Search Results (3,498)

If intraday price data are unavailable, then using daily returns to construct realized measures of the variances of lower-frequency returns is a natural substitute for using high-frequency returns in this context. Notably, a suitable application of this approach yields realized measures that are unbiased estimators of the unconditional and conditional variances of holding period returns for any investment horizon. I use a long sample of daily S&P 500 index returns to investigate the merits of constructing realized measures in this fashion. First, I conduct a Monte Carlo study using a data generating process that reproduces the key dynamic properties of index returns. The results of the study suggest that using realized measures constructed from daily returns to estimate the conditional and unconditional variances of lower-frequency returns should lead to substantial increases in efficiency. Next, I fit a multiplicative error model to the realized measures for weekly and monthly index returns to obtain out-of-sample forecasts of their conditional variances. Using the forecasts produced by a generalized autoregressive conditional heteroskedasticity model as a benchmark, I find that the forecasts produced by the multiplicative error model always generate lower mean absolute errors. Furthermore, the improvements in forecasting performance are statistically significant in most cases. Full article

Global modern renewable energy based on geothermal, wind, solar, and marine resources has grown rapidly over the last decades despite low energy density, intermittent supply, and other qualities inferior to those of fossil fuels. What is the explanation for this growth? The main drivers of growth are assessed using economic theories and verified with statistical data. From the neo-classic viewpoint that focuses on price substitutions, the growth can be explained by the shift from energy-intensive agriculture and industry to labour-intensive services. However, the energy resources complemented rather than substituted for each other. In the evolutionary idea, investments supported by policies enabled cost-reducing technological change. Still, policies alone are insufficient to generate the growth of modern renewable energy as they are inconsistent across countries and in time. From the behavioural perspective that is preoccupied with innovative entrepreneurs, the value addition of electrification can explain the introduction of modern renewable energy in market niches, but not its fast growth. Instead of these mono-causalities, the growth of modern renewable energy is explained by technology diffusion during the pioneering, growth, and maturation phases. Possibilities that postpone the maturation are pinpointed. Full article

Recipes available on the web often lack nutritional transparency and clear indicators of dietary suitability. While searching by title is straightforward, exploring recipes that meet combined dietary needs, nutritional goals, and ingredient-level preferences remains challenging. Most existing recipe search systems do not effectively support flexible multi-dietary reasoning in combination with user preferences and restrictions. For example, users may seek gluten-free and dairy-free dinners with suitable substitutions, or compound goals such as vegan and low-fat desserts. Recent systematic reviews report that most food recommender systems are content-based and often non-personalized, with limited support for dietary restrictions, ingredient-level exclusions, and multi-criteria nutrition goals. This paper introduces DietQA, an end-to-end, language-adaptable chatbot system that integrates a Knowledge Graph (KG), Retrieval-Augmented Generation (RAG), and a Large Language Model (LLM) to support personalized, dietary-aware recipe search and question answering. DietQA crawls Greek-language recipe websites to extract structured information such as titles, ingredients, and quantities. Nutritional values are calculated using validated food composition databases, and dietary tags are inferred automatically based on ingredient composition. All information is stored in a Neo4j-based knowledge graph, enabling flexible querying via Cypher. Users interact with the system through a natural language chatbot friendly interface, where they can express preferences for ingredients, nutrients, dishes, and diets, and filter recipes based on multiple factors such as ingredient availability, exclusions, and nutritional goals. DietQA supports multi-diet recipe search by retrieving both compliant recipes and those adaptable via ingredient substitutions, explaining how each result aligns with user preferences and constraints. An LLM extracts intents and entities from user queries to support rule-based Cypher retrieval, while the RAG pipeline generates contextualized responses using the user query and preferences, retrieved recipes, statistical summaries, and substitution logic. The system integrates real-time updates of recipe and nutritional data, supporting up-to-date, relevant, and personalized recommendations. It is designed for language-adaptable deployment and has been developed and evaluated using Greek-language content. DietQA provides a scalable framework for transparent and adaptive dietary recommendation systems powered by conversational AI. Full article

Background/Objectives: Colorectal carcinoma (CRC) is among the most commonly diagnosed cancers in both men and women. Although CRC mortality is generally decreasing, new therapeutic options are needed for unresponsive subgroups of CRC patients. Methods: A series of known and new tyrphostin derivatives was tested for their efficacy against three CRC cell lines with varying KRAS, p53, and/or BRAF statuses. Growth inhibition, apoptosis induction, and inhibition of EGFR and VEGFR-2 were investigated. Results: Tyrphostin A9, the known RG13022-related tyrphostin 1a and its dichlorido(p-cymene)ruthenium(II) complex 1b, and the new SF₅-substituted compounds 2a and 2b showed selective antiproliferative activity against KRAS-mutant HCT-116 CRC cells expressing wildtype p53, while p53-knockout HCT-116 and KRAS-wildtype BRAF/p53-mutant HT-29 CRC cells were distinctly less sensitive. In HCT-116 cells, only tyrphostin A9 increased mRNA expression of caspases 3 and 8, as well as the kinases MEK1 and MEK2, whereas 2a reduced caspase 8 mRNA levels. Tyrphostin A9 increased caspase 3 activity and induced apoptosis in HCT-116 p53-wildtype cells while simultaneously inhibiting the receptor tyrosine kinases EGFR and VEGFR-2 at low nanomolar concentrations. Conclusions: Tyrphostin A9 could be a promising therapeutic option for the treatment of KRAS-mutant CRC that expresses wildtype p53. Full article

This study investigates the interpretation of hand gestures in nonverbal communication, with particular attention paid to cases where gesture form does not reliably convey the intended meaning. Hand gestures are a key medium for expressing impressions, complementing or substituting verbal communication. For example, the “Thumbs Up” gesture is generally associated with approval, yet its interpretation can vary across contexts and individuals. Using participant-generated descriptive words, sentiment analysis with the VADER method, and fuzzy membership modeling, this research examines the variability and ambiguity in gesture–intention mappings. Our results show that Negative gestures, such as “Thumbs Down,” consistently align with Negative sentiment, while Positive and Neutral gestures, including “Thumbs Sideways” and “So-so,” exhibit greater interpretive flexibility, often spanning adjacent sentiment categories. These findings demonstrate that rigid, category-based classification systems risk oversimplifying nonverbal communication, particularly for gestures with higher interpretive uncertainty. The proposed fuzzy logic-based framework offers a more context-sensitive and human-aligned approach to modeling gesture intention, with implications for affective computing, behavioral analysis, and human–computer interaction. Full article

Chrysin (5,7-dihydroxyflavone) is a flavonoid widely distributed in propolis, honey, and various plant sources. It exhibits a wide range of pharmacological activities, including anti-inflammatory, antioxidant, anticancer, antimicrobial, and anti-diabetic effects. However, its clinical translation is hampered by poor aqueous solubility, low bioavailability, and rapid metabolic clearance. To address these limitations and expand the chemical space of this natural scaffold, extensive synthetic efforts have focused on generating structurally diverse chrysin derivatives that possess improved drug-like properties. This review systematically categorizes synthetic methodologies—such as etherification, esterification, transition-metal-mediated couplings, sigmatropic rearrangements, and electrophilic substitutions—and integrates them with corresponding biological outcomes. Particular emphasis is placed on recent (2020–present) advances that directly link structural modifications with pharmacological enhancements, thereby offering comparative structure–activity relationship (SAR) insights. In addition, transition-metal-catalyzed C–C bond-forming reactions are highlighted in a dedicated section, underscoring their growing role in accessing bioactive chrysin analogs previously unattainable by conventional chemistry. Unlike prior reviews that mainly summarized biological activities or broadly covered flavonoid scaffolds, this article bridges synthetic diversification with pharmacological evaluation. It provides both critical synthesis and mechanistic interpretation. Overall, this work consolidates current knowledge and suggests future directions that integrate synthetic innovation with pharmacological validation and address pharmacokinetic challenges in chrysin derivatives. Full article

Soft-furred tree mice (genus Typhlomys), which are native to southern China and northern Vietnam, are unique rodents capable of echolocation. Little is known about their taxonomy, ecology, and natural history. In this study, we generated the complete mitochondrial genomes of seven species/putative species of Typhlomys. We conducted a comprehensive comparative analysis of these mitochondrial genomes focusing on sequence length, A+T content, A/T bias, A+T-rich regions, overlapping and intergenic spacer regions, nucleotide composition, relative synonymous codon usage, ancestral distributions, and the non-synonymous/synonymous substitution ratio (Ka/Ks). Additionally, we analyzed the phylogeny and adaptive evolution of these species/putative species. The mitogenomes of Typhlomys ranged from 16,487 to 17,380 bp in length, encoding the complete set of 37 genes typically found in mammalian mitogenomes. The base composition exhibited an A+T bias. The most frequently used codons were CUA (Leu), AGC (Ser), GGA (Gly) and UUA (Leu), UUG, CUG, CGU and GCG were the less frequently used codons. Ancestral distribution reconstruction suggests that Typhlomys originated in Central or Southwestern China. Notably, we found that the Ka/Ks ratio of the ND5 gene in T. huangshanensis was greater than 1, indicating that this gene has undergone positive selection for efficient respiration in higher elevations and colder climates. Full article

This study details a biorefinery approach to valorize Dosidicus gigas squid pen waste. The process starts with the enzymatic deproteinization of squid pens, which prove effective with both Alcalase and Novozym, with the latter exhibiting a slightly higher efficiency to yield a material with 73% chitin content. Subsequent alkaline hydrolysis produces highly deacetylated chitosan (>90% degree of deacetylation), followed by controlled depolymerization to obtain polymers with molecular weights ranging from 50 to 251 kDa. Both native and depolymerized chitosan exhibit antimicrobial activity against Escherichia coli and Bacillus cereus, with B. cereus demonstrating greater resistance to chitosan compared to E. coli. The research also explores the bioconversion of deproteinization and deacetylation effluents. Deproteinization effluents prove superior in sustaining microbial growth, supporting comparable growth and lactic acid production for human probiotic strains (Lactobacillus plantarum and Leuconostoc mesenteroides) when substituting commercial peptones. Marine bacteria (Pseudomonas fluorescens and Phaeobacter sp.) show lower productivity. Integrating these processes into a biorefinery framework enables the conversion of 1 kg of dry squid pens into 350 g of chitosan, and facilitates the production of 937–949 g of lactic acid using human lactic acid bacteria cultures in media formulated with squid pen-derived effluents, glucose, yeast extract, and mineral salts. This integrated approach highlights the potential for maximizing resource utilization from squid pen waste, reducing environmental impact and generating high-value bioproducts. Full article

Background: The ESR2 gene encodes Estrogen Receptor-β1 (ERβ1), a putative tumor suppressor in hormone-dependent malignancies. Although ERβ biology has been studied extensively at the expression level, the functional impact of nonsynonymous SNPs (nsSNPs) and untranslated-region (UTR) variants in ESR2 remains underexplored. Methods: We retrieved variants from Ensembl and performed an integrative in silico assessment using PredictSNP, I-Mutant, MUpro, HOPE, MutPred2, and CScape for pathogenicity, oncogenicity and structural stability; STRING/KEGG/GO for pathway context; RegulomeDB and polymiRTS for regulatory effects; and cBioPortal for pan-cancer clinical outcomes (breast (BRCA), endometrial (UCEC), and ovarian (OV)). We evaluated effects of nsSNPs on ERβ1 stability, ligand-binding/DNA-binding domains, co-factor recruitment, and post-transcriptional regulation. Results: Across tools, 93 missense nsSNPs were consistently predicted to be deleterious. Notably, several variants were found to destabilize ERβ1, particularly within the ligand-binding domains (LBD) and DNA-binding domains (DBD). Putative oncogenic drivers R198P and D154N showed high CScape scores and very low population frequencies, consistent with pathogenicity. Several substitutions were predicted to impair coactivator binding and disrupt interactions with key transcriptional partners, including JUN, NCOA1, and SP1. At the post-transcriptional level, rs139004885 was predicted to disrupt miRNA binding, while 3′UTR rs4986938 showed strong regulatory potential and comparatively high population frequency; by contrast, most other identified SNPs were rare. Clinically, pan-cancer survival analyses indicated worse overall survival (OS) in BRCA for ESR2-Altered cases (HR ≈ 2.25; q < 0.001), but better OS in UCEC (HR ≈ 0.24; q ≈ 0.014) and OV (HR ≈ 0.29; q < 0.001), highlighting a tumor-type-specific association. Conclusions: This integrative analysis prioritizes high-impact ESR2 variants that likely impair ERβ1 structure and shows context-dependent clinical effects. Despite their generally low frequency (except for rs4986938), prospective validation linking variant class to ERβ expression and survival outcomes is needed to support biomarker development and therapeutic applications. Full article

Introduction: For pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia (FNAIT) or hemolytic disease of the fetus and newborn (HDFN), prenatal intervention in subsequent pregnancies may be necessary to prevent complications for the fetus. A non-invasive prenatal diagnostic procedure (NIPD) is recommended for fetal blood group genotyping. RT-PCR is used for fetal RHD determination as a reliable screening method with high sensitivity and specificity. For other antigens with variants involving single-base substitutions, droplet digital PCR (ddPCR) and next-generation sequencing (NGS) are recommended to reduce the risk of false-negative results. Only NGS offers the possibility of determining the cell-free fetal DNA (cffDNA) fraction in maternal plasma by sequencing additional gene fragments in parallel, but no standard exists for assay validation. Material and Methods: A custom-made primer panel was designed to target the common platelet and red cell antigens involved in fetal red cell and platelet incompatibilities, as well as additional anonymous single-nucleotide polymorphism (SNP) targets for use as an internal control. Amplicon-based NGS was carried out using semiconductor sequencing. For HPA-1a (HPA*1A, ITGB3) and K (KEL*01.01, KEL) assay validation, the limit of detection (LOD) and limit of quantification (LOQ) were estimated, as were false-positive antithetic alleles, linearity, and inter-assay variation, using cell-free DNA (cfDNA) extracted from the blood samples of healthy blood donors. An additional analysis was performed using 23 diagnostic samples from 21 pregnant women. Results: Regression analysis of dilution series using HPA-1a- and K-positive cell-free plasma samples in antigen-negative donor plasma showed that recovery is definitely feasible up to an HPA*1A and KEL*01.01 allele frequency of 1%. Base calls of false-positive antithetic alleles were detected with a maximum of 0.25% using 21 healthy blood donors. The LOD was estimated to be 0.2057% (mean + 3 SD) for HPA*1A with a LOQ of 0.6298% (mean + 10 SD). For KEL*01.01, the LOD was 0.1706% (mean + 3 SD) and the LOQ was 0.5314% (mean + 10 SD). The analysis of 15 of 21 cases with diagnostic samples from pregnant women with neonatal blood available for confirmatory testing resulted in 100% concordant results. The fetal fraction of these samples was calculated with a median of 11.03% (95% CI: 8.89, 13.20). Conclusions: NGS for non-invasive fetal blood group genotyping is an accurate and reliable method. In-house validation of the used assays can be performed using healthy donors to determine the LOD, LOQ and sensitivity. The threshold for paternally inherited fetal HPA*1A and KEL*01.01 alleles could be set at 1% (i.e., 2% fetal fraction) to obtain reliable test results. Internal controls for assessing the fetal fraction are essential to avoid false-negative test results. Full article

Photodynamic inactivation and antimicrobial photodynamic therapy (PDI/APDT) based on the toxic properties of reactive oxygen species (ROS), which are generated by a number of photoexcited dyes, are promising for preventing and treating infections, especially those associated with drug-resistant pathogens. The negatively charged bacterial cell surface attracts polycationic photosensitizers, which contribute to the vulnerability of the bacterial plasma membrane to ROS. The integrity of the plasma membrane is critical for the viability of the bacterial cell. Polycationic phthalocyanines are regarded as promising photosensitizers due to their high quantum yields of ROS generation (mainly singlet oxygen), high extinction coefficients in the far-red spectral range, and low dark toxicity. For application in PDI/APDT, the wide range of possibilities of modifying the chemical structure of phthalocyanines is particularly valuable, especially by introducing various peripheral and non-peripheral substituents into the benzene rings. Depending on the type and location of such substituents, it is possible to obtain photosensitizers with different photophysical properties, photochemical activity, solubility in an aqueous medium, biocompatibility, and tropism for certain structures of photoinactivation targets. In this study, we tested novel water-soluble Zn (II) phthalocyanines bearing four 4-((diethylmethylammonium)methyl)phenoxy substituents with symmetric and asymmetric charge distributions for photodynamic antibacterial activity and compared them with those of water-soluble octacationic zinc octakis(cholinyl)phthalocyanine. The obtained results allow us to conclude that the studied tetracationic aryloxy-substituted Zn(II) phthalocyanines effectively bind to the oppositely charged cell wall of the Gram-negative bacteria E. coli. This finding is supported by data on bacteria’s zeta potential neutralization in the presence of phthalocyanine derivatives and fluorescence microscopy images of stained bacterial cells. Asymmetric substitution influences the aggregation and fluorescent characteristics but has little effect on the ability of the studied tetracationic phthalocyanines to sensitize the bioluminescent E. coli K12 TG1 strain. Both symmetric and asymmetric aryloxy-substituted phthalocyanines are no less effective in PDI than the water-soluble zinc octakis(cholinyl)phthalocyanine, a photosensitizer with proven antibacterial activity, and have significant potential for further studies as antibacterial photosensitizers. Full article

Bioplastics are gaining attention as eco-friendly alternatives to conventional plastics, with Polybutylene Adipate Terephthalate (PBAT) emerging as a promising biodegradable substitute for polyethylene (PE) in food packaging. Commercial PBAT is often blended with other plastics or bio-based fillers to improve mechanical properties and reduce costs, though these additives can influence its environmental footprint. Therefore, this study quantifies the environmental impacts of producing PBAT resin blends reinforced with common inorganic fillers and compares end-of-life (EoL) performance against PE. While prior studies have largely assessed virgin PBAT or PBAT/Polylactic Acid (PLA) systems, systematic LCA of commercial-style PBAT blends with inorganic fillers and screening LCA level for comparisons of composting vs. landfill remain limited. The contributions of this study are to: (i) map gate-to-gate environmental hotspots for PBAT-blend conversion, (ii) provide a screening gate-to-grave comparison of PBAT composting vs. PE landfill using ReCiPe 2016 and IPCC GWP100 methods, and (iii) discuss theoretical implications for material substitution in the context of EoL strategies. The results indicated that producing 1 kg of PBAT blend generated a single score impact of 921 mPt with Human Health and Resource categories contributing similarly, and a GWP of 8.64 kg CO₂-eq, dominated by mixing and drying processes. EoL screening showed PBAT composting offered clear advantages over landfilling PE, yielding −53.9 mPt and 11.35 kg CO₂-eq savings, effectively offsetting production emissions. In contrast, landfilling PE resulted in 288.8 mPt and 2.2 kg CO₂-eq emissions. Sensitivity analysis further demonstrated that a 30% reduction in electricity use could decrease impacts by up to 10%, underscoring the importance of energy efficiency improvements and renewable energy adoption for sustainable PBAT development. Full article

Optimizing in vitro culture conditions for cryopreserved–thawed human ovarian cortical fragments (OCFs) represents a critical step in fertility preservation strategies. OCFs predominantly contain primordial follicles (PMFs), whose survival and integrity are essential for ex vivo folliculogenesis. This study aimed to evaluate the impact of different culture media supplementations on PMF survival and tissue morphology by comparing alpha-Minimum Essential Medium (αMEM) supplemented with Human Serum Albumin (HSA), Human Serum (HS), or Serum Substitute Supplement (SSS). Twenty-nine OCFs were cultured for three days, and follicular density and were morphology assessed. Generalized linear mixed model analysis showed that PMF density was significantly higher in OCFs cultured in medium supplemented with SSS (213 PMFs/mm³) compared to those cultured with HSA (107 PMFs/mm³) or HS (93 PMFs/mm³). Furthermore, SSS supplementation was associated with a significant increase in the number of PMFs showing healthy morphologies. These findings indicate that SSS supplementation to αMEM enhances the survival and preserves better morphologies of the human PMFs in short-term culture, highlighting its potential as a suitable culture supplement for ovarian tissue preservation. Full article

The construction sector accounts for one-third of Europe’s total greenhouse gas (GHG) emissions, offering significant potential for emission reduction. Emission reduction can be achieved by substituting conventional building materials with wood- or bio-based alternatives; the difference in GHG emissions is referred to as the substitution potential (SP). In this study, a literature review was conducted to identify studies in which SPs had been determined. The calculation methods used for these SPs were then analysed in detail. The analysis considered the general conditions, outcomes, and scaling effects, revealing that differing initial conditions lead to inconsistent results. Therefore, transparent allocation of SPs and comparable product life cycle assessments (LCAs) based on functional equivalence are essential. To reliably extrapolate the benefits of wood use to the entire construction sector, scaling effects must be justified by consistent functional equivalence. For policy relevance, it is crucial that SPs are determined using the standardised rules and that the building level, as the actual place of material use, is not overlooked. This is particularly important when scaling up the effects of increased wood use to the landscape level. Only with these measures SPs at the product level can provide reliable results in a broader context. Additionally, the studies reviewed indicate that changes in forest management have not yet been considered. Full article

Discourse markers have been extensively studied in spoken languages from different perspectives, covering monolingual, contrastive, and translation studies. However, research on these items remains limited for signed languages, with only a handful of scattered publications. Following a corpus-based approach, this paper aims to investigate discourse markers in French Belgian Sign Language (LSFB), including their types, functions, and translation/s into written French. An 18 min sample of three dialogues and six signers was analyzed using a two-level independent taxonomy (domain and function) previously applied to spoken and signed data. Overall, 251 discourse markers were identified in the LSFB sample. They can be manual, nonmanual, or a combination of both, the latter type being the most frequent. In contrast to the previous literature, discourse markers cannot be spatial in LSFB. Regarding their functional spectrum, most discourse markers belong to the sequential domain (i.e., they are mostly used to structure discourse) and express ‘addition’ (i.e., providing more information) or ‘monitoring’ (i.e., keeping control over one’s turn or over the interaction). When examining the translation of DMs, most are either omitted or substituted by other non-discourse marking items in the target texts. Although these results are generally similar to previous studies on DMs in spoken languages, more research on these items in other signed languages is needed to obtain a precise overview of their role in human communication. Full article