A Local Model for the Energy Transfer in a Saturated Static Mixture

In the present work the transient energy transfer in a nonsaturated porous medium is studied, using a mixture theory viewpoint. The porous matrix is assumed homogeneous, rigid and isotropic, while the fluid is a Newtonian incompressible one and both are assumed static. Since the homogeneous matrix is not saturated, gradients of concentration are present. The porous medium and the fluid (a liquid) will be regarded as continuous constituents of a mixture that will have also a third constituent, an inert gas, assumed with zero mass density and thermal conductivity. The problem is described by a set of two partial differential equations which represent the energy balances for the fluid and the solid constituents. Isovalues for these two constituents are plotted, considering representative time instants and selected values for the energy equations coefficients and for the saturation.     

Application of the finite volume method in the simulation of saturated flows of binary Mixtures with particular emphasis on Non-Darcy motions through porous media

Non-Darcy flows in saturated porous media with significative boundary and inertia effects are modelled applying the Continuum Theory of Mixtures approach and simulated by discretization of the governing equations by the finite volume method.

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Sommario Flussi di tipo ‘Non-Darcy’ in mezzi porosi saturi, con significativi effetti di bordo ed inerziali, vengono modellati applicando l'approccio della Teoria delle Miscele per il Continuo e simulati mediante discretizzazione delle equazioni governanti con il metodo del volume finito.

     

Development and validation of a multiplex UHPLC‐MS/MS assay with stable isotopic internal standards for the monitoring of the plasma concentrations of the antiretroviral drugs bictegravir,cabotegravir, doravirine,and rilpivirine in people living with HIV

The widespread use of highly active antiretroviral treatments has dramatically changed the prognosis of people living with HIV (PLWH). However, such treatments have to be taken lifelong raising issues regarding the maintenance of both therapeutic effectiveness and long‐term tolerability. Recently approved or investigational antiretroviral drugs present considerable advantages, allowing once daily oral dosage along with activity against resistant variants (eg, bictegravir and doravirine) and also parenteral intramuscular administration that facilitates treatment adherence (eg, long‐acting injectable formulations such as cabotegravir and rilpivirine). Still, there remains a risk of insufficient or exaggerated circulating exposure due to absorption issues, abnormal elimination, drug‐drug interactions, and others. In this context, a multiplex ultra‐high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC‐MS/MS) bioassay has been developed for the monitoring of plasma levels of bictegravir, cabotegravir, doravirine, and rilpivirine in PLWH. A simple and convenient protein precipitation was performed followed by direct injection of the supernatant into the UHPLC‐MS/MS system. The four analytes were eluted in less than 3 minutes using a reversed‐phase chromatography method coupled with triple quadrupole mass spectrometry detection. This bioassay was fully validated following international guidelines and achieved good performances in terms of trueness (94.7%‐107.5%), repeatability (2.6%‐11%), and intermediate precision (3.0%‐11.2%) over the clinically relevant concentration ranges (from 30 to 9000 ng/mL for bictegravir, cabotegravir, and doravirine and from 10 to 1800 ng/mL for rilpivirine). This sensitive, accurate, and rapid UHPLC‐MS/MS assay is currently applied in our laboratory for routine therapeutic drug monitoring of the oral drugs bictegravir and doravirine and is also intended to be applied for the monitoring of cabotegravir/rilpivirine levels in plasma from PLWH receiving once monthly or every 2‐month intramuscular injection of these long‐acting antiretroviral drugs.     

Higher order difference methods for second order two-point boundary-value problems

Using methods of numerical integration, difference schemes of sixth order with off-step points have been obtained and applied to the second order differential equation, with and without mixed boundary conditions. Numerical results obtained by these methods have been compared with those obtained by using h⁴-extrapolation of the Numerov method. It is found that the sixth-order method based upon 4-point Lobatto quadrature with approximation 2 is more economical and accurate from the computational viewpoint than the existing sixth-order methods.     

Scaling tests of late stages of spinodal decomposition in PC/PMMA blends

Time-resolved light scattering studies were undertaken to elucidate the kinetics of phase separation in polycarbonate (PC)/polymethyl methacrylate (PMMA) blends. The 40:60 PC/PMMA blend undergoes thermally induced phase separation through spinodal decomposition. Temperature jump experiments were carried out from a single-phase to a two-phase temperature region. The general trend of spinodal decomposition in this blend system is nonlinear in character and obeys the power laws. The time evolution of scattering curves was analyzed in accordance with dynamical scaling laws for self-similarity and the shape of scaled structure functions.     

The Asymptotics of Wilkinson’s Shift: Loss of Cubic Convergence

One of the most widely used methods for eigenvalue computation is the QR iteration with Wilkinson’s shift: Here, the shift s is the eigenvalue of the bottom 2×2 principal minor closest to the corner entry. It has been a long-standing question whether the rate of convergence of the algorithm is always cubic. In contrast, we show that there exist matrices for which the rate of convergence is strictly quadratic. More precisely, let $T_{ {\mathcal {X}}}One of the most widely used methods for eigenvalue computation is the QR iteration with Wilkinson’s shift: Here, the shift s is the eigenvalue of the bottom 2×2 principal minor closest to the corner entry. It has been a long-standing question whether the rate of convergence of the algorithm is always cubic. In contrast, we show that there exist matrices for which the rate of convergence is strictly quadratic. More precisely, let T _XT_{ {\mathcal {X}}} be the 3×3 matrix having only two nonzero entries (T _X)₁₂=(T _X)₂₁=1(T_{ {\mathcal {X}}})_{12}=(T_{ {\mathcal {X}}})_{21}=1 and let T_\varLambda {\mathcal {T}}_{\varLambda } be the set of real, symmetric tridiagonal matrices with the same spectrum as T _XT_{ {\mathcal {X}}} . There exists a neighborhood U ì T_\varLambda \boldsymbol {{\mathcal {U}}}\subset {\mathcal {T}}_{\varLambda } of T _XT_{ {\mathcal {X}}} which is invariant under Wilkinson’s shift strategy with the following properties. For T₀ ? UT_{0}\in \boldsymbol {{\mathcal {U}}} , the sequence of iterates (T _k ) exhibits either strictly quadratic or strictly cubic convergence to zero of the entry (T _k )₂₃. In fact, quadratic convergence occurs exactly when limT_k=T _X\lim T_{k}=T_{ {\mathcal {X}}} . Let X\boldsymbol {{\mathcal {X}}} be the union of such quadratically convergent sequences (T _k ): The set X\boldsymbol {{\mathcal {X}}} has Hausdorff dimension 1 and is a union of disjoint arcs X^s\boldsymbol {{\mathcal {X}}}^{\sigma} meeting at T _XT_{ {\mathcal {X}}} , where σ ranges over a Cantor set.     

Cut-and-paste of quadriculated disks and arithmetic properties of the adjacency matrix

We define cut-and-paste, a construction which, given a quadriculated disk obtains a disjoint union of quadriculated disks of smaller total area. We provide two examples of the use of this procedure as a recursive step. Tilings of a disk Δ receive a parity: we construct a perfect or near-perfect matching of tilings of opposite parities. Let B_Δ be the black-to-white adjacency matrix: we factor , where L and U are lower and upper triangular matrices, is obtained from a larger identity matrix by removing rows and columns and all entries of L, and U are equal to 0, 1 or -1.     

Fibrinogen-β-Estradiol Binding Studied by Fluorescence Spectroscopy: Denaturation and pH Effects

Fibrinogen is a blood plasma protein that plays a crucial role in hemostasis. It is known that erythrocyte aggregation increases in the presence of fibrinogen, and that β-estradiol decreases erythrocyte aggregation with a constant fibrinogen concentration. In this work, we have used intrinsic tryptophan fluorescence to obtain information on the conformational changes of fibrinogen upon the recently proposed interaction with β-estradiol. To evaluate the effect on the conformational changes during fibrinogen-β-estradiol binding, fluorescence experiments were performed using guanidine hydrochloride (0–6 M) as denaturant, at different pH values. The results obtained for pH 6.5 and 8.0 showed no effect during the binding. The main differences were observed between pH 4.2 and 7.4, in the absence and in the presence of two different denaturant concentrations (1 and 5 M). A red shift of the fluorescence emission from 344 to 354 nm is observed when denaturant concentration is above 3 M for all studied pH values. This phenomenon may be explained by the loss of compact structure of the protein in the presence of denaturant, with tryptophan residues exposure to the aqueous environment and alteration of fibrinogen-β-estradiol binding. These results demonstrate that the binding sites of fibrinogen are strongly dependent on the conformational state of the protein.