A Longitudinal Investigation of the Relationship between Motivation and Late Second Language Speech Learning in Classroom Settings.

The current study set out to examine the role of learner motivation in second language (L2) speech learning in English-as-a-Foreign-Language classrooms. The motivational orientations of 40 first-year university Japanese students were surveyed via a tailored questionnaire and linked to their spontaneous speech development, elicited via a timed picture description task at the onset and end of one academic semester, in terms of perceived comprehensibility (i.e., ease of understanding) and accentedness (i.e., linguistic nativelikeness). Significant improvement in comprehensibility (but not accentedness) was found among certain individuals. These students likely showed a strong motivation to study English for their future career development as a vague and long-term goal, as well as a high degree of concern for improving comprehensibility, grammatical accuracy and complexity.

Molecular Design of Bisphosphonate-Modified Proteins for Efficient Bone Targeting In Vivo.

To establish a rational molecular design for bisphosphonate (BP)-modified proteins for efficient bone targeting, a pharmacokinetic study was performed using a series of alendronate (ALN), a nitrogen-containing BP, modified proteins with various molecular weights and varying degrees of modification. Four proteins with different molecular weight-yeast glutathione reductase (GR; MW: 112,000 Da), bovine serum albumin (BSA; MW: 67,000 Da), recombinant human superoxide dismutase (SOD; MW: 32,000 Da), and chicken egg white lysozyme (LZM; MW: 14,000 Da)-were modified with ALN to obtain ALN-modified proteins. Pharmacokinetic analysis of the tissue distribution of the ALN-modified and unmodified proteins was performed after radiolabeling them with indium-111 (111In) by using a bifunctional chelating agent. Calculation of tissue uptake clearances revealed that the bone uptake clearances of 111In-ALN-modified proteins were proportional to the degree of ALN modification. 111In-GR-ALN and BSA-ALN, the two high-molecular-weight proteins, efficiently accumulated in bones, regardless of the degree of ALN modification. Approximately 36 and 34% of the dose, respectively, was calculated to be delivered to the bones. In contrast, the maximum amounts taken up by bone were 18 and 13% of the dose for 111In-SOD-ALN(32) and LZM-ALN(9), respectively, because of their high renal clearance. 111In-SOD modified with both polyethylene glycol (PEG) and ALN (111In-PEG-SOD-ALN) was efficiently delivered to the bone. Approximately 36% of the dose was estimated to be delivered to the bones. In an experimental bone metastasis mouse model, treatment with PEG-SOD-ALN significantly reduced the number of tumor cells in the bone of the mice. These results indicate that the combination of PEG and ALN modification is a promising approach for efficient bone targeting of proteins with a high total-body clearance.