Experimental Studies on Non-Metallic Composite Bone Implants With a Special Reference to Staphylococcal Biofilm Infection

Non-metallic implants made of bioresorbable or biostable synthetic polymers are attractive options in many surgical procedures, ranging from bioresorbable suture anchors of arthroscopic surgery to reconstructive skull implants made of biostable fiber-reinforced composites. Among other benefits, non-metallic implants produce less interference in imaging. Bioresorbable polymer implants may be true multifunctional, serving as osteoconductive scaffolds and as matrices for simultaneous delivery of bone enhancement agents. As a major advantage for loading conditions, mechanical properties of biostable fiber-reinforced composites can be matched with those of the bone. Unsolved problems of these biomaterials are related to the risk of staphylococcal biofilm infections and to the low osteoconductivity of contemporary bioresorbable composite implants. This thesis was focused on the research and development of a multifunctional implant model with enhanced osteoconductivity and low susceptibility to infection. In addition, the experimental models for assessment, diagnostics and prophylaxis of biomaterial-related infections were established. The first experiment (Study I) established an in vitro method for simultaneous evaluation of calcium phosphate and biofilm formation on bisphenol-Aglycidyldimethacrylate and triethylenglycoldimethacrylate (BisGMA-TEGDMA) thermosets with different content of bioactive glass 45S5. The second experiment (Study II) showed no significant difference in osteointegration of nanostructured and microsized polylactide-co-glycolide/β-tricalcium phosphate (PLGA /β-TCP) composites in a minipig model. The third experiment (Study III) demonstrated that positron emission tomography (PET) imaging with the novel 68Ga labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) CD33 related sialic-acid immunoglobulin like lectins (Siglec-9) tracer was able to detect inflammatory response to S. epidermidis and S. aureus peri-implant infections in an intraosseous polytetrafluoroethylene catheter model. In the fourth experiment (Study IV), BisGMATEGDMA thermosets coated with lactose-modified chitosan (Chitlac) and silver nanoparticles exhibited antibacterial activity against S. aureus and P. aeruginosa strains in an in vitro biofilm model and showed in vivo biocompatibility in a minipig model. In the last experiment (Study V), a selective androgen modulator (SARM) released from a poly(lactide)-co-ε-caprolactone (PLCL) polymer matrix failed to produce a dose-dependent enhancement of peri-implant osteogenesis in a bone marrow ablation model.

Toimittajayhteistyön arviointi, luokittelu ja mittaaminen

Toimittajien arviointi, luokittelu sekä suorituskyvyn mittaaminen ovat nousseet yhdeksi merkittäväksi tekijäksi yritysten pyrkiessä kilpailukyvyn parantamiseen. Sisäisten prosessien kehittämisen lisäksi painopistettä ollaan siirtämässä yhä enemmän toimittajien koordinointiin ja jopa heidän omien prosessiensa kehittämiseen. Globaalit markkinat ovat mahdollistaneet uusien toimittajien löytämisen, minkä seurauksena toimittajamäärä on kasvanut rajusti. Jatkuvan resurssien kiristämisen takia toimittajien kanssa tehtävän yhteistyön jatkuva seuranta ei kuitenkaan ole mahdollista. Yritysten tulee löytää juuri ne potentiaalisimmat toimittajat, joiden kanssa tehty yhteistyö tuottaa parhaimmat tulokset. Tutkimuksen tavoitteena on selvittää, kuinka toimittajayhteistyötä voitaisiin kehittää kokonaisvaltaisesti sekä tilaajan että toimittajan näkökulmasta. Tutkimuksen teoriaosuudessa keskitytään toimittajien arviointiin, luokitteluun ja suorituskyvyn mittaamiseen. Tutkimuksen empiriaosuus muodostuu teemahaastatteluista, jossa haastateltiin sekä toimittajia että tilaajia yhteistyön tekemisen näkökulmasta. Saatuja vastauksia analysoitiin aiempaa kirjallisuutta vastaan. Tuloksena esitetään kohdeyritykselle malli, jonka avulla voidaan löytää potentiaalisimmat toimittajat ja auttaa kehittämään yhteistyötä heidän kanssaan. Tutkimuksen merkittävimpinä havaintoina voidaan pitää liikevaihdon osuuden merkitystä kehitysaktiivisuuteen sekä ei-taloudellisten mittareiden huomioon ottamista.

Semantic and fuzzy modelling for human behaviour recognition in smart spaces : a case study on ambient assisted living.

Human activity recognition in everyday environments is a critical, but challenging task in Ambient Intelligence applications to achieve proper Ambient Assisted Living, and key challenges still remain to be dealt with to realize robust methods. One of the major limitations of the Ambient Intelligence systems today is the lack of semantic models of those activities on the environment, so that the system can recognize the speci c activity being performed by the user(s) and act accordingly. In this context, this thesis addresses the general problem of knowledge representation in Smart Spaces. The main objective is to develop knowledge-based models, equipped with semantics to learn, infer and monitor human behaviours in Smart Spaces. Moreover, it is easy to recognize that some aspects of this problem have a high degree of uncertainty, and therefore, the developed models must be equipped with mechanisms to manage this type of information. A fuzzy ontology and a semantic hybrid system are presented to allow modelling and recognition of a set of complex real-life scenarios where vagueness and uncertainty are inherent to the human nature of the users that perform it. The handling of uncertain, incomplete and vague data (i.e., missing sensor readings and activity execution variations, since human behaviour is non-deterministic) is approached for the rst time through a fuzzy ontology validated on real-time settings within a hybrid data-driven and knowledgebased architecture. The semantics of activities, sub-activities and real-time object interaction are taken into consideration. The proposed framework consists of two main modules: the low-level sub-activity recognizer and the high-level activity recognizer. The rst module detects sub-activities (i.e., actions or basic activities) that take input data directly from a depth sensor (Kinect). The main contribution of this thesis tackles the second component of the hybrid system, which lays on top of the previous one, in a superior level of abstraction, and acquires the input data from the rst module's output, and executes ontological inference to provide users, activities and their in uence in the environment, with semantics. This component is thus knowledge-based, and a fuzzy ontology was designed to model the high-level activities. Since activity recognition requires context-awareness and the ability to discriminate among activities in di erent environments, the semantic framework allows for modelling common-sense knowledge in the form of a rule-based system that supports expressions close to natural language in the form of fuzzy linguistic labels. The framework advantages have been evaluated with a challenging and new public dataset, CAD-120, achieving an accuracy of 90.1% and 91.1% respectively for low and high-level activities. This entails an improvement over both, entirely data-driven approaches, and merely ontology-based approaches. As an added value, for the system to be su ciently simple and exible to be managed by non-expert users, and thus, facilitate the transfer of research to industry, a development framework composed by a programming toolbox, a hybrid crisp and fuzzy architecture, and graphical models to represent and con gure human behaviour in Smart Spaces, were developed in order to provide the framework with more usability in the nal application. As a result, human behaviour recognition can help assisting people with special needs such as in healthcare, independent elderly living, in remote rehabilitation monitoring, industrial process guideline control, and many other cases. This thesis shows use cases in these areas.

Metal-Ion-Binding Oligonucleotides: High-Affinity Probes for Nucleic Acid Sequences

Small non-coding RNAs have numerous biological functions in cell and are divided into different classes such as: microRNA, snoRNA, snRNA and siRNA. MicroRNA (miRNA) is the most studied non-coding RNA to date and is found in plants, animals and some viruses. miRNA with short sequences is involved in suppressing translation of target genes by binding to their mRNA post-transcriptionally and silencing it. Their function besides silencing of the viral gene, can be oncogenic and therefore the cause of cancer. Hence, their roles are highlighted in human diseases, which increases the interest in using them as biomarkers and drug targets. One of the major problems to overcome is recognition of miRNA. Owing to a stable hairpin structure, chain invasion by conventional Watson-Crick base-pairing is difficult. One way to enhance the hybridization is exploitation of metal-ion mediated base-pairing, i. e. oligonucleotide probes that tightly bind a metal ions and are able to form a coordinative bonds between modified and natural nucleobases. This kind of metallo basepairs containing short modified oligonucleotides can also be useful for recognition of other RNA sequences containing hairpin-like structural motives, such as the TAR sequence of HIV. In addition, metal-ion-binding oligonucleotides will undoubtedly find applications in DNA-based nanotechnology. In this study, the 3,5-dimethylpyrazol-1-yl substituted purine derivatives were successfully incorporated within oligonucleotides, into either a terminal or non-terminal position. Among all of the modified oligonucleotides studied, a 2-(3,5-dimethylpyrazol-1-yl)-6-oxopurine base containing oligonucleotide was observed to bind most efficiently to their unmodified complementary sequences in the presence of both Cu2+ or Zn2+. The oligonucleotide incorporating 2,6-bis(3,5-dimethylpyrazol-1-yl)purine base also markedly increased the stability of duplexes in the presence of Cu2+ without losing the selectivity.

Competitive Effects of Non-Controlling Minority Acquisitions – Sufficient to merit further EU merger regulation?

Partial ownership interests are a widespread phenomenon in modern corporate environment. Unless minority shareholding affords the target to exercise control over the target, they do currently not have to be notified to the European Commission under EU merger regime. However, economic research has long suggested that when linking competing or non-horizontally positioned undertakings particularly in industries with few competitors, minority shareholdings even far below the majority of shares or voting rights could lead to higher prices or lower output volumes to the detriment of consumers. The Commission has recognized this issue and proceeded to suggest an extension of the merger regime to catch also certain non-controlling minority acquisitions. Horizontal non-controlling minority shareholdings create a positive correlation between the sales revenues of the partial acquirer and target. Through the equity interest the acquirer will internalise a fraction, proportional to the financial rights attached to the shareholding, of the profit of the target. This will incentivise the acquirer to contribute to increasing the target’s business profits by increasing its own sales price (horizontal unilateral effects). When a minority stake is held in a vertically related or a conglomerate company, the minority acquirer could be allowed to hamper or eliminate the target’s rivals’ access either to inputs (input foreclosure) or customers (customer foreclosure), depending on which level of the supply chain the parties are (vertical unilateral effects). Under certain circumstances minority share acquisitions could also lessen competition because they facilitate collusion between companies active in the market (coordinated effects). Economic theory confirms that non-controlling minority shareholdings may under certain circumstances create anti-competitive effects that are unlikely to be remedies by pro-competitive effects. However, they are likely to be of less significant nature than anticompetitive effects created by full mergers. This derives fore mostly from the fact that a minority share acquirer carries all the costs associated with its unilateral action but will internalise only a fraction of the lost profits. This is likely to limit the acquirer’s incentive to raise price and the profitability of such behavior. Having in mind that the number of potentially problematic cases is expected to be next to negligible, the limited potential competitive effects of non-controlling minority share acquisitions cannot be seen to clearly merit extension of the scope of the EUMR. The system suggested by the Commission is particularly ill-fitted for such purpose given the clear lack of legal certainty and considerable administrative burden associated with it.

Novissima nec non perfectissima Scandinaviæ tabula comprehendens regnorum Sueciæ, Daniæ et Norvegiæ distincté divisam descriptionem

Amstelodami ex officina I. Covens et C. Mortens cum privilegio ord Hollandie et Westfrisiae.

Value co-creation in bio-based chemicals value network

The purpose of this Master’s thesis is to study value co-creation in emerging value network. The main objective is to examine how value is co-created in bio-based chemicals value network. The study provides insights to different actors’ perceived value in the value network and enlightens their motivations to commit to the collaborative partnerships with other actors. Empirical study shows that value co-creation is creation of mutual value for both parties of the relationship by combining their non-competing resources to achieve a common goal. Value co-creation happens in interactions, and trust, commitment and information sharing are essential prerequisites for value co-creation. Value co-creation is not only common value creation, but it is also value that emerges for each actor because of the co-operation with the other actor. Even though the case companies define value mainly in economic terms, the other value elements like value of the partnership, knowledge transfer and innovation are more important for value co-creation.