bluuebunny/crossref_metadata_2025 huggingface dataset:
HNG, A Humanin Analogue, Promotes Hair Growth by Inhibiting Anagen-to-Catagen Transition
Authors: Kim Sung Min , Kang Jung-Il , Yoon Hoon-Seok , Choi Youn Kyung , Go Ji Soo , Oh Sun Kyung , Ahn Meejung , Kim Jeongtae , Koh Young Sang , Hyun Jin Won , Yoo Eun-Sook , Kang Hee-Kyoung
Published: June 2020

The hair follicle goes through repetitive cycles including anagen, catagen, and telogen. The interaction of dermal papilla cells (DPCs) and keratinocytes regulates the hair cycle and hair growth. Humanin was discovered in the surviving brain cells of patients with Alzheimer’s disease. HNG, a humanin analogue, activates cell growth, proliferation, and cell cycle progression, and it protects cells from apoptosis. This study was performed to investigate the promoting effect and action mechanisms of HNG on hair growth. HNG significantly increased DPC proliferation. HNG significantly increased hair shaft elongation in vibrissa hair follicle organ culture. In vivo experiment showed that HNG prolonged anagen duration and inhibited hair follicle cell apoptosis, indicating that HNG inhibited the transition from the anagen to catagen phase mice. Furthermore, HNG activated extracellular signal-regulated kinase (Erk)1/2, Akt, and signal transducer and activator of transcription (Stat3) within minutes and up-regulated vascular endothelial growth factor (VEGF) levels on DPCs. This means that HNG could induce the anagen phase longer by up-regulating VEGF, which is a Stat3 target gene and one of the anagen maintenance factors. HNG stimulated the anagen phase longer with VEGF up-regulation, and it prevented apoptosis by activating Erk1/2, Akt, and Stat3 signaling.
Host Epigenetics in Intracellular Pathogen Infections
Authors: Fol Marek , Włodarczyk Marcin , Druszczyńska Magdalena
Published: June 2020

Some intracellular pathogens are able to avoid the defense mechanisms contributing to host epigenetic modifications. These changes trigger alterations tothe chromatin structure and on the transcriptional level of genes involved in the pathogenesis of many bacterial diseases. In this way, pathogens manipulate the host cell for their own survival. The better understanding of epigenetic consequences in bacterial infection may open the door for designing new vaccine approaches and therapeutic implications. This article characterizes selected intracellular bacterial pathogens, including Mycobacterium spp., Listeria spp., Chlamydia spp., Mycoplasma spp., Rickettsia spp., Legionella spp. and Yersinia spp., which can modulate and reprogram of defense genes in host innate immune cells.
Impaired ECM Remodeling and Macrophage Activity Define Necrosis and Regeneration Following Damage in Aged Skeletal Muscle
Authors: Rahman Fasih Ahmad , Angus Sarah Anne , Stokes Kyle , Karpowicz Phillip , Krause Matthew Paul
Published: June 2020

Regenerative capacity of skeletal muscle declines with age, the cause of which remains largely unknown. We investigated extracellular matrix (ECM) proteins and their regulators during early regeneration timepoints to define a link between aberrant ECM remodeling, and impaired aged muscle regeneration. The regeneration process was compared in young (three month old) and aged (18 month old) C56BL/6J mice at 3, 5, and 7 days following cardiotoxin-induced damage to the tibialis anterior muscle. Immunohistochemical analyses were performed to assess regenerative capacity, ECM remodeling, and the macrophage response in relation to plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), and ECM protein expression. The regeneration process was impaired in aged muscle. Greater intracellular and extramyocellular PAI-1 expression was found in aged muscle. Collagen I was found to accumulate in necrotic regions, while macrophage infiltration was delayed in regenerating regions of aged muscle. Young muscle expressed higher levels of MMP-9 early in the regeneration process that primarily colocalized with macrophages, but this expression was reduced in aged muscle. Our results indicate that ECM remodeling is impaired at early time points following muscle damage, likely a result of elevated expression of the major inhibitor of ECM breakdown, PAI-1, and consequent suppression of the macrophage, MMP-9, and myogenic responses.
Targeted Therapy in Melanoma and Mechanisms of Resistance
Authors: Czarnecka Anna M. , Bartnik Ewa , Fiedorowicz Michał , Rutkowski Piotr
Published: June 2020

The common mutation BRAFV600 in primary melanomas activates the mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathway and the introduction of proto-oncogene B-Raf (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors (BRAFi and MEKi) was a breakthrough in the treatment of these cancers. However, 15–20% of tumors harbor primary resistance to this therapy, and moreover, patients develop acquired resistance to treatment. Understanding the molecular phenomena behind resistance to BRAFi/MEKis is indispensable in order to develop novel targeted therapies. Most often, resistance develops due to either the reactivation of the MAPK/ERK pathway or the activation of alternative kinase signaling pathways including phosphatase and tensin homolog (PTEN), neurofibromin 1 (NF-1) or RAS signaling. The hyperactivation of tyrosine kinase receptors, such as the receptor of the platelet-derived growth factor β (PDFRβ), insulin-like growth factor 1 receptor (IGF-1R) and the receptor for hepatocyte growth factor (HGF), lead to the induction of the AKT/3-phosphoinositol kinase (PI3K) pathway. Another pathway resulting in BRAFi/MEKi resistance is the hyperactivation of epidermal growth factor receptor (EGFR) signaling or the deregulation of microphthalmia-associated transcription factor (MITF).
Antimicrobial Peptides Display Strong Synergy with Vancomycin Against Vancomycin-Resistant E. faecium, S. aureus, and Wild-Type E. coli
Authors: Wu Chih-Lung , Hsueh Ju-Yun , Yip Bak-Sau , Chih Ya-Han , Peng Kuang-Li , Cheng Jya-Wei
Published: June 2020

There is an urgent and imminent need to develop new antimicrobials to fight against antibiotic-resistant bacterial and fungal strains. In this study, a checkerboard method was used to evaluate the synergistic effects of the antimicrobial peptide P-113 and its bulky non-nature amino acid substituted derivatives with vancomycin against vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, and wild-type Escherichia coli. Boron-dipyrro-methene (BODIPY) labeled vancomycin was used to characterize the interactions between the peptides, vancomycin, and bacterial strains. Moreover, neutralization of antibiotic-induced releasing of lipopolysaccharide (LPS) from E. coli by the peptides was obtained. Among these peptides, Bip-P-113 demonstrated the best minimal inhibitory concentrations (MICs), antibiotics synergism, bacterial membrane permeabilization, and supernatant LPS neutralizing activities against the bacteria studied. These results could help in developing antimicrobial peptides that have synergistic activity with large size glycopeptides such as vancomycin in therapeutic applications.
Promoter Methylation of Selected Genes in Non-Small-Cell Lung Cancer Patients and Cell Lines
Authors: Sarne Victoria , Huter Samuel , Braunmueller Sandrina , Rakob Lisa , Jacobi Nico , Kitzwögerer Melitta , Wiesner Christoph , Obrist Peter , Seeboeck Rita
Published: June 2020

Specific gene promoter DNA methylation is becoming a powerful epigenetic biomarker in cancer diagnostics. Five genes (CDH1, CDKN2Ap16, RASSF1A, TERT, and WT1) were selected based on their frequently published potential as epigenetic markers. Diagnostic promoter methylation assays were generated based on bisulfite-converted DNA pyrosequencing. The methylation patterns of 144 non-small-cell lung cancer (NSCLC) and 7 healthy control formalin-fixed paraffin-embedded (FFPE) samples were analyzed to evaluate the applicability of the putative diagnostic markers. Statistically significant changes in methylation levels are shown for TERT and WT1. Furthermore, 12 NSCLC and two benign lung cell lines were characterized for promoter methylation. The in vitro tests involved a comparison of promoter methylation in 2D and 3D cultures, as well as therapeutic tests investigating the impact of CDH1/CDKN2Ap16/RASSF1A/TERT/WT1 promoter methylation on sensitivity to tyrosine kinase inhibitor (TKI) and DNA methyl-transferase inhibitor (DNMTI) treatments. We conclude that the selected markers have potential and putative impacts as diagnostic or even predictive marker genes, although a closer examination of the resulting protein expression and pathway regulation is needed.
Participation of Amyloid and Tau Protein in Neuronal Death and Neurodegeneration after Brain Ischemia
Authors: Pluta Ryszard , Ułamek-Kozioł Marzena , Januszewski Sławomir , Czuczwar Stanisław J.
Published: June 2020

Current evidence indicates that postischemic brain injury is associated with the accumulation of folding proteins, such as amyloid and tau protein, in the intra- and extracellular spaces of neuronal cells. In this review, we summarize protein changes associated with Alzheimer’s disease and their gene expression (amyloid protein precursor and tau protein) after brain ischemia, and their roles in the postischemic period. Recent advances in understanding the postischemic mechanisms in development of neurodegeneration have revealed dysregulation of amyloid protein precursor, α-, β- and γ-secretase and tau protein genes. Reduced expression of the α-secretase gene after brain ischemia with recirculation causes neuronal cells to be less resistant to injury. We present the latest data that Alzheimer’s disease-related proteins and their genes play a crucial role in postischemic neurodegeneration. Understanding the underlying processes of linking Alzheimer’s disease-related proteins and their genes in development of postischemic neurodegeneration will provide the most significant goals to date for therapeutic development.
Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients
Authors: Plana Emma , Gálvez Laura , Medina Pilar , Navarro Silvia , Fornés-Ferrer Victoria , Panadero Joaquín , Miralles Manuel
Published: June 2020

microRNAs (miRNAs) are small RNAs that regulate different biological processes. Our objective was to identify miRNAs dysregulated in plasma and tissue of patients with abdominal aortic aneurysm (AAA) and explore new potential targets involved in AAA. Fifty-seven subjects were recruited for a plasma study (30 AAA patients, 16 healthy volunteers and 11 patients with atherosclerosis). The expression level of 179 miRNAs was screened in plasma from a subset of samples, and dysregulated miRNAs were validated in the entire study population. Dysregulated miRNAs were also quantified in aortic tissue of 21 AAA patients and 8 organ donors. Applying a gene set enrichment analysis, an interaction map of dysregulated miRNAs and their targets was built, and selected targets were quantified in tissue samples. miR-27b-3p and miR-221-3p were overexpressed in plasma of AAA patients compared with healthy controls, 1.6 times and 1.9 times, respectively. In AAA tissue, six miRNAs (miR-1, miR-27b-3p, miR-29b-3p, miR-133a-3p, miR-133b, and miR-195-5p) were underexpressed from 1.6 to 4.8 times and four miRNAs (miR-146a-5p, miR-21-5p, miR-144-3p, and miR-103a-3p) were overexpressed from 1.3 to 7.2 times. Thrombospondin-2, a target of miR-195-5p, was increased in AAA tissue and negatively correlated with the expression of miR-195-5p, suggesting their involvement in a common regulatory mechanism.
Heterologous Expression of Dehydration-Inducible MfWRKY17 of Myrothamnus Flabellifolia Confers Drought and Salt Tolerance in Arabidopsis
Authors: Huang Zhuo , Guo Han-Du , Liu Ling , Jin Si-Han , Zhu Pei-Lei , Zhang Ya-Ping , Jiang Cai-Zhong
Published: June 2020

As the only woody resurrection plant, Myrothamnus flabellifolia has a strong tolerance to drought and can survive long-term in a desiccated environment. However, the molecular mechanisms related to the stress tolerance of M. flabellifolia are largely unknown, and few tolerance-related genes previously identified had been functionally characterized. WRKYs are a group of unique and complex plant transcription factors, and have reported functions in diverse biological processes, especially in the regulation of abiotic stress tolerances, in various species. However, little is known about their roles in response to abiotic stresses in M. flabellifolia. In this study, we characterized a dehydration-inducible WRKY transcription factor gene, MfWRKY17, from M. flabellifolia. MfWRKY17 shows high degree of homology with genes from Vitis vinifera and Vitis pseudoreticulata, belonging to group II of the WRKY family. Unlike known WRKY17s in other organisms acting as negative regulators in biotic or abiotic stress responses, overexpression of MfWRKY17 in Arabidopsis significantly increased drought and salt tolerance. Further investigations indicated that MfWRKY17 participated in increasing water retention, maintaining chlorophyll content, and regulating ABA biosynthesis and stress-related gene expression. These results suggest that MfWRKY17 possibly acts as a positive regulator of stress tolerance in the resurrection plant M. flabellifolia.
Perspectives in Manipulating EVs for Therapeutic Applications: Focus on Cancer Treatment
Authors: Nazimek Katarzyna , Bryniarski Krzysztof
Published: June 2020

Extracellular vesicles (EVs) receive special attention from oncologists due to their assumed usefulness as prognostic markers, vaccines to induce anti-cancer immune response, and physiological delivery tools. The latter application, which supports the reduction of side effects of treatment, is still fraught with many challenges, including established methods for loading EVs with selected cargo and directing them towards target cells. EVs could be loaded with selected cargo either in vitro using several physicochemical techniques, or in vivo by modification of parental cell, which may have an advantage over in vitro procedures, since some of them significantly influence EVs’ properties. Otherwise, our research findings suggest that EVs could be passively supplemented with micro RNAs (miRNAs) or miRNA antagonists to induce expected biological effect. Furthermore, our observations imply that antigen-specific antibody light chains could coat the surface of EVs to increase the specificity of cell targeting. Finally, the route of EVs’ administration also determines their bioavailability and eventually induced therapeutic effect. Besides, EV membrane lipids may possibly possess immune adjuvant activity. The review summarizes the current knowledge on the possibilities to manipulate EVs to use them as a delivery tool, with the special emphasis on anti-cancer therapy.
Scalable High-Performance Production of Recombinant Horseradish Peroxidase from E. coli Inclusion Bodies
Authors: Humer Diana , Ebner Julian , Spadiut Oliver
Published: June 2020

Horseradish peroxidase (HRP), an enzyme omnipresent in biotechnology, is still produced from hairy root cultures, although this procedure is time-consuming and only gives low yields. In addition, the plant-derived enzyme preparation consists of a variable mixture of isoenzymes with high batch-to-batch variation preventing its use in therapeutic applications. In this study, we present a novel and scalable recombinant HRP production process in Escherichia coli that yields a highly pure, active and homogeneous single isoenzyme. We successfully developed a multi-step inclusion body process giving a final yield of 960 mg active HRP/L culture medium with a purity of ≥99% determined by size-exclusion high-performance liquid chromatography (SEC-HPLC). The Reinheitszahl, as well as the activity with 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 3,3′,5,5′-tetramethylbenzidine (TMB) as reducing substrates, are comparable to commercially available plant HRP. Thus, our preparation of recombinant, unglycosylated HRP from E. coli is a viable alternative to the enzyme from plant and highly interesting for therapeutic applications.
The Novel gem-Dihydroperoxide 12AC3O Suppresses High Phosphate-Induced Calcification via Antioxidant Effects in p53LMAco1 Smooth Muscle Cells
Authors: Takase Naoko , Inden Masatoshi , Hirai Shunsuke , Yamada Yumeka , Kurita Hisaka , Takeda Mitsumi , Yamaguchi Eiji , Itoh Akichika , Hozumi Isao
Published: June 2020

The excessive intake of phosphate (Pi), or chronic kidney disease (CKD), can cause hyperphosphatemia and eventually lead to ectopic calcification, resulting in cerebrovascular diseases. It has been reported that reactive oxygen species (ROS), induced by high concentrations of Pi loading, play a key role in vascular calcification. Therefore, ROS suppression may be a useful treatment strategy for vascular calcification. 12AC3O is a newly synthesized gem-dihydroperoxide (DHP) that has potent antioxidant effects. In the present study, we investigated whether 12AC3O inhibited vascular calcification via its antioxidative capacity. To examine whether 12AC3O prevents vascular calcification under high Pi conditions, we performed Alizarin red and von Kossa staining, using the mouse aortic smooth muscle cell line p53LMAco1. Additionally, the effect of 12AC3O against oxidative stress, induced by high concentrations of Pi loading, was investigated using redox- sensitive dyes. Further, the direct trapping effect of 12AC3O on reactive oxygen species (ROS) was investigated by ESR analysis. Although high concentrations of Pi loading exacerbated vascular smooth muscle calcification, calcium deposition was suppressed by the treatment of both antioxidants and 12AC3O, suggesting that the suppression of ROS may be a candidate therapeutic approach for treating vascular calcification induced by high concentrations of Pi loading. Importantly, 12AC3O also attenuated oxidative stress. Furthermore, 12AC3O directly trapped superoxide anion and hydroxyl radical. These results suggest that ROS are closely involved in high concentrations of Pi-induced vascular calcification and that 12AC3O inhibits vascular calcification by directly trapping ROS.
Expert Refined Topic Models to Edit Topic Clusters in Image Analysis Applied to Welding Engineering
Authors: Allen Theodore T. , Xiong Hui , Tseng Shih-Hsien
Published: June 2020

This paper proposes a new method to generate edited topics or clusters to analyze images for prioritizing quality issues. The approach is associated with a new way for subject matter experts to edit the cluster definitions by “zapping” or “boosting” pixels. We refer to the information entered by users or experts as “high-level” data and we are apparently the first to allow in our model for the possibility of errors coming from the experts. The collapsed Gibbs sampler is proposed that permits efficient processing for datasets involving tens of thousands of records. Numerical examples illustrate the benefits of the high-level data related to improving accuracy measured by Kullback–Leibler (KL) distance. The numerical examples include a Tungsten inert gas example from the literature. In addition, a novel laser aluminum alloy image application illustrates the assignment of welds to groups that correspond to part conformance standards.
Evaluation of Five Medicinal Plant Extracts on Aphis craccivora (Hemiptera: Aphididae) and Its Predator, Chrysoperla carnea (Neuroptera: Chrysopidae) under Laboratory Conditions
Authors: Sayed Samy M. , Alotaibi Saqer S. , Gaber Nevien , Elarrnaouty Sayed-Ashraf
Published: June 2020

Botanical insecticides that degrade rapidly are safer than persistent synthetic chemical insecticides, less harmful to the environment, decrease production costs and are not likely to cause insecticide resistance among pests. This study aimed to evaluate the effect of five different botanical extracts on the bean aphid, Aphis craccivora and the 2nd larval instar of the green lacewing, Chrysoperla carnea under laboratory conditions. Also, the flavonoids in the methanolic extracts of these tested plants were detected using HPLC analysis. The data from the HPLC analysis indicated that the tested plants differed in their flavonoid components. The total flavonoids were 869.4, 1125.6, 721.4, 1667.8 and 2025.9 mg/kg in Psiadia penninervia, Salvia officinalis, Ochradenus baccatus, Pulicaria crispa and Euryops arabicus, respectively. Moreover, there were many variations among these plants in the amount of each compound. The lethal concentration (LC50) value of P. penninervia extract on aphids was the lowest among all of the plants (128.546 µg/mL) followed by O. baccatus (626.461 µg/mL). Also, the LC50 value of P. penninervia extract on the 2nd larval instar of C. carnea (232.095 µg/mL) was significantly lower than those of all other four plant species extracts, while the other four plants did not show significant differences among them according to relative median potency analyses. Accordingly, O. baccatus extract had a strong effect on aphids and was safest for the predator. This finding suggests that O. baccatus could be exploited and further developed as an effective plant extract-based insecticide to be utilized in integrated pest management (IPM) programs against A. craccivora.
The Mitochondrial Theory of g Is Incompatible with Genetic Evidence and Does Not Explain Statistical Phenomena
Authors: Przemyslaw Ujma Péter , Kovacs Kristof
Published: June 2020

In two recent reviews (Geary 2018, 2019), Geary attributed a substantial role in generating individual differences in the general factor of intelligence, g, to mitochondrial functioning [...]
Image-Based Measurement of Wave Interactions with Rubble Mound Breakwaters
Authors: Douglas Steven , Cornett Andrew , Nistor Ioan
Published: June 2020

Over the past decade, the use of imaging devices to perform quantitative measurements has seen wide-scale adoption and has become integral to the emerging fields of research, such as computer vision and artificial intelligence. Recent studies, published across a wide variety of fields, have demonstrated a vast number of ways through which image-based measurement systems can be used in their respective fields. A growing number of studies have demonstrated applications in coastal and ocean research. Edge detection methods have been used to measure water surface and bedform elevation from recorded video taken during wave flume experiments. The turbulent mixing of air and water, induced by the breaking waves and the runup processes, poses a particular problem for the edge-detection methods, since they rely on a sharp contrast between air and water. In this paper, an alternative method for tracking water surface, based on color segmentation, is presented. A set of experiments were conducted whereby the proposed method was used to detect water surface profiles for various types of breaking waves interacting with a rubble mound breakwater. The results were further processed to compute the surface velocity during runup. The time-history of surface velocity is shown to closely parallel the point measurements taken nearby the instrumented armor unit. These velocities can potentially serve as boundary conditions for determining the dynamic loads exerted on the armour units. Further, the image processing results are used to remove the time-varying buoyant force from the measured force acting on an individual armour unit, providing additional insight into how the forces develop over time.
Marine Autopilots’ Multipurpose Control Laws Synthesis for Actuators Time Delay
Authors: Veremey Evgeny I. , Pogozhev Sergei V. , Sotnikova Margarita V.
Published: June 2020

One analytical design problem involves constructing control laws for marine autopilot systems. Despite numerous known solutions, this problem can still be further developed by taking into account the actual conditions of the control system operation. An important issue for discussion is the feedback synthesis for marine ships with time delays in their rudders’ actuators. In this work, a new approach is proposed for providing all the desirable dynamic features of a closed-loop system with autopilot while taking into account the presence of a time delay. This approach is based on the predictive compensation of time delays via the specific transformation of an initially given reference controller with a special multipurpose structure. The applicability and effectiveness of the proposed method is further illustrated by a practical example of a controller design.
Semantic Priming in Mild Cognitive Impairment and Healthy Subjects: Effect of Different Time of Presentation of Word-Pairs
Authors: Guglielmi Valeria , Quaranta Davide , Mega Ilaria , Costantini Emanuele Maria , Carrarini Claudia , Innocenti Alice , Marra Camillo
Published: June 2020

Introduction: Semantic memory is impaired in mild cognitive impairment (MCI). Two main hypotheses about this finding are debated and refer to the degradation of stored knowledge versus the impairment of semantic access mechanisms. The aim of our study is to evaluate semantic impairment in MCI versus healthy subjects (HS) by an experiment evaluating semantic priming. Methods: We enrolled 27 MCI and 20 HS. MCI group were divided, according to follow up, into converters-MCI and non converters-MCI. The semantic task consisted of 108 pairs of words, 54 of which were semantically associated. Stimuli were presented 250 or 900 ms later the appearance of the target in a randomized manner. Data were analyzed using factorial ANOVA. Results: Both HS and MCI answered more quickly for word than for non-word at both stimulus onset asynchrony (SOA) intervals. At 250 ms, both MCI and HS experienced a shorter time of response for related-word than for unrelated words (priming effect), while only the converters-MCI subgroup lost the priming effect. Further, we observed a rather larger Cohen’s d effect size in non converters-MCI than in converters-MCI. Conclusion: Our data, and in particular the absence of a semantic priming effect in converters-MCI, could reflect the impairment of semantic knowledge rather than the accessibility of semantic stores in MCI individuals that progress to dementia.
A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS
Authors: Connolly Owen , Le Gall Laura , McCluskey Gavin , Donaghy Colette G , Duddy William J , Duguez Stephanie
Published: June 2020

Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechanisms that lead to the onset of ALS and as a result there are no reliable biomarkers that aid in the early detection of the disease nor is there an effective treatment. This review first considers the clinical phenotypes associated with ALS, and discusses the broad categorisation of ALS and ALS-mimic diseases into upper and lower motor neuron diseases, before focusing on the genetic aetiology of ALS and considering the potential relationship of mutations of different genes to variations in phenotype. For this purpose, a systematic review is conducted collating data from 107 original published clinical studies on monogenic forms of the disease, surveying the age and site of onset, disease duration and motor neuron involvement. The collected data highlight the complexity of the disease’s genotype–phenotype relationship, and thus the need for a nuanced approach to the development of clinical assays and therapeutics.
In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes
Authors: Navarro-Paya Carlos , Sanz-Hernandez Maximo , De Simone Alfonso
Published: June 2020

The membrane binding by α-synuclein (αS), a presynaptic protein whose aggregation is strongly linked with Parkinson’s disease, influences its biological behavior under functional and pathological conditions. This interaction requires a conformational transition from a disordered-unbound to a partially helical membrane-bound state of the protein. In the present study, we used enhanced coarse-grained MD simulations to characterize the sequence and conformational determinants of the binding to synaptic-like vesicles by the N-terminal region of αS. This region is the membrane anchor and is of crucial importance for the properties of the physiological monomeric state of αS as well as for its aberrant aggregates. These results identify the key factors that play a role in the binding of αS with synaptic lipid bilayers in both membrane-tethered and membrane-locked conformational states.
Molybdenum Oxide and Nickel Nitrate as Cooperative Sintering Aids for Yttria-Stabilized Zirconia
Authors: Hunt Clay , Allemeier John Kyle , Driscoll David , Weisenstein Adam , Sofie Stephen
Published: June 2020

The entirely accidental observation of increased sintering performance of nickel-infiltrated yttria-stabilized zirconia (8YSZ) in a molybdenum and oxygen rich atmosphere was explored. Molybdenum and nickel were found to be synergistic sintering aids for 8YSZ. However, sintering had to take place in an atmosphere of flowing oxygen. Samples sintered in air consistently burst. The sintering performance, microstructure, and crystal structure of 8YSZ with additions of both Mo and Ni together are compared to the sintering performance, microstructure, and crystal structure of pure 8YSZ, 8YSZ with only Ni added as a sintering aid, and 8YSZ with only Mo added as a sintering aid. Enhanced densification and grain growth is observed in the Mo–Ni 8YSZ samples when compared to all other sintering samples. Order of magnitude sintering rate increases are observed in the Mo–Ni 8YSZ over that of pure 8YSZ. With a maximum sintering temperature of 1200 °C and a one-hour dwell, sintered densities of 85% theoretical density (5.02 g⁄cm3) are achieved with the Mo–Ni samples: a 57% increase in density over pure 8YSZ sintered with the same sintering profile. EIS results suggest conductivity may not be negatively impacted by the use of these two sintering aids at temperatures above 750 °C. Finally, the spontaneous generation of nickel-molybdenum nano-rods was observed on the 5, and 10 mol.% Mo–Ni infiltrated 8YSZ samples after being left under vacuum in a scanning electron microscope chamber, suggesting evaporation of a possible nickel–molybdenum compound from the sample fracture surfaces.
A New Proposal: A Digital Flow for the Construction of a Haas-Inspired Rapid Maxillary Expander (HIRME)
Authors: Cozzani Mauro , Antonini Salima , Lupini Daniela , Decesari Davide , Anelli Fabrizio , Doldo Tiziana
Published: June 2020

Maxillary expansion is a common orthodontic treatment used for the correction of posterior crossbite resulting from reduced maxillary width. Transverse maxillomandibular discrepancies are a major cause of several malocclusions and may be corrected in different manners; in particular, the rapid maxillary expansion (RME) performed in the early mixed dentition has now become a routine procedure in orthodontic practice. The aim of this study is to propose a procedure that reduces the patient cooperation as well as the lab work required in preparing a customized Haas-inspired rapid maxillary expander (HIRME) that can be anchored to deciduous teeth and can be utilized in mixed dentition with tubes on the molars and hooks and brackets on the canines. This article thus presents an expander that is completely digitally developed, from the first moment of taking the impression with an optical scanner to the final solidification phase by the use of a 3D printer. This digital flow takes place in a CAD environment and it starts with the creation of the appliance on the optical impression; this design is then exported as an stl extension and is sent to the print service to obtain a solid model of the device through a laser sintering process. This “rough” device goes through a post-processing procedure; finally, a commercial expansion screw is laser-welded. This expander has all the advantages of a cast-metal Haas-type RME that rests on deciduous teeth; moreover, it has the characteristic of being developed with a completely digitized and individualized process, for the mouth of the young patient, as well as being made completely of cobalt-chrome, thus ensuring greater adaptability and stability in the patient’s mouth.
Existence Results for Sequential Riemann–Liouville and Caputo Fractional Differential Inclusions with Generalized Fractional Integral Conditions
Authors: Tariboon Jessada , Ntouyas Sotiris K. , Ahmad Bashir , Alsaedi Ahmed
Published: June 2020

Under different criteria, we prove the existence of solutions for sequential fractional differential inclusions containing Riemann–Liouville and Caputo type derivatives and supplemented with generalized fractional integral boundary conditions. Our existence results rely on the endpoint theory, the Krasnosel’skiĭ’s fixed point theorem for multivalued maps and Wegrzyk’s fixed point theorem for generalized contractions. We demonstrate the application of the obtained results with the help of examples.
Hydrothermal Processing of Laminaria ochroleuca for the Production of Crude Extracts Used to Formulate Polymeric Nanoparticles
Authors: Flórez-Fernández Noelia , Álvarez-Viñas Milena , Guerreiro Filipa , Torres María Dolores , Grenha Ana , Domínguez Herminia
Published: June 2020

A green extraction process using only water was proposed for the simultaneous extraction of alginate and bioactive compounds from Laminaria ochroleuca. Operation was carried out during non-isothermal heating up to maximal temperatures over the range of 70 °C to 100 °C. Once separated, the alginate and the crude extract were characterised and the biological activities and cytotoxicity of the extracts was studied, the latter in intestinal epithelial cells. Those alginates obtained at 90 °C exhibited the highest extraction yields and viscoelastic features of the corresponding hydrogels. The obtained results show that the extracts obtained by non-isothermal extraction were suitable to formulate nanoparticles, which showed the smallest size (≈250–350 nm) when the higher content of fucoidan extract was present. Given the evidenced properties, the extracts may find an application in the formulation of nanoparticulate carriers for drug delivery.
Chermebilaenes A and B, New Bioactive Meroterpenoids from Co-Cultures of Marine-Derived Isolates of Penicillium bilaiae MA-267 and Penicillium chermesinum EN-480
Authors: Meng Ling-Hong , Li Xiao-Ming , Li Hong-Lei , Wang Bin-Gui
Published: June 2020

The co-cultivation of two or more different microbial strains in one culture vessel was supposed to be a viable experimental approach for enhancing the diversity of the compounds produced. Two new meroterpenoid derivatives, chermebilaenes A (1) and B (2), together with three known sesquiterpenoids, sesquicaranoic acid B (3), cyclonerodiol (4) and bisabol-l-on-13-säuremethylester (5), were characterized from a co-culture of the marine-derived fungal isolates of Penicillium bilaiae MA-267 and Penicillium chermesinum EN-480. Neither fungus produced these compounds when cultured alone under the same conditions. Compound 1 represents an unprecedented acorane-type sesquiterpene hybridized with an octadecadienoic acid skeleton. The structures were elucidated on the basis of spectroscopic analysis, and the absolute configurations were assumed on the basis of acidic hydrolysis combined with modified Mosher’s method and electronic circular dichroism (ECD) calculations. Compound 1 showed potent inhibitory activities against Ceratobasidium cornigerum and Edwardsiella tarda.
In-Situ Combination of Bipolar Membrane Electrodialysis with Monovalent Selective Anion-Exchange Membrane for the Valorization of Mixed Salts into Relatively High-Purity Monoprotic and Diprotic Acids
Authors: Yan Haiyang , Li Wei , Zhou Yongming , Irfan Muhammad , Wang Yaoming , Jiang Chenxiao , Xu Tongwen
Published: June 2020

The crystalized mixed salts from the zero liquid discharge process are a hazardous threat to the environment. In this study, we developed a novel electrodialysis (SBMED) method by assembling the monovalent selective anion-exchange membrane (MSAEM) into the bipolar membrane electrodialysis (BMED) stack. By taking the advantages of water splitting in the bipolar membrane and high perm-selectivity of MSAEM for the Cl− ions against the SO42− ions, this combination allows the concurrent separation of Cl−/SO42− and conversion of mixed salts into relatively high-purity monoprotic and diprotic acids. The current density has a significant impact on the acid purity. Both the monoprotic and diprotic acid purities were higher than 80% at a low current density of 10 mA/cm2. The purities of the monoprotic acids decreased with an increase in the current density, indicating that the perm-selectivity of MSAEM decreases with increasing current density. An increase in the ratio of monovalent to divalent anions in the feed was beneficial to increase the purity of monoprotic acids. High-purity monoprotic acids in the range of 93.9–96.1% were obtained using this novel SBMED stack for treating simulated seawater. Therefore, it is feasible for SBMED to valorize the mixed salts into relatively high-purity monoprotic and diprotic acids in one step.
Steel Surface Defect Classification Using Deep Residual Neural Network
Authors: Konovalenko Ihor , Maruschak Pavlo , Brezinová Janette , Viňáš Ján , Brezina Jakub
Published: June 2020

An automated method for detecting and classifying three classes of surface defects in rolled metal has been developed, which allows for conducting defectoscopy with specified parameters of efficiency and speed. The possibility of using the residual neural networks for classifying defects has been investigated. The classifier based on the ResNet50 neural network is accepted as a basis. The model allows classifying images of flat surfaces with damage of three classes with the general accuracy of 96.91% based on the test data. The use of ResNet50 is shown to provide excellent recognition, high speed, and accuracy, which makes it an effective tool for detecting defects on metal surfaces.
Alloy Optimization for Reducing Delayed Fracture Sensitivity of 2000 MPa Press Hardening Steel
Authors: Mohrbacher Hardy , Senuma Takehide
Published: June 2020

Press hardening steel (PHS) is widely applied in current automotive body design. The trend of using PHS grades with strengths above 1500 MPa raises concerns about sensitivity to hydrogen embrittlement. This study investigates the hydrogen delayed fracture sensitivity of steel alloy 32MnB5 with a 2000 MPa tensile strength and that of several alloy variants involving molybdenum and niobium. It is shown that the delayed cracking resistance can be largely enhanced by using a combination of these alloying elements. The observed improvement appears to mainly originate from the obstruction of hydrogen-induced damage incubation mechanisms by the solutes as well as the precipitates of these alloying elements.
Correlation between Microstructure and Mechanical Properties of Heat-Treated Ti–6Al–4V with Fe Alloying
Authors: Liu Yongwei , Chen Fuwen , Xu Guanglong , Cui Yuwen , Chang Hui
Published: June 2020

The microstructure and mechanical properties of a newly developed Fe-microalloyed Ti–6Al–4V titanium alloy were investigated after different heat treatments. The volume fraction and the morphological features of the lamellar α phase had significant effects on the alloy’s mechanical performance. A dataset showing the relationship between microstructural features and tensile strength, elongation, and fracture toughness was developed. A high aging temperature resulted in high plasticity and fracture toughness, but relatively low strength. The high strength favored the fine α and the slender β. The high aspect ratio of lamellar α led to high strength but low fracture toughness. The alloy with ~84 vol % α exhibited the highest strength and lowest fracture toughness because the area of its α/β-phase interface was the highest. Optimal comprehensive mechanical performance and heat-treatment procedures were thus obtained from the dataset. Optimal tensile strength, yield strength, elongation, and fracture toughness were 999 and 919 MPa, 10.4%, and 94.4 MPa·m1/2, respectively.
Comparative Study on the Cavitation Erosion and Sliding Wear of Cold-Sprayed Al/Al2O3 and Cu/Al2O3 Coatings, and Stainless Steel, Aluminium Alloy, Copper and Brass
Authors: Szala Mirosław , Łatka Leszek , Walczak Mariusz , Winnicki Marcin
Published: June 2020

The paper investigates the cavitation erosion (CE) and sliding wear (SW) resistance of cold-sprayed Al/Al2O3 and Cu/Al2O3 composites and studies them in relation to a set of metallic materials such as aluminium alloy (AlCu4Mg1), pure copper (Cu110), brass (CuZn40Pb2) and stainless steel (AISI 304). The coatings were deposited on stainless steel by low-pressure cold spray (LPCS) using Al (40 wt.%) and Cu (50 wt.%) blended with Al2O3 (60 and 50 wt.%, respectively) feedstocks. CE resistance was estimated by the stationary sample method according to the ASTM G32 standard. The SW test was conducted using a ball-on-disc tester with compliance to the ASTM G99 standard. Results obtained for the LPCS coatings show that the Cu/Al2O3 coating exhibits a denser structure but lower adhesion and microhardness than Al/Al2O3. The Al/Al2O3 and Cu/Al2O3 resistance to cavitation is lower than for bulk alloys; however, composites present higher sliding wear resistance to that of AlCu4Mg1, CuZn40Pb2 and stainless steel. The CE wear mechanisms of LPCS composites start at the structural discontinuities and non-uniformities. The cavitation erosion degradation mechanism of Al/Al2O3 relies on chunk material detachment while that of Cu/Al2O3 initiates by alumina removal and continues as layer-like Cu-metallic material removal. CE damage of metal alloys relies on the fatigue-induced removal of deformed material. The SW mechanism of bulk alloys has a dominant adhesive mode. The addition of Al2O3 successfully reduces the material loss of LPCS composites but increases the friction coefficient. Coatings’ wear mechanism has an adhesive-abrasive mode. In both CE and SW environment, the behaviour of the cold-sprayed Cu/Al2O3 composite is much more promising than that of the Al/Al2O3.
Effect of Sample-Size on the Compression Deformation Behavior of a CuZr-Based Bulk Metallic Glass Composite
Authors: Chen Yongsheng , Liang Weizhong , Wang Longxing , Qi Kai , Wang Yang , Sun Xiaomei , Fang Naiwen
Published: June 2020

The compressive deformation behaviors and microstructures of Cu45Zr48Al4Nb3 bulk metallic glass composites with diameters of 3, 2, and 1 mm were investigated systematically. It was found that the smallest sample showed the highest yield strength and compressive plasticity. The yield strength of the samples was found to depend on the fraction of their crystalline phases in the glassy matrix. The smaller samples showed larger free volumes, which is favorable for plastic deformation. The deformation behavior of the samples was found to depend on their size. The results obtained in this study will be helpful for investigating the mechanical behavior of metallic glass composites.
Austenite Reverse Transformation in a Q&P Route of Mn and Ni Added Steels
Authors: Arribas Maribel , Gutiérrez Teresa , Del Molino Eider , Arlazarov Artem , De Diego-Calderón Irene , Martin David , De Caro Daniele , Ayenampudi Sudhindra , Santofimia Maria J.
Published: June 2020

In this work, four low carbon steels with different contents of Mn and Ni were heat treated by quenching and partitioning (Q&P) cycles where high partitioning temperatures, in the range of 550 °C–650 °C, were applied. In order to elucidate the effect of applying these high partitioning temperatures with respect to more common Q&P cycles, the materials were also heat treated considering a partitioning temperature of 400 °C. The microstructure evolution during the Q&P cycles was studied by means of dilatometry tests. The microstructural characterization of the treated materials revealed that austenite retention strongly depended on the alloy content and partitioning conditions. It was shown that the occurrence of austenite reverse transformation (ART) in the partitioning stage in some of the alloys and conditions was a very effective mechanism to increase the austenite content in the final microstructure. However, the enhancement of tensile properties achieved by the application of high partitioning temperature cycles was not significant.
Fatigue Design and Defects in Metals and Alloys
Authors: Fontanari Vigilio , Benedetti Matteo
Published: June 2020

The effort to correctly understand and account for the detrimental influence of defects in the design of components undergoing in service complex time-varying loads characterizes the major part of the history of metal fatigue [...]
A High-Precision Magnetic-Assisted Heading Angle Calculation Method Based on a 1D Convolutional Neural Network (CNN) in a Complicated Magnetic Environment
Authors: Hu Guanghui , Wan Hong , Li Xinxin
Published: June 2020

Due to its widespread presence and independence from artificial signals, the application of geomagnetic field information in indoor pedestrian navigation systems has attracted extensive attention from researchers. However, for indoors environments, geomagnetic field signals can be severely disturbed by the complicated magnetic, leading to reduced positioning accuracy of magnetic-assisted navigation systems. Therefore, there is an urgent need for methods which screen out undisturbed geomagnetic field data for realizing the high accuracy pedestrian inertial navigation indoors. In this paper, we propose an algorithm based on a one-dimensional convolutional neural network (1D CNN) to screen magnetic field data. By encoding the magnetic data within a certain time window to a time series, a 1D CNN with two convolutional layers is designed to extract data features. In order to avoid errors arising from artificial labels, the feature vectors will be clustered in the feature space to classify the magnetic data using unsupervised methods. Our experimental results show that this method can distinguish the geomagnetic field data from indoors disturbed magnetic data well and further significantly improve the calculation accuracy of the heading angle. Our work provides a possible technical path for the realization of high-precision indoor pedestrian navigation systems.
Clinical Detection of Chronic Rhinosinusitis through Next-Generation Sequencing of the Oral Microbiota
Authors: Yuan Ben-Chih , Yeh Yao-Tsung , Lin Ching-Chiang , Huang Cheng-Hsieh , Liu Hsueh-Chiao , Chiang Chih-Po
Published: June 2020

Chronic rhinosinusitis (CRS) is the chronic inflammation of the sinus cavities of the upper respiratory tract, which can be caused by a disrupted microbiome. However, the role of the oral microbiome in CRS is not well understood. Polymicrobial and anaerobic infections of CRS frequently increased the difficulty of cultured and antibiotic therapy. This study aimed to elucidate the patterns and clinical feasibility of the oral microbiome in CRS diagnosis. Matched saliva and nasal swabs were collected from 18 CRS patients and 37 saliva specimens from normal volunteers were collected for 16S rRNA sequencing. The α-diversity of the saliva displayed no significant difference between control and CRS patients, whereas the β-diversity was significantly different (p = 0.004). Taxonomic indices demonstrated that Veillonella dispar, Rothia mucilaginosa, and Porphyromonas endodontalis were enriched, while Campylobacter and Cardiobacterium were reduced in the saliva of CRS patients. These microbial markers could significantly distinguish CRS patients from control (AUC = 0.939). It is noted that the 16S rRNA results of the nasal swab were consistent with the nasopharynx aerobic culture, and additionally detected multiple pathogens in CRS patients. In summary, these results indicated these oral microbiomes may provide a novel signal for CRS detection and that NGS may be an alternative approach for CRS diagnosis.