A method for generating a quasi-linear convective system suitable for observing system simulation experiments

To understand the impact of different assimilated observations on convection-allowing model forecast skill, a diverse range of observing system simulation experiment (OSSE) case studies are required (different storm modes and environments). Many previous convection-allowing OSSEs predicted the evolution of an isolated supercell generated via a warm air perturbation in a horizontally homogenous environment. This study introduces a new methodology in which a quasi-linear convective system is generated in a highly sheared and modestly unstable environment. Wind, temperature, and moisture perturbations superimposed on a horizontally homogeneous environment simulate a cold front that initiates an organized storm system that spawns multiple mesovortices. Mature boundary layer turbulence is also superimposed onto the initial environment to account for typical convective-scale uncertainties. Creating an initial forecast ensemble remains a challenge for convection-allowing OSSEs because mesoscale uncertainties are difficult to quantify and represent. The generation of the forecast ensemble is described in detail. The forecast ensemble is initialized by 24 h full-physics simulations (e.g., radiative forcing, surface friction, and microphysics). The simulations assume different surface conditions to alter surface moisture and heat fluxes and modify the effects of friction. The subsequent forecast ensemble contains robust non-Gaussian errors that persist until corrected by the data assimilation system. This purposely degraded initial forecast ensemble provides an opportunity to assess whether assimilated environmental observations can improve, e.g., the wind profile. An example OSSE suggests that a combination of radar and conventional (surface and soundings) observations are required to produce a skilled quasi-linear convective system forecast, which is consistent with real-world case studies. The OSSE framework introduced in this study will be used to understand the impact of assimilated environmental observations on forecast skill.</p

Identification of levothyroxine antichagasic activity through computer-aided drug repurposing

Cruzipain (Cz) is the major cysteine protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. A conformation-independent classifier capable of identifying Cz inhibitors was derived from a 163-compound dataset and later applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 3 of which were acquired and tested on Cz and T. cruzi epimastigotes proliferation. Among them, levothyroxine, traditionally used in hormone replacement therapy in patients with hypothyroidism, showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite.Facultad de Ciencias Exacta

Labour market trajectories following sickness absence due to self-reported all cause morbidity—a longitudinal study

Abstract Background To investigate differences in return to work (RTW) and employment trajectories in individuals on sick leave for either mental health reasons or other health related reasons. Methods This study was based on 2036 new sickness absence cases who completed a questionnaire on social characteristics, expectations for RTW and reasons for sickness absence. They were divided into two exposure groups according to their self-reported sickness absence reason: mental health reasons or other health reasons. The outcome was employment status during the following 51 weeks and was measured both as time-to-event analysis and with sequence analysis. Results Individuals with mental health reasons for sickness absence had a higher risk of not having returned to work (RR 0.87 (0.80;0.93)). Adjusting for gender, age, education and employment did not change the estimate, however, after adding RTW expectations to the model, the excess risk was no longer present (RR 1.01 (0.95;1.08)). In relation to the sequence analysis, individuals with mental health related absence had significantly higher odds of being in the sickness absence cluster and significantly lower odds for being in the fast RTW cluster, but when adjusting for RTW expectations, the odds were somewhat attenuated and no longer significant. Conclusions Employees on sick leave due to self-reported mental health problems spent more weeks in sickness absence and temporary benefits and had a higher risk of not having returned to work within a year compared to employees on sick leave due to other health reasons. The difference could be explained by their lower RTW expectations at baseline. This emphasises the need to develop suitable and specific interventions to facilitate RTW for this group of sickness absentees

Endoplasmic Reticulum Calcium Regulates the Retrotranslocation of Trypanosoma Cruzi Calreticulin to the Cytosol

For most secretory pathway proteins, crossing the endoplasmic reticulum (ER) membrane is an irreversible process. However, in some cases this flow can be reversed. For instance, misfolded proteins retained in the ER are retrotranslocated to the cytosol to be degraded by the proteasome. This mechanism, known as ER associated degradation (ERAD), is exploited by several bacterial toxins to gain access to the cytosol. Interestingly, some ER resident proteins can also be detected in the cytosol or nucleus, calreticulin (CRT) being the most studied. Here we show that in Trypanosoma cruzi a minor fraction of CRT localized to the cytosol. ER calcium depletion, but not increasing cytosolic calcium, triggered the retrotranslocation of CRT in a relatively short period of time. Cytosolic CRT was subsequently degraded by the proteasome. Interestingly, the single disulfide bridge of CRT is reduced when the protein is located in the cytosol. The effect exerted by ER calcium was strictly dependent on the C-terminal domain (CRT-C), since a CRT lacking it was totally retained in the ER, whereas the localization of an unrelated protein fused to CRT-C mirrored that of endogenous CRT. This finding expands the regulatory mechanisms of protein sorting and may represent a new crossroad between diverse physiological processes

Algunos aspectos no cartesianos del racionalismo de Spinoza y de Leibniz. Sobre la naturaleza de los cuerpos

Tras recordar en la primera parte algunos vestigios de la herencia neoplatónica y cabalística de la tradición animista en las obras de Spinoza y del joven Leibniz, analizo en la segunda parte aspectos del conatus, que son comunes a ambos filósofos: mens idea corporis y mens harmonia conatuum respectivamente. Por fin, en una tercera parte, describo la «transvaloración » que del conatus de Hobbes y de Spinoza, así como de las regulae motus de Huygens, trató de hacer Leibniz: por una parte, de la resistencia o inertia naturalis de los cuerpos a la vis insita rebus: i. e. potentia absoluta corporum; y por otra parte, de la relatividad del movimiento de los experimentos mecánicos a la universalidad del principio de la equipolencia de la causa plena y del efecto entero, cuyo último fundamento es el principio de individuación: la universalidad de todas las leyes mecánicas y la singularidad de cada suceso del universo.Després de recordar en la primera part alguns vestigis de l'herència neoplatònica i cabalística de la tradició animista en les obres de Spinoza i del jove Leibniz, analitzo en la segona part aspectes del conatus, que són comuns a ambdós filòsofs: mens idea corporis i mens harmonia conatuum respectivament. Finalment, en una tercera part, descric la «transvaloració» que del conatus de Hobbes i de Spinoza, així com de les regulae motus de Huygens, va tractar de fer Leibniz: d'una banda, de la resistència o inertia naturalis dels cossos a la vis insita rebus: i. e. potentia absoluta corporum; i de l'altra, de la relativitat del moviment dels experiments mecànics a la universalitat del principi de l'equipol·lència de la causa plena i de l'efecte enter, l'últim fonament del qual és el principi d'individuació: la universalitat de totes les lleis mecàniques i la singularitat de cada succés de l'univers.Remembering in the first part some vestiges of the neoplatonic and kabbalistic heritage of the animistic tradition in the work of Spinoza and the young Leibniz, I analyze in the second part the common aspects of the conatus in both philosophers: mens idea corporis and mens harmonia conatuum, respectively. Finally, in the third part, I describe the "transvaloration" of Hobbes's and Spinoza's conatus and Huygens's regulae motus Leibniz intended to add: from the "resistance or inertia naturalis" of bodies to the vis insita rebus (i.e., potentia absoluta corporum) and from the "relativity" of motion of mechanical experiments to the "universality" of the principle of equipolentia causae plenae et effectus integri grounded in the principle of individuation, that is, the universality of all mechanical rules and the singularity of every fact of the universe