Multiscale climate emulator of multimodal wave spectra: MUSCLE-spectra

Characterization of multimodal directional wave spectra is important for many offshore and coastal applications, such as marine forecasting, coastal hazard assessment, and design of offshore wave energy farms and coastal structures. However, the multivariate and multiscale nature of wave climate variability makes this complex problem tractable using computationally expensive numerical models. So far, the skill of statistical-downscaling model-based parametric (unimodal) wave conditions is limited in large ocean basins such as the Pacific. The recent availability of long-term directional spectral data from buoys and wave hindcast models allows for development of stochastic models that include multimodal sea-state parameters. This work introduces a statistical downscaling framework based on weather types to predict multimodal wave spectra (e.g., significant wave height, mean wave period, and mean wave direction from different storm systems, including sea and swells) from large-scale atmospheric pressure fields. For each weather type, variables of interest are modeled using the categorical distribution for the sea-state type, the Generalized Extreme Value (GEV) distribution for wave height and wave period, a multivariate Gaussian copula for the interdependence between variables, and a Markov chain model for the chronology of daily weather types. We apply the model to the southern California coast, where local seas and swells from both the Northern and Southern Hemispheres contribute to the multimodal wave spectrum. This work allows attribution of particular extreme multimodal wave events to specific atmospheric conditions, expanding knowledge of time-dependent, climate-driven offshore and coastal sea-state conditions that have a significant influence on local nearshore processes, coastal morphology, and flood hazards.We thank Jorge Perez for the ESTELA code. A.R., J.A.A.A., and F.J.M. acknowledge the support of the Spanish ‘‘Ministerio de Economia y Competitividad’’ under grant BIA2014-59643-R. P.C. acknowledges the support of the Spanish ‘‘Ministerio de Economia y Competitividad’’ under grant BIA2015-70644-R. J.A.A.A. is indebted to the MEC (Ministerio de Educacion, Cultura y Deporte, Spain) for the funding provided in the FPU (Formacion del ProfesoradoUniversitario) studentship (BOE-A-2013-12235). This material is based upon work supported by the U.S. Geological Survey under grant/cooperative agreement G15AC00426. P.R. acknowledges the support of the National Oceanic and Atmospheric Administration Climate Program Office via award NA15OAR4310145. Support was provided from the US DOD Strategic Environmental Research and Development Program (SERDP Project RC-2644) through the NOAA National Centers for Environmental Information (NCEI). Atmospheric data from CFSR are available online at https://climatedataguide.ucar.edu/climatedata/climate-forecast-system-reanalysis-cfsr. Marine data from global reanalysis are lodge with the IHData center from IHCantabria and are available for research purposes upon request (contact: [email protected])

Liposomes in Biology and Medicine

Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS

The Extended Deterrent Value of Nuclear Weapons

Three questions are addressed in this study: (1) Does a nuclear retaliatory capability contribute to extended deterrence against a nonnuclear power? (2) If so, is the deterrent value of nuclear weapons contingent upon the prior credible threat of conventional armed engagement by the defender? (3) Or, is the deterrent impact of nuclear weapons so potent that the conventional balance of forces has little deterrent impact? Competing hypotheses are formulated and then tested by probit analysis. The empirical findings indicate that (a) nuclear weapons do contribute to extended deterrence success, but (b) that effect is not contingent upon the prior threat of conventional armed conflict, and (c) there is an inverse relationship between the conventional balance of forces and the extended deterrent role of nuclear weapons.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67765/2/10.1177_0022002790034002005.pd