Computer Chess: From Idea to DeepMind

Computer chess has stimulated human imagination over some two hundred and fifty years. In 1769 Baron Wolfgang von Kempelen promised Empress Maria Theresia in public: “I will invent a machine for a more compelling spectacle [than the magnetism tricks by Pelletier] within half a year.” The idea of an intelligent chess machine was born. In 1770 the first demonstration was given.The real development of artificial intelligence (AI) began in 1950 and contains many well-known names, such as Turing and Shannon. One of the first AI research areas was chess. In 1997, a high point was to be reported: world champion Gary Kasparov had been defeated by Deep Blue. The techniques used included searching, knowledge representation, parallelism, and distributed systems. Adaptivity, machine learning and the recently developed deep learning mechanism were only later on added to the computer chess research techniques.The major breakthrough for games in general (including chess) took place in 2017 when (1) the AlphaGo Zero program defeated the world championship program AlphaGo by 100-0 and (2) the technique of deep learning also proved applicable to chess. In the autumn of 2017, the Stockfish program was beaten by AlphaZero by 28-0 (with 72 draws, resulting in a 64-36 victory). However, the end of the disruptive advance is not yet in reach. In fact, we have just started. The next milestone will be to determine the theoretical game value of chess (won, draw, or lost). This achievement will certainly be followed by other surprising developments.Algorithms and the Foundations of Software technolog

Deconstructing the carcinogenome: cancer genomics and exposome data generation, analysis, an tool development to further cancer prevention and therapy

The rise in large-scale cancer genomics data collection initiatives has paved the way for extensive research aimed at understanding the biology of human cancer. While the majority of this research is motivated by clinical applications aimed at advancing targeted therapy, cancer prevention initiatives are less emphasized. Many cancers are not attributable to known heritable genetic factors, making environmental exposure a main suspect in driving cancer risk. A major aspect of cancer prevention involves the identification of chemical carcinogens, substances linked to increased cancer susceptibility. Traditional methods for chemical carcinogens testing, including epidemiological studies and rodent bioassays, are expensive to conduct, not scalable to a large number of chemicals, and not capable of detecting specific mechanisms of actions of carcinogenicity. Thus, there exists a dire need for improvement in data generation and computational method development for chemical carcinogenicity testing. Here, we coin the term "carcinogenome" to denote the complete cancer genomic landscape encompassing both its repertoire of environmental chemical exposures, as well as its germ-line and somatic mutations and epi-genetic regulators. To study the carcinogenome, we analyze both the genomic behavior of real human tumors as well as profiles of the exposome, that is, data derived from chemical exposures in human, animal or cell line models. My thesis consists of two distinct projects that, through the generation and innovative analysis of multi-omics data, aim at advancing our understanding of the molecular mechanisms of cancer initiation and progression, and of the role environmental exposure plays in these processes. First, I detail our effort at data generation and method development for characterizing environmental contributions to carcinogenesis using transcriptional profiles of chemical perturbations. Second, I present the tool iEDGE (Integration of Epi-DNA and Gene Expression) and its applications to the integrative analysis of multi-level cancer genomics data from human primary tumors of multiple cancer types. These projects collectively further our understanding of the carcinogenome and will hopefully foster both cancer prevention, through the identification of environmental chemical carcinogens, and cancer therapy, through the discovery of novel cancer gene drivers and therapeutic targets

The 1995 Goddard Conference on Space Applications of Artificial Intelligence and Emerging Information Technologies

This publication comprises the papers presented at the 1995 Goddard Conference on Space Applications of Artificial Intelligence and Emerging Information Technologies held at the NASA/Goddard Space Flight Center, Greenbelt, Maryland, on May 9-11, 1995. The purpose of this annual conference is to provide a forum in which current research and development directed at space applications of artificial intelligence can be presented and discussed

Structure-based function assignment for archaellum regulatory network proteins of Sulfolobus acidocaldarius

Der Ursprung des Lebens ist ein komplexes Thema, das weltweit wissenschaftliche Diskussionen befeuert. Im Allgemeinen ist es akzeptiert, dass die Endosymbiose eine zentrale Rolle bei der Eukaryogenese spielt. Für diese Arbeit wurde die inside-out Hypothese, welche sich auf die Asgard Archaeen stützt und ein frühes Endomembransystem voraussetzt, als Ausgangslage angenommen. Da Asgard Archaeen noch nicht kultiviert wurden, stellen die TACK Archaeen mit ihrem archaealen Modellorganismus Sulfolobus acidocaldarius einen der nächsten, verfügbaren Verwandten der Eukaryoten dar. Interessanterweise wurde das Protein ArnB des archaellum regulatory networks (Arn), welches strukturelle Homologien mit dem Sec23/24 Protein des COPII-systems aufweist, in S. acidocaldarius Exosomen gefunden. Entsprechend erweist sich ArnB als vielversprechendes Protein, um den prä-endosymbiotischen Transport in Archaeen zu untersuchen. Diese Arbeit umfasst eine Zusammenfassung der Forschungsergebnisse zu ArnB und seinen assoziierten Proteinen. Hervorzuheben ist dabei die Untersuchung der Interaktion von ArnB mit dem ZnF- und FHA-Domänen enthaltenden ArnA, welche eine sequenzielle, phosphorylierungsabhängige strukturelle Transition mit globalen Änderungen offenbart. Die Untersuchung des ArnAB-Komplexes ergab zum einen neuartigen sequenziellen Phosphorylierungsmechanismus und zeigte die Gegenwart des Sec23/24-Kernmotivs in allen Domänen des Lebens auf. In Zuge dieser Analysen, konnten dem ArnAB-Komplex bzw. dem Sec23/24-Kernmotiv zahlreiche potenzielle Funktionen zugeschrieben werden, die von der Beteiligung am Ubiquitin-Netzwerk bis zur Bildung von COPII-Vesikeln und Assemblierungsrollen reichen. Zudem beinhaltet diese Arbeit die Charakterisierung einer GPN-Loop-GTPase aus S. acidocaldarius, SaGPN, welche ebenfalls mit dem Arn-System assoziiert ist und potentiell mit dem ArnAB-Komplex interagiert. GPN-Loop-GTPasen stellen einen eigenen interessanten GTPase-Typ dar, der durch nukleotidunabhängige Homodimere gekennzeichnet ist. Durch die Kristallstrukturen die in dieser Arbeit gelöst wurden, lassen sich mechanistische Unklarheiten im Zusammenhang mit GPN-Loop-GTPasen lösen und ein Lock-Switch-Rock-Mechanismus für archaeale GPN-Loop-GTPasen ableiten. Zusammenfassend trägt diese Arbeit zum allgemeinen Verständnis der GPN-Loop- GTPasen bei und hebt das ArnAB-Sec23/24-Kernmotiv als eine der häufigsten und funktional vielfältigsten Protein-Faltungen in allen Bereichen des Lebens hervor

Criticality of infrastructure networks under consideration of resilience-based maintenance strategies using the example of inland waterways

Transportation infrastructures as backbone of modern, globalized, and networked societies ensure flows of people and goods and thus sustain social and economic prosperity. Concurrently, more and more infrastructure construction assets are facing the problem of systematic obsolescence due to deficient structural conditions, maintenance backlogs, and a lack of or misallocation of resources for the construction and maintenance of infrastructure buildings. This problem construct necessitates a resilience-based maintenance strategy for the asset portfolio. In particular, inland navigation as a mode of transport features large transport volumes and few redundancies. Combined with its increasing importance due to its comparatively high environmental friendliness, a predestined, yet in the literature underrepresented research subject results. This dissertation aims to investigate essential factors of infrastructure management and thereby identify the potential for improvement in the complex construct of maintenance management and related areas. The emphasis is on enhancing the resilience of inland waterways as a complex System-of-Systems with all its interdependencies. Thus, a holistic risk and resilience assessment is essential and is underlined with the aspects infrastructure availability and business decisions (Study A, B, C and D) and stakeholder communication and risk analysis (Study E, F, G) which are addressed by seven studies published as companion articles. Study A deals with assessing the reliability of transport infrastructure networks as part of supply chains, highlighting the importance of available and thus maintained infrastructure assets for functioning supply chains. Study B aims to identify critical warning times before closures of transport infrastructure networks and therefore suggests a mixed-methods approach, making it possible to derive and evaluate critical thresholds. Study C examines the corresponding company decisions, i.e., decisions as reaction towards neglected maintenance of public transport infrastructure, which comprises risk coping strategies, examined by empirical investigations. Study D extends this problem observation by showing that companies could see incentives for outsourcing if they face a lack of access to available transport infrastructure. Hence, the study analyzes facility relocation problems in dependence on infrastructure availability. Study E heads toward stakeholder communication and risk analysis and examines the processes across stakeholders, using an approach of collaborative serious gaming, which simultaneously enhances situation awareness and communication among stakeholders. Study F provides the implementation of a systemic approach and its visualization as a GIS-based risk dashboard, shedding light on interdependencies among critical infrastructures and cascading effects. Study G closes with an examination of the evaluation of the potential of infrastructure funds. For this purpose, the study conducts an online survey to determine investors’ willingness to pay for various fund mechanisms, integrating the option of private coverage. Despite the geographic focus of the case studies on Germany, valuable insights can be gained for infrastructure management that can also apply to other countries. In addition to the case study findings, general recommendations for infrastructure owners are derived. As a result, it can be stated that it is essential that maintenance strategies have to be more resilience-based than traditional strategies, which are mainly based on fixed time intervals for maintenance. Moreover, the application of both serious gaming and GIS visualization can help to enhance situation awareness and thus the resilience of infrastructure systems. An essential finding for which this dissertation provides methodological approaches is that considering the local area’s attractiveness for business locations should receive more attention regarding investment decisions. Thereby a focus should be set on the realistic threat of relocations as response to deteriorating infrastructure conditions. Eventually, public debates should strengthen the knowledge about infrastructure and its funding, while deficits in alongside mechanisms in infrastructure funding must be encountered. Consequently, this dissertation provides insights into the potential of infrastructure management. Mainly, it offers the potential to improve the resilience of the waterway transportation system and address stakeholders accordingly

Design, fabrication and stiffening of soft pneumatic robots

Although compliance allows the soft robot to be under-actuated and generalise its control, it also impacts the ability of the robot to exert forces on the environment. There is a trade-off between robots being compliant or precise and strong. Many mechanisms that change robots' stiffness on demand have been proposed, but none are perfect, usually compromising the device's compliance and restricting its motion capabilities. Keeping the above issues in mind, this thesis focuses on creating robust and reliable pneumatic actuators, that are designed to be easily manufactured with simple tools. They are optimised towards linear behaviour, which simplifies modelling and improve control strategies. The principle idea in relation to linearisation is a reinforcement strategy designed to amplify the desired, and limit the unwanted, deformation of the device. Such reinforcement can be achieved using fibres or 3D printed structures. I have shown that the linearity of the actuation is, among others, a function of the reinforcement density and shape, in that the response of dense fibre-reinforced actuators with a circular cross-section is significantly more linear than that of non-reinforced or non-circular actuators. I have explored moulding manufacturing techniques and a mixture of 3D printing and moulding. Many aspects of these techniques have been optimised for reliability, repeatability, and process simplification. I have proposed and implemented a novel moulding technique that uses disposable moulds and can easily be used by an inexperienced operator. I also tried to address the compliance-stiffness trade-off issue. As a result, I have proposed an intelligent structure that behaves differently depending on the conditions. Thanks to its properties, such a structure could be used in applications that require flexibility, but also the ability to resist external disturbances when necessary. Due to its nature, individual cells of the proposed system could be used to implement physical logic elements, resulting in embodied intelligent behaviours. As a proof-of-concept, I have demonstrated use of my actuators in several applications including prosthetic hands, octopus, and fish robots. Each of those devices benefits from a slightly different actuation system but each is based on the same core idea - fibre reinforced actuators. I have shown that the proposed design and manufacturing techniques have several advantages over the methods used so far. The manufacturing methods I developed are more reliable, repeatable, and require less manual work than the various other methods described in the literature. I have also shown that the proposed actuators can be successfully used in real-life applications. Finally, one of the most important outcomes of my research is a contribution to an orthotic device based on soft pneumatic actuators. The device has been successfully deployed, and, at the time of submission of this thesis, has been used for several months, with good results reported, by a patient

The neurobiology of cortical music representations

Music is undeniable one of humanity’s defining traits, as it has been documented since the earliest days of mankind, is present in all knowcultures and perceivable by all humans nearly alike. Intrigued by its omnipresence, researchers of all disciplines started the investigation of music’s mystical relationship and tremendous significance to humankind already several hundred years ago. Since comparably recently, the immense advancement of neuroscientific methods also enabled the examination of cognitive processes related to the processing of music. Within this neuroscience ofmusic, the vast majority of research work focused on how music, as an auditory stimulus, reaches the brain and howit is initially processed, aswell as on the tremendous effects it has on and can evoke through the human brain. However, intermediate steps, that is how the human brain achieves a transformation of incoming signals to a seemingly specialized and abstract representation of music have received less attention. Aiming to address this gap, the here presented thesis targeted these transformations, their possibly underlying processes and how both could potentially be explained through computational models. To this end, four projects were conducted. The first two comprised the creation and implementation of two open source toolboxes to first, tackle problems inherent to auditory neuroscience, thus also affecting neuroscientific music research and second, provide the basis for further advancements through standardization and automation. More precisely, this entailed deteriorated hearing thresholds and abilities in MRI settings and the aggravated localization and parcellation of the human auditory cortex as the core structure involved in auditory processing. The third project focused on the human’s brain apparent tuning to music by investigating functional and organizational principles of the auditory cortex and network with regard to the processing of different auditory categories of comparable social importance, more precisely if the perception of music evokes a is distinct and specialized pattern. In order to provide an in depth characterization of the respective patterns, both the segregation and integration of auditory cortex regions was examined. In the fourth and final project, a highly multimodal approach that included fMRI, EEG, behavior and models of varying complexity was utilized to evaluate how the aforementioned music representations are generated along the cortical hierarchy of auditory processing and how they are influenced by bottom-up and top-down processes. The results of project 1 and 2 demonstrated the necessity for the further advancement of MRI settings and definition of working models of the auditory cortex, as hearing thresholds and abilities seem to vary as a function of the used data acquisition protocol and the localization and parcellation of the human auditory cortex diverges drastically based on the approach it is based one. Project 3 revealed that the human brain apparently is indeed tuned for music by means of a specialized representation, as it evoked a bilateral network with a right hemispheric weight that was not observed for the other included categories. The result of this specialized and hierarchical recruitment of anterior and posterior auditory cortex regions was an abstract music component ix x SUMMARY that is situated in anterior regions of the superior temporal gyrus and preferably encodes music, regardless of sung or instrumental. The outcomes of project 4 indicated that even though the entire auditory cortex, again with a right hemispheric weight, is involved in the complex processing of music in particular, anterior regions yielded an abstract representation that varied excessively over time and could not sufficiently explained by any of the tested models. The specialized and abstract properties of this representation was furthermore underlined by the predictive ability of the tested models, as models that were either based on high level features such as behavioral representations and concepts or complex acoustic features always outperformed models based on single or simpler acoustic features. Additionally, factors know to influence auditory and thus music processing, like musical training apparently did not alter the observed representations. Together, the results of the projects suggest that the specialized and stable cortical representation of music is the outcome of sophisticated transformations of incoming sound signals along the cortical hierarchy of auditory processing that generate a music component in anterior regions of the superior temporal gyrus by means of top-down processes that interact with acoustic features, guiding their processing.Musik ist unbestreitbarer Weise eine der definierenden Eigenschaften des Menschen. Dokumentiert seit den frühesten Tagen der Menschheit und in allen bekannten Kulturen vorhanden, ist sie von allenMenschen nahezu gleichwahrnehmbar. Fasziniert von ihrerOmnipräsenz haben Wissenschaftler aller Disziplinen vor einigen hundert Jahren begonnen die mystische Beziehung zwischen Musik und Mensch, sowie ihre enorme Bedeutung für selbigen zu untersuchen. Seit einem vergleichsweise kurzem Zeitraum ist es durch den immensen Fortschritt neurowissenschafticher Methoden auch möglich die kognitiven Prozesse, welche an der Verarbeitung von Musik beteiligt, sind zu untersuchen. Innerhalb dieser Neurowissenschaft der Musik hat sich ein Großteil der Forschungsarbeit darauf konzentriert wie Musik, als auditorischer Stimulus, das menschliche Gehirn erreicht und wie sie initial verarbeitet wird, als auch welche kolossallen Effekte sie auf selbiges hat und auch dadurch bewirken kann. Jedoch haben die Zwischenschritte, also wie das menschliche Gehirn eintreffende Signale in eine scheinbar spezialisierte und abstrakte Repräsentation vonMusik umwandelt, vergleichsweise wenig Aufmerksamkeit erhalten. Um die dadurch entstandene Lücke zu adressieren, hat die hier vorliegende Dissertation diese Prozesse und wie selbige durch Modelle erklärt werden können in vier Projekten untersucht. Die ersten beiden Projekte beinhalteten die Herstellung und Implementierung von zwei Toolboxen um erstens, inhärente Probleme der auditorischen Neurowissenschaft, daher auch neurowissenschaftlicher Untersuchungen von Musik, zu verbessern und zweitens, eine Basis für weitere Fortschritte durch Standardisierung und Automatisierung zu schaffen. Im genaueren umfasste dies die stark beeinträchtigten Hörschwellen und –fähigkeiten in MRT-Untersuchungen und die erschwerte Lokalisation und Parzellierung des menschlichen auditorischen Kortex als Kernstruktur auditiver Verarbeitung. Das dritte Projekt befasste sich mit der augenscheinlichen Spezialisierung von Musik im menschlichen Gehirn durch die Untersuchung funktionaler und organisatorischer Prinzipien des auditorischen Kortex und Netzwerks bezüglich der Verarbeitung verschiedener auditorischer Kategorien vergleichbarer sozialer Bedeutung, im genaueren ob die Wahrnehmung von Musik ein distinktes und spezialisiertes neuronalenMuster hervorruft. Umeine ausführliche Charakterisierung der entsprechenden neuronalen Muster zu ermöglichen wurde die Segregation und Integration der Regionen des auditorischen Kortex untersucht. Im vierten und letzten Projekt wurde ein hochmultimodaler Ansatz,welcher fMRT, EEG, Verhalten undModelle verschiedener Komplexität beinhaltete, genutzt, umzu evaluieren, wie die zuvor genannten Repräsentationen von Musik entlang der kortikalen Hierarchie der auditorischen Verarbeitung generiert und wie sie möglicherweise durch Bottom-up- und Top-down-Ansätze beeinflusst werden. Die Ergebnisse von Projekt 1 und 2 demonstrierten die Notwendigkeit für weitere Verbesserungen von MRTUntersuchungen und die Definition eines Funktionsmodells des auditorischen Kortex, daHörxi xii ZUSAMMENFASSUNG schwellen und –fähigkeiten stark in Abhängigkeit der verwendeten Datenerwerbsprotokolle variierten und die Lokalisation, sowie Parzellierung des menschlichen auditorischen Kortex basierend auf den zugrundeliegenden Ansätzen drastisch divergiert. Projekt 3 zeigte, dass das menschliche Gehirn tatsächlich eine spezialisierte Repräsentation vonMusik enthält, da selbige als einzige auditorische Kategorie ein bilaterales Netzwerk mit rechtshemisphärischer Gewichtung evozierte. Aus diesemNetzwerk, welches die Rekrutierung anteriorer und posteriorer Teile des auditorischen Kortex beinhaltete, resultierte eine scheinbar abstrakte Repräsentation von Musik in anterioren Regionen des Gyrus temporalis superior, welche präferiert Musik enkodiert, ungeachtet ob gesungen oder instrumental. Die Resultate von Projekt 4 deuten darauf hin, dass der gesamte auditorische Kortex, erneut mit rechtshemisphärischer Gewichtung, an der komplexen Verarbeitung vonMusik beteiligt ist, besonders aber anteriore Regionen, die bereits genannten abstrakte Repräsentation hervorrufen, welche sich exzessiv über die Zeitdauer derWahrnehmung verändert und nicht hinreichend durch eines der getestetenModelle erklärt werden kann. Die spezialisierten und abstrakten Eigenschaften dieser Repräsentationen wurden weiterhin durch die prädiktiven Fähigkeiten der getestetenModelle unterstrichen, daModelle, welche entweder auf höheren Eigenschaften wie Verhaltensrepräsentationen und mentalen Konzepten oder komplexen akustischen Eigenschaften basierten, stets Modelle, welche auf niederen Attributen wie simplen akustischen Eigenschaften basierten, übertrafen. Zusätzlich konnte kein Effekt von Faktoren, wie z.B. musikalisches Training, welche bekanntermaßen auditorische und daherMusikverarbeitung beeinflussen, nachgewiesen werden. Zusammengefasst deuten die Ergebnisse der Projekte darauf, hin dass die spezialisierte und stabile kortikale Repräsentation vonMusik ein Resultat komplexer Prozesse ist, welche eintreffende Signale entlang der kortikalen Hierarchie auditorischer Verarbeitung in eine abstrakte Repräsentation vonMusik innerhalb anteriorer Regionen des Gyrus temporalis superior durch Top-Down-Prozesse, welche mit akustischen Eigenschaften interagieren und deren Verarbeitung steuern, umwandeln