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With a steady increase of regulatory requirements for business processes, automation support of compliance management is a field garnering increasing attention in Information Systems research. Several approaches have been developed to support compliance checking of process models. One major challenge for such approaches is their ability to handle different modeling techniques and compliance rules in order to enable widespread adoption and application. Applying a structured literature search strategy, we reflect and discuss compliance-checking approaches in order to provide an insight into their generalizability and evaluation. The results imply that current approaches mainly focus on special modeling techniques and/or a restricted set of types of compliance rules. Most approaches abstain from real-world evaluation which raises the question of their practical applicability. Referring to the search results, we propose a roadmap for further research in model-based business process compliance checking.
Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line
(2012)
The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(−/−)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial characterization of a mouse line humanized for MRP2 (huMRP2), which is nulled for the mouse Mrp2 gene and expresses the human transporter in the organs and cell types where MRP2 is normally expressed. Analysis of the mRNA expression for selected cytochrome P450 and transporter genes revealed no major changes in huMRP2 mice compared with wild-type controls. We show that human MRP2 is able to compensate functionally for the loss of the mouse transporter as demonstrated by comparable bilirubin levels in the humanized mice and wild-type controls, in contrast to the hyperbilirubinemia phenotype that is observed in MRP2(−/−) mice. The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2.
Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.
Disruption experiments targeted at the Bacillus licheniformis degSU operon and GFP-reporter analysis provided evidence for promoter activity immediately upstream of degU. pMutin mediated concomitant introduction of the degU32 allele – known to cause hypersecretion in Bacillus subtilis – resulted in a marked increase in protease activity. Application of 5-fluorouracil based counterselection through establishment of a phosphoribosyltransferase deficient Δupp strain eventually facilitated the marker-free introduction of degU32 leading to further protease enhancement achieving levels as for hypersecreting wild strains in which degU was overexpressed. Surprisingly, deletion of rapG – known to interfere with DegU DNA-binding in B. subtilis – did not enhance protease production neither in the wild type nor in the degU32 strain. The combination of degU32 and Δupp counterselection in the type strain is not only equally effective as in hypersecreting wild strains with respect to protease production but furthermore facilitates genetic strain improvement aiming at biological containment and effectiveness of biotechnological processes.
Geotechnik
(2012)
In der nationalen und der europäischen Normung werden die geotechnischen Aufgaben zwecks Mindestanforderungen an Baugrunduntersuchung, rechnerische Nachweise und Überwachung der Ausführung in drei Klassen (Kategorien) eingeteilt. Sie richten sich nach der zu erwartenden Reaktion des Baugrundes, nach dem geotechnischen Schwierigkeitsgrad des Tragwerks und seiner Einflüsse auf dieUmgebung.
Geotechnik
(2012)
In this article, we report on the heat-transfer resistance at interfaces as a novel, denaturation-based method to detect single-nucleotide polymorphisms in DNA. We observed that a molecular brush of double-stranded DNA grafted onto synthetic diamond surfaces does not notably affect the heat-transfer resistance at the solid-to-liquid interface. In contrast to this, molecular brushes of single-stranded DNA cause, surprisingly, a substantially higher heat-transfer resistance and behave like a thermally insulating layer. This effect can be utilized to identify ds-DNA melting temperatures via the switching from low- to high heat-transfer resistance. The melting temperatures identified with this method for different DNA duplexes (29 base pairs without and with built-in mutations) correlate nicely with data calculated by modeling. The method is fast, label-free (without the need for fluorescent or radioactive markers), allows for repetitive measurements, and can also be extended toward array formats. Reference measurements by confocal fluorescence microscopy and impedance spectroscopy confirm that the switching of heat-transfer resistance upon denaturation is indeed related to the thermal on-chip denaturation of DNA.
Gräser sind in der Lage, einen großen Teil der für eine biobasierte Wirtschaft benötigten Biomasse zur Verfügung zustellen. Um eine ganzjährige Nutzung des Grases zu gewährleisten, muss eine stabile Lagerung des Grases erreicht werden, was z. B. durch Silieren möglich ist. Die konservierende Wirkung der Silierung beruht auf der Bildung organischer Säuren. Um diese zu gewinnen, wird die Silage gepresst, die organischen Säuren über Flüssig/Flüssig-Extraktion aus dem Presssaft abgetrenntund mittels chromatographischer Methoden weiter aufgereinigt. Im präsentierten Konzept werden die im Presskuchen enthaltenen Lignocellulosen hydrolysiert und die erhaltenen Monosaccharide zu Ethanol fermentiert. Die Phenolsäuren, die in Gräsern die Rolle des Lignins übernehmen, können simultan mit der Hydrolyse der Polysaccharide enzymatisch abgetrennt und als Nebenprodukt gewonnen werden. Die nach der Abtrennung des Ethanols verbleibenden Fermentationsreststoffe werden für die Herstellung von Biogas verwendet.
Heterogeneous Composites on the Basis of Microbial Cells and Nanostructured Carbonized Sorbents
(2012)
The fact that microorganisms prefer to grow on liquid/solid phase surfaces rather than in the surrounding aqueous phase was noticed long time ago [1]. Virtually any surface – animal, mineral, or vegetable – is a subject for microbial colonization and subsequent biofilm formation. It would be adequate to name just a few notorious examples on microbial colonization of contact lenses, ship hulls, petroleum pipelines, rocks in streams and all kinds of biomedical implants. The propensity of microorganisms to become surface-bound is so profound and ubiquitous that it vindicates the advantages for attached forms over their free-ranging counterparts [2]. Indeed, from ecological and evolutionary standpoints, for many microorganisms the surface-bound state means dwelling in nutritionally favorable, non-hostile environments [3]. Therefore, in most of natural and artificial ecosystems surface-associated microorganisms vastly outnumber organisms in suspension and often organize into complex communities with features that differ dramatically from those of free cells [4].
Solar thermal concentrated power is an emerging technology that provides clean electricity for the growing energy market. To the solar thermal concentrated power plant systems belong the parabolic trough, the Fresnel collector, the solar dish, and the central receiver system.
For high-concentration solar collector systems, optical and thermal analysis is essential. There exist a number of measurement techniques and systems for the optical and thermal characterization of the efficiency of solar thermal concentrated systems.
For each system, structure, components, and specific characteristics types are described. The chapter presents additionally an outline for the calculation of system performance and operation and maintenance topics. One main focus is set to the models of components and their construction details as well as different types on the market. In the later part of this chapter, different criteria for the choice of technology are analyzed in detail.
Light-addressable potentiometric sensors (LAPS) are field-effect-based sensors. A modulated light source is used to define the particular measurement spot to perform spatially resolved measurements of chemical species and to generate chemical images. In this work, an organic-LED (OLED) display has been chosen as a light source. This allows high measurement resolution and miniaturisation of the system. A new developed driving method for the OLED display optimised for LAPS-based measurements is demonstrated. The new method enables to define modulation frequencies between 1 kHz and 16 kHz and hence, reduces the measurement time of a chemical image by a factor of 40 compared to the traditional addressing of an OLED display.
Bei der Ausarbeitung des nationalen Anwendungsdokumentes zur DIN EN 1998-1 waren die in der ENV-Fassung enthaltenen vereinfachten Regeln im Lichte aktueller Forschungsergebnisse zu überprüfen und zu überarbeiten. Die gleiche Aufgabe stellte sich auch für die Neufassung der DIN 4149. In beiden Fällen sind neben konstruktiven Regeln für die Art und Anordnung der zur Gebäudeaussteifung heranzuziehenden Wände im Grundriss Tabellen enthalten, die unter bestimmten Bedingungen den Entfall eines rechnerischen Nachweises der Tragwände im Erdbebenfall ermöglichen. Dies ist für Schwachbebengebiete, wie sie in Deutschland und anderen Ländern Mitteleuropas anzutreffen sind, sinnvoll, um unnötigen Rechenaufwand sowie Probleme mit der Führbarkeit von Nachweisen so weit wie möglich auszuschalten. Im vorliegenden Beitrag werden die Hintergründe der vereinfachten Regeln diskutiert und die Ergebnisse der Anwendung mit verschiedenen Rechenverfahren verglichen und bewertet.
Der Erhalt möglichst hoher Zuckerkonzentrationen für nachfolgende Fermentationen und eine Steigerung der Produktivität sind Ziele der Hydrolyse bei hohen Feststoffkonzentrationen im Rahmen des Projekts „Lignocellulose Bioraffinerie“. Verwendet wird durch ein Organosolv-Verfahren aufgeschlossenes Buchenholz. Die Hydrolyse des Faserstoffes erfolgt mithilfe von CTec2-Enzymen (Fa. Novozymes). Zurzeit können unter Einsatz eines neuen Feststoffreaktors Cellulosefasern in einer Konzentration bis 400 g L⁻¹ enzymatisch hydrolysiert werden. Dabei werden Ausbeuten (g Glucose/g Cellulose im Faserstoff) bis 0,86 g g⁻¹ und Glucosekonzentrationenvon 120 g L⁻¹ erreicht. Ein Nachteil ist jedoch die hierbei auftretende Abnahme der Hydrolyseausbeuten. Zahlreiche Limitierungen bezüglich der Hydrolysierbarkeit von Lignocellulose werden zurzeit diskutiert und publiziert. Ziel der Untersuchungen ist die Identifizierung hydrolysehemmender Substanzen sowie die Erhöhung der Ausbeute an Zuckermonomeren durch den Einsatz lignolytischer Enzyme. Hierbei wird eine HPLC-MS-Methode zur Charakterisierung hemmender Substanzen eingesetzt, um potenzielle Inhibitoren zu erfassen.
Agil ist im Trend und immer mehr Unternehmen, die ihre Projekte bisher nach klassischen Prinzipien durchführten, denken über den Einsatz agiler Methoden nach. Doch selbst wenn die Organisation bereits beide Philosophien unterstützt, gilt für ein Projekt meist die klare Vorgabe: agil oder klassisch. Es gibt aber noch einen anderen Ansatz, mit diesen "unterschiedlichen Welten" umzugehen: Und zwar die beiden Philosophien innerhalb eines Projekts zu kombinieren. Wie dies in der Praxis aussehen und gelingen kann, zeigen Dr. Michael Kirchhof und Prof. Dr. Bodo Kraft in diesem Beitrag.
The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.
Mit Gesetz vom 29.7.2009 (BGBl 2009 I S. 2355) hat der deutsche Gesetzgeber die EU-Verbraucherkreditrichtlinie 2008/48/EG vom 23.4.2008 NWB PAAAD-28762 in nationales Recht umgesetzt. In diesem Gesetz ist auch der Immobiliardarlehensvertrag neu geregelt worden. Auf diese besondere Kreditform sind grds. die Vorschriften zum Verbraucherkredit anzuwenden, so dass der Darlehensgeber auch im Fall einer Immobilienfinanzierung zu vorvertraglicher Information des Verbrauchers verpflichtet ist. Beim finanzierten Immobilienerwerb werden Veräußerer und kreditgebende Bank häufig in Abstimmung und Zusammenarbeit tätig, so dass für die Bank besondere Aufklärungspflichten gegenüber dem Verbraucher entstehen. Im Fall der Verletzung dieser Pflichten drohen ihr Schadensersatzansprüche oder ein Widerrufsrecht des Verbrauchers.
We present an effective finite difference formulation for implementing and modeling multiple borehole heat exchangers (BHE) in the general 3-D coupled heat and flow transport code SHEMAT. The BHE with arbitrary length can be either coaxial or double U-shaped. It is particularly suitable for modeling deep BHEs which contain varying pipe diameters and materials.
Usually, in numerical simulations, a fine discretization of the BHE assemblage is required, due to the large geometric aspect ratios involved. This yields large models and long simulation times. The approach avoids this problem by considering heat transport between fluid and the soil through pipes and grout via thermal resistances. Therefore, the simulation time can be significantly reduced.
The coupling with SHEMAT is realized by introducing an effective heat generation. Due to this connection, it is possible to consider heterogeneous geological models, as well as the influence of groundwater flow. This is particularly interesting when studying the long term behavior of a single BHE or a BHE field. Heating and cooling loads can enter the model with an arbitrary interval, e.g. from hourly to monthly values. When dealing with large BHE fields, computing times can be further significantly reduced by focusing on the temperature field around the BHEs, without explicitly modeling inlet and outlet temperatures. This allows to determine the possible migration of cold and warm plumes due to groundwater flow, which is of particular importance in urban areas with a high BHE installation density.
The model is validated against the existing BHE modeling codes EWS and EED. A comparison with monitoring data from a deep BHE in Switzerland shows a good agreement. Synthetic examples demonstrate the field of application of this model.
In current clinical cardiovascular MR (CMR) practice cardiac motion is commonly dealt with using ECG based synchronization. However, ECG is corrupted by magneto-hydrodynamic (MHD) effects in magnetic fields. This leads to artifacts in the ECG trace and evokes severe T-wave elevations, which might be misinterpreted as R-waves resulting in erroneous triggering. At (ultra)high field strengths, the propensity of ECG recordings to MHD effects is further pronounced. Pulse oximetry (POX) being inherently sensitive to blood oxygenation provides an alternative approach for cardiac gating. However, due to the travel time of the blood the peak of maximum oxygenation and hence the trigger is delayed by approx. 300 ms with respect to the ECG's R-wave. Also the peak of maximum oxygenation shows a jitter of up to 65 ms. Alternative triggering approaches include acoustic cardiac triggering (ACT). In current clinical practice cardiac gating / triggering commonly relies on using single physiological signals only. Realizing this limitation this study proposes a combined triggering approach which exploits multiple physiological signals including ECG, POX or ACT to track cardiac activity. The feasibility of the coupled approach is examined for LV function assessment at 7.0 T. For this purpose, breath-held 2D-CINE imaging in conjunction with cardiac synchronization was performed paralleled by real time logging of physiological waveforms to track (mis)synchronization between the cardiac cycle and data acquisition. Combinations of the ECG, POX and ACT signals were evaluated and processed in real time to facilitate reliable trigger information.
31P MR spectroscopic imaging of the human prostate provides information about phosphorylated metabolites that could be used for prostate cancer characterization. The sensitivity of a magnetic field strength of 7 T might enable 3D 31P MR spectroscopic imaging with relevant spatial resolution in a clinically acceptable measurement time. To this end, a 31P endorectal coil was developed and combined with an eight-channel 1H body-array coil to relate metabolic information to anatomical location. An extensive safety validation was performed to evaluate the specific absorption rate, the radiofrequency field distribution, and the temperature distribution of both coils. This validation consisted of detailed Finite Integration Technique simulations, confirmed by MR thermometry and Burn:x-wiley:07403194:media:MRM24175:tex2gif-stack-1 measurements in a phantom and in vivo temperature measurements. The safety studies demonstrated that the presence of the 31P endorectal coil had no influence on the specific absorption rate levels and temperature distribution of the external eight-channel 1H array coil. To stay within a 10 g averaged local specific absorption rate of 10 W/kg, a maximum time-averaged input power of 33 W for the 1H array coil was allowed. For transmitting with the 31P endorectal coil, our safety limit of less than 1°C temperature increase in vivo during a 15-min MR spectroscopic imaging experiment was reached at a time-averaged input power of 1.9 W. With this power setting, a second in vivo measurement was performed on a healthy volunteer. Using adiabatic excitation, 3D 31P MR spectroscopic imaging produced spectra from the entire prostate in 18 min with a spatial resolution of 4 cm3. The spectral resolution enabled the separate detection of phosphocholine, phosphoethanolamine, inorganic phosphate, and other metabolites that could play an important role in the characterization of prostate cancer.
Influence of a freeze–thaw cycle on the stress–stretch curves of tissues of porcine abdominal organs
(2012)
The paper investigates both fresh porcine spleen and liver and the possible decomposition of these organs under a freeze–thaw cycle. The effect of tissue preservation condition is an important factor which should be taken into account for protracted biomechanical tests. In this work, tension tests were conducted for a large number of tissue specimens from twenty pigs divided into two groups of 10. Concretely, the first group was tested in fresh state; the other one was tested after a freeze-thaw cycle which simulates the conservation conditions before biomechanical experiments. A modified Fung model for isotropic behavior was adopted for the curve fitting of each kind of tissues. Experimental results show strong effects of the realistic freeze–thaw cycle on the capsule of elastin-rich spleen but negligible effects on the liver which virtually contains no elastin. This different behavior could be explained by the autolysis of elastin by elastolytic enzymes during the warmer period after thawing. Realistic biomechanical properties of elastin-rich organs can only be expected if really fresh tissue is tested. The observations are supported by tests of intestines.
Since several decades, dam-break waves have been of main research interest. Mathematical approaches have been developed by analytical, physical and numerical models within the past 120 years. During the past 10 years, the number of research investigations has increased due to improved measurement techniques as well as significantly increased computer memories and performances. In this context, the present research deals with the initial stage of two-dimensional dam-break waves by comparing physical and numerical model results as well as analytical approaches. High-speed images and resulting particle image velocimetry calculations are thereby compared with the numerical volume-of-fluid (VOF) method, included in the commercial code FLOW-3D. Wave profiles and drag forces on placed obstacles are analysed in detail. Generally, a good agreement between the laboratory and VOF results is found.
Inkompressible Strömungen
(2012)
Moderne Mauerwerksbauten müssen nach heutigen Anforderungen architektonisch, statisch, energetisch sowie schall- und brandschutztechnisch optimal ausgelegt sein. Aufgrund der Komplexität und engen Verzahnung der einzelnen Anforderungen ist eine integrale Gebäudeplanung zur Erzielung einer qualitativ hochwertigen Bauwerkslösung unbedingt notwendig. Diese erfordert von den Fachplanern vertieftes Spezialwissen in den verschiedenen Bereichen, um insbesondere die Schnittstellen und Bauwerksdetails korrekt zu planen und auszuführen. Der Beitrag stellt die integrale Gebäudeplanung am Beispiel eines Geschossbaus in Ziegelbauweise mit Lösungen für wesentliche Detailpunkte vor
There is common agreement within the scientific community that in order to understand our local galactic environment it will be necessary to send a spacecraft into the region beyond the solar wind termination shock. Considering distances of 200 AU for a new mission, one needs a spacecraft traveling at a speed of close to 10 AU/yr in order to keep the mission duration in the range of less than 25 yrs, a transfer time postulated by European Space Agency (ESA). Two propulsion options for the mission have been proposed and discussed so far: the solar sail propulsion and the ballistic/radioisotope-electric propulsion (REP). As a further alternative, we here investigate a combination of solar-electric propulsion (SEP) and REP. The SEP stage consists of six 22-cms diameter RIT-22 ion thrusters working with a high specific impulse of 7377 s corresponding to a positive grid voltage of 5 kV. Solar power of 53 kW at begin of mission (BOM) is provided by a lightweight solar array.
Aus hölzernen Cellulosen und Hemicellulosen können durch enzymatische Hydrolyse fermentierbare Zucker für die Herstellung von Chemikalien und Treibstoffen gewonnen werden. Die bisherige Forschung fokussiert sich oft auf die Nutzung dieser Zucker zur Gewinnung von Ethanol. Daneben muss aber auch die stoffliche Nutzung zur Gewinnung von Grundchemikalien berücksichtigt werden. Eine solche Grundchemikalie ist Itakonsäure. Obwohl die biotechnologische Itaconsäureproduktion bereits eingehend untersucht und etabliert ist, gestaltet sie sich im Rahmen von Bioraffinerien der zweiten Generation als schwierig, da der überwiegend verwendete Produktionsorganismus gegen eine weite Bandbreite von Inhibitoren sensibel ist. Die Herstellung von Itaconsäure aus Buchenholzhydrolysaten wird im Rahmen der deutschen Lignocellulose-Bioraffinerie entwickelt. Die unbehandelten Hydrolysate ermöglichen weder das Wachstum von Aspergillus terreus noch die Bildung von Itaconsäure. Daher werden Möglichkeiten zur Konditionierung des Hydrolysates mit dem Ziel einer Itaconsäureproduktion mit hohen Ausbeuten und Konzentrationen vorgestellt.
Label-free electrical detection of consecutive deoxyribonucleic acid (DNA) hybridization/denaturation by means of an array of individually addressable field-effect-based nanoplate silicon-on-insulator (SOI) capacitors modified with gold nanoparticles (Au-NP) is investigated. The proposed device detects charge changes on Au-NP/DNA hybrids induced by the hybridization or denaturation event. DNA hybridization was performed in a high ionic-strength solution to provide a high hybridization efficiency. On the other hand, to reduce the screening of the DNA charge by counter ions and to achieve a high sensitivity, the sensor signal induced by the hybridization and denaturation events was measured in a low ionic-strength solution. High sensor signals of about 120, 90, and 80 mV were registered after the DNA hybridization, denaturation, and re-hybridization events, respectively. Fluorescence microscopy has been applied as reference method to verify the DNA immobilization, hybridization, and denaturation processes. An electrostatic charge-plane model for potential changes at the gate surface of a nanoplate field-effect sensor induced by the DNA hybridization has been developed taking into account both the Debye length and the distance of the DNA charge from the gate surface.
The laser beam-submerged arc hybrid welding method originates from the knowledge that, with increasing penetration depth, the laser beam process has a tendency to pore formation in the lower weld regions. The coupling with the energy-efficient submerged-arc process improves degassing and reduces the tendency to pore formation. The high deposition rate of the SA process in combination with the laser beam process offers, providing the appropriate choice of weld preparation, the possibility of welding plates with a thickness larger than 20° mm in a single pass, and also of welding thicker plates with the double-sided single pass technique.