Ezra Cohen folio

An English-language folio of poetry by Ezra Cohen

Optical imaging through scattering media via magnetically modulated fluorescence

A weak (< 1000 G) magnetic field can influence photochemical processes through its effect on electron spin dynamics in a photogenerated radical pair. In a solution of pyrene and dimethylaniline this effect manifests as magnetic field-dependent exciplex fluorescence. Here we describe magnetofluorescence imaging (MFI). A localized magnetic null defines a fluorescence detection volume, which is scanned through a sample to create an image. MFI forms an image without lenses and in the presence of arbitrarily strong optical scattering. The resolution of MFI is in principle not limited by optical diffraction, although the present implementation is far from the diffraction limit.Chemistry and Chemical Biolog

Chiroptical Hot Spots in Twisted Nanowire Plasmonic Oscillators

We image the chiroptical response of crossed nanowire junctions as a function of the vertical offset between the nanowires and the incident wavelength. These samples show chiroptical “hot spots” with strongly localized circular differential scattering at the nanowire crossing points. These chiroptical hot spots are not apparent in the spatially averaged spectra. The sign and magnitude of the chiroptical enhancement show a complex dependence on sample geometry, which we reproduce with a fully retarded analytical scattering model. These results suggest strategies for engineering devices with enhanced chiral light-matter interactions.Chemistry and Chemical BiologyEngineering and Applied SciencesPhysic

Convex Lens-Induced Confinement for Imaging Single Molecules

Fluorescence imaging is used to study the dynamics of a wide variety of single molecules in solution or attached to a surface. Two key challenges in this pursuit are (1) to image immobilized single molecules in the presence of a high level of fluorescent background and (2) to image freely diffusing single molecules for long times. Strategies that perform well by one measure often perform poorly by the other. Here, we present a simple modification to a wide-field fluorescence microscope that addresses both challenges and dramatically improves single-molecule imaging. The technique of convex lens-induced confinement (CLIC) restricts molecules to a wedge-shaped gap of nanoscale depth, formed between a plano-convex lens and a planar coverslip. The shallow depth of the imaging volume leads to 20-fold greater rejection of background fluorescence than is achieved with total internal reflection fluorescence (TIRF) imaging. Elimination of out-of-plane diffusion leads to an approximately 10 000-fold longer diffusion-limited observation time per molecule than is achieved with confocal fluorescence correlation spectroscopy. The CLIC system also provides a new means to determine molecular size. The CLIC system does not require any nanofabrication, nor any custom optics, electronics, or computer control.Chemistry and Chemical BiologyPhysic

Reason in action: a realist account

This thesis argues against the Humean theory of practical reasons, criticising its foundations in philosophical and moral psychology. It develops a realist account of value-based reasons, underpinned by a distinctive cognitivist moral psychology, and a non-causalist account of the rational explanation of action. Contemporary Humeans reject Hume’s own theory of thought, but this leaves the Humean theory of practical reasons without justification for a conception of desire as non-cognitive and not open to fundamental rational evaluation. Two possible strategies for filling this justificatory gap are (i) an appeal to grammatical considerations about the attribution of desires and their content, or (ii) an appeal to distinctions in respect of direction of fit. I argue that neither is successful. Kant’s moral psychology provides the key to an alternative account, but is unsatisfactory due to its acceptance of a theory of thought which is relevantly similar to Hume’s, and of non-compulsory rationalist presuppositions. Separated from these aspects, Kant’s insights open a path to developing a conception of desire as essentially rationally evaluable. I argue that, in addition to such a conception, we should accept an account of rational attitudes as constitutively normative. On the basis of these two views, I argue that desire is a kind of evaluative belief. An independently plausible account of reasons takes them to be evaluative facts, and this neatly connects to the normative philosophical psychology. I consider the implications of such a view for the rational explanation of action, arguing that while causal theories of action and action-explanation are unacceptable, the normative philosophical psychology allows the development of non-causal alternatives to them. The non-causal account of action and action-explanation leaves space for an explanatory role for reasons themselves, beyond that provided by merely psychological explanation, as well as an explanatory role for an agent’s character and emotions

Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo.

Epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in squamous cell carcinoma of the head and neck (SCCHN). In addition to EGFR, other ErbB family members are expressed and activated in SCCHN. Afatinib is an ErbB family blocker that has been approved for treating patients with EGFR-mutated nonsmall cell lung cancer. We sought to determine the efficacy of afatinib in preclinical models and compare this to other EGFR-targeted agents. Afatinib efficacy was characterized in a panel of ten SCCHN cell lines and found to be most effective against cell lines amplified for EGFR. Afatinib had lower IC(50) values than did gefitinib against the same panel. Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib. Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo. Both afatinib and cetuximab were effective in tumor xenograft model. Afatinib is an effective agent in SCCHN especially in models with EGFR amplification