Absorption Parameters Research Articles

Determination of Pharmacokinetic and Toxicological Parameters of Some Commonly Used Statin Group Drugs

Statins work as inhibitors of the HMG-CoA reductase enzyme and are the most commonly prescribed cholesterol-lowering drug group for people with cardiovascular disease or risk. This study aimed to determine the pharmacokinetic parameters and toxicities of conventional and new-generation cholesterol drugs such as atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, rosuvastatin and pitavastatin. Absorption, distribution, metabolism, and excretion (ADME) parameters and toxicity predictions of drugs were made using in silico modeling, which gives faster results than animal experiments and does not involve any laboratory costs. In calculations made using structural similarity, compounds' pharmacokinetic properties and toxicity predictions are obtained based on previously known structure-activity data. The study results showed that the toxicity classifications of the drugs were 5 (LD: 5000 mg/kg) for atorvastatin and 6 (LD: 8939 mg/kg) for pravastatin, respectively. The toxicity classes were found to be 4 for all the other statin group drugs. The results showed that pravastatin had the lowest toxicity among investigated cholesterol drugs, while pitavastatin and fluvastatin had the highest toxic effects. Accordingly, it is recommended that the consequences of using pravastatin and atorvastatin, cholesterol drugs with lower toxicity classes, should be investigated more seriously in terms of minimum toxic substance intake for patient groups requiring high doses of medication.

Multifunction and switchable hybrid metasurface based on graphene and gold

This paper presents the design and numerical investigation of a graphene-based switchable terahertz (THz) metasurface for ultrawideband absorption and multiband cross polarization conversion. The device’s operational mode can be altered to absorption or reflection by using the electrostatic capabilities exhibited by graphene. The numerical calculations yield results indicating that in absorption mode, it maintains a bandwidth ratio of 152% within the frequency range of 1.04–7.74 THz. In polarization conversion mode, the design demonstrates the ability to convert linearly polarized and circularly polarized waves to their respective cross-polarization states within the frequency ranges of 1.8–2.5 THz, 3.5–4.1 THz, and 5.6 THz. Moreover, calculated results indicate that linear-to-circular conversion can be realized at 2.64, 3.45, and 5.4 THz frequencies. In addition, the absorption and polarization conversion ratio parameters were analyzed using the multiple reflection theory, which demonstrated significant agreement with the simulation results. The designed metasurface exhibits significant potential in the field of terahertz devices, including stealth technology, smart switches, and other related applications.

Numerical studies of the energy absorption capacities and deformation mechanisms of 2D cellular topologies

This paper investigates the energy absorption capacities of selected cellular topologies under quasi-static loading conditions. Twenty topologies with nearly identical relative densities belonging to 4 groups were examined: honeycomb, re-entrant, bioinspired and chiral. The topologies were modeled using an experimentally validated numerical ABSplus model and subsequently subjected to in-plane uniaxial compression tests. The findings revealed the topologies with the most favorable energy absorption parameters and the main deformation mechanisms. The topologies were classified by mechanism, and a parametric study of basic material properties, namely modulus of elasticity, yield stress, and ductility, was performed for a representative topology from each mechanism. The results indicated that the honeycomb group topologies were characterized by the largest average absorbed energy, and yield stress was found to have the greatest impact on energy absorption efficiency regardless of the main deformation mechanism.

New insights from seasonal and weekly evolutions of aerosol absorption properties and their association with PM2.5 and NO2 concentrations at a central Mediterranean site

Aerosol absorption parameters were investigated in this study using the measurements performed by an aethalometer during a monitoring campaign from December 2021 to July 2022 in a suburban area in south-eastern Italy. The aerosol absorption coefficient was compared to both PM2.5 and NO2 concentrations from two nearby stations (a rural and an urban site). Different seasonal evolutions were identified for these extensive parameters, even if they also showed a common feature because all these parameters presented a higher variability in winter due to the highly variable meteorological conditions during that season. Intensive parameters like the aerosol absorption Ångström exponent and the PM2.5/PM10 ratio were also investigated showing the effects of wood burning from domestic heating and of vehicular traffic, especially both in the urban and in the suburban site. Then, the weekly evolution of both selected extensive and intensive parameters was also analyzed to identify potential impacts due to the weekly cycle of human activities. Most of the selected parameters presented a significant increase starting from Tuesday to Friday and then they generally decreased during the weekends due to the relevant reduction of the human activities. The selection of different types of monitoring sites (urban, suburban, and rural) and temporal scales (seasonal and weekly) has been proved for a proper characterization of the aerosol absorption properties at the monitored area due to its geographical location at the center of the Mediterranean area.

Modeling the subcutaneous pharmacokinetics of antibodies co-administered with rHuPH20.

Predicting the subcutaneous (SC) pharmacokinetics (PK) of antibodies in humans is challenging, with clinical data currently being the only reliable data source for modeling SC absorption and bioavailability. Recombinant human hyaluronidase PH20 (rHuPH20) is an enzyme that facilitates SC delivery of high-dose, high-volume therapeutics. Numerous monoclonal antibodies have been co-administered SC with rHuPH20 in a clinical setting, establishing an extensive PK database. The goal of this work is to demonstrate how aggregated clinical data can be leveraged in a universal modeling framework for characterizing SC antibody PK, resulting in parameterization that can be used in predictive simulations of new antibodies. Data for 10 individual antibodies co-administered SC with rHuPH20 were obtained from publicly available sources. PK modeling of each antibody was conducted using the same model structure, but uniquely parameterized. The model structure consisted of a two-compartment model to capture linear kinetics, plus a target-binding mechanism to accommodate nonlinear kinetics driven by antibody-target complex formation and elimination. The clinical PK profiles for all antibodies were accurately described using the universal modeling framework. The SC PK parameters of absorption and bioavailability were consistent across the range of antibody and target properties evaluated. SC administration with rHuPH20 yielded a 30% increase in absorption rate on average and similar or better bioavailability. These parameter values can serve as initial conditions for model-based PK predictions for new antibodies co-administered SC with rHuPH20 to enable evaluation of optimal SC dose and schedule regimens prior to and during clinical development.

Analysis of Soil Permeability Batu Bulan Dam’s Right Secondary Irrigation Canal in Sumbawa, Indonesia

The assessment of soil and water conditions is crucial in planning and management of an irrigation system. This study focused primarily on investigating the fine aggregate flow absorption conditions of the soil from the secondary irrigation canal of the Batu Bulan Dam’s right bank in Sumbawa Regency, Indonesia. Soil permeability level was determined in a laboratory setting using standard water absorption parameters of an irrigation canal. Analysis of specific gravity and absorption of fine aggregate showed that sand sample (A) had a bulk specific gravity of 2.53, a saturated surface dried specific gravity of 2.55, and a water absorption of 0.92 percent. Sand sample (B) had a specific gravity of 2.53, a saturated surface dried specific gravity of 2.56 and an absorption rate of 1.02%. According to the characteristics of fine aggregate (sand) standard, the specific gravity range is between 1.6 and 3.3. Thus, the mud content value of the sand samples follows the standards set by SNI. The sand sample (A) exhibited a water absorption rate of 0.92%, whereas sand sample (B) displayed a water absorption rate of 1.02%. As per the Fine Aggregate Inspection Standard, the upper limit for water absorption in fine aggregate is prescribed as 3% of dry weight for concrete with abrasion and 5% of dry weight for non-abrasive concrete. Thus, the mud content value of the sand samples complies with SNI standards. The results suggest that future irrigation strategies should consider the distinct characteristics of native aquifers, the routes of groundwater movement, and the conveyance of soil nutrients to ensure the sustainability of agricultural development in secondary irrigation areas adjacent to reservoirs.

Rational designing of phenothiazine dioxide based hole transporting materials for efficient perovskite solar cells

In this study, we design five novel non-fullerene end capped acceptor based efficient hole transporting materials (HTMs) from phenothiazine dioxide-based core. MPW1PW91 functional with a 6-31G basis set was employed for all DFT calculations and simulation analysis. By substituting acceptor groups in PDO2, numbers of parameters like band gaps, the frontier molecular orbitals (FMOs), higher absorption parameters, and electronic properties like ionization potential, electron affinity, binding energy, and light harvesting efficiency (LHE) were well tuned. In addition, significant variations in other geometrical parameters such as dipole moment, and reorganizational energy parameters were also noticed for the derived molecules compared to the reference molecule (R). Device performance was analyzed by performing calculations of open circuit voltage (VOC) and fill factor (FF). Consequently, all the designed derivatives demonstrated an improved VOC of 0.84 V for an optimized designed structure. In comparison, it was limited to a VOC of 0.57 V for the reference (R) PDO2, displaying an increment in efficiency which is essential to use these molecules as highly efficient HTMs for perovskite solar cell devices in the future.

The Effect of Dominant and Non-dominant Upper Limb Splinting on 3-D Mechanical Muscle Power of Ankle Joint During Walking

Background: Although immobilizing the upper limb is known to aid rehabilitation and improve symptoms for specific conditions, there is evidence suggesting that casting or splinting the upper limb can substantially alter walking biomechanics, including kinetics, kinematics, and spatiotemporal aspects. Objectives: This study aimed to explore how unilateral casting of either the dominant or non-dominant upper limb affects the maximum three-dimensional mechanical power of the ankle joint during walking. Methods: In this quasi-experimental study, 30 healthy women (average age ± standard deviation: 29.5 ± 3.45 years) participated. They walked under three conditions: Without immobilization, with immobilization of the dominant upper limb, and with immobilization of the non-dominant upper limb, along a path equipped with force plates and cameras. The instantaneous muscle power at the ankle joint in each plane was measured. A repeated measures analysis of variance (ANOVA) was conducted to identify significant differences among the three conditions. Results: Significant changes were observed in all parameters of maximum power generation and absorption at the ankle joint across all planes when walking with the dominant and non-dominant upper limbs splinted (P ≤ 0.05). Conclusions: Considering that muscle power is a crucial biomechanical parameter during walking, the observed alterations in this parameter due to upper limb splinting highlight the need for awareness to prevent potential walking difficulties when using upper limb braces.

Predicting Drug-Drug Interactions Involving Rifampicin Using a Semi-mechanistic Hepatic Compartmental Model.

To develop a semi-mechanistic hepatic compartmental model to predict the effects of rifampicin, a known inducer of CYP3A4 enzyme, on the metabolism of five drugs, in the hope of informing dose adjustments to avoid potential drug-drug interactions. A search was conducted for DDI studies on the interactions between rifampicin and CYP substrates that met specific criteria, including the availability of plasma concentration-time profiles, physical and absorption parameters, pharmacokinetic parameters, and the use of healthy subjects at therapeutic doses. The semi-mechanistic model utilized in this study was improved from its predecessors, incorporating additional parameters such as population data (specifically for Chinese and Caucasians), virtual individuals, gender distribution, age range, dosing time points, and coefficients of variation. Optimal parameters were identified for our semi-mechanistic model by validating it with clinical data, resulting in a maximum difference of approximately 2-fold between simulated and observed values. PK data of healthy subjects were used for most CYP3A4 substrates, except for gilteritinib, which showed no significant difference between patients and healthy subjects. Dose adjustment of gilteritinib co-administered with rifampicin required a 3-fold increase of the initial dose, while other substrates were further tuned to achieve the desired drug exposure. The pharmacokinetic parameters AUCR and CmaxR of drugs metabolized by CYP3A4, when influenced by Rifampicin, were predicted by the semi-mechanistic model to be approximately twice the empirically observed values, which suggests that the semi-mechanistic model was able to reasonably simulate the effect. The doses of four drugs adjusted via simulation to reduce rifampicin interaction.

Abstract 4482: Development of small molecule inhibitors of lipocalin 2 for the treatment of aggressive cancers

Abstract Lipocalin-2 (LCN2), a secreted protein pivotal in iron homeostasis, immune responses, siderophore transport, and epithelial cell differentiation. LCN2 is highly abundant in aggressive forms of many cancers including breast, pancreatic, ovarian, and esophageal cancer. Elevated LCN2 levels in aggressive tumors correlate with heightened cancer cell motility, proliferation, angiogenesis, invasion, and metastasis. After the protein folds it makes a barrel structure which encloses a three-calyx pocket that can bind and transport molecules. A first generation of small molecule inhibitors (SMIs) targeting LCN2 demonstrated efficacy in attenuating the proliferative capacity of Inflammatory breast cancer (IBC) cells. IBC stands as a rare and highly aggressive variant, accounting for 1 to 5% of all BC cases, with 20-30% presenting as de novo metastatic disease. In the previous studies the concentration of LCN2 inhibitors to reduce cell proliferation in 50% was around 10 µM. In pursuit of better LCN2 SMIs, we conducted in-silico analysis using a library of 369,000 ligands. Through the High-Performance Computer Facility at UPR Río Piedras, we employed AutoDock Vina for virtual screening, targeting the LCN2-calyx with Lys134 as the central coordinate. Docking protocols, predicting binding affinities, identified 8,162 out of 327,638 ligands that have been docked already with values below -9.6 kcal/mol for further consideration. The next phase involves subjecting these potential inhibitors to the SwissADME tool for a comprehensive evaluation of absorption, distribution, metabolism, and excretion parameters, as well as pharmacokinetics, drug-likeness, and medicinal chemistry considerations. The parameters to be evaluated are the Lipinski rules, which states that an orally active drug may have a maximum of one violation and the pann-assay interference compounds (PAINS) alerts tool, a source of false positives for biologically active compounds. The top candidates, exhibit binding affinities within the range of -11.5 to -12.2. After SwissADME filtering, we will re-rank the ligand list, identifying 30 commercially available candidates for subsequent cell viability assays in SUM149 (TNBC) and SUM190 (HER2+) cell lines. This multifaceted approach integrates computational methodologies with rigorous experimental validation, paving the way for potential therapeutic interventions in IBC treatment. Citation Format: Marienid Flores-Colón, Cristal A. Peña-Vázquez, Eliud Hernández-O'Farril, Luis E. Vázquez-Quiñones, Pablo E. Vivas-Mejía. Development of small molecule inhibitors of lipocalin 2 for the treatment of aggressive cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4482.

Numerical Study of the Thermal Performance of the combined effect of solar energy and variable density around a Laminar Vertical jet

A computational analysis due to the thermal performance of combined effects of solar radiation and variable density around a laminar vertical jet is carried out. For this purpose, a mathematical model in terms of nonlinear coupled partial differential equations, keeping in view the coordinate system of the proposed problem, is established. Further, to get insight to the physical significance of the proposed problem, numerical data is obtained. For this purpose, the finite difference method is used to integrate the primitive form of the partial differential equations. The coefficient matrices of the unknown variables involved in the model are solved by using the Gaussian elimination technique with the help of Fortran-Laher 90. The obtained numerical results for different parameters involved in the flow model, that is density parameter m, Prandtl number Pr, radiation parameter Rd, and fluid's absorption parameter D, are highlighted graphically by using Techplot-360. The primary findings show that enhancing values of the density variation parameter m leads to an increase in the velocity profile and a decrease in the thermal profile. On the other hand, for increasing values of Rd, the boundary layer profiles decline. Also, the heat transfer rate prominently declines with the rise in numeric value of m, Rd, and D. The main novelty of the current work is to improve the thermal performance of natural convection heat transfer with the inclusion of solar energy and variable density.

Experimental, analytical, and numerical studies of the energy absorption capacity of bi-material lattice structures based on quadrilateral bipyramid unit cell

The present study investigates the mechanical performance and energy absorption capacity of bi-material 3D lattice structures via experimental, analytical, and numerical approaches. The analytical model has been developed to obtain the effective parameters in energy absorption, such as equivalent elastic modulus and yield stress. Analytical relations based on hyperbolic shear deformation beam theory were extended to calculate the mechanical properties of an extracted unit cell from the lattice structure subjected to applied loads and appropriate boundary conditions. Then, experimental and nonlinear numerical studies have been conducted to analyze the energy absorption properties of the bi-material lattice structure. Quasi-static compression tests were conducted to analyze this lattice structure's mechanical properties and energy absorption capacity. As the numerical study, the elastic-plastic damage behavior was implemented in finite element analyses to examine the nonlinear response of considered structures. The obtained results reveal that the numerical models exhibit an acceptable prediction. According to the results, not only does the use of hybrid structures provide more energy absorption and improve mechanical properties, but also, in comparison to the usual lattice structures fabricated with a single material, the rational combination of two materials makes the bi-material three-dimensional lattice structure to inherit the optimum energy absorption and stiffness.

Numerical investigation of 3-D rotating hybrid nanofluid Forchheimer flow with radiation absorption over a stretching sheet

Examining the movement of MHD hybrid nanofluid flows along linearly extending regions provides valuable insights for improving heat transfer efficiency. Many researchers have investigated various factors, such as the Forchheimer number, porosity, radiation, aligned magnetic field and mixed convection, in the context of incorporating hybrid nanofluids into these flows. The existing literature lacks discussion on the effect of radiation absorption along with porosity, magnetic parameter and an aligned magnetic field on the Forchheimer flow of a 3-D rotating Ag−CuO/H2O hybrid nanofluid through a linearly expanded sheet. The current research endeavours to address this gap and offer valuable insights into these particular factors.BVP-5C shooting scheme through MATLAB is utilized to solve the system that governs nonlinear PDEs by converting them to nonlinear ODEs. The influences of dimensionless parameters, including radiation absorption (1 ≤ Q ≤ 2), Forchheimer number (0 ≤ Fr ≤ 9), porosity parameter (0 ≤ K ≤ 4), magnetic parameter (0 ≤ M ≤ 4), aligned magnetic field (0 ≤ α ≤ π/2), on the velocity along x and y-axes, temperature profile and concentration distributions are discussed. Also, skin friction, heat and mass transfer rate impacts are demonstrated traverse tables. Velocity along both x and y-axes is decreasing as Forchheimer number increases. As the values of radiation absorption and porosity parameter rise, there is a corresponding decrease in the temperature field. Greater Forchheimer number and aligned magnetic field leads to increase in the concentration profile of Ag−CuO/H2O hybrid nanofluid. The Nusselt number demonstrates an upward trend when Forchheimer number, porosity parameter, radiation absorption, magnetic parameter and aligned magnetic field experience an increase, whereas the Sherwood number exhibits a contrary behaviour with these identical parameters. The current study demonstrates a compatibility rate of 99.9% with the preceding research across diverse values of the stretching ratio parameter.

Capillary water absorption and strength of solidified marine soft soil

In order to reveal the capillary water absorption properties and durability of soft soil solidified with industrial wastes, soda residue (SR), ground granulated blast furnace slag (GGBS), and carbide slag (CS) were used as solidifiers to solidify marine soil. The effects of solidifier content and water absorption path on capillary water absorption properties, strength, and microscopic mechanism were investigated through capillary water absorption, unconfined compressive strength (UCS), X-ray diffraction, and nuclear magnetic resonance tests. And the properties were compared with cement solidified soil. Results showed that capillary absorption parameters, including sorptivity coefficient, capillary coefficient, and diffusion coefficient, decreased with solidifier content and increased with water absorption times. The capillary absorption parameters of SR-GGBS-CS solidified soil were lower than those of cement solidified soil. For samples with 28d-UCS greater than 1390.9 kPa, the UCS after capillary absorption tended to increase up to 1.28 times. With increasing water absorption time, NaCl migrated upward and accumulated, accompanied by the change of hydrated products such as calcium chloroaluminate hydrate and ettringite, which contributed to a decrease in the strength of solidified soil. The carbon emission index of cement solidified soil was approximately 41 times that of SR-GGBS-CS solidified soil, and the soil with SR, GGBS, and CS content of 25%, 10%, and 4% respectively had the lowest carbon emission index.

A new workflow for the effective curation of membrane permeability data from open ADME information.

Membrane permeability is an in vitro parameter that represents the apparent permeability (Papp) of a compound, and is a key absorption, distribution, metabolism, and excretion parameter in drug development. Although the Caco-2 cell lines are the most used cell lines to measure Papp, other cell lines, such as the Madin-Darby Canine Kidney (MDCK), LLC-Pig Kidney 1 (LLC-PK1), and Ralph Russ Canine Kidney (RRCK) cell lines, can also be used to estimate Papp. Therefore, constructing in silico models for Papp estimation using the MDCK, LLC-PK1, and RRCK cell lines requires collecting extensive amounts of in vitro Papp data. An open database offers extensive measurements of various compounds covering a vast chemical space; however, concerns were reported on the use of data published in open databases without the appropriate accuracy and quality checks. Ensuring the quality of datasets for training in silico models is critical because artificial intelligence (AI, including deep learning) was used to develop models to predict various pharmacokinetic properties, and data quality affects the performance of these models. Hence, careful curation of the collected data is imperative. Herein, we developed a new workflow that supports automatic curation of Papp data measured in the MDCK, LLC-PK1, and RRCK cell lines collected from ChEMBL using KNIME. The workflow consisted of four main phases. Data were extracted from ChEMBL and filtered to identify the target protocols. A total of 1661 high-quality entries were retained after checking 436 articles. The workflow is freely available, can be updated, and has high reusability. Our study provides a novel approach for data quality analysis and accelerates the development of helpful in silico models for effective drug discovery. Scientific Contribution: The cost of building highly accurate predictive models can be significantly reduced by automating the collection of reliable measurement data. Our tool reduces the time and effort required for data collection and will enable researchers to focus on constructing high-performance in silico models for other types of analysis. To the best of our knowledge, no such tool is available in the literature.

Development and verification of mechanistic vaginal absorption and metabolism model to predict systemic exposure after vaginal ring and gel application.

The current work describes the development of mechanistic vaginal absorption and metabolism model within Simcyp Simulator to predict systemic concentrations following vaginal application of ring and gel formulations. Vaginal and cervix physiology parameters were incorporated in the model development. The study highlights the model assumptions including simulation results comparing systemic concentrations of 5 different compounds, namely, dapivirine, tenofovir, lidocaine, ethinylestradiol and etonogestrel, administered as vaginal ring or gel. Due to lack of data, the vaginal absorption parameters were calculated based on assumptions or optimized. The model uses release rate/in vitro release profiles with formulation characteristics to predict drug mass transfer across vaginal tissue into the systemic circulation. For lidocaine and tenofovir vaginal gel, the predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits. The average fold error (AFE) and absolute AFE indicating bias and precision of predictions range from 0.62 to 1.61. For dapivirine, the pharmacokinetic parameters are under and overpredicted in some studies due to lack of formulation composition details and relevance of release rate used in ring model. The predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits for etonogestrel and ethinylestradiol vaginal ring (AFEs and absolute AFEs from 0.84 to 1.83). The current study provides first of its kind physiologically based pharmacokinetic framework integrating physiology, population and formulation data to carry out in silico mechanistic vaginal absorption studies, with the potential for virtual bioequivalence assessment in the future.

Multi-Directional Viscous Damping Absorbing Boundary in Numerical Simulation of Elastic Wave Dynamic Response

Numerical seismic wave field simulation is essential for studying the dynamic responses in semi-infinite space, and the absorbing boundary setting is critical for simulation accuracy. This study addresses spherical waves incident from the free boundary by applying dynamic equations and Rayleigh damping. A new multi-directional viscous damping absorbing boundary (MVDB) method is proposed based on regional attenuation. An approximate formula for the damping value is established, which can achieve absorbing the boundary setting by only solving the mass damping coefficients without increasing the absorbing region grid cells or depending on the spatial and temporal walking distance. The validity and stability of the proposed method are proven through numerical calculations with seismic sources incident from different angles. Meanwhile, the key parameters affecting the absorption of the MVDB are analyzed, and the best implementation scheme is provided. In order to meet the requirements of mediums with different elastic parameters for boundary absorption and ensure the high efficiency of numerical calculations, the damping amplitude control coefficients k can be set between 1.02 and 1.12, the thickness of the absorbing region L is set to 2–3 times of the wavelength of the incident transverse wave, and the thickness of the single absorbing layer is set to the size of the discrete mesh of the model Δl.

Multi-antenna probing of absorbing regions inside and outside Cassiopeia A

Context. Cassiopeia A occupies an important place among supernova remnants (SNRs) in low-frequency radio astronomy. Located in our Galaxy, this powerful radio source emits synchrotron radiation that propagates through the SNR environment and the ionized interstellar medium. The analysis of its continuum spectrum from low frequency observations reveals the evolution of the SNR absorption properties over time and suggests a method for probing unshocked ejecta and the SNR interaction with the circumstellar medium (CSM). Aims. In this paper, we present low-frequency measurements of the integrated spectrum of Cassiopeia A to find the typical values of free-free absorption parameters towards this SNR in the middle of 2023. We also add new results to track its slowly evolving and decreasing integrated flux density. Methods. We used the New Extension in Nançay Upgrading LOFAR (NenuFAR) and the Ukrainian Radio Interferometer of NASU (URAN–2, Poltava) for measuring the continuum spectrum of Cassiopeia A within the frequency range of 8–66 MHz. The radio flux density of Cassiopeia A relative to the calibration source, the radio galaxy Cygnus A, has been obtained on June–July, 2023 with two sub-arrays for each radio telescope, used as a two-element correlation interferometer. Results. We measured the values of parameters such as the emission measure, electron temperature and average number of ion charges, for both the internal and external absorbing ionized gas towards Cassiopeia A from its integrated spectrum. Generally, their values are comparable to those presented in the literature, but their slight differences demonstrate the evolution of free-free absorption parameters in this SNR. Based on high accuracy of the measurements, we have detected the SNR–CSM interaction. This led to the fact that the maximum of this continuous spectrum, decreasing in intensity, changed in frequency from past higher values to lower ones over time. Probably, such changes occur periodically in which the spectral peak can move in the direction of both higher frequencies and lower ones. This effect is mainly caused by the evolution of emission measure outside Cassiopeia A. Conclusions. The integrated flux-density spectrum of Cassiopeia A obtained with the NenuFAR and URAN–2 interferometric observations opens up new possibilities for continuous monitoring the ionized gas properties in and around Cassiopeia A to observe the evolution of unshocked ejecta and the SNR-CSM interaction in future studies.

BAL outflow in quasar B0254-3327B: analysis and comparison with other extreme UV outflows

ABSTRACT We have identified a broad absorption line (BAL) outflow in the HST/STIS spectrum of the quasar QSO B0254-3327B at velocity v = −3200 km s−1. The outflow has absorption troughs from ions such as Ne viii, Na ix, Si xii, and Ne v. We also report the first detection of S xiv absorption troughs, implying very high ionization. Via measurement of the ionic column densities, photoionization analysis, and determination of the electron number density of the outflow, we found the kinetic luminosity of the outflow system to be up to ∼1 per cent of the quasar’s Eddington luminosity, or ∼5 per cent of the bolometric luminosity, making it a potential contributor to AGN feedback. A solution with two ionization phases was needed, as a single phase was not sufficient to satisfy the constraints from the measured ionic column densities. We find that the ionization parameter of the very high-ionization phase of the outflow is within the expected range of an X-ray warm absorber. We also examined the physical properties of the outflow of Q0254-334 along with previously studied extreme UV outflows, with a total sample of 24 outflow systems, finding a weak negative correlation between outflow velocity and distance from the central source, with larger distances corresponding to slower velocities. The very high-ionization phase of the Q0254-334 outflow has one of the highest ionization parameters of UV absorption outflows to date, which we attribute to the presence of S xiv.

Exploring Lead-Like Molecules of Traditional Chinese Medicine for Treatment Quest against Aliarcobacter butzleri: In Silico Toxicity Assessment, Dynamics Simulation, and Pharmacokinetic Profiling.

Aliarcobacter butzleri is a Gram-negative, curved or spiral-shaped, microaerophilic bacterium and causes human infections, specifically diarrhea, fever, and sepsis. The research objective of this study was to employ computer-aided drug design techniques to identify potential natural product inhibitors of a vital enzyme in this bacterium. The pyrimidine biosynthesis pathway in its core genome fraction is crucial for its survival and presents a potential target for novel therapeutics. Hence, novel small molecule inhibitors were identified (from traditional Chinese medicinal (TCM) compound library) against it, which may be used for possible curbing of infection by A. butzleri. Methods. A comprehensive subtractive genomics approach was utilized to identify a key enzyme (orotidine-5'-phosphate decarboxylase) cluster conserved in the core genome fraction of A. butzleri. It was selected for inhibitor screening due to its vital role in pyrimidine biosynthesis. TCM library (n > 36,000 compounds) was screened against it using pharmacophore model based on orotidylic acid (control), and the obtained lead-like molecules were subjected to structural docking using AutoDock Vina. The top-scoring compounds, ZINC70454134, ZINC85632684, and ZINC85632721, underwent further scrutiny via a combination of physiological-based pharmacokinetics, toxicity assessment, and atomic-scale dynamics simulations (100 ns). Among the screened compounds, ZINC70454134 displayed the most favorable characteristics in terms of binding, stability, absorption, and safety parameters. Overall, traditional Chinese medicine (TCM) compounds exhibited high bioavailability, but in diseased states (cirrhosis, renal impairment, and steatosis), there was a significant decrease in absorption, Cmax, and AUC of the compounds compared to the healthy state. Furthermore, MD simulation demonstrated that the ODCase-ZINC70454134 complex had a superior overall binding affinity, supported by PCA proportion of variance and eigenvalue rank analysis. These favorable characteristics underscore its potential as a promising drug candidate. The computer-aided drug design approach employed for this study helped expedite the discovery of antibacterial compounds against A. butzleri, offering a cost-effective and efficient approach to address infection by it. It is recommended that ZINC70454134 should be considered for further experimental analysis due to its indication as a potential therapeutic agent for combating A. butzleri infections. This study provides valuable insights into the molecular basis of biophysical inhibition of A. butzleri through TCM compounds.