A Design Approach for Collaboration Processes: A Multi-Method Design Science Study in Collaboration Engineering

Collaboration Engineering is an approach for the design and deployment of repeatable collaboration processes that can be executed by practitioners without the support of collaboration professionals such as facilitators. A critical challenge in Collaboration Engineering concerns how the design activities have to be executed and which design choices have to be made to create a process design. We report on a four year design science study, in which we developed a design approach for Collaboration Engineering thatincorporates existing process design methods, pattern based design principles, and insights from expert facilitators regarding design challenges and choices. The resulting approach was evaluated and continuously improved in four trials with 37 students. Our findings suggest that this approach is useful to support the design of repeatable collaboration processes. Our study further serves as an example of how a design approach can be developed and improved following a multi-method design science approach.Multi Actor SystemsTechnology, Policy and Managemen

Chemical moieties associated with CYP inhibition.

<p>Chemical moieties associated with CYP inhibition.</p

Trends of control 1 (closed circles, solvent only control, 0% inhibition), control 2 (open circles, reaction in absence of bactosomes, 100% inhibition) and Z’ (grey squares) of representative high-throughput screening runs of <i>T</i>. <i>cruzi</i> CYP51 FLINT (a) and cytochrome c reductase absorbance (b) assays in 384 well format.

<p>Error bars are the standard deviations of 16 replicates for each control and plate.</p

IC₅₀ Determination of a test set of compounds.

<p>^<b>a</b> Coefficient of variation for all IC₅₀’s were lower than 1%</p><p>IC₅₀ Determination of a test set of compounds.</p

DDD compounds are trypanocidal against purified intracellular amastigotes.

<p>Total number of parasites in each well was counted to evaluate the cytotoxicity of the compounds <b>1</b>, <b>5</b>, and <b>8</b> against purified ICA (<b>A</b>) and Epi (<b>B</b>). C, controls: Untreated, DMSO, and H₂O₂.</p

Alignment of <i>T</i>. <i>cruzi</i> NMT with NMTs from <i>T</i>. <i>brucei</i>, <i>L</i>. <i>major</i> and human.

<p>The deduced open reading frame of <i>Tc</i>NMT (AI069625) was aligned with <i>Tb</i>NMT (TRYP10.0.001826–6), <i>Lm</i>NMT (AF3059561), and human NMT (<i>Hs</i>NMT) (<i>HUMAN</i>, P30419) using the ClustalW2 multiple sequence alignment program (<a href="http://www.ebi.ac.uk/Tools/msa/clustalw2/" target="_blank">http://www.ebi.ac.uk/Tools/msa/clustalw2/</a>). Strictly conserved residues are shown in red. The insertions in protozoan NMTs (<i>Tc</i>NMT, <i>Tb</i>NMT, and <i>Lm</i>NMT) are underlined. Red boxes indicate key residues involved in myristoyl-CoA binding; black boxes indicate residues involved in peptide binding identified in yeast species. Arrows identify the pocket floor residues in <i>C</i>. <i>albicans</i>.</p

DDD compounds inhibit intracellular proliferation of <i>T</i>. <i>cruzi</i>.

<p>(<b>A</b>) Representative images of cells treated with the vehicle control (DMSO), untreated, treated with 800 μM benznidazole (BZ) or 10 μM compound <b>8</b>, stained with Draq5 (left panel), and analyzed by HCI. Artificial images created after segmentation on the fluorescence bioimager (right panel). Host cells are shown in blue, extracellular parasites in red and intracellular parasites in pink. (<b>B</b>) The multiparametric data obtained on a cell-by-cell basis by HCI was analyzed to determine several parameters associated to infection of host cells by <i>T</i>. <i>cruzi</i> including the percentage of cells infected with at least five parasites (percentage of cells in which the parasite proliferated), treated or not with DDD compounds <b>1–8</b>. C, controls: 40, 400, and 800 μM BZ, DMSO, and Untreated.</p

Anti-TcNMT shows no cross-reactivity with human cells.

<p>Immunofluorescence microscopy of non-infected and infected cells 72- and 96-h post-infection stained with anti-TcNMT (red), co-stained with DAPI (blue) to visualize host cell and parasite DNA. Scale bar, 10 μm.</p

EC₅₀ values and selectivity index (S.I.) of DDD compounds in noninfected and <i>T</i>. <i>cruzi</i>-infected U2OS cells, and purified intracellular amastigotes.

<p>(<b>a</b> and <b>b</b>) Non-infected and infected U2OS cells, respectively, were incubated for 48 h at 37°C with DDD compounds 1–8. (<b>c</b>) Purified ICAs were incubated for 24 h at 37°C with DDD compounds 1–8. (<b>d</b>) Not determined.</p

TcNMT is overexpressed in epimastigotes treated with DDD compounds.

<p>Epi forms were treated for 12 h with or without 10 μM of compound <b>1</b>, <b>5</b>, or <b>8</b>. Levels of NMT expression were confirmed by western blotting using anti-TcNMT. BiP (binding protein) was used as a loading control.</p