bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateral Angular Co-Extrusion: Geometrical and Mechanical Properties of Compound Profiles
Authors: Thürer Susanne Elisabeth , Peddinghaus Julius , Heimes Norman , Bayram Ferdi Caner , Bal Burak , Uhe Johanna , Behrens Bernd-Arno , Maier Hans Jürgen , Klose Christian
Published: August 2020

A novel co-extrusion process for the production of coaxially reinforced hollow profiles has been developed. Using this process, hybrid hollow profiles made of the aluminum alloy EN AW-6082 and the case-hardening steel 20MnCr5 (AISI 5120) were produced, which can be forged into hybrid bearing bushings by subsequent die forging. For the purpose of co-extrusion, a modular tooling concept was developed where steel tubes made of 20MnCr5 are fed laterally into the tool. This LACE (lateral angular co-extrusion) process allows for a variation of the volume fraction of the reinforcement by using steel tubes with different wall thicknesses, which enabled the production of compound profiles having reinforcement contents of either 14 vol.% or 34 vol.%. The shear strength of the bonding area of these samples was determined in push-out tests. Additionally, mechanical testing of segments of the hybrid profiles using shear compression tests was employed to provide information about the influence of different bonding mechanisms on the strength of the composite zone.
Identification of Potential Biomarkers in the Cervicovaginal Fluid by Metabolic Profiling for Preterm Birth
Authors: Ansari AbuZar , Lee Heeyeon , You Young-Ah , Jung Youngae , Park Sunwha , Kim Soo Min , Hwang Geum-Sook , Kim Young Ju
Published: August 2020

During pregnancy, dysbiosis in the vaginal microbiota directly affects the metabolic profiles, which might impact preterm birth (PTB). In this study, we performed cervicovaginal fluid (CVF) metabolic profiling using nuclear magnetic resonance (NMR) spectroscopy and identified the metabolic markers for predicting PTB. In this nested case-control study, 43 South Korean pregnant women with PTB (n = 22), and term birth (TB; n = 21) were enrolled with their demographic profiles, and CVF samples were collected by vaginal swabs. The PTB group had two subgroups based on post-CVF sampling birth: PTB less than (PTB < 7 d) and more than 7 days (PTB ≥ 7 d). We observed significant differences in the gestational age at birth (GAB), cervical length (CL), and neonatal birth weight among the groups. The principal component analysis (PCA), and partial least square discriminant analysis (PLS-DA) scatter plot showed the separation between the PTB < 7 d group, and the TB group. Out of 28 identified metabolites, acetone, ethanol, ethylene glycol, formate, glycolate, isopropanol, methanol, and trimethylamine N-oxide (TMAO) were significantly increased in the PTB group compared with the TB group. The ROC curve analysis revealed that the acetone, ethylene glycol, formate, glycolate, isopropanol, methanol, and TMAO had the best predictive values for PTB. Additionally, the correlation analysis of these metabolites showed a strong negative correlation with GAB and CL. These metabolites could be beneficial markers for the clinical application of PTB prediction.
The Development of a Pipeline for the Identification and Validation of Small-Molecule RelA Inhibitors for Use as Anti-Biofilm Drugs
Authors: Hall Donald C. , Król Jarosław E. , Cahill John P. , Ji Hai-Feng , Ehrlich Garth D.
Published: August 2020

Biofilm infections have no approved effective medical treatments and can only be disrupted via physical means. This means that any biofilm infection that is not addressable surgically can never be eliminated and can only be managed as a chronic disease. Therefore, there is an urgent need for the development of new classes of drugs that can target the metabolic mechanisms within biofilms which render them recalcitrant to traditional antibiotics. Persister cells within the biofilm structure may play a large role in the enhanced antibiotic recalcitrance of bacteria biofilms. Biofilm persister cells can be resistant to up to 1000 times the minimal inhibitory concentrations of many antibiotics, as compared to their planktonic envirovars; they are thought to be the prokaryotic equivalent of metazoan stem cells. Their metabolic resistance has been demonstrated to be an active process induced by the stringent response that is triggered by the ribosomally-associated enzyme RelA in response to amino acid starvation. This 84-kD pyrophosphokinase produces the “magic spot” alarmones, collectively called (p)ppGpp. These alarmones act by directly regulating transcription by binding to RNA polymerase. These transcriptional changes lead to a major shift in cellular function to both upregulate oxidative stress-combating enzymes and down regulate major cellular functions associated with growth and replication. These changes in gene expression produce the quiescent persister cells. In this work, we describe a hybrid in silico laboratory pipeline for identifying and validating small-molecule inhibitors of RelA for use in the combinatorial treatment of bacterial biofilms as re-potentiators of classical antibiotics.
Chiral Mesoporous Silica Materials: A Review on Synthetic Strategies and Applications
Authors: Cui Mingshu , Zhang Wei , Xie Luyao , Chen Lu , Xu Lu
Published: August 2020

Because of its tunable textural properties and chirality feature, chiral mesoporous silica (CMS) gained significant consideration in many fields and has been developed rapidly in recent years. In this review, we provide an overview of synthesis strategies for fabricating CMS together with its main applications. The properties of CMS, including morphology and mesostructures and enantiomer excess (ee), can be altered according to the synthetic conditions during the synthesis process. Despite its primary stage, CMS has attracted extensive attention in many fields. In particular, CMS nanoparticles are widely used for enantioselective resolution and adsorption of chiral compounds with desirable separation capability. Also, CMS acts as a promising candidate for the effective delivery of chiral or achiral drugs to produce a chiral-responsive manner. Moreover, CMS also plays an important role in chromatographic separations and asymmetric catalysis. There has been an in-depth review of the synthetic methods and mechanisms of CMS. And this review aims to give a deep insight into the synthesis and application of CMS, especially in recent years, and highlights the significance that it may have in the future.
Different Electrochemical Sensor Designs Based on Diazonium Salts and Gold Nanoparticles for Pico Molar Detection of Metals
Authors: Ait-Touchente Zouhair , Falah Sana , Scavetta Erika , Chehimi Mohamed M. , Touzani Rachid , Tonelli Domenica , Taleb Abdelhafed
Published: August 2020

We report a comparison of sensors’ performance of different hybrid nanomaterial architectures modifying an indium tin oxide (ITO) electrode surface. Diazonium salts and gold nanoparticles (AuNPs) were used as building units to design hybrid thin films of successive layers on the ITO electrode surface. Different architectures of hybrid thin films were prepared and characterized with different techniques, such as TEM, FEG-SEM, XPS, and EIS. The prepared electrodes were used to fabricate sensors for heavy metal detection and their performances were investigated using the square wave voltammetry (SWV) method. The comparison of the obtained results shows that the deposition of AuNPs on the ITO surface, and their subsequent functionalization by diazonium salt, is the best performing architecture achieving a high sensitivity in terms of the lower detection limit of pico molar.
New Hybrids of 4-Amino-2,3-polymethylene-quinoline and p-Tolylsulfonamide as Dual Inhibitors of Acetyl- and Butyrylcholinesterase and Potential Multifunctional Agents for Alzheimer’s Disease Treatment
Authors: Makhaeva Galina F. , Kovaleva Nadezhda V. , Boltneva Natalia P. , Lushchekina Sofya V. , Astakhova Tatiana Yu. , Rudakova Elena V. , Proshin Alexey N. , Serkov Igor V. , Radchenko Eugene V. , Palyulin Vladimir A. , Bachurin Sergey O. , Richardson Rudy J.
Published: August 2020

New hybrid compounds of 4-amino-2,3-polymethylene-quinoline containing different sizes of the aliphatic ring and linked to p-tolylsulfonamide with alkylene spacers of increasing length were synthesized as potential drugs for treatment of Alzheimer’s disease (AD). All compounds were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity toward BChE. The lead compound 4-methyl-N-(5-(1,2,3,4-tetrahydro-acridin-9-ylamino)-pentyl)-benzenesulfonamide (7h) exhibited an IC50 (AChE) = 0.131 ± 0.01 µM (five times more potent than tacrine), IC50(BChE) = 0.0680 ± 0.0014 µM, and 17.5 ± 1.5% propidium displacement at 20 µM. The compounds possessed low activity against carboxylesterase, indicating a likely absence of unwanted drug-drug interactions in clinical use. Kinetics studies were consistent with mixed-type reversible inhibition of both cholinesterases. Molecular docking demonstrated dual binding sites of the conjugates in AChE and clarified the differences in the structure-activity relationships for AChE and BChE inhibition. The conjugates could bind to the AChE peripheral anionic site and displace propidium, indicating their potential to block AChE-induced β-amyloid aggregation, thereby exerting a disease-modifying effect. All compounds demonstrated low antioxidant activity. Computational ADMET profiles predicted that all compounds would have good intestinal absorption, medium blood-brain barrier permeability, and medium cardiac toxicity risk. Overall, the results indicate that the novel conjugates show promise for further development and optimization as multitarget anti-AD agents.
Synthesis, In Silico and In Vitro Evaluation for Acetylcholinesterase and BACE-1 Inhibitory Activity of Some N-Substituted-4-Phenothiazine-Chalcones
Authors: Tran Thai-Son , Le Minh-Tri , Nguyen Thi-Cam-Vi , Tran The-Huan , Tran Thanh-Dao , Thai Khac-Minh
Published: August 2020

Acetylcholinesterase (AChE) and beta-secretase (BACE-1) are two attractive targets in the discovery of novel substances that could control multiple aspects of Alzheimer’s disease (AD). Chalcones are the flavonoid derivatives with diverse bioactivities, including AChE and BACE-1 inhibition. In this study, a series of N-substituted-4-phenothiazine-chalcones was synthesized and tested for AChE and BACE-1 inhibitory activities. In silico models, including two-dimensional quantitative structure–activity relationship (2D-QSAR) for AChE and BACE-1 inhibitors, and molecular docking investigation, were developed to elucidate the experimental process. The results indicated that 13 chalcone derivatives were synthesized with relatively high yields (39–81%). The bioactivities of these substances were examined with pIC50 3.73–5.96 (AChE) and 5.20–6.81 (BACE-1). Eleven of synthesized chalcones had completely new structures. Two substances AC4 and AC12 exhibited the highest biological activities on both AChE and BACE-1. These substances could be employed for further researches. In addition to this, the present study results suggested that, by using a combination of two types of predictive models, 2D-QSAR and molecular docking, it was possible to estimate the biological activities of the prepared compounds with relatively high accuracy.
Antitumor Activity and Mechanism of Robustic Acid from Dalbergia benthami Prain via Computational Target Fishing
Authors: Huang Juanjuan , Liang Ying , Tian Wenyu , Ma Jing , Huang Ling , Li Benjie , Chen Rui , Li Dianpeng
Published: August 2020

Dalbergia benthami Prain (D.benthami) is an important legume species of the Dalbergia family, due to the use of its trunk and root heart in traditional Chinese medicine (TCM). In the present study, we reported the isolation, characterization and pharmacological activities of robustic acid (RA) from the ethyl acetate extract of D. benthami Prain. The SwissADME prediction showed that the RA satisfied the Lipinski’s rule of five (molecule weight (MW): 380.39 g/mol, lipid-water partition coefficient (log P): 3.72, hydrogen bond donors (Hdon): 1, hydrogen bond acceptors (Hacc): 6, rotatable bonds (Rbon): 3. Other chemical and pharmacological properties of this RA were also evaluated, including topological polar surface area (TPSA) = 78.13 Å and solubility (Log S) = −4.8. The probability values of the antineoplastic, anti-free radical activities and topoisomerase I (TopoI) inhibitory activity were found to be 0.784, 0.644 and 0.379, respectively. The molecular docking experiment using the Surflex-Dock showed that the Total Score and C Score of RNA binding with the human DNA-Topo I complex were 7.80 and 4. The MTS assay experiment showed that the inhibitory rates of RA on HL-60, MT4, Hela, HepG2, SK-OV-3 and MCF-7 cells were 37.37%, 97.41%, 81.22%, 34.4%, 32.68% and 51.4%, respectively. In addition, RA exhibited an inhibitory effect on the angiogenesis of zebrafish embryo, a good TopoI inhibitory activity at a 10 mM concentration and in a dose-dependent manner, excellent radical scavenging in the DPPH and ABTS assays, and the free radical scavenging rate was close to the positive control (BHT) at different concentrations (0.5–2.0 mg/mL). Furthermore, 18 potential targets were found for this RA by PharmMapper, including ANXA3, SRC, FGFR2, GSK3B, CSNK2B, YARS, LCK, EPHA2, MAPK14, RORA, CRABP2, PPP1CC, METAP2, MME, TTR, MET and KDR. The GO and KEGG pathway analysis revealed that the “protein tyrosine kinase activity”, “rap1 signaling pathway” and “PI3K-Akt signaling pathway” were significantly enriched by the RA target genes. Our results will provide new insights into the pharmaceutical use of this species. More importantly, our data will expand our understanding of the molecular mechanisms of RA functions.
Evaluation of Supercritical CO2-Assisted Protocols in a Model of Ovine Aortic Root Decellularization
Authors: Gafarova Elvira R. , Grebenik Ekaterina A. , Lazhko Alexey E. , Frolova Anastasia A. , Kuryanova Anastasia S. , Kurkov Alexandr V. , Bazhanov Ilya A. , Kapomba Byron S. , Kosheleva Nastasia V. , Novikov Ivan A. , Shekhter Anatoly B. , Golubeva Elena N. , Soloviova Anna B. , Timashev Peter S.
Published: August 2020

One of the leading trends in the modern tissue engineering is the development of new effective methods of decellularization aimed at the removal of cellular components from a donor tissue, reducing its immunogenicity and the risk of rejection. Supercritical CO2 (scCO2)-assisted processing has been proposed to improve the outcome of decellularization, reduce contamination and time costs. The resulting products can serve as personalized tools for tissue-engineering therapy of various somatic pathologies. However, the decellularization of heterogeneous 3D structures, such as the aortic root, requires optimization of the parameters, including preconditioning medium composition, the type of co-solvent, values of pressure and temperature inside the scCO2 reactor, etc. In our work, using an ovine aortic root model, we performed a comparative analysis of the effectiveness of decellularization approaches based on various combinations of these parameters. The protocols were based on the combinations of treatments in alkaline, ethanol or detergent solutions with scCO2-assisted processing at different modes. Histological analysis demonstrated favorable effects of the preconditioning in a detergent solution. Following processing in scCO2 medium provided a high decellularization degree, reduced cytotoxicity, and increased ultimate tensile strength and Young’s modulus of the aortic valve leaflets, while the integrity of the extracellular matrix was preserved.
New Arctic Bacterial Isolates with Relevant Enzymatic Potential
Authors: Piegza Michał , Łaba Wojciech , Kačániová Miroslava
Published: August 2020

Fragments of wood drifting in the vicinity of Spitzbergen were used for the isolation of microorganisms, carried out using atypical carbon sources: colloidal chitin, cellulose and carboxymethylcellulose, xylan, casein, tributrin and olive oil. Purified cultures were subjected to a three-step identification: with classical methods, using MALDI-TOF MS Biotyper whole-cell protein fingerprinting, and molecular analysis of 16S rDNA. Subsequently, a preliminary assessment of the enzymatic potential of isolates was carried out. As a result, cellulolytic activity was observed in more than 50% of the bacterial strains, exhibiting activity of 0.30–0.40 U/mL. Over 53% of the isolates demonstrated xylanolytic activity, of which the highest reached from 0.40 to 0.90 U. Polygalacturonase activity of 0.003–1.6 was also demonstrated in half of the bacterial strains studied. Proteolytic activity of isolates did not exceed 0.3 U. An important highlight was the ability of fluorescent dye production by certain strains, grown on skim milk-agar, but also on pure meat extract.
Diarylphosphate as a New Route for Design of Highly Luminescent Ln Complexes
Authors: Kalugin Alexey E. , Minyaev Mikhail E. , Puntus Lada N. , Taydakov Ilya V. , Varaksina Evgenia A. , Lyssenko Konstantin A. , Nifant'ev Ilya E. , Roitershtein Dmitrii M.
Published: August 2020

Organophosphate-chloride complexes [{(2,6-iPr2C6H3-O)2POO}2LnCl(CH3OH)4]·2CH3OH, Ln = Nd (1), Eu (2), Gd (3), and Tb (4) have been obtained and structurally characterized. Their reaction with 2,2′:6′,2″-terpyridine leads to the formation of 1:1 adducts ([{(2,6-iPr2C6H3-O)2POO}2LnCl(terpy)(H2O)2(CH3OH)], Ln = Eu (5), Gd (6), Tb (7) with exception of Nd, where tris-diisopropylphenylphosphate complex [{(2,6-iPr2C6H3-O)2POO}3Nd) (terpy)(H2O)(CH3OH)] (8) was obtained due to the ligand metathesis. A bright luminescence observed for the Eu and Tb organophosphate complexes is the first example of an application of organophosphate ligands for 4f-ions luminescence sensitization. Photophysical properties of all complexes were analyzed by optical spectroscopy and an energy transfer scheme was discussed. A combination of two types of ligands into the coordination sphere (phosphate and phenanthroline) allows designing the Eu surrounding with very high intrinsic quantum yield QEuEu (0.92) and highly luminescent Ln complexes for both visible and near-infrared (NIR) regions.
Biochemical and Computational Approach of Selected Phytocompounds from Tinospora crispa in the Management of COVID-19
Authors: Rakib Ahmed , Paul Arkajyoti , Chy Md. Nazim Uddin , Sami Saad Ahmed , Baral Sumit Kumar , Majumder Mohuya , Tareq Abu Montakim , Amin Mohammad Nurul , Shahriar Asif , Uddin Md. Zia , Dutta Mycal , Tallei Trina Ekawati , Emran Talha Bin , Simal-Gandara Jesus
Published: August 2020

A pandemic caused by the novel coronavirus (SARS-CoV-2 or COVID-19) began in December 2019 in Wuhan, China, and the number of newly reported cases continues to increase. More than 19.7 million cases have been reported globally and about 728,000 have died as of this writing (10 August 2020). Recently, it has been confirmed that the SARS-CoV-2 main protease (Mpro) enzyme is responsible not only for viral reproduction but also impedes host immune responses. The Mpro provides a highly favorable pharmacological target for the discovery and design of inhibitors. Currently, no specific therapies are available, and investigations into the treatment of COVID-19 are lacking. Therefore, herein, we analyzed the bioactive phytocompounds isolated by gas chromatography–mass spectroscopy (GC-MS) from Tinospora crispa as potential COVID-19 Mpro inhibitors, using molecular docking study. Our analyses unveiled that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules, with three of them exerting biological activity and warranting further optimization and drug development to combat COVID-19.
The Role of Active-Site Plasticity in Damaged-Nucleotide Recognition by Human Apurinic/Apyrimidinic Endonuclease APE1
Authors: Bulygin Anatoly A. , Kuznetsova Alexandra A. , Vorobjev Yuri N. , Fedorova Olga S. , A. Kuznetsov Nikita
Published: August 2020

Human apurinic/apyrimidinic (AP) endonuclease APE1 hydrolyzes phosphodiester bonds on the 5′ side of an AP-site, and some damaged nucleotides such as 1,N6-ethenoadenosine (εA), α-adenosine (αA), and 5,6-dihydrouridine (DHU). To investigate the mechanism behind the broad substrate specificity of APE1, we analyzed pre-steady-state kinetics of conformational changes in DNA and the enzyme during DNA binding and damage recognition. Molecular dynamics simulations of APE1 complexes with one of damaged DNA duplexes containing εA, αA, DHU, or an F-site (a stable analog of an AP-site) revealed the involvement of residues Asn229, Thr233, and Glu236 in the mechanism of DNA lesion recognition. The results suggested that processing of an AP-site proceeds faster in comparison with nucleotide incision repair substrates because eversion of a small abasic site and its insertion into the active site do not include any unfavorable interactions, whereas the insertion of any target nucleotide containing a damaged base into the APE1 active site is sterically hindered. Destabilization of the α-helix containing Thr233 and Glu236 via a loss of the interaction between these residues increased the plasticity of the damaged-nucleotide binding pocket and the ability to accommodate structurally different damaged nucleotides. Nonetheless, the optimal location of εA or αA in the binding pocket does not correspond to the optimal conformation of catalytic amino acid residues, thereby significantly decreasing the cleavage efficacy for these substrates.
ZnO Nanowires on Single-Crystalline Aluminum Film Coupled with an Insulating WO3 Interlayer Manifesting Low Threshold SPP Laser Operation
Authors: Agarwal Aanchal , Tien Wei-Yang , Huang Yu-Sheng , Mishra Ragini , Cheng Chang-Wei , Gwo Shangjr , Lu Ming-Yen , Chen Lih-Juann
Published: August 2020

ZnO nanowire-based surface plasmon polariton (SPP) nanolasers with metal–insulator–semiconductor hierarchical nanostructures have emerged as potential candidates for integrated photonic applications. In the present study, we demonstrated an SPP nanolaser consisting of ZnO nanowires coupled with a single-crystalline aluminum (Al) film and a WO3 dielectric interlayer. High-quality ZnO nanowires were prepared using a vapor phase transport and condensation deposition process via catalyzed growth. Subsequently, prepared ZnO nanowires were transferred onto a single-crystalline Al film grown by molecular beam epitaxy (MBE). Meanwhile, a WO3 dielectric interlayer was deposited between the ZnO nanowires and Al film, via e-beam technique, to prevent the optical loss from dominating the metallic region. The metal–oxide–semiconductor (MOS) structured SPP laser, with an optimal WO3 insulating layer thickness of 3.6 nm, demonstrated an ultra-low threshold laser operation (lasing threshold of 0.79 MW cm−2). This threshold value was nearly eight times lower than that previously reported in similar ZnO/Al2O3/Al plasmonic lasers, which were ≈2.4 and ≈3 times suppressed compared to the SPP laser, with WO3 insulating layer thicknesses of 5 nm and 8 nm, respectively. Such suppression of the lasing threshold is attributed to the WO3 insulating layer, which mediated the strong confinement of the optical field in the subwavelength regime.
Head-To-Head Comparison of Biological Behavior of Biocompatible Polymers Poly(Ethylene Oxide), Poly(2-Ethyl-2-Oxazoline) and Poly[N-(2-Hydroxypropyl)Methacrylamide] as Coating Materials for Hydroxyapatite Nanoparticles in Animal Solid Tumor Model
Authors: Novy Zbynek , Lobaz Volodymyr , Vlk Martin , Kozempel Jan , Stepanek Petr , Popper Miroslav , Vrbkova Jana , Hajduch Marian , Hruby Martin , Petrik Milos
Published: August 2020

Nanoparticles (NPs) represent an emerging platform for diagnosis and treatment of various diseases such as cancer, where they can take advantage of enhanced permeability and retention (EPR) effect for solid tumor accumulation. To improve their colloidal stability, prolong their blood circulation time and avoid premature entrapment into reticuloendothelial system, coating with hydrophilic biocompatible polymers is often essential. Most studies, however, employ just one type of coating polymer. The main purpose of this study is to head-to-head compare biological behavior of three leading polymers commonly used as “stealth” coating materials for biocompatibilization of NPs poly(ethylene oxide), poly(2-ethyl-2-oxazoline) and poly[N-(2-hydroxypropyl)methacrylamide] in an in vivo animal solid tumor model. We used radiolabeled biodegradable hydroxyapatite NPs as a model nanoparticle core within this study and we anchored the polymers to the NPs core by hydroxybisphosphonate end groups. The general suitability of polymers for coating of NPs intended for solid tumor accumulation is that poly(2-ethyl-2-oxazoline) and poly(ethylene oxide) gave comparably similar very good results, while poly[N-(2-hydroxypropyl)methacrylamide] was significantly worse. We did not observe a strong effect of molecular weight of the coating polymers on tumor and organ accumulation, blood circulation time, biodistribution and biodegradation of the NPs.
Molecular Dynamics Simulation on Creep Behavior of Nanocrystalline TiAl Alloy
Authors: Zhao Fei , Zhang Jie , He Chenwei , Zhang Yong , Gao Xiaolei , Xie Lu
Published: August 2020

TiAl alloy represents a new class of light and heat-resistant materials. In this study, the effect of temperature, pressure, and grain size on the high-temperature creep properties of nanocrystalline TiAl alloy have been studied through the molecular dynamics method. Based on this, the deformation mechanism of the different creep stages, including crystal structure, dislocation, and diffusion, has been explored. It is observed that the high-temperature creep performance of nanocrystalline TiAl alloy is significantly affected by temperature and stress. The higher is the temperature and stress, the greater the TiAl alloy’s steady-state creep rate and the faster the rapid creep stage. Smaller grain size accelerates the creep process due to the large volume fraction of the grain boundary. In the steady-state deformation stage, two kinds of creep mechanisms are manly noted, i.e., dislocation motion and grain boundary diffusion. At the same temperature, the creep mechanism is dominated by the dislocation motion in a high-stress field, and the creep mechanism is dominated by the diffusion creep in the low-stress field. However, it is observed to be mainly controlled by the grain boundary diffusion and lattice diffusion in the rapid creep stage.
TGR5 Signaling in Hepatic Metabolic Health
Authors: Holter Marlena M. , Chirikjian Margot K. , Govani Viraj N. , Cummings Bethany P.
Published: August 2020

TGR5 is a G protein-coupled bile acid receptor that is increasingly recognized as a key regulator of glucose homeostasis. While the role of TGR5 signaling in immune cells, adipocytes and enteroendocrine L cells in metabolic regulation has been well described and extensively reviewed, the impact of TGR5-mediated effects on hepatic physiology and pathophysiology in metabolic regulation has received less attention. Recent studies suggest that TGR5 signaling contributes to improvements in hepatic insulin signaling and decreased hepatic inflammation, as well as metabolically beneficial improvements in bile acid profile. Additionally, TGR5 signaling has been associated with reduced hepatic steatosis and liver fibrosis, and improved liver function. Despite the beneficial effects of TGR5 signaling on metabolic health, TGR5-mediated gallstone formation and gallbladder filling complicate therapeutic targeting of TGR5 signaling. To this end, there is a growing need to identify cell type-specific effects of hepatic TGR5 signaling to begin to identify and target the downstream effectors of TGR5 signaling. Herein, we describe and integrate recent advances in our understanding of the impact of TGR5 signaling on liver physiology and how its effects on the liver integrate more broadly with whole body glucose regulation.
Omega-3 Polyunsaturated Fatty Acids EPA and DHA as an Adjunct to Non-Surgical Treatment of Periodontitis: A Randomized Clinical Trial
Authors: Stańdo Mirella , Piatek Paweł , Namiecinska Magdalena , Lewkowicz Przemysław , Lewkowicz Natalia
Published: August 2020

Periodontitis is a chronic multifactorial inflammatory disease that leads to the loss of supportive tissues around the teeth with gradual deterioration of masticatory function and esthetics, resulting eventually in the decrease of the life quality. Host immune response triggered by bacterial biofilm is responsible for the chronic periodontal inflammation and ongoing tissue loss. Omega-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory properties, thus may be used for the treatment of chronic inflammatory diseases. In this study, we aimed to evaluate the effect of dietary supplementation with omega-3 PUFA in the patients with stage III and IV periodontitis. Thirty otherwise healthy patients were treated with scaling and root planning (SRP). In the test group (n = 16), patients were additionally supplemented with 2.6 g of EPA and 1.8 g of DHA. In the control group (n = 14), patients received only SRP. Periodontal examination was performed at baseline and three months following initial therapy. Salivary samples were taken twice at baseline and at the end of the experiment. We found that there was a statistically significant reduction in the bleeding on probing (BOP) and improvement of clinical attachment loss (CAL) at three months in the test group compared to the control group. Moreover, a statistically significant higher percentage of closed pockets (probing depth ≤ 4 mm without BOP) was achieved in the test group vs. control group after three months of treatment. Accordingly, the levels of pro-inflammatory cytokines/chemokines interleukin (IL)-8 and IL-17 were markedly lower, while the level of anti-inflammatory IL-10 was significantly higher in the salivary samples of the patients supplemented with omega-3 PUFA at three months in comparison to the patients treated with SRP alone. Our findings demonstrate that dietary intervention with high-dose of omega-3 PUFA during non-surgical therapy may have potential benefits in the management of periodontitis.
Type II Restriction-Modification System from Gardnerella vaginalis ATCC 14018
Authors: Bulavaitė Aistė , Dalgediene Indre , Michailoviene Vilma , Pleckaityte Milda
Published: August 2020

Intensive horizontal gene transfer may generate diversity and heterogeneity within the genus Gardnerella. Restriction-modification (R-M) systems and CRISPR-Cas are the principal defense tools against foreign DNA in bacteria. Nearly half of the tested Gardnerella spp. isolates harbored the CRISPR-Cas system. Several putative R-M systems of Gardnerella spp. strains were identified in the REBASE database. However, there was no experimental evidence for restriction endonuclease (REase) activity in the isolates. We showed that G. vaginalis strain ATCC 14018 contains the REase R.Gva14018I, which recognizes GGCC and most probably generates blunt ends on cleavage. Bioinformatics evidence and the activity of recombinant methyltransferase M.Gva14018I in vivo indicate that ATCC 14018 possesses a HaeIII-like R-M system. The truncated R.Gva14018I-4 lacking the C-terminal region was expressed in Escherichia coli and displayed wild-type REase specificity. Polyclonal antibodies against R.Gva14018I-4 detected the wild-type REase in the cell lysate of ATCC 14018. The cofactor requirements for activity and bioinformatics analysis indicated that R.Gva14018I belongs to the PD-(D/E)XK family of REases. The REase-like activity was observed in 5 of 31 tested Gardnerella spp. strains, although none of these matched the DNA digestion pattern of R.Gva14018I.
The Role of Proteomics in Bacterial Response to Antibiotics
Authors: Tsakou Foteini , Jersie-Christensen Rosa , Jenssen Håvard , Mojsoska Biljana
Published: August 2020

For many years, we have tried to use antibiotics to eliminate the persistence of pathogenic bacteria. However, these infectious agents can recover from antibiotic challenges through various mechanisms, including drug resistance and antibiotic tolerance, and continue to pose a global threat to human health. To design more efficient treatments against bacterial infections, detailed knowledge about the bacterial response to the commonly used antibiotics is required. Proteomics is a well-suited and powerful tool to study molecular response to antimicrobial compounds. Bacterial response profiling from system-level investigations could increase our understanding of bacterial adaptation, the mechanisms behind antibiotic resistance and tolerance development. In this review, we aim to provide an overview of bacterial response to the most common antibiotics with a focus on the identification of dynamic proteome responses, and through published studies, to elucidate the formation mechanism of resistant and tolerant bacterial phenotypes.
The Fabrication of Geopolymer Foam Composites Incorporating Coke Dust Waste
Authors: Katarzyna Buczkowska , Le Chi Hiep , Louda Petr , Michał Szczypiński , Bakalova Totka , Tadeusz Pacyniak , Prałat Karol
Published: August 2020

This paper reports the results of an experimental investigation on the mechanical properties of geopolymer foams incorporating filler from the coke dust waste (CDW). In this work, CDW was used to replace a part of geopolymer paste at 5%, 10%, 20%, and 30% by geopolymer binder mass. The physico-mechanical properties and thermal resistance against high temperatures of CDW/geopolymer foams are presented. The primary results obtained show that the use of CDW in the production of geopolymer foam composites made it possible for them to achieve relatively good mechanical properties. However, the incorporation of the CDW into the geopolymer had a slightly negative effect on thermal conductivity, but significantly improved the mechanical strength of the final product. Moreover, this waste also helped the composite foam to achieve a structure with more uniform open pores distribution, compared to the pure foam. After exposure to elevated temperatures, the residual strength of the composite foams maintained well compared to the pure foams.
Electrochemiluminescence Enhancement and Particle Structure Stabilization of Polymer Nanoparticle by Doping Anionic Polyelectrolyte and Cationic Polymer Containing Tertiary Amine Groups and Its Highly Sensitive Immunoanalysis
Authors: Ul Ain Noor , Wang Tian-Yu , Wu Xiao-Ning , Wei Tong-Hong , Zhang Jing-Shuo , Xie Hong-Ping
Published: August 2020

A doped polymer nanoparticle (dPNP) of electrochemiluminescence (ECL) was prepared via doping the anionic polyelectrolyte polyacrylic acid (PAA) and the cationic polymer poly-ethyleneimine (PEI) into the polymer nanoparticle (PNP), which was self-assembled by Ru(bpy)32+ derivative-grafted PAA (PAA–Ru) with both cations and anions. The good electrical conductivity of the doped polyelectrolyte PAA enhanced the ECL intensity of PNP to 109.1%, and the involvement of a large number of tertiary amine groups of the doped PEI further enhanced that to 127.3%; meanwhile, doping low-molecular-weight PEI into PNP, while simultaneously doping high-molecular-weight PAA, avoided the precipitation of PAA and PEI, due to interaction of the two oppositely charged polymers; and these also made the self-assembly procedure more effective and the nanoparticle structure more stable than PNP and also led to the production of rich residual PAA chains on the surface of dPNP. The storage results showed that the average hydrated particle diameter kept almost constant (197.5–213.1 nm) during 15-day storage and that the nanoparticles have rich surface charge of −11.47 mV (zeta potential), well suspension stability and good dispersity without detectable aggregation in the solution during the storage. Therefore, the nanoparticle is quite suitable for the antibody labeling, immunoassay and the storage. As a result, a high-sensitive ECL immunoassay approach with good precision, accuracy and selectivity was established and an ultra-low detection limit of 0.049 pg mL−1 (S/N = 3) for magnetic bead-based detection of Hepatitis B surface antigen was observed.
Automatic Detection of Regional Snow Avalanches with Scattering and Interference of C-band SAR Data
Authors: Yang Jinming , Li Chengzhi , Li Lanhai , Ding Jianli , Zhang Run , Han Tao , Liu Yang
Published: August 2020

Avalanche disasters are extremely destructive and catastrophic, often causing serious casualties, economic losses and surface erosion. However, far too little attention has been paid to utilizing remote sensing mapping avalanches quickly and automatically to mitigate calamity. Such endeavors are limited by formidable natural conditions, human subjective judgement and insufficient understanding of avalanches, so they have been incomplete and inaccurate. This paper presents an objective and widely serviceable method for regional auto-detection using the scattering and interference characteristics of avalanches extracted from Sentinel-1 SLC images. Six indices are established to distinguish avalanches from surrounding undisturbed snow. The active avalanche belts in Kizilkeya and Aktep of the Western TianShan Mountains in China lend urgency to this research. Implementation found that smaller avalanches can be consistently identified more accurately in descending images. Specifically, 281 and 311 avalanches were detected in the ascending and descending of Kizilkeya, respectively. The corresponding numbers on Aktep are 104 and 114, respectively. The resolution area of single avalanche detection can reach 0.09 km2. The performance of the model was excellent in all cases (areas under the curve are 0.831 and 0.940 in descending and ascending of Kizilkeya, respectively; and 0.807 and 0.938 of Aktep, respectively). Overall, the evaluation of statistical indices are POD > 0.75, FAR < 0.34, FOM < 0.13 and TSS > 0.75. The results indicate that the performance of the innovation proposed in this paper, which employs multivariate comprehensive descriptions of avalanche characteristics to actualize regional automatic detection, can be more objective, accurate, applicable and robust to a certain extent. The latest and more complete avalanche inventory generated by this design can effectively assist in addressing the increasingly severe avalanche disasters and improving public awareness of avalanches in alpine areas.
THz Signal Generator Using a Single DFB Laser Diode and the Unbalanced Optical Fiber Interferometer
Authors: Pongrac Blaž , Đonlagic Denis , Njegovec Matej , Gleich Dušan
Published: August 2020

This paper presents a frequency-modulated optical signal generator in the THz band. The proposed method is based on a fast optical frequency sweep of a single narrowband laser diode used together with an optical fiber interferometer. The optical frequency sweep using a single laser diode is achieved by generating short current pulses with a high amplitude, which are driving the laser diode. Theoretical analysis showed that the modulation frequency could be changed by the optical path difference of the interferometer or optical frequency sweep rate of a laser diode. The efficiency of the optical signal generator with Michelson and Fabry–Perot interferometers is theoretically analyzed and experimentally evaluated for three different scenarios. Interferometers with different optical path differences and a fixed optical frequency sweep rate were used in the first scenario. Different optical frequency sweep rates and fixed optical path differences of the interferometers were used in the second scenario. This paper presents a method for optical chirp generation using a programmable current pulse waveform, which drives a laser diode to achieve nonlinear optical sweep with a fixed optical path difference of the interferometer. The experimental results showed that the proposed signals could be generated within a microwave (1–30 GHz) and THz band (0.1–0.3 THz).
Factors Associated with Callus Formation in the Plantar Region through Gait Measurement in Patients with Diabetic Neuropathy: An Observational Case-Control Study
Authors: Amemiya Ayumi , Noguchi Hiroshi , Oe Makoto , Takehara Kimie , Ohashi Yumiko , Suzuki Ryo , Yamauchi Toshimasa , Kadowaki Takashi , Sanada Hiromi , Mori Taketoshi
Published: August 2020

Callus has been identified as a risk factor leading to severe diabetic foot ulcer; thus, it is necessary to prevent its formation. Callus formation under the first, second, and fifth metatarsal heads (MTHs) is associated with external forces (pressure and shear stress) during walking. However, the gait factors increasing the external forces remain undetermined. Thus, this study aims to identify the factors increasing the external forces to prevent callus formation. In 59 patients with diabetic neuropathy wearing their usual shoes, the external forces, and the lower extremity joint angles were measured using MEMS force sensors and motion sensors. The external forces and their relationship with the lower extremity joint angles and footwear size were determined. Risk factors causing high external forces on the first MTH included small flexion of the knee joint (p = 0.015) and large ankle pronation motion (p = 0.034) to obtain propulsion. For the second MTH, wearing excessively long footwear was identified (p = 0.026). For the fifth MTH, high external force was related to tight width footwear (p = 0.005). An effective intervention for preventing callus formation for the first MTH would involve assisting the push-off foot motion using rocker-sole footwear or gait training. For the second and fifth MTHs, wearing appropriate size footwear would be effective.
Daily Life Benefits and Usage Characteristics of Dynamic Arm Supports in Subjects with Neuromuscular Disorders
Authors: Essers Johannes , Murgia Alessio , Peters Anneliek , Meijer Kenneth
Published: August 2020

Neuromuscular disorders cause progressive muscular weakness, which limits upper extremity mobility and performance during activities of daily life. Dynamic arm supports can improve mobility and quality of life. However, their use is often discontinued over time for unclear reasons. This study aimed to evaluate whether users of dynamic arm supports demonstrate and perceive quantifiable mobility benefits over a period of two months. Nine users of dynamic arm supports were included in this observational study. They had different neuromuscular disorders and collectively used four different arm supports. They were observed for three consecutive weeks during which they were equipped with a multi-sensor network of accelerometers to assess the actual use of the arm support and they were asked to provide self-reports on the perceived benefits of the devices. Benefits were experienced mainly during anti-gravity activities and the measured use did not change over time. The self-reports provided contextual information in domains such as participation to social life, in addition to the sensor system. However self-reports overestimated the actual use by up to three-fold compared to the accelerometer measures. A combination of objective and subjective methods is recommended for meaningful and quantifiable mobility benefits during activities of daily life.
Evaluation of the Vertical Accuracy of Open Global DEMs over Steep Terrain Regions Using ICESat Data: A Case Study over Hunan Province, China
Authors: Liu Zhiwei , Zhu Jianjun , Fu Haiqiang , Zhou Cui , Zuo Tingying
Published: August 2020

The global digital elevation model (DEM) is important for various scientific applications. With the recently released TanDEM-X 90-m DEM and AW3D30 version 2.2, the open global or near-global coverage DEM datasets have been further expanded. However, the quality of these DEMs has not yet been fully characterized, especially in the application for regional scale studies. In this study, we assess the quality of five freely available global DEM datasets (SRTM-1 DEM, SRTM-3 DEM, ASTER GDEM2, AW3D30 DEM and TanDEM-X 90-m DEM) and one 30-m resampled TanDEM-X DEM (hereafter called TDX30) over the south-central Chinese province of Hunan. Then, the newly-released high precision ICESat-2 (Ice, Cloud, and land Elevation Satellite-2) altimetry points are introduced to evaluate the accuracy of these DEMs. Results show that the SRTM1 DEM offers the best quality with a Root Mean Square Error (RMSE) of 8.0 m, and ASTER GDEM2 has the worst quality with the RMSE of 10.1 m. We also compared the vertical accuracies of these DEMs with respect to different terrain morphological characteristics (e.g., elevation, slope and aspect) and land cover types. It reveals that the DEM accuracy decreases when the terrain elevation and slope value increase, whereas no relationship was found between DEM error and terrain aspect. Furthermore, the results show that the accuracy increases as the land cover type changes from vegetated to non-vegetated. Overall, the SRTM1 DEM, with high spatial resolution and high vertical accuracy, is currently the most promising dataset among these DEMs and it could, therefore, be utilized for the studies and applications requiring accurate DEMs.
A High-Performance Face Illumination Processing Method via Multi-Stage Feature Maps
Authors: Ling Shenggui , Lin Ye , Fu Keren , You Di , Cheng Peng
Published: August 2020

In recent years, Generative Adversarial Networks (GANs)-based illumination processing of facial images has made favorable achievements. However, some GANs-based illumination-processing methods only pay attention to the image quality and neglect the recognition accuracy, whereas others only crop partial face area and ignore the challenges to synthesize photographic face, background and hair when the original face image is under extreme illumination (Image under extreme illumination (extreme illumination conditions) means that we cannot see the texture and structure information clearly and most pixel values tend to 0 or 255.). Moreover, the recognition accuracy is low when the faces are under extreme illumination conditions. For these reasons, we present an elaborately designed architecture based on convolutional neural network and GANs for processing the illumination of facial image. We use ResBlock at the down-sampling stage in our encoder and adopt skip connections in our generator. This special design together with our loss can enhance the ability to preserve identity and generate high-quality images. Moreover, we use different convolutional layers of a pre-trained feature network to extract varisized feature maps, and then use these feature maps to compute loss, which is named multi-stage feature maps (MSFM) loss. For the sake of fairly evaluating our method against state-of-the-art models, we use four metrics to estimate the performance of illumination-processing algorithms. A variety of experimental data indicate that our method is superior to the previous models under various illumination challenges in illumination processing. We conduct qualitative and quantitative experiments on two datasets, and the experimental data indicate that our scheme obviously surpasses the state-of-the-art algorithms in image quality and identification accuracy.