6 resultados para NEAR MISS NEONATAL MORBIDITY

em CaltechTHESIS


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The two most important digital-system design goals today are to reduce power consumption and to increase reliability. Reductions in power consumption improve battery life in the mobile space and reductions in energy lower operating costs in the datacenter. Increased robustness and reliability shorten down time, improve yield, and are invaluable in the context of safety-critical systems. While optimizing towards these two goals is important at all design levels, optimizations at the circuit level have the furthest reaching effects; they apply to all digital systems. This dissertation presents a study of robust minimum-energy digital circuit design and analysis. It introduces new device models, metrics, and methods of calculation—all necessary first steps towards building better systems—and demonstrates how to apply these techniques. It analyzes a fabricated chip (a full-custom QDI microcontroller designed at Caltech and taped-out in 40-nm silicon) by calculating the minimum energy operating point and quantifying the chip’s robustness in the face of both timing and functional failures.

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The neonatal Fe receptor (FeRn) binds the Fe portion of immunoglobulin G (IgG) at the acidic pH of endosomes or the gut and releases IgG at the alkaline pH of blood. FeRn is responsible for the maternofetal transfer of IgG and for rescuing endocytosed IgG from a default degradative pathway. We investigated how FeRn interacts with IgG by constructing a heterodimeric form of the Fe (hdFc) that contains one FeRn binding site. This molecule was used to characterize the interaction between one FeRn molecule and one Fe and to determine under what conditions FeRn forms a dimer. The hdFc binds one FeRn molecule at pH 6.0 with a K_d of 80 nM. In solution and with FeRn anchored to solid supports, the heterodimeric Fe does not induce a dimer of FeRn molecules. FcRnhdFc complex crystals were obtained and the complex structure was solved to 2.8 Å resolution. Analysis of this structure refined the understanding of the mechanism of the pH-dependent binding, shed light on the role played by carbohydrates in the Fe binding, and provided insights on how to design therapeutic IgG antibodies with longer serum half-lives. The FcRn-hdFc complex in the crystal did not contain the FeRn dimer. To characterize the tendency of FeRn to form a dimer in a membrane we analyzed the tendency of the hdFc to induce cross-phosphorylation of FeRn-tyrosine kinase chimeras. We also constructed FeRn-cyan and FeRn-yellow fluorescent proteins and have analyzed the tendency of these molecules to exhibit fluorescence resonance energy transfer. As of now, neither of these analyses have lead to conclusive results. In the process of acquiring the context to appreciate the structure of the FcRn-hdFc interface, we developed a study of 171 other nonobligate protein-protein interfaces that includes an original principal component analysis of the quantifiable aspects of these interfaces.

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The work in this thesis develops two types of microimplants for the application of cardiovascular in vivo biomedical sensing, one for short-term diagnosis and the other for long-term monitoring.

Despite advances in diagnosis and therapy, atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in the Western world. Predicting metabolically active atherosclerotic plaques has remained an unmet clinical need. A stretchable impedance sensor manifested as a pair of quasi-concentric microelectrodes was developed to detect unstable intravascular. By integrating the impedance sensor with a cardiac catheter, high-resolution Electrochemical Impedance Spectroscopy (EIS) measurements can be conducted during cardiac catheterization. An inflatable silicone balloon is added to the sensor to secure a well-controlled contact with the plaque under test in vivo. By deploying the device to the explants of NZW rabbit aorta and live animals, distinct EIS measurements were observed for unstable atherosclerotic plaques that harbored active lipids and inflammatory cells.

On the other hand, zebrafish (Danio rerio) is an emerging genetic model for heart regenerative medicine. In humans, myocardial infarction results in the irreversible loss of cardiomyocytes. Zebrafish hearts can fully regenerate after two months with 20% ventricular resection. Long-term electrocardiogram (ECG) recording can characterize the heart regeneration in a functional dimension. A flexible microelectrode membrane was developed to be percutaneously implanted onto a zebrafish heart and record epicardial ECG signals from specific regions on it. Region-specific aberrant cardiac signals were obtained from injured and regenerated hearts. Following that, in order to achieve continuous and wireless recording from non-sedated and non-restricted small animal models, a wireless ECG recording system was designed for the microelectrode membrane, prototyped on a printed circuit board and demonstrated on a one-day-old neonatal mouse. Furthermore, a flexible and compact parylene C printed circuit membrane was used as the integration platform for the wireless ECG recording electronics. A substantially miniature wireless ECG recording system was achieved.

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This thesis presents the results of an experimental investigation of the initiation of brittle fracture and the nature of discontinuous yielding in small plastic enclaves in an annealed mild steel. Upper and lower yield stress data have been obtained from unnotched specimens and nominal fracture stress data have been obtained from specimens of two scale factors and two grain sizes over a range of nominal stress rates from 10^2 to 10^7 lb/in.^2 sec at -111°F and -200°F. The size and shape of plastic enclaves near the notches were revealed by an etch technique.

A stress analysis utilizing slip-line field theory in the plastic region has been developed for the notched specimen geometry employed in this investigation. The yield stress of the material in the plastic enclaves near the notch root has been correlated with the lower yield stress measured on unnotched specimens through a consideration of the plastic boundary velocity under dynamic loading. A maximum tensile stress of about 122,000 lb/in.^2 at the instant of fracture initiation was calculated with the aid of the stress analysis for the large scale specimens of ASTM grain size 8 1/4.

The plastic strain state adjacent to a plastic-elastic interface has been shown to cause the maximum shear stress to have a larger value on the elastic than the plastic side of the interface. This characteristic of dis continuous yielding is instrumental in causing the plastic boundaries to be nearly parallel to the slip-line field where the plastic strain is of the order of the Lüder's strain.

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We present the first experimental evidence that the heat capacity of superfluid 4He, at temperatures very close to the lambda transition temperature, Tλ,is enhanced by a constant heat flux, Q. The heat capacity at constant Q, CQ,is predicted to diverge at a temperature Tc(Q) < Tλ at which superflow becomes unstable. In agreement with previous measurements, we find that dissipation enters our cell at a temperature, TDAS(Q),below the theoretical value, Tc(Q). Our measurements of CQ were taken using the discrete pulse method at fourteen different heat flux values in the range 1µW/cm2 ≤ Q≤ 4µW /cm2. The excess heat capacity ∆CQ we measure has the predicted scaling behavior as a function of T and Q:∆CQ • tα ∝ (Q/Qc)2, where QcT) ~ t is the critical heat current that results from the inversion of the equation for Tc(Q). We find that if the theoretical value of Tc( Q) is correct, then ∆CQ is considerably larger than anticipated. On the other hand,if Tc(Q)≈ TDAS(Q),then ∆CQ is the same magnitude as the theoretically predicted enhancement.

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The assembly history of massive galaxies is one of the most important aspects of galaxy formation and evolution. Although we have a broad idea of what physical processes govern the early phases of galaxy evolution, there are still many open questions. In this thesis I demonstrate the crucial role that spectroscopy can play in a physical understanding of galaxy evolution. I present deep near-infrared spectroscopy for a sample of high-redshift galaxies, from which I derive important physical properties and their evolution with cosmic time. I take advantage of the recent arrival of efficient near-infrared detectors to target the rest-frame optical spectra of z > 1 galaxies, from which many physical quantities can be derived. After illustrating the applications of near-infrared deep spectroscopy with a study of star-forming galaxies, I focus on the evolution of massive quiescent systems.

Most of this thesis is based on two samples collected at the W. M. Keck Observatory that represent a significant step forward in the spectroscopic study of z > 1 quiescent galaxies. All previous spectroscopic samples at this redshift were either limited to a few objects, or much shallower in terms of depth. Our first sample is composed of 56 quiescent galaxies at 1 < z < 1.6 collected using the upgraded red arm of the Low Resolution Imaging Spectrometer (LRIS). The second consists of 24 deep spectra of 1.5 < z < 2.5 quiescent objects observed with the Multi-Object Spectrometer For Infra-Red Exploration (MOSFIRE). Together, these spectra span the critical epoch 1 < z < 2.5, where most of the red sequence is formed, and where the sizes of quiescent systems are observed to increase significantly.

We measure stellar velocity dispersions and dynamical masses for the largest number of z > 1 quiescent galaxies to date. By assuming that the velocity dispersion of a massive galaxy does not change throughout its lifetime, as suggested by theoretical studies, we match galaxies in the local universe with their high-redshift progenitors. This allows us to derive the physical growth in mass and size experienced by individual systems, which represents a substantial advance over photometric inferences based on the overall galaxy population. We find a significant physical growth among quiescent galaxies over 0 < z < 2.5 and, by comparing the slope of growth in the mass-size plane dlogRe/dlogM with the results of numerical simulations, we can constrain the physical process responsible for the evolution. Our results show that the slope of growth becomes steeper at higher redshifts, yet is broadly consistent with minor mergers being the main process by which individual objects evolve in mass and size.

By fitting stellar population models to the observed spectroscopy and photometry we derive reliable ages and other stellar population properties. We show that the addition of the spectroscopic data helps break the degeneracy between age and dust extinction, and yields significantly more robust results compared to fitting models to the photometry alone. We detect a clear relation between size and age, where larger galaxies are younger. Therefore, over time the average size of the quiescent population will increase because of the contribution of large galaxies recently arrived to the red sequence. This effect, called progenitor bias, is different from the physical size growth discussed above, but represents another contribution to the observed difference between the typical sizes of low- and high-redshift quiescent galaxies. By reconstructing the evolution of the red sequence starting at z ∼ 1.25 and using our stellar population histories to infer the past behavior to z ∼ 2, we demonstrate that progenitor bias accounts for only half of the observed growth of the population. The remaining size evolution must be due to physical growth of individual systems, in agreement with our dynamical study.

Finally, we use the stellar population properties to explore the earliest periods which led to the formation of massive quiescent galaxies. We find tentative evidence for two channels of star formation quenching, which suggests the existence of two independent physical mechanisms. We also detect a mass downsizing, where more massive galaxies form at higher redshift, and then evolve passively. By analyzing in depth the star formation history of the brightest object at z > 2 in our sample, we are able to put constraints on the quenching timescale and on the properties of its progenitor.

A consistent picture emerges from our analyses: massive galaxies form at very early epochs, are quenched on short timescales, and then evolve passively. The evolution is passive in the sense that no new stars are formed, but significant mass and size growth is achieved by accreting smaller, gas-poor systems. At the same time the population of quiescent galaxies grows in number due to the quenching of larger star-forming galaxies. This picture is in agreement with other observational studies, such as measurements of the merger rate and analyses of galaxy evolution at fixed number density.