Data-efficient Deep Reinforcement Learning for Vehicle Trajectory Control

Advanced vehicle control is a fundamental building block in the development of autonomous driving systems. Reinforcement learning (RL) promises to achieve control performance superior to classical approaches while keeping computational demands low during deployment. However, standard RL approaches like soft-actor critic (SAC) require extensive amounts of training data to be collected and are thus impractical for real-world application. To address this issue, we apply recently developed data-efficient deep RL methods to vehicle trajectory control. Our investigation focuses on three methods, so far unexplored for vehicle control: randomized ensemble double Q-learning (REDQ), probabilistic ensembles with trajectory sampling and model predictive path integral optimizer (PETS-MPPI), and model-based policy optimization (MBPO). We find that in the case of trajectory control, the standard model-based RL formulation used in approaches like PETS-MPPI and MBPO is not suitable. We, therefore, propose a new formulation that splits dynamics prediction and vehicle localization. Our benchmark study on the CARLA simulator reveals that the three identified data-efficient deep RL approaches learn control strategies on a par with or better than SAC, yet reduce the required number of environment interactions by more than one order of magnitude

A Vision Based Top-View Transformation Model for a Vehicle Parking Assistant

This paper proposes the Top-View Transformation Model for image coordinate transformation, which involves transforming a perspective projection image into its corresponding bird's eye vision. A fitting parameters searching algorithm estimates the parameters that are used to transform the coordinates from the source image. Using this approach, it is not necessary to provide any interior and exterior orientation parameters of the camera. The designed car parking assistant system can be installed at the rear end of the car, providing the driver with a clearer image of the area behind the car. The processing time can be reduced by storing and using the transformation matrix estimated from the first image frame for a sequence of video images. The transformation matrix can be stored as the Matrix Mapping Table, and loaded into the embedded platform to perform the transformation. Experimental results show that the proposed approaches can provide a clearer and more accurate bird's eye view to the vehicle driver

Investigation of the Plasmodium falciparum Food Vacuole through Inducible Expression of the Chloroquine Resistance Transporter (PfCRT)

Haemoglobin degradation during the erythrocytic life stages is the major function of the food vacuole (FV) of Plasmodium falciparum and the target of several anti-malarial drugs that interfere with this metabolic pathway, killing the parasite. Two multi-spanning food vacuole membrane proteins are known, the multidrug resistance protein 1 (PfMDR1) and Chloroquine Resistance Transporter (PfCRT). Both modulate resistance to drugs that act in the food vacuole. To investigate the formation and behaviour of the food vacuole membrane we have generated inducible GFP fusions of chloroquine sensitive and resistant forms of the PfCRT protein. The inducible expression system allowed us to follow newly-induced fusion proteins, and corroborated a previous report of a direct trafficking route from the ER/Golgi to the food vacuole membrane. These parasites also allowed the definition of a food vacuole compartment in ring stage parasites well before haemozoin crystals were apparent, as well as the elucidation of secondary PfCRT-labelled compartments adjacent to the food vacuole in late stage parasites. We demonstrated that in addition to previously demonstrated Brefeldin A sensitivity, the trafficking of PfCRT is disrupted by Dynasore, a non competitive inhibitor of dynamin-mediated vesicle formation. Chloroquine sensitivity was not altered in parasites over-expressing chloroquine resistant or sensitive forms of the PfCRT fused to GFP, suggesting that the PfCRT does not mediate chloroquine transport as a GFP fusion protein

Plasmodium falciparum Heterochromatin Protein 1 Marks Genomic Loci Linked to Phenotypic Variation of Exported Virulence Factors

Epigenetic processes are the main conductors of phenotypic variation in eukaryotes. The malaria parasite Plasmodium falciparum employs antigenic variation of the major surface antigen PfEMP1, encoded by 60 var genes, to evade acquired immune responses. Antigenic variation of PfEMP1 occurs through in situ switches in mono-allelic var gene transcription, which is PfSIR2-dependent and associated with the presence of repressive H3K9me3 marks at silenced loci. Here, we show that P. falciparum heterochromatin protein 1 (PfHP1) binds specifically to H3K9me3 but not to other repressive histone methyl marks. Based on nuclear fractionation and detailed immuno-localization assays, PfHP1 constitutes a major component of heterochromatin in perinuclear chromosome end clusters. High-resolution genome-wide chromatin immuno-precipitation demonstrates the striking association of PfHP1 with virulence gene arrays in subtelomeric and chromosome-internal islands and a high correlation with previously mapped H3K9me3 marks. These include not only var genes, but also the majority of P. falciparum lineage-specific gene families coding for exported proteins involved in host–parasite interactions. In addition, we identified a number of PfHP1-bound genes that were not enriched in H3K9me3, many of which code for proteins expressed during invasion or at different life cycle stages. Interestingly, PfHP1 is absent from centromeric regions, implying important differences in centromere biology between P. falciparum and its human host. Over-expression of PfHP1 results in an enhancement of variegated expression and highlights the presence of well-defined heterochromatic boundaries. In summary, we identify PfHP1 as a major effector of virulence gene silencing and phenotypic variation. Our results are instrumental for our understanding of this widely used survival strategy in unicellular pathogens

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

The Plasmodium food vacuole: protein targeting of transmembrane proteins

© 2011 Dr. Florian EhlgenThe causative agent of severe malaria in humans is Plasmodium falciparum – a parasite whose complex life cycle includes an asexual proliferation within human erythrocytes. Adaptations to the intra-erythrocytic lifestyle have created new and in some cases unique organelles, such as an endosomal/ lysosomal-like organelle, the food vacuole (FV). The only verified function of the FV is haemoglobin degradation and detoxification of the breakdown byproduct, haem. Several anti-malarial drugs interfere with this detoxification and thus kill the parasite. Two multi-spanning membrane proteins in the bounding membrane of the FV, Multidrug Resistant 1 (PfMDR1) and the Chloroquine Resistance Transporter (PfCRT), are associated with resistance against anti-malarial drugs. Protein targeting has been investigated for PfCRT, yet insights from this study are not readily transferable to PfMDR1. In this thesis I investigate the functions of the FV and underlying targeting processes by analysing its membrane proteome. I have expressed PfCRT as a green fluorescence protein (GFP)-tagged fusion and performed further studies on underlying targeting events, and on the biogenesis and development of the FV. I demonstrate that PfCRT targeting is dynamin-dependent and show the hitherto uncharacterised dynamic nature of the FV during intra-erythrocytic life stages. We are confronted with a limited knowledge about the functions and targeting events of membrane proteins to the FV. I have addressed these questions by applying bioinformatic approaches and thereby predicted 74 candidate FV membrane proteins. I have successfully expressed PfMDR1 and four candidate FV membrane proteins as epitope- or GFP-tagged proteins, as well as identifying a sixth likely FV membrane protein using a generated anti-peptide antibody. The subcellular localisation of four candidate proteins confirmed their FV association. Bioinformatic analysis of the putative functions of these revealed two transporter proteins, a pore-forming protein and a subunit of a targeting complex that is involved in retrograde transport from endosomes to the Golgi apparatus in other organisms. Further bioinformatic analysis of the remaining 70 candidate FV membrane proteins revealed eight putative transporter proteins involved in transport of ions, metabolites and amino acids in other organisms (two of which are localised to endosomes and lysosomes). To study the targeting processes of these known and novel FV membrane proteins, I investigated FV membrane trafficking routes using treatment of parasites with the fungal metabolite Brefeldin A, a compound inhibiting early secretory pathway processes. Finally, I have studied the contribution of the adaptin protein (AP) complexes to FV membrane protein targeting. The AP complexes mediate targeting of membrane proteins to endosomes and lysosomes in other organisms. The bioinformatic identification of four distinct AP complexes is described, as well as their subcellular localisation. I show that all four AP complexes are partially associated with the FV, and that AP-1 and AP-2 are strongly linked with the FV membrane. This suggests that AP complexes are involved in targeting of FV membrane proteins. Additionally, I have characterised the four P. falciparum AP complexes in regard to their sensitivity to Brefeldin A

A comparison of solution methods for real business cycle methods

SIGLEAvailable from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel W 1198 (66) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman