bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbazole Derivatives as STAT Inhibitors: An Overview
Authors: Caruso Anna , Barbarossa Alexia , Carocci Alessia , Salzano Giovanni , Sinicropi Maria Stefania , Saturnino Carmela
Published: July 2021

The carbazole class is made up of heterocyclically structured compounds first isolated from coal tar. Their structural motif is preponderant in different synthetic materials and naturally occurring alkaloids extracted from the taxonomically related higher plants of the genus Murraya, Glycosmis, and Clausena from the Rutaceae family. Concerning the biological activity of these compounds, many research groups have assessed their antiproliferative action of carbazoles on different types of tumoral cells, such as breast, cervical, ovarian, hepatic, oral cavity, and small-cell lung cancer, and underlined their potential effects against psoriasis. One of the principal mechanisms likely involved in these effects is the ability of carbazoles to target the JAK/STATs pathway, considered essential for cell differentiation, proliferation, development, apoptosis, and inflammation. In this review, we report the studies carried out, over the years, useful to synthesize compounds with carbazole moiety designed to target these kinds of kinases.
Analysis of the Possibility of Using Various Time-Frequency Transformation Methods to Barkhausen Noise Characterization for the Need of Magnetic Anisotropy Evaluation in Steels
Authors: Maciusowicz Michal , Psuj Grzegorz
Published: July 2021

Magnetic Barkhausen Noise (MBN) is a method being currently considered by many research and development centers, as it provides knowledge about the properties and current state of the examined material. Due to the practical aspects, magnetic anisotropy evaluation is one of such key areas. However, due to the non-stationary and stochastic nature of MBN, it requires searching for postprocessing procedures, allowing the extraction of crucial information on factors influencing the phenomenon. Advances in the field of the analysis of non-stationary signals by various transformations or decompositions resulting into new time- and frequency-related representations, allow the interpretation of complex sets of signals. Therefore, in this paper, several time-frequency transformations were used to analyze the data of MBN for the purpose of the magnetic anisotropy evaluation of electrical steel. The three main transform types with their modifications were considered and compared: the Short-Time Fourier Transform, the Continuous Wavelet Transform and the Smoothed Pseudo Wigner–Ville Transform. By using Exploratory Data Analysis methods and the parametrization of time-frequency representation, the qualitative and quantitative analysis was made. The STFT presented good performance on providing useful information on MBN changes while simultaneously leading to the lowest computational efforts.
Aromachology and Customer Behavior in Retail Stores: A Systematic Review
Authors: Giacalone Davide , Pierański Bartłomiej , Borusiak Barbara
Published: July 2021

Interest in the use of scents in retail environments for creating better customer experiences is growing. Yet, knowledge of the effectiveness of aromachology to affect actual customer behavior and ultimately increase turnover is incomplete, as published results present inconsistencies and are often based on highly controlled environments rather than actual store environments. Situated within this context, this paper offers a systematic review on research in aromachology with a focus on effects on actual customer behavior in actual retail environments. As expected, the available research on actual environments (relative to laboratory-based studies) is limited, with only 20 articles meeting the inclusion criteria. While reported results are, overall, indicative of the positive effects of scent on customers’ emotional states and on their in-store behavior (dwell time, product choices) and attitudes (purchase intention, intention to revisit), several critical issues with the available literature emerged. These pertain primarily to a lack of sufficient methodological details (specifically on the scents, their compositions, intensity and methods of delivery), a narrow focus on scents without considering interactions with other atmospherics factors, and a general disregard of individual differences in olfaction. The review provides suggestions for addressing these shortcomings and improving the quality and actionability of this line of research.
Visual Attention Software: A New Tool for Understanding the “Subliminal” Experience of the Built Environment
Authors: Lavdas Alexandros , Salingaros Nikos , Sussman Ann
Published: July 2021

Eye-tracking technology is a biometric tool that has found many commercial and research applications. The recent advent of affordable wearable sensors has considerably expanded the range of these possibilities to fields such as computer gaming, education, entertainment, health, neuromarketing, psychology, etc. The Visual Attention Software by 3M (3M-VAS) is an artificial intelligence application that was formulated using experimental data from eye-tracking. It can be used to predict viewer reactions to images, generating fixation point probability maps and fixation point sequence estimations, thus revealing pre-attentive processing of visual stimuli with a very high degree of accuracy. We have used 3M-VAS software in an innovative implementation to analyze images of different buildings, either in their original state or photographically manipulated, as well as various geometric patterns. The software not only reveals non-obvious fixation points, but also overall relative design coherence, a key element of Christopher Alexander’s theory of geometrical order. A more evenly distributed field of attention seen in some structures contrasts with other buildings being ignored, those showing instead unconnected points of splintered attention. Our findings are non-intuitive and surprising. We link these results to both Alexander’s theory and Neuroscience, identify potential pitfalls in the software’s use, and also suggest ways to avoid them.
Dimension-Wise Particle Swarm Optimization: Evaluation and Comparative Analysis
Authors: Schlauwitz Justin , Musilek Petr
Published: July 2021

This article evaluates a recently introduced algorithm that adjusts each dimension in particle swarm optimization semi-independently and compares it with the traditional particle swarm optimization. In addition, the comparison is extended to differential evolution and genetic algorithm. This presented comparative study provides a clear exposition of the effects introduced by the proposed algorithm. Performance of all evaluated optimizers is evaluated based on how well they perform in finding the global minima of 24 multi-dimensional benchmark functions, each having 7, 14, or 21 dimensions. Each algorithm is put through a session of self-tuning with 100 iterations to ensure convergence of their respective optimization parameters. The results confirm that the new variant is a significant improvement over the traditional algorithm. It also obtained notably better results than differential evolution when applied to problems with high-dimensional spaces relative to the number of available particles.
Characterization of Black Carbon and Its Correlations with VOCs in the Northern Region of Hangzhou Bay in Shanghai, China
Authors: Wang Fangfang , Xu Jialuo , Huang Yinzhi , Xiu Guangli
Published: July 2021

Ozone and PM2.5 (all particulate matter with diameter of 2.5 µm or smaller) are currently two disturbing environmental issues in most cities of China. Black carbon (BC), mainly from incomplete combustion, is one of the most important components of PM2.5 because it can absorb light and contribute to haze pollution and global warming. Meanwhile, volatile organic compounds (VOCs) have become a major air pollutant due to their association with haze, ozone (O3), global warming and human health by direct or indirect processes. In this study, one year-long observation campaign of BC, VOCs and other conventional air pollutants was conducted in the Northern Region of the Hangzhou Bay (NRHB) in Shanghai, China. The results indicated that higher concentration of BC mainly occurred in the autumn and winter, especially in December. In December, higher BC concentrations were found when the air mass came from northwest where there is an important local freeway, or southwest where some adjacent southwest chemical industrial parks are located. Different from the characteristics of BC in urban areas reported by previous studies, the diurnal variation of BC exhibited three peaks, two of which coincided with the morning and evening rush hours which are related to the heavy diesel traffic from a nearby freeway, and the third peak was often found late at night, around 2 am, which might be associated with abnormal emissions from an industrial park or marine traffic in the ocean waterway. BC had weakly negative correlation with O3 and NO, and a strongly positive correlation with PM2.5, SO2, NO2 and NOx, which implies that some incomplete combustion sources might occur in the nearby regions. With regard to VOCs, BC had a strong positive correlation with alkane, alkenes, alkynes, aromatic and non-sulfur VOCs, particularly with aromatic organic matter. Unlike the stronger correlation with aromatics in the morning rush hours, a stronger correlation between BC and alkenes and alkynes during the evening rush hour was observed. The relationships between BC and VOCs, particularly with some specific VOCs species related to the neighboring chemical industrial park, demonstrated that the contribution of the surrounding chemical industrial parks to BC should not be neglected.
Blood Plasma Self-Separation Technologies during the Self-Driven Flow in Microfluidic Platforms
Authors: Wang Yudong , Nunna Bharath Babu , Talukder Niladri , Etienne Ernst Emmanuel , Lee Eon Soo
Published: July 2021

Blood plasma is the most commonly used biofluid in disease diagnostic and biomedical analysis due to it contains various biomarkers. The majority of the blood plasma separation is still handled with centrifugation, which is off-chip and time-consuming. Therefore, in the Lab-on-a-chip (LOC) field, an effective microfluidic blood plasma separation platform attracts researchers’ attention globally. Blood plasma self-separation technologies are usually divided into two categories: active self-separation and passive self-separation. Passive self-separation technologies, in contrast with active self-separation, only rely on microchannel geometry, microfluidic phenomena and hydrodynamic forces. Passive self-separation devices are driven by the capillary flow, which is generated due to the characteristics of the surface of the channel and its interaction with the fluid. Comparing to the active plasma separation techniques, passive plasma separation methods are more considered in the microfluidic platform, owing to their ease of fabrication, portable, user-friendly features. We propose an extensive review of mechanisms of passive self-separation technologies and enumerate some experimental details and devices to exploit these effects. The performances, limitations and challenges of these technologies and devices are also compared and discussed.
Impacts of the Invasive Impatiens glandulifera: Lessons Learned from One of Europe’s Top Invasive Species
Authors: Coakley Stephanie , Petti Carloalberto
Published: July 2021

Biological invasions are renowned for their negative ecological and economic implications, however from studying invasions invaluable insights can be gained in the fields of ecology and evolution- potentially contributing towards conservation plans to deal, not only with biological invasion, but with other concerning issues, such as climate change. Impatiens glandulifera, or Himalayan balsam, is widely considered to be a highly problematic invasive, having spread across more than thirty countries during the past century. This paper will examine the findings which have arose from studying I. glandulifera and its impacts on the invaded ecosystem.
Identification of HSP47 Binding Site on Native Collagen and Its Implications for the Development of HSP47 Inhibitors
Authors: Cai Haiyan , Sasikumar Parvathy , Little Gemma , Bihan Dominique , Hamaia Samir W. , Zhou Aiwu , Gibbins Jonathan M. , Farndale Richard W.
Published: July 2021

HSP47 (heat shock protein 47) is a collagen-specific molecular chaperone that is essential for procollagen folding and function. Previous studies have shown that HSP47 binding requires a critical Arg residue at the Y position of the (Gly-Xaa-Yaa) repeats of collagen; however, the exact binding sites of HSP47 on native collagens are not fully defined. To address this, we mapped the HSP47 binding sites on collagens through an ELISA binding assay using collagen toolkits, synthetic collagen peptides covering the entire amino acid sequences of collagen types II and III assembled in triple-helical conformation. Our results showed that HSP47 binds to only a few of the GXR motifs in collagen, with most of the HSP47 binding sites identified located near the N-terminal part of the triple-helical region. Molecular modelling and binding energy calculation indicated that residues flanking the key Arg in the collagen sequence also play an important role in defining the high-affinity HSP47 binding site of collagen. Based on this binding mode of HSP47 to collagen, virtual screening targeting both the Arg binding site and its neighboring area on the HSP47 surface, and a subsequent bioassay, we identified two novel compounds with blocking activity towards HSP47 binding of collagen. Overall, our study revealed the native HSP47 binding sites on collagen and provided novel information for the design of small-molecule inhibitors of HSP47.
New Challenges for Biobanks: Accreditation to the New ISO 20387:2018 Standard Specific for Biobanks
Authors: De Blasio Pasquale , Biunno Ida
Published: July 2021

Background: The emergence of “multi-omics” and “multi-parametric” types of analysis based on a high number of biospecimens enforces the use of a great number of high-quality “Biological Materials and Associated Data” (BMaD). To meet the demands of biomedical research, several Biological Resource Centers (BRCs) or Biobanks world-wide have implemented a specific Quality Management System (QMS) certified ISO 9001:2015 or accredited by CAP9 ISO 20387:2018. For the first time, ISO, with the support of several Biobanking experts, issued the ISO 20387:2018 which is the first ISO norm specific for Biobanks. The fundamental difference with present certification/accreditation standards is that the ISO 20387:2018 focuses not only on the operational aspects of the Biobank, but also on the “competence of the Biobank to carry our specific Biobanking tasks”. Methods: The accreditation process for ISO 20387:2018 required the definition of: (1) objectives, goals and organizational structure of the Biobank, including procedures for governance, confidentiality and impartiality policies; (2) standard operating procedures (SOPs) of all activities performed, including acquisition, analysis, collection, data management, distribution, preparation, preservation, testing facility and equipment maintenance, calibration, and monitoring; (3) procedures for control of documents and records, the identification of risks and opportunities, improvements, corrective actions, nonconforming records and evaluation of external providers (4) an internal audit and management reviews, verification of QMS performance, monitoring of quality objectives and personnel qualification and competency in carrying out specific Biobanking tasks. Results: The accreditation process is performed by an independent authorized organization which certifies that all processes are performed according to the QMS, and that the infrastructure is engineered and managed according to the GDP and/or GMP guidelines. Conclusion: Accreditation is given by an accreditation body, which recognizes formally that the Biobank is “competent to carry out specific Biobanking tasks”.
Structural and Drug Targeting Insights on Mutant p53
Authors: Gomes Ana Sara , Ramos Helena , Inga Alberto , Sousa Emília , Saraiva Lucília
Published: July 2021

p53 is a transcription factor with a pivotal role in cell homeostasis and fate. Its impairment is a major event in tumor onset and development. In fact, about half of human cancers bear TP53 mutations that not only halt the normal function of p53, but also may acquire oncogenic gain of functions that favor tumorigenesis. Although considered undruggable for a long time, evidence has proven the capability of many compounds to restore a wild-type (wt)-like function to mutant p53 (mutp53). However, they have not reached the clinic to date. Structural studies have strongly contributed to the knowledge about p53 structure, stability, dynamics, function, and regulation. Importantly, they have afforded relevant insights into wt and mutp53 pharmacology at molecular levels, fostering the design and development of p53-targeted anticancer therapies. Herein, we provide an integrated view of mutp53 regulation, particularly focusing on mutp53 structural traits and on targeting agents capable of its reactivation, including their biological, biochemical and biophysical features. With this, we expect to pave the way for the development of improved small molecules that may advance precision cancer therapy by targeting p53.
Comprehensive Profiling of Hypoxia-Related miRNAs Identifies miR-23a-3p Overexpression as a Marker of Platinum Resistance and Poor Prognosis in High-Grade Serous Ovarian Cancer
Authors: Todeschini Paola , Salviato Elisa , Romani Chiara , Raimondi Vittoria , Ciccarese Francesco , Ferrari Federico , Tognon Germana , Marchini Sergio , D’Incalci Maurizio , Zanotti Laura , Ravaggi Antonella , Odicino Franco , Sartori Enrico , D’Agostino Donna M. , Samaja Michele , Romualdi Chiara , Bignotti Eliana
Published: July 2021

The onset of chemo-resistant recurrence represents the principal cause of high-grade serous ovarian carcinoma (HGSOC) death. HGSOC masses are characterized by a hypoxic microenvironment, which contributes to the development of this chemo-resistant phenotype. Hypoxia regulated-miRNAs (HRMs) represent a molecular response of cancer cells to hypoxia and are involved in tumor progression. We investigated the expression of HRMs using miRNA expression data from a total of 273 advanced-stage HGSOC samples. The miRNAs associated with chemoresistance and survival were validated by RT-qPCR and target prediction, and comparative pathway analysis was conducted for target gene identification. Analysis of miRNA expression profiles indicated miR-23a-3p and miR-181c-5p over-expression as associated with chemoresistance and poor PFS. RT-qPCR data confirmed upregulation of miR-23a-3p in tumors from chemoresistant HGSOC patients and its significant association with shorter PFS. In silico miR-23a-3p target prediction and comparative pathway analysis identified platinum drug resistance as the pathway with the highest number of miR-23a-3p target genes. Among them, APAF-1 emerged as the most promising, being downregulated in platinum-resistant patients and in HGSOC chemo-resistant cells. These results highlight miR-23a-3p as a potential biomarker for HGSOC platinum response and prognosis and the miR23a-3p/APAF1 axis as a possible target to overcome platinum-resistance.
Cancer-Associated Fibroblasts Modulate Transcriptional Signatures Involved in Proliferation, Differentiation and Metastasis in Head and Neck Squamous Cell Carcinoma
Authors: Wiechec Emilia , Magan Mustafa , Matic Natasa , Ansell-Schultz Anna , Kankainen Matti , Monni Outi , Johansson Ann-Charlotte , Roberg Karin
Published: July 2021

Cancer-associated fibroblasts (CAFs) are known to increase tumor growth and to stimulate invasion and metastasis. Increasing evidence suggests that CAFs mediate response to various treatments. HNSCC cell lines were co-cultured with their patient-matched CAFs in 2D and 3D in vitro models, and the tumor cell gene expression profiles were investigated by cDNA microarray and qRT-PCR. The mRNA expression of eight candidate genes was examined in tumor biopsies from 32 HNSCC patients and in five biopsies from normal oral tissue. Differences in overall survival (OS) were tested with Kaplan–Meier long-rank analysis. Thirteen protein coding genes were found to be differentially expressed in tumor cells co-cultured with CAFs in 2D and 81 in 3D when compared to tumor cells cultured without CAFs. Six of these genes were upregulated both in 2D and 3D (POSTN, GREM1, BGN, COL1A2, COL6A3, and COL1A1). Moreover, two genes upregulated in 3D, MMP9 and FMOD, were significantly associated with the OS. In conclusion, we demonstrated in vitro that CAF-derived signals alter the tumor cell expression of multiple genes, several of which are associated with differentiation, epithelial-to-mesenchymal transition (EMT) phenotype, and metastasis. Moreover, six of the most highly upregulated genes were found to be overexpressed in tumor tissue compared to normal tissue.
The Arabidopsis Root Tip (Phospho)Proteomes at Growth-Promoting versus Growth-Repressing Conditions Reveal Novel Root Growth Regulators
Authors: Nikonorova Natalia , Murphy Evan , Fonseca de Lima Cassio Flavio , Zhu Shanshuo , van de Cotte Brigitte , Vu Lam Dai , Balcerowicz Daria , Li Lanxin , Kong Xiangpei , De Rop Gieljan , Beeckman Tom , Friml Jiří , Vissenberg Kris , Morris Peter C. , Ding Zhaojun , De Smet Ive
Published: July 2021

Auxin plays a dual role in growth regulation and, depending on the tissue and concentration of the hormone, it can either promote or inhibit division and expansion processes in plants. Recent studies have revealed that, beyond transcriptional reprogramming, alternative auxin-controlled mechanisms regulate root growth. Here, we explored the impact of different concentrations of the synthetic auxin NAA that establish growth-promoting and -repressing conditions on the root tip proteome and phosphoproteome, generating a unique resource. From the phosphoproteome data, we pinpointed (novel) growth regulators, such as the RALF34-THE1 module. Our results, together with previously published studies, suggest that auxin, H+-ATPases, cell wall modifications and cell wall sensing receptor-like kinases are tightly embedded in a pathway regulating cell elongation. Furthermore, our study assigned a novel role to MKK2 as a regulator of primary root growth and a (potential) regulator of auxin biosynthesis and signalling, and suggests the importance of the MKK2 Thr31 phosphorylation site for growth regulation in the Arabidopsis root tip.
Extracellular Vesicles Derived from Endothelial Progenitor Cells Protect Human Glomerular Endothelial Cells and Podocytes from Complement- and Cytokine-Mediated Injury
Authors: Medica Davide , Franzin Rossana , Stasi Alessandra , Castellano Giuseppe , Migliori Massimiliano , Panichi Vincenzo , Figliolini Federico , Gesualdo Loreto , Camussi Giovanni , Cantaluppi Vincenzo
Published: July 2021

Glomerulonephritis are renal inflammatory processes characterized by increased permeability of the Glomerular Filtration Barrier (GFB) with consequent hematuria and proteinuria. Glomerular endothelial cells (GEC) and podocytes are part of the GFB and contribute to the maintenance of its structural and functional integrity through the release of paracrine mediators. Activation of the complement cascade and pro-inflammatory cytokines (CK) such as Tumor Necrosis Factor α (TNF-α) and Interleukin-6 (IL-6) can alter GFB function, causing acute glomerular injury and progression toward chronic kidney disease. Endothelial Progenitor Cells (EPC) are bone-marrow-derived hematopoietic stem cells circulating in peripheral blood and able to induce angiogenesis and to repair injured endothelium by releasing paracrine mediators including Extracellular Vesicles (EVs), microparticles involved in intercellular communication by transferring proteins, lipids, and genetic material (mRNA, microRNA, lncRNA) to target cells. We have previously demonstrated that EPC-derived EVs activate an angiogenic program in quiescent endothelial cells and renoprotection in different experimental models. The aim of the present study was to evaluate in vitro the protective effect of EPC-derived EVs on GECs and podocytes cultured in detrimental conditions with CKs (TNF-α/IL-6) and the complement protein C5a. EVs were internalized in both GECs and podocytes mainly through a L-selectin-based mechanism. In GECs, EVs enhanced the formation of capillary-like structures and cell migration by modulating gene expression and inducing the release of growth factors such as VEGF-A and HGF. In the presence of CKs, and C5a, EPC-derived EVs protected GECs from apoptosis by decreasing oxidative stress and prevented leukocyte adhesion by inhibiting the expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin). On podocytes, EVs inhibited apoptosis and prevented nephrin shedding induced by CKs and C5a. In a co-culture model of GECs/podocytes that mimicked GFB, EPC-derived EVs protected cell function and permeselectivity from inflammatory-mediated damage. Moreover, RNase pre-treatment of EVs abrogated their protective effects, suggesting the crucial role of RNA transfer from EVs to damaged glomerular cells. In conclusion, EPC-derived EVs preserved GFB integrity from complement- and cytokine-induced damage, suggesting their potential role as therapeutic agents for drug-resistant glomerulonephritis.
Role of Neutrophils in Cardiac Injury and Repair Following Myocardial Infarction
Authors: Ma Yonggang
Published: July 2021

Neutrophils are first-line responders of the innate immune system. Following myocardial infarction (MI), neutrophils are quickly recruited to the ischemic region, where they initiate the inflammatory response, aiming at cleaning up dead cell debris. However, excessive accumulation and/or delayed removal of neutrophils are deleterious. Neutrophils can promote myocardial injury by releasing reactive oxygen species, granular components, and pro-inflammatory mediators. More recent studies have revealed that neutrophils are able to form extracellular traps (NETs) and produce extracellular vesicles (EVs) to aggravate inflammation and cardiac injury. On the contrary, there is growing evidence showing that neutrophils also exert anti-inflammatory, pro-angiogenic, and pro-reparative effects, thus facilitating inflammation resolution and cardiac repair. In this review, we summarize the current knowledge on neutrophils’ detrimental roles, highlighting the role of recently recognized NETs and EVs, followed by a discussion of their beneficial effects and molecular mechanisms in post-MI cardiac remodeling. In addition, emerging concepts about neutrophil diversity and their modulation of adaptive immunity are discussed.
PFKFB3 Inhibition Impairs Erlotinib-Induced Autophagy in NSCLCs
Authors: Lypova Nadiia , Dougherty Susan M. , Lanceta Lilibeth , Chesney Jason , Imbert-Fernandez Yoannis
Published: July 2021

Tyrosine kinase inhibitors (TKIs) targeting the kinase domain of the epidermal growth factor receptor (EGFR), such as erlotinib, have dramatically improved clinical outcomes of patients with EGFR-driven non-small cell lung carcinomas (NSCLCs). However, intrinsic or acquired resistance remains a clinical barrier to the success of FDA-approved EGFR TKIs. Multiple mechanisms of resistance have been identified, including the activation of prosurvival autophagy. We have previously shown that the expression and activity of PFKFB3—a known driver of glycolysis—is associated with resistance to erlotinib and that PFKFB3 inhibition improves the response of NSCLC cells to erlotinib. This study focuses on investigating the role of PFKFB3 in regulating erlotinib-driven autophagy to escape resistance to erlotinib. We evaluated the consequence of pharmacological inhibition of PFKFB3 on erlotinib-driven autophagy in NSCLC cells with different mutation statuses. Here, we identify PFKFB3 as a mediator of erlotinib-induced autophagy in NSCLCs. We demonstrate that PFKFB3 inhibition sensitizes NCSLCs to erlotinib via impairing autophagy flux. In summary, our studies uncovered a novel crosstalk between PFKFB3 and EGFR that regulates erlotinib-induced autophagy, thus contributing to erlotinib sensitivity in NSCLCs.
Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?
Authors: Baiocchi Leonardo , Lenci Ilaria , Milana Martina , Kennedy Lindsey , Sato Keisaku , Zhang Wenjun , Ekser Burcin , Ceci Ludovica , Meadows Vik , Glaser Shannon , Alpini Gianfranco , Francis Heather
Published: July 2021

Cholangiocarcinoma is a lethal disease with scarce response to current systemic therapy. The rare occurrence and large heterogeneity of this cancer, together with poor knowledge of its molecular mechanisms, are elements contributing to the difficulties in finding an appropriate cure. Cholangiocytes (and their cellular precursors) are considered the liver component giving rise to cholangiocarcinoma. These cells respond to several hormones, neuropeptides and molecular stimuli employing the cAMP/PKA system for the translation of messages in the intracellular space. For instance, in physiological conditions, stimulation of the secretin receptor determines an increase of intracellular levels of cAMP, thus activating a series of molecular events, finally determining in bicarbonate-enriched choleresis. However, activation of the same receptor during cholangiocytes’ injury promotes cellular growth again, using cAMP as the second messenger. Since several scientific pieces of evidence link cAMP signaling system to cholangiocytes’ proliferation, the possible changes of this pathway during cancer growth also seem relevant. In this review, we summarize the current findings regarding the cAMP pathway and its role in biliary normal and neoplastic cell proliferation. Perspectives for targeting the cAMP machinery in cholangiocarcinoma therapy are also discussed.
The MicroRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts
Authors: Martens Geert A. , Stangé Geert , Piemonti Lorenzo , Anckaert Jasper , Ling Zhidong , Pipeleers Daniel G. , Gorus Frans K. , Mestdagh Pieter , De Smet Dieter , Vandesompele Jo , Keymeulen Bart , Roels Sarah
Published: July 2021

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. microRNA-375 (miR-375) ranks among the top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 h before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to the identification of eight microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome, and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.
Substituted Hydroxyapatite, Glass, and Glass-Ceramic Thin Films Deposited by Nanosecond Pulsed Laser Deposition (PLD) for Biomedical Applications: A Systematic Review
Authors: Teghil Roberto , Curcio Mariangela , De Bonis Angela
Published: July 2021

The deposition of thin films of bioactive materials is the most common approach to improve the bone bonding ability of an implant surface. With this purpose, several wet and plasma assisted deposition methods were proposed in the scientific literature. In this review, we considered films obtained by nanosecond Pulsed Laser Deposition (PLD). Since hydroxyapatite (HA) has composition and structure similar to that of the mineral component of the bone, the initial studies focused on the selection of experimental conditions that would allow the deposition of films that retain HA stoichiometry and crystallinity. However, biological apatite was found to be a poorly crystalline and multi-substituted mineral; consequently, the attention of researchers was oriented towards the deposition of substituted HA, glass (BG), and glass-ceramic (BGC) bioactive materials to exploit the biological relevance of foreign ions and crystallinity. In this work, after a description of the nanosecond ablation and film growth of ceramic materials, we reported studies on the mechanism of HA ablation and deposition, evidencing the peculiarities of PLD. The literature concerning the PLD of ion substituted HA, BG, and BGC was then reviewed and the performances of the coatings were discussed. We concluded by describing the advantages, limitations, and perspectives of PLD for biomedical applications.
Histological Patterns of Skin Lesions in Tuberous Sclerosis Complex: A Panorama
Authors: Cascarino Marine , Leclerc-Mercier Stéphanie
Published: July 2021

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disease characterized by cutaneous and extracutaneous hamartomas. The diagnosis is based on the association of major and minor criteria, defined by a consensus conference updated in 2012. The clinical examination of the skin is crucial because seven diagnostic criteria are dermatological: four major (hypomelanotic macules, angiofibroma or fibrous cephalic plaques, ungual fibromas, shagreen patches) and three minor criteria (confetti skin lesions, dental enamel pits, intraoral fibromas). Skin biopsy is commonly performed to assert the diagnosis of TSC when the clinical aspect is atypical. Histopathology of TSC cutaneous lesions have been poorly reported until now. In this article, we review the histologic features described in the literature and share our experience of TSC skin biopsies in our pediatric hospital specialized in genetic disorders. Both hypomelanotic lesions and cutaneous hamartomas (angiofibroma/fibrous cephalic plaques, ungual fibromas, shagreen patches) are discussed, including the recent entity called folliculocystic and collagen hamartoma, with a special emphasis on helpful clues for TSC in such lesions.
An Information-Theoretic Perspective on Proper Quaternion Variational Autoencoders
Authors: Grassucci Eleonora , Comminiello Danilo , Uncini Aurelio
Published: July 2021

Variational autoencoders are deep generative models that have recently received a great deal of attention due to their ability to model the latent distribution of any kind of input such as images and audio signals, among others. A novel variational autoncoder in the quaternion domain H, namely the QVAE, has been recently proposed, leveraging the augmented second order statics of H-proper signals. In this paper, we analyze the QVAE under an information-theoretic perspective, studying the ability of the H-proper model to approximate improper distributions as well as the built-in H-proper ones and the loss of entropy due to the improperness of the input signal. We conduct experiments on a substantial set of quaternion signals, for each of which the QVAE shows the ability of modelling the input distribution, while learning the improperness and increasing the entropy of the latent space. The proposed analysis will prove that proper QVAEs can be employed with a good approximation even when the quaternion input data are improper.
Uniform Magnetic Field Characteristics Based UHF RFID Tag for Internet of Things Applications
Authors: Sharif Abubakar , Yan Yi , Ouyang Jun , Chattha Hassan Tariq , Arshad Kamran , Assaleh Khaled , Alotabi Abdullah Alhumaidi , Althobaiti Turke , Ramzan Naeem , Abbasi Qammer Hussain , Imran Muhammad Ali
Published: July 2021

This paper presents a novel inkjet-printed near-field ultra-high-frequency (UHF) radio frequency identification (RFID) tag/sensor design with uniform magnetic field characteristics. The proposed tag is designed using the theory of characteristics mode (TCM). Moreover, the uniformity of current and magnetic field performance is achieved by further optimizing the design using particle swarm optimization (PSO). Compared to traditional electrically small near-field tags, this tag uses the logarithmic spiral as the radiating structure. The benefit of the logarithmic spiral structure lies in its magnetic field receiving area that can be extended to reach a higher reading distance. The combination of TCM and PSO is used to get the uniform magnetic field and desired resonant frequency. Moreover, the PSO was exploited to get a uniform magnetic field in the horizontal plane of the normal phase of the UHF RFID near-field reader antenna. As compared with the frequently-used commercial near field tag (Impinj J41), our design can be readable up to a three times greater read distance. Furthermore, the proposed near-field tag design shows great potential for commercial item-level tagging of expensive jewelry products and sensing applications, such as temperature monitoring of the human body.
Optical Fiber Sensor for PVC Sheet Piles Monitoring
Authors: Lakomski Mateusz , Tosik Grzegorz , Niedzielski Przemyslaw
Published: July 2021

This paper examined the impact of optical fiber sensor design, and its integration to PVC (polyvinyl chloride) sheet piles, on deflection and strain monitoring. Optical fiber sensors based on Brillouin light backscattering (BLS) were prepared, as they can provide accurate strain and deflection measurement results. However, depending on the application of sheet piles systems, high deformation of PVC elements can be observed. Therefore, a fiber sensor design is not trivial. Three types of optical fiber coatings and their integration with PVC sheet piles were investigated. The effect on the value of compressive and tensile strain were analyzed. It has been experimentally proven that PVC sheet piles monitoring, based on BLS method, can be realized using optical fibers with 250 µm, 900 µm, and 3 mm coating diameter. Achieved results are in line with theory. Correction coefficient necessary for 900 µm and 3 mm coatings has been proposed and used to ensure proper strain measurement. It was found that 250 µm coating fiber based sensors can be utilized for PVC strain measurement under low deflection (>1.2 m beam length). On the other hand, sensors based on 3 mm coating fiber, due to a high level of linearity, can be applied to deflection distance measurement under high deformation.
An Empirical Study of How Household Energy Consumption Is Affected by Co-Owning Different Technological Means to Produce Renewable Energy and the Production Purpose
Authors: Roth Lucas , Lowitzsch Jens , Yildiz Özgür
Published: July 2021

The transition from fossil fuel-based to renewable energy sources is one of the main economic and social challenges of the early 21st century. Due to the volatile character of wind and solar power production, matching supply and demand is essential for this transition to be successful. In this context, the willingness of private consumers to use energy flexibly has gained growing attention. Research indicates that a viable driver to motivate consumers to be demand flexible is to make them (co-)owners of renewable energy production facilities. However, existing research has only analyzed this question from an aggregated perspective. This article analyses whether behavioral changes triggered by (co-)ownership in renewables differ according to the type of installation; be it solar, wind, or bioenergy. In addition, the prosumption options self-consumption/self-consumption and sale/sale are considered. To do so, we collected 2074 completed questionnaires on energy consumption that entered an econometric model using propensity score matching to control for estimation biases. We find significant differences in the willingness to consume electricity in a flexible manner for (co-)owners of solar installations. However, only the usage of household appliances proves to be statistically significant (p-value = 0.04). Furthermore, the results show that within the group of (co-)owners of solar installation, the choice between self-consumption and sale of the produced energy has a significant effect on the inclination to become demand flexible (p-value ≤ 0.001; p-value = 0.003).
Modeling the Temperature Field in the Ground with an Installed Slinky-Coil Heat Exchanger
Authors: Gwadera Monika , Kupiec Krzysztof
Published: July 2021

In order to find the temperature field in the ground with a heat exchanger, it is necessary to determine temperature responses of the ground caused by heat sources and the influence of the environment. To determine the latter, a new model of heat transfer in the ground under natural conditions was developed. The heat flux of the evaporation of moisture from the ground was described by the relationship taking into account the annual amount of rainfall. The analytical solution for the equations of this model is presented. Under the conditions for which the calculations were performed, the following data were obtained: the average ground surface temperature Tsm = 10.67 °C, the ground surface temperature amplitude As = 13.88 K, and the phase angle Ps = 0.202 rad. This method makes it possible to easily determine the undisturbed ground temperature at any depth and at any time. This solution was used to find the temperature field in the ground with an installed slinky-coil heat exchanger that consisted of 63 coils. The results of calculations according to the presented model were compared with the results of measurements from the literature. The 3D model for the ground with an installed heat exchanger enables the analysis of the influence of miscellaneous parameters of the process of extracting or supplying heat from/to the ground on its temperature field.
Investigation of Broadband Printed Biconical Antenna with Tapered Balun for EMC Measurements
Authors: Abdulhameed Abdulghafor A. , Kubík Zdeněk
Published: July 2021

This article investigates the design, modeling, and fabrication of small-size (150 × 90 × 1.6 mm) broadband printed biconical antenna. The proposed antenna is intended for use a reference antenna for electromagnetic interference measurement inside the EMC chamber. The reflection coefficient (S11-parameter) is verified by modeling the equivalent circuit of the structure in terms of lumped elements. This structure offers a −10 dB impedance bandwidth (from 0.65 GHz to 2.3 GHz) with the tapered balun feeding method. Therefore, it has a high probability of estimating the electromagnetic waves emitted from several applications such as GSM, LTE, UMTS, 3G, Wi-fi, Bluetooth, ZigBee and more. The simulated standard antenna parameters are compatible with the measured parameters results. Furthermore, azimuth omnidirectional radiation pattern and well-realized gain (3.8 dBi) are achieved, reflecting good values of antenna factor compared to the commercial design.
Study on the Convective Heat Transfer and Fluid Flow of Mini-Channel with High Aspect Ratio of Neutron Production Target
Authors: Sun Peng , Lu Yiping , Tong Jianfei , Lu Youlian , Liang Tianjiao , Zhu Lingbo
Published: July 2021

In order to provide a theoretical basis for the thermal design of the neutron production target, flow and heat transfer characteristics are studied by using numerical simulations and experiments. A rectangular mini-channel experimental model consistent with the geometric shape of the heat dissipation structure of neutron production target was established, in which the aspect ratio and gap thickness of the test channel were 53.8:1 and 1.3 mm, respectively. The experimental results indicate that the critical Re of the mini-channel is between 3500 and 4000, and when Re reaches 21,000, Nu can reach 160. The simulation results are in good agreement with the experimental data, and the numerical simulation method can be used for the variable structure optimization design of the target in the later stage. The relationship between the flow pressure drop of the target mini-channel and the aspect ratio and Re is obtained by numerical simulation. The maximum deviation between the correlation and the experimental value is 6%.
MPC Based Energy Management System for Hosting Capacity of PVs and Customer Load with EV in Stand-Alone Microgrids
Authors: Ryu Kyung-Sang , Kim Dae-Jin , Ko Heesang , Boo Chang-Jin , Kim Jongrae , Jin Young-Gyu , Kim Ho-Chan
Published: July 2021

This paper presents the improvements of the hosting capacity of photovoltaics (PVs) and electric vehicles (EVs) in a stand-alone microgrid (MG) with an energy storage system (ESS) by consider-ing a model predictive control (MPC) based energy management system. The system is configured as an MG, including PVs, an ESS, a diesel generator (DG), and several loads with EVs. The DG is controlled to operate at rated power and the MPC algorithm is used in a stand-alone MG, which supplies the energy demanded for several loads with EVs. The hosting capacity of the load in-cluding the EV and PVs can be expanded through the ESS to the terminal node of the microgrid. In this case, the PVs and the load can be connected in excess of the capacity of the diesel genera-tor, and each bus in the feeder complies with the voltage range required by the grid. The effec-tiveness of the proposed algorithm to resolve the hosting capacity is demonstrated by numerical simulations.
Sex Differences in Renal Function: Participation of Gonadal Hormones and Prolactin
Authors: Franco-Acevedo Adriana , Echavarria Raquel , Melo Zesergio
Published: July 2021

Kidney pathophysiology is influenced by gender. Evidence suggests that kidney damage is more severe in males than in females and that sexual hormones contribute to this. Elevated prolactin concentration is common in renal impairment patients and is associated with an unfavorable prognosis. However, PRL is involved in the osmoregulatory process and promotes endothelial proliferation, dilatation, and permeability in blood vessels. Several proteinases cleavage its structure, forming vasoinhibins. These fragments have antagonistic PRL effects on endothelium and might be associated with renal endothelial dysfunction, but its role in the kidneys has not been enough investigated. Therefore, the purpose of this review is to describe the influence of sexual dimorphism and gonadal hormones on kidney damage, emphasizing the role of the hormone prolactin and its cleavage products, the vasoinhibins.