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Computational budget is a severe limitation on the automatic calibration of expensive hydrodynamic and water quality models. To tackle this limitation, the present work formulated a metamodeling-based approach for parameter estimation of such models and assessed the computational gains of this approach compared to a benchmark alternative (a derivative-free optimization method). A response surface proxy of the original model was designed to emulate the behavior of the underlying system, employing Latin hypercube sampling as a strategy for the design of computer experiments and kriging as the technique for the analysis of computer experiments. The response surface proxy of the original model was employed in the automatic fine-tuning of model parameters and, finally, the computational gain over the benchmark alternative was estimated. The metamodeling-based approach was tested in the calibration of the hydrodynamic and water quality models of two water reservoirs. The benchmark alternative analysis indicated that the metamodeling-based approach required 20% to 38% less function evaluations to reach a solution with the same quality compared to the benchmark alternative.

Satellite remote sensing provides valuable data for understanding spatial and temporal variability of water quality parameters. In particular, PRISMA and DESIS are showing increasing capabilities in water quality mapping even if further studies might be needed to fully exploit these relatively new data. In this context, high-resolution airborne hyperspectral sensors might support preliminary tests to evaluate satellite-based systems, while represent enhanced mapping tools. In the context of the H2020 PrimeWater project, this study presents the use of HySpex hyperspectral airborne data of the freshwater reservoir Mulargia (Italy) to: i) calibrate and validate algorithms to retrieve optically active parameters; ii) assess the feasibility of retrieve water quality parameters; iii) export of this knowledge on PRISMA and DESIS data. The Hyspex images were acquired on 24 September 2020 in coincidence with in situ data, both radiometric and water quality. HySpex data were geocoded with PARGE and atmospherically corrected with ATCOR code and the results showed a good consistency between water reflectance with in situ data. The retrieval of the optical properties from imagery was achieved with a spectral inversion of bio-optical modelling (namely BOMBER), parametrized with absorption and backscattering data of the site. The estimates matched well field data (r2> 0.8) and depicted the mesotrophic conditions of the reservoir with higher Total Suspended Matter in shallow coastal waters.

Il Ripostiglio n. 1 di Frattesina è stato trovato nel 1978, dopo dei lavori agricoli Come gli altri tre di Frattesina, consiste in pezzi di lingotti e vecchi oggetti di bronzo rotti, nel complesso di più di 200 pezzi, tra cui, lingotti e palette a cannone incavate; pesa circa quattro chilogrammi. Come I reperti metallici sono cronologicamente omogenei e appartengono a una fase tarda dell'età del Bronzo finale; hanno paralleli con i materiali di altre regioni “protovillanoviane” della Penisola Italiana

Indagini archeometallurgiche sono state condotte sui numerosi reperti in lega di rame di Frattesina. Oltre a chiarire le tecniche di fabbricazione e le leghe usate, esse hanno permesso di ricostruire le sequenze operative impiegate per produrre i manufatti metallici. Inoltre da Frattesina provengono due oggetti in ferro provengono, uno dei quali è una fibula ad arco di violino frammentaria.

The present document offers guidance on data management issues related to all work packages of PrimeWater in the context of the Open Research Data Pilot (it will be referred to as the Pilot from this point onward), which the European Commission is running within its research framework programme Horizon2020. This guidance document details the data that the project will collect, generate and manage, following what methodology and standards, whether and how the data will be exploited or made accessible for verification and re-use (during and after the lifetime of the project), and how it will be curated and preserved with respect to the FAIR principles. This first version of the Data Management Plan (DMP) offers the essential principles that encompass data management and guide all the processes that will be devised to assist all project partners to efficiently manage their data. Yet, it is a living document that will be regularly updated to support the data management processes of PrimeWater for all data collected, processed, or generated by it. The DMP will be regularly updated to offer more elaborate and concise definitions, standards, and guidelines to be followed.

This document describes (a) the concepts that are embodied in the formulation of the Earth Observation Science Virtual Lab (EOSVL) that will be developed into the PrimeWater project and (b) major scientific questions posed by part of the experiments to be included in the EOSVL (only experiments related to Work Package (WP) 2 are discussed herein; the remaining experiments are part of deliverables linked to WP3).

This document presents the first version of the Climate Assessment Report (CAR), which will be updated in 2021, to summarize the added value of Lakes_cci products and the activities of the Climate Research Group (CRG). Overall, the CAR first introduces the products generated by Lakes_cci. A second section on initial data exploration at global scale is also presented along with sample associated methodological steps. The specific activities from the CRG on five pre-defined use cases is then presented for addressing a variety of scientific questions. The CAR concludes confronting the progress made towards meeting user requirements and also includes main outcomes from the Lake_cci user workshop. This is followed by an updated list of publications, a summary of outreach activities and key conclusions.

Easy access and targeted analysis on data such as sediment concentrations and hydrological parameters are essential for hydropower managers. Information on the sediment regime, sediment sources and sinks in the river network and basin are key to estimate major operation costs and investment risks. However, such information is usually rare in the planning phase of hydropower installations. The HYPOS online portal provides such information - to lower project risks with actual data - even data one couldn't get thinking just about traditional measurements. It provides direct online access to satellite-based water quality data worldwide, hydrological modelled data and in-situ data. Here, we will showcase and discuss the capabilities of the online system in the frame of concrete hydropower projects in Switzerland, Georgia, and Albania.

This document summarises the user requirements for the Essential Climate Variable (ECV) 'Lakes' collected within the framework of the European Space Agency's Lakes Climate Change Initiative (http://cci.esa.int/lakes) (Lakes_cci). It presents the synthesised information obtained through review of existing documents, and of publications and projects, plus a user survey of 53 respondents. A perspective to update the understanding of user requirements, more focused on climate community needs, it is also outlined in the last section.

The paper shows a brief summary of the evidence of prehistoric metallurgy in Oman.

Indagini archeometriche su un'ascia protostorica dal ripostiglio di Piediluco patinata artificialmente.

L'uso della pietra da lancio nella preistoria del Vicino Oriente e in Europa.

The paper explains the archaeological discoveries at ʿUqdat al-Bakrah, a relevant prehistoric metal-working atelier found in the Omani desert.

Il testo descrive la localizzazione e lo scavo del sito archeometallurgico dell'età del Ferro di 'Uqdat al-Bakrah (Sultanato di Oman).

Indagini archeometriche tramite XRF su manufatti metallici del sito dell'età del Ferro di 'Uqdat al-Bakrah (Sultanato di Oman)

Sentinel-2 (S2) offers a great potential coral reef mapping as its spatial resolution up to 10 m is comparable to the patchy distribution typically met in coral environments, and data acquired in 13 spectral bands offer improved spectral diversity for assessing the variety of coral colors. With a revisit time of 10 days, that will be five in 2017 when the second satellite will be in orbit, S2 will enable the observation of ecosystems processes such as coral bleaching, coral mortality or shifts to macroalgal domination. Nevertheless, the acquisition plan needs adjustments to include coral reefs globally in remote oceanic reef environments. The aim of the study is to present a freely available operational processing chain for mapping submersed habitats from space to support coral reef monitoring and research. Implemented algorithms encompass image-based methods (e.g. pseudo-invariant-features) and physic-based approaches, such as optimization techniques for bio-optical models inversion. The algorithm performances are shown for selected test areas (e.g. Lizard Island, Australia and Lampi Island, Myanmar) where reference field data have been collected in coincidence with S2. The preliminary results show the capability of S2 in describing colonization patterns of corals, to detect seagrass and to produce realistic bottom depths. The preliminary results show the capability of S2 to describe colonization patterns of corals, sea grass and marine habitats, and produce validated depths. With respect to this last point, an ongoing aim is to assess the capability for deriving bathymetry with S2 data in the context of the International Hydrographic Organisation standards.

This investigation sought to explore the contributory factors that impact the attitudes and beliefs of elderly people toward organ donation. Two studies were conducted to assess elderly people's attitudes toward common myths and misconceptions about donation, as well as attitudes toward ethical practices involved with donation. The effects of a brief informational DVD containing narrative and statistical messages designed to educate and dispel myths about organ donation were examined. Participants included 33 elderly people from two senior residences in the Northeast. Data were compared to extant data already existing on college students in order to gain new insight into the impact of accurate, positive messages on attitudes about donation and the likelihood of becoming an organ donor. Higher donor registration rates were observed in the elderly in this sample (63.16%) compared to college students (17.85%). Relationships were found between age and being currently registered as a donor, willingness...

This cross-cultural study examined the nature and correlates of muscle dysmorphia (MD) in Mexicans who lift weights, compared symptomatology in Mexicans to that in Americans, and investigated the roles of bodybuilding and acculturation in the presentation of MD symptoms. The sample consisted of 46 Mexicans and 67 Americans who lift weights (N = 113). Participants completed measures regarding symptoms of MD, engagement in bodybuilding, acculturation, exercise dependency, eating pathology, and steroid use. Contrary to predictions, results indicated similar occurrences of MD symptoms in both samples. MD symptoms were correlated with bodybuilding, exercise dependence and eating pathology in both Mexican and American men, as well as American women. Engagement in bodybuilding in men was similar in both samples; however, in the American sample, bodybuilding behaviors were more related to MD. Acculturation to American culture was not related to symptoms of MD. Steroid use was greater in both samples than in previous studies. Findings are discussed in terms of cross-cultural and clinical implications.

This study expanded on previous investigations exploring public attitudes toward the human rights issues involved in organ donation practices and personal support for these practices. Participants included college and graduate students, and senior citizens (N = 99). Attitudes were assessed prior to and following the presentation of a brief informational DVD on major organ donation practices. Results indicated that participants were largely divided in their attitudes toward human rights issues, as well as in personal support for donation practices. Registration status was correlated with education, r = .47, p < .001. Support for donation incentive programs varied. Registered donors showed a change in attitudes toward human rights issues, t(22) = 2.18, p = .04. For non-registered donors, personal support for donation practices decreased after viewing the DVD, t(51) = - 3.06, p = .004. Results are discussed in terms of implications for increasing donation.

Acyl-CoA:diacylglycerol acyltransferase (DGAT) catalyzes the terminal step in triglyceride (TG) synthesis using diacylglycerol (DAG) and fatty acyl-CoA as substrates. In the liver, the production of VLDL permits the delivery of hydrophobic TG from the liver to peripheral tissues for energy metabolism. We describe here a novel high-content, high-throughput LC/MS/MS-based cellular assay for determining DGAT activity. We treated endogenous DGAT-expressing cells with stable isotope-labeled [13C18]oleic acid. The [13C18]oleoyl-incorporated TG and DAG lipid species were profiled. The TG synthesis pathway assay was optimized to a one-step extraction, followed by LC/MS/MS quantification. Further, we report a novel LC/MS/MS method for tracing hepatic TG synthesis and VLDL-TG secretion in vivo by administering [13C18]oleic acid to rats. The [13C18]oleic acid-incorporated VLDL-TG was detected after one-step extraction without conventional separation of TG and recovery by derivatizing [13C18]oleic acid for detection. Using potent and selective DGAT1 inhibitors as pharmacological tools, we measured changes in [13C18]oleoyl-incorporated TG and DAG and demonstrated that DGAT1 inhibition significantly reduced [13C18]oleoyl-incorporated VLDL-TG. This DGAT1-selective assay will enable researchers to discern differences between the roles of DGAT1 and DGAT2 in TG synthesis in vitro and in vivo.

Whereas heparin functions as an antithrombotic agent by promoting antithrombin III-based inhibition of thrombin and factor Xa, there is less appreciation for the combination behavior with small-molecule, direct inhibitors of these proteases. We conducted a study in a high-shear arterial environment to explore the potential for a cooperative antithrombotic effect with a thrombin inhibitor (argatroban), a factor Xa inhibitor (YM-60828), and a dual thrombin/factor Xa inhibitor (RWJ-445167). We employed a platelet-dependent vascular injury model in which rats were subjected to an acute electrical injury to the carotid artery. Antithrombotic efficacy was measured for thrombin inhibitor argatroban and factor Xa inhibitor YM-60828 administered alone or in combination. The results indicate that there is a cooperative antithrombotic effect in vivo when both thrombin and factor Xa are inhibited simultaneously. The dual thrombin/factor Xa inhibitor RWJ-445167 was found to have potent antithrombotic activity in this high-shear environment. A comparison of results for RWJ-445167 and argatroban showed additional efficacy with RWJ-445167, suggestive of drug synergy.

This report details the in situ IOP, AOP, biogeochemical data with concurrent airborne hyperspectral images (at the Curonian lagoon) and satellite (Sentinel-2 MSI, Sentinel-3 OLCI, Landsat-8 OLI and SPOT 5)images that were acquired in 2 015 and 2016 during the campaigns organized at Lake Marken in the Netherlands, Lake Balaton and Kis-Balaton in Hungary, Lakes Mantua, Lake Garda, Po River delta and Venice Lagoon in Italy, Loch Leven and Lomond in the UK, Danube Delta and the Black Sea in Romania and the Curonian Lagoon in Lithuania. The data sets acquired in 2015 and 2016 are available for the INFORM project partners for algorithm development and validation within the INFORM project (WP5), for EO-model integration work in (WP6), for demonstration purposes (WP7) and for end-user interaction (WP3)

Certain leukocytes release serine proteases that sustain inflammatory processes and cause disease conditions, such as asthma and chronic obstructive pulmonary disease. We identified beta-ketophosphonate 1 (JNJ-10311795; RWJ-355871) as a novel, potent dual inhibitor of neutrophil cathepsin G (K(i) = 38 nm) and mast cell chymase (K(i) = 2.3 nm). The x-ray crystal structures of 1 complexed with human cathepsin G (1.85 A) and human chymase (1.90 A) reveal the molecular basis of the dual inhibition. Ligand 1 occupies the S(1) and S(2) subsites of cathepsin G and chymase similarly, with the 2-naphthyl in S(1), the 1-naphthyl in S(2), and the phosphonate group in a complex network of hydrogen bonds. Surprisingly, however, the carboxamido-N-(naphthalene-2-carboxyl)piperidine group is found to bind in two distinct conformations. In cathepsin G, this group occupies the hydrophobic S(3)/S(4) subsites, whereas in chymase, it does not; rather, it folds onto the 1-naphthyl group of the inhibitor itself. Compound 1 exhibited noteworthy anti-inflammatory activity in rats for glycogen-induced peritonitis and lipopolysaccharide-induced airway inflammation. In addition to a marked reduction in neutrophil influx, 1 reversed increases in inflammatory mediators interleukin-1alpha, interleukin-1beta, tissue necrosis factor-alpha, and monocyte chemotactic protein-1 in the glycogen model and reversed increases in airway nitric oxide levels in the lipopolysaccharide model. These findings demonstrate that it is possible to inhibit both cathepsin G and chymase with a single molecule and suggest an exciting opportunity in the treatment of asthma and chronic obstructive pulmonary disease.

The antithrombotic, anticoagulant, and kinetic properties of RWJ-50353, a novel, reversible, active-site-directed thrombin inhibitor, were evaluated. RWJ-50353 inhibited the catalytic activity of human alpha-thrombin with a K(i) of 0.19+/-0.02 nM. It showed a 16-fold selectivity relative to inhibition of trypsin and at least 330-fold selectivity relative to inhibition of other biologically important serine proteases. In a gel-filtered platelet preparation, RWJ-50353 inhibited alpha-thrombin-induced aggregation with an IC(50) of 32+/-6 nM. In a canine arteriovenous shunt antithrombotic model, RWJ-50353 demonstrated a significant dose-related (0.1-1.0 mg/kg, i.v.) reduction in thrombus formation with 50% inhibition (ID(50)) obtained at 0.46+/-0.1 mg/kg. In a rabbit deep vein thrombosis model, RWJ-50353 dose-dependently (0.1-1. 0 mg/kg, i.v.) reduced thrombus formation with an ID(50) of 0.25+/-0. 03 mg/kg. The antithrombotic activity in both of these models was associated with only mild prolongations in bleeding time and coagulation parameters. These results demonstrate that RWJ-50353 is a potent, selective thrombin inhibitor that is an effective antithrombotic agent after intravenous administration in models of arterial and venous thrombosis and may be useful in the management of various thrombotic disorders.

CARTELGIS (Diffusione e sperimentazione della Cartografia, del Telerilevamento e dei Sistemi Informativi Geografici), come tecnologie didattiche applicate allo studio del territorio e dell'ambiente, è un progetto proposto dall'Università di Bologna e IREA del CNR di Milano, finanziato dal MIUR e svolto negli anni 2004-2006. Suo obiettivo è diffondere la conoscenza delel discipline che a vario titolo si occupano dell'osservazione della Terra e di sperimentare la loro efficacia come strumenti conoscitivi del territorio e dell'ambiente a supporto delle attività didattiche interdiscipolinari a livello scolastico ed universitario. Vengono descritte le caratteristiche del progetto e si traccia un bilancio dell'esperienza e delle sue possibili prospettive.

Freshwater is a fundamental resource for human life, and the services provided by surface freshwater ecosystems underpin global water and food security and economic productivity. To improve understanding of global freshwater responses to multiple stressors, standardized, accurate data are needed. Timely, spatially explicit information from optical remote sensing can provide important input into managing and mitigating negative effects of human land management and climate change and variability. High spectral resolution ( ...

RWJ-29009, (6S)-trans(-)-1-(6,7-dihydro-6-hydroxy-5,5-dimethyl-2-nitro-5 H-thieno[3,2-b]pyran-7-yl)-2-piperidinone, is a structurally novel and extremely potent potassium channel activator that may be useful for treatment of hypertension and ischemic heart disease. We assessed the cardiovascular profile of RWJ 29009 in anesthetized and conscious dogs. RWJ 29009 (0.1-2 micrograms/kg intravenously, i.v.) dose-relatedly increased coronary blood flow (CBF) and decreased arterial pressure in anesthetized dogs. Total peripheral resistance and coronary vascular resistance were concurrently reduced without significant changes in heart rate (HR) or cardiac output (CO). Left ventricular (LV) dP/dtmax and myocardial contractile force were decreased only at the highest dose of 10 micrograms/kg. Cromakalim (3-100 micrograms/kg), although much less potent, had a qualitatively similar profile. Glyburide pretreatment (5 mg/kg i.v.) shifted the dose response of RWJ 29009 for increasing CBF and decreasing arterial pressure to the right. The dose responses of cromakalim were similarly shifted to the right, whereas the effects of nifedipine on CBF and arterial pressure were not affected by glyburide. RWJ 29009 (0.3 and 1 microgram/kg) had no effect on myocardial O2 consumption (MVO2) except for a transient increase immediately after administration of 1 microgram/kg. MVO2 returned to control 15 min after dosing, although CBF remained significantly increased. In conscious dogs, RWJ 29009 (0.3-10 micrograms/kg, i.v. and orally, p.o.) produced dose-related increases in CBF and decreases in arterial pressure similar to those produced in anesthetized dogs, except that HR was increased concurrently. The i.v. and p.o. potency of RWJ 29009 were comparable, indicating high oral bioavailability. Thus, RWJ 29009 is an extremely potent coronary and peripheral vasodilator with a cardiovascular profile similar to that of other potassium channel activators. Like those of other potassium channel activators, its mechanism of action appears to involve activation of ATP-regulated potassium channels.

The synthesis and antihypertensive activity of novel 7-(subsituted benzamido)-6-hydroxy-5,5- dimethylthieno[3,2-b]pyrans are described. Acetyl substitution on the thiophene significantly increases potency of these benzamides in contrast to the nitro substitution which gives the best results in the 7-(cyclic amido)-6- hydroxythieno[3,2-b]pyran series. Compound 21 is 3-fold more potent than the benzopyran cromakalim(2).

We have identified RWJ-671818 (8) as a novel, low molecular weight, orally active inhibitor of human alpha-thrombin (K(i) = 1.3 nM) that is potentially useful for the acute and chronic treatment of venous and arterial thrombosis. In a rat deep venous thrombosis model used to assess antithrombotic efficacy, oral administration of 8 at 30 and 50 mg/kg reduced thrombus weight by 87 and 94%, respectively. In an anesthetized rat antithrombotic model, where electrical stimulation of the carotid artery created a thrombus, 8 prolonged occlusion time 2- and 3-fold at 0.1 and 1.0 mg/kg, i.v., respectively, and more than doubled activated clotting time and activated partial thromboplastin time at the higher dose. This compound had excellent oral bioavailability of 100% in dogs with an estimated half-life of approximately 3 h. On the basis of its noteworthy preclinical data, 8 was advanced into human clinical trials and successfully progressed through phase 1 studies.

OBJECTIVE Torcetrapib, a prototype cholesteryl ester transfer protein (CETP) inhibitor with potential for decreasing atherosclerotic disease, increased cardiovascular events in clinical trials. The identified hypertensive and aldosterone-elevating actions of torcetrapib may not fully account for this elevated cardiovascular risk. Therefore, we evaluated the effects of torcetrapib on endothelial mediated vasodilation in vivo. METHODS AND RESULTS In vivo endothelial mediated vasodilation was assessed using ultrasound imaging of acetylcholine-induced changes in rabbit central ear artery diameter. Torcetrapib, in addition to producing hypertension and baseline vasoconstriction, markedly inhibited acetylcholine-induced vasodilation. A structurally distinct CETP inhibitor, JNJ-28545595, did not affect endothelial function despite producing similar degrees of CETP inhibition and high-density lipoprotein elevation. Nitroprusside normalized torcetrapib's basal vasoconstriction and elicited dose-dependent vasodilation of norepinephrine preconstricted arteries in torcetrapib-treated animals, indicating torcetrapib did not impair smooth muscle function. CONCLUSIONS Torcetrapib significantly impairs endothelial function in vivo, independent of CETP inhibition and high-density lipoprotein elevation. Given the well-documented association of endothelial dysfunction with cardiovascular disease and risk, this activity of torcetrapib may have contributed to increased cardiovascular risk in clinical trials.

The synthesis and cardiovascular evaluation of a novel series of [4-alkyl(aryl)quinazolin-2-one-1-yl]alkanoic esters and acids ( II ) as renal vasodilators is presented. The compound 3-[6,7-dihydroxy-4-methyl-(1 H )-quinazoline-2-one-1-yl]propanoic acid (7) was found to be a potent and selective renal vasodilator.

2-Cyano-6-fluorophenylacetamide was explored as a novel P2 scaffold in the design of thrombin inhibitors. Optimization around this structural motif culminated in 14, which is a potent thrombin inhibitor (Ki = 1.2 nM) that exhibits robust efficacy in canine anticoagulation and thrombosis models upon oral administration.