Trying to square a circle: A theoretically embedded test for measuring complex problem solving

Scientific Conference (2009, August)

Tschick – ein »Abenteuer- und auch ein Bildungsroman«? Relektüre eines aktuellen Klassikers der Jugendliteratur mit Blick auf das ihm zugrundeliegende Bildungsverständnis

Report (2017)

TSN timing QoS mechanisms: what did we learn over the past 10 years?

Scientific Conference (2023, September 21)

It has been more than 10 years since the inception of the Time-Sensitive Networking Task Group (TG) in IEEE802.1. Since then, TSN has become a rich toolbox of mechanisms and protocols to address Quality ... [more ▼]

It has been more than 10 years since the inception of the Time-Sensitive Networking Task Group (TG) in IEEE802.1. Since then, TSN has become a rich toolbox of mechanisms and protocols to address Quality-of-Service (QoS) requirements pertaining to timing and reliability. While IEEE 802.1CB, AS and Qci are natural choices for dependability, the designer has much more possibilities when it comes to timing QoS. The selection and configuration of a suitable TSN scheduling solution is not straightforward, as many mechanisms are available (priorities, preemption, CBS, TAS, CQF, ATS), most of them being complex to configure, and they can be used in a combined manner to meet the needs of applications comprising mixed types of traffic. In this talk, based on the academic literature and the observation of industrial practices, we review the well-understood and the emerging use-cases of the different timing QoS mechanisms and what we have learned in terms of their configuration. Ultimately, this talk aims at shedding new light on what to expect from TSN QoS mechanisms and how to introduce the least complexity needed to meet the application's timing requirements. [less ▲]

TU DO@50 -- ein froher Wunsch für die Zukunft

in Gruehn, Dietwald; Reicher, Christa; Wiechmann, Thorsten (Eds.) 50 Jahre Dortmunder Raumplanung (2019)

Tumaco: Collaboration of Mobile Devices in Hypermedia-based In-Vehicle Infotainment Systems

in Libro de Actas del XXI Congreso Argentino de Ciencias de la Computación (CACIC 2015) (2015)

In-Vehicle Infotainment systems nowadays are largely limited to one-to-one relationships with the drivers' mobile phone. In this paper, we propose Tumaco, a SOA-based IVI system, which enables the ... [more ▼]

In-Vehicle Infotainment systems nowadays are largely limited to one-to-one relationships with the drivers' mobile phone. In this paper, we propose Tumaco, a SOA-based IVI system, which enables the seamless integration of all devices of all passengers. Collaborative services can be executed within a cross-platform ecosystem through the use of semantic hypermedia. In addition, passengers may customize their own user experience in order to reduce mental workload. Our prototypical implementation showed the benefits of opening the user experience to all passengers on a car. Finally, we present a framework that enables developers to provide their own services within our ecosystem. [less ▲]

Tumor suppressor miR-215 counteracts hypoxia-induced colon cancer stem cell activity

in Cancer Letters (2019), 450

Cancer stem cells, also known as tumor-initiating cells (TICs), are a population of aggressive and self-renewing cells that are responsible for the initiation and progression of many cancers, including ... [more ▼]

Cancer stem cells, also known as tumor-initiating cells (TICs), are a population of aggressive and self-renewing cells that are responsible for the initiation and progression of many cancers, including colorectal carcinoma. Intratumoral hypoxia, i.e. reduced oxygen supply following uncontrolled proliferation of cancer cells, is thought to support TIC activity by inducing specific hypoxia-responsive mechanisms that are not yet entirely understood. Using previously established and fully characterized patient-derived TIC cultures, we could observe increased sphere and colony formation under hypoxic conditions. Mechanistically, microRNA (miRNA)-profiling experiments allowed us to identify miR-215 as one of the main hypoxia-induced miRNAs in primary colon TICs. Through stable overexpression of miR-215, followed by a set of functional in vitro and in vivo investigations, miR-215 was pinpointed as a negative feedback regulator, working against the TIC-promoting effects of hypoxia. Furthermore, we could single out LGR5, a bona fide marker of non-neoplastic intestinal stem cells, as a downstream target of hypoxia/miR-215 signaling. The strong tumor- and TIC-suppressor potential of miR-215 and the regulatory role of the hypoxia/miR-215/LGR5 axis may thus represent interesting points of attack for the development of innovative anti-CSC therapy approaches. [less ▲]

Tumor-Initiating Cells: a criTICal review of isolation approaches and new challenges in targeting strategies

in Molecular Cancer (2017)

Most cancers contain a subpopulation of highly tumorigenic cells, known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). Targeting TICs may be essential to achieve cure, because of their self ... [more ▼]

Most cancers contain a subpopulation of highly tumorigenic cells, known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). Targeting TICs may be essential to achieve cure, because of their self-renewal and tumorigenic properties as well as their resistance to conventional therapies. Despite significant advances in TIC biology, their isolation and identification remain largely disputed and incompletely established. In this review, we discuss the latest developments in isolation and culturing approaches of TICs, with focus on colorectal cancer (CRC). We feature recent findings on TIC-relevant signaling pathways and the metabolic identity of TICs, as well as their current clinical implications. Lastly, we highlight the influence of inter- and intra-tumoral heterogeneity on TIC function and targeting approaches. [less ▲]

Tumour immune evasion is promoted by actin cytoskeleton-driven polarization of inhibitory signals to the immunological synapse

Doctoral thesis (2021)

Natural killer (NK) cells are innate immune cells that are the first line of defence against infection and malignant transformation. They have the ability to recognize and destroy virally infected or ... [more ▼]

Natural killer (NK) cells are innate immune cells that are the first line of defence against infection and malignant transformation. They have the ability to recognize and destroy virally infected or cancerous cells without the need for priming or activation and therefore represent a promising target for new immunotherapeutic approaches against cancer. For their anti-tumour function, NK cells rely on actin cytoskeleton remodelling, in particular during the formation of the lytic immunological synapse (IS) with prospective target cells. The IS is characterized by an extensive assembly of filamentous actin (F-actin) and polarization of the NK cell for directed delivery of lytic granules. However, the IS allows bi-directional exchange of information, and anti-tumour effector functions of NK cells are often impaired through inhibitory signals that are transmitted through killer immunoglobulin-like receptors (KIRs) or the CD94/NK group 2 member A (NKG2A) heterodimeric receptor. Moreover, resistant tumour cells can polarize their own actin cytoskeleton to the IS in a process called actin response, enforcing the formation of an evasion IS or actin response-IS (AR-IS). This PhD thesis focuses on the evaluation of associated resistance mechanisms that occur at the AR-IS, the conservation of these processes and their translation to in vivo models of cancer. For this purpose, individual cancer-NK cell conjugates were analysed by high-throughput imaging flow cytometry (IFC) to investigate the accumulation of F-actin at the IS and the distribution of inhibitory and activating ligands in relation to the IS. The AR was associated with a wider synaptic cleft, prominent recruitment of predominantly inhibitory ligands and inhibition of NK cell-induced target cell death. Further, the AR could also be applied to cytotoxic T lymphocyte (CTL) attack during antigen specific IS formation. To explore the in vivo relevance of the AR, modified murine cancer cell lines were established that allowed for the evaluation of impact of the AR on tumour progression, the tumour immune landscape, immune cell activation and exhaustion. Reduction of the actin response was associated with a reduction of tumour volume, enhanced infiltration of CTLs and NK cells and higher numbers of effector T cells. In summary, this study reports a novel, highly conserved immune-escape mechanism that exploits fast remodelling of the actin cytoskeleton of cancer cells to induce clustering of inhibitory ligands at the AR-IS and prevent NK cell activation. This AR is characterized by fine synaptic filopodia-like protrusions (SFPs) that are decorated with inhibitory ligands and probe the surface of the NK cell in addition to providing a steric hindrance for NK cell attachment to target cells. In our pre-clinical mouse model, we could demonstrate that a reduction of the AR results in the restoration of anti-tumour immunity. Understanding the mechanism that enables or initiates the AR and finding new ways to target this mechanism has the potential to improve cancer immunotherapy, especially for NK cell-based approaches. [less ▲]

TUMOUR-ASSOCIATED MICROGLIA/MACROPHAGE HETEROGENEITY IN GLIOBLASTOMA

Doctoral thesis (2021)

Glioblastoma (GBM) is the most common and aggressive primary brain tumour in adults, characterized by high degrees of both inter- and intra-tumour heterogeneity. GBM cells secrete numerous factors ... [more ▼]

Glioblastoma (GBM) is the most common and aggressive primary brain tumour in adults, characterized by high degrees of both inter- and intra-tumour heterogeneity. GBM cells secrete numerous factors promoting the recruitment and infiltration of cellular players to the local tumour microenvironment. Tumour-associated microglia/macrophages (TAMs) represent the major cell type of the stromal compartment in GBM playing important roles along tumour development. Along GBM progression, these cells are supposed to be geared towards a tumour-supportive phenotype, therefore TAMs are pursued as key targets for the development of novel strategies aimed at re-educating them towards anti-tumour phenotypes. However, it is yet unclear how these immune suppressive properties are acquired and whether TAM subsets may phenotypically and functionally differently contribute to tumour development. Hence, the main goal of the present PhD project was to elucidate TAM diversity under defined temporal and spatial settings in GBM. Taking advantage of the GBM GL261 syngeneic and patient-derived orthotopic xenograft mouse models, we comprehensively studied the cellular and transcriptional heterogeneity of TAMs by combining single-cell RNA-sequencing, multicolour flow cytometry, immunohistological and functional analyses. We demonstrated that, as observed in patients, the myeloid compartment is the most affected and heterogeneous stromal compartment, with microglia and macrophage-like cells acquiring key transcriptional differences and rapidly adapting along GBM progression. Specifically, we uncovered that TAM transcriptional programmes converge over time, suggesting a context-dependent symbiosis mechanism characterized by decreased antigen-presenting cell signatures at late tumour stages. In the absence of Acod1/Irg1, a key gene involved in the metabolic reprogramming of macrophages towards an anti-inflammatory phenotype, we detected higher TAM diversity in the TME displaying increased immunogenicity and correlating with increased lymphocytic recruitment to the tumour site. Additionally, we uncovered that TAMs exhibit niche-specific functional adaptations in the tumour microenvironment, with microglia in the invasive landscapes displaying higher immune reactive profiles when compared to the corresponding cells in the angiogenic tumour phenotypes. Taken together, our data provide insights into the spatial and molecular heterogeneity of TAMs dynamically adapting along tumour progression or across specific tumour sites and revealing potential reactive anti-tumorigenic cell subsets that may be harnessed for therapeutic intervention in GBM. [less ▲]

TUNA: TUning Naturalness-based Analysis

in 34th IEEE International Conference on Software Maintenance and Evolution, Madrid, Spain, 26-28 September 2018 (2018, September 26)

Natural language processing techniques, in particular n-gram models, have been applied successfully to facilitate a number of software engineering tasks. However, in our related ICSME ’18 paper, we have ... [more ▼]

Natural language processing techniques, in particular n-gram models, have been applied successfully to facilitate a number of software engineering tasks. However, in our related ICSME ’18 paper, we have shown that the conclusions of a study can drastically change with respect to how the code is tokenized and how the used n-gram model is parameterized. These choices are thus of utmost importance, and one must carefully make them. To show this and allow the community to benefit from our work, we have developed TUNA (TUning Naturalness-based Analysis), a Java software artifact to perform naturalness-based analyses of source code. To the best of our knowledge, TUNA is the first open- source, end-to-end toolchain to carry out source code analyses based on naturalness. [less ▲]