Expression cartography of human tissues using self organizing maps

Background: The availability of parallel, high-throughput microarray and sequencing experiments poses a challenge how to best arrange and to analyze the obtained heap of multidimensional data in a concerted way. Self organizing maps (SOM), a machine learning method, enables the parallel sample- and gene-centered view on the data combined with strong visualization and second-level analysis capabilities. The paper addresses aspects of the method with practical impact in the context of expression analysis of complex data sets.
Results: The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues). SOM mapping reduces the dimension of expression data from ten thousands of genes to a few thousands of metagenes where each metagene acts as representative of a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of gene sets well corresponding to molecular processes in the respective tissues. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering provide a better signal-to-noise ratio and a better representativeness of the method if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues into essentially three clusters containing nervous, immune system and the remaining tissues. 
Conclusions: The global view on the behavior of a few well-defined modules of correlated and differentially expressed genes is more intuitive and more informative than the separate discovery of the expression levels of hundreds or thousands of individual genes. The metagene approach is less sensitive to a priori selection of genes. It can detect a coordinated expression pattern whose components would not pass single-gene significance thresholds and it is able to extract context-dependent patterns of gene expression in complex data sets.
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Screening for multicopy suppressors of a yeast mrs3/4Δ mutant

Es wurde ein genetischer Screen durchgeführt, um Suppressoren einer mrs3/4Δ Mutante (und somit mitochondriale Eisentransporter) zu finden. Leider wurden keine Eisentransporter gefunden, aber es konnte belegt werden, dass der Pyrimidintransporter RIM2 (MRS12) Eisen transportieren kann.A genetic screen was carried out to find suppressors of a yeast mrs3/4Δ mutant and therefore to reaveal novel mitochondrial iron transporters. Unfortunately no iron transporters were found, but it was demonstrated that the pyrimidine transporter RIM2 (MRS12) is able to transport iron

Ultrakultur in Frankreich und Österreich

Diese Arbeit vergleicht den Diskurs österreichischer und französischer Tageszeitungen in Bezug auf die Ultrakultur des jeweiligen Landes. Ultras werden als Kategorie von Fußballfans definiert, deren Mitglieder zumeist im Jugendalter sind. Die Ultrakultur wird dabei als Protest-, Demonstrations-, Provokations- und Zuneigungskultur gesehen. Ziel der Arbeit ist es, der Heterogenität der Ultras in einer ausführlichen Beschreibung ihrer Ausdrucksformen gerecht zu werden. Dabei sollen auch jene Aspekte zur Sprache kommen, die im öffentlichen Diskurs häufig verschwiegen werden, was zu einer Stigmatisierung jugendlicher Fußballfans führt. Mithilfe der „Kritischen Diskursanalyse“ sollen im analytischen Teil Medienberichte von jeweils zwei französischen und österreichischen Tageszeitungen betrachtet werden. Für Österreich betrifft es die Berichterstattung der Kronen Zeitung und des Standard der Monate Mai und Juni 2011. Dabei wurden all jene Berichte einer Analyse unterzogen, die sich mit dem Platzsturm von Rapid Fans im Rahmen des Wiener Derbys auseinandersetzten. Was die Analyse der französischen Berichterstattung angeht, so wurden die Berichte der Monate Februar und März 2010 in Le Parisien und Le Monde untersucht. Es handelt sich dabei um jene Berichte, welche die Tageszeitungen infolge einer Auseinandersetzung mit Todesfolge innerhalb der Fanszene von Paris Saint-Germain publizierten. In Bezug auf die österreichischen Medien kann gesagt werden, dass Ultras einer starken Diskriminierung ausgesetzt sind. Zumeist wird nur der Aspekt der Gewalt betrachtet und jugendliche Mitglieder der Gruppen mit diskriminierenden Begriffen abgewertet. Insgesamt lässt sich der Diskurs der österreichischen Tageszeitungen als „autoritär-radikal“ beschreiben. Der Diskurs der französischen Berichterstattung ist im Gegensatz dazu nicht so eindeutig auszumachen. Das liegt vor allem daran, dass die betrachteten Tageszeitungen jeweils unterschiedlichen Fantribünen die Schuld am beschriebenen Vorfall geben. Die Ultrakultur wird dabei differenzierter betrachtet, was alleine das Fehlen diskriminierender Begriffe deutlich macht. Zudem wird die Pariser Fanszene vor allem in Le Monde detailliert beschrieben. Zusammenfassend lässt sich sagen, dass die Berichterstattung der Heterogenität der Ultrakultur nicht gerecht wird und jugendliche Fußballfans stigmatisiert. Den Lesern wird so kein wahrheitsgetreues Bild der Ultras vermittelt

An evaluation of recirculating artificial stream designs for acute toxicity testing using two South African Ephemeroptera species exposed to sodium sulphate

Three artificial stream designs, termed Large Artificial Stream Units (LASUs), Raceways, and Channels, at two major scales (1700 L, 12.5 L and 20 L recirculated volume) were developed at the Institute for Water Research, Rhodes University, Grahamstown, in order to explore the possibilities of using indigenous rheophilic macroinvertebrates in routine toxicity tests. This study compared these systems, using 96h-EC50 values from sodium sulphate toxicity tests as the experimental response. Two local Ephemeroptera (Leptophlebiidae: Adenophlebia auriculata Eaton, and Baetidae: Afroptilum sudafricanum Lestage) were evaluated for their suitability in routine toxicity tests; and the possible effects of elevated salinity levels in South African rivers on the test species were assessed. Two sets of experiments with each mayfly species were conducted, following an unreplicated regression design. Dechlorinated tap water was used as the water source. Experiments in the Channels were repeated to determine experimental variability. Results were compared statistically by testing for overlap of 95% confidence limits (95%Cls) of EC50 values. The differences between A. auriculata EC50 values in the different systems were statistically significant (no overlap of 95%CLs), but they were not more variable than has been considered normal for biological systems (Coefficient of variation 20.1 %; ratio of greatest EC50 / smallest EC50 1.63). The differences were not related to the scale or the average current velocity characteristic of each stream design (average current velocity LASUs - Raceways - Channels 0.090 - 0.083 - 0.038 m/s). The Channels proved to be most efficient with regard to practical performance as they are portable and easily transportable, user-friendly, reliable, splash-free, cost effective to construct, and can easily be adapted to specific requirements. These systems are therefore recommended for regular use. The suitability of the two mayfly species for routine toxicity testing was evaluated. A. auriculata EC50 values showed a significant negative correlation with the corresponding average body-size (range 1476 - 1610 μm, mean 1555 μm). The different average body-sizes probably reflected the abundance of a certain size range present in the Palmiet River at the time of collection. Both species reacted similarly to Na₂S0₄ (similar slopes of the toxicity curves), identifying this salt as a slow acting toxicant. A. sudafricanum populations were more sensitive to Na₂S0₄ (EC50 3.404 g/L) than A. auriculata (EC50 8.090 g/L), probably because of its smaller body-size (mean 709 μm) and a lack of extremely tolerant individuals. In comparison to other freshwater macro invertebrates, including the standard toxicity test organism Daphnia spp., both mayfly species seemed to be moderately tolerant of Na₂S0₄; therefore there was no particular advantage to using these indigenous taxa rather than Daphnia spp. An assessment of the effects of elevated salinity/TDS levels on the test taxa yielded preliminary insights. A NaCI-EC50 for A. sudafricanum could be extrapolated and suggested a higher sensitivity to Na₂S0₄ than to NaCl. When Na₂S0₄ EC50 values of both species were compared to selected TDS levels of South African rivers, 4. auriculata would mostly not be affected, but A. sudafricanum might occasionally suffer from sub-lethal effects, depending on the sulphate proportion of the TDS. The South African guideline for TDS seemed to protect both species sufficiently

Fermion loop simulation of the lattice Gross-Neveu model

We present a numerical simulation of the Gross-Neveu model on the lattice using a new representation in terms of fermion loops. In the loop representation all signs due to Pauli statistics are eliminated completely and the partition function is a sum over closed loops with only positive weights. We demonstrate that the new formulation allows to simulate volumes which are two orders of magnitude larger than those accessible with standard methods

Simulation of magnetic active polymers for versatile microfluidic devices

We propose to use a compound of magnetic nanoparticles (20-100 nm) embedded in a flexible polymer (Polydimethylsiloxane PDMS) to filter circulating tumor cells (CTCs). The analysis of CTCs is an emerging tool for cancer biology research and clinical cancer management including the detection, diagnosis and monitoring of cancer. The combination of experiments and simulations lead to a versatile microfluidic lab-on-chip device. Simulations are essential to understand the influence of the embedded nanoparticles in the elastic PDMS when applying a magnetic gradient field. It combines finite element calculations of the polymer, magnetic simulations of the embedded nanoparticles and the fluid dynamic calculations of blood plasma and blood cells. With the use of magnetic active polymers a wide range of tunable microfluidic structures can be created. The method can help to increase the yield of needed isolated CTCs

Large-scale Simulation of the Two-dimensional Kinetic Ising Model

We present Monte Carlo simulation results for the dynamical critical exponent $z$ of the two-dimensional kinetic Ising model using a lattice of size $10^6 \times 10^6$ spins. We used Glauber as well as Metropolis dynamics. The $z$-value of $2.16\pm 0.005$ was calculated from the magnetization and energy relaxation from an ordered state towards the equilibrium state at $T_c$.Comment: 6 pages + 2 figures as separate uuencoded compressed tar file, Postscipt also available at http://wwwcp.tphys.uni-heidelberg.de/papers

iGraph: Intelligent Enterprise Information Logistics

Engineers in the automotive domain are confronted with a huge load of information making it difficult for them to identify the information relevant for performing their tasks. Particularly challenging is the alignment of process information, such as office files, checklists, and guidelines with business processes. In previous work, we introduced the concept of process-oriented information logistics (POIL) enabling the intelligent delivery of process information along business processes. In this paper, we present iGraph, an application implementing POIL. Specifically, iGraph demonstrates how engineers can be supported with relevant process information during the review of product requirements

Harmonization of growth hormone measurements with different immunoassays by data adjustment

Background: The aim of our study was to evaluate the between-assay variability of commercially available immunoassays for the measurement of human growth hormone (hGH). In addition, we asked whether the comparability of the diagnosis of childhood onset growth hormone deficiency could be improved by adjusting hGH results by statistical methods, such as linear regression, conversion factors, and quantile transformation. Methods: In archived sera from 312 children and adolescents (age: 17 days-17 years) hGH values between 0.01 and 16.5 ng/mL were determined by using the following immunoassays: AutoDELFIA (PerkinElmer), BC-IRMA (Beckman-Coulter), ELISA (Mediagnost), IMMULITE 2000 (Siemens), iSYS (IDS), Liaison (DiaSorin), UniCel DxI 800 Access (BeckmanCoulter) and "In house"-RIA (Tubingen). Results: The assays differed in median hGH concentrations by as much as 5.44 ng/mL (Immulite), and as little as 2.67 ng/mL (BC-IRMA). The mean difference between assays ranged from 0.35 to 2.71 ng/mL, whereas several samples displayed differences up to 11.4 ng/mL. The best correlation (r=0.992) was found between AutoDELFIA and Liasion, the lowest (r=0.864) was between an in-house RIA and iSYS. The between-assay CV (mean +/- SD) of values within the cut-off range was 24.3%+/- 7.4%, resulting in an assay-dependent diagnosis of growth hormone deficiency (GHD) in more than 27% of patients. Yet, adjustment of this data by linear regression or a conversion factor reduced the CV below 14%, and the ratio of assay-dependent diagnoses below 8%. Using quantile transformation, the CV and ratio were reduced to 11.4% and < 1%, respectively. Conclusions: hGH measurements using different assays vary significantly. Linear regression, conversion factors, or particularly quantile transformation are useful tools to improve comparability in the diagnostic procedure for the confirmation of GHD in childhood and adolescence

The influence of knee position on ankle dorsiflexion - a biometric study

Background: Musculus gastrocnemius tightness (MGT) can be diagnosed by comparing ankle dorsiflexion (ADF) with the knee extended and flexed. Although various measurement techniques exist, the degree of knee flexion needed to eliminate the effect of the gastrocnemius on ADF is still unknown. The aim of this study was to identify the minimal degree of knee flexion required to eliminate the restricting effect of the musculus gastrocnemius on ADF. Methods: Bilateral ADF of 20 asymptomatic volunteers aged 18-40 years (50% female) was assessed prospectively at six different degrees of knee flexion (0 degrees, 20 degrees, 30 degrees, 45 degrees, 60 degrees, 75 degrees, Lunge). Tests were performed following a standardized protocol, non weightbearing and weightbearing, by two observers. Statistics comprised of descriptive statistics, t-tests, repeated measurement ANOVA and ICC. Results: 20 individuals with a mean age of 27 +/- 4 years were tested. No significant side to side differences were observed. The average ADF [95% confidence interval] for non weightbearing was 4 degrees{[}1 degrees-8 degrees] with the knee extended and 20 degrees [16 degrees-24 degrees] for the knee 75 flexed. Mean weightbearing ADF was 25 degrees[22 degrees-28 degrees] for the knee extended and 39 degrees[36 degrees-42 degrees] for the knee 75 degrees flexed. The mean differences between 20 degrees knee flexion and full extension were 15 degrees[12 degrees-18 degrees] non weightbearing and 13 degrees[11 degrees-16 degrees] weightbearing. Significant differences of ADF were only found between full extension and 20 degrees of knee flexion. Further knee flexion did not increase ADF. Conclusion: Knee flexion of 20 degrees fully eliminates the ADF restraining effect of the gastrocnemius. This knowledge is essential to design a standardized clinical examination assessing MGT