Leo5 Is a Z Cam Type Dwarf Nova

Photometry of Leo5 = 1H 1025+220 show that it is a dwarf nova of the Z Cam subtype. Two long standstills have been observed in the last five years.Comment: Accepted for publication in JAAVS

Predicting drug penetration across the blood-brain barrier: comparison of micellar liquid chromatography and immobilized artificial membrane liquid chromatography

Several in vitro methods have been investigated for mimicking drug penetration across the blood-brain barrier (BBB) into the central nervous system (CNS). Both micellar liquid chromatography (MLC) and immobilized artificial membrane (IAM) liquid chromatography were tested in this contribution in order to construct models for BBB transfer prediction. MLC measurements were performed on a C18-column with sodium dodecyl sulfate (SDS), polyoxyethylene (23) lauryl ether (Brij35) or sodium deoxycholate (SDC) as surfactants in the micellar mobile phase. IAM liquid chromatography measurements were performed with a Dulbecco’s phosphate-buffered saline (DPBS) and a certain percentage of methanol as organic modifier in the mobile phase. This study aimed to obtain a high correlation between in vivo and predicted log BB values (= concentration of the drug molecule in the brain to concentration in the blood)

Editorial introduction [to Strategic uncertainties: ethics, politics and risk in contemporary educational research]

Strategic Uncertainties: Ethics, Politics and Risk in Contemporary Educational Research offers new perspectives on contemporary educational research in a wide range of contexts and settings. The authors provide fresh insights into the ethics, politics and risks of educational research through their deployment of up-to-date concepts and methods. They also bring educational research ‘to life’ as a series of meaningful and significant issues and dilemmas, and by drawing on the voices of ‘real-life’ research participants and practitioners. In 2001, a theme issue of the Queensland Journal of Educational Research (Coombes & Danaher, 2001) was published under the title Cui Bono?: Investigating Benefits and Interests in Educational Research. In that issue, a group of authors from a range of academic disciplines explored the notion of who benefits from educational research and how such benefits might be identified, evaluated and weighed against potential costs to the research participants. The purpose of the contributors was not to view the intentions and results of research through rose-coloured glasses (‘everyone benefits and everyone is happy’) but to establish, as honestly as possible, whether the perceived benefits of a particular research project would actually occur without some cost to those involved. The key concepts, which were the focus of each article, were therefore the benefits and costs of educational research. In Strategic Uncertainties, the focus of attention shifts to the potential risks of educational research and to the strategies that researchers might employ to minimise or from some perspectives try to eliminate these risks (and from other perspectives to embrace and celebrate such risks). Educational research, by its very nature, is concerned with people; it cannot function in a sterile vacuum. Where people are concerned, complete agreement among the participants can never be guaranteed. Thus stakeholders may compete for powerful speaking positions. Research projects, though conceived with the best of intentions, may serve to highlight the gap between researcher and researched by reinforcing the socioeconomic and educational inequities of their relationships with one another. These particular risks, among many others, emphasise the ethical and political dimensions of relationships among the participants and subject to critical scrutiny claims that research projects confer particular kinds of benefits. Educational research is indeed a ‘risky business’, but this should not deter researchers from engaging in the practice. It is the purpose of Strategic Uncertainties to apply theoretically informed, methodologically rigorous and experientially grounded critique to the ‘murky shadows’ and ‘no-go areas’ of contemporary educational research. The title of this book, Strategic Uncertainties, is taken from the text of Ian Stronach and Maggie MacLure (1997), Educational Research Undone: The Postmodern embrace. The authors focused on postmodern researchers’ efforts to avoid being caught in the snares of: the binary oppositions that have traditionally promised the comforts of certainty in philosophical thinking – between reality and appearance, reason and superstition, causes and effects, meaning and language, identity and imposture, local and universal etc. – they choose not to choose between them, not to work to transcend them, nor, importantly, to ignore them, but instead to complicate the relations between them. (p. 5; emphasis in original) According to Stronach and MacLure (1997): The kind of opening which such work attempts is that of the rupture – or interruption and disruption – in the (uncertain) hope that this will generate possibilities for things to happen that are closed off by the epistemologies of certainty….These are uncanny openings, then. They rupture things, not in order to let the light pour in, but to make it harder to see clearly. They open spaces which turn out not to be spaces, but knots, complications, folds and partial connections. It is impossible even to tell for sure whether they are openings or closings, since they are also blocking manoeuvres, which would prevent escape routes to happy endings…We try to practise this kind of strategic uncertainty throughout, and within this book. Our aim is to mobilise meaning…rather than to fix it. (p, 5; emphasis in original; emphasis added) Elaborating and expanding on these propositions by Stronach and MacLure (1997), the content of Strategic Uncertainties is a set of accounts by contemporary educational researchers of the ethics, politics and risk of their own research projects. While those accounts draw on a multiplicity of theoretical, methodological and empirical resources to frame and inform their respective engagements with educational research, they have in common a general commitment to, and at the same time an ongoing interrogation of, the ideas encapsulated in the term ‘strategic uncertainties’

Biochemical Investigations on Microbial Prenyltransferases in the Presence of DMAPP Analogues

Plants, bacteria and fungi provide a plethora of diverse structures derived from the primary as well as the secondary metabolism. Representative substances from secondary metabolite pathways are flavonoids, coumarins, xanthones and indole alkaloids. Although not necessary for the growth and reproduction of the respective organisms, nevertheless these compounds give them an advantage over other organisms in the form of, e.g. attractants or protection agents against natural enemies as well as competitors. The attachment of isoprene units (n  C-5) such as dimethylallyl, geranyl or farnesyl moieties to aromatic secondary metabolites as backbones is a further step in the broad diversification of these compounds. Enzymes of the class of prenyltransferases accomplish this prenyl transfer reaction in nature. The prenylated natural products often exhibit strong pharmacological activities in contrast to their substrates. Therefore, prenylated compounds represent interesting targets for drug development. Investigations on alternative alkyl residues transferable via prenyltransferases, i.e. prenyl diphosphate analogues, could have the potential to play an important role in the understanding of the catalytic mechanism of these enzymes as well as in the finding process of new drugs. As the first project in this thesis, the acceptance of four chemically synthesized alkyl and allyl diphosphates in the presence of three L-tryptophan prenyltransferases (FgaPT2, 5 DMATS, 7 DMATS) was elucidated. Retaining the double bond in β position and performing alterations on the methyl groups of the allyl residue led to regular alkylated products and thereby showed successful utilization of DMAPP analogues. However, depending on the DMAPP analogue, the regiospecificity of the applied prenyltransferases was shifted partially or completely. Furthermore, the enzymes did not catalyze the transfer reaction of alkyl diphosphates onto the L tryptophan scaffold, if no double bond was present or if it was relocated to  position compared to DMAPP. Subsequently, the behavior of cyclic dipeptide prenyltransferases (AnaPT, CdpNPT, CdpC3PT, FtmPT1, BrePT) towards the unnatural alkyl and allyl donors was examined. The cyclic dipeptide prenyltransferases also used the unsaturated DMAPP analogues resulting in the formation of multiple products. Regardless of the prenylation position and orientation for the prenyl attachment (C 2 or C 3; regular or reverse) in the presence of DMAPP, the enzymatic reactions with both DMAPP analogues, i.e. MAPP and 2-pentenyl-PP, yielded a mixture of C2 reverse as well as C3 reverse alkylated diastereomers in different ratios depending on the donor and used enzyme. After the successful alkylation of L tryptophan and tryptophan-containing cyclic dipeptides utilizing simple unnatural allyl DMAPP analogues, the acceptance of the structurally more complex DMAPP analogue benzyl diphosphate was tested. Preliminary investigations showed the successful usage of this benzyl donor by several L tryptophan and cyclic dipeptide prenyltransferases, whereas FgaPT2 showed the highest activity. FgaPT2 also displayed a remarkable promiscuity using tryptophan analogues as substrates and catalyzing a highly regiospecific C5 benzylation. Consequently, the usage of benzyl diphosphate instead of dimethylallyl diphosphate results in a complete shift of the prenylation position from C 4 to C 5. To complete our findings regarding the acceptance of unnatural alkyl and benzyl analogues by prenyltransferases, several tryptophan C5-, C6- and C7-prenylating enzymes of fungal and bacterial origin have been assayed with the three analogues. Depending on the enzyme used, one to four products could be identified from the incubation mixtures. The predominant products were regular C6-alkylated or C6-benzylated derivatives in all cases. Therefore, for the tested tryptophan C5-, C6- and C7-prenylating enzymes, C-6 seemed to be the preferred position for attachment of the alkyl or benzyl moiety. The results obtained during this thesis show that allyl as well as benzyl analogues of DMAPP are potential alternatives for chemoenzymatic FriedelCrafts alkylations of simple indole derivatives and tryptophan-containing cyclic dipeptides and could be used for the production of alkylated compounds

New radiocarbon dates from the Bapot-1 site in Saipan and Neolithic dispersal by stratified diffusion

The colonisation of the Mariana Islands in Western Micronesia is likely to represent an early ocean dispersal of more than 2000 km. Establishing the date of human arrival in the archipelago is important for modelling Neolithic expansion in Island Southeast Asia and the Pacific, particularly the role of long-distance dispersals. This paper presents new ¹⁴C results and a ΔR estimate from the Bapot-1 site on Saipan Island, which indicate human arrival at ca. 3400-3200 cal. BP. Archaeological chronologies of long-distance dispersal to Western Micronesia and the Lapita expansion (Bismarcks to Samoa) show that the Neolithic dispersal rate was increasing during the period ca. 3400-2900 cal. BP. The range-versus-time relationship is similar to stratified diffusion whereby a period of relatively slow expansion is succeeded by long-distance movement. An increase in new colonies created by long-distance migrants results in accelerating range expansion

Predicting drug penetration across the blood-brain barrier: comparison of different stationary phases for immobilized artificial membrane liquid chromatography

Several in vitro methods have been tested for their ability to predict drug penetration across the blood-brain barrier into the central nervous system. In this article, the performance of three stationary phases for immobilized artificial membrane (IAM) liquid chromatographic approaches were compared on a set of 49 compounds. IAM liquid chromatography measurements were performed with Dulbecco’s phosphate-buffered saline and methanol as organic modifier in the mobile phase. Transport across the blood-brain barrier (log BB) was predicted using computed descriptor data and the retention factor of all compounds. All data were correlated with experimental log BB values and the relative performance of the approaches was studied. The IAM.PC.DD2 column proved to be the best suited for prediction of log BB values, although all three columns performed very good

Foundations for the Social Economy

At present the strategies, policies and tools employed by the social economy in most countries are diffuse. There is no integrated narrative to bring together the small parts to form a more cohesive whole. This cross-cutting project, led by Mike Lewis and Pat Conaty, is intended to review the scope and success of emergent systemic approaches in order to explore the implications for developing a new social and ecological economy at the sub-regional level. The investigation will produce a new conceptual framework for understanding the foundations for a more strategic approach by social economy actors. In the wake of the credit crunch and developing recession, the project will appraise social economy needs including equitable access to land & premises, patient capital and enabling legal structures.BC-Alberta Social Economy Research Alliance (BALTA