bluuebunny/crossref_metadata_2025 huggingface dataset:
Degradation of Transcriptional Repressor ATF4 during Long-Term Synaptic Plasticity
Authors: Smith Spencer G. , Haynes Kathryn A. , Hegde Ashok N.
Published: November 2020

Maintenance of long-term synaptic plasticity requires gene expression mediated by cAMP-responsive element binding protein (CREB). Gene expression driven by CREB can commence only if the inhibition by a transcriptional repressor activating transcription factor 4 (ATF4; also known as CREB2) is relieved. Previous research showed that the removal of ATF4 occurs through ubiquitin-proteasome-mediated proteolysis. Using chemically induced hippocampal long-term potentiation (cLTP) as a model system, we investigate the mechanisms that control ATF4 degradation. We observed that ATF4 phosphorylated at serine-219 increases upon induction of cLTP and decreases about 30 min thereafter. Proteasome inhibitor β-lactone prevents the decrease in ATF4. We found that the phosphorylation of ATF4 is mediated by cAMP-dependent protein kinase. Our initial experiments towards the identification of the ligase that mediates ubiquitination of ATF4 revealed a possible role for β-transducin repeat containing protein (β-TrCP). Regulation of ATF4 degradation is likely to be a mechanism for determining the threshold for gene expression underlying maintenance of long-term synaptic plasticity and by extension, long-term memory.
Invertebrate Gonadotropin-Releasing Hormone Receptor Signaling and Its Relevant Biological Actions
Authors: Sakai Tsubasa , Yamamoto Tatsuya , Matsubara Shin , Kawada Tsuyoshi , Satake Honoo
Published: November 2020

Gonadotropin-releasing hormones (GnRHs) play pivotal roles in reproduction via the hypothalamus-pituitary-gonad axis (HPG axis) in vertebrates. GnRHs and their receptors (GnRHRs) are also conserved in invertebrates lacking the HPG axis, indicating that invertebrate GnRHs do not serve as “gonadotropin-releasing factors” but, rather, function as neuropeptides that directly regulate target tissues. All vertebrate and urochordate GnRHs comprise 10 amino acids, whereas amphioxus, echinoderm, and protostome GnRH-like peptides are 11- or 12-residue peptides. Intracellular calcium mobilization is the major second messenger for GnRH signaling in cephalochordates, echinoderms, and protostomes, while urochordate GnRHRs also stimulate cAMP production pathways. Moreover, the ligand-specific modulation of signal transduction via heterodimerization between GnRHR paralogs indicates species-specific evolution in Ciona intestinalis. The characterization of authentic or putative invertebrate GnRHRs in various tissues and their in vitro and in vivo activities indicate that invertebrate GnRHs are responsible for the regulation of both reproductive and nonreproductive functions. In this review, we examine our current understanding of and perspectives on the primary sequences, tissue distribution of mRNA expression, signal transduction, and biological functions of invertebrate GnRHs and their receptors.
Extended Cleavage Specificity of the Rat Vascular Chymase, a Potential Blood Pressure Regulating Enzyme Expressed by Rat Vascular Smooth Muscle Cells
Authors: Berglund Petter , Akula Srinivas , Fu Zhirong , Thorpe Michael , Hellman Lars
Published: November 2020

Serine proteases constitute the major protein content of the cytoplasmic granules of several hematopoietic cell lineages. These proteases are encoded from four different loci in mammals. One of these loci, the chymase locus, has in rats experienced a massive expansion in the number of functional genes. The human chymase locus encodes 4 proteases, whereas the corresponding locus in rats contains 28 such genes. One of these new genes has changed tissue specificity and has been found to be expressed primarily in vascular smooth muscle cells, and therefore been named rat vascular chymase (RVC). This β-chymase has been claimed to be a potent angiotensin-converting enzyme by cleaving angiotensin (Ang) I into Ang II and thereby having the potential to regulate blood pressure. To further characterize this enzyme, we have used substrate phage display and a panel of recombinant substrates to obtain a detailed quantitative view of its extended cleavage specificity. RVC was found to show a strong preference for Phe and Tyr in the P1 position, but also to accept Leu and Trp in this position. A strong preference for Ser or Arg in the P1’ position, just C-terminally of the cleavage site, and a preference for aliphatic amino acids in most other positions surrounding the cleavage site was also seen. Interesting also was a relatively strict preference for Gly in positions P3’ and P4’. RVC thereby shares similarity in its specificity to the mouse mucosal mast cell chymase mMCP-1, which efficiently converts Ang I to Ang II. This similarity adds support for the role of β-chymases as potent angiotensin converters in rodents, as their α-chymases, which have the capacity to efficiently convert Ang I into Ang II in other mammalian lineages, have become elastases. However, interestingly we found that RVC cleaved both after Arg2 and Phe8 in Ang I. Furthermore this cleavage was more than two hundred times less efficient than the consensus site obtained from the phage display analysis, indicating that RVC has a very low ability to cleave Ang I, raising serious doubts about its role in Ang I conversion.
Therapeutic Potential of the Natural Compound S-Adenosylmethionine as a Chemoprotective Synergistic Agent in Breast, and Head and Neck Cancer Treatment: Current Status of Research
Authors: Mosca Laura , Vitiello Francesca , Coppola Alessandra , Borzacchiello Luigi , Ilisso Concetta Paola , Pagano Martina , Caraglia Michele , Cacciapuoti Giovanna , Porcelli Marina
Published: November 2020

The present review summarizes the most recent studies focusing on the synergistic antitumor effect of the physiological methyl donor S-adenosylmethionine (AdoMet) in association with the main drugs used against breast cancer and head and neck squamous cell carcinoma (HNSCC), two highly aggressive and metastatic malignancies. In these two tumors the chemotherapy approach is recommended as the first choice despite the numerous side effects and recurrence of metastasis, so better tolerated treatments are needed to overcome this problem. In this regard, combination therapy with natural compounds, such as AdoMet, a molecule with pleiotropic effects on multiple cellular processes, is emerging as a suitable strategy to achieve synergistic anticancer efficacy. In this context, the analysis of studies conducted in the literature highlighted AdoMet as one of the most effective and promising chemosensitizing agents to be taken into consideration for inclusion in emerging antitumor therapeutic modalities such as nanotechnologies.
TLR2 Deficiency Exacerbates Imiquimod-Induced Psoriasis-Like Skin Inflammation through Decrease in Regulatory T Cells and Impaired IL-10 Production
Authors: Nakao Momoko , Sugaya Makoto , Fujita Hideki , Miyagaki Tomomitsu , Morimura Sohshi , Shibata Sayaka , Asano Yoshihide , Sato Shinichi
Published: November 2020

Emerging evidence has demonstrated that Toll-like receptors (TLRs) are associated with autoimmune diseases. In this study, we investigated the role of TLR2 in psoriasis using imiquimod-induced psoriasis-like dermatitis. Although TLR2 signaling is known to play a critical role in the induction of proinflammatory cytokines by immune cells, such as dendritic cells (DCs), macrophages, and monocytes, TLR2 deficiency unexpectedly exacerbated psoriasiform skin inflammation. Importantly, messenger RNA (mRNA) levels of Foxp-3 and IL-10 in the lesional skin were significantly decreased in TLR2 KO mice compared with wild-type mice. Furthermore, flow cytometric analysis of the lymph nodes revealed that the frequency of regulatory T cells (Tregs) among CD4-positive cells was decreased. Notably, stimulation with Pam3CSK4 (TLR2/1 ligand) or Pam2CSK4 (TLR2/6 ligand) increased IL-10 production from Tregs and DCs and the proliferation of Tregs. Finally, adoptive transfer of Tregs from wild-type mice reduced imiquimod-induced skin inflammation in TLR2 KO mice. Taken together, our results suggest that TLR2 signaling directly enhances Treg proliferation and IL-10 production by Tregs and DCs, suppressing imiquimod-induced psoriasis-like skin inflammation. Enhancement of TLR2 signaling may be a new therapeutic strategy for psoriasis.
Natural Genetic Resources from Diverse Plants to Improve Abiotic Stress Tolerance in Plants
Authors: Yolcu Seher , Alavilli Hemasundar , Lee Byeong-ha
Published: November 2020

The current agricultural system is biased for the yield increase at the cost of biodiversity. However, due to the loss of precious genetic diversity during domestication and artificial selection, modern cultivars have lost the adaptability to cope with unfavorable environments. There are many reports on variations such as single nucleotide polymorphisms (SNPs) and indels in the stress-tolerant gene alleles that are associated with higher stress tolerance in wild progenitors, natural accessions, and extremophiles in comparison with domesticated crops or model plants. Therefore, to gain a better understanding of stress-tolerant traits in naturally stress-resistant plants, more comparative studies between the modern crops/model plants and crop progenitors/natural accessions/extremophiles are required. In this review, we discussed and summarized recent progress on natural variations associated with enhanced abiotic stress tolerance in various plants. By applying the recent biotechniques such as the CRISPR/Cas9 gene editing tool, natural genetic resources (i.e., stress-tolerant gene alleles) from diverse plants could be introduced to the modern crop in a non-genetically modified way to improve stress-tolerant traits.
TGF-β in the Secretome of Irradiated Peripheral Blood Mononuclear Cells Supports In Vitro Osteoclastogenesis
Authors: Panahipour Layla , Kargarpour Zahra , Laggner Maria , Mildner Michael , Ankersmit Hendrik J. , Gruber Reinhard
Published: November 2020

Osteoclastogenesis required for bone remodeling is also a key pathologic mechanism of inflammatory osteolysis being controlled by paracrine factors released from dying cells. The secretome of irradiated, dying peripheral blood mononuclear cells (PBMCs) has a major impact on the differentiation of myeloid cells into dendritic cells, and macrophage polarization. The impact on osteoclastogenesis, however, has not been reported. For this aim, we used murine bone marrow macrophages exposed to RANKL and M-CSF to initiate osteoclastogenesis, with and without the secretome obtained from γ-irradiated PBMCs. We reported that the secretome significantly enhanced in vitro osteoclastogenesis as determined by means of histochemical staining of the tartrate-resistant acid phosphatase (TRAP), as well as the expression of the respective target genes, including TRAP and cathepsin K. Considering that TGF-β enhanced osteoclastogenesis, we confirmed the TGF-β activity in the secretome with a bioassay that was based on the increased expression of IL11 in fibroblasts. Neutralizing TGF-β by an antibody decreased the ability of the secretome to support osteoclastogenesis. These findings suggested that TGF-β released by irradiated PBMCs could enhance the process of osteoclastogenesis in vitro.
C-Src Is Activated by the EGF Receptor in a Pathway that Mediates JNK and ERK Activation by Gonadotropin-Releasing Hormone in COS7 Cells
Authors: Kraus Sarah , Benard Outhiriaradjou , Naor Zvi , Seger Rony
Published: November 2020

The key participants in G-protein-coupled receptor (GPCR) signaling are the mitogen-activated protein kinase (MAPK) signaling cascades. The mechanisms involved in the activation of the above cascades by GPCRs are not fully elucidated. The prototypical GPCR is the receptor for gonadotropin-releasing hormone (GnRHR), which serves as a key regulator of the reproductive system. Here, we expressed GnRHR in COS7 cells and found that GnRHR transmits its signals to MAPKs mainly via Gαi and the EGF receptor, without the involvement of Hb-EGF or PKCs. The main pathway that leads to JNK activation downstream of the EGF receptor involves a sequential activation of c-Src and PI3K. ERK activation by GnRHR is mediated by the EGF receptor, which activates Ras either directly or via c-Src. Beside the main pathway, the dissociated Gβγ and β-arrestin may initiate additional (albeit minor) pathways that lead to MAPK activation in the transfected COS7 cells. The pathways detected are significantly different from those in other GnRHR-bearing cells, indicating that GnRH can utilize various signaling mechanisms for MAPK activation. The unique pathway elucidated here, in which c-Src and PI3K are sequentially activated downstream of the EGF receptor, may serve as a prototype of signaling mechanisms by GnRHR and additional GPCRs in various cell types.
Cryopreservation of Mesenchymal Stem Cells Using Medical Grade Ice Nucleation Inducer
Authors: Wragg Nicholas M. , Tampakis Dimitris , Stolzing Alexandra
Published: November 2020

Mesenchymal stem cells (MSCs) can differentiate into multiple different tissue lineages and have favourable immunogenic potential making them an attractive prospect for regenerative medicine. As an essential part of the manufacturing process, preservation of these cells whilst maintaining potential is of critical importance. An uncontrolled area of storage remains the rate of change of temperature during freezing and thawing. Controlled-rate freezers attempted to rectify this; however, the change of phase from liquid to solid introduces two extreme phenomena; a rapid rise and a rapid fall in temperature in addition to the intended cooling rate (normally −1 °C/min) as a part of the supercooling event in cryopreservation. Nucleation events are well known to initiate the freezing transition although their active use in the form of ice nucleation devices (IND) are in their infancy in cryopreservation. This study sought to better understand the effects of ice nucleation and its active instigation with the use of an IND in both a standard cryotube with MSCs in suspension and a high-throughput adhered MSC 96-well plate set-up. A potential threshold nucleation temperature for best recovery of dental pulp MSCs may occur around −10 °C and for larger volume cell storage, IND and fast thaw creates the most stable process. For adhered cells, an IND with a slow thaw enables greatest metabolic activity post-thaw. This demonstrates a necessity for a medical grade IND to be used in future regenerative medicine manufacturing with the parameters discussed in this study to create stable products for clinical cellular therapies.
ASC, IL-18 and Galectin-3 as Biomarkers of Non-Alcoholic Steatohepatitis: A Proof of Concept Study
Authors: Cyr Brianna , Keane Robert W. , de Rivero Vaccari Juan Pablo
Published: November 2020

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease that is growing in prevalence. Symptoms of NASH become apparent when the disease has progressed significantly. Thus, there is a need to identify biomarkers of NASH in order to detect the disease earlier and to monitor disease severity. The inflammasome has been shown to play a role in liver diseases. Here, we performed a proof of concept study of biomarker analyses (cut-off points, positive and negative predictive values, receiver operating characteristic (ROC) curves, and likelihood ratios) on the serum of patients with NASH and healthy controls on apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18, Galectin-3 (Gal-3), and C-reactive protein (CRP). ASC, IL-18, and Gal-3 were elevated in the serum of NASH patients when compared to controls. The area under the curve (AUC) for ASC was the highest (0.7317) with an accuracy of 68%, followed by IL-18 (0.7036) with an accuracy of 66% and Gal-3 (0.6891) with an accuracy of 61%. Moreover, we then fit a stepwise multivariate logistic regression model using ASC, IL-18, and Gal-3 to determine the probability of patients having a NASH diagnosis, which resulted in an AUC of 0.71 and an accuracy of 79%, indicating that combining these biomarkers increases their diagnostic potential for NASH. These results indicate that ASC, IL-18, and Gal-3 are reliable biomarkers of NASH and that combining these analytes increases the biomarker potential of these proteins.
Distributed Simulation with Multi-Agents for IoT in a Retail Pharmacy Facility
Authors: Basingab Mohammed
Published: November 2020

Nowadays, internet of things (IoT) technology is considered as one of the key future technologies. The adoption of such technology is receiving quick attention from many industries as competitive pressures inspire them to move forward and invest. As technologies continue to advance, such as IoT, there is a vital need for an approach to identify its viability. This research proposes the adoption of IoT technology and the use of a simulation paradigm to capture the complexity of a system, offer reliable and continuous perceptions into its present and likely future state, and evaluate the economic feasibility of such adoption. A case study of one of the largest pharmacy retail chain is presented. IoT devices are suggested to be used to remotely monitor the failures of a geographically distributed system of refrigeration units. Multi-agents distributed system is proposed to simulate the operational behavior of the refrigerators and calculate the return of investment (ROI) of the proposed IoT implementation.
Species Separation within, and Preliminary Phylogeny for, the Leafhopper Genus Anoscopus with Particular Reference to the Putative British Endemic Anoscopus duffieldi (Hemiptera: Cicadellidae)
Authors: Redihough Joanna , Russo Isa-Rita M. , Stewart Alan J. A. , Malenovský Igor , Stockdale Jennifer E. , Moorhouse-Gann Rosemary J. , Wilson Michael R. , Symondson William O. C.
Published: November 2020

The subfamily Aphrodinae (Hemiptera: Cicadellidae) contains ~33 species in Europe within four genera. Species in two genera in particular, Aphrodes and Anoscopus, have proved to be difficult to distinguish morphologically. Our aim was to determine the status of the putative species Anoscopus duffieldi, found only on the RSPB Nature Reserve at Dungeness, Kent, a possible rare UK endemic. DNA from samples of all seven UK Anoscopus species (plus Anoscopusalpinus from the Czech Republic) were sequenced using parts of the mitochondrial cytochrome oxidase I and 16S rRNA genes. Bayesian inference phylogenies were created. Specimens of each species clustered into monophyletic groups, except for Anoscopusalbifrons, A. duffieldi and Anoscopuslimicola. Two A. albifrons specimens grouped with A. duffieldi repeatedly with strong support, and the remaining A. albifrons clustered within A. limicola. Genetic distances suggest that A. albifrons and A. limicola are a single interbreeding population (0% divergence), while A. albifrons and A. duffieldi diverged by only 0.28%. Shared haplotypes between A. albifrons, A. limicola and A. duffieldi strongly suggest interbreeding, although misidentification may also explain these topologies. However, all A. duffieldi clustered together in the trees. A conservative approach might be to treat A. duffieldi, until other evidence is forthcoming, as a possible endemic subspecies.
An Explicit Algebraic Closure for Passive Scalar-Flux: Applications in Channel Flows at a Wide Range of Reynolds Numbers
Authors: Panagiotou Constantinos F. , Stylianou Fotos S. , Gravanis Elias , Akylas Evangelos , Michailides Constantine
Published: November 2020

In this paper, we propose an algebraic model for turbulent scalar-flux vector that stems from tensor representation theory. The resulting closure contains direct dependence on mean velocity gradients and quadratic products of the Reynolds stress tensor. Model coefficients are determined from Direct Numerical Simulations (DNS) data of homogeneous shear flows subjected to arbitrary mean scalar gradient orientations, while a correction function was applied at one model coefficient based on a turbulent channel flow case. Model performance is evaluated in Poiseuille and Couette flows at several Reynolds numbers for Pr=0.7, along with a case at a higher Prandtl number (Pr=7.0) that typically occurs in water–boundary interaction applications. Overall, the proposed model provides promising results for wide near-wall interaction applications. To put the performance of the proposed model into context, we compare with Younis algebraic model, which is known to provide reasonable predictions for several engineering flows.
Biomarker Development for Metastatic Renal Cell Carcinoma: Omics, Antigens, T-cells, and Beyond
Authors: Miron Benjamin , Xu David , Zibelman Matthew
Published: November 2020

The treatment of metastatic renal cell carcinoma has evolved quickly over the last few years from a disease managed primarily with sequential oral tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) pathway, to now with a combination of therapies incorporating immune checkpoint blockade (ICB). Patient outcomes have improved with these innovations, however, controversy persists regarding optimal sequence and patient selection amongst the available combinations. Ideally, predictive biomarkers would aid in guiding treatment decisions and personalizing care. However, clinically-actionable biomarkers have remained elusive. We aim to review the available evidence regarding biomarkers for both TKIs and ICB and will present where the field may be headed in the years to come.
Locoregional Surgery in Metastatic Breast Cancer: Do Concomitant Metabolic Aspects Have a Role on the Management and Prognosis in this Setting?
Authors: Amabile Maria Ida , Frusone Federico , De Luca Alessandro , Tripodi Domenico , Imbimbo Giovanni , Lai Silvia , D’Andrea Vito , Sorrenti Salvatore , Molfino Alessio
Published: November 2020

Although they cannot be considered curative, the new therapeutic integrated advances in metastatic breast cancer (MBC) have substantially improved patient outcomes. Traditionally, surgery was confined to palliation of symptomatic or ulcerating lumps. Data suggest, in some cases, a possible additive role for more aggressive locoregional surgical therapy in combination with systemic treatments in the metastatic setting, although a low level of evidence has been shown in terms of improvement in overall survival in MBC patients treated with surgery and medical treatment compared to medical treatment alone. In this light, tumor heterogeneity remains a challenge. To effectively reshape the therapeutic approach to MBC, careful consideration of who is a good candidate for locoregional resection is paramount. The patient’s global health condition, impacting on cancer progression and morbidity and their associated molecular targets, have to be considered in treatment decision-making. In particular, more recently, research has been focused on the role of metabolic derangements, including the presence of metabolic syndrome, which represent well-known conditions related to breast cancer recurrence and distant metastasis and are, therefore, involved in the prognosis. In the present article, we focus on locoregional surgical strategies in MBC and whether concomitant metabolic derangements may have a role in prognosis.
Forecasting the Returns of Cryptocurrency: A Model Averaging Approach
Authors: Xiao Hui , Sun Yiguo
Published: November 2020

This paper aims to enrich the understanding and modelling strategies for cryptocurrency markets by investigating major cryptocurrencies’ returns determinants and forecast their returns. To handle model uncertainty when modelling cryptocurrencies, we conduct model selection for an autoregressive distributed lag (ARDL) model using several popular penalized least squares estimators to explain the cryptocurrencies’ returns. We further introduce a novel model averaging approach or the shrinkage Mallows model averaging (SMMA) estimator for forecasting. First, we find that the returns for most cryptocurrencies are sensitive to volatilities from major financial markets. The returns are also prone to the changes in gold prices and the Forex market’s current and lagged information. Then, when forecasting cryptocurrencies’ returns, we further find that an ARDL(p,q) model estimated by the SMMA estimator outperforms the competing estimators and models out-of-sample.
Application of Plasma Sprayed Cu Intermediate Layers in the Soldering Process of Graphite Composite to 6060 Aluminum Alloy
Authors: Wojdat Tomasz , Sokołowski Paweł , Łatka Leszek , Chmielewska Julia , Kurantowicz Weronika
Published: November 2020

The work focuses on issues related to the soldering of graphite composite to 6060 aluminum alloy. The graphite composite is of great interest of the transportation industry as it is widely used in slides responsible for current collection from overhead catenary. The slides should meet various criteria resulting from relatively complex working conditions, e.g., in terms of electrical conductivity, self-lubricating, resistance to changing weather conditions, etc. Such an application has extensive requirements, mainly for a joint of graphite slide with aluminum body. The direct soldering of slide plates made of graphite composite to aluminum alloy collector head causes many technological problems and is not possible. In this study, the application of thin plasma sprayed (APS) copper intermediate layers is investigated for that purpose. After soldering process, the microstructural analysis confirmed the proper joint formulation, i.e., the soldering gap of 0.2 mm was well-filled with the solder over the entire width of joint. The soldered joints were then subjected for static shear testing. The obtained shear strength was in a relatively wide range of 13.04 to 20.50 MPa, which was influenced by various fracture mechanisms. Finally, the fact that reaction zones were not formed in investigated joints during soldering was confirmed by EDS analysis and micro hardness values, which were very similar to the ones of raw materials.
Oxidized Low-Density Lipoprotein Promotes In Vitro Calcification
Authors: Yamashita Mamiko , Nomura Yoshiaki , Ishikawa Misao , Shimoda Shinji , Hanada Nobuhiro
Published: November 2020

Calcification plays an important role in the human body in maintaining homeostasis. In the human body, the presence of a high amount of oxidized low-density lipoprotein (ox-LDL) is a consistent feature of the local areas that are common sites of ectopic calcification, namely dental calculus, renal calculus, and the areas affected by arteriosclerosis. Hence, ox-LDL may have some effect on calcification. Scanning electron microscopy (SEM) observation revealed a high amount of amorphous calcium phosphate (ACP) when ox-LDL was included in the solution. In the in vitro experiment, the highest amount of precipitation of calcium phosphate was observed in the solution containing ox-LDL compared to the inclusion of other biomaterials and was 4.2 times higher than that of deionized water for 4.86 mM calcium and 2.71 mM phosphate. The morphology of calcium phosphate precipitates in the solution containing ox-LDL differed from that of the precipitates in solutions containing other biomaterials, as determined by transmission electron microscopy (TEM). Through the time course observation of the sediments using TEM, it was observed that the sediments changed from spherical or oval shape to a thin film shape. These results indicate that sediments acquired a long-range order array, and the phase transitioned from non-crystalline to crystalline with an increased time and density of ACP. Thus, it is concluded that ox-LDL promoted ACP precipitation and it plays an important role in ectopic calcification.
Relationship between Three-Dimensional Steel Fiber Statistics and Electromagnetic Shielding Effectiveness of High-Performance, Fiber-Reinforced Cementitious Composites
Authors: Lee Namkon , Park Gijoon , Pae Junil , Moon Juhyuk , Kim Sungwook
Published: November 2020

This study aims to investigate the relationship between the steel fibers and the electromagnetic wave shielding effectiveness of a high-performance fiber-reinforced cementitious composite (HPFRCC). The distribution characteristics of the steel fibers and the variation of the electrical conductivity of HPFRCC as a function of the fiber content were quantified based on micro computed tomography (CT) and impedance measurements to determine their correlations with the electromagnetic shielding effectiveness. The impedance results showed that no electrical network was formed in the composite by the steel fibers and it is difficult to manufacture HPFRCC with high-electrical conductivity using steel fibers alone without CNTs or other carbon-based materials. For the steel fiber content of greater than 0.5%, the number of contact points between the steel fibers increased significantly, and the relationship between the fiber content and the number of contact points was observed. Despite the improvement of the electrical conductivity owing to the presence of the steel fibers and to the increase in the contact points between the steel fibers, the shielding effectiveness did not increase further for the steel fiber contents equal or above 1.5%. Consequently, it was found that the factor that controls the shielding effectiveness of HPFRCC is not the electrical network of the steel fibers, but the degree of the dispersion of the individual steel fibers.
Calculating Power Parameters of Rolling Mill Based on Model of Deformation Zone with Four-Roll Passes
Authors: Samodurova Marina N. , Karandaeva Olga I. , Khramshin Vadim R. , Liubimov Ivan V.
Published: November 2020

Making “digital twins” for rolling processes and mill equipment should begin with the development of mathematical models of the deformation zone. The deformation zone of two-high flat mill rolling have been studied in detail, relevant models are available in many academic papers. However, the same cannot be said about the most complex deformation zones in stands with multi-roll gauge. Therefore, the task of their reliable mathematical description is of immediate interest. The development of mathematical models is necessary for the design of new wire mills and rolling-drawing units. The combination of rolling in stands with multi-roll gauge and drawing is a promising direction in the production of wire from difficult-to-form steels and alloys. Digital models for pressure-based metal treatment are also necessary for calculating the rolling-mill power parameters during the development of new assortments at the operating mills. The models of deformation zones present the basis for developing the multivariable control systems of process conditions of continuous mills. This research is devoted to the study of the deformation zone and the development of a procedure for calculating the power parameters of rolling in a stand with four-roll passes. The solution of these challenges is given using the example of an operating five-stand wire mill. The authors analysed the known analytical dependencies for calculating the rolling mill force and torque. A mathematical model of the deformation zone and a program for calculating the power parameters have been developed. The paper compares the results obtained from calculations based on analytical dependence and on modelling. A comparison with the experimental parameters obtained at the mill is given. The authors assess the feasibility of using the known formulas and analyse the impact of the front and rear tensions on the power parameters of rolling mill. The problem of developing an automatic tension control system for continuous mills with multi-roll groove is substantiated.
A Sarmanov Distribution with Beta Marginals: An Application to Motor Insurance Pricing
Authors: Bolancé Catalina , Guillen Montserrat , Pitarque Albert
Published: November 2020

Background: The Beta distribution is useful for fitting variables that measure a probability or a relative frequency. Methods: We propose a Sarmanov distribution with Beta marginals specified as generalised linear models. We analyse its theoretical properties and its dependence limits. Results: We use a real motor insurance sample of drivers and analyse the percentage of kilometres driven above the posted speed limit and the percentage of kilometres driven at night, together with some additional covariates. We fit a Beta model for the marginals of the bivariate Sarmanov distribution. Conclusions: We find negative dependence in the high quantiles indicating that excess speed and night-time driving are not uniformly correlated.
High Temperature Performance of Spark Plasma Sintered W0.5(TaTiVCr)0.5 Alloy
Authors: Alvi Sajid , Waseem Owais Ahmed , Akhtar Farid
Published: November 2020

The phase stability, compressive strength, and tribology of tungsten alloy containing low activation elements, W0.5(TaTiVCr)0.5, at elevated temperature up to 1400 °C were investigated. The spark plasma sintered W0.5(TaTiVCr)0.5 alloy showed body centered cubic (BCC) structure, which was stable up to 1400 °C using in-situ high temperature XRD analysis and did not show formation of secondary phases. The W0.5(TaTiVCr)0.5 alloy showed exceptionally high compressive yield strength of 1136 ± 40 MPa, 830 ± 60 MPa and 425 ± 15 MPa at 1000 °C, 1200 °C and 1400 °C, respectively. The high temperature tribology at 400 °C showed an average coefficient of friction (COF) and low wear rate of 0.55 and 1.37 × 10−5 mm3/Nm, respectively. The superior compressive strength and wear resistance properties were attributed to the solid solution strengthening of the alloy. The low activation composition, high phase stability, superior high temperature strength, and good wear resistance at 400 °C of W0.5(TaTiVCr)0.5 suggest its potential utilization in extreme applications such as plasma facing materials, rocket nozzles and industrial tooling.
Streamlining the Analysis of Dynamic 13C-Labeling Patterns for the Metabolic Engineering of Corynebacterium glutamicum as l-Histidine Production Host
Authors: Feith André , Schwentner Andreas , Teleki Attila , Favilli Lorenzo , Blombach Bastian , Takors Ralf
Published: November 2020

Today’s possibilities of genome editing easily create plentitudes of strain mutants that need to be experimentally qualified for configuring the next steps of strain engineering. The application of design-build-test-learn cycles requires the identification of distinct metabolic engineering targets as design inputs for subsequent optimization rounds. Here, we present the pool influx kinetics (PIK) approach that identifies promising metabolic engineering targets by pairwise comparison of up- and downstream 13C labeling dynamics with respect to a metabolite of interest. Showcasing the complex l-histidine production with engineered Corynebacterium glutamicuml-histidine-on-glucose yields could be improved to 8.6 ± 0.1 mol% by PIK analysis, starting from a base strain. Amplification of purA, purB, purH, and formyl recycling was identified as key targets only analyzing the signal transduction kinetics mirrored in the PIK values.
Divergent Impact of Glucose Availability on Human Virus-Specific and Generically Activated CD8 T Cells
Authors: Sanchez Jenifer , Jackson Ian , Flaherty Katie R. , Muliaditan Tamara , Schurich Anna
Published: November 2020

Upon activation T cells engage glucose metabolism to fuel the costly effector functions needed for a robust immune response. Consequently, the availability of glucose can impact on T cell function. The glucose concentrations used in conventional culture media and common metabolic assays are often artificially high, representing hyperglycaemic levels rarely present in vivo. We show here that reducing glucose concentration to physiological levels in culture differentially impacted on virus-specific compared to generically activated human CD8 T cell responses. In virus-specific T cells, limiting glucose availability significantly reduced the frequency of effector-cytokine producing T cells, but promoted the upregulation of CD69 and CD103 associated with an increased capacity for tissue retention. In contrast the functionality of generically activated T cells was largely unaffected and these showed reduced differentiation towards a residency phenotype. Furthermore, T cells being cultured at physiological glucose concentrations were more susceptible to viral infection. This setting resulted in significantly improved lentiviral transduction rates of primary cells. Our data suggest that CD8 T cells are exquisitely adapted to their niche and provide a reminder of the need to better mimic physiological conditions to study the complex nature of the human CD8 T cell immune response.
Applications of CMOS Devices for the Diagnosis and Control of Infectious Diseases
Authors: Forouhi Saghi , Ghafar-Zadeh Ebrahim
Published: November 2020

Emerging infectious diseases such as coronavirus disease of 2019 (COVID-19), Ebola, influenza A, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) in recent years have threatened the health and security of the global community as one of the greatest factors of mortality in the world. Accurate and immediate diagnosis of infectious agents and symptoms is a key to control the outbreak of these diseases. Rapid advances in complementary metal-oxide-semiconductor (CMOS) technology offers great advantages like high accuracy, high throughput and rapid measurements in biomedical research and disease diagnosis. These features as well as low cost, low power and scalability of CMOS technology can pave the way for the development of powerful devices such as point-of-care (PoC) systems, lab-on-chip (LoC) platforms and symptom screening devices for accurate and timely diagnosis of infectious diseases. This paper is an overview of different CMOS-based devices such as optical, electrochemical, magnetic and mechanical sensors developed by researchers to mitigate the problems associated with these diseases.
Interactions with a Complex Microbiota Mediate a Trade-Off between the Host Development Rate and Heat Stress Resistance
Authors: Slowinski Samuel , Ramirez Isabella , Narayan Vivek , Somayaji Medha , Para Maya , Pi Sarah , Jadeja Niharika , Karimzadegan Siavash , Pees Barbara , Shapira Michael
Published: November 2020

Animals and plants host diverse communities of microorganisms, and these microbiotas have been shown to influence host life history traits. Much has been said about the benefits that host-associated microbiotas bestow on the host. However, life history traits often demonstrate tradeoffs among one another. Raising Caenorhabditis elegans nematodes in compost microcosms emulating their natural environment, we examined how complex microbiotas affect host life history traits. We show that soil microbes usually increase the host development rate but decrease host resistance to heat stress, suggesting that interactions with complex microbiotas may mediate a tradeoff between host development and stress resistance. What element in these interactions is responsible for these effects is yet unknown, but experiments with live versus dead bacteria suggest that such effects may depend on bacterially provided signals.
Approach to Optimization of FRAP Methodology for Studies Based on Selected Monoterpenes
Authors: Wojtunik-Kulesza Karolina A.
Published: November 2020

Terpenes, wide-spread secondary plant metabolites, constitute important parts of many natural compounds that hold various biological activities, including antioxidant, calming, antiviral, and analgesic activities. Due to their high volatility and low solubility in water, studies of compounds based on terpenes are difficult, and methodologies must be adjusted to their specific characteristics. Considering the significant influence of iron ions on dementia development, the activity of terpenes in reducing Fe3+ represents an important area to be determined. Previously obtained results were unreliable because ferric-reducing antioxidant power (FRAP) methodology was not adjusted regarding studying terpenes. Taking this fact into account, the aim of this study was to optimize the method for monoterpene assessment. The study included three modifications, namely, (1) slightly adjusting the entire FRAP procedure, (2) replacing methanol with other solvents (heptane, butanone, or ethyl acetate), and (3) adding Tween 20. Additionally, a thin layer chromatography (TLC) -FRAP assay was performed. The obtained results revealed significant improvement in the reduction activity of selected terpenes (linalool, α-phellandrene, and α-terpinene) in studies with Tween 20, whereas replacing methanol with other solvents did not show the expected effects.
Phenolic Composition and Biological Properties of Wild and Commercial Dog Rose Fruits and Leaves
Authors: Polumackanycz Milena , Kaszuba Mateusz , Konopacka Agnieszka , Marzec-Wróblewska Urszula , Wesolowski Marek , Waleron Krzysztof , Buciński Adam , Viapiana Agnieszka
Published: November 2020

Rosa canina L. (dog rose) is a rich source of phenolic compounds that offer great hope for the prevention of chronic human diseases. Herein, wild and commercial samples of dog rose were chemically characterized with respect to their phenolic composition by liquid chromatography coupled to diode array detection and electrospray ionization tandem mass spectrometry (LC-DAD-ESI/MS). Furthermore, in vitro antioxidant properties and antibacterial activity of dog rose fruits and leaves hydromethanolic extracts and infusions were also evaluated. The results revealed that wild and commercial fruits of dog rose are similar in terms of l(+)-ascorbic acid, total phenolics (TPC), total flavonoids (TFC) and total phenolic acids (TPAC) content, individual phenolic constituents and antioxidant activity. Moreover, the fruits had lower levels of phenolic compounds and also revealed lower biological activity than the leaves. On the other hands, the highest content of TPC, TFC, TPAC, individual phenolic constituents, DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity and FRAP (ferric reducing antioxidant power) were found in the leaf’s infusions. They were also the only ones to show antibacterial activity. Overall, these finding confirmed usefulness of R. canina L. leaves and fruits as a rich source of bioactive phenolic compounds with potential use in food, pharmaceutical, and cosmetic industries.
Simple Derivatization–Gas Chromatography–Mass Spectrometry for Fatty Acids Profiling in Soil Dissolved Organic Matter
Authors: Musadji Neil Yohan , Geffroy-Rodier Claude
Published: November 2020

Dissolved organic matter is an important component of the global carbon cycle that allows the distribution of carbon and nutrients. Therefore, analysis of soil dissolved organic matter helps us to better understand climate change impacts as it is the most dynamic and reactive fraction in terrestrial ecosystems. Its characterization at the molecular level is still challenging due to complex mixtures of hundreds of compounds at low concentration levels in percolating water. This work presents simple methods, such as thermochemolysis– or derivatization–gas chromatography, as an alternative for the analysis of fatty acids in dissolved organic matter without any purification step. The variables of the protocols were examined to optimize the processing conditions for the C9–C18 range. As a proof of concept, fatty acid distributions of soil percolating water samples from a long-term field experiment were successfully assessed. The variability of dissolved organic acid distributions was pronounced through depth profile and soil treatment but no major change in composition was observed. However, although the optimization was done from C9 to C18, detection within the C6-C32 fatty acids range was performed for all samples.
Design, Synthesis and Biological Evaluation of (2′,5′ and 3′5′-Linked) cGAMP Analogs that Activate Stimulator of Interferon Genes (STING)
Authors: Xie Xin , Liu Junyi , Wang Xiaowei
Published: November 2020

Stimulator of interferon genes (STING) is an endoplasmic reticulum adaptor transmembrane protein that plays a pivotal role in innate immune system. STING agonists, such as endogenous cyclic dinucleotide (CDN) cyclic GMP-AMP (cGAMP), have been used in diverse clinical research for immunogenic tumor clearance, antiviral treatments and vaccine adjuvants. CDNs containing noncanonical mixed 3′-5′ and 2′-5′ phosphodiester linkages show higher potency in the activation of the STING pathway. In this study, a series of 2′3′-CDNs were designed and synthesized through a modified one-pot strategy. We then established a surface plasmon resonance (SPR)-based binding assay to quantify the binding affinities of synthesized CDNs for human STING, which requested a minuscule amount of sample without any pretreatment. Using this assay, we identified compound 8d (KD = 0.038 μM), a novel CDN that showed higher binding affinity with hSTING than cGAMP (KD = 0.543 μM). Cellular assays confirmed that 8d could trigger the expression of type I IFNs and other proinflammatory cytokines more robust than cGAMP. 8d also exhibited more resistant than cGAMP to enzymatic cleavage in vitro, indicating the successful improvement in drug availability. These findings provide guidelines for the design and structural optimization of CDNs as STING agonists.
Antioxidant and Anti-Inflammatory Activities of Six Flavonoids from Smilax glabra Roxb
Authors: Zhao Xinyu , Chen Ruyi , Shi Yueyue , Zhang Xiaoxi , Tian Chongmei , Xia Daozong
Published: November 2020

This study aimed to isolate, prepare and identify the main flavonoids from a standardized Smilax glabra flavonoids extract (SGF) using preparative HPLC, MS, 1H NMR and 13C NMR, determine the contents of these flavonoids using UPLC, then compare their pharmacological activities in vitro. We obtained six flavonoids from SGF: astilbin (18.10%), neoastilbin (11.04%), isoastilbin (5.03%), neoisoastilbin (4.09%), engeletin (2.58%) and (−)-epicatechin (1.77%). The antioxidant activity of six flavonoids were evaluated by determining the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2′-Azinobis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS+) radical scavenging activity and ferric reducing antioxidant power (FRAP). In addition, the anti-inflammatory activity of six flavonoids were evaluated by determining the production of cytokines (IL-1β, IL-6), nitric oxide (NO) using enzyme linked immunosorbent assay and the NF-κB p65 expression using Western blotting in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results showed that (−)-epicatechin, astilbin, neoastilbin, isoastilbin and neoisoastilbin had strong antioxidant activities, not only in DPPH and ABTS+ radicals scavenging capacities, but in FRAP system. Furthermore, all the six flavonoids could significantly inhibit the secretion of IL-1β, IL-6, NO (p < 0.01) and the protein expression of NF-κB p-p65 (p < 0.01) in LPS-stimulated RAW264.7 cells. This study preliminarily verified the antioxidant and anti-inflammatory activities of six flavonoids in S. glabra.