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Peer Reviewed
See detailTrying to square a circle: A theoretically embedded test for measuring complex problem solving
Greiff, Samuel UL; Funke, Joachim

Scientific Conference (2009, August)

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See detailTTCA: an R package for the identification of differentially expressed genes in time course microarray data
Albrecht, Marco UL; Stichel, Damian; Müller, Benedikt et al

in BMC Bioinformatics (2017), 18(1), 33

Background: The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes ... [more ▼]

Background: The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes respond with quick, transient dynamics, while other genes change their expression slowly over time. The existing methods for detecting significant expression dynamics often fail when the expression dynamics show a large heterogeneity. Moreover, these methods often cannot cope with irregular and sparse measurements. Results: The method proposed here is specifically designed for the analysis of perturbation responses. It combines different scores to capture fast and transient dynamics as well as slow expression changes, and performs well in the presence of low replicate numbers and irregular sampling times. The results are given in the form of tables including links to figures showing the expression dynamics of the respective transcript. These allow to quickly recognise the relevance of detection, to identify possible false positives and to discriminate early and late changes in gene expression. An extension of the method allows the analysis of the expression dynamics of functional groups of genes, providing a quick overview of the cellular response. The performance of this package was tested on microarray data derived from lung cancer cells stimulated with epidermal growth factor (EGF). Conclusion: Here we describe a new, efficient method for the analysis of sparse and heterogeneous time course data with high detection sensitivity and transparency. It is implemented as R package TTCA (transcript time course analysis) and can be installed from the Comprehensive R Archive Network, CRAN. The source code is provided with the Additional file 1. [less ▲]

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See detailTU DO@50 -- ein froher Wunsch für die Zukunft
Hesse, Markus UL

in Gruehn, Dietwald; Reicher, Christa; Wiechmann, Thorsten (Eds.) 50 Jahre Dortmunder Raumplanung (2019)

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See detailTumaco: Collaboration of Mobile Devices in Hypermedia-based In-Vehicle Infotainment Systems
Grevisse, Christian UL; Rothkugel, Steffen UL

in Libro de Actas del XXI Congreso Argentino de Ciencias de la Computación (CACIC 2015) (2015)

In-Vehicle Infotainment systems nowadays are largely limited to one-to-one relationships with the drivers' mobile phone. In this paper, we propose Tumaco, a SOA-based IVI system, which enables the ... [more ▼]

In-Vehicle Infotainment systems nowadays are largely limited to one-to-one relationships with the drivers' mobile phone. In this paper, we propose Tumaco, a SOA-based IVI system, which enables the seamless integration of all devices of all passengers. Collaborative services can be executed within a cross-platform ecosystem through the use of semantic hypermedia. In addition, passengers may customize their own user experience in order to reduce mental workload. Our prototypical implementation showed the benefits of opening the user experience to all passengers on a car. Finally, we present a framework that enables developers to provide their own services within our ecosystem. [less ▲]

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See detailTumor necrosis factor alpha induces gamma-glutamyltransferase expression via nuclear factor-kappaB in cooperation with Sp1
Reuter, Simone; Schnekenburger, Michael; Cristofanon, Silvia et al

in Biochemical Pharmacology (2009), 77(3), 397-411

Gamma-glutamyltransferase (GGT) cleaves the gamma-glutamyl moiety of glutathione (GSH), an endogenous antioxidant, and is involved in mercapturic acid metabolism and in cancer drug resistance when ... [more ▼]

Gamma-glutamyltransferase (GGT) cleaves the gamma-glutamyl moiety of glutathione (GSH), an endogenous antioxidant, and is involved in mercapturic acid metabolism and in cancer drug resistance when overexpressed. Moreover, GGT converts leukotriene (LT) C4 into LTD4 implicated in various inflammatory pathologies. So far the effect of inflammatory stimuli on regulation of GGT expression and activity remained to be addressed. We found that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) induced GGT promoter transactivation, mRNA and protein synthesis, as well as enzymatic activity. Remicade, a clinically used anti-TNFalpha antibody, small interfering RNA (siRNA) against p50 and p65 nuclear factor-kappaB (NF-kappaB) isoforms, curcumin, a well characterized natural NF-kappaB inhibitor, as well as a dominant negative inhibitor of kappaB alpha (IkappaBalpha), prevented GGT activation at various levels, illustrating the involvement of this signaling pathway in TNFalpha-induced stimulation. Over-expression of receptor of TNFalpha-1 (TNFR1), TNFR-associated factor-2 (TRAF2), TNFR-1 associated death domain (TRADD), dominant negative (DN) IkappaBalpha or NF-kappaB p65 further confirmed GGT promoter activation via NF-kappaB. Linker insertion mutagenesis of 536 bp of the proximal GGT promoter revealed NF-kappaB and Sp1 binding sites at -110 and -78 relative to the transcription start site, responsible for basal GGT transcription. Mutation of the NF-kappaB site located at -110 additionally inhibited TNFalpha-induced promoter induction. Chromatin immunoprecipitation (ChIP) assays confirmed mutagenesis results and further demonstrated that TNFalpha treatment induced in vivo binding of both NF-kappaB and Sp1, explaining increased GGT expression, and led to RNA polymerase II recruitment under inflammatory conditions. [less ▲]

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See detailTumor suppressor Ras-association domain family 1 isoform A is a novel regulator of cardiac hypertrophy.
Oceandy, Delvac; Pickard, Adam; Prehar, Sukhpal et al

in Circulation (2009), 120(7), 607-16

BACKGROUND: Ras signaling regulates a number of important processes in the heart, including cell growth and hypertrophy. Although it is known that defective Ras signaling is associated with Noonan ... [more ▼]

BACKGROUND: Ras signaling regulates a number of important processes in the heart, including cell growth and hypertrophy. Although it is known that defective Ras signaling is associated with Noonan, Costello, and other syndromes that are characterized by tumor formation and cardiac hypertrophy, little is known about factors that may control it. Here we investigate the role of Ras effector Ras-association domain family 1 isoform A (RASSF1A) in regulating myocardial hypertrophy. METHODS AND RESULTS: A significant downregulation of RASSF1A expression was observed in hypertrophic mouse hearts, as well as in failing human hearts. To further investigate the role of RASSF1A in cardiac (patho)physiology, we used RASSF1A knock-out (RASSF1A(-)(/)(-)) mice and neonatal rat cardiomyocytes with adenoviral overexpression of RASSF1A. Ablation of RASSF1A in mice significantly enhanced the hypertrophic response to transverse aortic constriction (64.2% increase in heart weight/body weight ratio in RASSF1A(-)(/)(-) mice compared with 32.4% in wild type). Consistent with the in vivo data, overexpression of RASSF1A in cardiomyocytes markedly reduced the cellular hypertrophic response to phenylephrine stimulation. Analysis of molecular signaling events in isolated cardiomyocytes indicated that RASSF1A inhibited extracellular regulated kinase 1/2 activation, likely by blocking the binding of Raf1 to active Ras. CONCLUSIONS: Our data establish RASSF1A as a novel inhibitor of cardiac hypertrophy by modulating the extracellular regulated kinase 1/2 pathway. [less ▲]

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See detailTumor-Initiating Cells: a criTICal review of isolation approaches and new challenges in targeting strategies
qureshi-baig, komal; Ullmann, Pit UL; Haan, Serge UL et al

in Molecular Cancer (2017)

Most cancers contain a subpopulation of highly tumorigenic cells, known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). Targeting TICs may be essential to achieve cure, because of their self ... [more ▼]

Most cancers contain a subpopulation of highly tumorigenic cells, known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). Targeting TICs may be essential to achieve cure, because of their self-renewal and tumorigenic properties as well as their resistance to conventional therapies. Despite significant advances in TIC biology, their isolation and identification remain largely disputed and incompletely established. In this review, we discuss the latest developments in isolation and culturing approaches of TICs, with focus on colorectal cancer (CRC). We feature recent findings on TIC-relevant signaling pathways and the metabolic identity of TICs, as well as their current clinical implications. Lastly, we highlight the influence of inter- and intra-tumoral heterogeneity on TIC function and targeting approaches. [less ▲]

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See detailTumorigenesis and eye abnormalities in transgenic mice expressing MSV-SV40 large T-antigen.
Theuring, F.; Gotz, W.; Balling, Rudi UL et al

in Oncogene (1990), 5(2), 225-32

Transgenic mice which expressed SV40 large T-antigen under the control of the MSV enhancer and the SV40 promoter were generated. In animals containing an intact MSV enhancer, total lens cataracts and ... [more ▼]

Transgenic mice which expressed SV40 large T-antigen under the control of the MSV enhancer and the SV40 promoter were generated. In animals containing an intact MSV enhancer, total lens cataracts and neuroectodermal brain tumors, originating in the pineal organ were observed. In contrast, 5' deletion of the MSV enhancer to a residual 53 bp resulted in a different spectrum of pathologies. Whilst lens cataracts still occurred, no brain tumors could be detected. Instead, fibrosarcomas and adenocarcinomas of the kidneys were induced. In addition, tumors of the endocrine pancreas were observed with both transgene constructs. We conclude that the MSV enhancer element is sufficient to direct the expression of the viral reporter gene to the lens and the pineal organ in transgenic mice. Deletion of the MSV enhancer correlates with the loss of DNA elements responsible for the pineal cell specific expression of SV40 large T-antigen. [less ▲]

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See detailThe tumour suppressor Ras-association domain family protein 1A (RASSF1A) regulates TNF-alpha signalling in cardiomyocytes.
Mohamed, Tamer M. A.; Zi, Min; Prehar, Sukhpal et al

in Cardiovascular research (2014), 103(1), 47-59

AIMS: Tumour necrosis factor-alpha (TNF-alpha) plays a key role in the regulation of cardiac contractility. Although cardiomyocytes are known to express the TNF-alpha receptors (TNFRs), the mechanism of ... [more ▼]

AIMS: Tumour necrosis factor-alpha (TNF-alpha) plays a key role in the regulation of cardiac contractility. Although cardiomyocytes are known to express the TNF-alpha receptors (TNFRs), the mechanism of TNF-alpha signal transmission is incompletely understood. The aim of this study was to investigate whether the tumour suppressor Ras-association domain family protein 1 isoform A (RASSF1A) modulates TNF-alpha signalling in cardiomyocytes. METHODS AND RESULTS: We used RASSF1A knockout (RASSF1A(-/-)) mice and wild-type (WT) littermates in this study. Acute stimulation with a low dose of TNF-alpha (10 microg/kg iv) increased cardiac contractility and intracellular calcium transients' amplitude in WT mice. In contrast, RASSF1A(-/-) mice showed a blunted contractile response. Mechanistically, RASSF1A was essential in the formation of the TNFR complex (TNFRC), where it functions as an adaptor molecule to facilitate the recruitment of TNFR type 1-associated death domain protein and TNFR-associated factor 2 to form the TNF-alpha receptor complex. In the absence of RASSF1A, signal transmission from the TNF-alpha receptor complex to the downstream effectors, such as cytoplasmic phospholipase A2 and protein kinase A, was attenuated leading to the reduction in the activation of calcium handling molecules, such as L-type Ca(2+) channel and ryanodine receptors. CONCLUSION: Our data indicate an essential role of RASSF1A in regulating TNF-alpha signalling in cardiomyocytes, with RASSF1A being key in the formation of the TNFRC and in signal transmission to the downstream targets. [less ▲]

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See detailTUNA: TUning Naturalness-based Analysis
Jimenez, Matthieu UL; Cordy, Maxime UL; Le Traon, Yves UL et al

in 34th IEEE International Conference on Software Maintenance and Evolution, Madrid, Spain, 26-28 September 2018 (2018, September 26)

Natural language processing techniques, in particular n-gram models, have been applied successfully to facilitate a number of software engineering tasks. However, in our related ICSME ’18 paper, we have ... [more ▼]

Natural language processing techniques, in particular n-gram models, have been applied successfully to facilitate a number of software engineering tasks. However, in our related ICSME ’18 paper, we have shown that the conclusions of a study can drastically change with respect to how the code is tokenized and how the used n-gram model is parameterized. These choices are thus of utmost importance, and one must carefully make them. To show this and allow the community to benefit from our work, we have developed TUNA (TUning Naturalness-based Analysis), a Java software artifact to perform naturalness-based analyses of source code. To the best of our knowledge, TUNA is the first open- source, end-to-end toolchain to carry out source code analyses based on naturalness. [less ▲]

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See detailTunable magnetoplasmonics in lattices of Ni/SiO2/Au dimers
Pourjamal, Sara; Kataja, Mikko; Maccaferri, Nicolò UL et al

in Scientific Reports (2019), 9

We present a systematic study on the optical and magneto-optical properties of Ni/SiO2/Au dimer lattices. By consideringthe excitation of orthogonal dipoles in the Ni and Au nanodisks, we analytically ... [more ▼]

We present a systematic study on the optical and magneto-optical properties of Ni/SiO2/Au dimer lattices. By consideringthe excitation of orthogonal dipoles in the Ni and Au nanodisks, we analytically demonstrate that the magnetoplasmonicresponse of dimer lattices is governed by a complex interplay of near- and far-field interactions. Near-field coupling betweendipoles in Ni and low-loss Au enhances the polarizabilty of single dimers compared to that of isolated Ni nanodisks. Far-fielddiffractive coupling in periodic lattices of these two particle types enlarges the difference in effective polarizability further.This effect is explained by an inverse relationship between the damping of collective surface lattice resonances and theimaginary polarizability of individual scatterers. Optical reflectance measurements, magneto-optical Kerr effect spectra, andfinite-difference time-domain simulations confirm the analytical results. Hybrid dimer arrays supporting intense plasmonexcitations are a promising candidate for active magnetoplasmonic devices. [less ▲]

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See detailTuneable Multicoloured Patterns From Photonic Cross Communication Between Cholesteric Liquid Crystal Droplets
Noh, Junghyun UL; Liang, Hsin-Ling; Drevensek-Olenik, Irena et al

in Journal of Materials Chemistry C (2014), 2(5), 806-810

Monodisperse droplets of planar-aligned cholesteric (N*) liquid crystal exhibit an intriguing capacity for photonic cross-communication, giving rise to colourful patterns that depend sensitively on the N ... [more ▼]

Monodisperse droplets of planar-aligned cholesteric (N*) liquid crystal exhibit an intriguing capacity for photonic cross-communication, giving rise to colourful patterns that depend sensitively on the N* pitch, droplet positions and illuminated area. The phenomenon results from a combination of omnidirectional selective reflection of N* droplets—which thus act as spherically symmetric self-assembled photonic crystals—and total internal reflection at the continuous phase surface. We outline how the unique optical properties can be employed in numerous applications. [less ▲]

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See detailTuning Intermolecular Interactions with Nanostructured Environments
Chattopadhyaya, Mausumi; Hermann, Jan; Poltavsky, Igor et al

in Chemistry of Materials (2016), ASAP

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See detailTuning Self-Assembly in Liquid Crystal shells: from Interfacial- to Polymer-stabilization
Noh, Junghyun UL

Doctoral thesis (2018)

Liquid crystals form a subclass of soft materials which is easily influenced and deformed by a surface, an interface and the geometry. Of particular interest, in this thesis, is the confinement of liquid ... [more ▼]

Liquid crystals form a subclass of soft materials which is easily influenced and deformed by a surface, an interface and the geometry. Of particular interest, in this thesis, is the confinement of liquid crystals in shell geometry, imposing real or virtual defects that the liquid crystal cannot avoid. With the help of microfluidics, we prepare our research platform, liquid crystal shells, which contain and are surrounded by aqueous phases. In order to maintain such a shell structure in the aqueous phases, immiscible with the liquid crystal, appropriate stabilization is required. Here we explore two different pathways of interfacial stabilization and polymer stabilization and their impact on liquid crystal self-assembly. We primarily use either a polymeric or an ionic surfactant dissolving in water to stabilize shells and tune boundary conditions of shells. Depending on symmetrically or asymmetrically imposed boundary conditions, the nematic–isotropic phase transition appears as a single transi- tion or separated into two steps. We propose that the latter phenomenon can be understood as a result of an ordering-enhancing effect by surfactants. The nematic–smectic A phase transition is also investigated under varying boundary conditions. With a precise temperature control, we explore equilibrium smectic structures and introduce a new arrangement of focal conic arrays in shell geometry. Beyond stabilizing the shell from the shell exterior, but we also incorporate a photosensitive surface agent within the shell, enabling dynamic and reversible photoswitching of the liquid crystal alignment in real time. However, shells with interfacial stabilization cannot survive more than several weeks due to their intrinsic fluid interfaces. In particular, a liquid crystal shell can serve as a permeable mem- brane which lets the constituents of aqueous phases pass through, giving a significant influence on the liquid crystalline order. To tame liquid crystal self-assembly and make the shell struc- ture permanent, we use photopolymerization to stabilize the shells. With only 5% monomer, the entire configuration of each liquid crystal shell is locked and shell lifetime extends beyond several months. The liquid crystalline order is visualized on the nanoscale via the polymer network and we further demonstrate that the shell configurations can be a unique template for creating complex polymer networks. Finally a new experimental approach is introduced to making ultrathin shells and several issues on shell instability and alignment determination are addressed. [less ▲]

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See detailTuning the defect configurations in nematic and smectic liquid crystalline shells.
Liang, H. L.; Noh, Junghyun UL; Zentel, R. et al

in Philosophical Transactions of the Royal Society of London. Series A : Mathematical and Physical Sciences (2013), 371(1988), 20120258

Thin liquid crystalline shells surrounding and surrounded by aqueous phases can be conveniently produced using a nested capillary microfluidic system, as was first demonstrated by Fernandez-Nieves et al ... [more ▼]

Thin liquid crystalline shells surrounding and surrounded by aqueous phases can be conveniently produced using a nested capillary microfluidic system, as was first demonstrated by Fernandez-Nieves et al. in 2007. By choosing particular combinations of stabilizers in the internal and external phases, different types of alignment, uniform or hybrid, can be ensured within the shell. Here, we investigate shells in the nematic and smectic phases under varying boundary conditions, focusing in particular on textural transformations during phase transitions, on the interaction between topological defects in the director field and inclusions in the liquid crystal (LC), and on the possibility to relocate defects within the shell by rotating the shell in the gravitational field. We demonstrate that inclusions in a shell can seed defects that cannot form in a pristine shell, adding a further means of tuning the defect configuration, and that shells in which the internal aqueous phase is not density matched with the LC will gently rearrange the internal structure upon a rotation that changes the influence of gravity. Because the defects can act as anchor points for added linker molecules, allowing self-assembly of adjacent shells, the various arrangements of defects developing in these shells and the possibility of tuning the result by modifying boundary conditions, LC phase, thickness and diameter of the shell or applying external forces make this new LC configuration very attractive. [less ▲]

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See detailTuning the Magneto-Optical Response of Nanosize Ferromagnetic Ni Disks Using the Phase of Localized Plasmons
Maccaferri, Nicolò UL; Berger, Andreas; Bonetti, Stefano et al

in Physical Review Letters (2013), 111(16), 167401

We explore the influence of the phase of localized plasmon resonances on the magneto-optical activity of nanoferromagnets. We demonstrate that these systems can be described as two orthogonal damped ... [more ▼]

We explore the influence of the phase of localized plasmon resonances on the magneto-optical activity of nanoferromagnets. We demonstrate that these systems can be described as two orthogonal damped oscillators coupled by the spin-orbit interaction. We prove that only the spin-orbit induced transverse plasmon plays an active role on the magneto-optical properties by controlling the relative amplitude and phase lag between the two oscillators. Our theoretical predictions are fully confirmed by magneto-optical Kerr effect and optical extinction measurements in nanostructures of different size and shape. [less ▲]

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See detailTuning the Pseudospin Polarization of Graphene by a Pseudomagnetic Field
Georgi, Alexander; Nemes-Incze, Peter; Carrillo-Bastos, Ramon et al

in Nano Letters (2017), 17

One of the intriguing characteristics of honeycomb lattices is the appearance of a pseudomagnetic field as a result of mechanical deformation. In the case of graphene, the Landau quantization resulting ... [more ▼]

One of the intriguing characteristics of honeycomb lattices is the appearance of a pseudomagnetic field as a result of mechanical deformation. In the case of graphene, the Landau quantization resulting from this pseudomagnetic field has been measured using scanning tunneling microscopy. Here we show that a signature of the pseudomagnetic field is a local sublattice symmetry breaking observable as a redistribution of the local density of states. This can be interpreted as a polarization of graphene’s pseudospin due to a strain induced pseudomagnetic field, in analogy to the alignment of a real spin in a magnetic field. We reveal this sublattice symmetry breaking by tunably straining graphene using the tip of a scanning tunneling microscope. The tip locally lifts the graphene membrane from a SiO2 support, as visible by an increased slope of the I(z) curves. The amount of lifting is consistent with molecular dynamics calculations, which reveal a deformed graphene area under the tip in the shape of a Gaussian. The pseudomagnetic field induced by the deformation becomes visible as a sublattice symmetry breaking which scales with the lifting height of the strained deformation and therefore with the pseudomagnetic field strength. Its magnitude is quantitatively reproduced by analytic and tight-binding models, revealing fields of 1000 T. These results might be the starting point for an effective THz valley filter, as a basic element of valleytronics. [less ▲]

Detailed reference viewed: 69 (2 UL)