bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular and Circulating Biomarkers of Brain Tumors
Authors: Jelski Wojciech , Mroczko Barbara
Published: June 2021

Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain tumors release molecular information into the circulation. Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a substitute for tumor tissue. Tumor-derived biomarkers include nucleic acids, proteins, and tumor-derived extracellular vesicles that accumulate in blood or cerebrospinal fluid. In recent years, circulating tumor cells have also been identified in the blood of glioblastoma patients. In this review of the literature, the authors highlight the significance, regulation, and prevalence of molecular biomarkers such as O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor, and isocitrate dehydrogenase. Herein, we critically review the available literature on plasma circulating tumor cells (CTCs), cell-free tumors (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), and circulating extracellular vesicles (EVs) for the diagnosis and monitoring of brain tumor. Currently available markers have significant limitations. While much research has been conductedon these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature.
Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG2T(G3T)3] and Its Derivatives with an Abasic Site Replacing Single Thymidine
Authors: Virgilio Antonella , Benigno Daniela , Pecoraro Annalisa , Russo Annapina , Russo Giulia , Esposito Veronica , Galeone Aldo
Published: June 2021

In this paper, we report our investigations on five T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to the central core of stacked guanosines in biological activity. The collected NMR (Nuclear Magnetic Resonance), CD (Circular Dichroism), and PAGE (Polyacrylamide Gel Electrophoresis) data strongly suggest that all of them adopt G-quadruplex (G4) structures strictly similar to that of the parent aptamer with the ability to fold into a dimeric structure composed of two identical G-quadruplexes, each characterized by parallel strands, three all-anti-G-tetrads and four one-thymidine loops (one bulge and three propeller loops). Furthermore, their antiproliferative (MTT assay) and anti-motility (wound healing assay) properties against lung and colorectal cancer cells were tested. Although all of the oligodeoxynucleotides (ODNs) investigated here exhibited anti-proliferative activity, the unmodified T30175 aptamer showed the greatest effect on cell growth, suggesting that both its characteristic folding in dimeric form and its presence in the sequence of all thymidines are crucial elements for antiproliferative activity. This straightforward approach is suitable for understanding the critical requirements of the G-quadruplex structures that affect antiproliferative potential and suggests its application as a starting point to facilitate the reasonable development of G-quadruplexes with improved anticancer properties.
Peptide/β-Peptoid Hybrids with Ultrashort PEG-Like Moieties: Effects on Hydrophobicity, Antibacterial Activity and Hemolytic Properties
Authors: Frederiksen Nicki , Louka Stavroula , Mudaliar Chirag , Domraceva Ilona , Kreicberga Agrita , Pugovics Osvalds , Żabicka Dorota , Tomczak Magdalena , Wygoda Weronika , Björkling Fredrik , Franzyk Henrik
Published: June 2021

PEGylation of antimicrobial peptides as a shielding tool that increases stability toward proteolytic degradation typically leads to concomitant loss of activity, whereas incorporation of ultrashort PEG-like amino acids (sPEGs) remains essentially unexplored. Here, modification of a peptide/β-peptoid hybrid with sPEGs was examined with respect to influence on hydrophobicity, antibacterial activity and effect on viability of mammalian cells for a set of 18 oligomers. Intriguingly, the degree of sPEG modification did not significantly affect hydrophobicity as measured by retention in reverse-phase HPLC. Antibacterial activity against both wild-type and drug-resistant strains of Escherichia coli and Acinetobacter baumannii (both Gram-negative pathogens) was retained or slightly improved (MICs in the range 2–16 µg/mL equal to 0.7–5.2 µM). All compounds in the series exhibited less than 10% hemolysis at 400 µg/mL. While the number of sPEG moieties appeared not to be clearly correlated with hemolytic activity, a trend toward slightly increased hemolytic activity was observed for analogues displaying the longest sPEGs. In contrast, within a subseries the viability of HepG2 liver cells was least affected by analogues displaying the longer sPEGs (with IC50 values of ~1280 µg/mL) as compared to most other analogues and the parent peptidomimetic (IC50 values in the range 330–800 µg/mL).
Taking a Step Back: Insights into the Mechanisms Regulating Gut Epithelial Dedifferentiation
Authors: Ouladan Shaida , Gregorieff Alex
Published: June 2021

Despite the environmental constraints imposed upon the intestinal epithelium, this tissue must perform essential functions such as nutrient absorption and hormonal regulation, while also acting as a critical barrier to the outside world. These functions depend on a variety of specialized cell types that are constantly renewed by a rapidly proliferating population of intestinal stem cells (ISCs) residing at the base of the crypts of Lieberkühn. The niche components and signals regulating crypt morphogenesis and maintenance of homeostatic ISCs have been intensely studied over the last decades. Increasingly, however, researchers are turning their attention to unraveling the mechanisms driving gut epithelial regeneration due to physical damage or infection. It is now well established that injury to the gut barrier triggers major cell fate changes, demonstrating the highly plastic nature of the gut epithelium. In particular, lineage tracing and transcriptional profiling experiments have uncovered several injury-induced stem-cell populations and molecular markers of the regenerative state. Despite the progress achieved in recent years, several questions remain unresolved, particularly regarding the mechanisms driving dedifferentiation of the gut epithelium. In this review, we summarize the latest studies, primarily from murine models, that define the regenerative processes governing the gut epithelium and discuss areas that will require more in-depth investigation.
The Arcuate Nucleus of the Hypothalamus and Metabolic Regulation: An Emerging Role for Renin–Angiotensin Pathways
Authors: Mehay Darren , Silberman Yuval , Arnold Amy C.
Published: June 2021

Obesity is a chronic state of energy imbalance that represents a major public health problem and greatly increases the risk for developing hypertension, hyperglycemia, and a multitude of related pathologies that encompass the metabolic syndrome. The underlying mechanisms and optimal treatment strategies for obesity, however, are still not fully understood. The control of energy balance involves the actions of circulating hormones on a widely distributed network of brain regions involved in the regulation of food intake and energy expenditure, including the arcuate nucleus of the hypothalamus. While obesity is known to disrupt neurocircuits controlling energy balance, including those in the hypothalamic arcuate nucleus, the pharmacological targeting of these central mechanisms often produces adverse cardiovascular and other off-target effects. This highlights the critical need to identify new anti-obesity drugs that can activate central neurocircuits to induce weight loss without negatively impacting blood pressure control. The renin–angiotensin system may provide this ideal target, as recent studies show this hormonal system can engage neurocircuits originating in the arcuate nucleus to improve energy balance without elevating blood pressure in animal models. This review will summarize the current knowledge of renin–angiotensin system actions within the arcuate nucleus for control of energy balance, with a focus on emerging roles for angiotensin II, prorenin, and angiotensin-(1–7) pathways.
Peculiarities of Neurostimulation by Intense Nanosecond Pulsed Electric Fields: How to Avoid Firing in Peripheral Nerve Fibers
Authors: Kim Vitalii , Gudvangen Emily , Kondratiev Oleg , Redondo Luis , Xiao Shu , Pakhomov Andrei G.
Published: June 2021

Intense pulsed electric fields (PEF) are a novel modality for the efficient and targeted ablation of tumors by electroporation. The major adverse side effects of PEF therapies are strong involuntary muscle contractions and pain. Nanosecond-range PEF (nsPEF) are less efficient at neurostimulation and can be employed to minimize such side effects. We quantified the impact of the electrode configuration, PEF strength (up to 20 kV/cm), repetition rate (up to 3 MHz), bi- and triphasic pulse shapes, and pulse duration (down to 10 ns) on eliciting compound action potentials (CAPs) in nerve fibers. The excitation thresholds for single unipolar but not bipolar stimuli followed the classic strength–duration dependence. The addition of the opposite polarity phase for nsPEF increased the excitation threshold, with symmetrical bipolar nsPEF being the least efficient. Stimulation by nsPEF bursts decreased the excitation threshold as a power function above a critical duty cycle of 0.1%. The threshold reduction was much weaker for symmetrical bipolar nsPEF. Supramaximal stimulation by high-rate nsPEF bursts elicited only a single CAP as long as the burst duration did not exceed the nerve refractory period. Such brief bursts of bipolar nsPEF could be the best choice to minimize neuromuscular stimulation in ablation therapies.
Differential Effects of Halofuginone Enantiomers on Muscle Fibrosis and Histopathology in Duchenne Muscular Dystrophy
Authors: Mordechay Sharon , Smullen Shaun , Evans Paul , Genin Olga , Pines Mark , Halevy Orna
Published: June 2021

Progressive loss of muscle and muscle function is associated with significant fibrosis in Duchenne muscular dystrophy (DMD) patients. Halofuginone, an analog of febrifugine, prevents fibrosis in various animal models, including those of muscular dystrophies. Effects of (+)/(−)-halofuginone enantiomers on motor coordination and diaphragm histopathology in mdx mice, the mouse model for DMD, were examined. Four-week-old male mice were treated with racemic halofuginone, or its separate enantiomers, for 10 weeks. Controls were treated with saline. Racemic halofuginone-treated mice demonstrated better motor coordination and balance than controls. However, (+)-halofuginone surpassed the racemic form’s effect. No effect was observed for (−)-halofuginone, which behaved like the control. A significant reduction in collagen content and degenerative areas, and an increase in utrophin levels were observed in diaphragms of mice treated with racemic halofuginone. Again, (+)-halofuginone was more effective than the racemic form, whereas (−)-halofuginone had no effect. Both racemic and (+)-halofuginone increased diaphragm myofiber diameters, with no effect for (−)-halofuginone. No effects were observed for any of the compounds tested in an in-vitro cell viability assay. These results, demonstrating a differential effect of the halofuginone enantiomers and superiority of (+)-halofuginone, are of great importance for future use of (+)-halofuginone as a DMD antifibrotic therapy.
Metformin Protects against Radiation-Induced Acute Effects by Limiting Senescence of Bronchial-Epithelial Cells
Authors: Hansel Christine , Barr Samantha , Schemann Alina V. , Lauber Kirsten , Hess Julia , Unger Kristian , Zitzelsberger Horst , Jendrossek Verena , Klein Diana
Published: June 2021

Radiation-induced damage to normal lung parenchyma remains a dose-limiting factor in thorax-associated radiotherapy (RT). Severe early and late complications with lungs can increase the risk of morbidity in cancer patients after RT. Herein, senescence of lung epithelial cells following RT-induced cellular stress, or more precisely the respective altered secretory profile, the senescence-associated secretory phenotype (SASP), was suggested as a central process for the initiation and progression of pneumonitis and pulmonary fibrosis. We previously reported that abrogation of certain aspects of the secretome of senescent lung cells, in particular, signaling inhibition of the SASP-factor Ccl2/Mcp1 mediated radioprotection especially by limiting endothelial dysfunction. Here, we investigated the therapeutic potential of a combined metformin treatment to protect normal lung tissue from RT-induced senescence and associated lung injury using a preclinical mouse model of radiation-induced pneumopathy. Metformin treatment efficiently limited RT-induced senescence and SASP expression levels, thereby limiting vascular dysfunctions, namely increased vascular permeability associated with increased extravasation of circulating immune and tumor cells early after irradiation (acute effects). Complementary in vitro studies using normal lung epithelial cell lines confirmed the senescence-limiting effect of metformin following RT finally resulting in radioprotection, while fostering RT-induced cellular stress of cultured malignant epithelial cells accounting for radiosensitization. The radioprotective action of metformin for normal lung tissue without simultaneous protection or preferable radiosensitization of tumor tissue might increase tumor control probabilities and survival because higher radiation doses could be used.
Molecular Landscape of Vulvar Squamous Cell Carcinoma
Authors: Carreras-Dieguez Núria , Guerrero José , Rodrigo-Calvo Maria Teresa , Ribera-Cortada Inmaculada , Trias Isabel , Jares Pedro , López del Campo Ricardo , Saco Adela , Munmany Meritxell , Marimon Lorena , Ferrando Melania , Vega Naiara , del Pino Marta , Torné Aureli , Ordi Jaume , Rakislova Natalia
Published: June 2021

Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with dual pathogenesis, Human papillomavirus (HPV)-associated and HPV-independent, with a poorly explored molecular landscape. We aimed to summarize the findings of the series analyzing molecular hallmarks of this neoplasm. In January 2021, we conducted a comprehensive literature search using Pubmed Medline and Scopus to identify publications focused on genomic profiling of VSCC. Observational studies, including both prospective and retrospective designs, evaluating molecular alterations in VSCC were deemed eligible. A total of 14 studies analyzing 749 VSCC were identified. The study series were heterogeneous in HPV testing and sequencing strategies, included small sets of tumors and cancer genes, and commonly lacked survival analysis. Only one extensive targeted next-generation sequencing-based study comprised a large cohort of 280 VSCC. The mutated genes, their number, and frequencies were highly variable between the series. Overall, TP53 and CDKN2A, followed by PIK3CA, HRAS, and PTEN, were the most frequently studied and mutated genes. Mutations involved in the PI3K/AKT/mTOR pathway, including TP53, HRAS, KRAS, and PIK3CA, have been consistently reported across the studies. However, the role of individual mutations or pathways in the development of VSCC remains unclear. In conclusion, heterogeneity and the small sample size of available molecular series contribute to a limited view of the molecular landscape of VSCC. Large-scale genome- or exome-wide studies with robust HPV testing are necessary to improve the molecular characterization of VSCC.
Profile of miR-23 Expression and Possible Role in Regulation of Glutamic Acid Decarboxylase during Postnatal Retinal Development
Authors: Pöstyéni Etelka , Kovács-Valasek Andrea , Urbán Péter , Czuni Lilla , Sétáló György , Fekete Csaba , Gabriel Robert
Published: June 2021

As neurotransmitter, GABA is fundamental for physiological processes in the developing retina. Its synthesis enzymes are present during retinal development, although the molecular regulatory mechanisms behind the changes in expression are not entirely understood. In this study, we revealed the expression patterns of glutamic acid decarboxylase 67(GAD67) and its coding gene (GAD1) and its potential miRNA-dependent regulation during the first three postnatal weeks in rat retina. To gain insight into the molecular mechanisms, miRNA-sequencing supported by RT-qPCR and in situ hybridization were carried out. GAD1 expression shows an increasing tendency, peaking at P15. From the in silico-predicted GAD1 targeting miRNAs, only miR-23 showed similar expression patterns, which is a known regulator of GAD1 expression. For further investigation, we made an in situ hybridization investigation where both GAD67 and miR-23 also showed lower expression before P7, with the intensity of expression gradually increasing until P21. Horizontal cells at P7, amacrine cells at P15 and P21, and some cells in the ganglion cell layer at several time points were double labelled with miR-23 and GAD67. Our results highlight the complexity of these regulatory networks and the possible role of miR-23 in the regulation of GABA synthesizing enzyme expression during postnatal retina development.
Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells
Authors: Cheng Shu-Yu , Chen Nan-Fu , Wen Zhi-Hong , Yao Zhi-Kang , Tsui Kuan-Hao , Kuo Hsiao-Mei , Chen Wu-Fu
Published: June 2021

Glioblastoma multiforme (GBM) is a malignant primary brain tumor. The 5-year relative survival rate of patients with GBM remains <30% on average despite aggressive treatments, and secondary therapy fails in 90% of patients. In chemotherapeutic failure, detoxification proteins are crucial to the activity of chemotherapy drugs. Usually, glutathione S-transferase (GST) superfamily members act as detoxification enzymes by activating xenobiotic metabolites through conjugation with glutathione in healthy cells. However, some overexpressed GSTs not only increase GST activity but also trigger chemotherapy resistance and tumorigenesis-related signaling transductions. Whether GSTM3 is involved in GBM chemoresistance remains unclear. In the current study, we found that T98G, a GBM cell line with pre-existing temozolomide (TMZ) resistance, has high glycolysis and GSTM3 expression. GSTM3 knockdown in T98G decreased glycolysis ability through lactate dehydrogenase A activity reduction. Moreover, it increased TMZ toxicity and decreased invasion ability. Furthermore, we provide next-generation sequencing–based identification of significantly changed messenger RNAs of T98G cells with GSTM3 knockdown for further research. GSTM3 was downregulated in intrinsic TMZ-resistant T98G with a change in the expression levels of some essential glycolysis-related genes. Thus, GSTM3 was associated with glycolysis in chemotherapeutic resistance in T98G cells. Our findings provide new insight into the GSTM3 mechanism in recurring GBM.
RAB10 Interacts with ABCB4 and Regulates Its Intracellular Traffic
Authors: Ben Saad Amel , Vauthier Virginie , Lapalus Martine , Mareux Elodie , Bennana Evangéline , Durand-Schneider Anne-Marie , Bruneau Alix , Delaunay Jean-Louis , Gonzales Emmanuel , Housset Chantal , Aït-Slimane Tounsia , Guillonneau François , Jacquemin Emmanuel , Falguières Thomas
Published: June 2021

ABCB4 (ATP-binding cassette subfamily B member 4) is an ABC transporter expressed at the canalicular membrane of hepatocytes where it ensures phosphatidylcholine secretion into bile. Genetic variations of ABCB4 are associated with several rare cholestatic diseases. The available treatments are not efficient for a significant proportion of patients with ABCB4-related diseases and liver transplantation is often required. The development of novel therapies requires a deep understanding of the molecular mechanisms regulating ABCB4 expression, intracellular traffic, and function. Using an immunoprecipitation approach combined with mass spectrometry analyses, we have identified the small GTPase RAB10 as a novel molecular partner of ABCB4. Our results indicate that the overexpression of wild type RAB10 or its dominant-active mutant significantly increases the amount of ABCB4 at the plasma membrane expression and its phosphatidylcholine floppase function. Contrariwise, RAB10 silencing induces the intracellular retention of ABCB4 and then indirectly diminishes its secretory function. Taken together, our findings suggest that RAB10 regulates the plasma membrane targeting of ABCB4 and consequently its capacity to mediate phosphatidylcholine secretion.
Juvenile Idiopathic Arthritis-Associated Chronic Uveitis: Recent Therapeutic Approaches
Authors: Quartier Pierre
Published: June 2021

Pediatric patients with early onset (before the age of 6 years), antinuclear antibody positive, oligoarticular or polyarticular juvenile idiopathic arthritis (JIA), and some children with no arthritis may develop chronic, anterior uveitis. Recent recommendations insist on the need to perform slit lamp examination every 3 months for at least 5 years in early onset JIA patients in order to diagnose uveitis before complications develop. Local steroid therapy is usually the first-line treatment. However, in patients requiring steroid eye drops for several months, systemic immunomodulatory therapy is indicated. Methotrexate (MTX) is then prescribed in most cases; however, some patients also need anti-tumor necrosis factor alpha monoclonal antibody therapy and, in some cases, other biologics to control uveitis and avoid long-term ocular damage. Expert ophthalmologists and pediatricians must be involved in taking care of such patients. Immunomodulatory treatment must not be too easily interrupted and may even be intensified in some cases, particularly if there is a need for optimal disease control before ophthalmologic surgery. In good responders to MTX and/or biologics, treatment must be maintained at least 1 year, possibly even 2 years after achieving remission before tapering treatment intensity.
Usefulness of Cerebral Oximetry in TBI by NIRS
Authors: Barud Małgorzata , Dabrowski Wojciech , Siwicka-Gieroba Dorota , Robba Chiara , Bielacz Magdalena , Badenes Rafael
Published: June 2021

Measurement of cerebral oximetry by near-infrared spectroscopy provides continuous and non-invasive information about the oxygen saturation of haemoglobin in the central nervous system. This is especially important in the case of patients with traumatic brain injuries. Monitoring of cerebral oximetry in these patients could allow for the diagnosis of inadequate cerebral oxygenation caused by disturbances in cerebral blood flow. It could enable identification of episodes of hypoxia and cerebral ischemia. Continuous bedside measurement could facilitate the rapid diagnosis of intracranial bleeding or cerebrovascular autoregulation disorders and accelerate the implementation of treatment. However, it should be remembered that the method of monitoring cerebral oximetry by means of near-infrared spectroscopy also has its numerous limitations, resulting mainly from its physical properties. This paper summarizes the usefulness of monitoring cerebral oximetry by near-infrared spectroscopy in patients with traumatic brain injury, taking into account the advantages and the disadvantages of this technique.
Bilateral Choanal Atresia and Endoscopic Surgery: A Chance for CHARGE Patients
Authors: Baldovin Maria , Cazzador Diego , Zanotti Claudia , Frasson Giuliana , Saratziotis Athanasios , Pagella Fabio , Pelucchi Stefano , Emanuelli Enzo
Published: June 2021

Bilateral choanal atresia (CA) is a rare congenital malformation frequently associated with other anomalies. CHARGE association is closely linked to bilateral CA. The aim of this study was to describe the outcomes of the endoscopic repair in bilateral CA, and to assess the role of postoperative nasal stenting in two cohorts of CHARGE-associated and non-syndromic CA. Thirty-nine children were retrospectively analyzed (16 patients had CHARGE-associated CA). The rate of postoperative neochoanal restenosis was 31.3% in the CHARGE population, and 47.8% in the non-syndromic CA cohort. Data on postoperative synechiae and granulation tissue formation, need for endonasal toilette and dilation procedures, and number of procedures per patient were presented. Stent positioning led to a higher number of postoperative dilation procedures per patient in the non-syndromic cohort (p = 0.018), and to a higher rate of restenosis both in the CHARGE-associated, and non-syndromic CA populations. Children with CHARGE-associated and non-syndromic bilateral CA benefitted from endonasal endoscopic CA correction. The postoperative application of an endonasal stent should be carefully evaluated.
A Review on Filament Materials for Fused Filament Fabrication
Authors: Dey Arup , Roan Eagle Isnala Nanjin , Yodo Nita
Published: June 2021

Fused filament fabrication (FFF) is one of the most popular additive manufacturing (AM) processes that utilize thermoplastic polymers to produce three-dimensional (3D) geometry products. The FFF filament materials have a significant role in determining the properties of the final part produced, such as mechanical properties, thermal conductivity, and electrical conductivity. This article intensively reviews the state-of-the-art materials for FFF filaments. To date, there are many different types of FFF filament materials that have been developed. The filament materials range from pure thermoplastics to composites, bioplastics, and composites of bioplastics. Different types of reinforcements such as particles, fibers, and nanoparticles are incorporated into the composite filaments to improve the FFF build part properties. The performance, limitations, and opportunities of a specific type of FFF filament will be discussed. Additionally, the challenges and requirements for filament production from different materials will be evaluated. In addition, to provide a concise review of fundamental knowledge about the FFF filament, this article will also highlight potential research directions to stimulate future filament development. Finally, the importance and scopes of using bioplastics and their composites for developing eco-friendly filaments will be introduced.
Safety Barrier Management: Risk-Based Approach for the Oil and Gas Sector
Authors: Hosseinnia Davatgar Behnaz , Paltrinieri Nicola , Bubbico Roberto
Published: June 2021

In the Oil and Gas sector, risk assessment and management have always been critical due to the possibility of significant accidents associated with the presence of large amounts of flammable hydrocarbons. Methods to provide accurate and reliable risk analysis for an oil platform usually focus on critical equipment and identify causes and consequences of loss of containment. Safety barriers are important elements of such accident scenarios, aiming to reduce the frequency of unwanted events. Estimating the performance of safety barriers is essential for the prevention of major accidents. This work first focuses on the application of risk-based analysis on the process area equipment of the floating platform Goliat. Such an approach is secondly extended to the most relevant safety systems to prevent fires and explosions and consequent catastrophic domino effects. An additional challenge resides in the fact that safety barriers cannot always be classified as equipment, as they are often composed of operational and organizational elements. Through the application of the ARAMIS Project (Accidental Risk Assessment Methodology for Industries in the Context of the Seveso II Directive) results, the frequency modification methodology based on TEC2O (TEChnical Operational and Organizational factors) and the REWI (Resilience-based Early Warning Indicators) method, it is possible to quantify the safety barrier performance, to reduce the frequency of unwanted events. While conducting this study, the importance of the management factor in combination with technical and technological aspects of safety barrier performance was analyzed. Starting from the initial project conditions, applying worsening technical factors, and simulating n organizational management for the safety systems, it is possible to quantify the performance of the safety barriers, highlighting the importance of management factors in terms of prevention of major accidents, and to assess the dynamic risk for the overall plant.
Effect of the Diameter of Pressure-Balance Pipe on Axial Hydraulic Thrust
Authors: Zhang Fei , Lv Yue , Gui Zhonghua , Wang Zhengwei
Published: June 2021

The axial hydraulic thrust has great influence on the safety and stability of a pump turbine. A common way to balance hydraulic thrust is to install a pressure-balance pipe, and the change in pipe diameter is one of the important factors affecting axial hydraulic thrust. In this paper, the influence of the diameter changes in a pressure-balance pipe on axial hydraulic thrust of a pump turbine, plus the seal clearance flow, is studied and analyzed under three work conditions, i.e., 100%, 75%, and 50% loads. It is found that under 100% and 75% load conditions, the axial hydraulic thrust increases vertically with the increase in pipe diameter; whereas, under 50% load condition, the axial hydraulic thrust increases first and then decreases with the increase in pipe diameter. The results aim to give guidelines for the choice of pressure-balance pipe diameters and to control the axial hydraulic thrust of a pumped-storage power station, so that the hydraulic excitation force can be better matched with the hydraulic mechanism.
Micafungin-Induced Cell Wall Damage Stimulates Morphological Changes Consistent with Microcycle Conidiation in Aspergillus nidulans
Authors: Reese Samantha , Chelius Cynthia , Riekhof Wayne , Marten Mark R. , Harris Steven D.
Published: June 2021

Fungal cell wall receptors relay messages about the state of the cell wall to the nucleus through the Cell Wall Integrity Signaling (CWIS) pathway. The ultimate role of the CWIS pathway is to coordinate repair of cell wall damage and to restore normal hyphal growth. Echinocandins such as micafungin represent a class of antifungals that trigger cell wall damage by affecting synthesis of β-glucans. To obtain a better understanding of the dynamics of the CWIS response and its multiple effects, we have coupled dynamic transcriptome analysis with morphological studies of Aspergillus nidulans hyphae in responds to micafungin. Our results reveal that expression of the master regulator of asexual development, BrlA, is induced by micafungin exposure. Further study showed that micafungin elicits morphological changes consistent with microcycle conidiation and that this effect is abolished in the absence of MpkA. Our results suggest that microcycle conidiation may be a general response to cell wall perturbation which in some cases would enable fungi to tolerate or survive otherwise lethal damage.
The Clinical Features and Prognostic Factors for Treatment Outcomes of Dematiaceous Fungal Keratitis over 9 Years at a Tertiary Eye Care in Northern Thailand
Authors: Tangmonkongvoragul Chulaluck , Chokesuwattanaskul Susama , Tananuvat Napaporn , Pongpom Monsicha , Upaphong Phit , Saysithidej Sinthirath , Niparugs Muanploy , Chongkae Siriporn
Published: June 2021

Dematiaceous fungal keratitis is an important etiology of visual loss, particularly in an agricultural society. From a retrospective review of medical records from 2012 to 2020, 50 keratitis cases of cultured-positive for dematiaceous fungi were presented at a tertiary care hospital in Northern Thailand. The study aimed to identify the isolated causative dematiaceous species using the PCR technique and to explore their related clinical features, including treatment prognoses. Sequencing of the amplified D1/D2 domains and/or ITS region were applied and sequenced. Of the 50 dematiaceous fungal keratitis cases, 41 patients were males (82%). In most cases, the onset happened during the monsoon season (June to September) (48%). The majority of the patients (72%) had a history of ocular trauma from an organic foreign body. The most common species identified were Lasiodiplodia spp. (19.35%), followed by Cladosporium spp. and Curvularia spp. (12.90% each). About half of the patients (52%) were in the medical failure group where surgical intervention was required. In summary, ocular trauma from an organic foreign body was the major risk factor of dematiaceous fungal keratitis in Northern Thailand. The brown pigmentation could be observed in only 26%. Significant prognostic factors for medical failure were visual acuity at presentation, area of infiltrate, depth of the lesions, and hypopyon.
Is HSD17B13 Genetic Variant a Protector for Liver Dysfunction? Future Perspective as a Potential Therapeutic Target
Authors: Motomura Takashi , Amirneni Sriram , Diaz-Aragon Ricardo , Faccioli Lanuza , Malizio Michelle , Coard Michael , Kocas-Kilicarslan Zehra , Frau Carla , Haep Nils , Ostrowska Alina , Florentino Rodrigo , Soto-Gutierrez Alejandro
Published: June 2021

As diet and lifestyle have changed, fatty liver disease (FLD) has become more and more prevalent. Many genetic risk factors, such as variants of PNPLA3, TM6SF2, GCKR, and MBOAT7, have previously been uncovered via genome wide association studies (GWAS) to be associated with FLD. In 2018, a genetic variant (rs72613567, T > TA) of hydroxysteroid 17-β dehydrogenase family 13 (HSD17B13) was first associated with a lower risk of developing alcoholic liver disease and non-alcoholic fatty liver disease (NAFLD) in minor allele carriers. Other HSD17B13 variants were also later linked with either lower inflammation scores among NAFLD patients or protection against NAFLD (rs6834314, A > G and rs9992651, G > A) respectively. HSD17B13 is a lipid droplet-associated protein, but its function is still ambiguous. Compared to the other genetic variants that increase risk for FLD, HSD17B13 variants serve a protective role, making this gene a potential therapeutic target. However, the mechanism by which these variants reduce the risk of developing FLD is still unclear. Because studies in cell lines and mouse models have produced conflicting results, human liver tissue modeling using induced pluripotent stem cells may be the best way to move forward and solve this mystery.
Factors Influencing County Commissioners’ Decisions about Burn Bans in the Southern Plains, USA
Authors: McDaniel Thomas W. , Wonkka Carissa L. , Treadwell Morgan L. , Kreuter Urs P.
Published: June 2021

Woody plant encroachment in North American rangelands has led to calls for greater use of prescribed fire to reduce fuel loads and restore grazing productivity and grassland biodiversity. However, the use of prescribed fire during periods when woody plant mortality is maximized has often been limited by temporary restrictions on outdoor burning enacted by regional or local governmental entities. This study reports the results of a survey assessing the familiarity with and attitudes toward prescribed fire in Texas and Oklahoma, USA, of officials tasked with implementing restrictions on outdoor burning and how these attitudes influence their decisions. Most responding officials considered prescribed fire to be a safe and beneficial land management tool that should be used more frequently. Self-reported familiarity with prescribed fire was the most significant explanatory variable for this attitude. Further, familiarity with prescribed fire was influenced by respondent participation in or being invited to participate in a prescribed fire. Such invitations came mostly from private landowners. Landowners wishing to use prescribed fire may benefit from building trust with local officials by demonstrating they are qualified to conduct such fires safely. This could help reduce the frequency of burn restrictions and may increase the likelihood that officials will grant burn ban exemptions to qualified burn managers. Additionally, because officials’ primary sources of prescribed fire information were reported to be local fire departments and emergency services, educating those entities about the benefits of prescribed fire for reducing wildfire risks could help reduce pressure on officials to enact or maintain burning restrictions. These findings highlight opportunities for reducing the frequency of burning restrictions, increasing opportunities for land managers to effectively halt or reverse woody plant encroachment.
Assessing the Role of Kettle Holes for Providing and Connecting Amphibian Habitats in Agricultural Landscapes
Authors: Savić Biljana , Evgrafova Alevtina , Donmez Cenk , Vasić Filip , Glemnitz Michael , Paul Carsten
Published: June 2021

The intensification of agriculture over the last few decades has caused habitat loss, which poses a significant threat to the survival of populations and species. Where habitats are connected, populations may escape the destruction of their habitat by migrating to another one. Consequently, the functional connectivity of landscapes has become an important focus for species conservation. Kettle holes are hotspots of biodiversity that provide suitable conditions for wildlife species (i.e., amphibians, insects, aquatic plants) and contribute to landscape heterogeneity. They are also considered to function as stepping stone habitats that contribute to habitat connectivity. This study assesses the contribution of kettle holes for (i) habitat provision and (ii) the functional connectivity of three amphibian species with different movement ranges, and (iii) the study identifies areas where the creation of stepping stone biotopes could improve functional connectivity. The contribution of kettle holes was assessed using GIS-based clustering within three research areas in Germany. It was found that the importance of kettle holes for providing amphibian habitats in the three studied areas was equal to or higher than that of other wetland habitats. The state of functional connectivity and the contribution of kettle holes differed strongly depending on the species’ range. For the short-range species, landscapes were highly fragmented, and the contribution of kettle holes was much smaller than that of corridor habitats. For the long-range species, all habitats suited for amphibian reproduction were connected, and the contribution of kettle holes was similar to that of corridor habitats. However, the contribution of both was mostly redundant. Overall, the results showed that kettle holes play a crucial role in habitat provision and function as important stepping stone biotopes in agricultural landscapes. The clustering method applied in this study provides a simple tool for landscape planning and environmental protection agencies, which can be easily adapted to analyze functional connectivity and habitat interactions for different species or landscapes.
Site-Specific and Common Prostate Cancer Metastasis Genes as Suggested by Meta-Analysis of Gene Expression Data
Authors: Samaržija Ivana
Published: June 2021

Anticancer therapies mainly target primary tumor growth and little attention is given to the events driving metastasis formation. Metastatic prostate cancer, in comparison to localized disease, has a much worse prognosis. In the work presented here, groups of genes that are common to prostate cancer metastatic cells from bones, lymph nodes, and liver and those that are site-specific were delineated. The purpose of the study was to dissect potential markers and targets of anticancer therapies considering the common characteristics and differences in transcriptional programs of metastatic cells from different secondary sites. To that end, a meta-analysis of gene expression data of prostate cancer datasets from the GEO database was conducted. Genes with differential expression in all metastatic sites analyzed belong to the class of filaments, focal adhesion, and androgen receptor signaling. Bone metastases undergo the largest transcriptional changes that are highly enriched for the term of the chemokine signaling pathway, while lymph node metastasis show perturbation in signaling cascades. Liver metastases change the expression of genes in a way that is reminiscent of processes that take place in the target organ. Survival analysis for the common hub genes revealed involvements in prostate cancer prognosis and suggested potential biomarkers.
Study on the Influence of Nanosilica Sol on the Hydration Process of Different Kinds of Cement and Mortar Properties
Authors: Liu Haibao , Li Qiuyi , Su Dunlei , Yue Gongbing , Wang Liang
Published: June 2021

Compared with nanosilica collected in a gaseous state, nanosilica sol has great economic value and application significance for improving the performance of concrete and mortar. In this study, the influence of nanosilica sol on the hydration process of different kinds of cement is studied by means of hydration heat analysis, X-ray diffraction analysis (XRD) and other methods, and the properties of mortar such as setting time, mechanical properties and porosity are also studied to characterize the influence of nanosilica sol on the macroscopic properties of mortar. The experimental results show that nanosilica sol can accelerate the hydration rate of two kinds of cement and promote the hydration reaction degree of cement, and this promotion effect increases with the increase in nanosilica sol content. At the same time, nanosilica sol can significantly shorten the setting time of the two kinds of cement, and it is more obvious with the increase in content. Excessive content of nanosilica sol will adversely affect the permeability resistance of mortar. It may be caused by the weak interval formed by nanosilica particle clusters in the mortar matrix, which can be supported by the mortar pore structure distribution test. At the same time, the influence of nanosilica sol on the hydration of the two kinds of cement is different, and the compressive strength of HBSAC cement mortar increases first and then decreases after adding nanosilica sol; However, the compressive strength of P·O 42.5 cement mortar increases gradually after adding nanometer silica sol. This shows that nanosilica sol does not effectively promote the hydration of β-C2S in high belite sulfoaluminate cement (HBSAC) mortar. Based on the above experimental results, it can be concluded that when the content of nanosilica sol is about 1%, it has the best promotion effect on the hydration of the two kinds of cement and the performance of mortar.
Effects of Pre- and Post-Carburizing Surface Modification on the Tribological and Adhesion Properties of Heat-Resistant KHR 45A Steel for Cracking Tubes
Authors: Amanov Auezhan , Choi Joo-Hyun , Pyun Young-Sik
Published: June 2021

In this study, the effects of ultrasonic nanocrystal surface modification (UNSM) technology on the tribological properties and scratch-induced adhesion behavior of a heat-resistant KHR 45A steel cracking tube, which is used for the pyrolysis process, were investigated. The main objective of this study is to investigate the effects of pre- and post-carburizing UNSM treatment on the tribological and adhesion performances of carburized domestic KHR 45A (A) steel and to compare the results with the existing carburized Kubota-made KHR 45A steel (B). A carburizing process was carried out on the polished and UNSM-treated KHR 45A steel substrates, which were cut out from the cracking tube, at 300 °C heat exposure for 300 h. The thickness of the carburizing layer was about 10 μm. UNSM technology was applied as pre- and post-carburizing surface treatment; both reduced the friction coefficient and wear rate compared to that of the carburized KHR 45A steel substrate. It was also found that the application of UNSM technology increased the critical load, which implies the improvement of adhesion behavior between the carburizing layer and the KHR steel substrate. The application of UNSM technology as pre- and post-carburizing surface treatment could help replace carburized Kubota-made KHR 45A steel (B) thanks to the improved tribological performance, enhanced scratch resistance, load bearing capacity, and adhesion of domestic KHR 45A (A) steel.
Thin Films Deposition of Ta2O5 and ZnO by E-Gun Technology on Co-Cr Alloy Manufactured by Direct Metal Laser Sintering
Authors: Băilă Diana-Irinel , Vițelaru Cătălin , Trușcă Roxana , Constantin Lidia Ruxandra , Păcurar Ancuța , Parau Constantina Anca , Păcurar Răzvan
Published: June 2021

In recent years in the dental field, new types of materials and techniques for the manufacturing of dental crowns and analog implants have been developed to improve the quality of these products. The objective of this article was to perform the surface characterization and determine the properties of Co-Cr alloy samples fabricated by the direct metal laser sintering (DMLS) process and coated by e-gun technology with thin films of Ta2O5 and ZnO. Both oxides are frequently used for dental products, in pharmacology, cosmetics, and medicine, due to their good anticorrosive, antibacterial, and photo-catalytic properties. Following the deposition of thin oxide films on the Co-Cr samples fabricated by DMLS, a very fine roughness in the order of nanometers was obtained. Thin films deposition was realized to improve the hardness and the roughness of the Co-Cr parts fabricated by the DMLS process. Surface characterization was performed using SEM-EDS, AFM, and XRD. AFM was used to determine the roughness of the samples and the nanoindentation curves were determined to establish the hardness values and modulus of elasticity.
Study of Micro/Nano Structuring and Mechanical Properties of KrF Excimer Laser Irradiated Al for Aerospace Industry and Surface Engineering Applications
Authors: Umm-i-Kalsoom  , Ali Nisar , Bashir Shazia , Alshehri Ali Mohammad , Begum Narjis
Published: June 2021

Micro/nano structuring of KrF Excimer laser-irradiated Aluminum (Al) has been correlated with laser-produced structural and mechanical changes. The effect of non-reactive Argon (Ar) and reactive Oxygen (O2) environments on the surface, structural and mechanical characteristics of nano-second pulsed laser-ablated Aluminum (Al) has been revealed. KrF Excimer laser with pulse duration 20 ns, central wavelength of 248 nm and repetition rate of was utilized for this purpose. Exposure of targets has been carried out for 0.86, 1, 1.13 and 1.27 J·cm−2 laser fluences in non-reactive (Ar) and reactive (O2) ambient environments at a pressure of 100 torr. A variety of characteristics of the irradiated targets like the morphology of the surface, chemical composition, crystallinity and nano hardness were investigated by using Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Energy Dispersive X-ray Spectroscopy (EDS), X-ray Diffractometer (XRD), Raman spectroscopy and Nanohardness tester techniques, respectively. The nature (reactive or non-reactive) and pressure of gas played an important role in modification of materials. In this study, a strong correlation is observed between the surface structuring, chemical composition, residual stress variation and the variation in hardness of Al surface after ablation in both ambient (Ar, O2). In the case of reactive environment (O2), the interplay among the deposition of laser energy and species of plasma of ambient gas enhances chemical reactivity, which causes the formation of oxides of aluminum (AlO, Al2O3) with high mechanical strength. That makes it useful in the field of process and aerospace industry as well as in surface engineering.
Magnetoelectricity in Jahn–Teller Elastics
Authors: Kaplan Michael
Published: June 2021

The magnetoelectric effects in Jahn–Teller crystals are discussed on the basis of phenomenology and microscopic theory. New magnetoelectric effects—metamagnetoelectricity—are analyzed. Formation of multiferroic crystal states as the consequence of the cooperative Jahn–Teller effect is discussed.