The role of spin-orbit coupling in the optical spectroscopy of atomic sodium isolated in solid xenon

Molecular dynamics calculations, based on the diatomics-in-molecules method, have been used to probe the manifestations of spin-orbit (SO) coupling in the experimental absorption bands of atomic sodium isolated in solid xenon. Inclusion of SO coupling of –320 cm−1 in spectral simulations of the 3p 2P 3s 2S transition leads to unequal band spacings which very closely match the asymmetrical bandshape observed for blue single vacancy (SV) site occupancy. This SO value, extracted in a previous MCD study, reveals the dramatic change in the effective SO coupling constant of the Na atom (from the gas phase value of +17 cm−1 ) in solid Xe when it is close to the 12 xenon atoms in the first surrounding sphere. In contrast, the symmetrical three-fold split band of the red tetra vacancy (TV) site in Na/Xe is not affected nearly as much by SO coupling. This reflects a greatly reduced “external heavy atom” effect when the 24 Xe atoms surrounding the Na atom in TV are located at greater distances. The contrasting behavior of sodium in the SV and TV sites suggests a strong dependence of the SO coupling strength on the Na–Xe distance

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterisation and RALA complexation

DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity. Of these devices, dissolvable microneedles promise a safe, pain-free delivery system which may simultaneously improve DNA stability within a solid matrix and increase DNA delivery compared to solid arrays. However, to date little work has directly compared the suitability of different dissolvable matrices for formulation of DNA-loaded microneedles. Therefore, the current study examined the ability of 4 polymers to formulate mechanically robust, functional DNA loaded dissolvable microneedles. Additionally, complexation of DNA to a cationic delivery peptide, RALA, prior to incorporation into the dissolvable matrix was explored as a means to improve transfection efficacies following release from the polymer matrix. Our data demonstrates that DNA is degraded following incorporation into PVP, but not PVA matrices. The complexation of DNA to RALA prior to incorporation into polymers resulted in higher recovery from dissolvable matrices, and increased transfection efficiencies in vitro. Additionally, RALA/DNA nanoparticles released from dissolvable PVA matrices demonstrated up to 10-fold higher transfection efficiencies than the corresponding complexes released from PVP matrices, indicating that PVA is a superior polymer for this microneedle application

Essential Role of TGF-β/Smad Pathway on Statin Dependent Vascular Smooth Muscle Cell Regulation

BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins) exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta) in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs) statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII), and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs

Основы творческой деятельности веб-журналиста. Учебная программа учреждения высшего образования по учебной дисциплине для специальности: 1-23 01 08 Журналистика (по направлениям) направления специальности 1-23 01 08-03 Журналистика (веб-журналистика)

Wildfires pose a serious threat to life in many countries. For police, fire and emergency services authorities in most jurisdictions in North America and Australia evacuation is now the option that is preferred overwhelmingly. Wildfire evacuation modeling can assist authorities in planning evacuation responses to future threats. Understanding residents' behavior under wildfire threat may assist in wildfire evacuation modeling. This paper reviews North American and Australian research into wildfire evacuation behavior published between January 2005 and June 2017. Wildfire evacuation policies differ across the two regions: in North America mandatory evacuations are favored, in Australia most are advisory. Research from both regions indicates that following a wildfire evacuation warning some threatened residents will wish to remain on their property in order to protect it, many will delay evacuating, and some residents who are not on their property when an evacuation warning is issued may seek to return. Mandatory evacuation is likely to result in greater compliance, enforcement policies are also likely to be influential. Self-delayed evacuation is likely if warnings are not sufficiently informative: residents are likely to engage in information search rather than initiating evacuation actions. The wildfire warning and threat histories of a location may influence residents' decisions and actions. The complexities of behavioral factors influencing residents' actions following an evacuation warning pose challenges for wildfire evacuation modeling. Suggestions are offered for ways in which authorities might reduce the numbers of residents who delay evacuating following a wildfire warning. © 2018 Springer Science+Business Media, LLC, part of Springer Natur

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population

Crystal field splitting on D↔S transitions of atomic manganese isolated in solid krypton

Narrow excitation features present on the [Ar]3d64s1a6D(J = 9/2−1/2)←[Ar]3d54s2a6S1/2 transitions of manganese atoms isolated in solid Kr are analyzed within the framework of weak crystal field splitting. Use of the Wp optical lineshape function allowed identification of multiple zero-phonon lines for individual spin-orbit J states of the a a6D←a6S transition recorded with laser-induced excitation spectroscopy. Excellent agreement exists between the predicted crystal field splitting patterns for the J levels of the a6D state isolated in the «red» tetravacancy site of solid Kr. The tetrahedral crystal field of the «red» trapping site splits J>3/2 levels of the a6DJ and a4D7/2 states by approximately 30 cm−1. This report represents the first definitive evidence of crystal field splitting, induced by the weak van der Waals interactions between a neutral metal atom and the rare gas atoms surrounding it in a well-defined solid-state site