bluuebunny/crossref_metadata_2025 huggingface dataset:
Heparin-Binding Protein 17/Fibroblast Growth Factor-Binding Protein-1 Knockout Inhibits Proliferation and Induces Differentiation of Squamous Cell Carcinoma Cells
Authors: Shintani Tomoaki , Higaki Mirai , Okamoto Tetsuji
Published: May 2021

Heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) has been observed to induce the tumorigenic potential of epithelial cells and is highly expressed in oral cancer cell lines and tissues. It is also recognized as a pro-angiogenic molecule because of its interaction with fibroblast growth factor (FGF)-2. In this study, we examined the functional role of HBp17/FGFBP-1 in A431 and HO-1-N-1 cells. Originally, HBp17/FGFBP-1 was purified from A431 cell-conditioned media based on its capacity to bind to FGF-1 and FGF-2. We isolated and established HBp17/FGFBP-1-knockout (KO)-A431 and KO-HO-1-N-1 cell lines using the clusters of regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) gene editing technology. The amount of FGF-2 secreted into conditioned medium decreased for A431-HBp17-KO and HO-1-N-1-HBp17-KO cells compared to their WT counterparts. Functional assessment showed that HBp17/FGFBP-1 KO inhibited cell proliferation, colony formation, and cell motility in vitro. It also inhibited tumor growth in vivo compared to controls, which confirmed the significant difference in growth in vitro between HBp17-KO cells and wild-type (WT) cells, indicating that HBp17/FGFBP-1 is a potent therapeutic target in squamous cell carcinomas (SCC) and oral squamous cell carcinomas (OSCC). In addition, complementary DNA/protein expression analysis followed by Gene Ontology and protein–protein interaction (PPI) analysis using the Database for Visualization and Integrated Discovery and Search Tool for the Retrieval of Interacting Genes/Proteins showed that both gene and protein expression related to epidermal development, cornification, and keratinization were upregulated in A431-HBp17-KO and HO-1-N-1-KO cells. This is the first discovery of a novel role of HBp17/FGFBP-1 that regulates SCC and OSCC cell differentiation.
Reactivation of Multiple Fetal miRNAs in Lung Adenocarcinoma
Authors: Cohn David E. , Barros-Filho Mateus C. , Minatel Brenda C. , Pewarchuk Michelle E. , Marshall Erin A. , Vucic Emily A. , Sage Adam P. , Telkar Nikita , Stewart Greg L. , Jurisica Igor , Reis Patricia P. , Robinson Wendy P. , Lam Wan L.
Published: May 2021

MicroRNAs (miRNAs) play vital roles in the regulation of normal developmental pathways. However, cancer cells can co-opt these miRNAs, and the pathways that they regulate, to drive pro-tumourigenic phenotypes. Characterization of the miRNA transcriptomes of fetal organs is essential for identifying these oncofetal miRNAs, but it has been limited by fetal sample availability. As oncofetal miRNAs are absent from healthy adult lungs, they represent ideal targets for developing diagnostic and therapeutic strategies. We conducted small RNA sequencing of a rare collection of 25 human fetal lung (FL) samples and compared them to two independent cohorts (n = 140, n = 427), each comprised of adult non-neoplastic lung (ANL) and lung adenocarcinoma (LUAD) samples. We identified 13 oncofetal miRNAs that were expressed in FL and LUAD but not in ANL. These oncofetal miRNAs are potential biomarkers for LUAD detection (AUC = 0.963). Five of these miRNAs are derived from the imprinted C14MC miRNA cluster at the 14q32 locus, which has been associated with cancer development and abnormal fetal and placental development. Additionally, we observed the pulmonary expression of 44 previously unannotated miRNAs. The sequencing of these fetal lung samples also provides a baseline resource against which aberrant samples can be compared.
Involvement of Thyroid Hormones in Brain Development and Cancer
Authors: Schiera Gabriella , Di Liegro Carlo Maria , Di Liegro Italia
Published: May 2021

The development and maturation of the mammalian brain are regulated by thyroid hormones (THs). Both hypothyroidism and hyperthyroidism cause serious anomalies in the organization and function of the nervous system. Most importantly, brain development is sensitive to TH supply well before the onset of the fetal thyroid function, and thus depends on the trans-placental transfer of maternal THs during pregnancy. Although the mechanism of action of THs mainly involves direct regulation of gene expression (genomic effects), mediated by nuclear receptors (THRs), it is now clear that THs can elicit cell responses also by binding to plasma membrane sites (non-genomic effects). Genomic and non-genomic effects of THs cooperate in modeling chromatin organization and function, thus controlling proliferation, maturation, and metabolism of the nervous system. However, the complex interplay of THs with their targets has also been suggested to impact cancer proliferation as well as metastatic processes. Herein, after discussing the general mechanisms of action of THs and their physiological effects on the nervous system, we will summarize a collection of data showing that thyroid hormone levels might influence cancer proliferation and invasion.
Risk-Reducing Mastectomy and Reconstruction Following Prophylactic Breast Irradiation: Hope Sustained
Authors: Ben David Merav A. , Evron Ella , Rasco Adi F. , Shai Ayelet , Corn Benjamin W.
Published: May 2021

Risk-reducing mastectomy (RRM) is often advocated for BRCA1/2 mutation carriers who face a heightened lifetime risk of breast cancer. However, many carrier patients seek alternative risk-reducing measures. In a phase II nonrandomized trial, we previously reported that prophylactic irradiation to the contralateral breast among BRCA carriers undergoing breast-conserving treatment significantly reduced subsequent contralateral breast cancer. Herein, we report the outcome of salvage mastectomy and reconstruction in 11 patients that suffered reoccurrences of breast cancer in either the ipsilateral or contralateral breast or elected to have the procedure for risk reduction during the eight-year follow-up period. Patients’ satisfaction with the procedure and physicians’ assessment of the cosmetic outcome were not inferior for previously irradiated compared to non-irradiated breasts. Although the numbers are small, the results are encouraging and sustain hope in a challenging population. Our findings support continuing research as well as a discussion of risk-reduction alternatives besides mastectomy, including prophylactic breast irradiation, in BRCA1/2 mutation carriers.
STING Agonists as Cancer Therapeutics
Authors: Amouzegar Afsaneh , Chelvanambi Manoj , Filderman Jessica , Storkus Walter , Luke Jason
Published: May 2021

The interrogation of intrinsic and adaptive resistance to cancer immunotherapy has identified lack of antigen presentation and type I interferon signaling as biomarkers of non-T-cell-inflamed tumors and clinical progression. A myriad of pre-clinical studies have implicated the cGAS/stimulator of interferon genes (STING) pathway, a cytosolic DNA-sensing pathway that drives activation of type I interferons and other inflammatory cytokines, in the host immune response against tumors. The STING pathway is also increasingly understood to have other anti-tumor functions such as modulation of the vasculature and augmentation of adaptive immunity via the support of tertiary lymphoid structure development. Many natural and synthetic STING agonists have entered clinical development with the first generation of intra-tumor delivered cyclic dinucleotides demonstrating safety but only modest systemic activity. The development of more potent and selective STING agonists as well as novel delivery systems that would allow for sustained inflammation in the tumor microenvironment could potentially augment response rates to current immunotherapy approaches and overcome acquired resistance. In this review, we will focus on the latest developments in STING-targeted therapies and provide an update on the clinical development and application of STING agonists administered alone, or in combination with immune checkpoint blockade or other approaches.
Overcoming PD-1 Inhibitor Resistance with a Monoclonal Antibody to Secreted Frizzled-Related Protein 2 in Metastatic Osteosarcoma
Authors: Nasarre Patrick , Garcia Denise I. , Siegel Julie B. , Bonilla Ingrid V. , Mukherjee Rupak , Hilliard Eleanor , Chakraborty Paramita , Nasarre Cécile , Yustein Jason T. , Lang Margaret , Jaffa Aneese A. , Mehrotra Shikhar , Klauber-DeMore Nancy
Published: May 2021

Secreted frizzled-related protein 2 (SFRP2) promotes the migration/invasion of metastatic osteosarcoma (OS) cells and tube formation by endothelial cells. However, its function on T-cells is unknown. We hypothesized that blocking SFRP2 with a humanized monoclonal antibody (hSFRP2 mAb) can restore immunity by reducing CD38 and PD-1 levels, ultimately overcoming resistance to PD-1 inhibitors. Treating two metastatic murine OS cell lines in vivo, RF420 and RF577, with hSFRP2 mAb alone led to a significant reduction in the number of lung metastases, compared to IgG1 control treatment. While PD-1 mAb alone had minimal effect, hSFRP2 mAb combination with PD-1 mAb had an additive antimetastatic effect. This effect was accompanied by lower SFRP2 levels in serum, lower CD38 levels in tumor-infiltrating lymphocytes and T-cells, and lower PD-1 levels in T-cells. In vitro data confirmed that SFRP2 promotes NFATc3, CD38 and PD-1 expression in T-cells, while hSFRP2 mAb treatment counteracts these effects and increases NAD+ levels. hSFRP2 mAb treatment further rescued the suppression of T-cell proliferation by tumor cells in a co-culture model. Finally, hSFRP2 mAb induced apoptosis in RF420 and RF577 OS cells but not in T-cells. Thus, hSFRP2 mAb therapy could potentially overcome PD-1 inhibitor resistance in metastatic osteosarcoma.
Identification of the Neurokinin-1 Receptor as Targetable Stratification Factor for Drug Repurposing in Pancreatic Cancer
Authors: Beirith Iris , Renz Bernhard W. , Mudusetti Shristee , Ring Natalja Sergejewna , Kolorz Julian , Koch Dominik , Bazhin Alexandr V. , Berger Michael , Wang Jing , Angele Martin K. , D’Haese Jan G. , Guba Markus O. , Niess Hanno , Andrassy Joachim , Werner Jens , Ilmer Matthias
Published: May 2021

The SP/NK1R-complex plays an important role in tumor proliferation. Targeting of the neurokinin-1 receptor in previous studies with its antagonist aprepitant (AP) resulted in anti-tumoral effects in colorectal cancer and hepatoblastoma. However, there is still a lack of knowledge regarding its effects on pancreatic cancer. Therefore, we treated human pancreatic ductal adenocarcinoma (PDAC) cell lines (Capan-1, DanG, HuP-T3, Panc-1, and MIA PaCa-2) and their cancer stem cell-like cells (CSCs) with AP and analyzed functional effects by MTT-, colony, and sphere formation assays, respectively; moreover, we monitored downstream mechanisms by flow cytometry. NK1R inhibition resulted in dose-dependent growth reduction in both CSCs and non-CSCs without induction of apoptosis in most PDAC cell lines. More importantly, we identified striking AP dependent cell cycle arrest in all parental cells. Furthermore, gene expression and the importance of key genes in PDAC tumorigenesis were analyzed combining RT-qPCR in eight PDAC cell lines with publicly available datasets (TCGA, GEO, CCLE). Surprisingly, we found a better overall survival in patients with high NK1R levels, while at the same time, NK1R was significantly decreased in PDAC tissue compared to normal tissue. Interestingly, there is currently no differentiation between the isoforms of NK1R (truncated and full; NK1R-tr and -fl) in any of the indicated public transcriptomic records, although many publications already emphasize on important regulatory differences between the two isoforms of NK1R in many cancer entities. In conclusion, analysis of splice variants might potentially lead to a stratification of PDAC patients for NK1R-directed therapies. Furthermore, we presume PDAC patients with high expressions of NK1R-tr might benefit from treatment with AP to improve chemoresistance. Therefore, analysis of splice variants might potentially lead to a stratification of PDAC patients for NK1R-directed therapies.
CALD1 Modulates Gliomas Progression via Facilitating Tumor Angiogenesis
Authors: Cheng Quan , Tang Anliu , Wang Zeyu , Fang Ning , Zhang Zhuojing , Zhang Liyang , Li Chuntao , Zeng Yu
Published: May 2021

Angiogenesis is more prominent in anaplastic gliomas and glioblastoma (GBM) than that in pilocytic and diffuse gliomas. Caldesmon (CALD1) plays roles in cell adhesion, cytoskeletal organization, and vascularization. However, limited information is available on mechanisms underlying the effect of CALD1 on the microvascular facilitation and architecture in glioma. In this study, we explored the role of CALD1 in gliomas by integrating bulk RNA-seq analysis and single cell RNA-seq analysis. A positive correlation between CALD1 expression and the gliomas’ pathological grade was noticed, according to the samples from the TCGA and CGGA database. Moreover, higher CALD1 expression samples showed worse clinical outcomes than lower CALD1 expression samples. Biofunction prediction suggested that CALD1 may affect glioma progression through modulating tumor angiogenesis. The map of the tumor microenvironment also depicted that more stromal cells, such as endothelial cells and pericytes, infiltrated in high CALD1 expression samples. CALD1 was found to be remarkably upregulated in neoplastic cells and was involved in tumorigenic processes of gliomas in single cell sequencing analysis. Histology and immunofluorescence analysis also indicated that CALD1 associates with vessel architecture, resulting in glioma grade progression. In conclusion, the present study implies that CALD1 may serve as putative marker monitoring the progress of glioma.
Clinical Application of Next-Generation Sequencing of Plasma Cell-Free DNA for Genotyping Untreated Advanced Non-Small Cell Lung Cancer
Authors: Fernandes Maria Gabriela O. , Cruz-Martins Natália , Souto Moura Conceição , Guimarães Susana , Pereira Reis Joana , Justino Ana , Pina Maria João , Magalhães Adriana , Queiroga Henrique , Machado José Carlos , Hespanhol Venceslau , Costa José Luis
Published: May 2021

Background: Analysis of circulating tumor DNA (ctDNA) has remarkable potential as a non-invasive lung cancer molecular diagnostic method. This prospective study addressed the clinical value of a targeted-gene amplicon-based plasma next-generation sequencing (NGS) assay to detect actionable mutations in ctDNA in patients with newly diagnosed advanced lung adenocarcinoma. Methods: ctDNA test performance and concordance with tissue NGS were determined, and the correlation between ctDNA findings, clinical features, and clinical outcomes was evaluated in 115 patients with paired plasma and tissue samples. Results: Targeted-gene NGS-based ctDNA and NGS-based tissue analysis detected 54 and 63 genomic alterations, respectively; 11 patients presented co-mutations, totalizing 66 hotspot mutations detected, 51 on both tissue and plasma, 12 exclusively on tissue, and 3 exclusively on plasma. NGS-based ctDNA revealed a diagnostic performance with 81.0% sensitivity, 95.3% specificity, 94.4% PPV, 83.6% NPV, test accuracy of 88.2%, and Cohen’s Kappa 0.764. PFS and OS assessed by both assays did not significantly differ. Detection of ctDNA alterations was statistically associated with metastatic disease (p = 0.013), extra-thoracic metastasis (p = 0.004) and the number of organs involved (p = 0.010). Conclusions: This study highlights the potential use of ctDNA for mutation detection in newly diagnosed NSCLC patients due to its high accuracy and correlation with clinical outcomes.
Study of the Genetic Variants in BRCA1/2 and Non-BRCA Genes in a Population-Based Cohort of 2155 Breast/Ovary Cancer Patients, Including 443 Triple-Negative Breast Cancer Patients, in Argentina
Authors: Solano Angela R. , Mele Pablo G. , Jalil Fernanda S. , Liria Natalia C. , Podesta Ernesto J. , Gutiérrez Leandro G.
Published: May 2021

Gene/s sequencing in hereditary breast/ovary cancer (HBOC) in routine diagnosis is challenged by the analysis of panels. We aim to report a retrospective analysis of BRCA1/2 and non-BRCA gene sequencing in patients with breast/ovary cancer (BOC), including triple-negative breast cancer (TNBC), in our population. In total 2155 BOC patients (1900 analyzed in BRCA1/2 and 255 by multigenic panels) gave 372 (17.2.6%) and 107 (24.1%) likely pathogenic/pathogenic variants (LPVs/PVs), including BRCA and non-BRCA genes, for the total and TNBC patients, respectively. When BOC was present in the same proband, a 51.3% rate was found for LPVs/PVs in BRCA1/2. Most of the LPVs/PVs in the panels were in BRCA1/2; non-BRCA gene LPVs/PVs were in CDH1, CHEK2, CDKN2A, MUTYH, NBN, RAD51D, and TP53. TNBC is associated with BRCA1/2 at a higher rate than the rest of the breast cancer types. The more prevalent PVs in BRCA1/2 genes (mostly in BRCA1) do not rule out the importance to panels of genes, although they are certainly far from shedding light on the gap of the 85% predicted linkage association of BOC with BRCA1/2 and are still not elucidated.
Multi-Institutional Retrospective Analysis of Carbon-Ion Radiotherapy for Patients with Locally Advanced Adenocarcinoma of the Uterine Cervix
Authors: Okonogi Noriyuki , Ando Ken , Murata Kazutoshi , Wakatsuki Masaru , Noda Shin-ei , Irie Daisuke , Tsuji Hiroshi , Shozu Makio , Ohno Tatsuya
Published: May 2021

The clinical significance of carbon-ion radiotherapy (CIRT) for adenocarcinoma (AC) of the uterine cervix has been assessed in several single-institutional studies. To validate the significance, we conducted a multi-institutional survey of CIRT for locally advanced AC (LAAC) of the uterine cervix. We retrospectively analyzed the clinical outcomes of patients with stage IIB–IVA LAAC of the uterine cervix who underwent chemo-CIRT or CIRT alone between April 2010 and April 2016. Patients received 74.4 Gy (relative biological effectiveness [RBE]) in 20 fractions of CIRT or 55.2 Gy (RBE) in 16 fractions of CIRT plus three sessions of brachytherapy. Patients aged ≤ 70 years with adequate bone marrow and organ function were administered cisplatin weekly (40 mg/m2 per week for up to 5 weeks). Fifty-five patients were enrolled in this study. The median follow-up period was 67.5 months. The 5-year overall survival (OS) and local control (LC) rates were 68.6% and 65.2%, respectively. Multivariate analysis showed that the initial tumor response within 6 months was significantly associated with LC and OS. The present study represents promising outcomes of CIRT or chemo-CIRT for LAAC of the uterine cervix, especially in the cases showing initial rapid regression of the tumor.
Vitamin D: Promises on the Horizon and Challenges Ahead for Fighting Pancreatic Cancer
Authors: Wei Daoyan , Wang Liang , Zuo Xiangsheng , Bresalier Robert S.
Published: May 2021

Pancreatic cancer has a dismal prognosis, while its incidence is increasing. This is attributed, in part, to a profound desmoplastic and immunosuppressive tumor microenvironment associated with this cancer and resistance to current available therapies. Novel and effective intervention strategies are urgently needed to improve the outcomes of patients with pancreatic cancer. Vitamin D has pleiotropic functions beyond calcium–phosphate homeostasis and has been extensively studied both in the laboratory and clinic as a potential preventive agent or adjunct to standard therapies. Accumulating evidence from ecological, observational, and randomized controlled trials suggests that vitamin D has beneficial effects on risk, survival, and mortality in pancreatic cancer, although controversies still exist. Recent advances in demonstrating the important functions of vitamin D/vitamin D receptor (VDR) signaling in the regulation of stromal reprogramming, the microbiome, and immune response and the emergence of checkpoint immunotherapy provide opportunities for using vitamin D or its analogues as an adjunct for pancreatic cancer intervention. Many challenges lie ahead before the benefits of vitamin D can be fully realized in pancreatic cancer. These challenges include the need for randomized controlled trials of vitamin D to assess its impact on the risk and survival of pancreatic cancer, optimizing the timing and dosage of vitamin D or its analogues as an adjunct for pancreatic cancer intervention and elucidating the specific role of vitamin D/VDR signaling in the different stages of pancreatic cancer. Nevertheless, vitamin D holds great promise for reducing risk and improving outcomes of this disease.
Structural and Functional Modulation of Perineuronal Nets: In Search of Important Players with Highlight on Tenascins
Authors: Jakovljević Ana , Tucić Milena , Blažiková Michaela , Korenić Andrej , Missirlis Yannis , Stamenković Vera , Andjus Pavle
Published: May 2021

The extracellular matrix (ECM) of the brain plays a crucial role in providing optimal conditions for neuronal function. Interactions between neurons and a specialized form of ECM, perineuronal nets (PNN), are considered a key mechanism for the regulation of brain plasticity. Such an assembly of interconnected structural and regulatory molecules has a prominent role in the control of synaptic plasticity. In this review, we discuss novel ways of studying the interplay between PNN and its regulatory components, particularly tenascins, in the processes of synaptic plasticity, mechanotransduction, and neurogenesis. Since enhanced neuronal activity promotes PNN degradation, it is possible to study PNN remodeling as a dynamical change in the expression and organization of its constituents that is reflected in its ultrastructure. The discovery of these subtle modifications is enabled by the development of super-resolution microscopy and advanced methods of image analysis.
Targeting Mitochondrial Damage as a Therapeutic for Ileal Crohn’s Disease
Authors: Alula Kibrom M. , Jackson Dakota N. , Smith Andrew D. , Kim Daniel S. , Turner Kevin , Odstrcil Elizabeth , Kaipparettu Benny A. , Dassopoulos Themistocles , Venuprasad K. , Feagins Linda A. , Theiss Arianne L.
Published: May 2021

Paneth cell defects in Crohn’s disease (CD) patients (called the Type I phenotype) are associated with worse clinical outcomes. Recent studies have implicated mitochondrial dysfunction in Paneth cells as a mediator of ileitis in mice. We hypothesized that CD Paneth cells exhibit impaired mitochondrial health and that mitochondrial-targeted therapeutics may provide a novel strategy for ileal CD. Terminal ileal mucosal biopsies from adult CD and non-IBD patients were characterized for Paneth cell phenotyping and mitochondrial damage. To demonstrate the response of mitochondrial-targeted therapeutics in CD, biopsies were treated with vehicle or Mito-Tempo, a mitochondrial-targeted antioxidant, and RNA transcriptome was analyzed. During active CD inflammation, the epithelium exhibited mitochondrial damage evident in Paneth cells, goblet cells, and enterocytes. Independent of inflammation, Paneth cells in Type I CD patients exhibited mitochondrial damage. Mito-Tempo normalized the expression of interleukin (IL)-17/IL-23, lipid metabolism, and apoptotic gene signatures in CD patients to non-IBD levels. When stratified by Paneth cell phenotype, the global tissue response to Mito-Tempo in Type I patients was associated with innate immune, lipid metabolism, and G protein-coupled receptor (GPCR) gene signatures. Targeting impaired mitochondria as an underlying contributor to inflammation provides a novel treatment approach for CD.
TSPO Expression Modulatory Effect of Acetylcholinesterase Inhibitor in the Ischemic Stroke Rat Model
Authors: Song Yoo Sung , Lee Sang Hee , Jung Jae Ho , Song In Ho , Park Hyun Soo , Moon Byung Seok , Kim Sang Eun , Lee Byung Chul
Published: May 2021

We performed in vivo PET imaging with 3-[18F]F-CP118,954 (1) for acetylcholinesterase (AChE) and [18F]fluoromethyl-PBR28-d2 (2) for translocator protein 18-kDa (TSPO) to investigate the inflammatory brain response after stroke. Imaging studies were performed in the middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model for a period of three weeks. The percentage injected dose per tissue weight (%ID/g) of striatum of 1, and cortex of 2 were obtained, respectively. To trace the sequential inflammatory responses, AChE imaging of 1 was done on post-MCAO day 2, after giving cold PK-11195 for 1 day, and TSPO imaging of 2 was carried out on post-MCAO day 11, after giving donepezil for 10 days. AChE activity in the MCAO-lesioned side were significantly higher than that of the contralateral side on day one, and TSPO activity was highest on day 11. TSPO inhibitor, PK-11195 did not affect AChE activity on day two, while AChE inhibitor, donepezil significantly lowered TSPO binding on day 12. Our study demonstrates that AChE level is elevated in the early course of brain ischemia as a trigger for the inflammatory response, and TSPO level is elevated persistently throughout the post-ischemic injury in the brain. Also, the AChE inhibitor may be able to inhibit or delay neurotoxic inflammatory responses and serve as a beneficial treatment option.
DNA-DAPI Interaction-Based Method for Cell Proliferation Rate Evaluation in 3D Structures
Authors: Šimoliūnas Egidijus , Kantakevičius Paulius , Kalvaitytė Miglė , Bagdzevičiūtė Lina , Alksnė Milda , Baltriukienė Daiva
Published: May 2021

Effective cell number monitoring throughout the three-dimensional (3D) scaffold is a key factor in tissue engineering. There are many methods developed to evaluate cell number in 2D environments; however, they often encounter limitations in 3D. Therefore, there is a demand for reliable methods to measure cell proliferation in 3D surroundings. Here, we report a novel technique for the DNA content-based evaluation of cell proliferation using DNA-binding dye DAPI. We demonstrated the method’s compatibility with four different cell cultures: cancer lines MCF-7 and MH-22a, embryonic fibroblast cell line Swiss 3T3, and primary mesenchymal stem cell culture isolated from rat’s incisors. The DAPI based method was able to successfully evaluate cell proliferation in 2D, 2.5D, and 3D environments. Even though the proposed method does not discriminate between viable and dead cells, it might give a convenient snapshot of the cell number at a given time point. This should help to more reliably evaluate various processes proceeding in 2.5D and 3D cultures.
Effect of Curing Agents on Electrical Properties of Low-Temperature Curing Conductive Coatings and Thermodynamic Analysis
Authors: Shu Junjie , Wang Yang , Guo Bei , Qin Weihua , Liu Lanxuan , Liu Xiusheng
Published: May 2021

Silver-based high-conductivity coatings are used in many advanced manufacturing equipment and components, and existing coatings require high-temperature curing. This paper studies the effects of different curing agents on the electrical properties of low-temperature curing (<100 °C) conductive coatings, and analyzes the effects of different curing temperatures and curing time on the surface resistance, square resistance and resistivity of conductive coatings. The response surface method in Design Expert was used to construct the model, and the curing thermodynamics of different curing agents were analyzed by DSC. It was found that curing agents with lower Tm and activation energy, higher pre-exponential factor and more flexible segments are beneficial to the preparation of highly conductive coatings.
Effect of Microcapsules of a Waterborne Core Material on the Properties of a Waterborne Primer Coating on a Wooden Surface
Authors: Yan Xiaoxing , Peng Wenwen
Published: May 2021

Microcapsules of a waterborne core material were prepared using a waterborne primer. The microcapsules of the waterborne core material were added to the waterborne primer to explore the effects of different core–shell ratios and mass fractions of the microcapsules on the property of the waterborne primer coating on the wooden surface. The results show that as the mass fraction of the microcapsules increased, the chromatic aberration increased by degrees, the glossiness decreased gradually, and the hardness increased by degrees, whilst—except for the coating with 0.50:1 microcapsules—the adhesion decreased gradually. When the mass fraction of the microcapsules increased, the impact resistance increased first and decreased later, or remained unchanged after reaching a certain value. When the mass fraction of the microcapsules increased, the elongation at the break increased first and decreased later. When the core–shell ratio was small and the mass fraction was between 5.0% and 15.0%, the coating had better liquid resistance. When the core–shell ratio was 0.67:1 and the mass fraction was 10.0%, the overall property of the coating on the Basswood was the best. The technology of microencapsulation provides a technical reference for the waterborne primer with self-repair qualities on the surface of wooden products.
Electrochemical Study of TA2 Titanium in a High-Temperature and -Pressure Water Environment
Authors: Chen Lin , Jin Xiaoyue , Pang Pan , Liao Bin , Xue Wenbin , Luo Jun
Published: May 2021

The corrosion behaviors of TA2 titanium were investigated by in situ electrochemical measurements in a solution of 2.3 ppm Li+ and 1500 ppm B3+ at a temperature of up to 300 °C. The morphology, phase structure, and composition of the oxide film, after 800 h exposure time in a solution at 300 °C and 14 MPa, were characterized by scanning electron microscopy (SEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), etc. The growth mechanism of the oxide film based on the activation energy was discussed. The potentiodynamic polarization and electrochemical impedance spectroscopy analyses showed that the corrosion resistance of titanium significantly weakened when increasing the solution temperature from 30 to 300 °C, but it increased in the initial stage of holding time (0–66 h) at 300 °C, then gradually decreased (66–378 h), and reached a stable state after 378 h. The oxide film, which was about 5 μm thick, consisted of anatase phase and a small amount of B2O3. The growth mechanism is a combination of layer by layer and island growth.
Evaluation of Adaptation and Yield Stability of Cocoa Progenies in Marginal Conditions: Results from an on Farm Cocoa Trial Set up in a Forest–Savannah Transition Area in Cameroon
Authors: Feumba de Tchoua Leblanc , Sounigo Olivier , Bourgoing Raymond , Efombagn Mousseni Ives Bruno , Abolo Dieudonné , Ambang Zachée , Cilas Christian
Published: May 2021

Cocoa is an important crop in Cameroon, where it is cultivated in different areas, including marginal areas, characterized by a rather low level of annual rainfall and marked dry seasons. In order to release cocoa varieties with a good level of adaptation to these marginal conditions, nine full-sib progenies, already released to farmers in other producing areas of the country, were assessed on twelve on farm cocoa plots, set up in 2006, in Mbam et Inoubou county, which is a forest–savannah transition zone. The traits assessed were mortality rate, yield and yield stability. Mortality rate and yield vary widely among trial plots and among progenies. Four out of the nine assessed progenies present a yield level significantly higher than the five others. The lowest level of yield stability (estimated by the contribution to total ecovalence) was observed in both the highest and the lowest yielding progenies. Recommendation for the large-scale release of these progenies to farmers of the county, and to other cocoa producing forest–savannah transition areas, are made, based on the results obtained from this study.
Associative Blockchain for Decentralized PKI Transparency
Authors: Boyen Xavier , Herath Udyani , McKague Matthew , Stebila Douglas
Published: May 2021

The conventional public key infrastructure (PKI) model, which powers most of the Internet, suffers from an excess of trust into certificate authorities (CAs), compounded by a lack of transparency which makes it vulnerable to hard-to-detect targeted stealth impersonation attacks. Existing approaches to make certificate issuance more transparent, including ones based on blockchains, are still somewhat centralized. We present decentralized PKI transparency (DPKIT): a decentralized client-based approach to enforcing transparency in certificate issuance and revocation while eliminating single points of failure. DPKIT efficiently leverages an existing blockchain to realize an append-only, distributed associative array, which allows anyone (or their browser) to audit and update the history of all publicly issued certificates and revocations for any domain. Our technical contributions include definitions for append-only associative ledgers, a security model for certificate transparency, and a formal analysis of our DPKIT construction with respect to the same. Intended as a client-side browser extension, DPKIT will be effective at fraud detection and prosecution, even under fledgling user adoption, and with better coverage and privacy than federated observatories, such as Google’s or the Electronic Frontier Foundation’s.
Reciprocal Garden Study Reveals Acute Spatial-Edaphic Adaptation for Cycas micronesica
Authors: Marler Thomas E.
Published: May 2021

A long-term reciprocal garden study was used to determine adaptive variation between Cycas micronesica K.D. Hill plants from north versus south Guam. Half-siblings from each location were planted as one-leaf seedlings in north and south gardens and monitored for 15 years. Stem height and diameter, and leaf number and maximum length were measured yearly. Survival and plant size traits were evaluated using a two-way factorial. In both locations, the local genotypes out-performed the foreign genotypes in terms of survival and growth. Survival of the foreign genotypes began to decline by year 4 and was less than 10% by year 15. Survival of the local genotypes was 70% for the north garden and 100% for the south garden. The north site was more hostile to plant performance because overall survival and plant growth were less than for the south site. The most likely environmental factor provoking local adaptation was highly contrasting soil characteristics between north and south Guam. The results indicates that long-term conservation success for C. micronesica and other cycad species must include the concept of local adaptation into decisions for transplantation and restoration projects.
Mesofauna at the Soil-Scree Interface in a Deep Karst Environment
Authors: Jureková Nikola , Raschmanová Natália , Miklisová Dana , Kováč Ľubomír
Published: May 2021

The community patterns of Collembola (Hexapoda) were studied at two sites along a microclimatically inversed scree slope in a deep karst valley in the Western Carpathians, Slovakia, in warm and cold periods of the year, respectively. Significantly lower average temperatures in the scree profile were noted at the gorge bottom in both periods, meaning that the site in the lower part of the scree, near the bank of creek, was considerably colder and wetter compared to the warmer and drier site at upper part of the scree slope. Relatively high diversity of Collembola was observed at two fieldwork scree sites, where cold-adapted species, considered climatic relicts, showed considerable abundance. The gorge bottom, with a cold and wet microclimate and high carbon content even in the deeper MSS horizons, provided suitable environmental conditions for numerous psychrophilic and subterranean species. Ecological groups such as trogloxenes and subtroglophiles showed decreasing trends of abundance with depth, in contrast to eutroglophiles and a troglobiont showing an opposite distributional pattern at scree sites in both periods. Our study documented that in terms of soil and subterranean mesofauna, colluvial screes of deep karst gorges represent (1) a transition zone between the surface and the deep subterranean environment, and (2) important climate change refugia.
Information Geometry of the Exponential Family of Distributions with Progressive Type-II Censoring
Authors: Zhang Fode , Shi Xiaolin , Ng Hon Keung Tony
Published: May 2021

In geometry and topology, a family of probability distributions can be analyzed as the points on a manifold, known as statistical manifold, with intrinsic coordinates corresponding to the parameters of the distribution. Consider the exponential family of distributions with progressive Type-II censoring as the manifold of a statistical model, we use the information geometry methods to investigate the geometric quantities such as the tangent space, the Fisher metric tensors, the affine connection and the α-connection of the manifold. As an application of the geometric quantities, the asymptotic expansions of the posterior density function and the posterior Bayesian predictive density function of the manifold are discussed. The results show that the asymptotic expansions are related to the coefficients of the α-connections and metric tensors, and the predictive density function is the estimated density function in an asymptotic sense. The main results are illustrated by considering the Rayleigh distribution.
The Concept of Multiple Impacts of Renewable Energy Sources: A Critical Review
Authors: Makešová Michaela , Valentová Michaela
Published: May 2021

Reaching climate neutrality by 2050 is one of the main long-term objectives of the European Union climate and energy policy, and renewable energy sources (RES) are integral parts of this transition. RES development results in many effects, direct and indirect, linked to each other, societal, local and individual, i.e., “multiple impacts of RES” (MI RES). These effects need to be carefully assessed and evaluated to obtain the full picture of energy field transformation and its context, and enable further development of RES. Nevertheless, the MI RES concept is often presented misleadingly and its scope varies throughout the literature. This paper provides a literature overview of the methodologies of this concept and presents a new concept of MI RES, respecting the difference between effects resulting from the implementation of RES and ultimate multiple impacts. We have summarized the effects into four groups: economic, social, environmental, and technical, which all lead to group of ultimate multiple impacts. Finally, we provide the complex overview of all MI RES and present the framework, which is used to analyze the multiple impacts and effects of RES and to show how the RES development leads and contributes to these impacts and effects. The concept is recommended to be considered in designing a robust energy policy by decision-makers.
Recent Advances in Covalent Organic Frameworks for Heavy Metal Removal Applications
Authors: Gatou Maria-Anna , Bika Panagiota , Stergiopoulos Thomas , Dallas Panagiotis , Pavlatou Evangelia A.
Published: May 2021

Covalent organic frameworks comprise a unique class of functional materials that has recently emerged as a versatile tool for energy-related, photocatalytic, environmental, and electrochromic device applications. A plethora of structures can be designed and implemented through a careful selection of ligands and functional units. On the other hand, porous materials for heavy metal absorption are constantly on the forefront of materials science due to the significant health issues that arise from the release of the latter to aquatic environments. In this critical review, we provide insights on the correlation between the structure of functional covalent organic frameworks and their heavy metal absorption. The elements we selected were Pb, Hg, Cr, Cd, and As metal ions, as well as radioactive elements, and we focused on their removal with functional networks. Finally, we outline their advantages and disadvantages compared to other competitive systems such as zeolites and metal organic frameworks (MOFs), we analyze the potential drawbacks for industrial scale applications, and we provide our outlook on the future of this emerging field.
Impact of Enclosure Boundary Patterns and Lift-Up Design on Optimization of Summer Pedestrian Wind Environment in High-Density Residential Districts
Authors: Jiang Zhengrong , Gao Weijun
Published: May 2021

A comfortable wind environment favors the sustainable development of urban residential districts and public health. However, the rapid growth of high-rise urban residential districts leads to low wind velocity environments in summer. This study examines the influence of enclosure boundary patterns and lift-up design on the wind environment and proposes an optimization strategy to improve the low wind velocity environment in residential districts in summer. A typical residential district in Hangzhou was selected; the average wind velocity, calm wind zone ratio and comfortable wind zone ratio were selected as the evaluation indexes. The wind environment for different enclosure boundary patterns and lift-up designs were obtained via computational fluid dynamics (CFD) simulations. The results indicate that the pedestrian wind environment is greatly improved in residential districts by reducing the height/width of the enclosure boundary, increasing the permeability rate and adopting a lift-up design in all buildings within residential districts. A combination of permeable railings and lift-up design is recommended; this can increase the average wind velocity and the ratio of comfortable wind zones by 70% and 200%, respectively. This study provides practical guidelines for the optimization of a low wind velocity environment in Chinese high-density residential districts in summer.
Multi-Criteria Analysis for the Selection of the Optimal Mining Design Solution—A Case Study on Quarry “Tambura”
Authors: Farkaš Branimir , Hrastov Ana
Published: May 2021

Mining design is usually evaluated with different multiple-criteria decision-making (MCDM) methods when it comes to large open pit or underground ore mines, but it is not used on quarry sites. Since Croatia is mostly mining stone, the implementation of such methods in decision making of the quarry mine design is imperative but left out. In this paper, the PROMETHEE II and AHP decision-making methods are implemented on the quarry site to find out the best final quarry design contour. By implementing the MCDM methods, the best quarry model was chosen based on 22 different criteria parameters out of three final quarry designs. The chosen model is not only financially sound but also has the least environmental impact.
Effect of Symmetrically Switched Rectifier Topologies on the Frequency Regulation of Standalone Micro-Hydro Power Plants
Authors: Bory Henry , Martin Jose L. , Martinez de Alegria Iñigo , Vazquez Luis
Published: May 2021

Micro-hydro power plants (μHPPs) are a major energy source in grid-isolated zones because they do not require reservoirs and dams to be built. μHPPs operate in a standalone mode, but a continuously varying load generates voltage unbalances and frequency fluctuations which can cause long-term damage to plant components. One method of frequency regulation is the use of alternating current-alternating current (AC-AC) converters as an electronic load controller (ELC). The disadvantage of AC-AC converters is reactive power consumption with the associated decrease in both the power factor and the capacity of the alternator to deliver current. To avoid this disadvantage, we proposed two rectifier topologies combined with symmetrical switching. However, the performance of the frequency regulation loop with each topology remains unknown. Therefore, the objective of this work was to evaluate the performance of the frequency regulation loop when each topology, with a symmetrical switching form, was inserted. A MATLAB® model was implemented to simulate the frequency loop. The results from a μHPP case study in a small Cuban rural community called ‘Los Gallegos’ showed that the performance of the frequency regulation loop using the proposed topologies satisfied the standard frequency regulation and increased both the power factor and current delivery capabilities of the alternator.
Crushing of Single-Walled Corrugated Board during Converting: Experimental and Numerical Study
Authors: Garbowski Tomasz , Gajewski Tomasz , Mrówczyński Damian , Jędrzejczak Radosław
Published: May 2021

Corrugated cardboard is an ecological material, mainly because, in addition to virgin cellulose fibers also the fibers recovered during recycling process are used in its production. However, the use of recycled fibers causes slight deterioration of the mechanical properties of the corrugated board. In addition, converting processes such as printing, die-cutting, lamination, etc. cause micro-damage in the corrugated cardboard layers. In this work, the focus is precisely on the crushing of corrugated cardboard. A series of laboratory experiments were conducted, in which the different types of single-walled corrugated cardboards were pressed in a fully controlled manner to check the impact of the crush on the basic material parameters. The amount of crushing (with a precision of 10 micrometers) was controlled by a precise FEMat device, for crushing the corrugated board in the range from 10 to 70% of its original thickness. In this study, the influence of crushing on bending, twisting and shear stiffness as well as a residual thickness and edge crush resistance of corrugated board was investigated. Then, a procedure based on a numerical homogenization, taking into account a partial delamination in the corrugated layers to determine the degraded material stiffness was proposed. Finally, using the empirical-numerical method, a simplified calculation model of corrugated cardboard was derived, which satisfactorily reflects the experimental results.
Usage of the Pareto Fronts as a Tool to Select Data in the Forecasting Process—A Short-Term Electric Energy Demand Forecasting Case
Authors: Sabat Michał , Baczyński Dariusz
Published: May 2021

Transmission, distribution, and micro-grid system operators are struggling with the increasing number of renewables and the changing nature of energy demand. This necessitates the use of prognostic methods based on ever shorter time series. This study depicted an attempt to develop an appropriate method by introducing a novel forecasting model based on the idea to use the Pareto fronts as a tool to select data in the forecasting process. The proposed model was implemented to forecast short-term electric energy demand in Poland using historical hourly demand values from Polish TSO. The study rather intended on implementing the range of different approaches—scenarios of Pareto fronts usage than on a complex evaluation of the obtained results. However, performance of proposed models was compared with a few benchmark forecasting models, including naïve approach, SARIMAX, kNN, and regression. For two scenarios, it has outperformed all other models by minimum 7.7%.
Future of Sustainable Management of Energy Companies in Terms of Attitudes and Preferences of the Younger Generation
Authors: Pabian Arnold , Bilińska-Reformat Katarzyna , Pabian Barbara
Published: May 2021

The future of the energy sector depends on the younger generation. The paper presents the results of the study, the aim of which was to determine to what extent younger generation is pro-ecological and pro-social, and whether they will include pro-ecological and pro-social activities in the management of energy companies. It is especially important to implement sustainable management in the energy sector. The study found that only 33.9% of young people are highly pro-ecological and 28.6% highly pro-social. As many as 83.0% of the younger generation show low and medium interest in environmental protection. Declarations of young people concerning high degree of inclusion of pro-ecological and pro-social activities in management are at the level of 49.9% and 58.1%. However, in many cases, these intentions do not coincide with the high pro-ecological and pro-social attitude of young people. This means that their future activity for sustainable management may be low. According to the survey, the younger generation to a large extent is not prepared to continue efforts for sustainable development in the future in the energy companies.