Offset fields in perpendicularly magnetized tunnel junctions

We study the offset fields affecting the free layer of perpendicularly magnetized tunnel junctions. In extended films, the free layer offset field results from interlayer exchange coupling with the reference layer through the MgO tunnel oxide. The free layer offset field is thus accompanied with a shift of the free layer and reference layer ferromagnetic resonance frequencies. The shifts depend on the mutual orientation of the two magnetizations. The offset field decreases with the resistance area product of the tunnel oxide. Patterning the tunnel junction into an STT-MRAM disk-shaped cell changes substantially the offset field, as the reduction of the lateral dimension comes with the generation of stray fields by the reference and the hard layer. The experimental offset field compares best with the spatial average of the sum of these stray fields, thereby providing guidelines for the offset field engineering.Comment: Special issue of J. Phys. D: Appl. Phys (2019) on STT-MRA

Niosomes and polymeric chitosan based vesicles bearing transferrin and glucose ligands for drug targeting

PURPOSE: To prepare polymeric vesicles and niosomes bearing glucose or transferrin ligands for drug targeting. METHODS: A glucose-palmitoyl glycol chitosan (PGC) conjugate was synthesised and glucose-PGC polymeric vesicles prepared by sonication of glucose-PGC/cholesterol. N-palmitoylglucosamine (NPG) was synthesised and NPG niosomes also prepared by sonication of NPG/ sorbitan monostearate/ cholesterol/ cholesteryl poly-24-oxyethylene ether. These 2 glucose vesicles were incubated with colloidal concanavalin A gold (Con-A gold), washed and visualised by transmission electron microscopy (TEM). Transferrin was also conjugated to the surface of PGC vesicles and the uptake of these vesicles investigated in the A431 cell line (over expressing the transferrin receptor) by fluorescent activated cell sorter analysis. RESULTS: TEM imaging confirmed the presence of glucose units on the surface of PGC polymeric vesicles and NPG niosomes. Transferrin was coupled to PGC vesicles at a level of 0.60+/-0.18 g of transferrin per g polymer. The proportion of FITC-dextran positive A431 cells was 42% (FITC-dextran solution), 74% (plain vesicles) and 90% (transferrin vesicles). CONCLUSIONS: Glucose and transferrin bearing chitosan based vesicles and glucose niosomes have been prepared. Glucose bearing vesicles bind Con-A to their surface. Chitosan based vesicles are taken up by A431 cells and transferrin enhances this uptake

SOT-MRAM 300mm integration for low power and ultrafast embedded memories

We demonstrate for the first time full-scale integration of top-pinned perpendicular MTJ on 300 mm wafer using CMOS-compatible processes for spin-orbit torque (SOT)-MRAM architectures. We show that 62 nm devices with a W-based SOT underlayer have very large endurance (> 5x10^10), sub-ns switching time of 210 ps, and operate with power as low as 300 pJ.Comment: presented at VLSI2018 session C8-

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Population pharmacokinetics of daptomycin in critically ill patients with various degrees of renal impairment

Objectives The objective of this study was to characterize the pharmacokinetics of unbound and total concentrations of daptomycin in infected ICU patients with various degrees of renal impairment. From these results, the probability of attaining antimicrobial efficacy and the risks of toxicity were assessed. Methods Twenty-four ICU patients with various renal functions and requiring treatment of complicated skin and soft-tissue infections, bacteraemia, or endocarditis with daptomycin were recruited. Daptomycin (Cubicin®) at 10 mg/kg was administered every 24 h for patients with creatinine clearance (CLCR) ≥30 mL/min and every 48 h for patients with CLCR <30 mL/min. Total and unbound plasma concentrations and urine concentrations of daptomycin were analysed simultaneously following a population pharmacokinetic approach. Simulations were conducted to estimate the probability of attaining efficacy (unbound AUCu/MIC >40 or >80) or toxicity (Cmin >24.3 mg/L) targets. Results Exposure to unbound daptomycin increased when the renal function decreased, thus increasing the probability of reaching the efficacy targets, but also the risk of toxicity. Modifications of the unbound fraction (fu) of daptomycin did not affect the pharmacokinetics of unbound daptomycin, but did affect the pharmacokinetics of total daptomycin. Conclusions Daptomycin at 10 mg/kg q24h allowed efficacy pharmacokinetic/pharmacodynamic targets for ICU patients with CLCR ≥30 mL/min to be reached. For patients with CLCR <30 mL/min, halving the rate of drug administration, i.e. 10 mg/kg q48h, was sufficient to reach these targets. No adverse events were observed, but the toxicity of the 10 mg/kg q24h dosing regimen should be further assessed, particularly for patients with altered renal function

Evidence of Magnetostrictive Effects on STT-MRAM Performance by Atomistic and Spin Modeling

For the first time, we demonstrate, using an atomistic description of a 30nm diameter spin-transfer-torque magnetic random access memories (STT-MRAM), that the difference in mechanical properties of its sub-nanometer layers induces a high compressive strain in the magnetic tunnel junction (MTJ) and leads to a detrimental magnetostrictive effect. Our model explains the issues met in engineering the electrical and magnetic performances in scaled STT-MRAM devices. The resulting high compressive strain built in the stack, particularly in the MgO tunnel barrier (t-MgO), and its associated non-uniform atomic displacements, impacts on the quality of the MTJ interface and leads to strain relieve mechanisms such as surface roughness and adhesion issues. We illustrate that the strain gradient induced by the different materials and their thicknesses in the stacks has a negative impact on the tunnel magneto-resistance (TMR), on the magnetic nucleation process and on the STT-MRAM performance

Modulation of cancer cell growth and progression by Caveolin-1 in the tumor microenvironment

Caveolin-1 (Cav-1), a major structural component of cell membrane caveolae, is involved in a variety of intracellular signaling pathways as well as transmembrane transport. Cav-1, as a scaffolding protein, modulates signal transduction associated with cell cycle progression, cellular senescence, cell proliferation and death, lipid homeostasis, etc. Cav-1 is also thought to regulate the expression or activity of oncoproteins, such as Src family kinases, H-Ras, protein kinase C, epidermal growth factor, extracellular signal-regulated kinase, and endothelial nitric oxide synthase. Because of its frequent overexpression or mutation in various tumor tissues and cancer cell lines, Cav-1 has been speculated to play a role as an oncoprotein in cancer development and progression. In contrast, Cav-1 may also function as a tumor suppressor, depending on the type of cancer cells and/or surrounding -stromal cells in the tumor microenvironment as well as the stage of tumors.