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The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.
Background
True date palms (Phoenix dactylifera L.) are impressive trees and have served as an indispensable source of food for mankind in tropical and subtropical countries for centuries. The aim of this study is to differentiate date palm tree varieties by analysing leaflet cross sections with technical/optical methods and artificial neural networks (ANN).
Results
Fluorescence microscopy images of leaflet cross sections have been taken from a set of five date palm tree cultivars (Hewlat al Jouf, Khlas, Nabot Soltan, Shishi, Um Raheem). After features extraction from images, the obtained data have been fed in a multilayer perceptron ANN with backpropagation learning algorithm.
Conclusions
Overall, an accurate result in prediction and differentiation of date palm tree cultivars was achieved with average prediction in tenfold cross-validation is 89.1% and reached 100% in one of the best ANN.
Objectives
The aim of this study was to identify characteristics of phosphorus (³¹P) spectra of the human prostate and to investigate changes of individual phospholipid metabolites in prostate cancer through in vivo ³¹P magnetic resonance spectroscopic imaging (MRSI) at 7 T.
Materials and Methods
In this institutional review board–approved study, 15 patients with biopsy-proven prostate cancer underwent T₂-weighted magnetic resonance imaging and 3-dimensional ³¹P MRSI at 7 T. Voxels were selected at the tumor location, in normal-appearing peripheral zone tissue, normal-appearing transition zone tissue, and in the base of the prostate close to the seminal vesicles. Phosphorus metabolite ratios were determined and compared between tissue types.
Results
Signals of phosphoethanolamine (PE) and phosphocholine (PC) were present and well resolved in most ³¹P spectra in the prostate. Glycerophosphocholine signals were observable in 43% of the voxels in malignant tissue, but in only 10% of the voxels in normal-appearing tissue away from the seminal vesicles. In many spectra, independent of tissue type, 2 peaks resonated in the chemical shift range of inorganic phosphate, possibly representing 2 separate pH compartments. The PC/PE ratio in the seminal vesicles was highly elevated compared with the prostate in 5 patients. A considerable overlap of ³¹P metabolite ratios was found between prostate cancer and normal-appearing prostate tissue, preventing direct discrimination of these tissues. The only 2 patients with high Gleason scores tumors (≥4+5) presented with high PC and glycerophosphocholine levels in their cancer lesions.
Conclusions
Phosphorus MRSI at 7 T shows distinct features of phospholipid metabolites in the prostate gland and its surrounding structures. In this exploratory study, no differences in ³¹P metabolite ratios were observed between prostate cancer and normal-appearing prostate tissue possibly because of the partial volume effects of small tumor foci in large MRSI voxels.
A microcavity-based deoxyribonucleic acid (DNA) optical biosensor is demonstrated for the first time using synthetic sapphire for the optical cavity. Transmitted and elastic scattering intensity at 1510 nm are analyzed from a sapphire microsphere (radius 500 μm, refractive index 1.77) on an optical fiber half coupler. The 0.43 nm angular mode spacing of the resonances correlates well with the optical size of the sapphire sphere. Probe DNA consisting of a 36-mer fragment was covalently immobilized on a sapphire microsphere and hybridized with a 29-mer target DNA. Whispering gallery modes (WGMs) were monitored before the sapphire was functionalized with DNA and after it was functionalized with single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). The shift in WGMs from the surface modification with DNA was measured and correlated well with the estimated thickness of the add-on DNA layer. It is shown that ssDNA is more uniformly oriented on the sapphire surface than dsDNA. In addition, it is shown that functionalization of the sapphire spherical surface with DNA does not affect the quality factor (Q≈104) of the sapphire microspheres. The use of sapphire is especially interesting because this material is chemically resilient, biocompatible, and widely used for medical implants.
Picosecond dynamics in haemoglobin from different species: A quasielastic neutron scattering study
(2014)
Planar and three-dimensional (3D) interdigitated electrodes (IDE) with electrode digits separated by an insulating barrier of different heights were electrochemically characterized and compared in terms of their sensing properties. Due to the impact of the surface resistance, both types of IDE structures display a non-linear behavior in low-ionic strength solutions. The experimental data were fitted to an electrical equivalent circuit and interpreted taking into account the surface-charge-governed properties. The effect of a charged polyelectrolyte layer electrostatically assembled onto the sensor surface on the surface resistance in solutions with different KCl concentration is studied. In case of the same electrode footprint, 3D-IDEs show a larger cell constant and a higher sensitivity to molecular adsorption than that of planar IDEs. The obtained results demonstrate the potential of 3D-IDEs as a new transducer structure for a direct label-free sensing of charged molecules.
In co-operation with the German Aerospace Center, the Solar-Institut Jülich has been analyzing the different technologies that are available for methanol production from CO2 using solar energy. The aim of the project is to extract CO2 from industrial exhaust gases or directly from the atmosphere to recycle it by use of solar energy. Part of the study was the modeling and simulating of a methane reformer for the production of synthesis gas, which can be operated by solar or hybrid heat sources. The reformer has been simplified in such a way that the model is accurate and enables fast calculations. The developed pseudo-homogeneous one- dimensional model can be regarded as a kind of counter-current heat exchanger and is able to incorporate a steam reforming reaction as well as a dry reforming reaction.
A major part of edible oil is subjected to bleaching procedures, primarily with minerals applied as adsorbers. Their recycling is currently done either by regaining the oil via organic solvent extraction or by using the spent bleaching earth (SBE) as additive for animal feed, etc. As a new method, the reutilization of the by-product SBE for the microbiologic formation of acetone, butanol, and ethanol (ABE) is presented as proof-of-concept. The SBE was taken from a palm oil cleaning process. The recycling concept is based on the application of lipolytic clostridia strains. Due to considerably long fermentation times, co-fermentation with Candida rugosa and enzymatic hydrolyses of the bound oil with a subsequent clostridia fermentation are shown as alternative routes. Anaerobic fermentations under comparison of different clostridia strains were performed with glycerol media, enzymatically hydrolyzed palm oil and SBE. Solutes, side product compositions and productivities were quantified via HPLC. A successful production of ABE solutes from SBE has been done with a yield of 0.15 g butanol per gram of bound glycerol. Thus, the biotechnological recycling of the waste stream is possible in principle. Inhibition of the substrate suspension has been observed. A chromatographic ion-exchange of substrates increased the biomass concentration.
Die erdbebensichere Auslegung von erdverlegten Rohrleitungssystemen ist von wesentlicher Bedeutung zur Sicherstellung der Funktionalität der Versorgungsinfrastruktur nach einem Erdbebenereignis. Zur Vermeidung von Netzausfällen ist es erforderlich, die räumlich weit ausgedehnten Leitungssysteme mit geeigneten rechnerischen Modellen seismisch zu bemessen. Der vorliegende Beitrag behandelt die Beanspruchung von Rohrleitungssystemen durch seismische Welleneinwirkung und stellt geeignete Näherungsansätze und ein detailliertes Rechenmodell für seismische Leitungsanalysen vor. Mit den Ansätzen wird in Berechnungsbeispielen der Einfluss wesentlicher Parameter auf die seismisch induzierten Dehnungen in Rohrleitungssystemen untersucht.
Die PIA GmbH prüft seit fast 8 Jahren die Standsicherheit von Behältern für Kleinkläranlagen. Diese bestehen in der Regel aus Kunststoff oder Beton und müssen über ihre gesamte Lebensdauer den Beanspruchungen aus Handhabung, Einbau und Betrieb standhalten. Die Standsicherheit kann nach EN 12566 wahlweise durch einen rechnerischen Nachweis oder durch einen praktischen Nachweis wie die Bruchlastprüfung oder die Prüfung in der Grube erfolgen.
The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found widely in nature and it is exploited in industrial processes for the manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its varied natural habitats and in industrial settings, B. licheniformis cells will be exposed to increases in the external osmolarity, conditions that trigger water efflux, impair turgor, cause the cessation of growth, and negatively affect the productivity of cell factories in biotechnological processes. We have taken here both systems-wide and targeted physiological approaches to unravel the core of the osmostress responses of B. licheniformis. Cells were suddenly subjected to an osmotic upshift of considerable magnitude (with 1 M NaCl), and their transcriptional profile was then recorded in a time-resolved fashion on a genome-wide scale. A bioinformatics cluster analysis was used to group the osmotically up-regulated genes into categories that are functionally associated with the synthesis and import of osmostress-relieving compounds (compatible solutes), the SigB-controlled general stress response, and genes whose functional annotation suggests that salt stress triggers secondary oxidative stress responses in B. licheniformis. The data set focusing on the transcriptional profile of B. licheniformis was enriched by proteomics aimed at identifying those proteins that were accumulated by the cells through increased biosynthesis in response to osmotic stress. Furthermore, these global approaches were augmented by a set of experiments that addressed the synthesis of the compatible solutes proline and glycine betaine and assessed the growth-enhancing effects of various osmoprotectants. Combined, our data provide a blueprint of the cellular adjustment processes of B. licheniformis to both sudden and sustained osmotic stress.
Two single-incision mini-slings used for treating urinary incontinence in women are compared with respect to the stresses they produce in their surrounding tissue. In an earlier paper we experimentally observed that these implants produce considerably different stress distributions in a muscle tissue equivalent. Here we perform 2D finite element analyses to compare the shear stresses and normal stresses in the tissue equivalent for the two meshes and to investigate their failure behavior. The results clearly show that the Gynecare TVT fails for increasing loads in a zipper-like manner because it gradually debonds from the surrounding tissue. Contrary to that, the tissue at the ends of the DynaMesh-SIS direct may rupture but only at higher loads. The simulation results are in good agreement with the experimental observations thus the computational model helps to interpret the experimental results and provides a tool for qualitative evaluation of mesh implants.
Poly(vinyl acetate), PVAc, with a degree of polymerization Xn = 10 was prepared by chain-transfer radical polymerization using carbon tetrachloride and used as oligomeric plasticizer for commercial PVAc. However, the chlorinated chain ends cause a low thermal stability requiring mild Cl/H substitution. The product exhibits high thermal stability and excellent melt-compounding properties. Blends of oligomeric and commercial PVAc show single glass transition temperatures which decrease with higher oligomer content and exhibit small negative deviations from Fox' linear additivity rule. This indicates plasticization and miscibility being mainly due to entropic effects. Injection-moulded thick specimens show ductile behaviour at oligomer contents >10 wt %, while sheets with a thickness of 0.2–0.5 mm appear flexible already at 7.5 wt %. The oxygen permeability coefficients are an order of magnitude lower than those of low-density polyethylene. Due to the sum of their properties, the plasticized sheets present a promising alternative in the preparation of barrier materials.
The light-addressable potentiometric sensor (LAPS) is a semiconductor-based potentiometric sensor using a light probe with an ability of detecting the concentration of biochemical species in a spatially resolved manner. As an important biomedical sensor, research has been conducted to improve its performance, for instance, to realize high-speed measurement. In this work, the idea of facilitating the device-level simulation, instead of using an equivalent-circuit model, is presented for detailed analysis and optimization of the performance of the LAPS. Both carrier distribution and photocurrent response have been simulated to provide new insight into both amplitude-mode and phase-mode operations of the LAPS. Various device parameters can be examined to effectively design and optimize the LAPS structures and setups for enhanced performance.
Therefore Fermat is right
(2014)
It was Fernat's idea to investigate how many numbers would fulfill the equation according to the Pythagorean Theorem if the exponent were increased to random, e.g. to a3 + b3 = c3. His question became therefore: are there two whole numbers the cubes of which add up to the volume of the cube of a third whole number? He posed this same question, of course, for all kinds of higher exponents, so that the equation could be generalized: is there an integral solution for the equation an + bn = cn, if the exponent n is higher than 2? Although in 1993, the English mathematician Andrew Wiles was able to produce an arithmetical proof for Fermat's famous theorem, I will show that there is a simple logical explanation which is also pragmatic and plausible and what is the result of a fundamental alternative idea how our world seems to be constructed.
The metabolic activity of Chinese hamster ovary (CHO) cells was observed using a light-addressable potentiometric sensor (LAPS). The dependency toward different glucose concentrations (17–200 mM) follows a Michaelis–Menten kinetics trajectory with Kₘ = 32.8 mM, and the obtained Kₘ value in this experiment was compared with that found in literature. In addition, the pH shift induced by glucose metabolism of tumor cells transfected with the HPV-16 genome (C3 cells) was successfully observed. These results indicate the possibility to determine the tumor cells metabolism with a LAPS-based measurement device.
In this work the transient simulations of four hybrid solar tower power plant concepts with open-volumetric receiver technology for a location in Barstow-Daggett, USA, are presented. The open-volumetric receiver uses ambient air as heat transfer fluid and the hybridization is realized with a gas turbine. The Rankine cycle is heated by solar-heated air and/or by the gas turbine's flue gases. The plant can be operated in solar-only, hybrid parallel or combined cycle-only mode as well as in any intermediate load levels where the solar portion can vary between 0 to 100%.
The simulated plant is based on the configuration of a solar-hybrid power tower project, which is in planning for a site in Northern Algeria. The meteorological data for Barstow-Daggett was taken from the software meteonorm. The solar power tower simulation tool has been developed in the simulation environment MATLAB/Simulink and is validated.
Validation of a novel method for detecting and stabilizing malfunctioning areas in fuel cell stacks
(2014)
In this paper a setup for detecting malfunctioning areas of MEAs in fuel cell stacks is described. Malfunctioning areas generate electric cross currents inside bipolar plates. To exploit this we suggest bipolar plates consisting not of two but of three layers. The third one is a highly conducting layer and segmented such that the cross currents move along the segments to the surface of the stack where they can be measured by an inductive sensor. With this information a realistic model can be used to detect the malfunctioning area. Furthermore the third layer will prevent any current inhomogeneity of a malfunctioning cell to spread to neighbouring cells in the stack. In this work the results of measurements in a realistic cell setup will be compared with the results obtained in simulation studies with the same configuration. The basis for the comparison is the reliable characterisation of the electrical properties of the cell components and the implication of these results into the simulation model. The experimental studies will also show the limits in the maximum number of segments, which can be used for a reliable detection of cross currents.
Following earlier studies, we present forward and inverse simulations of heat and fluid transport of the upper crust using a local 3-D model of the Kola area. We provide best estimates for palaeotemperatures and permeabilities, their errors and their dependencies. Our results allow discriminating between the two mentioned processes to a certain extent, partly resolving the non-uniqueness of the problem. We find clear indications for a significant contribution of advective heat transport, which, in turn, imply only slightly lower ground surface temperatures during the last glacial maximum relative to the present value. These findings are consistent with the general background knowledge of (i) the fracture zones and the corresponding fluid movements in the bedrock and (ii) the glacial history of the Kola area.
Vestibular effects of a 7 Tesla MRI examination compared to 1.5 T and 0 T in healthy volunteers
(2014)
Ultra-high-field MRI (7 Tesla (T) and above) elicits more temporary side-effects compared to 1.5 T and 3 T, e.g. dizziness or “postural instability” even after exiting the scanner. The current study aims to assess quantitatively vestibular performance before and after exposure to different MRI scenarios at 7 T, 1.5 T and 0 T. Sway path and body axis rotation (Unterberger's stepping test) were quantitatively recorded in a total of 46 volunteers before, 2 minutes after, and 15 minutes after different exposure scenarios: 7 T head MRI (n = 27), 7 T no RF (n = 22), 7 T only B₀ (n = 20), 7 T in & out B₀ (n = 20), 1.5 T no RF (n = 20), 0 T (n = 15). All exposure scenarios lasted 30 minutes except for brief one minute exposure in 7 T in & out B₀. Both measures were documented utilizing a 3D ultrasound system. During sway path evaluation, the experiment was repeated with eyes both open and closed. Sway paths for all long-lasting 7 T scenarios (normal, no RF, only B₀) with eyes closed were significantly prolonged 2 minutes after exiting the scanner, normalizing after 15 minutes. Brief exposure to 7 T B₀ or 30 minutes exposure to 1.5 T or 0 T did not show significant changes. End positions after Unterberger's stepping test were significantly changed counter-clockwise after all 7 T scenarios, including the brief in & out B₀ exposure. Shorter exposure resulted in a smaller alteration angle. In contrast to sway path, reversal of changes in body axis rotation was incomplete after 15 minutes. 1.5 T caused no rotational changes. The results show that exposure to the 7 Tesla static magnetic field causes only a temporary dysfunction or “over-compensation” of the vestibular system not measurable at 1.5 or 0 Tesla. Radiofrequency fields, gradient switching, and orthostatic dysregulation do not seem to play a role.
Heute wie damals werden die großzügigen und offenen Siedlungsstrukturen der ersten Nachkriegsjahrzehnte mit ihrem hohen Anteil an "Grün" vielfach geschätzt und als solche nicht grundlegend hinterfragt. "Grün" verheißt im Allgemeinen Licht, Luft und Sonne, Freizeit und Erholung und gilt als etwas Wünschenswertes im städtischen Kontext. Unbeachtet bleibt, dass dem Begriff "Grün" zunächst keine Eigenschaften oder Qualitäten zugewiesen sind - er sagt noch lange nichts über dessen räumliche Qualität, dessen Nutzbarkeit, Erreichbarkeit und Zugänglichkeit aus. Abstandsgrün und Straßenbegleitgrün ist eben auch "Grün". Neben einer quantitativen Argumentation, welche ökologischen Aspekte wie Biotopvernetzung, Stadt- und Mikroklima berücksichtigt, sollten wir verstärkt qualitativ denken und damit die Grundlage für einen erweiterten und wesentlich differenzierteren Diskurs über urbane Freiräume ebnen.
Wohnungseigentümergemeinschaft - Einstimmigkeitserfordernis bei Errichtung einer Mobilfunkantenne
(2014)
Der BGH (BGH v. 25.1.2014 – V ZR 48/13, MDR 2014, 399) hatte darüber zu befinden, ob auf dem Dach eines Hauses, das im Eigentum einer Wohnungseigentümergemeinschaft steht, auch gegen den Willen eines einzelnen Eigentümers eine Mobilfunkantenne angebracht werden kann. Das Urteil führt in das Spannungsfeld einer Abwägung zwischen Mehrheits- und Individualinteressen innerhalb einer WEG. Insoweit betont der BGH den grundsätzlichen Vorrang der Individualinteressen, jedenfalls soweit es um Beeinträchtigungen geht, die verständlicherweise von einem Eigentümer abgelehnt werden können. Der BGH verlangt im Ergebnis im Zweifel eine allseitige Zustimmung. Das Urteil ist zu begrüßen, lässt aber für die Zukunft Abgrenzungsfragen offen.
Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t₁⸝₂ = 3.97 h, Eavg,β⁺ = 1.47 MeV, branching ratio = 94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations.