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Search Results: 1 - 10 of 609 matches for " Knut Krohn "
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"Hook"-calibration of GeneChip-microarrays: Chip characteristics and expression measures
Hans Binder, Knut Krohn, Stephan Preibisch
Algorithms for Molecular Biology , 2008, DOI: 10.1186/1748-7188-3-11
Abstract: In this publication we summarize the essential chip characteristics provided by this method, analyze special benchmark experiments to estimate transcript related expression measures and illustrate the potency of the method to detect and to quantify the quality of a particular hybridization. It is shown that our single-chip approach provides expression measures responding linearly on changes of the transcript concentration over three orders of magnitude. In addition, the method calculates a detection call judging the relation between the signal and the detection limit of the particular measurement. The performance of the method in the context of different chip generations and probe set assignments is illustrated. The hook method characterizes the RNA-quality in terms of the 3'/5'-amplification bias and the sample-specific calling rate. We show that the proper judgement of these effects requires the disentanglement of non-specific and specific hybridization which, otherwise, can lead to misinterpretations of expression changes. The consequences of modifying probe/target interactions by either changing the labelling protocol or by substituting RNA by DNA targets are demonstrated.The single-chip based hook-method provides accurate expression estimates and chip-summary characteristics using the natural metrics given by the hybridization reaction with the potency to develop new standards for microarray quality control and calibration.DNA microarray technology enables conducting experiments that measure RNA-transcript abundance (so called gene expression or expression degree) on a large scale of genomic sequences. The quality of the measurement systematically depends on experimental factors such as the performance of the measuring "device", e.g., on the chosen array-type, the design of the chip-platform and -generation and on the particular probe design, on one hand; and also on the quality of the sample, e.g. on the source of RNA and the used hybridization-pipeline includ
Washing scaling of GeneChip microarray expression
Hans Binder, Knut Krohn, Conrad J Burden
BMC Bioinformatics , 2010, DOI: 10.1186/1471-2105-11-291
Abstract: We conducted experiments on GeneChip microarrays with altered protocols for washing, scanning and staining to study the probe-level intensity changes as a function of the number of washing cycles. For calibration and analysis of the intensity data we make use of the 'hook' method which allows intensity contributions due to non-specific and specific hybridization of perfect match (PM) and mismatch (MM) probes to be disentangled in a sequence specific manner. On average, washing according to the standard protocol removes about 90% of the non-specific background and about 30-50% and less than 10% of the specific targets from the MM and PM, respectively. Analysis of the washing kinetics shows that the signal-to-noise ratio doubles roughly every ten stringent washing cycles. Washing can be characterized by time-dependent rate constants which reflect the heterogeneous character of target binding to microarray probes. We propose an empirical washing function which estimates the survival of probe bound targets. It depends on the intensity contribution due to specific and non-specific hybridization per probe which can be estimated for each probe using existing methods. The washing function allows probe intensities to be calibrated for the effect of washing. On a relative scale, proper calibration for washing markedly increases expression measures, especially in the limit of small and large values.Washing is among the factors which potentially distort expression measures. The proposed first-order correction method allows direct implementation in existing calibration algorithms for microarray data. We provide an experimental 'washing data set' which might be used by the community for developing amendments of the washing correction.Gene expression profiling using microarrays has become a standard technique for the large scale estimation of transcript abundance [1]. The method is based on the hybridization of RNA prepared from samples of interest with gene-specific oligonucleoti
Glycerophosphoglycerol, Beta-Alanine, and Pantothenic Acid as Metabolic Companions of Glycolytic Activity and Cell Migration in Breast Cancer Cell Lines
Antje Hutschenreuther,Gerd Birkenmeier,Marina Bigl,Knut Krohn,Claudia Birkemeyer
Metabolites , 2013, DOI: 10.3390/metabo3041084
Abstract: In cancer research, cell lines are used to explore the molecular basis of the disease as a substitute to tissue biopsies. Breast cancer in particular is a very heterogeneous type of cancer, and different subgroups of cell lines have been established according to their genomic profiles and tumor characteristics. We applied GCMS metabolite profiling to five selected breast cancer cell lines and found this heterogeneity reflected on the metabolite level as well. Metabolite profiles of MCF-7 cells belonging to the luminal gene cluster proved to be more different from those of the basal A cell line JIMT-1 and the basal B cell lines MDA-MB-231, MDA-MB-435, and MDA-MB-436 with only slight differences in the intracellular metabolite pattern. Lactate release into the cultivation medium as an indicator of glycolytic activity was correlated to the metabolite profiles and physiological characteristics of each cell line. In conclusion, pantothenic acid, beta-alanine and glycerophosphoglycerol appeared to be related to the glycolytic activity designated through high lactate release. Other physiological parameters coinciding with glycolytic activity were high glyoxalase 1 (Glo1) and lactate dehydrogenase (LDH) enzyme activity as well as cell migration as an additional important characteristic contributing to the aggressiveness of tumor cells. Metabolite profiles of the cell lines are comparatively discussed with respect to known biomarkers of cancer progression.
Quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) using amplicon-fusion-site polymerase chain reaction (AFS-PCR)
Axel Weber, Sylvia Taube, Udo zur Stadt, Martin Horstmann, Knut Krohn, Jutta Bradtke, Andrea Teigler-Schlegel, Sabine Leiblein, Holger Christiansen
Experimental Hematology & Oncology , 2012, DOI: 10.1186/2162-3619-1-33
Abstract: Recently, we described a strategy for developing tumor cell specific PCRs for MYCN amplified neuroblastomas, using junction sites (amplicon fusion sites, AFS) of amplified genomic regions (ampGR) as template (AFS-PCR) [1]. All ampGR and thus, all AFS identified were absolute tumor cell specific and unique for each patient. AFS-PCR was highly sensitive and uncovered one tumor cell out of 106 - 107 control cells. We concluded this method is suitable for MRD quantification of MYCN amplified neuroblastoma. We furthermore hypothesized AFS-PCR might not only be limited to neuroblastoma, but transferable to other cancer types, provided that the individual tumor cells harbour ampGR.The detection and quantification of minimal amounts of residual or recurrent leukemic blasts significantly improved therapy management for adult and childhood acute lymphoblastic leukemia (ALL) patients [2-4]. Routinely, rearrangements in immunoglobulin-chain (Ig) or T-cell receptor genes (TCR) serve as template for the design of tumor cell specific PCRs (Ig/TCR-PCR) [4-7]. Amplification of a part of the long arm of chromosome 21 including the AML1/RUNX1 gene (iAMP21) occurs in 1-2% of ALL [8,9].Bone marrow specimens from initial diagnosis and subsequent time points of an ALL patient with iAMP21 were used to directly compare AFS-PCR to routinely used MRD diagnostic strategies and to give additional proof of concept for AFS-PCR as a method for tumor cell detection, not only for neuroblastoma.Multiple copies of AML1/RUNX1 had been identified by fluorescence-in-situ-hybridization (FISH) in a 9 year and 10 months old patient with precursor-B ALL. We confirmed AML1/RUNX1 to be part of a large amplified genomic region of chromomosome 21 (iAMP21) and excluded coamplified regions or additional ampGR on other chromosomes by whole genome Array (Affymetrix Cytogenetics Whole-Genome 2.7M Array) (Figure 1a). Besides iAMP21, several deletions were identified, with most relevant mapping to chromosomes 7p12.1-2
Integration of Genome-Wide SNP Data and Gene-Expression Profiles Reveals Six Novel Loci and Regulatory Mechanisms for Amino Acids and Acylcarnitines in Whole Blood
Ralph Burkhardt?,Holger Kirsten?,Frank Beutner?,Lesca M. Holdt?,Arnd Gross?,Andrej Teren?,Anke T?njes?,Susen Becker?,Knut Krohn,Peter Kovacs
PLOS Genetics , 2015, DOI: 10.1371/journal.pgen.1005510
Abstract: Profiling amino acids and acylcarnitines in whole blood spots is a powerful tool in the laboratory diagnosis of several inborn errors of metabolism. Emerging data suggests that altered blood levels of amino acids and acylcarnitines are also associated with common metabolic diseases in adults. Thus, the identification of common genetic determinants for blood metabolites might shed light on pathways contributing to human physiology and common diseases. We applied a targeted mass-spectrometry-based method to analyze whole blood concentrations of 96 amino acids, acylcarnitines and pathway associated metabolite ratios in a Central European cohort of 2,107 adults and performed genome-wide association (GWA) to identify genetic modifiers of metabolite concentrations. We discovered and replicated six novel loci associated with blood levels of total acylcarnitine, arginine (both on chromosome 6; rs12210538, rs17657775), propionylcarnitine (chromosome 10; rs12779637), 2-hydroxyisovalerylcarnitine (chromosome 21; rs1571700), stearoylcarnitine (chromosome 1; rs3811444), and aspartic acid traits (chromosome 8; rs750472). Based on an integrative analysis of expression quantitative trait loci in blood mononuclear cells and correlations between gene expressions and metabolite levels, we provide evidence for putative causative genes: SLC22A16 for total acylcarnitines, ARG1 for arginine, HLCS for 2-hydroxyisovalerylcarnitine, JAM3 for stearoylcarnitine via a trans-effect at chromosome 1, and PPP1R16A for aspartic acid traits. Further, we report replication and provide additional functional evidence for ten loci that have previously been published for metabolites measured in plasma, serum or urine. In conclusion, our integrative analysis of SNP, gene-expression and metabolite data points to novel genetic factors that may be involved in the regulation of human metabolism. At several loci, we provide evidence for metabolite regulation via gene-expression and observed overlaps with GWAS loci for common diseases. These results form a strong rationale for subsequent functional and disease-related studies.
Alu Elements in ANRIL Non-Coding RNA at Chromosome 9p21 Modulate Atherogenic Cell Functions through Trans-Regulation of Gene Networks
Lesca M. Holdt,Steve Hoffmann,Kristina Sass,David Langenberger,Markus Scholz,Knut Krohn,Knut Finstermeier,Anika Stahringer,Wolfgang Wilfert,Frank Beutner,Stephan Gielen,Gerhard Schuler,Gabor G?bel,Hendrik Bergert,Ingo Bechmann,Peter F. Stadler,Joachim Thiery,Daniel Teupser
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003588
Abstract: The chromosome 9p21 (Chr9p21) locus of coronary artery disease has been identified in the first surge of genome-wide association and is the strongest genetic factor of atherosclerosis known today. Chr9p21 encodes the long non-coding RNA (ncRNA) antisense non-coding RNA in the INK4 locus (ANRIL). ANRIL expression is associated with the Chr9p21 genotype and correlated with atherosclerosis severity. Here, we report on the molecular mechanisms through which ANRIL regulates target-genes in trans, leading to increased cell proliferation, increased cell adhesion and decreased apoptosis, which are all essential mechanisms of atherogenesis. Importantly, trans-regulation was dependent on Alu motifs, which marked the promoters of ANRIL target genes and were mirrored in ANRIL RNA transcripts. ANRIL bound Polycomb group proteins that were highly enriched in the proximity of Alu motifs across the genome and were recruited to promoters of target genes upon ANRIL over-expression. The functional relevance of Alu motifs in ANRIL was confirmed by deletion and mutagenesis, reversing trans-regulation and atherogenic cell functions. ANRIL-regulated networks were confirmed in 2280 individuals with and without coronary artery disease and functionally validated in primary cells from patients carrying the Chr9p21 risk allele. Our study provides a molecular mechanism for pro-atherogenic effects of ANRIL at Chr9p21 and suggests a novel role for Alu elements in epigenetic gene regulation by long ncRNAs.
Assistive Navigation Device for Visually Impaired—A Study on Reaction Time to Tactile Modality Stimuli  [PDF]
Jing Yu, Knut Moeller
Engineering (ENG) , 2013, DOI: 10.4236/eng.2013.510B041

A tactile system to support severe visually-impaired or blind people in the world for their orientation and navigation had been developed. To optimize the design, some parameters of tactile display device were evaluated. In the present paper,we focused on the reaction time to tactile stimuli. In the test, the stimuli were produced through a vibration belt that was worn around the participants’ waist. In the choice reaction time task, the participants had to click corresponding arrow keys according to the location of a tactile signal. The findings of this study provided a reference of the reaction time range, so as to design a more effective and safe tactile navigation system.

The Triune God who speaks: Calvin’s theological hermeneutics
J.B. Krohn
Koers : Bulletin for Christian Scholarship , 2001, DOI: 10.4102/koers.v66i1&2.387
Abstract: The purpose of this article is to make a contribution to the theme of “Calvin as servant of the Word” by exploring some hermeneutical implications of Calvin’s theological commitment to the doctrine of God as Triune. In doing so, it seeks to follow a hermeneutical principle Calvin himself held, that Biblical interpretation had to pass through three distinct but related phases; exegesis (represented by his commentaries), dogmatics (represented by the Institutes), and preaching (represented by his sermons). For Calvin, if any of these phases were omitted, the text would not be interpreted properly, and the message of Scripture would not rightly be applied to the life of the church. The place and importance of the doctrine of the Trinity in Calvin’s theology (often neglected in Calvin scholarship) are first explored, followed by displaying the importance Calvin attached to the integration of doctrine into the hermeneutical process (often disregarded by modern-day exegetes), and finally, all three phases of the interpretational process are brought to bear on Calvin’s sermonic treatment of John 1:1-5. Through expository preaching of the Scriptures, hermeneutics finds its completion, and believers will have a personal encounter with God. As such, Calvin will be shown to be a most excellent servant of the Word.
Ghost Systems Revisited: Modified Virasoro Generators and Logarithmic Conformal Field Theories
Marco Krohn,Michael Flohr
Physics , 2002, DOI: 10.1088/1126-6708/2003/01/020
Abstract: We study the possibility of extending ghost systems with higher spin to a logarithmic conformal field theory. In particular we are interested in c=-26 which turns out to behave very differently to the already known c=-2 case. The energy momentum tensor cannot be built anymore by a combination of derivatives of generalized symplectic fermion fields. Moreover, the logarithmically extended theory is only consistent when considered on nontrivial Riemann surfaces. This results in a LCFT with some unexpected properties. For instance the Virasoro mode L_0 is diagonal and for certain values of the deformation parameters even the whole global conformal group is non-logarithmic.
Four-Point Functions in Logarithmic Conformal Field Theories
Michael Flohr,Marco Krohn
Physics , 2005, DOI: 10.1016/j.nuclphysb.2006.02.036
Abstract: The generic structure of 4-point functions of fields residing in indecomposable representations of arbitrary rank is given. The used algorithm is described and we present all results for Jordan-rank $r=2$ and $r=3$ where we make use of permutation symmetry and use a graphical representation for the results. A number of remaining degrees of freedom which can show up in the correlator are discussed in detail. Finally we present the results for two-logarithmic fields for arbitrary Jordan-rank.
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