bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods
Authors: Ahmed Nuzhat , Kadife Elif , Raza Ali , Short Mary , Jubinsky Paul T. , Kannourakis George
Published: March 2020

Epithelial ovarian cancer (EOC) constitutes 90% of ovarian cancers (OC) and is the eighth most common cause of cancer-related death in women. The cancer histologically and genetically is very complex having a high degree of tumour heterogeneity. The pathogenic variability in OC causes significant impediments in effectively treating patients, resulting in a dismal prognosis. Disease progression is predominantly influenced by the peritoneal tumour microenvironment rather than properties of the tumor and is the major contributor to prognosis. Standard treatment of OC patients consists of debulking surgery, followed by chemotherapy, which in most cases end in recurrent chemoresistant disease. This review discusses the different origins of high-grade serous ovarian cancer (HGSOC), the major sub-type of EOC. Tumour heterogeneity, genetic/epigenetic changes, and cancer stem cells (CSC) in facilitating HGSOC progression and their contribution in the circumvention of therapy treatments are included. Several new treatment strategies are discussed including our preliminary proof of concept study describing the role of mitochondria-associated granulocyte macrophage colony-stimulating factor signaling protein (Magmas) in HGSOC and its unique potential role in chemotherapy-resistant disease.
An Overview on ERAP Roles in Infectious Diseases
Authors: Saulle Irma , Vicentini Chiara , Clerici Mario , Biasin Mara
Published: March 2020

Endoplasmic reticulum (ER) aminopeptidases ERAP1 and ERAP2 (ERAPs) are crucial enzymes shaping the major histocompatibility complex I (MHC I) immunopeptidome. In the ER, these enzymes cooperate in trimming the N-terminal residues from precursors peptides, so as to generate optimal-length antigens to fit into the MHC class I groove. Alteration or loss of ERAPs function significantly modify the repertoire of antigens presented by MHC I molecules, severely affecting the activation of both NK and CD8+ T cells. It is, therefore, conceivable that variations affecting the presentation of pathogen-derived antigens might result in an inadequate immune response and onset of disease. After the first evidence showing that ERAP1-deficient mice are not able to control Toxoplasma gondii infection, a number of studies have demonstrated that ERAPs are control factors for several infectious organisms. In this review we describe how susceptibility, development, and progression of some infectious diseases may be affected by different ERAPs variants, whose mechanism of action could be exploited for the setting of specific therapeutic approaches.
Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation
Authors: Balbi Carolina , Costa Ambra , Barile Lucio , Bollini Sveva
Published: March 2020

Ischaemic cardiac disease is associated with a loss of cardiomyocytes and an intrinsic lack of myocardial renewal. Recent work has shown that the heart retains limited cardiomyocyte proliferation, which remains inefficient when facing pathological conditions. While broadly active in the neonatal mammalian heart, this mechanism becomes quiescent soon after birth, suggesting loss of regenerative potential with maturation into adulthood. A key question is whether this temporary regenerative window can be enhanced via appropriate stimulation and further extended. Recently the search for novel therapeutic approaches for heart disease has centred on stem cell biology. The “paracrine effect” has been proposed as a promising strategy to boost endogenous reparative and regenerative mechanisms from within the cardiac tissue by exploiting the modulatory potential of soluble stem cell-secreted factors. As such, growing interest has been specifically addressed towards stem/progenitor cell-secreted extracellular vesicles (EVs), which can be easily isolated in vitro from cell-conditioned medium. This review will provide a comprehensive overview of the current paradigm on cardiac repair and regeneration, with a specific focus on the role and mechanism(s) of paracrine action of EVs from cardiac stromal progenitors as compared to exogenous stem cells in order to discuss the optimal choice for future therapy. In addition, the challenges to overcoming translational EV biology from bench to bedside for future cardiac regenerative medicine will be discussed.
Infectious Diseases and the Lymphoid Extracellular Matrix Remodeling: A Focus on Conduit System
Authors: Morgado Fernanda N. , da Silva Aurea Virgínia A. , Porrozzi Renato
Published: March 2020

The conduit system was described in lymphoid organs as a tubular and reticular set of structures compounded by collagen, laminin, perlecan, and heparin sulfate proteoglycan wrapped by reticular fibroblasts. This tubular system is capable of rapidly transport small molecules such as viruses, antigens, chemokines, cytokines, and immunoglobulins through lymphoid organs. This structure plays an important role in guiding the cells to their particular niches, therefore participating in cell cooperation, antigen presentation, and cellular activation. The remodeling of conduits has been described in chronic inflammation and infectious diseases to improve the transport of antigens to specific T and B cells in lymphoid tissue. However, malnutrition and infectious agents may induce extracellular matrix remodeling directly or indirectly, leading to the microarchitecture disorganization of secondary lymphoid organs and their conduit system. In this process, the fibers and cells that compound the conduit system may also be altered, which affects the development of a specific immune response. This review aims to discuss the extracellular matrix remodeling during infectious diseases with an emphasis on the alterations of molecules from the conduit system, which damages the cellular and molecular transit in secondary lymphoid organs compromising the immune response.
Enhanced Adipose Expression of Interferon Regulatory Factor (IRF)-5 Associates with the Signatures of Metabolic Inflammation in Diabetic Obese Patients
Authors: Sindhu Sardar , Kochumon Shihab , Thomas Reeby , Bennakhi Abdullah , Al-Mulla Fahd , Ahmad Rasheed
Published: March 2020

Interferon regulatory factors (IRFs) are emerging as the metabolic transcriptional regulators in obesity/type-2 diabetes (T2D). IRF5 is implicated with macrophage polarization toward the inflammatory M1-phenotype, nonetheless, changes in the adipose expression of IRF5 in T2D and relationship of these changes with other markers of adipose inflammation remain unclear. Therefore, we determined the IRF5 gene expression in subcutaneous adipose tissue samples from 46 T2D patients including 35 obese (Body Mass Index/BMI 33.83 ± 0.42 kg/m2) and 11 lean/overweight individuals (BMI 27.55 ± 0.46 kg/m2) using real-time qRT-PCR. IRF5 protein expression was assessed using immunohistochemistry and confocal microscopy. Fasting plasma glucose, insulin, HbA1c, C-reactive protein, cholesterol, low- and high-density lipoproteins (LDL/HDL), and triglycerides were measured using commercial kits. IRF5 gene expression was compared with that of signature inflammatory markers and several clinico-metabolic indicators. The data (mean ± SEM) show the enhanced adipose IRF5 gene (p = 0.03) and protein (p = 0.05) expression in obese compared to lean/overweight diabetic patients. Adipose IRF5 transcripts in diabetic obese individuals associated positively with those of TNF-α, IL-18, IL-23A, CXCL8, CCL2, CCL7, CCR1/5, CD11c, CD68, CD86, TLR4/7/10, Dectin-1, FGL-2, MyD88, NF-κB, IRF3, and AML1 (p < 0.05). In diabetic lean/overweight subjects, IRF5 expression associated with BMI, body fat %age, glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR, C-reactive protein (CRP), IL-5, and IL-1RL1 expression; while in all T2D patients, IRF5 expression correlated with that of IRF4, TLR2/8, and CD163. In conclusion, upregulated adipose tissue IRF5 expression in diabetic obese patients concurs with the inflammatory signatures and it may represent a potential marker for metabolic inflammation in obesity/T2D.
Impact of Chronic Fetal Hypoxia and Inflammation on Cardiac Pacemaker Cell Development
Authors: Frasch Martin G. , Giussani Dino A.
Published: March 2020

Chronic fetal hypoxia and infection are examples of adverse conditions during complicated pregnancy, which impact cardiac myogenesis and increase the lifetime risk of heart disease. However, the effects that chronic hypoxic or inflammatory environments exert on cardiac pacemaker cells are poorly understood. Here, we review the current evidence and novel avenues of bench-to-bed research in this field of perinatal cardiogenesis as well as its translational significance for early detection of future risk for cardiovascular disease.
Revisiting the Interaction of γδ T-Cells and B-Cells
Authors: Rampoldi Francesca , Ullrich Leon , Prinz Immo
Published: March 2020

Right after the discovery of γδ T-cells in 1984, people started asking how γδ T-cells interact with other immune cells such as B-cells. Early reports showed that γδ T-cells are able to help B-cells to produce antibodies and to sustain the production of germinal centers. Interestingly, the presence of γδ T-cells seems to promote the generation of antibodies against “self” and less against challenging pathogens. More recently, these hypotheses were supported using γδ T-cell-deficient mouse strains, in different mouse models of systemic lupus erythematous, and after induction of epithelial cell damage. Together, these studies suggest that the link between γδ T-cells and the production of autoantibodies may be more relevant for the development of autoimmune diseases than generally acknowledged and thus targeting γδ T-cells could represent a new therapeutic strategy. In this review, we focus on what is known about the communication between γδ T-cells and B-cells, and we discuss the importance of this interaction in the context of autoimmunity.
Centrioles and Ciliary Structures during Male Gametogenesis in Hexapoda: Discovery of New Models
Authors: Riparbelli Maria Giovanna , Persico Veronica , Dallai Romano , Callaini Giuliano
Published: March 2020

Centrioles are-widely conserved barrel-shaped organelles present in most organisms. They are indirectly involved in the organization of the cytoplasmic microtubules both in interphase and during the cell division by recruiting the molecules needed for microtubule nucleation. Moreover, the centrioles are required to assemble cilia and flagella by the direct elongation of their microtubule wall. Due to the importance of the cytoplasmic microtubules in several aspects of the cell life, any defect in centriole structure can lead to cell abnormalities that in humans may result in significant diseases. Many aspects of the centriole dynamics and function have been clarified in the last years, but little attention has been paid to the exceptions in centriole structure that occasionally appeared within the animal kingdom. Here, we focused our attention on non-canonical aspects of centriole architecture within the Hexapoda. The Hexapoda is one of the major animal groups and represents a good laboratory in which to examine the evolution and the organization of the centrioles. Although these findings represent obvious exceptions to the established rules of centriole organization, they may contribute to advance our understanding of the formation and the function of these organelles.
Spermatogonial Stem Cells for In Vitro Spermatogenesis and In Vivo Restoration of Fertility
Authors: Ibtisham Fahar , Honaramooz Ali
Published: March 2020

Spermatogonial stem cells (SSCs) are the only adult stem cells capable of passing genes onto the next generation. SSCs also have the potential to provide important knowledge about stem cells in general and to offer critical in vitro and in vivo applications in assisted reproductive technologies. After century-long research, proof-of-principle culture systems have been introduced to support the in vitro differentiation of SSCs from rodent models into haploid male germ cells. Despite recent progress in organotypic testicular tissue culture and two-dimensional or three-dimensional cell culture systems, to achieve complete in vitro spermatogenesis (IVS) using non-rodent species remains challenging. Successful in vitro production of human haploid male germ cells will foster hopes of preserving the fertility potential of prepubertal cancer patients who frequently face infertility due to the gonadotoxic side-effects of cancer treatment. Moreover, the development of optimal systems for IVS would allow designing experiments that are otherwise difficult or impossible to be performed directly in vivo, such as genetic manipulation of germ cells or correction of genetic disorders. This review outlines the recent progress in the use of SSCs for IVS and potential in vivo applications for the restoration of fertility.
Elevated PDK1 Expression Drives PI3K/AKT/MTOR Signaling Promotes Radiation-Resistant and Dedifferentiated Phenotype of Hepatocellular Carcinoma
Authors: Bamodu Oluwaseun Adebayo , Chang Hang-Lung , Ong Jiann-Ruey , Lee Wei-Hwa , Yeh Chi-Tai , Tsai Jo-Ting
Published: March 2020

Resistance to radiotherapy (IR), with consequent disease recurrence, continues to limit the efficacy of contemporary anticancer treatment for patients with hepatocellular carcinoma (HCC), especially in late stage. Despite accruing evidence implicating the PI3K/AKT signaling pathway in cancer-promoting hypoxia, cancerous cell proliferation and radiotherapy-resistance, it remains unclear which molecular constituent of the pathway facilitates adaptation of aggressive HCC cells to tumoral stress signals and drives their evasion of repeated IR-toxicity. This present study investigated the role of PDK1 signaling in IR-resistance, enhanced DNA damage repair and post-IR relapse, characteristic of aggressive HCC cells, while exploring potential PDK1-targetability to improve radiosensitivity. The study employed bioinformatics analyses of gene expression profile and functional protein–protein interaction, generation of IR-resistant clones, flow cytometry-based ALDH activity and side-population (SP) characterization, siRNA-mediated loss-of-PDK1function, western-blotting, immunohistochemistry and functional assays including cell viability, migration, invasion, clonogenicity and tumorsphere formation assays. We showed that the aberrantly expressed PDK1 characterizes poorly differentiated HCC CVCL_7955, Mahlavu, SK-HEP1 and Hep3B cells, compared to the well-differentiated Huh7 or normal adult liver epithelial THLE-2 cells, and independently activates the PI3K/AKT/mTOR signaling. Molecular ablation of PDK1 function enhanced susceptibility of HCC cells to IR and was associated with deactivated PI3K/AKT/mTOR signaling. Additionally, PDK1-driven IR-resistance positively correlated with activated PI3K signaling, enhanced HCC cell motility and invasiveness, augmented EMT, upregulated stemness markers ALDH1A1, PROM1, SOX2, KLF4 and POU5F1, increased tumorsphere-formation efficiency and suppressed biomarkers of DNA damage—RAD50, MSH3, MLH3 and ERCC2. Furthermore, the acquired IR-resistant phenotype of Huh7 cells was strongly associated with significantly increased ALDH activity, SP-enrichment, and direct ALDH1-PDK1 interaction. Moreover, BX795-mediated pharmacological inhibition of PDK1 synergistically enhances the radiosensitivity of erstwhile resistant cells, increased Bax/Bcl-2 apoptotic ratio, while suppressing oncogenicity and clonogenicity. We provide preclinical evidence implicating PDK1 as an active driver of IR-resistance by activation of the PI3K/AKT/mTOR signaling, up-modulation of cancer stemness signaling and suppression of DNA damage, thus, projecting PDK1-targeting as a putative enhancer of radiosensitivity and a potential new therapeutic approach for patients with IR-resistant HCC.
The S100B Inhibitor Pentamidine Ameliorates Clinical Score and Neuropathology of Relapsing—Remitting Multiple Sclerosis Mouse Model
Authors: Di Sante Gabriele , Amadio Susanna , Sampaolese Beatrice , Clementi Maria Elisabetta , Valentini Mariagrazia , Volonté Cinzia , Casalbore Patrizia , Ria Francesco , Michetti Fabrizio
Published: March 2020

S100B is an astrocytic protein acting either as an intracellular regulator or an extracellular signaling molecule. A direct correlation between increased amount of S100B and demyelination and inflammatory processes has been demonstrated. The aim of this study is to investigate the possible role of a small molecule able to bind and inhibit S100B, pentamidine, in the modulation of disease progression in the relapsing–remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the central nervous system, we observed that pentamidine is able to delay the acute phase of the disease and to inhibit remission, resulting in an amelioration of clinical score when compared with untreated relapsing–remitting experimental autoimmune encephalomyelitis mice. Moreover, we observed a significant reduction of proinflammatory cytokines expression levels in the brains of treated versus untreated mice, in addition to a reduction of nitric oxide synthase activity. Immunohistochemistry confirmed that the inhibition of S100B was able to modify the neuropathology of the disease, reducing immune infiltrates and partially protecting the brain from the damage. Overall, our results indicate that pentamidine targeting the S100B protein is a novel potential drug to be considered for multiple sclerosis treatment.
The Solo Play of TERT Promoter Mutations
Authors: Hafezi François , Perez Bercoff Danielle
Published: March 2020

The reactivation of telomerase reverse transcriptase (TERT) protein is the principal mechanism of telomere maintenance in cancer cells. Mutations in the TERT promoter (TERTp) are a common mechanism of TERT reactivation in many solid cancers, particularly those originating from slow-replicating tissues. They are associated with increased TERT levels, telomere stabilization, and cell immortalization and proliferation. Much effort has been invested in recent years in characterizing their prevalence in different cancers and their potential as biomarkers for tumor stratification, as well as assessing their molecular mechanism of action, but much remains to be understood. Notably, they appear late in cell transformation and are mutually exclusive with each other as well as with other telomere maintenance mechanisms, indicative of overlapping selective advantages and of a strict regulation of TERT expression levels. In this review, we summarized the latest literature on the role and prevalence of TERTp mutations across different cancer types, highlighting their biased distribution. We then discussed the need to maintain TERT levels at sufficient levels to immortalize cells and promote proliferation while remaining within cell sustainability levels. A better understanding of TERT regulation is crucial when considering its use as a possible target in antitumor strategies.
A Signaling Crosstalk between BMP9 and HGF/c-Met Regulates Mouse Adult Liver Progenitor Cell Survival
Authors: Addante Annalisa , Roncero Cesáreo , Lazcanoiturburu Nerea , Méndez Rebeca , Almalé Laura , García-Álvaro María , ten Dijke Peter , Fabregat Isabel , Herrera Blanca , Sánchez Aránzazu
Published: March 2020

During chronic liver disease, hepatic progenitor cells (HPC, oval cells in rodents) become activated, proliferate, and differentiate into cholangiocytes and/or hepatocytes contributing to the final outcome of the regenerative process in a context-dependent fashion. Here, we analyze the crosstalk between the hepatocyte growth factor (HGF)/c-Met signaling axis, key for liver regeneration, and bone morphogenetic protein (BMP)9, a BMP family ligand that has emerged as a critical regulator of liver pathology. Our results show that HGF/c-Met signaling blocks BMP9-mediated apoptotic cell death, while it potentiates small mothers against decapentaplegic (SMAD)1 signaling triggered by BMP9 in oval cells. Interestingly, HGF-induced overactivation of SMAD1, -5, -8 requires the upregulation of TGF-β type receptor activin receptor-like kinase (ALK)1, and both ALK1 and SMAD1 are required for the counteracting effect of HGF on BMP9 apoptotic activity. On the other hand, we also prove that BMP9 triggers the activation of p38MAPK in oval cells, which drives BMP9-apoptotic cell death. Therefore, our data support a model in which BMP9 and HGF/c-Met signaling axes establish a signaling crosstalk via ALK1 that modulates the balance between the two pathways with opposing activities, SMAD1 (pro-survival) and p38 mitogen-activated protein kinases (p38MAPK; pro-apoptotic), which determines oval cell fate. These data help delineate the complex signaling network established during chronic liver injury and its impact on the oval cell regenerative response.
Phenotyping of Rare CFTR Mutations Reveals Distinct Trafficking and Functional Defects
Authors: Ensinck Marjolein , De Keersmaecker Liesbeth , Heylen Lise , Ramalho Anabela S. , Gijsbers Rik , Farré Ricard , De Boeck Kris , Christ Frauke , Debyser Zeger , Carlon Marianne S.
Published: March 2020

Background. The most common CFTR mutation, F508del, presents with multiple cellular defects. However, the possible multiple defects caused by many rarer CFTR mutations are not well studied. We investigated four rare CFTR mutations E60K, G85E, E92K and A455E against well-characterized mutations, F508del and G551D, and their responses to corrector VX-809 and/or potentiator VX-770. Methods. Using complementary assays in HEK293T stable cell lines, we determined maturation by Western blotting, trafficking by flow cytometry using extracellular 3HA-tagged CFTR, and function by halide-sensitive YFP quenching. In the forskolin-induced swelling assay in intestinal organoids, we validated the effect of tagged versus endogenous CFTR. Results. Treatment with VX-809 significantly restored maturation, PM localization and function of both E60K and E92K. Mechanistically, VX-809 not only raised the total amount of CFTR, but significantly increased the traffic efficiency, which was not the case for A455E. G85E was refractory to VX-809 and VX-770 treatment. Conclusions. Since no single model or assay allows deciphering all defects at once, we propose a combination of phenotypic assays to collect rapid and early insights into the multiple defects of CFTR variants.
Cytotoxicity and Mineralization Potential of Four Calcium Silicate-Based Cements on Human Gingiva-Derived Stem Cells
Authors: Lee Donghee , Park Jun-Beom , Song Dani , Kim Hye-Min , Kim Sin-Young
Published: March 2020

The aim of this study was to evaluate the cytotoxicity and mineralization potential of four calcium silicate-based cements on human gingiva-derived stem cells (GDSCs). The materials evaluated in the present study were ProRoot MTA (Dentsply Tulsa Dental Specialties), Biodentine (Septodont), Endocem Zr (Maruchi), and RetroMTA (BioMTA). Experimental disks of 6 mm in diameter and 3 mm in height were produced and placed in a 100% humidified atmosphere for 48 h to set. We evaluated the cytotoxic effects of the cements using methyl-thiazoldiphenyl-tetrazolium (MTT) and live/dead staining assays. We used a scratch wound healing assay to evaluate cell migratory ability. Mineralization potential was determined with an Alizarin red S (ARS) staining assay. In the MTT assay, no significant differences were found among the ProRoot MTA, Biodentine, and control groups during the test period (p > 0.05). The Endocem Zr and RetroMTA groups showed relatively lower cell viability than the control group at day 7 (p < 0.05). In the wound healing assay, no significant differences were found among the ProRoot MTA, Biodentine, Endocem Zr, and control groups during the test period (p > 0.05). The RetroMTA group had slower cell migration compared to the control group at days 3 and 4 (p < 0.05). In the ARS assay, the ProRoot MTA, Biodentine, and RetroMTA groups exhibited a significant increase in the formation of mineralized nodules compared to the Endocem Zr and control groups on day 21 (p < 0.05). In conclusion, the four calcium silicate-based cements evaluated in the present study exhibited good biological properties on GDSCs. ProRoot MTA, Biodentine, and RetroMTA showed higher mineralization potential than the Endocem Zr and control groups.
Novel Synthesis of Core-Shell Biomaterials from Polymeric Filaments with a Bioceramic Coating for Biomedical Applications
Authors: Dascalu Catalina-Andreea , Miculescu Florin , Mocanu Aura-Catalina , Constantinescu Andreea Elena , Butte Tudor Mihai , Pandele Andreea Madalina , Ciocoiu Robert-Catalin , Voicu Stefan Ioan , Ciocan Lucian Toma
Published: March 2020

Bone tissue engineering is constantly in need of new material development with improved biocompatibility or mechanical features closer to those of natural bone. Other important factors are the sustainability, cost, and origin of the natural precursors involved in the technological process. This study focused on two widely used polymers in tissue engineering, namely polylactic acid (PLA) and thermoplastic polyurethane (TPU), as well as bovine-bone-derived hydroxyapatite (HA) for the manufacturing of core-shell structures. In order to embed the ceramic particles on the polymeric filaments surface, the materials were introduced in an electrical oven at various temperatures and exposure times and under various pressing forces. The obtained core-shell structures were characterized in terms of morphology and composition, and a pull-out test was used to demonstrate the particles adhesion on the polymeric filaments structure. Thermal properties (modulated temperature and exposure time) and the pressing force’s influence upon HA particles’ insertion degree were evaluated. More to the point, the form variation factor and the mass variation led to the optimal technological parameters for the synthesis of core-shell materials for prospect additive manufacturing and regenerative medicine applications.
Mechanisms-Based Transitional Viscoplasticity
Authors: Zubelewicz Aleksander
Published: March 2020

When metal is subjected to extreme strain rates, the conversation of energy to plastic power, the subsequent heat production and the growth of damages may lag behind the rate of loading. The imbalance alters deformation pathways and activates micro-dynamic excitations. The excitations immobilize dislocation, are responsible for the stress upturn and magnify plasticity-induced heating. The main conclusion of this study is that dynamic strengthening, plasticity-induced heating, grain size strengthening and the processes of microstructural relaxation are inseparable phenomena. Here, the phenomena are discussed in semi-independent sections, and then, are assembled into a unified constitutive model. The model is first tested under simple loading conditions and, later, is validated in a numerical analysis of the plate impact problem, where a copper flyer strikes a copper target with a velocity of 308 m/s. It should be stated that the simulations are performed with the use of the deformable discrete element method, which is designed for monitoring translations and rotations of deformable particles.
Mixed Oscillation Flow of Binary Fluid with Minus One Capillary Ratio in the Czochralski Crystal Growth Model
Authors: Wu Chunmei , Chen Jinhui , Li Yourong
Published: March 2020

This work presented a series of three-dimensional unsteady numerical simulations on the characteristics of the mixed oscillation flows of binary mixture in a Czochralski crystal growth model. The silicon-germanium melt is investigated and the capillary ratio is minus one. The simulation results showed that, for the special capillary ratio, the thermal and solutocapillary forces are imposed in opposite directions and counteract each other. With the effect of buoyancy, the balance between the capillary forces is disturbed. Mixed with the forced convection driven by rotation, the capillary-buoyancy convection is complex. The basic mixed flow streamlines are presented as various rolling cells. The directions of the rolls are dependent on the combinations of surface and body forces. With the increase of temperature gradient, the basic flow stability is broken, and the oscillations occur. The crucible rotation has an effective influence on the stability enhancement. However, affected by the crystal rotation, the critical condition experiences an increase to a turning point, and then undergoes a sharp reduction to zero. Once the instability is incubated, the surface oscillations are analyzed. For the three-dimensional steady flow, only spatial oscillations are observed circumferentially, and the surface patterns of spokes, rosebud, and pulsating ring are obtained. For the unsteady oscillation flow, the spiral hydrosoultal waves, rotating waves, and superimposition of spirals and spokes are observed, and the oscillation behaviors are also discussed.
Controlled Synthesis of Magnetic Iron Oxide Nanoparticles: Magnetite or Maghemite?
Authors: Schwaminger Sebastian , Syhr Christopher , Berensmeier Sonja
Published: March 2020

Today, magnetic nanoparticles are present in multiple medical and industrial applications. We take a closer look at the synthesis of magnetic iron oxide nanoparticles through the co-precipitation of iron salts in an alkaline environment. The variation of the synthesis parameters (ion concentration, temperature, stirring rate, reaction time and dosing rate) change the structure and diameter of the nanoparticles. Magnetic iron oxide nanoparticles are characterized by X-ray diffraction (XRD), Raman spectroscopy and transmission electron microscopy (TEM). Magnetic nanoparticles ranging from 5 to 16 nm in diameter were synthesized and their chemical structure was identified. Due to the evaluation of Raman spectra, TEM and XRD, the magnetite and maghemite nanoparticles can be observed and the proportion of phases and the particle size can be related to the synthesis conditions. We want to highlight the use of Raman active modes A1g of spinel structured iron oxides to determine the content of magnetite and maghemite in our samples. Magnetite nanoparticles can be derived from highly alkaline conditions even without establishing an inert atmosphere during the synthesis. The correlation between the particle properties and the various parameters of the synthesis was modelled with linear mixture models. The two models can predict the particle size and the oxidation state of the synthesized nanoparticles, respectively. The modeling of synthesis parameters not only helps to improve synthesis conditions for iron oxide nanoparticles but to understand crystallization of nanomaterials.
Point-of-Care RNA-Based Diagnostic Device for COVID-19
Authors: Yang Ting , Wang Yung-Chih , Shen Ching-Fen , Cheng Chao-Min
Published: March 2020

At the end of 2019, the novel coronavirus disease (COVID-19), a fast-spreading respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported in Wuhan, China and has now affected over 123 countries globally [...]
Radiative MHD Nanofluid Flow over a Moving Thin Needle with Entropy Generation in a Porous Medium with Dust Particles and Hall Current
Authors: Tlili Iskander , Ramzan Muhammad , Kadry Seifedine , Kim Hyun-Woo , Nam Yunyoung
Published: March 2020

This paper investigated the behavior of the two-dimensional magnetohydrodynamics (MHD) nanofluid flow of water-based suspended carbon nanotubes (CNTs) with entropy generation and nonlinear thermal radiation in a Darcy–Forchheimer porous medium over a moving horizontal thin needle. The study also incorporated the effects of Hall current, magnetohydrodynamics, and viscous dissipation on dust particles. The said flow model was described using high order partial differential equations. An appropriate set of transformations was used to reduce the order of these equations. The reduced system was then solved by using a MATLAB tool bvp4c. The results obtained were compared with the existing literature, and excellent harmony was achieved in this regard. The results were presented using graphs and tables with coherent discussion. It was comprehended that Hall current parameter intensified the velocity profiles for both CNTs. Furthermore, it was perceived that the Bejan number boosted for higher values of Darcy–Forchheimer number.
Semantic Segmentation Framework for Glomeruli Detection and Classification in Kidney Histological Sections
Authors: Altini Nicola , Cascarano Giacomo Donato , Brunetti Antonio , Marino Francescomaria , Rocchetti Maria Teresa , Matino Silvia , Venere Umberto , Rossini Michele , Pesce Francesco , Gesualdo Loreto , Bevilacqua Vitoantonio
Published: March 2020

The evaluation of kidney biopsies performed by expert pathologists is a crucial process for assessing if a kidney is eligible for transplantation. In this evaluation process, an important step consists of the quantification of global glomerulosclerosis, which is the ratio between sclerotic glomeruli and the overall number of glomeruli. Since there is a shortage of organs available for transplantation, a quick and accurate assessment of global glomerulosclerosis is essential for retaining the largest number of eligible kidneys. In the present paper, the authors introduce a Computer-Aided Diagnosis (CAD) system to assess global glomerulosclerosis. The proposed tool is based on Convolutional Neural Networks (CNNs). In particular, the authors considered approaches based on Semantic Segmentation networks, such as SegNet and DeepLab v3+. The dataset has been provided by the Department of Emergency and Organ Transplantations (DETO) of Bari University Hospital, and it is composed of 26 kidney biopsies coming from 19 donors. The dataset contains 2344 non-sclerotic glomeruli and 428 sclerotic glomeruli. The proposed model consents to achieve promising results in the task of automatically detecting and classifying glomeruli, thus easing the burden of pathologists. We get high performance both at pixel-level, achieving mean F-score higher than 0.81, and Weighted Intersection over Union (IoU) higher than 0.97 for both SegNet and Deeplab v3+ approaches, and at object detection level, achieving 0.924 as best F-score for non-sclerotic glomeruli and 0.730 as best F-score for sclerotic glomeruli.
Boiling Synchronization in Two Parallel Minichannels—Image Analysis
Authors: Rafałko Gabriela , Zaborowska Iwona , Grzybowski Hubert , Mosdorf Romuald
Published: March 2020

In this paper, the boiling synchronization of two-phase flow patterns in two parallel minichannels of 1 mm in diameter with connected compressible volumes was analyzed. The analysis was performed using images recorded with a high-speed camera. The degree of synchronization between channels was evaluated by assessing the presence of liquid flow in the small part of the minichannels. It can be concluded that boiling is synchronized when small bubble flow or wavy annular flow occur in neighboring channels. The occurrence of slug flow in one channel causes the boiling in neighboring channels to become unsynchronized. The result of the image analysis shows that the correlation coefficient based on the evaluation of the presence of liquid flow in the small part of the minichannels over a long enough time period allows for the detection of boiling synchronization.
Urban Electric Vehicle Fast-Charging Demand Forecasting Model Based on Data-Driven Approach and Human Decision-Making Behavior
Authors: Xing Qiang , Chen Zhong , Zhang Ziqi , Xu Xiao , Zhang Tian , Huang Xueliang , Wang Haiwei
Published: March 2020

Electric vehicles (EVs) have attracted growing attention in recent years. However, most existing research has not utilized actual traffic data and has not considered real psychological decision-making of owners in analyzing the charging demand. On this basis, an urban EV fast-charging demand forecasting model based on a data-driven approach and human decision-making behavior is presented in this paper. In this methodology, Didi ride-hailing order trajectory data are firstly taken as the original dataset. Through data mining and fusion technology, the regenerated data and rules of traffic operation are obtained. Then, the single EV model with driving and charging behavior parameters is established. Furthermore, a human behavior decision-making model based on Regret Theory is introduced, which comprises the utility of time consumption and charging cost to plan driving paths and recommend fast-charging stations for vehicles. The rules obtained from data mining together with established models are combined to construct the ‘Electric Vehicles–Power Grid–Traffic Network’ fusion architecture. At last, the actual urban traffic network in Nanjing is selected as an example to design the fast-charging demand load experiments in different scenarios. The results demonstrate that this proposed model is able to effectively predict the spatio-temporal distribution characteristics of urban fast-charging demands, and it more realistically simulates the decision-making psychology of owners’ charging behavior.
Thermal Comfort Analysis of Combined Radiation-Convection Floor Heating System
Authors: Park Beungyong , Ryu Seong Ryong , Cheong Chang Heon
Published: March 2020

In this paper, a novel combined radiation-convection floor heating system is shown. This study uses practice-based learning and investigated the thermal performance of a combined radiation-convection floor heating system with a water heat pump system by evaluating the thermal environment and energy consumption in an experimental test. A new method that analyzed the thermal performance of four different controls was developed and applied. The results of the surface temperature distributions demonstrated that Mode 1, which uses only convection, had the lowest floor temperature and was thus considered inappropriate for occupants who sleep on the floor. By contrast, Modes 2, 3, and 4 showed high floor surface temperatures as hot water was supplied to the radiant heating panel. The predicted mean vote (PMV) results suggest that radiant floor heating is not appropriate for intermittent heating. In other words, occupants of single residences who return home at night will experience a long period of discomfort if they heat their room using floor heating. In this case, Mode 1, which is convection heating, and Modes 3 and 4, which represent mixed modes provide a more comfortable environment. The difference between this experimental study and previous research is that four different control modes for a combined radiation-convection system were evaluated based on the same location of the equipment in a laboratory. Furthermore, we studied the long-term real-scale thermal performance using panel and energy consumption.
Distortion Load Identification Based on the Application of Compensating Devices
Authors: Shklyarskiy Yaroslav , Skamyin Aleksandr , Vladimirov Iaroslav , Gazizov Farit
Published: March 2020

The article provides an analysis of the existing methods of identifying the consumer’s contribution to voltage distortion at a point of common coupling. The considered methods do not allow correctly and fairly determining the source of harmonic distortions, or they have limited application and difficulties in implementation. The paper proposes new methods for determining the source of high harmonics. The developed methods and techniques are based on the analysis of the grid operation modes with two connected consumers using compensating devices, such as reactive power compensation devices and passive harmonic filters. It is shown that the most promising method is the application of harmonic filters, which allows determining the share of the consumer’s contribution to the voltage distortion. The present research is carried out using a computer simulation of the existing electrical grid, to which consumers with nonlinear electric load are connected. These methods can be implemented to assess the power quality and the shareholding of different consumers connected at the point of common coupling. Furthermore, such methods appear to be feasible, as almost every enterprise currently has such facilities in operation.
Response of Vegetation to Changes in Temperature and Precipitation at a Semi-Arid Area of Northern China Based on Multi-Statistical Methods
Authors: Wu Yifan , Zhang Xuan , Fu Yongshuo , Hao Fanghua , Yin Guodong
Published: March 2020

Hydrothermal and climatic conditions determine vegetation productivity and its dynamic changes. However, the legacy effect and the causal relationships between these climatic variables and vegetation growth are still unclear, especially in the dry regions. Based on multi-statistical methods, including bivariate correlation analysis and composite Granger causality tests, we investigated the correlation, causality, and lag length between temperature/precipitation and the vegetation growth (Normalized Difference Vegetation Index, NDVI) in three typical sub-watersheds in the Luanhe River Basin, China. The results show that: (1) Precipitation and temperature are the Granger causes of NDVI variation in the study catchment; (2) temperature and precipitation are not strictly positively correlated with NDVI during growing seasons along with the whole sequence, and excessive warmth and precipitation inhibits vegetative growth; (3) the lag length of vegetation growth in response to temperature/precipitation was shorter in agriculture areas (~2 months) than the forest-dominant area, which have indicated 3–4 months lag length; and (4) anthropogenic disturbance did not result in notable negative effects on vegetation growth at the Luanhe River Basin. Our study further suggests that use of these multi-statistical methods could be a valuable approach for comprehensively understanding the correlation between vegetation growth and climatic variations. We have also provided an avenue to bridge the gaps between stationary and non-stationary sequence, as well as to eliminate pseudo regression problems. These findings provide critical information for developing cost-efficient policies and land use management applications for forest conservation in arid and semi-arid area.
The Xylose Metabolizing Yeast Spathaspora passalidarum is a Promising Genetic Treasure for Improving Bioethanol Production
Authors: Selim Khaled A. , Easa Saadia M. , El-Diwany Ahmed I.
Published: March 2020

Currently, the fermentation technology for recycling agriculture waste for generation of alternative renewable biofuels is getting more and more attention because of the environmental merits of biofuels for decreasing the rapid rise of greenhouse gas effects compared to petrochemical, keeping in mind the increase of petrol cost and the exhaustion of limited petroleum resources. One of widely used biofuels is bioethanol, and the use of yeasts for commercial fermentation of cellulosic and hemicellulosic agricultural biomasses is one of the growing biotechnological trends for bioethanol production. Effective fermentation and assimilation of xylose, the major pentose sugar element of plant cell walls and the second most abundant carbohydrate, is a bottleneck step towards a robust biofuel production from agricultural waste materials. Hence, several attempts were implemented to engineer the conventional Saccharomyces cerevisiae yeast to transport and ferment xylose because naturally it does not use xylose, using genetic materials of Pichia stipitis, the pioneer native xylose fermenting yeast. Recently, the nonconventional yeast Spathaspora passalidarum appeared as a founder member of a new small group of yeasts that, like Pichia stipitis, can utilize and ferment xylose. Therefore, the understanding of the molecular mechanisms regulating the xylose assimilation in such pentose fermenting yeasts will enable us to eliminate the obstacles in the biofuels pipeline, and to develop industrial strains by means of genetic engineering to increase the availability of renewable biofuel products from agricultural biomass. In this review, we will highlight the recent advances in the field of native xylose metabolizing yeasts, with special emphasis on S. passalidarum for improving bioethanol production.
Pathogenic Effect of GDAP1 Gene Mutations in a Yeast Model
Authors: Rzepnikowska Weronika , Kaminska Joanna , Kabzińska Dagmara , Kochański Andrzej
Published: March 2020

The question of whether a newly identified sequence variant is truly a causative mutation is a central problem of modern clinical genetics. In the current era of massive sequencing, there is an urgent need to develop new tools for assessing the pathogenic effect of new sequence variants. In Charcot-Marie-Tooth disorders (CMT) with their extreme genetic heterogeneity and relatively homogenous clinical presentation, addressing the pathogenic effect of rare sequence variants within 80 CMT genes is extremely challenging. The presence of multiple rare sequence variants within a single CMT-affected patient makes selection for the strongest one, the truly causative mutation, a challenging issue. In the present study we propose a new yeast-based model to evaluate the pathogenic effect of rare sequence variants found within the one of the CMT-associated genes, GDAP1. In our approach, the wild-type and pathogenic variants of human GDAP1 gene were expressed in yeast. Then, a growth rate and mitochondrial morphology and function of GDAP1-expressing strains were studied. Also, the mutant GDAP1 proteins localization and functionality were assessed in yeast. We have shown, that GDAP1 was not only stably expressed but also functional in yeast cell, as it influenced morphology and function of mitochondria and altered the growth of a mutant yeast strain. What is more, the various GDAP1 pathogenic sequence variants caused the specific for them effect in the tests we performed. Thus, the proposed model is suitable for validating the pathogenic effect of known GDAP1 mutations and may be used for testing of unknown sequence variants found in CMT patients.
Genes, Pathways, and Mechanisms Involved in the Virulence of Mucorales
Authors: Lax Carlos , Pérez-Arques Carlos , Navarro-Mendoza María , Cánovas-Márquez José , Tahiri Ghizlane , Pérez-Ruiz José , Osorio-Concepción Macario , Murcia-Flores Laura , Navarro Eusebio , Garre Victoriano , Nicolás Francisco
Published: March 2020

The order Mucorales is a group of ancient fungi with limited tools for gene manipulation. The main consequence of this manipulation unwillingness is the limited knowledge about its biology compared to other fungal groups. However, the emerging of mucormycosis, a fungal infection caused by Mucorales, is attracting the medical spotlight in recent years because the treatments available are not efficient in reducing the high mortality associated with this disease. The result of this renewed interest in Mucorales and mucormycosis is an extraordinarily productive effort to unveil their secrets during the last decade. In this review, we describe the most compelling advances related to the genetic study of virulence factors, pathways, and molecular mechanisms developed in these years. The use of a few genetic study models has allowed the characterization of virulence factors in Mucorales that were previously described in other pathogens, such as the uptake iron systems, the mechanisms of dimorphism, and azole resistances. More importantly, recent studies are identifying new genes and mechanisms controlling the pathogenic potential of Mucorales and their interactions with the host, offering new alternatives to develop specific strategies against mucormycosis.