Search results for: Matthias Möller
45 Highly Selective Conversion of CO2 to CO on Cu Nanoparticles
Authors: Rauf Razzaq, Kaiwu Dong, Muhammad Sharif, Ralf Jackstell, Matthias Beller
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Carbon dioxide (CO2), a key greenhouse gas produced from both anthropogenic and natural sources, has been recently considered to be an important C1 building-block for the synthesis of many industrial fuels and chemicals. Catalytic hydrogenation of CO2 using a heterogeneous system is regarded as an efficient process for CO2 valorization. In this regard CO2 reduction to CO via the reverse water gas shift reaction (RWGSR) has attracted much attention as a viable process for large scale commercial CO2 utilization. This process can generate syn-gas (CO+H2) which can provide an alternative route to direct CO2 conversion to methanol and/or liquid HCs from FT reaction. Herein, we report a highly active and selective silica supported copper catalyst with efficient CO2 reduction to CO in a slurry-bed batch autoclave reactor. The reactions were carried out at 200°C and 60 bar initial pressure with CO2/H2 ratio of 1:3 with varying temperature, pressure and fed-gas ratio. The gaseous phase products were analyzed using FID while the liquid products were analyzed by using FID detectors. It was found that Cu/SiO2 catalyst prepared using novel ammonia precipitation-urea gelation method achieved 26% CO2 conversion with a CO and methanol selectivity of 98 and 2% respectively. The high catalytic activity could be attributed to its strong metal-support interaction with highly dispersed and stabilized Cu+ species active for RWGSR. So, it can be concluded that reduction of CO2 to CO via RWGSR could address the problem of using CO2 gas in C1 chemistry.Keywords: CO2 reduction, methanol, slurry reactor, synthesis gas
Procedia PDF Downloads 32744 Carbon Skimming: Towards an Application to Summarise and Compare Embodied Carbon to Aid Early-Stage Decision Making
Authors: Rivindu Nethmin Bandara Menik Hitihamy Mudiyanselage, Matthias Hank Haeusler, Ben Doherty
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Investors and clients in the Architectural, Engineering and Construction industry find it difficult to understand complex datasets and reports with little to no graphic representation. The stakeholders examined in this paper include designers, design clients and end-users. Communicating embodied carbon information graphically and concisely can aid with decision support early in a building's life cycle. It is essential to create a common visualisation approach as the level of knowledge about embodied carbon varies between stakeholders. The tool, designed in conjunction with Bates Smart, condenses Tally Life Cycle Assessment data to a carbon hot-spotting visualisation, highlighting the sections with the highest amounts of embodied carbon. This allows stakeholders at every stage of a given project to have a better understanding of the carbon implications with minimal effort. It further allows stakeholders to differentiate building elements by their carbon values, which enables the evaluation of the cost-effectiveness of the selected materials at an early stage. To examine and build a decision-support tool, an action-design research methodology of cycles of iterations was used along with precedents of embodied carbon visualising tools. Accordingly, the importance of visualisation and Building Information Modelling are also explored to understand the best format for relaying these results.Keywords: embodied carbon, visualisation, summarisation, data filtering, early-stage decision-making, materiality
Procedia PDF Downloads 8343 Data Driven Infrastructure Planning for Offshore Wind farms
Authors: Isha Saxena, Behzad Kazemtabrizi, Matthias C. M. Troffaes, Christopher Crabtree
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The calculations done at the beginning of the life of a wind farm are rarely reliable, which makes it important to conduct research and study the failure and repair rates of the wind turbines under various conditions. This miscalculation happens because the current models make a simplifying assumption that the failure/repair rate remains constant over time. This means that the reliability function is exponential in nature. This research aims to create a more accurate model using sensory data and a data-driven approach. The data cleaning and data processing is done by comparing the Power Curve data of the wind turbines with SCADA data. This is then converted to times to repair and times to failure timeseries data. Several different mathematical functions are fitted to the times to failure and times to repair data of the wind turbine components using Maximum Likelihood Estimation and the Posterior expectation method for Bayesian Parameter Estimation. Initial results indicate that two parameter Weibull function and exponential function produce almost identical results. Further analysis is being done using the complex system analysis considering the failures of each electrical and mechanical component of the wind turbine. The aim of this project is to perform a more accurate reliability analysis that can be helpful for the engineers to schedule maintenance and repairs to decrease the downtime of the turbine.Keywords: reliability, bayesian parameter inference, maximum likelihood estimation, weibull function, SCADA data
Procedia PDF Downloads 8642 The Discovery and Application of Perspective Representation in Modern Italy
Authors: Matthias Stange
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In the early modern period, a different image of man began to prevail in Europe. The focus was on the self-determined human being and his abilities. At first, these developments could be seen in Italian painting and architecture, which again oriented itself to the concepts and forms of antiquity. For example, through the discovery of perspective representation by Brunelleschi or later the orthogonal projection by Alberti, after the ancient knowledge of optics had been forgotten in the Middle Ages. The understanding of reality in the Middle Ages was not focused on the sensually perceptible world but was determined by ecclesiastical dogmas. The empirical part of this study examines the rediscovery and development of perspective. With the paradigm of antiquity, the figure of the architect was also recognised again - the cultural man trained theoretically and practically in numerous subjects, as Vitruvius describes him. In this context, the role of the architect, the influence on the painting of the Quattrocento as well as the influence on architectural representation in the Baroque period are examined. Baroque is commonly associated with the idea of illusionistic appearance as opposed to the tangible reality presented in the Renaissance. The study has shown that the central perspective projection developed by Filippo Brunelleschi enabled another understanding of seeing and the dissemination of painted images. Brunelleschi's development made it possible to understand the sight of nature as a reflection of what is presented to the viewer's eye. Alberti later shortened Brunelleschi's central perspective representation for practical use in painting. In early modern Italian architecture and painting, these developments apparently supported each other. The pictorial representation of architecture initially served the development of an art form before it became established in building practice itself.Keywords: Alberti, Brunelleschi, central perspective projection, orthogonal projection, quattrocento, baroque
Procedia PDF Downloads 8641 STAT6 Mediates Local and Systemic Fibrosis and Type Ii Immune Response via Macrophage Polarization during Acute and Chronic Pancreatitis in Murine Model
Authors: Hager Elsheikh, Matthias Sendler, Juliana Glaubnitz
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In pancreatitis, an inflammatory reaction occurs in the pancreatic secretory cells due to premature activation of proteases, leading to pancreatic self-digestion and necrotic cell death of acinar cells. Acute pancreatitis in patients is characterized by a severe immune reaction that could lead to serious complications, such as organ failure or septic shock, if left untreated. Chronic pancreatitis is a recurrence of episodes of acute pancreatitis resulting in a fibro-inflammatory immune response, in which the type 2 immune response is primarily driven by AAMs in the pancreas. One of the most important signaling pathways for M2 macrophage activation is the IL-4/STAT6 pathway. Pancreatic fibrosis is induced by the hyperactivation of pancreatic stellate cells by dysregulation in the inflammatory response, leading to further damage, autodigestion and possibly necrosis of pancreatic acinar cells. The aim of this research is to investigate the effect of STAT6 knockout in disease severity and development of fibrosis wound healing in the presence of different macrophage populations, regulated by the type 2 immune response, after inducing chronic and/or acute pancreatitis in mice models via cerulean injection. We further investigate the influence of the JAK/STAT6 signaling pathway on the balance of fibrosis and regeneration in STAT6 deficient and wild-type mice. The characterization of resident and recruited macrophages will provide insight into the influence of the JAK/STAT6 signaling pathway on infiltrating cells and, ultimately, tissue fibrosis and disease severity.Keywords: acute and chronic pancreatitis, tissue regeneration, macrophage polarization, Gastroenterology
Procedia PDF Downloads 6840 Architectural Visualization: From Ancient Civilizations to the Roman Empire
Authors: Matthias Stange
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Architectural visualization has been practiced for as long as there have been buildings. Visualization (lat.: visibilis "visible") generally refers to bringing abstract data and relationships into a graphically, visually comprehensible form. Particularly, visualization refers to the process of translating relationships that are difficult to formulate linguistically or logically into visual media (e.g., drawings or models) to make them comprehensible. Building owners have always been interested in knowing how their building will look before it is built. In the empirical part of this study, the roots of architectural visualization are examined, starting from the ancient civilizations to the end of the Roman Empire. Extensive literature research on architectural theory and architectural history forms the basis for this analysis. The focus of the analysis is basic research from the emergence of the first two-dimensional drawings in the Neolithic period to the triggers of significant further developments of architectural representation, as well as their importance for subsequent methods and the transmission of knowledge over the following epochs. The analysis focuses on the development of analog methods of representation from the first Neolithic house floor plans to the Greek detailed stone models and paper drawings in the Roman Empire. In particular, the question of socio-cultural, socio-political, and economic changes as possible triggers for the development of representational media and methods will be analyzed. The study has shown that the development of visual building representation has been driven by scientific, technological, and social developments since the emergence of the first civilizations more than 6000 years ago first by the change in human’s subsistence strategy, from food appropriation by hunting and gathering to food production by agriculture and livestock, and the sedentary lifestyle required for this.Keywords: ancient Greece, ancient orient, Roman Empire, architectural visualization
Procedia PDF Downloads 11639 Numerical Investigation of the Needle Opening Process in a High Pressure Gas Injector
Authors: Matthias Banholzer, Hagen Müller, Michael Pfitzner
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Gas internal combustion engines are widely used as propulsion systems or in power plants to generate heat and electricity. While there are different types of injection methods including the manifold port fuel injection and the direct injection, the latter has more potential to increase the specific power by avoiding air displacement in the intake and to reduce combustion anomalies such as backfire or pre-ignition. During the opening process of the injector, multiple flow regimes occur: subsonic, transonic and supersonic. To cover the wide range of Mach numbers a compressible pressure-based solver is used. While the standard Pressure Implicit with Splitting of Operators (PISO) method is used for the coupling between velocity and pressure, a high-resolution non-oscillatory central scheme established by Kurganov and Tadmor calculates the convective fluxes. A blending function based on the local Mach- and CFL-number switches between the compressible and incompressible regimes of the developed model. As the considered operating points are well above the critical state of the used fluids, the ideal gas assumption is not valid anymore. For the real gas thermodynamics, the models based on the Soave-Redlich-Kwong equation of state were implemented. The caloric properties are corrected using a departure formalism, for the viscosity and the thermal conductivity the empirical correlation of Chung is used. For the injector geometry, the dimensions of a diesel injector were adapted. Simulations were performed using different nozzle and needle geometries and opening curves. It can be clearly seen that there is a significant influence of all three parameters.Keywords: high pressure gas injection, hybrid solver, hydrogen injection, needle opening process, real-gas thermodynamics
Procedia PDF Downloads 46138 Clean Sky 2 Project LiBAT: Light Battery Pack for High Power Applications in Aviation – Simulation Methods in Early Stage Design
Authors: Jan Dahlhaus, Alejandro Cardenas Miranda, Frederik Scholer, Maximilian Leonhardt, Matthias Moullion, Frank Beutenmuller, Julia Eckhardt, Josef Wasner, Frank Nittel, Sebastian Stoll, Devin Atukalp, Daniel Folgmann, Tobias Mayer, Obrad Dordevic, Paul Riley, Jean-Marc Le Peuvedic
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Electrical and hybrid aerospace technologies pose very challenging demands on the battery pack – especially with respect to weight and power. In the Clean Sky 2 research project LiBAT (funded by the EU), the consortium is currently building an ambitious prototype with state-of-the art cells that shows the potential of an intelligent pack design with a high level of integration, especially with respect to thermal management and power electronics. For the latter, innovative multi-level-inverter technology is used to realize the required power converting functions with reduced equipment. In this talk the key approaches and methods of the LiBat project will be presented and central results shown. Special focus will be set on the simulative methods used to support the early design and development stages from an overall system perspective. The applied methods can efficiently handle multiple domains and deal with different time and length scales, thus allowing the analysis and optimization of overall- or sub-system behavior. It will be shown how these simulations provide valuable information and insights for the efficient evaluation of concepts. As a result, the construction and iteration of hardware prototypes has been reduced and development cycles shortened.Keywords: electric aircraft, battery, Li-ion, multi-level-inverter, Novec
Procedia PDF Downloads 16737 Disrupted or Discounted Cash Flow: Impact of Digitisation on Business Valuation
Authors: Matthias Haerri, Tobias Huettche, Clemens Kustner
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This article discusses the impact of digitization on business valuation. In order to become and remain ‘digital’, investments are necessary whose return on investment (ROI) often remains vague. This uncertainty is contradictory for a valuation, that rely on predictable cash flows, fixed capital structures and the steady state. However digitisation does not make a company valuation impossible, but traditional approaches must be reconsidered. The authors identify four areas that are to be changing: (1) Tools instead of intuition - In the future, company valuation will neither be art nor science, but craft. This does not require intuition, but experience and good tools. Digital evaluation tools beyond Excel will therefore gain in importance. (2) Real-time instead of deadline - At present, company valuations are always carried out on a case-by-case basis and on a specific key date. This will change with the digitalization and the introduction of web-based valuation tools. Company valuations can thus not only be carried out faster and more efficiently, but can also be offered more frequently. Instead of calculating the value for a previous key date, current and real-time valuations can be carried out. (3) Predictive planning instead of analysis of the past - Past data will also be needed in the future, but its use will not be limited to monovalent time series or key figure analyses. With pictures of ‘black swans’ and the ‘turkey illusion’ it was made clear to us that we build forecasts on too few data points of the past and underestimate the power of chance. Predictive planning can help here. (4) Convergence instead of residual value - Digital transformation shortens the lifespan of viable business models. If companies want to live forever, they have to change forever. For the company valuation, this means that the business model valid on the valuation date only has a limited service life.Keywords: business valuation, corporate finance, digitisation, disruption
Procedia PDF Downloads 13436 Hydraulic Optimization of an Adjustable Spiral-Shaped Evaporator
Authors: Matthias Feiner, Francisco Javier Fernández García, Michael Arneman, Martin Kipfmüller
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To ensure reliability in miniaturized devices or processes with increased heat fluxes, very efficient cooling methods have to be employed in order to cope with small available cooling surfaces. To address this problem, a certain type of evaporator/heat exchanger was developed: It is called a swirl evaporator due to its flow characteristic. The swirl evaporator consists of a concentrically eroded screw geometry in which a capillary tube is guided, which is inserted into a pocket hole in components with high heat load. The liquid refrigerant R32 is sprayed through the capillary tube to the end face of the blind hole and is sucked off against the injection direction in the screw geometry. Its inner diameter is between one and three millimeters. The refrigerant is sprayed into the pocket hole via a small tube aligned in the center of the bore hole and is sucked off on the front side of the hole against the direction of injection. The refrigerant is sucked off in a helical geometry (twisted flow) so that it is accelerated against the hot wall (centrifugal acceleration). This results in an increase in the critical heat flux of up to 40%. In this way, more heat can be dissipated on the same surface/available installation space. This enables a wide range of technical applications. To optimize the design for the needs in various fields of industry, like the internal tool cooling when machining nickel base alloys like Inconel 718, a correlation-based model of the swirl-evaporator was developed. The model is separated into 3 subgroups with overall 5 regimes. The pressure drop and heat transfer are calculated separately. An approach to determine the locality of phase change in the capillary and the swirl was implemented. A test stand has been developed to verify the simulation.Keywords: helically-shaped, oil-free, R-32, swirl-evaporator, twist-flow
Procedia PDF Downloads 10835 Localized Detection of ᴅ-Serine by Using an Enzymatic Amperometric Biosensor and Scanning Electrochemical Microscopy
Authors: David Polcari, Samuel C. Perry, Loredano Pollegioni, Matthias Geissler, Janine Mauzeroll
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ᴅ-serine acts as an endogenous co-agonist for N-methyl-ᴅ-aspartate receptors in neuronal synapses. This makes it a key component in the development and function of a healthy brain, especially given its role in several neurodegenerative diseases such as Alzheimer’s disease and dementia. Despite such clear research motivations, the primary site and mechanism of ᴅ-serine release is still currently unclear. For this reason, we are developing a biosensor for the detection of ᴅ-serine utilizing a microelectrode in combination with a ᴅ-amino acid oxidase enzyme, which produces stoichiometric quantities of hydrogen peroxide in response to ᴅ-serine. For the fabrication of a biosensor with good selectivity, we use a permselective poly(meta-phenylenediamine) film to ensure only the target molecule is reacted, according to the size exclusion principle. In this work, we investigated the effect of the electrodeposition conditions used on the biosensor’s response time and selectivity. Careful optimization of the fabrication process allowed for enhanced biosensor response time. This allowed for the real time sensing of ᴅ-serine in a bulk solution, and also provided in means to map the efflux of ᴅ-serine in real time. This was done using scanning electrochemical microscopy (SECM) with the optimized biosensor to measure localized release of ᴅ-serine from an agar filled glass capillary sealed in an epoxy puck, which acted as a model system. The SECM area scan simultaneously provided information regarding the rate of ᴅ-serine flux from the model substrate, as well as the size of the substrate itself. This SECM methodology, which provides high spatial and temporal resolution, could be useful to investigate the primary site and mechanism of ᴅ-serine release in other biological samples.Keywords: ᴅ-serine, enzymatic biosensor, microelectrode, scanning electrochemical microscopy
Procedia PDF Downloads 22834 Electron Bernstein Wave Heating in the Toroidally Magnetized System
Authors: Johan Buermans, Kristel Crombé, Niek Desmet, Laura Dittrich, Andrei Goriaev, Yurii Kovtun, Daniel López-Rodriguez, Sören Möller, Per Petersson, Maja Verstraeten
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The International Thermonuclear Experimental Reactor (ITER) will rely on three sources of external heating to produce and sustain a plasma; Neutral Beam Injection (NBI), Ion Cyclotron Resonance Heating (ICRH), and Electron Cyclotron Resonance Heating (ECRH). ECRH is a way to heat the electrons in a plasma by resonant absorption of electromagnetic waves. The energy of the electrons is transferred indirectly to the ions by collisions. The electron cyclotron heating system can be directed to deposit heat in particular regions in the plasma (https://www.iter.org/mach/Heating). Electron Cyclotron Resonance Heating (ECRH) at the fundamental resonance in X-mode is limited by a low cut-off density. Electromagnetic waves cannot propagate in the region between this cut-off and the Upper Hybrid Resonance (UHR) and cannot reach the Electron Cyclotron Resonance (ECR) position. Higher harmonic heating is hence preferred in heating scenarios nowadays to overcome this problem. Additional power deposition mechanisms can occur above this threshold to increase the plasma density. This includes collisional losses in the evanescent region, resonant power coupling at the UHR, tunneling of the X-wave with resonant coupling at the ECR, and conversion to the Electron Bernstein Wave (EBW) with resonant coupling at the ECR. A more profound knowledge of these deposition mechanisms can help determine the optimal plasma production scenarios. Several ECRH experiments are performed on the TOroidally MAgnetized System (TOMAS) to identify the conditions for Electron Bernstein Wave (EBW) heating. Density and temperature profiles are measured with movable Triple Langmuir Probes in the horizontal and vertical directions. Measurements of the forwarded and reflected power allow evaluation of the coupling efficiency. Optical emission spectroscopy and camera images also contribute to plasma characterization. The influence of the injected power, magnetic field, gas pressure, and wave polarization on the different deposition mechanisms is studied, and the contribution of the Electron Bernstein Wave is evaluated. The TOMATOR 1D hydrogen-helium plasma simulator numerically describes the evolution of current less magnetized Radio Frequency plasmas in a tokamak based on Braginskii’s legal continuity and heat balance equations. This code was initially benchmarked with experimental data from TCV to determine the transport coefficients. The code is used to model the plasma parameters and the power deposition profiles. The modeling is compared with the data from the experiments.Keywords: electron Bernstein wave, Langmuir probe, plasma characterization, TOMAS
Procedia PDF Downloads 9633 Systematic Analysis of Immune Response to Biomaterial Surface Characteristics
Authors: Florian Billing, Soren Segan, Meike Jakobi, Elsa Arefaine, Aliki Jerch, Xin Xiong, Matthias Becker, Thomas Joos, Burkhard Schlosshauer, Ulrich Rothbauer, Nicole Schneiderhan-Marra, Hanna Hartmann, Christopher Shipp
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The immune response plays a major role in implant biocompatibility, but an understanding of how to design biomaterials for specific immune responses is yet to be achieved. We aimed to better understand how changing certain material properties can drive immune responses. To this end, we tested immune response to experimental implant coatings that vary in specific characteristics. A layer-by-layer approach was employed to vary surface charge and wettability. Human-based in vitro models (THP-1 macrophages and primary peripheral blood mononuclear cells (PBMCS)) were used to assess immune responses using multiplex cytokine analysis, flow cytometry (CD molecule expression) and microscopy (cell morphology). We observed dramatic differences in immune response due to specific alterations in coating properties. For example altering the surface charge of coating A from anionic to cationic resulted in the substantial elevation of the pro-inflammatory molecules IL-1beta, IL-6, TNF-alpha and MIP-1beta, while the pro-wound healing factor VEGF was significantly down-regulated. We also observed changes in cell surface marker expression in relation to altered coating properties, such as CD16 on NK Cells and HLA-DR on monocytes. We furthermore observed changes in the morphology of THP-1 macrophages following cultivation on different coatings. A correlation between these morphological changes and the cytokine expression profile is ongoing. Targeted changes in biomaterial properties can produce vast differences in immune response. The properties of the coatings examined here may, therefore, be a method to direct specific biological responses in order to improve implant biocompatibility.Keywords: biomaterials, coatings, immune system, implants
Procedia PDF Downloads 18932 Chiral Amine Synthesis and Recovery by Using High Molecular Weight Amine Donors
Authors: Claudia Matassa, Matthias Hohne, Dominic Ormerod, Yamini Satyawali
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Chiral amines integrate the backbone of several active pharmaceutical ingredients (APIs) used in modern medicine for the treatment of a vast range of diseases. Despite the demand, their synthesis remains challenging. Besides a range of chemicals and enzymatical methods, chiral amine synthesis using transaminases (EC 2.6.1.W) represents a useful alternative to access this important class of compounds. Even though transaminases exhibit excellent stereo and regioselectivity and the potential for high yield, the reaction suffers from a number of challenges, including the thermodynamic equilibrium, product inhibition, and low substrate solubility. In this work, we demonstrate a membrane assisted strategy for addressing these challenges. It involves the use of high molecular weight (HMW) amine donors for the transaminase-catalyzed synthesis of 4-phenyl-2-butylamine in both aqueous and organic solvent media. In contrast to common amine donors such as alanine or isopropylamine, these large molecules, provided in excess for thermodynamic equilibrium shifting, are easily retained by commercial nanofiltration membranes; thus a selective permeation of the desired smaller product amine is possible. The enzymatic transamination in aqueous media, combined with selective product removal shifted the equilibrium enhancing substrate conversion by an additional 25% compared to the control reaction. Along with very efficient amine product removal, there was undesirable loss of ketone substrate and low product concentration was achieved. The system was therefore further improved by performing the reaction in organic solvent (n-heptane). Coupling the reaction system with membrane-assisted product removal resulted in a highly concentrated and relatively pure ( > 97%) product solution. Moreover, a product yield of 60% was reached, compared to 15% without product removal.Keywords: amine donor, chiral amines, in situ product removal, transamination
Procedia PDF Downloads 15431 Natural and Construction/Demolition Waste Aggregates: A Comparative Study
Authors: Debora C. Mendes, Matthias Eckert, Claudia S. Moço, Helio Martins, Jean-Pierre Gonçalves, Miguel Oliveira, Jose P. Da Silva
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Disposal of construction and demolition waste (C&DW) in embankments in the periphery of cities causes both environmental and social problems. To achieve the management of C&DW, a detailed analysis of the properties of these materials should be done. In this work we report a comparative study of the physical, chemical and environmental properties of natural and C&DW aggregates from 25 different origins. Assays were performed according to European Standards. Analysis of heavy metals and organic compounds, namely polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), were performed. Finally, properties of concrete prepared with C&DW aggregates are reported. Physical analyses of C&DW aggregates indicated lower quality properties than natural aggregates, particularly for concrete preparation and unbound layers of road pavements. Chemical properties showed that most samples (80%) meet the values required by European regulations for concrete and unbound layers of road pavements. Analyses of heavy metals Cd, Cr, Cu, Pb, Ni, Mo and Zn in the C&DW leachates showed levels below the limits established by the Council Decision of 19 December 2002. Identification and quantification of PCBs and PAHs indicated that few samples shows the presence of these compounds. The measured levels of PCBs and PAHs are also below the limits. Other compounds identified in the C&DW leachates include phthalates and diphenylmethanol. The characterized C&DW aggregates show lower quality properties than natural aggregates but most samples showed to be environmentally safe. A continuous monitoring of the presence of heavy metals and organic compounds should be made to trial safe C&DW aggregates. C&DW aggregates provide a good economic and environmental alternative to natural aggregates.Keywords: concrete preparation, construction and demolition waste, heavy metals, organic pollutants
Procedia PDF Downloads 35930 Coupling Static Multiple Light Scattering Technique With the Hansen Approach to Optimize Dispersibility and Stability of Particle Dispersions
Authors: Guillaume Lemahieu, Matthias Sentis, Giovanni Brambilla, Gérard Meunier
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Static Multiple Light Scattering (SMLS) has been shown to be a straightforward technique for the characterization of colloidal dispersions without dilution, as multiply scattered light in backscattered and transmitted mode is directly related to the concentration and size of scatterers present in the sample. In this view, the use of SMLS for stability measurement of various dispersion types has already been widely described in the literature. Indeed, starting from a homogeneous dispersion, the variation of backscattered or transmitted light can be attributed to destabilization phenomena, such as migration (sedimentation, creaming) or particle size variation (flocculation, aggregation). In a view to investigating more on the dispersibility of colloidal suspensions, an experimental set-up for “at the line” SMLS experiment has been developed to understand the impact of the formulation parameters on particle size and dispersibility. The SMLS experiment is performed with a high acquisition rate (up to 10 measurements per second), without dilution, and under direct agitation. Using such experimental device, SMLS detection can be combined with the Hansen approach to optimize the dispersing and stabilizing properties of TiO₂ particles. It appears that the dispersibility and the stability spheres generated are clearly separated, arguing that lower stability is not necessarily a consequence of poor dispersibility. Beyond this clarification, this combined SMLS-Hansen approach is a major step toward the optimization of dispersibility and stability of colloidal formulations by finding solvents having the best compromise between dispersing and stabilizing properties. Such study can be intended to find better dispersion media, greener and cheaper solvents to optimize particles suspensions, reduce the content of costly stabilizing additives or satisfy product regulatory requirements evolution in various industrial fields using suspensions (paints & inks, coatings, cosmetics, energy).Keywords: dispersibility, stability, Hansen parameters, particles, solvents
Procedia PDF Downloads 11129 RPM-Synchronous Non-Circular Grinding: An Approach to Enhance Efficiency in Grinding of Non-Circular Workpieces
Authors: Matthias Steffan, Franz Haas
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The production process grinding is one of the latest steps in a value-added manufacturing chain. Within this step, workpiece geometry and surface roughness are determined. Up to this process stage, considerable costs and energy have already been spent on components. According to the current state of the art, therefore, large safety reserves are calculated in order to guarantee a process capability. Especially for non-circular grinding, this fact leads to considerable losses of process efficiency. With present technology, various non-circular geometries on a workpiece must be grinded subsequently in an oscillating process where X- and Q-axis of the machine are coupled. With the approach of RPM-Synchronous Noncircular Grinding, such workpieces can be machined in an ordinary plung grinding process. Therefore, the workpieces and the grinding wheels revolutionary rate are in a fixed ratio. A non-circular grinding wheel is used to transfer its geometry onto the workpiece. The authors use a worldwide unique machine tool that was especially designed for this technology. Highest revolution rates on the workpiece spindle (up to 4500 rpm) are mandatory for the success of this grinding process. This grinding approach is performed in a two-step process. For roughing, a highly porous vitrified bonded grinding wheel with medium grain size is used. It ensures high specific material removal rates for efficiently producing the non-circular geometry on the workpiece. This process step is adapted by a force control algorithm, which uses acquired data from a three-component force sensor located in the dead centre of the tailstock. For finishing, a grinding wheel with a fine grain size is used. Roughing and finishing are performed consecutively among the same clamping of the workpiece with two locally separated grinding spindles. The approach of RPM-Synchronous Noncircular Grinding shows great efficiency enhancement in non-circular grinding. For the first time, three-dimensional non-circular shapes can be grinded that opens up various fields of application. Especially automotive industries show big interest in the emerging trend in finishing machining.Keywords: efficiency enhancement, finishing machining, non-circular grinding, rpm-synchronous grinding
Procedia PDF Downloads 28328 Influence of Ammonia Emissions on Aerosol Formation in Northern and Central Europe
Authors: A. Aulinger, A. M. Backes, J. Bieser, V. Matthias, M. Quante
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High concentrations of particles pose a threat to human health. Thus, legal maximum concentrations of PM10 and PM2.5 in ambient air have been steadily decreased over the years. In central Europe, the inorganic species ammonium sulphate and ammonium nitrate make up a large fraction of fine particles. Many studies investigate the influence of emission reductions of sulfur- and nitrogen oxides on aerosol concentration. Here, we focus on the influence of ammonia (NH3) emissions. While emissions of sulphate and nitrogen oxides are quite well known, ammonia emissions are subject to high uncertainty. This is due to the uncertainty of location, amount, time of fertilizer application in agriculture, and the storage and treatment of manure from animal husbandry. For this study, we implemented a crop growth model into the SMOKE emission model. Depending on temperature, local legislation, and crop type individual temporal profiles for fertilizer and manure application are calculated for each model grid cell. Additionally, the diffusion from soils and plants and the direct release from open and closed barns are determined. The emission data was used as input for the Community Multiscale Air Quality (CMAQ) model. Comparisons to observations from the EMEP measurement network indicate that the new ammonia emission module leads to a better agreement of model and observation (for both ammonia and ammonium). Finally, the ammonia emission model was used to create emission scenarios. This includes emissions based on future European legislation, as well as a dynamic evaluation of the influence of different agricultural sectors on particle formation. It was found that a reduction of ammonia emissions by 50% lead to a 24% reduction of total PM2.5 concentrations during winter time in the model domain. The observed reduction was mainly driven by reduced formation of ammonium nitrate. Moreover, emission reductions during winter had a larger impact than during the rest of the year.Keywords: ammonia, ammonia abatement strategies, ctm, seasonal impact, secondary aerosol formation
Procedia PDF Downloads 35127 Determinants of Carbon-Certified Small-Scale Agroforestry Adoption In Rural Mount Kenyan
Authors: Emmanuel Benjamin, Matthias Blum
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Purpose – We address smallholder farmers’ restricted possibilities to adopt sustainable technologies which have direct and indirect benefits. Smallholders often face little asset endowment due to small farm size und insecure property rights, therefore experiencing constraints in adopting agricultural innovation. A program involving payments for ecosystem services (PES) benefits poor smallholder farmers in developing countries in many ways and has been suggested as a means of easing smallholder farmers’ financial constraints. PES may also provide additional mainstay which can eventually result in more favorable credit contract terms due to the availability of collateral substitute. Results of this study may help to understand the barriers, motives and incentives for smallholders’ participation in PES and help in designing a strategy to foster participation in beneficial programs. Design/methodology/approach – This paper uses a random utility model and a logistic regression approach to investigate factors that influence agroforestry adoption. We investigate non-monetary factors, such as information spillover, that influence the decision to adopt such conservation strategies. We collected original data from non-government-run agroforestry mitigation programs with PES that have been implemented in the Mount Kenya region. Preliminary Findings – We find that spread of information, existing networks and peer involvement in such programs drive participation. Conversely, participation by smallholders does not seem to be influenced by education, land or asset endowment. Contrary to some existing literature, we found weak evidence for a positive correlation between the adoption of agroforestry with PES and age of smallholder, e.g., one increases with the other, in the Mount Kenyan region. Research implications – Poverty alleviation policies for developing countries should target social capital to increase the adoption rate of modern technologies amongst smallholders.Keywords: agriculture innovation, agroforestry adoption, smallholders, payment for ecosystem services, Sub-Saharan Africa
Procedia PDF Downloads 38226 Determination of Influence Lines for Train Crossings on a Tied Arch Bridge to Optimize the Construction of the Hangers
Authors: Martin Mensinger, Marjolaine Pfaffinger, Matthias Haslbeck
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The maintenance and expansion of the railway network represents a central task for transport planning in the future. In addition to the ultimate limit states, the aspects of resource conservation and sustainability are increasingly more necessary to include in the basic engineering. Therefore, as part of the AiF research project, ‘Integrated assessment of steel and composite railway bridges in accordance with sustainability criteria’, the entire lifecycle of engineering structures is involved in planning and evaluation, offering a way to optimize the design of steel bridges. In order to reduce the life cycle costs and increase the profitability of steel structures, it is particularly necessary to consider the demands on hanger connections resulting from fatigue. In order for accurate analysis, a number simulations were conducted as part of the research project on a finite element model of a reference bridge, which gives an indication of the internal forces of the individual structural components of a tied arch bridge, depending on the stress incurred by various types of trains. The calculations were carried out on a detailed FE-model, which allows an extraordinarily accurate modeling of the stiffness of all parts of the constructions as it is made up surface elements. The results point to a large impact of the formation of details on fatigue-related changes in stress, on the one hand, and on the other, they could depict construction-specific specifics over the course of adding stress. Comparative calculations with varied axle-stress distribution also provide information about the sensitivity of the results compared to the imposition of stress and axel distribution on the stress-resultant development. The calculated diagrams help to achieve an optimized hanger connection design through improved durability, which helps to reduce the maintenance costs of rail networks and to give practical application notes for the formation of details.Keywords: fatigue, influence line, life cycle, tied arch bridge
Procedia PDF Downloads 33025 Physical, Chemical and Environmental Properties of Natural and Construction/Demolition Recycled Aggregates
Authors: Débora C. Mendes, Matthias Eckert, Cláudia S. Moço, Hélio Martins, Jean-Pierre P. Gonçalves, Miguel Oliveira, José P. Da Silva
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Uncontrolled disposal of construction and demolition waste (C & DW) in embankments in the periphery of cities causes both environmental and social problems, namely erosion, deforestation, water contamination and human conflicts. One of the milestones of EU Horizon 2020 Programme is the management of waste as a resource. To achieve this purpose for C & DW, a detailed analysis of the properties of these materials should be done. In this work we report the physical, chemical and environmental properties of C & DW aggregates from 25 different origins. The results are compared with those of common natural aggregates used in construction. Assays were performed according to European Standards. Additional analysis of heavy metals and organic compounds such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), were performed to evaluate their environmental impact. Finally, properties of concrete prepared with C & DW aggregates are also reported. Physical analyses of C & DW aggregates indicated lower quality properties than natural aggregates, particularly for concrete preparation and unbound layers of road pavements. Chemical properties showed that most samples (80%) meet the values required by European regulations for concrete and unbound layers of road pavements. Analyses of heavy metals Cd, Cr, Cu, Pb, Ni, Mo and Zn in the C&DW leachates showed levels below the limits established by the Council Decision of 19 December 2002. Identification and quantification of PCBs and PAHs indicated that few samples shows the presence of these compounds. The measured levels of PCBs and PAHs are also below the limits. Other compounds identified in the C&DW leachates include phthalates and diphenylmethanol. In conclusion, the characterized C&DW aggregates show lower quality properties than natural aggregates but most samples showed to be environmentally safe. A continuous monitoring of the presence of heavy metals and organic compounds should be made to trial safe C&DW aggregates. C&DW aggregates provide a good economic and environmental alternative to natural aggregates.Keywords: concrete preparation, construction and demolition waste, heavy metals, organic pollutants
Procedia PDF Downloads 34924 Systematic Analysis of Logistics Location Search Methods under Aspects of Sustainability
Authors: Markus Pajones, Theresa Steiner, Matthias Neubauer
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Selecting a logistics location is vital for logistics providers, food retailing and other trading companies since the selection poses an essential factor for economic success. Therefore various location search methods like cost-benefit analysis and others are well known and under usage. The development of a logistics location can be related to considerable negative effects for the eco system such as sealing the surface, wrecking of biodiversity or CO2 and noise emissions generated by freight and commuting traffic. The increasing importance of sustainability demands for taking an informed decision when selecting a logistics location for the future. Sustainability considers economic, ecologic and social aspects which should be equally integrated in the process of location search. Objectives of this paper are to define various methods which support the selection of sustainable logistics locations and to generate knowledge about the suitability, assets and limitations of the methods within the selection process. This paper investigates the role of economical, ecological and social aspects when searching for new logistics locations. Thereby, related work targeted towards location search is analyzed with respect to encoded sustainability aspects. In addition, this research aims to gain knowledge on how to include aspects of sustainability and take an informed decision when searching for a logistics location. As a result, a decomposition of the various location search methods in there components leads to a comparative analysis in form of a matrix. The comparison within a matrix enables a transparent overview about the mentioned assets and limitations of the methods and their suitability for selecting sustainable logistics locations. A further result is to generate knowledge on how to combine the separate methods to a new method for a more efficient selection of logistics locations in the context of sustainability. Future work will especially investigate the above mentioned combination of various location search methods. The objective is to develop an innovative instrument, which supports the search for logistics locations with a focus on a balanced sustainability (economy, ecology, social). Because of an ideal selection of logistics locations, induced traffic should be reduced and a mode shift to rail and public transport should be facilitated.Keywords: commuting traffic, freight traffic, logistics location search, location search method
Procedia PDF Downloads 32123 Innovation Management in State-Owned-Enterprises in the Digital Transformation: An Empirical Case Study of Swiss Post
Authors: Jiayun Shen, Lorenz Wyss, Thierry Golliard, Matthias Finger
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Innovation is widely recognized as the key for private enterprises to win the market competition. The state-owned-enterprises need to be innovative to compete in the market after the privatization as well. However, it is a lack of research to study how state-owned-enterprises manage innovation to create new products and services. Swiss Post, a Swiss state-owned-enterprises, has established a department to transform the corporate culture and foster innovation to achieve digital transformation. This paper describes the innovation management process at the Swiss Post and analyzes the impacts of the instruments, the organizational structure, and explores the barriers of innovation. This study used qualitative methods based on a review of the literature on innovation management and semi-structured interviews. Being established for over five years, the Swiss Post’s innovation management department has established a software-assisted modularized platform with systematic instruments to help the internal employees with the different innovation processes. It guides the innovators from idea creation to piloting in markets and supports with a separate financing source, with knowledge inputs and coaching, as well as with connections to external partners through the open innovation and venturing team. The platform also adapts to different business units within the corporate with a customized tailor for the various operational business units. The separate financing instruments enabled the creation and further development of new ideas; the coaching services contribute greatly to the transformation of teams’ innovation culture by providing new knowledge, thinking methods, and use cases for inspiration. It also facilitates organizational learning to help the whole corporate with the digital transformation. However, it is also confronted with a big challenge in twofold. Internally, the disruptive projects often hardly overcome the obstacles of long-established operational processes in the traditional business units; externally, the expectations of the public and restrictions from the federal government have become high hurdles for the company to stay and compete in the innovation track.Keywords: empirical case study, innovation management, state-owned-enterprise, Swiss Post
Procedia PDF Downloads 12222 IL4/IL13 STAT6 Mediated Macrophage Polarization During Acute and Chronic Pancreatitis
Authors: Hager Elsheikh, Juliane Glaubitz, Frank Ulrich Weiss, Matthias Sendler
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Aim: Acute pancreatitis (AP) and chronic pancreatitis (CP) are both accompanied by a prominent immune response which influences the course of disease. Whereas during AP the pro-inflammatory immune response dominates, during CP a fibroinflammatory response regulates organ remodeling. The transcription factor signal transducer and activator of transcription 6 (STAT6) is a crucial part of the Type 2 immune response. Here we investigate the role of STAT6 in a mouse model of AP and CP. Material and Methods: AP was induced by hourly repetitive i.p. injections of caerulein (50µg/kg/bodyweight) in C57Bl/6 J and STAT6-/- mice. CP was induced by repetitive caerulein injections 6 times a day, 3 days a week over 4 weeks. Disease severity was evaluated by serum amylase/lipase measurement, H&E staining of pancreas. Pancreatic infiltrate was characterized by immunofluorescent labeling of CD68, CD206, CCR2, CD4 and CD8. Pancreas fibrosis was evaluated by Azan blue staining. qRT-PCR was performed of Arg1, Nos2, Il6, Il1b, Col3a, Socs3 and Ym1. Affymetrix chip array analyses were done to illustrate the IL4/IL13/STAT6 signaling in bone marrow derived macrophages. Results: AP severity is mitigated in STAT6-/- mice, as shown by decreased serum amylase and lipase, as well as histological damage. CP mice surprisingly showed only slightly reduced fibrosis of the pancreas. Also staining of CD206 a classical marker of alternatively activated macrophages showed no decrease of M2-like polarization in the absence of STAT6. In contrast, transcription profile analysis in BMDM showed complete blockade of the IL4/IL13 pathway in STAT6-/- animals. Conclusion: STAT6 signaling pathway is protective during AP and mitigates the pancreatic damage. During chronic pancreatitis the IL4/IL13 – STAT6 axisis involved in organ fibrogenesis. Notably, fibrosis is not dependent on a single signaling pathway, and alternative macrophage activation is also complex and involves different subclasses (M2a, M2b, M2c and M2d) which could be independent of the IL4/IL13 STAT6 axis.Keywords: chronic pancreatitis, macrophages, IL4/IL13, Type immune response
Procedia PDF Downloads 6721 Nanocomposite Effect Based on Silver Nanoparticles and Anemposis Californica Extract as Skin Restorer
Authors: Maria Zulema Morquecho Vega, Fabiola CarolinaMiranda Castro, Rafael Verdugo Miranda, Ignacio Yocupicio Villegas, Ana lidia Barron Raygoza, Martin enrique MArquez Cordova, Jose Alberto Duarte Moller
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Background: Anemopsis californica, also called (tame grass) belongs to the Saururaceae family small, green plant. The blade is long and wide. Gives a white flower. The plant population is only found in humid, swampy habitats, it grows where there is water, along the banks of streams and water holes. In the winter, it dries up. The leaves, rhizomes, or roots of this plant have been used to treat a range of diseases. Some of its healing properties are used to treat wounds, cold and flu symptoms, spasmodic cough, infection, pain and inflammation, burns, swollen feet, as well as lung ailments, asthma, circulatory problems (varicose veins), rheumatoid arthritis, purifies blood, helps in urinary and digestive tract diseases, sores and healing, for headache, sore throat, diarrhea, kidney pain. The tea made from the leaves and roots is used to treat uterine cancer, womb cancer, relieves menstrual pain and stops excessive bleeding after childbirth. It is also used as a gynecological treatment for infections, hemorrhoids, candidiasis and vaginitis. Objective: To study the cytotoxicity of gels prepared with silver nanoparticles in AC extract combined with chitosan, collagen and hyaluronic acid as an alternative therapy for skin conditions. Methods: The Ag NPs were synthesized according to the following method. A 0.3 mg/mL solution is prepared in 10 ml of deionized water, adjust to pH 12 with NaOH, stirring is maintained constant magnetic and a temperature of 80 °C. Subsequently, 100 ul of a 0.1 M AgNO3 solution and kept stirring constantly for 15 min. Once the reaction is complete, measurements are performed by UV-Vis. A gel was prepared in a 5% solution of acetic acid with the respective nanoparticles and AC extract of silver in the extract of AC. Chitosan is added until the process begins to occur gel. At that time, collagen will be added in a ratio of 3 to 5 drops, and later, hyaluronic acid in 2% of the total compound formed. Finally, after resting for 24 hours, the cytotoxic effect of the gels was studied. in the presence of highly positive bacteria Staphylococcus aureus and highly negative for Escherichia coli. Cultures will be incubated for 24 hours in the presence of the compound and compared with the reference. Results: Silver nanoparticles obtained had a spherical shape and sizes among 20 and 30 nm. UV-Vis spectra confirm the presence of silver nanoparticles showing a surface plasmon around 420 nm. Finally, the test in presence of bacteria yield a good antibacterial property of this nanocompound and tests in people were successful. Conclusion: Gel prepared by biogenic synthesis shown beneficious effects in severe acne, acne vulgaris and wound healing with diabetic patients.Keywords: anemopsis californica, nanomedicina, biotechnology, biomedicine
Procedia PDF Downloads 11520 Characterizing Solid Glass in Bending, Torsion and Tension: High-Temperature Dynamic Mechanical Analysis up to 950 °C
Authors: Matthias Walluch, José Alberto Rodríguez, Christopher Giehl, Gunther Arnold, Daniela Ehgartner
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Dynamic mechanical analysis (DMA) is a powerful method to characterize viscoelastic properties and phase transitions for a wide range of materials. It is often used to characterize polymers and their temperature-dependent behavior, including thermal transitions like the glass transition temperature Tg, via determination of storage and loss moduli in tension (Young’s modulus, E) and shear or torsion (shear modulus, G) or other testing modes. While production and application temperatures for polymers are often limited to several hundred degrees, material properties of glasses usually require characterization at temperatures exceeding 600 °C. This contribution highlights a high temperature setup for rotational and oscillatory rheometry as well as for DMA in different modes. The implemented standard convection oven enables the characterization of glass in different loading modes at temperatures up to 950 °C. Three-point bending, tension and torsional measurements on different glasses, with E and G moduli as a function of frequency and temperature, are presented. Additional tests include superimposing several frequencies in a single temperature sweep (“multiwave”). This type of test results in a considerable reduction of the experiment time and allows to evaluate structural changes of the material and their frequency dependence. Furthermore, DMA in torsion and tension was performed to determine the complex Poisson’s ratio as a function of frequency and temperature within a single test definition. Tests were performed in a frequency range from 0.1 to 10 Hz and temperatures up to the glass transition. While variations in the frequency did not reveal significant changes of the complex Poisson’s ratio of the glass, a monotonic increase of this parameter was observed when increasing the temperature. This contribution outlines the possibilities of DMA in bending, tension and torsion for an extended temperature range. It allows the precise mechanical characterization of material behavior from room temperature up to the glass transition and the softening temperature interval. Compared to other thermo-analytical methods, like Dynamic Scanning Calorimetry (DSC) where mechanical stress is neglected, the frequency-dependence links measurement results (e.g. relaxation times) to real applicationsKeywords: dynamic mechanical analysis, oscillatory rheometry, Poisson's ratio, solid glass, viscoelasticity
Procedia PDF Downloads 8319 In situ Grazing Incidence Small Angle X-Ray Scattering Study of Permalloy Thin Film Growth on Nanorippled Si
Authors: Sarathlal Koyiloth Vayalil, Stephan V. Roth, Gonzalo Santoro, Peng Zhang, Matthias Schwartzkopf, Bjoern Beyersdorff
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Nanostructured magnetic thin films have gained significant relevance due to its applications in magnetic storage and recording media. Self-organized arrays of nanoparticles and nanowires can be produced by depositing metal thin films on nano-rippled substrates. The substrate topography strongly affects the film growth giving rise to anisotropic properties (optical, magnetic, electronic transport). Ion-beam erosion (IBE) method can provide large-area patterned substrates with the valuable possibility to widely modify pattern length scale by simply acting on ion beam parameters (i.e. energy, ions, geometry, etc.). In this work, investigation of the growth mechanism of Permalloy thin films on such nano-rippled Si (100) substrates using in situ grazing incidence small angle x-ray scattering measurements (GISAXS) have been done. In situ GISAXS measurements during the deposition of thin films have been carried out at the P03/MiNaXS beam line of PETRA III storage ring of DESY, Hamburg. Nanorippled Si substrates prepared by low energy ion beam sputtering with an average wavelength of 33 nm and 1 nm have been used as templates. It has been found that the film replicates the morphology up to larger thickness regimes and also the growth is highly anisotropic along and normal to the ripple wave vectors. Various growth regimes have been observed. Further, magnetic measurements have been done using magneto-optical Kerr effect by rotating the sample in the azimuthal direction. Strong uniaxial magnetic anisotropy with its easy axis in a direction normal to the ripple wave vector has been observed. The strength of the magnetic anisotropy is found to be decreasing with increasing thin film thickness values. The mechanism of the observed strong uniaxial magnetic anisotropy and its depends on the thickness of the film has been explained by correlating it with the GISAXS results. In conclusion, we have done a detailed growth analysis of Permalloy thin films deposited on nanorippled Si templates and tried to explain the correlation between structure, morphology to the observed magnetic properties.Keywords: grazing incidence small angle x-ray scattering, magnetic thin films, magnetic anisotropy, nanoripples
Procedia PDF Downloads 31318 Membrane Permeability of Middle Molecules: A Computational Chemistry Approach
Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa
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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation
Procedia PDF Downloads 18917 Considering Uncertainties of Input Parameters on Energy, Environmental Impacts and Life Cycle Costing by Monte Carlo Simulation in the Decision Making Process
Authors: Johannes Gantner, Michael Held, Matthias Fischer
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The refurbishment of the building stock in terms of energy supply and efficiency is one of the major challenges of the German turnaround in energy policy. As the building sector accounts for 40% of Germany’s total energy demand, additional insulation is key for energy efficient refurbished buildings. Nevertheless the energetic benefits often the environmental and economic performances of insulation materials are questioned. The methods Life Cycle Assessment (LCA) as well as Life Cycle Costing (LCC) can form the standardized basis for answering this doubts and more and more become important for material producers due efforts such as Product Environmental Footprint (PEF) or Environmental Product Declarations (EPD). Due to increasing use of LCA and LCC information for decision support the robustness and resilience of the results become crucial especially for support of decision and policy makers. LCA and LCC results are based on respective models which depend on technical parameters like efficiencies, material and energy demand, product output, etc.. Nevertheless, the influence of parameter uncertainties on lifecycle results are usually not considered or just studied superficially. Anyhow the effect of parameter uncertainties cannot be neglected. Based on the example of an exterior wall the overall lifecycle results are varying by a magnitude of more than three. As a result simple best case worst case analyses used in practice are not sufficient. These analyses allow for a first rude view on the results but are not taking effects into account such as error propagation. Thereby LCA practitioners cannot provide further guidance for decision makers. Probabilistic analyses enable LCA practitioners to gain deeper understanding of the LCA and LCC results and provide a better decision support. Within this study, the environmental and economic impacts of an exterior wall system over its whole lifecycle are illustrated, and the effect of different uncertainty analysis on the interpretation in terms of resilience and robustness are shown. Hereby the approaches of error propagation and Monte Carlo Simulations are applied and combined with statistical methods in order to allow for a deeper understanding and interpretation. All in all this study emphasis the need for a deeper and more detailed probabilistic evaluation based on statistical methods. Just by this, misleading interpretations can be avoided, and the results can be used for resilient and robust decisions.Keywords: uncertainty, life cycle assessment, life cycle costing, Monte Carlo simulation
Procedia PDF Downloads 28616 Ultra-deformable Drug-free Sequessome™ Vesicles (TDT 064) for the Treatment of Joint Pain Following Exercise: A Case Report and Clinical Data
Authors: Joe Collins, Matthias Rother
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Background: Oral non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the relief of joint pain during and post-exercise. However, oral NSAIDs increase the risk of systemic side effects, even in healthy individuals, and retard recovery from muscle soreness. TDT 064 (Flexiseq®), a topical formulation containing ultra-deformable drug-free Sequessome™ vesicles, has demonstrated equivalent efficacy to oral celecoxib in reducing osteoarthritis-associated joint pain and stiffness. TDT 064 does not cause NSAID-related adverse effects. We describe clinical study data and a case report on the effectiveness of TDT 064 in reducing joint pain after exercise. Methods: Participants with a pain score ≥3 (10-point scale) 12–16 hours post-exercise were randomized to receive TDT 064 plus oral placebo, TDT 064 plus oral ketoprofen, or ketoprofen in ultra-deformable phospholipid vesicles plus oral placebo. Results: In the 168 study participants, pain scores were significantly higher with oral ketoprofen plus TDT 064 than with TDT 064 plus placebo in the 7 days post-exercise (P = 0.0240) and recovery from muscle soreness was significantly longer (P = 0.0262). There was a low incidence of adverse events. These data are supported by clinical experience. A 24-year-old male professional rugby player suffered a traumatic lisfranc fracture in March 2014 and underwent operative reconstruction. He had no relevant medical history and was not receiving concomitant medications. He had undergone anterior cruciate ligament reconstruction in 2008. The patient reported restricted training due to pain (score 7/10), stiffness (score 9/10) and poor function, as well as pain when changing direction and running on consecutive days. In July 2014 he started using TDT 064 twice daily at the recommended dose. In November 2014 he noted reduced pain on running (score 2-3/10), decreased morning stiffness (score 4/10) and improved joint mobility and was able to return to competitive rugby without restrictions. No side effects of TDT 064 were reported. Conclusions: TDT 064 shows efficacy against exercise- and injury-induced joint pain, as well as that associated with osteoarthritis. It does not retard muscle soreness recovery after exercise compared with an oral NSAID, making it an alternative approach for the treatment of joint pain during and post-exercise.Keywords: exercise, joint pain, TDT 064, phospholipid vesicles
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