982 resultados para Second Step


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It seems as if magazine publishers have only haphazardly listed multiple goals for their websites, and have not carefully reflectedon how to achieve them. We present a framework for defining a magazine's onlinestrategy based on previous studies and on secondary data from the industry. We identify three steps in the strategy process. The first is to determine whether the magazine would actually benefit from online presence: although most magazines will never make money from their websites, a web presence may still be justified. The second step is to choose an optimal online strategy that matches the magazine's competitive strategy. Finally, we argue that magazine publishers should carefully consider to what extent they should allow their readers to be involvedin the web pages. This interactivity could be seen as a key factor in exploiting the unique nature of the Internet. It is our understanding that virtual communities could, at best, be a way of creating more value for a magazine's readers, advertisers and editors, alike. We formulate a typology of five different onlinebusiness concepts for magazines based on these three strategic steps.

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Thanks to the continuous progress made in recent years, medical imaging has become an important tool in the diagnosis of various pathologies. In particular, magnetic resonance imaging (MRI) permits to obtain images with a remarkably high resolution without the use of ionizing radiation and is consequently widely applied for a broad range of conditions in all parts of the body. Contrast agents are used in MRI to improve tissue discrimination. Different categories of contrast agents are clinically available, the most widely used being gadolinium chelates. One can distinguish between extracellular gadolinium chelates such as Gd-DTPA, and hepatobiliary gadolinium chelates such as Gd-BOPTA. The latter are able to enter hepatocytes from where they are partially excreted into the bile to an extent dependent on the contrast agent and animal species. Due to this property, hepatobiliary contrast agents are particularly interesting for the MRI of the liver. Actually, a change in signal intensity can result from a change in transport functions signaling the presence of impaired hepatocytes, e.g. in the case of focal (like cancer) or diffuse (like cirrhosis) liver diseases. Although the excretion mechanism into the bile is well known, the uptake mechanisms of hepatobiliary contrast agents into hepatocytes are still not completely understood and several hypotheses have been proposed. As a good knowledge of these transport mechanisms is required to allow an efficient diagnosis by MRI of the functional state of the liver, more fundamental research is needed and an efficient MRI compatible in vitro model would be an asset. So far, most data concerning these transport mechanisms have been obtained by MRI with in vivo models or by a method of detection other than MRI with cellular or sub-cellular models. Actually, no in vitro model is currently available for the study and quantification of contrast agents by MRI notably because high cellular densities are needed to allow detection, and no metallic devices can be used inside the magnet room, which is incompatible with most tissue or cell cultures that require controlled temperature and oxygenation. The aim of this thesis is thus to develop an MRI compatible in vitro cellular model to study the transport of hepatobiliary contrast agents, in particular Gd-BOPTA, into hepatocytes directly by MRI. A better understanding of this transport and especially of its modification in case of hepatic disorder could permit in a second step to extrapolate this knowledge to humans and to use the kinetics of hepatobiliary contrast agents as a tool for the diagnosis of hepatic diseases.

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El treball que teniu a les mans és una recerca sociolingüística que té com a objectiu l’anàlisi dels coneixements i els usos lingüístics de la Universitat de Lleida, a partir de la comparació dels resultats obtinguts a “Coneixements i usos lingüístics de l’estudiantat de la Universitat de Lleida” (Curs 1993/1994), un estudi impulsat des dels Servei de Llengua i Terminologia l’any 1993. L’elaboració del treball es divideix en tres etapes: l’etapa d’investigació, l’etapa d’organització i l’etapa d’interpretació. La primera etapa ha estat destinada a la recollida de dades. He demanat a un total de 1046 alumnes provinents de vint-i-un graus o especialitat diferents que contestessin un qüestionari. La segona etapa consisteix en l’organització de les dades. El primer que he fet ha estat entrar els resultats de cadascuna de les enquestes al programa ACCES, el qual m’ha permès fer les posteriors agrupacions partint sempre del model de 1993. Una vegada he tingut totes les agrupacions fetes, he fet tots els percentatges, gràfiques i taules al programa Excel. Finalment, quan ja he tingut tots els gràfics i taules confeccionats he passat ja a l’última etapa del treball: la interpretació de les dades. Primer he fet una lectura de cadascun dels gràfics i taules, comparant-los posteriorment amb els resultats obtinguts el 1993. Una vegada he tingut tots els comentaris fets he passat ja al més important: la redacció de les conclusions, on intento explicar els canvis més importants que he copsat.

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Postmortem MRI (PMMR) examinations are seldom performed in legal medicine due to long examination times, unfamiliarity with the technique, and high costs. Furthermore, it is difficult to obtain access to an MRI device used for patients in clinical settings to image an entire human body. An alternative is available: ex situ organ examination. To our knowledge, there is no standardized protocol that includes ex situ organ preparation and scanning parameters for postmortem MRI. Thus, our objective was to develop a standard procedure for ex situ heart PMMR examinations. We also tested the oily contrast agent Angiofil® commonly used for PMCT angiography, for its applicability in MRI. We worked with a 3 Tesla MRI device and 32-channel head coils. Twelve porcine hearts were used to test different materials to find the best way to prepare and place organs in the device and to test scanning parameters. For coronary MR angiography, we tested different mixtures of Angiofil® and different injection materials. In a second step, 17 human hearts were examined to test the procedure and its applicability to human organs. We established two standardized protocols: one for preparation of the heart and another for scanning parameters based on experience in clinical practice. The established protocols enabled a standardized technical procedure with comparable radiological images, allowing for easy radiological reading. The performance of coronary MR angiography enabled detailed coronary assessment and revealed the utility of Angiofil® as a contrast agent for PMMR. Our simple, reproducible method for performing heart examinations ex situ yields high quality images and visualization of the coronary arteries.

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La stimulation cérébrale profonde (SCP) nécessite l'implantation chirurgicale d'un système comprenant électrodes cérébrales et boîtier(s) de stimulation. Les noyaux cérébraux visés par la méthodologie stéréotaxique d'implantation doivent être visualisés au mieux par une imagerie à haute résolution. La procédure chirurgicale d'implantation des électrodes se fait si possible en anesthésie locale pour faire des mesures électro-physiologiques et tester en peropératoire l'effet de la stimulation, afin d'optimiser la position de l'électrode définitive. Dans un deuxième temps, le ou les générateur(s) d'impulsions sont implantés en anesthésie générale. La SCP pour les mouvements anormaux a une très bonne efficacité et un risque de complications graves faible quoique non nul. Les complications liées au matériel sont les plus fréquentes. Deep brain stimulation (DBS) requires the surgical implantation of a system including brain electrodes and impulsion generator(s). The nuclei targeted by the stereotaxic implantation methodology have to be visualized at best by high resolution imaging. The surgical procedure for implanting the electrodes is performed if possible under local anaesthesia to make electro-physiological measurements and to test intra-operatively the effect of the stimulation, in order to optimize the position of the definitive electrode. In a second step, the impulsion generator(s) are implanted under general anaesthesia. DBS for movement disorders has a very good efficacy and a low albeit non-zero risk of serious complications. Complications related to the material are the most common.

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Using a database of 2,263 responses to R&D public calls in Catalonia, during the period 2007–2010, this paper proceeds to analyse the potential interaction of the territorial and policy dimensions with the propensity to apply for, and be awarded, a public R&D subsidy. Controlling for characteristics at the firm and project level, we estimate models using a twostep procedure. In the first step, our results suggest that large firms which export and which belong to high-tech manufactures are more likely to participate in a public R&D call. Furthermore, both urban location and past experience of such calls have a positive effect. Our territorial proxy of information spillovers shows a positive sign, but this is only significant at intra-industry level. Membership of one of the sectors prioritized by the Catalan government, perhaps surprisingly, does not have a significant impact. In the second step, our results show that cooperative projects, SMEs or old firms shows a positive effect on the probability of obtaining a public subsidy. Finally, the cluster policy does not show a clear relationship with the public R&D call, suggesting that cluster policies and R&D subsidies follow different goals. Our results are in line with previous results in the literature, but they highlight the unequal territorial distribution of the firms which apply and the fact that policymakers should interlink the decision criteria for their public call with other policies.

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This contribution (presented in the first International Conference on Public Policy (ICPP) in Grenoble in June 2013) explores the phenomena of innovation in action ("innovative implementation"). To do so, we operationalize "innovative implementation" as a strategy by which (coalitions of) non-state actors seek to develop ad hoc solutions to address a given environmental issue, going beyond what is provided for in formal policy designs. Following an inductive research strategy, we elaborate a conceptual framework whose main advantage is to bring the actors and their coalition (in all their diversity) back in the analysis. More concretely, we state that perceiving implementation as broader 'social interaction processes' (De Boer & Bressers 2011) within which actors play strategic 'games' (Bardach 1977, Scharpf 1997) opens interesting lines of research to better account for their innovative and strategic behaviours. In a second step, we apply this framework to three strategies of innovative implementation in different contexts, and identify on this basis empirical regularities in the individual pathways related to the emergence and success (or failure) of these strategies.

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Tärkeä tehtävä ympäristön tarkkailussa on arvioida ympäristön nykyinen tila ja ihmisen siihen aiheuttamat muutokset sekä analysoida ja etsiä näiden yhtenäiset suhteet. Ympäristön muuttumista voidaan hallita keräämällä ja analysoimalla tietoa. Tässä diplomityössä on tutkittu vesikasvillisuudessa hai vainuja muutoksia käyttäen etäältä hankittua mittausdataa ja kuvan analysointimenetelmiä. Ympäristön tarkkailuun on käytetty Suomen suurimmasta järvestä Saimaasta vuosina 1996 ja 1999 otettuja ilmakuvia. Ensimmäinen kuva-analyysin vaihe on geometrinen korjaus, jonka tarkoituksena on kohdistaa ja suhteuttaa otetut kuvat samaan koordinaattijärjestelmään. Toinen vaihe on kohdistaa vastaavat paikalliset alueet ja tunnistaa kasvillisuuden muuttuminen. Kasvillisuuden tunnistamiseen on käytetty erilaisia lähestymistapoja sisältäen valvottuja ja valvomattomia tunnistustapoja. Tutkimuksessa käytettiin aitoa, kohinoista mittausdataa, minkä perusteella tehdyt kokeet antoivat hyviä tuloksia tutkimuksen onnistumisesta.

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Tutkielman tavoitteena oli pyrkiä selvittämään Ilmatieteen laitoksen toiminnalliset ja taloudelliset riskit. Tämä toteutettiin Ilmatieteen laitoksen ulkoisten ja sisäisten sidosryhmien haastatteluiden perusteella. Riskeistä rakennettiin Ilmatieteen laitokselle riskianalyysimalli, jonka kautta riskejä voidaan laitoksessa systemaattisesti tarkastella. Riskianalyysin on myös tarkoitus toimia apuvälineenä laitoksen sisäistä valvontaa ja riskienhallintaa kehitettäessä. Riskianalyysissä riskejä arvioitiin riskiin sisältyvän kahden komponentin, todennäköisyyden ja seurausten, avulla. Näin saatiin riskit karkeasti vertailukelpoiseksi keskenään. Riskeistä muodostettiin ensin toimintokohtainen riskianalyysi, jonka jälkeen riskejä analysoitiin myös koko laitoksen tasolla. Riskejä ilmeni hyvin erilaisia: osaamiseen ja henkilöstöön liittyviä ja toisaalta pitkän tähtäimen strategisiin valintoihin liittyviä. Ilmatieteen laitoksen täytyy hallita toimintaansa ja toimintaympäristöönsä liittyvät muutokset ja olla uudistumiskykyinen. Täytyy myös huomata, että riskianalyysin lisäksi sisäisen valvonnan kehittämisessä on organisaation johdolla ja sisäisellä tarkastajalla tärkeä rooli.

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Diplomityön tarkoituksena oli tutkia ja kehittää käyttökohde kaivosteollisuudessa syntyvälle märälle kipsisivuvirralle, joka sisältää metalliepäpuhtauksina alumiinia, rautaa ja mangaania ja jonka määrä on noin 1 000 000 t/a. Kirjallisuuden pohjalta tutkittiin aluksi mahdollisuutta hyödyntää kipsiaines asfaltti- ja sementtiteollisuuden raaka-aineena. Sementin joukkoon lisätään tavallisesti noin 5 p-% kipsiä, mutta harvinaisimpiin sementtilaatuihin sitä voidaan lisätä jopa 30 p-%. Tästä huolimatta vain pieni osa tutkimuksen kohteessa syntyvästä kipsisivuvirrasta voitaisiin hyödyntää tässä sovelluksessa. Lisäksi kipsisivuvirran sisältämät epäpuhtaudet täytyisi poistaa tai saattaa inaktiiviseen muotoon. Myöskään sen kosteuspitoisuus ei saisi olla suuri. Näin ollen tämän kipsisivuvirran hyödyntäminen asfaltti- ja sementtiteollisuuden lisäaineena ei ole mahdollista Seuraavaksi harkittiin kipsin kierrättämistä, jolloin yhtenä vaihtoehtona oli hajottaa kipsi termisesti rikkioksideiksi ja valmistaa niistä rikkihappoa. Taloudellisista syistä hajoamistuotteen on oltava rikkitrioksidia, josta voitaisiin veteen imeyttämällä valmistaa rikkihappoa. Kipsin hajottaminen termovaa´alla osoitti, että kipsi vaatii noin 1400 ºC:n lämpötilan ja haihtuvat komponentit ovat H2O, SO ja SO2, muttei SO3. Alempien oksidien muuttaminen rikkihapoksi vaatisi katalyyttisen hapetuksen, mikä olisi käytännössä liian kallista. Toisena vaihtoehtona kipsin kierrättämiseksi tutkittiin sen biologista pelkistämistä rikkivedyksi ja kalsiumhydroksidilietteeksi. Laboratoriossa Ca(OH)2-lietteestä valmistettiin hiilidioksidin avulla kalsiumkarbonaattia, jolloin päästiin 90 %:n kalsiumhydroksidin konversiossa. Lisäksi alumiinihydroksidi saatiin erotettua kipsilietteestä kokeellisesti hydrosyklonin avulla. Diplomityössä päädyttiin siihen, että sulfaatin biologinen pelkistäminen ja alumiinihydroksidin mekaaninen erotus jatkuvatoimisesti on varteenotettava vaihtoehto kipsisivuvirran hyödyntämiseksi.

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The detection of testosterone abuse in sports is routinely achieved through the 'steroidal module' of the Athlete Biological Passport by GC-MS(/MS) quantification of selected endogenous anabolic androgenic steroids (EAAS) from athletes' urines. To overcome some limitations of the "urinary steroid profile" such as the presence of confounding factors (ethnicity, enzyme polymorphism, bacterial contamination, and ethanol), ultrahigh performance liquid chromatography (UHPLC) measurements of blood concentrations of testosterone, its major metabolites, and precursors could represent an interesting and complementary strategy. In this work, two UHPLC-MS/MS methods were developed for the quantification of testosterone and related compounds in human serum, including major progestogens, corticoids, and estrogens. The validated methods were then used for the analyses of serum samples collected from 19 healthy male volunteers after oral and transdermal testosterone administration. Results from unsupervised multiway analysis allowed variations of target analytes to be assessed simultaneously over a 96-h time period. Except for alteration of concentration values due to the circadian rhythm, which concerns mainly corticosteroids, DHEA, and progesterone, significant variations linked to the oral and transdermal testosterone administration were observed for testosterone, DHT, and androstenedione. As a second step of analysis, the longitudinal monitoring of these biomarkers using intra-individual thresholds showed, in comparison to urine, significant improvements in the detection of testosterone administration, especially for volunteers with del/del genotype for phase II UGT2B17 enzyme, not sensitive to the main urinary marker, T/E ratio. A substantial extension of the detection window after transdermal testosterone administration was also observed in serum matrix. The longitudinal follow-up proposed in this study represents a first example of 'blood steroid profile' in doping control analysis, which can be proposed in the future as a complement to the 'urinary module' for improving steroid abuse detection capabilities.

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Our research aims to analyze the causal relationships in the behavior of public debt issued by peripheral member countries of the European Economic and Monetary Union -EMU-, with special emphasis on the recent episodes of crisis triggered in the eurozone sovereign debt markets since 2009. With this goal in mind, we make use of a database of daily frequency of yields on 10-year government bonds issued by five EMU countries -Greece, Ireland, Italy, Portugal and Spain-, covering the entire history of the EMU from its inception on 1 January 1999 until 31 December 2010. In the first step, we explore the pair-wise causal relationship between yields, both for the whole sample and for changing subsamples of the data, in order to capture the possible time-varying causal relationship. This approach allows us to detect episodes of contagion between yields on bonds issued by different countries. In the second step, we study the determinants of these contagion episodes, analyzing the role played by different factors, paying special attention to instruments that capture the total national debt -domestic and foreign- in each country.

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Molecular docking is a computational approach for predicting the most probable position of ligands in the binding sites of macromolecules and constitutes the cornerstone of structure-based computer-aided drug design. Here, we present a new algorithm called Attracting Cavities that allows molecular docking to be performed by simple energy minimizations only. The approach consists in transiently replacing the rough potential energy hypersurface of the protein by a smooth attracting potential driving the ligands into protein cavities. The actual protein energy landscape is reintroduced in a second step to refine the ligand position. The scoring function of Attracting Cavities is based on the CHARMM force field and the FACTS solvation model. The approach was tested on the 85 experimental ligand-protein structures included in the Astex diverse set and achieved a success rate of 80% in reproducing the experimental binding mode starting from a completely randomized ligand conformer. The algorithm thus compares favorably with current state-of-the-art docking programs. © 2015 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

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Reversed phase liquid chromatography (RPLC) coupled to mass spectrometry (MS) is the gold standard technique in bioanalysis. However, hydrophilic interaction chromatography (HILIC) could represent a viable alternative to RPLC for the analysis of polar and/or ionizable compounds, as it often provides higher MS sensitivity and alternative selectivity. Nevertheless, this technique can be also prone to matrix effects (ME). ME are one of the major issues in quantitative LC-MS bioanalysis. To ensure acceptable method performance (i.e., trueness and precision), a careful evaluation and minimization of ME is required. In the present study, the incidence of ME in HILIC-MS/MS and RPLC-MS/MS was compared for plasma and urine samples using two representative sets of 38 pharmaceutical compounds and 40 doping agents, respectively. The optimal generic chromatographic conditions in terms of selectivity with respect to interfering compounds were established in both chromatographic modes by testing three different stationary phases in each mode with different mobile phase pH. A second step involved the assessment of ME in RPLC and HILIC under the best generic conditions, using the post-extraction addition method. Biological samples were prepared using two different sample pre-treatments, i.e., a non-selective sample clean-up procedure (protein precipitation and simple dilution for plasma and urine samples, respectively) and a selective sample preparation, i.e., solid phase extraction for both matrices. The non-selective pretreatments led to significantly less ME in RPLC vs. HILIC conditions regardless of the matrix. On the contrary, HILIC appeared as a valuable alternative to RPLC for plasma and urine samples treated by a selective sample preparation. Indeed, in the case of selective sample preparation, the compounds influenced by ME were different in HILIC and RPLC, and lower and similar ME occurrence was generally observed in RPLC vs. HILIC for urine and plasma samples, respectively. The complementary of both chromatographic modes was also demonstrated, as ME was observed only scarcely for urine and plasma samples when selecting the most appropriate chromatographic mode.

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Using a database of 2,263 responses to R&D public calls in Catalonia, during the period 2007–2010, this paper proceeds to analyse the potential interaction of the territorial and policy dimensions with the propensity to apply for, and be awarded, a public R&D subsidy. Controlling for characteristics at the firm and project level, we estimate models using a two-step procedure. In the first step, our results suggest that large firms which export and which belong to high-tech manufactures are more likely to participate in a public R&D call. Furthermore, both urban location and past experience of such calls have a positive effect. Our territorial proxy of information spillovers shows a positive sign, but this is only significant at intra-industry level. Membership of one of the sectors prioritized by the Catalan government, perhaps surprisingly, does not have a significant impact. In the second step, our results show that cooperative projects, SMEs or old firms shows a positive effect on the probability of obtaining a public subsidy. Finally, the cluster policy does not show a clear relationship with the public R&D call, suggesting that cluster policies and R&D subsidies follow different goals. Our results are in line with previous results in the literature, but they highlight the unequal territorial distribution of the firms which apply and the fact that policymakers should interlink the decision criteria for their public call with other policies. Keywords: Evaluation, R&D policies, territorial approach, clusters JEL Classifications: L53, L25, O38