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NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.
Characterization and evaluation of lignocellulosic biomass 130 hydrolysates for ABE fermentation
(2016)
Combined with the use of renewable energy sources for its production, Hydrogen represents a possible alternative gas turbine fuel within future low emission power generation. Due to the large difference in the physical properties of Hydrogen compared to other fuels such as natural gas, well established gas turbine combustion systems cannot be directly applied for Dry Low NOx (DLN) Hydrogen combustion. Thus, the development of DLN combustion technologies is an essential and challenging task for the future of Hydrogen fuelled gas turbines. The DLN Micromix combustion principle for hydrogen fuel has been developed to significantly reduce NOx-emissions. This combustion principle is based on cross-flow mixing of air and gaseous hydrogen which reacts in multiple miniaturized diffusion-type flames. The major advantages of this combustion principle are the inherent safety against flash-back and the low NOx-emissions due to a very short residence time of reactants in the flame region of the micro-flames. The Micromix Combustion technology has been already proven experimentally and numerically for pure Hydrogen fuel operation at different energy density levels. The aim of the present study is to analyze the influence of different geometry parameter variations on the flame structure and the NOx emission and to identify the most relevant design parameters, aiming to provide a physical understanding of the Micromix flame sensitivity to the burner design and identify further optimization potential of this innovative combustion technology while increasing its energy density and making it mature enough for real gas turbine application. The study reveals great optimization potential of the Micromix Combustion technology with respect to the DLN characteristics and gives insight into the impact of geometry modifications on flame structure and NOx emission. This allows to further increase the energy density of the Micromix burners and to integrate this technology in industrial gas turbines.
Cento Tavole
(2016)
This paper describes the development of a capacitively coupled high-pressure lamp with input power between 20 and 43 W at 2.45 GHz, using a coaxial line network. Compared with other electrodeless lamp systems, no cavity has to be used and a reduction in the input power is achieved. Therefore, this lamp is an alternative to the halogen incandescent lamp for domestic lighting. To serve the demands of domestic lighting, the filling of the lamp is optimized over all other resulting requirements, such as high efficacy at low induced powers and fast startups. A workflow to develop RF-driven plasma applications is presented, which makes use of the hot S-parameter technique. Descriptions of the fitting process inside a circuit and FEM simulator are given. Results of the combined ignition and operation network from simulations and measurements are compared. An initial prototype is built and measurements of the lamp's lighting properties are presented along with an investigation of the efficacy optimizations using large signal amplitude modulation. With this lamp, an efficacy of 135 lmW -1 is achieved.
To better understand what kinds of sports and exercise could be beneficial for the intervertebral disc (IVD), we performed a review to synthesise the literature on IVD adaptation with loading and exercise. The state of the literature did not permit a systematic review; therefore, we performed a narrative review. The majority of the available data come from cell or whole-disc loading models and animal exercise models. However, some studies have examined the impact of specific sports on IVD degeneration in humans and acute exercise on disc size. Based on the data available in the literature, loading types that are likely beneficial to the IVD are dynamic, axial, at slow to moderate movement speeds, and of a magnitude experienced in walking and jogging. Static loading, torsional loading, flexion with compression, rapid loading, high-impact loading and explosive tasks are likely detrimental for the IVD. Reduced physical activity and disuse appear to be detrimental for the IVD. We also consider the impact of genetics and the likelihood of a ‘critical period’ for the effect of exercise in IVD development. The current review summarises the literature to increase awareness amongst exercise, rehabilitation and ergonomic professionals regarding IVD health and provides recommendations on future directions in research.
Given the strong increase in regulatory requirements for business processes the management of business process compliance becomes a more and more regarded field in IS research. Several methods have been developed to support compliance checking of conceptual models. However, their focus on distinct modeling languages and mostly linear (i.e., predecessor-successor related) compliance rules may hinder widespread adoption and application in practice. Furthermore, hardly any of them has been evaluated in a real-world setting. We address this issue by applying a generic pattern matching approach for conceptual models to business process compliance checking in the financial sector. It consists of a model query language, a search algorithm and a corresponding modelling tool prototype. It is (1) applicable for all graph-based conceptual modeling languages and (2) for different kinds of compliance rules. Furthermore, based on an applicability check, we (3) evaluate the approach in a financial industry project setting against its relevance for decision support of audit and compliance management tasks.
Das Bundeskabinett hat sich am 14.9.2016 mit der sog. Flexi-Rente befasst und eine sog. Formulierungshilfe verabschiedet, der ein aus den Regierungsfraktionen des Bundestages einzubringender entsprechender Gesetzesentwurf zur „Flexibilisierung des Übergangs vom Erwerbsleben in den Ruhestand und zur Stärkung von Prävention und Rehabilitation im Erwerbsleben (Flexirentengesetz)“ folgen soll. Eine entsprechende Vorabfassung des Gesetzesentwurfs liegt bereits vor (BT-Drucks. 18/9787). Mit der Flexi-Rente sollen im Wesentlichen zwei Ziele erreicht werden: Das flexible Arbeiten bis zum Erreichen der Regelaltersgrenze soll gefördert und das Weiterarbeiten über die Regelaltersgrenze hinaus attraktiver gemacht werden. Hierfür ist eine Reihe von gesetzlichen Änderungen geplant, insbesondere im SGB VI und SGB III. Teile des Gesetzes sollen schon zum 1.1.2017 in Kraft treten. Grund genug, sich bereits jetzt einen ersten Überblick über die geplanten Neuerungen zu verschaffen.
The main objective of the BATIMASS project was to address how the energy balance in relatively lightweight steel buildings can be improved by building in ‘active thermal mass’ (ATM) into the building fabric. This was achieved through concept design, dynamic thermal modelling and testing of a number of potentially viable systems and concepts. A significant programme of thermal simulation modelling was undertaken utilising the thermally equivalent slab (TES) concept to model the passive thermal capacity effect of profiled, composite metal floor decks. It is apparent from the modelling results that thermal mass is a highly complex phenomenon which is highly dependent upon building type, occupancy patterns, climate and many other aspects of the building design and servicing strategy. The ATM systems developed, both conceptually and for prototype testing, focussed on water-cooled composite slabs, the Cofradal floor system and the phase change material (PCM) Energain. In addition to laboratory testing of prototypes, whole building monitoring was undertaken at the Kubik building in Spain and the RWTH test building in Germany. Advanced thermal modelling was also undertaken to estimate the likely benefits of the ATM concept designs developed and for comparison with the test results. In addition to thermal testing, structural tests were conducted on composite floor specimens incorporating embedded water pipes. This Final Report presents the results of the activities carried out under this RFCS contract RFSR CT 2012 00033. The work carried out is reported in six major sections corresponding to the technical Work Packages of the project. Only summaries of the work carried out are provided in this report; all work undertaken is fully reported in the formal project deliverables.
Boden, Baugrube, Verbau
(2016)
Die Lösung den Baugrund betreffender Fragestellungen beginnen i. d. R. mit der Durchführung von Baugrunderkundungen, um alle notwendigen Parameter zu erhalten, die für die Planung und Durchführung von Bauvorhaben notwendig sind. Im Folgenden werden die wichtigsten Erkundungen in Abhängigkeit der erforderlichen Güteklasse der Proben beschrieben und vorgestellt.
Für das Auftreten extremer Wetterereignisse werden für Kernkraftwerke Eintrittshäufigkeiten für nicht mehr beherrschbare Zustände von unter 10⁻⁴/a gefordert. Dies gilt auch für die Einwirkung von Blitzeinschlägen. Die bisherige Nachweisführung zu Blitz- und Überspannungsschutz eines KKW in Deutschland ist deterministisch. In diesem Bericht werden das Vorgehen für einen entsprechenden Nachweis für leittechnische Einrichtungen der Sicherheitstechnik von KKW, der zur geforderten Zielgröße der Eintrittshäufigkeit führt. Die Ergebnisse werden zusammenfassend bewertet.
Betriebsorganisation
(2016)
Das Kapitel behandelt, ausgehend von Begriffen und Aufgaben der Betriebsorganisation, die Aufbau- und Ablauforganisation der Bauunternehmung sowie die Gestaltung einer Projekt-organisation. Es folgt eine Darstellung der Managementsysteme für Qualität, Umwelt und Arbeitsschutz, die sich zunehmend als sog. integrierte Managementsysteme (IMS) auch in Bauunternehmen etablieren. Grundlagen des Personalmanagements und des betrieblichen Rechnungswesens, die für eine(n) Baubetriebler(in) relevant sein können, ergänzen das Kap. Betriebsorganisation. Den Abschluss bilden Hinweise zum Berichtswesen der Baustelle.
Bauwirtschaft und Baurecht
(2016)
Die Leistungen der Bauwirtschaft und deren wirtschaftliche Bedeutung in Deutschland werden anhand einer Vielzahl statistischer Daten verdeutlicht. Die im Vergleich zu anderen Wirtschaftsbereichen auftretenden branchenspezifischen Besonderheiten der Bauwirtschaft werden anhand von verschiedenen Kriterien herausgearbeitet. Das Zusammenspiel der einzelnen Akteure des Sektors und die dabei sich ergebenden bzw. zu beachtenden Rechts- und Vertragsgrundlagen werden dargestellt. Aufgrund der meist erheblichen Höhe des eingesetzten Kapitals aufseiten der Auftraggeber, aber auch seitens der Bauunternehmen während der Bauausführung sowie der besonderen Verantwortung der Beratenden Ingenieure werden auch notwendige Formen der Risikoabsicherungen und der in der Branche üblichen und teilweise vorgeschriebenen Versicherungsmöglichkeiten angesprochen. Intensive Beachtung finden auch die Auswirkungen des Öffentlichen Baurechts (Baugesetzbuch, Bauordnung NRW, Baunutzungsverordnung) auf Planung, Bau und Betrieb baulicher Anlagen und der dabei verwendeten Bauprodukte.
Baumaschinen
(2016)
Baukosten und Finanzierung
(2016)
In diesem Kapitel werden die Abrechnungsvorschriften wichtiger ATV kurz, aber umfassend zusammengestellt. Einigen Abrechnungsbestimmungen für Einzelleistungen, die keine Nebenleistungen sind ((siehe DIN 18299 und Abschnitt 4 der jeweiligen ATV), sind mit aufgenommen worden; die ATV enthalten jedoch weitergehende Festlegungen über Nebenleistungen und Besondere Leistungen.
Im Anschluss folgen Hinweise zu den Toleranzen im Hochbau sowie im Straßenbau.