Search results for: Marcel Verwey

Authors: Geanderson Eduardo Ambrósio, Dênis Antônio Da Cunha, Marcel Viana Pires

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Historically, human development has been based on economic gains associated with intensive energy activities, which often are exhaustive in the emission of Greenhouse Gases (GHGs). It requires the establishment of targets for mitigation of GHGs in order to disassociate the human development from emissions and prevent further climate change. Brazil presents itself as one of the most GHGs emitters and it is of critical importance to discuss such reductions in intra-national framework with the objective of distributional equity to explore its full mitigation potential without compromising the development of less developed societies. This research displays some incipient considerations about which Brazil’s micro-regions should reduce, when the reductions should be initiated and what its magnitude should be. We started with the methodological assumption that human development and GHGs emissions arise in the future as their behavior was observed in the past. Furthermore, we assume that once a micro-region became developed, it is able to maintain gains in human development without the need of keep growing GHGs emissions rates. The human development index and the carbon dioxide equivalent emissions (CO2e) were extrapolated to the year 2050, which allowed us to calculate when the micro-regions will become developed and the mass of GHG’s emitted. The results indicate that Brazil must throw 300 GT CO2e in the atmosphere between 2011 and 2050, of which only 50 GT will be issued by micro-regions before it’s develop and 250 GT will be released after development. We also determined national mitigation targets and structured reduction schemes where only the developed micro-regions would be required to reduce. The micro-region of São Paulo, the most developed of the country, should be also the one that reduces emissions at most, emitting, in 2050, 90% less than the value observed in 2010. On the other hand, less developed micro-regions will be responsible for less impactful reductions, i.e. Vale do Ipanema will issue in 2050 only 10% below the value observed in 2010. Such methodological assumption would lead the country to issue, in 2050, 56.5% lower than that observed in 2010, so that the cumulative emissions between 2011 and 2050 would reduce by 130 GT CO2e over the initial projection. The fact of associating the magnitude of the reductions to the level of human development of the micro-regions encourages the adoption of policies that favor both variables as the governmental planner will have to deal with both the increasing demand for higher standards of living and with the increasing magnitude of reducing emissions. However, if economic agents do not act proactively in local and national level, the country is closer to the scenario in which emits more than the one in which mitigates emissions. The research highlighted the importance of considering the heterogeneity in determining individual mitigation targets and also ratified the theoretical and methodological feasibility to allocate larger share of contribution for those who historically emitted more. It is understood that the proposals and discussions presented should be considered in mitigation policy formulation in Brazil regardless of the adopted reduction target.

Keywords: greenhouse gases, human development, mitigation, intensive energy activities

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Authors: Marcel Schulze, Behrem Aslan, Silke Lux, Alexandra Philipsen

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Objective: Patients with Attention Deficit/Hyperactivity Disorder (ADHD) often report that they are being flooded by sensory impressions. Studies investigating sensory processing show hypersensitivity for sensory inputs across the senses in children and adults with ADHD. Especially the auditory modality is affected by deficient acoustical inhibition and modulation of signals. While studying unimodal signal-processing is relevant and well-suited in a controlled laboratory environment, everyday life situations occur multimodal. A complex interplay of the senses is necessary to form a unified percept. In order to achieve this, the unimodal sensory modalities are bound together in a process called multisensory integration (MI). In the current study we investigate MI in an adult ADHD sample using the McGurk-effect – a well-known illusion where incongruent speech like phonemes lead in case of successful integration to a new perceived phoneme via late top-down attentional allocation . In ADHD neuronal dysregulation at rest e.g., aberrant within or between network functional connectivity may also account for difficulties in integrating across the senses. Therefore, the current study includes resting-state functional connectivity to investigate a possible relation of deficient network connectivity and the ability of stimulus integration. Method: Twenty-five ADHD patients (6 females, age: 30.08 (SD:9,3) years) and twenty-four healthy controls (9 females; age: 26.88 (SD: 6.3) years) were recruited. MI was examined using the McGurk effect, where - in case of successful MI - incongruent speech-like phonemes between visual and auditory modality are leading to a perception of a new phoneme. Mann-Whitney-U test was applied to assess statistical differences between groups. Echo-planar imaging-resting-state functional MRI was acquired on a 3.0 Tesla Siemens Magnetom MR scanner. A seed-to-voxel analysis was realized using the CONN toolbox. Results: Susceptibility to McGurk was significantly lowered for ADHD patients (ADHDMdn:5.83%, ControlsMdn:44.2%, U= 160.5, p=0.022, r=-0.34). When ADHD patients integrated phonemes, reaction times were significantly longer (ADHDMdn:1260ms, ControlsMdn:582ms, U=41.0, p<.000, r= -0.56). In functional connectivity medio temporal gyrus (seed) was negatively associated with primary auditory cortex, inferior frontal gyrus, precentral gyrus, and fusiform gyrus. Conclusion: MI seems to be deficient for ADHD patients for stimuli that need top-down attentional allocation. This finding is supported by stronger functional connectivity from unimodal sensory areas to polymodal, MI convergence zones for complex stimuli in ADHD patients.

Keywords: attention-deficit hyperactivity disorder, audiovisual integration, McGurk-effect, resting-state functional connectivity

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Authors: Marcel Meinhardt, Manfred Keuser, Thomas Braml

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Cracking of reinforced concrete is a complex phenomenon induced by direct loads or restraints affecting reinforced concrete structures as soon as the tensile strength of the concrete is exceeded. Hence it is important to predict where cracks will be located and how they will propagate. The bond theory and the crack formulas in the actual design codes, for example, DIN EN 1992-1-1, are all based on the assumption that the reinforcement bars are embedded in homogeneous concrete without taking into account the influence of transverse reinforcement and the real stress situation. However, it can often be observed that real structures such as walls, slabs or beams show a crack spacing that is orientated to the transverse reinforcement bars or to the stirrups. In most Finite Element Analysis studies, the smeared crack approach is used for crack prediction. The disadvantage of this model is that the typical strain localization of a crack on element level can’t be seen. The crack propagation in concrete is a discontinuous process characterized by different factors such as the initial random distribution of defects or the scatter of material properties. Such behavior presupposes the elaboration of adequate models and methods of simulation because traditional mechanical approaches deal mainly with average material parameters. This paper concerned with the modelling of the initiation and the propagation of cracks in reinforced concrete structures considering the influence of transverse reinforcement and the real stress distribution in reinforced concrete (R/C) beams/plates in bending action. Therefore, a parameter study was carried out to investigate: (I) the influence of the transversal reinforcement to the stress distribution in concrete in bending mode and (II) the crack initiation in dependence of the diameter and distance of the transversal reinforcement to each other. The numerical investigations on the crack initiation and propagation were carried out with a 2D reinforced concrete structure subjected to quasi static loading and given boundary conditions. To model the uncertainty in the tensile strength of concrete in the Finite Element Analysis correlated normally and lognormally distributed random filed with different correlation lengths were generated. The paper also presents and discuss different methods to generate random fields, e.g. the Covariance Matrix Decomposition Method. For all computations, a plastic constitutive law with softening was used to model the crack initiation and the damage of the concrete in tension. It was found that the distributions of crack spacing and crack widths are highly dependent of the used random field. These distributions are validated to experimental studies on R/C panels which were carried out at the Laboratory for Structural Engineering at the University of the German Armed Forces in Munich. Also, a recommendation for parameters of the random field for realistic modelling the uncertainty of the tensile strength is given. The aim of this research was to show a method in which the localization of strains and cracks as well as the influence of transverse reinforcement on the crack initiation and propagation in Finite Element Analysis can be seen.

Keywords: crack initiation, crack modelling, crack propagation, cracks, numerical simulation, random fields, reinforced concrete, stochastic

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Authors: Alena Semeradtova, Marcel Stofik, Lucie Mareckova, Petr Maly, Ondrej Stanek, Jan Maly

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Recently, novel strategies based on so-called molecular evolution were shown to be effective for the production of various peptide ligand libraries with high affinities to molecular targets of interest comparable or even better than monoclonal antibodies. The major advantage of these peptide scaffolds is mainly their prevailing low molecular weight and simple structure. This study describes a new high-affinity binding molecules based immunesensor using a simple optical system for human serum albumin (HSA) detection as a model molecule. We present a comparison of two variants of recombinant binders based on albumin binding domain of the protein G (ABD) performed on micropatterned glass chip. Binding domains may be tailored to any specific target of interest by molecular evolution. Micropatterened glass chips were prepared using UV-photolithography on chromium sputtered glasses. Glass surface was modified by (3-aminopropyl)trietoxysilane and biotin-PEG-acid using EDC/NHS chemistry. Two variants of high-affinity binding molecules were used to detect target molecule. Firstly, a variant is based on ABD domain fused with TolA chain. This molecule is in vivo biotinylated and each molecule contains one molecule of biotin and one ABD domain. Secondly, the variant is ABD domain based on streptavidin molecule and contains four gaps for biotin and four ABD domains. These high-affinity molecules were immobilized to the chip surface via biotin-streptavidin chemistry. To eliminate nonspecific binding 1% bovine serum albumin (BSA) or 6% fetal bovine serum (FBS) were used in every step. For both variants range of measured concentrations of fluorescently labelled HSA was 0 – 30 µg/ml. As a control, we performed a simultaneous assay without high-affinity binding molecules. Fluorescent signal was measured using inverse fluorescent microscope Olympus IX 70 with COOL LED pE 4000 as a light source, related filters, and camera Retiga 2000R as a detector. The fluorescent signal from non-modified areas was substracted from the signal of the fluorescent areas. Results were presented in graphs showing the dependence of measured grayscale value on the log-scale of HSA concentration. For the TolA variant the limit of detection (LOD) of the optical immunosensor proposed in this study is calculated to be 0,20 µg/ml for HSA detection in 1% BSA and 0,24 µg/ml in 6% FBS. In the case of streptavidin-based molecule, it was 0,04 µg/ml and 0,07 µg/ml respectively. The dynamical range of the immunosensor was possible to estimate just in the case of TolA variant and it was calculated to be 0,49 – 3,75 µg/ml and 0,73-1,88 µg/ml respectively. In the case of the streptavidin-based the variant we didn´t reach the surface saturation even with the 480 ug/ml concentration and the upper value of dynamical range was not estimated. Lower value was calculated to be 0,14 µg/ml and 0,17 µg/ml respectively. Based on the obtained results, it´s clear that both variants are useful for creating the bio-recognizing layer on immunosensors. For this particular system, it is obvious that the variant based on streptavidin molecule is more useful for biosensing on glass planar surfaces. Immunosensors based on this variant would exhibit better limit of detection and wide dynamical range.

Keywords: high affinity binding molecules, human serum albumin, optical immunosensor, protein G, UV-photolitography

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Authors: Lacramioara Ochiuz, Manuela Hortolomei, Aurelia Vasile, Iulian Stoleriu, Marcel Popa, Cristian Peptu

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Local antibiotherapy is one of the most effective acne therapies. Erythromycin (ER) is a macrolide antibiotic topically administered for over 30 years in the form of gel, ointment or hydroalcoholic solution for the acne therapy. The use of ER as a base for topical dosage forms raises some technological challenges due to the physicochemical properties of this substance. The main disadvantage of ER is the poor water solubility (2 mg/mL) that limits both formulation using hydrophilic bases and skin permeability. Cyclodextrins (CDs) are biocompatible cyclic oligomers of glucose, with hydrophobic core and hydrophilic exterior. CDs are used to improve the bioavailability of drugs by increasing their solubility and/or their rate of dissolution after including the poorly water soluble substances (such as ER) in the hydrophobic cavity of CDs. Adding CDs leads to the increase of solubility and improved stability of the drug substance, increased permeability of substances of low water solubility, decreased toxicity and even to active dose reduction as a result of increased bioavailability. CDs increase skin tolerability by reducing the irritant effect of certain substances. We have included ER to lactide modified β-cyclodextrin, in order to improve the therapeutic effect of topically administered ER. The aims of the present study were to synthesise and describe a new complex with prolonged release of ER with lactide modified β-cyclodextrin (CD-LA_E), to investigate the CD-LA_E complex by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), to analyse the effect of semisolid base on the in vitro and ex vivo release characteristics of ER in the CD-LA_E complex by assessing the permeability coefficient and the release kinetics by fitting on mathematical models. SEM showed that, by complexation, ER changes its crystal structure and enters the amorphous phase. FTIR analysis has shown that certain specific bands of some groups in the ER structure move during the incapsulation process. The structure of the CD-LA_E complex has a molar ratio of 2.12 to 1 between lactide modified β-cyclodextrin and ER. The three semisolid bases (2% Carbopol, 13% Lutrol 127 and organogel based on Lutrol and isopropyl myristate) show a good capacity for incorporating the CD-LA_E complex, having a content of active ingredient ranging from 98.3% to 101.5% as compared to the declared value of 2% ER. The results of the in vitro dissolution test showed that the ER solubility was significantly increased by CDs incapsulation. The amount of ER released from the CD-LA_E gels was in the range of 76.23% to 89.01%, whereas gels based on ER released a maximum percentage of 26.01% ER. The ex vivo dissolution test confirms the increased ER solubility achieved by complexation, and supports the assumption that the use of this process might increase ER permeability. The highest permeability coefficient was obtained in ER released from gel based on 2% Carbopol: in vitro 33.33 μg/cm2/h, and ex vivo 26.82 μg/cm2/h, respectively. The release kinetics of complexed ER is performed by Fickian diffusion, according to the results obtained by fitting the data in the Korsmeyer-Peppas model.

Keywords: erythromycin, acne, lactide, cyclodextrin

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