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Background: In medical device validation and verification studies, the area under the receiver operating characteristic curve (AUROC) is often used as a primary endpoint despite multiple reports showing its limitations. Hence, researchers are encouraged to consider alternative metrics as primary endpoints. A new metric called G4 is presented, which is the geometric mean of sensitivity, specificity, the positive predictive value, and the negative predictive value. G4 is part of a balanced metric family which includes the Unified Performance Measure (also known as P4) and the Matthews' Correlation Coefficient (MCC). The purpose of this manuscript is to unveil the benefits of using G4 together with the balanced metric family when analyzing the overall performance of binary classifiers. Results: Simulated datasets encompassing different prevalence rates of the minority class were analyzed under a multi-reader-multi-case study design. In addition, data from an independently published study that tested the performance of a unique ultrasound artificial intelligence algorithm in the context of breast cancer detection was also considered. Within each dataset, AUROC was reported alongside the balanced metric family for comparison. When the dataset prevalence and bias of the minority class approached 50%, all three balanced metrics provided equivalent interpretations of an AI's performance. As the prevalence rate increased / decreased and the data became more imbalanced, AUROC tended to overvalue / undervalue the true classifier performance, while the balanced metric family was resistant to such imbalance. Under certain circumstances where data imbalance was strong (minority-class prevalence < 10%), MCC was preferred for standalone assessments while P4 provided a stronger effect size when evaluating between-groups analyses. G4 acted as a middle ground for maximizing both standalone assessments and between-groups analyses. Conclusions: Use of AUROC as the primary endpoint in binary classification problems provides misleading results as the dataset becomes more imbalanced. This is explicitly noticed when incorporating AUROC in medical device validation and verification studies. G4, P4, and MCC do not share this limitation and paint a more complete picture of a medical device's performance in a clinical setting. Therefore, researchers are encouraged to explore the balanced metric family when evaluating binary classification problems. [ABSTRACT FROM AUTHOR]

We generate new evidence on disagreement among traders in the S&P 500 options market from high-frequency intraday price and volume data. Inference on disagreement is based on a model where investors observe public information but agree to disagree on its interpretation; disagreement among investors is captured by the volume–volatility elasticity. For options, there are two natural variables related to disagreement: moneyness and tenor, which we relate to disagreement about the distribution of the market index at different quantiles and times. The estimated volume–volatility elasticity equals unity for options near the money and close to expiration, which is consistent with the case of no disagreement among investors. In contrast, the elasticity estimates decrease with increases in the absolute value of moneyness, indicating investors have a higher disagreement about rare events. Likewise, the elasticity decreases with increases in tenor, implying higher investors' disagreement about more distant events. [ABSTRACT FROM AUTHOR]

In this paper, we infer how the estimates of firm value by "optimists" and "pessimists" evolve in response to information shocks. Specifically, we examine returns and disagreement measures for portfolios of short-sale-constrained stocks that have experienced large gains or large losses. Our analysis suggests the presence of two groups, one of which overreacts to new information and remains biased over about 5 years, and a second group, which underreacts and whose expectations are unbiased after about 1 year. Our results have implications for the belief dynamics that underlie the momentum and long-term reversal effect. Authors have furnished an Internet Appendix , which is available on the Oxford University Press Web site next to the link to the final published paper online. [ABSTRACT FROM AUTHOR]

Background: Cis-regulatory elements (CREs) are crucial for regulating gene expression, and G-quadruplexes (G4s), as prototypal non-canonical DNA structures, may play a role in this regulation. However, the relationship between G4s and CREs, especially with non-promoter-like functional elements, requires further systematic investigation. We aimed to investigate the associations between G4s and human cCREs (candidate CREs) inferred from the Encyclopedia of DNA Elements (ENCODE) data. Results: We found that G4s are prominently enriched in most types of cCREs, especially those with promoter-like signatures (PLS). The co-occurrence of CTCF signals with H3K4me3 or H3K27ac signals strengthens the association between cCREs and G4s. Genetic variants in G4s, particularly within their G-runs, exhibit higher regulatory potential and deleterious effects compared to cCREs. The G-runs within G4s near transcriptional start sites (TSSs) are more evolutionarily constrained compared to G-runs in cCREs, while those far from the TSS are relatively less conserved. The presence of G4s is often linked to a more favorable local chromatin environment for the activation and execution of regulatory function of cCREs, potentially attributable to the formation of G4 secondary structures. Finally, we discovered that G4-associated cCREs exhibit widespread activation in a variety of cancers. Conclusions: Our study suggests that G4s are integral components of human cis-regulatory elements, extending beyond their potential role in promoters. The G4 primary sequences are associated with the localization of CREs, while the G4 structures are linked to the activation of these elements. Therefore, we propose defining G4s as pivotal regulatory elements in the human genome. [ABSTRACT FROM AUTHOR]

G-quadruplexes (G4) are non-canonical, four-stranded, nucleic acid secondary structures formed in the guanine-rich sequences, where guanine nucleotides associate with each other via Hoogsteen hydrogen bonding. These structures are widely found near the functional regions of the mammalian genome, such as telomeres, oncogenic promoters, and replication origins, and play crucial regulatory roles in replication and transcription. Destabilization of G4 by various carcinogenic agents allows oncogene overexpression and extension of telomeric ends resulting in dysregulation of cellular growth–promoting oncogenesis. Therefore, targeting and stabilizing these G4 structures with potential ligands could aid cancer prevention and therapy. The field of G-quadruplex targeting is relatively nascent, although many articles have demonstrated the effect of G4 stabilization on oncogenic expressions; however, no previous study has provided a comprehensive analysis about the potency of a wide variety of nutraceuticals and some of their derivatives in targeting G4 and the lattice of oncogenic cell signaling cascade affected by them. In this review, we have discussed bioactive G4-stabilizing nutraceuticals, their sources, mode of action, and their influence on cellular signaling, and we believe our insight would bring new light to the current status of the field and motivate researchers to explore this relatively poorly studied arena. Schematic diagram depicting nutraceuticals' role in attenuating cancer progression [ABSTRACT FROM AUTHOR]

Background: G-quadruplex DNA (G4) is a non-canonical structure forming in guanine-rich regions, which play a vital role in cancer biology and are now being acknowledged in both nuclear and mitochondrial (mt) genome. However, the impact of G4-based targeted therapy on both nuclear and mt genome, affecting mt function and its underlying mechanisms remain largely unexplored. Methods: The mechanisms of action and therapeutic effects of a G4-binding platinum(II) complex, Pt-ttpy, on mitochondria were conducted through a comprehensive approaches with in vitro and in vivo models, including ICP-MS for platinum measurement, PCR-based genetic analysis, western blotting (WB), confocal microscope for mt morphology study, extracellular flux analyzer, JC1 and Annexin V apoptosis assay, flow cytometry and high content microscope screening with single-cell quantification of both ROS and mt specific ROS, as well as click-chemistry for IF study of mt translation. Decipher Pt-ttpy effects on nuclear-encoded mt related genes expression were undertaken via RNA-seq, Chip-seq and CUT-RUN assays. Results: Pt-ttpy, shows a highest accumulation in the mitochondria of A2780 cancer cells as compared with two other platinum(II) complexes with no/weak G4-binding properties, Pt-tpy and cisplatin. Pt-ttpy induces mtDNA deletion, copy reduction and transcription inhibition, hindering mt protein translation. Functional analysis reveals potent mt dysfunction without reactive oxygen species (ROS) induction. Mechanistic study provided first evidence that most of mt ribosome genes are highly enriched in G4 structures in their promoter regions, notably, Pt-ttpy impairs most nuclear-encoded mt ribosome genes' transcription through dampening the recruiting of transcription initiation and elongation factors of NELFB and TAF1 to their promoter with G4-enriched sequences. In vivo studies show Pt-ttpy's efficient anti-tumor effects, disrupting mt genome function with fewer side effects than cisplatin. Conclusion: This study underscores Pt-ttpy as a G4-binding platinum(II) complex, effectively targeting cancer mitochondria through dual action on mt and nuclear G4-enriched genomes without inducing ROS, offering promise for safer and effective platinum-based G4-targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4-related disease is an immune-mediated condition comprised of a number of various disorders sharing unique pathologic, serologic, and clinical features. Diagnosis of immunoglobulin G4-related sclerosing mastitis is challenging as the clinical and imaging findings mimic breast malignancies or other types of inflammatory mastitis. Herein, we describe a case of a female patient with a painless palpable mass in her right breast. An excisional core biopsy led to the rare diagnosis of immunoglobulin G4-related sclerosing mastitis, and the patient received steroid treatment for a month. To date, the patient has remained disease-free without any recurrence. As immunoglobulin G4-related sclerosing mastitis is a very rare disease, further studies are needed to reach conclusions about the pathogenesis, diagnosis, and treatment of this entity. [ABSTRACT FROM AUTHOR]

G-quadruplexes or G4s are non-canonical secondary structures of nucleic acids characterized by guanines arranged in stacked tetraplex arrays. Decades of research into these peculiar assemblies of DNA and RNA, fueled by the development and optimization of a vast array of techniques and assays, has resulted in a large amount of information regarding their structure, stability, localization, and biological significance in native systems. A plethora of articles have reported the roles of G-quadruplexes in multiple pathways across several species, ranging from gene expression regulation to RNA biogenesis and trafficking, DNA replication, and genome maintenance. Crucially, a large amount of experimental evidence has highlighted the roles of G-quadruplexes in cancer biology and other pathologies, pointing at these structurally unique guanine assemblies as amenable drug targets. Given the rapid expansion of this field of research, this review aims at summarizing all the relevant aspects of G-quadruplex biology by combining and discussing results from seminal works as well as more recent and cutting-edge experimental evidence. Additionally, the most common methodologies used to study G4s are presented to aid the reader in critically interpreting and integrating experimental data. [ABSTRACT FROM AUTHOR]

G-quadruplexes (G4s) are noncanonical nucleic acid structures that play significant roles in regulating various biological processes, including replication, transcription, translation, and recombination. Recent studies have identified G4s in the genomes of several viruses, such as herpes viruses, hepatitis viruses, and human coronaviruses. These structures are implicated in regulating viral transcription, replication, and virion production, influencing viral infectivity and pathogenesis. G4-stabilizing ligands, like TMPyP4, PhenDC3, and BRACO19, show potential antiviral properties by targeting and stabilizing G4 structures, inhibiting essential viral life-cycle processes. This review delves into the existing literature on G4's involvement in viral regulation, emphasizing specific G4-stabilizing ligands. While progress has been made in understanding how these ligands regulate viruses, further research is needed to elucidate the mechanisms through which G4s impact viral processes. More research is necessary to develop G4-stabilizing ligands as novel antiviral agents. The increasing body of literature underscores the importance of G4s in viral biology and the development of innovative therapeutic strategies against viral infections. Despite some ligands' known regulatory effects on viruses, a deeper comprehension of the multifaceted impact of G4s on viral processes is essential. This review advocates for intensified research to unravel the intricate relationship between G4s and viral processes, paving the way for novel antiviral treatments. [ABSTRACT FROM AUTHOR]

Copyright of Riwayat: Educational Journal of History & Humanities is the property of Riwayat: Educational Journal of History & Humanities and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

While the role of G quadruplex (G4) structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were used to detect SNVs present in G4s to identify sequence level changes and their effect on the alteration of the G4 secondary structure. A total of 37,515 G4 SNVs in the COSMIC database and 2378 in CLINVAR were identified. Of those, 7236 COSMIC (19.3%) and 457 (19%) of the CLINVAR variants result in G4 loss, while 2728 (COSMIC) and 129 (CLINVAR) SNVs gain a G4 structure. The remaining variants potentially affect the folding energy without affecting the presence of a G4. Analysis of mutational patterns in the G4 structure shows a higher selective pressure (3-fold) in the coding region on the template strand compared to the reverse strand. At the same time, an equal proportion of SNVs were observed among intronic, promoter, and enhancer regions across strands. [ABSTRACT FROM AUTHOR]

Using composite methods of quantum chemical calculations and the atomization method, the values of the enthalpy of formation for a test set of 79 compounds in gas phase have been calculated with accuracy of 3.8, 4.5, and 4.7 kJ/mol for the G4, G4MP2, and CBS-QB3 methods, respectively. According to the results of statistical analysis of deviations of theoretical values from experimental ones, the presence of an error occurring at the geometry optimization step due to neglected correlation effects has been revealed. For aliphatic amines and alcohols from the considered set of compounds, the values of the pKa for aqueous solutions have been calculated using the G4 method including solvent effects according to the CPCM model. The existence of a correlation between the error in the pKa calculation and the differences in energy values between the highest occupied and lowest unoccupied molecular orbitals for conjugated acid and base forms in the solution phase has been revealed. A method has been suggested to refine the calculation results, using which the pKa values for 20 amines and 20 alcohols have been determined with accuracy of 0.67 and 0.87 pKa units, respectively. [ABSTRACT FROM AUTHOR]

Purpose: The unexpected outbreak of COVID-19 has expedited the trend toward online education. To facilitate undisruptive learning, EdTech companies are continuously working on providing solutions to restore teaching and learning practices. This has caused a significant behavioral shift of the investors in the EdTech market. This study aims to analyze the effects of Web Market Traffic on the increased number of investors funding an EdTech Company in the market. Design/methodology/approach: By drawing on the multi-method web analytics approach, this study analyses the nexus between Web Market Traffic and Investor's Behavior in the US and India, proving the hypothesized relationship in the proposed Model using a data sample of 300 EdTech Players. Findings: There is a significant difference between the investor's behavior in India and the US. This study shows that the investors in the US are more inclined towards investing in EdTech companies in comparison to India. The Results demonstrate that monthly visits of consumers and the number of acquisitions by players positively affect the investor's behavior, while bounce rates take a toll on the number of investors. Practical implications: This Study suggests that EdTech investors in the US and India should harness Web Traffic to capture the EdTech market. Further, this study offers practical implications that EdTech players can use to attract potential investors and increase brand visibility by improving web market traffic parameters. Originality/value: This paper's original contribution is to empirically shed light on the effects of web market traffic on the investor's behavior. The study emphasizes the quintessentiality of managing the bounce rates and monthly visits for an EdTech market to attract more investors and capital inflow that enhance brand visibility. The study found that the investors behave distinctly in the developed and emerging markets in the US and India. [ABSTRACT FROM AUTHOR]

Is the trust that participants have in their pension fund affected by its funding ratio (i.e., asset/liabilities ratio)? Based on survey, carried out in October 2021, among Dutch pension fund participants we link our survey data to the funding ratio of their pension fund as registered by the pension regulator. First, we show that the level of the funding ratio of their pension fund is positively associated with the trust level of participants. Pension funds with large buffers are associated with a high level of trust. Second, sub-group analyses show that the trust of younger participants is weakly related to the level of the funding ratio and this association is strong and positive for older (55+)/retired participants. It suggests that an interest in or awareness about the financial health of one's pension fund is associated with a higher responsiveness of participants in terms of trust. And third, firm-based pension funds enjoy a higher level of trust compared to sector-based pension funds. [ABSTRACT FROM AUTHOR]

The aberrant expansion of GGGGCC hexanucleotide repeats within the first intron of the C9orf72 gene represent the predominant genetic etiology underlying amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). The transcribed r(GGGGCC)n RNA repeats form RNA foci, which recruit RNA binding proteins and impede their normal cellular functions, ultimately resulting in fatal neurodegenerative disorders. Furthermore, the non-canonical translation of the r(GGGGCC)n sequence can generate dipeptide repeats, which have been postulated as pathological causes. Comprehensive structural analyses of r(GGGGCC)n have unveiled its polymorphic nature, exhibiting the propensity to adopt dimeric, hairpin, or G-quadruplex conformations, all of which possess the capacity to interact with RNA binding proteins. Small molecules capable of binding to r(GGGGCC)n have been discovered and proposed as potential lead compounds for the treatment of ALS and FTD. Some of these molecules function in preventing RNA–protein interactions or impeding the phase transition of r(GGGGCC)n. In this review, we present a comprehensive summary of the recent advancements in the structural characterization of r(GGGGCC)n, its propensity to form RNA foci, and its interactions with small molecules and proteins. Specifically, we emphasize the structural diversity of r(GGGGCC)n and its influence on partner binding. Given the crucial role of r(GGGGCC)n in the pathogenesis of ALS and FTD, the primary objective of this review is to facilitate the development of therapeutic interventions targeting r(GGGGCC)n RNA. [ABSTRACT FROM AUTHOR]

The study aims to show the impact of financial knowledge among rural consumers' access to financial technology services. In general, knowledge regarding any particular fact helps consumers to select or reject different options. Therefore, knowledge regarding financial services is considered a factor that influences access to financial technology services. This study carries out a survey-oriented method with a structured questionnaire. According to the data category, this study uses three well-known econometric models: logistic regression, probit regression, and complementary log–log regression, have been experimented. This study finds that knowledge regarding various factors significantly impact on access to financial technology services. Mainly, this study has important practical significance for the use of rural finance and financial technology in rural areas, which affects the entire economy. [ABSTRACT FROM AUTHOR]

Because of the convergence of demographic, political, and economic trends, retirement has become a significant stage of human life, which currently requires thoughtful and careful planning. Therefore, social pension schemes – a type of system under which the benefits are being provided – and women's individual saving decisions should give consideration to the fact that it is necessary to accumulate additional funds which should be sufficient for several decades after retirement. Social pension schemes are widely discussed in all European countries, and in this context we can pose the following question: What is it exactly that makes women save for retirement? This paper has two objectives: to identify the factors that encourage women to save and to measure these factors and develop a model which shows correlations. A questionnaire survey was used for collecting the primary data. Subsequently, the analysis is based on 4 indexes created for the purposes of this paper. Then, the indexes were estimated on the basis of the unidimensional two-parameter IRT model, rho and CR coefficients, and multiple-group logistic regression analysis. The conducted calculations lead to the conclusion that regardless of age, several factors are statistically significant for the whole analysed group, e.g. a place of residence. This is the first paper that shows determinants important for women when it comes to saving for retirement. [ABSTRACT FROM AUTHOR]

Maintaining the health of the proteome is a critical cellular task. Recently, we found G-quadruplex (G4) nucleic acids are especially potent at preventing protein aggregation in vitro and could at least indirectly improve the protein folding environment of Escherichia coli. However, the roles of G4s in protein folding were not yet explored. Here, through in vitro protein folding experiments, we discover that G4s can accelerate protein folding by rescuing kinetically trapped intermediates to both native and near-native folded states. Time-course folding experiments in E. coli further demonstrate that these G4s primarily improve protein folding quality in E. coli as opposed to preventing protein aggregation. The ability of a short nucleic acid to rescue protein folding opens up the possibility of nucleic acids and ATP-independent chaperones to play considerable roles in dictating the ultimate folding fate of proteins. [ABSTRACT FROM AUTHOR]

This study aimed to examine the polymorphism of the BMP15 (FecXG and FecXI) and GDF9 (G1 and G4) genes and the association between genotypes and litter size in the Akkaraman breed. Blood samples were taken from 100 ewes in total. Genomic DNA was obtained from whole blood. The PCR-RFLP technique was employed to determine the polymorphisms of the genes under investigation. The G1 was the only polymorphic among the four loci analyzed. The frequencies for the GA and GG genotypes were 0.26 and 0.74, respectively, while the A and G allele frequencies were 0.13 and 0.87, respectively. The observed and expected heterozygosity values were 0.260 and 0.227, respectively. According to chi-square analysis, the tested Akkaraman population was in Hardy-Weinberg equilibrium (p > 0.05). The association analyses showed that the genotypic structure did not significantly affect litter size in the Akkaraman ewes (p > 0.05). However, ewes with one copy of the G1 mutation produced 0.13 more lambs than those without the mutation (p > 0.05), suggesting that heterozygous ewes have a proclivity to increase litter size, as evidenced by previous studies. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the growth response of G4 transgenic mutiara catfish reared at different stocking densities. The relative expression ratio levels of CgGH/ß-actin and IGF-1/ß-actin mRNA was measured using quantitative real-time PCR (qRT-P CR) in G4 mutiara catfish. Fish were kept for 8 weeks at different stocking densities (treatment A, 15 fish/100 L; B, 12 fish/100 L; C, 10 fish/100 L for transgenic fish; and A*, 15 fish/100 L for non-transgenic fish). The average increase in body weight of G4 mutiara catfish was 1.9–2.3 times higher compared to non-transgenic mutiara catfish at the same stocking densities. The growth response indicates an overexpression of the growth hormone (GH) in G4 mutiara catfish, displaying expression levels 1.3–2.9 higher than in non-transgenic fish. The use of high stocking density (treatment A, 15 fish/100 L) induced overexpression of the exogenous GH (CgGH) and increased the body protein content, as well as improved the feed conversion ratio, protein retention value, and fish protein efficiency ratio, leading to faster body weight gain of G4 transgenic versus non-transgenic mutiara catfish. The growth of G4 catfish in treatments B and C remained higher than in treatment A* (non-transgenic fish), but the growth of non-transgenic catfish was slower. The induction of the CgGH expression level caused an increase in the growth, protein retention, protein efficiency ratio, and IGF-1 expression level of G4 transgenic mutiara catfish. The permanent inheritance of CgGH in G4 fish has the potential to increase the mass production of commercial catfish culture. [ABSTRACT FROM AUTHOR]

G-quadruplexes (G4s) are short secondary DNA structures located throughout genomic DNA and transcribed RNA. Although G4 structures have been shown to form in vivo, no current search tools that examine these structures based on previously identified G-quadruplexes and filter them based on similar sequence, structure, and thermodynamic properties are known to exist. We present a framework for clustering G-quadruplex sequences into families using the CD-HIT, MeShClust, and DNACLUST methods along with a combination of Starcode and BLAST. Utilizing this framework to filter and annotate clusters, 95 families of G-quadruplex sequences were identified within the human genome. Profiles for each family were created using hidden Markov models to allow for the identification of additional family members and generate homology probability scores. The thermodynamic folding energy properties, functional annotation of genes associated with the sequences, scores from different prediction algorithms, and transcription factor binding motifs within a family were used to annotate and compare the diversity within and across clusters. The resulting set of G-quadruplex families can be used to further understand how different regions of the genome are regulated by factors targeting specific structures common to members of a specific cluster. [ABSTRACT FROM AUTHOR]

DNA and RNA can adopt a variety of stable higher‐order structural motifs, including G‐quadruplex (G4 s), mismatches, and bulges. Many of these secondary structures are closely related to the regulation of gene expression. Therefore, the higher‐order structure of nucleic acids is one of the candidate therapeutic targets, and the development of binding molecules targeting the higher‐order structure of nucleic acids has been pursued vigorously. Furthermore, as one of the methodologies for detecting the higher‐order structures of these nucleic acids, developing techniques for the selective chemical modification of the higher‐order structures of nucleic acids is also underway. In this personal account, we focus on the following higher‐order structures of nucleic acids, double‐stranded DNA containing the abasic site, T−T/U−U mismatch structure, and G‐quadruplex structure, and describe the development of molecules that bind to and chemically modify these structures. [ABSTRACT FROM AUTHOR]

The guanine base in nucleic acids is, among the other bases, the most susceptible to being converted into 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) when exposed to reactive oxygen species. In double-helix DNA, 8-oxodG can pair with adenine; hence, it may cause a G > T (C > A) mutation; it is frequently referred to as a form of DNA damage and promptly corrected by DNA repair mechanisms. Moreover, 8-oxodG has recently been redefined as an epigenetic factor that impacts transcriptional regulatory elements and other epigenetic modifications. It has been proposed that 8-oxodG exerts epigenetic control through interplay with the G-quadruplex (G4), a non-canonical DNA structure, in transcription regulatory regions. In this review, we focused on the epigenetic roles of 8-oxodG and the G4 and explored their interplay at the genomic level. [ABSTRACT FROM AUTHOR]

By performing appropriate empirical scaling of G4 energy differences, it is possible to calculate Hammett substituent constants σp, σm, σ−, σ+, and σ+m with a typical accuracy (mean absolute error) of ±0.1. The procedure is straightforward and easily carried out by non‐experts using the Gaussian software package. Values are provided for 41 substituents of widely varying electronic character, including some reactive species for which experimental values are unavailable. Additionally, comparison of calculated and experimental values suggests that some previously published numbers might be significantly in error, particularly for some ionic, acidic, and/or basic substituents. Values are also provided for a newly defined substituent constant, σ−m. [ABSTRACT FROM AUTHOR]

America's decoupling‐from‐China debate started after July 2018, reached its peak in August 2020, and is likely to continue even if it may not be a high priority for the Biden administration. Many studies have examined various aspects of this issue, especially the potential economic impacts on the US economy. Unlike previous research, this study looks at the response of stock markets. Using Google Trends data, this study created a weekly dataset from January 2020 to June 2021 to measure investor sentiment towards the US decoupling from China. Employing the generalised autoregressive conditional heteroskedasticity (GARCH) models, the study finds that concern over decoupling is associated with significant variations in stock market prices. From this we can infer that the overall effects of decoupling on the US economy are likely to be considerable. [ABSTRACT FROM AUTHOR]

Intramolecular guanine quadruplexes (G4s) are non-canonical nucleic acid structures formed by four guanine (G)-rich tracts that assemble into a core of stacked planar tetrads. G4-forming DNA sequences are enriched in gene promoters and are implicated in the control of gene expression. Most G4-forming DNA contains more G residues than can simultaneously be incorporated into the core resulting in a variety of different possible G4 structures. Although this kind of structural polymorphism is well recognized in the literature, there remain unanswered questions regarding possible connections between G4 polymorphism and biological function. Here we report a detailed bioinformatic survey of G4 polymorphism in human gene promoter regions. Our analysis is based on identifying G4-containing regions (G4CRs), which we define as stretches of DNA in which every residue can form part of a G4. We found that G4CRs with higher degrees of polymorphism are more tightly clustered near transcription sites and tend to contain G4s with shorter loops and bulges. Furthermore, we found that G4CRs with well-characterized biological functions tended to be longer and more polymorphic than genome-wide averages. These results represent new evidence linking G4 polymorphism to biological function and provide new criteria for identifying biologically relevant G4-forming regions from genomic data. [ABSTRACT FROM AUTHOR]

G-quadruplex (G4) oligonucleotides are higher-order DNA and RNA secondary structures of enormous relevance due to their implication in several biological processes and pathological states in different organisms. Strategies aiming at modulating human G4 structures and their interrelated functions are first-line approaches in modern research aiming at finding new potential anticancer treatments or G4-based aptamers for various biomedical and biotechnological applications. Plants offer a cornucopia of phytocompounds that, in many cases, are effective in binding and modulating the thermal stability of G4s and, on the other hand, contain almost unexplored G4 motifs in their genome that could inspire new biotechnological strategies. Herein, we describe some G4 structures found in plants, summarizing the existing knowledge of their functions and biological role. Moreover, we review some of the most promising G4 ligands isolated from vegetal sources and report on the known relationships between such phytochemicals and G4-mediated biological processes that make them potential leads in the pharmaceutical sector. [ABSTRACT FROM AUTHOR]

By means of the CCSD(T)/6-311++G(df,p) and G4 quantum-chemical calculation methods, the calculation of the molecular and electronic structures of boron–nitrogen compounds having the B3N3 composition was carried out and its results were discussed. It was noted that seven isomeric forms with different space structures can exist; wherein, the most stable form is a distorted flat hexagon with alternating B and N atoms, with both B and N atoms forming regular triangles, but with different side lengths. The values of geometric parameters of molecular structures in each of these compounds are presented. Also, the key thermodynamic parameters of formation (enthalpy ΔfH0, entropy S0, Gibbs' energy ΔfG0) and relative total energies of these compounds are calculated. [ABSTRACT FROM AUTHOR]

G-quadruplexes (G4s) are non-canonical secondary nucleic acid structures. Sequences with the potential to form G4s are abundant in regulatory regions of the genome including telomeres, promoters and 5′ non-coding regions, indicating they fulfill important genome regulatory functions. Generally, G4s perform various biological functions by interacting with proteins. In recent years, an increasing number of G-quadruplex-binding proteins have been identified with biochemical experiments. G4-binding proteins are involved in vital cellular processes such as telomere maintenance, DNA replication, gene transcription, mRNA processing. Therefore, G4-binding proteins are also associated with various human diseases. An intensive study of G4-protein interactions provides an attractive approach for potential therapeutics and these proteins can be considered as drug targets for novel medical treatment. In this review, we present biological functions and structural properties of G4-binding proteins, and discuss how to exploit G4-protein interactions to develop new therapeutic targets. [ABSTRACT FROM AUTHOR]

G-quadruplexes (G4s) are non-canonical DNA structures that could be considered as potential therapeutic targets for antimicrobial compounds, also known as G4-stabilizing ligands. While some of these ligands are shown in vitro to have a stabilizing effect, the precise mechanism of antibacterial action has not been fully investigated. Here, we employed genome-wide RNA-sequencing to analyze the response of Mycobacterium smegmatis to inhibitory concentrations of BRACO-19 and TMPyP4 G4 ligands. The expression profile changed (FDR < 0.05, log2FC > |1|) for 822 (515↑; 307↓) genes in M. smegmatis in response to BRACO-19 and for 680 (339↑; 341↓) genes in response to TMPyP4. However, the analysis revealed no significant ligand-induced changes in the expression levels of G4-harboring genes, genes under G4-harboring promoters, or intergenic regions located on mRNA-like or template strands. Meanwhile, for the BRACO-19 ligand, we found significant changes in the replication and repair system genes, as well as in iron metabolism genes which is, undoubtedly, evidence of the induced stress. For the TMPyP4 compound, substantial changes were found in transcription factors and the arginine biosynthesis system, which may indicate multiple biological targets for this compound. [ABSTRACT FROM AUTHOR]

This paper used a randomised field experiment to test if tailoring an email invitation induces pension scheme participants to delve into their online personal pension situation. Action perspective and degree of urgency conveyed in the invitation were tailored based on gender and age. Overall, our empirical findings show that such tailoring had no positive effects on (1) the probability that pension scheme participants click on the weblink to access information about their pension situation and (2) the probability to log in to a tool for pension check. [ABSTRACT FROM AUTHOR]

Accumulation of mutations such as deletions in mitochondrial DNA is associated with ageing, cancer and human genetic disorders. These deletions are often flanked by GC‐skewed sequence motifs that can potentially fold into secondary non‐B DNA conformations. G‐quadruplexes are emerging as key initiators of mitochondrial genomic instability. In this issue, Dahal et al provide an in silico analysis of sequence motifs that can fold into altered DNA structures in mitochondrial genomic regions that contain frequent deletions. They show the formation of five G‐quadruplexes near such frequent breakpoints using biochemical and biophysical approaches in vitro and more importantly inside mammalian cells. Comment on: https://doi.org/10.1111/febs.16113 [ABSTRACT FROM AUTHOR]

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Cell metabolism depends, to a large extent, on correct regulation of gene expression. One of the mechanisms of regulation is the formation of nucleic acid secondary structures, among which guanine quadruplexes (G-quadruplexes, or G4) are of particular importance. G-quadruplexes are dynamic structures whose stability is determined by their size, ionic composition, and the nature of the nucleic acids forming them. They are regulated by various protein factors. Guanine quadruplexes play an important role in the regulation of many processes occurring in DNA and RNA, from maintaining telomere homeostasis to determining the ribosome landing site on mRNA. Therefore, these structures are considered a promising target for antitumor therapy, and their detailed study is important to modern biology. This review is focused on the structure and thermodynamic properties of G-quadruplexes together with their interaction with some nuclear proteins. [ABSTRACT FROM AUTHOR]

This study attempts to examine the adaptive market hypothesis and evolving predictability of stock returns using four decades of daily data from the Bombay Stock Exchange (BSE) and the National Stock Exchange (NSE) in India. The recent developed automatic portmanteau ratio (AVR) and wild bootstrap automatic variance ratio (WAVR) test are used for analysis. We also estimate both the AVR and WAVR statistics in the rolling window framework to examine evolving predictability. The results revealed that BSE and NSE are informationally inefficient in the weak-form. The results of rolling window analysis suggested that the degree of predictable patterns evolves over the period due to global and regional economic and non-economic events. Further, the study compare which stock market is more efficient and found that NSE is more efficient than BSE. The findings of this study provide essential inputs to investors on trading strategies in dynamic economic situations and policymakers to formulate an appropriate policy that can make the Indian stock markets efficient. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has become a global public health emergency. G-quadruplex, one of the non-canonical secondary structures, has shown potential antiviral values. However, little is known about the G-quadruplexes of the emerging SARS-CoV-2. Herein, we characterized the potential G-quadruplexes in both positive and negative-sense viral strands. The identified potential G-quadruplexes exhibited similar features to the G-quadruplexes detected in the human transcriptome. Within some bat- and pangolin-related betacoronaviruses, the G-tracts rather than the loops were under heightened selective constraints. We also found that the amino acid sequence similar to SUD (SARS-unique domain) was retained in SARS-CoV-2 but depleted in some other coronaviruses that can infect humans. Further analysis revealed that the amino acid residues related to the binding affinity of G-quadruplexes were conserved among 16,466 SARS-CoV-2 samples. Moreover, the dimer of the SUD-homology structure in SARS-CoV-2 displayed similar electrostatic potential patterns to the SUD dimer from SARS. Considering the potential value of G-quadruplexes to serve as targets in antiviral strategy, our fundamental research could provide new insights for the SARS-CoV-2 drug discovery. [ABSTRACT FROM AUTHOR]

Genes encoding 45S ribosomal RNA (rDNA) are known for their abundance within eukaryotic genomes and for their unstable copy numbers in response to changes in various genetic and epigenetic factors. Commonly, we understand as epigenetic factors (affecting gene expression without a change in DNA sequence), namely DNA methylation, histone posttranslational modifications, histone variants, RNA interference, nucleosome remodeling and assembly, and chromosome position effect. All these were actually shown to affect activity and stability of rDNA. Here, we focus on another phenomenon – the potential of DNA containing shortly spaced oligo-guanine tracts to form quadruplex structures (G4). Interestingly, sites with a high propensity to form G4 were described in yeast, animal, and plant rDNAs, in addition to G4 at telomeres, some gene promoters, and transposons, suggesting the evolutionary ancient origin of G4 as a regulatory module. Here, we present examples of rDNA promoter regions with extremely high potential to form G4 in two model plants, Arabidopsis thaliana and Physcomitrella patens. The high G4 potential is balanced by the activity of G4-resolving enzymes. The ability of rDNA to undergo these "structural gymnastics" thus represents another layer of the rich repertoire of epigenetic regulations, which is pronounced in rDNA due to its highly repetitive character. [ABSTRACT FROM AUTHOR]

This paper explores the role of sentiment in style investing for a sample of eight Eurozone markets and makes a distinction between fundamentals-driven sentiment and sentiment based on non-fundamental information. The findings indicate that style portfolio returns are statistically and economically significant, however, their return differential is not. Style portfolio returns are sensitive to changes in sentiment with value portfolios exhibiting higher sensitivity, and sentiment variance explains a significant percentage of style portfolio return variance. For example, for Germany during the US financial crisis the variance of fundamentals-driven sentiment accounts for 19.65% of the value portfolio variance and the variance of non-fundamental sentiment for a further 24.67%. The results are robust to the choice of valuation ratios in defining investment style. Finally, style portfolio returns tend to be higher, on average, during optimistic months (high sentiment), for the majority of the markets. For instance, during the US crisis, when high non-fundamental sentiment prevails, for five northern Eurozone markets, value portfolio monthly returns range between 2.54 and 3.87%. [ABSTRACT FROM AUTHOR]

In this paper, we employ the Heston stochastic volatility model to describe the stock's volatility and apply the model to derive and analyze trading strategies for dealers in a security market with price discovery. The problem is formulated as a stochastic optimal control problem, and the controlled state process is the dealer's mark-to-market wealth. Dealers in the security market can optimally determine their ask and bid quotes on the underlying stocks continuously over time. Their objective is to maximize an expected profit from transactions with a penalty proportional to the variance of cumulative inventory cost. We provide an approximate, analytically tractable solution to the stochastic control problem. Numerical experiments are given to illustrate the effects of various parameters on the performances of trading strategies. [ABSTRACT FROM AUTHOR]

Based upon my experience in research, teaching, writing textbooks, and editing handbooks and journals, this review paper discusses how financial econometrics, mathematics, statistics, and financial technology can be used in research and teaching for students majoring in quantitative finance. A major portion of this paper discusses essential content of Lee and Lee (Handbook of financial econometrics, mathematics, statistics, and machine learning, World Scientific, Singapore, 2020). Then Lee (From east to west: memoirs of a finance professor on academia, practice, and policy, World Scientific, Singapore, 2017), Lee et al. (Financial econometrics, mathematics and statistics, Springer, New York, 2019a; Machine learning for predicting default of credit card holders and success of kickstarters. Working paper, 2019b), and Lee and Lee (Handbook of financial econometrics and statistics, Springer, New York, 2015) are used to enhance the content of this paper. In addition, important and relevant papers, which have been published in different journals are also used to support the issues discussed in this paper. I have found the applications of financial econometrics, mathematics, statistics, and technology have improved drastically over the last five decades. Therefore, both practitioners and academicians need to update their skills in this area to compete in both financial market and academic research. [ABSTRACT FROM AUTHOR]

Although methyl transfer reactions are important in both chemical and biological systems, there is a need for thermodynamic parameters related to methyl affinity and O–CH3 bond dissociation enthalpies (BDEs) relevant to a full understanding of the mechanisms of methyl transfer reactions. As a prelude to the construction of a database of O–CH3 BDEs, the present work examines the reliability of a series of theoretical methods for the prediction of O–CH3 BDEs using a set of 25 compounds that included both aromatic and non-aromatic molecules. The BDEs calculated by density functional theory (DFT) with traditional exchange–correlation functions exhibited much larger errors than those obtained by either the M06-2X or G4 methods. For the non-aromatic compounds, M06-2X/def2-TZVP performed slightly better than G4, but G4 was more accurate for the aromatic molecules. As a result, we recommend G4 as the preferred method for the theoretical estimation of O–CH3 bond dissociation enthalpies, although M06-2X may be a good alternative for large complex molecules when the use of G4 is impractical. [ABSTRACT FROM AUTHOR]

We document how online lenders exploit a flawed, new pricing mechanism in a peer-to-peer lending platform: Prosper.com. Switching from auctions to a posted-price mechanism in December 2010, Prosper assigned loan listings with different estimated loss rates into seven distinctive rating grades and adopted a single price for all listings with the same rating grade. We show that lenders adjusted their investment portfolios towards listings at the low end of the risk spectrum of each Prosper rating grade. We find heterogeneity in the speed of adjustment by lender experience, investment size, and diversification strategies. It took about 16–17 months for an average lender to take full advantage of the "cherry-picking" opportunity under the single-price regime, which is roughly when Prosper switched to a more flexible pricing mechanism. [ABSTRACT FROM AUTHOR]

I model the effect of associative memory on asset prices. The model includes mood-congruent memory, which predicts that the subjective goodness (or badness) of the agent's affective state (e.g., mood) is a cue for positive (negative) information stored in long-term memory. I also include rehearsal, which implies that data recalled in the recent past are more likely to be recalled in the present. I show that mood-congruent memory causes the set of recalled information to be biased, and rehearsal generates autocorrelation in the biases across periods. The theory provides novel explanations for short-run continued overreaction to news, long-run correction of these effects, and excess volatility. I also make the novel predictions that excess volatility is highest during downturns, price biases are increasing in fundamental volatility, knowledge/experience may intensify these biases, and asset prices exhibit excess comovement. [ABSTRACT FROM AUTHOR]

We conduct a series of experiments to examine the effects of the make and take fee structure currently used by equity exchanges in the U.S. We examine the effects of these fees on measures of market quality (efficiency, book depth, and the bid-ask spread). We find spreads to be smaller in the presence of make and take fees, and we note that this fee structure seems to induce buyers (moreso than sellers) to compete for rebates from the exchange leading to higher prices and lower profits. To test whether our results are due to the make and take fee structure or are artefacts of trading fees in general, we performed a second set of experiments in which traders on both sides of a transaction were assessed an identical fee. These identical trading fees do not appear to significantly affect our market quality measures. [ABSTRACT FROM AUTHOR]

This study uses a dynamic herding model that considers intertemporal and cross‐sectional correlation to confirm that loan herding occurs among joint‐stock commercial banks (JSCBs) and city commercial banks (CCBs). We clarify the motivations for bank loan herding. We find that loan herding by both JSCBs and CCBs results more from following the behavior of other same‐type banks than different‐type banks because of characteristic herding or reputational concerns. Loan herding by JSCBs is motivated by investigative herding, whereas loan herding by CCBs results from informational cascades. Moreover, loan herding has a significantly harmful impact on the operating performance of CCBs but not JSCBs, which may be explained by the irrational behavior of CCBs. Our results will help Chinese bank supervisors develop appropriate policies for handling loan herding. [ABSTRACT FROM AUTHOR]

In recent years, thematic exchange-traded funds (ETF) have increased in economic significance. Investors in thematic ETFs have more than just financial objectives and gain a non-monetary added value from a thematic portion in their portfolios. Therefore, traditional portfolio optimization models which target only financial criteria cannot suit these investors' needs anymore. Nevertheless, to account for their thematic interests, investors adapt a core satellite strategy in which conventional core portfolios and thematic satellite portfolios are combined. Thus, these portfolios are separately optimized without further considering inter-portfolio correlation effects. Since modern portfolio theory has originally been established to, inter alia, optimize these correlation effects, portfolios can only be efficient by chance. Therefore, this study targets the correlation effects between conventional and thematic portfolios and uses a tri-criterion thematic portfolio optimization model as an overall framework. Throughout a two-part analysis with tradable ETFs and a simulation with 250,000 draws and 1,750,000 portfolio optimizations performed, the status quo is compared to the tri-criterion model. Quantifying the suboptimality, simulation results show a mean portfolio improvement of 6.23% measured as relative yield enhancement. Further, our analysis concludes that the more narrowly a theme is defined and the more particular it is, relative yield enhancements can increase up to 46.88%. [ABSTRACT FROM AUTHOR]

We evaluate monetary policy divergence in the G4. A Taylor rule is extended that admits a global element and also allows for unconventional monetary policy to be reflected in a shadow policy rate. We propose a policy divergence index based on observed, fitted, or shadow policy rates but which interprets the stance of monetary as dictated by the real interest rate. In spite of flexible exchange rates, each economy's monetary policy is significantly impacted by a global element, pre and post-crisis. Our divergence index also suggests more divergence in the stance of monetary policy than if nominal policy rates alone are compared, whether observed or shadow rates are used. Nevertheless, we conclude that US monetary policy's impact among other systemically important economies has increased since the global financial crisis although divergences persist. [ABSTRACT FROM AUTHOR]

We define quality as characteristics that investors should be willing to pay a higher price for. Theoretically, we provide a tractable valuation model that shows how stock prices should increase in their quality characteristics: profitability, growth, and safety. Empirically, we find that high-quality stocks do have higher prices on average but not by a large margin. Perhaps because of this puzzlingly modest impact of quality on price, high-quality stocks have high risk-adjusted returns. Indeed, a quality-minus-junk (QMJ) factor that goes long high-quality stocks and shorts low-quality stocks earns significant risk-adjusted returns in the United States and across 24 countries. The price of quality varies over time, reaching a low during the internet bubble, and a low price of quality predicts a high future return of QMJ. Analysts' price targets and earnings forecasts imply systematic quality-related errors in return and earnings expectations. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this paper is to provide insight to practitioners who wish to forecast market returns based on event occurrences.Design/methodology/approach Using 64 distinct events that reoccurred from 2007 to 2016 in six different nations of both developing and developed economies, this study used an event study methodology to test whether or not sentiment impacted market returns.Findings This study found that investor sentiment did impact market returns. Furthermore, events that were in developed economies or were negative impacted the market returns more than events that are in developing economies or positive. The study also provides important information on the speed of price adjustment to new information. The events selected include festive holidays, bombings, natural disasters and sports matches, among other events which had been found to alter mood. This paper also found no empirical difference between using the statistical mean and economic capital asset pricing models. However, the Wilcoxon rank test did provide more significant events than the more conservative Corrado rank test.Originality/value Most comprehensive investor sentiment impact on market returns paper using an event study methodology. The results have implications for those who wish to forecast market returns based on event occurrences. [ABSTRACT FROM AUTHOR]

Is a firm that is known for positively engaging stakeholders expected to voluntarily disclose bad financial news? If it makes the announcement, does its corporate goodness help to mitigate the stock price reaction? We examine these issues using a sample of profit warnings, and a sample of firms with negative earnings surprises that did not warn. Firms that have positive corporate social responsibility ratings are more likely to provide earnings warnings than other firms. When they do provide a profit warning, the event negative abnormal returns are of significantly smaller magnitude than the returns of other firms providing warnings. This effect does not occur for social firms that decide not to warn. They suffer the same negative stock price impact on the earnings announcement day as other firms. [ABSTRACT FROM AUTHOR]