Efficient Analysis in Multimedia Databases

The rapid progress of digital technology has led to a situation where computers have become ubiquitous tools. Now we can find them in almost every environment, be it industrial or even private. With ever increasing performance computers assumed more and more vital tasks in engineering, climate and environmental research, medicine and the content industry. Previously, these tasks could only be accomplished by spending enormous amounts of time and money. By using digital sensor devices, like earth observation satellites, genome sequencers or video cameras, the amount and complexity of data with a spatial or temporal relation has gown enormously. This has led to new challenges for the data analysis and requires the use of modern multimedia databases. This thesis aims at developing efficient techniques for the analysis of complex multimedia objects such as CAD data, time series and videos. It is assumed that the data is modeled by commonly used representations. For example CAD data is represented as a set of voxels, audio and video data is represented as multi-represented, multi-dimensional time series. The main part of this thesis focuses on finding efficient methods for collision queries of complex spatial objects. One way to speed up those queries is to employ a cost-based decompositioning, which uses interval groups to approximate a spatial object. For example, this technique can be used for the Digital Mock-Up (DMU) process, which helps engineers to ensure short product cycles. This thesis defines and discusses a new similarity measure for time series called threshold-similarity. Two time series are considered similar if they expose a similar behavior regarding the transgression of a given threshold value. Another part of the thesis is concerned with the efficient calculation of reverse k-nearest neighbor (RkNN) queries in general metric spaces using conservative and progressive approximations. The aim of such RkNN queries is to determine the impact of single objects on the whole database. At the end, the thesis deals with video retrieval and hierarchical genre classification of music using multiple representations. The practical relevance of the discussed genre classification approach is highlighted with a prototype tool that helps the user to organize large music collections. Both the efficiency and the effectiveness of the presented techniques are thoroughly analyzed. The benefits over traditional approaches are shown by evaluating the new methods on real-world test datasets

Bladder cancer - the neglected tumor: a descriptive analysis of publications referenced in MEDLINE and data from the register clinicaltrials.gov

Background: Uro-oncological neoplasms have both a high incidence and mortality rate and are therefore a major public health problem. The aim of this study was to evaluate research activity in uro-oncology over the last decade. Methods: We searched MEDLINE and ClinicalTrials.gov systematically for studies on prostatic, urinary bladder, kidney, and testicular neoplasms. The increase in newly published reports per year was analyzed using linear regression. The results are presented with 95% confidence intervals, and a p value <0.05 was considered statistically significant. Results: The number of new publications per year increased significantly for prostatic, kidney and urinary bladder neoplasms (all <0.0001). We identified 1,885 randomized controlled trials (RCTs); also for RCTs, the number of newly published reports increased significantly for prostatic (p = 0.001) and kidney cancer (p = 0.005), but not for bladder (p = 0.09) or testicular (p = 0.44) neoplasms. We identified 3,114 registered uro-oncological studies in ClinicalTrials.gov. However, 85% of these studies are focusing on prostatic (45%) and kidney neoplasms (40%), whereas only 11% were registered for bladder cancers. Conclusions: While the number of publications on uro-oncologic research rises yearly for prostatic and kidney neoplasms, urothelial carcinomas of the bladder seem to be neglected despite their important clinical role. Clinical research on neoplasms of the urothelial bladder must be explicitly addressed and supported

Förderung des Transfers materialwissenschaftlicher Forschungsergebnisse hin zur Markteinführung durch ein strukturiertes Rahmenprogramm zur interdisziplinären Kompetenzaneignung und Demonstrator-Entwicklung: eine Fallstudie

Das vorliegende Paper beschreibt ein Vorgehen zur Förderung des Transfers materialwissenschaftlicher Forschungsergebnisse hin zur Marktfähigkeit durch ein strukturiertes Rahmenprogramm zur Kompetenzaneignung und zur interdisziplinären kollaborativen Demonstrator-Entwicklung anhand eines Fallbeispiels. Das Rahmenprogramm dient der Vermittlung von Kompetenzen aus Design und Geschäftsmodellentwicklung zur Überwindung des „Valley of Death“, also des scheiternden Transfers von Forschungsergebnissen hin zur Marktreife. Es werden Methodik und Vorgehen im Vorhaben betrachtet. Darüber hinaus werden die observierten Limitationen beschrieben, die bei der Arbeit mit den Methoden beobachtet wurden und das Feld noch weiter einschränken. Die Ergebnisse wurden auf Basis von a) Literaturanalysen, b) einer Umfrage unter Materialwissenschaftlern und c) Beobachtungen bei der Konzeption, Durchführung und Auswertung von Trainings im „Material Demo Lab“ bewertet. Zu den Kernerkenntnissen gehört, die gesteigerte Akzeptanz der neu erlernten Methoden, wenn diese vorrangig die Technologieentwicklung vor dem Hintergrund der Geschäftsmodellentwicklung adressieren. Die Entwicklung eines Technologiedemonstrators wurde als treibende Kraft und Motivationsgeber im beschriebenen Rahmenprogramm identifiziert

Di-(2-Ethylhexyl)-Phthalate (DEHP) Causes Impaired Adipocyte Function and Alters Serum Metabolites

Di-(2-ethylhexyl)-phthalate (DEHP), an ubiquitous environmental contaminant, has been shown to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies, but the underlying mechanisms are still unknown. We therefore tested the hypothesis that chronic DEHP exposure causes impaired insulin sensitivity, affects body weight, adipose tissue (AT) function and circulating metabolic parameters of obesity resistant 129S6 mice in vivo. An obesity-resistant mouse model was chosen to reduce a potential obesity bias of DEHP effects on metabolic parameters and AT function. The metabolic effects of 10-weeks exposure to DEHP were tested by insulin tolerance tests and quantitative assessment of 183 metabolites in mice. Furthermore, 3T3-L1 cells were cultured with DEHP for two days, differentiated into mature adipocytes in which the effects on insulin stimulated glucose and palmitate uptake, lipid content as well as on mRNA/protein expression of key adipocyte genes were investigated.We observed in female mice that DEHP treatment causes enhanced weight gain, fat mass, impaired insulin tolerance, changes in circulating adiponectin and adipose tissue Pparg, adiponectin and estrogen expression. Serum metabolomics indicated a general increase in phospholipid and carnitine concentrations. In vitro, DEHP treatment increases the proliferation rate and alters glucose uptake in adipocytes. Taken together, DEHP has significant effects on adipose tissue (AT) function and alters specific serum metabolites. Although, DEHP treatment led to significantly impaired insulin tolerance, it did not affect glucose tolerance, HOMA-IR, fasting glucose, insulin or triglyceride serum concentrations. This may suggest that DEHP treatment does not cause impaired glucose metabolism at the whole body level

A rapid and sensitive assay for quantification of siRNA efficiency and specificity

RNA Interference has rapidly emerged as an efficient procedure for knocking down gene expression in model systems. However, cross-reactivity, whereby multiple genes may be simultaneously targeted by a single short interfering RNA (siRNA), can potentially jeopardize correct interpretation of gene function. As such, it is essential to test the specificity of a siRNA prior to a full phenotypic analysis. To this end, we have adapted a reporter-based assay harnessing the sensitivity of luciferase activity to provide a quantitative readout of relative RNAi efficacy and specificity. We have tested different siRNAs directed against Thymosin β4 (Tβ4); determined their effectiveness at silencing Tβ4 and have both excluded off-target silencing of the Tβ4 homologue Thymosin β10 (Tβ10) and demonstrated partial knockdown of Tβ10 despite significant (12/23; 52%) sequence mismatch. This assay system is applicable to any RNAi study where there is a risk of targeting homologous genes and to the monitoring of off-target effects at the genome level following microarray expression profiling

Rapamycin Regulates Autophagy and Cell Adhesion in Induced Pluripotent Stem Cells

Background Cellular reprogramming is a stressful process, which requires cells to engulf somatic features and produce and maintain stemness machineries. Autophagy is a process to degrade unwanted proteins and is required for the derivation of induced pluripotent stem cells (iPSCs). However, the role of autophagy during iPSC maintenance remains undefined. Methods Human iPSCs were investigated by microscopy, immunofluorescence, and immunoblotting to detect autophagy machinery. Cells were treated with rapamycin to activate autophagy and with bafilomycin to block autophagy during iPSC maintenance. High concentrations of rapamycin treatment unexpectedly resulted in spontaneous formation of round floating spheres of uniform size, which were analyzed for differentiation into three germ layers. Mass spectrometry was deployed to reveal altered protein expression and pathways associated with rapamycin treatment. Results We demonstrate that human iPSCs express high basal levels of autophagy, including key components of APMKα, ULK1/2, BECLIN-1, ATG13, ATG101, ATG12, ATG3, ATG5, and LC3B. Block of autophagy by bafilomycin induces iPSC death and rapamycin attenuates the bafilomycin effect. Rapamycin treatment upregulates autophagy in iPSCs in a dose/time-dependent manner. High concentration of rapamycin reduces NANOG expression and induces spontaneous formation of round and uniformly sized embryoid bodies (EBs) with accelerated differentiation into three germ layers. Mass spectrometry analysis identifies actin cytoskeleton and adherens junctions as the major targets of rapamycin in mediating iPSC detachment and differentiation. Conclusions High levels of basal autophagy activity are present during iPSC derivation and maintenance. Rapamycin alters expression of actin cytoskeleton and adherens junctions, induces uniform EB formation, and accelerates differentiation. IPSCs are sensitive to enzyme dissociation and require a lengthy differentiation time. The shape and size of EBs also play a role in the heterogeneity of end cell products. This research therefore highlights the potential of rapamycin in producing uniform EBs and in shortening iPSC differentiation duration

Characterisation of the Fibroblast Growth Factor Dependent Transcriptome in Early Development

BACKGROUND: FGF signaling has multiple roles in regulating processes in animal development, including the specification and patterning of the mesoderm. In addition, FGF signaling supports self renewal of human embryonic stem cells and is required for differentiation of murine embryonic stem cells into a number of lineages. METHODOLOGY/PRINCIPAL FINDINGS: Given the importance of FGF signaling in regulating development and stem cell behaviour, we aimed to identify the transcriptional targets of FGF signalling during early development in the vertebrate model Xenopus laevis. We analysed the effects on gene expression in embryos in which FGF signaling was inhibited by dominant negative FGF receptors. 67 genes positively regulated by FGF signaling and 16 genes negatively regulated by FGF signaling were identified. FGF target genes are expressed in distinct waves during the late blastula to early gastrula phase. Many of these genes are expressed in the early mesoderm and dorsal ectoderm. A widespread requirement for FGF in regulating genes expressed in the Spemann organizer is revealed. The FGF targets MKP1 and DUSP5 are shown to be negative regulators of FGF signaling in early Xenopus tissues. FoxD3 and Lin28, which are involved in regulating pluripotency in ES cells are shown to be down regulated when FGF signaling is blocked. CONCLUSIONS: We have undertaken a detailed analysis of FGF target genes which has generated a robust, well validated data set. We have found a widespread role for FGF signaling in regulating the expression of genes mediating the function of the Spemann organizer. In addition, we have found that the FGF targets MKP1 and DUSP5 are likely to contribute to the complex feedback loops involved in modulating responses to FGF signaling. We also find a link between FGF signaling and the expression of known regulators of pluripotency

Global Chromatin Architecture Reflects Pluripotency and Lineage Commitment in the Early Mouse Embryo

An open chromatin architecture devoid of compact chromatin is thought to be associated with pluripotency in embryonic stem cells. Establishing this distinct epigenetic state may also be required for somatic cell reprogramming. However, there has been little direct examination of global structural domains of chromatin during the founding and loss of pluripotency that occurs in preimplantation mouse development. Here, we used electron spectroscopic imaging to examine large-scale chromatin structural changes during the transition from one-cell to early postimplantation stage embryos. In one-cell embryos chromatin was extensively dispersed with no noticeable accumulation at the nuclear envelope. Major changes were observed from one-cell to two-cell stage embryos, where chromatin became confined to discrete blocks of compaction and with an increased concentration at the nuclear envelope. In eight-cell embryos and pluripotent epiblast cells, chromatin was primarily distributed as an extended meshwork of uncompacted fibres and was indistinguishable from chromatin organization in embryonic stem cells. In contrast, lineage-committed trophectoderm and primitive endoderm cells, and the stem cell lines derived from these tissues, displayed higher levels of chromatin compaction, suggesting an association between developmental potential and chromatin organisation. We examined this association in vivo and found that deletion of Oct4, a factor required for pluripotency, caused the formation of large blocks of compact chromatin in putative epiblast cells. Together, these studies show that an open chromatin architecture is established in the embryonic lineages during development and is sufficient to distinguish pluripotent cells from tissue-restricted progenitor cells

MUSE: Multi-Represented Similarity Estimation

Abstract — In modern multimedia databases, objects can be specified by a large variety of feature representations. In this paper, we present a novel technique for multi-represented similarity estimation. We transform the distance between two objects in each representation into so-called similarity and dissimilarity estimates which are used to derive a meaningful similarity score. To determine the parameters for our new similarity measure, we present methods with and without user feedback. I