13 resultados para TEMPLATE

em CaltechTHESIS


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Part I. Complexes of Biological Bases and Oligonucleotides with RNA

The physical nature of complexes of several biological bases and oligonucleotides with single-stranded ribonucleic acids have been studied by high resolution proton magnetic resonance spectroscopy. The importance of various forces in the stabilization of these complexes is also discussed.

Previous work has shown that purine forms an intercalated complex with single-stranded nucleic acids. This complex formation led to severe and stereospecific broadening of the purine resonances. From the field dependence of the linewidths, T1 measurements of the purine protons and nuclear Overhauser enhancement experiments, the mechanism for the line broadening was ascertained to be dipole-dipole interactions between the purine protons and the ribose protons of the nucleic acid.

The interactions of ethidium bromide (EB) with several RNA residues have been studied. EB forms vertically stacked aggregates with itself as well as with uridine, 3'-uridine monophosphate and 5'-uridine monophosphate and forms an intercalated complex with uridylyl (3' → 5') uridine and polyuridylic acid (poly U). The geometry of EB in the intercalated complex has also been determined.

The effect of chain length of oligo-A-nucleotides on their mode of interaction with poly U in D20 at neutral pD have also been studied. Below room temperatures, ApA and ApApA form a rigid triple-stranded complex involving a stoichiometry of one adenine to two uracil bases, presumably via specific adenine-uracil base pairing and cooperative base stacking of the adenine bases. While no evidence was obtained for the interaction of ApA with poly U above room temperature, ApApA exhibited complex formation of a 1:1 nature with poly U by forming Watson-Crick base pairs. The thermodynamics of these systems are discussed.

Part II. Template Recognition and the Degeneracy of the Genetic Code

The interaction of ApApG and poly U was studied as a model system for the codon-anticodon interaction of tRNA and mRNA in vivo. ApApG was shown to interact with poly U below ~20°C. The interaction was of a 1:1 nature which exhibited the Hoogsteen bonding scheme. The three bases of ApApG are in an anti conformation and the guanosine base appears to be in the lactim tautomeric form in the complex.

Due to the inadequacies of previous models for the degeneracy of the genetic code in explaining the observed interactions of ApApG with poly U, the "tautomeric doublet" model is proposed as a possible explanation of the degenerate interactions of tRNA with mRNA during protein synthesis in vivo.

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Nucleic acids are most commonly associated with the genetic code, transcription and gene expression. Recently, interest has grown in engineering nucleic acids for biological applications such as controlling or detecting gene expression. The natural presence and functionality of nucleic acids within living organisms coupled with their thermodynamic properties of base-pairing make them ideal for interfacing (and possibly altering) biological systems. We use engineered small conditional RNA or DNA (scRNA, scDNA, respectively) molecules to control and detect gene expression. Three novel systems are presented: two for conditional down-regulation of gene expression via RNA interference (RNAi) and a third system for simultaneous sensitive detection of multiple RNAs using labeled scRNAs.

RNAi is a powerful tool to study genetic circuits by knocking down a gene of interest. RNAi executes the logic: If gene Y is detected, silence gene Y. The fact that detection and silencing are restricted to the same gene means that RNAi is constitutively on. This poses a significant limitation when spatiotemporal control is needed. In this work, we engineered small nucleic acid molecules that execute the logic: If mRNA X is detected, form a Dicer substrate that targets independent mRNA Y for silencing. This is a step towards implementing the logic of conditional RNAi: If gene X is detected, silence gene Y. We use scRNAs and scDNAs to engineer signal transduction cascades that produce an RNAi effector molecule in response to hybridization to a nucleic acid target X. The first mechanism is solely based on hybridization cascades and uses scRNAs to produce a double-stranded RNA (dsRNA) Dicer substrate against target gene Y. The second mechanism is based on hybridization of scDNAs to detect a nucleic acid target and produce a template for transcription of a short hairpin RNA (shRNA) Dicer substrate against target gene Y. Test-tube studies for both mechanisms demonstrate that the output Dicer substrate is produced predominantly in the presence of a correct input target and is cleaved by Dicer to produce a small interfering RNA (siRNA). Both output products can lead to gene knockdown in tissue culture. To date, signal transduction is not observed in cells; possible reasons are explored.

Signal transduction cascades are composed of multiple scRNAs (or scDNAs). The need to study multiple molecules simultaneously has motivated the development of a highly sensitive method for multiplexed northern blots. The core technology of our system is the utilization of a hybridization chain reaction (HCR) of scRNAs as the detection signal for a northern blot. To achieve multiplexing (simultaneous detection of multiple genes), we use fluorescently tagged scRNAs. Moreover, by using radioactive labeling of scRNAs, the system exhibits a five-fold increase, compared to the literature, in detection sensitivity. Sensitive multiplexed northern blot detection provides an avenue for exploring the fate of scRNAs and scDNAs in tissue culture.

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Iterative in situ click chemistry (IISCC) is a robust general technology for development of high throughput, inexpensive protein detection agents. In IISCC, the target protein acts as a template and catalyst, and assembles its own ligand from modular blocks of peptides. This process of ligand discovery is iterated to add peptide arms to develop a multivalent ligand with increased affinity and selectivity. The peptide based protein capture agents (PCC) should ideally have the same degree of selectivity and specificity as a monoclonal antibody, along with improved chemical stability. We had previously reported developing a PCC agent against bovine carbonic anhydrase II (bCAII) that could replace a polyclonal antibody. To further enhance the affinity or specificity of the PCC agent, I explore branching the peptide arms to develop branched PCC agents against bCAII. The developed branched capture agents have two to three fold higher affinities for the target protein. In the second part of my thesis, I describe the epitope targeting strategy, a strategy for directing the development of a peptide ligand against specific region or fragment of the protein. The strategy is successfully demonstrated by developing PCC agents with low nanomolar binding affinities that target the C-terminal hydrophobic motif of Akt2 kinase. One of the developed triligands inhibits the kinase activity of Akt. This suggests that, if targeted against the right epitope, the PCC agents can also influence the functional properties of the protein. The exquisite control of the epitope targeting strategy is further demonstrated by developing a cyclic ligand against Akt2. The cyclic ligand acts as an inhibitor by itself, without any iteration of the ligand discovery process. The epitope targeting strategy is a cornerstone of the IISCC technology and opens up new opportunities, leading to the development of protein detection agents and of modulators of protein functions.

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Observational and theoretical work towards the separation of foreground emission from the cosmic microwave background is described. The bulk of this work is in the design, construction, and commissioning of the C-Band All-Sky Survey (C-BASS), an experiment to produce a template of the Milky Way Galaxy's polarized synchrotron emission. Theoretical work is the derivation of an analytical approximation to the emission spectrum of spinning dust grains.

The performance of the C-BASS experiment is demonstrated through a preliminary, deep survey of the North Celestial Pole region. A comparison to multiwavelength data is performed, and the thermal and systematic noise properties of the experiment are explored. The systematic noise has been minimized through careful data processing algorithms, implemented both in the experiment's Field Programmable Gate Array (FPGA) based digital backend and in the data analysis pipeline. Detailed descriptions of these algorithms are presented.

The analytical function of spinning dust emission is derived through the application of careful approximations, with each step tested against numerical calculations. This work is intended for use in the parameterized separation of cosmological foreground components and as a framework for interpreting and comparing the variety of anomalous microwave emission observations.

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With the advent of well-defined ruthenium olefin metathesis catalysts that are highly active and stable to a variety of functional groups, the synthesis of complex organic molecules and polymers is now possible; this is reviewed in Chapter 1. The majority of the rest of this thesis describes the application of these catalysts towards the synthesis of novel polymers that may be useful in biological applications and investigations into their efficacy.

A method was developed to produce polyethers by metathesis, and this is described in Chapters 2 and 3. An unsaturated 12-crown-4 analog was made by template- directed ring-closing metathesis (RCM) and utilized as a monomer for the synthesis of unsaturated polyethers by ring-opening metathesis polymerization (ROMP). The yields were high and a range of molecular weights was accessible. In a similar manner, substituted polyethers with various backbones were synthesized: polymers with benzo groups along the backbone and various concentrations of amino acids were prepared. The results from in vitro toxicity tests of the unsubstituted polyethers are considered.

The conditions necessary to synthesize polynorbornenes with pendent bioactive peptides were explored as illustrated in Chapter 4. First, the polymerization of various norbornenyl monomers substituted with glycine, alanine or penta(ethylene glycol) is described. Then, the syntheses of polymers substituted with peptides GRGD and SRN, components of a cell binding domain of fibronectin, using newly developed ruthenium initiators are discussed.

In Chapter 5, the syntheses of homopolymers and a copolymer containing GRGDS and PHSRN, the more active forms of the peptides, are described. The ability of the polymers to inhibit human dermal fibroblast cell adhesion to fibronectin was assayed using an in vitro competitive inhibition assay, and the results are discussed. It was discovered that the copoymer substituted with both GRGDS and PHSR peptides was more active than both the GRGDS-containing homopolymer and the GRGDS free peptide.

Historically, one of the drawbacks to using metathesis is the removal of the residual ruthenium at the completion of the reaction. Chapter 6 describes a method where the water soluble tris(hydroxymethyl)phosphine is utilized to facilitate the removal of residual ruthenium from RCM reaction products.

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General Relativity predicts the existence of gravitational waves, which carry information about the physical and dynamical properties of their source. One of the many promising sources of gravitational waves observable by ground-based instruments, such as in LIGO and Virgo, is the coalescence of two compact objects (neutron star or black hole). Black holes and neutron stars sometimes form binaries with short orbital periods, radiating so strongly in gravitational waves that they coalesce on astrophysically short timescales. General Relativity gives precise predictions for the form of the signal emitted by these systems. The most recent searches for theses events used waveform models that neglected the effects of black hole and neutron star spin. However, real astrophysical compact objects, especially black holes, are expected to have large spins. We demonstrate here a data analysis infrastructure which achieves an improved sensitivity to spinning compact binaries by the inclusion of spin effects in the template waveforms. This infrastructure is designed for scalable, low-latency data analysis, ideal for rapid electromagnetic followup of gravitational wave events.

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While concentrator photovoltaic cells have shown significant improvements in efficiency in the past ten years, once these cells are integrated into concentrating optics, connected to a power conditioning system and deployed in the field, the overall module efficiency drops to only 34 to 36%. This efficiency is impressive compared to conventional flat plate modules, but it is far short of the theoretical limits for solar energy conversion. Designing a system capable of achieving ultra high efficiency of 50% or greater cannot be achieved by refinement and iteration of current design approaches.

This thesis takes a systems approach to designing a photovoltaic system capable of 50% efficient performance using conventional diode-based solar cells. The effort began with an exploration of the limiting efficiency of spectrum splitting ensembles with 2 to 20 sub cells in different electrical configurations. Incorporating realistic non-ideal performance with the computationally simple detailed balance approach resulted in practical limits that are useful to identify specific cell performance requirements. This effort quantified the relative benefit of additional cells and concentration for system efficiency, which will help in designing practical optical systems.

Efforts to improve the quality of the solar cells themselves focused on the development of tunable lattice constant epitaxial templates. Initially intended to enable lattice matched multijunction solar cells, these templates would enable increased flexibility in band gap selection for spectrum splitting ensembles and enhanced radiative quality relative to metamorphic growth. The III-V material family is commonly used for multijunction solar cells both for its high radiative quality and for the ease of integrating multiple band gaps into one monolithic growth. The band gap flexibility is limited by the lattice constant of available growth templates. The virtual substrate consists of a thin III-V film with the desired lattice constant. The film is grown strained on an available wafer substrate, but the thickness is below the dislocation nucleation threshold. By removing the film from the growth substrate, allowing the strain to relax elastically, and bonding it to a supportive handle, a template with the desired lattice constant is formed. Experimental efforts towards this structure and initial proof of concept are presented.

Cells with high radiative quality present the opportunity to recover a large amount of their radiative losses if they are incorporated in an ensemble that couples emission from one cell to another. This effect is well known, but has been explored previously in the context of sub cells that independently operate at their maximum power point. This analysis explicitly accounts for the system interaction and identifies ways to enhance overall performance by operating some cells in an ensemble at voltages that reduce the power converted in the individual cell. Series connected multijunctions, which by their nature facilitate strong optical coupling between sub-cells, are reoptimized with substantial performance benefit.

Photovoltaic efficiency is usually measured relative to a standard incident spectrum to allow comparison between systems. Deployed in the field systems may differ in energy production due to sensitivity to changes in the spectrum. The series connection constraint in particular causes system efficiency to decrease as the incident spectrum deviates from the standard spectral composition. This thesis performs a case study comparing performance of systems over a year at a particular location to identify the energy production penalty caused by series connection relative to independent electrical connection.

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We present a complete system for Spectral Cauchy characteristic extraction (Spectral CCE). Implemented in C++ within the Spectral Einstein Code (SpEC), the method employs numerous innovative algorithms to efficiently calculate the Bondi strain, news, and flux.

Spectral CCE was envisioned to ensure physically accurate gravitational wave-forms computed for the Laser Interferometer Gravitational wave Observatory (LIGO) and similar experiments, while working toward a template bank with more than a thousand waveforms to span the binary black hole (BBH) problem’s seven-dimensional parameter space.

The Bondi strain, news, and flux are physical quantities central to efforts to understand and detect astrophysical gravitational wave sources within the Simulations of eXtreme Spacetime (SXS) collaboration, with the ultimate aim of providing the first strong field probe of the Einstein field equation.

In a series of included papers, we demonstrate stability, convergence, and gauge invariance. We also demonstrate agreement between Spectral CCE and the legacy Pitt null code, while achieving a factor of 200 improvement in computational efficiency.

Spectral CCE represents a significant computational advance. It is the foundation upon which further capability will be built, specifically enabling the complete calculation of junk-free, gauge-free, and physically valid waveform data on the fly within SpEC.

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Fast radio bursts (FRBs), a novel type of radio pulse, whose physics is not yet understood at all. Only a handful of FRBs had been detected when we started this project. Taking account of the scant observations, we put physical constraints on FRBs. We excluded proposals of a galactic origin for their extraordinarily high dispersion measures (DM), in particular stellar coronas and HII regions. Therefore our work supports an extragalactic origin for FRBs. We show that the resolved scattering tail of FRB 110220 is unlikely to be due to propagation through the intergalactic plasma. Instead the scattering is probably caused by the interstellar medium in the FRB's host galaxy, and indicates that this burst sits in the central region of that galaxy. Pulse durations of order $\ms$ constrain source sizes of FRBs implying enormous brightness temperatures and thus coherent emission. Electric fields near FRBs at cosmological distances would be so strong that they could accelerate free electrons from rest to relativistic energies in a single wave period. When we worked on FRBs, it was unclear whether they were genuine astronomical signals as distinct from `perytons', clearly terrestrial radio bursts, sharing some common properties with FRBs. Recently, in April 2015, astronomers discovered that perytons were emitted by microwave ovens. Radio chirps similar to FRBs were emitted when their doors opened while they were still heating. Evidence for the astronomical nature of FRBs has strengthened since our paper was published. Some bursts have been found to show linear and circular polarizations and Faraday rotation of the linear polarization has also been detected. I hope to resume working on FRBs in the near future. But after we completed our FRB paper, I decided to pause this project because of the lack of observational constraints.

The pulsar triple system, J0733+1715, has its orbital parameters fitted to high accuracy owing to the precise timing of the central $\ms$ pulsar. The two orbits are highly hierarchical, namely $P_{\mathrm{orb,1}}\ll P_{\mathrm{orb,2}}$, where 1 and 2 label the inner and outer white dwarf (WD) companions respectively. Moreover, their orbital planes almost coincide, providing a unique opportunity to study secular interaction associated purely with eccentricity beyond the solar system. Secular interaction only involves effect averaged over many orbits. Thus each companion can be represented by an elliptical wire with its mass distributed inversely proportional to its local orbital speed. Generally there exists a mutual torque, which vanishes only when their apsidal lines are parallel or anti-parallel. To maintain either mode, the eccentricity ratio, $e_1/e_2$, must be of the proper value, so that both apsidal lines precess together. For J0733+1715, $e_1\ll e_2$ for the parallel mode, while $e_1\gg e_2$ for the anti-parallel one. We show that the former precesses $\sim 10$ times slower than the latter. Currently the system is dominated by the parallel mode. Although only a little anti-parallel mode survives, both eccentricities especially $e_1$ oscillate on $\sim 10^3\yr$ timescale. Detectable changes would occur within $\sim 1\yr$. We demonstrate that the anti-parallel mode gets damped $\sim 10^4$ times faster than its parallel brother by any dissipative process diminishing $e_1$. If it is the tidal damping in the inner WD, we proceed to estimate its tidal quantity parameter ($Q$) to be $\sim 10^6$, which was poorly constrained by observations. However, tidal damping may also happen during the preceding low-mass X-ray binary (LMXB) phase or hydrogen thermal nuclear flashes. But, in both cases, the inner companion fills its Roche lobe and probably suffers mass/angular momentum loss, which might cause $e_1$ to grow rather than decay.

Several pairs of solar system satellites occupy mean motion resonances (MMRs). We divide these into two groups according to their proximity to exact resonance. Proximity is measured by the existence of a separatrix in phase space. MMRs between Io-Europa, Europa-Ganymede and Enceladus-Dione are too distant from exact resonance for a separatrix to appear. A separatrix is present only in the phase spaces of the Mimas-Tethys and Titan-Hyperion MMRs and their resonant arguments are the only ones to exhibit substantial librations. When a separatrix is present, tidal damping of eccentricity or inclination excites overstable librations that can lead to passage through resonance on the damping timescale. However, after investigation, we conclude that the librations in the Mimas-Tethys and Titan-Hyperion MMRs are fossils and do not result from overstability.

Rubble piles are common in the solar system. Monolithic elements touch their neighbors in small localized areas. Voids occupy a significant fraction of the volume. In a fluid-free environment, heat cannot conduct through voids; only radiation can transfer energy across them. We model the effective thermal conductivity of a rubble pile and show that it is proportional the square root of the pressure, $P$, for $P\leq \epsy^3\mu$ where $\epsy$ is the material's yield strain and $\mu$ its shear modulus. Our model provides an excellent fit to the depth dependence of the thermal conductivity in the top $140\,\mathrm{cm}$ of the lunar regolith. It also offers an explanation for the low thermal inertias of rocky asteroids and icy satellites. Lastly, we discuss how rubble piles slow down the cooling of small bodies such as asteroids.

Electromagnetic (EM) follow-up observations of gravitational wave (GW) events will help shed light on the nature of the sources, and more can be learned if the EM follow-ups can start as soon as the GW event becomes observable. In this paper, we propose a computationally efficient time-domain algorithm capable of detecting gravitational waves (GWs) from coalescing binaries of compact objects with nearly zero time delay. In case when the signal is strong enough, our algorithm also has the flexibility to trigger EM observation {\it before} the merger. The key to the efficiency of our algorithm arises from the use of chains of so-called Infinite Impulse Response (IIR) filters, which filter time-series data recursively. Computational cost is further reduced by a template interpolation technique that requires filtering to be done only for a much coarser template bank than otherwise required to sufficiently recover optimal signal-to-noise ratio. Towards future detectors with sensitivity extending to lower frequencies, our algorithm's computational cost is shown to increase rather insignificantly compared to the conventional time-domain correlation method. Moreover, at latencies of less than hundreds to thousands of seconds, this method is expected to be computationally more efficient than the straightforward frequency-domain method.

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Techniques are described for mounting and visualizing biological macromolecules for high resolution electron microscopy. Standard techniques are included in a discussion of new methods designed to provide the highest structural resolution. Methods are also discussed for handling samples on the grid, for making accurate size measurements at the 20 Å level, and for photographically enhancing image contrast.

The application of these techniques to the study of the binding of DNA polymerase to DNA is described. It is shown that the electron micrographs of this material are in agreement with the model proposed by Dr. Arthur Kornberg. A model is described which locates several active sites on the enzyme.

The chromosomal material of the protozoan tetrahymena has been isolated and characterized by biochemical techniques and by electron microscopy. This material is shown to be typical of chromatin of higher creatures.

Comparison with other chromatins discloses that the genome of tetrahymena is highly template active and has a relatively simple genetic construction.

High resolution electron microscope procedures developed in this work have been combined with standard biochemical techniques to give a comprehensive picture of the structure of interphase chromosome fibers. The distribution of the chromosomal proteins along its DNA is discussed.

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After artificial activation or fertilization of non-nucleate fragments or eggs of the sea urchin, the mitochondria actively synthesize RNA. The RNA made in non-nucleate fragments is shown to be mostly single stranded and to be associated primarily with the low speed pellet of centrifuged cellular homogenates.

Protein synthesis is observed in non-nucleate fragments in the presence or absence of the mitochondrial RNA synthesis: it is found to be qualitatively similar but quantitatively less in the absence of the RNA synthesis. The continued syntheses of proteins in the non-nucleate fragments in the absence of mitochondrial RNA synthesis provides additional evidence for the presence of a stable messenger RNA component in the unfertilized sea urchin egg.

Since the uptake or actinomycin D was found to be inhibited by the presence of a fertilization membrane, ethidium bromide, at 10 μgs/ml, is used as an effective inhibitor of RNA synthesis in non-nucleate fragments and in early cleavage stage embryos. However, this same concentration of ethidium bromide is found to be only partially effective in blocking RNA synthesis at the mesenchyme blastula stage of development.

Low concentrations of ethidium bromide (2 and 5 μgs/ml) are found not to be lethal but to be capable of producing moderate developmental defects. In the presence of concentrations of ethidium bromide adequate to inhibit all the mitochondrial RNA synthesis (10 μgs/ml of ethidium bromide), from fertilization on, the embryos do not cleave beyond the 4-8 cell stages. When similar concentrations of ethidium bromide are added at an early mesenchyme blastula stage, the embryos do not gastrulate but continue to swim for more than 24 additional hours (adequate for control embryos to develop to a late prism stage). These results lead to the conclusion that mitochondrial RNA synthesis may be very essential for normal development to occur.

DNA is synthesized in the non-nucleate fragments of sea urchin eggs. None of the newly synthesized DNA is found in the closed circular form. When phenol extracted directly from the fragments, the DNA is found to sediment at approximately 38 and 27s in sucrose gradients but neither of these size classes could be found associated with the isolated mitochondria. The template for the synthesis of DNA in non-nucleate fragments remains unknown.

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Studies on the dissociation of histones from chromatin by increasing concentrations of sodium deoxycholate (DOC) have shown that histrone II is removed at lowest concentrations of DOC, while slightly higher concentrations remove histones III and IV. Still higher concentrations remove histone I.

The complete separation of chromatin and 14C-DOC by sucrose sedimentation indicated that the binding of DOC to chromatin is readily and completely reversible.

The dissociation of histones from chromatin by increasing concentrations of related cholanic acids and some of their conjugated derivatives were studied. The results suggested that the driving force for the interaction between the cholanic acid anion and histones is the lowering of the activity coefficient of the cholanic acid anion which occurs when it is partially removed from solution by interaction with hydrophobic regions of the positively charged histones.

The role of histones in the structure of chromatin has been studied by comparing the effects of selective removal of histones from chromatin by increasing concentrations of DOC with those caused by NaCl (removes histone I at lowest concentrations, while higher concentrations remove histones II, III, and IV). Properties studied included thermal denaturation, sedimentation velocity, flow dichroism, relaxation times of molecules oriented in a flow field, and the irreversible disruption of a 130 S, cross-linked component of sheared chromatin. The data indicated that none of the structural or chemical parameters with which these properties are correlated show a dependence on the presence of one particular histone fraction.

The template activity (ability to prime a 0.2 M KC1 DNA-dependent RNA synthesis system catalyzed by E. coli RNA polymerase) increases from that of native chromatin (approximately 25 per cent of that pure DNA) to that of pure DNA in a fashion which shows a nearly linear relationship to the amount of histone coverage of the template. The precipitability of partially dehistonized chromatin samples in 0.15 M NaCl shows a large dependence on the presence of histone I.

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The first part of this thesis combines Bolocam observations of the thermal Sunyaev-Zel’dovich (SZ) effect at 140 GHz with X-ray observations from Chandra, strong lensing data from the Hubble Space Telescope (HST), and weak lensing data from HST and Subaru to constrain parametric models for the distribution of dark and baryonic matter in a sample of six massive, dynamically relaxed galaxy clusters. For five of the six clusters, the full multiwavelength dataset is well described by a relatively simple model that assumes spherical symmetry, hydrostatic equilibrium, and entirely thermal pressure support. The multiwavelength analysis yields considerably better constraints on the total mass and concentration compared to analysis of any one dataset individually. The subsample of five galaxy clusters is used to place an upper limit on the fraction of pressure support in the intracluster medium (ICM) due to nonthermal processes, such as turbulent and bulk flow of the gas. We constrain the nonthermal pressure fraction at r500c to be less than 0.11 at 95% confidence, where r500c refers to radius at which the average enclosed density is 500 times the critical density of the Universe. This is in tension with state-of-the-art hydrodynamical simulations, which predict a nonthermal pressure fraction of approximately 0.25 at r500c for the clusters in this sample.

The second part of this thesis focuses on the characterization of the Multiwavelength Sub/millimeter Inductance Camera (MUSIC), a photometric imaging camera that was commissioned at the Caltech Submillimeter Observatory (CSO) in 2012. MUSIC is designed to have a 14 arcminute, diffraction-limited field of view populated with 576 spatial pixels that are simultaneously sensitive to four bands at 150, 220, 290, and 350 GHz. It is well-suited for studies of dusty star forming galaxies, galaxy clusters via the SZ Effect, and galactic star formation. MUSIC employs a number of novel detector technologies: broadband phased-arrays of slot dipole antennas for beam formation, on-chip lumped element filters for band definition, and Microwave Kinetic Inductance Detectors (MKIDs) for transduction of incoming light to electric signal. MKIDs are superconducting micro-resonators coupled to a feedline. Incoming light breaks apart Cooper pairs in the superconductor, causing a change in the quality factor and frequency of the resonator. This is read out as amplitude and phase modulation of a microwave probe signal centered on the resonant frequency. By tuning each resonator to a slightly different frequency and sending out a superposition of probe signals, hundreds of detectors can be read out on a single feedline. This natural capability for large scale, frequency domain multiplexing combined with relatively simple fabrication makes MKIDs a promising low temperature detector for future kilopixel sub/millimeter instruments. There is also considerable interest in using MKIDs for optical through near-infrared spectrophotometry due to their fast microsecond response time and modest energy resolution. In order to optimize the MKID design to obtain suitable performance for any particular application, it is critical to have a well-understood physical model for the detectors and the sources of noise to which they are susceptible. MUSIC has collected many hours of on-sky data with over 1000 MKIDs. This work studies the performance of the detectors in the context of one such physical model. Chapter 2 describes the theoretical model for the responsivity and noise of MKIDs. Chapter 3 outlines the set of measurements used to calibrate this model for the MUSIC detectors. Chapter 4 presents the resulting estimates of the spectral response, optical efficiency, and on-sky loading. The measured detector response to Uranus is compared to the calibrated model prediction in order to determine how well the model describes the propagation of signal through the full instrument. Chapter 5 examines the noise present in the detector timestreams during recent science observations. Noise due to fluctuations in atmospheric emission dominate at long timescales (less than 0.5 Hz). Fluctuations in the amplitude and phase of the microwave probe signal due to the readout electronics contribute significant 1/f and drift-type noise at shorter timescales. The atmospheric noise is removed by creating a template for the fluctuations in atmospheric emission from weighted averages of the detector timestreams. The electronics noise is removed by using probe signals centered off-resonance to construct templates for the amplitude and phase fluctuations. The algorithms that perform the atmospheric and electronic noise removal are described. After removal, we find good agreement between the observed residual noise and our expectation for intrinsic detector noise over a significant fraction of the signal bandwidth.