No abstract

In this work, we introduce a four-step scoring and filtering procedure, furnishing target specific virtual screening (TS-VS), which serves to minimize false positives resulting from conformational artifacts of the docking process and is optimized to converge on novel chemotypes of estrogen receptor alpha (ERalpha). As a proof of concept, VS of a commercial compound database was undertaken (SPECs database release: Aug 2005, 202 054 compounds in total), resulting in the identification of both previously known and novel putative ER scaffolds. Application of distance constraints within TS-VS allowed facile identification of three novel active ligands with ERalpha binding affinities (IC50) of 1.4 microM, 57 nM, and 53 nM. Importantly, they all exhibited ERalpha over ERbeta selectivity, with the most selective being 17-fold. The ligands also displayed low micomolar antiproliferative activity (7-15 microM) in the human MCF-7 breast cancer cell line.

Purpose -The purpose of this paper is to examine funding models for Open Access (OA) digital data repositories whose costs are not wholly core funded. Whilst such repositories are free to access, they are not without significant cost to build and maintain and the lack of both full core costs and a direct funding stream through payment-for-use poses a considerable financial challenge, placing their future and the digital collections they hold at risk. Design/methodology/approach -The authors document 14 different potential funding streams for OA digital data repositories, grouped into six classes (institutional, philanthropy, research, audience, service, volunteer), drawing on the ongoing experiences of seeking a sustainable funding for the Digital Repository of Ireland (DRI). Findings -There is no straight forward solution to funding OA digital data repositories that are not wholly core funded, with a number of general and specific challenges facing each repository, and each funding model having strengths and weaknesses. The proposed DRI solution is the adoption of a blended approach that seeks to ameliorate cyclical effects across funding streams by generating income from a number of sources rather than overly relying on a single one, though it is still reliant on significant state core funding to be viable. Practical implications -The detailing of potential funding streams offers practical financial solutions to other OA digital data repositories which are seeking a means to become financially sustainable in the absence of full core funding. Originality/value -The review assesses and provides concrete advice with respect to potential funding streams in order to help repository owners address the financing conundrum they face.

No abstract