Lynx1 Modulation of Nicotinic Acetylcholine Receptors

Nicotinic receptors are the target of nicotine in the brain. They are pentameric ion channels. The pentamer structure allows many combinations of receptors to be formed. These various subtypes exhibit specific properties determined by their subunit composition. Each brain region contains a fixed complement of nicotinic receptor subunits. The midbrain region is of particular interest because the dopaminergic neurons of the midbrain express several subtypes of nicotinic receptors, and these dopaminergic neurons are important for the rewarding effects of nicotine. The α6 nicotinic receptor subunit has garnered intense interest because it is present in dopaminergic neurons but very few other brain regions. With its specific and limited presence in the brain, targeting this subtype of nicotinic receptor may prove advantageous as a method for smoking cessation. However, we do not fully understand the trafficking and membrane localization of this receptor or its effects on dopamine release in the striatum. We hypothesized that lynx1, a known modulator of other nicotinic receptor subtypes, is important for the proper function of α6 nicotinic receptors. lynx1 has been found to act upon several classes of nicotinic receptors, such as α4β2 and α7, the two most common subtypes in the brain. To determine whether lynx1 affects α6 containing nicotinic receptors we used biochemistry, patch clamp electrophysiology, fast scan cyclic voltammetry, and mouse behavior. We found that lynx1 has effects on α6 containing nicotinic receptors, but the effects were subtle. This thesis will detail the observed effects of lynx1 on α6 nicotinic receptors.

Generalizations and extensions of the Fokker-Planck-Kolmogorov equations

The problem of determining probability density functions of general transformations of random processes is considered in this thesis. A method of solution is developed in which partial differential equations satisfied by the unknown density function are derived. These partial differential equations are interpreted as generalized forms of the classical Fokker-Planck-Kolmogorov equations and are shown to imply the classical equations for certain classes of Markov processes. Extensions of the generalized equations which overcome degeneracy occurring in the steady-state case are also obtained.

The equations of Darling and Siegert are derived as special cases of the generalized equations thereby providing unity to two previously existing theories. A technique for treating non-Markov processes by studying closely related Markov processes is proposed and is seen to yield the Darling and Siegert equations directly from the classical Fokker-Planck-Kolmogorov equations.

As illustrations of their applicability, the generalized Fokker-Planck-Kolmogorov equations are presented for certain joint probability density functions associated with the linear filter. These equations are solved for the density of the output of an arbitrary linear filter excited by Markov Gaussian noise and for the density of the output of an RC filter excited by the Poisson square wave. This latter density is also found by using the extensions of the generalized equations mentioned above. Finally, some new approaches for finding the output probability density function of an RC filter-limiter-RC filter system driven by white Gaussian noise are included. The results in this case exhibit the data required for complete solution and clearly illustrate some of the mathematical difficulties inherent to the use of the generalized equations.

Investigations into the structure and function of the exocrine pancreas of lampreys. [Translation from: Morph.Jb. 110 245-269, 1967.]

As representatives of the most primitive of recent vertebrate groups, lampreys show fundamental differences in different features of organisation to the species of the remaining classes of vertebrates. The topical distinction between exocrine and endocrine pancreas is also considered among the morphological peculiarities of Petromyzontida. This study aims to contribute to a further explanation of this phenomenon. 50 brook lampreys were histologically examined.

Enantioselective Total Synthesis of Diketopiperazinecontaining Natural Products: (–)-Lansai B, (+)-Nocardioazines A and B, and (–)-Acetylapoaranotin

Diketopiperazine (DKP) motif is found in a wide range of biologically active natural products. This work details our efforts toward two classes of DKP-containing natural products.

Class one features the pyrroloindoline structure, derived from tryptophans. Our group developed a highly enantioselective (3 + 2) formal cycloaddition between indoles and acrylates to provide pyrroloindoline products possessing three stereocenters. Utilizing this methodology, we accomplished asymmetric total synthesis of three natural products: (–)-lansai B, (+)-nocardioazines A and B. Total synthesis of (–)-lansai B was realized in six steps, and featured an amino acid dimerization strategy. The total synthesis of (+)-nocardioazine B was also successfully completed in ten steps. Challenges were met in approaching (+)-nocardioazine A, where a seemingly easy last-step epoxidization did not prove successful. After re-examining our synthetic strategy, an early-stage epoxidation strategy was pursued, which eventually yielded a nine-step total synthesis of (+)-nocardioazine A.

Class two is the epidithiodiketopiperazine (ETP) natural products, which possesses an additional episulfide bridge in the DKP core. With the goal of accessing ETPs with different peripheral structures for structure-activity relationship studies, a highly divergent route was successfully developed, which was showcased in the formal synthesis of (–)-emethallicin E and (–)-haematocin, and the first asymmetric synthesis of (–)-acetylapoaranotin.

Comparison of permanent and temporary streams of calcareous Provence [Translation from: Annales de Limnologie 9(3) 273-292, 1973]

The rainfall regime and the karstic nature of the subsoil determines the alternation of a period of flow and a period of drought for a large number of Mediterranean streams. Amongst this type of stream it is possible to distinguish temporary streams, characterised by a period of flow for several months permitting the establishment of the principal groups of aquatic insects; and ephemeral streams whose very brief period of flow permits the establishment of a community reduced to a few species of Diptera. This paper aims to study the structure of the communities which colonise this particular type of stream and the ecology of the principal species which constitute these communities. Four French temporary streams were examined and temperature regimes, dissolved oxygen, calcium and magnesium measured. Samples of fauna were taken regularly and the biotic composition established. The analysis of similarities between the three permanent streams are discussed and compared with permanent streams.

Recolonisation of temporary streams and evolution of a degree of stability of the zoocenose [Translation from: Ecologia Mediterranea No.1 149-164, 1976]

When flow returns to a temporary stream a certain number of plant and animal species establish themselves more or less rapidly on the stream-bed constituting the initial phase of evolution of the re-population. This phase is essentially characterised by the ”awakening” of animal species that passed the dry season in a dormant state and by the development of the first unicellular algae that constitute the periphyton. Then they are succeeded by more or less stable animal groups and the structural complexity increases. The authors of the present study aim to analyse the dynamics of community succession from the return of water to the biotope until its drying up. It is attempted to determine the influence of the duration of flow on this evolution. This work is based on the analysis of population diversity with reference to its two complementary aspects, species richness and equitability. The River Destel which was studied for this project is situated in the Gorge of Ollioules near the town of Toulon.

The Atmospheric Dynamics of Pulsar Companions

Pulsars emit radiation over an extremely wide frequency range, from radio through gamma. Recently, systems in which this radiation significantly alters the atmospheres of low-mass pulsar companions have been discovered. These systems, ranging from ones with highly anisotropic heating to those with transient X-ray emissions, represent an exciting opportunity to investigate pulsars through the changes they induce in their companions. In this work, we present both analytic and numerical work investigating these phenomena, with a particular focus on atmospheric heat transport, transient phenomena, and the possibility of deep heating via gamma rays. We find that certain classes of binary systems may explain decadal-timescale X-ray transient phenomena, as well as the formation of so-called redback companion systems. We also posit an explanation for the formation of high-eccentricity millisecond pulsars with white dwarf companions. In addition, we examine the temperature anisotropy induced by the Pulsar in its companion, and demonstrate that this may be used to infer properties of both the companion and the Pulsar wind. Finally, we explore the possibility of spontaneously generated banded winds in rapidly rotating convecting objects.

A computer-aided investigation of motion detection units in the fly

This work deals with two related areas: processing of visual information in the central nervous system, and the application of computer systems to research in neurophysiology.

Certain classes of interneurons in the brain and optic lobes of the blowfly Calliphora phaenicia were previously shown to be sensitive to the direction of motion of visual stimuli. These units were identified by visual field, preferred direction of motion, and anatomical location from which recorded. The present work is addressed to the questions: (1) is there interaction between pairs of these units, and (2) if such relationships can be found, what is their nature. To answer these questions, it is essential to record from two or more units simultaneously, and to use more than a single recording electrode if recording points are to be chosen independently. Accordingly, such techniques were developed and are described.

One must also have practical, convenient means for analyzing the large volumes of data so obtained. It is shown that use of an appropriately designed computer system is a profitable approach to this problem. Both hardware and software requirements for a suitable system are discussed and an approach to computer-aided data analysis developed. A description is given of members of a collection of application programs developed for analysis of neuro-physiological data and operated in the environment of and with support from an appropriate computer system. In particular, techniques developed for classification of multiple units recorded on the same electrode are illustrated as are methods for convenient graphical manipulation of data via a computer-driven display.

By means of multiple electrode techniques and the computer-aided data acquisition and analysis system, the path followed by one of the motion detection units was traced from open optic lobe through the brain and into the opposite lobe. It is further shown that this unit and its mirror image in the opposite lobe have a mutually inhibitory relationship. This relationship is investigated. The existence of interaction between other pairs of units is also shown. For pairs of units responding to motion in the same direction, the relationship is of an excitatory nature; for those responding to motion in opposed directions, it is inhibitory.

Experience gained from use of the computer system is discussed and a critical review of the current system is given. The most useful features of the system were found to be the fast response, the ability to go from one analysis technique to another rapidly and conveniently, and the interactive nature of the display system. The shortcomings of the system were problems in real-time use and the programming barrier—the fact that building new analysis techniques requires a high degree of programming knowledge and skill. It is concluded that computer system of the kind discussed will play an increasingly important role in studies of the central nervous system.

Range of validity of the method of averaging

Sufficient conditions are derived for the validity of approximate periodic solutions of a class of second order ordinary nonlinear differential equations. An approximate solution is defined to be valid if an exact solution exists in a neighborhood of the approximation.

Two classes of validity criteria are developed. Existence is obtained using the contraction mapping principle in one case, and the Schauder-Leray fixed point theorem in the other. Both classes of validity criteria make use of symmetry properties of periodic functions, and both classes yield an upper bound on a norm of the difference between the approximate and exact solution. This bound is used in a procedure which establishes sufficient stability conditions for the approximated solution.

Application to a system with piecewise linear restoring force (bilinear system) reveals that the approximate solution obtained by the method of averaging is valid away from regions where the response exhibits vertical tangents. A narrow instability region is obtained near one-half the natural frequency of the equivalent linear system. Sufficient conditions for the validity of resonant solutions are also derived, and two term harmonic balance approximate solutions which exhibit ultraharmonic and subharmonic resonances are studied.

Symmetric representation of an integral domain over a subdomain

Let F(θ) be a separable extension of degree n of a field F. Let Δ and D be integral domains with quotient fields F(θ) and F respectively. Assume that Δ ᴝ D. A mapping φ of Δ into the n x n D matrices is called a Δ/D rep if (i) it is a ring isomorphism and (ii) it maps d onto dI_n whenever d ϵ D. If the matrices are also symmetric, φ is a Δ/D symrep.

Every Δ/D rep can be extended uniquely to an F(θ)/F rep. This extension is completely determined by the image of θ. Two Δ/D reps are called equivalent if the images of θ differ by a D unimodular similarity. There is a one-to-one correspondence between classes of Δ/D reps and classes of Δ ideals having an n element basis over D.

The condition that a given Δ/D rep class contain a Δ/D symrep can be phrased in various ways. Using these formulations it is possible to (i) bound the number of symreps in a given class, (ii) count the number of symreps if F is finite, (iii) establish the existence of an F(θ)/F symrep when n is odd, F is an algebraic number field, and F(θ) is totally real if F is formally real (for n = 3 see Sapiro, “Characteristic polynomials of symmetric matrices” Sibirsk. Mat. Ž. 3 (1962) pp. 280-291), and (iv) study the case D = Z, the integers (see Taussky, “On matrix classes corresponding to an ideal and its inverse” Illinois J. Math. 1 (1957) pp. 108-113 and Faddeev, “On the characteristic equations of rational symmetric matrices” Dokl. Akad. Nauk SSSR 58 (1947) pp. 753-754).

The case D = Z and n = 2 is studied in detail. Let Δ’ be an integral domain also having quotient field F(θ) and such that Δ’ ᴝ Δ. Let φ be a Δ/Z symrep. A method is given for finding a Δ’/Z symrep ʘ such that the Δ’ ideal class corresponding to the class of ʘ is an extension to Δ’ of the Δ ideal class corresponding to the class of φ. The problem of finding all Δ/Z symreps equivalent to a given one is studied.

Entrainment of fine sediments by turbulent flows

A study was made of the means by which turbulent flows entrain sediment grains from alluvial stream beds. Entrainment was considered to include both the initiation of sediment motion and the suspension of grains by the flow. Observations of grain motion induced by turbulent flows led to the formulation of an entrainment hypothesis. It was based on the concept of turbulent eddies disrupting the viscous sublayer and impinging directly onto the grain surface. It is suggested that entrainment results from the interaction between fluid elements within an eddy and the sediment grains.

A pulsating jet was used to simulate the flow conditions in a turbulent boundary layer. Evidence is presented to establish the validity of this representation. Experiments were made to determine the dependence of jet strength, defined below, upon sediment and fluid properties. For a given sediment and fluid, and fixed jet geometry there were two critical values of jet strength: one at which grains started to roll across the bed, and one at which grains were projected up from the bed. The jet strength K, is a function of the pulse frequency, ω, and the pulse amplitude, A, defined by

K = Aω^-s

Where s is the slope of a plot of log A against log ω. Pulse amplitude is equal to the volume of fluid ejected at each pulse divided by the cross sectional area of the jet tube.

Dimensional analysis was used to determine the parameters by which the data from the experiments could be correlated. Based on this, a method was devised for computing the pulse amplitude and frequency necessary either to move or project grains from the bed for any specified fluid and sediment combination.

Experiments made in a laboratory flume with a turbulent flow over a sediment bed are described. Dye injection was used to show the presence, in a turbulent boundary layer, of two important aspects of the pulsating jet model and the impinging eddy hypothesis. These were the intermittent nature of the sublayer and the presence of velocities with vertical components adjacent to the sediment bed.

A discussion of flow conditions, and the resultant grain motion, that occurred over sediment beds of different form is given. The observed effects of the sediment and fluid interaction are explained, in each case, in terms of the entrainment hypothesis.

The study does not suggest that the proposed entrainment mechanism is the only one by which grains can be entrained. However, in the writer’s opinion, the evidence presented strongly suggests that the impingement of turbulent eddies onto a sediment bed plays a dominant role in the process.

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).

Turbulent buoyant jets into stratified or flowing ambient fluids

Theoretical and experimental studies were made on two classes of buoyant jet problems, namely:

1) an inclined, round buoyant yet in a stagnant environment with linear density-stratification;

2) a round buoyant jet in a uniform cross stream of homogenous density.

Using the integral technique of analysis, assuming similarity, predictions can be made for jet trajectory, widths, and dilution ratios, in a density-stratified or flowing environment. Such information is of great importance in the design of disposal systems for sewage effluent into the ocean or waste gases into the atmosphere.

The present study of a buoyant jet in a stagnant environment has extended the Morton type of analysis to cover the effect of the initial angle of discharge. Numerical solutions have been presented for a range of initial conditions. Laboratory experiments were conducted for photographic observations of the trajectories of dyed jets. In general the observed jet forms agreed well with the calculated trajectories and nominal half widths when the value of the entrainment coefficient was taken to be α = 0.082, as previously suggested by Morton.

The problem of a buoyant jet in a uniform cross stream was analyzed by assuming an entrainment mechanism based upon the vector difference between the characteristic jet velocity and the ambient velocity. The effect of the unbalanced pressure field on the sides of the jet flow was approximated by a gross drag term. Laboratory flume experiments with sinking jets which are directly analogous to buoyant jets were performed. Salt solutions were injected into fresh water at the free surface in a flume. The jet trajectories, dilution ratios and jet half widths were determined by conductivity measurements. The entrainment coefficient, α, and drag coefficient, C_d, were found from the observed jet trajectories and dilution ratios. In the ten cases studied where jet Froude number ranged from 10 to 80 and velocity ratio (jet: current) K from 4 to 16, α varied from 0.4 to 0.5 and C_d from 1.7 to 0.1. The jet mixing motion for distance within 250D was found to be dominated by the self-generated turbulence, rather than the free-stream turbulence. Similarity of concentration profiles has also been discussed.

Aerodynamics of vertical-axis wind turbines in full-scale and laboratory-scale experiments

Within a wind farm, multiple turbine wakes can interact and have a substantial effect on the overall power production. This makes an understanding of the wake recovery process critically important to optimizing wind farm efficiency. Vertical-axis wind turbines (VAWTs) exhibit features that are amenable to dramatically improving this efficiency. However, the physics of the flow around VAWTs is not well understood, especially as it pertains to wake interactions, and it is the goal of this thesis to partially fill this void. This objective is approached from two broadly different perspectives: a low-order view of wind farm aerodynamics, and a detailed experimental analysis of the VAWT wake.

One of the contributions of this thesis is the development of a semi-empirical model of wind farm aerodynamics, known as the LRB model, that is able to predict turbine array configurations to leading order accuracy. Another contribution is the characterization of the VAWT wake as a function of turbine solidity. It was found that three distinct regions of flow exist in the VAWT wake: (1) the near wake, where periodic blade shedding of vorticity dominates; (2) a transition region, where growth of a shear-layer instability occurs; (3) the far wake, where bluff-body oscillations dominate. The wake transition can be predicted using a new parameter, the dynamic solidity, which establishes a quantitative connection between the wake of a VAWT and that of a circular cylinder. The results provide insight into the mechanism of the VAWT wake recovery and the potential means to control it.

The unsteady forces on slender delta wing hydrofoils oscillating in heave

The investigations described herein are both experimental and theoretical. An experimental technique is described by which the models tested could be oscillated sinusoidally in heave. The apparatus used to gather the unsteady lift, drag and pitching moment data is also described.

The models tested were two flat delta wings with apex angles of 15° and 30° and they had sharp leading edges to insure flow separation. The models were fabricated from 0.25 inch aluminum plate and were approximately one foot in length.

Three distinct types of flow were investigated: 1) fully wetted, 2) ventilated and 3) planing. The experimental data are compared with existing theories for steady motions in the case of fully wetted delta wings. Ventilation measurements, made only for the 30° model at 20° angle of attack, of lift and drag are presented.

A correction of the theory proposed by M.P. Tulin for high speed planing of slender bodies is presented and it is extended to unsteady motions. This is compared to the experimental measurements made at 6° and 12° angle of attack for the two models previously described.

This is the first extensive measurement of unsteady drag for any shape wing, the first measurement of unsteady planing forces, the first quantitative documentation of unstable oscillations near a free surface, and the first measurements of the unsteady forces on ventilated delta wings. The results of these investigations, both theoretical and experimental, are discussed and further investigations suggested.