10,000 publications from this institution
Reactive oxygen species (ROS), such as hydrogen peroxide, are important products of oxygen metabolism that, when misregulated, can accumulate and cause oxidative stress inside cells. Accordingly, organisms have evolved molecular systems, including antioxidant metalloenzymes (such as superoxide dismutase and catalase) and an array of thiol-based redox couples, to neutralize this threat to the cell when it occurs. On the other hand, emerging evidence shows that the controlled generation of ROS, particularly H(2)O(2), is necessary to maintain cellular fitness. The identification of NADPH oxidase enzymes, which generate specific ROS and reside in virtually all cell types throughout the body, is a prime example. Indeed, a growing body of work shows that H(2)O(2) and other ROS have essential functions in healthy physiological signaling pathways. The signal-stress dichotomy of H(2)O(2) serves as a source of motivation for disentangling its beneficial from its detrimental effects on living systems. Molecular imaging of this oxygen metabolite with reaction-based probes is a powerful approach for real-time, noninvasive monitoring of H(2)O(2) chemistry in biological specimens, but two key challenges to studying H(2)O(2) in this way are chemoselectivity and bioorthogonality of probe molecules. Chemoselectivity is problematic because traditional methods for ROS detection suffer from nonspecific reactivity with other ROS. Moreover, some methods require enzymatic additives not compatible with live-cell or live-animal specimens. Additionally, bioorthogonality requires that the reactions must not compete with or disturb intrinsic cellular chemistry; this requirement is particularly critical with thiol- or metal-based couples mediating the major redox events within the cell. Chemoselective bioorthogonal reactions, such as alkyne-azide cycloadditions and related click reactions, the Staudinger-Bertozzi ligation, and the transformations used in various reaction-based molecular probes, have found widespread application in the modification, labeling, and detection of biological molecules and processes. In this Account, we summarize H(2)O(2) studies from our laboratory using the H(2)O(2)-mediated oxidation of aryl boronates to phenols as a bioorthogonal approach to detect fluxes of this important ROS in living systems. We have installed this versatile switch onto organic and inorganic scaffolds to serve as "turn-on" probes for visible and near-infrared (NIR) fluorescence, ratiometric fluorescence, time-gated lanthanide luminescence, and in vivo bioluminescence detection of H(2)O(2) in living cells and animals. Further chemical and genetic manipulations target these probes to specific organelles and other subcellular locales and can also allow them to be trapped intracellularly, enhancing their sensitivity. These novel chemical tools have revealed fundamental new biological insights into the production, localization, trafficking, and in vivo roles of H(2)O(2) in a wide variety of living systems, including immune, cancer, stem, and neural cell models.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
The problem of designing reinforced concrete intake-outlet towers, partially submerged in water, to withstand earthquake ground motion is examined in general terms. It is shown that water, surrounding as well as inside, significantly affects the response to ground motion and these hydrodynamic effects should be considered in the design of towers. A rational method for elastic design including the hydrodynamic effects is proposed. It is recommended that towers be designed to elastically resist ground motions which they may experience several times during their useful life. The ductility requirements that would be imposed on code-designed towers by the intense ground motions expected near the causative fault during high magnitude earthquakes are evaluated; they appear to be rather large. It is recommended that forces for elastic design be increased so that the lateral displacement ductility requirements imposed by the most intense ground motion that can occur at the site would be no larger than a ductility factor of two.
An analysis procedure in the frequency domain for determining the earthquake responses of a dam was developed. The procedure inclides hydrodynamic interaction and water compressibility effects. Linear responses of idealized, two dimensional gravity dams and three dimensional dams, including arch dams were obtained. For an infinite uniform region a finite element discretization provides for a proper transmission of pressure waves. Hydrodynamic effects are equivalent to an added mass and added load in the frequency domain equations of motion of the dam. Complex frequency response functions for acceleration at the dam crest are presented for two dimensional concrete gravity and earth dams and for a three dimensional arch dam. Water compressibility and fluid foundation interaction significantly influence the response of concrete gravity dams and are even more important for each dam.
: Fracture by the progressive growth of incipient flaws under cyclically varying loads, i.e., by fatigue, must now be considered as the principal cause of in-service failures of engineering structures and components, whether associated with mechanical sliding and friction (fretting fatigue), rolling contact, aggressive environments (corrosion fatigue), or elevated temperatures (creep-fatigue). Of particular importance are the early stages of fatigue damage, involving the initial extension of microcracks and their subsequent growth at very low velocities, as these processes tend to dominate overall lifetime. This has been reflected by trends in fatigue research over the past five years, which have focused largely on so-called 'small cracks,' of dimensions comparable with the scale of microstructure or local plasticity, and on crack growth in the near-threshold regime, i.e., at stress intensities approaching the fatigue threshold below which cracks are presumed dormant. In addition, associated mechanistic studies have highlighted the critical role of crack tip shielding in fatigue, which arises predominantly from crack closure and deflection, and this has proved to be important in modeling aspects of environmentally-assisted cracking and behavior under variable amplitude loads, and in rationalizing the classical stress/strain-life and defect-tolerant design approaches. The series of international conferences 'Fatigue '87' covered a wide range of diverse views of the fundamental and applied aspects of fatigue. This included questions of cyclic deformation, crack initiation and propagation, small cracks, crack closure, variable amplitude effects, and environmentally-influenced behavior.
Yttria $({\mathrm{Y}}_{2}{\mathrm{O}}_{3})$ has become a promising gate oxide material to replace silicon dioxide in metal-oxide-semiconductor devices. Using a first-principles approach the electronic structure, defect structure, and formation energy of native point defects in ${\mathrm{Y}}_{2}{\mathrm{O}}_{3}$ are studied. Vacancies, interstitials, and antisites in their relevant charge states are considered. We find that within the band gap of ${\mathrm{Y}}_{2}{\mathrm{O}}_{3}$ oxygen vacancies, oxygen interstitials, yttrium vacancies, and yttrium interstitials can be stable depending on the Fermi level and external chemical potentials. When the Fermi level is constrained to be within the band gap of silicon, oxygen vacancies are the dominant defect type under low oxygen chemical potential condition. A higher oxygen chemical potential leads to oxygen interstitials and ultimately yttrium vacancies.
