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Showing papers by "Mannheim University of Applied Sciences published in 2012"


Journal ArticleDOI
TL;DR: This work has identified human and mouse ceramide synthase 3 (CerS3), among CerS1-6, to be exclusively required for the ULC-Cer synthesis in vitro and of mouse CerS3 in vivo.
Abstract: The stratum corneum as the outermost epidermal layer protects against exsiccation and infection. Both the underlying cornified envelope (CE) and the intercellular lipid matrix contribute essentially to these two main protective barriers. Epidermis-unique ceramides with ultra-long-chain acyl moities (ULC-Cers) are key components of extracellular lipid lamellae (ELL) and are bound to CE proteins, thereby contributing to the cornified lipid envelope (CLE). Here, we identified human and mouse ceramide synthase 3 (CerS3), among CerS1-6, to be exclusively required for the ULC-Cer synthesis in vitro and of mouse CerS3 in vivo. Deficiency of CerS3 in mice results in complete loss of ULC-Cers (≥C26), lack of continuous ELL and a non-functional CLE. Consequently, newborn mutant mice die shortly after birth from transepidermal water loss. Mutant skin is prone to Candida albicans infection highlighting ULC-Cers to be pivotal for both barrier functions. Persistent periderm, hyperkeratosis and deficient cornification are hallmarks of mutant skin demonstrating loss of Cers to trigger a keratinocyte maturation arrest at an embryonic pre-barrier stage.

223 citations


Journal ArticleDOI
06 Aug 2012-PLOS ONE
TL;DR: The properties of macrophages originating from monocytes cultured in serum-free media displayed enhanced tumoricidal activity for M1 and tumor promoting property for M2Macrophages in contrast to MDM differentiated in the presence of serum, which confirmed the tumor promoting properties of M2 macrophage in vitro and encourage the targeting of TAMs for cancer therapy.
Abstract: The tumor promoting role of M2 macrophages has been described in in vivo models and the presence of macrophages in certain tumor types has been linked to a poor clinical outcome. In light of burgeoning activities to clinically develop new therapies targeting tumor-associated macrophages (TAMs), reliable in vitro models faithfully mimicking the tumor promoting functions of TAMs are required. Generation and activation of human monocyte-derived macrophages (MDM) in vitro, described as M1 or M2 macrophages attributed with tumoricidal or tumor-promoting functions, respectively, has been widely reported using mainly serum containing culture methods. In this study, we compared the properties of macrophages originating from monocytes cultured either in media containing serum together with M-CSF for M2 and GM-CSF for M1 macrophages or in serum-free media supplemented with M-CSF or GM-CSF and cytokines such as IL-4, IL-10 to induce activated M2 or LPS together with IFN-γ to generate activated M1 phenotype. We observed differences in cell morphology as well as increased surface receptor expression levels in serum-containing culture whereas similar or higher cytokine production levels were detected under serum-free culture conditions. More importantly, MDM differentiated under serum-free conditions displayed enhanced tumoricidal activity for M1 and tumor promoting property for M2 macrophages in contrast to MDM differentiated in the presence of serum. Moreover, evaluation of MDM phagocytic activity in serum free condition resulted in greater phagocytic properties of M2 compared to M1. Our data therefore confirm the tumor promoting properties of M2 macrophages in vitro and encourage the targeting of TAMs for cancer therapy.

220 citations


Journal ArticleDOI
TL;DR: It is found that the NP surface chemistry had a great impact on the amount of bound protein with distinct ligands for each of the tested particles, which might support the interpretation of in vivo experiments were NPs come directly into contact with blood plasma.

91 citations


Journal ArticleDOI
TL;DR: These experiments demonstrate that the ribB FMN riboswitch of S. davawensis is able to discriminate between the two very similar flavins FMN and RoFMN and shows opposite responses to the latter ligands.
Abstract: Streptomyces davawensis is the only organism known to synthesize the antibiotic roseoflavin, a riboflavin (vitamin B2) analog. Roseoflavin is converted to roseoflavin mononucleotide (RoFMN) and roseoflavin adenine dinucleotide in the cytoplasm of target cells. (Ribo-)Flavin mononucleotide (FMN) riboswitches are genetic elements, which in many bacteria control genes responsible for the biosynthesis and transport of riboflavin. Streptomyces davawensis is roseoflavin resistant, and the closely related bacterium Streptomyces coelicolor is roseoflavin sensitive. The two bacteria served as models to investigate roseoflavin resistance of S. davawensis and to analyze the mode of action of roseoflavin in S. coelicolor. Our experiments demonstrate that the ribB FMN riboswitch of S. davawensis (in contrast to the corresponding riboswitch of S. coelicolor) is able to discriminate between the two very similar flavins FMN and RoFMN and shows opposite responses to the latter ligands.

72 citations


Journal ArticleDOI
TL;DR: MRI provides a new method for measuring these important microanatomical markers of disease risk and leads the way to in vivo analysis of these parameters, including longitudinal studies of animal models of CKD.
Abstract: Background Glomerular number and size are important risk factors for chronic kidney disease (CKD) and cardiovascular disease and have traditionally been estimated using invasive techniques. Here, we report a novel technique to count and size every glomerulus in the rat kidney using magnetic resonance imaging (MRI). Methods The ferromagnetic nature of cationized ferritin allowed visualization of single glomeruli in high-resolution susceptibility-weighted MRI. A segmentation algorithm was used to identify and count all glomeruli within the whole kidney. To prove our concept, we estimated total glomerular number and mean glomerular volume of each kidney using design-based stereology. Results The glomerular counts obtained with MRI agreed well with estimates obtained using traditional methods [MRI, 32 785 (3117); stereology, 35 132 (3123)]. For the first time, the glomerular volume distribution for the entire kidney is shown. Additionally, the method is substantially faster than the current methods. Conclusions MRI provides a new method for measuring these important microanatomical markers of disease risk and leads the way to in vivo analysis of these parameters, including longitudinal studies of animal models of CKD.

71 citations


Journal ArticleDOI
TL;DR: The data show that these new biomarkers are robust and measurable for longer term studies to predict different types of kidney toxicities, and the most promising biomarkers were NGAL, Kim-1, osteopontin, clusterin, RPA- 1, and GSTYb1, detected by multiplexing technologies.
Abstract: Novel urinary protein biomarkers for the detection of acute renal damage, recently accepted by the U.S. Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency (Japan), now have to be validated in practice. Limited data regarding the performance of these acute markers after subacute or subchronic treatment are publicly available. To increase the area of applicability of these markers, it is important to evaluate the ability to detect them after 28 days of treatment or even longer. Wistar rats were treated with three doses of cisplatin, vancomycin, or puromycin to induce renal damage. Twelve candidate proteins were measured by Luminex xMAP-based WideScreen assays, MesoScale Discovery-based MULTI-SPOT technology, or RENA-strip dipstick assay after 28 days. Treatment with all three model compounds resulted in a dose-dependent increase in urinary biomarkers, specific for the observed areas within the nephron, determined histopathologically. The most promising biomarkers in this study were NGAL, Kim-1, osteopontin, clusterin, RPA-1, and GSTYb1, detected by multiplexing technologies. The RENA-strip dipstick assay delivered good diagnostic results for vancomycin-treated but not for cisplatin- or puromycin-treated rats. Taken together, the data show that these new biomarkers are robust and measurable for longer term studies to predict different types of kidney toxicities.

64 citations


Journal ArticleDOI
TL;DR: In this paper, a methodology was developed to select adequate commercially available micromixers for mixing sensitive chemical reactions, and the range of flow rates at which the selected microreactors have to be operated to ensure the required mixing intensity.

63 citations


Journal ArticleDOI
TL;DR: Phylogenetic analysis revealed that S. davawensis is a close relative of Streptomyces cinnabarinus, and much to the authors' surprise, it was found that the latter bacterium is a roseoflavin producer as well.
Abstract: Streptomyces davawensis JCM 4913 synthesizes the antibiotic roseoflavin, a structural riboflavin (vitamin B 2 ) analog Here, we report the 9,466,619-bp linear chromosome of S davawensis JCM 4913 and a 89,331-bp linear plasmid The sequence has an average G+C content of 7058% and contains six rRNA operons (16S-23S-5S) and 69 tRNA genes The 8,616 predicted protein-coding sequences include 32 clusters coding for secondary metabolites, several of which are unique to S davawensis The chromosome contains long terminal inverted repeats of 33,255 bp each and atypical telomeres Sequence analysis with regard to riboflavin biosynthesis revealed three different patterns of gene organization in Streptomyces species Heterologous expression of a set of genes present on a subgenomic fragment of S davawensis resulted in the production of roseoflavin by the host Streptomyces coelicolor M1152 Phylogenetic analysis revealed that S davawensis is a close relative of Streptomyces cinnabarinus, and much to our surprise, we found that the latter bacterium is a roseoflavin producer as well

50 citations


Journal ArticleDOI
TL;DR: It is shown that rapsyn anchors PKA type I in close proximity to the postsynaptic membrane and suggests that this function is essential for synapse maintenance.
Abstract: The stabilisation of acetylcholine receptors (AChRs) at the neuromuscular junction depends on muscle activity and the cooperative action of myosin Va and protein kinase A (PKA) type I. To execute its function, PKA has to be present in a subsynaptic microdomain where it is enriched by anchoring proteins. Here, we show that the AChR-associated protein, rapsyn, interacts with PKA type I in C2C12 and T-REx293 cells as well as in live mouse muscle beneath the neuromuscular junction. Molecular modelling, immunoprecipitation and bimolecular fluorescence complementation approaches identify an α-helical stretch of rapsyn to be crucial for binding to the dimerisation and docking domain of PKA type I. When expressed in live mouse muscle, a peptide encompassing the rapsyn α-helical sequence efficiently delocalises PKA type I from the neuromuscular junction. The same peptide, as well as a rapsyn construct lacking the α-helical domain, induces severe alteration of acetylcholine receptor turnover as well as fragmentation of synapses. This shows that rapsyn anchors PKA type I in close proximity to the postsynaptic membrane and suggests that this function is essential for synapse maintenance.

38 citations


Journal ArticleDOI
TL;DR: It is demonstrated that intact cell mass spectrometric signatures of different cell lines start to resemble each other at higher trifluoroacetic acid (TFA) concentrations and that therefore low concentrations of TFA in the matrix solution are preferred.
Abstract: Intact cell mass spectrometry biotyping, a collection of methods for classification of cells based on mass spectrometric fingerprints, is an established method in clinical and environmental microbiology. It has recently also been applied to the investigation of mammalian cells including primary blood cells and cultured cells. However, few automated procedures suitable for higher throughput and little analytical standardization of mammalian biotyping approaches have been reported so far. Here, we present a novel automated method that robustly classifies as few as 250 cells per spot. Automatically acquired cell fingerprints from cultured and primary cells show high technical (R > 0.95) and biological reproducibility (R = 0.83–0.96), with a median peak variance below 12 %. Ion suppression is shown to be a major concern at higher cell numbers and needs to be carefully monitored. We demonstrate that intact cell mass spectrometric signatures of different cell lines start to resemble each other at higher trifluoroacetic acid (TFA) concentrations and that therefore low concentrations of TFA in the matrix solution are preferred. We show that in vitro differentiation of HL-60 cells into a neutrophil-like phenotype can be rapidly and robustly monitored. We utilize the method for global analysis of person-to-person differences in mass spectral signatures of intact polymorphonuclear neutrophils and monocytes obtained from healthy volunteers. Our data suggest that automated MALDI mass spectrometry cell biotyping could be a useful complementary approach in clinical cell analysis.

33 citations


Journal ArticleDOI
TL;DR: KillerRed was found to be the most harmful, followed by mRFP and DsRed2 while bacteria expressing mCherry and controls without fluorescent proteins survived after application of identical illumination doses.
Abstract: Red fluorescent proteins can generate reactive oxygen species (ROS) if their fluorochrome is stimulated e.g. by visible light illumination. ROS compounds have very reactive, highly toxic properties leading to cell damage which results in cell killing. In this context, the toxicity of the various red fluorochromes KillerRed, DsRed2, mCherry, and mRFP expressed in Escherichia coli bacteria was tested after illumination with white light. The toxic effect was determined by measurement of the colony forming ability 24h after transfection and illumination. KillerRed was found to be the most harmful, followed by mRFP and DsRed2 while bacteria expressing mCherry and controls without fluorescent proteins survived after application of identical illumination doses. Their application and a possible bactericide role is discussed.

Journal ArticleDOI
TL;DR: It is concluded that GATA4 is a key modifier of gonadectomy-induced adrenocortical neoplasia, postovariectomy obesity, and sex steroidogenic cell differentiation.
Abstract: In response to gonadectomy certain inbred mouse strains develop sex steroidogenic adrenocortical neoplasms. One of the hallmarks of neoplastic transformation is expression of GATA4, a transcription factor normally present in gonadal but not adrenal steroidogenic cells of the adult mouse. To show that GATA4 directly modulates adrenocortical tumorigenesis and is not merely a marker of gonadal-like differentiation in the neoplasms, we studied mice with germline or conditional loss-of-function mutations in the Gata4 gene. Germline Gata4 haploinsufficiency was associated with attenuated tumor growth and reduced expression of sex steroidogenic genes in the adrenal glands of ovariectomized B6D2F1 and B6AF1 mice. At 12 months after ovariectomy, wild-type B6D2F1 mice had biochemical and histological evidence of adrenocortical estrogen production, whereas Gata4+/− B6D2F1 mice did not. Germline Gata4 haploinsufficiency exacerbated the secondary phenotype of postovariectomy obesity in B6D2F1 mice, presumably by limiting ectopic estrogen production in the adrenal glands. Amhr2-cre-mediated deletion of floxed Gata4 (Gata4F) in nascent adrenocortical neoplasms of ovariectomized B6.129 mice reduced tumor growth and the expression of gonadal-like markers in a Gata4F dose-dependent manner. We conclude that GATA4 is a key modifier of gonadectomy-induced adrenocortical neoplasia, postovariectomy obesity, and sex steroidogenic cell differentiation.

Journal ArticleDOI
TL;DR: It was proved that the optimal control function has at most one switch point in both monotonic and non-monotonic cases for most relevant parameter values with the help of Pontryagin’s Maximum Principle.
Abstract: A mathematical model for leukemia therapy based on the Gompertzian law of cell growth is studied. It is assumed that the chemotherapeutic agents kill leukemic as well as normal cells. Effectiveness of the medicine is described in terms of a therapy function. Two types of therapy functions are considered: monotonic and non-monotonic. In the former case the level of the effect of the chemotherapy directly depends on the quantity of the chemotherapeutic agent. In the latter case the therapy function achieves its peak at a threshold value and then the effect of the therapy decreases. At any given moment the amount of the applied chemotherapeutic is regulated by a control function with a bounded maximum. Additionally, the total quantity of chemotherapeutic agent which can be used during the treatment process is bounded too. The problem is to find an optimal strategy of treatment to minimize the number of leukemic cells while at the same time retaining as many normal cells as possible. With the help of Pontryagin’s Maximum Principle it was proved that the optimal control function has at most one switch point in both monotonic and non-monotonic cases for most relevant parameter values. A control strategy called alternative is suggested. This strategy involves increasing the amount of the chemotherapeutical medicine up to a certain value within the shortest possible period of time, and holding this level until the end of the treatment. The comparison of the results from the numerical calculation using the Pontryagin’s Maximum Principle with the alternative control strategy shows that the difference between the values of cost functions is negligibly small.

Journal ArticleDOI
TL;DR: In this work, the detection of ethanol and CO(2) in the exhaust gas during aerobic yeast fermentation was performed by two photometric gas analyzers, and dry yeast biomass was monitored using a fiber optic backscatter set-up.

17 Apr 2012
TL;DR: In this article, a cosinor analysis based on the theory of circadian rhythms as a special representative of regression analysis, a histogram-based approach based on movement data, and a probabilistic model of behavior (PMB) based on a person's activities of daily living (ADL).
Abstract: Rendering and offering adequate reminder services in a situation-aware, proactive manner and providing information for diagnosis support is a major issue for Ambient Assisted Living systems when it comes to dealing with persons suffering from mild dementia. One great challenge therefore is to reliably recognize and assess the long-term behavior of assisted persons. In the context of diagnosis support for caregivers or practitioners, deviations in the daily routine of a person with mild dementia might be an indicator of a deterioration of the affected person's cognitive condition. Based on this information, adequate help can be provided. We developed an approach to processing information regarding the modeling of daily routines and a comparison to previous days. Our solution can be seen as a combination of three approaches: a cosinor analysis based on the theory of circadian rhythms as a special representative of regression analysis, a histogram-based approach based on movement data, and a probabilistic model of behavior (PMB) based on the person's activities of daily living (ADL).

Journal ArticleDOI
16 Jul 2012-PLOS ONE
TL;DR: The data show a correlation between the subsynaptic accumulation of myosin Va and PKA type I on the one hand and NMJ regeneration status and morphology, AChR stability and specificity ofSubsynaptic cAMP handling on the other hand, which suggests an important role ofMyosinVa and Pka type I for the maturation of NMJs in regenerating muscle.
Abstract: Background: The unconventional motor protein, myosin Va, is crucial for the development of the mouse neuromuscular junction (NMJ) in the early postnatal phase. Furthermore, the cooperative action of protein kinase A (PKA) and myosin Va is essential to maintain the adult NMJ. We here assessed the involvement of myosin Va and PKA in NMJ recovery during muscle regeneration. Methodology/Principal Findings: To address a putative role of myosin Va and PKA in the process of muscle regeneration, we used two experimental models the dystrophic mdx mouse and Notexin-induced muscle degeneration/regeneration. We found that in both systems myosin Va and PKA type I accumulate beneath the NMJs in a fiber maturation-dependent manner. Morphologically intact NMJs were found to express stable nicotinic acetylcholine receptors and to accumulate myosin Va and PKA type I in the subsynaptic region. Subsynaptic cAMP signaling was strongly altered in dystrophic muscle, particularly in fibers with severely subverted NMJ morphology. Conclusions/Significance: Our data show a correlation between the subsynaptic accumulation of myosin Va and PKA type I on the one hand and NMJ regeneration status and morphology, AChR stability and specificity of subsynaptic cAMP handling on the other hand. This suggests an important role of myosin Va and PKA type I for the maturation of NMJs in regenerating muscle.

Journal ArticleDOI
TL;DR: Autofluorescence spectra, images, and decay kinetics of U251-MG glioblastoma cells prior and subsequent to activation of tumor suppressor genes are compared and additional information on cell metabolism is obtained from spectral imaging and fluorescence lifetime imaging microscopy.
Abstract: Autofluorescence spectra, images, and decay kinetics of U251-MG glioblastoma cells prior and subse- quent to activation of tumor suppressor genes are compared. While phase contrast images and fluorescence inten- sity patterns of tumor (control) cells and less malignant cells are similar, differences can be deduced from autofluorescence spectra and decay kinetics. In particular, upon near UV excitation, the fluorescence ratio of the free and protein-bound coenzyme nicotinamid adenine dinucleotide depends on the state of malignancy and reflects different cytoplasmic (including lysosomal) and mitochondrial contributions. While larger numbers of fluorescence spectra are evaluated by principal component analysis, a multivariate data analysis method, addi- tional information on cell metabolism is obtained from spectral imaging and fluorescence lifetime imaging micro-

Journal ArticleDOI
31 May 2012-PLOS ONE
TL;DR: A transactivator mouse line (TPH2-tTA) that allows temporal and spatial control of tetracycline (Ptet) controlled transgene expression as well as gene deletion in 5-HT neurons throughout life is generated.
Abstract: The serotonergic (5-HT) neuronal system has important and diverse physiological functions throughout development and adulthood. Its dysregulation during development or later in adulthood has been implicated in many neuropsychiatric disorders. Transgenic animal models designed to study the contribution of serotonergic susceptibility genes to a pathological phenotype should ideally allow to study candidate gene overexpression or gene knockout selectively in serotonergic neurons at any desired time during life. For this purpose, conditional expression systems such as the tet-system are preferable. Here, we generated a transactivator (tTA) mouse line (TPH2-tTA) that allows temporal and spatial control of tetracycline (Ptet) controlled transgene expression as well as gene deletion in 5-HT neurons. The tTA cDNA was inserted into a 196 kb PAC containing a genomic mouse Tph2 fragment (177 kb) by homologous recombination in E. coli. For functional analysis of Ptet-controlled transgene expression, TPH2-tTA mice were crossed to a Ptet-regulated lacZ reporter line (Ptet-nLacZ). In adult double-transgenic TPH2-tTA/Ptet-nLacZ mice, TPH2-tTA founder line L62-20 showed strong serotonergic β-galactosidase expression which could be completely suppressed with doxycycline (Dox). Furthermore, Ptet-regulated gene expression could be reversibly activated or inactivated when Dox was either withdrawn or added to the system. For functional analysis of Ptet-controlled, Cre-mediated gene deletion, TPH2-tTA mice (L62-20) were crossed to double transgenic Ptet-Cre/R26R reporter mice to generate TPH2-tTA/Ptet-Cre/R26R mice. Without Dox, 5-HT specific recombination started at E12.5. With permanent Dox administration, Ptet-controlled Cre-mediated recombination was absent. Dox withdrawal either postnatally or during adulthood induced efficient recombination in serotonergic neurons of all raphe nuclei, respectively. In the enteric nervous system, recombination could not be detected. We generated a transgenic mouse tTA line (TPH2-tTA) which allows both inducible and reversible transgene expression and inducible Cre-mediated gene deletion selectively in 5-HT neurons throughout life. This will allow precise delineation of serotonergic gene functions during development and adulthood.

Journal ArticleDOI
TL;DR: In this work an optimization problem for a leukemia treatment model based on the Gompertzian law of cell growth is considered and the quantities of the leukemic and of the healthy cells at the end of the therapy are chosen as the criterion of the treatment quality.
Abstract: In this work an optimization problem for a leukemia treatment model based on the Gompertzian law of cell growth is considered. The quantities of the leukemic and of the healthy cells at the end of the therapy are chosen as the criterion of the treatment quality. In the case where the number of healthy cells at the end of the therapy is higher than a chosen desired number, an analytical solution of the optimization problem for a wide class of therapy processes is given. If this is not the case, a control strategy called alternative is suggested.


Journal ArticleDOI
TL;DR: It is shown that during all stages of cell division, secretory granules were competent for regulated exocytosis, which facilitates their release from the F-actin-rich cortex and active transport along spindle microtubules.
Abstract: The biogenesis, maturation, and exocytosis of secretory granules in interphase cells have been well documented, whereas the distribution and exocytosis of these hormone-storing organelles during cell division have received little attention. By combining ultrastructural analyses and time-lapse microscopy, we here show that, in dividing PC12 cells, the prominent peripheral localization of secretory granules is retained during prophase but clearly reduced during prometaphase, ending up with only few peripherally localized secretory granules in metaphase cells. During anaphase and telophase, secretory granules exhibited a pronounced movement towards the cell midzone and, evidently, their tracks colocalized with spindle microtubules. During cytokinesis, secretory granules were excluded from the midbody and accumulated at the bases of the intercellular bridge. Furthermore, by measuring exocytosis at the single granule level, we showed, that during all stages of cell division, secretory granules were competent for regulated exocytosis. In conclusion, our data shed new light on the complex molecular machinery of secretory granule redistribution during cell division, which facilitates their release from the F-actin-rich cortex and active transport along spindle microtubules.

Journal ArticleDOI
TL;DR: This work examines the optimal control problem that arises in the mathematical modeling of leukemia therapy, to solve which the Pontryagin maximum principle and the penalty function method are employed.
Abstract: We examine the optimal control problem that arises in the mathematical modeling of leukemia therapy, to solve which the Pontryagin maximum principle and the penalty function method are employed. It is assumed that the drug is capable of killing not only diseased cells, but healthy cells as well. The character of the drug’s interaction with cells is described by appropriate therapy functions.

Proceedings ArticleDOI
17 Jun 2012
TL;DR: In 2007, the German-Austrian-Swiss-Czech working group published the 2nd edition of the technical rules for the assessment of network disturbances as mentioned in this paper, which were used in the 4 countries to assess the emission limits of large consuming and generating installations (in Germany consuming installations only).
Abstract: In 2007 the German-Austrian-Swiss-Czech working group “D-A-CH-CZ EMC” published the 2nd edition of the “Technical Rules for the Assessment of Network Disturbances”. They are used in the 4 countries to assess the emission limits of large consuming and generating installations (in Germany consuming installations only). The rules define assessment methods and emission limits for LV and MV distribution networks. The HV distribution networks are not covered, because assessment methodologies are usually different to those used for LV and MV distribution networks.

Book ChapterDOI
25 Jul 2012
TL;DR: Two examples of advanced applications of a new version of this in situ microscope with unprecedented resolution and frame rate are shown: Adaptation to double glass jacket equipped bench top reactors and longer term application in a perfused 30 L steel reactor.
Abstract: Cell concentration is one of the key parameters to be monitored during cell cultivation processes. This is very often done off-line by sterile sampling and subsequent counting using a hemocytometer or an electronic cell counter. A direct optical measurement of cell density via an in situ microscope (ISM) eliminates the need for sampling and allows for continuous monitoring of this key parameter. Two such systems have been described in the literature, one of them has been developed at Mannheim University of Applied Sciences. This system has the advantage of not using any moving mechanical parts within or outside the fermentation vessel. Here we show two examples of advanced applications of a new version of this ISM with unprecedented resolution and frame rate: Adaptation to double glass jacket equipped bench top reactors and longer term application in a perfused 30 L steel reactor. Results in both cases show the performance of the ISM, the comparability of cell culture data obtained by ISM and traditional methods and the potential for further development of the ISM.

Book ChapterDOI
01 Jan 2012
TL;DR: Kappner's "Hangt ihn einfach niedriger" as discussed by the authors is der Titel eines von J. Kappner in der Suddeutschen Zeitung verfassten Essays (SZ 5/2011, V 2/1) zum wieder einmal boomenden Kriminalroman, dessen Klassiker von Sir Arthur Conan Doyle uber Agatha Christie bis hin zu Friedrich Durrenmatt.
Abstract: „Hangt ihn einfach niedriger“… ist der Titel eines von J. Kappner in der Suddeutschen Zeitung verfassten Essays (SZ 5/2011, V 2/1) zum wieder einmal boomenden Kriminalroman, dessen Klassiker von Sir Arthur Conan Doyle uber Agatha Christie bis hin zu Friedrich Durrenmatt langst Teil des literarischen Kanons wie auch des cineastischen Angebotes geworden sind. Mal ist der ‚Morder immer der Gartner‘, mal ist der Morder „weis, mannlich und sehr, sehr reich wie im Schwedenkrimi“ und immer haufiger hangt in nahezu jedem Zimmer eine Leiche.

Journal ArticleDOI
TL;DR: The mathematical models of the chosen process are presented in detail for batch, fed-batch, and continuous mode of operation, and some comments on the development of an adapted strain of the microorganisms to the medium as the basis for a successful fermentation execution are concluded.

Book ChapterDOI
01 Jan 2012
TL;DR: Auf eine einfache Checkliste zur Gestaltung der Kommunikation von Luxusmarken kann angesichts der Vielfalt der Luxusbranchen, ihrer Segmente und ihr Produkte and Dienstleistungen nicht gehofft werden as discussed by the authors.
Abstract: Auf eine einfache Checkliste zur Gestaltung der Kommunikation von Luxusmarken kann angesichts der Vielfalt der Luxusbranchen, ihrer Segmente und – erst recht – ihrer Produkte und Dienstleistungen nicht gehofft werden. Und doch gibt es akzeptierte und vom Kunden erwartete Gestaltungskriterien, die Luxus-Kommunikation zu erfullen hat. Daruber hinaus soll den Gestaltern der Kommunikation von Luxusmarken mit dem erprobten Ansatz der „5 Handlungsebenen strategischer Markenkommunikation“ eine Vorgehensweise zur Entwicklung spezifischer Profilkriterien an die Hand gegeben werden, mit dessen Hilfe sich eine Luxusmarke kommunikativ von ihren Wettbewerbern differenzieren lasst.

Book ChapterDOI
01 Jan 2012
TL;DR: In this article, verschiedene Aspekte zusammengetragen and diskutiert werden, die das Aufwachsen von Kindern und Jugendlichen in stadtischen arealen beeinflussen konnen.
Abstract: In diesem Beitrag sollen verschiedene Aspekte zusammengetragen und diskutiert werden, die das Aufwachsen von Kindern und Jugendlichen in stadtischen Arealen beeinflussen konnen. Dabei soll am Anfang hypothetisch auf den moglichen Zusammenhang von baulichen Strukturen und sozialen Phanomenen eingegangen werden; in einem zweiten Abschnitt folgt die Betrachtung segregationstypischer Einflussfaktoren, bevor die im stadtischen Kontext identifizierten kindes- und jugendtypischen Verhaltensphanomene in den Zusammenhang von deren sozialen Lagen, in den Betrachtungszusammenhang von schulischen und kommunalen Bildungs-, Freizeit- und Betreuungsangeboten gestellt werden.

Patent
17 Aug 2012
TL;DR: In this paper, the authors present a method for displaying a film with 5 to 20 images per second on an image monitor, where the intensity distribution is presented as a film and the values correspond to the time axis.
Abstract: The method involves displaying a film with 5 to 20 images per second on an image monitor. The values correspond to the time axis. The three-dimensional intensity distribution is presented as a film. The time axis of the film corresponds to the third dimension of the measurement signal. An independent claim is included for a device for visual analysis in the imaging mass spectrometry.

Proceedings ArticleDOI
01 Sep 2012
TL;DR: For less than 30 US$ a precise supply current measurement of FRAM microcontrollers MSP430FR5739 can be realized with a MSP-EXP430FR 5739 experimenter board and three cheap resistors using the internal analog-digital converter.
Abstract: For less than 30 US$ a precise supply current measurement of FRAM microcontrollers MSP430FR5739 can be realized with a MSP-EXP430FR5739 experimenter board and three cheap resistors using the internal analogdigital converter. This can be combined with an evaluation of the dependency of microcontroller performance data on programming structures due to distribution of code between cache, FRAM and SRAM.