A meteo-hydrological prediction system based on a multi-model approach for precipitation forecasting

International audienceThe precipitation forecasted by a numerical weather prediction model, even at high resolution, suffers from errors which can be considerable at the scales of interest for hydrological purposes. In the present study, a fraction of the uncertainty related to meteorological prediction is taken into account by implementing a multi-model forecasting approach, aimed at providing multiple precipitation scenarios driving the same hydrological model. Therefore, the estimation of that uncertainty associated with the quantitative precipitation forecast (QPF), conveyed by the multi-model ensemble, can be exploited by the hydrological model, propagating the error into the hydrological forecast. The proposed meteo-hydrological forecasting system is implemented and tested in a real-time configuration for several episodes of intense precipitation affecting the Reno river basin, a medium-sized basin located in northern Italy (Apennines). These episodes are associated with flood events of different intensity and are representative of different meteorological configurations responsible for severe weather affecting northern Apennines. The simulation results show that the coupled system is promising in the prediction of discharge peaks (both in terms of amount and timing) for warning purposes. The ensemble hydrological forecasts provide a range of possible flood scenarios that proved to be useful for the support of civil protection authorities in their decision

A hydrometeorological model intercomparison as a tool to quantify the forecast uncertainty in a medium size basin

Abstract. In the framework of AMPHORE, an INTERREG III B EU project devoted to the hydrometeorological modeling study of heavy precipitation episodes resulting in flood events and the improvement of the operational hydrometeorological forecasts for the prediction and prevention of flood risks in the Western Mediterranean area, a hydrometeorological model intercomparison has been carried out, in order to estimate the uncertainties associated with the discharge predictions. The analysis is performed for an intense precipitation event selected as a case study within the project, which affected northern Italy and caused a flood event in the upper Reno river basin, a medium size catchment in the Emilia-Romagna Region. Two different hydrological models have been implemented over the basin: HEC-HMS and TOPKAPI which are driven in two ways. Firstly, stream-flow simulations obtained by using precipitation observations as input data are evaluated, in order to be aware of the performance of the two hydrological models. Secondly, the rainfall-runoff models have been forced with rainfall forecast fields provided by mesoscale atmospheric model simulations in order to evaluate the reliability of the discharge forecasts resulting by the one-way coupling. The quantitative precipitation forecasts (QPFs) are provided by the numerical mesoscale models COSMO and MM5. Furthermore, different configurations of COSMO and MM5 have been adopted, trying to improve the description of the phenomena determining the precipitation amounts. In particular, the impacts of using different initial and boundary conditions, different mesoscale models and of increasing the horizontal model resolutions are investigated. The accuracy of QPFs is assessed in a threefold procedure. First, these are checked against the observed spatial rainfall accumulations over northern Italy. Second, the spatial and temporal simulated distributions are also examined over the catchment of interest. And finally, the discharge simulations resulting from the one-way coupling with HEC-HMS and TOPKAPI are evaluated against the rain-gauge driven simulated flows, thus employing the hydrological models as a validation tool. The different scenarios of the simulated river flows – provided by an independent implementation of the two hydrological models each one forced with both COSMO and MM5 – enable a quantification of the uncertainties of the precipitation outputs, and therefore, of the discharge simulations. Results permit to highlight some hydrological and meteorological modeling factors which could help to enhance the hydrometeorological modeling of such hazardous events. Main conclusions are: (1) deficiencies in precipitation forecasts have a major impact on flood forecasts; (2) large-scale shift errors in precipitation patterns are not improved by only enhancing the mesoscale model resolution; and (3) weak differences in flood forecasting performance are found by using either a distributed continuous or a semi-distributed event-based hydrological model for this catchment

Design and pharmacological evaluation of Ibuprofen amides derivatives as dual FAAH/COX inhibitors

Fatty acid amide hydrolase (FAAH) is a serine hydrolase enzyme responsible of the hydrolytic degradation of N-acylethanolamine endocannabinoids, such as the Arachidonoylethanolamide (anandamide, AEA), which it has been shown to alleviate pain and inflammation (1). In particular, the anti-nociceptive and anti-inflammatory effects of AEA could be enhanced by the simultaneous block of FAAH and COX enzymes (2). For this reason, several studies have been carried out in order to develop new FAAH/COX inhibitors (2). In 1997 it was reported that the NSAID ibuprofen inhibited FAAH, although with a modest potency (3), and successively the first dual inibhitor, the amide derivative of ibuprofen with a 2-amino-3-methylpyridine side chain (Ibu-AM5) was reported (4). -5). Benzylamides and piperazinoamides analogs of Ibuprofen have been also designed as less potent FAAH inhibitors than Ibu-AM5 (5). Here, I discuss the computational studies and the structure–activity relationships leading to the design, of novel Ibuprofen amide derivatives with a higher inhibition potency of FAAH and COX, which represent novel powerful anti-nociceptive agents

Winding mandrel design for the wide cable SSC dipole

The 50 mm coil i.d. SSC dipole magnets use wider cables to give a greater operational margin between quench field and operating field. The cable used for the inner coil has 30 strands of the same size (0.808 mm) instead of 23 and the outer has 36 strands of the same size (0.648 mm) instead of 30 and the cable widths are increased in proportion. Although the coil inner diameter has been increased from 40 mm, the coil ends are noticeably harder to wind. This report describes the computational and experimental effort to design winding mandrels or center posts for the constant-perimeter ends. 1 ref., 2 figs., 2 tabs

Evaluation of downscaled DEMETER multi‐model ensemble seasonal hindcasts in a northern Italy location by means of a model of wheat growth and soil water balance

In this paper we explore the new possibilities for early crop yield assessment at the local scale arising from the availability of dynamic crop growth models and of downscaled multi-model ensemble seasonal forecasts.We compare the use of the latter with other methods, based on crop growth models driven by observed climatic data only. The soil water balance model developed and used at ARPA Emilia-Romagna (CRITERIA) was integrated with crop growth routines from the model WOFOST 7.1. Some validation runs were first carried out and we verified with independent field data that the new integrated model satisfactorily simulated above-ground biomass and leaf area index. The model was then used to test the feasibility of using downscaled multi-model ensemble seasonal hindcasts, coming from the DEMETER European research project, in order to obtain early (i.e. 90, 60 and 30 d before harvest) yield assessments for winter wheat in northern Italy. For comparison, similar runs with climatology instead of hindcasts were also carried out. For the same purpose, we also produced six simple linear regression models of final crop yields on within season (end of March, April and May) storage organs and above-ground biomass values. Median yields obtained using downscaled DEMETER hindcasts always outperformed the simple regression models and were substantially equivalent to the climatology runs, with the exception of the June experiment, where the downscaled seasonal hindcasts were clearly better than all other methods in reproducing the winter wheat yields simulated with observed weather data. The crop growth model output dispersion was almost always significantly lower than the dispersion of the downscaled ensemble seasonal hindcast used as input for crop simulations

Design, synthesis and in vitro and in vivo biological evaluation of flurbiprofen amides as new fatty acid amide hydrolase/cyclooxygenase-2 dual inhibitory potential analgesic agents

Compounds combining dual inhibitory action against FAAH and cyclooxygenase (COX) may be potentially useful analgesics. Here, we describe a novel flurbiprofen analogue, N-(3-bromopyridin-2-yl)-2-(2-fluoro-(1,1'-biphenyl)-4-yl)propanamide (Flu-AM4). The compound is a competitive, reversible inhibitor of FAAH with a Ki value of 13 nM and which inhibits COX activity in a substrate-selective manner. Molecular modelling suggested that Flu-AM4 optimally fits a hydrophobic pocket in the ACB region of FAAH, and binds to COX-2 similarly to flurbiprofen. In vivo studies indicated that at a dose of 10 mg/kg, Flu-AM4 was active in models of prolonged (formalin) and neuropathic (chronic constriction injury) pain and reduced the spinal expression of iNOS, COX-2, and NFκB in the neuropathic model. Thus, the present study identifies Flu-AM4 as a dual-action FAAH/substrate-selective COX inhibitor with anti-inflammatory and analgesic activity in animal pain models. These findings underscore the potential usefulness of such dual-action compounds

Complete response to capecitabine in a frail, elderly patient with metastatic colorectal cancer: A case report

The clinical management of frail, elderly patients affected by colorectal cancer (CRC) remains a subject of debate. The present study reports the case of an elderly man with metastatic CRC (mCRC) who was successfully treated with capecitabine. The patient survived for 29 months, thus highlighting its potential activity in terms of obtaining a complete response and high efficacy. A 77-year-old man presented with adenocarcinoma of the rectum with multiple and synchronous liver metastases, in addition to several comorbidities. The patient received single‑agent capecitabine chemotherapy (825 mg/mq twice a day) on days 1-14 of a 21-day cycle. Following 12 cycles of well-tolerated therapy, a computed tomography scan revealed a complete response with no evidence of liver metastases. An overall survival of 29 months was documented, and the patient eventually succumbed to a diabetes-related complication. In compromised patients with mCRC, reduced-dose capecitabine is an excellent therapeutic option due to its positive safety profile, activity and efficacy

Exploring the DNA2-PNA heterotriplex formation in targeting the Bcl-2 gene promoter: A structural insight by physico-chemical and microsecond-scale MD investigation

Peptide Nucleic Acids (PNAs) represent a promising tool for gene modulation in anticancer treatment. The uncharged peptidyl backbone and the resistance to chemical and enzymatic degradation make PNAs highly advantageous to form stable hybrid complexes with complementary DNA and RNA strands, providing higher stability than the corresponding natural analogues. Our and other groups’ research has successfully shown that tailored PNA sequences can effectively downregulate the expression of human oncogenes using antigene, antisense, or anti-miRNA approaches. Specifically, we identified a seven bases-long PNA sequence, complementary to the longer loop of the main G-quadruplex structure formed by the bcl2midG4 promoter sequence, capable of downregulating the expression of the antiapoptotic Bcl-2 protein and enhancing the anticancer activity of an oncolytic adenovirus. Here, we extended the length of the PNA probe with the aim of including the double-stranded Bcl-2 promoter among the targets of the PNA probe. Our investigation primarily focused on the structural aspects of the resulting DNA2-PNA heterotriplex that were determined by employing conventional and accelerated microsecond-scale molecular dynamics simulations and chemical-physical analysis. Additionally, we conducted preliminary biological experiments using cytotoxicity assays on human A549 and MDA-MB-436 adenocarcinoma cell lines, employing the oncolytic adenovirus delivery strategy