The role of observation uncertainty in the calibration of hydrologic rainfall-runoff models

International audienceHydrologic rainfall-runoff models are usually calibrated with reference to a limited number of recorded flood events, for which rainfall and runoff measurements are available. In this framework, model's parameters consistency depends on the number of both events and hydrograph points used for calibration, and on measurements reliability. Recently, to make users aware of application limits, major attention has been devoted to the estimation of uncertainty in hydrologic modelling. Here a simple numerical experiment is proposed, that allows the analysis of uncertainty in hydrologic rainfall-runoff modelling associated to both quantity and quality of available data. A distributed rainfall-runoff model based on geomorphologic concepts has been used. The experiment involves the analysis of an ensemble of model runs, and its overall set up holds if the model is to be applied in different catchments and climates, or even if a different hydrologic model is used. With reference to a set of 100 synthetic rainfall events characterized by a given rainfall volume, the effect of uncertainty in parameters calibration is studied. An artificial truth ? perfect observation ? is created by using the model in a known configuration. An external source of uncertainty is introduced by assuming realistic, i.e. uncertain, discharge observations to calibrate the model. The range of parameters' values able to "reproduce" the observation is studied. Finally, the model uncertainty is evaluated and discussed. The experiment gives useful indications about the number of both events and data points needed for a careful and stable calibration of a specific model, applied in a given climate and catchment. Moreover, an insight on the expected and maximum error in flood peak discharge simulations is given: errors ranging up to 40% are to be expected if parameters are calibrated on insufficient data sets

Regional scale analysis of the altimetric stream network evolution

International audienceFloods result from the limited carrying capacity of stream channels when compared to the discharge peak value. The transit of flood waves - with the associated erosion and sedimentation processes - often modifies local stream geometry. In some cases this results in a reduction of the stream carrying capacity, and consequently in an enhancement of the flooding risk. A mathematical model for the prediction of potential altimetric stream network evolution due to erosion and sedimentation processes is here formalized. It works at the regional scale, identifying the tendency of river segments to sedimentation, stability, or erosion. The model builds on geomorphologic concepts, and derives its parameters from extensive surveys. As a case study, tendencies of rivers pertaining to the Valle d'Aosta region are analyzed. Some validation is provided both at regional and local scales of analysis. Local validation is performed both through a mathematical model able to simulate the temporal evolution of the stream profile, and through comparison of the prediction with ante and post-event river surveys, where available. Overall results are strongly encouraging. Possible use of the information derived from the model in the context of flood and landslide hazard mitigation is briefly discussed

Enzyme kinetics and inhibition of histone acetyltransferase KAT8

Lysine acetyltransferase 8 (KAT8) is a histone acetyltransferase (HAT) responsible for acetylating lysine 16 on histone H4 (H4K16) and plays a role in cell cycle progression as well as acetylation of the tumor suppressor protein p53. Further studies on its biological function and drug discovery initiatives will benefit from the development of small molecule inhibitors for this enzyme. As a first step towards this aim we investigated the enzyme kinetics of this bi-substrate enzyme. The kinetic experiments indicate a ping-pong mechanism in which the enzyme binds Ac-CoA first, followed by binding of the histone substrate. This mechanism is supported by affinity measurements of both substrates using isothermal titration calorimetry (ITC). Using this information, the KAT8 inhibition of a focused compound collection around the non-selective HAT inhibitor anacardic acid has been investigated. Kinetic studies with anacardic acid were performed, based on which a model for the catalytic activity of KAT8 and the inhibitory action of anacardic acid (AA) was proposed. This enabled the calculation of the inhibition constant Ki of anacardic acid derivatives using an adaptation of the Cheng-Prusoff equation. The results described in this study give insight into the catalytic mechanism of KAT8 and present the first well-characterized small-molecule inhibitors for this HAT

Effect of pre-season training phase on anthropometric, hormonal and fitness parameters in young soccer players

The aims of the study were to investigate 1) the effect of 8 weeks of PSP training on anthropometrics, salivary hormones and fitness parameters in youth soccer players, 2) the correlations between fitness and hormonal parameters, and 3) the impact of the experience of the coach and his methodology of training on these parameters. Weight, height, BMI, pubertal development (PDS), salivary Cortisol (sC), salivary Testosterone (sT), salivary sDHEAS, intermittent tests (VO2max), and countermovement jump test (CMJ) modifications of 35 youth soccer players (age: 14±0 yrs; BMI: 20.8±1.8 k/m2 ) from two Italian clubs (“Lupa Frascati” -LF-; “Albalonga” -AL) were analysed. A significant (p<0.05) time by club effect was observed in sC (F(1,31) = 9.7, ES = 1.13), sT (F(1,31) = 4.2, ES = 0.74), CMJ (F(1,28) = 26.5, ES = 1.94), and VO2max (F(1,28) = 8.5, ES = 1.10). Statistical differences (p<0.05) in weight (F(1,32) = 25.5, ES = 0.11), sC (F(1,31) = 32.1, ES = 1.43), sT/sC ratio (F(1,31) = 10.1, ES = 0.97), sDHEAS/sC ratio (F(1,31) = 6.3, ES = 0.70), and VO2max (F(1,28) = 64.3, ES = 1.74) were found within time factor. Between clubs, differences (p<0.05) in sC (F(1,32) = 8.5, ES = 1.17), sT (F(1,31) = 4.2, ES = 0.74), CMJ (F(1,28) = 26.5, ES = 1.50), and VO2max (F(1,28) = 8.5, ES = 1.10) were found. CMJ was inversely correlated with sDHEAS (r = -0.38) before PSP, while Δ of CMJ showed significant correlations with Δ of sC (r = 0.43) and ΔVO2max was inversely correlated with ΔBMI (r = -0.54) and ΔsC (r = -0.37) in all subjects. Considering each single club, ΔVO2max showed correlations with ΔBMI (r = -0.45) in AL, while ΔCMJ showed correlations with ΔPDS (r = 0.72) in LF club. Since the PSP is often limited training time to simultaneously develop physical, technical and tactical qualities, an efficient method to distribute the training load is important in youth soccer players to increase the performance and to avoid injuries

Arbuscular Mycorrhizal Fungi and Plant Growth Promoting Rhizobacteria Avoid Processing Tomato Leaf Damage during Chilling Stress

Chilling stress limits processing tomato growth and yield, leading to high losses. An approach to increase the sustainability of crop production could involve the use of beneficial microorganisms. The objectives of this research were to investigate: (i) the ecacy of Funneliformis mosseae and Paraburkholderia graminis C4D1M in avoiding processing tomato damage during severe chilling stress; (ii) the synergic eect of the two microorganisms inoculated as a consortium; (iii) if the putative microorganism eects depended on the processing tomato genotype. To achieve these objectives, two experiments were carried out. In the first experiment, a modern genotype was assessed, while three genotypes were evaluated in the second experiment. At sowing, F. mosseae was mixed with peat. Nine days after sowing, P. graminis was inoculated close to the plant\u2019s root collar. After 40 days of seed sowing, chilling treatment was performed at 1 C for 24 h. F. mosseae mainly reduced the cell membrane injuries in term of electrolytic leakage and eciency of photosystem II, after the chilling stress in both experiments. Conversely, in the second experiment, the consortium improved the seedling regrowth, increasing the eciency of photosystem II. In addition, modern genotypes inoculated with microorganisms showed a better seedling regrowth.Chilling stress limits processing tomato growth and yield, leading to high losses. An approach to increase the sustainability of crop production could involve the use of beneficial microorganisms. The objectives of this research were to investigate: (i) the efficacy of Funneliformis mosseae and Paraburkholderia graminis C4D1M in avoiding processing tomato damage during severe chilling stress; (ii) the synergic effect of the two microorganisms inoculated as a consortium; (iii) if the putative microorganism effects depended on the processing tomato genotype. To achieve these objectives, two experiments were carried out. In the first experiment, a modern genotype was assessed, while three genotypes were evaluated in the second experiment. At sowing, F. mosseae was mixed with peat. Nine days after sowing, P. graminis was inoculated close to the plant's root collar. After 40 days of seed sowing, chilling treatment was performed at 1 \ub0C for 24 h. F. mosseae mainly reduced the cell membrane injuries in term of electrolytic leakage and efficiency of photosystem II, after the chilling stress in both experiments. Conversely, in the second experiment, the consortium improved the seedling regrowth, increasing the efficiency of photosystem II. In addition, modern genotypes inoculated with microorganisms showed a better seedling regrowth

Double gamers—can modified natural regulators of higher plants act as antagonists against phytopathogens? The case of jasmonic acid derivatives

As key players in biotic stress response of plants, jasmonic acid (JA) and its derivatives cover a specific and prominent role in pathogens-mediated signaling and hence are promising candidates for a sustainable management of phytopathogenic fungi. Recently, JA directed antimicrobial effects on plant pathogens has been suggested, supporting the theory of oxylipins as double gamers in plant-pathogen interaction. Based on these premises, six derivatives (dihydrojasmone and cis-jasmone, two thiosemicarbazonic derivatives and their corresponding complexes with copper) have been evaluated against 13 fungal species affecting various economically important herbaceous and woody crops, such as cereals, grapes and horticultural crops: Phaeoacremonium minimum, Neofusicoccum parvum, Phaeomoniella chlamydospora, Fomitiporia mediterranea, Fusarium poae, F. culmorum, F. graminearum, F. oxysporum f. sp. lactucae, F. sporotrichioides, Aspergillus flavus, Rhizoctonia solani, Sclerotinia spp. and Verticillium dahliae. The biological activity of these compounds was assessed in terms of growth inhibition and, for the two mycotoxigenic species A. flavus and F. sporotrichioides, also in terms of toxin containment. As expected, the inhibitory effect of molecules greatly varied amongst both genera and species; cis-jasmone thiosemicarbazone in particular has shown the wider range of effectiveness. However, our results show that thiosemicarbazones derivatives are more effective than the parent ketones in limiting fungal growth and mycotoxins production, supporting possible applications for the control of pathogenic fungi

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

<p>Abstract</p> <p>Background</p> <p>Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.</p> <p>Methods</p> <p>This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.</p> <p>Discussion</p> <p>The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.</p> <p>Trial Registration</p> <p>Clinical Trials <a href="http://www.clinicaltrials.gov/ct2/show/NCT00970931">NCT00970931</a>.</p

Rational design and validation of a Tip60 histone acetyltransferase inhibitor

Histone acetylation is required for many aspects of gene regulation, genome maintenance and metabolism and dysfunctional acetylation is implicated in numerous diseases, including cancer. Acetylation is regulated by histone acetyltransferases (HATs) and histone deacetylases and currently, few general HAT inhibitors have been described. We identified the HAT Tip60 as an excellent candidate for targeted drug development, as Tip60 is a key mediator of the DNA damage response and transcriptional co-activator. Our modeling of Tip60 indicated that the active binding pocket possesses opposite charges at each end, with the positive charges attributed to two specific side chains. We used structure based drug design to develop a novel Tip60 inhibitor, TH1834, to fit this specific pocket. We demonstrate that TH1834 significantly inhibits Tip60 activity in vitro and treating cells with TH1834 results in apoptosis and increased unrepaired DNA damage (following ionizing radiation treatment) in breast cancer but not control cell lines. Furthermore, TH1834 did not affect the activity of related HAT MOF, as indicated by H4K16Ac, demonstrating specificity. The modeling and validation of the small molecule inhibitor TH1834 represents a first step towards developing additional specific, targeted inhibitors of Tip60 that may lead to further improvements in the treatment of breast cancer