GroEL-GroES-mediated protein folding requires an intact central cavity

The chaperonin GroEL is an oligomeric double ring structure that, together with the cochaperonin GroES, assists protein folding. Biochemical analyses indicate that folding occurs in a cis ternary complex in which substrate is sequestered within the GroEL central cavity underneath GroES. Recently, however, studies of GroEL “minichaperones” containing only the apical substrate binding subdomain have questioned the functional importance of substrate encapsulation within GroEL-GroES complexes. Minichaperones were reported to assist folding despite the fact that they are monomeric and therefore cannot form a central cavity. Here we compare directly the folding activity of minichaperones with that of the full GroEL-GroES system. In agreement with earlier studies, minichaperones assist folding of some proteins. However, this effect is observed only under conditions where substantial spontaneous folding is also observed and is indistinguishable from that resulting from addition of the nonchaperone protein α-casein. By contrast, the full GroE system efficiently promotes folding of several substrates under conditions where essentially no spontaneous folding is observed. These data argue that the full GroEL folding activity requires the intact GroEL-GroES complex, and in light of previous studies, underscore the importance of substrate encapsulation for providing a folding environment distinct from the bulk solution.

Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target

Synthetic C peptides, corresponding to the C helix of the HIV type 1 (HIV-1) gp41 envelope protein, are potent inhibitors of HIV-1 membrane fusion. One such peptide is in clinical trials. The crystal structure of the gp41 core, in its proposed fusion-active conformation, is a trimer of helical hairpins in which three C helices pack against a central coiled coil. Each C helix shows especially prominent contacts with one of three symmetry-related, hydrophobic cavities on the surface of the coiled coil. We show that the inhibitory activity of the C peptide C34 depends on its ability to bind to this coiled-coil cavity. Moreover, examining a series of C34 peptide variants with modified cavity-binding residues, we find a linear relationship between the logarithm of the inhibitory potency and the stability of the corresponding helical-hairpin complexes. Our results provide strong evidence that this coiled-coil cavity is a good drug target and clarify the mechanism of C peptide inhibition. They also suggest simple, quantitative assays for the identification and evaluation of analogous inhibitors of HIV-1 entry.

A GIS-based methodology to quantitatively define an Adjacent Protected Area in a shallow karst cavity: The case of Altamira cave

Different types of land use are usually present in the areas adjacent to many shallow karst cavities. Over time, the increasing amount of potentially harmful matter and energy, of mainly anthropic origin or influence, that reaches the interior of a shallow karst cavity can modify the hypogeal ecosystem and increase the risk of damage to the Palaeolithic rock art often preserved within the cavity. This study proposes a new Protected Area status based on the geological processes that control these matter and energy fluxes into the Altamira cave karst system. Analysis of the geological characteristics of the shallow karst system shows that direct and lateral infiltration, internal water circulation, ventilation, gas exchange and transmission of vibrations are the processes that control these matter and energy fluxes into the cave. This study applies a comprehensive methodological approach based on Geographic Information Systems (GIS) to establish the area of influence of each transfer process. The stratigraphic and structural characteristics of the interior of the cave were determined using 3D Laser Scanning topography combined with classical field work, data gathering, cartography and a porosity–permeability analysis of host rock samples. As a result, it was possible to determine the hydrogeological behavior of the cave. In addition, by mapping and modeling the surface parameters it was possible to identify the main features restricting hydrological behavior and hence direct and lateral infiltration into the cave. These surface parameters included the shape of the drainage network and a geomorphological and structural characterization via digital terrain models. Geological and geomorphological maps and models integrated into the GIS environment defined the areas involved in gas exchange and ventilation processes. Likewise, areas that could potentially transmit vibrations directly into the cave were identified. This study shows that it is possible to define a Protected Area by quantifying the area of influence related to each transfer process. The combined maximum area of influence of all the processes will result in the new Protected Area. This area will thus encompass all the processes that account for most of the matter and energy carried into the cave and will fulfill the criteria used to define the Protected Area. This methodology is based on the spatial quantification of processes and entities of geological origin and can therefore be applied to any shallow karst system that requires protection.

Tight-Binding Approximations in 1D and 2D Coupled-Cavity Photonic Crystal Structures

Light confinement and controlling an optical field has numerous applications in the field of telecommunications for optical signals processing. When the wavelength of the electromagnetic field is on the order of the period of a photonic microstructure, the field undergoes reflection, refraction, and coherent scattering. This produces photonic bandgaps, forbidden frequency regions or spectral stop bands where light cannot exist. Dielectric perturbations that break the perfect periodicity of these structures produce what is analogous to an impurity state in the bandgap of a semiconductor. The defect modes that exist at discrete frequencies within the photonic bandgap are spatially localized about the cavity-defects in the photonic crystal. In this thesis the properties of two tight-binding approximations (TBAs) are investigated in one-dimensional and two-dimensional coupled-cavity photonic crystal structures We require an efficient and simple approach that ensures the continuity of the electromagnetic field across dielectric interfaces in complex structures. In this thesis we develop \textrm{E} -- and \textrm{D} --TBAs to calculate the modes in finite 1D and 2D two-defect coupled-cavity photonic crystal structures. In the \textrm{E} -- and \textrm{D} --TBAs we expand the coupled-cavity \overrightarrow{E} --modes in terms of the individual \overrightarrow{E} -- and \overrightarrow{D} --modes, respectively. We investigate the dependence of the defect modes, their frequencies and quality factors on the relative placement of the defects in the photonic crystal structures. We then elucidate the differences between the two TBA formulations, and describe the conditions under which these formulations may be more robust when encountering a dielectric perturbation. Our 1D analysis showed that the 1D modes were sensitive to the structure geometry. The antisymmetric \textrm{D} mode amplitudes show that the \textrm{D} --TBA did not capture the correct (tangential \overrightarrow{E} --field) boundary conditions. However, the \textrm{D} --TBA did not yield significantly poorer results compared to the \textrm{E} --TBA. Our 2D analysis reveals that the \textrm{E} -- and \textrm{D} --TBAs produced nearly identical mode profiles for every structure. Plots of the relative difference between the \textrm{E} and \textrm{D} mode amplitudes show that the \textrm{D} --TBA did capture the correct (normal \overrightarrow{E} --field) boundary conditions. We found that the 2D TBA CC mode calculations were 125-150 times faster than an FDTD calculation for the same two-defect PCS. Notwithstanding this efficiency, the appropriateness of either TBA was found to depend on the geometry of the structure and the mode(s), i.e. whether or not the mode has a large normal or tangential component.

Maintenance of coelomic fluid pH in sea urchins exposed to elevated CO2: the role of body cavity epithelia and stereom dissolution

Experimental ocean acidification leads to a shift in resource allocation and to an increased [HCO3-] within the perivisceral coelomic fluid (PCF) in the Baltic green sea urchin Strongylocentrotus droebachiensis. We investigated putative mechanisms of this pH compensation reaction by evaluating epithelial barrier function and the magnitude of skeleton (stereom) dissolution. In addition, we measured ossicle growth and skeletal stability. Ussing chamber measurements revealed that the intestine formed a barrier for HCO3- and was selective for cation diffusion. In contrast, the peritoneal epithelium was leaky and only formed a barrier for macromolecules. The ossicles of 6 week high CO2-acclimatised sea urchins revealed minor carbonate dissolution, reduced growth but unchanged stability. On the other hand, spines dissolved more severely and were more fragile following acclimatisation to high CO2. Our results indicate that epithelia lining the PCF space contribute to its acid-base regulation. The intestine prevents HCO3- diffusion and thus buffer leakage. In contrast, the leaky peritoneal epithelium allows buffer generation via carbonate dissolution from the surrounding skeletal ossicles. Long-term extracellular acid-base balance must be mediated by active processes, as sea urchins can maintain relatively high extracellular [HCO3-]. The intestinal epithelia are good candidate tissues for this active net import of HCO3- into the PCF. Spines appear to be more vulnerable to ocean acidification which might significantly impact resistance to predation pressure and thus influence fitness of this keystone species.

Shell size, body mass and average pO2 in mantle cavity water of different marine mollusc species

Marine invertebrates with open circulatory system establish low and constant oxygen partial pressure (Po2) around their tissues. We hypothesized that as a first step towards maintenance of low haemolymph and tissue oxygenation, the Po2 in molluscan mantle cavity water should be lowered against normoxic (21 kPa) seawater Po2, but balanced high enough to meet the energetic requirements in a given species. We recorded Po2 in mantle cavity water of five molluscan species with different lifestyles, two pectinids (Aequipecten opercularis, Pecten maximus), two mud clams (Arctica islandica, Mya arenaria), and a limpet (Patella vulgata). All species maintain mantle cavity water oxygenation below normoxic Po2. Average mantle cavity water Po2 correlates positively with standard metabolic rate (SMR): highest in scallops and lowest in mud clams. Scallops show typical Po2 frequency distribution, with peaks between 3 and 10 kPa, whereas mud clams and limpets maintain mantle water Po2 mostly <5 kPa. Only A. islandica and P. vulgata display distinguishable temporal patterns in Po2 time series. Adjustment of mantle cavity Po2 to lower than ambient levels through controlled pumping prevents high oxygen gradients between bivalve tissues and surrounding fluid, limiting oxygen flux across the body surface. The patterns of Po2 in mantle cavity water correspond to molluscan ecotypes.

Greenland and Antarctic ice sheet topography, cavity geometry, and global bathymetry (RTopo-2), links to NetCDF files

The ocean plays an important role in modulating the mass balance of the polar ice sheets by interacting with the ice shelves in Antarctica and with the marine-terminating outlet glaciers in Greenland. Given that the flux of warm water onto the continental shelf and into the sub-ice cavities is steered by complex bathymetry, a detailed topography data set is an essential ingredient for models that address ice-ocean interaction. We followed the spirit of the global RTopo-1 data set and compiled consistent maps of global ocean bathymetry, upper and lower ice surface topographies and global surface height on a spherical grid with now 30-arc seconds resolution. We used the General Bathymetric Chart of the Oceans (GEBCO, 2014) as the backbone and added the International Bathymetric Chart of the Arctic Ocean version 3 (IBCAOv3) and the Interna- tional Bathymetric Chart of the Southern Ocean (IBCSO) version 1. While RTopo-1 primarily aimed at a good and consistent representation of the Antarctic ice sheet, ice shelves and sub-ice cavities, RTopo-2 now also contains ice topographies of the Greenland ice sheet and outlet glaciers. In particular, we aimed at a good representation of the fjord and shelf bathymetry sur- rounding the Greenland continent. We corrected data from earlier gridded products in the areas of Petermann Glacier, Hagen Bræ and Sermilik Fjord assuming that sub-ice and fjord bathymetries roughly follow plausible Last Glacial Maximum ice flow patterns. For the continental shelf off northeast Greenland and the floating ice tongue of Nioghalvfjerdsfjorden Glacier at about 79°N, we incorporated a high-resolution digital bathymetry model considering original multibeam survey data for the region. Radar data for surface topographies of the floating ice tongues of Nioghalvfjerdsfjorden Glacier and Zachariæ Isstrøm have been obtained from the data centers of Technical University of Denmark (DTU), Operation Icebridge (NASA/NSF) and Alfred Wegener Institute (AWI). For the Antarctic ice sheet/ice shelves, RTopo-2 largely relies on the Bedmap-2 product but applies corrections for the geometry of Getz, Abbot and Fimbul ice shelf cavities.

Ramp into cavity

IMB (Irvine, Michigan, Brookline), a collaboration between the University of Michigan, the University of California at Irvine, and the U.S. Department of Energy, was an experiment designed to determine the ultimate stability of matter. Construction image. Finished cavity -- looking through tunnel to main part of mine.

Integrated approach to cavity system seismic evaluation /

Mode of access: Internet.

Frequency-modulation oscillator cavity system for synchrotron acceleration in the Illinois 300 MeV betatron,

Mode of access: Internet.

Experiments on circular arc and flat plate hydrofoils in noncavitating and full cavity flows.

"Department of the Navy. Bureau of Ships. Contract Nonr-220 (12)."

Entangled two-photon source using biexciton emission of an asymmetric quantum dot in a cavity

A semiconductor based scheme has been proposed for generating entangled photon pairs from the radiative decay of an electrically pumped biexciton in a quantum dot. Symmetric dots produce polarization entanglement, but experimentally realized asymmetric dots produce photons entangled in both polarization and frequency. In this work, we investigate the possibility of erasing the “which-path” information contained in the frequencies of the photons produced by asymmetric quantum dots to recover polarization-entangled photons. We consider a biexciton with nondegenerate intermediate excitonic states in a leaky optical cavity with pairs of degenerate cavity modes close to the nondegenerate exciton transition frequencies. An open quantum system approach is used to compute the polarization entanglement of the two-photon state after it escapes from the cavity, measured by the visibility of two-photon interference fringes. We explicitly relate the two-photon visibility to the degree of the Bell-inequality violation, deriving a threshold at which Bell-inequality violations will be observed. Our results show that an ideal cavity will produce maximally polarization-entangled photon pairs, and even a nonideal cavity will produce partially entangled photon pairs capable of violating a Bell-inequality.

Determining the age of adult wild dogs (Canis lupus dingo, C-l. domesticus and their hybrids). I. Pulp cavity: tooth width ratios

In order to determine the age of adult wild dogs, we compared two methods ( that of Thomson and Rose (TR method) and that of Knowlton and Whittemore (KW method)) of measuring and calculating pulp cavity : tooth width ratios on upper and lower canine teeth from 68 mixed-sex, known-age wild dogs of 9 months to 13 years of age reared at two localities. Although significant relationships ( P = 0.0001) were found between age and pulp cavity ratios by both methods, the TR ratio calculation and measurement showed heteroscedasity in error variance whereas the KW ratios had a more stable error variance and were normally distributed. The KW method also found significant differences between pulp cavity ratios between teeth of the upper and lower jaws ( P < 0.0001) and sex ( P = 0.01) but not geographic origin ( P = 0.1). Regressions and formulae for fitted curves are presented separately for male and female wild dogs. Males show greater variability in pulp cavity decrements with age than do females, suggesting a physiological difference between the sexes. We conclude that the KW method of using pulp cavity as a proportion of tooth width, measured 15 mm from the root tip and averaged over both upper canines, is the more accurate method of estimating the age of adult wild dogs.

High-fidelity measurement and quantum feedback control in circuit QED

Circuit QED is a promising solid-state quantum computing architecture. It also has excellent potential as a platform for quantum control-especially quantum feedback control-experiments. However, the current scheme for measurement in circuit QED is low efficiency and has low signal-to-noise ratio for single-shot measurements. The low quality of this measurement makes the implementation of feedback difficult, and here we propose two schemes for measurement in circuit QED architectures that can significantly improve signal-to-noise ratio and potentially achieve quantum-limited measurement. Such measurements would enable the implementation of quantum feedback protocols and we illustrate this with a simple entanglement-stabilization scheme.

Follicular dendritic cell sarcoma associated with Castelmans disease presenting in the oral cavity

Follicular dendritic cell sarcoma (FDCS) is a rare intermediate grade malignant neoplasm of reticular dendritic origin. Castleman’s disease (CD) represents a non-neoplastic lymphoproliferative disorder with various clinical and morphological features. FDCS has been reported to be associated with CD. In this article, we describe the first case of follicular dendritic cell sarcoma associated with Castleman’s disease presenting in the oral cavity. Copyright © 2005 Elsevier Ltd All rights reserved.