Neural routing circuits for forming invariant representations of visual objects

This thesis presents a biologically plausible model of an attentional mechanism for forming position- and scale-invariant representations of objects in the visual world. The model relies on a set of control neurons to dynamically modify the synaptic strengths of intra-cortical connections so that information from a windowed region of primary visual cortex (Vl) is selectively routed to higher cortical areas. Local spatial relationships (i.e., topography) within the attentional window are preserved as information is routed through the cortex, thus enabling attended objects to be represented in higher cortical areas within an object-centered reference frame that is position and scale invariant. The representation in V1 is modeled as a multiscale stack of sample nodes with progressively lower resolution at higher eccentricities. Large changes in the size of the attentional window are accomplished by switching between different levels of the multiscale stack, while positional shifts and small changes in scale are accomplished by translating and rescaling the window within a single level of the stack. The control signals for setting the position and size of the attentional window are hypothesized to originate from neurons in the pulvinar and in the deep layers of visual cortex. The dynamics of these control neurons are governed by simple differential equations that can be realized by neurobiologically plausible circuits. In pre-attentive mode, the control neurons receive their input from a low-level "saliency map" representing potentially interesting regions of a scene. During the pattern recognition phase, control neurons are driven by the interaction between top-down (memory) and bottom-up (retinal input) sources. The model respects key neurophysiological, neuroanatomical, and psychophysical data relating to attention, and it makes a variety of experimentally testable predictions.

Pharmacology and pore-forming domains of the cystic fibrosis transmembrane conductance regulator

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel member of the ATP-binding cassette (ABC) superfamily of membrane proteins. CFTR has two homologous halves, each consisting of six transmembrane spanning domains (TM) followed by a nucleotide binding fold, connected by a regulatory (R) domain. This thesis addresses the question of which domains are responsible for Cl^- selectivity, i.e., which domains line the channel pore.

To address this question, novel blockers of CFTR were characterized. CFTR was heterologously expressed in Xenopus oocytes to study the mechanism of block by two closely related arylaminobenzoates, diphenylamine-2-carboxylic acid (DPC) and flufenamic acid (FFA). Block by both is voltage-dependent, with a binding site ≈ 40% through the electric field of the membrane. DPC and FFA can both reach their binding site from either side of the membrane to produce a flickering block of CFTR single channels. In addition, DPC block is influenced by Cl^- concentration, and DPC blocks with a bimolecular forward binding rate and a unimolecular dissociation rate. Therefore, DPC and FFA are open-channel blockers of CFTR, and a residue of CFTR whose mutation affects their binding must line the pore.

Screening of site-directed mutants for altered DPC binding affinity reveals that TM-6 and TM-12 line the pore. Mutation of residue 5341 in TM-6 abolishes most DPC block, greatly reduces single-channel conductance, and alters the direction of current rectification. Additional residues are found in TM-6 (K335) and TM-12 (T1134) whose mutations weaken or strengthen DPC block; other mutations move the DPC binding site from TM-6 to TM-12. The strengthened block and lower conductance due to mutation T1134F is quantitated at the single-channel level. The geometry of DPC and of the residues mutated suggest α-helical structures for TM-6 and TM-12. Evidence is presented that the effects of the mutations are due to direct side-chain interaction, and not to allosteric effects propagated through the protein. Mutations are also made in TM-11, including mutation S1118F, which gives voltage-dependent current relaxations. The results may guide future studies on permeation through ABC transporters and through other Cl^- channels.

A mathematical study of finite-amplitude rock-folding

The problem of the finite-amplitude folding of an isolated, linearly viscous layer under compression and imbedded in a medium of lower viscosity is treated theoretically by using a variational method to derive finite difference equations which are solved on a digital computer. The problem depends on a single physical parameter, the ratio of the fold wavelength, L, to the "dominant wavelength" of the infinitesimal-amplitude treatment, L_d. Therefore, the natural range of physical parameters is covered by the computation of three folds, with L/L_d = 0, 1, and 4.6, up to a maximum dip of 90°.

Significant differences in fold shape are found among the three folds; folds with higher L/L_d have sharper crests. Folds with L/L_d = 0 and L/L_d = 1 become fan folds at high amplitude. A description of the shape in terms of a harmonic analysis of inclination as a function of arc length shows this systematic variation with L/L_d and is relatively insensitive to the initial shape of the layer. This method of shape description is proposed as a convenient way of measuring the shape of natural folds.

The infinitesimal-amplitude treatment does not predict fold-shape development satisfactorily beyond a limb-dip of 5°. A proposed extension of the treatment continues the wavelength-selection mechanism of the infinitesimal treatment up to a limb-dip of 15°; after this stage the wavelength-selection mechanism no longer operates and fold shape is mainly determined by L/L_d and limb-dip.

Strain-rates and finite strains in the medium are calculated f or all stages of the L/L_d = 1 and L/L_d = 4.6 folds. At limb-dips greater than 45° the planes of maximum flattening and maximum flattening rat e show the characteristic orientation and fanning of axial-plane cleavage.

The intergalactic and circumgalactic medium surrounding star-forming galaxies at redshifts 2 < z < 3

We present measurements of the spatial distribution, kinematics, and physical properties of gas in the circumgalactic medium (CGM) of 2.0<z<2.8 UV color-selected galaxies as well as within the 2<z<3 intergalactic medium (IGM). These measurements are derived from Voigt profile decomposition of the full Lyα and Lyβ forest in 15 high-resolution, high signal-to-noise ratio QSO spectra resulting in a catalog of ∼6000 HI absorbers.

Chapter 2 of this thesis focuses on HI surrounding high-z star-forming galaxies drawn from the Keck Baryonic Structure Survey (KBSS). The KBSS is a unique spectroscopic survey of the distant universe designed to explore the details of the connection between galaxies and intergalactic baryons within the same survey volumes. The KBSS combines high-quality background QSO spectroscopy with large densely-sampled galaxy redshift surveys to probe the CGM at scales of ∼50 kpc to a few Mpc. Based on these data, Chapter 2 presents the first quantitative measurements of the distribution, column density, kinematics, and absorber line widths of neutral hydrogen surrounding high-z star-forming galaxies.

Chapter 3 focuses on the thermal properties of the diffuse IGM. This analysis relies on measurements of the ∼6000 absorber line widths to constrain the thermal and turbulent velocities of absorbing "clouds." A positive correlation between the column density of HI and the minimum line width is recovered and implies a temperature-density relation within the low-density IGM for which higher-density regions are hotter, as is predicted by simple theoretical arguments.

Chapter 4 presents new measurements of the opacity of the IGM and CGM to hydrogen-ionizing photons. The chapter begins with a revised measurement of the HI column density distribution based on this new absorption line catalog that, due to the inclusion of high-order Lyman lines, provides the first statistically robust measurement of the frequency of absorbers with HI column densities 14 ≲ log(N_HI/cm^-2) ≲ 17.2. Also presented are the first measurements of the column density distribution of HI within the CGM (50 <d < 300 pkpc) of high-z galaxies. These distributions are used to calculate the total opacity of the IGM and IGM+CGM and to revise previous measurements of the mean free path of hydrogen-ionizing photons within the IGM. This chapter also considers the effect of the surrounding CGM on the transmission of ionizing photons out of the sites of active star-formation and into the IGM.

This thesis concludes with a brief discussion of work in progress focused on understanding the distribution of metals within the CGM of KBSS galaxies. Appendix B discusses my contributions to the MOSFIRE instrumentation project.

Carbon-carbon bond forming reactions from bis(carbene)-platinum(II) complexes and olefin polymerization and oligomerization using group 4 post-metallocene complexes

A long-standing challenge in transition metal catalysis is selective C–C bond coupling of simple feedstocks, such as carbon monoxide, ethylene or propylene, to yield value-added products. This work describes efforts toward selective C–C bond formation using early- and late-transition metals, which may have important implications for the production of fuels and plastics, as well as many other commodity chemicals.

The industrial Fischer-Tropsch (F-T) process converts synthesis gas (syngas, a mixture of CO + H₂) into a complex mixture of hydrocarbons and oxygenates. Well-defined homogeneous catalysts for F-T may provide greater product selectivity for fuel-range liquid hydrocarbons compared to traditional heterogeneous catalysts. The first part of this work involved the preparation of late-transition metal complexes for use in syngas conversion. We investigated C–C bond forming reactions via carbene coupling using bis(carbene)platinum(II) compounds, which are models for putative metal–carbene intermediates in F-T chemistry. It was found that C–C bond formation could be induced by either (1) chemical reduction of or (2) exogenous phosphine coordination to the platinum(II) starting complexes. These two mild methods afforded different products, constitutional isomers, suggesting that at least two different mechanisms are possible for C–C bond formation from carbene intermediates. These results are encouraging for the development of a multicomponent homogeneous catalysis system for the generation of higher hydrocarbons.

A second avenue of research focused on the design and synthesis of post-metallocene catalysts for olefin polymerization. The polymerization chemistry of a new class of group 4 complexes supported by asymmetric anilide(pyridine)phenolate (NNO) pincer ligands was explored. Unlike typical early transition metal polymerization catalysts, NNO-ligated catalysts produce nearly regiorandom polypropylene, with as many as 30-40 mol % of insertions being 2,1-inserted (versus 1,2-inserted), compared to <1 mol % in most metallocene systems. A survey of model Ti polymerization catalysts suggests that catalyst modification pathways that could affect regioselectivity, such as C–H activation of the anilide ring, cleavage of the amine R-group, or monomer insertion into metal–ligand bonds are unlikely. A parallel investigation of a Ti–amido(pyridine)phenolate polymerization catalyst, which features a five- rather than a six-membered Ti–N chelate ring, but maintained a dianionic NNO motif, revealed that simply maintaining this motif was not enough to produce regioirregular polypropylene; in fact, these experiments seem to indicate that only an intact anilide(pyridine)phenolate ligated-complex will lead to regioirregular polypropylene. As yet, the underlying causes for the unique regioselectivity of anilide(pyridine)phenolate polymerization catalysts remains unknown. Further exploration of NNO-ligated polymerization catalysts could lead to the controlled synthesis of new types of polymer architectures.

Finally, we investigated the reactivity of a known Ti–phenoxy(imine) (Ti-FI) catalyst that has been shown to be very active for ethylene homotrimerization in an effort to upgrade simple feedstocks to liquid hydrocarbon fuels through co-oligomerization of heavy and light olefins. We demonstrated that the Ti-FI catalyst can homo-oligomerize 1-hexene to C₁₂ and C₁₈ alkenes through olefin dimerization and trimerization, respectively. Future work will include kinetic studies to determine monomer selectivity by investigating the relative rates of insertion of light olefins (e.g., ethylene) vs. higher α-olefins, as well as a more detailed mechanistic study of olefin trimerization. Our ultimate goal is to exploit this catalyst in a multi-catalyst system for conversion of simple alkenes into hydrocarbon fuels.

Chain-forming zintl antimonides as novel thermoelectric materials

Zintl phases, a subset of intermetallic compounds characterized by covalently-bonded "sub-structures," surrounded by highly electropositive cations, exhibit precisely the characteristics desired for thermoelectric applications. The requirement that Zintl compounds satisfy the valence of anions through the formation of covalent substructures leads to many unique, complex crystal structures. Such complexity often leads to exceptionally low lattice thermal conductivity due to the containment of heat in low velocity optical modes in the phonon dispersion. To date, excellent thermoelectric properties have been demonstrated in several Zintl compounds. However, compared with the large number of known Zintl phases, very few have been investigated as thermoelectric materials.

From this pool of uninvestigated compounds, we selected a class of Zintl antimonides that share a common structural motif: anionic moieties resembling infinite chains of linked MSb₄ tetrahedra, where $M$ is a triel element. The compounds discussed in this thesis (A₅M₂Sb₆ and A₃MSb₃, where A = Ca or Sr and M = Al, Ga and In) crystallize as four distinct, but closely related "chain-forming" structure types. This thesis describes the thermoelectric characterization and optimization of these phases, and explores the influence of their chemistry and structure on the thermal and electronic transport properties. Due to their large unit cells, each compound exhibits exceptionally low lattice thermal conductivity (0.4 - 0.6 W/mK at 1000 K), approaching the predicted glassy minimum at high temperatures. A combination of Density Functional calculations and classical transport models were used to explain the experimentally observed electronic transport properties of each compound. Consistent with the Zintl electron counting formalism, A₅M₂Sb₆ and A₃MSb₃ phases were found to have filled valence bands and exhibit intrinsic electronic properties. Doping with divalent transition metals (Zn²⁺ and Mn²⁺) on the M³⁺ site, or Na¹⁺ on the A³⁺ site allowed for rational control of the carrier concentration and a transition towards degenerate semiconducting behavior. In optimally-doped samples, promising peak zT values between 0.4 and 0.9 were obtained, highlighting the value of continued investigations of complex Zintl phases.

Interaction of aqueous inorganic orthophosphate and phosphate rock

An experimental study was made of the interaction of phosphate rock and aqueous inorganic orthophosphate, calcium, and hydroxyl ions. A model of the reaction was developed by observing electron diffraction patterns in conjunction with concentration changes of chemical components. The model was applied in explaining the performance of batch suspensions of powdered phosphate rock and packed columns of granular phosphate rock. In both cases the reaction consisted initially of a rapid nucleation phase that occurred in a time period of minutes. In the batch system the calcium phosphate nuclei then ripened into larger micro-crystals of hydroxyapatite, which eventually became indistinguishable from the original phosphate rock surface. During column operation the high supersaturation ratio that existed after the rapid nucleation phase resulted in a layer of small nuclei that covered a slowly growing hydroxyapatite crystal.

The column steady-state rate constant was found to increase with increasing temperature, pH, and fluoride concentration, and to decrease with increasing concentrations of magnesium sulfate, ammonium chloride, and bicarbonate ion.

An engineering feasibility study indicated that, based on economic considerations, nucleation of apatite on phosphate rock ore has a potential use as a wastewater phosphate removal treatment process.

Reconstructing Past Depositional and Diagenetic Processes through Quantitative Stratigraphic Analysis of the Martian Sedimentary Rock Record

High-resolution orbital and in situ observations acquired of the Martian surface during the past two decades provide the opportunity to study the rock record of Mars at an unprecedented level of detail. This dissertation consists of four studies whose common goal is to establish new standards for the quantitative analysis of visible and near-infrared data from the surface of Mars. Through the compilation of global image inventories, application of stratigraphic and sedimentologic statistical methods, and use of laboratory analogs, this dissertation provides insight into the history of past depositional and diagenetic processes on Mars. The first study presents a global inventory of stratified deposits observed in images from the High Resolution Image Science Experiment (HiRISE) camera on-board the Mars Reconnaissance Orbiter. This work uses the widespread coverage of high-resolution orbital images to make global-scale observations about the processes controlling sediment transport and deposition on Mars. The next chapter presents a study of bed thickness distributions in Martian sedimentary deposits, showing how statistical methods can be used to establish quantitative criteria for evaluating the depositional history of stratified deposits observed in orbital images. The third study tests the ability of spectral mixing models to obtain quantitative mineral abundances from near-infrared reflectance spectra of clay and sulfate mixtures in the laboratory for application to the analysis of orbital spectra of sedimentary deposits on Mars. The final study employs a statistical analysis of the size, shape, and distribution of nodules observed by the Mars Science Laboratory Curiosity rover team in the Sheepbed mudstone at Yellowknife Bay in Gale crater. This analysis is used to evaluate hypotheses for nodule formation and to gain insight into the diagenetic history of an ancient habitable environment on Mars.

Investigations of group IVA transition metal mediated carbon-carbon bond forming reactions

Zirconocene aldehyde and ketone complexes were synthesized in high yield by treatment of zirconocene acyl complexes with trimethylaluminum or diisobutylaluminum hydride. These complexes, which are activated by dialkylaluminum chloride ligands, inserted unsaturated substrates such as alkynes, allenes, ethylene, nitriles, ketenes, aldehydes, ketones, lactones, and acid chlorides with moderate to high conversion. Insertion of aldehyde substrates yielded zirconocene diolate complexes with up to 20:1 (anti:syn) diastereoselectivity. The zirconocene diolates were hydrolyzed to afford unsymmetrical 1,2-diols in 40-80% isolated yield. Unsymmetrical ketones gave similar insertion yields with little or no diastereoselectivity. A high yielding one-pot method was developed that coupled carbonyl substrates with zirconocene aldehyde complexes that were derived from olefins by hydrozirconation and carbonylation. The zirconocene aldehyde complexes also inserted carbon monoxide and gave acyloins in 50% yield after hydrolysis.

The insertion reaction of aryl epoxides with the trimethylphoshine adduct of titanocene methylidene was examined. The resulting oxytitanacyclopentanes were carbonylated and oxidatively cleaved with dioxygen to afford y-lactones in moderate yields. Due to the instability and difficult isolation of titanocene methylidene trimethylphoshine adducts, a one-pot method involving the addition of catalytic amounts of trimethylphosphine to β,β-dimethyltitanacyclobutane was developed. A series of disubstituted aryl epoxides were examined which gave mixtures of diastereomeric insertion products. Based on these results, as well as earlier Hammett studies and labeling experiments, a biradical transition state intermediate is proposed. The method is limited to aryl substituted epoxide substrates with aliphatic examples showing no insertion reactivity.

The third study involved the use of magnesium chloride supported titanium catalysts for the Lewis acid catalyzed silyl group transfer condensation of enol silanes with aldehydes. The reaction resulted in silylated aldol products with as many as 140 catalytic turnovers before catalyst inactivation. Low diastereoselectivities favoring the anti-isomer were consistent with an open transition state involving a titanium atom bound to the catalyst surface. The catalysts were also used for the aldol group transfer polymerization of t-butyldimethylsilyloxy-1-ethene resulting in polymers with molecular weights of 5000-31,000 and molar mass dispersities of 1.5-2.8. Attempts to polymerize methylmethacrylate using GTP proved unsuccessful with these catalysts.

Manganese: Minerals, Microbes, and the Evolution of Oxygenic Photosynthesis

Oxygenic photosynthesis fundamentally transformed our planet by releasing molecular oxygen and altering major biogeochemical cycles, and this exceptional metabolism relies on a redox-active cubane cluster of four manganese atoms. Not only is manganese essential for producing oxygen, but manganese is also only oxidized by oxygen and oxygen-derived species. Thus the history of manganese oxidation provides a valuable perspective on our planet’s environmental past, the ancient availability of oxygen, and the evolution of oxygenic photosynthesis. Broadly, the general trends of the geologic record of manganese deposition is a chronicle of ancient manganese oxidation: manganese is introduced into the fluid Earth as Mn(II) and it will remain only a trace component in sedimentary rocks until it is oxidized, forming Mn(III,IV) insoluble precipitates that are concentrated in the rock record. Because these manganese oxides are highly favorable electron acceptors, they often undergo reduction in sediments through anaerobic respiration and abiotic reaction pathways.

The following dissertation presents five chapters investigating manganese cycling both by examining ancient examples of manganese enrichments in the geologic record and exploring the mineralogical products of various pathways of manganese oxide reduction that may occur in sediments. The first chapter explores the mineralogical record of manganese and reports abundant manganese reduction recorded in six representative manganese-enriched sedimentary sequences. This is followed by a second chapter that further analyzes the earliest significant manganese deposit 2.4 billon years ago, and determines that it predated the origin of oxygenic photosynthesis and thus is supporting evidence for manganese-oxidizing photosynthesis as an evolutionary precursor prior to oxygenic photosynthesis. The lack of oxygen during this early manganese deposition was partially established using oxygen-sensitive detrital grains, and so a third chapter delves into what these grains mean for oxygen constraints using a mathematical model. The fourth chapter returns to processes affecting manganese post-deposition, and explores the relationships between manganese mineral products and (bio)geochemical reduction processes to understand how various manganese minerals can reveal ancient environmental conditions and biological metabolisms. Finally, a fifth chapter considers whether manganese can be mobilized and enriched in sedimentary rocks and determines that manganese was concentrated secondarily in a 2.5 billion-year-old example from South Africa. Overall, this thesis demonstrates how microbial processes, namely photosynthesis and metal oxide-reducing metabolisms, are linked to and recorded in the rich complexity of the manganese mineralogical record.