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Machine component design has become a prominent topic for researchers in recent years. The analysis of bearing systems has received considerable attention in order to avoid detrimental contact. Among the most important studies in this area are the transient problems of journal bearings, which are usually performed by coupling the Reynolds equation with the motion equations. Many techniques have been presented in the literature and are still being explored to ensure the accurate findings and efficient solution prediction of unsteady state Reynolds equation. In this paper, the Proper Generalized Decomposition (PGD) approach is expanded for the analysis of the lubricant behavior of dynamically loaded journal bearing considering Swift-Stieber boundary conditions. The PGD model is applied in this problem, seeking the approximate solution in its separated form of the partial differential Reynolds equation at each time step during the load applied cycle employing the alternating direction strategy. Compared to the classical resolution, the PGD solution has a considerably low computational cost. To verify the accuracy and efficiency of this approach, three cases have been considered, infinitely short, infinitely long and finite journal bearings under the dynamic load. The results of the suggested methodology when compared to the full discretized model (FDM) show that, the new scheme is more efficient, converges quickly, and gives the accurate solutions with a very low CPU time consumption.

The present study deals with the in silico of 45 indolyl-aryl-sulfones known as anti-HIV1. The data were collected from recent previously reported inhibitors and divided into a sub-set of 33 compounds as the training set and the remaining 12 compounds were kept in the test set. The selected pharmacophore–ADRRR–yielded a statistically significant 3D-QSAR model containing high confidence scores (R2 = 0.930, Q2 = 0.848, and RMSE = 0.460). The predictive power of the established pharmacophore model was validated with an external test (r2 = 0.848). A systematic virtual screening workflow shows an enrichment factor and has revealed a high predictive power. Then the model was used to screen the filtered PubChem database mapping all chemical features of model pharmacophore. The recognized hits were further assessed by in silico ADMET studies. Molecular dynamics also used to explore the stability of obtained complexes. Finally, these selected compounds are probably to become a good lead molecule for the development of effective anti-HIV-1 drugs.

In our previous study, Schiff base (1) complexes derived from 2,3‐diaminophenazine and metal ions Co(II) (2), Ni(II) (3), Cu(II) (4), and Cd(II) (5) were synthesized and characterized, demonstrating a significant biological activity. This study investigates their anticancer potential, specifically against prostate cancer. The complexes exhibited notable reductions in cancer cell viability, with IC50 values of 0.531 μM Ni(II), 0.630 μM Cu(II), and 0.655 μM Co(II), comparable with the standard drug enzalutamide. The Co(II) complex showed the highest efficacy, while Cd(II) displayed the lowest (IC50 = 0.648 μM). The presence of a phenazine ring in these complexes enhances DNA binding, contributing to their anticancer effects. HOMO‐LUMO calculations revealed energy gaps ranging from 2.525 to 3.294 eV, indicating varying reactivity and potential for biological interactions. Molecular docking studies revealed that compound (1) exhibited the highest binding affinity (−9.19 kcal/mol) for the prostate cancer‐related receptor, with significant hydrogen bond interactions. Molecular dynamics simulations over 100 ns demonstrated stable binding, with RMSD values below 1.5 Å, and RMSF analysis provided insights into protein flexibility. ADMET studies revealed favorable drug‐like properties, including good gastrointestinal absorption (> 30%), high blood–brain barrier permeability (LogBBB = 0.64), and high human intestinal absorption (68.47%–88.79%). No inhibition of CYP2D6 was observed, suggesting low risk for drug–drug interactions. These Schiff base‐metal complexes show promising anticancer activity and favorable ADMET profiles, indicating their potential as therapeutic agents for prostate cancer treatment. [ABSTRACT FROM AUTHOR]

Background/Objectives: RNA polymerase (NS5B), serves as a crucial target for pharmaceutical interventions aimed at combating the hepatitis C virus (HCV), which poses significant health challenges worldwide. The present research endeavors to explore and implement a variety of advanced molecular modeling techniques that aim to create and identify innovative and highly effective inhibitors that specifically target the RNA polymerase enzyme. Methods: In this study, a QSAR investigation was carried out on a set of thirty-eight isothiazole derivatives targeting NS5B inhibition and thus hepatitis C virus (HCV) treatment. The research methodology made use of various statistical techniques including multiple linear regression (MLR) and artificial neural networks (ANNs) to develop satisfactory models in terms of internal and external validation parameters, indicating their reliability in predicting the activity of new inhibitors. Accordingly, a series of potent NS5B inhibitors is designed, and their inhibitory potential is confirmed through molecular docking simulations. Results: These simulations showed that the interactions between these inhibitors and the active site 221 binding pocket of the NS5B protein are hydrophobic and hydrogen bond interactions, as well as carbon–hydrogen bonds and electrostatic interactions. Additionally, these newly formulated compounds displayed favorable ADMET characteristics, with molecular dynamics investigations revealing a stable energetic state and dynamic equilibrium. Conclusions: Our work highlights the importance of NS5B inhibition for the treatment of HCV. [ABSTRACT FROM AUTHOR]

Aim: Obstructive sleep apnea (OSA) is a growing health problem affecting nearly 1 billion people worldwide. The landmark feature of OSA is chronic intermittent hypoxia (CIH), accounting for multiple organ damage, including heart disease. CIH profoundly alters both visceral white adipose tissue (WAT) and heart structure and function, but little is known regarding inter‐organ interaction in the context of CIH. We recently showed that visceral WAT senescence drives myocardial alterations in aged mice without CIH. Here, we aimed at investigating whether CIH induces a premature visceral WAT senescent phenotype, triggering subsequent cardiac remodeling. Methods: In a first experiment, 10‐week‐old C57bl6J male mice (n = 10/group) were exposed to 14 days of CIH (8 h daily, 5%–21% cyclic inspired oxygen fraction, 60 s per cycle). In a second series, mice were submitted to either epididymal WAT surgical lipectomy or sham surgery before CIH exposure. Finally, we used p53 deficient mice or Wild‐type (WT) littermates, also exposed to the same CIH protocol. Epididymal WAT was assessed for fibrosis, DNA damages, oxidative stress, markers of senescence (p16, p21, and p53), and inflammation by RT‐qPCR and histology, and myocardium was assessed for fibrosis and cardiomyocyte hypertrophy. Results: CIH‐induced epididymal WAT remodeling characterized by increased fibrosis, oxidative stress, DNA damage response, inflammation, and increased expression of senescent markers. CIH‐induced epididymal WAT remodeling was associated with subtle and early myocardial interstitial fibrosis. Both epididymal WAT surgical lipectomy and p53 deletion prevented CIH‐induced myocardial fibrosis. Conclusion: Short‐term exposure to CIH induces epididymal WAT senescent remodeling and cardiac interstitial fibrosis, the latter being prevented by lipectomy. This finding strongly suggests visceral WAT senescence as a new target to mitigate OSA‐related cardiac disorders. [ABSTRACT FROM AUTHOR]

Flow losses in centrifugal pumps handling non-Newtonian fluids are of great importance for design optimization, performance prediction, and energy savings. Traditional methods are very limited in determining energy losses due to the complex rheological behavior of such fluids. This study aims to investigate the hydraulic losses and performance degradation mechanism of centrifugal volute pumps handling non-Newtonian emulsions using the entropy production method, focusing on the influence of emulsion type on the loss mechanism. The influence of pump size on fluid’s non-Newtonian behavior and energy loss in a centrifugal pump is also investigated by comparing the entropy distribution in two geometrically similar pumps operating with different emulsions exhibiting shear-thinning behavior. The flow field and entropy production are predicted by computational fluid dynamics (CFD) based on the Reynolds-averaged Navier-Stokes (RANS) equations coupled with the k-epsilon turbulence model. The latter is used to acquire the dissipative entropic components of the flow. The results showed that for a non-Newtonian fluid, energy loss occurs primarily in the impeller, regardless of pump size and flow rate. In addition, the shear-thinning behavior of concentrated emulsions significantly affects hydraulic losses, especially in small-size pumps. Most importantly, small-size pumps generate relatively the highest entropy loss over the entire flow range and the entropy loss increases with the lower limit of the non-Newtonian plateau. This approach showed that the predominance of losses in centrifugal volute pumps operating with non-Newtonian fluids depends on the pump size. Thus, indicating that the hydrodynamic characteristics of two geometrically similar pumps do not scale when the liquid has non-Newtonian rheology.

Background: The aim of this retrospective study was to analyze early relapse in multiple myeloma (MM) in real life and to evaluate its impact on overall survival (OS) and progression-free survival (PFS). Methods: Two groups of patients were identified according to the date of occurrence of relapse after autologous transplantation, within less than 24 months, defining early relapse (G1), or after more than 24 months, defining late relapse (G2). Results: A total of 307 patients with MM were enrolled, including 93 patients (30%) who had experienced relapse. There were 56 early relapses (18%) and 37 late relapses (12%). In G1 the median follow-up was 19.5 months (3-93), as compared to59 months (24-117) in G2. The median of PFS was 18 months (14.8-21.14) in G1 and was not attained in G2 (p=0.0001). The median of OS was 29 months (18.2-39.7) in G1 and was not attained in G2 (p=0.0001). In a univariate analysis, age>60 years (p=0.003), performance status>1 (p=0.036), LDH>normal (p=0.002), ISS III (p=0.0002) and an absence of maintenance therapy (p=0.002) were found to be predictive factors for early relapse. In a multivariate analysis, only a delay from the initiation of treatment to ASCT of>12 months (p=0.02) and an absence of maintenance therapy (p=0.002) were predictive of early relapse. Conclusion: The predictive factors identified here should allow us to adapt the therapeutic strategy.

The discovery of antibacterials is considered one of the greatest medical achievements of all time. In this work, a combination of three computational analyzes: 3D-QSAR, molecular docking and ADME evaluation were applied in thienopyrimidine derivatives intended toward gram-positive bacterium Staphylococcus aureus. The validity of 3D-QSAR model was tested with a set of data which is divided into a training and a test set. The two models constructed (CoMFA and CoMSIA) show good statistical reliability (q2 = 0.758; r2 = 0.96; r2pred = 0.783) and (q2 = 0.744; r2 = 0.97; r2pred = 0.625) respectively. In addition, docking methods were applied to understand the structural features responsible for the affinity of the ligands in the binding of S. aureus DNA gyrase. Drug likeness and ADME analysis applied in this series of new proposed compounds, have shown that the five lead molecules would have the potential to be effective drugs and could be used as a starting point for designing compounds against Staphylococcus aureus.

Electronic structures, the effect of the substitution, structure physicochemical property/activity relationships and drug-likeness applied in pyrazine derivatives, have been studied at ab initio (HF, MP2) and B3LYP/DFT (density functional theory) levels. In the paper, the calculated values, i.e., NBO (natural bond orbitals) charges, bond lengths, dipole moments, electron affinities, heats of formation and quantitative structure-activity relationships (QSAR) properties are presented. For the QSAR studies, we used multiple linear regression (MLR) and artificial neural network (ANN) statistical modeling. The results show a high correlation between experimental and predicted activity values, indicating the validation and the good quality of the derived QSAR models. In addition, statistical analysis reveals that the ANN technique with (9-4-1) architecture is more significant than the MLR model. The virtual screening based on the molecular similarity method and applicability domain of QSAR allowed the discovery of novel anti-proliferative activity candidates with improved activity.

In the present paper, we investigate the $\left[p,q\right] $-order of solutions of higher order linear differential equations \begin{equation*} A_{k}\left(z\right) f^{\left( k\right) }+A_{k-1}\left( z\right) f^{\left(k-1\right)}+\cdots +A_{1}\left( z\right) f^{\prime }+A_{0}\left( z\right) f=0 \end{equation*} and \begin{equation*} A_{k}\left( z\right) f^{\left( k\right) }+A_{k-1}\left( z\right) f^{\left(k-1\right) }+\cdots +A_{1}\left( z\right) f^{\prime }+A_{0}\left( z\right) f=F\left( z\right), \end{equation*} where $A_{0}\left( z\right) ,$ $A_{1}\left( z\right) ,...,A_{k}\left(z\right) \not\equiv 0$ and $F\left( z\right) \not\equiv 0$ are meromorphic functions of finite $\left[ p,q\right] $-order. We improve and extend some results of the authors by using the concept $\left[ p,q\right] $-order.

In this paper, the initial and maximum load was studied using the Finite Element Modeling (FEM) analysis during impact testing (CVN) of pipeline X70 steel. The Gurson-Tvergaard-Needleman (GTN) constitutive model has been used to simulate the growth of voids during deformation of pipeline steel at different temperatures. FEM simulations results used to study the sensitivity of the initial and maximum load with GTN parameters values proposed and the variation of temperatures. Finally, the applied artificial neural network (ANN) is used to predict the initial and maximum load for a given set of damage parameters X70 steel at different temperatures, based on the results obtained, the neural network is able to provide a satisfactory approximation of the load initiation and load maximum in impact testing of X70 Steel.

Les mortiers de restauration doivent avoir une composition similaire aux matériaux anciens. Pour assurer cette compatibilité, le liant de chaux aérienne peut être utilisé avec un composant hydraulique actif¶. Le but de ce travail est l’élaboration des mortiers de chaux à caractère hydraulique, compatible avec les matériaux de l’ancien bâti. Différentes compositions ont été élaborées avec un rapport volumique liant: agrégat de 1: 3. Des mélanges de mortiers contenant 10, 20, 30, 40 et 50% de métakaolin par substitution à la chaux aérienne ont été préparés. Afin d’améliorer la fluidité des mélanges, un superplastifiant -Médaflow 30- a été incorporé. Une caractérisation physico-mécanique des échantillons de mortiers élaborés a été effectuée à différentes échéances de durcissement. Les résultats obtenus ont montré que la valeur maximale de la résistance à la flexion et à la compression à 28 jours a été enregistrée par la composition contenant 10% de métakaolin et 2% d’adjuvant. Enfin, on peut conclure que l’incorporation du métakaolin aux échantillons de mortiers de chaux, même à faible dosage, provoque des variations considérables dans les valeurs des résistances mécaniques (résistance à la flexion et à la compression) et les propriétés physiques particulièrement l’absorption d’eau.