A comprehensive integrated drug similarity resource for in-silico drug repositioning and beyond.

Drug similarity studies are driven by the hypothesis that similar drugs should display similar therapeutic actions and thus can potentially treat a similar constellation of diseases. Drug-drug similarity has been derived by variety of direct and indirect sources of evidence and frequently shown high predictive power in discovering validated repositioning candidates as well as other in-silico drug development applications. Yet, existing resources either have limited coverage or rely on an individual source of evidence, overlooking the wealth and diversity of drug-related data sources. Hence, there has been an unmet need for a comprehensive resource integrating diverse drug-related information to derive multi-evidenced drug-drug similarities. We addressed this resource gap by compiling heterogenous information for an exhaustive set of small-molecule drugs (total of 10 367 in the current version) and systematically integrated multiple sources of evidence to derive a multi-modal drug-drug similarity network. The resulting database, 'DrugSimDB' currently includes 238 635 drug pairs with significant aggregated similarity, complemented with an interactive user-friendly web interface (http://vafaeelab.com/drugSimDB.html), which not only enables database ease of access, search, filtration and export, but also provides a variety of complementary information on queried drugs and interactions. The integration approach can flexibly incorporate further drug information into the similarity network, providing an easily extendable platform. The database compilation and construction source-code has been well-documented and semi-automated for any-time upgrade to account for new drugs and up-to-date drug information

Do interventions using threshold concepts assist learning in Biology?

The current interest in threshold concepts in the disciplines (Meyer & Land 2003, 2005) may provide a powerful heuristic for academics to help students to pass through conceptual gateways associated with previously inaccessible and possibly troublesome ways of thinking. Meyer and Land used three critical descriptors to identify threshold concepts, namely being transformative, irreversible and integrative experiences which are typified by cognitive and ontological shifts often accompanied by an extension of the student's use of language. Ross et al (2009), as part of an ALTC funded research project on Threshold Concepts in Biology, have developed a framework of discipline and threshold concepts which identifies a web of threshold concepts in biology, some of which are equivalent to epistemes. Interventions were then designed, to test the threshold properties of one of these concepts, which we predicted would assist students to make the link between the submicroscopic and the macroscopic cellular world and their connections at various spatial scales. All students in an introductory molecular and cellular biology course, offered in their first year at university, were surveyed at the commencement of the course about their conceptual understanding of scale. Half this cohort was then given two different interventions relating to scale and the remainder were provided with material similar in format, but which only reinforced relevant curricular content. Students were then surveyed following these interventions to determine the effectiveness of the intervention. Our results demonstrate the effectiveness of such an intervention in assessing whether once students cross one threshold, in a context such as cells and protein synthesis, they can subsequently transfer this way of thinking to aid in crossing thresholds in other contexts and other similarly difficult concepts in biology

Threshold Concepts: Challenging the Way We Think, Teach and Learn in Biology and Science

Meyer and Land (2003, 2005) proposed the notion of ‘threshold concepts’, which are central to the mastery of a specific discipline due to their transformative, irreversible and integrative nature. Using the methodology of Davies and Mangan (2007) we interviewed novice students (58) and expert academic staff (11) from three Australian universities and conducted an international survey of academics (55) to identify differences in novice and expert conceptions. We matched these data with understandings from the ‘misconceptions’ literature to create the ‘biology thresholds matrix’. The matrix demonstrates that threshold concepts in biology are not necessarily the troublesome content, but rather the tacit understandings of the discipline (Taylor, 2006, 2008; Ross & Tronson, 2007, Ross, Taylor, Hughes, Kofod, Whitaker, Lutze-Mann & Tzioumis, 2010). These are often not explicitly taught (Perkins, 2006) yet underpin difficult content areas including: energy and energy transformation, variation, probability and randomness, proportionality and surface area to volume ratio, dynamic equilibrium, linking the subcellular (submicroscopic) with the macroscopic, temporal and spatial scales (Ross et al., 2010), and the formulation and testing of hypotheses (Taylor & Meyer, 2010). These threshold concepts are not hierarchical in nature, but form a web of epistemes which has commonalities with tacit understandings in other science disciplines

Using Threshold Concepts to generate a new understanding of teaching and learning Biology

Students come to tertiary institutions with misconceptions of key concepts in the disciplines they are studying. Their misconceptions commonly relate to conceptually difficult or troublesome knowledge (Perkins 1999) and can be: incomplete, contradictory, stable and highly resistant to change and remain intact despite repeated instruction at successively higher levels, being perhaps reinforced by teachers and textbooks (Driver 1983; Driver, Guesne and Tiberghien, 1985; Gabel 1994). For sometime, we have known that a range of concepts in Biology are conceptually difficult e.g. biochemical pathways, evolution and genetics (Brown 1995; Ross and Tronson 2007, Taylor 2006, 2008), but whether these are the ‘threshold concepts’ of (Meyer and Land 1995) is a question that needs to be explored further. We propose an alternative perspective where threshold crossing can be envisaged more productively as a cognitive process with students transported across a conceptual chasm or threshold. Misconceptions may then lie with an underlying ‘cognitive threshold’ and not a ‘threshold concept’ (Ross et al 2008). This current ALTC funded collaborative project involves three Australian universities and aims to identify the cognitive processes which underlie difficult Biological concepts; develop intervention strategies to improve students’ framework of conceptual understanding, in one or more related concept areas (that is, to help the students cross a conceptual threshold); test whether students can subsequently transfer this thinking process to aid their understanding of other similarly difficult concepts (that is, to see if they have learnt how to cross unfamiliar thresholds). In this paper we present the preliminary results of a survey which asked biology academics (both nationally and internationally) to identify troublesome biological concepts in their teaching, describe the cognitive process that underlies them which may determine why they are troublesome, and to identify the links they perceive with our nominated cognitive thresholds

Milionella subrotunda (Montague 1803), a miliolid foraminifer building large agglutinated tubes for a temporary epibenthic livestyle.

Live observations, cytological characteristics and biometrical measurements on Miliolinella subrotunda (Montagu, 1803) sampled from the northern and southern Atlantic Ocean are presented.M. subrotunda facultatively constructs a long, detritic tube lifting the test several millimeters above the sediment surface. A thickened conical base anchors the construction on the sediment surface and a long, flexible tube protrudes into the velocity profile of the bottom currents. The miliolid test is placed on top, surrounded by the uppermost part of the tube. This construction allows the organisms to feed in the particle stream above the sediment surface. In comparison to species living in and on the surface sediments,M. subrotunda apparently shows higher nutritional values in food ingested and larger amounts of reserve substances. Characteristics of the shape and structure that reduce drag on the tubes include a broadened conical base, a flexible tube, and a rounded top. From biometrical measurements it is concluded, that the tubes are constructed over a short period of their ontogeny

Final Report - Effects of High Spinel and Chromium Oxide Crystal Contents on Simulated HLW Vitrification in DM100 Melter Tests, VSL-09R1520-1, Rev. 0, dated 6/22/09

The principal objective of the work was to evaluate the effects of spinel and chromium oxide particles on WTP HLW melter operations and potential impacts on melter life. This was accomplished through a combination of crucible-scale tests, settling and rheological tests, and tests on the DM100 melter system. Crucible testing was designed to develop and identify HLW glass compositions with high waste loadings that exhibit formation of crystalline spinel and/or chromium oxide phases up to relatively high crystal contents (i.e., > 1 vol%). Characterization of crystal settling and the effects on melt rheology was performed on the HLW glass formulations. Appropriate candidate HLW glass formulations were selected, based on characterization results, to support subsequent melter tests. In the present work, crucible melts were formulated that exhibit up to about 4.4 vol% crystallization

Increased risk of venous thromboembolism in patients with acute leukaemia

Patients with malignancies have an increased risk for venous thromboembolisms (VTE), but data on patients with acute leukaemia are very limited so far. We found VTE in 12% of 455 patients with acute leukaemia, half of which occurred in association with central venous catheters, with equal risk of ALL and AML