The biological sense of smell: olfactory search behavior and a metabolic view for olfactory perception

Part I of the thesis describes the olfactory searching and scanning behaviors of rats in a wind tunnel, and a detailed movement analysis of terrestrial arthropod olfactory scanning behavior. Olfactory scanning behaviors in rats may be a behavioral correlate to hippocampal place cell activity.

Part II focuses on the organization of olfactory perception, what it suggests about a natural order for chemicals in the environment, and what this in tum suggests about the organization of the olfactory system. A model of odor quality space (analogous to the "color wheel") is presented. This model defines relationships between odor qualities perceived by human subjects based on a quantitative similarity measure. Compounds containing Carbon, Nitrogen, or Sulfur elicit odors that are contiguous in this odor representation, which thus allows one to predict the broad class of odor qualities a compound is likely to elicit. Based on these findings, a natural organization for olfactory stimuli is hypothesized: the order provided by the metabolic process. This hypothesis is tested by comparing compounds that are structurally similar, perceptually similar, and metabolically similar in a psychophysical cross-adaptation paradigm. Metabolically similar compounds consistently evoked shifts in odor quality and intensity under cross-adaptation, while compounds that were structurally similar or perceptually similar did not. This suggests that the olfactory system may process metabolically similar compounds using the same neural pathways, and that metabolic similarity may be the fundamental metric about which olfactory processing is organized. In other words, the olfactory system may be organized around a biological basis.

The idea of a biological basis for olfactory perception represents a shift in how olfaction is understood. The biological view has predictive power while the current chemical view does not, and the biological view provides explanations for some of the most basic questions in olfaction, that are unanswered in the chemical view. Existing data do not disprove a biological view, and are consistent with basic hypotheses that arise from this viewpoint.

How far from Jerusalem? Tropical customs and the question of race in the Book of John Mandeville

The Book of John Mandeville, while ostensibly a pilgrimage guide documenting an English knight’s journey into the East, is an ideal text in which to study the developing concept of race in the European Middle Ages. The Mandeville-author’s sense of place and morality are inextricably linked to each other: Jerusalem is the center of his world, which necessarily forces Africa and Asia to occupy the spiritual periphery. Most inhabitants of Mandeville’s landscapes are not monsters in the physical sense, but at once startlingly human and irreconcilably alien in their customs. Their religious heresies, disordered sexual appetites, and monstrous acts of cannibalism label them as fallen state of the European Christian self. Mandeville’s monstrosities lie not in the fantastical, but the disturbingly familiar, coupling recognizable humans with a miscarriage of natural law. In using real people to illustrate the moral degeneracy of the tropics, Mandeville’s ethnography helps shed light on the missing link between medieval monsters and modern race theory.

Projections in a normed linear space and a generalization of the pseudo-inverse

The concept of a "projection function" in a finite-dimensional real or complex normed linear space H (the function P_M which carries every element into the closest element of a given subspace M) is set forth and examined.

If dim M = dim H - 1, then P_M is linear. If P_N is linear for all k-dimensional subspaces N, where 1 ≤ k < dim M, then P_M is linear.

The projective bound Q, defined to be the supremum of the operator norm of P_M for all subspaces, is in the range 1 ≤ Q < 2, and these limits are the best possible. For norms with Q = 1, P_M is always linear, and a characterization of those norms is given.

If H also has an inner product (defined independently of the norm), so that a dual norm can be defined, then when P_M is linear its adjoint P_M^H is the projection on (kernel P_M)^⊥ by the dual norm. The projective bounds of a norm and its dual are equal.

The notion of a pseudo-inverse F⁺ of a linear transformation F is extended to non-Euclidean norms. The distance from F to the set of linear transformations G of lower rank (in the sense of the operator norm ∥F - G∥) is c/∥F⁺∥, where c = 1 if the range of F fills its space, and 1 ≤ c < Q otherwise. The norms on both domain and range spaces have Q = 1 if and only if (F⁺)⁺ = F for every F. This condition is also sufficient to prove that we have (F⁺)^H = (F^H)⁺, where the latter pseudo-inverse is taken using dual norms.

In all results, the real and complex cases are handled in a completely parallel fashion.

Stability of parametrically excited differential equations

Sufficient stability criteria for classes of parametrically excited differential equations are developed and applied to example problems of a dynamical nature.

Stability requirements are presented in terms of 1) the modulus of the amplitude of the parametric terms, 2) the modulus of the integral of the parametric terms and 3) the modulus of the derivative of the parametric terms.

The methods employed to show stability are Liapunov’s Direct Method and the Gronwall Lemma. The type of stability is generally referred to as asymptotic stability in the sense of Liapunov.

The results indicate that if the equation of the system with the parametric terms set equal to zero exhibits stability and possesses bounded operators, then the system will be stable under sufficiently small modulus of the parametric terms or sufficiently small modulus of the integral of the parametric terms (high frequency). On the other hand, if the equation of the system exhibits individual stability for all values that the parameter assumes in the time interval, then the actual system will be stable under sufficiently small modulus of the derivative of the parametric terms (slowly varying).

Nature of the radical intermediates in a substituted cyclopropylcarbiny-allylcarbinyl system

We have sought to determine the nature of the free-radical precursors to ring-opened hydrocarbon 5 and ring-closed hydrocarbon 6. Reasonable alternative formulations involve the postulation of hydrogen abstraction (a) by a pair of rapidly equilibrating classical radicals (the ring-opened allylcarbinyl-type radical 3 and the ring-closed cyclopropylcarbinyl-type 4), or (b) by a nonclassical radical such as homoallylic radical 7.

[Figure not reproduced.]

Entry to the radical system is gained via degassed thermal decomposition of peresters having the ring-opened and the ring-closed structures. The ratio of 6:5 is essentially independent of the hydrogen donor concentration for decomposition of the former at 125° in the presence of triethyltin hydrdride. A deuterium labeling study showed that the α and β methylene groups in 3 (or the equivalent) are rapidly interchanged under these conditions.

Existence of two (or more) product-forming intermediates is indicated (a) by dependence of the ratio 6:5 on the tin hydride concentration for decomposition of the ring-closed perester at 10 and 35°, and (b) by formation of cage products having largely or wholly the structure (ring-opened or ring-closed) of the starting perester.

Relative rates of hydrogen abstraction by 3 could be inferred by comparison of ratios of rate constants for hydrogen abstraction and ortho-ring cyclization:

[Figure not reproduced.]

At 100° values of k_a/k_r are 0.14 for hydrogen abstraction from 1,4-cyclohexadiene and 7 for abstraction from triethyltin hydride. The ratio 6:5 at the same temperature is ~0.0035 for hydrogen abstraction from 1,4-cyclohexadiene, ~0.078 for abstraction from the tin hydride, and ≥ 5 for abstraction from cyclohexadienyl radicals. These data indicate that abstraction of hydrogen from triethyltin hydride is more rapid than from 1,4-cyclohexadiene by a factor of ~1000 for 4, but only ~50 for 3.

Measurements of product ratios at several temperatures allowed the construction of an approximate energy-level scheme. A major inference is that isomerization of 3 to 4 is exothermic by 8 ± 3 kcal/mole, in good agreement with expectations based on bond dissociation energies. Absolute rate-constant estimates are also given.

The results are nicely compatible with a classical-radical mechanism, but attempted interpretation in terms of a nonclassical radical precursor of product ratios formed even from equilibrated radical intermediates leads, it is argued, to serious difficulties.

The roles played by hydrogen abstraction from 1,4,-cyclohexadiene and from the derived cyclohexadienyl radicals were probed by fitting observed ratios of 6:5 and 5:10 in the sense of least-squares to expressions derived for a complex mechanistic scheme. Some 30 to 40 measurements on each product ratio, obtained under a variety of experimental conditions, could be fit with an average deviation of ~6%. Significant systematic deviations were found, but these could largely be redressed by assuming (a) that the rate constant for reaction of 4 with cyclohexadienyl radical is inversely proportional to the viscosity of the medium (i.e., is diffusion-controlled), and (b) that k_a/k_r for hydrogen abstraction from 1,4-cyclohexadiene depends slightly on the composition of the medium. An average deviation of 4.4% was thereby attained.

Degassed thermal decomposition of the ring-opened perester in the presence of the triethyltin hydride occurs primarily by attack on perester of triethyltin radicals, presumably at the –O-O- bond, even at 0.01 M tin hydride at 100 and 125°. Tin ester and tin ether are apparently formed in closely similar amounts under these conditions, but the tin ester predominates at room temperature in the companion air-induced decomposition, indicating that attack on perester to give the tin ether requires an activation energy approximately 5 kcal/mole in excess of that for the formation of tin ester.