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This article is a study of melodic expectancy in North Sami yoiks, a style of music quite distinct from Western tonal music. Three different approaches were taken. The first approach was a statistical style analysis of tones in a representative corpus of 18 yoiks. The analysis determined the relative frequencies of tone onsets and two- and three-tone transitions. It also identified style characteristics, such as pentatonic orientation, the presence of two reference pitches, the frequency of large consonant intervals, and a relatively large set of possible melodic continuations. The second approach was a behavioral experiment in which listeners made judgments about melodic continuations. Three groups of listeners participated. One group was from the Sami culture, the second group consisted of Finnish music students who had learned some yoiks, and the third group consisted of Western musicians unfamiliar with yoiks. Expertise was associated with stronger veridical expectations (for the correct next tone) than schematic expectations (based on general style characteristics). Familiarity with the particular yoiks was found to compensate for lack of experience with the musical culture. The third approach simulated melodic expectancy with neural network models of the self-organizing map (SOM) type (Kohonen, T. (1997). Self-organizing maps (2nd ed.). Berlin: Springer). One model was trained on the excerpts of yoiks used in the behavioral experiment including the correct continuation tone, while another was trained with a set of Finnish folk songs and Lutheran hymns. The convergence of the three approaches showed that both listeners and the SOM model are influenced by the statistical distributions of tones and tone sequences. The listeners and SOM models also provided evidence supporting a core set of psychological principles underlying melody formation whose relative weights appear to differ across musical styles.

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AimsWe evaluated for the first time the effects of angiogenic and lymphangiogenic AdVEGF-DΔNΔC gene therapy in patients with refractory angina.Methods and resultsThirty patients were randomized to AdVEGF-DΔNΔC (AdVEGF-D) or placebo (control) groups. Electromechanical NOGA mapping and radiowater PET were used to identify hibernating viable myocardium where treatment was targeted. Safety, severity of symptoms, quality of life, lipoprotein(a) [Lp(a)] and routine clinical chemistry were measured. Myocardial perfusion reserve (MPR) was assessed with radiowater PET at baseline and after 3- and 12-months follow-up. Treatment was well tolerated. Myocardial perfusion reserve increased significantly in the treated area in the AdVEGF-D group compared with baseline (1.00 ± 0.36) at 3 months (1.31 ± 0.46, P = 0.045) and 12 months (1.44 ± 0.48, P = 0.009) whereas MPR in the reference area tended to decrease (2.05 ± 0.69, 1.76 ± 0.62, and 1.87 ± 0.69; baseline, 3 and 12 months, respectively, P = 0.551). Myocardial perfusion reserve in the control group showed no significant change from baseline to 3 and 12 months (1.26 ± 0.37, 1.57 ± 0.55, and 1.48 ± 0.48; respectively, P = 0.690). No major changes were found in clinical chemistry but anti-adenovirus antibodies increased in 54% of the treated patients compared with baseline. AdVEGF-D patients in the highest Lp(a) tertile at baseline showed the best response to therapy (MPR 0.94 ± 0.32 and 1.76 ± 0.41 baseline and 12 months, respectively, P = 0.023).ConclusionAdVEGF-DΔNΔC gene therapy was safe, feasible, and well tolerated. Myocardial perfusion increased at 1 year in the treated areas with impaired MPR at baseline. Plasma Lp(a) may be a potential biomarker to identify patients that may have the greatest benefit with this therapy.

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Vascular endothelial growth factors (VEGFs) and their tyrosine kinase receptors (VEGFR-1-3) are central mediators of angiogenesis and lymphangiogenesis. VEGFR-3 ligands VEGF-C and VEGF-D are produced as precursor proteins with long N- and C-terminal propeptides and show enhanced VEGFR-2 and VEGFR-3 binding on proteolytic removal of the propeptides. Two different proteolytic cleavage sites have been reported in the VEGF-D N-terminus. We report here the crystal structure of the human VEGF-D Cys117Ala mutant at 2.9 Å resolution. Comparison of the VEGF-D and VEGF-C structures shows similar extended N-terminal helices, conserved overall folds, and VEGFR-2 interacting residues. Consistent with this, the affinity and the thermodynamic parameters for VEGFR-2 binding are very similar. In comparison with VEGF-C structures, however, the VEGF-D N-terminal helix was extended by 2 more turns because of a better resolution. Both receptor binding and functional assays of N-terminally truncated VEGF-D polypeptides indicated that the residues between the reported proteolytic cleavage sites are important for VEGF-D binding and activation of VEGFR-3, but not of VEGFR-2. Thus, we define here a VEGFR-2–specific form of VEGF-D that is angiogenic but not lymphangiogenic. These results provide important new insights into VEGF-D structure and function.

We report on an implementation of a new method to calculate RPA strength functions with iterative non-hermitian Arnoldi diagonalization method, which does not explicitly calculate and store the RPA matrix. We discuss the treatment of spurious modes, numerical stability, and how the method scales as the used model space is enlarged. We perform the particle-hole RPA benchmark calculations for double magic nucleus 132 Sn and compare the resulting electromagnetic strength functions against those obtained within the standard RPA.

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