Molecular cloning and functional characterization of the Xenopus Ca(2+)-binding protein frequenin.

Frequenin was originally identified in Drosophila melanogaster as a Ca(2+)-binding protein facilitating transmitter release at the neuromuscular junction. We have cloned the Xenopus frequenin (Xfreq) by PCR using degenerate primers combined with low-stringency hybridization. The deduced protein has 70% identity with Drosophila frequenin and about 38-58% identity with other Ca(2+)-binding proteins. The most prominent features are the four EF-hands, Ca(2+)-binding motifs. Xfreq mRNA is abundant in the brain and virtually nondetectable from adult muscle. Western blot analysis indicated that Xfreq is highly concentrated in the adult brain and is absent from nonneural tissues such as heart and kidney. During development, the expression of the protein correlated well with the maturation of neuromuscular synapses. To determine the function of Xfreq at the developing neuromuscular junction, the recombinant protein was introduced into Xenopus embryonic spinal neurons by early blastomere injection. Synapses made by spinal neurons containing exogenous Xfreq exhibited a much higher synaptic efficacy. These results provide direct evidence that frequenin enhances transmitter release at the vertebrate neuromuscular synapse and suggest its potential role in synaptic development and plasticity.

A possible role of vitamin D receptors in regulating vitamin D activation in the kidney.

The vitamin D endocrine system is regulated reciprocally by renal 25-hydroxyvitamin D3 1 alpha- and 24-hydroxylases. Previously, we reported that renal proximal convoluted tubules, the major site of 1 alpha, 25-dihydroxyvitamin D3 production, have vitamin D receptors. In the presence of vitamin D receptors, renal proximal convoluted tubules cannot maintain the state of enhanced production of 1 alpha, 25-dihydroxyvitamin D3. To clarify this discrepancy, we proposed a working hypothesis for the reciprocal control of renal 25-hydroxyvitamin D3 1 alpha- and 24-hydroxylase activities. In rat models of enhanced renal production of 1 alpha, 25-dihydroxyvitamin D3, expression of vitamin D receptors and 25-hydroxyvitamin D3 24-hydroxylase mRNAs was strikingly suppressed in renal proximal convoluted tubules but not in the cortical collecting ducts. In vitamin D-deficient rats with up-regulated renal 25-hydroxyvitamin D3 1 alpha-hydroxylase activity, expression of vitamin D receptor mRNA in renal proximal convoluted tubules was also down-regulated, indicating that the down-regulation of vitamin D receptor mRNA is not the result of the enhanced production of 1 alpha, 25-dihydroxyvitamin D3. In Japanese quail models with up-regulated renal 25-hydroxyvitamin D3 1 alpha-hydroxylase activity by sex steroids, expression of vitamin D receptor mRNA was also down-regulated in the kidney but not in the duodenum. These results suggest that the down-regulation of vitamin D receptors plays a critical role in production of 1 alpha, 25-dihydroxyvitamin D3 in renal proximal convoluted tubules.

Early termination of R&D projects

Early project termination is one of the most difficult decisions to be made by Research and Development managers. While there is the risk of terminating good projects, there is also the opposite risk of not terminating bad projects and overspend resources in unproductive research. Criteria used for identifying these projects are common subject of research in Business Administration. In addition, companies might take important lessons from its interrupted projects that could improve their overall portfolio technical and commercial success. Finally, the set and weight of criteria, as well as the procedures companies use for achieve learning from cancelled projects may vary depending on the project type. This research intends to contribute to the understanding of policies applied to projects that were once considered attractive, but by some reason is not appreciated anymore. The research addressed the question: How companies deal with projects that become unattractive? More specifically, this research tried to answer the following questions: (1) Are projects killed or (otherwise) they die naturally by lack of resources? (2) What criteria are used to terminate projects during development? (3) How companies learn from the terminated projects to improve the overall portfolio performance? (4) Are the criteria and learning procedures different for different types of projects? In order to answer these questions, we performed a multiple case study with four companies that are reference in business administration and innovation: (1) Oxiteno, considered the base case, (2) Natura, the literal replication, (3) Mahle and (4) AES, the theoretical replications. The case studies were performed using a semi-structured protocol for interviews, which were recorded and analyzed for comparison. We found that the criteria companies use for selecting projects for termination are very similar to those anticipated by the literature, except for a criteria related to compliance. We have evidences to confirm that the set of criteria is not altered when dealing with different project types, however the weight they are applied indeed varies. We also found that learning with cancelled projects is yet very incipient, with very few structured formal procedures being described for capturing learning with early-terminated projects. However, we could observe that these procedures are more common when dealing with projects labeled as innovative, risky, big and costly, while those smaller and cheaper derivative projects aren\'t subject of a complete investigation on the learning they brought to the company. For these, the most common learning route is the informal, where the project team learns and passes the knowledge though interpersonal information exchange. We explain that as a matter of cost versus benefit of spending time to deeply investigate projects with little potential to bring new knowledge to the project team and the organization

The University of Alicante Library copy of Palmerin d'Oliva (London, 1637): A Bibliographical Description

The purpose of this article is to provide bibliographical information about a copy of the fourth edition of the two parts of Anthony Munday's translation of Palmerin d'Oliva (London, 1637; STC 19160) recently purchased by the University of Alicante Library and not mentioned in the standard bibliographies. The article contains a detailed bibliographical description based on Bowers's principles (1949) and is designed to be useful to scholars by making direct consultation of the copy in most cases unnecessary. The description is preceded by a short introduction to the literary text and its publication in England.

XI. Catalogue of Harvard graduates, [ca. 1810]

This paper notebook contains a handwritten, alphabetical listing of graduates of the Harvard Classes of 1642 to 1809 presumably compiled from the published Triennial Catalogues.

Eulogy of George Washington, ca. 1800

This manuscript, which White entitled A faint sketch of the character, history & services of the Immortal Washington, appears to be a draft of the eulogy on Washington that he delivered publicly in Methuen and which was printed by Seth H. Moore and published by in February 1800.

Outlines of Holden Chapel, [ca. 1801]

Pen and ink drawings with measurements of the interior ground plot, arch, and side of Holden Chapel.

Sundry extracts on the subject of the taxation of College &c., ca. 1798-1801

Notebook with brown paper cover containing handwritten extracts from the charters and related legislation of New England academic, charitable, and commercial institutions regarding their ability to hold real estate and related tax exemptions. Most of the listed documents are dated in the 1780s and 1790s. The notebook also contains extracts from "Argument in the case of Poor's rate, charged on the College of Christ & Emmanuel in the University of Cambridge 1768." The item title is transcribed from a handwritten inscription on the back cover.