Transition from geostrophic turbulence to inertia–gravity waves in the atmospheric energy spectrum

Midlatitude fluctuations of the atmospheric winds on scales of thousands of kilometers, the most energetic of such fluctuations, are strongly constrained by the Earth’s rotation and the atmosphere’s stratification. As a result of these constraints, the flow is quasi-2D and energy is trapped at large scales—nonlinear turbulent interactions transfer energy to larger scales, but not to smaller scales. Aircraft observations of wind and temperature near the tropopause indicate that fluctuations at horizontal scales smaller than about 500 km are more energetic than expected from these quasi-2D dynamics. We present an analysis of the observations that indicates that these smaller-scale motions are due to approximately linear inertia–gravity waves, contrary to recent claims that these scales are strongly turbulent. Specifically, the aircraft velocity and temperature measurements are separated into two components: one due to the quasi-2D dynamics and one due to linear inertia–gravity waves. Quasi-2D dynamics dominate at scales larger than 500 km; inertia–gravity waves dominate at scales smaller than 500 km.United States. Office of Naval Research (Grant ONR-N-00014-09-1-0458)National Science Foundation (U.S.) (Grant NSF-CMG-1024198

Estructuras privilegiadas de especies de la familia celastraceae-fuente para el diseño de nuevos agentes terapéuticos

Uno de los grandes retos a los que se enfrenta la medicina en la actualidad es la aparición de resistencia a los fármacos en uso clínico, fenómeno que está presente no sólo en enfermedades infecciosas, sino también en cáncer. En esta línea, los Productos Naturales (PNs), estructuras privilegiadas con una extraordinaria diversidad y complejidad estructural, se presentan como una solución prometedora, constituyendo un excelente punto de partida para el diseño de fármacos. En esta Tesis Doctoral, llevamos a cabo el aislamiento y determinación estructural de 28 sesquiterpenos dihidro-ß-agarofuranos de Celastrus vulcanicola (Celastracaea). A fin de optimizar las propiedades biológicas del cabeza de serie como revertidor de la multirresistencia a fármacos (MDR) en cáncer, se preparó y evaluó una quimioteca de 82 análogos. Estos sesquiterpenos se compartan como revertidores no transportados de la P-glicoproteína y además una baja toxicidad. Asimismo, se describe la preparación de una quimioteca de 48 análogos con esqueleto de triterpeno pentacíclico de la serie del lupano, con un nuevo patrón de regiosustitución. Esta quimioteca fue evaluada por su efecto inhibidor de la replicación del Virus de la Inmunodeficiencia Humana (VIH). El estudio de su mecanismo de acción estableció que uno de los compuestos seleccionados para su estudio presenta un perfil polifarmacológico, actuando a nivel de la entrada y la transcripción del VIH-1, lo que incrementa su potencial aplicación en clínica. Estos trabajos se complementaron con estudios SAR y QSAR, dirigidos a definir los requisitos estructurales y posibles interacciones ligando-receptor implicados en la actividad evaluada. Los excelentes resultados obtenidos revelan que los sesquiterpenos con esqueleto de dihidro-ß-agarofurano y los triterpenos de la serie del lupano se perfilan como candidatos para posteriores estudios, dirigidos a explorar su potencial como agentes terapéuticos en el tratamiento del cáncer y VIH, respectivamente

FUENTE DE FÁRMACOS EN EL SIGLO XXI

La naturaleza ha sido fuente de fármacos desde el inicio de la historia y en muchas culturas lo sigue siendo hoy en día, como en la medicina tradicional china o la ayurveda. Por otra parte, un 50% de los fármacos actualmente usados en la medicina del mundo occidental derivan directa o indirectamente de la naturaleza, como la Aspirina® o el Taxol®. El camino que una sustancia recorre desde la naturaleza hasta convertirse en un nuevo fármaco es largo, laborioso y, en general, muy costoso. Los pasos más importantes a lo largo de este camino son el aislamiento de la fuente natural, elucidación estructural de los metabolitos aislados, sus ensayos en diferentes sistemas biológicos, hasta llegar a las fases clínicas y, finalmente - si todo va bien - la aprobación por la FDA o EMEA. La aparición de nuevas enfermedades infecciosas, la persistencia de enfermedades que aún no tienen tratamiento o la aparición de resistencia, amenazan la eficacia de los medicamentos actualmente en uso. La naturaleza nos puede proporcionar nuevas sustancias más eficaces y quizá con menos efectos secundarios para enfrentarnos a las enfermedades más impactantes de nuestro tiempo y del futuro

Wave–vortex decomposition of one-dimensional ship-track data

We present a simple two-step method by which one-dimensional spectra of horizontal velocity and buoyancy measured along a ship track can be decomposed into a wave component consisting of inertia–gravity waves and a vortex component consisting of a horizontal flow in geostrophic balance. The method requires certain assumptions for the data regarding stationarity, homogeneity, and horizontal isotropy. In the first step an exact Helmholtz decomposition of the horizontal velocity spectra into rotational and divergent components is performed and in the second step an energy equipartition property of hydrostatic inertia–gravity waves is exploited that allows a diagnosis of the wave energy spectrum solely from the observed horizontal velocities. The observed buoyancy spectrum can then be used to compute the residual vortex energy spectrum. Further wave–vortex decompositions of the observed fields are possible if additional information about the frequency content of the waves is available. We illustrate the method on two recent oceanic data sets from the North Pacific and the Gulf Stream. Notably, both steps in our new method might be of broader use in the theoretical and observational study of atmosphere and ocean fluid dynamics.United States. Office of Naval Research (Grant N-00014-09-1-0458)Grant GMG-102419

The Dynamics of Mesoscale Winds in the Upper Troposphere and Lower Stratosphere

Spectral analysis is applied to infer the dynamics of mesoscale winds from aircraft observations in the upper troposphere and lower stratosphere. Two datasets are analyzed: one collected aboard commercial aircraft and one collected using a dedicated research aircraft. A recently developed wave–vortex decomposition is used to test the observations’ consistency with linear inertia–gravity wave dynamics. The decomposition method is shown to be robust in the vicinity of the tropopause if flight tracks vary sufficiently in altitude. For the lower stratosphere, the decompositions of both datasets confirm a recent result that mesoscale winds are consistent with the polarization and dispersion relations of inertia–gravity waves. For the upper troposphere, however, the two datasets disagree: only the research aircraft data indicate consistency with linear wave dynamics at mesoscales. The source of the inconsistency is a difference in mesoscale variance of the measured along-track wind component. To further test the observed flow’s consistency with linear wave dynamics, the ratio between tropospheric and stratospheric mesoscale energy levels is compared to a simple model of upward-propagating waves that are partially reflected at the tropopause. For both datasets, the observed energy ratio is roughly consistent with the simple wave model, but wave frequencies diagnosed from the data draw into question the applicability of the monochromatic theory at wavelengths smaller than 10 km

Transition from geostrophic turbulence to inertia–gravity waves in the atmospheric energy spectrum

Midlatitude fluctuations of the atmospheric winds on scales of thousands of kilometers, the most energetic of such fluctuations, are strongly constrained by the Earth’s rotation and the atmosphere’s stratification. As a result of these constraints, the flow is quasi-2D and energy is trapped at large scales—nonlinear turbulent interactions transfer energy to larger scales, but not to smaller scales. Aircraft observations of wind and temperature near the tropopause indicate that fluctuations at horizontal scales smaller than about 500 km are more energetic than expected from these quasi-2D dynamics. We present an analysis of the observations that indicates that these smaller-scale motions are due to approximately linear inertia–gravity waves, contrary to recent claims that these scales are strongly turbulent. Specifically, the aircraft velocity and temperature measurements are separated into two components: one due to the quasi-2D dynamics and one due to linear inertia–gravity waves. Quasi-2D dynamics dominate at scales larger than 500 km; inertia–gravity waves dominate at scales smaller than 500 km

Applications of sesquiterpene lactones : a review of some potential success cases

Sesquiterpene lactones, a vast range of terpenoids isolated from Asteraceae species, exhibit a broad spectrum of biological effects and several of them are already commercially available, such as artemisinin. Here the most recent and impactful results of in vivo, preclinical and clinical studies involving a selection of ten sesquiterpene lactones (alantolactone, arglabin, costunolide, cynaropicrin, helenalin, inuviscolide, lactucin, parthenolide, thapsigargin and tomentosin) are presented and discussed, along with some of their derivatives. In the authors’ opinion, these compounds have been neglected compared to others, although they could be of great use in developing important new pharmaceutical products. The selected sesquiterpenes show promising anticancer and anti-inflammatory effects, acting on various targets. Moreover, they exhibit antifungal, anxiolytic, analgesic, and antitrypanosomal activities. Several studies discussed here clearly show the potential that some of them have in combination therapy, as sensitizing agents to facilitate and enhance the action of drugs in clinical use. The derivatives show greater pharmacological value since they have better pharmacokinetics, stability, potency, and/or selectivity. All these natural terpenoids and their derivatives exhibit properties that invite further research by the scientific community.Portuguese Foundation for Science and Technology; European Commission; QREN; European Commission; COMPETE; cE3c centre (UIDB/00329/2020); LAQV-REQUIMTE (UIDB/50006/2020); QOPNA UID/QUI/00062/2019), Spanish Ministry Science and Research (MINECO RTI2018-094356-B-C21)info:eu-repo/semantics/publishedVersio

La farmacia naturaleza – fuente de fármacos en el siglo XXI

La naturaleza ha sido fuente de fármacos desde el inicio de la historia y en muchas culturas lo sigue siendo hoy en día, como en la medicina tradicional china o la ayurveda. Por otra parte, un 50% de los fármacos actualmente usados en la medicina del mundo occidental derivan directa o indirectamente de la naturaleza, como la Aspirina® o el Taxol®. El camino que una sustancia recorre desde la naturaleza hasta convertirse en un nuevo fármaco es largo, laborioso y, en general, muy costoso. Los pasos más importantes a lo largo de este camino son el aislamiento de la fuente natural, elucidación estructural de los metabolitos aislados, sus ensayos en diferentes sistemas biológicos, hasta llegar a las fases clínicas y, finalmente - si todo va bien - la aprobación por la FDA o EMEA. La aparición de nuevas enfermedades infecciosas, la persistencia de enfermedades que aún no tienen tratamiento o la aparición de resistencia, amenazan la eficacia de los medicamentos actualmente en uso. La naturaleza nos puede proporcionar nuevas sustancias más eficaces y quizá con menos efectos secundarios para enfrentarnos a las enfermedades más impactantes de nuestro tiempo y del futuro

Application of isothermal titration calorimetry as a tool to study natural product interactions

Over the past twenty-five years, isothermal titration calorimetry (ITC) has become a potent tool for the study a great variety of molecular interactions. This technique is able to provide a complete thermodynamic profile of an interaction process in a single experiment, with a series of advantages in comparison to other comparable techniques, such as less amount of sample or no need of chemical modification or labelling. It is thus not surprising that ITC has been applied to study the manifold types of interactions of natural products to get new insights into the molecular key factors implied in the complexation process of this type of compounds. This review provides an overview over the applications of ITC as a potent tool to investigate interactions of natural products with proteins, nucleic acids, oligosaccharides, and other types of receptors. The examples have been selected depending on the impact that this technique had during the investigation and revision of the interactions involved in the bioactivity of a compound, lead optimization or technical applications.Peer reviewe