Title Promoter Affiliations Abstract "A Study of Oxide Defects in III-V MOS Devices using Electrical and Mathematical Methods" "Kristin De Meyer" "Associated Section of ESAT - INSYS, Integrated Systems" "III-V compound semiconductors are considered as potential channel materials for replacing Silicon in commercial logic devices. One of the major roadblock is the difficulty in developing the gate stack of sufficiently high quality to enable a III-V metal-oxide-semiconductor (MOS) device with high and reliable On performance. The defects in high-k dielectrics are, therefore, one of the key areas of focus for research on III-V based MOS devices. Due to the pervasive nature of the impact of these defects on the device performance, it becomes extremely important to gain a better understanding of these defects in order to explain various physical phenomena observed through characterization techniques in use today.This work, therefore, concentrates on the investigation of these defects through electrical and mathematical methods. A detailed investigation on 2 experimental observations, in particular, form the major part of this thesis: the frequency dispersion in the accumulation region, and hysteresis in the capacitance of a III-V MOS capacitors (MOSCAPs). The frequency dispersion is ascribed to a 2-step inelastic border trap (BT) capture/emission process based on the experimentally observed temperature dependence and a new, physically correct, model is proposed and validated for BT-electron interaction. Furthermore, from the mathematical model, a new quality metric (for bench-marking), and a new set of equations for defect density extraction is developed. Their applicability and efficiency is validated for different gate stacks.The hysteresis, irrespective of the gate stack, is found to be dependent on the measurement parameters and is ascribed to a broad defect distribution in the III-V gate stack, a property shown to be very specific to these materials. A mathematical model is developed to confirm the hypothesis which shows a very close correlation with the experimental data. Interestingly, this effect is found to be useful in extracting the information on the defect density in the gate stack. A characterization methodology is developed to use this feature and is validated on different dielectric stacks. It is observed that Al2O3 has a very broad defect distribution across the InGaAs band-gap which explains the poor reliability shown by MOS devices with this dielectric.The model is also used to understand and predict the impact of various engineering techniques on reliability improvement. It is predicted that an improvement in the energy profile of the defect distribution (and not the density) would produce a significant boost in reliability. This hypothesis is experimentally shown to be confirmed by a case study of a gate stack consisting of a new interfacial layer. It is demonstrated, using the hysteresis model, that due to a combined effect of a favorable energy misalignment and better defect profile, for the first time, a reliability performance very close to the target could be achieved on III-V MOS devices." "Syntenin, a novel target to counteract cancer progression" "Pascale Zimmermann" "Laboratory of Protein Phosphorylation and Proteomics, Department of Human Genetics" "Multiple studies indicate that the gain-of-function of syntenin-1 (hereupon referred to as ‘syntenin’) acts as a positive regulator of invasion and metastasis, in various tumors. Consistently, syntenin affects several signaling pathways that are of known relevance for the cancer process. For example, syntenin enhances the fibronectin-induced assembly of integrin-β1 signaling complexes with FAK and c-Src, resulting in the activation of FAK and downstream signaling pathways, important for regulating the migration machinery.Syntenin was originally identified in the host laboratory, as a PDZ-scaffold protein that is interacting with the syndecan heparan sulfate proteoglycans, co-receptors for a plethora of adhesion and growth factor receptor systems. Further functional studies established that syntenin controls (at least) two different aspects of vesicular trafficking that are regulated by the small GTPase ADP ribosylation factor 6 (ARF6). Syntenin promotes syndecan recycling from endosomes to the plasma membrane, and also promotes exosome secretion. Syntenin thus allows syndecan cargo, i.e. various signaling receptors to escape degradation and thereby potentially functions as a booster of cellular signaling, both in cis (recycling) and in trans (exosomes). Consistently, syntenin networking with syndecans and ARF6 controls cell migration during vertebrate embryogenesis. Of note, the function of syntenin strictly depends on its PDZ domains that operate as protein-protein and protein-phospholipid (PtdInsPs) interaction modules.Thus, currently available data not solely support a possible role for syntenin in cancer cell growth, invasion and metastasis, but also highlight a most probable molecular basis for this function.The main goal of this work was to clarify whether or not syntenin can be envisioned as a novel therapeutic and pharmacological target in cancer therapy. To test for the potential benefit of syntenin inhibition, I evaluated the impact of syntenin loss-of-function in different cancer cell lines. To test whether syntenin inhibition is safe, I characterized syntenin knock-out mice. To test whether syntenin is druggable, I screened compound libraries for chemicals inhibiting syntenin-syndecan interaction and tested for the selectivity and biological specificity of their effects.Using shRNA, siRNA and CRISPR/Cas9 silencing approaches, I showed that syntenin controls the migration, growth, proliferation and cell cycle progression of different human and mouse cancer cell models. I documented that syntenin knock-out mice are viable and fertile although embryonic fibroblasts isolated from these mice are impaired in their migration and proliferation in vitro. In depth analysis of mouse embryonic fibroblasts revealed that the exosomal function of syntenin is important for the effects on cell migration and proliferation. Surprisingly, it further revealed that syntenin also plays a role in exosomal uptake, by controlling the levels of the syndecan heparan sulfate proteoglycans at the cell surface that function as exosome-receptors. This might in part be explained by the fact that, besides its exosomal function, syntenin also supports the recycling of intact syndecans to the cell surface. Yet, syntenin directly or indirectly also controls syndecan mRNA levels, indicative of feedback loops operating at different levels.Finally, I set up a Homogeneous Time Resolved Fluorescence (HTRF) assay to study syntenin PDZ interactions and screened various protein-protein interaction inhibition (2P2I) oriented libraries of chemicals. I identified several inhibitors and proceeded with one of them, to show it selectively blocks syntenin PDZ domains in vitro and displays syntenin-specific biological effects.In conclusion, I showed (i) that syntenin inhibition could be of potential benefit in various cancers, (ii) that an anti-syntenin therapy holds promises to be relatively safe and might broadly act in exosomal cancer communication (in the emission, but also reception of exosomal signals) and (iii) that PDZ domains might represent a new class of promising therapeutic targets, as specific inhibition of syntenin function is amenable pharmacologically.     " "Dynamic Adaptation Techniques for Large-scale Distributed Systems" "Wouter Joosen" "Informatics Section" "In the Cloud Computing paradigm, Software-as-a-Service (SaaS) is a delivery model that allows small-to-mid-sized organizations (called tenants) to out-source the operation of their business applications to a SaaS provider, and consume the (software) service on-demand and remotely via the Internet. For tenants, key requirements to that service are (i) cost efficiency and (ii) reliable service quality. Moreover, (iii.a) business applications are often subject to fast-changing requirements, and (iii.b) tenants appreciate being able to benefit from trending technologies. In addressing those requirements, SaaS providers rely on sharing resources among tenants (called multi tenancy), typically up to the application level, and operate the application at large scale.The SaaS delivery model, while providing many benefits additional to cost efficiency, inherently limits control by a tenant. As a result, its success is bound to establishing and maintaining tenants' trust into the SaaS application's operation. To that end, evolving multi-tenant SaaS applications are insufficiently supported: For some upgrades scenarios, either service quality or cost efficiency can be maintained during their enactment, but not both. In practice, necessary trade-offs are decided for on a per-upgrade basis and affect all tenants of the SaaS application equally and simultaneously.In this dissertation, we present a middleware and a complementary software (upgrade) development process to (i) efficiently support customization of tenant-perceived behaviour during an upgrade enactment, called transition behaviour. Moreover, our middleware (ii) improves on the service degradation imposed to tenants, and (iii) supports efficient operation of tenant-specific generations of the application that result from tenants delaying or rejecting an upgrade.We have evaluated a prototype of our middleware (built on top of OSGi) and relying on a case study of an industrial multi-tenant SaaS provider. Our evaluation shows that customizable transition behaviours are able to satisfy a spectrum of tenant requirements within a shared application, reducing the impact of an upgrade enactment to their business up to an acceptable level. Moreover, we show that our middleware supports multi tenancy across generations, rendering the operation of tenant-specific generations nearly cost neutral, and discuss the deployments and effects of our middleware at large scale.More generally, our approach successfully addresses the prominently perceived lack of control in Cloud Computing, paving the way for trust into remotely consumed software services that support quick time-to-market." "Vertical Transistors: a slippery path towards the ultimate CMOS scaling" "Kristin De Meyer" "Associated Section of ESAT - INSYS, Integrated Systems" "The semiconductor industry has largely relied on Moore’s law, based on the observation that every new generation of transistors has been better than the previous one in Power, Performance, Area and Cost (PPAC) metrics simultaneously. However, this trend is under a pressure now. The main issue is related to the enormous complexity of both technology and design, which drastically raises not only the manufacturing, but also the R&D costs. Therefore, in order to minimize risks and maximize benefits of a new technology, it is being co-optimized hand in hand with a design relying on this technology.The scaling of lateral transistors is going to reach its limit soon because it mainly relies on the scaling of contacted gate pitch (CGP), which, in turn, forces the scaling of gate length, S/D spacers and contacts. Reduction of any of these dimensions is undesirable as it leads to poorer electrostatic control, increased parasitic capacitance and increased access resistance, respectively. There are lateral devices, like nanowire-based FETs, which may postpone the problem of CGP budgeting but they cannot solve it.The focus of this PhD work is on the vertical devices. These devices are less constrained on gate length and spacer thickness as they are oriented vertically and thus should demonstrate better scalability than lateral transistors. We quantify the advantages of the vertical devices in terms of PPA metrics through a holistic benchmark by combining the design techniques and technology limitations which are likely to be in place at the 5nm technology. In order to do this, we perform the layouts analysis, model and evaluate RC parasitics, calibrate compact models to TCAD and experimental data. Afterwards, we run simulations on a ring oscillator level to extract the PPA metrics.We have not limited ourselves to the conventional MOSFETs only, but we also benchmark vertical III-V heterojunction Tunnel FETs in order to get a better understanding under which conditions the vertical architecture is the most advantageous. This allows us to shed light on the ultimate CMOS scaling and to understand whether the introduction of vertical transistors can enable the next technological nodes." "Middleware for Data Management in Multi-Cloud" "Wouter Joosen" "Informatics Section" "Cloud storage is an essential service model of cloud computing that involves outsourcing the deployment, provisioning, and management of storage resources to external third-party providers. Additionally, multi-cloud (federated cloud) storage setups integrate and utilize storage resources, technologies, and services from multiple cloud storage providers. This approach has become increasingly popular and attractive for a wide range of cloud-based applications and services such as Software-as-a-Service (SaaS) and Internet-of-Things (IoT) applications.However, this increased popularity also introduces substantial challenges for service providers, in particular, with respect to the complexity of managing a federated cloud storage setup. As such, service providers have to deal with the problem of lack of standardization (e.g., in terms of heterogeneous technologies, APIs, and data models). Furthermore, the extent of heterogeneity in cloud storage providers (different SLA guarantees, trust models) and the need to address different storage- and privacy-related requirements of the application lead inevitably to the problem of exploding implementation complexity.Moreover, considering the limited trust in external third-party cloud storage providers, relying on traditional data protection strategies for providing secure data management services leads to significant performance and scalability degradation. Finally, the run-time dynamicity in cloud storage providers (e.g., in terms of performance characteristics, availability, offered SLAs, etc) contributes significantly to the problem of exploding management complexity as it demands continuous supervision and a sequence of manual actions to be performed by a human operator. Additionally, obliviousness to run-time dynamicity inherent in cloud providers (e.g., performance fluctuation, cost, availability, etc) may result in both sub-optimal data management decisions and costly SLA violations.This dissertation focuses on the above-mentioned challenges through targeted contributions at the middleware level. As such, it involves the design of an effective middleware framework for coping with these key challenges in order to facilitate the wider adoption of a federated cloud storage setup. In particular, special attention is paid to aspects of performance overhead on the application and the required development, management, and integration cost.In this regard, this dissertation makes five complementary contributions: (i) it provides a comprehensive trade-off analysis study between the performance impact and the application portability of existing Object-NoSQL Datastore Mapper (ONDM) frameworks, (ii) it describes an overarching and coherent middleware framework for federated cloud data management, (iii) it presents PERSIST, a middleware for data management in federated cloud storage setup, (iv) it introduces a scalable and reusable data protection strategy for secure data management, and finally (v) it presents SCOPE, a self-adaptive and autonomic middleware for SLA-aware data management.These contributions have been validated and extensively evaluated in the context of two distinct industrial SaaS applications: a log management and a document processing service offering. We have performed a thorough evaluation of our contributions to assess the benefits in terms of reduced development and management effort and also to quantify the impact in terms of introduced performance overhead."