The truth of a madman: the works of Art Spiegelman

Art Spiegelman is one of the most important figures in the history of American comics. His work Maus (1980 and 1991) is arguably the landmark text in the field of comic book studies. Given the relatively recent reissue of his first collection Breakdowns (2008) and the publication of his interview/essay collection/scrapbook Metamaus (2011), it is likely that his work will continue to be the subject of critical interest. This thesis concerns the collections Breakdowns (1977 and 2008), Maus (1980 and 1991) and In the Shadow of No Towers (2004). It represents the first book-length extended study of Spiegelman s three major works. The central argument put forth in this thesis is that the Spiegelman oeuvre articulates and manifests a madness which its author perceives to underlie supposedly rational society. In support of this thesis I will employ critical models from the following fields: Holocaust studies, trauma theory, the anti-psychiatry movement, theories concerning the representation of madness, formalist analyses of comics, and Genette s narratological taxonomy

Coherent Picosecond Exciton Dynamics in a Photosynthetic Reaction Center

Photosynthetic reaction centers convert sunlight into a transmembrane electrochemical potential difference, providing chemical energy to almost all life on earth. Light energy is efficiently transferred through chromophore cofactors to the sites, where charge separation occurs. We applied two-dimensional electronic spectroscopy to assess the role of coherences in the photoresponse of the bacterial reaction center of Rhodobacter sphaeroides. By controlling the polarization of the laser beams, we were able to assign unambiguously the oscillatory dynamics to electronic (intermolecular) coherences. The data show that these coherences are sustained for more than 1 ps, indicating that the protein coherently retains some excitation energy on this time scale. Our finding provides a mechanism for effective delocalization of the excitations on the picosecond time scale by electronic coherence, setting the stage for efficient charge separation

Community Structure Comparison: Libshuff and Parsimony Statistical Analysis of Colon-Associated Bacterial Populations.

<p>Community Structure Comparison: Libshuff and Parsimony Statistical Analysis of Colon-Associated Bacterial Populations.</p

Richness, diversity and taxonomic analysis of the WT and Nod2 KO colon tissue-associated bacterial communities.

<p>Top panel: Incidence of phyla from treatment groups of WT and Nod2 KO littermates. Mean +/− SEM (n = 4–6) for each group is shown. * p≤0.05, ** p<0.01 by 2 way ANOVA with Bonferroni's multiple comparison test. Bottom panels: the Chao and Shannon estimates for richness and diversity were calculated from individual mice from each group as indicated (n = 4–6). The mean +/− SEM are shown. No differences were statistically significant by ANOVA.</p

Comparison of physical and histological parameters and bacterial load of WT and Nod2 KO littermates following DSS damage.

<p><b>A.</b> Timelines and histology assessment for individual mice. No significant difference was observed between the two genotypes for physical parameters (body weight loss, colon length: not shown) nor histological scores between the two groups (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030273#pone.0030273.s004" target="_blank">Figure S4</a> for data from 2 additional independent experiments). <b>B.</b> Colon, mesenteric lymph node and spleen tissue-associated bacterial loads assessed by FACS 42 days following DSS damage. ** = p≤0.01 by Anova with Bonferroni's multiple comparison test. <b>C.</b> Residence of commensal bacteria in the muscle layer in Nod2 KO mice. Examples of bacterial staining by EUB338 FISH probes are indicated by closed arrows in these representative images.</p

Phylogenetic tree visualisation of full length 16S rRNA sequences from WT and Nod2 KO mouse colon tissue 42 days post DSS or control as indicated.

<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030273#s4" target="_blank">Materials and Methods</a> for parameters.</p

Infiltration of colon by immune cells assessed by immunohistochemistry following DSS damage.

<p>Top panel provides timeline for the experiment with arrows indicating times of histological and immunohistochemical assessment. Representative images for each of the cell markers and from each of the time points are shown. H&E (haematoxylin/eosin histochemical stain), CD3 (T cell marker), F4/80 (macrophage marker) and GR-1/Ly-6G (granulocyte marker).</p

Temporal physical, histological and biomarker analysis of DSS damage.

<p>Mice were administered DSS in their drinking water from day 0 to day 5 and individual parameters outlined in each panel assessed by criteria described previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030273#pone.0030273-Smith1" target="_blank">[41]</a>. * = p≤0.05, ** = p≤0.01, *** = p≤0.001 by 1-way Anova with Bonferroni's multiple comparison test. <b>A.</b> Body weight (physiological parameter for progression of inflammation) expressed as mean +/− SEM, n = 7. <b>B.</b> Fecal Score (combined weighted score of intestinal damage based on the presence of blood in the stool and subjective assessment of diarrhea) as a physiological indicator of colon tissue damage expressed as mean +/− SEM, n = 7. <b>C.</b> Colon length (physiological parameter for progression of inflammation) expressed as mean +/− SEM, n = 7. Statistical comparisons are versus Naive (no DSS-treatment) mice. <b>D.</b> Histology Score (quantitative assessment of microscopic tissue damage identical to that described previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030273#pone.0030273-Smith1" target="_blank">[41]</a>) expressed as mean +/− SEM, n = 7. Statistical comparisons are versus Naive (no DSS-treatment) mice. <b>E.</b> Temporal cytokine (as indicated) profiles in colon homogenates from treated mice expressed as mean +/− SEM, n = 7. Statistical comparisons by Anova/Bonferroni. @ = p≤0.05 vs day 5, # = p≤0.05 vs day 8.</p

Proximity and progression of host/commensal interactions following DSS damage.

<p><b>A.</b> Localisation of commensal bacteria by EUB338 FISH probe analysis of FFPE sections from DSS-treated mice. Open arrows highlight examples of luminal or mucosal bacteria, closed arrows indicate bacteria associated with the muscle layers. E, epithelium. M, muscle. Bar = 50 µm. <b>B.</b> Quantification of colon tissue bacteria load in individual mice by FACS following DSS damage. * = p≤0.05, ** = p≤0.01, *** = p≤0.001 vs day 0 (no DSS treatment) by 1-way Anova with Bonferroni's correction.</p

Discovery of the First Potent, Selective, and Orally Bioavailable Signal Peptide Peptidase-Like 2a (SPPL2a) Inhibitor Displaying Pronounced Immunomodulatory Effects In Vivo

Signal peptide peptidase-like 2a (SPPL2a) is an aspartic intramembrane protease which has recently been shown to play an important role in the development and function of antigen presenting cells such as B lymphocytes and dendritic cells. In this paper, we describe the discovery of the first selective and orally active SPPL2a inhibitor (<i>S</i>)-2-cyclopropyl-<i>N</i>1-((<i>S</i>)-5,11-dioxo-10,11-dihydro-1<i>H</i>,3<i>H</i>,5<i>H</i>-spiro­[benzo­[<i>d</i>]­pyrazolo­[1,2-<i>a</i>]­[1,2]­diazepine-2,1′-cyclopropan]-10-yl)-<i>N</i>4-(5-fluoro-2-methylpyridin-3-yl)­succinamide <b>40</b> (<b>SPL-707</b>). This compound shows adequate selectivity against the closely related enzymes γ-secretase and SPP and a good pharmacokinetic profile in mouse and rat. Compound <b>40</b> significantly inhibited processing of the SPPL2a substrate CD74/p8 fragment in rodents at doses ≤10 mg/kg b.i.d. po. Oral dosing of <b>40</b> for 11 days at ≥10 mg/kg b.i.d. recapitulated the phenotype seen in Sppl2a knockout (ko) and ENU mutant mice (reduced number of specific B cells and myeloid dendritic cells). Thus, we believe that SPPL2a represents an interesting and druggable pharmacological target, potentially providing a novel approach for the treatment of autoimmune diseases by targeting B cells and dendritic cells