dust Mitigation
Authors: Yakubu Mubarak , Yilbas Bekir Sami , Abubakr Abba A. , Al-Qahtani Hussain
Published: July 2020

The motion of a water droplet in a hydrophobic wedge fixture was examined to assess droplet rolling and spinning for improved dust mitigation from surfaces. A wedge fixture composed of two inclined hydrophobic plates had different wetting states on surfaces. Droplet rolling and spinning velocities were analyzed and findings were compared with the experiments. A wedge fixture was designed and realized using a 3D printing facility and a high speed recording system was adopted to evaluate droplet motion in the wedge fixture. Polycarbonate sheets were used as plates in the fixture, and solution crystallization and functionalized silica particles coating were adopted separately on plate surfaces, which provided different wetting states on each plate surface while generating different droplet pinning forces on each hydrophobic plate surface. This arrangement also gave rise to the spinning of rolling droplets in the wedge fixture. Experiments were extended to include dust mitigation from inclined hydrophobic surfaces while incorporating spinning- and rolling droplet and rolling droplet-only cases. The findings revealed the wedge fixture arrangement resulted in spinning and rolling droplets and spinning velocity became almost 25% of the droplet rolling velocity, which agrees well with both predictions and experiments. Rolling and spinning droplet gave rise to parallel edges droplet paths on dusty hydrophobic surfaces while striations in droplet paths were observed for rolling droplet-only cases. Spinning and rolling droplets mitigated a relatively larger area of dust on inclined hydrophobic surfaces as compared to their counterparts corresponding to rolling droplet-only cases.
Neopapillarine, an Unusual Coumarino-Alkaloid from the Root Extract of Neocryptodiscus papillaris with Cytotoxic Activity on Renal Cancer Cells
Authors: Tosun Fatma , Mıhoğlugil Feyyaz , Beutler John A. , Eroğlu Özkan Esra , Miski Mahmut
Published: July 2020

Several simple and prenylated coumarin derivatives were isolated from the dichloromethane extract of the root of Neocryptodiscus papillaris based on moderate cytotoxic activity of the extract in COLO205, KM12 and MCF7 cancer cells. While the major prenylated furanocoumarin derivatives and osthol isolated from the dichloromethane extract were responsible for the activity in the colon and breast cancer cell lines, the 4′-acylated osthol derivatives including a novel coumarino-alkaloid; neopapillarine) demonstrated selective cytotoxic activity in A498 and UO31 renal cancer cell lines.
AMP–Chitosan Coating with Bactericidal Activity in the Presence of Human Plasma Proteins
Authors: Monteiro Cláudia , Fernandes Hélia , Oliveira Diana , Vale Nuno , Barbosa Mariana , Gomes Paula , L. Martins M. Cristina
Published: July 2020

Antibiotic resistance is increasing and new strategies are needed to fight infection. Advanced materials are promising tools that can be combined with innovative alternatives to conventional antibiotics to allow more targeted and efficient treatment. In this work, we explored the activity against Staphylococcus epidermidis (S. epidermidis) of the α-helical antimicrobial peptide (AMP) MSI-78(4-20) (KFLKKAKKFGKAFVKIL) when covalently bound to a chitosan coating. The AMP MSI-78(4-20) (17 mer) is an improved version of its parent MSI-78 (22 mer; commercially known as Pexiganan), a cost-effective short AMP, which was demonstrated to be as effective as MSI-78 and less toxic to eukaryotic cells. An MSI-78(4-20)–chitosan coating could be applied in several infection scenarios, ranging from bone implants to wound dressings, as chitosan possesses osteoconductive and hemostatic properties. Cysteine-modified MSI-78(4-20) was covalently immobilized onto the chitosan coating through a succinimidyl-[(N-maleimidopropionamido)-octaethyleneglycol] ester (SM(PEG)8), a heterobifuncional crosslinker, with N-hydroxysuccinimide (NHS) ester and maleimide groups, by its N- and C- termini. The MSI-78(4-20)–chitosan coating demonstrated bactericidal properties independently of the tethering site and an improved performance in the presence of plasma proteins, which mimics conditions that will be encountered in vivo. This AMP–chitosan coating has therefore great potential for applications in medical devices such as implants or even wound dressings.
Towards Robust Delivery of Antimicrobial Peptides to Combat Bacterial Resistance
Authors: Drayton Matthew , Kizhakkedathu Jayachandran N. , Straus Suzana K.
Published: July 2020

Antimicrobial peptides (AMPs), otherwise known as host defence peptides (HDPs), are naturally occurring biomolecules expressed by a large array of species across the phylogenetic kingdoms. They have great potential to combat microbial infections by directly killing or inhibiting bacterial activity and/or by modulating the immune response of the host. Due to their multimodal properties, broad spectrum activity, and minimal resistance generation, these peptides have emerged as a promising response to the rapidly concerning problem of multidrug resistance (MDR). However, their therapeutic efficacy is limited by a number of factors, including rapid degradation, systemic toxicity, and low bioavailability. As such, many strategies have been developed to mitigate these limitations, such as peptide modification and delivery vehicle conjugation/encapsulation. Oftentimes, however, particularly in the case of the latter, this can hinder the activity of the parent AMP. Here, we review current delivery strategies used for AMP formulation, focusing on methodologies utilized for targeted infection site release of AMPs. This specificity unites the improved biocompatibility of the delivery vehicle with the unhindered activity of the free AMP, providing a promising means to effectively translate AMP therapy into clinical practice.
A Biocompatible, Stimuli-Responsive, and Injectable Hydrogel with Triple Dynamic Bonds
Authors: Chen Yujie , Zhang Runjing , Zheng Baiqin , Cai Chao , Chen Zhen , Li Hua , Liu Hezhou
Published: July 2020

Injectable hydrogels have attracted growing interests as promising biomaterials for clinical applications, due to their minimum invasive implanting approach and easy-handling performance. Nevertheless, natural biomaterials-based injectable hydrogels with desirable nontoxicity are suffering from limited functions, failing to fulfill the requirements of clinical biomaterials. The development of novel injectable biomaterials with a combination of biocompatibility and adequate functional properties is a growing urgency toward biomedical applications. In this contribution, we report a simple and effective approach to fabricate multi-functional CMC-OSA-DTP hydrogels. Two kinds of natural polysaccharide derived polymers, carboxymethyl chitosan (CMC) and oxidized alginate (OSA) along with 3,3′-dithiopropionic acid dihydrazide (DTP) were utilized to introduce three dynamic covalent bonds. Owing to the existence of triple dynamic bonds, this unique CMC-OSA-DTP hydrogel possessed smart redox and pH stimuli-responsive property, injectability as well as self-healing ability. In addition, the CCK-8 and live/dead assays demonstrated satisfying cytocompatibility of the CMC-OSA-DTP hydrogel in vitro. Based on its attractive properties, this easy-fabricated and multi-functional hydrogel demonstrated the great potential as an injectable biomaterial in a variety of biomedical applications.
Synthesis and Biological Evaluation of Analogs of Didehydroepiandrosterone as Potential New Anticancer Agents
Authors: J. Solum Eirik , Liekens Sandra , Hansen Trond Vidar
Published: July 2020

The synthesis, cytotoxicity and inhibition of CDK8 by thirteen analogs of cortistatin A are reported. These efforts revealed that the analogs with either a 6- or 7-isoquinoline or 5-indole side chain in the 17-position are the most promising anti-proliferative agents. These compounds showed potent cytotoxic effects in CEM, HeLa and HMEC-1 cells. All three compounds exhibited IC50 values < 10µM. The most interesting 10l analog exhibited an IC50 value of 0.59 µM towards the human dermal microvascular endothelial cell line (HMEC-1), significantly lower than the reference standard 2-methoxyestradiol. At a concentration at 50 nM the most potent 10h compound reduced the activity of CDK8 to 35%.
Synthesis and Antimicrobial Activity of Novel 4-Hydroxy-2-quinolone Analogs
Authors: Khamkhenshorngphanuch Thitiphong , Kulkraisri Kittipat , Janjamratsaeng Alongkorn , Plabutong Napasawan , Thammahong Arsa , Manadee Kanitta , Na Pombejra Sarisa , Khotavivattana Tanatorn
Published: July 2020

Alkyl quinolone has been proven to be a privileged scaffold in the antimicrobial drug discovery pipeline. In this study, a series of new 4-hydroxy-2-quinolinone analogs containing a long alkyl side chain at C-3 and a broad range of substituents on the C-6 and C-7 positions were synthesized. The antibacterial and antifungal activities of these analogs against Staphylococcus aureus, Escherichia coli, and Aspergillus flavus were investigated. The structure-activity relationship study revealed that the length of the alkyl chain, as well as the type of substituent, has a dramatic impact on the antimicrobial activities. Particularly, the brominated analogs 3j with a nonyl side chain exhibited exceptional antifungal activities against A. flavus (half maximal inhibitory concentration (IC50) = 1.05 µg/mL), which surpassed that of the amphotericin B used as a positive control. The antibacterial activity against S. aureus, although not as potent, showed a similar trend to the antifungal activity. The data suggest that the 4-hydroxy-2-quinolone is a promising framework for the further development of new antimicrobial agents, especially for antifungal treatment.
Effects of Sesamin, the Major Furofuran Lignan of Sesame Oil, on the Amplitude and Gating of Voltage-Gated Na+ and K+ Currents
Authors: Kuo Ping-Chung , Kao Zi-Han , Lee Shih-Wei , Wu Sheng-Nan
Published: July 2020

Sesamin (SSM) and sesamolin (SesA) are the two major furofuran lignans of sesame oil and they have been previously noticed to exert various biological actions. However, their modulatory actions on different types of ionic currents in electrically excitable cells remain largely unresolved. The present experiments were undertaken to explore the possible perturbations of SSM and SesA on different types of ionic currents, e.g., voltage-gated Na+ currents (INa), erg-mediated K+ currents (IK(erg)), M-type K+ currents (IK(M)), delayed-rectifier K+ currents (IK(DR)) and hyperpolarization-activated cation currents (Ih) identified from pituitary tumor (GH3) cells. The exposure to SSM or SesA depressed the transient and late components of INa with different potencies. The IC50 value of SSM needed to lessen the peak or sustained INa was calculated to be 7.2 or 0.6 μM, while that of SesA was 9.8 or 2.5 μM, respectively. The dissociation constant of SSM-perturbed inhibition on INa, based on the first-order reaction scheme, was measured to be 0.93 μM, a value very similar to the IC50 for its depressant action on sustained INa. The addition of SSM was also effective at suppressing the amplitude of resurgent INa. The addition of SSM could concentration-dependently inhibit the IK(M) amplitude with an IC50 value of 4.8 μM. SSM at a concentration of 30 μM could suppress the amplitude of IK(erg), while at 10 μM, it mildly decreased the IK(DR) amplitude. However, the addition of neither SSM (10 μM) nor SesA (10 μM) altered the amplitude or kinetics of Ih in response to long-lasting hyperpolarization. Additionally, in this study, a modified Markovian model designed for SCN8A-encoded (or NaV1.6) channels was implemented to evaluate the plausible modifications of SSM on the gating kinetics of NaV channels. The model demonstrated herein was well suited to predict that the SSM-mediated decrease in peak INa, followed by increased current inactivation, which could largely account for its favorable decrease in the probability of the open-blocked over open state of NaV channels. Collectively, our study provides evidence that highlights the notion that SSM or SesA could block multiple ion currents, such as INa and IK(M), and suggests that these actions are potentially important and may participate in the functional activities of various electrically excitable cells in vivo.
Biological Activities of Selected Plants and Detection of Bioactive Compounds from Ardisia elliptica Using UHPLC-Q-Exactive Orbitrap Mass Spectrometry
Authors: Wong Pei Lou , Fauzi Nurul Azila , Mohamed Yunus Siti Norhamimah , Abdul Hamid Nur Ashikin , Abd Ghafar Siti Zulaikha , Azizan Awanis , Zolkeflee Nur Khaleeda Zulaikha , Abas Faridah
Published: July 2020

Plants and plant-based products have been used for a long time for medicinal purposes. This study aimed to determine the antioxidant and anti-α-glucosidase activities of eight selected underutilized plants in Malaysia: Leucaena leucocephala, Muntingia calabura, Spondias dulcis, Annona squamosa, Ardisia elliptica, Cynometra cauliflora, Ficus auriculata, and Averrhoa bilimbi. This study showed that the 70% ethanolic extract of all plants exhibited total phenolic content (TPC) ranging from 51 to 344 mg gallic acid equivalent (GAE)/g dry weight. A. elliptica showed strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging activities, with half maximal inhibitory concentration (IC50) values of 2.17 and 49.43 μg/mL, respectively. Most of the tested plant extracts showed higher inhibition of α-glucosidase enzyme activity than the standard, quercetin, particularly A. elliptica, F. auriculata, and M. calabura extracts with IC50 values of 0.29, 0.36, and 0.51 μg/mL, respectively. A total of 62 metabolites including flavonoids, triterpenoids, benzoquinones, and fatty acids were tentatively identified in the most active plant, i.e., A. elliptica leaf extract, by using ultra-high-performance liquid chromatography (UHPLC)–electrospray ionization (ESI) Orbitrap MS. This study suggests a potential natural source of antioxidant and α-glucosidase inhibitors from A. elliptica.
Molecular Structure Modulated Trap Distribution and Carrier Migration in Fluorinated Epoxy Resin
Authors: Li Jin , Wang Yufan , Ran Zhaoyu , Yao Hang , Du Boxue , Takada Tatsuo
Published: July 2020

Surface charge accumulation on epoxy insulators is one of the most serious problems threatening the operation safety of the direct current gas-insulated transmission line (GIL), and can be efficiently inhibited by the surface modification technology. This paper investigated the mechanisms of fluorination modulated surface charge behaviors of epoxy resin through quantum chemical calculation (QCC) analysis of the molecular structure. The results show that after fluorination, the surface charge dissipation process of the epoxy sample is accelerated by the introduced shallow trap sites, which is further clarified by the carrier mobility model. The electron distribution probability of the highest occupied molecular orbitals (HOMO) under positive charging and the lowest unoccupied molecular orbitals (LUMO) under negative charging shows distinctive patterns. It is illustrated that electrons are likely to aggregate locally around benzenes for the positively charged molecular structure, while electrons tend to distribute all along the epoxy chain under negatively charging. The calculated results verify that fluorination can modulate surface charge behaviors of epoxy resin through redesigning its molecular structure, trap distribution and charging patterns.
New Terpendole Congeners, Inhibitors of Sterol O-Acyltransferase, Produced by Volutella citrinella BF-0440
Authors: Nur Elyza Aiman Azizah , Kobayashi Keisuke , Amagai Ai , Ohshiro Taichi , Tomoda Hiroshi
Published: July 2020

New terpendoles N-P (1–3) were isolated along with 8 structurally related known compounds including terpendoles and voluhemins from a culture broth of the fungus Volutella citrinella BF-0440. The structures of 1–3 were elucidated using various spectroscopic experiments including 1D- and 2D-NMR. All compounds 1–3 contained a common indole–diterpene backbone. Compounds 2 and 3 had 7 and 6 consecutive ring systems with an indole ring, respectively, whereas 1 had a unique indolinone plus 4 consecutive ring system. Compounds 2 and 3 inhibited both sterol O-acyltransferase 1 and 2 isozymes, but 1 lost the inhibitory activity. Structure–activity relationships of fungal indole–diterpene compounds are discussed.