Stability landscape interpretation of how resilience of the normal mode of brain activity can be lost at high levels of base-line excitability as determined by genetically coded or other physiological conditions.

<p>The catastrophe fold at the base plane corresponds to the one depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072514#pone-0072514-g002" target="_blank">figure 2c</a>.</p

Graphical model showing how a tipping point for cortical spreading depression can arise.

<p>a) Three equilibriums may occur at intersection points where the rate of generation of new pulses (sigmoidal curve) equals the rate of decay (dashed line) of neural pulses. Activity increases when the generation of new pulses exceeds the decay of pulses (sections I and III) and decreases in the other sections (sections II and IV). It can be seen from the arrows representing this direction of change that the middle intersection point is a repellor that marks the border between the basins of attraction of the two alternative stable states. b) Increasing base-line excitability promotes the generation of new pulses causing the unstable equilibrium (open dot) and the stable normal state (left hand solid dot) to move closer together. This reduces resilience of the normal state in the sense that a smaller perturbation is needed to invoke a shift to the Aura state (horizontal dashed arrows in panel). c) Plotting how the intersection points representing equilibriums move as a function of base-line excitability, a catastrophe fold arises. The fold bifurcation point (F) marks the loss of stability of the normal state.</p

Causal structure that may lead to a tipping point for autonomous firing, as illustrated by the minimal model.

<p>Causal structure that may lead to a tipping point for autonomous firing, as illustrated by the minimal model.</p

Microtissue formation in the stamped Petri dish.

<p>(A) Pictures extracted from the movie presented in supplementary materials and showing the formation of C2C12 microtissues. (B) C2C12 spheroids array 24 h after cell seeding in a stamped Petri dish; enlarged view on 18 microtissues. (C) HepG2 spheroids in a stamped Petri dish after 24 h of culture; enlarged view on 4 microtissues. (D) Box-plot of the microtissue size 24 h after seeding showing that all four cell lines form homogenous microtissues (HeLa 369±33 μm; MCF-7 331±35 μm; Hep G2; 311±35 μm; and C2C12 206±34 μm).</p

Actin organization in microtissues.

<p>Off-Petri dish confocal imaging of HeLa monolayers (A) and microtissues (B) after staining of their nucleus with Hoechst (blue) and actin (green) using FITC-phalloidin showing complete reorganisation of the cell matrix protein (actin).</p

Butterfly with Wings Spread Stands Below Spider View 1

Play/Playwright: The Butterfly by Bijan Mofid.Irene Corey's Design Contribution: Costume, Mask, and Set Design.Characters: Spider (top), Butterfly (bottom).Company: Everyman Players.Duplicate: View 1

Fabrication of the stamped Petri dish.

<p>PDMS mold (A) employed for stamping microwell arrays in polystyrene-based Petri dish by hot embossing and presenting three arrays of 42 pits (200 μm height; 400 μm diameter, and 800 μm spacing). (B). Picture of a Petri dish after hot embossing of the microwell array. (C) Microscopy picture showing 21 independent wells in the polystyrene substrate.</p

Live/dead assay using SECM and fluorescence microscopy (membrane integrity markers).

<p>(A) SECM measurements performed at a constant height of 15 μm above the microtissue surface (scanning in a line across the center of the microtissues). (B) Variations in the oxygen concentration determined as relative variations in the oxygen reduction current for viable tissues (black line) and after exposure to 50% ethanol (grey line). Currents are normalized with respect to the current value far away from the microtissue (>250 μm, bulk concentration). Measurements performed in HEPES buffer at −0.6 V vs. Ag/AgCl with a 10 μm Hg-coated Pt working electrode; scan rate of 10 μm/s. (C &D) Corresponding (fluorescence) microscopy measurements using membrane integrity markers; tissues are initially loaded with calcein (green) (C) which is released out of the cells after ethanol treatment, while PI is taken up (D). Insets in C & D: bright field images of microtissues before and after ethanol treatment.</p

SECM assessment of the microtissue respiratory activity.

<p>(A) and (B) variations of the oxygen reduction current in solution as a function of the microelectrode surface distance when the microelectrode is approached from the bulk towards the Petri dish or the microtissue surface (center of the microtissue). (C) and (D) SECM scans over a 2-day old HeLa microtissue at different heights, along a line above the center of the microtissues, to monitor the microtissue oxygen consumption (Hg-coated Pt microelectrodel −0.6 V vs. Ag wire (reference electrode); scan rate of 10 μm/s). Currents are normalized with respect to the current value far away from the microtissue (>250 μm, bulk concentration).</p

Lab-on-a-Chip: Frontier Science in the Classroom

Lab-on-a-chip technology is brought into the classroom through development of a lesson series with hands-on practicals. Students can discover the principles of microfluidics with different practicals covering laminar flow, micromixing, and droplet generation, as well as trapping and counting beads. A quite affordable novel production technique using scissor-cut and laser-cut lamination sheets is presented, which provides good insight into how scientific lab-on-a-chip devices are produced. In this way high school students can now produce lab-on-a-chip devices using lamination sheets and their own lab-on-a-chip design. We begin with a review of previous reports on the use of lab-on-a-chip technology in classrooms, followed by an overview of the practicals and projects we have developed with student safety in mind. We conclude with an educational scenario and some initial promising results for student learning outcomes