Search Results (76)

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by chronic intestinal inflammation and impaired epithelial barrier function. Emerging evidence highlights the critical role of vascular remodeling and angiogenesis in IBD pathogenesis. This review explores the intricate relationship between blood vessels and the intestinal epithelial barrier, emphasizing how aberrant vascularization contributes to barrier dysfunction and disease progression. In IBD, excessive angiogenesis is driven by hypoxia, immune cell infiltration, and pro-inflammatory cytokines, further perpetuating inflammation and tissue damage. Key angiogenic factors, such as vascular endothelial growth factor (VEGF), angiopoietins, and platelet-derived growth factor (PDGF), are upregulated in IBD, promoting pathological vessel formation. These newly formed vessels are often immature and hyperpermeable, exacerbating leukocyte recruitment and inflammatory responses. Given the pivotal role of angiogenesis in IBD, anti-angiogenic therapies have emerged as a potential therapeutic strategy. Preclinical and clinical studies targeting VEGF and other angiogenic pathways have shown promise in reducing inflammation and promoting mucosal healing. This review summarizes current knowledge on vascular–epithelial interactions in IBD, the mechanisms driving pathological angiogenesis, and the therapeutic potential of anti-angiogenic approaches, providing insights for future research and treatment development. Full article

We introduce a fairly general, recombining trinomial tree model in the natural world. Market completeness is ensured by considering a market consisting of two risky assets, a riskless asset and a European option. The two risky assets consist of a stock and a perpetual derivative of that stock. The option has the stock and its derivative as its underlying. Using a replicating portfolio, we develop prices for European options and generate the unique relationships between the risk-neutral and real-world parameters of the model. We discuss calibration of the model to empirical data in the cases in which the risky asset returns are treated as either arithmetic or logarithmic. From historical price and call option data for select large cap stocks, we develop implied parameter surfaces for the real-world parameters in the model. Full article

Mood disorders, including major depressive disorder and bipolar disorder, are among the most prevalent mental health conditions globally, yet their underlying mechanisms remain incompletely understood. This review critically examines the neuronal atrophy hypothesis, which posits that chronic stress and associated neurobiological changes lead to structural and functional deficits in critical brain regions, contributing to mood disorder pathogenesis. Key mechanisms explored include dysregulation of neurotrophic factors such as brain-derived neurotrophic factor (BDNF), elevated glucocorticoids from stress responses, neuroinflammation mediated by cytokines, and mitochondrial dysfunction disrupting neuronal energy metabolism. These processes collectively impair synaptic plasticity, exacerbate structural atrophy, and perpetuate mood dysregulation. Emerging evidence from neuroimaging, genetic, and epigenetic studies underscores the complexity of these interactions and highlights the role of environmental factors such as early-life stress and urbanization. Furthermore, therapeutic strategies targeting neuroplasticity, including novel pharmacological agents, lifestyle interventions, and anti-inflammatory treatments, are discussed as promising avenues for improving patient outcomes. Advancing our understanding of the neuronal atrophy hypothesis could lead to more effective, sustainable interventions for managing mood disorders and mitigating their global health burden. Full article

This research explores the systemic nature of competitiveness within the cereal sector of the European Union (EU) and addresses the structural interdependencies among key competitiveness drivers through a network-based model. The goal of this research is to offer policy alignment solutions based on the empirical findings derived from a sparse Gaussian graphical model that was operationalized to identify conditional dependencies, synergies, and decouplings across five dimensions: factor endowments, self-sufficiency, trade strategy, resource productivity, and environmental impact. The results showed systemic vulnerabilities, including the decoupling of factor endowments from strategic trade specialization, a pronounced East–West productivity divide, and the asymmetry between the economic valorization of harvested land and its environmental impact, reflected in land management practices. Research findings underscore the need for synergy-driven strategies to coherently align agricultural competitiveness outcomes with the economic and structural potential of each EU country. A critical policy incongruency has been identified: the current prioritization of ecological performance under the Common Agricultural Policy overlooks essential agricultural infrastructural disparities, thereby perpetuating competitiveness asymmetries across the Union. In response, this study introduces a systemic amelioration framework designed to reconcile environmental priorities with agricultural infrastructure development, fostering cohesive and resilient competitiveness throughout the EU cereal sector. Full article

Cystic fibrosis (CF) is characterized by chronic respiratory infections and excessive inflammation, driven by both host- and pathogen-derived proteases. The dysregulated activity of proteolytic enzymes such as neutrophil elastase (NE), cathepsin G, and matrix metalloproteases (MMPs) degrades lung tissue, exacerbates airway remodeling, and perpetuates inflammatory cycles. Concurrently, bacterial proteases from pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus contribute to immune evasion and tissue destruction, compounding disease severity. Despite advances in antimicrobial and anti-inflammatory therapies, protease-driven lung damage remains a critical challenge. This review examines the dual role of host and bacterial proteases in CF pathophysiology, highlighting emerging protease-targeted therapies aimed at mitigating lung damage and inflammation. Strategies explored include the inhibition of NE, MMPs, and bacterial proteases, with a focus on innovative therapeutic approaches such as dual-function inhibitors, biologics, and advanced drug delivery systems. By restoring the protease–antiprotease balance, these interventions offer the potential to improve clinical outcomes and quality of life for CF patients. Full article

Risk is often the most concerning factor in financial transactions. Option Greeks provide valuable insights into the risks inherent in option trading and serve as tools for risk mitigation. Traditionally, scholars compute option Greeks through extensive calculations. This article introduces an alternative method that bypasses conventional derivative computation using the Mellin transform and its properties. Specifically, we derive Greeks for perpetual American options with general payoffs, represented as piecewise linear functions, and examine higher-order risk metrics for practical implications. Examples are provided to illustrate the effectiveness of our approach, offering a novel perspective on calculating and interpreting option Greeks. Full article

The characterization of the lunar surface and subsurface through the utilization of synthetic aperture radar data has assumed a pivotal role in the domain of lunar exploration science. This investigation concentrated on the polarimetric analysis aimed at identifying water ice within a specific crater, designated Erlanger, located at the lunar north pole, which is fundamentally a region that is perpetually shaded from solar illumination. The area that is perpetually shaded on the moon is defined as that region that is never exposed to sunlight due to the moon’s slightly tilted rotational axis. These permanently shaded regions serve as cold traps for water molecules. To ascertain the presence of water ice within the designated study area, we conducted an analysis of two datasets from the Chandrayaan mission: Mini-SAR data from Chandrayaan-1 and Dual-Frequency Synthetic Aperture Radar (DFSAR) data from Chandrayaan-2. The polarimetric analysis of the Erlanger Crater, located in a permanently shadowed region of the lunar north pole, utilizes data from the Dual-Frequency Synthetic Aperture Radar (DFSAR) and the Mini-SAR. This study focuses exclusively on the L-band DFSAR data due to the unavailability of S-band data for the Erlanger Crater. The crater, identified by the PSR ID NP_869610_0287570, is of particular interest for its potential water ice deposits. The analysis employs three decomposition models—m-delta, m-chi, and m-alpha—derived from the Mini-SAR data, along with the H-A-Alpha model known as an Eigenvector and Eigenvalue model, applied to the DFSAR data. The H-A-Alpha helps in assessing the entropy and anisotropy of the lunar surface. The results reveal a correlation between the hybrid polarimetric models (m-delta, m-chi, and m-alpha) and fully polarimetric parameters (entropy, anisotropy, and alpha), suggesting that volume scattering predominates inside the crater walls, while surface and double bounce scattering are more prevalent in the right side of the crater wall and surrounding areas. Additionally, the analysis of the circular polarization ratio (CPR) from both datasets suggests the presence of water ice within and around the crater, as values greater than 1 were observed. This finding aligns with other studies indicating that the high CPR values are indicative of ice deposits in the lunar polar regions. The polarimetric analysis of the Erlanger Crater contributes to the understanding of lunar polar regions and highlights the potential for future exploration and resource utilization on the Moon. Full article

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by self-antibody production and widespread inflammation affecting various body tissues. This disease is driven by the breakdown of immune tolerance, which promotes the activation of autoreactive B and T cells. A key feature of SLE is dysregulation in antigen presentation, where antigen-presenting cells (APCs) play a central role in perpetuating immune responses. Dendritic cells (DCs) are highly specialized for antigen presentation among APCs. At the same time, myeloid-derived suppressor cells (MDSCs) can also express MHC-II molecules, although their role in SLE is less understood. Utilizing the SLE model, MRL/MpJ-Fas^lpr/J, we determined the presence of different phenotypes of DCs and MDSCs expressing MHC-II in secondary lymphoid organs, along with the gene expression of ICOSL, CD80 and CD86 in the spleen. Our study determined that the most abundant population of APCs in secondary lymphoid organs corresponds to cDC CD103⁻CD11b⁺ MHC-II⁺ throughout SLE development. Additionally, ICOSL expression increased over time, becoming more preponderant in week 16 in the SLE model, which could indicate that it is a crucial pathway for the development and progression of the pathology. In week 16, we observed a positive correlation between M-MDSC MHC-II and IFN-γ-producing CD4⁺ T cells. Full article

Pathologic mast cells and basophils, key effector cells in allergic reactions, play pivotal roles in initiating and perpetuating IgE-mediated allergic responses. Conventional therapies for allergies have limitations, prompting exploration into alternative approaches such as small-molecule natural compounds derived from botanical sources. This review synthesizes the existing literature on the effects of these compounds on pathologic mast cells and basophils, highlighting their potential in allergy management, and utilizes the PubMed database for literature acquisition, employing keyword-based searches to identify relevant peer-reviewed sources. Additionally, mechanistic insights were evaluated to contextualize how small-molecule natural compounds can inhibit mast cell/basophil activation, degranulation, and signaling pathways crucial for IgE-mediated allergic reactions. Small-molecule natural compounds exhibit promising anti-allergic effects, yet despite these findings, challenges persist in the development and translation of natural compound-based therapies, including bioavailability and standardization issues. Future research directions include optimizing dosing regimens, exploring synergistic effects with existing therapies, and employing systems pharmacology approaches for a holistic understanding of their mechanisms of action. By harnessing the therapeutic potential of small-molecule natural compounds, effective treatments for allergic diseases may be realized, offering hope for individuals with allergies. Full article

Background: It has been demonstrated that the concept of infinite absorption time, associated with the absorption rate constant, which drives a drug’s gastrointestinal absorption rate, is not physiologically sound. The recent analysis of oral drug absorption data based on the finite absorption time (F.A.T.) concept and the relevant physiologically based finite-time pharmacokinetic (PBFTPK) models developed provided a better physiologically sound description of oral drug absorption. Methods: In this study, we re-analyzed, using PBFTPK models, seven data sets of ketoprofen, amplodipine, theophylline (three formulations), and two formulations (reference, test) from a levonorgestrel bioequivalence study. Equations for one-compartment-model drugs, for the estimation of fraction of dose absorbed or the bioavailable fraction exclusively from oral data, were developed. Results: In all cases, meaningful estimates for (i) the number of absorption stages, namely, one for ketoprofen and the levonorgestrel formulations, two for amlodipine, the immediate-release theophylline formulation, and the extended-release Theotrim formulation, and three for the extended-release Theodur formulation, (ii) the duration of each absorption stage and the corresponding drug input rate, and (iii) the total duration of drug absorption, which ranged from 0.75 h (ketoprofen) to 11.6 h for Theodur were derived. Estimates for the bioavailable fraction of ketoprofen and two theophylline formulations exhibiting one-compartment-model kinetics were derived. Conclusions: This study provides insights into the detailed characteristics of oral drug absorption. The use of PBFTPK models in drug absorption analysis can be leveraged as a computational framework to discontinue the perpetuation of the mathematical fallacy of classical pharmacokinetic analysis based on the absorption rate constant as well as in the physiologically based pharmacokinetic (PBPK) studies and pharmacometrics. The present study is an additional piece of evidence for the scientific and regulatory changes required to be implemented by the regulatory agencies in the not-too-distant future. Full article

As the largest terrestrial ecosystem covering extensive expanses of the Earth’s surface, forests offer crucial health benefits to humans, both directly and indirectly. Presently, health services derived from forest resources have presented significant opportunities for enhancing human well-being. Nonetheless, the absence of a comprehensive understanding regarding the mechanisms by which forests impact human health jeopardizes the potential gains in health. Regrettably, there remains a dearth of scholarly work elucidating these pathways. This paper aims to furnish a thorough examination of how forests influence human health. We initiate by formulating a conceptual framework upon which we delineate the various pathways through which forests impact human health. These encompass the provisioning of resources, preventive services, and forest therapies. Concurrently, we outline the moderating influence of social, economic, and individual characteristics as mediators within this pathway. These characteristics are classified into two overarching dimensions: accessibility and behavioral choices, which notably affect marginalized demographics such as those with lower socioeconomic status, women, the elderly, individuals with disabilities, and children in developing nations. Consequently, we build upon these foundational insights to propose six strategies aimed at perpetuating the positive impact of forests on human health in the foreseeable future. In the future, the development of forest management policies, the assessment of long-term health benefits, social practices, and international cooperation must be considered holistically to attain the dual objective of sustainable forest management and the advancement of human well-being. Full article

We present a unified, market-complete model that integrates both Bachelier and Black–Scholes–Merton frameworks for asset pricing. The model allows for the study, within a unified framework, of asset pricing in a natural world that experiences the possibility of negative security prices or riskless rates. Unlike the classical Black–Scholes–Merton, we show that option pricing in the unified model differs depending on whether the replicating, self-financing portfolio uses riskless bonds or a single riskless bank account. We derive option price formulas and extend our analysis to the term structure of interest rates by deriving the pricing of zero-coupon bonds, forward contracts, and futures contracts. We identify a necessary condition for the unified model to support a perpetual derivative. Discrete binomial pricing under the unified model is also developed. In every scenario analyzed, we show that the unified model simplifies to the standard Black–Scholes–Merton pricing under specific limits and provides pricing in the Bachelier model limit. We note that the Bachelier limit within the unified model allows for positive riskless rates. The unified model prompts us to speculate on the possibility of a mixed multiplicative and additive deflator model for risk-neutral option pricing. Full article

The perpetually fluctuating economic and environmental climate significantly increases the demand for alternative fuel sources. The utilization of hydrogen gas is a viable option for such a fuel source. Hydrogen is one of the most energy-dense known substances; however, it is unfortunately also highly volatile, especially in the diatomic gaseous state most commonly used to store it. The utilization of a hydrogen feedstock material such as sodium borohydride (NaBH₄) may prove to mitigate this danger. When NaBH₄ reacts with water, hydrogen stored within its chemical structure is released. However, the rate of hydrogen release is slow and thus necessitates a catalyst. Platinum nanoparticles were chosen to act as a catalyst for the reaction, and to prevent them from conglomerating, they were embedded in a backbone of mesoporous carbon material (MCM) derived from a sustainable corn starch source. The nanocomposite (Pt-MCM) was characterized via transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD). Pt-MCM underwent catalytic testing, revealing that the catalytic activity of the Pt-MCM composite catalysts increased with increasing quantities of sodium borohydride, lower pH levels, and higher temperatures. The activation energy of the catalyzed reaction was found to be 37.7 kJ mol⁻¹. Reusability experiments showed an initial drop off in hydrogen production after the first trial but subsequent stability. This Pt-MCM catalyst’s competitive activation energy and sustainable MCM backbone derived from readily available corn starch make it a promising option for optimizing the hydrogen generation reaction of NaBH₄. Full article

Our comprehension of the real world remains perpetually incomplete, compelling us to rely on models to decipher intricate real-world phenomena. However, these models, at their pinnacle, serve merely as close approximations of the systems they seek to emulate, inherently laden with uncertainty. Therefore, investigating the disparities between observed system behaviors and model-derived predictions is of paramount importance. Although achieving absolute quantification of uncertainty in the model-building process remains challenging, there are avenues for both mitigating and highlighting areas of uncertainty. Central to this study are three key sources of uncertainty, each exerting significant influence: (i) structural uncertainty arising from inadequacies in mathematical formulations within the conceptual models; (ii) scenario uncertainty stemming from our limited foresight or inability to forecast future conditions; and (iii) input factor uncertainty resulting from vaguely defined or estimated input factors. Through uncertainty analysis, this research endeavors to understand these uncertainty domains within compartmental models, which are instrumental in depicting the complexities of the global carbon cycle. The results indicate that parameter uncertainty has the most significant impact on model outputs, followed by structural and scenario uncertainties. Evident deviations between the observed atmospheric CO₂ content and simulated data underscore the substantial contribution of certain uncertainties to the overall estimated uncertainty. The conclusions emphasize the need for comprehensive uncertainty quantification to enhance model reliability and the importance of addressing these uncertainties to improve predictions related to global carbon dynamics and inform policy decisions. This paper employs partitioning techniques to discern the contributions of the aforementioned primary sources of uncertainty to the overarching prediction uncertainty. Full article

Leaders who lack leadership energy may struggle to demonstrate sustained competence and achieve effectiveness in difficult leadership situations. This research investigates the sources of leadership energy and examines the impact of leadership energy on the development and sustainability of leadership effectiveness and competence. This study employed a hypothetico-deductive research design, wherein the formulated hypotheses were tested through structural equation modelling (SEM). Data were collected using a questionnaire survey. A total of 272 responses were received from leaders of various industries, indicating a response rate of 66%. The findings of this study indicate that a leader’s capacity to respond to various situations, comprehend the importance of being directive, prioritize the development of positive attitudes and supportiveness, and recognize the significance of achievement are all factors that contribute to the internal mechanisms necessary for the leader’s manifestation of leadership energy. The study additionally discovered that leaders’ skills, qualities, and abilities are derived and maintained through their internal capacity and personal resilience emanating from their leadership energy. The hypotheses that were validated suggest a direct causal relationship, indicating that leadership motivation, leadership personality, and leadership orientation are significant factors in the generation of leadership energy. This study’s conclusions suggest that to sustain leadership competence and effectiveness, leaders must cultivate a culture that prioritizes both effectiveness and competence. The findings also imply that individuals must establish precise developmental objectives, as well as exhibit cognizance of and the acquisition of leadership expertise, knowledge and approaches. Thus, the need to reevaluate the competency-based approach to leadership is overwhelming. This study introduces the concept of leadership energy as a catalyst for perpetuating leadership effectiveness and competence. The study claims that the energy emanating from the intricate interplay of leaders’ orientation, experience, development, personality, and motivation engenders and perpetuates their efficacy and aptitude. Full article