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Showing papers by "Mannheim University of Applied Sciences published in 2015"


Journal ArticleDOI
TL;DR: In this article, a temperature-controlled aluminum plate microreactor was developed and tested in the exothermic synthesis of 3-piperidino propionic acid ethyl ester by Michael addition.

60 citations


Journal ArticleDOI
TL;DR: This article studies the symmetries and transformations that connect different circular codes and shows that the class of 216 $$C^3$$C3 maximal self-complementary codes can be partitioned into 27 equivalence classes defined by a particular set of transformations.
Abstract: Circular codes, putative remnants of primeval comma-free codes, have gained considerable attention in the last years. In fact they represent a second kind of genetic code potentially involved in detecting and maintaining the normal reading frame in protein coding sequences. The discovering of an universal code across species suggested many theoretical and experimental questions. However, there is a key aspect that relates circular codes to symmetries and transformations that remains to a large extent unexplored. In this article we aim at addressing the issue by studying the symmetries and transformations that connect different circular codes. The main result is that the class of 216 $$C^3$$ maximal self-complementary codes can be partitioned into 27 equivalence classes defined by a particular set of transformations. We show that such transformations can be put in a group theoretic framework with an intuitive geometric interpretation. More general mathematical results about symmetry transformations which are valid for any kind of circular codes are also presented. Our results pave the way to the study of the biological consequences of the mathematical structure behind circular codes and contribute to shed light on the evolutionary steps that led to the observed symmetries of present codes.

54 citations


Journal ArticleDOI
TL;DR: The authors' data show that the E. coli ribB FMN riboswitch is unusual because it operates at the transcriptional and also at the translational level, and constitutes a target for the antibiotic roseoflavin produced by Streptomyces davawensis.
Abstract: FMN riboswitches are genetic elements that, in many bacteria, control genes responsible for biosynthesis and/or transport of riboflavin (vitamin B2 ). We report that the Escherichia coli ribB FMN riboswitch controls expression of the essential gene ribB coding for the riboflavin biosynthetic enzyme 3,4-dihydroxy-2-butanone-4-phosphate synthase (RibB; EC 4.1.99.12). Our data show that the E. coli ribB FMN riboswitch is unusual because it operates at the transcriptional and also at the translational level. Expression of ribB is negatively affected by FMN and by the FMN analog roseoflavin mononucleotide, which is synthesized enzymatically from roseoflavin and ATP. Consequently, in addition to flavoenzymes, the E. coli ribB FMN riboswitch constitutes a target for the antibiotic roseoflavin produced by Streptomyces davawensis.

54 citations


Journal ArticleDOI
TL;DR: It is concluded that Tubastatin A is capable of counteracting the microtubule defects observed in MeCP2-deficient cells, which could in turn lead to the restoration of molecular trafficking along themicrotubules and thus could be a potentially new therapeutic option for RTT.
Abstract: Rett syndrome (RTT) is a severe neurodevelopmental disorder, predominantly caused by loss of function mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Despite the genetic cause being known in the majority of cases, the pathophysiology of the neurological phenotype of RTT is largely unknown. Tubulin and the microtubule network play an essential role in neuronal function whereby the acetylation state of microtubules dictates the efficiency of neuronal migration and differentiation, synaptic targeting and molecular motor trafficking of mRNA, high-energy mitochondria and brain-derived neurotrophic factor (BDNF)-containing vesicles. Recent reports have shown perturbations in tubulin and microtubule dynamics in MeCP2-deficient cells, suggesting a link between the aberrations of these cellular entities and the neurobiology of RTT. We have interrogated the functional state of the microtubule network in fibroblasts derived from two patients with RTT as well as cortical neurons from a RTT mouse model and observed a reduction in acetylated α-tubulin and an increase in the tubulin-specific deacetylase, histone deacetylase 6 (HDAC6). Furthermore, we show that inhibition of HDAC6 by Tubastatin A can restore tubulin acetylation levels. We also demonstrate microtubule instability in the RTT patient fibroblasts in response to nocodazole, which is progressively ameliorated in a mutation-dependent manner by Tubastatin A. We conclude that Tubastatin A is capable of counteracting the microtubule defects observed in MeCP2-deficient cells, which could in turn lead to the restoration of molecular trafficking along the microtubules and thus could be a potentially new therapeutic option for RTT.

50 citations


Journal ArticleDOI
TL;DR: It is reported here that the protein RibR counteracts the FMN-induced “turn-off” activities of both FMN riboswitches in Bacillus subtilis, allowing rib gene expression even in the presence of high levels of FMN.
Abstract: Flavin mononucleotide (FMN) riboswitches are genetic elements, which in many bacteria control genes responsible for biosynthesis and/or transport of riboflavin (rib genes). Cytoplasmic riboflavin is rapidly and almost completely converted to FMN by flavokinases. When cytoplasmic levels of FMN are sufficient ("high levels"), FMN binding to FMN riboswitches leads to a reduction of rib gene expression. We report here that the protein RibR counteracts the FMN-induced "turn-off" activities of both FMN riboswitches in Bacillus subtilis, allowing rib gene expression even in the presence of high levels of FMN. The reason for this secondary metabolic control by RibR is to couple sulfur metabolism with riboflavin metabolism.

29 citations


Journal ArticleDOI
TL;DR: In this article, a combination of transcriptome analysis and DNA methylation mapping was used to identify novel genetic and epigenetic markers of GDX-induced adrenocortical neoplasia in female DBA/2J mice.

28 citations


Journal ArticleDOI
TL;DR: This work adopts the group theoretic approach used for trinucleotide codes in Fimmel et al. (2015) to study dinucleotide circular codes and highlight their symmetry properties and characterize such codes in terms of n-circularity and provide a graph representation that allows to visualize them geometrically.

25 citations


Journal ArticleDOI
TL;DR: The results implicate the macrophage-TCRαβ combinatorial immunoreceptor in atherosclerosis and thus identify an as yet unknown adaptive component in the innate response-to-injury process that underlies this macrophages-driven disease.

24 citations


Proceedings ArticleDOI
01 Oct 2015
TL;DR: MIND, an open-source tool which is, to the best of the knowledge, the first tool supporting the quantification and visualization of the interest, is described and evaluated by using it to analyze a software project stored in a dataset of more than a million lines of code.
Abstract: Current tools for managing technical debt are able to report the principal of the debt, i.e., the amount of effort required to fix all the quality rules violated in a project. However, they do not report the interest, i.e., the disadvantages the project had or will have due to quality rules violations. As a consequence, the user lacks support in understanding how much the principal should be reduced and why. We claim that information about the interest is, at least, as important as the information about the principal; the interest should be quantified and treated as a first-class entity like the principal. In this paper we aim to advance the state of the art of how the interest is measured and visualized. The goal of the paper is to describe MIND, an open-source tool which is, to the best of our knowledge, the first tool supporting the quantification and visualization of the interest. MIND, by analyzing historical data coming from Redmine and Git repositories, reports the interest incurring in a software project in terms of how many extra defects occurred, or will occur, due to quality rules violations. We evaluated MIND by using it to analyze a software project stored in a dataset of more than a million lines of code. Results suggest that MIND accurately measures the interest of technical debt.

22 citations


Journal ArticleDOI
TL;DR: Data suggests that DBS-based quantification of drugs by DESI-MS on pre-manufactured three-layer cartridges may be a promising approach for future near-patient therapeutic drug monitoring.
Abstract: Desorption electrospray ionization (DESI) mass spectrometry is an emerging technology for direct therapeutic drug monitoring in dried blood spots (DBS). Current DBS methods require manual application of small molecules as internal standards for absolute drug quantification. With industrial standardization in mind, we superseded the manual addition of standard and built a three-layer setup for robust quantification of salicylic acid directly from DBS. We combined a dioctyl sodium sulfosuccinate weave facilitating sample spreading with a cellulose layer for addition of isotope-labeled salicylic acid as internal standard and a filter paper for analysis of the standard-containing sample by DESI-MS. Using this setup, we developed a quantification method for salicylic acid from whole blood with a validated linear curve range from 10 to 2000 mg/L, a relative standard deviation (RSD%) ≤14%, and determination coefficients of 0.997. The limit of detection (LOD) was 8 mg/L and the lower limit of quantification (LLOQ) was 10 mg/L. Recovery rates in method verification by LC-MS/MS were 97 to 101% for blinded samples. Most importantly, a study in healthy volunteers after administration of a single dose of Aspirin provides evidence to suggest that the three-layer setup may enable individual pharmacokinetic and endpoint testing following blood collection by finger pricking by patients at home. Taken together, our data suggests that DBS-based quantification of drugs by DESI-MS on pre-manufactured three-layer cartridges may be a promising approach for future near-patient therapeutic drug monitoring.

22 citations


Journal ArticleDOI
TL;DR: Five hierarchically ordered classes of trinucleotide codes including the well-known comma-free and circular codes are introduced and it is proved combinatorically that it is impossible to encode all amino acids using codes from four out of the five classes that have the strongest error detecting properties, however, it is possible to encoded all 20 amino acids with codes from the largest class with the weakest properties.

Journal ArticleDOI
TL;DR: It is concluded that miRs are not only aberrantly expressed and regulated, but also differentially compartmentalized in cells with different metastatic potential and has far reaching potential in defining metastasis-critical subpopulations within a given heterogeneous cancer cell population.
Abstract: We describe a novel approach for the detection of small non-coding RNAs in single cells by Single-Molecule Localization Microscopy (SMLM). We used a modified SMLM-setup and applied this instrument in a first proof-of-principle concept to human cancer cell lines. Our method is able to visualize single microRNA (miR)-molecules in fixed cells with a localization accuracy of 10-15 nm, and is able to quantify and analyse clustering and localization in particular subcellular sites, including exosomes. We compared the metastasis-site derived (SW620) and primary site derived (SW480) human colorectal cancer (CRC) cell lines, and (as a proof of principle) evaluated the metastasis relevant miR-31 as a first example. We observed that the subcellular distribution of miR-31 molecules in both cell lines was very heterogeneous with the largest subpopulation of optically acquired weakly metastatic cells characterized by a low number of miR-31 molecules, as opposed to a significantly higher number in the majority of the highly metastatic cells. Furthermore, the highly metastatic cells had significantly more miR-31-molecules in the extracellular space, which were visualized to co-localize with exosomes in significantly higher numbers. From this study, we conclude that miRs are not only aberrantly expressed and regulated, but also differentially compartmentalized in cells with different metastatic potential. Taken together, this novel approach, by providing single molecule images of miRNAs in cellulo can be used as a powerful supplementary tool in the analysis of miRNA function and behaviour and has far reaching potential in defining metastasis-critical subpopulations within a given heterogeneous cancer cell population.

Journal ArticleDOI
TL;DR: A recently developed longitudinal radioiodine assay is employed that is based on repetitive measurements of radio emission from the same animals over long periods of time in combination with systematic variation of the time elapsed between AChR pulse-labeling and muscle denervation corroborating earlier findings of a two-step stabilization of AChRs.
Abstract: The turnover of nicotinic acetylcholine receptors (AChR) is a critical factor that determines function and safety of neuromuscular transmission at the nerve-muscle synapses, ie neuromuscular junctions (NMJs) Previously, three different populations of AChRs exhibiting distinct stereotypic and activity-dependent half-life values were observed in mouse muscles To address AChR turnover in more detail, we here employed a recently developed longitudinal radioiodine assay that is based on repetitive measurements of radio emission from the same animals over long periods of time in combination with systematic variation of the time elapsed between AChR pulse-labeling and muscle denervation Modeling of the data revealed profiles of AChR de novo synthesis and receptor incorporation into the postsynaptic membrane Furthermore, decay of pre-existing AChRs upon denervation showed a peculiar pattern corroborating earlier findings of a two-step stabilization of AChRs

Journal ArticleDOI
TL;DR: This paper investigates what partitions can be generated when a set of different BDAs is applied sequentially to the set of codons and presents models that describe the standard genetic code with only few errors.
Abstract: In this paper we introduce the concept of a BDA-generated model of the genetic code which is based on binary dichotomic algorithms (BDAs). A BDA-generated model is based on binary dichotomic algorithms (BDAs). Such a BDA partitions the set of 64 codons into two disjoint classes of size 32 each and provides a generalization of known partitions like the Rumer dichotomy. We investigate what partitions can be generated when a set of different BDAs is applied sequentially to the set of codons. The search revealed that these models are able to generate code tables with very different numbers of classes ranging from 2 to 64. We have analyzed whether there are models that map the codons to their amino acids. A perfect matching is not possible. However, we present models that describe the standard genetic code with only few errors. There are also models that map all 64 codons uniquely to 64 classes showing that BDAs can be used to identify codons precisely. This could serve as a basis for further mathematical analysis using coding theory, for example. The hypothesis that BDAs might reflect a molecular mechanism taking place in the decoding center of the ribosome is discussed. The scan demonstrated that binary dichotomic partitions are able to model different aspects of the genetic code very well. The search was performed with our tool Beady-A. This software is freely available at http://mi.informatik.hs-mannheim.de/beady-a . It requires a JVM version 6 or higher.

Proceedings ArticleDOI
13 Apr 2015
TL;DR: This contribution outlines challenges of testing context-aware mobile applications relating to their context factors and presents the approach for a context simulator that provides support for modeling and simulation of context in different levels: physical and logical context, situations and scenarios.
Abstract: Context-aware mobile applications gain more and more influence on our daily life. Since mobile devices are equipped with various sensors to detect their environment, it is possible to receive and process information from beyond application and device borders. Within the development, these context-aware applications have to be verified to assure that they do not cause any failures. This contribution outlines challenges of testing context-aware mobile applications relating to their context factors and present our approach for a context simulator that provides support for modeling and simulation of context in different levels: physical and logical context, situations and scenarios. The simulator supports test case derivation and enables test case execution for several context sources as part of testing mobile applications.

Journal ArticleDOI
TL;DR: A coupled in silico thermodynamic and probabilistic metabolic control analysis methodology was verified by applying it to the glycerol biosynthetic pathway in Saccharomyces cerevisiae, verifying the efficacy of the proposed methodology.
Abstract: A coupled in silico thermodynamic and probabilistic metabolic control analysis methodology was verified by applying it to the glycerol biosynthetic pathway in Saccharomyces cerevisiae. The methodology allows predictions even when detailed knowledge of the enzyme kinetics is lacking. In a metabolic steady state, we found that glycerol-3-phosphate dehydrogenase operates far from thermodynamic equilibrium ( $$\varDelta_{r} G^{\prime}_{1}$$ −15.9 to −47.5 kJ mol−1, where $$\varDelta_{r} G^{\prime}_{1}$$ is the transformed Gibbs energy of the reaction). Glycerol-3-phosphatase operates in modes near the thermodynamic equilibrium, far from the thermodynamic equilibrium or in between ( $$ \varDelta_{r} G^{\prime}_{2} $$ ≈ 0 to −23.7 kJ mol−1). From the calculated distribution of the scaled flux control coefficients (median = 0.81), we inferred that the pathway flux is primarily controlled by glycerol-3-phosphate dehydrogenase. This prediction is consistent with previous findings, verifying the efficacy of the proposed methodology.

Journal ArticleDOI
TL;DR: RP-PCA preprocessing can enhance signals of low-intensity amyloid-β peptide isoforms such as Aβ1-26 even in sparsely distributed Alzheimer’s β-amyloid plaques and that it enables enhanced imaging of multiply acetylated histone H4 isoforms in response to pharmacological histone deacetylase inhibition in vivo.
Abstract: Conventional mass spectrometry image preprocessing methods used for denoising, such as the Savitzky-Golay smoothing or discrete wavelet transformation, typically do not only remove noise but also weak signals. Recently, memory-efficient principal component analysis (PCA) in conjunction with random projections (RP) has been proposed for reversible compression and analysis of large mass spectrometry imaging datasets. It considers single-pixel spectra in their local context and consequently offers the prospect of using information from the spectra of adjacent pixels for denoising or signal enhancement. However, little systematic analysis of key RP-PCA parameters has been reported so far, and the utility and validity of this method for context-dependent enhancement of known medically or pharmacologically relevant weak analyte signals in linear-mode matrix-assisted laser desorption/ionization (MALDI) mass spectra has not been explored yet. Here, we investigate MALDI imaging datasets from mouse models of Alzheimer’s disease and gastric cancer to systematically assess the importance of selecting the right number of random projections k and of principal components (PCs) L for reconstructing reproducibly denoised images after compression. We provide detailed quantitative data for comparison of RP-PCA-denoising with the Savitzky-Golay and wavelet-based denoising in these mouse models as a resource for the mass spectrometry imaging community. Most importantly, we demonstrate that RP-PCA preprocessing can enhance signals of low-intensity amyloid-β peptide isoforms such as Aβ1-26 even in sparsely distributed Alzheimer’s β-amyloid plaques and that it enables enhanced imaging of multiply acetylated histone H4 isoforms in response to pharmacological histone deacetylase inhibition in vivo. We conclude that RP-PCA denoising may be a useful preprocessing step in biomarker discovery workflows.

Journal ArticleDOI
TL;DR: In this paper, an optimal control problem for a mathematical model of tumour-immune dynamics under the influence of chemotherapy is considered, where the toxicity effect of the chemotherapeutic agent on both tumour and immunocompetent cells is taken into account.
Abstract: Summary An optimal control problem for a mathematical model of tumour–immune dynamics under the influence of chemotherapy is considered. The toxicity effect of the chemotherapeutic agent on both tumour and immunocompetent cells is taken into account. A standard linear pharmacokinetic equation for the chemotherapeutic agent is added to the system. The aim is to find an optimal strategy of treatment to minimize the tumour volume while keeping the immune response not lower than a fixed permissible level as far as possible. Sufficient conditions for the existence of not more than one switching and not more than two switchings without singular regimes are obtained. The surfaces in the extended phase space, on which the last switching appears, are constructed analytically.Copyright © 2013 John Wiley & Sons, Ltd.

Journal ArticleDOI
TL;DR: An automated method to monitor reconstitution of a freeze-dried protein drug product in its primary packaging using a newly developed measuring device and apparatus that delivered both accurate and precise results.


Journal ArticleDOI
TL;DR: The influence of NADD on transplantation relevant entities, i.e. cold inflicted injury, cytoprotection, I/R-injury, immune-modulation and inflammation will be summarized.

Journal ArticleDOI
TL;DR: In this article, a two-phase reaction of valeraldehyde with oxygen to valeric acid was carried out in a microreactor, which is designed for process development and intensification and can be applied in the scale-up process to small-scale commercial production.

Journal ArticleDOI
TL;DR: In this article, a mid-infrared attenuated total reflectance (MIR-ATR) sensor was developed for chemical reaction monitoring, which consists of an IR emitter as light source, a zinc selenide (ZnSe) ATR prism as boundary to the process, and four thermopile detectors, each equipped with an optical bandpass filter.
Abstract: A mid-infrared attenuated total reflectance (MIR-ATR) sensor has been developed for chemical reaction monitoring. The optical setup of the compact and low-priced sensor consists of an IR emitter as light source, a zinc selenide (ZnSe) ATR prism as boundary to the process, and four thermopile detectors, each equipped with an optical bandpass filter. The practical applicability was tested during esterification of ethanol and formic acid to ethyl formate and water as a model reaction with subsequent distillation. For reference analysis, a Fourier transform mid-infrared (FT-MIR) spectrometer with diamond ATR module was applied. On-line measurements using the MIR-ATR sensor and the FT-MIR spectrometer were performed in a bypass loop. The sensor was calibrated by multiple linear regression in order to link the measured absorbance in the four optical channels to the analyte concentrations. The analytical potential of the MIR-ATR sensor was demonstrated by simultaneous real-time monitoring of all four chemical substances involved in the esterification and distillation process. The temporal courses of the sensor signals are in accordance with the concentration values achieved by the commercial FT-MIR spectrometer. The standard error of prediction for ethanol, formic acid, ethyl formate, and water were 0.38 mol L − 1, 0.48 mol L − 1, 0.38 mol L − 1, and 1.12 mol L − 1, respectively. A procedure based on MIR spectra is presented to simulate the response characteristics of the sensor if the transmission ranges of the filters are varied. Using this tool analyte specific bandpass filters for a particular chemical reaction can be identified. By exchanging the optical filters, the sensor can be adapted to a wide range of processes in the chemical, pharmaceutical, and beverage industries.

Journal ArticleDOI
TL;DR: An optical measuring technique combining Planar Laser Induced Fluorescence (PLIF) with the effect of fluorescence quenching is used for the local concentration analysis of a gas absorbed and desorbed in a thin liquid film flow.
Abstract: An optical measuring technique, combining Planar Laser Induced Fluorescence (PLIF) with the effect of fluorescence quenching, is used for the local concentration analysis of a gas absorbed and desorbed in a thin liquid film flow. The absorption and desorption process is visualized by using oxygen in a mixture of water, ethanol and glycerol. Fluorescence is strongly reduced by the presence of molecular oxygen as a result of dynamic quenching. The resulting decrease in intensity is detected and interpreted through image processing. The image analysis provides a spatiotemporal value of fluorescence intensity and therefore enables the direct characterization of local transport phenomena in the liquid film flow. In this way, the impact of a single pyramidal microstructure on mass transfer into the film flow is examined. The results are compared to liquid film flow over a smooth surface. The measuring methodology is validated through diffusion experiments.

Journal ArticleDOI
25 Jun 2015-PLOS ONE
TL;DR: The TReCCA Analyser program is developed to perform standard cell assay analyses efficiently and make sophisticated in-depth analyses easily available and to encourage more systematic use of time-resolved assays and lead researchers to fully exploit their data.
Abstract: Time-resolved cell culture assays circumvent the need to set arbitrary end-points and reveal the dynamics of quality controlled experiments. However, they lead to the generation of large data sets, which can represent a complexity barrier to their use. We therefore developed the Time-Resolved Cell Culture Assay (TReCCA) Analyser program to perform standard cell assay analyses efficiently and make sophisticated in-depth analyses easily available. The functions of the program include data normalising and averaging, as well as smoothing and slope calculation, pin-pointing exact change time points. A time-resolved IC50/EC50 calculation provides a better understanding of drug toxicity over time and a more accurate drug to drug comparison. Finally the logarithmic sensor recalibration function, for sensors with an exponential calibration curve, homogenises the sensor output and enables the detection of low-scale changes. To illustrate the capabilities of the TReCCA Analyser, we performed on-line monitoring of dissolved oxygen in the culture media of the breast cancer cell line MCF-7 treated with different concentrations of the anti-cancer drug Cisplatin. The TReCCA Analyser is freely available at www.uni-heidelberg.de/fakultaeten/biowissenschaften/ipmb/biologie/woelfl/Research.html. By introducing the program, we hope to encourage more systematic use of time-resolved assays and lead researchers to fully exploit their data.

Journal ArticleDOI
TL;DR: A high-resolution ISM is demonstrated which, unlike others, is built as an entirely rigid construction, requiring no adjustments at all, and the imaging performance with submicron resolution within moving suspensions of microorganisms is demonstrated.
Abstract: In the past years, in situ microscopy has been demonstrated as a technique for monitoring the concentration and morphology of moving microparticles in agitated suspensions. However, up until now, this technique can only achieve a high resolution if a certain manual or automated effort is established for continuous precise focusing. Therefore, the application of in situ microscopes (ISMs) as sensors is inhibited in the cases where unattended operation is required. Here, we demonstrate a high-resolution ISM which, unlike others, is built as an entirely rigid construction, requiring no adjustments at all. This ISM is based on a specially designed water immersion objective with numerical aperture = 0.75 and a working distance of 15 μm. The objective can be built exclusively from off-the-shelf parts and the front surface directly interfaces with the moving suspension. We show various applications of the system and demonstrate the imaging performance with submicron resolution within moving suspensions of microorganisms.

Journal ArticleDOI
TL;DR: It is inferred that the control over the riboflavin producing flux is shared among several enzyme activities and mostly resides in the initial reactions of the pathway.
Abstract: In this study, we applied a coupled in silico thermodynamic and probabilistic metabolic control analysis methodology to investigate the control mechanisms of the commercially relevant riboflavin biosynthetic pathway in bacteria. Under the investigated steady-state conditions, we found that several enzyme reactions of the pathway operate far from thermodynamic equilibrium (transformed Gibbs energies of reaction below about −17 kJ mol−1). Using the obtained thermodynamic information and applying enzyme elasticity sampling, we calculated the distributions of the scaled concentration control coefficients (CCCs) and scaled flux control coefficients (FCCs). From the statistical analysis of the calculated distributions, we inferred that the control over the riboflavin producing flux is shared among several enzyme activities and mostly resides in the initial reactions of the pathway. More precisely, the guanosine triphosphate (GTP) cyclohydrolase II activity, and therefore the bifunctional RibA protein of Bacillus subtilis because it catalyzes this activity, appears to mainly control the riboflavin producing flux (mean FCCs = 0.45 and 0.55, respectively). The GTP cyclohydrolase II activity and RibA also exert a high positive control over the riboflavin concentration (mean CCCs = 2.43 and 2.91, respectively). This prediction is consistent with previous findings for microbial riboflavin overproducing strains.

Proceedings ArticleDOI
TL;DR: A framework is presented for the definition of the corresponding surgical workflow, which combines semantically enriched surgical expert knowledge with a biomechanical simulation for mitral valve reconstruction and the simulation's integration into a knowledge-based surgery assistance system.
Abstract: A mitral valve reconstruction (MVR) is a complex operation in which the functionality of incompetent mitral valves is re-established by applying surgical techniques. This work deals with predictive biomechanical simulations of operation scenarios for an MVR, and the simulation's integration into a knowledge-based surgery assistance system. We present a framework for the definition of the corresponding surgical workflow, which combines semantically enriched surgical expert knowledge with a biomechanical simulation. Using an ontology, 'surgical rules' which describe decision and assessment criteria for surgical decision-making are represented in a knowledge base. Through reasoning these 'rules' can then be applied on patient-specific data in order to be converted into boundary conditions for the biomechanical soft tissue simulation, which is based on the Finite Elements Method (FEM). The simulation, which is implemented in the open-source C++ FEM software HiFlow3, is controlled via the Medical Simulation Markup Language (MSML), and makes use of High Performance Computing (HPC) methods to cope with real-time requirements in surgery. The simulation results are presented to surgeons to assess the quality of the virtual reconstruction and the consequential remedial effects on the mitral valve and its functionality. The whole setup has the potential to support the intraoperative decision-making process during MVR where the surgeon usually has to make fundamental decision under time pressure.

Journal ArticleDOI
07 Apr 2015-PLOS ONE
TL;DR: A low-cost online unit allowing movement tracking of flagellated bacteria on a single-cell level during fermentation processes and its ability to distinguish different metabolic states (viability) of bacteria by movement velocity was investigated.
Abstract: In this technical report we demonstrate a low-cost online unit allowing movement tracking of flagellated bacteria on a single-cell level during fermentation processes. The system’s ability to distinguish different metabolic states (viability) of bacteria by movement velocity was investigated. A flow-through cuvette with automatically adjustable layer thickness was developed. The cuvette can be used with most commercially available laboratory microscopes equipped with 40× amplification and a digital camera. In addition, an automated sample preparation unit and a software module was developed measuring size, moved distance, and speed of bacteria. In a proof of principle study the movement velocities of Bacillus amyloliquefaciens FZB42 during three batch fermentation processes were investigated. In this process the bacteria went through different metabolic states, vegetative growth, diauxic shift, vegetative growth after diauxic shift, and sporulation. It was shown that the movement velocities during the different metabolic states significantly differ from each other. Therefore, the described setup has the potential to be used as a bacteria viability monitoring tool. In contrast to some other techniques, such as electro-optical techniques, this method can even be used in turbid production media.

Journal ArticleDOI
TL;DR: Zusammenfassung medizinische Informatik bietet anwendungsorientierte Lösungen durch den Einsatz oder die Anpassung bestehender Ideen, Methoden and Ergebnisse der Informatika.
Abstract: Medizin ist ein wichtiges Anwendungsgebiet der Informatik. Medizinische Informatik bietet anwendungsorientierte Losungen durch den Einsatz oder die Anpassung bestehender Ideen, Methoden und Ergebnisse der Informatik. Umgekehrt gibt es in der Medizinischen Informatik auch eigenstandige Entwicklungen, die die Informatik im Allgemeinen mit wesentlichen grundlegenden Losungen beeinflussen und bereichern. Solche Bereiche sind vor allem Bildverarbeitung, Informationssysteme, Prozessunterstutzung, Klassifikationen und Terminologien (Ontologien) sowie datenschutzfordernde Techniken und Beweis- und IT-Sicherheit.