Total OH reactivity measurements at the biosphere-atmosphere interface

The biosphere emits copiously volatile organic compounds (VOCs) into the atmosphere, which are removed again depending on the oxidative capacity of the atmosphere and physical processes such as mixing, transport and deposition. Biogenic VOCs react with the primary oxidant of the atmosphere, the hydroxyl radical (OH), and potentially lead to the formation tropospheric ozone and aerosol, which impact regional climate and air quality. The rate of OH decay in the atmosphere, the total OH reactivity is a function of the atmospheric, reactive compound's concentration and reaction velocity with OH. One way to measure the total OH reactivity, the total OH sink, is with the Comparative Reactivity Method - CRM. Basically, the reaction of OH with a reagent (here pyrrole) in clean air and in the presence of atmospheric, reactive molecules is compared. This thesis presents measurements of the total OH reactivity at the biosphere-atmosphere interface to analyze various influences and driving forces. For measurements in natural environment the instrument was automated and a direct, undisturbed sampling method developed. Additionally, an alternative detection system was tested and compared to the originally used detector (Proton Transfer Reaction-Mass Spectrometer, PTR-MS). The GC-PID (Gas Chromatographic Photo-Ionization Detector) was found as a smaller, less expensive, and robust alternative for total OH reactivity measurements. The HUMPPA-COPEC 2010 measurement campaign in the Finish forest was impacted by normal boreal forest emissions as well as prolonged heat and biomass burning emissions. The measurement of total OH reactivity was compared with a comprehensive set of monitored individual species ambient concentration levels. A significant discrepancy between those individually measured OH sinks and the total OH reactivity was observed, which was characterized in detail by the comparison of within and above the forest canopy detected OH reactivity. Direct impact of biogenic emissions on total OH reactivity was examined on Kleiner Feldberg, Germany, 2011. Trans-seasonal measurements of an enclosed Norway spruce branch were conducted via PTR-MS, for individual compound's emission rates, and CRM, for total OH reactivity emission fluxes. Especially during summertime, the individually monitored OH sink terms could not account for the measured total OH reactivity. A controlled oxidation experiment in a low NOx environment was conducted in the EUPHORE reaction chamber (CHEERS, Spain 2011). The concentration levels of the reactant isoprene and its major products were monitored and compared to total OH reactivity measurements as well as to the results of two models. The individually measured compounds could account for the total OH reactivity during this experiment as well as the traditional model-degradation scheme for isoprene (MCM 3.2). Due to previous observations of high OH levels in the isoprene-rich environment of the tropics, a novel isoprene mechanism was recently suggested. In this mechanism (MIME v4) additional OH is generated during isoprene oxidation, which could not be verified in the conditions of the CHEERS experiment.

Sviluppo di un sistema di sovralimentazione assistito elettricamente per un motore diesel 3.0L V6 ad alta potenza specifica

Questa tesi di laurea nasce dall’esperienza maturata presso l’azienda FCA Italy (Fiat Chrysler Automobiles S.p.A., ex VM Motori) nello stabilimento situato a Cento in provincia di Ferrara, in particolare all’interno dell’ufficio di Ricerca Avanzata CRM (Centro Ricerca Motori), divisione del reparto R&D (Research and Development). Tale esperienza viene riassunta (in piccola parte) in questo elaborato di Tesi, che tratta tematiche inerenti allo sviluppo di un sistema di sovralimentazione assistito elettricamente, applicato ad un propulsore Diesel 3.0L V6 destinato ai segmenti “Premium” del mercato. Il sistema utilizzato, che ha come componente principale un compressore attuato da una macchina elettrica, appartiene all’insieme delle tecnologie cosiddette di e-boosting. Questo tipo di tecnologia, fortemente innovativa e ad oggi non ancora presente sul mercato, ha le potenzialità per rappresentare un significativo passo avanti nel processo di riduzione delle emissioni, dei consumi e del miglioramento delle performance dei moderni motori endotermici alternativi, al punto che un numero crescente di costruttori di motori sta oggi studiando soluzioni come quella oggetto di questo elaborato. L’obiettivo è stato quindi quello di definire, applicare e gestire il sistema di e-boost a banco motore e, successivamente, caratterizzarlo dal punto di vista energetico e testarne le effettive potenzialità. Le fasi in cui ho apportato il mio contributo sono state, in particolare, quelle di definizione e integrazione dei nuovi componenti all’interno del layout motore preesistente, di realizzazione e implementazione delle strategie di controllo in un sistema dedicato in grado di gestire efficacemente i componenti, e di sperimentazione al banco prova. I risultati conseguiti al termine dell’attività sono quindi inerenti allo sviluppo e validazione del sistema di controllo, alla valutazione delle performance del propulsore risultante e alla caratterizzazione e analisi critica del sistema di e-boost dal punto di vista energetico.

Understanding the Continual Reassessment Method for Dose Finding Studies: An Overview for Non-Statisticians

The Continual Reassessment Method (CRM) has gained popularity since its proposal by O’Quigley et al. [1]. Many variations have been published and discussed in the statistical literature, but there has been little attention to making the design considerations accessible to non-statisticians. As a result, some clinicians or reviewers of clinical trials tend to be wary of the CRM due to safety concerns. This paper presents the CRM in a non-technical way, describing the original CRM with some of its modified versions. It also describes the specifications that define a CRM design, along with two simulated examples of CRMs for illustration.

Effektives Customer Relationship Management durch Intermediation

Bestehende Modelle im Customer Relationship Management (CRM) weisen diverse Schwachstellen auf. Erstens sind viele Kunden durch die große zu verarbeitende Informationsmenge überfordert, zweitens gelingt es vielen Anbietern nicht, die Konsistenz und Relevanz der gesammelten Kundendaten zu gewährleisten, und drittens bringen Kunden den Anbietern nicht das Vertrauen entgegen, das für eine umfassendere Offenlegung von Kundendaten erforderlich wäre. Durch die Einschaltung eines Intermediärs können diese Schwachstellen gemildert werden. Zusätzlich bietet die Intermediation die Möglichkeit, Transaktionskosten zu senken, die Macht der Kunden zu bündeln und die Beziehungen zu Kunden zu intensivieren. Ermöglicht wird dies durch die engere Verknüpfung der Kommunikations- und der Einkaufsfunktionalitäten des Internets. Als Erfolgsfaktoren gilt es, die kritische Masse und das erforderliche Vertrauen zu erreichen sowie einen wesentlichen Beitrag zur Wertschöpfung zu leisten.

A certified plasmid reference material for the standardisation of BCR-ABL1 mRNA quantification by real-time quantitative PCR.

Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 10(6), 1.08±0.11 × 10(5), 1.03±0.10 × 10(4), 1.02±0.09 × 10(3), 1.04±0.10 × 10(2) and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR-ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f).

Die Bedeutung von Business Rules im Customer Relationship Management

Der Beitrag diskutiert Möglichkeiten zur Automatisierung von Kundenbeziehungsprozessen im Customer Relationship Management mit Hilfe von Business Rules. Anhand einer CRM-Architektur werden Anwendungsmöglichkeiten erörtert und am Beispiel einer Cross-Selling-Kampagne vertieft. Technische Aspekte werden dabei nicht im Detail betrachtet. Der Schwerpunkt liegt vielmehr in der Diskussion von Automatisierungs- und Integrationspotenzialen durch den Einsatz von Business Rules, wie sie in zunehmend individualisierten Kundenbeziehungen in Massenmärkten gegeben sind.

Decomposition Rates and Nitrogen Release of Turf Grass Clippings

Decomposition rates and N release patterns of turfgrass clippings from lawns are not well understood. Litter bags containing clippings were inserted into the thatch layer of a coolseason turf. The experiment was arranged as a 2 × 4 factorial in a randomized complete block design with three replicates. Treatments included four rates of N fertilizer (0, 98, 196, and 392 kg N ha-1 yr-1) and two clipping treatments (returned vs. removed). Litter bags were removed periodically over the growing season and samples were analyzed for biomass, N and C concentrations, and C:N ratio on an ash-free basis. Percentage N loss from the clippings after 16 weeks ranged from 88% to 93% at the 0 and 392 kg N ha-1 rates, respectively, and from 86% to 94% when clippings were removed (CRM) or returned (CRT), respectively. Percentage C loss from the clippings ranged from 94% to 95% at the 0 and 392 kg N ha-1 rates, respectively, and from 92% to 96% with CRM and CRT, respectively. Cumulative N release was similar across N fertilization rates, (ranging from 131 g N kg-1 to 135 g N kg-1 tissue) but was higher for CRT (151 g N kg-1 tissue) than for CRM (128 g N kg-1 tissue). Grass clippings decomposed rapidly and released N quickly when returned to the turf thatch layer. This indicates the potential for reduced N fertilization when clippings are returned. Such rapid decomposition also suggests that the contribution of grass clippings to thatch development is negligible.

On Bayesian seamless phase I-II designs

Early phase clinical trial designs have long been the focus of interest for clinicians and statisticians working in oncology field. There are several standard phse I and phase II designs that have been widely-implemented in medical practice. For phase I design, the most commonly used methods are 3+3 and CRM. A newly-developed Bayesian model-based mTPI design has now been used by an increasing number of hospitals and pharmaceutical companies. The advantages and disadvantages of these three top phase I designs have been discussed in my work here and their performances were compared using simulated data. It was shown that mTPI design exhibited superior performance in most scenarios in comparison with 3+3 and CRM designs. ^ The next major part of my work is proposing an innovative seamless phase I/II design that allows clinicians to conduct phase I and phase II clinical trials simultaneously. Bayesian framework was implemented throughout the whole design. The phase I portion of the design adopts mTPI method, with the addition of futility rule which monitors the efficacy performance of the tested drugs. Dose graduation rules were proposed in this design to allow doses move forward from phase I portion of the study to phase II portion without interrupting the ongoing phase I dose-finding schema. Once a dose graduated to phase II, adaptive randomization was used to randomly allocated patients into different treatment arms, with the intention of more patients being assigned to receive more promising dose(s). Again simulations were performed to compare the performance of this innovative phase I/II design with a recently published phase I/II design, together with the conventional phase I and phase II designs. The simulation results indicated that the seamless phase I/II design outperform the other two competing methods in most scenarios, with superior trial power and the fact that it requires smaller sample size. It also significantly reduces the overall study time. ^ Similar to other early phase clinical trial designs, the proposed seamless phase I/II design requires that the efficacy and safety outcomes being able to be observed in a short time frame. This limitation can be overcome by using validated surrogate marker for the efficacy and safety endpoints.^

Modified 3+3 design for phase I clinical trials

Phase I clinical trial is mainly designed to determine the maximum tolerated dose (MTD) of a new drug. Optimization of phase I trial design is crucial to minimize the number of enrolled patients exposed to unsafe dose levels and to provide reliable information to the later phases of clinical trials. Although it has been criticized about its inefficient MTD estimation, nowadays the traditional 3+3 method remains dominant in practice due to its simplicity and conservative estimation. There are many new designs that have been proven to generate more credible MTD estimation, such as the Continual Reassessment Method (CRM). Despite its accepted better performance, the CRM design is still not widely used in real trials. There are several factors that contribute to the difficulties of CRM adaption in practice. First, CRM is not widely accepted by the regulatory agencies such as FDA in terms of safety. It is considered to be less conservative and tend to expose more patients above the MTD level than the traditional design. Second, CRM is relatively complex and not intuitive for the clinicians to fully understand. Third, the CRM method take much more time and need statistical experts and computer programs throughout the trial. The current situation is that the clinicians still tend to follow the trial process that they are comfortable with. This situation is not likely to change in the near future. Based on this situation, we have the motivation to improve the accuracy of MTD selection while follow the procedure of the traditional design to maintain simplicity. We found that in 3+3 method, the dose transition and the MTD determination are relatively independent. Thus we proposed to separate the two stages. The dose transition rule remained the same as 3+3 method. After getting the toxicity information from the dose transition stage, we combined the isotonic transformation to ensure the monotonic increasing order before selecting the optimal MTD. To compare the operating characteristics of the proposed isotonic method and the other designs, we carried out 10,000 simulation trials under different dose setting scenarios to compare the design characteristics of the isotonic modified method with standard 3+3 method, CRM, biased coin design (BC) and k-in-a-row design (KIAW). The isotonic modified method improved MTD estimation of the standard 3+3 in 39 out of 40 scenarios. The improvement is much greater when the target is 0.3 other than 0.25. The modified design is also competitive when comparing with other selected methods. A CRM method performed better in general but was not as stable as the isotonic method throughout the different dose settings. The results demonstrated that our proposed isotonic modified method is not only easily conducted using the same procedure as 3+3 but also outperforms the conventional 3+3 design. It can also be applied to determine MTD for any given TTL. These features make the isotonic modified method of practical value in phase I clinical trials.^

Inorganic carbon and geochemistry measurements from landfast sea ice in Resolute Passage, Nunavut, Canada, as part of the Arctic-ICE project, May - June 2010

We conducted a six-week investigation of the sea ice inorganic carbon system during the winter-spring transition in the Canadian Arctic Archipelago. Samples for the determination of sea ice geochemistry were collected in conjunction with physical and biological parameters as part of the 2010 Arctic-ICE (Arctic - Ice-Covered Ecosystem in a Rapidly Changing Environment) program, a sea ice-based process study in Resolute Passage, Nunavut. The goal of Arctic-ICE was to determine the physical-biological processes controlling the timing of primary production in Arctic landfast sea ice and to better understand the influence of these processes on the drawdown and release of climatically active gases. The field study was conducted from 1 May to 21 June, 2010.

Magnetic properties of ODP Hole 109-670A

Magnetic fabrics of serpentinized peridotites are related to anisomorphic magnetite formed during serpentinization. In the less serpentinized facies they are, however, mainly mimetic of the high temperature deformation prior to serpentinization. In more serpentinized peridotites, the magnetic fabrics, related to magnetite veins which are more developed in this case, are superimposed on mimetic fabrics. Remanent properties, hysteresis loop parameters, and Curie temperatures were measured. Natural remanent magnetizations (NRM) have crystallization remanent magnetic (CRM) origin. Measured magnetic parameters suggest that pseudo-single domain (PSD) grains of magnetite are present in samples with low degree of serpentinization. The samples with high degree of serpentinization contain mainly multi-domain (MD) magnetite grains.

Component NRM Directions for two sediment cores from the Arctic Ocean

Inclination patterns of natural remanent magnetization (NRM) in Quaternary sediment cores from the Arctic Ocean have been widely used for stratigraphic correlation and the construction of age models, however, shallow and negative NRM inclinations in sediments deposited during the Brunhes Chron in the Arctic Ocean appear to have a partly diagenetic origin. Rock magnetic and mineralogical studies demonstrate the presence of titanomagnetite and titanomaghemite. Thermal demagnetization of the NRM indicates that shallow and negative inclination components are largely "unblocked" below ~300 °C, consistent with a titanomaghemite remanence carrier. Following earlier studies on the Mendeleev-Alpha Ridge, shallow and negative NRM inclination intervals in cores from the Lomonosov Ridge and Yermak Plateau are attributed to partial self-reversed chemical remanent magnetization (CRM) carried by titanomaghemite formed during seafloor oxidation of host (detrital) titanomagnetite grains. Distortion of paleomagnetic records due to seafloor maghemitization appears to be especially important in the perennially ice covered western (Mendeleev-Alpha Ridge) and central Arctic Ocean (Lomonosov Ridge) and, to a lesser extent, near the ice edge (Yermak Plateau). On the Yermak Plateau, magnetic grain size parameters mimic the global benthic oxygen isotope record back to at least marine isotope stage 6, implying that magnetic grain size is sensitive to glacial-interglacial changes in bottom-current velocity and/or detrital provenance.

Arsenic speciation in edible alga samples by microwave-assisted extraction and high performance liquid chromatography coupled to atomic fluorescence spectrometry

Twelve commercially available edible marine algae from France, Japan and Spain and the certified reference material (CRM) NIES No. 9 Sargassum fulvellum were analyzed for total arsenic and arsenic species. Total arsenic concentrations were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) after microwave digestion and ranged from 23 to 126 μg g−1. Arsenic species in alga samples were extracted with deionized water by microwave-assisted extraction and showed extraction efficiencies from 49 to 98%, in terms of total arsenic. The presence of eleven arsenic species was studied by high performance liquid chromatography–ultraviolet photo-oxidation–hydride generation atomic–fluorescence spectrometry (HPLC–(UV)–HG–AFS) developed methods, using both anion and cation exchange chromatography. Glycerol and phosphate sugars were found in all alga samples analyzed, at concentrations between 0.11 and 22 μg g−1, whereas sulfonate and sulfate sugars were only detected in three of them (0.6-7.2 μg g−1). Regarding arsenic toxic species, low concentration levels of dimethylarsinic acid (DMA) (<0.9 μg g−1) and generally high arsenate (As(V)) concentrations (up to 77 μg g−1) were found in most of the algae studied. The results obtained are of interest to highlight the need to perform speciation analysis and to introduce appropriate legislation to limit toxic arsenic species content in these food products.

Development of a 3-Dimensional Mathematical Collision Risk Model Based on Recorded Aircraft Trajectories to Estimate the Safety Level in High Density En-Route Airspaces

Como en todos los medios de transporte, la seguridad en los viajes en avión es de primordial importancia. Con los aumentos de tráfico aéreo previstos en Europa para la próxima década, es evidente que el riesgo de accidentes necesita ser evaluado y monitorizado cuidadosamente de forma continúa. La Tesis presente tiene como objetivo el desarrollo de un modelo de riesgo de colisión exhaustivo como método para evaluar el nivel de seguridad en ruta del espacio aéreo europeo, considerando todos los factores de influencia. La mayor limitación en el desarrollo de metodologías y herramientas de monitorización adecuadas para evaluar el nivel de seguridad en espacios de ruta europeos, donde los controladores aéreos monitorizan el tráfico aéreo mediante la vigilancia radar y proporcionan instrucciones tácticas a las aeronaves, reside en la estimación del riesgo operacional. Hoy en día, la estimación del riesgo operacional está basada normalmente en reportes de incidentes proporcionados por el proveedor de servicios de navegación aérea (ANSP). Esta Tesis propone un nuevo e innovador enfoque para evaluar el nivel de seguridad basado exclusivamente en el procesamiento y análisis trazas radar. La metodología propuesta ha sido diseñada para complementar la información recogida en las bases de datos de accidentes e incidentes, mediante la provisión de información robusta de los factores de tráfico aéreo y métricas de seguridad inferidas del análisis automático en profundidad de todos los eventos de proximidad. La metodología 3-D CRM se ha implementado en un prototipo desarrollado en MATLAB © para analizar automáticamente las trazas radar y planes de vuelo registrados por los Sistemas de Procesamiento de Datos Radar (RDP) e identificar y analizar todos los eventos de proximidad (conflictos, conflictos potenciales y colisiones potenciales) en un periodo de tiempo y volumen del espacio aéreo. Actualmente, el prototipo 3-D CRM está siendo adaptado e integrado en la herramienta de monitorización de prestaciones de Aena (PERSEO) para complementar las bases de accidentes e incidentes ATM y mejorar la monitorización y proporcionar evidencias de los niveles de seguridad. ABSTRACT As with all forms of transport, the safety of air travel is of paramount importance. With the projected increases in European air traffic in the next decade and beyond, it is clear that the risk of accidents needs to be assessed and carefully monitored on a continuing basis. The present thesis is aimed at the development of a comprehensive collision risk model as a method of assessing the European en-route risk, due to all causes and across all dimensions within the airspace. The major constraint in developing appropriate monitoring methodologies and tools to assess the level of safety in en-route airspaces where controllers monitor air traffic by means of radar surveillance and provide aircraft with tactical instructions lies in the estimation of the operational risk. The operational risk estimate normally relies on incident reports provided by the air navigation service providers (ANSPs). This thesis proposes a new and innovative approach to assessing aircraft safety level based exclusively upon the process and analysis of radar tracks. The proposed methodology has been designed to complement the information collected in the accident and incident databases, thereby providing robust information on air traffic factors and safety metrics inferred from the in depth assessment of proximate events. The 3-D CRM methodology is implemented in a prototype tool in MATLAB © in order to automatically analyze recorded aircraft tracks and flight plan data from the Radar Data Processing systems (RDP) and identify and analyze all proximate events (conflicts, potential conflicts and potential collisions) within a time span and a given volume of airspace. Currently, the 3D-CRM prototype is been adapted and integrated in AENA’S Performance Monitoring Tool (PERSEO) to complement the information provided by the ATM accident and incident databases and to enhance monitoring and providing evidence of levels of safety.