bluuebunny/crossref_metadata_2025 huggingface dataset:
Fire Danger Harmonization Based on the Fire Weather Index for Transboundary Events between Portugal and Spain
Authors: Alves Daniela , Almeida Miguel , Viegas Domingos Xavier , Novo Ilda , Luna M. Yolanda
Published: August 2021

Portugal and Spain have a cross-border cooperation protocol on wildfires response for a buffer strip of 25 km for each side of the border. In spite of the success of this collaboration, there are issues to be improved, since Portuguese and Spanish authorities use different methodologies to assess the daily fire danger. A methodology to harmonize fire danger and its interpretation by the Portuguese and Spanish Civil protection authorities in the transboundary buffer strip area is hereby presented. The fire danger index used is the Canadian Fire Weather Index (FWI), which requires input from meteorological data and gives an indication of fire intensity. The fire danger class is an important decision support tool for preventing and fighting wildfires. Since the meaning of FWI values change from region-to-region according to its specific characteristics, a calibration process was performed based on statistical data of the daily FWI values, the number of fires and burned area between 2005 and 2013. The results of the FWI calibration and harmonization of the data for the five danger classes minimizes the fire danger discrepancies across the border. This methodology has the potential to be reproduced in other areas.
Life Cycle Modelling of Extraction and Processing of Battery Minerals—A Parametric Approach
Authors: Manjong Nelson Bunyui , Usai Lorenzo , Burheim Odne Stokke , Strømman Anders Hammer
Published: August 2021

Sustainable battery production with low environmental footprints requires a systematic assessment of the entire value chain, from raw material extraction and processing to battery production and recycling. In order to explore and understand the variations observed in the reported footprints of raw battery materials, it is vital to re-assess the footprints of these material value chains. Identifying the causes of these variations by combining engineering and environmental system analysis expands our knowledge of the footprints of these battery materials. This article disaggregates the value chains of six raw battery materials (aluminum, copper, graphite, lithium carbonate, manganese, and nickel) and identifies the sources of variabilities (levers) for each process along each value chain. We developed a parametric attributional process-based life cycle model to explore the effect of these levers on the greenhouse gas (GHG) emissions of the value chains, expressed in kg of CO2e. The parametric life cycle inventory model is used to conduct distinct life cycle assessments (LCA) for each material value chain by varying the identified levers within defined engineering ranges. 570 distinct LCAs are conducted for the aluminum value chain, 450 for copper, 170 for graphite, 39 for lithium carbonate via spodumene, 20 for lithium carbonate via brine, 260 for manganese, and 440 for nickel. Three-dimensional representations of these results for each value chain in kg of CO2e are presented as contour plots with gradient lines illustrating the intensity of lever combinations on the GHG emissions. The results of this study convey multidimensional insights into how changes in the lever settings of value chains yield variations in the overall GHG emissions of the raw materials. Parameterization of these value chains forms a flexible and high-resolution backbone, leading towards a more reliable life cycle assessment of lithium-ion batteries (LIB).
Storage of Mutant Human SOD1 in Non-Neural Cells from the Type-1 Amyotrophic Lateral Sclerosis ratG93A Model Correlated with the Lysosomes’ Dysfunction
Authors: Bicchi Ilaria , Morena Francesco , Argentati Chiara , Nodari Laura Rota , Emiliani Carla , Gelati Maurizio , Vescovi Angelo L. , Martino Sabata
Published: August 2021

Herein, we explored the impact of the lysosome dysfunction during the progression of Amyotrophic Lateral Sclerosis type-1 (ALS1). We conducted the study in non-neural cells, primary fibroblasts (rFFFs), and bone marrow-mesenchymal stem cells (rBM-MSCs), isolated from the animal model ratG93A for ALS1 at two stages of the disease: Pre-symptomatic-stage (ALS1-PreS) and Terminal-stage (ALS1-EndS). We documented the storage of human mutant Superoxide Dismutase 1, SOD1G93A (SOD1*) in the lysosomes of ALS1-rFFFs and ALS1-rBM-MSCs and demonstrated the hallmarks of the disease in non-neural cells as in ratG93A-ALS1-tissues. We showed that the SOD1* storage is associated with the altered glycohydrolases and proteases levels in tissues and both cell types from ALS1-PreS to ALS1-EndS. Only in ALS1-rFFFs, the lysosomes lost homeostasis, enlarge drastically, and contribute to the cell metabolic damage. Contrariwise, in ALS1-rBM-MSCs, we found a negligible metabolic dysfunction, which makes these cells’ status similar to WT. We addressed this phenomenon to a safety mechanism perhaps associated with an enhanced lysosomal autophagic activity in ALS1-rBM-MSCs compared to ALS1-rFFFs, in which the lysosomal level of LC3-II/LC3I was comparable to that of WT-rFFFs. We suggested that the autophagic machinery could balance the storage of SOD1* aggregates and the lysosomal enzyme dysfunction even in ALS1-EndS-stem cells.
The NF-κB Nucleolar Stress Response Pathway
Authors: Thoms Hazel C. , Stark Lesley A.
Published: August 2021

The nuclear organelle, the nucleolus, plays a critical role in stress response and the regulation of cellular homeostasis. P53 as a downstream effector of nucleolar stress is well defined. However, new data suggests that NF-κB also acts downstream of nucleolar stress to regulate cell growth and death. In this review, we will provide insight into the NF-κB nucleolar stress response pathway. We will discuss apoptosis mediated by nucleolar sequestration of RelA and new data demonstrating a role for p62 (sequestosome (SQSTM1)) in this process. We will also discuss activation of NF-κB signalling by degradation of the RNA polymerase I (PolI) complex component, transcription initiation factor-IA (TIF-IA (RRN3)), and contexts where TIF-IA-NF-κB signalling may be important. Finally, we will discuss how this pathway is targeted by aspirin to mediate apoptosis of colon cancer cells.
The Synergistic Anti-Tumor Activity of EZH2 Inhibitor SHR2554 and HDAC Inhibitor Chidamide through ORC1 Reduction of DNA Replication Process in Diffuse Large B Cell Lymphoma
Authors: Wang Xing , Wang Dedao , Ding Ning , Mi Lan , Yu Hui , Wu Meng , Feng Feier , Hu Luni , Zhang Yime , Zhong Chao , Ye Yingying , Li Jiao , Fang Wei , Shi Yunfei , Deng Lijuan , Ying Zhitao , Song Yuqin , Zhu Jun
Published: August 2021

Background: Upregulation of H3K27me3 induced by EZH2 overexpression or somatic heterozygous mutations were implicated in lymphomagenesis. It has been demonstrated that several EZH2-target agents have notable therapeutic effects in EZH2-mutant B-cell lymphoma patients. Here we present a novel highly selective EZH2 inhibitor SHR2554 and possible combination strategy in diffuse large B-cell lymphoma (DLBCL). Methods: Cell proliferation, cell cycle and apoptosis were analyzed by CellTiter-Glo Luminescent Cell Viability Assay and flow cytometry. Western Blot was used to detect the expression of related proteins. The gene expression profiling post combination treatment was analyzed by RNA-Seq. Finally, CDX and PDX models were used to evaluate the synergistic anti-tumor effects of the combination treatment in vivo. Results: The novel EZH2 inhibitor SHR2554 inhibited proliferation and induced G1 phase arrest in EZH2-mutant DLBCL cell lines. The combination of EZH2 inhibitor SHR2554 with histone deacetylase (HDAC) inhibitor chidamide (hereafter referred to as HBI8000) exerted synergistic anti-proliferative activity in vitro and in vivo. Gene expression profile analysis revealed dramatic inhibition of the DNA replication process in combined treatment. Conclusions: SHR2554, a potent, highly selective small molecule inhibitor of EZH2, inhibited EZH2-mutant DLBCL more significantly in vitro and in vivo. The combination of HDAC inhibitor HBI8000 with EZH2 inhibitor SHR2554 exhibited dramatic anti-tumor activity in both mutant and wild-type DLBCL, which may become a potential therapeutic modality for the treatment of DLBCL patients.
Thyroid Hormone Receptor Beta as Tumor Suppressor: Untapped Potential in Treatment and Diagnostics in Solid Tumors
Authors: Davidson Cole D. , Gillis Noelle E. , Carr Frances E.
Published: August 2021

There is compelling evidence that the nuclear receptor TRβ, a member of the thyroid hormone receptor (TR) family, is a tumor suppressor in thyroid, breast, and other solid tumors. Cell-based and animal studies reveal that the liganded TRβ induces apoptosis, reduces an aggressive phenotype, decreases stem cell populations, and slows tumor growth through modulation of a complex interplay of transcriptional networks. TRβ-driven tumor suppressive transcriptomic signatures include repression of known drivers of proliferation such as PI3K/Akt pathway, activation of novel signaling such as JAK1/STAT1, and metabolic reprogramming in both thyroid and breast cancers. The presence of TRβ is also correlated with a positive prognosis and response to therapeutics in BRCA+ and triple-negative breast cancers, respectively. Ligand activation of TRβ enhances sensitivity to chemotherapeutics. TRβ co-regulators and bromodomain-containing chromatin remodeling proteins are emergent therapeutic targets. This review considers TRβ as a potential biomolecular diagnostic and therapeutic target.
CD47-SIRPα Checkpoint Inhibition Enhances Neutrophil-Mediated Killing of Dinutuximab-Opsonized Neuroblastoma Cells
Authors: Martínez-Sanz Paula , Hoogendijk Arjan J. , Verkuijlen Paul J. J. H. , Schornagel Karin , van Bruggen Robin , van den Berg Timo K. , Tytgat Godelieve A. M. , Franke Katka , Kuijpers Taco W. , Matlung Hanke L.
Published: August 2021

High-risk neuroblastoma, especially after recurrence, still has a very low survival rate. Immune checkpoint inhibitors targeting T cells have shown remarkable clinical efficacy in adult solid tumors, but their effects in pediatric cancers have been limited so far. On the other hand, targeting myeloid immune checkpoints, such as CD47-SIPRα, provide the opportunity to enhance antitumor effects of myeloid cells, including that of neutrophils, especially in the presence of cancer-opsonizing antibodies. Disialoganglioside (GD2)-expressing neuroblastoma cells targeted with anti-GD2 antibody dinutuximab are in part eradicated by neutrophils, as they recognize and bind the antibody targeted tumor cells through their Fc receptors. Therapeutic targeting of the innate immune checkpoint CD47-SIRPα has been shown to promote the potential of neutrophils as cytotoxic cells in different solid tumor indications using different cancer-targeting antibodies. Here, we demonstrate that the capacity of neutrophils to kill dinutuximab-opsonized neuroblastoma cells is also controlled by the CD47-SIRPα axis and can be further enhanced by antagonizing CD47-SIRPα interactions. In particular, CD47-SIRPa checkpoint inhibition enhanced neutrophil-mediated ADCC of dinutuximab-opsonized adrenergic neuroblastoma cells, whereas mesenchymal neuroblastoma cells may evade immune recognition by a reduction of GD2 expression. These findings provide a rational basis for targeting CD47-SIRPα interactions to potentiate dinutuximab responsiveness in neuroblastomas with adrenergic phenotype.
The Role of Bacteria in KSHV Infection and KSHV-Induced Cancers
Authors: Markazi Ashley , Meng Wen , Bracci Paige M. , McGrath Michael S. , Gao Shou-Jiang
Published: August 2021

The objective of this article is to review the current status of the bacteria-virus interplay in Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and KSHV-driven cancers. KSHV is the etiological agent of several cancers, including Kaposi’s sarcoma (KS) and primary effusion lymphoma. Due to immunosuppression, patients with KSHV are at an increased risk for bacterial infections. Moreover, among patients coinfected by HIV and KSHV, patients with KS have distinct oral microbiota compared to non-KS patients. Bacterial biomarkers associated with KSHV-driven cancers can provide insights in discerning the mechanisms of KSHV-induced oncogenesis. For example, pathogen-associated molecular patterns and bacterial products of certain bacterial species can regulate the expression of KSHV lytic and latent genes, thereby affecting viral replication and dissemination. In addition, infection with distinct opportunistic bacterial species have been associated with increased cell proliferation and tumorigenesis in KSHV-induced cancers through activation of pro-survival and -mitogenic cell signaling pathways. By elucidating the various mechanisms in which bacteria affect KSHV-associated pathogenesis, we will be able to pinpoint therapeutic targets for KSHV infection and KSHV-related cancers.
NUB1 and FAT10 Proteins as Potential Novel Biomarkers in Cancer: A Translational Perspective
Authors: Arshad Maria , Abdul Hamid Nazefah , Chan Mun Chiang , Ismail Fuad , Tan Geok Chin , Pezzella Francesco , Tan Ka-Liong
Published: August 2021

Cancer increases the global disease burden substantially, but it remains a challenge to manage it. The search for novel biomarkers is essential for risk assessment, diagnosis, prognosis, prediction of treatment response, and cancer monitoring. This paper examined NEDD8 ultimate buster-1 (NUB1) and F-adjacent transcript 10 (FAT10) proteins as novel biomarkers in cancer. This literature review is based on the search of the electronic database, PubMed. NUB1 is an interferon-inducible protein that mediates apoptotic and anti-proliferative actions in cancer, while FAT10 is a ubiquitin-like modifier that promotes cancer. The upregulated expression of both NUB1 and FAT10 has been observed in various cancers. NUB1 protein binds to FAT10 non-covalently to promote FAT10 degradation. An overexpressed FAT10 stimulates nuclear factor-kappa β, activates the inflammatory pathways, and induces the proliferation of cancer. The FAT10 protein interacts with the mitotic arrest deficient 2 protein, causing chromosomal instability and breast tumourigenesis. FAT10 binds to the proliferating cell nuclear antigen protein and inhibits the DNA damage repair response. In addition, FAT10 involves epithelial–mesenchymal transition, invasion, apoptosis, and multiplication in hepatocellular carcinoma. Our knowledge about them is still limited. There is a need to further develop NUB1 and FAT10 as novel biomarkers.
Low-Power Ultra-Small Edge AI Accelerators for Image Recognition with Convolution Neural Networks: Analysis and Future Directions
Authors: Lin Weison , Adetomi Adewale , Arslan Tughrul
Published: August 2021

Edge AI accelerators have been emerging as a solution for near customers’ applications in areas such as unmanned aerial vehicles (UAVs), image recognition sensors, wearable devices, robotics, and remote sensing satellites. These applications require meeting performance targets and resilience constraints due to the limited device area and hostile environments for operation. Numerous research articles have proposed the edge AI accelerator for satisfying the applications, but not all include full specifications. Most of them tend to compare the architecture with other existing CPUs, GPUs, or other reference research, which implies that the performance exposé of the articles are not comprehensive. Thus, this work lists the essential specifications of prior art edge AI accelerators and the CGRA accelerators during the past few years to define and evaluate the low power ultra-small edge AI accelerators. The actual performance, implementation, and productized examples of edge AI accelerators are released in this paper. We introduce the evaluation results showing the edge AI accelerator design trend about key performance metrics to guide designers. Last but not least, we give out the prospect of developing edge AI’s existing and future directions and trends, which will involve other technologies for future challenging constraints.
Climate-Driven Differences in Growth Performance of Cohabitant Fir and Birch in a Subalpine Forest in Dhorpatan Nepal
Authors: Bista Raju , Chhetri Parveen K. , Johnson Jeremy S. , Sinha Ashish , Shrestha Krishna B.
Published: August 2021

Himalayan Silver Fir (Abies spectabilis) and Himalayan Birch (Betula utilis) are tree species often found coexisting in sub-alpine forests of the Nepal Himalayas. To assess species-specific growth performances of these species, tree-ring samples were collected from the subalpine forest in the Dhorpatan Hunting Reserve, Nepal. Standard ring width chronologies of both species were correlated with climatic variables in both static and running windows. Differential and contrasting temporal responses of radial growth of these species to climate were found. Warmer and drier springs appeared to limit birch radial growth. Whereas radial growth of fir showed weakened climate sensitivity. Moving correlation analyses revealed divergent influences of spring climate on both fir and birch. Significant warming that occurred in the 1970s coincided with growth declines in birch and an increase in fir, as indicated by basal area increment. In summary, recent warming has been unfavorable for birch, and favorable to fir radial growth.
The Potential Distribution of Juniperus rigida Sieb. et Zucc. Vary Diversely in China under the Stringent and High GHG Emission Scenarios Combined Bioclimatic, Soil, and Topographic Factors
Authors: Lv Zhenjiang , Li Dengwu
Published: August 2021

Global warming poses an enormous threat to particular species with shifts to their suitable habitat. Juniperus rigida Sieb. et Zucc., an endemic species to East Asia and a pioneer species in the Loess plateau region, is endangered because of the shrinking and scattered habitat threatened by climate change. For the sake of analyzing the impact of climate warming on its possible habitat, we herein projected the current and future potential habitats of J. rigida in China and comparatively analyzed the ecological habitat changes in three main distribution regions. There were 110 specimen records of J. rigida collected across China and 22 environmental datasets, including bioclimatic variables and soil and topographical factors, selected by the Pearson Correlation Coefficient. The MaxEnt model based on specimen presence and environmental factors was used for projecting the potential habitats of J. rigida in China in the 2050s and the 2070s of RCP 2.6 and RCP 8.5 scenarios. The results indicated an excellence model performance with the average value of the area under curve (AUC) is 0.928. The mean temperature of the driest quarter (MTDq) and the temperature annual range (TAR) provided important contributions to the potential distribution of J. rigida. There were three main distribution areas in China, the Xinjiang region, the Loess-Inner Mongolian Plateau region, and the Changbai Mountain region. The distribution increased overall in area under RCP 2.6 and decreased for RCP 8.5. The mean altitude of the core distribution shifted upward in general under both scenarios. The Loess–Inner Mongolian Plateau region is the biggest distribution, encompassing ca. 61.39 × 104 km2 (86.87 × 104 km2 in China). The region threatened most by climate change is located in the Changbai Mountain distribution, with the centroid of the cord suitable habitat migrating southwest about 227.47 and 260.32 km under RCP 2.6 and RCP 8.5 by the 2070s. In summary, these findings provided a well-grounded understanding of the effect of climate change on ecological distribution and furnished theory evidence for the protection, management, and sustainable use of J. rigida.
Determining an Accurate and Cost-Effective Individual Height-Diameter Model for Mongolian Pine on Sandy Land
Authors: Han Yangang , Lei Zeyong , Ciceu Albert , Zhou Yanping , Zhou Fengyan , Yu Dapao
Published: August 2021

Height-diameter (H-D) models are important tools for forest management practice. Sandy Mongolian pine plantations (Pinus sylvestris var. mongolica) are a major component of the Three-North Afforestation Shelterbelt in Northern China. However, few H-D models are available for Mongolian pine plantations. In this paper we compared different equations found in the literature for predicting tree height, using diameter at breast height and additional stand-level predictor variables. We tested if the additional stand-level predictor variable is necessary to produce more accurate results. The dominant height was used as a stand-level predictor variable to describe the variation of the H-D relationship among plots. We found that the basic mixed-effects H-D model provided a similar predictive accuracy as the generalized mixed-effects H-D model. Moreover, it had the advantage of reducing the sampling effort. The basic mixed-effects H-D model calibration, in which the heights of the two thickest trees in the plot were included to calibrate the random effects, resulted in accurate and reliable individual tree height estimations. Thus, the basic mixed-effects H-D model with the above-described calibration design can be an accurate and cost-effective solution for estimating the heights of Mongolian pine trees in northern China.
Targeted NGS Yields Plentiful Ultra-Rare Variants in Inborn Errors of Immunity Patients
Authors: Grossi Alice , Miano Maurizio , Lanciotti Marina , Fioredda Francesca , Guardo Daniela , Palmisani Elena , Terranova Paola , Santamaria Giuseppe , Caroli Francesco , Caorsi Roberta , Volpi Stefano , Gattorno Marco , Dufour Carlo , Ceccherini Isabella
Published: August 2021

Inborn errors of immunity (IEI) include a large group of inherited diseases sharing either poor, dysregulated, or absent and/or acquired function in one or more components of the immune system. Next-generation sequencing (NGS) has driven a rapid increase in the recognition of such defects, though the wide heterogeneity of genetically diverse but phenotypically overlapping diseases has often prevented the molecular characterization of the most complex patients. Two hundred and seventy-two patients were submitted to three successive NGS-based gene panels composed of 58, 146, and 312 genes. Along with pathogenic and likely pathogenic causative gene variants, accounting for the corresponding disorders (37/272 patients, 13.6%), a number of either rare (probably) damaging variants in genes unrelated to patients’ phenotype, variants of unknown significance (VUS) in genes consistent with their clinics, or apparently inconsistent benign, likely benign, or VUS variants were also detected. Finally, a remarkable amount of yet unreported variants of unknown significance were also found, often recurring in our dataset. The NGS approach demonstrated an expected IEI diagnostic rate. However, defining the appropriate list of genes for these panels may not be straightforward, and the application of unbiased approaches should be taken into consideration, especially when patients show atypical clinical pictures.
Assessment of Pharmacists’ Knowledge and Practices towards Prescribed Medications for Dialysis Patients at a Tertiary Hospital in Riyadh Saudi Arabia
Authors: Al-Abdelmuhsin Lolwa , Al-Ammari Maha , Babelghaith Salmeen D. , Wajid Syed , Alwhaibi Abdulrahman , Alghadeer Sultan M. , Al Arifi Mohamed N. , Alrabiah Ziyad
Published: August 2021

Objective: The present study examined pharmacists’ knowledge and practices towards prescribed medications for hemodialysis patients. The impact of a pharmacist’s current positions and years of experience on practices and knowledge was also assessed. Methods: A cross-sectional survey was distributed to pharmacists working at King Abdul-Aziz Medical City-Central Region over a period of 4 months from July to October in 2015. Results: Of the 85 approached pharmacists, 66 pharmacists completed the questionnaire, among which 45 (68.2%), 9 (13.6%), and 12 (18.2%) of them were outpatient hospital pharmacists, discharge counselling pharmacists, and pharmacy practice residents, respectively. In total, 47 (55.3%) of the pharmacists sought drug information resources for newly prescribed medications to hemodialysis patients. Among the surveyed pharmacists, around two-thirds of them (63.6%) were completely confident during counselling hemodialysis patients, while 32% were moderately confident, and only 4.5% were not confident. All of the participating pharmacists checked each patient’s allergic status before dispensing hemodialysis medications. The majority of the outpatient hospital pharmacists (35; 77.8%), discharge pharmacists (8; 88.9%), and the pharmacy practice residents (11; 91.7%) agreed that oral ciprofloxacin should be given after dialysis session on the same dialysis days, while 18 (40%), 5 (55.6%), and 9 (75%) of the outpatient hospital pharmacists, discharge pharmacists, and pharmacy practice residents agreed that IV route is preferred for hemodialysis patients to administer epoetin alfa, respectively. Sixty-six percent of discharge pharmacists (n = 6), 91.7% (n = 11) of the pharmacy practice residents, and 55.6% (n = 25) of the outpatient hospital pharmacists checked patient laboratory results prior to dispensing medications (p = 0.001). Conclusions: Despite the limited knowledge regarding some prescribed medications, most of the hospital pharmacists showed good practices toward dialysis patients.
Nectar Feeding by a Honey Bee’s Hairy Tongue: Morphology, Dynamics, and Energy-Saving Strategies
Authors: Wang Hao , Wu Zhigang , Zhao Jieliang , Wu Jianing
Published: August 2021

Most flower-visiting insects have evolved highly specialized morphological structures to facilitate nectar feeding. As a typical pollinator, the honey bee has specialized mouth parts comprised of a pair of galeae, a pair of labial palpi, and a glossa, to feed on the nectar by the feeding modes of lapping or sucking. To extensively elucidate the mechanism of a bee’s feeding, we should combine the investigations from glossa morphology, feeding behaviour, and mathematical models. This paper reviews the interdisciplinary research on nectar feeding behaviour of honey bees ranging from morphology, dynamics, and energy-saving strategies, which may not only reveal the mechanism of nectar feeding by honey bees but inspire engineered facilities for microfluidic transport.
The Use of β-Blockers in Heart Failure with Reduced Ejection Fraction
Authors: Masarone Daniele , Martucci Maria Luigia , Errigo Vittoria , Pacileo Giuseppe
Published: August 2021

Treatment with β-blockers is the main strategy for managing patients with heart failure and reduced ejection fraction because of their ability to reverse the neurohumoral effects of the sympathetic nervous system, with consequent prognostic and symptomatic benefits. However, to date, they are underused, mainly because of the misconception that hypotension and bradycardia may worsen the haemodynamic status of patients with HFrEF and because of the presence of comorbidities falsely believed to be absolute contraindications to their use. To promote proper use of β-blockers in this article, we review the clinical pharmacology of β-blockers, the evidence of the beneficial effects of these drugs in heart failure with reduced ejection fraction, and the current guidelines for their use in clinical practice and in the presence of comorbidities (e.g., pulmonary disease, diabetes, atrial fibrillation, peripheral arterial disease, etc.). It is hoped that the practical approach discussed in this review will allow for a proper diffusion of knowledge about the correct use of β-blockers and the drug-disease interactions to achieve their increased use and titration, as well as for the selection of a specific agent with a view to a properly tailored approach for HFrEF patients.
The Behavioural Aspects of Financial Literacy
Authors: Gerth Florian , Lopez Katia , Reddy Krishna , Ramiah Vikash , Wallace Damien , Muschert Glenn , Frino Alex , Jooste Leonie
Published: August 2021

In this paper, we investigate the contribution of behavioural characteristics to the financial literacy of UAE residents after controlling for demographic factors. Specifically, we test the relationship between financial literacy and behavioural biases such as representativeness, self-serving, overconfidence, loss aversion, and hindsight bias. Using data collected through survey questionnaires, we apply the methodology developed by the Organization of Economic Co-operation and Development (OECD) to compute financial literacy scores. Our overall results show that all behavioural biases except for overconfidence bias are positively related to financial literacy. Furthermore, some biases exhibit a stronger quantitative relationship with financial literacy than others. For example, hindsight bias displays the strongest link to financial literacy, followed by self-serving bias. The weakest but still statistically significant effect is loss aversion bias. Although biases, in general, have negative connotations, behavioural biases appear to be related to higher levels of financial literacy.
A New Extended Model with Bathtub-Shaped Failure Rate: Properties, Inference, Simulation, and Applications
Authors: Al Mutairi Alya , Iqbal Muhammad Z. , Arshad Muhammad Z. , Alnssyan Badr , Al-Mofleh Hazem , Afify Ahmed Z.
Published: August 2021

Theoretical and applied researchers have been frequently interested in proposing alternative skewed and symmetric lifetime parametric models that provide greater flexibility in modeling real-life data in several applied sciences. To fill this gap, we introduce a three-parameter bounded lifetime model called the exponentiated new power function (E-NPF) distribution. Some of its mathematical and reliability features are discussed. Furthermore, many possible shapes over certain choices of the model parameters are presented to understand the behavior of the density and hazard rate functions. For the estimation of the model parameters, we utilize eight classical approaches of estimation and provide a simulation study to assess and explore the asymptotic behaviors of these estimators. The maximum likelihood approach is used to estimate the E-NPF parameters under the type II censored samples. The efficiency of the E-NPF distribution is evaluated by modeling three lifetime datasets, showing that the E-NPF distribution gives a better fit over its competing models such as the Kumaraswamy-PF, Weibull-PF, generalized-PF, Kumaraswamy, and beta distributions.
Regular and Intra-Regular Semigroups in Terms of m-Polar Fuzzy Environment
Authors: Bashir Shahida , Shahzadi Sundas , Al-Kenani Ahmad N. , Shabir Muhammad
Published: August 2021

The central objective of the proposed work in this research is to introduce the innovative concept of an m-polar fuzzy set (m-PFS) in semigroups, that is, the expansion of bipolar fuzzy set (BFS). Our main focus in this study is the generalization of some important results of BFSs to the results of m-PFSs. This paper provides some important results related to m-polar fuzzy subsemigroups (m-PFSSs), m-polar fuzzy ideals (m-PFIs), m-polar fuzzy generalized bi-ideals (m-PFGBIs), m-polar fuzzy bi-ideals (m-PFBIs), m-polar fuzzy quasi-ideals (m-PFQIs) and m-polar fuzzy interior ideals (m-PFIIs) in semigroups. This research paper shows that every m-PFBI of semigroups is the m-PFGBI of semigroups, but the converse may not be true. Furthermore this paper deals with several important properties of m-PFIs and characterizes regular and intra-regular semigroups by the properties of m-PFIs and m-PFBIs.
Conditions for the Existence of Absolutely Optimal Portfolios
Authors: Rădulescu Marius , Rădulescu Constanta Zoie , Zbăganu Gheorghiță
Published: August 2021

Let Δn be the n-dimensional simplex, ξ = (ξ1, ξ2,…, ξn) be an n-dimensional random vector, and U be a set of utility functions. A vector x*∈ Δn is a U -absolutely optimal portfolio if EuξTx*≥EuξTx for every x∈ Δn and u ∈ U. In this paper, we investigate the following problem: For what random vectors, ξ, do U-absolutely optimal portfolios exist? If U2 is the set of concave utility functions, we find necessary and sufficient conditions on the distribution of the random vector, ξ, in order that it admits a U2-absolutely optimal portfolio. The main result is the following: If x0 is a portfolio having all its entries positive, then x0 is an absolutely optimal portfolio if and only if all the conditional expectations of ξi, given the return of portfolio x0, are the same. We prove that if ξ is bounded below then CARA-absolutely optimal portfolios are also U2-absolutely optimal portfolios. The classical case when the random vector ξ is normal is analyzed. We make a complete investigation of the simplest case of a bi-dimensional random vector ξ = (ξ1, ξ2). We give a complete characterization and we build two dimensional distributions that are absolutely continuous and admit U2-absolutely optimal portfolios.
Pricing the Volatility Risk Premium with a Discrete Stochastic Volatility Model
Authors: Posedel Šimović Petra , Tafro Azra
Published: August 2021

Investors’ decisions on capital markets depend on their anticipation and preferences about risk, and volatility is one of the most common measures of risk. This paper proposes a method of estimating the market price of volatility risk by incorporating both conditional heteroscedasticity and nonlinear effects in market returns, while accounting for asymmetric shocks. We develop a model that allows dynamic risk premiums for the underlying asset and for the volatility of the asset under the physical measure. Specifically, a nonlinear in mean time series model combining the asymmetric autoregressive conditional heteroscedastic model with leverage (NGARCH) is adapted for modeling return dynamics. The local risk-neutral valuation relationship is used to model investors’ preferences of volatility risk. The transition probabilities governing the evolution of the price of the underlying asset are adjusted for investors’ attitude towards risk, presenting the asset returns as a function of the risk premium. Numerical studies on asset return data show the significance of market shocks and levels of asymmetry in pricing the volatility risk. Estimated premiums could be used in option pricing models, turning options markets into volatility trading markets, and in measuring reactions to market shocks.
Experimental Models to Study Skin Wound Healing with a Focus on Angiogenesis
Authors: Grambow Eberhard , Sorg Heiko , Sorg Christian G. G. , Strüder Daniel
Published: August 2021

A large number of models are now available for the investigation of skin wound healing. These can be used to study the processes that take place in a phase-specific manner under both physiological and pathological conditions. Most models focus on wound closure, which is a crucial parameter for wound healing. However, vascular supply plays an equally important role and corresponding models for selective or parallel investigation of microcirculation regeneration and angiogenesis are also described. In this review article, we therefore focus on the different levels of investigation of skin wound healing (in vivo to in virtuo) and the investigation of angiogenesis and its parameters.
Structure–Activity Relationship Studies on Novel Antiviral Agents for Norovirus Infections
Authors: Ferla Salvatore , Varricchio Carmine , Knight William , Ho Pui Kei , Saporito Fabiana , Tropea Beatrice , Fagan Giulio , Flude Ben Matthew , Bevilacqua Federica , Santos-Ferreira Nanci , Van Dycke Jana , Neyts Johan , Brancale Andrea , Rocha-Pereira Joana , Bassetto Marcella
Published: August 2021

Human norovirus is the leading cause of acute gastroenteritis worldwide, affecting every year 685 million people. Norovirus outbreaks are associated with very significant economic losses, with an estimated societal cost of 60 billion USD per year. Despite this, no therapeutic options or vaccines are currently available to treat or prevent this infection. An antiviral therapy that can be used as treatment and as a prophylactic measure in the case of outbreaks is urgently needed. We previously described the computer-aided design and synthesis of novel small-molecule agents able to inhibit the replication of human norovirus in cell-based systems. These compounds are non-nucleoside inhibitors of the viral polymerase and are characterized by a terminal para-substituted phenyl group connected to a central phenyl ring by an amide-thioamide linker, and a terminal thiophene ring. Here we describe new modifications of these scaffolds focused on exploring the role of the substituent at the para position of the terminal phenyl ring and on removing the thioamide portion of the amide-thioamide linker, to further explore structure-activity relationships (SARs) and improve antiviral properties. According to three to four-step synthetic routes, we prepared thirty novel compounds, which were then evaluated against the replication of both murine (MNV) and human (HuNoV) norovirus in cells. Derivatives in which the terminal phenyl group has been replaced by an unsubstituted benzoxazole or indole, and the thioamide component of the amide-thioamide linker has been removed, showed promising results in inhibiting HuNoV replication at low micromolar concentrations. Particularly, compound 28 was found to have an EC50 against HuNoV of 0.9 µM. Although the most active novel derivatives were also associated with an increased cytotoxicity in the human cell line, these compounds represent a very promising starting point for the development of new analogues with reduced cytotoxicity and improved selectivity indexes. In addition, the experimental biological data have been used to create an initial 3D quantitative structure-activity relationship model, which could be used to guide the future design of novel potential anti-norovirus agents.
Elucidating Pathfinding Elements from the Kubi Gold Mine in Ghana
Authors: Nzulu Gabriel K. , Bakhit Babak , Högberg Hans , Hultman Lars , Magnuson Martin
Published: August 2021

X-ray photoelectron spectroscopy (XPS) and energy dispersive X-ray spectroscopy (EDX) are applied to investigate the properties of fine-grained concentrates on artisanal, small-scale gold mining samples from the Kubi Gold Project of the Asante Gold Corporation near Dunwka-on-Offin in the Central Region of Ghana. Both techniques show that the Au-containing residual sediments are dominated by the host elements Fe, Ag, Al, N, O, Si, Hg, and Ti that either form alloys with gold or with inherent elements in the sediments. For comparison, a bulk nugget sample mainly consisting of Au forms an electrum, i.e., a solid solution with Ag. Untreated (impure) sediments, fine-grained Au concentrate, coarse-grained Au concentrate, and processed ore (Au bulk/nugget) samples were found to contain clusters of O, C, N, and Ag, with Au concentrations significantly lower than that of the related elements. This finding can be attributed to primary geochemical dispersion, which evolved from the crystallization of magma and hydrothermal liquids as well as the migration of metasomatic elements and the rapid rate of chemical weathering of lateralization in secondary processes. The results indicate that Si and Ag are strongly concomitant with Au because of their eutectic characteristics, while N, C, and O follow alongside because of their affinity to Si. These non-noble elements thus act as pathfinders for Au ores in the exploration area. This paper further discusses relationships between gold and sediments of auriferous lodes as key to determining indicator minerals of gold in mining sites.
Structural Insight into the Binding of Cyanovirin-N with the Spike Glycoprotein, Mpro and PLpro of SARS-CoV-2: Protein–Protein Interactions, Dynamics Simulations and Free Energy Calculations
Authors: Naidoo Devashan , Kar Pallab , Roy Ayan , Mutanda Taurai , Bwapwa Joseph , Sen Arnab , Anandraj Akash
Published: August 2021

The emergence of COVID-19 continues to pose severe threats to global public health. The pandemic has infected over 171 million people and claimed more than 3.5 million lives to date. We investigated the binding potential of antiviral cyanobacterial proteins including cyanovirin-N, scytovirin and phycocyanin with fundamental proteins involved in attachment and replication of SARS-CoV-2. Cyanovirin-N displayed the highest binding energy scores (−16.8 ± 0.02 kcal/mol, −12.3 ± 0.03 kcal/mol and −13.4 ± 0.02 kcal/mol, respectively) with the spike protein, the main protease (Mpro) and the papainlike protease (PLpro) of SARS-CoV-2. Cyanovirin-N was observed to interact with the crucial residues involved in the attachment of the human ACE2 receptor. Analysis of the binding affinities calculated employing the molecular mechanics-Poisson–Boltzmann surface area (MM-PBSA) approach revealed that all forms of energy, except the polar solvation energy, favourably contributed to the interactions of cyanovirin-N with the viral proteins. With particular emphasis on cyanovirin-N, the current work presents evidence for the potential inhibition of SARS-CoV-2 by cyanobacterial proteins, and offers the opportunity for in vitro and in vivo experiments to deploy the cyanobacterial proteins as valuable therapeutics against COVID-19.
Carotenoids Do Not Protect Bacteriochlorophylls in Isolated Light-Harvesting LH2 Complexes of Photosynthetic Bacteria from Destructive Interactions with Singlet Oxygen
Authors: Makhneva Zoya K. , Bolshakov Maksim A. , Moskalenko Andrey A.
Published: August 2021

The effect of singlet oxygen on light-harvesting (LH) complexes has been studied for a number of sulfur (S+) and nonsulfur (S−) photosynthetic bacteria. The visible/near-IR absorption spectra of the standard LH2 complexes (B800-850) of Allochromatium (Alc.) vinosum (S+), Rhodobacter (Rba.) sphaeroides (S−), Rhodoblastus (Rbl.) acidophilus (S−), and Rhodopseudomonas (Rps.) palustris (S−), two types LH2/LH3 (B800-850 and B800-830) of Thiorhodospira (T.) sibirica (S+), and an unusual LH2 complex (B800-827) of Marichromatium (Mch.) purpuratum (S+) or the LH1 complex from Rhodospirillum (Rsp.) rubrum (S−) were measured in aqueous buffer suspensions in the presence of singlet oxygen generated by the illumination of the dye Rose Bengal (RB). The content of carotenoids in the samples was determined using HPLC analysis. The LH2 complex of Alc. vinosum and T. sibirica with a reduced content of carotenoids was obtained from cells grown in the presence of diphenylamine (DPA), and LH complexes were obtained from the carotenoidless mutant of Rba. sphaeroides R26.1 and Rps. rubrum G9. We found that LH2 complexes containing a complete set of carotenoids were quite resistant to the destructive action of singlet oxygen in the case of Rba. sphaeroides and Mch. purpuratum. Complexes of other bacteria were much less stable, which can be judged by a strong irreversible decrease in the bacteriochlorophyll (BChl) absorption bands (at 850 or 830 nm, respectively) for sulfur bacteria and absorption bands (at 850 and 800 nm) for nonsulfur bacteria. Simultaneously, we observe the appearance of the oxidized product 3-acetyl-chlorophyll (AcChl) absorbing near 700 nm. Moreover, a decrease in the amount of carotenoids enhanced the spectral stability to the action of singlet oxygen of the LH2 and LH3 complexes from sulfur bacteria and kept it at the same level as in the control samples for carotenoidless mutants of nonsulfur bacteria. These results are discussed in terms of the current hypothesis on the protective functions of carotenoids in bacterial photosynthesis. We suggest that the ability of carotenoids to quench singlet oxygen (well-established in vitro) is not well realized in photosynthetic bacteria. We compared the oxidation of BChl850 in LH2 complexes of sulfur bacteria under the action of singlet oxygen (in the presence of 50 μM RB) or blue light absorbed by carotenoids. These processes are very similar: {[BChl + (RB or carotenoid) + light] + O2} → AcChl. We speculate that carotenoids are capable of generating singlet oxygen when illuminated. The mechanism of this process is not yet clear.
Supramolecular Association between γ-Cyclodextrin and Preyssler-Type Polyoxotungstate
Authors: Leclerc Nathalie , Haouas Mohamed , Falaise Clément , Al Bacha Serge , Assaud Loïc , Cadot Emmanuel
Published: August 2021

The development of hybrid materials based on polyoxometalates constitutes a strategy for the design of multifunctional materials. The slow evaporation of an aqueous solution of [NaP5W30O110]14− in the presence of γ-Cyclodextrin (γ-CD) led to the crystallization of a K6Na8{[NaP5W30O110]•(C48H80O40)}•23H2O (NaP5W30•1CD) supramolecular compound, which was characterized by single-crystal X-ray diffraction, IR-spectroscopy, thermogravimetric and elemental analyses. Structural analysis revealed the formation of 1:1 {[NaP5W30O110]•[γ-CD]}14− adduct in the solid state. Studies in solution by cyclic voltammetry, electrochemical impedance spectroscopy, 1H NMR spectroscopy, and 31P DOSY, have demonstrated weak interactions between the inorganic anion and the macrocyclic organic molecule.
Gluconeogenesis in Plants: A Key Interface between Organic Acid/Amino Acid/Lipid and Sugar Metabolism
Authors: Walker Robert P. , Chen Zhi-Hui , Famiani Franco
Published: August 2021

Gluconeogenesis is a key interface between organic acid/amino acid/lipid and sugar metabolism. The aims of this article are four-fold. First, to provide a concise overview of plant gluconeogenesis. Second, to emphasise the widespread occurrence of gluconeogenesis and its utilisation in diverse processes. Third, to stress the importance of the vacuolar storage and release of Krebs cycle acids/nitrogenous compounds, and of the role of gluconeogenesis and malic enzyme in this process. Fourth, to outline the contribution of fine control of enzyme activity to the coordinate-regulation of gluconeogenesis and malate metabolism, and the importance of cytosolic pH in this.
Tuning the Reduction of Graphene Oxide Nanoflakes Differently Affects Neuronal Networks in the Zebrafish
Authors: Di Mauro Giuseppe , Rauti Rossana , Casani Raffaele , Chimowa George , Galibert Anne Marie , Flahaut Emmanuel , Cellot Giada , Ballerini Laura
Published: August 2021

The increasing engineering of biomedical devices and the design of drug-delivery platforms enriched by graphene-based components demand careful investigations of the impact of graphene-related materials (GRMs) on the nervous system. In addition, the enhanced diffusion of GRM-based products and technologies that might favor the dispersion in the environment of GRMs nanoparticles urgently requires the potential neurotoxicity of these compounds to be addressed. One of the challenges in providing definite evidence supporting the harmful or safe use of GRMs is addressing the variety of this family of materials, with GRMs differing for size and chemistry. Such a diversity impairs reaching a unique and predictive picture of the effects of GRMs on the nervous system. Here, by exploiting the thermal reduction of graphene oxide nanoflakes (GO) to generate materials with different oxygen/carbon ratios, we used a high-throughput analysis of early-stage zebrafish locomotor behavior to investigate if modifications of a specific GRM chemical property influenced how these nanomaterials affect vertebrate sensory-motor neurophysiology—exposing zebrafish to GO downregulated their swimming performance. Conversely, reduced GO (rGO) treatments boosted locomotor activity. We concluded that the tuning of single GRM chemical properties is sufficient to produce differential effects on nervous system physiology, likely interfering with different signaling pathways.