[Suite for String Orchestra]

Soitinnus: jousiorkesteri.

Musikalisk lärandemiljö : planerade musikaktiviteter med småbarn i daghem

A musically stimulating nvironment is of great significance when considering the opportunities for development and learning that are offered to children in day nurseries. Moreover, the quality of musical activities also has great significance for the musical development of growing children. Young children are always striving to create meaning and understanding; they influence and are influenced by the context in which they are situated. The purpose of this study is to investigate the planned music activities in the musical learning environment of seven toddler’s groups in day nurseries, based on four different aspects: the texts of children’s songs, the melodies of children’s songs, the basic elements of music and the use of instrumentation. The data has been gathered by video observation of the planned music activities. The age of the children studied ranged from 11 months to 3 years and 11 months, and on average there were 13 children in each group. The study involved a total of just over 90 children and nine educators. The methodological approaches are hermeneutic as well as videographic, and they are applied to the analysis as required. The approaches are well suited to an understanding of the planned music activities where the individual’s communications and actions are studied. The results of the study show that educators impart a cultural heritage to the children in the form of old traditional songs, but they also act as intermediaries for newer children's songs. They focus on actively on the text content of the children’s songs in their interaction with the children, but do not address the meaning of the text. Furthermore, while the educators use music sessions for the children to develop, among other things, an understanding of language and social skills, they do not use the sessions to develop the children’s musical skills. The educators could, to a much greater extent than they now do, direct the children's attention to the basic elements of music, and conduct meta-cognitive dialogues with the children. They use a large repertoire of children's songs, which are, however, often too demanding for the children’s voices to cope with. In addition, the educators do not plan, in any significant way, activities for the toddlers in order to help them develop the accuracy of their vocal tones. With regard to the use of instruments, the educators focus, in their interaction with the children, is placed on both the usage of the instruments and knowledge about the instruments. Regarding the use of instruments the study shows that the children’s musical expression takes place in an environment that includes both melody and rhythm instruments. It is clear that children are actively interested in the constructed instrument environment, because for long periods of time they independently play and experiment with instruments.

Symphony no. 1

Soitinnus: orkesteri.

Sinfonietta for two string orchestras

Digitoitu 16. 10. 2008.

Novel Players in the Integrin Signaling Orchestra: TCPTP and MDGI

Metastases are the major cause of cancer deaths. Tumor cell dissemination from the primary tumor utilizes dysregulated cellular adhesion and upregulated proteolytic degradation of the extracellular matrix for progeny formation in distant organs. Integrins are transmembrane adhesive receptors mediating cellcell and cellmatrix interactions that are crucial for regulating cell migration, invasion, proliferation, and survival. Consequently, increased integrin activity is associated with augmented migration and invasion capacity in several cancer types. Heterodimeric integrins consist of an alpha - and beta-subunit that are held together in a bent conformation when the receptor is inactive, but extension and separation of subdomains is observed during receptor activation. Either inside-out or outside-in activation of receptors is possible through the intracellular molecule binding to an integrin cytoplasmic domain or extracellular ligand association with an integrin ectodomain, respectively. Several regulatory binding partners have been characterized for integrin cytoplasmic beta-domains, but the regulators interacting with the cytoplasmic alpha-domains have remained elusive. In this study, we performed yeast two-hybrid screens to identify novel binding partners for the cytoplasmic integrin alpha-domains. Further examination of two plausible candidates revealed a significant coregulatory role of an integrin alpha-subunit for cellular signaling processes. T-cell protein tyrosine phosphatase (TCPTP) showed a specific interaction with the cytoplasmic tail of integrin alpha1. This association stimulated TCPTP phosphatase activity, leading to negative regulation of epidermal growth factor receptor (EGFR) signaling and diminished anchorage-independent growth. Another candidate, mammary-derived growth inhibitor (MDGI), exhibited binding to several different integrin cytoplasmic alpha-tails through a conserved GFFKR sequence. MDGI overexpression in breast cancer cells altered EGFR trafficking and caused a remarkable accumulation of EGFR in the cytoplasm. We further demonstrated in vivo that MDGI expression induced a novel form of anti-EGFR therapy resistance. Moreover, MDGI binding to α-tails retained integrin in an inactive conformation attenuating integrin-mediated adhesion, migration, and invasion. In agreement with these results, sustained MDGI expression in breast cancer patients correlated with an increased 10-year distant disease-free survival. Taken together, the integrin signaling network is far from a complete view and future work will doubtless broaden our understanding further.