Evolution of domain combinations in protein kinases and its implications for functional diversity

Protein kinases phosphorylating Ser/Thr/Tyr residues in several cellular proteins exert tight control over their biological functions. They constitute the largest protein family in most eukaryotic species. Protein kinases classified based on sequence similarity in their catalytic domains, cluster into subfamilies, which share gross functional properties. Many protein kinases are associated or tethered covalently to domains that serve as adapter or regulatory modules,naiding substrate recruitment, specificity, and also serve as scaffolds. Hence the modular organisation of the protein kinases serves as guidelines to their functional and molecular properties. Analysis of genomic repertoires of protein kinases in eukaryotes have revealed wide spectrum of domain organisation across various subfamilies of kinases. Occurrence of organism-specific novel domain combinations suggests functional diversity achieved by protein kinases in order to regulate variety of biological processes. In addition, domain architecture of protein kinases revealed existence of hybrid protein kinase subfamilies and their emerging roles in the signaling of eukaryotic organisms. In this review we discuss the repertoire of non-kinase domains tethered to multi-domain kinases in the metazoans. Similarities and differences in the domain architectures of protein kinases in these organisms indicate conserved and unique features that are critical to functional specialization. (C) 2009 Elsevier Ltd. All rights reserved.

Aspects of Inflationary Models at Low Energy Scales

Cosmological inflation is the dominant paradigm in explaining the origin of structure in the universe. According to the inflationary scenario, there has been a period of nearly exponential expansion in the very early universe, long before the nucleosynthesis. Inflation is commonly considered as a consequence of some scalar field or fields whose energy density starts to dominate the universe. The inflationary expansion converts the quantum fluctuations of the fields into classical perturbations on superhorizon scales and these primordial perturbations are the seeds of the structure in the universe. Moreover, inflation also naturally explains the high degree of homogeneity and spatial flatness of the early universe. The real challenge of the inflationary cosmology lies in trying to establish a connection between the fields driving inflation and theories of particle physics. In this thesis we concentrate on inflationary models at scales well below the Planck scale. The low scale allows us to seek for candidates for the inflationary matter within extensions of the Standard Model but typically also implies fine-tuning problems. We discuss a low scale model where inflation is driven by a flat direction of the Minimally Supersymmetric Standard Model. The relation between the potential along the flat direction and the underlying supergravity model is studied. The low inflationary scale requires an extremely flat potential but we find that in this particular model the associated fine-tuning problems can be solved in a rather natural fashion in a class of supergravity models. For this class of models, the flatness is a consequence of the structure of the supergravity model and is insensitive to the vacuum expectation values of the fields that break supersymmetry. Another low scale model considered in the thesis is the curvaton scenario where the primordial perturbations originate from quantum fluctuations of a curvaton field, which is different from the fields driving inflation. The curvaton gives a negligible contribution to the total energy density during inflation but its perturbations become significant in the post-inflationary epoch. The separation between the fields driving inflation and the fields giving rise to primordial perturbations opens up new possibilities to lower the inflationary scale without introducing fine-tuning problems. The curvaton model typically gives rise to relatively large level of non-gaussian features in the statistics of primordial perturbations. We find that the level of non-gaussian effects is heavily dependent on the form of the curvaton potential. Future observations that provide more accurate information of the non-gaussian statistics can therefore place constraining bounds on the curvaton interactions.

Control aspects in proportionality Markov manpower systems

In this paper, the control aspects of a hierarchical organization under the influence of "proportionality" policies are analyzed. Proportionality policies are those that restrict the recruitment to every level of the hierarchy (except the bottom most level or base level) to be in strict proportion to the promotions into that level. Both long term and short term control analysis have been discussed. In long term control the specific roles of the parameters of the system with regard to control of the shape and size of the system have been analyzed and yield suitable control strategies. In short term control, the attainability of a target or goal structure within a specific time from a given initial structure has been analyzed and yields the required recruitment strategies. The theoretical analyses have been illustrated with computational examples and also with real world data.

Existence and approximations of solutions to some fractional order functional integral equations

In this paper we shall study a fractional order functional integral equation. In the first part of the paper, we proved the existence and uniqueness of mile and global solutions in a Banach space. In the second part of the paper, we used the analytic semigroups theory oflinear operators and the fixed point method to establish the existence, uniqueness and convergence of approximate solutions of the given problem in a separable Hilbert space. We also proved the existence and convergence of Faedo-Galerkin approximate solution to the given problem. Finally, we give an example.

Uuden median murros Alma Mediassa, Sanoma Oy:ssä ja Yleisradiossa 1994-2004

This is a qualitative and multimethodological comparative study, which consists of two main parts: examining the development of new media and analysing and comparing the new media strategies of the three companies studied (Alma Media, Sanoma and the Finnish Broadcasting Company Yleisradio). The study includes the first large-scale review in Finnish of the development of new media, paying attention to the birth of the Internet as well as to mobile media, web TV and any other element of new media. It also concentrates on the function of electronic distribution channels before the age of the Internet, e.g. cable text and videotext. Answers about how the three traditional Finnish media houses began spreading their content to the Internet and wireless applications in 1994–2004 are also given. In researching the new media strategies the study pays special attention to the attitudes that the three media companies adopted towards the Internet and other forms of new media in their strategies during the years in question. By analysing and comparing, e.g., the companies’ strategies and their investments, the study ascertains whether the companies had a joint functional model in adopting new media or acted totally on their own without taking too much notice of the media field overall. The study makes extensive use of previously published material. The researcher has also interviewed almost twenty people who were involved in getting the companies’ new media functions under way. The methods for the interviews were dialogue and snowball sampling. The researcher has created a classification in which he divides the business strategies into four different categories: active strategy, careful strategy, permissive strategy, and passive strategy. In comparing and analysing the companies the researcher has used the classification devised by Allan Afuah & Christopher L. Tucci. The seven element classification consists of dominant managerial logic, competency trap, fear of cannibalisation and loss of revenue, channel conflict, political power, co-opetitor power and emotional attachment. In analysing the company strategies the researcher has also noted the classifications of convergence made by Everette E. Dennis and Graham Murdock as well as the aspects formulated by Sylvia Chan-Olmsted and Louisa Ha concerning the success of the companies in adopting the Internet into their functions. Based on all these classifications and by further developing them the researcher analyses and compares the success of the new media strategies of the three Finnish companies. The outcome of the study is a conclusion as to what kind of strategies the companies have carried out their new media functions and how they have succeeded in it.

Opettajien teknologiasuhteen luonne ja muodostuminen

This study investigates primary and secondary school teachers’ social representations and ways to conceptualise new technologies. The focus is both on teachers’ descriptions, interpretations and conceptions of technology and on the adoption and formation of these conceptions. In addition, the purpose of this study is to analyse how the national objectives of the information society and the implementation of information and communication technologies (ICT) in schools reflect teachers’ thinking and everyday practices. The starting point for the study is the idea of a dynamic and mutual relationship between teachers and technology so that technology does not affect one-sidedly teachers’ thinking. This relationship is described in this study as the teachers’ technology relationship. This concept emphasises that technology cannot be separated from society, social relations and the context where it is used but it is intertwined with societal practices and is therefore formed in interaction with the material and social factors. The theoretical part of this study encompasses three different research traditions: 1) the social shaping of technology, 2) research on how schools and teachers use technology and 3) social representations theory. The study was part of the Helmi Project (Holistic development of e-Learning and business models) in 2001–2005 at the Helsinki University of Technology, SimLab research unit. The Helmi Project focused on different aspects of the utilisation of ICT in teaching. The research data consisted of interviews of teachers and principals. Altogether 37 interviews were conducted in 2003 and 2004 in six different primary and secondary schools in Espoo, Finland. The data was analysed applying grounded theory. The results showed that the teachers’ technology relationship was diverse and context specific. Technology was interpreted differently depending on the context: the teachers’ technology related descriptions and metaphors illustrated on one hand the benefits and the possibilities and on the other hand the problems and threats of different technologies. The dualist nature of technology was also expressed in the teachers’ thinking about technology as a deterministic and irrevocable force and as a controllable and functional tool at the same time. Teachers did not consider technology as having a stable character but they interpreted technology in relation to the variable context of use. This way they positioned or anchored technology into their everyday practices. The study also analysed the formation of the teachers’ technology relationship and the ways teachers familiarise themselves with new technologies. Comparison of different technologies as well as technology related metaphors turned out to be significant in forming the technology relationship. Also the ways teachers described the familiarisation process and the interpretations of their own technical skills affected the formation of technology relationship. In addition, teachers defined technology together with other teachers, and the discussions reflected teachers’ interpretations and descriptions.

Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2

Aneuploidy is among the most obvious differences between normal and cancer cells. However, mechanisms contributing to development and maintenance of aneuploid cell growth are diverse and incompletely understood. Functional genomics analyses have shown that aneuploidy in cancer cells is correlated with diffuse gene expression signatures and that aneuploidy can arise by a variety of mechanisms, including cytokinesis failures, DNA endoreplication and possibly through polyploid intermediate states. Here, we used a novel cell spot microarray technique to identify genes with a loss-of-function effect inducing polyploidy and/or allowing maintenance of polyploid cell growth of breast cancer cells. Integrative genomics profiling of candidate genes highlighted GINS2 as a potential oncogene frequently overexpressed in clinical breast cancers as well as in several other cancer types. Multivariate analysis indicated GINS2 to be an independent prognostic factor for breast cancer outcome (p = 0.001). Suppression of GINS2 expression effectively inhibited breast cancer cell growth and induced polyploidy. In addition, protein level detection of nuclear GINS2 accurately distinguished actively proliferating cancer cells suggesting potential use as an operational biomarker.

Control aspects in proportionality Markov manpower systems

In this paper, the control aspects of a hierarchical organization under the influence of "proportionality" policies are analyzed. Proportionality policies are those that restrict the recruitment to every level of the hierarchy (except the bottom most level or base level) to be in strict proportion to the promotions into that level. Both long term and short term control analysis have been discussed. In long term control the specific roles of the parameters of the system with regard to control of the shape and size of the system have been analyzed and yield suitable control strategies. In short term control, the attainability of a target or goal structure within a specific time from a given initial structure has been analyzed and yields the required recruitment strategies. The theoretical analyses have been illustrated with computational examples and also with real world data. The control of such proportionality systems is then compared with that of the general systems (which do not follow such policies) with some significant conclusions. The control relations of such proportionality systems are found to be simpler and more practically feasible than those of general Markov systems, which do not have such restrictions. Such proportionality systems thus not only retain and match the flexibility of general Markov systems but also have the added advantage of simpler and more practically feasible controls. The proportionality policies hence act as an alternative and more practicably feasible means of control. (C) 2004 Elsevier Inc. All rights reserved.