Search Results (3,938)

Background/Objectives: Phase II oncology trials often rely on single-arm designs to test $H_0:\pi ={\pi }_0$ versus $H_a:\pi >{\pi }_0$, especially when randomized trials are infeasible due to cost or disease rarity. Traditional approaches, such as the exact binomial test and Simon’s two-stage design, tend to be conservative, with actual Type I error rates falling below the nominal $\alpha$ due to the discreteness of the underlying binomial distribution. This study aims to develop a more efficient and flexible method that maintains accurate Type I error control in such settings. Methods: We propose a convolution-based method that combines the binomial distribution with a simulated normal variable to construct an unbiased estimator of $\pi$. This method is designed to precisely control the Type I error rate while enabling more efficient trial designs. We derive its theoretical properties and assess its performance against traditional exact tests in both one-stage and two-stage trial designs. Results: The proposed method results in more efficient designs with reduced sample sizes compared to standard approaches, without compromising the control of Type I error rates. We introduce a new two-stage design incorporating interim futility analysis and compare it with Simon’s design. Simulations and real-world examples demonstrate that the proposed approach can significantly lower trial cost and duration. Conclusions: This convolution-based approach offers a flexible and efficient alternative to traditional methods for early-phase oncology trial design. It addresses the conservativeness of existing designs and provides practical benefits in terms of resource use and study timelines. Full article

Hormone-dependent breast cancer, particularly in its treatment-resistant forms, remains a significant therapeutic challenge. In this study, we applied a fully computational strategy to design steroid-based compounds capable of simultaneously targeting three key receptors involved in disease progression: progesterone receptor (PR), estrogen receptor alpha (ER-α), and HER2. Using a robust 3D-QSAR model (R² = 0.86; Q²_LOO = 0.86) built from 52 steroidal structures, we identified molecular features associated with high anticancer potential, specifically increased polarizability and reduced electronegativity. From a virtual library of 271 DFT-optimized analogs, 31 compounds were selected based on predicted potency (pIC₅₀ > 7.0) and screened via molecular docking against PR (PDB 2W8Y), HER2 (PDB 7JXH), and ER-α (PDB 6VJD). Seven candidates showed strong binding affinities (ΔG ≤ −9 kcal/mol for at least two targets), with Estero-255 emerging as the most promising. This compound demonstrated excellent conformational stability, a robust hydrogen-bonding network, and consistent multitarget engagement. Molecular dynamics simulations over 100 nanoseconds confirmed the structural integrity of the top ligands, with low RMSD values, compact radii of gyration, and stable binding energy profiles. Key interactions included hydrophobic contacts, π–π stacking, halogen–π interactions, and classical hydrogen bonds with conserved residues across all three targets. These findings highlight Estero-255, alongside Estero-261 and Estero-264, as strong multitarget candidates for further development. By potentially disrupting the PI3K/AKT/mTOR signaling pathway, these compounds offer a promising strategy for overcoming resistance in hormone-driven breast cancer. Experimental validation, including cytotoxicity assays and ADME/Tox profiling, is recommended to confirm their therapeutic potential. Full article

Cystic echinococcosis is a zoonosis caused by the cestode Echinococcus granulosus sensu stricto. Population genetic studies and phylogeographic patterns are essential to understanding the transmission dynamics of this parasite under varying environmental conditions. In this study, the genetic diversity of E. granulosus s.s. was evaluated using 46 hydatid cyst samples obtained from sheep, goats, cattle, and humans across three regions of Chile: Coquimbo, La Araucanía, and Magallanes. Mitochondrial cox1 gene sequences were analyzed and compared with reference sequences reported from South America, Europe, Africa, Asia, and Oceania. In Chile, the EG01 haplotype was the predominant haplotype. A total of four haplotypes were identified, with low haplotype diversity (Hd = 0.461 ± 0.00637) and low nucleotide diversity (π = 0.00181 ± 0.00036). The haplotype network displayed a star-like configuration, with the EG01 genotype at the center, suggesting a potentially ancestral or widely distributed lineage. In Coquimbo (Tajima’s D = −0.93302, p = 0.061; Fu’s Fs = −0.003, p = 0.502) and Magallanes (Tajima’s D = −0.17406, p = 0.386; Fu’s Fs = −0.121, p = 0.414), both neutrality tests were non-significant, indicating no strong evidence for recent population expansion or selection. Star-like haplotype network patterns were also observed in populations from Europe, the Middle East, Asia, Africa, and Oceania, with the EG01 genotype occupying the central position. The population genetic structure of Echinococcus granulosus s.s. in Chile demonstrates considerable complexity, with EG01 as the predominant haplotype. Further comprehensive studies are required to assess the intraspecific genetic variability of E. granulosus s.s. throughout Chile and to determine whether this variability influences the key biological traits of the parasite. This structure may prove even more complex when longer fragments are analyzed, which could allow for the detection of finer-scale microdiversity among isolates from different hosts. We recommended that future cystic echinococcosis control programs take into account the genetic variability of E. granulosus s.s. strains circulating in each endemic region, to better understand their epidemiological, immunological, and possibly pathological differences. Full article

The elastic and photoelastic coefficients of Ba₃TaGa₃Si₂O₁₄ (BTGS) crystals were determined by the quantum–mechanical calculation technique. Based on these data, extreme piezo-optic surfaces π′°_km were constructed, which describe the change in the path difference in light beams in the crystal under the influence of mechanical stress. The results for BTGS crystals are compared with the ones for other crystals of the langasite group (La₃Ga₅SiO₁₄, Ca₃Ga₂Ge₄O₁₄, Ca₃TaGa₃Si₂O₁₄ and Ca₃NbGa₃Si₂O₁₄). The global maxima of the π′°_km surfaces for BTGS crystals significantly exceed the ones for the other crystals mentioned above and, accordingly, BTGS crystals can be suitable for use in polarization-optic light modulators and devices based on them. The acousto-optic efficiency of BTGS crystals was evaluated. The correlations between the magnitude of the piezo- and elasto-optic coefficients and the parameters of the unit cell of the studied crystals were determined. Full article

In this paper, the accuracy of basic and advanced spiral inductor models for gallium nitride (GaN) integrated inductors is evaluated. Specifically, the experimental measurements of geometrically scaled circular spiral inductors, fabricated in a radio frequency (RF) GaN-on silicon technology, are exploited to estimate the errors of two lumped geometrically scalable models, i.e., a simple π-model with seven components and an advanced model with thirteen components. The comparison is performed by using either the standard performance parameters, such as inductance (L), quality factor (Q-factor), and self-resonance frequency (SRF), or the two-port scattering parameters (S-parameters). The comparison reveals that despite a higher complexity, the developed advanced model achieves a significant reduction in SRF percentage errors in a wide range of geometrical parameters, while enabling an accurate estimation of two-port S-parameters. Indeed, the correct evaluation of both SRF and two-port S-parameters is crucial to exploit the model in an actual circuit design environment by properly setting the inductor geometrical parameters to optimize RF performance. Full article

Using density functional theory (M06-2X-D3/def2-TZVP), we investigated the 1,2-addition reactions of NH₃ with a series of heavy imine analogues, G13=P-Rea (where G13 denotes a Group 13 element; Rea = reactant), featuring a mixed G13–P–Ga backbone. Theoretical analyses revealed that the bonding nature of the G13=P moiety in G13=P-Rea molecules varies with the identity of the Group 13 center. For G13=B, Al, Ga, and In, the bonding is best described as a donor–acceptor (singlet–singlet) interaction, whereas for G13=Tl, it is characterized by an electron-sharing (triplet–triplet) interaction. According to our theoretical studies, all G13=P-Rea species—except the Tl=P analogue—undergo 1,2-addition with NH₃ under favorable energetic conditions. Energy decomposition analysis combined with natural orbitals for chemical valence (EDA–NOCV), along with frontier molecular orbital (FMO) theory, reveals that the primary bonding interaction in these reactions originates from electron donation by the lone pair on the nitrogen atom of NH₃ into the vacant p-π* orbital on the G13 center. In contrast, a secondary, weaker interaction involves electron donation from the phosphorus lone pair of the G13=P-Rea species into the empty σ* orbital of the N–H bond in NH₃. The calculated activation barriers are primarily governed by the deformation energy of ammonia. Specifically, as the atomic weight of the G13 element increases, the atomic radius and G13–P bond length also increase, requiring a greater distortion of the H₂N–H bond to reach the transition state. This leads to a higher geometrical deformation energy of NH₃, thereby increasing the activation barrier for the 1,2-addition reaction involving these Lewis base-stabilized, heavy imine-like G13=P-Rea molecules and ammonia. Full article

The crystal structures of the 2-amino-5-halogenopyridines (halogen = Cl (1), Br (2)) and 2,3-diamino-5-halogenopyridines (halogen = Cl (3), Br (4)) were compared with respect to their intermolecular interactions. An ab-initio-based method for evaluating the interaction energies between molecules was employed to estimate the driving forces of crystal formation. As a result, regularities in crystal structure organization were identified. For compounds 1 and 2, a dimeric building unit is formed by two N–H…N_pyr hydrogen bonds. These dimers are further connected to neighboring units by C–H…π, C–H…N, N…X (X = Cl, Br), and non-specific interactions. The aforementioned intermolecular interactions give rise to layered structures that are similar but not isotypical. No significant contributions from π–π or N–H…N(H₂) interactions are observed in 1 and 2. The structures of 3 and 4 are isotypical and crystallize in the non-centrosymmetric space group P2₁2₁2₁. The most important intermolecular interactions are N–H…N_pyr, N–H…N(H₂), and stacking interactions. These interactions lead to identical columnar-layered structures in both 3 and 4. No significant contributions from halogen bonds of the type N…X (X = Cl, Br) are found in 3 and 4. Full article

A bijective product k-cordial labeling f of a graph G with vertex set V and edge set E is a bijection from V to $\{1,2,\dots ,|V|\}$ such that the induced edge labeling $f^{\times }:E\left(G\right)\to {\mathbb{Z}}_k=\{i|0\le i\le k-1\}$ defined as $f^{\times }\left(uv\right)\equiv f\left(u\right)f\left(v\right)(\mathrm{mod}k)$ for every edge $uv\in E$ satisfies the condition $|e_f^{\times }\left(i\right)-e_f^{\times }\left(j\right)|\le 1$, where $i,j\in {\mathbb{Z}}_k$ and $e_f^{\times }\left(i\right)$ is the number of edges labeled with i under $f^{\times }$. A graph which admits a bijective product k-cordial labeling is called a bijective product k-cordial graph. In this paper, we study bijective product $\pi$-cordiality for paths and cycles, where $\pi$ is an odd prime. We determine bijective product $\pi$-cordiality for paths and cycles for $3\le \pi \le 13$. Also, we establish the bijective product k-cordial labeling of stars. Further, we find the bijective product 4-cordial labeling of bistars and the splitting graphs of stars and bistars. Full article

The efficiency decline of Francis turbines, a key component of hydroelectric power generation, presents a multifaceted challenge influenced by interconnected factors such as water quality, incidence angle, erosion, and runner wear. This paper is structured into two main sections to address these issues. The first section applies the Buckingham π theorem to establish a dimensional analysis (DA) framework, providing insights into the relationships among the operational variables and their impact on turbine wear and efficiency loss. Dimensional analysis offers a theoretical basis for understanding the relationships among operational variables and efficiency within the scope of this study. This understanding, in turn, informs the selection and interpretation of features for machine learning (ML) models aimed at the predictive maintenance of the target variable and important features for the next stage. The second section analyzes an extensive dataset collected from a Francis turbine in Colombia, a country that is heavily reliant on hydroelectric power. The dataset consisted of 60,501 samples recorded over 15 days, offering a robust basis for assessing turbine behavior under real-world operating conditions. An exploratory data analysis (EDA) was conducted by integrating linear regression and a time-series analysis to investigate efficiency dynamics. Key variables, including power output, water flow rate, and operational time, were extracted and analyzed to identify patterns and correlations affecting turbine performance. This study seeks to develop a comprehensive understanding of the factors driving Francis turbine efficiency loss and to propose strategies for mitigating wear-induced performance degradation. The synergy lies in DA’s ability to reduce dimensionality and identify meaningful features, which enhances the ML models’ interpretability, while ML leverages these features to model non-linear and time-dependent patterns that DA alone cannot address. This integrated approach results in a linear regression model with a performance (R²-Test = 0.994) and a time series using ARIMA with a performance (R²-Test = 0.999) that allows for the identification of better generalization, demonstrating the power of combining physical principles with advanced data analysis. The preliminary findings provide valuable insights into the dynamic interplay of operational parameters, contributing to the optimization of turbine operation, efficiency enhancement, and lifespan extension. Ultimately, this study supports the sustainability and economic viability of hydroelectric power generation by advancing tools for predictive maintenance and performance optimization. Full article

The introduction of axions gives rise to additional one-loop diagrams for the two-photon decays of neutral pions via axion-pion mixing. We compute this correction that has been overlooked in existing calculations, within the framework of SU(2) chiral perturbation theory. Our analysis shows that the correction is proportional to the axion-photon coupling and the square of the axion mass. In the classical axion parameter space, this correction is strongly suppressed by the axion decay constant. However, for QCD axions in the MeV or higher mass range, the correction may become significant. Furthermore, when combined with experimental measurements of the decay width of the ${\pi }^0\to \gamma \gamma$ process, our results rule out the standard QCD axion as a viable explanation for the observed discrepancy between chiral perturbation theory predictions and experimental data. Full article

The Millard’s rat (Dacnomys millardi), a threatened murid endemic to Southeast Asian montane rainforests and the sole member of its monotypic genus, faces escalating endangered risks as a Near Threatened species in China’s Biodiversity Red List. This ecologically specialized rodent exhibits diagnostic morphological adaptations—hypertrophied upper molars and cryptic pelage—that underpin niche differentiation in undisturbed tropical/subtropical forests. Despite its evolutionary distinctiveness, the conservation prioritization given to Dacnomys is hindered due to a deficiency of data and unresolved phylogenetic relationships. Here, we integrated morphological analyses with the first complete mitogenome (16,289 bp in size; no structural rearrangements) of D. millardi to validate its phylogenetic placement within the subfamily Murinae and provide novel insights into genetic diversity erosion. Bayesian and maximum likelihood phylogenies robustly supported Dacnomys as sister to Leopoldamys (PP = 1.0; BS = 100%), with an early Pliocene divergence (~4.8 Mya, 95% HPD: 3.65–5.47 Mya). Additionally, based on its basal phylogenetic position within Murinae, we propose reclassifying Micromys from Rattini to the tribe Micromyini. Codon usage bias analyses revealed pervasive purifying selection (Ka/Ks < 1), constraining mitogenome evolution. Genetic diversity analyses showed low genetic variation (CYTB: π = 0.0135 ± 0.0023; COX1: π = 0.0101 ± 0.0025) in fragmented populations. We propose three new insights into this genetic diversity erosion. (1) Evolutionary constraints: genome-wide evolutionary conservation and shallow evolutionary history (~4.8 Mya) limited mutation accumulation. (2) Anthropogenic pressures: deforestation-driven fragmentation of habitats (>20,000 km²/year loss since 2000) has reduced effective population size, exacerbating genetic drift. (3) Ecological specialization: long-term adaptation to stable niches favored genomic optimization over adaptive flexibility. These findings necessitate suitable conservation action by enforcing protection of core habitats to prevent deforestation-driven population collapses and advocating IUCN reclassification of D. millardi from Data Deficient to Near Threatened. Full article

In this study, the design and synthesis of a novel series of cinnamic acid and 1,2,4-triazole hybrids were reported, aiming to enhance antioxidant and lipoxygenase inhibitory activities through pharmacophore combination. Cinnamic acid derivatives and 1,2,4-triazoles exhibit a broad spectrum of biological activities; therefore, by synthesizing hybrid molecules, we would like to exploit the beneficial characteristics of each scaffold. The general synthetic procedure comprises three synthetic steps, starting from the reaction of appropriate substituted cinnamic acid with hydrazine monohydrate in acetonitrile with cyclohexane and resulting in the formation of hydrazides. Consequently, the hydrazides reacted with phenylisothiocyanate under microwave irradiation conditions. Then, cyclization proceeded to the 1,2,4-triazole after the addition of NaOH solution and microwave irradiation. All the synthesized derivatives have been studied for their ability (a) to interact with the free radical DPPH, (b) inhibit lipid peroxidation induced by AAPH, and (c) inhibit soybean lipoxygenase. The synthesized derivatives have shown significant antioxidant activity and have been proved to be very good lipoxygenase inhibitors. Compounds 4b and 4g (IC₅₀ = 4.5 μM) are the most potent within the series followed by compound 6a (IC₅₀ = 5.0 μM). All the synthesized derivatives have been subjected to docking studies related to soybean lipoxygenase. Compound 4g exhibited a docking score of −9.2 kcal/mol and formed hydrophobic interactions with Val126, Tyr525, Lys526, Arg533, and Trp772, as well as a π−cation interaction with Lys526. Full article

The Ising model is famous in condensed matter and statistical physics. In this work we present a free-fermion formulation of the two-dimensional classical Ising models on honeycomb, triangular and Kagomé lattices. Each Ising model is studied in the cases of a zero field and of an imaginary field $i(\pi /2)k_{B}T$. We employ the decorated lattice technique, star-triangle transformation, and weak-graph expansion method to exactly map each Ising model in both cases into an eight-vertex model on the square lattice. The resulting vertex weights are shown to satisfy the free-fermion condition. In the zero-field case, each Ising model is an even free-fermion model. In the case of the imaginary field, the Ising model on the honeycomb lattice is an even free-fermion model, while the models on the triangular and Kagomé lattices are odd free-fermion models. We obtain the exact solution of the Kagomé lattice Ising model under the imaginary field $i(\pi /2)k_{B}T$, a result not previously reported in the literature. We also show that the frustrated Ising models on the triangular and Kagomé lattices in the imaginary field still exhibit a non-zero residual entropy. Full article

(1) Background: The urate-lowering effects of three iridoid glycosides, which are paederosidic acid, paederosidic acid methyl ester, and paederoside, isolated from Paederia foetida and the protection they provide against hyperuricemia-induced kidney injury were investigated in a rat model. (2) Methods: A hyperuricemia (HUA) rat model was established in Sprague-Dawley (SD) rats through intraperitoneal potassium oxonate (PO) and intragastrical adenine for 2 weeks. Subsequently, rats in the pharmaceutical intervention groups received corresponding drug treatments at a concentration of 40 mg/kg/day, maintained consistently for 7 days. (3) Results: The results showed that three compounds reduced serum urate (SU), creatinine (CRE), and blood urea nitrogen (BUN) levels and that the urinary excretion levels of uric acid, urine urea nitrogen, and creatinine increased. Furthermore, the administration of three iridoid glycosides enhanced renal filtration capacity, as demonstrated by the elevated 24 h creatinine clearance rate (CCR) and 24 h uric acid clearance rate (CUA); improved the fraction excretion of uric acid (FEUA); and attenuated renal damage. Finally, three iridoid glycosides promoted uric acid excretion in HUA rats by downregulating URAT1 and GLUT9 and upregulating ABCG2, OAT1, and OAT3. Moreover, the molecular docking results further corroborated the finding that the three compounds can bind to multiple sites of the uric acid transporter via hydrogen, P-π, and hydrophobic bonds. (4) Conclusions: The three iridoid glycosides were found to lower SU levels by increasing uric acid excretion. They are promising natural products for the prevention of HUA and HUA-induced kidney injury. Full article

Access to clean water is a pressing global concern and membrane technologies play a vital role in addressing this challenge. Thin-film composite membranes prepared via interfacial polymerization (IPol) using meta-phenylenediamine (MPD) and trimesoyl chloride (TMC) exhibit excellent separation performance, but face limitations such as fouling and low hydrophilicity. This study investigated the interaction between MPD and sulfonated zinc phthalocyanine, Zn(SO₂⁻)₄Pc, as a potential strategy for enhancing membrane properties. Using Density Functional Theory (DFT) and Time-Dependent DFT (TD-DFT), we analyzed the optimized geometries, electronic structures, UV–Vis absorption spectra, FT-IR vibrational spectra, and molecular electrostatic potentials of MPD, Zn(SO₂⁻)₄Pc, and their complexes. The results show that MPD/Zn(SO₂⁻)₄Pc exhibits reduced HOMO-LUMO energy gaps and enhanced charge delocalization, particularly in aqueous environments, indicating improved stability and reactivity. Spectroscopic features confirmed strong interactions via hydrogen bonding and π–π stacking, suggesting that Zn(SO₂⁻)₄Pc can act as a co-monomer or additive during IPol to improve polyamide membrane functionality. A conformational analysis of MPD/Zn(SO₂⁻)₄Pc was conducted using density functional theory (DFT) to evaluate the impact of dihedral rotation on molecular stability. The 120° conformation was identified as the most stable, due to favorable π–π interactions and intramolecular hydrogen bonding. These findings offer computational evidence for the design of high-performance membranes with enhanced antifouling, selectivity, and structural integrity for sustainable water treatment applications. Full article