Acquiring Conceptual Knowledge about How Systems Behave

There is a need for software that supports learners in actively dealing with theoretical concepts by having them create models and perform concept prediction and explanation (e.g. [3,4,5]). DynaLearn seeks to address this by developing a domain independent Interactive Learning Environment (ILE) based on Qualitative Reasoning (QR) [1]. The QR vocabulary fits the nature of conceptual knowledge, and the explicit representation of these notions in the software provides the handles to support an automated communicative interaction that actually discusses and provides feedback at the conceptual level

DynaLearn: Architecture and Approach for Investigating Conceptual System Knowledge Acquisition

DynaLearn is an Interactive Learning Environment that facilitates a constructive approach to developing a conceptual understanding of how systems work. The software can be put in different interactive modes facilitating alternative learning experiences, and as such provides a toolkit for educational research

Reconsidering the Effectiveness of Scientific Tools for Negotiating Local Solutions to Conflicts between Recreation and Conservation with Stakeholders

The conflict between the conservation of biodiversity and recreation activities in the European landscape is intensifying. Managers of large nature areas are confronted with increasing numbers of visitors and decreasing biodiversity values. To accommodate the visitors while simultaneously protecting the biodiversity values they need to make changes in the landscape. Current legislation, a lack of knowledge on the recreation-biodiversity relationship, and the diverging point of view of stakeholders make it difficult to find consensual solutions. New approaches such as adaptive management and boundary management can help managers and stakeholders in the process of decision making. In these approaches the role of scientists has changed, as has the use of their tools. Using two research projects in Europe we explore how scientific tools are used in this new context. We argue that such tools (1) should be built on the interactions between recreation and biodiversity functions, (2) can be used interactively to encourage stakeholders to engage in a learning process, (3) allow local knowledge and data to be incorporated into them, and (4) generate output in the form of a map showing where the conflict areas and opportunities are located. These four key features will help managers to improve communication between themselves, stakeholders, and scientists, increase consensus between stakeholders on how the conflict should be perceived, explore solutions, and generate new knowledge. For future research we suggest investigating how adaptive management and boundary management can be used in a stepwise learning strategy and how uncertainties in the tools affect the learning process

Using GPS tracking to understand the impact of management interventions on visitor densities and bird populations

To manage the potential conflict between outdoor recreation and nature conservation, managers of nature areas need information to select effective interventions. For large nature areas information on visitor use is often lacking and managers often make decisions based on expert judgement. In this paper we use monitoring data gathered with GPS devices to develop a tool and derive rules of thumb managers can use to estimate the impact of management actions on visitor densities. Using a dataset of 1563 tracks from the New Forest, UK, we developed a random forest model and identified which landscape and environmental features account for the spatial variation in visitor densities. The random forest model shows that distance to car park, distance to roads and openness are the most important factors for predicting visitor densities. The model was used as a tool to assess the impact of potential management interventions on the population of Nightjar. As developing this type of tool requires a lot of data we also derived rules of thumb and a simple algorithm that managers of other nature areas can use to estimate the impact of their interventions on visitor densities. The derived rules of thumb show that changing the location of car parks in relation to tarmac roads can help managers to reduce local visitor densities by 80%. Further research in other nature areas should verify the feasibility of these rules of thumb and the simple algorithm.</p

In vitro evaluation of pathogen-inactivated buffy coat-derived platelet concentrates during storage: psoralen-based photochemical treatment step-by-step.

BACKGROUND: The Intercept Blood SystemTM (Cerus) is used to inactivate pathogens in platelet concentrates (PC). The aim of this study was to elucidate the extent to which the Intercept treatment modifies the functional properties of platelets. MATERIAL AND METHODS: A two-arm study was conducted initially to compare buffy coat-derived pathogen-inactivated PC to untreated PC (n=5) throughout storage. A four-arm study was then designed to evaluate the contribution of the compound adsorbing device (CAD) and ultraviolet (UV) illumination to the changes observed upon Intercept treatment. Intercept-treated PC, CAD-incubated PC, and UV-illuminated PC were compared to untreated PC (n=5). Functional characteristics were assessed using flow cytometry, hypotonic shock response (HSR), aggregation, adhesion assays and flow cytometry for the detection of CD62P, CD42b, GPIIb-IIIa, phosphatidylserine exposure and JC-1 aggregates. RESULTS: Compared to fresh platelets, end-of-storage platelets exhibited greater passive activation, disruption of the mitochondrial transmembrane potential (Δψm), and phosphatidylserine exposure accompanied by a decreased capacity to respond to agonist-induced aggregation, lower HSR, and CD42b expression. The Intercept treatment resulted in significantly lower HSR and CD42b expression compared to controls on day 7, with no significant changes in CD62P, Δψm, or phosphatidylserine exposure. GPIIbIIIa expression was significantly increased in Intercept-treated platelets throughout the storage period. The agonist-induced aggregation response was highly dependent on the type and concentration of agonist used, indicating a minor effect of the Intercept treatment. The CAD and UV steps alone had a negligible effect on platelet aggregation. DISCUSSION: The Intercept treatment moderately affects platelet function in vitro. CAD and UV illumination alone make negligible contributions to the changes in aggregation observed in Intercept-treated PC

The effects of all-trans retinoic acid on estrogen receptor signaling in the estrogen-sensitive MCF/BUS subline

Estrogen receptor alpha (ERα) and retinoic acid receptors (RARs) play important and opposite roles in breast cancer growth. While exposure to ERα agonists such as 17β-estradiol (E2) is related to proliferation, RAR agonists such as all-trans retinoic acid (AtRA) induce anti-proliferative effects. Although crosstalk between these pathways has been proposed, the molecular mechanisms underlying this interplay are still not completely unraveled. The aim of this study was to evaluate the effects of AtRA on ERα-mediated signaling in the ERα positive cell lines MCF7/BUS and U2OS-ERα-Luc to investigate some of the possible underlying modes of action. To do so, this study assessed the effects of AtRA on different ERα-related events such as ERα-mediated cell proliferation and gene expression, ERα-coregulator binding and ERα subcellular localization. AtRA-mediated antagonism of E2-induced signaling was observed in the proliferation and gene expression studies. However, AtRA showed no remarkable effects on the E2-driven coregulator binding and subcellular distribution of ERα. Interestingly, in the absence of E2, ERα-mediated gene expression, ERα-coregulator binding and ERα subcellular mobilization were increased upon exposure to micromolar concentrations of AtRA found to inhibit cell proliferation after long-term exposure. Nevertheless, experiments using purified ERα showed that direct binding of AtRA to ERα does not occur. Altogether, our results using MCF7/BUS and U2OS-ERα-Luc cells suggest that AtRA, without being a direct ligand of ERα, can indirectly interfere on basal ERα-coregulator binding and basal ERα subcellular localization in addition to the previously described crosstalk mechanisms such as competition of ERs and RARs for DNA binding sites

Characterization of the differential coregulator binding signatures of the Retinoic Acid Receptor subtypes upon (ant)agonist action

Retinoic Acid Receptor alpha (RARα/NR1B1), Retinoic Acid Receptor beta (RARβ/NR1B2) and Retinoic Acid Receptor gamma (RARγ/NR1B3) are transcription factors regulating gene expression in response to retinoids. Within the RAR genomic pathways, binding of RARs to coregulators is a key intermediate regulatory phase. However, ligand-dependent interactions between the wide variety of coregulators that may be present in a cell and the different RAR subtypes are largely unknown. The aim of this study is to characterize the coregulator binding profiles of RARs in the presence of the pan-agonist all-trans-Retinoic Acid (AtRA); the subtype-selective agonists Am80 (RARα), CD2314 (RARβ) and BMS961 (RARγ); and the antagonist Ro415253. To this end, we used a microarray assay for coregulator-nuclear receptor interactions to assess RAR binding to 154 motifs belonging to > 60 coregulators. The results revealed a high number of ligand-dependent RAR-coregulator interactions among all RAR variants, including many binding events not yet described in literature. Next, this work confirmed a greater ligand-independent activity of RARβ compared to the other RAR subtypes based on both higher basal and lower ligand-driven coregulator binding. Further, several coregulator motifs showed selective binding to a specific RAR subtype. Next, this work showed that subtype-selective agonists can be successfully discriminated by using coregulator binding assays. Finally this study demonstrated the possible applications of a coregulator binding assay as a tool to discriminate between agonistic/antagonistic actions of ligands. The RAR-coregulator interactions found will be of use to direct further studies to better understand the mechanisms driving the eventual actions of retinoids.</p

Transcriptome analysis for the scale-down of a CHO cell fed-batch process

Transcriptome and metabolism analysis were performed to evaluate the scale-down of a CHO cell fed-batch process from a 10 L bioreactor to an ambr 15® (ambr) system. Two different agitation scale-down principles were applied, resulting in two different agitation rates in the ambr system: 1300 RPM based on the agitator tip speed, and 800 rpm based on the volumetric power input (P/V). Culture performance including cell growth, product titer, glycosylation, and specific consumption/production rates of metabolites was the same for both agitation rates in the ambr and was comparable to that of the 10 L system. The initial variation in gene expression between the inocula for the ambr and 10 L system was no longer present after three days of culture, indicating comparable culture conditions in both systems. Based on principal component analysis, changes in gene expression over time were similar between both scales with less than 6% variation. 2455 genes were uniquely regulated in the ambr system compared to 1604 genes in the 10 L system. Functional analysis of these genes did not reveal their relations with scale or cellular function. This study further strengthens that the ambr system gives representative culture performance for the 10 L bench-scale bioreactor.</p