Technische Universität Dresden: Qucosa
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A comprehensive genomic study of 390 H3F3A‑mutant pediatric and adult difuse high‑grade gliomas, CNS WHO grade 4
Get PDFMalignant brain tumors, known as H3K27-altered diffuse midline glioma (DMG) and H3G34-mutant diffuse hemispheric glioma (DHG), can affect individuals of all ages and are classified as CNS WHO grade 4. We comprehensively characterized 390 H3F3A-mutant diffuse gliomas (201 females, 189 males) arising in pediatric patients (under 20 years old) and adults (20 years and older) evaluated by the CGP program at Foundation Medicine between 2013 and 2020. We assessed information from pathology reports, histopathology review, and clinical data. The cohort included 304 H3K27M-mutant DMG (156 females, 148 males) and 86 H3G34-mutant DHG (45 females, 41 males). Median patient age was 20 years (1–74 years). The frequency of H3K27M-mutant DMG was similar in both pediatric and adult patients in our cohort—48.6% of the patients were over 20 years old, 31.5% over 30, and 18% over 40 at initial diagnosis. FGFR1 hotspot point mutations (N546K and K656E) were exclusively identified in H3K27M-mutant DMG tumors (64/304, 21%; p = 0.0001); these tend to occur in older patients (median age: 32.5 years) and mainly arose in the diencephalon. H3K27M-mutant DMG had higher rates of mutations in NF1 (31.0 vs 8.1%; p = 0.0001) and PIK3CA/PIK3R1 (27.9% vs 15.1%; p = 0.016) compared to H3G34-mutant DHG. However, H3G34-mutant DHG had higher rates of targetable alterations in cell-cycle pathway genes (CDK4 and CDK6 amplification; CDKN2A/B deletion) (27.0 vs 9.0%). Potentially targetable PDGFRA alterations were identified in ~ 20% of both H3G34-mutant DHG and H3K27M-mutant DMG. Overall, in the present study H3K27M-mutant DMG occurred at similar rates in both adult and patient patients. Through our analysis, we were able to identify molecular features characteristic of DMG and DHG. By identifying the recurrent co-mutations including actionable FGFR1 point mutations found in nearly one-third of H3K27M-mutant DMG in young adults, our findings can inform clinical translational studies, patient diagnosis, and clinical trial design
A comparative study of fully implicit staggered and monolithic solution methods.: Part II: Coupled excitation–contraction equations of cardiac electromechanics
Get PDFA comparative study of fully implicit staggered and monolithic solution algorithms for the coupled bidomain equations of cardiac electrophysiology was discussed in Part I (JCAM 407:114021, 2022). In this follow-up study, we further employ the similar approach and present an extensive comparative analysis between the staggered and monolithic solution techniques for the coupled partial differential equations (PDEs) of cardiac electromechanics both in the monodomain and bidomain setting. For the monolithic solution technique, we adopt the work of Göktepe et al. (CM 45: 227-243, 2010) and Dal et al. (CMAME 253: 353-336, 2013), where the governing PDEs of the excitation–contraction problem are solved simultaneously and all rate equations are treated with an implicit time integration scheme. For the staggered scheme, however, we simply suggest a decoupled solution of the governing PDEs while keeping other aspects of the monolithic algorithm the same, such as utilization of the implicit time integration scheme and coupling of ordinary differential equations, which describe the state variables of cardiac electrophysiology, to the parabolic PDE of the electrophysiology. Both solution algorithms are applied to several problems, where we simulate regular planar wave propagations and scroll waves for different spatial and temporal resolution and material parameters. The comparison between the solution schemes is performed in terms of accuracy, efficiency and stability. We reveal that for regular wave propagation the results of different solution algorithms are identical. The only deviation is observed during scroll wave propagation, if the parameters controlling the mutual interaction between the mechanical and electrical field are relatively large and at the same time if the time increment is big, e.g., = 2.0 ms. Nevertheless, the suggested staggered solution scheme yields almost identical results even for high coupling if smaller time increments are used. Besides, the staggered scheme provides an enormous gain in computational efficiency, particularly, as the number of degrees of freedom is increased and we do not encounter any stability issue arising specifically from the decoupled solution of the governing PDEs. Similar to the conclusion that was made for cardiac electrophysiology in Part I, we report that the suggested fully implicit staggered solution algorithm has a tremendous application potential for computer simulations of excitation–contraction coupling of the heart both in the monodomain and bidomain setting
Transient response of pavement structures under moving wheel loads using the ALE methodology
Get PDFThe dynamic response of long structures (e.g., pavements) subjected to moving loads is generally difficult to simulate using conventional methods like the finite element method in the Lagrangian setting. This is because the entire length of the structure in the path of the moving load would need to be discretized, and in turn would require large meshes. Additionally, if improvement in quality of results through the use of finer mesh sizes is sought, the entire region of the mesh in the load path would require refinement. As a direct result, long simulation run-times can be expected when using conventional methods. To overcome these drawbacks, and improve the efficiency of the finite element simulations, the Arbitrary Lagrangian Eulerian (ALE) approach can be used to simulate pavement structures, provided longitudinal homogeneity is assumed. This contribution uses an extension of the quasi-static ALE framework to the transient domain, enabling the study of the dynamic response of pavement structures subjected to moving loads. In this work, some case studies are considered to highlight the capabilities of this dynamic ALE framework
Entwicklung und Operationalisierung von Netzwerken zur Beförderung von Personen im Rahmen von Advanced Air Mobility
Get PDFDie fortschreitende Urbanisierung resultiert in zunehmenden Mobilitätsbedürfnissen und infrastrukturellen Herausforderungen für Städte und ländliche Räume. Auf Basis dessen sind Überlegungen entstanden, die das bestehende Mobilitäts- und Transportsystem in Richtung des Luftraums erweitern wollen, was unter der Begrifflichkeit Advanced Air Mobility zusammengefasst werden kann. Dabei werden elektrisch betriebene, senkrecht start- und landende (eVTOL-)Fluggeräte für die Personenbeförderung vorgesehen. Die bevorstehende Integration derartiger Fluggeräte erfordert Infrastrukturen in urbanen und ruralen Gebieten, welche die Schnittstelle zwischen der Land- und Luftseite bilden, analog zu Flughäfen der konventionellen Luftfahrt. Aufgrund fehlender praktischer Erfahrungswerte hinsichtlich operationeller Fähigkeiten der Fluggeräte, betrieblicher Anforderungen der benötigten Bodeninfrastruktur, des Umfangs eines möglichen Flugtaxibetriebs und resultierender Netzwerkgestaltung werden diese spezifischen Herausforderungen innerhalb dieser Arbeit analysiert.
Die Netzwerkentwicklung basiert auf drei verschiedenen Datengrundlagen (Verkehrs-/Mobilitätsdaten, bestehende Verkehrsinfrastrukturen in Sachsen und kombinierte Betrachtung von Verkehrs-/Mobilitätsdaten im Kontext bestehender Infrastrukturen), die in jeweils eigenständige Nachfrageschätzungen überführt werden. Die resultierenden Erkenntnisse fließen innerhalb eines p-Hub Single Allocation Problems zusammen, so dass unterschiedliche Netzwerkentwürfe am Beispiel Sachsen in Abhängigkeit der geschätzten Passagierströme entstehen. Für diese Netzwerke werden zukünftige Einsatzmöglichkeiten der genannten Fluggeräte auf Basis bestimmter Energiebedarfe je Netzwerkkante diskutiert. Abschließend erfolgt eine Schätzung maximaler Reichweiten für die Kategorien Vectored Thrust, Lift & Cruise und Multicopter in Abhängigkeit zu Abfluggewichten (Auslastung), vertikalen Verweildauern der Fluggeräte und möglichen spezifischen Energiedichten der Batterieeinheiten in den Fluggeräten.
Diese Arbeit liefert erste nachvollziehbare Erkenntnisse zur Vorbereitung eines zukünftigen Flugtaxibetriebs und thematisiert durch die Berücksichtigung von bereits versiegelten (Verkehrs-)Flächen gleichzeitig eine möglichst bedarfs- und stadtgerechte Integration dieses neuen Verkehrsträgers in bestehende Mobilitätssysteme.The advancing process of urbanization leads to increasing mobility demands and infrastructural challenges for both urban and rural areas. Consequently, considerations have emerged to expand the existing mobility and transportation system towards the airspace, encapsulated under the term Ädvanced Air Mobility'(AAM). This involves the provision of electrically powered, vertical take-off and landing (eVTOL) aircraft for passenger transportation. The forthcoming integration of such aircraft necessitates infrastructures in urban and rural areas, serving as the interface between the land and air domains, akin to airports in conventional aviation. Due to the lack of practical experience regarding the operational capabilities of these aircraft, operational requirements of the necessary ground infrastructure, the scale of potential air taxi operations, and resulting network design, these specific challenges are analyzed within this study.
The network development relies on three different sets of data (traffic/mobility data, existing transportation infrastructures in Saxony, and combined analysis of traffic/mobility data in the context of existing infrastructures), each translated into independent demand estimations. The resulting insights are synthesized within a p-Hub Single Allocation Problem framework, generating various network designs for the case of Saxony depending on estimated passenger flows. For these networks, future applications of the mentioned aircraft are discussed based on specific energy requirements per network edge. Finally, maximum range estimations are provided for Vectored Thrust, Lift & Cruise, and Multicopter categories, depending on takeoff weights (occupancy), vertical dwell times of the aircraft, and potential specific energy densities of battery units in the aircraft.
This study delivers initial comprehensible insights to prepare for future air taxi operations, simultaneously addressing, through the consideration of already sealed (transport) areas, the most demand- and city-appropriate integration of this new mode of transportation into existing mobility systems
Traversing Cognitive Spaces. Material Samples for Harnessing Tacit Knowledge: Workshop on Experimental Negotiation Methods
Get PDFSOCIAL INNOVATION AND DESIGN CHALLENGE
Tacit and Situated Knowledge
Get PDFDESIGNING GOVERNANCE – POWER AND COMPLICITY:1 Introduction
2 Theoretischer Rahmen
3 Methodik
3.1 Partizipative Co-Creation-Workshops
3.2 Workshop 1: Erfassen von Wissen & Forschungsmethodik
3.3 Workshop 2: Wissenslücken füllen und Handlungsbereitschaft wecken
3.4 Datenauswertung und -aufbereitung
4 Ergebnisse
5 Diskussion
6 Fazit und Ausblick
Acknowledgement
LiteraturverzeichnisIm Fokus dieses Papers steht die Einbindung von implizitem und situiertem Wissen in den Gestaltungsprozess von Lösungen für die Klimakrise, demonstriert am Forschungsprojekt «MEnergie – Meine Energiewende». Es wird argumentiert, dass die Anerkennung dieser Wissensformen durch Co-Creation essentiell für die Erreichung transdisziplinärer Anschlussfähigkeit und die Förderung von Handlungskompetenzen ist. Die Studie zeigt, wie Co-Creation Literacy innerhalb des Projekts entwickelt wurde und nicht nur den Umgang der verschiedenen Disziplinen miteinander fördert, sondern auch dazu beiträgt, dass alle Beteiligten befähigt werden, transformative Wissenschaft effektiv umzusetzen. Die Ergebnisse betonen die Bedeutung eines integrativen Ansatzes in Forschung und Praxis.:1 Introduction
2 Theoretischer Rahmen
3 Methodik
3.1 Partizipative Co-Creation-Workshops
3.2 Workshop 1: Erfassen von Wissen & Forschungsmethodik
3.3 Workshop 2: Wissenslücken füllen und Handlungsbereitschaft wecken
3.4 Datenauswertung und -aufbereitung
4 Ergebnisse
5 Diskussion
6 Fazit und Ausblick
Acknowledgement
Literaturverzeichni
Sustainability by Design: The use of design methodologies in transferring ecological and economic theories into everyday life
Get PDFDESIGNING GOVERNANCE – POWER AND COMPLICITY:Introduction
Transfer as adaptation and concretisation
Transferring Theories trough design methodologies
Foundation: Doughnut economics
Reflection on the impact of Design
Scientific tandems
Monitoring transfer projects
Outlook
Acknowledgements
ReferencesSustainability by Design (SBYD) investigates how design methodologies can be used to transfer knowledge from sustainability research into society and the economy. In this paper, we use the concept of mode 2 science to examine how the understanding of knowledge transfer has changed. Drawing on this, we examine why design methodologies are particularly well-suited as a transfer medium. We argue that their use is promising within sustainable transformation, to bring theories and scientific findings into new contexts, to disseminate these to a wider audience, and to concretise and develop transformative knowledge further in the process. Furthermore, the paper presents the underlying theories and structures of SBYD and shows how, in our practical work, these theories are translated into concrete methods and formats. Finally, we discuss the possibilities of
evaluating the use of design within transfer processes, thus assessing its impact and limitations.:Introduction
Transfer as adaptation and concretisation
Transferring Theories trough design methodologies
Foundation: Doughnut economics
Reflection on the impact of Design
Scientific tandems
Monitoring transfer projects
Outlook
Acknowledgements
Reference
Jenseits der Paralyse: Designlehre zwischen Dringlichkeit und Exploration
Get PDFIMPACT AND MEASUREMENT – MANAGING RISK?:1 Zukunftsfähigkeit von Design
2 Anlass, Ausrichtung und Einordnung der Untersuchung
Das Konzept Nachhaltigkeit
Nachhaltigkeitsvermittlung im Design - Momentaufnahme und Rückblick
3 Analyse nachhaltigkeitsbezogener Design-Lehrformate
3.1 Trashlab - Phänomen Müll als Vermittler des Konzepts Nachhaltigkeit (KHK)
3.2 Biolab - Mikroorganismen als Partner im More-Than-Human Design (KHK)
3.3 Sustainable Design by default (KUL)
3.4 Überblick und Vergleich der Formate
4 Diskussion
5 Fazit
ReferencesDer Artikel untersucht den Beitrag der Designdisziplin zur Vermittlung von nachhaltigkeitsbezogenen Inhalten. Ausgehend vom sich intensivierenden Diskurs zu Nachhaltigkeit im Design und den darin entstandenen Wissensbeständen werden drei Fälle von nachhaltigkeitsbezogenen Lehrformaten und -konzepten an Designhochschulen in Deutschland und Österreich exemplarisch analysiert und diskutiert. Die Gemeinsamkeit der betrachteten Fälle ist die Etablierung von Nachhaltigkeit als theoriegeleitetes Fach bzw.
Lehrgebiet an Kunsthochschulen und Universitäten im Gegensatz zu den praxisorientierten Lehrgebieten im Bereich Design. Die Analyse mündet in eine erste Momentaufnahme, die diesbezüglich kritische Reflexion als entscheidendes Element in einer sich dynamisch entfaltenden Designdisziplin begreift.:1 Zukunftsfähigkeit von Design
2 Anlass, Ausrichtung und Einordnung der Untersuchung
Das Konzept Nachhaltigkeit
Nachhaltigkeitsvermittlung im Design - Momentaufnahme und Rückblick
3 Analyse nachhaltigkeitsbezogener Design-Lehrformate
3.1 Trashlab - Phänomen Müll als Vermittler des Konzepts Nachhaltigkeit (KHK)
3.2 Biolab - Mikroorganismen als Partner im More-Than-Human Design (KHK)
3.3 Sustainable Design by default (KUL)
3.4 Überblick und Vergleich der Formate
4 Diskussion
5 Fazit
Reference
Learning to foster sustainability transitions: Disruption and change of everyday practices in sociospatial configurations
Get PDFThe framework of the dissertation addresses the dynamics of social learning and practice change in sustainability transitions. It outlines an overall research question and summarizes the contributions of three articles. It draws general implications and conceptual lessons from all three articles
Stochastic aspects of the second law of thermodynamics
Get PDFThis thesis explores the second law of thermodynamics at scales where fluctuations in thermodynamic quantities become significant, revealing the inherent stochastic characteristics of thermodynamic principles. The results are structured into two sections, each dedicated to addressing particular facets and scenarios.
The first part of the thesis focuses on the behavior of two-level systems undergoing instantaneous changes in the energy level difference. Specifically, it examines the probability of observing microscopic realizations where the work is smaller than the Helmholtz free energy difference, which somewhat overstated can be referred to as microscopic second law 'violations'. As the number of two-level systems increases and the thermodynamic limit is approached, a non-monotonic behavior of the probability of second law 'violations' is observed. Surprisingly, the addition of just one additional two-level system can significantly increase the probability of second law 'violations', which at first sight seems counterintuitive but can be attributed to the discreteness of the system.
In the second part of the thesis we derive a work fluctuation theorem similar to the Jarzynski equality, but applicable to a Brownian particle confined in a potential well with finite depth that is changed in time by an external protocol. Due to the weak confining effect of the potential well such a system is unable to relax to an equilibrium state, resulting in a mean squared displacement of the Brownian particle that diverges with time. This divergence leads to an additional term in the fluctuation theorem that differs from the Jarzynski equality. The inequality resulting from this theorem places a fundamental lower bound on the work required to change the potential over time.:Contents
1 Introduction 1
2 Equilibrium thermodynamics 5
2.1 Macroscopic vs. microscopic descriptions . . . . . . . . . . . . . . . . 5
2.2 First law of thermodynamics . . . . . . . . . . . . . . . . . . . . . . . 6
2.3 Thermodynamic equilibrium . . . . . . . . . . . . . . . . . . . . . . . 7
2.4 Thermodynamic state variables and properties . . . . . . . . . . . . . 7
2.5 Work and heat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.6 Second law of thermodynamics for an isothermal process . . . . . . . 11
2.7 Quasi-static and adiabatic processes . . . . . . . . . . . . . . . . . . . 12
3 A non-equilibrium description: The Langevin equation 15
3.1 The Langevin equation . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
3.2 From the Langevin to the Fokker-Planck equation . . . . . . . . . . . 17
3.3 The overdamped limit . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
3.4 Diffusion equation for non-Gaussian noise . . . . . . . . . . . . . . . 22
3.5 A probability measure for a single trajectory . . . . . . . . . . . . . . 25
4 The Jarzynski equality 31
4.1 Definition of thermodynamic work for small systems . . . . . . . . . 31
4.2 Introducing the Jarzynski equality . . . . . . . . . . . . . . . . . . . . 33
4.3 What the Jarzynski equality does not say . . . . . . . . . . . . . . . . 35
4.4 Unzipping the Jarzynski equality . . . . . . . . . . . . . . . . . . . . . 37
4.5 The underlying symmetry of the Jarzynski equality: the Crooks theorem 40
4.6 Mean second law 'violations' . . . . . . . . . . . . . . . . . . . . . . . 40
4.7 Derivation of the Jarzynski equality based on the Feynman-Kac for-
mula . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
4.8 The Feynman-Kac formula . . . . . . . . . . . . . . . . . . . . . . . . 46
VI Contents
5 Stochastic Thermodynamics 51
5.1 The laws of stochastic thermodynamics . . . . . . . . . . . . . . . . . 51
6 Second law 'violations' in two level systems 57
6.1 The toy model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
6.2 Verification of JE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
6.3 Apparent second law 'violations' . . . . . . . . . . . . . . . . . . . . 59
6.4 Work distribution in the thermodynamic limit . . . . . . . . . . . . . 60
6.5 Second law 'violations' in the thermodynamic limit . . . . . . . . . . 63
6.6 Quasi-static limit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
6.7 Second law 'violations' in the quasistatic limit . . . . . . . . . . . . . 68
6.8 Outlook: Towards coupled two level systems . . . . . . . . . . . . . . 69
6.9 Closing remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
7 An extension of the Jarzynski equality 71
7.1 Setting the stage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
7.2 A motivating special case: The infinitely fast protocol . . . . . . . . . 73
7.3 Derivation of the work fluctuation theorem . . . . . . . . . . . . . . . 75
7.4 A possible physical Interpretation . . . . . . . . . . . . . . . . . . . . 77
7.5 Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
7.6 A comparison with Seifert’s fluctuation theorem . . . . . . . . . . . . 90
7.7 Closing remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
8 Conclusion 9