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Institute
A central concern in genetics is to identify mechanisms of transcriptional regulation. The aim is to unravel the mapping between the DNA sequence and gene expression. However, it turned out that this is extremely complex. Gene regulation is highly cell type-specific and even moderate changes in gene ex- pression can have functional consequences.
Important contributors to gene regulation are transcription factors (TFs), that are able to directly interact with the DNA. Often, a first step in understanding the effect of a TF on the gene’s regulation is to identify the genomic regions a TF binds to. Therefore, one needs to be aware of the TF’s binding preferences, which are commonly summarized in TF binding motifs. Although for many TFs the binding motif is experimentally validated, there is still a large number of TFs where no binding motif is known. There exist many tools that link TF binding motifs to TFs. We developed the method Massif that improves the performance of such tools by incorporating a domain score that uses the DNA binding domain of the studied TF as additional information.
TF binding sites are often enriched in regulatory elements (REMs) such as promoters or enhancers, where the latter can be located megabases away from its target gene. However, to understand the regulation of a gene it is crucial to know where the REMs of a gene are located. We introduced the EpiRegio webserver that holds REMs associated to target genes predicted across many cell types and tissues using STITCHIT, a previously established method. Our publicly available webserver enables to query for REMs associated to genes (gene query) and REMs overlapping genomic regions (region query). We illus- trated the usefulness of EpiRegio by pointing to a TF that occurs enriched in the REMs of differential expressed genes in circPLOD2 depleted pericytes. Further, we highlighted genes, which are affected by CRISPR-Cas induced mutations in non-coding genomic regions using EpiRegio’s region query. Non-coding genetic variants within REMs may alter gene expression by modifying TF binding sites, which can lead to various kinds of traits or diseases. To understand the underlying molecular mechanisms, one aims to evaluate the effect of such genetic variations on TF binding sites. We developed an accurate and fast statistical approach, that can assess whether a single nucleotide polymorphism (SNP) is regulatory. Further, we combined this approach with epigenetic data and additional analyses in our Sneep workflow. For instance, it enables to identify TFs whose binding preferences are affected by the analyzed SNPs, which is illustrated on eQTL datasets for different cell types. Additionally, we used our Sneep workflow to highlight cardiovascular disease genes using regulatory SNPs and REM-gene interactions.
Overall, the described results allow a better understanding of REM-gene interactions and their interplay with TFs on gene regulation.
Programmable hardware in the form of FPGAs found its place in various high energy physics experiments over the past few decades. These devices provide highly parallel and fully configurable data transport, data formatting, and data processing capabilities with custom interfaces, even in rigid or constrained environments. Additionally, FPGA functionalities and the number of their logic resources have grown exponentially in the last few years, making FPGAs more and more suitable for complex data processing tasks. ALICE is one of the four main experiments at the LHC and specialized in the study of heavy-ion collisions. The readout chain of the ALICE detectors makes use of FPGAs at various places. The Read-Out Receiver Cards (RORCs) are one example of FPGA-based readout hardware, building the interface between the custom detector electronics and the commercial server nodes in the data processing clusters of the Data Acquisition (DAQ) system as well as the High Level Trigger (HLT). These boards are implemented as server plug-in cards with serial optical links towards the detectors. Experimental data is received via more than 500 optical links, already partly pre-processed in the FPGAs, and pushed towards the host machines. Computer clusters consisting of a few hundred nodes collect, aggregate, compress, reconstruct, and prepare the experimental data for permanent storage and later analysis. With the end of the first LHC run period in 2012 and the start of Run 2 in 2015, the DAQ and HLT systems were renewed and several detector components were upgraded for higher data rates and event rates. Increased detector link rates and obsolete host interfaces rendered it impossible to reuse the previous RORCs in Run 2.
This thesis describes the development, integration, and maintenance of the next generation of RORCs for ALICE in Run 2. A custom hardware platform, initially developed as a joint effort between the ALICE DAQ and HLT groups in the course of this work, found its place in the Run 2 readout systems of the ALICE and ATLAS experiments. The hardware fulfills all experiment requirements, matches its target performance, and has been running stable in the production systems since the start of Run 2. Firmware and software developments for the hardware evaluation, the design of the board, the mass production hardware tests, as well as the operation of the final board in the HLT, were carried out as part of this work. 74 boards were integrated into the HLT hardware and software infrastructure, with various firmware and software developments, to provide the main experimental data input and output interface of the HLT for Run 2. The hardware cluster finder, an FPGA-based data pre-processing core from the previous generation of RORCs, was ported to the new hardware. It has been improved and extended to meet the experimental requirements throughout Run 2. The throughput of this firmware component could be doubled and the algorithm extended, providing an improved noise rejection and an increased overall mean data compression ratio compared to its previous implementation. The hardware cluster finder forms a crucial component in the HLT data reconstruction and compression scheme with a processing performance of one board equivalent to around ten server nodes for comparable processing steps in software.
The work on the firmware development, especially on the hardware cluster finder, once more demonstrated that developing and maintaining data processing algorithms with the common low-level hardware description methods is tedious and time-consuming. Therefore, a high-level synthesis (HLS) hardware description method applying dataflow computing at an algorithmic level to FPGAs was evaluated in this context. The hardware cluster finder served as an example of a typical data processing algorithm in a high energy physics readout application. The existing and highly optimized low-level implementation provided a reference for comparisons in terms of throughput and resource usage. The cluster finder algorithm could be implemented in the dataflow description with comparably little effort, providing fast development cycles, compact code and at, the same time, simplified extension and maintenance options. The performance results in terms of throughput and resource usage are comparable to the manual implementation. The dataflow environment proved to be highly valuable for design space explorations. An integration of the dataflow description into the HLT firmware and software infrastructure could be demonstrated as a proof of concept. A high-level hardware description could ease both the design space exploration, the initial development, the maintenance, and the extension of hardware algorithms for high energy physics readout applications.
Cyber Physical Systems (CPS) are growing more and more complex due to the availability of cheap hardware, sensors, actuators and communication links. A network of cooperating CPSs (CPN) additionally increases the complexity. This poses challenges as well as it offers chances: the increasing complexity makes it harder to design, operate, optimize and maintain such CPNs. However, on the other side an appropriate use of the increasing resources in computational nodes, sensors, actuators can significantly improve the system performance, reliability and flexibility. Therefore, self-X features like self-organization, self-adaptation and self-healing are key principles for such systems.
Additionally, CPNs are often deployed in dynamic, unpredictable environments and safety-critical domains, such as transportation, energy, and healthcare. In such domains, usually applications of different criticality level exist. In an automotive environment for example, the brake has a higher criticality level regarding safety as the infotainment. As a result of mixed-criticality, applications requiring hard real-time guarantees compete with those requiring soft real-time guarantees and best-effort application for the given resources within the overall system. This leads to the need to accommodate multiple levels of criticality while ensuring safety and reliability, which increases the already high complexity even more.
This thesis deals with the question on how to conveniently, effectively and efficiently handle the management and complexity of mixed-critical CPNs (MC-CPNs). Since this cannot be done by the system developer without the assistance of the system itself any longer, it is essential to develop new approaches and techniques to ensure that such systems can operate under a range of conditions while meeting stringent requirements.
Based on five research hypothesis, this thesis introduces a comprehensive adaptive mixed-criticality supporting middleware for Cyber-Physical Networks (Chameleon), which efficiently and autonomously takes care of the management and complexity of CPNs with regard to the mixed-criticality aspect.
Chameleon contributes to the state-of-art by introducing and combining the following concepts:
- A comprehensive self-adaption mechanism on all levels of the system model is provided.
- This mechanism allows a flexible combination of parametric and structural adaptation actions (relocation, scheduling, tuning, ...) to modify the behavior of the system.
- Real-time constraints of mixed-critical applications (hard real-time, soft real-time, best-effort) are considered in all possible adaptation conditions and actions by the use of the importance parameter.
- CPNs are supported by the introduction of different scopes (local, system, global) for the adaptation conditions and actions. This also enables the combination of different scopes for conditions and actions.
- The realization of the adaptation with a MAPE-K loop instantiated by a distributed LCS allows for real-time capable reasoning of adaptation actions which also works on resource-spare systems.
- The developed rule language Rango offers an intuitive way to specify an initial rule set for LCS in the context of CPS/CPNs and supports the system administrators in the process of rule set generation.
The constantly increasing memory density and performance of recent Field Programmable Gate Arrays (FPGA) has boosted a usage in many technical applications such as particle accelerators, automotive industry as well as defense and space. Some of these fields of interest are characterized by the presence of ionizing radiation as caused by natural decay or artificial excitation processes. Unfortunately, this type of radiation affects various digital circuits, including transistors forming Static Random Access Memory (SRAM) storage cells that constitute the technology node for high performance FPGAs. Various digital misbehavior in temporal or permanent manner as well as physical destruction of transistors are the consequence. Therefore, the mitigation of such effects becomes an essential design rule when using SRAM FPGAs in ionizing radiation environments. Tolerance against soft errors can be handled across various layers of modern FPGA design, starting with the most basic silicon manufacturing process, towards configuration, firmware, and system design, until finally ending up with application and software engineering. But only a highly optimized, joint concept of system-wide fault tolerance provides sufficient resilience against ionizing radiation effects without losing too much valuable device resources to the safety approach. This concept is introduced, analyzed, improved and validated in the present work. It includes, but is not limited to, static configuration scrubbing, various firmware redundancy approaches, dynamic memory conservation as well as state machine protection. Guidelines are given to improve manual design practices concerning fault tolerance and tools are shown to reduce necessary efforts. Finally, the SysCore development platform has been maintained to support the recommended design methods and act as Device Under Test (DUT) for all particle irradiation experiments that prove the efficiency of the proposed concept of system-wide fault tolerance for SRAM FPGAs in ionizing radiation environments.
Autonomous steering of an electric bicycle based on sensor fusion using model predictive control
(2019)
In this thesis a control and steering module for an autonomous bicycle was developed. Based on sensor fusion and model predictive control, the module is able to trace routes autonomously.
The system is developed to run on a Raspberry Pi. An ultrasonic sensor and a 2D Lidar sensor are used for distance measurements. The vehicle’s position is determined by using GPS signals. Additionally, a camera is used to capture pictures for the roadside detection. In order to recognize the road and the position of the vehicle on it, computer vision techniques are used. The captured images are denoised, Canny edge detection is performed and a perspective transformation is applied. Thereafter a sliding window algorithm selects the edges belonging to the roadside and a second order polynomial is fitted to the selected data. Based on this, the road curvature and the lateral position of the vehicle on the road are calculated. The implemented software is thus able to detect straight and curved roads as well as the vehicle’s lateral offset.
A route planning module was implemented to navigate the vehicle from the start to the destination coordinates. This is done by creating an abstract graph of the roads and using Dijkstra’s algorithm to determine the shortest path.
Four MPC controllers were implemented to control the movements of the vehicle. They are based on state space equations derived from the linear single-track vehicle model. This relatively straightforward model makes it possible to predict the vehicle behavior and is efficient to compute. Each controller was built with different parameters for different vehicle speeds to account for the non-linearity of the system. The controllers simulate the future states of the system at each timeslot and select appropriate control signals for steering, throttle and brakes.
In this thesis, all the components of the steering and control module were individually validated. It was established that the each individual component works as expected and certain constraints and accuracy limits were identified. Finally, the closed loop capabilities of the system were assessed using a test vehicle. Despite some limitations imposed by this setup, it was shown that the control module is indeed capable of autonomously navigating a vehicle and avoiding collisions.
This work describes development of a comprehensive methodology for analyzing vibro-acoustic and wear mechanisms in transmission systems. The thesis addresses certain gaps present in the fields of structure dynamics and abrasion mechanism and opens new areas for further research.
The paper attempts to understand new and relatively unexplored challenges like influences of wear on the dynamics of drive train. It also focuses on developing new techniques for analyzing the vibration and acoustic behavior of the drive unit structures and surrounding fluids respectively.
The developed methodology meets the requirements of both the complete system and component level modeling by using specially identified combination of different simulation techniques. Based on the created template model, a three-stage spur plus helical gearbox is constructed and simulated as an application example. In addition to the internal mechanical excitation mechanisms, the transmission model also includes the rotational and translational dynamics of the gears, shafts and bearings. It is followed by illustration of wear among the rotating components.
Different kinds of static and dynamic analyses are performed and coupled at various levels depending on the mechanical complexities involved. Furthermore, the structure dynamic vibration of the housing and the associated sound particle radiations are mapped into the surrounding fluid. Additionally, the approach for selection of the potential parameters for optimization is depicted. Final part focuses on the measurements of different system states used for validation of the model. In the end, results obtained from both simulations and experiments are analyzed and assessed for there respective performances.
Hierarchical self-organizing systems for task-allocation in large scaled distributed architectures
(2019)
This thesis deals with the subject of autonomous, decentralized task allocation in a large scaled multi-core network. The self-organization of such interconnected systems becomes more and more important for upcoming developments. It is to be expected that the complexity of those systems becomes hardly manageable to human users. Self-organization is part of a research field of the Organic Computing initiative, which aims to find solutions for technical systems by imitating natural systems and their processes. Within this initiative, a system for task allocation in a small scaled multi-core network was already developed, researched and published. The system is called the Artificial Hormone System (AHS), since it is inspired by the endocrine system of mammals. The AHS produces a high amount of communication load in case the multi-core network is of a bigger scale.
The contribution of this thesis is two new approaches, both based on the AHS in order to cope with large scaled architectures. The major idea of those two approaches is to introduce a hierarchy into the AHS in order to reduce the produced communication load. The first and more detailed researched approach is called the Hierarchical Artificial Hormone System (HAHS), which orders the processing elements in clusters and builds an additional communication layer between them. The second approach is the Recursive Artificial Hormone System (RAHS), which also clusters the system’s processing elements and orders the clusters into a topological tree structure for communication.
Both approaches will be explained in this thesis by their principle structure as well as some optional methods. Furthermore, this thesis presents estimations for the worst case timing behavior and the worst-case communication load of the HAHS and RAHS. At last, the evaluation results of both approaches, especially in comparison to the AHS, will be shown and discussed.
A Large Ion Collider Experiment (ALICE) is one of the four large experiments at the Large Hadron Collider (LHC) at the European Organization for Particle Physics (CERN). ALICE focuses on the physics of the strong interaction and in particular on the Quark-Gluon Plasma. This is a state of matter in which quarks are de-confined. It is believed that it existed in the earliest moments of the evolution of the universe. The ALICE detector studies the products of the collisions between heavy-nuclei, between protons, and between protons and heavy-nuclei. The sub-detector closest to the interaction point is the Inner Tracking System (ITS), which is used to measure the momentum and trajectory of the particles generated by the collisions and allows reconstructing primary and secondary interaction vertices. The ITS needs to have an accurate spatial resolution, together with a low material budget to limit the effect of multiple scattering on low-energetic particles to precisely reconstruct their trajectory. During the Long Shutdown 2 (2019-2020) of the LHC, the current ITS will be replaced by a completely redesigned sub-detector, which will improve readout rate and particle tracking performance especially at low-momentum.
The ALice PIxel DEtector (ALPIDE) chip was designed to meet the requirements of the upgraded ITS in terms of resolution, material budget, radiation hardness, and readout rate. The ALPIDE chip is a Monolithic Active Pixel Sensor (MAPS) realised in Complementary Metal-Oxide Semiconductor (CMOS) technology. Sensing element, analogue front-end, and its digital readout are integrated into the same silicon die. The readout architecture of the new ITS foresees that data is transmitted via a high-speed serial link directly from the ALPIDE to the off-detector electronics. The data is transmitted off-chip by a so-called Data Transmission Unit (DTU) which needs to be tolerant to Single-Event Effects induced by radiation, in order to guarantee reliable operation. The ALPIDE chip will operate in a radiation field with a High-Energy Hadron peak flux of 7.7·10^5 cm^-2s^-1.
The data are sent by the ALPIDE on copper cables to the readout system, which aggregates them and re-transmits them via optical fibres to the counting room. The position where the readout electronics will be placed is constrained by the maximum transmission distance reasonably achievable by the ALPIDE Data Transmission Unit and mechanical constraints of the ALICE experiment. The radiation field at that location is not negligible for its effects on electronics: the high-energy hadrons flux can reach 10^3 cm^-2s^-1. Static RAM (SRAM)-based Field Programmable Gate Arrays (FPGAs) are favoured over Application Specific Integrated Circuits (ASICs) or Radiation Hard by Design (RHBD) commercial devices because of cost effectiveness. Moreover, SRAM-based FPGAs are re-configurable and provide the data throughput required by the ITS. The main issue with SRAM-based FPGAs, for the intended application, is the susceptibility of their Configuration RAM (CRAM) to Single-Event Upsets: the number of CRAM bits is indeed much higher than the logic they configure. Total Ionizing Dose (TID) at the readout designed position is indeed still acceptable for Component Off The Shelf (COTS), provided that proper verification is carried out.
This dissertation focuses on two parts of the design of the readout system: the Data Transmission Unit of the ALPIDE chip and the design of fundamental modules for the SRAM-based FPGA of the readout electronics. In the first part, a module of the Data Transmission Unit is designed, optimising the trade-off between power consumption, radiation tolerance, and jitter performance. The design was tested and thoroughly characterised, including tests while under irradiation with a 30 MeV protons. Furthermore the Data Transmission Unit performance was validated after the integration into the first prototypes of ITS modules. In the second part, the problem of developing a radiation-tolerant SRAM-based FPGA design is investigated and a solution is provided. First, a general methodology for designing radiation-tolerant Finite State Machines in SRAM-based FPGAs is analysed, implemented, and verified. Later, the radiation-tolerant FPGA design for the ITS readout is described together with the radiation effects mitigation techniques that were selectively applied to the different modules. The design was tested with multiple irradiation tests and the results are stated below.
Detectors of modern high-energy physics experiments generate huge data rates during operation. The efficient read-out of this data from the front-end electronics is a sophisticated task, the main challenges, however, may vary from experiment to experiment. The Compressed Baryonic Matter (CBM) experiment that is currently under construction at the Facility for Antiproton and Ion Research (FAIR) in Darmstadt/Germany foresees a novel approach for data acquisition.
Unlike previous comparable experiments that organize data read-out based on global, hierarchical trigger decisions, CBM is based on free-running and self-triggered front-end electronics. Data is pushed to the next stage of the read-out chain rather than pulled from the buffers of the previous stage. This new paradigm requires a completely new development of read-out electronics.
As one part of this thesis, a firmware for a read-out controller to interface such a free-running and self-triggered front-end ASIC, the GET4 chip, was implemented. The firmware in question was developed to run on a Field Programmable Gate Array (FPGA). An FPGA is an integrated circuit whose behavior can be reconfigured "in the field" which offers a lot of flexibility, bugs can be fixed and also completely new features can be added, even after the hardware has already been installed. Due to these general advantages, the usage of FPGAs is desired for the final experiment. However, there is also a drawback to the usage of FPGAs. The only affordable FPGAs today are based on either SRAM or Flash technology and both cannot easily be operated in a radiation environment.
SRAM-based devices suffer severely from Single Event Upsets (SEUs) and Flash-based FPGAs deteriorate too fast from Total Ionizing Dose (TID) effects.
Several radiation mitigation techniques exist for SRAM-based FPGAs, but careful evaluation for each use case is required. For CBM it is not clear if the higher resource consumption of added redundancy, that more or less directly translates in to additional cost, outweighs the advantaged of using FPGAs. In addition, it is even not clear if radiation mitigation techniques (e.g. scrubbing) that were already successfully put into operation in space applications also work as efficiently at the much higher particle rates expected at CBM.
In this thesis, existing radiation mitigation techniques have been analyzed and eligible techniques have been implemented for the above-mentioned read-out controller. To minimize additional costs, redundancy was only implemented for selected parts of the design.
Finally, the radiation mitigated read-out controller was tested by mounting the device directly into a particle beam at Forschungszentrum Jülich. The tests show that the radiation mitigation effect of the implemented techniques remains sound, even at a very high particle flux and with only part of the design protected by costly redundancy.
The promising results of the in-beam tests suggest to use FPGAs in the read-out chain of the CBM-ToF detector.