Wind sea behind a cold front and deep ocean acoustics

Author Posting. © American Meteorological Society, 2016. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 46 (2016): 1705-1716, doi:10.1175/JPO-D-15-0221.1.A rapid and broadband (1 h, 1 < f < 400 Hz) increase in pressure and vertical velocity on the deep ocean floor was observed on seven instruments comprising a 20-km array in the northeastern subtropical Pacific. The authors associate the jump with the passage of a cold front and focus on the 4- and 400-Hz spectra. At every station, the time of the jump is consistent with the front coming from the northwest. The apparent rate of progress, 10–20 km h−1 (2.8–5.6 m s−1), agrees with meteorological observations. The acoustic radiation below the front is modeled as arising from a moving half-plane of uncorrelated acoustic dipoles. The half-plane is preceded by a 10-km transition zone, over which the radiator strength increases linearly from zero. With this model, the time derivative of the jump at a station yields a second and independent estimate of the front’s speed, 8.5 km h−1 (2.4 m s−1). For the 4-Hz spectra, the source physics is taken to be Longuet-Higgins radiation. Its strength depends on the quantity , where Fζ is the wave amplitude power spectrum and I the overlap integral. Thus, the 1-h time constant observed in the bottom data implies a similar time constant for the growth of the wave field quantity behind the front. The spectra at 400 Hz have a similar time constant, but the jump occurs 25 min later. The implications of this difference for the source physics are uncertain.The OBSANP cruise was funded by the Office of Naval Research under Grants N00014-10-1-0987, N00014-14-1-0324, N00014-10-1-0510, and N00014-10-1-0990

Cholesterol Reduces Partitioning of Antifungal Drug Itraconazole into Lipid Bilayers

Cholesterol plays a crucial role in modulating the physicochemical properties of biomembranes, both increasing mechanical strength and decreasing permeability. Cholesterol is also a common component of vesicle-based delivery systems, including liposome-based drug delivery systems (LDSs). However, its effect on the partitioning of drug molecules to lipid membranes is very poorly recognized. Herein, we performed a combined experimental/computational study of the potential for the use of the LDS formulation for the delivery of the antifungal drug itraconazole (ITZ). We consider the addition of cholesterol to the lipid membrane. Since ITZ is only weakly soluble in water, its bioavailability is limited. Use of an LDS has thus been proposed. We studied lipid membranes composed of cholesterol, 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC), and ITZ using a combination of computational molecular dynamics (MD) simulations of lipid bilayers and Brewster angle microscopy (BAM) experiments of monolayers. Both experimental and computational results show separation of cholesterol and ITZ. Cholesterol has a strong preference to orient parallel to the bilayer normal. However, ITZ, a long and relatively rigid molecule with weakly hydrophilic groups along the backbone, predominantly locates below the interface between the hydrocarbon chain region and the polar region of the membrane, with its backbone oriented parallel to the membrane surface; the orthogonal orientation in the membrane could be the cause of the observed separation. In addition, fluorescence measurements demonstrated that the affinity of ITZ for the lipid membrane is decreased by the presence of cholesterol, which is thus probably not a suitable formulation component of an LDS designed for ITZ delivery.Peer reviewe

Nanostructural hybrid sensitizers for photodynamic therapy

Photodynamic therapy (PDT) is a clinically approved method for treatment of cancer, microbial infections, and some other diseases. PDT has proved effective in the treatment of malignancies of various organs, including lung, bladder, gastrointestinal tract, and skin, and in the therapy of bacterial infection of skin wounds and carious lesions. It employs a combination of light and a drug (photosensitizer, PS) to induce phototoxicity against cancerous cells or bacteria. The efficiency of currently used PSs is limited due to their hydrophobic nature, which causes aggregation of the PS in aqueous media and low tumor selectivity (a low value of the tumor-to-normal tissue ratio). The purpose of this review is to present some aspects of the current state of knowledge on nanostructural carriers for the PS delivery. In this paper we reviewed studies on the development of nanostructural materials for PDT, especially those based on the polymeric and liposomal formulation of PS. We focused mainly on the nanostructural PSs obtained by the covalent attachment of hydrophilic polymer chain to the low-molecular-weight PS, the incorporation of PS into polymeric nanostructures such as micelles, and the solubilization of PS in liposome carrier

Effects of membrane PEGylation on entry and location of antifungal drug itraconazole and their pharmacological implications

Itraconazole (ITZ) is an antifungal agent used clinically to treat mycotic infections. However, its therapeutic effects are limited by low solubility in aqueous media. Liposome-based delivery systems (LDS) have been proposed as a delivery mechanism for ITZ to alleviate this problem. Furthermore, PEGylation, the inclusion in the formulation of a protective “stealth sheath” of poly­(ethylene glycol) around carrier particles, is widely used to increase circulation time in the bloodstream and hence efficacy. Together, these themes highlight the importance of mechanistic and structural understanding of ITZ incorporation into liposomes both with and without PEGylation because it can provide a potential foundation for the rational design of LDS-based systems for delivery of ITZ, using alternate protective polymers or formulations. Here we have combined atomistic simulations, cryo-TEM, Langmuir film balance, and fluorescence quenching experiments to explore how ITZ interacts with both pristine and PEGylated liposomes. We found that the drug can be incorporated into conventional and PEGylated liposomes for drug concentrations up to 15 mol % without phase separation. We observed that, in addition to its protective properties, PEGylation significantly increases the stability of liposomes that host ITZ. In a 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphocholine (POPC) bilayer without PEGylation, ITZ was found to reside inside the lipid bilayer between the glycerol and the double-bond regions of POPC, adopting a largely parallel orientation along the membrane surface. In a PEGylated liposome, ITZ partitions mainly to the PEG layer. The results provide a solid basis for further development of liposome-based delivery systems

Clinically silent, right and left ventricular outflow tract obstructions in an adult patient

Right ventricular outflow tract obstruction is a narrowing of the way that conducts blood from the right ventricle to the pulmonary ar‑ tery. Left ventricular outflow tract obstruction is a stenosis of the path that leads blood from the left ventricle to the aorta. Combination of right and left ventricular outflow tract obstruction is a very rare finding. We report a case of a 67‑year‑old male with asymptomatic bi‑ ventricular outflow tract obstruction. We discuss the clinical presentation, diagnostic procedures, treatment opportunities for the patient based on review of literature and actual recommendations. <br