Reversal Activity and Toxicity of Heparin-Binding Copolymer after Subcutaneous Administration of Enoxaparin in Mice

Uncontrolled bleeding after enoxaparin (ENX) is rare but may be life-threatening. The only registered antidote for ENX, protamine sulfate (PS), has 60% efficacy and can cause severe adverse side effects. We developed a diblock copolymer, heparin-binding copolymer (HBC), that reverses intravenously administered heparins. Here, we focused on the HBC inhibitory activity against subcutaneously administered ENX in healthy mice. BALB/c mice were subcutaneously injected with ENX at the dose of 5 mg/kg. After 110 min, vehicle, HBC (6.25 and 12.5 mg/kg), or PS (5 and 10 mg/kg) were administered into the tail vein. The blood was collected after 3, 10, 60, 120, 360, and 600 min after vehicle, HBC, or PS administration. The activities of antifactors Xa and IIa and biochemical parameters were measured. The main organs were collected for histological analysis. HBC at the lower dose reversed the effect of ENX on antifactor Xa activity for 10 min after antidote administration, whereas at the higher dose, HBC reversed the effect on antifactor Xa activity throughout the course of the experiment. Both doses of HBC completely reversed the effect of ENX on antifactor IIa activity. PS did not reverse antifactor Xa activity and partially reversed antifactor IIa activity. HBC modulated biochemical parameters. Histopathological analysis showed changes in the liver, lungs, and spleen of mice treated with HBC and in the lungs and heart of mice treated with PS. HBC administered in an appropriate dose might be an efficient substitute for PS to reverse significantly increased anticoagulant activity that may be connected with major bleeding in patients receiving ENX subcutaneously.     

The Impact of Selected Bacterial Sexually Transmitted Diseases on Pregnancy and Female Fertility

Sexually transmitted infections (STIs) caused by Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium are a common cause of pelvic inflammatory disease (PID) which can lead to tubal factor infertility (TFI). TFI is one of the most common causes of infertility, accounting for 30% of female fertility problems. STIs can also have an impact on pregnancy, leading to adverse pregnancy outcomes. Escalating antibiotic resistance in Neisseria gonorrhoeae and Mycoplasma genitalium represents a significant problem and can be therapeutically challenging. We present a comprehensive review of the current treatment options, as well as the molecular approach to this subject. We have given special attention to molecular epidemiology, molecular diagnostics, current and new treatments, and drug resistance.     

Nonlinear Absorption of Submicrometer Grain‐Size Cobalt‐Doped Magnesium Aluminate Transparent Ceramics

Transparent cobalt‐doped magnesium aluminate spinel (Co:MgAl₂O₄) ceramics with a submicrometer grain size were prepared by spark plasma sintering. For the first time, the nonlinear absorption of Co:MgAl₂O₄ transparent ceramics was experimentally demonstrated. Both ground state absorption (σ_GSA) and excited state absorption (σ_ESA) were estimated using the solid‐state slow saturable absorber model based on absorption saturation measurements performed at 1.535 μm. σ_GSA and σ_ESA for 0.03 at.% Co:MgAl₂O₄ were found to be 4.1 × 10^?19 cm² and 4.0 × 10^?20 cm², respectively. In the case of 0.06 at.% Co:MgAl₂O₄ ceramics, σ_GSA = 2.6 × 10^?19 cm² and σ_ESA= 5.3 × 10^?20 cm² were determined.     

Maximum principle for optimal control of two-directionally continuous linear repetitive processes

In the paper, maximum principle for a two-directionally continuous variant of a linear autonomous repetitive process with cost functional depending on a fixed “end-function” is obtained. Maximum condition has a pointwise form, a conjugate system has a Fornasini-Marchesini form. The result is derived from the extremum principle for smooth-convex problems, due to Ioffe and Tikhomirov.     

Reduction of Freckle Defect in Single-Crystal Blade Root by Controlling Local Cooling Conditions

Metallurgical and Materials Transactions A - The reduction of freckle defect in the single-crystal blade root by controlling local cooling conditions was investigated. Application of the IRBs...     

Makespan minimization of multi-slot just-in-time scheduling on single and parallel machines

The paper addresses the problem of multi-slot just-in-time scheduling. Unlike the existing literature on this subject, it studies a more general criterion—the minimization of the schedule makespan rather than the minimization of the number of slots used by schedule. It gives an O(nlog ² n)-time optimization algorithm for the single machine problem. For arbitrary number of m>1 identical parallel machines it presents an O(nlog n)-time optimization algorithm for the case when the processing time of each job does not exceed its due date. For the general case on m>1 machines, it proposes a polynomial time constant factor approximation algorithm.     

Semi-empirical model of efficiency of wire electrical discharge machining of hard-to-machine materials

In this study, the efficiency of wire electrical discharge machining of hard-to-machine materials was investigated experimentally. Uncoated brass wire, 0.25 mm diameter, zinc oxide coated brass wire and brass CuZn20 coated brass CuZn50 wire were utilized in the conducted research. The following variables were chosen as important WEDM parameters: discharge time t_on, average working voltage U. The following properties of machined materials, such as: melting point T_t, electrical conductivity σ, thermal conductivity K, thermal expansion coefficient k, density ρ, heat capacity c_p, were selected to develop the semi-empirical model of volumetric efficiency of WEDM. The variation of the WEDM efficiency in cutting different materials and applying different wire electrodes and different process parameters was modelled semi-empirically by employing dimensional analysis.     

On the dynamic extent of delimited continuations

We show that breadth-first traversal exploits the difference between the static delimited-control operator shift (alias S) and the dynamic delimited-control operator control (alias F). For the last 15 years, this difference has been repeatedly mentioned in the literature but it has only been illustrated with one-line toy examples. Breadth-first traversal fills this vacuum.