Multifunctional System for Combined Chemodynamic–Photodynamic Therapy Employing the Endothelin Axis Based on Conjugated Polymer Nanoparticles

Most nanomedicines that attack tumors by Reactive Oxygen Species (ROS) based on lipid peroxidation mechanisms require external activation to work. The leading example is Photodynamic Therapy (PDT), for which an...

Modulation of Wnt/β-catenin signaling promotes blood-brain barrier phenotype in cultured brain endothelial cells

Wnt/β-catenin signaling is important for blood-brain barrier (BBB) development and is implicated in BBB breakdown under various pathophysiological conditions. In the present study, a comprehensive characterization of the relevant genes, transport and permeability processes influenced by both the autocrine and external activation of Wnt signaling in human brain endothelial cells was examined using hCMEC/D3 culture model. The hCMEC/D3 expressed a full complement of Wnt ligands and receptors. Preventing Wnt ligand release from hCMEC/D3 produced minimal changes in brain endothelial function, while inhibition of intrinsic/autocrine Wnt/β-catenin activity through blocking β-catenin binding to Wnt transcription factor caused more modest changes. In contrast, activation of Wnt signaling using exogenous Wnt ligand (Wnt3a) or LiCl (GSK3 inhibitor) improved the BBB phenotypes of the hCMEC/D3 culture model, resulting in reduced paracellular permeability, and increased P-glycoprotein (P-gp) and breast cancer resistance associated protein (BCRP) efflux transporter activity. Further, Wnt3a reduced plasmalemma vesicle associated protein (PLVAP) and vesicular transport activity in hCMEC/D3. Our data suggest that this in vitro model of the BBB has a more robust response to exogenous activation of Wnt/β-catenin signaling compared to autocrine activation, suggesting that BBB regulation may be more dependent on external activation of Wnt signaling within the brain microvasculature.

To change the properties of magnetic fluids in an alternating magnetic field

Provides an overview of magnetic fluids and their external activation methods weak energy impacts. Considered the physical basis of magnetic fuel activation with a view to change their molecular and nadmolekuljarnyh structures. A new design of magnetic liquid Activator Wednesday with a high rate of utilization of capacity. Shows comparative testing fuels combustion engine, resulting in significant increase recorded their energy and environmental performance after magnetic fuel activation. Considered a prerequisite applying magnetic rocket fuels activation.

INTERNAL AND EXTERNAL FLUCTUATION ACTIVATED NONEQUILIBRIUM REACTIVE RATE PROCESS

An externally activated nonequilibrium anomalous reactive rate process is studied by taking into account both internal and external fluctuations in a unified way. The probability of diffusion passing over the saddle point and the reactive rate together with the effective transmission coefficient are calculated by the method of reactive flux. It is found that the fierceness of internal fluctuation is always harmful to the diffusion of particles. However, the external activation may be beneficial to the rate process.

382 SYNCHRONIZING ACTIVATION TIME WITH MAXIMUM MATURATION PROMOTING FACTOR AND MITOGEN-ACTIVATED PROTEIN KINASE LEVELS DOES NOT IMPROVE BOVINE INTRACYTOPLASMIC SPERM INJECTION

The success of bovine intracytoplasmic sperm injection (ICSI) remains low because of the tightly packed sperm nucleus failing to decondense and the need for additional external activation. Maturation promoting factor (MPF) and mitogen-activated protein kinase (MAPK) assist the breakdown of the nuclear envelope. Activities are high at the early metaphase II (MII) stage but decrease with time. We assessed MPF and MAPK dynamics during the MII stage from 24 h postmaturation (hpm) onward. We then tested the hypothesis that ICSI may be more successful if the external activation is performed following sperm exposure to maximum MPF and MAPK levels. Bovine oocytes were matured in M199 with 10% FCS, 5 µg mL−1 FSH, 5 µg mL−1 LH, 1 µg mL−1 estradiol, and 50 µL mL−1 gentamycin, and cumulus cells were removed at 18 hpm. Groups of 10 MII oocytes were sampled from 24 hpm and analyzed for MPF and MAPK activities as previously described (Ye et al. 2003 Reproduction 125, 645–656). For ICSI, MII oocytes were moved to HSOF supplemented with amino acids and BSA (HSOFaa) and injected with sperm from 19 to 22 hpm. Further MII oocytes were subjected to sham or no injections at this time. Injections were performed manually using a 1480-nm diode laser (XY-clone; Hamilton-Thorne, Beverly, MA, USA) to breach the zona pellucida. Because the maximum kinase activities were reached at 28 hpm, oocytes were activated in 2 groups: at either 24 or 28 hpm, using HSOFaa containing 7% ethanol followed by culture in mSOFaa with 10 µg mL−1 cycloheximide for 6 h, and then transferred to mSOFaa medium until cleavage assessment on Day 2. Differences in the percentage of cleaved oocytes in the different groups were analyzed by a chi-squared test. From 24 to 28 hpm, there was an increase in both MPF (24.6%) and MAPK (58.7%) levels, followed by a slow decline. There were no significant differences in cleavage rates for sham-injected or control oocytes at the different activation times (P < 0.05). However, a significantly higher cleavage rate was observed following ICSI with activation at 24 hpm compared with 28 hpm (P < 0.001), even though kinase levels appeared maximal at 28 hpm. The manual injection procedure appeared detrimental, because oocytes in the control group showed a significantly higher cleavage rate than sham-injected oocytes (P < 0.01). In conclusion, bovine oocytes subjected to ICSI showed a better cleavage rate if external activation was performed at 24 hpm rather than at 28 hpm, even though the MPF and MAPK levels were maximal at 28 hpm (P < 0.001), even though kinase levels appeared maximal at 28 hpm. The manual injection procedure appeared detrimental, because oocytes in the control group showed a significantly higher cleavage rate than sham-injected oocytes (P < 0.01). In conclusion, bovine oocytes subjected to ICSI showed a better cleavage rate if external activation was performed at 24 hpm rather than at 28 hpm, even though the MPF and MAPK levels were maximal at 28 hpm. Table 1. Percentage of Day 2 cleaved oocytes after intracytoplasmic sperm injection, sham or no injection at 2 different activation times

Reflexive Substantion of an One-Way Ascendancy of Mathematics over Ethics

Russell and Popper are concordant with Plato with respect to the independence of mathematics upon the sensations. Beth shares the opinion of the complete independence between the world of science and mathematics and that of psychology. Essenin-Vol'pin's opinion is of an ascendance of ethics and jurisprudence over mathematics. For the first time, the position of Plato, Russell, and Popper are substantiated in this paper through Hegel's reflexive natural scientific method. The external activation of numbers into interaction through arithmetical operations, adopted by him, has been taken as a basis of this substantion. This is the reason why mathematical rules of reasoning are exact-they represent a pure product of the 'third world.' The rules of ethics and the related humanities are their reflective approximate reverberations. Ascendancy of the rules of such types of science over mathematics is impossible due to the irreversibility of the reflexion.