Coming to Nonviolence

A contributor to the second book that marked AEPL’s influence on scholarship traces the growth of his personal commitment to one of the organization’s foundational principles

Vielleicht hier, um zu sagen: Bildung and Elegy in the Duineser Elegien, Du côté de chez Swann, and Misérable miracle

In the wake of the industrialization, urbanization, and global conflicts of the late nineteenth and early twentieth centuries, Europe was forced to call into question its Enlightenment faith. In particular, Bildung—as the cultural education of the individual that emerged out of the Enlightenment—lost its footing amidst experience’s new texture of trauma. This thesis will examine Rilke’s Duineser Elegien, Proust’s Du côté de chez Swann, and Michaux’s Misérable miracle as each work pertains to and reconceives of the intertwining of Bildung and elegy, as a literary form both underpinned by and unconvinced of Bildung. For them, I will argue, elegy served as a potential form for re-writing historical indifference and for preparing, through limit-experience and loss, linguistic antidotes for the elision of difference produced in history’s wake

A duopoly of transportation network companies and traditional radio-taxi dispatch service agencies

Transportation network companies commonly enter the market for taxi ride intermediation and alter the market outcome. Compared to cooperatively organized radio-taxi dispatch service agencies, transportation network companies run larger fleets and serve more customers with lower fares, when the fixed costs of the dispatch office are relatively small. The same holds for private dispatch firms, when the fixed costs of a taxicab are not too small. These results are shown in a two-stage duopoly of fare and fleet size competition with fare- and waiting-timedependent demand

The LDL Receptor Clustering Motif Interacts with the Clathrin Terminal Domain in a Reverse Turn Conformation

Previously the hexapeptide motif FXNPXY807 in the cytoplasmic tail of the LDL receptor was shown to be essential for clustering in clathrin-coated pits. We used nuclear magnetic resonance line-broadening and transferred nuclear Overhauser effect measurements to identify the molecule in the clathrin lattice that interacts with this hexapeptide, and determined the structure of the bound motif. The wild-type peptide bound in a single conformation with a reverse turn at residues NPVY. Tyr807Ser, a peptide that harbors a mutation that disrupts receptor clustering, displayed markedly reduced interactions. Clustering motif peptides interacted with clathrin cages assembled in the presence or absence of AP2, with recombinant clathrin terminal domains, but not with clathrin hubs. The identification of terminal domains as the primary site of interaction for FXNPXY807 suggests that adaptor molecules are not required for receptor-mediated endocytosis of LDL, and that at least two different tyrosine-based internalization motifs exist for clustering receptors in coated pits

Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation

© Ankers et al. Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-κB) signalling and the cell cycle are prioritised differently depending on the timing of an inflammatory signal. Using iterative experimental and computational analyses, we show physical and functional interactions between NF-κB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. These interactions modulate the NF-κB response. In S-phase, the NF-κB response was delayed or repressed, while cell cycle progression was unimpeded. By contrast, activation of NF-κB at the G1/S boundary resulted in a longer cell cycle and more synchronous initial NF-κB responses between cells. These data identify new mechanisms by which the cellular response to stress is differentially controlled at different stages of the cell cycle

Phosphoinositide-AP-2 interactions required for targeting to plasma membrane clathrin-coated pits.

The clathrin-associated AP-2 adaptor protein is a major polyphosphoinositide-binding protein in mammalian cells. A high affinity binding site has previously been localized to the NH(2)-terminal region of the AP-2 alpha subunit (Gaidarov et al. 1996. J. Biol. Chem. 271:20922-20929). Here we used deletion and site- directed mutagenesis to determine that alpha residues 21-80 comprise a discrete folding and inositide-binding domain. Further, positively charged residues located within this region are involved in binding, with a lysine triad at positions 55-57 particularly critical. Mutant peptides and protein in which these residues were changed to glutamine retained wild-type structural and functional characteristics by several criteria including circular dichroism spectra, resistance to limited proteolysis, and clathrin binding activity. When expressed in intact cells, mutated alpha subunit showed defective localization to clathrin-coated pits; at high expression levels, the appearance of endogenous AP-2 in coated pits was also blocked consistent with a dominant-negative phenotype. These results, together with recent work indicating that phosphoinositides are also critical to ligand-dependent recruitment of arrestin-receptor complexes to coated pits (Gaidarov et al. 1999. EMBO (Eur. Mol. Biol. Organ.) J. 18:871-881), suggest that phosphoinositides play a critical and general role in adaptor incorporation into plasma membrane clathrin-coated pits

Neutrophils-A key component of ischemia-reperfusion injury

Ischemia-reperfusion injury (IRI) is a common occurrence following myocardial infarction, transplantation, stroke, and trauma that can lead to multiple organ failure, which remains the foremost cause of death in critically ill patients. Current therapeutic strategies for IRI are mainly palliative, and there is an urgent requirement for a therapeutic that could prevent or reverse tissue damage caused by IRI. Neutrophils are the primary responders following ischemia and reperfusion and represent important components in the protracted inflammatory response and severity associated with IRI. Experimental studies demonstrate neutrophil infiltration at the site of ischemia and show that inducing neutropenia can protect organs from IRI. In this review, we highlight the mechanisms involved in neutrophil recruitment, activation, and adherence and how this contributes to disease severity in IRI. Inhibiting neutrophil mobilization, tissue recruitment, and ultimately neutrophil-associated activation of local and systemic inflammatory responses may have therapeutic potential in the amelioration of local and remote tissue damage following IRI. Copyrigh