bluuebunny/crossref_metadata_2025 huggingface dataset:
Simvastatin Induces Unfolded Protein Response and Enhances Temozolomide-Induced Cell Death in Glioblastoma Cells
Authors: Dastghaib Sanaz , Shojaei Shahla , Mostafavi-Pour Zohreh , Sharma Pawan , Patterson John B. , Samali Afshin , Mokarram Pooneh , Ghavami Saeid
Published: October 2020

Glioblastoma (GBM) is the most prevalent malignant primary brain tumor with a very poor survival rate. Temozolomide (TMZ) is the common chemotherapeutic agent used for GBM treatment. We recently demonstrated that simvastatin (Simva) increases TMZ-induced apoptosis via the inhibition of autophagic flux in GBM cells. Considering the role of the unfolded protein response (UPR) pathway in the regulation of autophagy, we investigated the involvement of UPR in Simva–TMZ-induced cell death by utilizing highly selective IRE1 RNase activity inhibitor MKC8866, PERK inhibitor GSK-2606414 (PERKi), and eIF2α inhibitor salubrinal. Simva–TMZ treatment decreased the viability of GBM cells and significantly increased apoptotic cell death when compared to TMZ or Simva alone. Simva–TMZ induced both UPR, as determined by an increase in GRP78, XBP splicing, eukaryote initiation factor 2α (eIF2α) phosphorylation, and inhibited autophagic flux (accumulation of LC3β-II and inhibition of p62 degradation). IRE1 RNase inhibition did not affect Simva–TMZ-induced cell death, but it significantly induced p62 degradation and increased the microtubule-associated proteins light chain 3 (LC3)β-II/LC3β-I ratio in U87 cells, while salubrinal did not affect the Simva–TMZ induced cytotoxicity of GBM cells. In contrast, protein kinase RNA-like endoplasmic reticulum kinase (PERK) inhibition significantly increased Simva–TMZ-induced cell death in U87 cells. Interestingly, whereas PERK inhibition induced p62 accumulation in both GBM cell lines, it differentially affected the LC3β-II/LC3β-I ratio in U87 (decrease) and U251 (increase) cells. Simvastatin sensitizes GBM cells to TMZ-induced cell death via a mechanism that involves autophagy and UPR pathways. More specifically, our results imply that the IRE1 and PERK signaling arms of the UPR regulate Simva–TMZ-mediated autophagy flux inhibition in U251 and U87 GBM cells.
A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System
Authors: Henson Hannah E. , Taylor Michael R.
Published: October 2020

The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways.
Human P2X7 Receptor Causes Cycle Arrest in RPMI-8226 Myeloma Cells to Alter the Interaction with Osteoblasts and Osteoclasts
Authors: Agrawal Ankita , S. Kruse Lars , J. Vangsted Annette , Gartland Alison , R. Jørgensen Niklas
Published: October 2020

Multiple myeloma is a malignant expansion of plasma cells and aggressively affects bone health. We show that P2X7 receptor altered myeloma growth, which affects primary bone cells in vitro. Expression on six human myeloma cell lines confirmed the heterogeneity associated with P2X7 receptor. Pharmacology with 2′(3′)-O-(4-benzoylbenzoyl) adenosine 5′-triphosphate (BzATP) as agonist showed dose-dependent membranal pores on RPMI-8226 (p = 0.0027) and blockade with P2X7 receptor antagonists. Ca2+ influx with increasing doses of BzATP (p = 0.0040) was also inhibited with antagonists. Chronic P2X7 receptor activation reduced RPMI-8226 viability (p = 0.0208). No apoptosis or RPMI-8226 death was observed by annexin V/propidium iodide (PI) labeling and caspase-3 cleavage, respectively. However, bromodeoxyuridine (BrdU) labelling showed an accumulation of RPMI-8226 in the S phase of cell cycle progression (61.5%, p = 0.0114) with significant decline in G0/G1 (5.2%, p = 0.0086) and G2/M (23.5%, p = 0.0015) phases. As myeloma pathology depends on a positive and proximal interaction with bone, we show that P2X7 receptor on RPMI-8226 inhibited the myeloma-induced suppression on mineralization (p = 0.0286) and reversed the excessive osteoclastic resorption. Our results demonstrate a view of how myeloma cell growth is halted by P2X7 receptor and the consequences on myeloma–osteoblast and myeloma–osteoclast interaction in vitro.
The PTEN Conundrum: How to Target PTEN-Deficient Prostate Cancer
Authors: Turnham Daniel J. , Bullock Nicholas , Dass Manisha S. , Staffurth John N. , Pearson Helen B.
Published: October 2020

Loss of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which negatively regulates the PI3K–AKT–mTOR pathway, is strongly linked to advanced prostate cancer progression and poor clinical outcome. Accordingly, several therapeutic approaches are currently being explored to combat PTEN-deficient tumors. These include classical inhibition of the PI3K–AKT–mTOR signaling network, as well as new approaches that restore PTEN function, or target PTEN regulation of chromosome stability, DNA damage repair and the tumor microenvironment. While targeting PTEN-deficient prostate cancer remains a clinical challenge, new advances in the field of precision medicine indicate that PTEN loss provides a valuable biomarker to stratify prostate cancer patients for treatments, which may improve overall outcome. Here, we discuss the clinical implications of PTEN loss in the management of prostate cancer and review recent therapeutic advances in targeting PTEN-deficient prostate cancer. Deepening our understanding of how PTEN loss contributes to prostate cancer growth and therapeutic resistance will inform the design of future clinical studies and precision-medicine strategies that will ultimately improve patient care.
The SARS-CoV-2 Spike Glycoprotein as a Drug and Vaccine Target: Structural Insights into Its Complexes with ACE2 and Antibodies
Authors: Papageorgiou Anastassios C. , Mohsin Imran
Published: October 2020

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the Coronavirus disease (COVID-19) pandemic, has so far resulted in more than 1.1 M deaths and 40 M cases worldwide with no confirmed remedy yet available. Since the first outbreak in Wuhan, China in December 2019, researchers across the globe have been in a race to develop therapies and vaccines against the disease. SARS-CoV-2, similar to other previously identified Coronaviridae family members, encodes several structural proteins, such as spike, envelope, membrane, and nucleocapsid, that are responsible for host penetration, binding, recycling, and pathogenesis. Structural biology has been a key player in understanding the viral infection mechanism and in developing intervention strategies against the new coronavirus. The spike glycoprotein has drawn considerable attention as a means to block viral entry owing to its interactions with the human angiotensin-converting enzyme 2 (ACE2), which acts as a receptor. Here, we review the current knowledge of SARS-CoV-2 and its interactions with ACE2 and antibodies. Structural information of SARS-CoV-2 spike glycoprotein and its complexes with ACE2 and antibodies can provide key input for the development of therapies and vaccines against the new coronavirus.
Divergent Effects of G2019S and R1441C LRRK2 Mutations on LRRK2 and Rab10 Phosphorylations in Mouse Tissues
Authors: Iannotta Lucia , Biosa Alice , Kluss Jillian H. , Tombesi Giulia , Kaganovich Alice , Cogo Susanna , Plotegher Nicoletta , Civiero Laura , Lobbestael Evy , Baekelandt Veerle , Cookson Mark R. , Greggio Elisa
Published: October 2020

Mutations in LRRK2 cause familial Parkinson’s disease and common variants increase disease risk. LRRK2 kinase activity and cellular localization are tightly regulated by phosphorylation of key residues, primarily Ser1292 and Ser935, which impacts downstream phosphorylation of its substrates, among which Rab10. A comprehensive characterization of LRRK2 activity and phosphorylation in brain as a function of age and mutations is missing. Here, we monitored Ser935 and Ser1292 phosphorylation in midbrain, striatum, and cortex of 1, 6, and 12 months-old mice carrying G2019S and R1441C mutations or murine bacterial artificial chromosome (BAC)-Lrrk2-G2019S. We observed that G2019S and, at a greater extent, R1441C brains display decreased phospho-Ser935, while Ser1292 autophosphorylation increased in G2019S but not in R1441C brain, lung, and kidney compared to wild-type. Further, Rab10 phosphorylation, is elevated in R1441C carrying mice, indicating that the effect of LRRK2 mutations on substrate phosphorylation is not generalizable. In BAC-Lrrk2-G2019S striatum and midbrain, Rab10 phosphorylation, but not Ser1292 autophosphorylation, decreases at 12-months, pointing to autophosphorylation and substrate phosphorylation as uncoupled events. Taken together, our study provides novel evidence that LRRK2 phosphorylation in mouse brain is differentially impacted by mutations, brain area, and age, with important implications as diagnostic markers of disease progression and stratification.
Metabolite Sensing GPCRs: Promising Therapeutic Targets for Cancer Treatment?
Authors: Cosín-Roger Jesús , Ortiz-Masia Dolores , Barrachina Maria Dolores , Calatayud Sara
Published: October 2020

G-protein-coupled receptors constitute the most diverse and largest receptor family in the human genome, with approximately 800 different members identified. Given the well-known metabolic alterations in cancer development, we will focus specifically in the 19 G-protein-coupled receptors (GPCRs), which can be selectively activated by metabolites. These metabolite sensing GPCRs control crucial processes, such as cell proliferation, differentiation, migration, and survival after their activation. In the present review, we will describe the main functions of these metabolite sensing GPCRs and shed light on the benefits of their potential use as possible pharmacological targets for cancer treatment.
“How about We Give It a Go?”: A Case Study on Supporting Breastfeeding Families in an Australian Child Care Centre
Authors: Woolley Emma , Wyver Shirley
Published: October 2020

The World Health Organization (WHO) recommends exclusive breastfeeding for six months and continuation of breastfeeding for up to two years. Formal child care has an important role in supporting breastfeeding, as many Australian infants commence care before two years of age. Currently, little is known about support or barriers in child care contexts. The present qualitative instrumental case study explores practices which protect, promote and support breastfeeding at a child care centre located in the Australian Capital Territory’s outer suburbs. Extending from a previously published collective case study, a cultural-institutional focus of analysis was used to explore the roles of proximity, flexibility and communication in supporting breastfeeding within a child care centre located close to an infant’s home. Interviews with centre staff and mothers, triangulated with observations of the centre environment and policy documents provide insight into the environment. Affirming the roles of flexibility in routine and staff rostering and two-way communication, findings suggest longer-term benefits may be derived from selecting a child care centre close to an infant’s home, provided mothers can overcome barriers to breastmilk expression in the workplace. The study recognises the role of non-lactating caregivers in the transition to formal child care, and of the support culture for educators who breastfeed. This study extends the knowledge base of breastfeeding support interventions in the child care setting to inform future research and policy.
The Effect of General Anaesthesia on Circadian Rhythms in Behaviour and Clock Gene Expression of Drosophila melanogaster
Authors: Li Nina , Stanewsky Ralf , Popay Tessa , Warman Guy , Cheeseman James
Published: October 2020

General anaesthesia (GA) is implicated as a cause of postoperative sleep disruption and fatigue with part of the disturbance being attributed to a shift of the circadian clock. In this study, Drosophila melanogaster was used as a model to determine how Isoflurane affects the circadian clock at the behavioural and molecular levels. We measured the response of the clock at both of these levels caused by different durations and different concentrations of Isoflurane at circadian time 4 (CT4). Once characterized, we held the duration and concentration constants (at 2% in air for 6 h) and calculated the phase responses over the entire circadian cycle in both activity and period expression. Phase advances in behaviour were observed during the subjective day, whereas phase delays were associated with subjective night time GA interventions. The corresponding pattern of gene expression preceded the behavioural pattern by approximately four hours. We discuss the implications of this effect for clinical and research practice.
Characterization of Dark-Colored Nanoporous Anodic Films on Zinc
Authors: Masuda Ryoya , Kowalski Damian , Kitano Sho , Aoki Yoshitaka , Nozawa Taisuke , Habazaki Hiroki
Published: October 2020

In this study, zinc is anodized at different voltages in 0.1 mol·dm−3 KOH electrolyte to form nanoporous anodic films. Dark-colored anodic films are formed at anodizing voltages ≤6 V, whereas colorless anodic films are developed at voltages ≥7 V. The anodic films formed at all voltages consist of crystalline ZnO, which was identified by X-ray diffraction and Raman spectroscopy. The Raman spectra of the dark-colored anodic films show the enhanced intensity of the LO phonon mode due to electric-field-induced Raman scattering, which may be associated with the presence of metallic Zn nanoparticles in the anodic films. Scanning electron micrographs and transmission electron micrographs of the cross-section of the dark-colored anodized zinc reveal the formation of two-layer porous anodic films with a highly rough metal/film interface. In contrast, nanoporous anodic films of uniform thickness with a relatively flat metal/film interface are formed for the colorless anodized zinc. The transmission electron microscopy (TEM)/energy dispersive X-ray spectroscopy (EDS) analysis suggested the presence of zinc nanoparticles in the dark-colored anodic films. The non-uniform anodizing and the formation of metal-nanoparticle-dispersed porous anodic films cause the formation of dark-colored anodic films on zinc.
A Novel Approach to Friction Surfacing: Experimental Analysis of Deposition from Radial Surface of a Consumable Tool
Authors: Seidi Ebrahim , Miller Scott F.
Published: October 2020

The friction surfacing technique is an advanced method for creating coatings of various materials onto the surface of a similar or dissimilar material substrate. In this method, there is no external source of heat energy, and all the heat energy required in this method is generated by friction. In this paper, a novel method of friction surfacing from the side of the consumable tool is introduced. The most significant difference in this technique is that material transfer will occur from the radial surface of the consumable tool as opposed to the end of the tool as in conventional friction surfacing. In lateral friction surfacing, the side of the rotating consumable tool is pressed against the substrate surface, which generates frictional heating and shear forces at the interface between tool and substrate. A layer of tool material is transferred from the consumable rod to the substrate surface as the tool moves across. In this study, 6063 aluminum alloy and AISI 1018 carbon steel are used as the materials of consumable tool and substrate, respectively. The impact of process factors, surface roughness values, tool mass loss, and deposition thickness are discussed in detail. The experimental results of this study reveal that lateral friction surfacing produces a very smooth ultra-thin deposition with full coverage, with coating layers with roughness values in the order of 1 µm. Additionally, there is no flash formed in this technique which reduces material consumption. Moreover, temperatures at the interface between the consumable tool and workpiece were measured to be lower than for that in friction surfacing from the end of the tool, which is beneficial for the metallurgical characteristics of the deposited material.
Special Issue “Recent Developments on Functional Coatings for Industrial Applications”
Authors: Calabrese Luigi , Proverbio Edoardo
Published: October 2020

“Recent Developments on Functional Coatings for Industrial Applications” assessed some emerging aspects concerning the recent research progress in the designing, manufacturing and tailoring of new functional coatings for industrial applications. The purpose was to address the recent development in functional coatings synthesis, characterization and optimization, highlighting its emerging industrial applicability in many industrial fields, such as self-healing, self-cleaning or sustainable energy technologies. The multidisciplinary nature of the issue represents an added value aimed at better enhancing the practical relevance and the technological versatility of the functional surface engineering design.
Porous Aluminium Oxide Coating for the Development of Spectroscopic Ellipsometry Based Biosensor: Evaluation of Human Serum Albumin Adsorption
Authors: Maciulis Vincentas , Malinovskis Uldis , Erts Donats , Ramanavicius Arunas , Ramanaviciene Almira , Balevicius Saulius , Juciute Silvija , Plikusiene Ieva
Published: October 2020

An electrochemically synthesised porous anodic aluminium oxide (pAAO) layer has been analysed by means of spectroscopic ellipsometry. The determined thickness of the formed pAAO layer obtained from spectroscopic ellipsometry measurements and modelling was 322.75 ± 0.12 nm. The radius of the nanopores estimated from SEM images was 39 ± 5 nm and the distance between nanopores was 107 ± 6 nm. The investigation of human serum albumin (HSA) adsorption on the pAAO coating showed that: (i) the protein concentration inside nanopores, depending on exposure time, approximately was from 200 up to 600 times higher than that determined in buffer solution; (ii) the initial phase of the adsorption process is slow (3.23 mg·cm−3·min−1) in comparison with the protein desorption rate (21.2 mg·cm−3·min−1) by means of pAAO layer washing; (iii) conventional washing with PBS solution and deionised water does not completely remove HSA molecules from pAAO pores and, therefore, the HSA concentration inside nanopores after 16 h of washing still remains almost 100 times higher than that present in PBS solution. Thus, due to such binding ability, HSA can be successfully used for the blocking of the remaining free surface, which is applied for the reduction in non-specific binding after the immobilisation of biorecognition molecules on the pAAO surface. It was determined that some desorption of HSA molecules from the pAAO layer occurred during the sensor’s surface washing step; however, HSA concentration inside the nanopores still remained rather high. These results recommend the continued application of pAAO in the development of biosensors.
Effects of pH and Fineness of Phosphogypsum on Mechanical Performance of Cement–Phosphogypsum-Stabilized Soil and Classification for Road-Used Phosphogypsum
Authors: Peng Bo , Yang Zhongchang , Yang Zhengwen , Peng Jingwen
Published: October 2020

This article investigates the effects of phosphogypsum (PG) pH and particle fineness on the mechanical properties of cement–PG-stabilized soil. Using solutions of calcium hydroxide (Ca(OH)2) and sulfate (H2SO4) to adjust pH value of PG from 2 to 8. The key pore size used to characterize PG fineness was determined to be 200 μm based on the Grey relational analysis (GRA), and the fineness of PG was controlled from 12.31% to 56.32% by grinding different time. Cement–PG cementitious materials (CPCM) and cement–PG-stabilized soil with different mixture ratios were formed at an optimum moisture content; following this, the unconfined compressive strength and California bearing ratio values of the samples were tested. Results show that the increased pH or the decreased fineness leads to continuous increases in the unconfined compressive strength of CPCM and cement-PG stabilized soil as well as the CBR value of cement–PG-stabilized soil. However, once PG pH value exceeded 5 or fineness was less than 20%, the mechanical properties of cement–PG-stabilized soil remained stable. A classification standard for road usage PG was established based on the analyses regarding cement-PG stabilized soil’s mechanical properties, which has great significance of selecting or disposing road-used PG.
Large Delta T Thermal Cycling Induced Stress Accelerates Equilibrium and Transformation in Super DSS
Authors: Yu Ping-Jui , Chen Shih-Che , Yen Hung-Wei , Chang Horng-Yi , Yang Jer-Ren , Wang Shing-Hoa , Chiu Po-Kai , Lin Tzy-Rong
Published: October 2020

Based on the predicted phase diagram of super duplex stainless steel (DSS) calculated by Thermo-Calc, the maximum peak temperature 1100 °C was selected to ensure no σ phase existence. This target temperature fell into the two-phase solid solution (SS) region. A series of different thermal cycling tests were carried out with the notations of 2SS, 2SS + 3 cycles, 2SS + 7 cycles, 2SS + 13 cycles, and 2SS + 20 cycles. It was found that the trend of two-phase volume ratio variation by thermal cycling followed the predicted thermodynamic equilibrium trend. After 2SS + 7 cycles, the ratio of two-phase δ/γ tended toward the ideal 1:1. According to the electron backscatter diffraction (EBSD) analysis, the δ phase crystal orientation changed from the most frequent directions of <001> and <111> of the as-received sample to the most frequent orientation of <113> after two SS treatments. While the γ phase grain always remained at <101> orientation. The grain boundary misorientation angles of the γ grains were relatively stable, ranging from 53° to 63°, but those of the δ grains were widely distributed actively presuming the lattice rotation. The Kernel Average Misorientation (KAM) value of the local strain in face center cubic (fcc) γ grains was varied and greater than that of the body center cubic (bcc) δ phase, indicating that the former, with a large grain boundary misorientation had larger local deformation than the latter, which possesses wide random misorientation angle distribution.
Clinical and Radiological Analysis of Pyogenic Vertebral Osteomyelitis Immediately after Successful Antimicrobial Therapy: Considerations for Assessing Therapeutic Response
Authors: Jeon Ikchan , Kong Eunjung , Yu Dongwoo , Hong Cheol Pyo
Published: October 2020

Purpose: The clinical and radiological abnormal findings continue even after successful treatment in pyogenic vertebral osteomyelitis (PVO). We analyzed the clinical and radiological features of cured PVO based on 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (FDG-PET/MRI) and compared the radiological differences between FDG-PET and MRI for assessing therapeutic response in PVO. Methods: This study included 43 patients (28 men and 15 women) with lumbar PVO who had no recurrence after successful antimicrobial therapy. They were divided into two groups based on the location of maximum standardized FDG uptake value (SUVmax) of PVO lesion on FDG-PET/MRI when parenteral antibiotics were discontinued (31 in group A: Intervertebral structure; 12 in group B: Vertebral body and paravertebral muscle). The differences of clinical symptoms, hematological inflammatory indices, and radiological features were retrospectively analyzed. Results: The patients were treated with 42.28 ± 14.58 (21–89) days of parenteral antibiotics. There were significant differences in C-reactive protein (0.97 ± 1.10 vs. 0.51 ± 0.31 mg/dL, p = 0.041; normal range of CRP < 0.5), back pain (4.29 ± 1.13 vs. 3.50 ± 1.00, p = 0.040; visual analog scale), and SUVmax (4.34 ± 1.24 vs. 5.89 ± 1.57, p < 0.001) between the two groups. In the distribution pattern of PVO lesions, FDG-PET overall showed recovery pattern earlier than MRI did (p < 0.001). Conclusions: In cured PVO, the clinical features vary depending on the location of major structural damage of PVO lesion. The involvement of intervertebral structure is related with sustained back pain and elevation of CRP, and vertebral body/paravertebral muscle shows favorable clinical features despite advanced structural damages.
Super-Resolution Imaging with Ultrasound for Visualization of the Renal Microvasculature in Rats Before and After Renal Ischemia: A Pilot Study
Authors: Andersen Sofie Bech , Taghavi Iman , Hoyos Carlos Armando Villagómez , Søgaard Stinne Byrholdt , Gran Fredrik , Lönn Lars , Hansen Kristoffer Lindskov , Jensen Jørgen Arendt , Nielsen Michael Bachmann , Sørensen Charlotte Mehlin
Published: October 2020

In vivo monitoring of the microvasculature is relevant since diseases such as diabetes, ischemia, or cancer cause microvascular impairment. Super-resolution ultrasound imaging allows in vivo examination of the microvasculature by detecting and tracking sparsely distributed intravascular microbubbles over a minute-long period. The ability to create detailed images of the renal vasculature of Sprague-Dawley rats using a modified clinical ultrasound platform was investigated in this study. Additionally, we hypothesized that early ischemic damage to the renal microcirculation could be visualized. After a baseline scan of the exposed kidney, 10 rats underwent clamping of the renal vein (n = 5) or artery (n = 5) for 45 min. The kidneys were rescanned at the onset of clamp release and after 60 min of reperfusion. Using a processing pipeline for tissue motion compensation and microbubble tracking, super-resolution images with a very high level of detail were constructed. Image filtration allowed further characterization of the vasculature by isolating specific vessels such as the ascending vasa recta with a 15–20 μm diameter. Using the super-resolution images alone, it was only possible for six assessors to consistently distinguish the healthy renal microvasculature from the microvasculature at the onset of vein clamp release. Future studies will aim at attaining quantitative estimations of alterations in the renal microvascular blood flow using super-resolution ultrasound imaging.
Soluble Syndecan-1 Levels Are Associated with Survival in Platinum-Treated Bladder Cancer Patients
Authors: Olah Csilla , Tschirdewahn Stephan , Hoffmann Michèle J. , Krafft Ulrich , Hadaschik Boris , Nyirady Peter , Szendröi Attila , Módos Orsolya , Csizmarik Anita , Kovalszky Ilona , Reis Henning , Szarvas Tibor
Published: October 2020

Cisplatin-containing chemotherapy represents the first-line treatment for patients with locally advanced or metastatic muscle-invasive bladder cancer. Recently, novel therapies have become available for cisplatin-ineligible or -resistant patients. Therefore, prediction of cisplatin response is required to optimize therapy decisions. Syndecan-1 (SDC1) tissue expression and serum concentration may be associated with cisplatin resistance. Thus, pre-treatment serum levels of SDC1 and its expression in chemo-naïve tissues were assessed in 121 muscle-invasive bladder cancer patients who underwent postoperative platinum-based chemotherapy. SDC1 concentrations were evaluated by ELISA in 52 baseline and 90 follow-up serum samples and tissue expressions were analyzed by immunohistochemistry in an independent cohort of 69 formalin-fixed paraffin-embedded tumor samples. Pre-treatment SDC1 serum levels were significantly higher in lymph node metastatic (p = 0.009) and female patients (p = 0.026). SDC1 tissue expression did not correlate with clinicopathological parameters. High pre-treatment SDC1 serum level and the presence of distant metastasis were independent risk factors for overall survival (Hazard ratio (HR): 1.439, 95% Confidence interval (CI): 1.003–2.065, p = 0.048; HR: 2.269, 95%CI: 1.053–4.887, p = 0.036). Our results demonstrate an independent association between high baseline serum SDC1 concentration and poor survival in platinum-treated patients. Analyzing baseline serum SDC1 levels may help to predict platinum-containing chemotherapy and could help to optimize therapeutic decision-making.
Analysis of the Gene Expression Profile of Stromal Pro-Tumor Factors in Cancer-Associated Fibroblasts from Luminal Breast Carcinomas
Authors: Eiro Noemi , Cid Sandra , Fraile María , Cabrera Jorge Ruben , Gonzalez Luis O. , Vizoso Francisco J.
Published: October 2020

Luminal tumors are the most frequent type of breast carcinomas showing less tumor aggressiveness, although heterogeneity exists in their clinical outcomes. Cancer-associated fibroblasts (CAFs) are a key component of the tumor stroma which contribute to tumor progression. We investigated by real-time PCR the gene expression of 19 factors implicated in tumor progression. Those factors included the calcium-binding protein S100A4, several growth factors (FGF2, FGF7, HGF, PDGFA, PDGFB, TGFβ, VEGFA, and IGF2), and we also studied inflammatory cytokines (IL6 and IL8), chemokines (CCL2, CXCL12), important proteases (uPA, MMP2, MMP9 and MMP11), the nuclear factor NFκB, and the metalloprotease inhibitor TIMP1, from luminal A and luminal B breast carcinoma CAFs. We performed a similar analysis after co-culturing CAFs with MCF-7 and MDA-MB-231 breast cancer cell lines. MMP-9 and CCL2 gene expressions were higher in CAFs from luminal B tumors. We also found different patterns in the induction of pro-tumoral factors from different CAFs populations co-cultured with different cancer cell lines. Globally, CAFs from luminal B tumors showed a higher expression of pro-tumor factors compared to CAFs from luminal A tumors when co-cultured with breast cancer cell lines. Moreover, we found that CAFs from metastatic tumors had higher IGF-2 gene expression, and we detected the same after co-culture with cell lines. Our results show the variability in the capacities of CAFs from luminal breast carcinomas, which may contribute to a better biological and clinical characterization of these cancer subtypes.
Nucleic Acid and Immunological Diagnostics for SARS-CoV-2: Processes, Platforms and Pitfalls
Authors: Premraj Avinash , Aleyas Abi George , Nautiyal Binita , Rasool Thaha J
Published: October 2020

Accurate diagnosis at an early stage of infection is essential for the successful management of any contagious disease. The coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus is a pandemic that has affected 214 countries affecting more than 37.4 million people causing 1.07 million deaths as of the second week of October 2020. The primary diagnosis of the infection is done either by the molecular technique of RT-qPCR by detecting portions of the RNA of the viral genome or through immunodiagnostic tests by detecting the viral proteins or the antibodies produced by the host. As the demand for the test increased rapidly many naive manufacturers entered the market with novel kits and more and more laboratories also entered the diagnostic arena making the test result more error-prone. There are serious debates globally and regionally on the sensitivity and specificity of these tests and about the overall accuracy and reliability of the tests for decision making on control strategies. The significance of the test is also complexed by the presence of asymptomatic carriers, re-occurrence of infection in cured patients as well as by the varied incubation periods of the infection and shifting of the viral location in the host tissues. In this paper, we review the techniques available for SARS-CoV-2 diagnosis and probable factors that can reduce the sensitivity and specificity of the different test methods currently in vogue. We also provide a checklist of factors to be considered to avoid fallacious practices to reduce false positive and false negative results by the clinical laboratories.
The Effects of Multilinguality on the Development of Causal Speech Acts in the Geography Classroom
Authors: Heuzeroth Johannes , Budke Alexandra
Published: October 2020

This explorative, qualitative study examines the use and effectiveness of resources of multilinguality, with particular regard to the development of causal links in geography classes. Contentual and linguistic strategies of multilingual pupils in creating causal links were collected and evaluated systematically. This was done by means of a qualitative content analysis of oral, cooperative lesson sequences. A model on how to deal with multilingual, systemic learning settings is presented as a resulting hypothesis.
Frequency and Voltage Supports by Battery-Fed Smart Inverters in Mixed-Inertia Microgrids
Authors: S. Pilehvar Mohsen , Mirafzal Behrooz
Published: October 2020

This paper presents a piecewise linear-elliptic (PLE) droop control scheme to improve the dynamic behavior of islanded microgrids. Islanded microgrids are typically vulnerable to voltage and frequency fluctuations, particularly if a combination of high- and low-inertia power generation units are used in a microgrid. The intermittent nature of renewable energy sources can cause sudden power mismatches, and thus, voltage and frequency fluctuations. The proposed PLE droop control scheme can be employed in a battery energy storage system (BESS) to effectively mitigate voltage and frequency fluctuations in an islanded microgrid. Though the PLE shape can be implemented for any droop control scheme, it has been applied for active power-frequency (P-f) and reactive power-voltage (Q-v) droops in this paper. In addition, the dynamic response of a battery-fed smart inverter equipped with the proposed PLE droops has been compared with the results obtained from a linear droop control scheme in an islanded microgrid containing high- and low-inertia power-generation units. In this paper, the results of several case studies are presented to confirm the capability of the PLE droop control in mitigating voltage and frequency fluctuations in islanded microgrids.
Distributed Fog Computing for Internet of Things (IoT) Based Ambient Data Processing and Analysis
Authors: Ahmed Mehreen , Mumtaz Rafia , Zaidi Syed Mohammad Hassan , Hafeez Maryam , Zaidi Syed Ali Raza , Ahmad Muneer
Published: October 2020

Urban centers across the globe are under immense environmental distress due to an increase in air pollution, industrialization, and elevated living standards. The unmanageable and mushroom growth of industries and an exponential soar in population has made the ascent of air pollution intractable. To this end, the solutions that are based on the latest technologies, such as the Internet of things (IoT) and Artificial Intelligence (AI) are becoming increasingly popular and they have capabilities to monitor the extent and scale of air contaminants and would be subsequently useful for containing them. With centralized cloud-based IoT platforms, the ubiquitous and continuous monitoring of air quality and data processing can be facilitated for the identification of air pollution hot spots. However, owing to the inherent characteristics of cloud, such as large end-to-end delay and bandwidth constraint, handling the high velocity and large volume of data that are generated by distributed IoT sensors would not be feasible in the longer run. To address these issues, fog computing is a powerful paradigm, where the data are processed and filtered near the end of the IoT nodes and it is useful for improving the quality of service (QoS) of IoT network. To further improve the QoS, a conceptual model of distributed fog computing and a machine learning based data processing and analysis model is proposed for the optimal utilization of cloud resources. The proposed model provides a classification accuracy of 99% while using a Support Vector Machines (SVM) classifier. This model is also simulated in iFogSim toolkit. It affords many advantages, such as reduced load on the central server by locally processing the data and reporting the quality of air. Additionally, it would offer the scalability of the system by integrating more air quality monitoring nodes in the IoT network.
An Approach for the Application of a Dynamic Multi-Class Classifier for Network Intrusion Detection Systems
Authors: Larriva-Novo Xavier , Sánchez-Zas Carmen , Villagrá Víctor A. , Vega-Barbas Mario , Rivera Diego
Published: October 2020

Currently, the use of machine learning models for developing intrusion detection systems is a technology trend which improvement has been proven. These intelligent systems are trained with labeled datasets, including different types of attacks and the normal behavior of the network. Most of the studies use a unique machine learning model, identifying anomalies related to possible attacks. In other cases, machine learning algorithms are used to identify certain type of attacks. However, recent studies show that certain models are more accurate identifying certain classes of attacks than others. Thus, this study tries to identify which model fits better with each kind of attack in order to define a set of reasoner modules. In addition, this research work proposes to organize these modules to feed a selection system, that is, a dynamic classifier. Finally, the study shows that when using the proposed dynamic classifier model, the detection range increases, improving the detection by each individual model in terms of accuracy.
Emotion Analysis in Human–Robot Interaction
Authors: Szabóová Martina , Sarnovský Martin , Maslej Krešňáková Viera , Machová Kristína
Published: October 2020

This paper connects two large research areas, namely sentiment analysis and human–robot interaction. Emotion analysis, as a subfield of sentiment analysis, explores text data and, based on the characteristics of the text and generally known emotional models, evaluates what emotion is presented in it. The analysis of emotions in the human–robot interaction aims to evaluate the emotional state of the human being and on this basis to decide how the robot should adapt its behavior to the human being. There are several approaches and algorithms to detect emotions in the text data. We decided to apply a combined method of dictionary approach with machine learning algorithms. As a result of the ambiguity and subjectivity of labeling emotions, it was possible to assign more than one emotion to a sentence; thus, we were dealing with a multi-label problem. Based on the overview of the problem, we performed experiments with the Naive Bayes, Support Vector Machine and Neural Network classifiers. Results obtained from classification were subsequently used in human–robot experiments. Despise the lower accuracy of emotion classification, we proved the importance of expressing emotion gestures based on the words we speak.
Advanced Control for Electric Drives: Current Challenges and Future Perspectives
Authors: Merabet Adel
Published: October 2020

In the Special Issue “Advanced Control for Electric Drives”, the objective is to address a variety of issues related to advances in control techniques for electric drives, implementation challenges, and applications in emerging fields such as electric vehicles, unmanned aerial vehicles, maglev trains and motion applications. This issue includes 15 selected and peer-reviewed articles discussing a wide range of topics, where intelligent control, estimation and observation schemes were applied to electric drives for various applications. Different drives were studied such as induction motors, permanent magnet synchronous motors and brushless direct current motors.
Design and Implementation of an Accelerated Error Convergence Criterion for Norm Optimal Iterative Learning Controller
Authors: Riaz Saleem , Lin Hui , Akhter Muhammad Pervez
Published: October 2020

Designing an optimal iterative learning control is a huge challenge for linear and nonlinear dynamic systems. For such complex systems, standard Norm optimal iterative learning control (NOILC) is an important consideration. This paper presents a novel NOILC error convergence technique for a discrete-time method. The primary effort of the controller is to converge the error efficiently and quickly in an optimally successful way. A new iterative learning algorithm based on feedback based on reliability against input disruption was proposed in this paper. The illustration of the simulations authenticates the process suggested. The numerical example simulated on MATLAB@2019 and the mollified results affirm the validation of the designed algorithm.
Real-Time Energy Management of Parallel Hybrid Electric Vehicles Using Linear Quadratic Regulation
Authors: Nguyễn Bảo-Huy , Trovão João Pedro F. , German Ronan , Bouscayrol Alain
Published: October 2020

Optimization-based methods are of interest for developing energy management strategies due to their high performance for hybrid electric vehicles. However, these methods are often complicated and may require strong computational efforts, which can prevent them from real-world applications. This paper proposes a novel real-time optimization-based torque distribution strategy for a parallel hybrid truck. The strategy aims to minimize the engine fuel consumption while ensuring battery charge-sustaining by using linear quadratic regulation in a closed-loop control scheme. Furthermore, by reformulating the problem, the obtained strategy does not require the information of the engine efficiency map like the previous works in literature. The obtained strategy is simple, straightforward, and therefore easy to be implemented in real-time platforms. The proposed method is evaluated via simulation by comparison to dynamic programming as a benchmark. Furthermore, the real-time ability of the proposed strategy is experimentally validated by using power hardware-in-the-loop simulation.
Experimental Study on a Hydrogen Stratification Induced by PARs Installed in a Containment
Authors: Kim Jongtae , Hong Seongho , Park Ki Han , Kim Jin Heok , Oh Jeong Yun
Published: October 2020

Hydrogen can be produced in undesired ways such as a high temperature metal oxidation during an accident. In this case, the hydrogen must be carefully managed. A hydrogen mitigation system (HMS) should be installed to protect a containment of a nuclear power plant (NPP) from hazards of hydrogen produced by an oxidation of the fuel cladding during a severe accident in an NPP. Among hydrogen removal devices, passive auto-catalytic recombiners (PARs) are currently applied to many NPPs because of passive characteristics, such as not requiring a power supply nor an operators’ manipulations. However, they offer several disadvantages, resulting in issues related to hydrogen control by PARs. One of the issues is a hydrogen stratification in which hydrogen is not well-mixed in a compartment due to the high temperature exhaust gas of PARs and accumulation in the lower part. Therefore, experimental simulation on hydrogen stratification phenomenon by PARs is required. When the hydrogen stratification by PARs is observed in the experiment, the verification and improvement of a PAR analysis model using the experimental results can be performed, and the hydrogen removal characteristics by PARs installed in an NPP can be evaluated using the improved PAR model.
Application of Industry 4.0 to the Product Development Process in Project-Type Production
Authors: Urban Wieslaw , Łukaszewicz Krzysztof , Krawczyk-Dembicka Elżbieta
Published: October 2020

Currently, the concept of Industry 4.0 (I4.0) is reaching most companies by changing the characteristics of their production systems. The aim of this study was to determine the possibilities of applying I4.0 concepts and tools to the product development process in a small- to medium-sized enterprise (SME)—a food processing technology supplier that offers individually tailored solutions. The study employs the case study methodology along with conceptual studies. Based on the available I4.0 concepts/technologies, the areas of the process that could be improved were identified. The study concludes with proposing several modifications in the process in the context of I4.0. Some of the process stages can be shortened by implementing I4.0 tools. It was found that the length of the process can be shortened from 36 to 26 months, and possible gains also include energy savings. Technological tools, referred to as augmented/virtual reality, along with simulations and virtual manufacturing, seem to have particular applicability. The energy savings estimation emerged as a check gate evaluating if technological implementations are justified. Directions for further research with reference to I4.0 and studied processes are determined.
Pollen Morphology and Variability of Abies alba Mill. Genotypes from South-Western Poland
Authors: Wrońska-Pilarek Dorota , Dering Monika , Bocianowski Jan , Lechowicz Kacper , Kowalkowski Wojciech , Barzdajn Władysław , Hauke-Kowalska Maria
Published: October 2020

The objective of this study was to investigate pollen morphology and ranges of intraspecific variability of Abies alba Mill. Pollen grains were collected from nine clonal seed orchards of A. alba in the Sudety Mountains, (South-Western Poland). At each seed orchard, 4–6 grafts were selected. Each individual (graft) was represented by 30 pollen grains and 1440 pollen grains were measured totally. Eight quantitative and four qualitative features of pollen grains were analysed. The diagnostic features of pollen grains for the studied species were: Exine surface of pollen corpus (cappa and leptoma) and sacci, the length of the polar axis (P), pollen shape (P/E ratio), and a new trait—saccus shape (A/B ratio — saccus width (A) to his length (B)). Pollen features made possible to differentiate seven individual genotypes (samples). To our knowledge, this is the first time that the intraspecific and interindividual variability of pollen grains of A. alba were investigated. The most different were the pollen grains from samples—genotypes 13 (Bystrzyca Kłodzka) and 18 (Jugów), and also (although to a lesser extent) genotypes—11 (Kamienna Góra), 30, 31 (Jugów), and 44 (Szklarska Poręba). No significant relationships were observed between the pollen grain traits and the geographical location of the collection sites.