From chemotherapy to targeted treatment

Today, melanoma is considered as a spectrum of melanocytic malignancies that can be characterized by clinical and molecular features, including targetable mutations in several kinases. The successful development of therapies, targeting mutated BRaF (v-raf murine sarcoma viral oncogene homolog B1) or c-KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog), has resulted in new treatment options including vemurafenib, imatinib and mitogen-activated protein kinase inhibitors. These molecules are selected if the respective mutation is present. after this first progress in the treatment of advanced melanoma, there is expectation that combinations of kinase inhibitor will additionally improve the overall survival rates and progression-free survival in advanced melanom

Design and practical Realization of an innovative Flywheel Concept for industrial Applications

The joint industry project ‘ETA-Fabrik’ at TU Darmstadt demonstrates different approaches to improve the energy efficiency of manufacturing processes. Within this project an innovative flywheel concept was designed and realized in order to provide energy storage and load smoothing services. The flywheel design is an outerrotor setup. The rotor is a hubless hollow cylinder made of fiber reinforced plastic (FRP). All functional components are fully integrated into the rotor. For the radial suspension homopolar active magnetic bearings (AMBs) made of soft magnetic composite are used. A permanent magnetic bearing provides axial levitation. In order to increase the systems robustness a newly developed backup bearing system in a planetary arrangement with multiple independent bearing elements is integrated. The motor generator unit is a permanent magnet synchronous machine which is connected to the factory gird via a frequency inverter. The system is operated in high vacuum in order to reduce gaseous friction. Design challenges are the segmented  sensor planes for the AMBs, the diametric enlargement of the rotor due to centrifugal forces, the anisotropic  FRP as well as the thermal stability of the rotor in vacuum environment which leads to the demand of very low rotor losses. The  paper describes the system and component design process and solutions which were incorporated in order   to meet the design restrictions and challenges

First record of Tetrastylus Ameghino, 1886 (RODENTIA; DINOMYIDAE) from the upper miocene of Uruguay

The first record for Uruguay of the dinomyid rodent Tetrastylus Ameghino, an almost complete right mandible from the upper Miocene Camacho Formation, is described. According to the p4 and m3 morphology it is inferred a juvenile-subadult ontogenetic stage for this specime

Adapting the control of the magnetic bearings of a highly flexible and gyroscopic rotor to the excitations by the motor

A test rig was built to perform fatigue tests on thick-walled cylinders made of fibre reinforced plastic (FRP). During the fatigue test, the rotational speed of an FRP cylinder is periodically varied until it fails. The FRP cylinder is connected to a drive spindle that accelerates and decelerates it using a permanent magnet synchronous machine (PMSM). To avoid excessive wear, the rotor is supported by active magnetic bearings (AMB). After the fatigue test was finished with the first cylinder, a new cylinder was attached to the test stand. With this new specimen, previously uncritical radial vibrations became more severe. For high accelerations, these vibrations led to instability of the rotor. However, high accelerations are desirable to perform the fatigue tests in the shortest possible time. Hence, the AMB control should be made insensitive to these vibrations. Since the vibrations depend on the acceleration of the rotor, it is reasonable to assume that they are induced by the PMSM. To reduce the vibrations, these excitations from the PMSM are included in the model-based controller parametrization process for the radial AMB, in which the parameters are adjusted via optimization. With the adjusted control, the amplitude of the vibration was significantly reduced and higher accelerations were possible. The described parameter tuning process can easily be adapted to different AMB systems with disturbances and changes in the system

A fundamental investigation of the interaction and impact of controlled torque ripples on gear mesh dynamics

Gear trains are plagued by self-excited vibrations that are concentrated at the mesh frequency and its harmonics due to their varying mesh stiffness and deviations from the ideal involute profile. This is even more pronounced in spur gears due to their lower contact ratio in comparison to helical gears. For an electric vehicle, due to the absence of an internal combustion engine, noise and vibration signature of the gearbox becomes an important aspect of the vehicle's comfort. However, the presence of a traction motor offers the advantage of having a potential actuator for actively countering these vibrations without adding any additional weight or packaging constraints. This paper presents a fundamental insight into the effect of introducing controlled torque ripples at the mesh frequency and its harmonics, on the noise and vibration characteristics, and the efficiency of the gear mesh. The study utilises a dynamic model of a single stage gear train that accounts for the time varying mesh stiffness and sliding friction at the gear teeth contact. This model is used to provide an understanding of gear mesh dynamics and their resulting interaction with the imposed torque ripples. The study demonstrates the positive effects that controlled torque ripples can have on the noise and vibration behaviour of gear trains and the underlying mechanics that govern this improvement

Neutron time-of-flight measurements of charged-particle energy loss in inertial confinement fusion plasmas

Neutron spectra from secondary ^{3}H(d,n)α reactions produced by an implosion of a deuterium-gas capsule at the National Ignition Facility have been measured with order-of-magnitude improvements in statistics and resolution over past experiments. These new data and their sensitivity to the energy loss of fast tritons emitted from thermal ^{2}H(d,p)^{3}H reactions enable the first statistically significant investigation of charged-particle stopping via the emitted neutron spectrum. Radiation-hydrodynamic simulations, constrained to match a number of observables from the implosion, were used to predict the neutron spectra while employing two different energy loss models. This analysis represents the first test of stopping models under inertial confinement fusion conditions, covering plasma temperatures of k_{B}T≈1-4  keV and particle densities of n≈(12-2)×10^{24}  cm^{-3}. Under these conditions, we find significant deviations of our data from a theory employing classical collisions whereas the theory including quantum diffraction agrees with our data

Simulation of Integrated Actuators for Electrostatic Self-Assembly

Die Montage ist ein Kostentreiber in der Produktion, insbesondere wenn die Anforderungen an die Präzision stei-gen. Ein Ansatz für die kostengünstige Feinpositionierung von planaren Bauteilen ist die elektrostatische Self-Assembly, bei dem Aktoren in die Bauteile integriert werden. In diesem Artikel werden die Grundlagen des Designs solcher Systeme thematisiert, da diese Ausschlaggebend für die resultierenden Positionierkräfte sind. Zum Feststellen der Zusammenhänge werden Simulationen für einzelne Elektrodenpaare durchgeführt, wobei die Geometrien Kreis, Quadrat, Rechteck, Sechseck und Dreieck miteinander verglichen werden. Die Auswertung erfolgt mit der simulierten Maximalkraft und der Kraftverteilung innerhalb der xy-Ebene. In Hinblick auf die Prozessgrößen Präzision und maximalen Wirkbereich werden die Ergebnisse interpretiert und Rückschlüsse auf die sinnvolle Gestaltung von Self-Assembly Systemen gezogen. Abschließend erfolgt ein Ausblick auf weitere Forschungen zu elektrostatischen Self-Assembly Systemen.Assembly is a high-cost process in production, especially when the precision requirements are high. One approach for cost-effective fine positioning of planar components is electrostatic self-assembly. Therefore, actuators are integrated into the components. This paper deals with the fundamental design principles of such systems, because they are significantly influencing the alignment force. This paper presents simulations of individual electrode pairs, comparing the geometries circle, square, rectangle, hexagon and triangle. The evaluation shows the results of the simulated maximum force and the force distribution within the xy-plane. Aiming for high precision and a wide range of force distribution, conclusions are made about the appropriate design of self-assembly systems. In conclusion, there is an outlook on additional research into electrostatic self-assembly systems

Automation of flexible handling of hot forged Tailored Forming components

Universalgreifer sind flexibel einsetzbar und können sich an verschiedene Situationen und Objekte anpassen. Aktuelle formvariable Universalgreifer bestehen überwiegend aus monolithischen polymeren Werkstoffen, deren maximale Einsatztemperaturen bei 300 °C liegen. Somit kann von der Formflexibilität nicht in Bereich profitiert werden in denen höhere Temperaturen vorherrschen und die zu handhabenden Objekte Umformungsprozesse durchschreiten. Solch ein Bereich ist der Schmiedesektor, bei dem die Objekte Temperaturen von bis zu 1250 °C erreichen. Die vorliegende Diskrepanz zwischen der Formvariabilität der Greifer und den Prozesstemperaturen im Schmiedesektor versuchen wir zu schließen. In dieser Arbeit stellen wir das von uns entwickelte Konzept eines formvariablen hochtemperaturbeständigem Handhabungssystem und deren praktische Umsetzung vor, sowie die noch zu lösenden Herausforderungen.Universal grippers are flexible and can adapt to different situations and objects. The shape variability has limitations, for example, the temperature. For manufacturing such shape variable grippers, elastic polymer materials are used. The material has an upper limit of the operating temperature of 300 °C. In the forging sector, the manufactured object change their geometry during the process and reaches temperature up 1250 °C. Here, we see the potential of the utilization of shape variable grippers. Therefore, we developed a system that overcomes the gap between the temperature limitation of current shape variable grippers and the high temperature in forging environments. This paper presents our gripper and the task to be solved in future works

Assessment of ion kinetic effects in shock-driven inertial confinement fusion implosions using fusion burn imaging

The significance and nature of ion kinetic effects in D3He-filled, shock-driven inertial confinement fusion implosions are assessed through measurements of fusion burn profiles. Over this series of experiments, the ratio of ion-ion mean free path to minimum shell radius (the Knudsen number, NK) was varied from 0.3 to 9 in order to probe hydrodynamic-like to strongly kinetic plasma conditions; as the Knudsen number increased, hydrodynamic models increasingly failed to match measured yields, while an empirically-tuned, first-step model of ion kinetic effects better captured the observed yield trends [Rosenberg et al., Phys. Rev. Lett. 112, 185001 (2014)]. Here, spatially resolved measurements of the fusion burn are used to examine kinetic ion transport effects in greater detail, adding an additional dimension of understanding that goes beyond zero-dimensional integrated quantities to one-dimensional profiles. In agreement with the previous findings, a comparison of measured and simulated burn profiles shows that models including ion transport effects are able to better match the experimental results. In implosions characterized by large Knudsen numbers (NK3), the fusion burn profiles predicted by hydrodynamics simulations that exclude ion mean free path effects are peaked far from the origin, in stark disagreement with the experimentally observed profiles, which are centrally peaked. In contrast, a hydrodynamics simulation that includes a model of ion diffusion is able to qualitatively match the measured profile shapes. Therefore, ion diffusion or diffusion-like processes are identified as a plausible explanation of the observed trends, though further refinement of the models is needed for a more complete and quantitative understanding of ion kinetic effects