Multi-Disciplinary Project-Based Paradigm That Uses Hands-On Desktop Learning Modules and modern Learning Pedagogies

It has been established that traditional lectures ARE NOT best for student learning – yet that is what the community almost universally does! Furthermore, engineers work in broad multidisciplinary teams while classroom learning is individual and narrow. Yet, educators rarely invest the time and resources necessary to employ such innovations. In this CCLI type II award we are further refining Desktop Learning Modules (DLMs) within a Cooperative, Hands-on, Active, Problem based, Learning (CHAPL) setting for Chemical, Civil, Mechanical, Bio- and Electrical Engineering courses at a diverse set of institutions, including a community college engaged through a distance learning mode. A workbook is being developed and tested for easier adoption of the hands-on units and accompanying pedagogy. Existing concept inventories are not always showing significant gains in apparent student learning either for control or experimental groups and we are concluding these assessments are not well aligned with the macroscale design calculations being emphasized in the course. Therefore, new concept question assessments are being developed consisting of some macroscale questions from past inventories along with conceptual essay and calculation based questions aligned more specifically with the DLM processes at hand. Past implementations like this show students learn key concepts at least as well from each other in a guided inquiry as they do from lecture. Also, a mixed qualitative / quantitative assessment using a critical reasoning rubric reveals student abilities become better aligned with what is expected of graduating engineers ready for industry and that the CHAPL/DLM environment serves to reinforce understanding of physical phenomena, and to develop analytical and evaluative problem-solving skills. Interviews, surveys and team reports reveal students are better able to visualize concepts and that classroom exercises are promoting team skills and academic rigor. Faculty interviews reveal enhanced awareness of student misconceptions and improved monitoring of student growth in conceptual understanding and interpersonal skills. The poster and paper will highlight our findings and illustrate the CHAPL environment. Hands-on DLMs with cartridges used in teaching principles in the various disciplines will be demonstrated. A survey will be offered to those viewing the poster to assess potential interest in adoption of the DLMs and in participating in a follow-on NSF Type III proposal for Transforming Undergraduate Engineering Education through use of the DLMs and associated CHAPL pedagogies

Legitimacy intermediation in the multilevel European polity and its collapse in the euro crisis

This essay re-examines the dual – republican and liberal – foundations of democratic legitimacy in the Western traditions of normative political theory. Considered in isolation, the European Union conforms to liberal standards but cannot satisfy republican criteria. Given these conflicting standards, debates on the alleged European democratic deficit have remained inconclusive. Moreover, they have failed to pay sufficient attention to the multilevel character of the European polity and to the normative potential of legitimacy intermediation in its two-step compliance and legitimating relationships. I argue, however, that the capacity of democratic member states to legitimate the exercise of European governing functions is being destroyed in the present euro crisis, and I briefly discuss the implications of this new constellation.In der westlichen Tradition der normativen politischen Theorie beruht demokratische Legitimität auf der doppelten Grundlage republikanischer und liberaler Prinzipien. Für sich betrachtet entspricht die Europäische Union zwar liberalen Kriterien, aber eben nicht den republikanischen Anforderungen. Angesichts so unterschiedlicher Kriterien konnte es auch im Streit über das angebliche europäische Demokratiedefizit keine Einigung geben. Überdies ignorierte diese Diskussion den Mehrebenen-Charakter der europäischen Politik und das normative Potenzial der Legitimationsvermittlung zwischen Union und Bürgern durch die demokratisch verfassten Mitgliedstaaten. Die gegenwärtige Eurokrise allerdings zerstört die Fähigkeit demokratischer Mitgliedstaaten, die Ausübung europäischer Herrschaftsfunktionen zu legitimieren. Der Aufsatz erörtert die Implikationen dieser neuen Konstellation.1 Introduction 2 Legitimacy discourses The republican discourse The liberal discourse Differences 3 Constitutional democracies – and the European Union? 4 Legitimacy intermediation in the multilevel European polity 5 The end of legitimacy intermediation in the euro crisis Monetary Union and the failure of output legitimacy Rescuing the euro through supranational intervention 6 Legitimate supranational government? Input-oriented European legitimacy? 7 Reducing the burden on European legitimacy Reference

Multi-Disciplinary Project-Based Paradigm that Uses Hands-on Desktop Learning Modules and Modern Learning Pedagogies

Multi-Disciplinary Project-Based Paradigm that Uses Hands-on Desktop Learning Modules and Modern Learning PedagogiesIn this CCLI Type II Program we are promoting adoption of research-based teaching pedagogiesof collaborative, hands-on, active, and problem- or project-based learning (CHAPL). It has beenestablished that traditional lectures ARE NOT best for student learning – yet that is what thecommunity almost universally does! Furthermore, engineers work in broad multidisciplinaryteams while classroom learning is individual and narrow. Yet, educators rarely invest the timeand resources necessary to employ such innovations.We are further refining Desktop Learning Modules (DLMs) within a CHAPL setting forChemical, Civil, Mechanical, Bio- and Electrical Engineering courses at a diverse set ofinstitutions, including a community college engaged through a distance learning mode. Aworkbook is being developed and tested for easier adoption of the hands-on units andaccompanying pedagogy. Both quantitative and qualitative assessments are showing positiveimpacts. Concept inventories are showing students learn key concepts at least as well from eachother in a guided inquiry as they do from lecture. Critical reasoning assessments reveal studentsbecome better aligned with what is expected of graduating engineers ready for industry and thatthe CHAPL/DLM environment serves to reinforce understanding of emergent phenomena, and todevelop analytical, evaluative and problem-solving skills. Interviews, surveys and team reportsreveal students are better able to visualize concepts and that classroom exercises are promotingteam skills and academic rigor. Faculty interviews reveal enhanced awareness of studentmisconceptions and improved monitoring of student growth in conceptual understanding andinterpersonal skills.The poster and paper will highlight our findings and illustrate the CHAPL environment. Hands-on DLMs with cartridges used in teaching principles in the various disciplines will bedemonstrated. A survey will be offered to those viewing the poster to assess potential interest inadoption of the DLMs and in participating in an NSF Type III proposal for TransformingUndergraduate Engineering Education through use of the DLMs and associated CHAPLpedagogies

On Cartan matrices with two parameters (Cohomology theory of finite groups and related topics)

A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts

Malaria Box Heatmap.

<p>Shown are selected data from the HeatMap (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005763#ppat.1005763.s002" target="_blank">S1 Table</a>) for the 400 Malaria Box compounds. Each column represents an assay (grouped by category), compounds are represented in rows. The red-green gradient represents higher to lower activity. Favorable PK activities are scored green. <i>Pf</i>: <i>Plasmodium falciparum</i>, <i>Pb</i>: <i>Plasmodium berghei</i>, PK: pharmacokinetics, sol.: solubility, hERG: human ether-a-go-go channel inhibition, DDI: drug-drug interactions (predicted).</p

Metabolomic and chemogenomic profiling.

<p>(A) Metabolic profiling: Heat map showing metabolic fingerprints of 80 Malaria Box compounds and atovaquone control. Parasite extracts were analyzed by LC-MS, and changes in metabolite pools were calculated for drug-treated parasites as compared to untreated controls. Hierarchical clustering was performed on ²log-fold changes in metabolites (data in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005763#ppat.1005763.s003" target="_blank">S2 Table</a>), scaled from -3 to +3. Six of seven compounds (indicated in red) reported to target <i>Pf</i>ATP4 [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005763#ppat.1005763.ref025" target="_blank">25</a>] showed a distinct metabolic response characterized by the accumulation of dNTPs and a decrease in hemoglobin-derived peptides. A large cluster of compounds (indicated in blue) clustered with the atovaquone control (indicated in orange), and exhibit an atovaquone-like signature characterized by dysregulation of pyrimidine biosynthesis, and showed a distinct metabolic response characterized by the accumulation of dNTPs and a decrease in hemoglobin-derived peptides. (B) Chemogenomic profiling: A collection of 35 <i>P</i>. <i>falciparum</i> single insertion <i>piggyBac</i> mutants were profiled with 53 MMV compounds and 3 artemisinin (ART) compounds [Artesunate (AS), Artelinic acid (AL) and Artemether (AM)] for changes in IC₅₀ relative to the wild-type parent NF54 (data in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005763#ppat.1005763.s004" target="_blank">S3 Table</a>, genes queried in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005763#ppat.1005763.s005" target="_blank">S4 Table</a>). Clone PB58 carried a <i>piggyBac</i> insertion in the promoter region of the K13 gene and has an increased sensitivity to ART compounds as do PB54 and PB55 [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005763#ppat.1005763.ref033" target="_blank">33</a>]. Drug-drug relationships based on similarities in IC₅₀ deviations of compounds generated with <i>piggyBac</i> mutants created chemogenomic profiles used to define drug-drug relationships. The significance of similarity in MoA between Malaria Box compounds and ART was evaluated by Pearson’s correlation calculations from pairwise comparisons. The X axis shows the chemogenomic profile correlation between a Malaria Box compound and AS, the Y axis with AM; the color gradient indicates the average correlation with all ART derivatives tested. Five Malaria Box compounds (MMV006087, MMV006427, MMV020492, MMV665876, MMV396797) were identified as having similar drug-drug chemogenomic profiles to the ART sensitivity cluster.</p

Antiprotozoal Malaria Box compounds with activity in biological assays and lacking toxicity at therapeutic levels.

<p>Selectivity Index, SI, is toxicity level/activity level; p, probe-like; d, drug-like.</p