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Chelate stabilization of a titanium(IV)–salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model.
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.
All cells generate contractile tension. This strain is crucial for mechanically controlling the cell shape, function and survival. In this study, the CellDrum technology quantifying cell's (the cellular) mechanical tension on a pico-scale was used to investigate the effect of lipopolysaccharide (LPS) on human aortic endothelial cell (HAoEC) tension. The LPS effect during gram-negative sepsis on endothelial cells is cell contraction causing endothelium permeability increase. The aim was to finding out whether recombinant activated protein C (rhAPC) would reverse the endothelial cell response in an in-vitro sepsis model. In this study, the established in-vitro sepsis model was confirmed by interleukin 6 (IL-6) levels at the proteomic and genomic levels by ELISA, real time-PCR and reactive oxygen species (ROS) activation by florescence staining. The thrombin cellular contraction effect on endothelial cells was used as a positive control when the CellDrum technology was applied. Additionally, the Ras homolog gene family, member A (RhoA) mRNA expression level was checked by real time-PCR to support contractile tension results. According to contractile tension results, the mechanical predominance of actin stress fibers was a reason of the increased endothelial contractile tension leading to enhanced endothelium contractility and thus permeability enhancement. The originality of this data supports firstly the basic measurement principles of the CellDrum technology and secondly that rhAPC has a beneficial effect on sepsis influenced cellular tension. The technology presented here is promising for future high-throughput cellular tension analysis that will help identify pathological contractile tension responses of cells and prove further cell in-vitro models.
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.
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
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.
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.
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.
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.
N,N-Dialkylamino(thiocarbonyl)-N′-picolylbenzamidines react with (NEt4)2[M(CO)3X3] (M = Re, X = Br; M = Tc, X = Cl) under formation of neutral [M(CO)3L] complexes in high yields. The monoanionic NNS ligands bind in a facial coordination mode and can readily be modified at the (CS)NR1R2 moiety. The complexes [99Tc(CO)3(LPyMor)] and [Re(CO)3(L)] (L = LPyMor, LPyEt) were characterized by X-ray diffraction. Reactions of [99mTc(CO)3(H2O)3]+ with the N′-thiocarbamoylpicolylbenzamidines give the corresponding 99mTc complexes. The ester group in HLPyCOOEt allows linkage between biomolecules and the metal core.
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.
s the magnetic field strength and therefore the operational frequency in MRI are increased, the radiofrequency wavelength approaches the size of the human head/body, resulting in wave effects which cause signal decreases and dropouts. Especially, whole-body imaging at 7 T and higher is therefore challenging. Recently, an acquisition scheme called time-interleaved acquisition of modes has been proposed to tackle the inhomogeneity problems in high-field MRI. The basic premise is to excite two (or more) different Burn:x-wiley:07403194:media:MRM23081:tex2gif-stack-1 modes using static radiofrequency shimming in an interleaved acquisition, where the complementary radiofrequency patterns of the two modes can be exploited to improve overall signal homogeneity. In this work, the impact of time-interleaved acquisition of mode on image contrast as well as on time-averaged specific absorption rate is addressed in detail. Time-interleaved acquisition of mode is superior in Burn:x-wiley:07403194:media:MRM23081:tex2gif-stack-2 homogeneity compared with conventional radiofrequency shimming while being highly specific absorption rate efficient. Time-interleaved acquisition of modes can enable almost homogeneous high-field imaging throughout the entire field of view in PD, T2, and T2*-weighted imaging and, if a specified homogeneity criterion is met, in T1-weighted imaging as well.
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.
This contribution discusses the utilization of RF power in an MRI system with RF mode shimming which enables the superposition of circularly polarized modes of a transmit RF coil array driven by a Butler matrix. Since the required power for the individual modes can vary widely, mode-shimming can result in a significant underutilization of the total available RF power. A variable power combiner (VPC) is proposed to improve the power utilization: it can be realized as a reconfiguration of the MRI transmit system by the inclusion of one additional matrix network which receives the power from all transmit amplifiers at its input ports and provides any desired (combined) power distribution at its output ports by controlling the phase and amplitude of the amplifiers’ input signals. The power distribution at the output ports of the VPC is then fed into the “mode” ports of the coil array Butler matrix in order to superimpose the spatial modes at the highest achievable power utilization. The VPC configuration is compared to the standard configuration of the transmit chain of our MRI system with 8 transmit channels and 16 coils. In realistic scenarios, improved power utilization was achieved from 17% to 60% and from 14% to 55% for an elliptical phantom and a region of interest in the abdomen, respectively, and an increase of the power utilization of 1 dB for a region of interest in the upper leg. In general, it is found that the VPC allows significant improvement in power utilization when the shimming solution demands only a few modes to be energized, while the technique can yield loss in power utilization in cases with many modes required at high power level.
Prioritization is an essential task within requirements engineering to cope with complexity and to establish focus properly. The 3rd Workshop on Requirements Prioritization for customer oriented Software Development (RePriCo’12) focused on requirements prioritization and adjacent themes in the context of customer oriented development of bespoke and standard software. Five submissions have been accepted for the proceedings and for presentation. The report summarizes and points out key findings.
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
Thermodynamic stability, configurational motions and internal forces of haemoglobin (Hb) of three endotherms (platypus, Ornithorhynchus anatinus; domestic chicken, Gallus gallus domesticus and human, Homo sapiens) and an ectotherm (salt water crocodile, Crocodylus porosus) were investigated using circular dichroism, incoherent elastic neutron scattering and coarse-grained Brownian dynamics simulations. The experimental results from Hb solutions revealed a direct correlation between protein resilience, melting temperature and average body temperature of the different species on the 0.1 ns time scale. Molecular forces appeared to be adapted to permit conformational fluctuations with a root mean square displacement close to 1.2 Å at the corresponding average body temperature of the endotherms. Strong forces within crocodile Hb maintain the amplitudes of motion within a narrow limit over the entire temperature range in which the animal lives. In fully hydrated powder samples of human and chicken, Hb mean square displacements and effective force constants on the 1 ns time scale showed no differences over the whole temperature range from 10 to 300 K, in contrast to the solution case. A complementary result of the study, therefore, is that one hydration layer is not sufficient to activate all conformational fluctuations of Hb in the pico- to nanosecond time scale which might be relevant for biological function. Coarse-grained Brownian dynamics simulations permitted to explore residue-specific effects. They indicated that temperature sensing of human and chicken Hb occurs mainly at residues lining internal cavities in the β-subunits.
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.
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.
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.
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.
The construction of a statistical test is investigated which is based only on “reliability” and “precision” as quality criteria. The reliability of a statistical test is quantifiedin a straightforward way by the probability that the decision of the test is correct. However, the quantification of the precision of a statistical test is not at all evident. Thereforethe paper presents and discusses several approaches. Moreover the distinction of “nullhypothesis” and “alternative hypothesis” is not necessary any longer.
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.
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.
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
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.
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.
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.
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.
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.
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.
Climate change is challenging forestry management and practices. Among other things, tree species with the ability to cope with more extreme climate conditions have to be identified. However, while environmental factors may severely limit tree growth or even cause tree death, assessing a tree species' potential for surviving future aggravated environmental conditions is rather demanding. The aim of this study was to find a tree-ring-based method suitable for identifying very drought-tolerant species, particularly potential substitute species for Scots pine (Pinus sylvestris L.) in Valais. In this inner-Alpine valley, Scots pine used to be the dominating species for dry forests, but today it suffers from high drought-induced mortality. We investigate the growth response of two native tree species, Scots pine and European larch (Larix decidua Mill.), and two non-native species, black pine (Pinus nigra Arnold) and Douglas fir (Pseudotsuga menziesii Mirb. var. menziesii), to drought. This involved analysing how the radial increment of these species responded to increasing water shortage (abandonment of irrigation) and to increasingly frequent drought years. Black pine and Douglas fir are able to cope with drought better than Scots pine and larch, as they show relatively high radial growth even after irrigation has been stopped and a plastic growth response to drought years. European larch does not seem to be able to cope with these dry conditions as it lacks the ability to recover from drought years. The analysis of trees' short-term response to extreme climate events seems to be the most promising and suitable method for detecting how tolerant a tree species is towards drought. However, combining all the methods used in this study provides a complete picture of how water shortage could limit species.
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.
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.
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.
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.
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.
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.
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.
Using a cell-based gas biosensor for investigation of adverse effects of acetone vapors in vitro
(2013)
We present a sensor concept based on copper(II)oxide (CuO) nanofibres for the detection of hydrogen peroxide (H2O2) vapour in the percent per volume (% v/v) range. The fibres were produced by using the electrospinning technique. To avoid water condensation in the pores, the fibres were initially modified by an exposure to H2S to get an enclosed surface. By a thermal treatment at 350 °C the fibres were oxidised back to CuO. Thereby, the visible pores disappear which was verified by SEM analysis. The fibres show a decrease of resistance with increasing H2O2 concentration which is due to the fact that hydrogen peroxide is an oxidising gas and CuO a p-type semiconductor. The sensor shows a change of resistance within the minute range to the exposure until the maximum concentration of 6.9% v/v H2O2. At operating temperatures below 450 °C the corresponding sensor response to a concentration of 4.1% v/v increases. The sensor shows a good reproducibility of the signal at different measurements. CuO seems to be a suitable candidate for the detection of H2O2 vapour at high concentrations.
Resistance behaviour of the sensor under exposure to H2O2 vapours between 2.3 and 6.9% v/v at an operating temperature of 450 °C.
In this work, a multi-sensor chip for the investigation of the sensing properties of different types of metal oxides towards hydrogen peroxide in the ppm range is presented. The fabrication process and physical characterization of the multi-sensor chip are described. Pure SnO2 and WO3 as well as Pd- and Pt-doped SnO2 films are characterized in terms of their sensitivity to H2O2. The sensing films have been prepared by drop-coating of water-dispensed nano-powders. A physical characterization, including scanning electron microscopy and X-ray diffraction analysis of the deposited metal-oxide films, was done. From the measurements in hydrogen peroxide atmosphere, it could be shown, that all of the tested metal oxide films are suitable for the detection of H2O2 in the ppm range. The highest sensitivity and reproducibility was achieved using Pt-doped SnO2.
Calibration plot of a SnO2, WO3, Pt-, and Pd-doped SnO2 gas sensor for H2O2 concentrations in the ppm range.
An increasing amount of popular articles focus on making models and sculptures by 3D Printing thus making more and more even private users aware of this technology. Unfortunately they mostly draw an incomplete picture of how our daily life will be influenced by this new technology. Often this is caused by a very technical point of view based on not very representative examples. This article focuses on the peoples needs as they have been structured by the so-called Maslow pyramid. Doing so, it underlines that 3D Printing (called Additive Manufacturing or Rapid Prototyping as well) already touches all aspects of life and is about to revolutionize most of them.
A wireless sensor system based on the industrial ZigBee standard for low-rate wireless networking was developed that enables real-time monitoring of gaseous H2O2 during the package sterilization in aseptic food processes. The sensor system consists of a remote unit connected to a calorimetric gas sensor, which was already established in former works, and an external base unit connected to a laptop computer. The remote unit was built up by an XBee radio frequency (RF) module for data communication and a programmable system-on-chip controller to read out the sensor signal and process the sensor data, whereas the base unit is a second XBee RF module. For the rapid H2O2 detection on various locations inside the package that has to be sterilized, a novel read-out strategy of the calorimetric gas sensor was established, wherein the sensor response is measured within the short sterilization time and correlated with the present H2O2 concentration. In an exemplary measurement application in an aseptic filling machinery, the suitability of the new, wireless sensor system was demonstrated, wherein the influence of the gas velocity on the H2O2 distribution inside a package was determined and verified with microbiological tests.
The chemical imaging sensor is a device to visualize the spatial distribution of chemical species based on the principle of LAPS (light-addressable potentiometric sensor), which is a field-effect chemical sensor based on semiconductor. In this study, the chemical imaging sensor has been applied to investigate the ion profile of laminar flows in a microfluidic channel. The chemical images (pH maps) were collected in a Y-shaped microfluidic channel while injecting HCl and NaCl solutions into two branches. From the chemical images, it was clearly observed that the injected solutions formed laminar flows in the channel. In addition, ion diffusion across the laminar flows was observed, and the diffusion coefficient could be derived by fitting the pH profiles to the Fick's equation.
Semiconductor-based chemical imaging sensors, like the light-addressable potentiometric sensor (LAPS) or the pH-imaging sensor based on a charge-coupled device (CCD), are becoming a powerful tool for label-free imaging of biological phenomena. We have proposed a polyion-based enzymatic membrane to develop an acetylcholine (ACh) imaging sensor for neural cell-activity observations. In this study, a CCD-type ACh-imaging sensor and a LAPS-type ACh-imaging sensor were fabricated and the prospect of both sensors was clarified by making a comparison of their basic characteristics.
In the present work, a novel method for monitoring sterilisation processes with gaseous H2O2 in combination with heat activation by means of a specially designed calorimetric gas sensor was evaluated. Therefore, the sterilisation process was extensively studied by using test specimens inoculated with Bacillus atrophaeus spores in order to identify the most influencing process factors on its microbicidal effectiveness. Besides the contact time of the test specimens with gaseous H2O2 varied between 0.2 and 0.5 s, the present H2O2 concentration in a range from 0 to 8% v/v (volume percent) had a strong influence on the microbicidal effectiveness, whereas the change of the vaporiser temperature, gas flow and humidity were almost negligible. Furthermore, a calorimetric H2O2 gas sensor was characterised in the sterilisation process with gaseous H2O2 in a wide range of parameter settings, wherein the measurement signal has shown a linear response against the H2O2 concentration with a sensitivity of 4.75 °C/(% v/v). In a final step, a correlation model by matching the measurement signal of the gas sensor with the microbial inactivation kinetics was established that demonstrates its suitability as an efficient method for validating the microbicidal effectiveness of sterilisation processes with gaseous H2O2.
Light-addressable potentiometric sensors (LAPS) are semiconductor-based potentiometric sensors, with the advantage to detect the concentration of a chemical species in a liquid solution above the sensor surface in a spatially resolved manner. The addressing is achieved by a modulated and focused light source illuminating the semiconductor and generating a concentration-depending photocurrent. This work introduces a LAPS set-up that is able to monitor the electrical impedance in addition to the photocurrent. The impedance spectra of a LAPS structure, with and without illumination, as well as the frequency behaviour of the LAPS measurement are investigated. The measurements are supported by electrical equivalent circuits to explain the impedance and the LAPS-frequency behaviour. The work investigates the influence of different parameters on the frequency behaviour of the LAPS. Furthermore, the phase shift of the photocurrent, the influence of the surface potential as well as the changes of the sensor impedance will be discussed.
The chemical imaging sensor is a semiconductor-based chemical sensor that can visualize the spatial distribution of specific ions on the sensing surface. The conventional chemical imaging system based on the light-addressable potentiometric sensor (LAPS), however, required a long time to obtain a chemical image, due to the slow mechanical scan of a single light beam. For high-speed imaging, a plurality of light beams modulated at different frequencies can be employed to measure the ion concentrations simultaneously at different locations on the sensor plate by frequency division multiplex (FDM). However, the conventional measurement geometry of back-side illumination limited the bandwidth of the modulation frequency required for FDM measurement, because of the low-pass filtering characteristics of carrier diffusion in the Si substrate. In this study, a high-speed chemical imaging system based on front-side-illuminated LAPS was developed, which achieved high-speed spatiotemporal recording of pH change at a rate of 70 frames per second.
Mass transfer correlation for evaporation–condensation thermal process in the range of 70 °C–95 °C
(2013)
Modeling contribution to risk assessment of thermal production power for geothermal reservoirs
(2013)
A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants
(2013)
Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b
(2013)
Size unlimited markerless deletions by a transconjugative plasmid-system in Bacillus licheniformis
(2013)
The carbonized rice husk (CRH) was evaluated for its wound healing activity in rats using excision models. In this study, the influences of CRH on wound healing in rat skin in vivo and cellular behavior of human dermal fibroblasts in vitro were investigated. The obtained results showed that the CRH treatment promoted wound epithelization in rats and exhibited moderate inhibition of cell proliferation in vitro. CRH with lanolin oil treated wounds were found to epithelize faster as compared to controls.