PPARγ and MEK Interactions in Cancer

Peroxisome proliferator-activated receptor-gamma (PPARγ) exerts multiple functions in determination of cell fate, tissue metabolism, and host immunity. Two synthetic PPARγ ligands (rosiglitazone and pioglitazone) were approved for the therapy of type-2 diabetes mellitus and are expected to serve as novel cures for inflammatory diseases and cancer. However, PPARγ and its ligands exhibit a janus-face behaviour as tumor modulators in various systems, resulting in either tumor suppression or tumor promotion. This may be in part due to signaling crosstalk to the mitogen-activated protein kinase (MAPK) cascades. The genomic activity of PPARγ is modulated, in addition to ligand binding, by phosphorylation of a serine residue by MAPKs, such as extracellular signal-regulated protein kinases-1/2 (ERK-1/2), or by nucleocytoplasmic compartmentalization through the ERK activators MAPK kinases-1/2 (MEK-1/2). PPARγ ligands themselves activate the ERK cascade through nongenomic and often PPARγ-independent signaling. In the current review, we discuss the molecular mechanisms and physiological implications of the crosstalk of PPARγ with MEK-ERK signaling and its potential as a novel drug target for cancer therapy in patients

Random amplified polymorphic DNA analysis of a Globodera pallida population selected for virulence

La sélection, pendant sept générations, d'une population de #Globodera pallida pour sa virulence envers le cultivar de pomme de terre partiellement résistant Darwina (Marijke x VTN2 62.33.3) provoque une augmentation du taux de reproduction indiquant un rapport élevé de génotypes virulents au sein de la sélection ainsi réalisée. Les modèles d'ADN polymorphes amplifiés au hasard (RAPD) appartenant aux populations sélectionnée et non sélectionnée se sont révélés généralement très similaires pour les 40 amorces testées. Pour deux de ces amorces cependant, deux fragments additionnels non homologués d'ADN ont été amplifiés dans la population sélectionnée. L'analyse par RAPD de kystes isolés démontre que les propriétés de l'ADN conduisant à ces fragments amplifiés sont très enrichies en ce qui concerne la population sélectionnée. L'un de ces fragments d'ADN a été cloné et utilisé pour tester l'ADN amplifié de seize populations de #G. pallida. Une hybridation n'est observée qu'avec les populations montrant un taux de reproduction élevé sur le cv. Darwina, ce qui peut indiquer une corrélation entre le fragment d'ADN et un type particulier de virulence. (Résumé d'auteur

Development and characterization of a linear ion trap for an improved optical clock performance

Single ion frequency standards have demonstrated in several experiments excellent results and are approaching fractional frequency uncertainties of 10^-18. As dominant contributions to the uncertainty are linked to the ion trap properties a further reduction would be possible by an improved ion trap. Due to the interrogation of a single ion these frequency standards are currently limited by the intrinsically low signal-to-noise ratio and require long averaging times on the order of several days. This limitation is critical for various applications that require a high frequency resolution on short timescales. One possibility to improve the clock stability is to increase the number of clock ions. However, this approach further increases the requirements for the ion trap. Therefore, for the realization of a multi-ion clock that aims at simultaneously reducing the frequency stability and uncertainty the control over the characteristics of the ion trap is crucial. This thesis continues previous work towards the realization of a multi-ion optical clock based on ion Coulomb crystals of 115In+ ions which are sympathetically cooled by 172Yb+ ions. The existing design for a segmented linear ion trap has been refined and a reliable trap manufacturing process for a trap based on gold coated aluminium nitride wafers has been developed. Manufacturing tolerances below 10 μm allowed to reduce the axial micromotion amplitudes substantially. For a region of more than 300 μm the uncertainty contribution of the three-dimensional micromotion amplitude is shown to be below 10^-19. Additionally the radial ion heating rate of the trap has been measured to be 1.1 phonons/s for a trap frequency of 490 kHz. The time dilation shift due to the heating rate on the radial trap axis is found to be (2.1 ± 0.3) x 10^-20 1/s. The trap design has also been optimized for a low trap temperature rise due to the applied rf voltage. Trap temperature measurements with Pt100 sensors installed on the trap showed a maximum temperature increase of 1.21 K at an rf voltage amplitude of 1 kV. By comparing the measurement results to FEM simulations the uncertainty contribution of the trap temperature to the black-body radiation shift has been deduced to be 2.4 x 10^-20. As the ion trap provides a high level of control on Coulomb crystals it also provides an ideal test bed for studying atomic many-body systems. This work presents results of the investigations on topological defects in two-dimensional Coulomb crystals. The emphasis was placed on the effects of mass defects and external electric fields on the stability of the topological defects. It is shown that these effects can be used to manipulate and create topological defects deterministically.In mehreren Experimenten haben Frequenzstandards auf der Basis von einzelnen Ionen hervorragende Ergebnisse erzielt und nähern sich einer relativen Frequenzunsicherheit von 10^-18 an. Eine weitere Reduzierung der Frequenzunsicherheit wäre durch eine verbesserte Ionenfalle möglich, da dominante Beiträge der Frequenzunsicherheit auf die Eigenschaften der Ionenfalle zurückzuführen sind. Aufgrund der Abfrage eines einzelnen Ions sind diese Frequenznormale zur Zeit durch das intrinsisch niedrige Signal-Rausch-Verhältnis limitiert und benötigen lange Mittelungszeiten in der Größenordnung von mehreren Tagen. Diese Limitierung ist für verschiedene Anwendungen, die eine hohe Frequenzauflösung nach kurzen Mittelungszeiten erfordern, ein kritischer Punkt. Die Frequenzstabilität kann durch eine höhere Anzahl von Uhrenionen verbessert werden. Allerdings werden durch diesen Ansatz auch die Anforderungen an die Ionenfalle weiter erhöht. Aus diesem Grund ist für die Realisierung einer Multi-Ionen Uhr, die gleichzeitig die Frequenzstabilität und -unsicherheit weiter verringern soll, die Kontrolle über die Eigenschaften der Ionenfalle von entscheidender Bedeutung. Diese Dissertation setzt frühere Arbeiten zur Realisierung einer optischen Multi-Ionen-Uhr auf der Basis von Coulomb-Kristallen aus 115In+-Ionen, die durch 172Yb+-Ionen sympathisch gekühlt werden, fort. Das existierende Design einer segmentierten linearen Ionenfalle wurde optimiert und es wurde ein zuverlässiger Herstellungsprozess basierend auf goldbeschichteten Aluminiumnitrid-Wafern entwickelt. Durch Fertigungstoleranzen von weniger als 10 μm konnte die axiale Mikrobewegungsamplitude deutlich reduziert werden. Es wird gezeigt, dass in einem Bereich von über 300 μm der Beitrag der dreidimensionalen Mikrobewegung zur Frequenzunsicherheit unterhalb von 10^-19 ist. Zusätzlich wurde die radiale Heizrate der Falle mit 1,1 Phononen/s bei einer Fallenfrequenz von 490 kHz bestimmt. Die Frequenzverschiebung durch Zeitdilatation durch die Heizrate der radialen Fallenachse beträgt damit (2,1 ± 0,3) x 10^-20 1/s. Das Fallendesign wurde ebenso auf einen geringen Anstieg der Fallentemperatur durch die angelegte HF-Spannung optimiert. Die Messungen der Fallentemperatur mit den auf der Falle installierten Pt100 Sensoren zeigten einen maximalen Temperaturanstieg von 1,21 K bei einer HF-Spannungsamplitude von 1 kV. Durch den Vergleich der Messergebnisse mit FEM-Simulationen wurde der Beitrag der Fallentemperatur zur Frequenzverschiebung durch die Schwarzkörperstrahlung mit 2,4 x 10^-20 bestimmt. Da die Ionenfalle eine sehr gute Kontrolle über Coulomb-Kristalle bietet, eignet sie sich auch hervorragend für Experimente mit atomaren Vielteilchensystemen. Hierzu werden in dieser Arbeit Untersuchungen topologischer Defekte in zweidimensionalen Coulomb-Kristallen vorgestellt. Der Schwerpunkt lag dabei auf der Analyse des Einflusses von Massendefekten und externen elektrischen Feldern auf die Stabilität der topologischen Defekte. Es wird gezeigt wie dieser Einfluss genutzt werden kann, um die Defekte gezielt zu manipulieren und sie deterministisch zu produzieren

Data simulation in deep learning-based human recognition

Human recognition is an important part of perception systems, such as those used in autonomous vehicles or robots. These systems often use deep neural networks for this purpose, which rely on large amounts of data that ideally cover various situations, movements, visual appearances, and interactions. However, obtaining such data is typically complex and expensive. In addition to raw data, labels are required to create training data for supervised learning. Thus, manual annotation of bounding boxes, keypoints, orientations, or actions performed is frequently necessary. This work addresses whether the laborious acquisition and creation of data can be simplified through targeted simulation. If data are generated in a simulation, information such as positions, dimensions, orientations, surfaces, and occlusions are already known, and appropriate labels can be generated automatically. A key question is whether deep neural networks, trained with simulated data, can be applied to real data. This work explores the use of simulated training data using examples from the field of pedestrian detection for autonomous vehicles. On the one hand, it is shown how existing systems can be improved by targeted retraining with simulation data, for example to better recognize corner cases. On the other hand, the work focuses on the generation of data that hardly or not occur at all in real standard datasets. It will be demonstrated how training data can be generated by targeted acquisition and combination of motion data and 3D models, which contain finely graded action labels to recognize even complex pedestrian situations. Through the diverse annotation data that simulations provide, it becomes possible to train deep neural networks for a wide variety of tasks with one dataset. In this work, such simulated data is used to train a novel deep multitask network that brings together diverse, previously mostly independently considered but related, tasks such as 2D and 3D human pose recognition and body and orientation estimation

Sub-kelvin temperature management in ion traps for optical clocks

The uncertainty of the ac Stark shift due to thermal radiation represents a major contribution to the systematic uncertainty budget of state-of-the-art optical atomic clocks. In the case of optical clocks based on trapped ions, the thermal behavior of the rf-driven ion trap must be precisely known. This determination is even more difficult when scalable linear ion traps are used. Such traps enable a more advanced control of multiple ions and have become a platform for new applications in quantum metrology, simulation and computation. Nevertheless, their complex structure makes it more difficult to precisely determine its temperature in operation and thus the related systematic uncertainty. We present here scalable linear ion traps for optical clocks, which exhibit very low temperature rise under operation. We use a finite-element model refined with experimental measurements to determine the thermal distribution in the ion trap and the temperature at the position of the ions. The trap temperature is investigated at different rf-drive frequencies and amplitudes with an infrared camera and integrated temperature sensors. We show that for typical trapping parameters for $\mathrm{In}^{+}$, $\mathrm{Al}^{+}$, $\mathrm{Lu}^{+}$, $\mathrm{Ca}^{+}$, $\mathrm{Sr}^{+}$ or $\mathrm{Yb}^{+}$ ions, the temperature rise at the position of the ions resulting from rf heating of the trap stays below 700 mK and can be controlled with an uncertainty on the order of a few 100 mK maximum.Comment: 18 page