Gegenwartsdiagnosen Alkemeyer, Thomas; Buschmann, Nikolaus; Etzemüller, Thomas
2019, 201907
eBook
Das Geschäft der Gegenwartsdiagnose hat Konjunktur: Diagnostiziert werden in naher Zukunft drohende Klimakriege, der Kollaps der Energieversorgung oder gleich die Auslöschung der gesamten Menschheit, ...aber auch ein Verlust von ›Heimat‹, ›Werten‹ oder - im Zuge der Digitalisierung - kognitiven Fähigkeiten in der ›Jugend‹.
Vor dem Hintergrund einer tiefen diagnostischen Prägung der modernen Welt- und Selbstwahrnehmung, in der tendenziell alles und jeder einem untersuchenden Blick unterzogen, vermessen und im Hinblick auf mögliche Fehlentwicklungen, Abweichungen und Bedrohungspotenziale ausgekundschaftet wird, untersuchen die Beiträge des Bandes, wie als Diagnosen auftretende Gegenwartsdeutungen entstehen und wirksam werden.
Autonomous navigation in complex environments featuring obstacles, varying ground compositions, and external disturbances requires real-time motion generation and stabilization simultaneously. In ...this paper, we present and evaluate a strategy for rejection of external disturbances and real-time motion generation in the presence of obstacles and non-flat ground. We propose different solutions for combining the associated algorithms and analyze them in simulations The promising method is validated in experiments with our robot
Lola
. We found a hierarchical approach to be effective for solving these complex motion generation problems, because it allows us to decompose the problem into sub-problems that can be tackled separately at different levels. This makes the approach suitable for real-time applications and robust against perturbations and errors. Our results show that real-time motion planning and disturbance rejection can be combined to improve the autonomy of legged robots.
Walking is the most common terrestrial form of locomotion in animals. Its great versatility and flexibility has led to many attempts at building walking machines with similar capabilities. The ...control of walking is an active research area both in neurobiology and robotics, with a large and growing body of work. This paper gives an overview of the current knowledge on the control of legged locomotion in animals and machines and attempts to give walking control researchers from biology and robotics an overview of the current knowledge in both fields. We try to summarize the knowledge on the neurobiological basis of walking control in animals, emphasizing common principles seen in different species. In a section on walking robots, we review common approaches to walking controller design with a slight emphasis on biped walking control. We show where parallels between robotic and neurobiological walking controllers exist and how robotics and biology may benefit from each other. Finally, we discuss where research in the two fields diverges and suggest ways to bridge these gaps.
The p53 tumor suppressor protein, a key regulator of cellular responses to genotoxic stress, is stabilized and activated after DNA damage. The rapid activation of p53 by ionizing radiation and ...radiomimetic agents is largely dependent on the ATM kinase. p53 is phosphorylated by ATM shortly after DNA damage, resulting in enhanced stability and activity of p53. The Mdm2 oncoprotein is a pivotal negative regulator of p53. In response to ionizing radiation and radiomimetic drugs, Mdm2 undergoes rapid ATM-dependent phosphorylation prior to p53 accumulation. This results in a decrease in its reactivity with the 2A10 monoclonal antibody. Phage display analysis identified a consensus 2A10 recognition sequence, possessing the core motif DYS. Unexpectedly, this motif appears twice within the human Mdm2 molecule, at positions corresponding to residues 258-260 and 393-395. Both putative 2A10 epitopes are highly conserved and encompass potential phosphorylation sites. Serine 395, residing within the carboxy-terminal 2A10 epitope, is the major target on Mdm2 for phosphorylation by ATM in vitro. Mutational analysis supports the conclusion that Mdm2 undergoes ATM-dependent phosphorylation on serine 395 in vivo in response to DNA damage. The data further suggests that phosphorylated Mdm2 may be less capable of promoting the nucleo-cytoplasmic shuttling of p53 and its subsequent degradation, thereby enabling p53 accumulation. Our findings imply that activation of p53 by DNA damage is achieved, in part, through attenuation of the p53-inhibitory potential of Mdm2.
Mdm2 is an E3 ubiquitin ligase for the p53 tumor suppressor protein. We demonstrate that Mdm2 is conjugated with SUMO-1 (sumoylated) at Lys-446, which is located within the RING finger domain and ...plays a critical role in Mdm2 self-ubiquitination. Whereas mutant Mdm2K446R is stabilized, it elicits increased degradation of p53 and concomitant inhibition of p53-mediated apoptosis. In vitro sumoylation of Mdm2 abrogates its self-ubiquitination and increases its ubiquitin ligase activity toward p53. Radiation caused a dose- and time-dependent decrease in the degree of Mdm2 SUMO-1 modification, which is inversely correlated with the levels of p53. Our results suggest that the maintenance of the intrinsic activity of a RING finger E3 ubiquitin ligase is sumoylation dependent and that reduced Mdm2 sumoylation in response to DNA damage contributes to p53 stability.
Torso height optimization for bipedal locomotion Hildebrandt, Arne-Christoph; Ritt, Konstantin; Wahrmann, Daniel ...
International journal of advanced robotic systems,
09/2018, Letnik:
15, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Bipedal robots can be better alternatives to other robots in certain applications, but their full potential can only be used if their entire kinematic range is cleverly exploited. Generating motions ...that are not only dynamically feasible but also take into account the kinematic limits as well as collisions in real time is one of the main challenges towards that goal. We present an approach to generate adaptable torso height trajectories to exploit the full kinematic range in bipedal locomotion. A simplified 2D model approximates the robot’s full kinematic model for multiple steps ahead. It is used to optimize the torso height trajectories while taking future motion kinematics into account. The method significantly improves the robot’s motion not only while walking in uneven terrain, but also during normal walking. Furthermore, we integrated the method in our framework for autonomous walking and we validated its real-time character in successfully conducted experiments.
In this study we elucidated the role of nonactive JNK in regulating p53 stability. The amount of p53-JNK complex was inversely correlated with p53 level. A peptide corresponding to the JNK binding ...site on p53 efficiently blocked ubiquitination of p53. Similarly, p53 lacking the JNK binding site exhibits a longer half-life than p53(wt). Outcompeting JNK association with p53 increased the level of p53, whereas overexpression of a phosphorylation mutant form of JNK inhibited p53 accumulation. JNK-p53 and Mdm2-p53 complexes were preferentially found in G0/G1 and S/G2M phases of the cell cycle, respectively. Altogether, these data indicate that JNK is an Mdm2-independent regulator of p53 stability in nonstressed cells.
The protein product of the tumor suppressor gene p53 is phosphorylated on multiple residues by several protein kinases. Using a battery of 10 antibodies developed against different phosphorylated and ...acetylated residues of p53, we compared the pattern of p53 phosphorylation and acetylation in tumor-derived cell lines, tumor samples, and non-neoplastic cells. Irrespective of tumor types or the presence of p53 mutation, phosphorylation and acetylation of p53 was substantially higher in samples obtained from tumor tissues than those found in non-transformed samples. Among the 10 sites analysed, phosphorylation of residues 15, 81, 392, and acetylation were among the more frequent modifications. Analysis of two of the more abundant phosphorylation or acetylation sites on p53 is sufficient to detect 72% of tumor-derived p53 proteins. The distinct pattern of p53 phosphorylation and acetylation in human tumors may offer a new means to monitor the status and activity of p53 in the course of tumor development and progression.
Covalent attachment of SUMO-1 to Mdm2 requires the activation of a heterodimeric Aos1-Uba2 enzyme (ubiquitin-activating enzyme (E1)) followed by the conjugation of Sumo-1 to Mdm2 by Ubc9, a protein ...with a strong sequence similarity to ubiquitin carrier proteins (E2s). Upon Sumo-1 conjugation, Mdm2 is protected from self-ubiquitination and elicits greater ubiquitin-protein isopeptide ligase (E3) activity toward p53, thereby increasing its oncogenic potential. Because of the biological implication of Mdm2 sumoylation, we mapped Ubc9 binding on Mdm2. Here we demonstrate that Ubc9 can associate with Mdm2 only if amino acids 40–59 within the N terminus of Mdm2 are present. Mdm2 from which amino acids 40–59 have been deleted can no longer be sumoylated. Furthermore, addition of a peptide that corresponds to amino acids 40–59 on Mdm2 to a sumoylation reaction efficiently inhibits Mdm2 sumoylation in vitro and in vivo. In UV-treated cells Mdm2 exhibits reduced association with Ubc9, which coincides with decreased Mdm2 sumoylation. Our findings regarding the association of Ubc9 with Mdm2, and the effect of UV-irradiation on Ubc9 binding, point to an additional level in the regulation of Mdm2 sumoylation under normal growth conditions as well as in response to stress conditions.