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Muller A.,Schmalkalden University of Applied Sciences | Seul T.,Schmalkalden University of Applied Sciences
Annual Technical Conference - ANTEC, Conference Proceedings | Year: 2015

The product development process can be divided into the following phases: Planning-, Concept-, Development-, Elaboration-and Product Optimization Phase [1]. Especially in the development-, elaboration and product optimization phase, the statistical experimental design can support the development process of medical products considerably. In practice however the tool of the Design of Experiments (DoE) is in most cases only used in a limited area of the development process. Consequently the qualification of injection molds is increasingly planned, analyzed and documented with the help of a DoE. However, the statistical experimental design not only provides benefits for the qualification of production tools. Because a DoE can already be utilized in advance and after the start of series production, in order to analyze and optimize product and process features. In this work new scientific approaches are demonstrated, how the statistical experimental design can be utilized profitably in the entire development process of medical products. This first-time compilation has been implemented in our own work and successfully tested in practice.


Seidel E.,Schmalkalden University of Applied Sciences | Seul T.,Schmalkalden University of Applied Sciences
Annual Technical Conference - ANTEC, Conference Proceedings | Year: 2015

Fiber-reinforced composites assume a key function in lightweight design. Due to high material and manufacturing costs, the objective is the near net shape manufacture of composite components via the forming processes. Subsequent cutting processes such as deburring are, however, still necessary. This post-processing leads to a reduction in the mechanical properties, not only through the cutting of the continuous fibres but also through potential production-related damage. The excellent durability properties of fiber-reinforced composites are thus lost. In this paper it is assumed that the productionrelated reduction in the mechanical properties of composites with thermoplastic matrix is not only caused and influenced by the design of the machining process but also through the method of clamping the parts which is necessary during the process. The qualitative evaluation is done through microscopical determination of the surface damage and the inter-laminar damage through ultrasonic inspection. Following an accelerated ageing process under the influence of bending loads, the determination of the flexural strength is carried out.


Kusch J.,Friedrich - Schiller University of Jena | Thon S.,Friedrich - Schiller University of Jena | Schulz E.,Schmalkalden University of Applied Sciences | Biskup C.,Friedrich - Schiller University of Jena | And 4 more authors.
Nature Chemical Biology | Year: 2012

Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are tetrameric membrane proteins that generate electrical rhythmicity in specialized neurons and cardiomyocytes. The channels are primarily activated by voltage but are receptors as well, binding the intracellular ligand cyclic AMP. The molecular mechanism of channel activation is still unknown. Here we analyze the complex activation mechanism of homotetrameric HCN2 channels by confocal patch-clamp fluorometry and kinetically quantify all ligand binding steps and closed-open isomerizations of the intermediate states. For the binding affinity of the second, third and fourth ligand, our results suggest pronounced cooperativity in the sequence positive, negative and positive, respectively. This complex interaction of the subunits leads to a preferential stabilization of states with zero, two or four ligands and suggests a dimeric organization of the activation process: within the dimers the cooperativity is positive, whereas it is negative between the dimers. © 2012 Nature America, Inc. All rights reserved.


Benndorf K.,Friedrich - Schiller University of Jena | Thon S.,Friedrich - Schiller University of Jena | Schulz E.,Schmalkalden University of Applied Sciences
Biophysical Journal | Year: 2012

In a multimeric receptor protein, the binding of a ligand can modulate the binding of a succeeding ligand. This phenomenon, called cooperativity, is caused by the interaction of the receptor subunits. By using a complex Markovian model and a set of parameters determined previously, we analyzed how the successive binding of four ligands leads to a complex cooperative interaction of the subunits in homotetrameric HCN2 pacemaker channels. The individual steps in the model were characterized by Gibbs free energies for the equilibria and activation energies, specifying the affinity of the binding sites and the transition rates, respectively. Moreover, cooperative free energies were calculated for each binding step in both the closed and the open channel. We show that the cooperativity sequence positive-negative-positive determined for the binding affinity is generated by the combined effect of very different cooperativity sequences determined for the binding and unbinding rates, which are negative-negative-positive and no-negative-no, respectively. It is concluded that in the ligand-induced activation of HCN2 channels, the sequence of cooperativity based on the binding affinity is caused by two even qualitatively different sequences of cooperativity that are based on the rates of ligand binding and unbinding. © 2012 Biophysical Society.


Benndorf K.,Friedrich - Schiller University of Jena | Kusch J.,Friedrich - Schiller University of Jena | Schulz E.,Schmalkalden University of Applied Sciences
PLoS Computational Biology | Year: 2012

Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are voltage-gated tetrameric cation channels that generate electrical rhythmicity in neurons and cardiomyocytes. Activation can be enhanced by the binding of adenosine-3′,5′-cyclic monophosphate (cAMP) to an intracellular cyclic nucleotide binding domain. Based on previously determined rate constants for a complex Markovian model describing the gating of homotetrameric HCN2 channels, we analyzed probability fluxes within this model, including unidirectional probability fluxes and the probability flux along transition paths. The time-dependent probability fluxes quantify the contributions of all 13 transitions of the model to channel activation. The binding of the first, third and fourth ligand evoked robust channel opening whereas the binding of the second ligand obstructed channel opening similar to the empty channel. Analysis of the net probability fluxes in terms of the transition path theory revealed pronounced hysteresis for channel activation and deactivation. These results provide quantitative insight into the complex interaction of the four structurally equal subunits, leading to non-equality in their function. © 2012 Benndorf et al.


Nache V.,Friedrich - Schiller University of Jena | Eick T.,Friedrich - Schiller University of Jena | Schulz E.,Schmalkalden University of Applied Sciences | Schmauder R.,Friedrich - Schiller University of Jena | Benndorf K.,Friedrich - Schiller University of Jena
Nature Communications | Year: 2013

Tetrameric cyclic nucleotide-gated (CNG) channels mediate receptor potentials in olfaction and vision. The channels are activated by the binding of cyclic nucleotides to a binding domain embedded in the C terminus of each subunit. Here using a fluorescent cGMP derivative (fcGMP), we show for homotetrameric CNGA2 channels that ligand unbinding is ∼50 times faster at saturating than at subsaturating fcGMP. Analysis with complex Markovian models reveals two pathways for ligand unbinding; the partially liganded open channel unbinds its ligands from closed states only, whereas the fully liganded channel reaches a different open state from which it unbinds all four ligands rapidly. Consequently, the transition pathways for ligand binding and activation of a fully liganded CNGA2 channel differ from that of ligand unbinding and deactivation, resulting in pronounced hysteresis of the gating mechanism. This concentration-dependent gating mechanism allows the channels to respond to changes in the cyclic nucleotide concentration with different kinetics. © 2013 Macmillan Publishers Limited. All rights reserved.


Krajewski J.,University of Wuppertal | Schnieder S.,University of Wuppertal | Sommer D.,Schmalkalden University of Applied Sciences | Batliner A.,Friedrich - Alexander - University, Erlangen - Nuremberg | Schuller B.,TU Munich
Neurocomputing | Year: 2012

Comparing different novel feature sets and classifiers for speech processing based fatigue detection is the primary aim of this study. Thus, we conducted a within-subject partial sleep deprivation design (20.00-04.00. h,. N=77 participants) and recorded 372 speech samples of sustained vowel phonation. The self-report on the Karolinska Sleepiness Scale (KSS) and an observer report on the KSS, the KSS Observer Scale were applied to determine sleepiness reference values. Feature extraction methods of non-linear dynamics (NLD) provide additional information regarding the dynamics and structure of sleepiness speech. In all, 395 NLD features and the 170 phonetic features, which have been computed partially, represent so far unknown auditive-perceptual concepts. Several NLD and phonetic features show significant correlations to KSS ratings, e.g., from the NLD features for male speakers the skewness of vector length within reconstructed phase space (r=.56), and for female speaker the mean of Cao's minimum embedding dimensions (r=-.39). After a correlation-filter feature subset selection different classification models and ensemble classifiers (by AdaBoost, Bagging) were trained. Bagging procedures turned out to achieve best performance for male and female speakers on the phonetic and the NLD feature set. The best models for the phonetic feature set achieved 78.3% (NaïveBayes) for male and 68.5% (Bagging Bayes Net) for female speaker classification accuracy in detecting sleepiness. The best model for the NLD feature set achieved 77.2% (Bagging Bayes Net) for male and 76.8% (Bagging Bayes Net) for female speakers. Nevertheless, employing the combined phonetic and NLD feature sets provided additional information and thus resulted in an improved highest UA of 79.6% for male (Bayes Net) and 77.1% for female (AdaBoost Nearest Neighbor) speakers. © 2011 Elsevier B.V.


Englmeier K.,Schmalkalden University of Applied Sciences | Murtagh F.,University of Derby
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2016

Information Discovery (ID) is predominantly addressed by approaches from Artificial Intelligence (AI). Automatic ID scans large amounts of data and identifies as many potential candidates for discovery as possible. Mass discovery may in fact serve the needs of many information consumers. However, that does not mean that it addresses a broad range of user interests, too. Economies of scale urge the development of automatic tools to address user needs only from a certain critical mass. Hence, many user needs remain unaddressed. This is where HCI comes into play and provides fundamentals for pattern languages that empower information consumers to stage their own information discovery. With this paper we want to draw attention to an approach that is developed around the paradigm of human-centered interaction design. We present an Open Discovery Language that can completely be controlled by information consumers. © Springer International Publishing Switzerland 2016.


Sommer D.,Schmalkalden University of Applied Sciences | Golz M.,Schmalkalden University of Applied Sciences
2010 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC'10 | Year: 2010

In an overnight driving simulation study three commercially available devices of fatigue monitoring technologies (FMT) were applied to test their accuracy. 16 volunteers performed driving tasks during eight sessions (40 min each) separated by 15 minutes breaks. The main output variable of FMT devices, which is the percentage of eye closure (PERCLOS), the driving performance (standard deviation of lateral position in lane, SDL), the electroencephalogram (EEG) and electrooculogram (EOG) were recorded during driving. In addition, the subjective self-rated Karolinska sleepiness scale (KSS) was assessed every 2 min. As expected, Pearson productmoment correlation coefficient (PMCC) yielded significant linear dependence between KSS and PERCLOS as well as between SDL and PERCLOS. However, if PMCC was estimated within smaller data segments (3 min) as well as without averaging across subjects then strongly decreased correlation coefficients resulted. To further validate PERCLOS at higher temporal resolution its ability to discriminate between mild and strong fatigue was investigated and compared to the results of the same analysis for EEG/EOG. Spectral-domain features of both types of signals were classified using Support- Vector Machines (SVM). Results suggest that EEG/EOG indicate driver fatigue much better than PERCLOS. Therefore, current FMT devices perform acceptably if temporal resolution is low (> 20 min). But, even under laboratory conditions large errors have to be expected if fatigue is estimated on an individual level and with high temporal resolution. © 2010 IEEE.


Holl K.,Schmalkalden University of Applied Sciences | Seul T.,Schmalkalden University of Applied Sciences
Polymer Engineering and Science | Year: 2016

Microorganisms on components should be killed through sterilization in order to ensure the safe use of medical products for patients. Therefore, polymer parts are treated particularly with gamma radiation, ethylene oxide, or superheated steam; such treatment may result in a modified structure or the degradation of the polymer. The present paper shall demonstrate how the mechanical properties of tension bars and welded samples of polypropylene and polycarbonate change during the sterilization procedure. The resulting changes in the structure and the degradation respectively will be analyzed by Fourier transform infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) and structural property relationships shall be derived. The conducted analyses showed that the changes in the mechanical properties depend on the sample, the sterilization procedure, and the corresponding polymer; and that those changes must be considered when designing the respective products. © 2016 Society of Plastics Engineers.

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