bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a New Spectral Index for Detecting Cadmium-Induced Stress in Rice on a Regional Scale
Authors: Wu Chuanyu , Liu Meiling , Liu Xiangnan , Wang Tiejun , Wang Lingyue
Published: November 2019

In natural farmland ecosystems, cadmium (Cd) pollution in rice has attracted increasing attention because of its high toxicity, relative mobility, and high water solubility. This study aims to develop a spectral index for detecting Cd stress in rice on a regional scale. Three experimental sites are selected in Zhuzhou City, Hunan Province. The hyperspectral data, chlorophyll (Chl) content, leaf area index, average leaf angle, Cd concentration in soil, and Sentinel-2A images from 2017 and 2018 are collected. A new spectral index sensitive to Cd stress in rice is established based on the global sensitivity analysis of the radiative transfer model PROSPECT + SAIL (commonly called PROSAIL) model with the auxiliary of the field-measured data. The heavy metal Cd stress-sensitive spectral index (HCSI) is devised as an indicator of the degree of Cd stress in rice. Results indicate that (1) the HCSI developed based on Chl is a good indicator of rice damage caused by Cd stress, that is, low values of HCSI occur in rice subject to relatively high pollution; (2) compared with common spectral indices, such as red-edge position and red-edge Chl index, HCSI is more sensitive to Chl content with higher Pearson correlation coefficients with respect to Chl content, ranging from 0.85 to 0.95; (3) HCSI is successfully applied in Sentinel-2A images from the two different years of monitoring rice Cd stress on a regional scale. Cd stress levels in rice stabilized, and the largest area percentage of each pollution levels of Cd decreased in the following order: No pollution (i.e., 40%), low pollution (i.e., 35%), and high pollution (i.e., 25%). This study indicates that a combination of simulation data from the PROSAIL model and measured data appears to be a promising method for establishing a sensitivity spectral index to heavy metal stress, which can accurately detect regional Cd stress in crops.
Effects of Heavy Metal Exposure on Shipyard Welders: A Cautionary Note for 8-Hydroxy-2′-Deoxyguanosine
Authors: Su Ting-Yao , Pan Chih-Hong , Hsu Yuan-Ting , Lai Ching-Huang
Published: November 2019

Oxidative stress plays a crucial role in the development of diseases induced by welding fumes. To our knowledge, little information is available on the relationship between multiple heavy metal exposure and oxidative stress in welders. We assessed the relationship between multiple heavy metal exposure and oxidative damage by analyzing 174 nonsmoking male welders in a shipyard. Urinary metals were used as the internal dose of exposure to metals in welding fumes, and urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) was used as an oxidative DNA damage marker. The relationship between workers’ metal levels and 8-OHdG was estimated using a multiple linear regression model. The geometric mean levels of urinary chromium (Cr), nickel (Ni), cadmium (Cd), and lead (Pb) were considerably higher in welders than in controls. Urinary Cr and Ni were determined as effective predictors of urinary 8-OHdG levels after adjusting for covariates. Oxidative DNA damage was associated with both Cr and Ni of welding fume exposure in shipyard welders (Ln Cr: β = 0.33, 95%C.I. = 0.16–0.49; Ln Ni: β = 0.27, 95%C.I. = 0.12–0.43). In this study, we investigated the significantly positive relationship between urinary metals (especially Cr and Ni) and 8-OHdG in nonsmoking shipyard welders. Moreover, the use of particulate respirators did not reduce metal exposure and oxidative damage. Therefore, we infer that hazard identification for welders should be conducted.
Growth Plate Chondrocytes: Skeletal Development, Growth and Beyond
Authors: Hallett Shawn A. , Ono Wanida , Ono Noriaki
Published: November 2019

Growth plate chondrocytes play central roles in the proper development and growth of endochondral bones. Particularly, a population of chondrocytes in the resting zone expressing parathyroid hormone-related protein (PTHrP) is now recognized as skeletal stem cells, defined by their ability to undergo self-renewal and clonally give rise to columnar chondrocytes in the postnatal growth plate. These chondrocytes also possess the ability to differentiate into a multitude of cell types including osteoblasts and bone marrow stromal cells during skeletal development. Using single-cell transcriptomic approaches and in vivo lineage tracing technology, it is now possible to further elucidate their molecular properties and cellular fate changes. By discovering the fundamental molecular characteristics of these cells, it may be possible to harness their functional characteristics for skeletal growth and regeneration. Here, we discuss our current understanding of the molecular signatures defining growth plate chondrocytes.
Effects of Cadmium on ZO-1 Tight Junction Integrity of the Blood Brain Barrier
Authors: Branca Jacopo Junio Valerio , Maresca Mario , Morucci Gabriele , Mello Tommaso , Becatti Matteo , Pazzagli Luigia , Colzi Ilaria , Gonnelli Cristina , Carrino Donatello , Paternostro Ferdinando , Nicoletti Claudio , Ghelardini Carla , Gulisano Massimo , Di Cesare Mannelli Lorenzo , Pacini Alessandra
Published: November 2019

Cadmium (Cd) is a highly toxic environmental pollutant released from the smelting and refining of metals and cigarette smoking. Oral exposure to cadmium may result in adverse effects on a number of tissues, including the central nervous system (CNS). In fact, its toxicity has been related to neurological disorders, as well as neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Under normal conditions, Cd barely reaches the brain in adults because of the presence of the blood–brain barrier (BBB); however, it has been demonstrated that Cd-dependent BBB alteration contributes to pathogenesis of neurodegeneration. However, the mechanism underlying Cd-dependent BBB alteration remain obscure. Here, we investigated the signaling pathway of Cd-induced tight junction (TJ), F-actin, and vimentin protein disassembly in a rat brain endothelial cell line (RBE4). RBE4 cells treated with 10 μM cadmium chloride (CdCl2) showed a dose- and time-dependent significant increase in reactive oxygen species (ROS) production. This phenomenon was coincident with the alteration of the TJ zonula occludens-1 (ZO-1), F-actin, and vimentin proteins. The Cd-dependent ROS increase elicited the upregulation of GRP78 expression levels, a chaperone involved in endoplasmic reticulum (ER) stress that induces caspase-3 activation. Further signal profiling by the pannexin-1 (PANX1) specific inhibitor 10Panx revealed a PANX1-independent increase in ATP spillage in Cd-treated endothelial cells. Our results point out that a ROS-dependent ER stress-mediated signaling pathway involving caspase-3 activation and ATP release is behind the BBB morphological alterations induced by Cd.
Effects of Hyperoxia on the Refraction in Murine Neonatal and Adult Models
Authors: Mori Kiwako , Kurihara Toshihide , Jiang Xiaoyan , Ikeda Shin-ichi , Ishida Ayako , Torii Hidemasa , Tsubota Kazuo
Published: November 2019

Whether hyperoxia affects the refraction in neonatal and adult mice is unknown. The mice exposed to 85% oxygen at postnatal 8 days (P8d) for 3 days and the mice exposed to normal air were assigned to the neonatal hyperoxia and normoxia groups, respectively. The refraction, the corneal curvature radius (CR) and the axial length (AL) were measured at P30d and P47d. Postnatal 6 weeks (P6w) adult mice were divided into the adult hyperoxia and normoxia groups. These parameters were measured before oxygen exposure, after 1 and 6 weeks, and every 7 weeks. The lens elasticity was measured at P7w and P26w by enucleation. The neonatal hyperoxia group showed a significantly larger myopic change than the neonatal normoxia group (P47d −6.56 ± 5.89 D, +4.11 ± 2.02 D, p < 0.001), whereas the changes in AL were not significantly different (P47d, 3.31 ± 0.04 mm, 3.31 ± 0.05 mm, p = 0.852). The adult hyperoxia group also showed a significantly larger myopic change (P12w, −7.20 ± 4.09 D, +7.52 ± 2.54 D, p < 0.001). The AL did not show significant difference (P12w, 3.44 ± 0.03 mm, 3.43 ± 0.01 mm, p = 0.545); however, the CR in the adult hyperoxia group was significantly smaller than the adult normoxia group (P12w, 1.44 ± 0.03 mm, 1.50 ± 0.03 mm, p = 0.003). In conclusion, hyperoxia was demonstrated to induce myopic shift both in neonatal and adult mice, which was attributed to the change in the CR rather than the AL. Elucidation of the mechanisms of hyperoxia and the application of this result to humans should be carried out in future studies.
On the Road to Accurate Biomarkers for Cardiometabolic Diseases by Integrating Precision and Gender Medicine Approaches
Authors: Scola Letizia , Giarratana Rosa Maria , Torre Salvatore , Argano Vincenzo , Lio Domenico , Balistreri Carmela Rita
Published: November 2019

The need to facilitate the complex management of cardiometabolic diseases (CMD) has led to the detection of many biomarkers, however, there are no clear explanations of their role in the prevention, diagnosis or prognosis of these diseases. Molecules associated with disease pathways represent valid disease surrogates and well-fitted CMD biomarkers. To address this challenge, data from multi-omics types (genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, and nutrigenomics), from human and animal models, have become available. However, individual omics types only provide data on a small part of molecules involved in the complex CMD mechanisms, whereas, here, we propose that their integration leads to multidimensional data. Such data provide a better understanding of molecules related to CMD mechanisms and, consequently, increase the possibility of identifying well-fitted biomarkers. In addition, the application of gender medicine also helps to identify accurate biomarkers according to gender, facilitating a differential CMD management. Accordingly, the impact of gender differences in CMD pathophysiology has been widely demonstrated, where gender is referred to the complex interrelation and integration of sex (as a biological and functional marker of the human body) and psychological and cultural behavior (due to ethnical, social, and religious background). In this review, all these aspects are described and discussed, as well as potential limitations and future directions in this incipient field.
Pre-Clinical Drug Testing in 2D and 3D Human In Vitro Models of Glioblastoma Incorporating Non-Neoplastic Astrocytes: Tunneling Nano Tubules and Mitochondrial Transfer Modulates Cell Behavior and Therapeutic Response
Authors: Civita Prospero , M. Leite Diana , Pilkington Geoffrey
Published: November 2019

The role of astrocytes in the glioblastoma (GBM) microenvironment is poorly understood; particularly with regard to cell invasion and drug resistance. To assess this role of astrocytes in GBMs we established an all human 2D co-culture model and a 3D hyaluronic acid-gelatin based hydrogel model (HyStem™-HP) with different ratios of GBM cells to astrocytes. A contact co-culture of fluorescently labelled GBM cells and astrocytes showed that the latter promotes tumour growth and migration of GBM cells. Notably, the presence of non-neoplastic astrocytes in direct contact, even in low amounts in co-culture, elicited drug resistance in GBM. Recent studies showed that non-neoplastic cells can transfer mitochondria along tunneling nanotubes (TNT) and rescue damaged target cancer cells. In these studies, we explored TNT formation and mitochondrial transfer using 2D and 3D in vitro co-culture models of GBM and astrocytes. TNT formation occurs in glial fibrillary acidic protein (GFAP) positive “reactive” astrocytes after 48 h co-culture and the increase of TNT formations was greater in 3D hyaluronic acid-gelatin based hydrogel models. This study shows that human astrocytes in the tumour microenvironment, both in 2D and 3D in vitro co-culture models, could form TNT connections with GBM cells. We postulate that the association on TNT delivery non-neoplastic mitochondria via a TNT connection may be related to GBM drug response as well as proliferation and migration.
Charge Transfer, Complexes Formation and Furan Fragmentation Induced by Collisions with Low-Energy Helium Cations
Authors: Wasowicz Tomasz J. , Łabuda Marta , Pranszke Boguslaw
Published: November 2019

The present work focuses on unraveling the collisional processes leading to the fragmentation of the gas-phase furan molecules under the He+ and He2+ cations impact in the energy range 5–2000 eV. The presence of different mechanisms was identified by the analysis of the optical fragmentation spectra measured using the collision-induced emission spectroscopy (CIES) in conjunction with the ab initio calculations. The measurements of the fragmentation spectra of furan were performed at the different kinetic energies of both cations. In consequence, several excited products were identified by their luminescence. Among them, the emission of helium atoms excited to the 1s4d 1D2, 3D1,2,3 states was recorded. The structure of the furan molecule lacks an He atom. Therefore, observation of its emission lines is spectroscopic evidence of an impact reaction occurring via relocation of the electronic charge between interacting entities. Moreover, the recorded spectra revealed significant variations of relative band intensities of the products along with the change of the projectile charge and its velocity. In particular, at lower velocities of He+, the relative cross-sections of dissociation products have prominent resonance-like maxima. In order to elucidate the experimental results, the calculations have been performed by using a high level of quantum chemistry methods. The calculations showed that in both impact systems two collisional processes preceded fragmentation. The first one is an electron transfer from furan molecules to cations that leads to the neutralization and further excitation of the cations. The second mechanism starts from the formation of the He−C4H4O+/2+ temporary clusters before decomposition, and it is responsible for the appearance of the narrow resonances in the relative cross-section curves.
p53 Isoforms in Cellular Senescence- and Ageing-Associated Biological and Physiological Functions
Authors: Fujita Kaori
Published: November 2019

Cellular senescence, a term originally used to define the characteristics of normal human fibroblasts that reached their replicative limit, is an important factor for ageing, age-related diseases including cancer, and cell reprogramming. These outcomes are mediated by senescence-associated changes in gene expressions, which sometimes lead to the secretion of pro-inflammatory factors, or senescence-associated secretory phenotype (SASP) that contribute to paradoxical pro-tumorigenic effects. p53 functions as a transcription factor in cell-autonomous responses such as cell-cycle control, DNA repair, apoptosis, and cellular senescence, and also non-cell-autonomous responses to DNA damage by mediating the SASP function of immune system activation. The human TP53 gene encodes twelve protein isoforms, which provides an explanation for the pleiotropic p53 function on cellular senescence. Recent reports suggest that some short isoforms of p53 may modulate gene expressions in a full-length p53-dependent and -independent manner, in other words, some p53 isoforms cooperate with full-length p53, whereas others operate independently. This review summarizes our current knowledge about the biological activities and functions of p53 isoforms, especially Δ40p53, Δ133p53α, and p53β, on cellular senescence, ageing, age-related disorder, reprogramming, and cancer. Numerous cellular and animal model studies indicate that an unbalance in p53 isoform expression in specific cell types causes age-related disorders such as cancer, premature ageing, and degenerative diseases.
Oxidative Stress-Induced Pentraxin 3 Expression Human Retinal Pigment Epithelial Cells Is Involved in the Pathogenesis of Age-Related Macular Degeneration
Authors: Hwang Narae , Kwon Min-Young , Woo Je Moon , Chung Su Wol
Published: November 2019

(1) Background: Age-related macular degeneration (AMD) is closely related with retinal pigment epithelial (RPE) cell dysfunction. Although the exact pathogenesis of AMD remains largely unknown, oxidative stress-induced RPE damage is believed to be one of the primary causes. We investigated the molecular mechanisms of pentraxin 3 (PTX3) expression and its biological functions during oxidative injury. (2) Methods: Using enzyme-linked immunosorbent assays and real-time reverse transcription-polymerase chain reaction, we analyzed mRNA and protein levels of PTX3 in the presence or absence of oxidative stress inducer, sodium iodate (NaIO3), in primary human H-RPE and ARPE-19 cells. Furthermore, we assessed cell death, antioxidant enzyme expression, and AMD-associated gene expression to determine the biological functions of PTX3 under oxidative stress. (3) Results: NaIO3 increased PTX3 expression, in a dose- and time-dependent manner, in H-RPE and ARPE-19 cells. We found phosphorylated Akt, a downstream target of the PI3 kinase pathway, phosphor- mitogen-activated protein kinase kinase 1/2 (ERK), and intracellular reactive oxygen species (ROS) were predominantly induced by NaIO3. NaIO3-induced PTX3 expression was decreased in the presence of phosphoinositide 3 (PI3) kinase inhibitors, ERK inhibitors, and ROS scavengers. Furthermore, NaIO3 enhanced mRNA expression of antioxidant enzymes such as glucose-6-phosphate dehydrogenase (G6PDH), catalase (CAT), and glutathione S-reductase (GSR) in the control shRNA expressing RPE cells, but not in hPTX3 shRNA expressing RPE cells. Interestingly, NaIO3 did not induce mRNA expression of AMD marker genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), and toll-like receptor 4 (TLR4) in hPTX3 shRNA expressing RPE cells. 4) Conclusions: These results suggest that PTX3 accelerates RPE cell death and might be involved in AMD development in the presence of oxidative stress.
The Phylogeny and Biological Function of Gastric Juice—Microbiological Consequences of Removing Gastric Acid
Authors: Martinsen Tom C. , Fossmark Reidar , Waldum Helge L.
Published: November 2019

Gastric juice is a unique combination of hydrochloric acid (HCl), lipase, and pepsin. Acidic gastric juice is found in all vertebrates, and its main function is to inactivate microorganisms. The phylogenetic preservation of this energy-consuming and, at times, hazardous function (acid-related diseases) reflects its biological importance. Proton pump inhibitors (PPIs) are one of the most widely used drugs in the world. Due to the reduced prevalence of Helicobacter pylori infection as well as the increased use of inhibitors of gastric acid secretion, the latter has become the most important cause of gastric hypoacidity. In the present manuscript, we review the microbiological consequences of removing gastric acidity. The resulting susceptibility to infections has not been studied extensively, and focus has mainly been restricted to bacterial and parasitic agents only. The strongest evidence concerning the relationship between hypochlorhydria and predisposition to infections relates to bacterial infections affecting the gastrointestinal tract. However, several other clinical settings with increased susceptibility to infections due to inhibited gastric acidity are discussed. We also discuss the impact of hypochlorhydria on the gut microbiome.
A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (Glassia®) in the Treatment of Recent-Onset Type 1 Diabetes
Authors: Lebenthal Yael , Brener Avivit , Hershkovitz Eli , Shehadeh Naim , Shalitin Shlomit , Lewis Eli C. , Elias Dana , Haim Alon , Barash Galia , Loewenthal Neta , Zuckerman-Levin Nehama , Stein Michal , Tov Naveh , Rachmiel Marianna
Published: November 2019

Our aim was to assess the efficacy, safety, and tolerability of alpha-1 antitrypsin (AAT) as a therapeutic modality for β-cell preservation in patients with recent-onset type 1 diabetes. Seventy type 1 diabetes patients (37 males; mean age 13.1 ± 4.1years) were randomized to treatment with 22 infusions of AAT (Glassia®) (60 or 120 mg/kg) or placebo. The primary outcome was the area under the curve (AUC) of C-peptide from a 2-h mixed-meal tolerance test after 52 weeks. At week 52, C-peptide was 0.9, 0.45, and 0.48 pmol/mL in the AAT-120, AAT-60, and placebo groups (p = 0.170 and p = 0.866 vs. placebo, respectively). The declines in C-peptide glycated hemoglobin (HbA1c) and the total insulin dose (U/kg) were similar across groups. Within the predefined 12–18-years subgroup, the C-peptide AUC decreased significantly in the placebo and AAT-60 groups (−0.34 and −0.54 pmol/mL, respectively, p < 0.01), with a borderline decrease in the AAT-120 group (−0.29 pmol/mL, p = 0.047). The mean HbA1c level was significantly lower in the AAT-120 group compared to the placebo (6.7% ± 0.9% vs. 8.2 ± 1.4%, p = 0.05), and a higher percentage of patients attained HbA1c ≤ 7% (75% vs. 25%, p = 0.05). AAT was tolerated well, with a similar safety profile between groups. The AAT intervention showed promise in the subgroup of adolescents with recent-onset type 1 diabetes. Further studies are warranted to determine the impact and proposed mechanism of action of AAT in β-cell preservation.
A Paradigm in Immunochemistry, Revealed by Monoclonal Antibodies to Spatially Distinct Epitopes on Syntenin-1
Authors: Johnson Ian R. D. , Sorvina Alexandra , Logan Jessica M. , Moore Courtney R. , Heatlie Jessica K. , Parkinson-Lawrence Emma J. , Selemidis Stavros , O’Leary John J. , Butler Lisa M. , Brooks Douglas A.
Published: November 2019

Syntenin-1 is an essential multi-functional adaptor protein, which has multiple roles in membrane trafficking and exosome biogenesis, as well as scaffolding interactions with either the actin cytoskeleton or focal adhesions. However, how this functional multiplicity relates to syntenin-1 distribution in different endosome compartments or other intracellular locations and its underlying involvement in cancer pathogenesis have yet to be fully defined. To help facilitate the investigation of syntenin-1 biology, we developed two specific monoclonal antibodies (Synt-2C6 and Synt-3A11) to spatially distinct linear sequence epitopes on syntenin-1, which were each designed to be unique at the six-amino acid level. These antibodies produced very different intracellular staining patterns, with Synt-2C6 detecting endosomes and Synt-3A11 producing a fibrillar staining pattern suggesting a cytoskeletal localisation. Treatment of cells with Nocodazole altered the intracellular localisation of Synt-3A11, which was consistent with the syntenin-1 protein interacting with microtubules. In prostate tissue biopsies, Synt-3A11 defined atrophy and early-stage prostate cancer, whereas Synt-2C6 only showed minimal interaction with atrophic tissue. This highlights a critical need for site-specific antibodies and a knowledge of their reactivity to define differential protein distributions, interactions and functions, which may differ between normal and malignant cells.
A Novel Obstacle Localization Method for an Underwater Robot Based on the Flow Field
Authors: Lin Xinghua , Wu Jianguo , Qin Qing
Published: November 2019

Because the underwater environment is complex, autonomous underwater vehicles (AUVs) have difficulty locating their surroundings autonomously. In order to improve the adaptive ability of AUVs, this paper presents a novel obstacle localization strategy based on the flow features. Like fish, the strategy uses the flow field information directly to locate the object obstacles. Two different localization methods are provided and compared. The first method, which is named the Method of Spatial Distribution (MSD), is based on the spatial distribution of the flow field. The second method, which is named the Method of Amplitude Variation (MAV), is provided by the amplitude variation of the flow field. The flow field around spherical targets is obtained by a numerical method, and both methods use the parallel velocity component on the virtual lateral line. During the study, different target numbers, detective ratios, spacing ratios, and flow velocities are taken into account. It is demonstrated that both methods are able to locate object obstacles. However, the prediction accuracy of MAV is higher than that of MSD. That implies that MAV is more robust than MSD. These new findings indicate that the object obstacles can be directly located based on the flow field information and robust flow sensing is perhaps not based on the spatial distribution of the flow field but rather, on its fluctuation range.
The Effect of Hydrogen on Martensite Transformations and the State of Hydrogen Atoms in Binary TiNi-Based Alloy with Different Grain Sizes
Authors: Baturin Anatoly , Lotkov Aleksandr , Grishkov Victor , Rodionov Ivan , Kabdylkakov Yerzhan , Kudiiarov Victor
Published: November 2019

The analysis presented here shows that in B2-phase of Ti49.1Ni50.9 (at%) alloy, hydrogenation with further aging at room temperature decreases the temperatures of martensite transformations and then causes their suppression, due to hydrogen diffusion from the surface layer of specimens deep into its bulk. When hydrogen is charged, it first suppresses the transformations B2↔B19′ and R↔B19′ in the surface layer, and when its distribution over the volume becomes uniform, such transformations are suppressed throughout the material. The kinetics of hydrogen redistribution is determined by the hydrogen diffusion coefficient DH, which depends on the grain size. In nanocrystalline Ti49.1Ni50.9 (at%) specimens, DH is three times greater than its value in coarse-grained ones, which is likely due to the larger free volume and larger contribution of hydrogen diffusion along grain boundaries in the nanocrystalline material. According to thermal desorption spectroscopy, two states of hydrogen atoms with low and high activation energies of desorption exist in freshly hydrogenated Ti49.1Ni50.9 (at%) alloy irrespective of the grain size. On aging at room temperature, the low-energy states disappear entirely. Estimates by the Kissinger method are presented for the binding energy of hydrogen in the two states, and the nature of these states in binary hydrogenated TiNi-based alloys is discussed.
Fracture Mechanisms of S355 Steel—Experimental Research, FEM Simulation and SEM Observation
Authors: Dzioba Ihor , Lipiec Sebastian
Published: November 2019

In this study, the fracture mechanisms of S355 ferritic steel were analyzed. In order to obtain different mechanisms of fracture (completely brittle, mixed brittle and ductile or completely ductile), tests were carried out over a temperature range of −120 to +20 °C. Our experimental research was supplemented with scanning electron microscopy (SEM) observations of the specimens’ fracture surfaces. Modeling and load simulations of specimens were performed using the finite element method (FEM) in the ABAQUS program, and accurate calibration of the true stress–strain material dependence was made. In addition, the development of mechanical fields before the crack tip of the cracking process in the steel was analyzed. The distributions of stresses and strains in the local area before the crack front were determined for specimens fractured according to different mechanisms. Finally, the conditions and characteristic values of stresses and strains which caused different mechanisms of fracture—fully brittle, mixed brittle and ductile or fully ductile—were determined.
Development and Validation of a Calibration Gauge for Length Measurement Systems
Authors: Brosed Francisco Javier , Acero Cacho Raquel , Aguado Sergio , Herrer Marta , Aguilar Juan José , Santolaria Mazo Jorge
Published: November 2019

Due to accuracy requirements, robots and machine-tools need to be periodically verified and calibrated through associated verification systems that sometimes use extensible guidance systems. This work presents the development of a reference artefact to evaluate the performance characteristics of different extensible precision guidance systems applicable to robot and machine tool verification. To this end, we present the design, modeling, manufacture and experimental validation of a reference artefact to evaluate the behavior of these extensible guidance systems. The system should be compatible with customized designed guides, as well as with commercial and existing telescopic guidance systems. Different design proposals are evaluated with finite element analysis, and two final prototypes are experimentally tested assuring that the design performs the expected function. An estimation of the uncertainty of the reference artefact is evaluated with a Monte Carlo simulation.
Estimation of Heating Temperature for Fire-Damaged Concrete Structures Using Adaptive Neuro-Fuzzy Inference System
Authors: Kang Hyun , Cho Hae-Chang , Choi Seung-Ho , Heo Inwook , Kim Heung-Youl , Kim Kang Su
Published: November 2019

The structural performance of concrete structures subjected to fire is greatly influenced by the heating temperature. Therefore, an accurate estimation of the heating temperature is of vital importance for deriving a reasonable diagnosis and assessment of fire-damaged concrete structures. In current practice, various heating temperature estimation methods are used, however, each of these estimation methods has limitations in accuracy and faces disadvantages that depend on evaluators’ empirical judgments in the process of deriving diagnostic results from measured data. Therefore, in this study, a concrete heating test and a non-destructive test were carried out to estimate the heating temperatures of fire-damaged concrete, and a heating temperature estimation method using an adaptive neuro-fuzzy inference system (ANFIS) algorithm was proposed based on the results. A total of 73 datasets were randomly extracted from a total of 87 concrete heating test results and we used them in the data training process of the ANFIS algorithm; the remaining 14 datasets were used for verification. The proposed ANFIS algorithm model provided an accurate estimation of heating temperature.
Influence of Manufacturing Technology on the Structure of 80W–20Re Heavy Sinters
Authors: Majewski Tomasz , Durejko Tomasz , Urbaniak Wiesław , Petelska Aneta D. , Łazińska Magdalena , Zasada Dariusz , Woźniak Ryszard
Published: November 2019

Preliminary measurement results of 80W–20Re heavy sinters are presented in this paper. Tested samples were taken from three different technology processes, i.e., resistance sintering (RS), pulse plasma sintering (PPS), and conventional sintering in a vacuum furnace. In the first two cases, the obtained sinters were of similar usable properties (porosity and microhardness), while for vacuum sintering, the material with high porosity was obtained. At the same time, it was found that sintering with the use of electric current (RS, PPS) generates microstructures with highly elongated grains.
Influence of Oxygen–Plasma Treatment on In-Situ SiN/AlGaN/GaN MOSHEMT with PECVD SiO2 Gate Insulator
Authors: Cho Geunho , Cha Ho-young , Kim Hyungtak
Published: November 2019

The influence of oxygen–plasma treatment on in situ SiN/AlGaN/GaN MOS high electron mobility transistor with SiO2 gate insulator was investigated. Oxygen–plasma treatment was performed on in situ SiN, before SiO2 gate insulator was deposited by plasma-enhanced chemical vapor deposition (PECVD). DC I-V characteristics were not changed by oxygen plasma treatment. However, pulsed I-V characteristics were improved, showing less dispersion compared to non-treated devices. During short-term gate bias stress, the threshold voltage shift was also smaller in a treated device than in an untreated one. X-ray photoemission spectroscopy also revealed that SiO2 on in situ SiN with oxygen–plasma treatment has an O/Si ratio close to the theoretical value. This suggests that the oxygen plasma treatment-modified surface condition of the SiN layer is favorable to SiO2 formation by PECVD.
Development and Validation of an HPLC Method for the Quantitative Analysis of Bromophenolic Compounds in the Red Alga Vertebrata lanosa
Authors: Hofer Stefanie , Hartmann Anja , Orfanoudaki Maria , Nguyen Ngoc Hieu , Nagl Markus , Karsten Ulf , Heesch Svenja , Ganzera Markus
Published: November 2019

Bromophenols are a class of compounds occurring in red algae that are thought to play a role in chemical protection; however, their exact function is still not fully known. In order to investigate their occurrence, pure standards of seven bromophenols were isolated from a methanolic extract of the epiphytic red alga Vertebrata lanosa collected in Brittany, France. The structures of all compounds were determined by NMR and MS. Among the isolated substances, one new natural product, namely, 2-amino-5-(3-(2,3-dibromo-4,5-dihydroxybenzyl)ureido)pentanoic acid was identified. An HPLC method for the separation of all isolated substances was developed using a Phenomenex C8(2) Luna column and a mobile phase comprising 0.05% trifluoroacetic acid in water and acetonitrile. Method validation showed that the applied procedure is selective, linear (R2 ≥ 0.999), precise (intra-day ≤ 6.28%, inter-day ≤ 5.21%), and accurate (with maximum displacement values of 4.93% for the high spikes, 4.80% for the medium spikes, and 4.30% for the low spikes). For all standards limits of detection (LOD) were lower than 0.04 μg/mL and limits of quantification (LOQ) lower than 0.12 μg/mL. Subsequently, the method was applied to determine the bromophenol content in Vertebrata lanosa samples from varying sampling sites and collection years showing values between 0.678 and 0.005 mg/g dry weight for different bromophenols with significant variations between the sampling years. Bioactivity of seven isolated bromophenols was tested in agar diffusion tests against Staphylococcus aureus and Escherichia coli bacteria. Three compounds showed a small zone of inhibition against both test organisms at a concentration of 100 µg/mL.
Flexible Microfluidics: Fundamentals, Recent Developments, and Applications
Authors: Fallahi Hedieh , Zhang Jun , Phan Hoang-Phuong , Nguyen Nam-Trung
Published: November 2019

Miniaturization has been the driving force of scientific and technological advances over recent decades. Recently, flexibility has gained significant interest, particularly in miniaturization approaches for biomedical devices, wearable sensing technologies, and drug delivery. Flexible microfluidics is an emerging area that impacts upon a range of research areas including chemistry, electronics, biology, and medicine. Various materials with flexibility and stretchability have been used in flexible microfluidics. Flexible microchannels allow for strong fluid-structure interactions. Thus, they behave in a different way from rigid microchannels with fluid passing through them. This unique behaviour introduces new characteristics that can be deployed in microfluidic applications and functions such as valving, pumping, mixing, and separation. To date, a specialised review of flexible microfluidics that considers both the fundamentals and applications is missing in the literature. This review aims to provide a comprehensive summary including: (i) Materials used for fabrication of flexible microfluidics, (ii) basics and roles of flexibility on microfluidic functions, (iii) applications of flexible microfluidics in wearable electronics and biology, and (iv) future perspectives of flexible microfluidics. The review provides researchers and engineers with an extensive and updated understanding of the principles and applications of flexible microfluidics.
Determination of the Membrane Transport Properties of Jurkat Cells with a Microfluidic Device
Authors: Yang Tianhang , Peng Ji , Shu Zhiquan , Sekar Praveen K. , Li Songjing , Gao Dayong
Published: November 2019

The Jurkat cell is an immortalized line of human acute lymphocyte leukemia cells that is widely used in the study of adoptive cell therapy, a novel treatment of several advanced forms of cancer. The ability to transport water and solutes across the cell membrane under different temperatures is an important factor for deciding the specific protocol for cryopreservation of the Jurkat cell. In this study we propose a comprehensive process for determination of membrane transport properties of Jurkat cell. using a novel microfluidic controlled single cell-trapping system. The osmotic behavior of an individual Jurkat cell to water and dimethyl sulfoxide (DMSO), a commonly used cryoprotective agent (CPA), under constant temperature, was recorded under a microscope utilizing the modified microfluidic system. The images of the Jurkat cell under osmotic change were processed to obtain a relationship between cell volume change and time. The experimental results were fitted using a two-parameter transport numeric model to calculate the Jurkat cell membrane permeability to water and DMSO at room temperature (22 °C). This model and the calculated parameters can help scientists optimize the cryopreservation protocol for any cell type with optimal cryoprotective agents and cooling rate for future experiments.
Thermosensitive Liposome-Mediated Drug Delivery in Chemotherapy: Mathematical Modelling for Spatio–temporal Drug Distribution and Model-Based Optimisation
Authors: Huang Yu , Gu Boram , Liu Cong , Stebbing Justin , Gedroyc Wladyslaw , Thanou Maya , Xu Xiao Yun
Published: November 2019

Thermosensitive liposome-mediated drug delivery has shown promising results in terms of improved therapeutic efficacy and reduced side effects compared to conventional chemotherapeutics. In order to facilitate our understanding of the transport mechanisms and their complex interplays in the drug delivery process, computational models have been developed to simulate the multiple steps involved in liposomal drug delivery to solid tumours. In this study we employ a multicompartmental model for drug-loaded thermosensitive liposomes, with an aim to identify the key transport parameters in determining therapeutic dosing and outcomes. The computational model allows us to not only examine the temporal and spatial variations of drug concentrations in the different compartments by utilising the tumour cord concept, but also assess the therapeutic efficacy and toxicity. In addition, the influences of key factors on systemic plasma concentration and intracellular concentration of the active drug are investigated; these include different chemotherapy drugs, release rate constants and heating duration. Our results show complex relationships between these factors and the predicted therapeutic outcome, making it difficult to identify the “best” parameter set. To overcome this challenge, a model-based optimisation method is proposed in an attempt to find a set of release rate constants and heating duration that can maximise intracellular drug concentration while minimising systemic drug concentration. Optimisation results reveal that under the operating conditions and ranges examined, the best outcome would be achieved with a low drug release rate at physiological temperature, combined with a moderate to high release rate at mild hyperthermia and 1 h heating after injection.
Validation of an Ex Vivo Permeation Method for the Intestinal Permeability of Different BCS Drugs and Its Correlation with Caco-2 In Vitro Experiments
Authors: B. Sánchez Aroha , C. Calpena Ana , Mallandrich Mireia , Clares Beatriz
Published: November 2019

The absorption study of drugs through different biological membranes constitutes an essential step in the development of new pharmaceutical dosage forms. Concerning orally administered forms, methods based on monolayer cell culture of Caco-2 (Caucasian colon adenocarcinoma) have been developed to emulate intestinal mucosa in permeability studies. Although it is widely accepted, it has disadvantages, such as high costs or high technical complexity, and limitations related to the simplified structure of the monolayer or the class of molecules that can be permeated according to the transport mechanisms. The aim of this work was to develop a new ex vivo methodology which allows the evaluation of the intestinal apparent permeability coefficient (Papp) while using fewer resources and to assess the correlation with Caco-2. To this end, pig (Sus scrofa) duodenum segments were mounted in Franz diffusion cells and used to permeate four different drugs: ketorolac tromethamine (Kt), melatonin (Mel), hydrochlorothiazide (Htz), and furosemide (Fur). No statistically significant differences (p > 0.05) were observed corelating Papp values from Franz diffusion cells and Caco-2 cell experiments for Kt, Htz, and Fur. However, there were statistically significant differences (p < 0.05) correlating Papp values and Mel. The difference is explained by the role of Mel in the duodenal epithelial paracellular permeability reduction. Ex vivo permeation may be an equivalent method to Caco-2 for drugs that do not produce intestinal membrane phenomena that could affect absorption.
Bioresorbable Stent in Anterior Cruciate Ligament Reconstruction
Authors: Ficek Krzysztof , Rajca Jolanta , Stolarz Mateusz , Stodolak-Zych Ewa , Wieczorek Jarosław , Muzalewska Małgorzata , Wyleżoł Marek , Wróbel Zygmunt , Binkowski Marcin , Błażewicz Stanisław
Published: November 2019

The exact causes of failure of anterior cruciate ligament (ACL) reconstruction are still unknown. A key to successful ACL reconstruction is the prevention of bone tunnel enlargement (BTE). In this study, a new strategy to improve the outcome of ACL reconstruction was analyzed using a bioresorbable polylactide (PLA) stent as a catalyst for the healing process. The study included 24 sheep with 12 months of age. The animals were randomized to the PLA group (n = 16) and control group (n = 8), subjected to the ACL reconstruction with and without the implantation of the PLA tube, respectively. The sheep were sacrificed 6 or 12 weeks post-procedure, and their knee joints were evaluated by X-ray microcomputed tomography with a 50 μm resolution. While the analysis of tibial and femoral tunnel diameters and volumes demonstrated the presence of BTE in both groups, the enlargement was less evident in the PLA group. Also, the microstructural parameters of the bone adjacent to the tunnels tended to be better in the PLA group. This suggested that the implantation of a bioresorbable PLA tube might facilitate osteointegration of the tendon graft after the ACL reconstruction. The beneficial effects of the stent were likely associated with osteogenic and osteoconductive properties of polylactide.
Role of Charge Regulation and Fluctuations in the Conformational and Mechanical Properties of Weak Flexible Polyelectrolytes
Authors: Blanco Pablo M. , Madurga Sergio , Narambuena Claudio F. , Mas Francesc , Garcés Josep L.
Published: November 2019

This work addresses the role of charge regulation (CR) and the associated fluctuations in the conformational and mechanical properties of weak polyelectrolytes. Due to CR, changes in the pH-value modifies the average macromolecular charge and conformational equilibria. A second effect is that, for a given average charge per site, fluctuations can alter the intensity of the interactions by means of correlation between binding sites. We investigate both effects by means of Monte Carlo simulations at constant pH-value, so that the charge is a fluctuating quantity. Once the average charge per site is available, we turn off the fluctuations by assigning the same average charge to every site. A constant charge MC simulation is then performed. We make use of a model which accounts for the main fundamental aspects of a linear flexible polyelectrolyte that is, proton binding, angle internal rotation, bond stretching and bending. Steric excluded volume and differentiated treatment for short-range and long-range interactions are also included. This model can be regarded as a kind of “minimal” in the sense that it contains a minimum number of parameters but still preserving the atomistic detail. It is shown that, if fluctuations are activated, gauche state bond probabilities increase and the persistence length decreases, so that the polymer becomes more folded. Macromolecular stretching is also analyzed in presence of CR (the charge depends on the applied force) and without CR (the charge is fixed to the value at zero force). The analysis of the low force scaling behavior concludes that Pincus exponent becomes pH-dependent. Both, with and without CR, a transition from 1/2 at high pH-values (phantom chain) to 3/5 at low pH-values (Pincus regime) is observed. Finally, the intermediate force stretching regime is investigated. It is found that CR induces a moderate influence in the force-extension curves and persistence length (which in this force regime becomes force-dependent). It is thus concluded that the effect of CR on the stretching curves is mainly due to the changes in the average charge at zero force. It is also found that, for the cases studied, the effect of steric excluded volume is almost irrelevant compared to electrostatic interactions.
Glycerolysis of Poly(lactic acid) as a Way to Extend the “Life Cycle” of This Material
Authors: Borowicz Marcin , Paciorek-Sadowska Joanna , Isbrandt Marek , Grzybowski Łukasz , Czupryński Bogusław
Published: November 2019

The article concerns the use of glycerolysis reaction as an alternative method of processing post-production and post-consumer waste from poly(lactic acid) (PLA). Management of waste is a very important issue from an environmental protection and economic point of view. Extending the “life cycle” of PLA is extremely important because it allows to make the most of this material. It also limits economic losses resulting from its disposal in the biodegradation process at the same time. This paper presents a method of glycerolysis of poly(lactic acid) waste using various amounts of anhydrous glycerol (mass ratio from 0.3 to 0.5 parts by weight of glycerol per 1.0 part by weight of PLA). This process was also carried out for pure, unmodified PLA Ingeo® (from NatureWorks) to compare the obtained results. The six liquid oligomeric polyhydric alcohols were obtained as a result of the synthesis. Then, they were subjected to physicochemical tests such as determination of color, smell, density, viscosity, and pH. In addition, the obtained raw materials were subjected to analytical tests such as determination of the hydroxyl value, acid value, water content, and elemental composition. The average molecular weights and dispersity were also tested by gel permeation chromatography (GPC). The assumed chemical structure of the obtained compounds was confirmed by spectroscopic methods such as FTIR, 1H NMR, 13C NMR. Glycerolysis products were also subjected to differential scanning calorimetry (DSC) to determine thermal parameters. The obtained research results have allowed the precise characterization of newly obtained products and determination of their suitability, e.g., for the synthesis of polyurethane (PUR) materials.