POST-PROCESSING OF ALADIN WIND SPEED PREDICTIONS WITH AN ANALOG-BASED METHOD

In this paper, different post-processing methods are described and evaluated for deterministic and probabilistic point-based 10-m wind speed forecast over Croatia. These methods are applied to forecasts of operational high-resolution dynamical adaptation model (DADA) run with 2 km horizontal resolution to address the following question: which point-based post-processing method is the best suited for wind forecasting in the operational suite at DHMZ (Meteorological and Hydrological Service of Croatia). The verification procedure includes several metrics computed considering wind speed as continuous, categorical and probabilistic predictand. Those metrics were used to optimize the configuration, and to test both the deterministic and probabilistic prediction performance. This study shows that deterministic analog-based predictions (AnEn) improve the correlation between predictions and measurements while reducing forecast error better than using Kalman filter based predictions (KF), even though KF shows better bias reduction. The best results are achieved when forecasting the mean of analog ensemble or the Kalman filter of the mean of analog ensemble. Probabilistic AnEn predictions are properly dispersive, while having better resolution, discrimination and skill than forecast generated via logistic regression. These results encourage the potential use of AnEn in an operational environment at the location of meteorological stations, as well as at wind farm s

Bayesian Exploration of Multivariate Orographic Precipitation Sensitivity for Moist Stable and Neutral Flows

Abstract Recent idealized studies examined the sensitivity of topographically forced rain and snowfall to changes in mountain geometry and upwind sounding in moist stable and neutral environments. These studies were restricted by necessity to small ensembles of carefully chosen simulations. Research presented here extends earlier studies by utilizing a Bayesian Markov chain Monte Carlo (MCMC) algorithm to create a large ensemble of simulations, all of which produce precipitation concentrated on the upwind slope of an idealized Gaussian bell-shaped mountain. MCMC-based probabilistic analysis yields information about the combinations of sounding and mountain geometry favorable for upslope rain, as well as the sensitivity of orographic precipitation to changes in mountain geometry and upwind sounding. Exploration of the multivariate sensitivity of rainfall to changes in parameters also reveals a nonunique solution: multiple combinations of flow, topography, and environment produce similar surface rainfall amount and distribution. Finally, the results also divulge that the nonunique solutions have different sensitivity profiles, and that changes in observation uncertainty also alter model sensitivity to input parameters

Challenges in Developing Better Observational Constraints and Models for Aerosols : Emerging Ideas for Design and Use of Future Observing Systems

No abstract availabl

The first-in-class alkylating deacetylase inhibitor molecule tinostamustine shows antitumor effects and is synergistic with radiotherapy in preclinical models of glioblastoma

Background: The use of alkylating agents such as temozolomide in association with radiotherapy (RT) is the therapeutic standard of glioblastoma (GBM). This regimen modestly prolongs overall survival, also if, in light of the still dismal prognosis, further improvements are desperately needed, especially in the patients with O6- methylguanine-DNA-methyltransferase (MGMT) unmethylated tumors, in which the benefit of standard treatment is less. Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor (AK-DACi) molecule that fuses the DNA damaging effect of bendamustine with the fully functional pan-histone deacetylase (HDAC) inhibitor, vorinostat, in a completely new chemical entity. Methods: Tinostamustine has been tested in models of GBM by using 13 GBM cell lines and seven patient-derived GBM proliferating/stem cell lines in vitro. U87MG and U251MG (MGMT negative), as well as T98G (MGMT positive), were subcutaneously injected in nude mice, whereas luciferase positive U251MG cells and patient-derived GBM stem cell line (CSCs-5) were evaluated the orthotopic intra-brain in vivo experiments. Results: We demonstrated that tinostamustine possesses stronger antiproliferative and pro-apoptotic effects than those observed for vorinostat and bendamustine alone and similar to their combination and irrespective of MGMT expression. In addition, we observed a stronger radio-sensitization of single treatment and temozolomide used as control due to reduced expression and increased time of disappearance of γH2AX indicative of reduced signal and DNA repair. This was associated with higher caspase-3 activation and reduction of RT-mediated autophagy. In vivo, tinostamustine increased time-to-progression (TTP) and this was additive/synergistic to RT. Tinostamustine had significant therapeutic activity with suppression of tumor growth and prolongation of DFS (disease-free survival) and OS (overall survival) in orthotopic intra-brain models that was superior to bendamustine, RT and temozolomide and showing stronger radio sensitivity. Conclusions: Our data suggest that tinostamustine deserves further investigation in patients with glioblastoma

Investigating Networked Music Performances in Pedagogical Scenarios for the InterMUSIC Project

With the big improvement of digital communication networks, Networked Music Performances (NMP) received a great interest from music live performance and music recording industry. The positive impact of NMP in pedagogical appli- cations, instead, has been only preliminary explored. Within the InterMUSIC project, we aim to investigate NMP from a pedagogical perspective, that has considerable differences with respect to music performances, and to develop tools to improve distance learning experiences. In this paper, we introduce a conceptual framework designed to be the foundation for all the experiments conducted in the project. We also present two preliminary experiments that investigate the sense of presence of geographically-distant musicians in a distance learning scenario. We discuss the comments provided by the musicians as a set of requirements and guidelines for future experiments

Dual PI3 K/mTOR inhibition reduces prostate cancer bone engraftment altering tumor-induced bone remodeling:

Morbidity in advanced prostate cancer patients is largely associated with bone metastatic events. The development of novel therapeutic strategies is imperative in order to effectively treat this incurable stage of the malignancy. In this context, Akt signaling pathway represents a promising therapeutic target able to counteract biochemical recurrence and metastatic progression in prostate cancer. We explored the therapeutic potential of a novel dual PI3 K/mTOR inhibitor, X480, to inhibit tumor growth and bone colonization using different in vivo prostate cancer models including the subcutaneous injection of aggressive and bone metastatic (PC3) and non-bone metastatic (22rv1) cell lines and preclinical models known to generate bone lesions. We observed that X480 both inhibited the primary growth of subcutaneous tumors generated by PC3 and 22rv1 cells and reduced bone spreading of PCb2, a high osteotropic PC3 cell derivative. In metastatic bone, X480 inhibited significantly the growth and osteolytic activit..