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Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of ‘gene-shuffled’ (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.
Many applications in computational science and engineering require the computation of eigenvalues and vectors of dense symmetric or Hermitian matrices. For example, in DFT (density functional theory) calculations on modern supercomputers 10% to 30% of the eigenvalues and eigenvectors of huge dense matrices have to be calculated. Therefore, performance and parallel scaling of the used eigensolvers is of upmost interest. In this article different routines of the linear algebra packages ScaLAPACK and Elemental for parallel solution of the symmetric eigenvalue problem are compared concerning their performance on the BlueGene/P supercomputer. Parameters for performance optimization are adjusted for the different data distribution methods used in the two libraries. It is found that for all test cases the new library Elemental which uses a two-dimensional element by element distribution of the matrices to the processors shows better performance than the old ScaLAPACK library which uses a block-cyclic distribution.
In this study we observed courses of micturition symptoms and differentiated degrees of symptoms for each point in time while also considering the impact of bothersomeness. Our data show that not only significantly more patients who have undergone BT suffer from OAB than those who have undergone RP, but also that those affected show significantly higher values for severity of OAB symptoms throughout the whole observation period of 36 months. Our data analysis further shows that variability of OAB symptoms as well as fluctuation of severity of OAB symptoms vary to a significantly higher degree after BT than after RP. Looking only at mean figures at a given point in time clearly underestimates the underlying problem. This fact is not reflected in the literature.
Generally, the quality of a weld joint is directly influenced by the welding input parameter settings. Selection of proper process parameters is important to obtain the desired weld bead profile and quality. In this research work, numerical and graphical optimization techniques of the CO2 laser beam welding of dual phase (DP600)/transformation induced plasticity (TRIP700) steel sheets were carried out using response surface methodology (RSM) based on Box–Behnken design. The procedure was established to improve the weld quality, increase the productivity and minimize the total operation cost by considering the welding parameters range of laser power (2–2.2 kW), welding speed (40–50 mm/s) and focus position (−1 to 0 mm). It was found that, RSM can be considered as a powerful tool in experimental welding optimization, even when the experimenter does not have a model for the process. Strong, efficient and low cost weld joints could be achieved using the optimum welding conditions.
Thin films of poly(ethyleneterephthalate) [PET]were exposed to radiation dose ranging from 10 to 30 kGy by using gamma rays in the range 12.8-177.8 MGy using swift light ions of hydrogen. There was no effect of the radiation dose on the optical behaviour of PET as a result of exposure to radiation dose up to 30 kGy brought about by gamma rays but a significant decrease in the optical band gap values was observed when PET was exposed to swift light ions of hydrogen. The data obtained are discussed in terms of optical studies carried out on PET using swift heavy ions.
A variety of transition metals, e.g., copper, zinc, cadmium, lead, etc. are widely used in industry as components for wires, coatings, alloys, batteries, paints and so on. The inevitable presence of transition metals in industrial processes implies the ambition of developing a proper analytical technique for their adequate monitoring. Most of these elements, especially lead and cadmium, are acutely toxic for biological organisms. Quantitative determination of these metals at low activity levels in different environmental and industrial samples is therefore a vital task. A promising approach to achieve an at-side or on-line monitoring on a miniaturized and cost efficient way is the combination of a common potentiometric sensor array with heavy metal-sensitive thin-film materials, like chalcogenide glasses and polymeric materials, respectively.
Suburethral slings as well as different meshes are widely used treating stress urinary incontinence and prolaps in women. With the development of MiniSlings and special meshes using less alloplastic material anchorage systems become more important to keep devices in place and to put some tension especially on the MiniSlings. To date, there are many different systems of MiniSlings of different companies on the market which differ in the structure of the used meshes and anchors. A new objective measurement method to compare different properties of MiniSling systems (mesh and anchor) is presented in this article. Ballistic gelatine acts as soft tissue surrogate. Significant differences in parameters like pull-out strength of anchors or shrinkage of meshes under loading conditions have been determined. The form and size of the anchors as well as the structural stability of the meshes are decisive for a proper integration. The tested anchorings sytems showed markedly different mechanical function at their respective load bearing capacity. As the stable fixation of the device in tissue is a prerequisite for a permanet reinforcement, the proposed test system permits further optimisation of anchor and mesh devices to improve the success of the surgical treatment
Cell-based sensors for the detection of gases have long been underrepresented, due to the cellular requirement of being cultured in a liquid environment. In this work we established a cell-based gas biosensor for the detection of toxic substances in air, by adapting a commercial sensor chip (Bionas®), previously used for the measurement of pollutants in liquids. Cells of the respiratory tract (A549, RPMI 2650, V79), which survive at a gas phase in a natural context, are used as biological receptors. The physiological cell parameters acidification, respiration and morphology are continuously monitored in parallel. Ammonia was used as a highly water-soluble model gas to test the feasibility of the sensor system. Infrared measurements confirmed the sufficiency of the medium draining method. This sensor system provides a basis for many sensor applications such as environmental monitoring, building technology and public security.
The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine.
Remotewords makes its mark on the picturesque "Bar Verbanella”, located in Stresa near Isola Bella on Lago Maggiore. The words CUM GRANO SALIS (with a grain of salt) by Sabine Fabo, art theorist on media contexts, were applied to its roof in collaboration with the German-Italian art organization "Lo spirito del Lago".
The chemical imaging sensor is a semiconductor-based chemical sensor that can visualize the two-dimensional distribution of specific ions or molecules in the solution. In this study, we developed a miniaturized chemical imaging sensor system with an OLED display panel as a light source that scans the sensor plate. In the proposed configuration, the display panel is placed directly below the sensor plate and illuminates the back surface. The measured area defined by illumination can be arbitrarily customized to fit the size and the shape of the sample to be measured. The waveform of the generated photocurrent, the current–voltage characteristics and the pH sensitivity were investigated and pH imaging with this miniaturized system was demonstrated.
Two types of microvalves based on temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and pH-responsive poly(sodium acrylate) (PSA) hydrogel films have been developed and tested. The PNIPAAm and PSA hydrogel films were prepared by means of in situ photopolymerization directly inside the fluidic channel of a microfluidic chip fabricated by combining Si and SU-8 technologies. The swelling/shrinking properties and height changes of the PNIPAAm and PSA films inside the fluidic channel were studied at temperatures of deionized water from 14 to 36 °C and different pH values (pH 3–12) of Titrisol buffer, respectively. Additionally, in separate experiments, the lower critical solution temperature (LCST) of the PNIPAAm hydrogel was investigated by means of a differential scanning calorimetry (DSC) and a surface plasmon resonance (SPR) method. Mass-flow measurements have shown the feasibility of the prepared hydrogel films to work as an on-chip integrated temperature- or pH-responsive microvalve capable to switch the flow channel on/off.
It is well known that the already large dielectric constants of some electrolytes like BaTiO₃ can be enhanced further by adding metallic (e.g. Ni, Cu or Ag) nanoparticles. The enhancement can be quite large, a factor of more than 1000 is possible. The consequences for the properties will be discussed in the present paper applying a brick-layer model (BLM) for calculating dc-resistivities of thin layers and a modified one (PBLM) that includes percolation for calculating dielectric properties of these materials. The PBLM results in an at least qualitative description and understanding of the physical phenomena: This model gives an explanation for the steep increase of the dielectric constant below the percolation threshold and why this increase is connected to a dramatic decrease of the breakdown voltage as well as the ability of storing electrical energy. We conclude that metallic electrolyte composites like BaTiO₃ are not appropriate for energy storage.
Electron beam plasma measurement was realised by means of DIABEAM system invented by ISF RWTH Aachen. The Langmuir probe method is used for measurement. The relative simplicity of the method and the possibility of dispersion of high power on the probe allow its application for the investigation of high-power electron beams. The key element of the method is a rotating thin tungsten wire, which intersects the beam transversely on its axis and collects part of the current by itself. The signals, which are registered in the DIABEAM as a voltage, were taken in the form of amplitude. The conversion of the probe current into the distribution along the beam radius was realised using the Abel’s method. A voltage-current characteristic was built for the beam current. The local electron density as well as the electron temperature, the floating potential and the plasma potential were measured and calculated by means of this characteristic.
Upper and lower bound theorems of limit analyses have been presented in part I of the paper. Part II starts with the finite element discretization of these theorems and demonstrates how both can be combined in a primal–dual optimization problem. This recently proposed numerical method is used to guide the development of a new class of closed-form limit loads for circumferential defects, which show that only large defects contribute to plastic collapse with a rapid loss of strength with increasing crack sizes. The formulae are compared with primal–dual FEM limit analyses and with burst tests. Even closer predictions are obtained with iterative limit load solutions for the von Mises yield function and for the Tresca yield function. Pressure loading of the faces of interior cracks in thick pipes reduces the collapse load of circumferential defects more than for axial flaws. Axial defects have been treated in part I of the paper.
This work describes the novel combination of the light-addressable electrode (LAE) and the light-addressable potentiometric sensor (LAPS) into a microsystem set-up. Both the LAE as well as the LAPS shares the principle of addressing the active spot by means of a light beam. This enables both systems to manipulate resp. to detect an analyte with a high spatial resolution. Hence, combining both principles into a single set-up enables the active stimulation e.g., by means of electrolysis and a simultaneous observation e.g., the response of an entrapped biological cell by detection of extracellular pH changes. The work will describe the principles of both technologies and the necessary steps to integrate them into a single set-up. Furthermore, examples of application and operation of such systems will be presented.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Spontaneous language has rarely been subjected to neuroimaging studies. This study therefore introduces a newly developed method for the analysis of linguistic phenomena observed in continuous language production during fMRI.
Most neuroimaging studies investigating language have so far focussed on single word or — to a smaller extent — sentence processing, mostly due to methodological considerations. Natural language production, however, is far more than the mere combination of words to larger units. Therefore, the present study aimed at relating brain activation to linguistic phenomena like word-finding difficulties or syntactic completeness in a continuous language fMRI paradigm. A picture description task with special constraints was used to provoke hesitation phenomena and speech errors. The transcribed speech sample was segmented into events of one second and each event was assigned to one category of a complex schema especially developed for this purpose. The main results were: conceptual planning engages bilateral activation of the precuneus. Successful lexical retrieval is accompanied – particularly in comparison to unsolved word-finding difficulties – by the left middle and superior temporal gyrus. Syntactic completeness is reflected in activation of the left inferior frontal gyrus (IFG) (area 44). In sum, the method has proven to be useful for investigating the neural correlates of lexical and syntactic phenomena in an overt picture description task. This opens up new prospects for the analysis of spontaneous language production during fMRI.
"Biologie trifft Mikroelektronik", das Motto des Instituts für Nano- und Biotechnologien (INB) an der FH Aachen, unterstreicht die zunehmende Bedeutung interdisziplinär geprägter Forschungsaktivitäten. Der thematische Zusammenschluss grundständiger Disziplinen, wie die Physik, Elektrotechnik, Chemie, Biologie sowie die Materialwissenschaften, lässt neue Forschungsgebiete entstehen, ein herausragendes Beispiel hierfür ist die Nanotechnologie: Hier werden neue Werkstoffe und Materialien entwickelt, einzelne Nanopartikel oder Moleküle und deren Wechselwirkung untersucht oder Schichtstrukturen im Nanometerbereich aufgebaut, die neue und vorher nicht bekannte Eigenschaften hervorbringen.
Vor diesem Hintergrund bündelt das im Jahre 2006 gegründete INB die an der FH Aachen vorhandenen Kompetenzen von derzeit insgesamt sieben Laboratorien auf den Gebieten der Halbleitertechnik und Nanoelektronik, Nanostrukturen und DNA-Sensorik, der Chemo- und Biosensorik, der Enzymtechnologie, der Mikrobiologie und Pflanzenbiotechnologie, der Zellkulturtechnik, sowie der Roten Biotechnologie synergetisch. In der Nano- und Biotechnologie steckt außergewöhnliches Potenzial! Nicht zuletzt deshalb stellen sich die Forscher der Herausforderung, in diesem Bereich gemeinsam zu forschen und Schnittstellen zu nutzen, um so bei der Gestaltung neuartiger Ideen und Produkte mitzuwirken, die zukünftig unser alltägliches Leben verändern werden.
Im Folgenden werden die verschiedenen Forschungsbereiche kurz zusammenfassend vorgestellt und vorhandene Interaktionen anhand von exemplarisch ausgewählten, aktuellen Forschungsprojekten skizziert.
The impact of surgical staplers on tissues has been studied mostly in an empirical manner. In this paper, finite element method was used to clarify the mechanics of tissue stapling and associated phenomena. Various stapling modalities and several designs of circular staplers were investigated to evaluate the impact of the device on tissues and mechanical performance of the end-to-end colorectal anastomosis. Numerical simulations demonstrated that a single row of staples is not adequate to resist leakage due to non-linear buckling and opening of the tissue layers between two adjacent staples. Compared to the single staple row configuration, significant increase in stress experienced by the tissue at the inner staple rows was observed in two and three rows designs. On the other hand, adding second and/or third staple row had no effect on strain in the tissue inside the staples. Variable height design with higher staples in outer rows significantly reduced the stresses and strains in outer rows when compared to the same configuration with flat cartridge.
Field-effect capacitive electrolyte-insulator-semiconductor (EIS) sensors functionalised with citrate-capped gold nanoparticles (AuNP) have been used for the electrostatic detection of macromolecules by their intrinsic molecular charge. The EIS sensor detects the charge changes in the AuNP/macromolecule hybrids induced by the adsorption or binding events. A feasibility of the proposed detection scheme has been exemplary demonstrated by realising EIS sensors for the detection of poly-D-lysine molecules.
A large strain collection comprising antagonistic bacteria was screened for novel detergent proteases. Several strains displayed protease activity on agar plates containing skim milk but were inactive in liquid media. Encapsulation of cells in alginate beads induced protease production. Stenotrophomonas maltophilia emerged as best performer under washing conditions. For identification of wash-active proteases, four extracellular serine proteases called StmPr1, StmPr2, StmPr3 and StmPr4 were cloned. StmPr2 and StmPr4 were sufficiently overexpressed in E. coli. Expression of StmPr1 and StmPr3 resulted in unprocessed, insoluble protein. Truncation of most of the C-terminal domain which has been identified by enzyme modeling succeeded in expression of soluble, active StmPr1 but failed in case of StmPr3.
From laundry application tests StmPr2 turned out to be a highly wash-active protease at 45 °C. Specific activity of StmPr2 determined with suc-l-Ala-l-Ala-l-Pro-l-Phe-p-nitroanilide as the substrate was 17 ± 2 U/mg. In addition we determined the kinetic parameters and cleavage preferences of protease StmPr2.
Diese Studie beschäftigte sich mit der Dämpfungswirkung von Schienbeinschonern, wie sie beim Fußball zum Einsatz kommen. Sie wurde mit Hilfe eines Pendelhammers durchgeführt, der verschiedene Aufschlagkräfte auf die Schoner ermöglichte. Dabei wurde deutlich, dass Schienbeinschoner die beste Wirkung bei Maximalkräften unterhalb von 5kN erreichen können, dass bei größerer Belastung allerdings Verbesserungsbedarf besteht. Hierfür konnte, u.a. durch den Einsatz neuer Materialien, ein guter Ansatzpunkt im „adäquaten Zusammenspiel von Schale und Polsterung“ der Schoner gefunden werden. Die Untersuchung hat weiterhin gezeigt, dass zumindest teilweise eine deutliche Verbesserung der Dämpfungswirkung der Schienbeinschoner in den letzten Jahren erreicht werden konnte.
Although Selective Laser Melting (SLM) process is an innovative manufacturing method, there are challenges such as inferior mechanical properties of fabricated objects. Regarding this, buckling deformation which is caused by thermal stress is one of the undesired mechanical properties which must be alleviated. As buckling deformation is more observable in hard to process materials, silver is selected to be studied theoretically and experimentally for this paper. Different scanning strategies are utilized and a Finite Element Method (FEM) is applied to calculate the temperature gradient in order to determine its effect on the buckling deformation of the objects from experiments.
In this paper we consider low Péclet number flow in bead packs. A series of relaxation exchange experiments has been conducted and evaluated by ILT analysis. In the resulting correlation maps, we observed a collapse of the signal and a translation towards smaller relaxation times with increasing flow rates, as well as a signal tilt with respect to the diagonal. In the discussion of the phenomena we present a mathematical theory for relaxation exchange experiments that considers both diffusive and advective transport. We perform simulations based on this theory and discuss them with respect to the conducted experiments.
Wir stellen einen USB-Baustein vor, der eine kostengünstige und universelle Möglichkeit schafft , im Unterricht den Themenkreis Messen-Steuern-Regeln zu behandeln. Die Funktionalität orientiert sich am CVK-Interface der Firma Fischertechnik. Im Gegensatz zu kommerziellen Lösungen erlaubt unser Aufbau auch den preiswerten Einsatz in Gruppen- oder Einzelarbeit. Abschließend berichten wir über ein Beispiel aus dem Unterrichtseinsatz.
Background
Minor changes in protein structure induced by small organic and inorganic molecules can result in significant metabolic effects. The effects can be even more profound if the molecular players are chemically active and present in the cell in considerable amounts. The aim of our study was to investigate effects of a nitric oxide donor (spermine NONOate), ATP and sodium/potassium environment on the dynamics of thermal unfolding of human hemoglobin (Hb). The effect of these molecules was examined by means of circular dichroism spectrometry (CD) in the temperature range between 25°C and 70°C. The alpha-helical content of buffered hemoglobin samples (0.1 mg/ml) was estimated via ellipticity change measurements at a heating rate of 1°C/min.
Results
Major results were:
1) spermine NONOate persistently decreased the hemoglobin unfolding temperature T u irrespectively of the Na + /K + environment,
2) ATP instead increased the unfolding temperature by 3°C in both sodium-based and potassium-based buffers and
3) mutual effects of ATP and NO were strongly influenced by particular buffer ionic compositions. Moreover, the presence of potassium facilitated a partial unfolding of alpha-helical structures even at room temperature.
Conclusion
The obtained data might shed more light on molecular mechanisms and biophysics involved in the regulation of protein activity by small solutes in the cell.
Die Detektion von Schadstoffen repräsentiert in der Umweltanalytik eine wichtige Aufgabenstellung. Gerade die Abwasser- bzw. Brauchwasseranalytik sowie die Prozesskontrolle haben einen hohen Stellenwert. Siliziumbasierte Dünnschichtsensoren bieten eine kostengünstige Möglichkeit, „online“-Messungen bzw. Vor-Ort-Messungen zeitnah durchzuführen. In dieser Arbeit wird ein potentiometrisches Sensorarray auf der Basis von Chalkogenidgläsern zur Detektion von Schwermetallen in wässrigen Medien vorgestellt.
Die Detektion von Schadstoffen repräsentiert in der Umweltanalytik eine wichtige Aufgabenstellung. Gerade die Abwasser- bzw. Brauchwasseranalytik sowie die Prozesskontrolle haben einen hohen Stellenwert. Siliziumbasierte Dünnschichtsensoren bieten eine kostengünstige Möglichkeit, „online“-Messungen bzw. Vor-Ort-Messungen zeitnah durchzuführen. In dieser Arbeit wird ein potentiometrisches Sensorarray auf der Basis von Chalkogenidgläsern zur Detektion von Schwermetallen in wässrigen Medien vorgestellt.
Im Folgenden sollen Anlass und Inhalt einer Due Diligence erläutert werden. Im Rahmen einer Checkliste werden Beratern und Unternehmen Hinweise zu möglichen Prüfungsgebieten sowie zu vorzuhaltenden oder zu prüfenden Unterlagen gegeben. Entstanden ist die Checkliste aus der langjährigen praktischen Tätigkeit der Autoren bei einer großen Wirtschaftsprüfungsgesellschaft bzw. einer deutschen Großbank.
An increasing number of studies have reported on forest declines and vegetation shifts triggered by drought. In the Swiss Rhone valley (Valais), one of the driest inner-Alpine regions, the species composition in low elevation forests is changing: The sub-boreal Scots pine (Pinus sylvestris L.) dominating the dry forests is showing high mortality rates. Concurrently the sub-Mediterranean pubescent oak (Quercus pubescens Willd.) has locally increased in abundance. However, it remains unclear whether this local change in species composition is part of a larger-scale vegetation shift. To study variability in mortality and regeneration in these dry forests we analysed data from the Swiss national forest inventory (NFI) on a regular grid between 1983 and 2003, and combined it with annual mortality data from a monitoring site. Pine mortality was found to be highest at low elevation (below 1000 m a.s.l.). Annual variation in pine mortality was correlated with a drought index computed for the summer months prior to observed tree death. A generalized linear mixed-effects model indicated for the NFI data increased pine mortality on dryer sites with high stand competition, particularly for small-diameter trees. Pine regeneration was low in comparison to its occurrence in the overstorey, whereas oak regeneration was comparably abundant. Although both species regenerated well at dry sites, pine regeneration was favoured at cooler sites at higher altitude and oak regeneration was more frequent at warmer sites, indicating a higher adaptation potential of oaks under future warming. Our results thus suggest that an extended shift in species composition is actually occurring in the pine forests in the Valais. The main driving factors are found to be climatic variability, particularly drought, and variability in stand structure and topography. Thus, pine forests at low elevations are developing into oak forests with unknown consequences for these ecosystems and their goods and services.
Purpose: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself.
Methods: A total of 12 young 25.5-year-old (24.0–28.8) [median(1st quartile–3rd quartile)] and 12 senior 68.5-year-old (63.8–71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8–65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5–35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated.
Results: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280–500] RU/s) and in validated healthy seniors (400 [320–510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains.
Conclusions: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV.
Für die Ermittlung der erforderlichen Einspanntiefe von eingespannten Stahlquerschnitten in Betonkonstruktionen existieren verschiedene Bemessungsmodelle. Diese basieren vorwiegend auf Grundlage nationaler Normen wie z. B. DIN 18800 [1] und DIN 1045 [2], die durch die europäische Normung ersetzt wurden. Aus diesem Grund wird in diesem Aufsatz ein Berechnungsmodell für die erforderliche Einspanntiefe von eingespannten Stahlquerschnitten in Betonkonstruktionen auf Grundlage des Eurocodes vorgestellt. Das Grundgerüst für dieses Berechnungsmodell bildet das Verfahren nach Kindmann und Laumann, welches in [3] behandelt wurde. Gleichzeitig werden neue Formeln zur direkten Ermittlung der Mindesteinspanntiefe vorgestellt. Behandelt werden gewalzte I-Profile für einachsige Biegung um die starke Achse (y-y) mit Drucknormalkraft.
Mit einer aktuellen Entscheidung hat der BGH, Urt. v. 11.5.2012 - V ZR 196/11, MDR 2012, 958 seine Rechtsprechung v. 5.6.2008 - V ZB 85/07 zur Entstehungsphase einer Wohnungseigentümergemeinschaft fortgeführt. In dieser Entscheidung sieht der BGH die Erwerber von Wohnungseigentum als Kostenschuldner gem. § 16 Abs. 2 WEG an, obwohl diese noch nicht im Grundbuch eingetragen sind. Eine andere Rechtslage besteht beim sog. Zweiterwerb. Die Abgrenzung von Erstund Zweierwerb ist aufgrund der völlig unterschiedlichen Rechtsfolgen für die Praxis von großer Bedeutung.
Die Aufrechnung des Insolvenzverwalters gegen eine Insolvenzforderung nach ihrer Feststellung
(2012)
In industrial processes there is a variety of heavy metals (e.g., copper, zinc, cadmium, and lead) in use for wires, coatings, paints, alloys, batteries, etc. Since the application of these transition metals for industry is inevitable, it is a vital task to develop proper analytical techniques for their monitoring at low activity levels, especially because most of these elements are acutely toxic for biological organisms. The determination of ions in solution by means of a simple and inexpensive sensor array is, therefore, a promising task. In this work, a sensor array with heavy metal-sensitive chalcogenide glass membranes for the simultaneous detection of the four ions Ag⁺, Cu2⁺, Cd2⁺, and Pb2⁺ in solution is realized. The results of the physical characterization by means of microscopy, profilometry, Rutherford backscattering spectroscopy (RBS), and scanning electron microscopy (SEM) as well as the electrochemical characterization by means of potentiometric measurements are presented. Additionally, the possibility to expand the sensor array by polymeric sensor membranes is discussed.
Chemical imaging systems allow the visualisation of the distribution of chemical species on the sensor surface. This work represents a new flexible approach to read out light-addressable potentiometric sensors (LAPS) with the help of a digital light processing (DLP) set-up. The DLP, known well for video projectors, consists of a mirror-array MEMS device, which allows fast and flexible generation of light patterns. With the help of these light patterns, the sensor surface of the LAPS device can be addressed. The DLP approach has several advantages compared to conventional LAPS set-ups, e.g., the spot size and the shape of the light pointer can be changed easily and no mechanical movement is necessary, which reduces the size of the set-up and increases the stability and speed of the measurement. In addition, the modulation frequency and intensity of the light beam are important parameters of the LAPS set-up. Within this work, the authors will discuss two different ways of light modulation by the DLP set-up, investigate the influence of different modulation frequencies and different light intensities as well as demonstrate the scanning capabilities of the new set-up by pH mapping on the sensor surface.
Determination of the frictional coefficient of the implant-antler interface : experimental approach
(2012)
The similar bone structure of reindeer antler to human bone permits studying the osseointegration of dental implants in the jawbone. As the friction is one of the major factors that have a significant influence on the initial stability of immediately loaded dental implants, it is essential to define the frictional coefficient of the implant-antler interface. In this study, the kinetic frictional forces at the implant-antler interface were measured experimentally using an optomechanical setup and a stepping motor controller under different axial loads and sliding velocities. The corresponding mean values of the static and kinetic frictional coefficients were within the range of 0.5–0.7 and 0.3–0.5, respectively. An increase in the frictional forces with increasing applied axial loads was registered. The measurements showed an evidence of a decrease in the magnitude of the frictional coefficient with increasing sliding velocity. The results of this study provide a considerable assessment to clarify the suitable frictional coefficient to be used in the finite element contact analysis of antler specimens.
Im Beitrag wird zunächst das Verfahren eines dynamischen elektro-geometrischen Modells vorgestellt. Dieses arbeitet im Gegensatz zum klassischen Blitzkugel-Verfahren nicht mit konstanten Radien; vielmehr wird der Radius der Blitzkugel variiert. Dabei werden ausschließlich vorhandene und in internationalen Normen anerkannte Ergebnisse, blitzphysikalische Grundlagen und Untersuchungen verwendet, und auf deren Grundlage ein numerisches Verfahren erarbeitet. Mit dem dynamischen elektro-geometrischen Modell werden dann einige Beispiele des Schutzes mit Fangstangen, die gemäß dem klassischen Blitzkugel-Verfahren nach DIN EN 62305-3 für die Schutzklassen I – II – III – IV geplant sind, untersucht. Es wird gezeigt, dass die Einfangwirksamkeiten wesentlich höher sind als in der Normenreihe DIN EN 62305 selbst angegeben. Grund dafür ist die Tatsache, dass das Blitzkugel-Verfahren sehr konservativ aufgebaut ist und dem Planer von Blitzschutzsystemen nur die möglichen Stellen für einen Einschlag aufzeigt, ohne eine Bewertung der Einschlagshäufigkeit zu liefern. Andererseits bedeutet dies jedoch, dass man mit dem klassischen Blitzkugel-Verfahren stets auf der „sicheren Seite“ liegt.
Purpose:
To investigate the feasibility of using magnetohydrodynamic (MHD) effects for synchronization of magnetic resonance imaging (MRI) with the cardiac cycle.
Materials and Methods:
The MHD effect was scrutinized using a pulsatile flow phantom at B0 = 7.0 T. MHD effects were examined in vivo in healthy volunteers (n = 10) for B0 ranging from 0.05–7.0 T. Noncontrast-enhanced MR angiography (MRA) of the carotids was performed using a gated steady-state free-precession (SSFP) imaging technique in conjunction with electrocardiogram (ECG) and MHD synchronization.
Results:
The MHD potential correlates with flow velocities derived from phase contrast MRI. MHD voltages depend on the orientation between B0 and the flow of a conductive fluid. An increase in the interelectrode spacing along the flow increases the MHD potential. In vivo measurement of the MHD effect provides peak voltages of 1.5 mV for surface areas close to the common carotid artery at B0 = 7.0 T. Synchronization of MRI with the cardiac cycle using MHD triggering is feasible. MHD triggered MRA of the carotids at 3.0 T showed an overall image quality and richness of anatomic detail, which is comparable to ECG-triggered MRAs.
Conclusion:
This feasibility study demonstrates the use of MHD effects for synchronization of MR acquisitions with the cardiac cycle. J. Magn. Reson. Imaging 2012;36:364–372. © 2012 Wiley Periodicals, Inc.
Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect.
Real-time and reliable monitoring of the biogas process is crucial for a stable and efficient operation of biogas production in order to avoid digester breakdowns. The concentration of dissolved hydrogen (H₂) represents one of the key parameters for biogas process control. In this work, a one-chip integrated combined amperometric/field-effect sensor for monitoring the dissolved H₂ concentration has been developed for biogas applications. The combination of two different transducer principles might allow a more accurate and reliable measurement of dissolved H₂ as an early warning indicator of digester failures. The feasibility of the approach has been demonstrated by simultaneous amperometric/field-effect measurements of dissolved H₂ concentrations in electrolyte solutions. Both, the amperometric and the field-effect transducer show a linear response behaviour in the H₂ concentration range from 0.1 to 3% (v/v) with a slope of 198.4 ± 13.7 nA/% (v/v) and 14.9 ± 0.5 mV/% (v/v), respectively.
The chemical imaging sensor is a chemical sensor which is capable of visualizing the spatial distribution of chemical species in sample solution. In this study, a novel measurement system based on the chemical imaging sensor was developed to observe the inside of a Y-shaped microfluidic channel while injecting two sample solutions from two branches. From the collected chemical images, it was clearly observed that the injected solutions formed laminar flows in the microfluidic channel. In addition, ion diffusion across the laminar flows was observed. This label-free method can acquire quantitative data of ion distribution and diffusion in microfluidic devices, which can be used to determine the diffusion coefficients, and therefore, the molecular weights of chemical species in the sample solution.
In vitro studies of the degradation kinetic of biopolymers are essential for the design and optimization of implantable biomedical devices. In the presented work, a field-effect capacitive sensor has been applied for the real-time and in situ monitoring of degradation processes of biopolymers for the first time. The polymer-covered field-effect sensor is, in principle, capable to detect any changes in bulk, surface and interface properties of the polymer induced by degradation processes. The feasibility of this approach has been experimentally proven by using the commercially available biomedical polymer poly(D,L-lactic acid) (PDLLA) as a model system. PDLLA films of different thicknesses were deposited on the Ta₂O₅-gate surface of the field-effect structure from a polymer solution by means of spin-coating method. The polymer-modified field-effect sensors have been characterized by means of capacitance–voltage and impedance-spectroscopy method. The degradation of the PDLLA was accelerated by changing the degradation medium from neutral (pH 7.2) to alkaline (pH 9) condition, resulting in drastic changes in the capacitance and impedance spectra of the polymer-modified field-effect sensor.
Characterisation of polymeric materials as passivation layer for calorimetric H2O2 gas sensors
(2012)
Calorimetric gas sensors for monitoring the H₂O₂ concentration at elevated temperatures in industrial sterilisation processes have been presented in previous works. These sensors are built up in form of a differential set-up of a catalytically active and passive temperature-sensitive structure. Although, various types of catalytically active dispersions have been studied, the passivation layer has to be established and therefore, chemically as well as physically characterised. In the present work, fluorinated ethylene propylene (FEP), perfluoralkoxy (PFA) and epoxy-based SU-8 photoresist as temperature-stable polymeric materials have been investigated for sensor passivation in terms of their chemical inertness against H₂O₂, their hygroscopic properties as well as their morphology. The polymeric materials were deposited via spin-coating on the temperature-sensitive structure, wherein spin-coated FEP and PFA show slight agglomerates. However, they possess a low absorption of humidity due to their hydrophobic surface, whereas the SU-8 layer has a closed surface but shows a slightly higher absorption of water. All of them were inert against gaseous H₂O₂ during the characterisation in H₂O₂ atmosphere that demonstrates their suitability as passivation layer for calorimetric H₂O₂ gas sensors.
In this paper we present CAESAR, an intelligent domestic service robot. In domestic settings for service robots complex tasks have to be accomplished. Those tasks benefit from deliberation, from robust action execution and from flexible methods for human–robot interaction that account for qualitative notions used in natural language as well as human fallibility. Our robot CAESAR deploys AI techniques on several levels of its system architecture. On the low-level side, system modules for localization or navigation make, for instance, use of path-planning methods, heuristic search, and Bayesian filters. For face recognition and human–machine interaction, random trees and well-known methods from natural language processing are deployed. For deliberation, we use the robot programming and plan language READYLOG, which was developed for the high-level control of agents and robots; it allows combining programming the behaviour using planning to find a course of action. READYLOG is a variant of the robot programming language Golog. We extended READYLOG to be able to cope with qualitative notions of space frequently used by humans, such as “near” and “far”. This facilitates human–robot interaction by bridging the gap between human natural language and the numerical values needed by the robot. Further, we use READYLOG to increase the flexible interpretation of human commands with decision-theoretic planning. We give an overview of the different methods deployed in CAESAR and show the applicability of a system equipped with these AI techniques in domestic service robotics
We analyze the trading behavior of individual investors in option-like securities, namely bankissued warrants, and thus expand the growing literature of investors behavior to a new kind of securities. A unique data set from a large German discount broker gives us the opportunity to analyze the trading behavior of 1,454 investors, making 89,958 transactions in 6,724 warrants on 397 underlyings. In different logit regression, we make use of the facts that investors can speculate on rising and falling prices of the underlying with call and put warrants and that we also have information about the stock portfolios of the investors. We report several facts about the trading behavior of individual investors in warrants that are consistent with the literature on the behavior of individual investors in the stock market. The warrant investors buy calls and sell puts if the price of the underlying has decreased over the past trading days and they sell calls and buy puts if the price of the underlying has increased. That means, the investors follow negative feedback trading strategies in all four trading categories observed. In addition, we find strong evidence for the disposition effect for call as well as put warrants, which is reversed in December. The trading behavior is also influenced if the underlying reaches some exceptionally prices, e.g. highs, lows or the strike price. We show that hedging, as one natural candidate to buy puts, does not play an important role in the market for bank-issued warrants.
Two of the main environmental problems of today’s society are the continuously increasing production of organic wastes as well as the increase of carbon dioxide in the atmosphere and the related green house effect. A way to solve these problems is the production of biogas. Biogas is a combustible gas consisting of methane, carbon dioxide and small amounts of other gases and trace elements. Production of biogas through anaerobic digestion of animal manure and slurries as well as of a wide range of digestible organic wastes and agricultural residues, converts these substrates into electricity and heat and offers a natural fertiliser for agriculture. The microbiological process of decomposition of organic matter, in the absence of oxygen takes place in reactors, called digesters. Biogas can be used as a fuel in a gas turbine or burner and can be used in a hybrid solar tower system offering a solution for waste treatment of agricultural and animal residues. A solar tower system consists of a heliostat field, which concentrates direct solar irradiation on an open volumetric central receiver. The receiver heats up ambient air to temperatures of around 700°C. The hot air’s heat energy is transferred to a steam Rankine cycle in a heat recovery steam generator (HRSG). The steam drives a steam turbine, which in turn drives a generator for producing electricity. In order to increase the operational hours of a solar tower power plant, a heat storage system and/ or hybridization may be considered. The advantage of solar-fossil hybrid power plants, compared to solar-only systems, lies in low additional investment costs due to an adaptable solar share and reduced technical and economical risks. On sunny days the hybrid system operates in a solar-only mode with the central receiver and on cloudy days and at night with the gas turbine only. As an alternative to methane gas, environmentally neutral biogas can be used for operating the gas turbine. Hence, the hybrid system is operated to 100% from renewable energy sources
Betriebskostenabrechnung - Die Pflicht des Vermieters zur Beachtung des Wirtschaftlichkeitsgebots
(2012)
Mit seiner aktuellen Entscheidung (BGH v. 6.11.2011 – VIII ZR 340/10, MDR 2011, 1095 = MietRB MDR 2011, 337) hat der BGH die Darlegungs- und Beweislast für einen Verstoß gegen das Gebot der Wirtschaftlichkeit bei der Abrechnung von Betriebskosten konkretisiert. Der Beitrag erläutert anhand der Hintergründe des Gebotes der Wirtschaftlichkeit die Konsequenzen für die Praxis.
Außerbilanzielle Korrekturen
(2012)
Auswahl der Herniennetze nach der “effektiven Porosität” - warum das Gewicht weniger wichtig ist
(2012)
Air- and water-stable phenyl complexes with nitridotechnetium(V) cores can be prepared by straightforward procedures. [TcNPh2(PPh3)2] is formed by the reaction of [TcNCl2(PPh3)2] with PhLi. The analogous N-heterocyclic carbene (NHC) compound [TcNPh2(HLPh)2], where HLPh is 1,3,4-triphenyl-1,2,4-triazol-5-ylidene, is available from (NBu4)[TcNCl4] and HLPh or its methoxo-protected form. The latter compound allows the comparison of different Tc–C bonds within one compound. Surprisingly, the Tc chemistry with such NHCs does not resemble that of corresponding Re complexes, where CH activation and orthometalation dominate.
Often, detailed simulations of heat conduction in complicated, porous media have large runtimes. Then homogenization is a powerful tool to speed up the calculations by preserving accurate solutions at the same time. Unfortunately real structures are generally non-periodic, which requires unpractical, complicated homogenization techniques. We demonstrate in this paper, that the application of simple, periodic techniques to realistic media, that are just close to periodic, gives accurate, approximative solutions. In order to obtain effective parameters for the homogenized heat equation, we have to solve a so called “cell problem”. In contrast to periodic structures it is not trivial to determine a suitable unit cell, which represents a non-periodic media. To overcome this problem, we give a rule of thumb on how to choose a good cell. Finally we demonstrate the efficiency of our method for virtually generated foams as well as real foams and compare these results to periodic structures.
Deoxyribonucleic acid (DNA) and protein recognition are now standard tools in biology. In addition, the special optical properties of microsphere resonators expressed by the high quality factor (Q-factor) of whispering gallery modes (WGMs) or morphology dependent resonances (MDRs) have attracted the attention of the biophotonic community. Microsphere-based biosensors are considered as powerful candidates to achieve label-free recognition of single molecules due to the high sensitivity of their WGMs. When the microsphere surface is modified with biomolecules, the effective refractive index and the effective size of the microsphere change resulting in a resonant wavelength shift. The transverse electric (TE) and the transverse magnetic (TM) elastic light scattering intensity of electromagnetic waves at 600 and 1400 nm are numerically calculated for DNA and unspecific binding of proteins to the microsphere surface. The effect of changing the optical properties was studied for diamond (refractive index 2.34), glass (refractive index 1.50), and sapphire (refractive index 1.75) microspheres with a 50 µm radius. The mode spacing, the linewidth of WGMs, and the shift of resonant wavelength due to the change in radius and refractive index, were analyzed by numerical simulations. Preliminary results of unspecific binding of biomolecules are presented. The calculated shift in WGMs can be used for biomolecules detection.
The esophageal Doppler monitor (EDM) is a minimally-invasive hemodynamic device which evaluates both cardiac output (CO), and fluid status, by estimating stroke volume (SV) and calculating heart rate (HR). The measurement of these parameters is based upon a continuous and accurate approximation of distal thoracic aortic blood flow. Furthermore, the peak velocity (PV) and mean acceleration (MA), of aortic blood flow at this anatomic location, are also determined by the EDM. The purpose of this preliminary report is to examine additional clinical hemodynamic calculations of: compliance (C), kinetic energy (KE), force (F), and afterload (TSVRi). These data were derived using both velocity-based measurements, provided by the EDM, as well as other contemporaneous physiologic parameters. Data were obtained from anesthetized patients undergoing surgery or who were in a critical care unit. A graphical inspection of these measurements is presented and discussed with respect to each patient’s clinical situation. When normalized to each of their initial values, F and KE both consistently demonstrated more discriminative power than either PV or MA. The EDM offers additional applications for hemodynamic monitoring. Further research regarding the accuracy, utility, and limitations of these parameters is therefore indicated.
Many tasks for autonomous agents or robots are best described by a specification of the environment and a specification of the available actions the agent or robot can perform. Combining such a specification with the possibility to imperatively program a robot or agent is what we call the actionbased imperative programming. One of the most successful such approaches is Golog. In this paper, we draft a proposal for a new robot programming language YAGI, which is based on the action-based imperative programming paradigm. Our goal is to design a small, portable stand-alone YAGI interpreter. We combine the benefits of a principled domain specification with a clean, small and simple programming language, which does not exploit any side-effects from the implementation language. We discuss general requirements of action-based programming languages and outline YAGI, our action-based language approach which particularly aims at embeddability.
This paper presents the latest prototype of the integrated emitter turn-off thyristor concept, which potentially ranks among thyristor high-power devices like the gate turn-off thyristor and the integrated gate-commutated thyristor (IGCT). Due to modifications of the external driver stage and mechanical press-pack design optimization, this prototype allows for full device characterization. The turn-off capability was increased to 1600 A with an active silicon area of 823mm2 . This leads to a transient peak power of 672.1kW/cm² . Within this paper, measurements and concept assessment are presented and a comparison to state-of-the-art IGCT devices is provided.
As the potential of a next generation network (NGN) is recognised, telecommunication companies consider switching to it. Although the implementation of an NGN seems to be merely a modification of the network infrastructure, it may trigger or require changes in the whole company, because it builds upon the separation between service and transport, a flexible bundling of services to products and the streamlining of the IT infrastructure. We propose a holistic framework, structured into the layers ‘strategy’, ‘processes’ and ‘information systems’ and incorporate into each layer all concepts necessary for the implementation of an NGN, as well as the alignment of these concepts. As a first proof-of-concept for our framework we have performed a case study on the introduction of NGN in a large telecommunication company; we show that our framework captures all topics that are affected by an NGN implementation.
South Africa in recent years is the establishment of a number of research hubs involved in AI activities ranging from mobile robotics and computational intelligence, to knowledge representation and reasoning, and human language technologies. In this survey we take the reader through a quick tour of the research being conducted at these hubs, and touch on an initiative to maintain and extend the current level of interest in AI research in the country.