Recombinant vaccines and the development of new vaccine strategies

Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks.

Development of the endocrine pancreas and novel strategies for β-cell mass restoration and diabetes therapy

Diabetes mellitus represents a serious public health problem owing to its global prevalence in the last decade. The causes of this metabolic disease include dysfunction and/or insufficient number of β cells. Existing diabetes mellitus treatments do not reverse or control the disease. Therefore, β-cell mass restoration might be a promising treatment. Several restoration approaches have been developed: inducing the proliferation of remaining insulin-producing cells, de novo islet formation from pancreatic progenitor cells (neogenesis), and converting non-β cells within the pancreas to β cells (transdifferentiation) are the most direct, simple, and least invasive ways to increase β-cell mass. However, their clinical significance is yet to be determined. Hypothetically, β cells or islet transplantation methods might be curative strategies for diabetes mellitus; however, the scarcity of donors limits the clinical application of these approaches. Thus, alternative cell sources for β-cell replacement could include embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. However, most differentiated cells obtained using these techniques are functionally immature and show poor glucose-stimulated insulin secretion compared with native β cells. Currently, their clinical use is still hampered by ethical issues and the risk of tumor development post transplantation. In this review, we briefly summarize the current knowledge of mouse pancreas organogenesis, morphogenesis, and maturation, including the molecular mechanisms involved. We then discuss two possible approaches of β-cell mass restoration for diabetes mellitus therapy: β-cell regeneration and β-cell replacement. We critically analyze each strategy with respect to the accessibility of the cells, potential risk to patients, and possible clinical outcomes.

Prodrug strategies of antiviral nucleotides: Studies on enzymatically and thermally removable phosphate protecting groups

Antiviral nucleosides are compounds that are used against viruses, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV). To act as therapeutic agent, the antiviral nucleoside needs to be phosphorylated to nucleotide in the body in three consecutive phosphorylation steps by cellular or viral enzymes. The first phosphorylation to the nucleoside monophosphate is often inefficient and leads to poor antiviral activity. The antiviral efficacy can be improved by applying a prodrug strategy and delivering the antiviral nucleoside directly as its monophosphate. In prodrug strategies of antiviral nucleotides, the negative charges on the phosphate moiety are temporarily masked with protecting groups. Once inside the cell, the protecting groups are removed by enzymatic or chemical processes. Many prodrug strategies apply biodegradable protecting groups, the removal of which is triggered by esterase enzymes. Several studies have, however, demonstrated that the removal rate of the second and subsequent esterase labile protecting groups significantly slows down after the first protecting group is removed due to the negative charge on the phosphodiester intermediate, which disturbs the catalytic site of the enzyme. In this thesis, esterase labile protecting group strategies where the issue of retardation could be avoided were studied. Prodrug candidates of antiviral nucleotides were synthesized and kinetic studies on the chemical and enzymatic stability were carried out. In the synthesized compounds, the second protecting group is cleaved from the monophosphate some other mechanism than esterase triggered activation or the structure of prodrug requires only one protecting group. In addition, esterase labile protecting group which is additionally thermally removable was studied. This protecting group was cleaved from oligomeric phosphodiesters both enzymatically and thermally and seems most attractive of the studied phosphate protecting groups. However, the rate of the thermal removal still is too slow to allow efficient protection of longer oligonucleotides and needs optimization. Key words: antiviral, nucleotide, prodrug, protecting group, biodegradable

Inclusion or Exclusion? Trade union strategies and Labor migration

Inclusion or Exclusion? Trade Union Strategies and Labor Migration This research identified and analyzed immigration-related strategies of the Finnish Construction Trade Union (FCTU) and the Service Union United (SUU); e.g. how the unions react to labor immigration, whether unions seek to include migrants in the unions, and what is migrants’ position in the unions. The two unions were chosen as the focus of the research because the workforce in the sectors they represent is migrant-dense. The study also analyzed the experiences that migrants who work in these sectors have with trade unions. The Estonian labor market situation –including the role of Estonian trade unions– was also examined as it has a considerable impact on the operating environment of the FCTU. The results of the study indicate that immigration is a contradictory issue for both unions. On the one hand, they strive to include migrants as trade union members and to defend migrants’ labor rights. On the other hand, they, together with their umbrella organization the Central Organisation of Finnish Trade Unions (SAK), seek to prevent labor immigration from outside the EU and EEA countries. They actively defend current labor immigration restrictions by drawing atten- tion to high unemployment figures and to the breaches of working conditions migrants encounter. In contrast, the employer organizations promote a more liberal state policy on labor immigration because they see it as a boost for business. Both the unions and the employer organizations ground their arguments on national interest. However, the position of the trade union movement is not uniform: unions belonging to the Confederation of Unions for Professionals and Managerial Staff in Finland (Akava) embrace more liberal labor immigration stances than the SAK. A key trade union strategy is to try to guarantee that migrants’ working condi- tions do not differ from those of the natives. The FCTU and the SUU inform migrants about Finnish collective agreements and trade union membership in the most common migrant languages. This is important for the unions because it is not in their interest that migrants’ working conditions are undercut. The interviewed migrants said that natives had more negotiating power with employers, which is often negatively portrayed in migrants’ working conditions. Migrants perceive that trade unions have an important role in protecting their working conditions. However, they stressed that migrants’ knowledge of unions is often very limited. The number of migrants in both two unions studied here is increasing. Espe- cially in the SUU, a considerable proportion of the new members are migrants. The FCTU is in a more challenging situation than the SUU because migrant construc- tion workers often work only for short periods in Finland and are consequently not interested in becoming union members. The unions’ strategies partly differ: the FCTU was the first Finnish trade union to establish a trade union branch/lo- cal for migrant members. The goal is to facilitate migrants’ inclusion in the union and to highlight the specific problems they face. The SUU, for its part, insists that such a special strategy would exclude migrants within the union organization. Despite the unions’ strategies, migrants are still underrepresented as union members and officials, which some of the interviewed migrants saw as a problem. Immigrants’ perception of trade unions was pragmatic: they had joined unions when membership yielded concrete benefits. In spite of the unions’ strategies, migrants –and temporary migrants– encoun- ter specific problems in terms of working conditions. Both unions demand more state intervention to protect migrants’ labor rights because overseeing working conditions consumes union resources. However, without the unions’ intervention, these problems would be more common than is currently the case. For instance, some of the interviewed migrants had received trade union assistance in claim- ing unpaid wages. The study demonstrated with the help of building on Walter Korpi’s power resources theory, that immigration is a power resource issue for the unions: suc- cessful immigration-related strategies strengthen unions –and vice versa. The research also showed how the unions’ operating environments constrain and enable their immigration-related strategies. This study has illuminated a previously ignored dimension: the immigrant- inclusive strategies of the Finnish trade unions. The research material consists of 78 qualitative interviews, observation in trade union events, and trade unions’ and employer organizations’ public state- ments.

Evaluating digital marketing content management strategies in an international company.

The purpose of this thesis is to explore a different kind of digital content management model and to propose a process in order to manage properly the content on an organization’s website. This process also defines briefly the roles and responsibilities of the different actors implicated. In order to create this process, the thesis has been divided into two parts. First, the theoretical analysis helps to find the two main different content management models, content management adaptation and content management localization model. Each of these models, have been analyzed through a SWOT model in order to identify their particularities and which of them is the best option according to particular organizational objectives. In the empirical part, this thesis has measured the organizational website performance comparing two main data. On one hand, the international website is analyzed in order to identify the results of the content management standardization. On the other hand, content management adaptation, also called content management localization model, is analyzed by looking through the key measure of the Dutch page from the same organization. The resulted output is a process model for localization as well as recommendations on how to proceed when creating a digital content management strategy. However, more research is recommended to provide more comprehensive managerial solutions.

The role of business model in computer game development organizations

The computer game industry has grown steadily for years, and in revenues it can be compared to the music and film industries. The game industry has been moving to digital distribution. Computer gaming and the concept of business model are discussed among industrial practitioners and the scientific community. The significance of the business model concept has increased in the scientific literature recently, although there is still a lot of discussion going on on the concept. In the thesis, the role of the business model in the computer game industry is studied. Computer game developers, designers, project managers and organization leaders in 11 computer game companies were interviewed. The data was analyzed to identify the important elements of computer game business model, how the business model concept is perceived and how the growth of the organization affects the business model. It was identified that the importance of human capital is crucial to the business. As games are partly a product of creative thinking also innovation and the creative process are highly valued. The same applies to technical skills when performing various activities. Marketing and customer relationships are also considered as key elements in the computer game business model. Financing and partners are important especially for startups, when the organization is dependent on external funding and third party assets. The results of this study provide organizations with improved understanding on how the organization is built and what business model elements are weighted.

Critical elements underpinning the emergence of the medical game ecosystem: gamifying traumatic brain injury rehabilitation in Finland

The healthcare sector is currently in the verge of a reform and thus, the medical game research provide an interesting area of research. The aim of this study is to explore the critical elements underpinning the emergence of the medical game ecosystem with three sub-objectives: (1) to seek who are the key actors involved in the medical game ecosystem and identify their needs, (2) to scrutinise what types of resources are required in medical game development and what types of relationships are needed to secure those resources, and (3) to identify the existing institutions (‘the rules of the game’) affecting the emergence of the medical game ecosystem. The theoretical background consists of service ecosystems literature. The empirical study conducted is based on the semi-structured theme interviews of 25 experts in three relevant fields: games and technology, health and funding. The data was analysed through a theoretical framework that was designed based upon service ecosystems literature. The study proposes that the key actors are divided into five groups: medical game companies, customers, funders, regulatory parties and complementors. Their needs are linked to improving patient motivation and enhancing the healthcare processes resulting in lower costs. Several types of resources, especially skills and knowledge, are required to create a medical game. To gain access to those resources, medical game companies need to build complex networks of relationships. Proficiency in managing those value networks is crucial. In addition, the company should take into account the underlying institutions in the healthcare sector affecting the medical game ecosystem. Three crucial institutions were identified: validation, lack of innovation supporting structures in healthcare and the rising consumerisation. Based on the findings, medical games cannot be made in isolation. A developmental trajectory model of the emerging medical game ecosystem was created based on the empirical data. The relevancy of relationships and resources is dependent on the trajectory that the medical game company at that time resides. Furthermore, creating an official and documented database for clinically valdated medical games was proposed to establish the medical game market and ensure an adequate status for the effective medical games. Finally, ecosystems approach provides interesting future opportunities for research on medical game ecosystems.