Guidelines for small embedded system companies aiming to enter the space industry

This guide summarizes useful information about the European Space Agency (ESA), the European space industry, the ECSS standards and product assurance for small and medium enterprises that are aiming to enter the industry. Additionally, the applicability of agile development in space projects is discussed.

Computational models for and from biology : simple gene assembly and reaction systems

The advancement of science and technology makes it clear that no single perspective is any longer sufficient to describe the true nature of any phenomenon. That is why the interdisciplinary research is gaining more attention overtime. An excellent example of this type of research is natural computing which stands on the borderline between biology and computer science. The contribution of research done in natural computing is twofold: on one hand, it sheds light into how nature works and how it processes information and, on the other hand, it provides some guidelines on how to design bio-inspired technologies. The first direction in this thesis focuses on a nature-inspired process called gene assembly in ciliates. The second one studies reaction systems, as a modeling framework with its rationale built upon the biochemical interactions happening within a cell. The process of gene assembly in ciliates has attracted a lot of attention as a research topic in the past 15 years. Two main modelling frameworks have been initially proposed in the end of 1990s to capture ciliates’ gene assembly process, namely the intermolecular model and the intramolecular model. They were followed by other model proposals such as templatebased assembly and DNA rearrangement pathways recombination models. In this thesis we are interested in a variation of the intramolecular model called simple gene assembly model, which focuses on the simplest possible folds in the assembly process. We propose a new framework called directed overlap-inclusion (DOI) graphs to overcome the limitations that previously introduced models faced in capturing all the combinatorial details of the simple gene assembly process. We investigate a number of combinatorial properties of these graphs, including a necessary property in terms of forbidden induced subgraphs. We also introduce DOI graph-based rewriting rules that capture all the operations of the simple gene assembly model and prove that they are equivalent to the string-based formalization of the model. Reaction systems (RS) is another nature-inspired modeling framework that is studied in this thesis. Reaction systems’ rationale is based upon two main regulation mechanisms, facilitation and inhibition, which control the interactions between biochemical reactions. Reaction systems is a complementary modeling framework to traditional quantitative frameworks, focusing on explicit cause-effect relationships between reactions. The explicit formulation of facilitation and inhibition mechanisms behind reactions, as well as the focus on interactions between reactions (rather than dynamics of concentrations) makes their applicability potentially wide and useful beyond biological case studies. In this thesis, we construct a reaction system model corresponding to the heat shock response mechanism based on a novel concept of dominance graph that captures the competition on resources in the ODE model. We also introduce for RS various concepts inspired by biology, e.g., mass conservation, steady state, periodicity, etc., to do model checking of the reaction systems based models. We prove that the complexity of the decision problems related to these properties varies from P to NP- and coNP-complete to PSPACE-complete. We further focus on the mass conservation relation in an RS and introduce the conservation dependency graph to capture the relation between the species and also propose an algorithm to list the conserved sets of a given reaction system.

Product Assurance in Agile Space Systems Development

Product assurance is an essential part of product development process if developers want to ensure that final product is safe and reliable. Product assurance can be supported withrisk management and with different failure analysis methods. Product assurance is emphasized in system development process of mission critical systems. The product assurance process in systems of this kind requires extra attention. Inthis thesis, mission critical systems are space systems and the product assurance processof these systems is presented with help of space standards. The product assurance process can be supported with agile development because agile emphasizes transparency of the process and fast response to changes. Even if the development process of space systems is highly standardized and reminds waterfall model, it is still possible to adapt agile development in space systems development. This thesisaims to support the product assurance process of space systems with agile developmentso that the final product would be as safe and reliable as possible. The main purpose of this thesis is to examine how well product assurance is performed in Finnish space organizations and how product assurance tasks and activities can besupported with agile development. The research part of this thesis is performed in survey form.

Product assurance in agile space systems development

Product assurance is an essential part of product development process if developers want to ensure that final product is safe and reliable. Product assurance can be supported with risk management and with different failure analysis methods. Product assurance is emphasized in system development process of mission critical systems. The product assurance process in systems of this kind requires extra attention. In this thesis, mission critical systems are space systems and the product assurance process of these systems is presented with help of space standards. The product assurance process can be supported with agile development because agile emphasizes transparency of the process and fast response to changes. Even if the development process of space systems is highly standardized and reminds waterfall model, it is still possible to adapt agile development in space systems development. This thesis aims to support the product assurance process of space systems with agile development so that the final product would be as safe and reliable as possible. The main purpose of this thesis is to examine how well product assurance is performed in Finnish space organizations and how product assurance tasks and activities can be supported with agile development. The research part of this thesis is performed in survey form.

Targeting oncogenic signaling proteins : new insights using a FRET-based chemical biology approach

Cancer affects more than 20 million people each year and this rate is increasing globally. The Ras/MAPK-pathway is one of the best-studied cancer signaling pathways. Ras proteins are mutated in almost 20% of all human cancers and despite numerous efforts, no effective therapy that specifically targets Ras is available to date. It is now well established that Ras proteins laterally segregate on the plasma membrane into transient nanoscale signaling complexes called nanoclusters. These Ras nanoclusters are essential for the high-fidelity signal transmission. Disruption of nanoclustering leads to reduction in Ras activity and signaling, therefore targeting nanoclusters opens up important new therapeutic possibilities in cancer. This work describes three different studies exploring the idea of membrane protein nanoclusters as novel anti-cancer drug targets. It is focused on the design and implementation of a simple, cell-based Förster Resonance Energy Transfer (FRET)-biosensor screening platform to identify compounds that affect Ras membrane organization and nanoclustering. Chemical libraries from different sources were tested and a number of potential hit molecules were validated on full-length oncogenic proteins using a combination of imaging, biochemical and transformation assays. In the first study, a small chemical library was screened using H-ras derived FRET-biosensors. Surprisingly from this screen, commonly used protein synthesis inhibitors (PSIs) were found to specifically increase H-ras nanoclustering and downstream signalling in a H-ras dependent manner. Using a representative PSI, increase in H-ras activity was shown to induce cancer stem cell (CSC)-enriched mammosphere formation and tumor growth of breast cancer cells. Moreover, PSIs do not increase K-ras nanoclustering, making this screening approach suitable for identifying Ras isoform-specific inhibitors. In the second study, a nanoncluster-directed screen using both H- and K-ras derived FRET biosensors identified CSC inhibitor salinomycin to specifically inhibit K-ras nanocluster organization and downstream signaling. A K-ras nanoclusteringassociated gene signature was established that predicts the drug sensitivity of cancer cells to CSC inhibitors. Interestingly, almost 8% of patient tumor samples in the The Cancer Genome Atlas (TCGA) database had the above gene signature and were associated with a significantly higher mortality. From this mechanistic insight, an additional microbial metabolite screen on H- and K-ras biosensors identified ophiobolin A and conglobatin A to specifically affect K-ras nanoclustering and to act as potential breast CSC inhibitors. In the third study, the Ras FRET-biosensor principle was used to investigate membrane anchorage and nanoclustering of myristoylated proteins such as heterotrimeric G-proteins, Yes- and Src-kinases. Furthermore, Yes-biosensor was validated to be a suitable platform for performing chemical and genetic screens to identify myristoylation inhibitors. The results of this thesis demonstrate the potential of the Ras-derived FRETbiosensor platform to differentiate and identify Ras-isoform specfic inhibitors. The results also highlight that most of the inhibitors identified predominantly perturb Ras subcellular distribution and membrane organization through some novel and yet unknown mechanisms. The results give new insights into the role of Ras nanoclusters as promising new molecular targets in cancer and in stem cells.

Macro- and Microevolution of Languages: Exploring Linguistic Divergence with Approaches from Evolutionary Biology

There are more than 7000 languages in the world, and many of these have emerged through linguistic divergence. While questions related to the drivers of linguistic diversity have been studied before, including studies with quantitative methods, there is no consensus as to which factors drive linguistic divergence, and how. In the thesis, I have studied linguistic divergence with a multidisciplinary approach, applying the framework and quantitative methods of evolutionary biology to language data. With quantitative methods, large datasets may be analyzed objectively, while approaches from evolutionary biology make it possible to revisit old questions (related to, for example, the shape of the phylogeny) with new methods, and adopt novel perspectives to pose novel questions. My chief focus was on the effects exerted on the speakers of a language by environmental and cultural factors. My approach was thus an ecological one, in the sense that I was interested in how the local environment affects humans and whether this human-environment connection plays a possible role in the divergence process. I studied this question in relation to the Uralic language family and to the dialects of Finnish, thus covering two different levels of divergence. However, as the Uralic languages have not previously been studied using quantitative phylogenetic methods, nor have population genetic methods been previously applied to any dialect data, I first evaluated the applicability of these biological methods to language data. I found the biological methodology to be applicable to language data, as my results were rather similar to traditional views as to both the shape of the Uralic phylogeny and the division of Finnish dialects. I also found environmental conditions, or changes in them, to be plausible inducers of linguistic divergence: whether in the first steps in the divergence process, i.e. dialect divergence, or on a large scale with the entire language family. My findings concerning Finnish dialects led me to conclude that the functional connection between linguistic divergence and environmental conditions may arise through human cultural adaptation to varying environmental conditions. This is also one possible explanation on the scale of the Uralic language family as a whole. The results of the thesis bring insights on several different issues in both a local and a global context. First, they shed light on the emergence of the Finnish dialects. If the approach used in the thesis is applied to the dialects of other languages, broader generalizations may be drawn as to the inducers of linguistic divergence. This again brings us closer to understanding the global patterns of linguistic diversity. Secondly, the quantitative phylogeny of the Uralic languages, with estimated times of language divergences, yields another hypothesis as to the shape and age of the language family tree. In addition, the Uralic languages can now be added to the growing list of language families studied with quantitative methods. This will allow broader inferences as to global patterns of language evolution, and more language families can be included in constructing the tree of the world’s languages. Studying history through language, however, is only one way to illuminate the human past. Therefore, thirdly, the findings of the thesis, when combined with studies of other language families, and those for example in genetics and archaeology, bring us again closer to an understanding of human history.

Static waves in corporate space : characterizing oscillating trading patterns in New York stock exchange

Various researches in the field of econophysics has shown that fluid flow have analogous phenomena in financial market behavior, the typical parallelism being delivered between energy in fluids and information on markets. However, the geometry of the manifold on which market dynamics act out their dynamics (corporate space) is not yet known. In this thesis, utilizing a Seven year time series of prices of stocks used to compute S&P500 index on the New York Stock Exchange, we have created local chart to the corporate space with the goal of finding standing waves and other soliton like patterns in the behavior of stock price deviations from the S&P500 index. By first calculating the correlation matrix of normalized stock price deviations from the S&P500 index, we have performed a local singular value decomposition over a set of four different time windows as guides to the nature of patterns that may emerge. I turns out that in almost all cases, each singular vector is essentially determined by relatively small set of companies with big positive or negative weights on that singular vector. Over particular time windows, sometimes these weights are strongly correlated with at least one industrial sector and certain sectors are more prone to fast dynamics whereas others have longer standing waves.

A Business Incubator, Accelerator, or Coworking Space? Case Health Innovation Village at GE

Health Innovation Village at GE is one of the new communities targeted for startup and growth-oriented companies. It has been established at the premises of a multinational conglomerate that will promote networking and growth of startup companies. The concept combines features from traditional business incubators, accelerators, and coworking spaces. This research compares Health Innovation Village to these concepts regarding its goals, target clients, source of income, organization, facilities, management, and success factors. In addition, a new incubator classification model is introduced. On the other hand, Health Innovation Village is examined from its tenants’ perspective and improvements are suggested. The work was implemented as a qualitative case study by interviewing GE staff with connections to Health Innovation Village as well as startup entrepreneurs and employees’ working there. The most evident features of Health Innovation Village correspond to those of business incubators although it is atypical as a non-profit corporate business incubator. Strong network orientation and connections to venture capitalists are common characteristics of these new types of accelerators. The design of the premises conforms to the principles of coworking spaces, but the services provided to the startup companies are considerably more versatile than the services offered by coworking spaces. The advantages of Health Innovation Village are that there are first-class premises and exceptionally good networking possibilities that other types of incubators or accelerators are not able to offer. A conglomerate can also provide multifaceted special knowledge for young firms. In addition, both GE and the startups gained considerable publicity through their cooperation, indeed a characteristic that benefits both parties. Most of the expectations of the entrepreneurs were exceeded. However, communication and the scope of cooperation remain challenges. Micro companies spend their time developing and marketing their products and acquiring financing. Therefore, communication should be as clear as possible and accessible everywhere. The startups would prefer to cooperate significantly more, but few have the time available to assume the responsibility of leadership. The entrepreneurs also expected to have more possibilities for cooperation with GE. Wider collaboration might be accomplished by curation in the same way as it is used in the well-functioning coworking spaces where curators take care of practicalities and promote cooperation. Communication issues could be alleviated if the community had its own Intranet pages where all information could be concentrated. In particular, a common calendar and a room reservation system could be useful. In addition, it could be beneficial to have a section of the Intranet open for both the GE staff and the startups so that those willing to share their knowledge and those having project offers could use it for advertising.