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Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives.
Manufacturing process simulation enables the evaluation and improvement of autoclave mold concepts early in the design phase. To achieve a high part quality at low cycle times, the thermal behavior of the autoclave mold can be investigated by means of simulations. Most challenging for such a simulation is the generation of necessary boundary conditions. Heat-up and temperature distribution in an autoclave mold are governed by flow phenomena, tooling material and shape, position within the autoclave, and the chosen autoclave cycle. This paper identifies and summarizes the most important factors influencing mold heat-up and how they can be introduced into a thermal simulation. Thermal measurements are used to quantify the impact of the various parameters. Finally, the gained knowledge is applied to develop a semi-empirical approach for boundary condition estimation that enables a simple and fast thermal simulation of the autoclave curing process with reasonably high accuracy for tooling optimization.
We present an effective and simple multiscale method for equilibrating Kremer Grest model polymer melts of varying stiffness. In our approach, we progressively equilibrate the melt structure above the tube scale, inside the tube and finally at the monomeric scale. We make use of models designed to be computationally effective at each scale. Density fluctuations in the melt structure above the tube scale are minimized through a Monte Carlo simulated annealing of a lattice polymer model. Subsequently the melt structure below the tube scale is equilibrated via the Rouse dynamics of a force-capped Kremer-Grest model that allows chains to partially interpenetrate. Finally the Kremer-Grest force field is introduced to freeze the topological state and enforce correct monomer packing. We generate 15 melts of 500 chains of 10.000 beads for varying chain stiffness as well as a number of melts with 1.000 chains of 15.000 monomers. To validate the equilibration process we study the time evolution of bulk, collective, and single-chain observables at the monomeric, mesoscopic, and macroscopic length scales. Extension of the present method to longer, branched, or polydisperse chains, and/or larger system sizes is straightforward.
Rubber materials filled with reinforcing fillers display nonlinear rheological behavior at small strain amplitudes below γ0 < 0.1. Nevertheless, rheological data are analyzed mostly in terms of linear parameters, such as shear moduli (G′, G″), which loose their physical meaning in the nonlinear regime. In this work styrene butadiene rubber filled with carbon black (CB) under large amplitude oscillatory shear (LAOS) is analyzed in terms of the nonlinear parameter I3/1. Three different CB grades are used and the filler load is varied between 0 and 70 phr. It is found that I3/1(φ) is most sensitive to changes of the total accessible filler surface area at low strain amplitudes (γ0 = 0.32). The addition of up to 70 phr CB leads to an increase of I3/1(φ) by a factor of more than ten. The influence of the measurement temperature on I3/1 is pronounced for CB levels above the percolation threshold.
Elastomers are exceptional materials owing to their ability to undergo large deformations before failure. However, due to their very low stiffness, they are not always suitable for industrial applications. Addition of filler particles provides reinforcing effects and thus enhances the material properties that render them more versatile for applications like tyres etc. However, deformation behavior of filled polymers is accompanied by several nonlinear effects like Mullins and Payne effect. To this day, the physical and chemical changes resulting in such nonlinear effect remain an active area of research. In this work, we develop a heterogeneous (or multiphase) constitutive model at the mesoscale explicitly considering filler particle aggregates, elastomeric matrix and their mechanical interaction through an approximate interface layer. The developed constitutive model is used to demonstrate cluster breakage, also, as one of the possible sources for Mullins effect observed in non-crystallizing filled elastomers.
Nach Stand von Wissenschaft und Technik werden Komponenten hinsichtlich ihrer Eigenschaften, wie Lebensdauer oder Energieeffizienz, optimiert. Allerdings können selbst hervorragende Komponenten zu ineffizienten oder instabilen Systemen führen, wenn ihr Zusammenspiel nur unzureichend berücksichtigt wird. Eine Systembetrachtung schafft ein größeres Optimierungspotential - dem erhöhten Potential steht jedoch auch ein erhöhter Komplexitätsgrad gegenüber. Die vorliegende Arbeit ist im Rahmen des Sonderforschungsbereichs 805 entstanden, dessen Ziel die Beherrschung von Unsicherheit in Systemen des Maschinenbaus ist. Die Arbeit zeigt anhand eines realen Systems aus dem Bereich der Hydraulik, wie Unsicherheit in der Entwicklungsphase beherrscht werden kann. Hierbei ist neu, dass die durch den späteren Betrieb zu erwartende Systemdegradation eines jeden möglichen Systemvorschlags antizipiert werden kann. Dadurch können Betriebs- und Wartungskosten vorausgesagt und minimiert werden und durch eine optimale Betriebs- und Wartungsstrategie die Verfügbarkeit des Systems garantiert werden. Wesentliche Fragen bei der optimalen Auslegung des betrachteten hydrostatischen Getriebes sind dessen physikalische Modellierung, die Darstellung des Optimierungsproblems als gemischt-ganzzahliges lineares Programm, und dessen algorithmische Behandlung zur Lösungsfindung. Hierzu werden Heuristiken zum schnelleren Auffinden sinnvoller Systemtopologien vorgestellt und mittels mathematischer Dekomposition eine Bewertung des dynamischen Verschleiß- und Wartungsverlaufs möglicher Systemvorschläge vorgenommen. Die Arbeit stellt die Optimierung technischer Systeme an der Schnittstelle von Mathematik, Informatik und Ingenieurwesen sowohl gründlich als auch anschaulich und nachvollziehbar dar.
Pure analytical or experimental methods can only find a control strategy for technical systems with a fixed setup. In former contributions we presented an approach that simultaneously finds the optimal topology and the optimal open-loop control of a system via Mixed Integer Linear Programming (MILP). In order to extend this approach by a closed-loop control we present a Mixed Integer Program for a time discretized tank level control. This model is the basis for an extension by combinatorial decisions and thus for the variation of the network topology. Furthermore, one is able to appraise feasible solutions using the global optimality gap.
Finding a good system topology with more than a handful of components is a
highly non-trivial task. The system needs to be able to fulfil all expected load cases, but at the
same time the components should interact in an energy-efficient way. An example for a system
design problem is the layout of the drinking water supply of a residential building. It may be
reasonable to choose a design of spatially distributed pumps which are connected by pipes in at
least two dimensions. This leads to a large variety of possible system topologies. To solve such
problems in a reasonable time frame, the nonlinear technical characteristics must be modelled
as simple as possible, while still achieving a sufficiently good representation of reality. The
aim of this paper is to compare the speed and reliability of a selection of leading mathematical
programming solvers on a set of varying model formulations. This gives us empirical evidence
on what combinations of model formulations and solver packages are the means of choice with the current state of the art.
Following the recent successful landings and occasional re-awakenings of PHILAE, the lander carried aboard ROSETTA to comet 67P/Churyumov-Gerasimenko, and the launch of the Mobile Asteroid Surface Scout, MASCOT, aboard the HAYABUSA2 space probe to asteroid (162173) Ryugu we present an overview of the characteristics and peculiarities of small spacecraft missions to small solar system bodies (SSSB). Their main purpose is planetary science which is transitioning from a ‘pure’ science of observation of the distant to one also supporting in-situ applications relevant for life on Earth. Here we focus on missions at the interface of SSSB science and planetary defence applications. We provide a brief overview of small spacecraft SSSB missions and on this background present recent missions, projects and related studies at the German Aerospace Center, DLR, that contribute to the worldwide planetary defence community. These range from Earth orbit technology demonstrators to active science missions in interplanetary space. We provide a summary of experience from recently flown missions with DLR participation as well as a number of studies. These include PHILAE, the lander of ESA’s ROSETTA comet rendezvous mission now on the surface of comet 67P/Churyumov-Gerasimenko, and the Mobile Asteroid Surface Scout, MASCOT, now in cruise to the ~1 km diameter C-type near-Earth asteroid (162173) Ryugu aboard the Japanese sample-return probe HAYABUSA2. We introduce the differences between the conventional methods employed in the design, integration and testing of large spacecraft and the new approaches developed by small spacecraft projects. We expect that the practical experience that can be gained from projects on extremely compressed timelines or with high-intensity operation phases on a newly explored small solar system body can contribute significantly to the study, preparation and realization of future planetary defence related missions. One is AIDA (Asteroid Impact & Deflection Assessment), a joint effort of ESA, JHU/APL, NASA, OCA and DLR, combining JHU/APL’s DART (Double Asteroid Redirection Test) and ESA’s AIM (Asteroid Impact Monitor) spacecraft in a mission towards near-Earth binary asteroid system (65803) Didymos. DLR is currently applying MASCOT heritage and lessons learned to the design of MASCOT2, a lander for the AIM mission to support a bistatic low frequency radar experiment with PHILAE/ROSETTA CONSERT heritage to explore the inner structure of Didymoon which is the designated impact target for DART.
There are different types of games that try to make use of the motivation of a gaming situation in learning contexts. This paper introduces the new terminology ‘Competence Developing Game’ (CDG) as an umbrella term for all games with this intention. Based on this new terminology, an assessment framework has been developed and validated in scope of an empirical study. Now, all different types of CDGs can be evaluated according to a defined and uniform set of assessment criteria and, thus, are comparable according to their characteristics and effectiveness.
This paper describes the results and methods used during the 8th Global Trajectory Optimization Competition (GTOC) of the DLR team. Trajectory optimization is crucial for most of the space missions and usually can be formulated as a global optimization problem. A lot of research has been done to different type of mission problems. The most demanding ones are low thrust transfers with e.g. gravity assist sequences. In that case the optimal control problem is combined with an integer problem. In most of the GTOCs we apply a filtering of the problem based on domain knowledge.
Future engineers are increasingly confronted with the so-called Megatrends which are the big social challenges society has to cope with. These Megatrends, such as “Silver Society”, “Globalization”, “Mobility” and “Female Shift” require an application-oriented perspective on Diversity especially in the engineering field. Therefore, it is necessary to enable future engineers not only to look at the technical perspectives of a problem, but also to be able to see the related questions within societies they are developing their artefacts for. The aim of teaching engineering should be to prepare engineers for these requirements and to draw attention to the diverse needs in a globalized world.
Bringing together technical knowledge and social competences which go beyond a mere training of the so-called “soft skills”, is a new approach followed at RWTH Aachen University, one of the leading technical universities in Germany. RWTH Aachen University has established the bridging professorship “Gender and Diversity in Engineering” (GDI) which educates engineers with an interdisciplinary approach to expand engineering limits. In the frame of a sustainable teaching concept the research group under the leadership of Prof. Carmen Leicht-Scholten has developed an approach which imparts a supplication-specific Gender and Diversity expertise to engineers. In workshops students gain theoretical knowledge about Gender and Diversity and learn how to transfer their knowledge in their special field of study and later work. To substantiate this, the course participants have to solve case studies from real life. The cases which are developed in collaboration with non-profit organizations and enterprises from economy rise the students to challenges which are inspired by professional life. Evaluation shows the success of this approach as well as an increasing demand for such teaching formats.
Engineers are of particular importance for the societies of tomorrow. The big social challenges society has to cope with in future, can only be mastered, if engineers link the development and innovation process closely with the requirements of people. As a result, in the frame of the innovation process engineers have to design and develop products for diverse users. Therefore, the consideration of diversity in this process is a core competence engineers should have. Implementing the consideration of diverse requirements into product design is also linked to the development of sustainable products and thus leads to social responsible research and development, the core concept formulated by the EU.
For this reason, future engineers should be educated to look at the technical perspectives of a problem embedded in the related questions within societies they are developing their artefacts for. As a result, the aim of teaching engineering should be to prepare engineers for these requirements and to draw attention to the diverse needs in a globalized world.
To match the competence profiles of future engineers to the global challenges and the resulting social responsibility, RWTH Aachen University, one of the leading technical universities in Germany, has established the bridging professorship “Gender and Diversity in Engineering” (GDI) which educates engineers with an interdisciplinary approach to expand engineering limits. The interdisciplinary teaching concept of the research group pursues an approach which imparts an application oriented Gender and Diversity expertise to future engineers. In the frame of an established teaching concept, which is a result of experiences and expertise of the research group, students gain theoretical knowledge about Gender and Diversity and learn how to transfer their knowledge into their later field of action.
In the frame of the conference the institutional approach will be presented as well as the teaching concept which will be introduced by concrete course examples.
The behaviour of infilled reinforced concrete frames under horizontal load has been widely investigated, both experimentally and numerically. Since experimental tests represent large investments, numerical simulations offer an efficient approach for a more comprehensive analysis. When RC frames with masonry infill walls are subjected to horizontal loading, their behaviour is highly non-linear after a certain limit, which makes their analysis quite difficult. The non-linear behaviour results from the complex inelastic material properties of the concrete, infill wall and conditions at the wall-frame interface. In order to investigate this non-linear behaviour in detail, a finite element model using a micro modelling approach is developed, which is able to predict the complex non-linear behaviour resulting from the different materials and their interaction. Concrete and bricks are represented by a non-linear material model, while each reinforcement bar is represented as an individual part installed in the concrete part and behaving elasto-plastically. Each brick is modelled individually and connected taking into account the non-linearity of a brick mortar interface. The same approach is followed using two finite element software packages and the results are compared with the experimental results. The numerical models show a good agreement with the experiments in predicting the overall behaviour, but also very good matching for strength capacity and drift. The results emphasize the quality and the valuable contribution of the numerical models for use in parametric studies, which are needed for the derivation of design recommendations for infilled frame structures.
Development of a subject-oriented reference process model for the telecommunications industry
(2016)
Generally the usage of reference models can be structured top-down or bottom-up. The practical need of agile change and flexible organizational implementation requires a consistent mapping to an operational level. In this context, well-established reference process models are typically structured top-down. The subject-oriented Business Process Management (sBPM) offers a modeling concept that is structured bottom-up and concentrates on the process actors on an
operational level. This paper applies sBPM to the enhanced Telecom Operations Map (eTOM), a well-accepted reference process model in the telecommunications industry. The resulting design artifact is a concrete example for a combination of a bottom-up and top-down developed reference model. The results are evaluated and confirmed in practical context through the involvement of the industry body TMForum.
The scientific interest for near-Earth asteroids as well as the interest in potentially hazardous asteroids from the perspective of planetary defense led the space community to focus on near-Earth asteroid mission studies. A multiple near-Earth asteroid rendezvous mission with close-up observations of several objects can help to improve the characterization of these asteroids. This work explores the design of a solar-sail spacecraft for such a mission, focusing on the search of possible sequences of encounters and the trajectory optimization. This is done in two sequential steps: a sequence search by means of a simplified trajectory model and a set of heuristic rules based on astrodynamics, and a subsequent optimization phase. A shape-based approach for solar sailing has been developed and is used for the first phase. The effectiveness of the proposed approach is demonstrated through a fully optimized multiple near-Earth asteroid rendezvous mission. The results show that it is possible to visit five near-Earth asteroids within 10 years with near-term solar-sail technology.
This paper describes the procedure on the evaluation of the masonry chapter for the next generation of Eurocode 8, the European Standard for earthquake-resistant design. In CEN, TC 250/SC8, working group WG 1 has been established to support the subcommittee on the topic of masonry on both design of new structures (EN1998-1) and assessment of existing structures (EN1998-3). The aim is to elaborate suggestions for amendments which fit the current state of the art in masonry and earthquake-resistant design. Focus will be on modelling, simplified methods, linear-analysis (q-values, overstrength-values), nonlinear procedures, out-of-plane design as well as on clearer definition of limit states. Beside these, topics related to general material properties, reinforced masonry, confined masonry, mixed structures and non-structural infills will be covered too. This paper presents the preliminary work and results up to the submission date.
At the present time, one of the most serious environmental problems of Central Asia and South Kazakhstan is the ongoing large-scale deterioration of principal urban tree populations. Several major centers of massive spread of invasive plant pests have been found in urban dendroflora of this region. The degree of damage of seven most wide-spread aboriginal tree species was found to range from 21.4±1.1 to 85.4±1.8%. In particular, the integrity of the native communities of sycamore (Platanus spp.), willow (Salix spp.), poplar (Populus spp.) and elm (Ulmus spp.) is highly endangered. Our taxonomic analysis of the most dangerous tree pests of the region has revealed them as neobiontic xylophilous insects such as Cossus cossus L. (Order: Lepidoptera L.) Monochamus urussovi Fisch., Monochamus sutor L., Acanthocinus aedelis L. and Ñetonia aureate L. (Order: Coleoptera L.). We relate the origin of this threatening trend with the import of industrial wood in the mid 90s of the last century that was associated with high degree of the constructional work in the region. Because of the absence of efficient natural predators of the pest species, the application of microbiological methods of the pest control and limitation is suggested.
Optical flow estimation is known from Computer Vision where it is used to determine obstacle movements through a sequence of images following an assumption of brightness conservation. This paper presents the first study on application of the optical flow method to aerated stepped spillway flows. For this purpose, the flow is captured with a high-speed camera and illuminated with a synchronized LED light source. The flow velocities, obtained using a basic Horn–Schunck method for estimation of the optical flow coupled with an image pyramid multi-resolution approach for image filtering, compare well with data from intrusive conductivity probe measurements. Application of the Horn–Schunck method yields densely populated flow field data sets with velocity information for every pixel. It is found that the image pyramid approach has the most significant effect on the accuracy compared to other image processing techniques. However, the final results show some dependency on the pixel intensity distribution, with better accuracy found for grey values between 100 and 150.
Retinal Vessel Analysis (RVA) in the context of subarachnoid hemorrhage: A proof of concept study
(2016)
Background
Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH.
Methods
In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2–14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling.
Results
Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion.
Conclusion
RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort.
Background and Objective
Effective leg extension training at a leg press requires high forces, which need to be controlled to avoid training-induced damage. In order to avoid high external knee adduction moments, which are one reason for unphysiological loadings on knee joint structures, both training movements and the whole reaction force vector need to be observed. In this study, the applicability of lateral and medial changes in foot orientation and position as possible manipulated variables to control external knee adduction moments is investigated. As secondary parameters both the medio-lateral position of the center of pressure and the frontal-plane orientation of the reaction force vector are analyzed.
Methods
Knee adduction moments are estimated using a dynamic model of the musculoskeletal system together with the measured reaction force vector and the motion of the subject by solving the inverse kinematic and dynamic problem. Six different foot conditions with varying positions and orientations of the foot in a static leg press are evaluated and compared to a neutral foot position.
Results
Both lateral and medial wedges under the foot and medial and lateral shifts of the foot can influence external knee adduction moments in the presented study with six healthy subjects. Different effects are observed with the varying conditions: the pose of the leg is changed and the direction and center of pressure of the reaction force vector is influenced. Each effect results in a different direction or center of pressure of the reaction force vector.
Conclusions
The results allow the conclusion that foot position and orientation can be used as manipulated variables in a control loop to actively control knee adduction moments in leg extension training.
This paper presents the results of an eigenvalue analysis of the Fatih Sultan Mehmet Bridge. A high-resolution finite element model was created directly from the available design documents. All physical properties of the structural components were included in detail, so no calibration to the measured data was necessary. The deck and towers were modeled with shell elements. A nonlinear static analysis was performed before the eigenvalue calculation. The calculated natural frequencies and corresponding mode shapes showed good agreement with the available measured ambient vibration data. The calculation of the effective modal mass showed that nine modes had single contributions higher than 5 % of the total mass. They were in a frequency range up to 1.2 Hz. The comparison of the results for the torsional modes especially demonstrated the advantage of using thin shell finite elements over the beam modeling approach.
The conjunction of (bio-)chemical recognition elements with nanoscale biological building blocks such as virus particles is considered as a very promising strategy for the creation of biohybrids opening novel opportunities for label-free biosensing. This work presents a new approach for the development of biosensors using tobacco mosaic virus (TMV) nanotubes or coat proteins (CPs) as enzyme nanocarriers. Sensor chips combining an array of Pt electrodes loaded with glucose oxidase (GOD)-modified TMV nanotubes or CP aggregates were used for amperometric detection of glucose as a model system for the first time. The presence of TMV nanotubes or CPs on the sensor surface allows binding of a high amount of precisely positioned enzymes without substantial loss of their activity, and may also ensure accessibility of their active centers for analyte molecules. Specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CPs was achieved via bioaffinity binding. These layouts were tested in parallel with glucose sensors with adsorptively immobilized [SA]-GOD, as well as [SA]-GOD crosslinked with glutardialdehyde, and came out to exhibit superior sensor performance. The achieved results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for future applications in biosensorics and biochips.
The LAPS (light-addressable potentiometric sensor) platform is one of the most attractive approaches for chemical and biological sensing with many applications ranging from pH and ion/analyte concentration measurements up to cell metabolism detection and chemical imaging. However, although it is generally accepted that LAPS measurements are spatially resolved, the light-addressability feature of LAPS devices has not been discussed in detail so far. In this work, an extended electrical equivalent-circuit model of the LAPS has been presented, which takes into account possible cross-talk effects due to the capacitive coupling of the non-illuminated region. A shunting effect of the non-illuminated area on the measured photocurrent and addressability of LAPS devices has been studied. It has been shown, that the measured photocurrent will be determined not only by the local interfacial potential in the illuminated region but also by possible interfacial potential changes in the non-illuminated region, yielding cross-talk effects. These findings were supported by the experimental investigations of a penicillin-sensitive multi-spot LAPS and a metal-insulator-semiconductor LAPS as model systems.
Optimisation of a urea selective catalytic reduction system with a coated ceramic mixing element
(2017)
SAR Simulations & Safety
(2017)
Enzyme-based logic gates and circuits - analytical applications and interfacing with electronics
(2017)
The paper is an overview of enzyme-based logic gates and their short circuits, with specific examples of Boolean AND and OR gates, and concatenated logic gates composed of multi-step enzyme-biocatalyzed reactions. Noise formation in the biocatalytic reactions and its decrease by adding a “filter” system, converting convex to sigmoid response function, are discussed. Despite the fact that the enzyme-based logic gates are primarily considered as components of future biomolecular computing systems, their biosensing applications are promising for immediate practical use. Analytical use of the enzyme logic systems in biomedical and forensic applications is discussed and exemplified with the logic analysis of biomarkers of various injuries, e.g., liver injury, and with analysis of biomarkers characteristic of different ethnicity found in blood samples on a crime scene. Interfacing of enzyme logic systems with modified electrodes and semiconductor devices is discussed, giving particular attention to the interfaces functionalized with signal-responsive materials. Future perspectives in the design of the biomolecular logic systems and their applications are discussed in the conclusion.
A graphene-functionalized carbon fiber electrode was modified with adsorbed polyethylenimine to introduce amino functionalities and then with trigonelline and 4-carboxyphenylboronic acid covalently bound to the amino groups. The trigonelline species containing quarterized pyridine groups produced positive charge on the electrode surface regardless of the pH value, while the phenylboronic acid species were neutral below pH 8 and negatively charged above pH 9 (note that their pKa=8.4). The total charge on the monolayer-modified electrode was positive at the neutral pH and negative at pH > 9. Note that 4-carboxyphenylboronic acid was attached to the electrode surface in molar excess to trigonelline, thus allowing the negative charge to dominate on the electrode surface at basic pH. Negatively charged fluorescent dye-labeled insulin (insulin-FITC) was loaded on the modified electrode surface at pH 7.0 due to its electrostatic attraction to the positively charged interface. The local pH in close vicinity to the electrode surface was increased to ca. 9–10 due to consumption of H+ ions upon electrochemical reduction of oxygen proceeding at the potential of −1.0 V (vs. Ag/AgCl) applied on the modified electrode. The process resulted in recharging of the electrode surface to the negative value due to the formation of the negative charge on the phenylboronic acid groups, thus resulting in the electrostatic repulsion of insulin-FITC and stimulating its release from the electrode surface. The insulin release was characterized by fluorescence spectroscopy (using the FITC-labeled insulin), by electrochemical measurements on an iridium oxide, IrOx, electrode and by mass spectrometry. The graphene-functionalized carbon fiber electrode demonstrated significant advantages in the signal-stimulated insulin release comparing with the carbon fiber electrode without the graphene species.
Control mechanisms like Industrial Controls Systems (ICS) and its subgroup SCADA (Supervisory Control and Data Acquisition) are a prerequisite to automate industrial processes. While protection of ICS on process management level is relatively straightforward – well known office IT security mechanisms can be used – protection on field bus level is harder to achieve as there are real-time and production requirements like 24x7 to consider. One option to improve security on field bus level is to introduce controls that help to detect and to react on attacks. This paper introduces an initial set of intrusion detection mechanisms for the field bus protocol EtherCAT. To this end existing Ethernet attack vectors including packet injection and man-in-the-middle attacks are tested in an EtherCAT environment, where they could interrupt the EtherCAT network and may even cause physical damage. Based on the signatures of such attacks, a preprocessor and new rule options are defined for the open source intrusion detection system Snort demonstrating the general feasibility of intrusion detection on field bus level.
Research collaborations provide opportunities for both practitioners and researchers: practitioners need solutions for difficult business challenges and researchers are looking for hard problems to solve and publish. Nevertheless, research collaborations carry the risk that practitioners focus on quick solutions too much and that researchers tackle theoretical problems, resulting in products which do not fulfill the project requirements.
In this paper we introduce an approach extending the ideas of agile and lean software development. It helps practitioners and researchers keep track of their common research collaboration goal: a scientifically enriched software product which fulfills the needs of the practitioner’s business model.
This approach gives first-class status to application-oriented metrics that measure progress and success of a research collaboration continuously. Those metrics are derived from the collaboration requirements and help to focus on a commonly defined goal.
An appropriate tool set evaluates and visualizes those metrics with minimal effort, and all participants will be pushed to focus on their tasks with appropriate effort. Thus project status, challenges and progress are transparent to all research collaboration members at any time.
An array of four independently wired indium tin oxide (ITO) electrodes was used for electrochemically stimulated DNA release and activation of DNA-based Identity, AND and XOR logic gates. Single-stranded DNA molecules were loaded on the mixed poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA)/poly(methacrylic acid) (PMAA) brush covalently attached to the ITO electrodes. The DNA deposition was performed at pH 5.0 when the polymer brush is positively charged due to protonation of tertiary amino groups in PDMAEMA, thus resulting in electrostatic attraction of the negatively charged DNA. By applying electrolysis at −1.0 V(vs. Ag/AgCl reference) electrochemical oxygen reduction resulted in the consumption of hydrogen ions and local pH increase near the electrode surface. The process resulted in recharging the polymer brush to the negative state due to dissociation of carboxylic groups of PMAA, thus repulsing the negatively charged DNA and releasing it from the electrode surface. The DNA release was performed in various combinations from different electrodes in the array assembly. The released DNA operated as input signals for activation of the Boolean logic gates. The developed system represents a step forward in DNA computing, combining for the first time DNA chemical processes with electronic input signals.
The capacitive electrolyte–insulator–semiconductor (EIS) structure is a typical device based on a field-effect sensor platform. With a simple silicon-based structure, EIS have been useful for several sensing applications, especially with incorporation of nanostructured films to modulate the ionic transport and the flat-band potential. In this paper, we report on ion transport and changes in flat-band potential in EIS sensors made with layer-by-layer films containing poly(amidoamine) (PAMAM) dendrimer and single-walled carbon nanotubes (SWNTs) adsorbed on p-Si/SiO 2 /Ta 2 O 5 chips with an Al ohmic contact. The impedance spectra were fitted using an equivalent circuit model, from which we could determine parameters such as the double-layer capacitance. This capacitance decreased with the number of bilayers owing to space charge accumulated at the electrolyte–insulator interface, up to three PAMAM/SWNTs bilayers, after which it stabilized. The charge-transfer resistance was also minimum for three bilayers, thus indicating that this is the ideal architecture for an optimized EIS performance. The understanding of the influence of nanostructures and the fine control of operation parameters pave the way for optimizing the design and performance of new EIS sensors.