DISPLACEMENT CASCADE SIMULATION IN TUNGSTEN UP TO 200 KEV OF DAMAGE ENERGY AT 300, 1025, AND 2050 K

DOE Office of Scientific and Technical Information (OSTI.GOV)

Setyawan, Wahyu; Nandipati, Giridhar; Roche, Kenneth J.

2015-09-22

We generated molecular dynamics database of primary defects that adequately covers the range of tungsten recoil energy imparted by 14-MeV neutrons. During this semi annual period, cascades at 150 and 200 keV at 300 and 1025 K were simulated. Overall, we included damage energy up to 200 keV at 300 and 1025 K, and up to 100 keV at 2050 K. We report the number of surviving Frenkel pairs (NF) and the size distribution of defect clusters. The slope of the NF curve versus cascade damage energy (EMD), on a log-log scale, changes at a transition energy (μ). For EMDmore » > μ, the cascade forms interconnected damage regions that facilitate the formation of large clusters of defects. At 300 K and EMD = 200 keV, the largest size of interstitial cluster and vacancy cluster is 266 and 335, respectively. Similarly, at 1025 K and EMD = 200 keV, the largest size of interstitial cluster and vacancy cluster is 296 and 338, respectively. At 2050 K, large interstitial clusters also routinely form, but practically no large vacancy clusters do« less

Theoretical investigation of microstructure evolution and deformation of zirconium under neutron irradiation

DOE PAGES

Barashev, A. V.; Golubov, S. I.; Stoller, R. E.

2015-06-01

We studied the radiation growth of zirconium using a reaction–diffusion model which takes into account intra-cascade clustering of self-interstitial atoms and one-dimensional diffusion of interstitial clusters. The observed dose dependence of strain rates is accounted for by accumulation of sessile dislocation loops during irradiation. Moreover, the computational model developed and fitted to available experimental data is applied to study deformation of Zr single crystals under irradiation up to hundred dpa. Finally, the effect of cold work and the reasons for negative prismatic strains and co-existence of vacancy and interstitial loops are elucidated.

INTERACTION OF INTERSTITIAL CLUSTERS WITH RHENIUM, OSMIUM, AND TANTALUM IN TUNGSTEN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Setyawan, Wahyu; Nandipati, Giridhar; Kurtz, Richard J.

2016-09-01

In the previous semi annual report, we explored the stability of interstitial clusters in W up to size seven. In this report, we study the binding of those clusters to Re, Os, and Ta atoms. For each cluster size, the three most stable configurations are considered to average the binding property. The average binding energy to a Re decreases from 0.79 eV for a size-1 cluster (a [111] dumbbell) to 0.65 eV for a size-7 cluster. For Os, the binding decreases from 1.61 eV for a [111] dumbbell to 1.34 eV for a size-7 cluster. Tantalum is repulsive to interstitialmore » clusters with binding energy ranges from -0.61 eV for a [111] dumbbell to -0.5 eV for a size-7 cluster.« less

Phosphorus-defect interactions during thermal annealing of ion implanted silicon

NASA Astrophysics Data System (ADS)

Keys, Patrick Henry

Ion implantation of dopant atoms into silicon generates nonequilibrium levels of crystal defects that can lead to the detrimental effects of transient enhanced diffusion (TED), incomplete dopant activation, and p-n junction leakage. In order to control these effects, it is vital to have a clear understanding of dopant-defect interactions and develop models that account for these interactions. This research focuses on experimentally investigating and modeling the clustering of phosphorus dopant atoms with silicon interstitials. Damage recovery of 40keV Si+ implants in phosphorus doped wells is experimentally analyzed. The effects of background phosphorus concentration, self implant dose, and anneal temperature are investigated. Phosphorus concentrations ranging from 2.0 x 1017 to 4.0 x 1019 cm-3 and Si+ doses ranging from 5.0 x 1013 cm-2 to 2.0 x 1014 cm-2 are studied during 650-800°C anneals. A dramatic reduction in the number of interstitials bound in {311} defects with increasing phosphorus background concentration is observed. It is suggested that the reduction of interstitials in {311} defects at high phosphorus concentrations is due to the formation of phosphorus-interstitial clusters (PICs). The critical concentration for clustering (approximately 1.0 x 1019 cm-3 at 750°C) is strongly temperature dependent and in close agreement with the kink concentration of phosphorus diffusion. Information gained from these "well experiments" is applied to the study of direct phosphorus implantation. An experimental study is conducted on 40keV phosphorus implanted to a dose of 1.0 x 1014 cm-2 during 650-800°C anneals. Electrically inactive PICs are shown to form at concentrations below the solid solubility limit due to high interstitial supersaturations. Data useful for developing a model to accurately predict phosphorus diffusion under nonequilibrium conditions are extracted from the experimental results. A cluster-mediated diffusion model is developed using the Florida Object Oriented Process Simulator (FLOOPS). The nucleation of defects is controlled by the diffusion-limited competition for excess interstitials between PICs and {311} clusters. The release of interstitials is driven by cluster dissolution. Modeling results show a strong correlation to those experimentally observed over a wide temporal and thermal domain using a single set of parameters. Improvements in process simulator accuracy are demonstrated with respect to dopant activation, TED, and dose loss.

Optimization of self-interstitial clusters in 3C-SiC with genetic algorithm

NASA Astrophysics Data System (ADS)

Ko, Hyunseok; Kaczmarowski, Amy; Szlufarska, Izabela; Morgan, Dane

2017-08-01

Under irradiation, SiC develops damage commonly referred to as black spot defects, which are speculated to be self-interstitial atom clusters. To understand the evolution of these defect clusters and their impacts (e.g., through radiation induced swelling) on the performance of SiC in nuclear applications, it is important to identify the cluster composition, structure, and shape. In this work the genetic algorithm code StructOpt was utilized to identify groundstate cluster structures in 3C-SiC. The genetic algorithm was used to explore clusters of up to ∼30 interstitials of C-only, Si-only, and Si-C mixtures embedded in the SiC lattice. We performed the structure search using Hamiltonians from both density functional theory and empirical potentials. The thermodynamic stability of clusters was investigated in terms of their composition (with a focus on Si-only, C-only, and stoichiometric) and shape (spherical vs. planar), as a function of the cluster size (n). Our results suggest that large Si-only clusters are likely unstable, and clusters are predominantly C-only for n ≤ 10 and stoichiometric for n > 10. The results imply that there is an evolution of the shape of the most stable clusters, where small clusters are stable in more spherical geometries while larger clusters are stable in more planar configurations. We also provide an estimated energy vs. size relationship, E(n), for use in future analysis.

Primary damage formation in bcc iron

NASA Astrophysics Data System (ADS)

Stoller, R. E.; Odette, G. R.; Wirth, B. D.

1997-11-01

Primary defect formation in bee iron has been extensively investigated using the methods of molecular dynamics (MD) and Monte Carlo (MC) simulation. This research has employed a modified version of the Finnis-Sinclair interatomic potential. MD was used in the simulation of displacement cascades with energies up to 40 keV and to examine the migration of the interstitial clusters that were observed to form in the cascade simulations. Interstitial cluster binding energies and the stable cluster configurations were determined by structural relaxation and energy minimization using a MC method with simulated annealing. Clusters containing up to 19 interstitials were examined. Taken together with the previous work, these new simulations provide a reasonably complete description of primary defect formation in iron. The results of the displacement cascade simulations have been used to characterize the energy and temperature dependence of primary defect formation in terms of two parameters: (1) the number of surviving point defects and (2) the fraction of the surviving defects that are contained in clusters. The number of surviving point defects is expressed as a fraction of the atomic displacements calculated using the secondary displacement model of Norgett-Robinson-Torrens (NRT). Although the results of the high energy simulations are generally consistent with those obtained at lower energies, two notable exceptions were observed. The first is that extensive subcascade formation at 40 keV leads to a higher defect survival fraction than would be predicted from extrapolation of the results obtained for energies up to 20 keV. The stable defect fraction obtained from the MD simulations is a smoothly decreasing function up to 20 keV. Subcascade formation leads to a slight increase in this ratio at 40 keV, where the value is about the same as at 10 keV. Secondly, the potential for a significant level of in-cascade vacancy clustering was observed. Previous cascade studies employing this potential have reported extensive interstitial clustering, but little evidence of vacancy clustering. Interstitial clusters were found to be strongly bound, with binding energies in excess of 1 eV. The larger clusters exhibited a complex, 3D structure and were composed of <111> crowdions. These clusters were observed to migrate by collective <111> translations with an activation energy on the order of 0.1 eV.

Off-stoichiometric defect clustering in irradiated oxides

NASA Astrophysics Data System (ADS)

Khalil, Sarah; Allen, Todd; EL-Azab, Anter

2017-04-01

A cluster dynamics model describing the formation of vacancy and interstitial clusters in irradiated oxides has been developed. The model, which tracks the composition of the oxide matrix and the defect clusters, was applied to the early stage formation of voids and dislocation loops in UO2, and the effects of irradiation temperature and dose rate on the evolution of their densities and composition was investigated. The results show that Frenkel defects dominate the nucleation process in irradiated UO2. The results also show that oxygen vacancies drive vacancy clustering while the migration energy of uranium vacancies is a rate-limiting factor for the nucleation and growth of voids. In a stoichiometric UO2 under irradiation, off-stoichiometric vacancy clusters exist with a higher concentration of hyper-stoichiometric clusters. Similarly, off-stoichiometric interstitial clusters form with a higher concentration of hyper-stoichiometric clusters. The UO2 matrix was found to be hyper-stoichiometric due to the accumulation of uranium vacancies.

A Wsbnd Ne interatomic potential for simulation of neon implantation in tungsten

NASA Astrophysics Data System (ADS)

Backman, Marie; Juslin, Niklas; Huang, Guiyang; Wirth, Brian D.

2016-08-01

An interatomic pair potential for Wsbnd Ne is developed for atomistic molecular dynamics simulations of neon implantation in tungsten. The new potential predicts point defect energies and binding energies of small clusters that are in good agreement with electronic structure calculations. Molecular dynamics simulations of small neon clusters in tungsten show that trap mutation, in which an interstitial neon cluster displaces a tungsten atom from its lattice site, occurs for clusters of three or more neon atoms. However, near a free surface, trap mutation can occur at smaller sizes, including even a single neon interstitial in close proximity to a (100) or (110) surface.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez, Danny, E-mail: danny-perez@lanl.gov; Sandoval, Luis; Voter, Arthur F.

Due to its enviable properties, tungsten is a leading candidate plasma facing material in nuclear fusion reactors. However, like many other metals, tungsten is known to be affected by the high doses of helium atoms incoming from the plasma. Indeed, the implanted interstitial helium atoms cluster together and, upon reaching a critical cluster size, convert into substitutional nanoscale He bubbles. These bubbles then grow by absorbing further interstitial clusters from the matrix. This process can lead to deleterious changes in microstructure, degradation of mechanical properties, and contamination of the plasma. In order to better understand the growth process, we usemore » traditional and accelerated molecular dynamics simulations to investigate the interactions between interstitial He clusters and pre-existing bubbles. These interactions are characterized in terms of thermodynamics and kinetics. We show that the proximity of the bubble leads to an enhancement of the trap mutation rate and, consequently, to the nucleation of satellite bubbles in the neighborhood of existing ones. We also uncover a number of mechanisms that can lead to the subsequent annihilation of such satellite nanobubbles.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez, Danny; Sandoval, Luis; Uberuaga, Blas P.

Due to its enviable properties, tungsten is a leading candidate plasma facing material in nuclear fusion reactors. But, like many other metals, tungsten is known to be affected by the high doses of helium atoms incoming from the plasma. Indeed, the implanted interstitial helium atoms cluster together and, upon reaching a critical cluster size, convert into substitutional nanoscale He bubbles. These bubbles then grow by absorbing further interstitial clusters from the matrix. This process can lead to deleterious changes in microstructure, degradation of mechanical properties, and contamination of the plasma. In order to better understand the growth process, we usemore » traditional and accelerated molecular dynamics simulations to investigate the interactions between interstitial He clusters and pre-existing bubbles. These interactions are characterized in terms of thermodynamics and kinetics. We also show that the proximity of the bubble leads to an enhancement of the trap mutation rate and, consequently, to the nucleation of satellite bubbles in the neighborhood of existing ones. Finally, we uncover a number of mechanisms that can lead to the subsequent annihilation of such satellite nanobubbles.« less

Towards understanding the mechanism of rhenium and osmium precipitation in tungsten and its implication for tungsten-based alloys

NASA Astrophysics Data System (ADS)

Li, Yu-Hao; Zhou, Hong-Bo; Deng, Huiqiu; Lu, Gang; Lu, Guang-Hong

2018-07-01

Using a first-principles method in combination with thermodynamic models, we investigate the interaction between rhenium/osmium (Re/Os) and defects to explore the mechanism of radiation-induced Re/Os precipitation in tungsten (W). We demonstrate that radiation-induced defects play a key role in the solute precipitation in W, especially for self-interstitial atoms (SIAs). The presence of SIAs can significantly reduce the total nucleation free energy change of Re/Os, and thus facilitate the nucleation of Re/Os in W. Further, SIA is shown to be easily trapped by Re/Os once overcoming a low energy barrier, forming a W-Re/Os mixed dumbbell. Such W-Re/Os dumbbell forms a high stable Re/Os-Re/Os dumbbell structure with the substitutional Re/Os atoms, which can serve as a trapping centre for subsequent interstitial-Re/Os, leading to the growth of Re/Os-rich clusters. Consequently, an interstitial-mediated migration and aggregation mechanism for Re/Os precipitation in W has been proposed. Our results reveale that the alloying elements-defects interaction has significantly effect on their behaviors under irradiation, which should be considered in the design of W-based alloys for future fusion devices.

The effects of cation–anion clustering on defect migration in MgAl 2O 4

DOE PAGES

Zamora, Richard J.; Voter, Arthur F.; Perez, Danny; ...

2016-06-28

Magnesium aluminate spinel (MgAl 2O 4), like many other ceramic materials, offers a range of technological applications, from nuclear reactor materials to military body armor. For many of these applications, it is critical to understand both the formation and evolution of lattice defects throughout the lifetime of the material. We use the Speculatively Parallel Temperature Accelerated Dynamics (SpecTAD) method to investigate the effects of di-vacancy and di-interstitial formation on the mobility of the component defects. From long-time trajectories of the state-to-state dynamics, we characterize the migration pathways of defect clusters, and calculate their self-diffusion constants across a range of temperatures.more » We find that the clustering of Al and O vacancies drastically reduces the mobility of both defects, while the clustering of Mg and O vacancies completely immobilizes them. For interstitials, we find that the clustering of Mg and O defects greatly reduces O interstitial mobility, but has only a weak effect on Mg. Lastly, these findings illuminate important new details regarding defect kinetics relevant to the application of MgAl 2O 4 in extreme environments.« less

Helium behavior in oxide dispersion strengthened (ODS) steel: Insights from ab initio modeling

NASA Astrophysics Data System (ADS)

Sun, Dan; Li, Ruihuan; Ding, Jianhua; Huang, Shaosong; Zhang, Pengbo; Lu, Zheng; Zhao, Jijun

2018-02-01

Using first-principles calculations, we systemically investigate the energetics and stability behavior of helium (He) atoms and small Hen (n = 2-4) clusters inside oxide dispersion strengthened (ODS) steel, as well as the incorporation of large amount of He atoms inside Y2O3 crystal. From the energetic point of view, He atom inside Y2O3 cluster is most stable, followed by the interstitial sites at the α-Fe/Y2O3 interface, and the tetrahedral interstitial sites inside α-Fe region. We further consider Hen (n = 2-4) clusters at the tetrahedral interstitial site surrounded by four Y atoms, which is the most stable site in the ODS steel model. The incorporation energies of all these Hen clusters are lower than that of single He atom in α-Fe, while the binding energy between two He atoms is relatively small. With insertion of 15 He atoms into 80-atom unit cell of Y2O3 crystal, the incorporation energy of He atoms is still lower than that of He4 cluster in α-Fe crystal. These theoretical results suggest that He atoms tend to aggregate inside Y2O3 clusters or at the α-Fe/Y2O3 interface, which is beneficial to prevent the He embrittlement in ODS steels.

Atomic diffusion in strain fields near solutes

NASA Astrophysics Data System (ADS)

Shropshire, Steven L.; Collins, Gary S.

1993-03-01

Annihilation reactions between mobile self-interstitial defects and complexes of vacancies with111In probe solutes in Au were studied. Measurements were made using the technique of perturbed angular correlations of gamma rays (PAC). Au samples were doped with complexes and plastically deformed at a low temperature to generate fluxes of self-interstitials. Changes in the concentrations of monovacancy (1V) to tetravacancy (4V) complexes induced by annihilation reactions were measured. These are now analysed using a system of coupled first-order equations in order to obtain interstitial annihilation cross sections of the complexes and the fractional amounts of different interstitial clusters in the flux. Relative cross sections obtained for Au are 1.0(1), 3.3(3), 1.2(2) and 7.5(2.5), respectively, for 1V to 4V complexes. The large increase in the cross sections with vacancy number is attributed to a progressive relaxation of the dilatational strain surrounding the oversized In solute as more vacancies are trapped. Also obtained from the analysis are values 0.34(5), 0.66(7), 0.0(1) and 0.0(2), respectively, for the fractions of mobile 1I to 4I clusters in deformed Au, indicating that di-interstitials are produced more readily than mono-interstitials during plastic deformation.

STABILITY OF SMALL SELF-INTERSTITIAL CLUSTERS IN TUNGSTEN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Setyawan, Wahyu; Nandipati, Giridhar; Kurtz, Richard J.

2015-12-31

Density functional theory was employed to explore the stability of interstitial clusters in W up to size seven. For each cluster size, the most stable configuration consists of parallel dumbbells. For clusters larger than size three, parallel dumbbells prefer to form in a multilayer fashion, instead of a planar structure. For size-7 clusters, the most stable configuration is a complete octahedron. The binding energy of a [111] dumbbell to the most stable cluster increases with cluster size, namely 2.49, 3.68, 4.76, 4.82, 5.47, and 6.85 eV for clusters of size 1, 2, 3, 4, 5, and 6, respectively. For amore » size-2 cluster, collinear dumbbells are still repulsive at the maximum allowable distance of 13.8 Å (the fifth neighbor along [111]). On the other hand, parallel dumbbells are strongly bound together. Two parallel dumbbells in which the axis-to-axis distance is within a cylindrical radius of 5.2 Å still exhibit a considerable binding of 0.28 eV. The most stable cluster in each size will be used to explore interactions with transmutation products.« less

Change of Energy of the Cubic Subnanocluster of Iron Under Influence of Interstitial and Substitutional Atoms.

PubMed

Nedolya, Anatoliy V; Bondarenko, Natalya V

2016-12-01

Energy change of an iron face-centred cubic subnanocluster was evaluated using molecular mechanics method depending on the position of a carbon interstitial atom and substitutional atoms of nickel. Calculations of all possible positions of impurity atoms show that the energy change of the system are discrete and at certain positions of the atoms are close to continuous.In terms of energy, when all impurity atoms are on the same edge of an atomic cluster, their positions are more advantageous. The presence of nickel atoms on the edge of a cubic cluster resulted in decrease of potential barrier for a carbon atom and decrease in energy in the whole cluster. A similar drift of a carbon atom from central octahedral interstitial site to the surface in the direction <011> occurred under the influence of surface factors.Such configuration corresponds to decreasing symmetry and increasing the number of possible energy states of a subnanocluster, and it corresponds to the condition of spontaneous crystallization process in an isolated system.Taking into account accidental positions of the nickel atom in the iron cluster, such behaviour of the carbon atom can explain the mechanism of growth of a new phase and formation of new clusters in the presence of other kind of atoms because of surface influence.

Cluster dynamics modeling and experimental investigation of the effect of injected interstitials

NASA Astrophysics Data System (ADS)

Michaut, B.; Jourdan, T.; Malaplate, J.; Renault-Laborne, A.; Sefta, F.; Décamps, B.

2017-12-01

The effect of injected interstitials on loop and cavity microstructures is investigated experimentally and numerically for 304L austenitic stainless steel irradiated at 450 °C with 10 MeV Fe5+ ions up to about 100 dpa. A cluster dynamics model is parametrized on experimental results obtained by transmission electron microscopy (TEM) in a region where injected interstitials can be safely neglected. It is then used to model the damage profile and study the impact of self-ion injection. Results are compared to TEM observations on cross-sections of specimens. It is shown that injected interstitials have a significant effect on cavity density and mean size, even in the sink-dominated regime. To quantitatively match the experimental data in the self-ions injected area, a variation of some parameters is necessary. We propose that the fraction of freely migrating species may vary as a function of depth. Finally, we show that simple rate theory considerations do not seem to be valid for these experimental conditions.

Evolution of Radiation Induced Defects in SiC: A Multiscale Simulation Approach

NASA Astrophysics Data System (ADS)

Jiang, Hao

Because of various excellent properties, SiC has been proposed for many applications in nuclear reactors including cladding layers in fuel rod, fission products container in TRISO fuel, and first wall/blanket in magnetic controlled fusion reactors. Upon exposure to high energy radiation environments, point defects and defect clusters are generated in materials in amounts significantly exceeding their equilibrium concentrations. The accumulation of defects can lead to undesired consequences such as crystalline-to-amorphous transformation1, swelling, and embrittlement, and these phenomena can adversely affect the lifetime of SiC based components in nuclear reactors. It is of great importance to understand the accumulation process of these defects in order to estimate change in properties of this material and to design components with superior ability to withstand radiation damages. Defect clusters are widely in SiC irradiated at the operation temperatures of various reactors. These clusters are believed to cause more than half of the overall swelling of irradiated SiC and can potentially lead to lowered thermal conductivity and mechanical strength. It is critical to understand the formation and growth of these clusters. Diffusion of these clusters is one importance piece to determine the growth rate of clusters; however it is unclear so far due to the challenges in simulating rare events. Using a combination of kinetic Activation Relaxation Technique with empirical potential and ab initio based climbing image nudged elastic band method, I performed an extensive search of the migration paths of the most stable carbon tri-interstitial cluster in SiC. This research reveals paths with the lowest energy barriers to migration, rotation, and dissociation of the most stable cluster. Based on these energy barriers, I concluded defect clusters are thermally immobile at temperatures lower than 1500 K and can dissociate into smaller clusters and single interstitials at temperatures beyond that. Even though clusters cannot diffuse by thermal vibrations, we found they can migrate at room temperature under the influence of electron radiation. This is the first direct observation of radiation-induced diffusion of defect clusters in bulk materials. We show that the underlying mechanism of this athermal diffusion is elastic collision between incoming electrons and cluster atoms. Our findings suggest that defect clusters may be mobile under certain irradiation conditions, changing current understanding of cluster annealing process in irradiated SiC. With the knowledge of cluster diffusion in SiC demonstrated in this thesis, we now become able to predict cluster evolution in SiC with good agreement with experimental measurements. This ability can enable us to estimate changes in many properties of irradiated SiC relevant for its applications in reactors. Internal interfaces such as grain boundaries can behave as sinks to radiation induced defects. The ability of GBs to absorb, transport, and annihilate radiation-induced defects (sink strength) is important to understand radiation response of polycrystalline materials and to better design interfaces for improved resistance to radiation damage. Nowadays, it is established GBs' sink strength is not a static property but rather evolves with many factors, including radiation environments, grain size, and GB microstructure. In this thesis, I investigated the response of small-angle tilt and twist GBs to point defects fluxes in SiC. First of all, I found the pipe diffusion of interstitials in tilt GBs is slower than bulk diffusion. This is because the increased interatomic distance at dislocation cores raises the migration barrier of interstitial dumbbells. Furthermore, I show that both the annihilation of interstitials at jogs and jog nucleation from clusters are diffusion-controlled and can occur under off-stoichiometric interstitial fluxes. Finally, a dislocation line model is developed to predict the role of tilt GBs in annihilating radiation damage. The model predicts the role of tilt GBs in annihilating defects depends on the rate of defects segregation to and diffusion along tilt GBs. Tilt GBs mainly serve as diffusion channel for defects to reach other sinks when defect diffusivity is high at boundaries. When defect diffusivity is low, most of the defects segregated to tilt GBs are annihilated by dislocation climb. Up-to-date, the response of twist GBs under irradiation has been rarely reported in literature and is still unclear. It is important to develop atom scale insight on this question in order to predict twist GBs' sink strength for a better understanding of radiation response of polycrystalline materials. By using a combination of molecular dynamics and grand canonical Monte Carlo, here I demonstrate the defect kinetics in {001} and {111} twist GBs and the microstructural evolution of these GBs under defect fluxes in SiC. I found due to the deep potential well for interstitials at dislocation intersections within the interface, the mobility of defects on dislocation grid is retard and this leads to defect accumulation at GBs for many cases. Furthermore, I conclude both types of twist GBs have to form mixed dislocations with edge component in order to absorb accumulated interstitials at the interface. The formation of mixed dislocation is either by interstitial loop nucleation or by dislocation reactions at the interface. The continuous formation and climb of these mixed dislocations make twist GBs unsaturatable sinks to radiation induced defects.

The behavior of small helium clusters near free surfaces in tungsten

NASA Astrophysics Data System (ADS)

Barashev, A. V.; Xu, H.; Stoller, R. E.

2014-11-01

The results of a computational study of helium-vacancy clusters in tungsten are reported. A recently developed atomistic kinetic Monte Carlo method employing empirical interatomic potentials was used to investigate the behavior of clusters composed of three interstitial-helium atoms near {1 1 1}, {1 1 0} and {1 0 0} free surfaces. Multiple configurations were examined and the local energy landscape was characterized to determine cluster mobility and the potential for interactions with the surface. The clusters were found to be highly mobile if far from the surface, but were attracted and bound to the surface when within a distance of a few lattice parameters. When near the surface, the clusters were transformed into an immobile configuration due to the creation of a Frenkel pair; the vacancy was incorporated into what became a He3-vacancy complex. The corresponding interstitial migrated to and became an adatom on the free surface. This process can contribute to He retention, and may be responsible for the observed deterioration of the plasma-exposed tungsten surfaces.

W and X Photoluminescence Centers in Crystalline Si: Chasing Candidates at Atomic Level Through Multiscale Simulations

NASA Astrophysics Data System (ADS)

Aboy, María; Santos, Iván; López, Pedro; Marqués, Luis A.; Pelaz, Lourdes

2018-04-01

Several atomistic techniques have been combined to identify the structure of defects responsible for X and W photoluminescence lines in crystalline Si. We used kinetic Monte Carlo simulations to reproduce irradiation and annealing conditions used in photoluminescence experiments. We found that W and X radiative centers are related to small Si self-interstitial clusters but coexist with larger Si self-interstitials clusters that can act as nonradiative centers. We used molecular dynamics simulations to explore the many different configurations of small Si self-interstitial clusters, and selected those having symmetry compatible with W and X photoluminescence centers. Using ab initio simulations, we calculated their formation energy, donor levels, and energy of local vibrational modes. On the basis of photoluminescence experiments and our multiscale theoretical calculations, we discuss the possible atomic configurations responsible for W and X photoluminescence centers in Si. Our simulations also reveal that the intensity of photoluminescence lines is the result of competition between radiative centers and nonradiative competitors, which can explain the experimental quenching of W and X lines even in the presence of the photoluminescence centers.

Investigation of defect clusters in ion-irradiated Ni and NiCo using diffuse X-ray scattering and electron microscopy

DOE PAGES

Olsen, Raina J.; Jin, Ke; Lu, Chenyang; ...

2015-11-23

The nature of defect clusters in Ni and Nimore » $$_{50}$$Co$$_{50}$$ (NiCo) irradiated at room temperature with 2–16 MeV Ni ions is studied using asymptotic diffuse X-ray scattering and transmission electron microscopy (TEM). Analysis of the scattering data provides separate size distributions for vacancy and interstitial type defect clusters, showing that both types of defect clusters have a smaller size and higher density in NiCo than in Ni. Diffuse scattering results show good quantitative agreement with TEM results for cluster sizes greater than 4 nm diameter, but find that the majority of vacancy clusters are under 2 nm in NiCo, which, if not detected, would lead to the conclusion that defect density was actually lower in the alloy. Interstitial dislocation loops and stacking fault tetrahedra are identified by TEM. Lastly comparison of diffuse scattering lineshapes to those calculated for dislocation loops and SFTs indicates that most of the vacancy clusters are SFTs.« less

DISPLACEMENT CASCADE SIMULATION IN TUNGSTEN AT 1025 K

DOE Office of Scientific and Technical Information (OSTI.GOV)

Setyawan, Wahyu; Nandipati, Giridhar; Roche, Kenneth J.

2013-09-30

Molecular dynamics simulation was employed to investigate the irradiation damage properties of bulk tungsten at 1025 K (0.25 melting temperature). A comprehensive data set of primary cascade damage was generated up to primary knock-on atom (PKA) energies 100 keV. The dependence of the number of surviving Frenkel pairs (NFP) on the PKA energy (E) exhibits three different characteristic domains presumably related to the different cascade morphologies that form. The low-energy regime < 0.2 keV is characterized by a hit-or-miss type of Frenkel pair (FP) production near the displacement threshold energy of 128 eV. The middle regime 0.3 – 30 keVmore » exhibits a sublinear dependence of log(NFP) vs log(E) associated with compact cascade morphology with a slope of 0.73. Above 30 keV, the cascade morphology consists of complex branches or interconnected damage regions. In this extended morphology, large interstitial clusters form from superposition of interstitials from nearby damage regions. Strong clustering above 30 keV results in a superlinear dependence of log(NFP) vs log(E) with a slope of 1.365. At 100 keV, an interstitial cluster of size 92 and a vacancy cluster of size 114 were observed.« less

Atomistic Simulation of Displacement Cascades in Zircon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Devanathan, Ram; Weber, William J.; Corrales, Louis R.

2002-05-06

Low energy displacement cascades in zircon (ZrSiO4) initiated by a Zr primary knock-on atom have been investigated by molecular dynamics simulations using a Coulombic model for long-range interactions, Buckingham potential for short-range interactions and Ziegler-Biersack potentials for close pair interactions. Displacements were found to occur mainly in the O sublattice, and O replacements by a ring mechanism were predominant. Clusters containing Si interstitials bridged by O interstitials, vacancy clusters and anti-site defects were found to occur. This Si-O-Si bridging is considerable in quenched liquid ZrSiO4.

Controlled Expansion of a Strong-Field Iron Nitride Cluster: Multi-Site Ligand Substitution as a Strategy for Activating Interstitial Nitride Nucleophilicity.

PubMed

Drance, Myles J; Mokhtarzadeh, Charles C; Melaimi, Mohand; Agnew, Douglas W; Moore, Curtis E; Rheingold, Arnold L; Figueroa, Joshua S

2018-05-02

Multimetallic clusters have long been investigated as molecular surrogates for reactive sites on metal surfaces. In the case of the μ 4 -nitrido cluster [Fe 4 (μ 4 -N)(CO) 12 ] - , this analogy is limited owing to the electron-withdrawing effect of carbonyl ligands on the iron nitride core. Described here is the synthesis and reactivity of [Fe 4 (μ 4 -N)(CO) 8 (CNAr Mes2 ) 4 ] - , an electron-rich analogue of [Fe 4 (μ 4 -N)(CO) 12 ] - , where the interstitial nitride displays significant nucleophilicity. This characteristic enables rational expansion with main-group and transition-metal centers to yield unsaturated sites. The resulting clusters display surface-like reactivity through coordination-sphere-dependent atom rearrangement and metal-metal cooperativity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Behaviors of transmutation elements Re and Os and their effects on energetics and clustering of vacancy and self-interstitial atoms in W

NASA Astrophysics Data System (ADS)

Li, Yu-Hao; Zhou, Hong-Bo; Jin, Shuo; Zhang, Ying; Deng, Huiqiu; Lu, Guang-Hong

2017-04-01

We investigate the behaviors of rhenium (Re) and osmium (Os) and their interactions with point defects in tungsten (W) using a first-principles method. We show that Re atoms are energetically favorable to disperse separately in bulk W due to the Re-Re repulsive interaction. Despite the attractive interaction between Os atoms, there is still a large activation energy barrier of 1.10 eV at the critical number of 10 for the formation of Os clusters in bulk W based on the results of the total nucleation free energy change. Interestingly, the presence of vacancy can significantly reduce the total nucleation free energy change of Re/Os clusters, suggesting that vacancy can facilitate the nucleation of Re/Os in W. Re/Os in turn has an effect on the stability of the vacancy clusters (V n ) in W, especially for small vacancy clusters. A single Re/Os atom can raise the total binding energies of V2 and V3 obviously, thus enhancing their formation. Further, we demonstrate that there is a strong attractive interaction between Re/Os and self-interstitial atoms (SIAs). Re/Os could increase the diffusion barrier of SIAs and decrease their rotation barrier, while the interstitial-mediated path may be the optimal diffusion path of Re/Os in W. Consequently, the synergistic effect between Re/Os and point defects plays a key role in Re/Os precipitation and the evolution of defects in irradiated W.

Depletion of interstitial oxygen in silicon and the thermal donor model

NASA Technical Reports Server (NTRS)

Borenstein, Jeffrey T.; Singh, Vijay A.; Corbett, James W.

1987-01-01

It is shown here that the experimental results of Newman (1985) and Tan et al. (1986) regarding the loss of oxygen interstitials during 450 C annealing of Czochralski silicon are consistent with the recently proposed model of Borenstein, Peak, and Corbett (1986) for thermal donor formation. Calculations were carried out for TD cores corresponding to O2, O3, O4, and/or O5 clusters. A simple model which attempts to capture the essential physics of the interstitial depletion has been constructed, and is briefly described.

Recombination radius of a Frenkel pair and capture radius of a self-interstitial atom by vacancy clusters in bcc Fe

NASA Astrophysics Data System (ADS)

Nakashima, Kenichi; Stoller, Roger E.; Xu, Haixuan

2015-08-01

The recombination radius of a Frenkel pair is a fundamental parameter for the object kinetic Monte Carlo (OKMC) and mean field rate theory (RT) methods that are used to investigate irradiation damage accumulation in irradiated materials. The recombination radius in bcc Fe has been studied both experimentally and numerically, however there is no general consensus about its value. The detailed atomistic processes of recombination also remain uncertain. Values from 1.0a0 to 3.3a0 have been employed as a recombination radius in previous studies using OKMC and RT. The recombination process of a Frenkel pair is investigated at the atomic level using the self-evolved atomistic kinetic Monte Carlo (SEAKMC) method in this paper. SEAKMC calculations reveal that a self-interstitial atom recombines with a vacancy in a spontaneous reaction from several nearby sites following characteristic pathways. The recombination radius of a Frenkel pair is estimated to be 2.26a0 by taking the average of the recombination distances from 80 simulation cases. In addition, we apply these procedures to the capture radius of a self-interstitial atom by a vacancy cluster. The capture radius is found to gradually increase with the size of the vacancy cluster. The fitting curve for the capture radius is obtained as a function of the number of vacancies in the cluster.

Point defect induced segregation of alloying solutes in α-Fe

NASA Astrophysics Data System (ADS)

You, Yu-Wei; Zhang, Yange; Li, Xiangyan; Xu, Yichun; Liu, C. S.; Chen, J. L.; Luo, G.-N.

2016-10-01

Segregation of alloying solute toward clusters and precipitates can result in hardening and embrittlement of ferritic and ferritic/martensitic steels in aging nuclear power plants. Thus, it is essential to study the segregation of solute in α-Fe. In this study, the segregation of eight kinds of alloying solutes (Al, Si, P, S, Ga, Ge, As, Se) in defect-free system and at vacancy, divacancy, and self-interstitial atom in α-Fe has been systematically studied by first-principles calculations. We find that it is energetically favorable for multiple solute S or Se atoms to segregate in defect-free system to form solute clusters, whereas it is very difficult for the other solute atoms to form the similar clusters. With the presence of vacancy and divacancy, the segregation of all the solutes are significantly promoted to form vacancy-solute and divacancy-solute clusters. The divacancy-solute cluster is more stable than the vacancy-solute cluster. The most-stable self-interstitial atom 〈110〉 dumbbell is also found to tightly bind with multiple solute atoms. The 〈110〉-S is even more stable than divacancy-S cluster. Meanwhile, the law of mass action is employed to predict the concentration evolution of vacancy-Si, vacancy-P, and vacancy-S clusters versus temperature and vacancy concentration.

An ab initio-based Er–He interatomic potential in hcp Er

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Li; ye, Yeting; Fan, K. M.

2014-09-01

We have developed an empirical erbium-helium (Er-He) potential by fitting to the results calculated from ab initio method. Based on the electronic hybridization between Er and He atoms, an s-band model, along with a repulsive pair potential, has been derived to describe the Er-He interaction. The atomic configurations and the formation energies of single He defects, small He interstitial clusters (Hen) and He-vacancy (HenV ) clusters obtained by ab initio calculations are used as the fitting database. The binding energies and relative stabilities of the HnVm clusters are studied by the present potential and compared with the ab initio calculations.more » The Er-He potential is also applied to study the migration of He in hcp-Er at different temperatures, and He clustering is found to occur at 600 K in hcp Er crystal, which may be due to the anisotropic migration behavior of He interstitials.« less

Primary radiation damage characterization of α-iron under irradiation temperature for various PKA energies

NASA Astrophysics Data System (ADS)

Sahi, Qurat-ul-ain; Kim, Yong-Soo

2018-04-01

The understanding of radiation-induced microstructural defects in body-centered cubic (BCC) iron is of major interest to those using advanced steel under extreme conditions in nuclear reactors. In this study, molecular dynamics (MD) simulations were implemented to examine the primary radiation damage in BCC iron with displacement cascades of energy 1, 5, 10, 20, and 30 keV at temperatures ranging from 100 to 1000 K. Statistical analysis of eight MD simulations of collision cascades were carried out along each [110], [112], [111] and a high index [135] direction and the temperature dependence of the surviving number of point defects and the in-cascade clustering of vacancies and interstitials were studied. The peak time and the corresponding number of defects increase with increasing irradiation temperature and primary knock-on atom (PKA) energy. However, the final number of surviving point defects decreases with increasing lattice temperature. This is associated with the increase of thermal spike at high PKA energy and its long timespan at higher temperatures. Defect production efficiency (i.e., surviving MD defects, per Norgett-Robinson-Torrens displacements) also showed a continuous decrease with the increasing irradiation temperature and PKA energy. The number of interstitial clusters increases with both irradiation temperature and PKA energy. However, the increase in the number of vacancy clusters with PKA energy is minimal-to-constant and decreases as the irradiation temperature increases. Similarly, the probability and cluster size distribution for larger interstitials increase with temperature, whereas only smaller size vacancy clusters were observed at higher temperatures.

Recombination radius of a Frenkel pair and capture radius of a self-interstitial atom by vacancy clusters in bcc Fe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakashima, Kenichi; Stoller, Roger E.; Xu, Haixuan

The recombination radius of a Frenkel pair is a fundamental parameter for the object kinetic Monte Carlo (OKMC) and mean field rate theory (RT) methods that are used to investigate irradiation damage accumulation in neutron irradiated nuclear materials. The recombination radius in bcc Fe has been studied both experimentally and numerically, however there is no general consensus about its value. The detailed atomistic processes of recombination also remain uncertain. Values from 1:0a₀ to 3:3a₀ have been employed as a recombination radius in previous studies using OKMC and RT. The recombination process of a Frenkel pair is investigated at the atomicmore » level using the self-evolved atomistic kinetic Monte Carlo (SEAKMC) method in this paper. SEAKMC calculations reveal that a self-interstitial atom recombines with a vacancy in a spontaneous reaction from several nearby sites following characteristic pathways. The recombination radius of a Frenkel pair is estimated to be 2.26a₀ by taking the average of the recombination distances from 80 simulation cases. This value agrees well with the experimental estimate. In addition, we apply these procedures to the capture radius of a self-interstitial atom by a vacancy cluster. The capture radius is found to gradually increase with the size of the vacancy cluster. The fitting curve for the capture radius is obtained as a function of the number of vacancies in the cluster.« less

Recombination radius of a Frenkel pair and capture radius of a self-interstitial atom by vacancy clusters in bcc Fe

DOE PAGES

Nakashima, Kenichi; Stoller, Roger E.; Xu, Haixuan

2015-08-04

The recombination radius of a Frenkel pair is a fundamental parameter for the object kinetic Monte Carlo (OKMC) and mean field rate theory (RT) methods that are used to investigate irradiation damage accumulation in neutron irradiated nuclear materials. The recombination radius in bcc Fe has been studied both experimentally and numerically, however there is no general consensus about its value. The detailed atomistic processes of recombination also remain uncertain. Values from 1:0a₀ to 3:3a₀ have been employed as a recombination radius in previous studies using OKMC and RT. The recombination process of a Frenkel pair is investigated at the atomicmore » level using the self-evolved atomistic kinetic Monte Carlo (SEAKMC) method in this paper. SEAKMC calculations reveal that a self-interstitial atom recombines with a vacancy in a spontaneous reaction from several nearby sites following characteristic pathways. The recombination radius of a Frenkel pair is estimated to be 2.26a₀ by taking the average of the recombination distances from 80 simulation cases. This value agrees well with the experimental estimate. In addition, we apply these procedures to the capture radius of a self-interstitial atom by a vacancy cluster. The capture radius is found to gradually increase with the size of the vacancy cluster. The fitting curve for the capture radius is obtained as a function of the number of vacancies in the cluster.« less

Identification of Clinical Phenotypes in Idiopathic Interstitial Pneumonia with Pulmonary Emphysema.

PubMed

Sato, Suguru; Tanino, Yoshinori; Misa, Kenichi; Fukuhara, Naoko; Nikaido, Takefumi; Uematsu, Manabu; Fukuhara, Atsuro; Wang, Xintao; Ishida, Takashi; Munakata, Mitsuru

2016-01-01

Objective Since the term "combined pulmonary fibrosis and emphysema" (CPFE) was first proposed, the co-existence of pulmonary fibrosis and pulmonary emphysema (PE) has drawn considerable attention. However, conflicting results on the clinical characteristics of patients with both pulmonary fibrosis and PE have been published because of the lack of an exact definition of CPFE. The goal of this study was thus to clarify the clinical characteristics and phenotypes of idiopathic interstitial pneumonia (IIP) with PE. Methods We retrospectively analyzed IIP patients who had been admitted to our hospital. Their chest high-resolution computed tomography images were classified into two groups according to the presence of PE. We then performed a cluster analysis to identify the phenotypes of IIP patients with PE. Results Forty-four (53.7%) out of 82 patients had at least mild emphysema in their bilateral lungs. The cluster analysis separated the IIP patients with PE into three clusters. The overall survival rate of one cluster that consisted of mainly idiopathic pulmonary fibrosis (IPF) patients was significantly worse than those of the other clusters. Conclusion Three different phenotypes can be identified in IIP patients with PE, and IPF with PE is a distinct clinical phenotype with a poor prognosis.

Modeling the suppression of boron transient enhanced diffusion in silicon by substitutional carbon incorporation

NASA Astrophysics Data System (ADS)

Ngau, Julie L.; Griffin, Peter B.; Plummer, James D.

2001-08-01

Recent work has indicated that the suppression of boron transient enhanced diffusion (TED) in carbon-rich Si is caused by nonequilibrium Si point defect concentrations, specifically the undersaturation of Si self-interstitials, that result from the coupled out-diffusion of carbon interstitials via the kick-out and Frank-Turnbull reactions. This study of boron TED reduction in Si1-x-yGexCy during 750 °C inert anneals has revealed that the use of an additional reaction that further reduces the Si self-interstitial concentration is necessary to describe accurately the time evolved diffusion behavior of boron. In this article, we present a comprehensive model which includes {311} defects, boron-interstitial clusters, a carbon kick-out reaction, a carbon Frank-Turnbull reaction, and a carbon interstitial-carbon substitutional (CiCs) pairing reaction that successfully simulates carbon suppression of boron TED at 750 °C for anneal times ranging from 10 s to 60 min.

[Nonspecific interstitial pneumonitis: a clinicopathologic entity, histologic pattern or unclassified group of heterogeneous interstitial pneumonitis?].

PubMed

Morais, António; Moura, M Conceição Souto; Cruz, M Rosa; Gomes, Isabel

2004-01-01

Nonspecific interstitial pneumonitis (NSIP) initially described by Katzenstein and Fiorelli in 1994, seems to be a distinct clinicopathologic entity among idiopathic interstitial pneumonitis (IIP). Besides different histologic features from other IIP, NSIP is characterized by a better long-term outcome, associated with a better steroids responsiveness than idiopathic pulmonar fibrosis (IPF), where usually were included. Thus, differentiating NSIP from other IIP, namely IPF is very significant, since it has important therapeutic and prognostic implications. NSIP encloses different pathologies, namely those with inflammatory predominance (cellular subtype) or fibrous predominance (fibrosing subtype). NSIP is reviewed and discussed by the authors, after two clinical cases description.

Dynamics of defect-loaded grain boundary under shear deformation in alpha iron

NASA Astrophysics Data System (ADS)

Yang, L.; Zhou, H. L.; Liu, H.; Gao, F.; Zu, X. T.; Peng, S. M.; Long, X. G.; Zhou, X. S.

2018-02-01

Two symmetric tilt grain boundaries (GBs) (Σ3〈110〉{112} and Σ11〈110〉{332}) in alpha iron were performed to investigate the dynamics of defect-loaded GBs under shear deformation. The results show that the loaded self-interstitial atoms (SIAs) reduce the critical stress of the coupled GB motion in the Σ3 GB, but increase the critical stress in the Σ11 GB. The loaded SIAs in the Σ3 GB easily form 〈111〉 clusters and remain in the bulk when the GB moves away. However, the SIAs move along with the Σ11 GB and combine with the vacancies in the bulk, leading to the defect self-healing. The helium (He) atoms loaded into the GBs significantly affect the coupled GB motion. Once He clusters emit interstitials, the Σ11 GB carries those interstitials away but the Σ3 does not. The loaded He atoms reduce the critical stress of the Σ3 GB, but increase the critical stress of the Σ11 GB.

Interstitial protein alterations in rabbit vocal fold with scar.

PubMed

Thibeault, Susan L; Bless, Diane M; Gray, Steven D

2003-09-01

Fibrous and interstitial proteins compose the extracellular matrix of the vocal fold lamina propria and account for its biomechanic properties. Vocal fold scarring is characterized by altered biomechanical properties, which create dysphonia. Although alterations of the fibrous proteins have been confirmed in the rabbit vocal fold scar, interstitial proteins, which are known to be important in wound repair, have not been investigated to date. Using a rabbit model, interstitial proteins decorin, fibromodulin, and fibronectin were examined immunohistologically, two months postinduction of vocal fold scar by means of forcep biopsy. Significantly decreased decorin and fibromodulin with significantly increased fibronectin characterized scarred vocal fold tissue. The implications of altered interstitial proteins levels and their affect on the fibrous proteins will be discussed in relation to increased vocal fold stiffness and viscosity, which characterizes vocal fold scar.

First principles calculations of point defect diffusion in CdS buffer layers: Implications for Cu(In,Ga)(Se,S){sub 2} and Cu{sub 2}ZnSn(Se,S){sub 4}-based thin-film photovoltaics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varley, J. B.; Lordi, V.; He, X.

2016-01-14

We investigate point defects in CdS buffer layers that may arise from intermixing with Cu(In,Ga)Se{sub 2} (CIGSe) or Cu{sub 2}ZnSn(S,Se){sub 4} (CZTSSe) absorber layers in thin-film photovoltaics (PV). Using hybrid functional calculations, we characterize the migration barriers of Cu, In, Ga, Se, Sn, Zn, Na, and K impurities and assess the activation energies necessary for their diffusion into the bulk of the buffer. We find that Cu, In, and Ga are the most mobile defects in CIGS-derived impurities, with diffusion expected to proceed into the buffer via interstitial-hopping and cadmium vacancy-assisted mechanisms at temperatures ∼400 °C. Cu is predicted to stronglymore » favor migration paths within the basal plane of the wurtzite CdS lattice, which may facilitate defect clustering and ultimately the formation of Cu-rich interfacial phases as observed by energy dispersive x-ray spectroscopic elemental maps in real PV devices. Se, Zn, and Sn defects are found to exhibit much larger activation energies and are not expected to diffuse within the CdS bulk at temperatures compatible with typical PV processing temperatures. Lastly, we find that Na interstitials are expected to exhibit slightly lower activation energies than K interstitials despite having a larger migration barrier. Still, we find both alkali species are expected to diffuse via an interstitially mediated mechanism at slightly higher temperatures than enable In, Ga, and Cu diffusion in the bulk. Our results indicate that processing temperatures in excess of ∼400 °C will lead to more interfacial intermixing with CdS buffer layers in CIGSe devices, and less so for CZTSSe absorbers where only Cu is expected to significantly diffuse into the buffer.« less

Image guidance, treatment planning and evaluation of cancer interstitial focal therapy using liposomal radionuclides

NASA Astrophysics Data System (ADS)

Ware, Steve William

Focally ablative therapy of cancer has gained significant interest recently. Improvements in diagnostic techniques have created possibilities for treatment which were once clinically unfeasible. Imaging must be capable of allowing accurate diagnosis, staging and planning upon initiation of therapy. Recent improvements in MRI and molecular imaging techniques have made it possible to accurately localize lesions and in so doing, improve the accuracy of proposed focal treatments. Using multimodality imaging it is now possible to target, plan and evaluate interstitial focal treatment using liposome encapsulated beta emitting radionuclides in a variety of cancer types. Since most absorbed dose is deposited early and heterogeneously in beta-radionuclide therapy, investigation of the resultant molecular and cellular events during this time is important for evaluating treatment efficacy. Additionally, investigating a multifocal entity such as prostate cancer is helpful for determining whether MRI is capable of discriminating the proper lesion for therapy. Correlation of MRI findings with histopathology can further improve the accuracy of interstitial focal radionuclide therapy by providing non-invasive surrogates for tissue compartment sizes. In the application of such therapies, compartmental sizes are known to heavily influence the distribution of injected agents. This has clear dosimetric implications with the potential to significantly alter the efficacy of treatment. The hypothesis of this project was that multimodality imaging with magnetic resonance imaging (MRI), autoradiography (AR), and single photon emission computed tomography (SPECT) could be used to target, plan, and evaluate interstitial focal therapy with non-sealed source, liposome-encapsulated 186Re beta emitting radionuclides. The specific aims of this project were to 1) Identify suitable targets for interstitial focal therapy. This was done by retrospectively analyzing MRI data to characterize the tumor microenvironment through correlation with in-plane compartmental sizes obtained from histopathology analysis of step-sectioned prostatectomy specimens; 2) Gauge the ability of a reader to plan an interstitial focal treatment using MRI. This was accomplished by objective measures of contrast and volume measurement with subjective reader analysis of tumor conspicuities; 3) Evaluation of the early biologic response to 186Re interstitial focal therapy. This was achieved by correlation of histochemistry (HC) markers: hetrochromatin protein alpha (HP1α), cluster of differentiation 34 (CD34), terminal deoxynucleotidal transferase nick end labeling (TUNEL), caspase 3, Ki-67 and hematoxylin & eosin (H&E) to the radiation distribution as seen on AR and radiation absorbed dose as computed from planar imaging. The conclusions of this study are that prostate MRI allows targeting of appropriate lesions for therapy by its ability to inform on the tumor microenvironment. MRI distinguishes prostatic tumors on the basis of tissue composition. Readers are better able reproduce volumes and thus plan interstitial therapy for tumors which have a denser, more homogeneous composition. The combination of SPECT and autoradiography showed a dose and position dependent expression of HC markers. These results demonstrate that multimodality imaging is capable of targeting, planning and evaluating interstitial focal therapy.

Displacement cascades and defects annealing in tungsten, Part I: Defect database from molecular dynamics simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Setyawan, Wahyu; Nandipati, Giridhar; Roche, Kenneth J.

Molecular dynamics simulations have been used to generate a comprehensive database of surviving defects due to displacement cascades in bulk tungsten. Twenty-one data points of primary knock-on atom (PKA) energies ranging from 100 eV (sub-threshold energy) to 100 keV (~780 × Ed, where Ed = 128 eV is the average displacement threshold energy) have been completed at 300 K, 1025 K and 2050 K. Within this range of PKA energies, two regimes of power-law energy-dependence of the defect production are observed. A distinct power-law exponent characterizes the number of Frenkel pairs produced within each regime. The two regimes intersect atmore » a transition energy which occurs at approximately 250 × Ed. The transition energy also marks the onset of the formation of large self-interstitial atom (SIA) clusters (size 14 or more). The observed defect clustering behavior is asymmetric, with SIA clustering increasing with temperature, while the vacancy clustering decreases. This asymmetry increases with temperature such that at 2050 K (~0.5 Tm) practically no large vacancy clusters are formed, meanwhile large SIA clusters appear in all simulations. The implication of such asymmetry on the long-term defect survival and damage accumulation is discussed. In addition, <100> {110} SIA loops are observed to form directly in the highest energy cascades, while vacancy <100> loops are observed to form at the lowest temperature and highest PKA energies, although the appearance of both the vacancy and SIA loops with Burgers vector of <100> type is relatively rare.« less

Effect of post-implantation annealing on Al-N isoelectronic trap formation in silicon: Al-N pair formation and defect recovery mechanisms

NASA Astrophysics Data System (ADS)

Mori, Takahiro; Morita, Yukinori; Matsukawa, Takashi

2018-05-01

The effect of post-implantation annealing (PIA) on Al-N isoelectronic trap (IET) formation in silicon has been experimentally investigated to discuss the Al-N IET formation and implantation-induced defect recovery mechanisms. We performed a photoluminescence study, which indicated that self-interstitial clusters and accompanying vacancies are generated in the ion implantation process. It is supposed that Al and N atoms move to the vacancy sites and form stable Al-N pairs in the PIA process. Furthermore, the PIA process recovers self-interstitial clusters while transforming their atomic configuration. The critical temperature for the formation/dissociation of Al-N pairs was found to be 450 °C, with which we describe the process integration for devices utilizing Al-N IET technology.

Development of a Scanning Microscale Fast Neutron Irradiation Platform for Examining the Correlation Between Local Neutron Damage and Graphite Microstructure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinhero, Patrick; Windes, William

2015-03-10

The fast particle radiation damage effect of graphite, a main material in current and future nuclear reactors, has significant influence on the utilization of this material in fission and fusion plants. Atoms on graphite crystals can be easily replaced or dislocated by fast protons and result in interstitials and vacancies. The currently accepted model indicates that after most of the interstitials recombine with vacancies, surviving interstitials form clusters and furthermore gather to create loops with each other between layers. Meanwhile, surviving vacancies and interstitials form dislocation loops on the layers. The growth of these inserted layers cause the dimensional increase,more » i.e. swelling, of graphite. Interstitial and vacancy dislocation loops have been reported and they can easily been observed by electron microscope. However, observation of the intermediate atom clusters becomes is paramount in helping prove this model. We utilize fast protons generated from the University of Missouri Research Reactor (MURR) cyclotron to irradiate highly- oriented pyrolytic graphite (HOPG) as target for this research. Post-irradiation examination (PIE) of dosed targets with high-resolution transmission electron microscopy (HRTEM) has permit observation and analysis of clusters and dislocation loops to support the proposed theory. Another part of the research is to validate M.I. Heggie’s Ruck and Tuck model, which introduced graphite layers may fold under fast particle irradiation. Again, we employed microscopy to image irradiated specimens to determine how the extent of Ruck and Tuck by calculating the number of folds as a function of dose. Our most significant accomplishment is the invention of a novel class of high-intensity pure beta-emitters for long-term lightweight batteries. We have filed four invention disclosure records based on the research conducted in this project. These batteries are lightweight because they consist of carbon and tritium and can be fabricated to conform to many geometric shapes. In addition, we have published eight peer-reviewed American Nuclear Society (ANS) transactions, and presented our findings at ANS National Meetings, and several universities.« less

First-Principles Study of Carbon and Vacancy Structures in Niobium

DOE PAGES

Ford, Denise C.; Zapol, Peter; Cooley, Lance D.

2015-04-03

The interstitial chemical impurities hydrogen, oxygen, nitrogen, and carbon are important for niobium metal production, and particularly for the optimization of niobium SRF technology. These atoms are present in refined sheets and can be absorbed into niobium during processing treatments, resulting in changes to the residual resistance and the performance of SRF cavities. A first-principles approach is taken to study the properties of carbon in niobium, and the results are compared and contrasted with the properties of the other interstitial impurities. The results indicate that C will likely form precipitates or atmospheres around defects rather than strongly bound complexes withmore » other impurities. Based on the analysis of carbon and hydrogen near niobium lattice vacancies and small vacancy chains and clusters, the formation of extended carbon chains and hydrocarbons is not likely to occur. Association of carbon with hydrogen atoms can, however, occur through the strain fields created by interstitial binding of the impurity atoms. In conclusion, calculated electronic densities of states indicate that interstitial C may have a similar effect as interstitial O on the superconducting transition temperature of Nb.« less

Atomistic simulations to characterize the influence of applied strain and PKA energy on radiation damage evolution in pure aluminum

NASA Astrophysics Data System (ADS)

Sahi, Qurat-ul-ain; Kim, Yong-Soo

2018-05-01

Knowledge of defects generation, their mobility, growth rate, and spatial distribution is the cornerstone for understanding the surface and structural evolution of a material used under irradiation conditions. In this study, molecular dynamics simulations were used to investigate the coupled effect of primary knock-on atom (PKA) energy and applied strain (uniaxial and hydrostatic) fields on primary radiation damage evolution in pure aluminum. Cascade damage simulations were carried out for PKA energy ranging between 1 and 20 keV and for applied strain values ranging between -2% and 2% at the fixed temperature of 300 K. Simulation results showed that as the atomic displacement cascade proceeds under uniaxial and hydrostatic strains, the peak and surviving number of Frenkel point defects increases with increasing tension; however, these increments were more prominent under larger volume changing deformations (hydrostatic strain). The percentage fraction of point defects that aggregate into clusters increases under tension conditions; compared to the reference conditions with no strain, these increases are around 13% and 7% for interstitials and vacancies, respectively (under 2% uniaxial strain), and 19% and 11% for interstitials and vacancies, respectively (under 2% hydrostatic strain). Clusters formed of vacancies and interstitials were both larger under tensile strain conditions, with increases in both the average and maximum cluster sizes. The rate of increase/decrease in the number of Frenkel pairs, their clustering, and their size distributions under expansion/compression strain conditions were higher for higher PKA energies. Overall, the present results suggest that strain effects should be considered carefully in radiation damage environments, specifically for conditions of low temperature and high radiation energy. Compressive strain conditions could be beneficial for materials used in nuclear reactor power systems.

Dynamics of Helium-Loaded Grain Boundaries under Shear Deformation in α-Fe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Fei; Yang, Li; Heinisch, Howard L.

2014-03-30

The defects produced in collision cascades will interact with microstructural features in materials, such as GBs and dislocations. The coupled motion of GBs under stress has been widely observed in simulations and experiments. Two symmetric tilt GBs with a common <110> tilt axis (Σ3 and Σ11) in bcc iron are used to investigate the coupled motion of GBs under shear deformation. Also, we have explored the effect of self-interstitial atoms (SIAs) loading on the GB motion, with different concentrations of interstitials randomly inserted around the GB plane. The simulation results show that the interstitial loading reduces the critical stress ofmore » the GB coupled motion for the Σ3 GB. Furthermore, the interstitials and vacancies are inserted randomly at the GB plane and at a distance of 1 nm away from the GB plane, respectively, to understand the self-healing mechanism of GBs under stress. The behavior of the defect-loaded GBs depends on the GB structure. The loaded interstitials in the Σ3 GB easily form <111> interstitial clusters that do not move along with the GB. The vacancies in the Σ3 GB impede the GB motion. However, the interstitials move along with the Σ11 GB and annihilate with vacancies when the GB moves into the vacancy-rich region, leading to the self-healing and damage recovery of the Σ11 GB.« less

The effects of self-interstitial clusters on cascade defect evolution beyond the primary damage state

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heinisch, H.L.

1997-04-01

The intracascade evolution of the defect distributions of cascades in copper is investigated using stochastic annealing simulations applied to cascades generated with molecular dynamics (MD). The temperature and energy dependencies of annihilation, clustering and free defect production are determined for individual cascades. The annealing simulation results illustrate the strong influence on intracascade evolution of the defect configuration existing in the primary damage state. Another factor significantly affecting the evolution of the defect distribution is the rapid one-dimensional diffusion of small, glissile interstitial loops produced directly in cascades. This phenomenon introduces a cascade energy dependence of defect evolution that is apparentmore » only beyond the primary damage state, amplifying the need for further study of the annealing phase of cascade evolution and for performing many more MD cascade simulations at higher energies.« less

Endohedral beryllium atoms in germanium clusters with eight and fewer vertices: how small can a cluster be and still encapsulate a central atom?

PubMed

Uţă, M M; King, R B

2012-05-31

Structures of the beryllium-centered germanium clusters Be@Ge(n)(z) (n = 8, 7, 6; z = -4, -2, 0, +2) have been investigated by density functional theory to provide some insight regarding the smallest metal cluster that can encapsulate an interstitial atom. The lowest energy structures of the eight-vertex Be@Ge(8)(z) clusters (z = -4, -2, 0, +2) all have the Be atom at the center of a closed polyhedron, namely, a D(4d) square antiprism for Be@Ge(8)(4-), a D(2d) bisdisphenoid for Be@Ge(8)(2-), an ideal O(h) cube for Be@Ge(8), and a C(2v) distorted cube for Be@Ge(8)(2+). The Be-centered cubic structures predicted for Be@Ge(8) and Be@Ge(8)(2+) differ from the previously predicted lowest energy structures for the isoelectronic Ge(8)(2-) and Ge(8). This appears to be related to the larger internal volume of the cube relative to other closed eight-vertex polyhedra. The lowest energy structures for the smaller seven- and six-vertex clusters Be@Ge(n)(z) (n = 7, 6; z = -4, -2, 0, +2) no longer have the Be atom at the center of a closed Ge(n) polyhedron. Instead, either the Ge(n) polyhedron has opened up to provide a larger volume for the Be atom or the Be atom has migrated to the surface of the polyhedron. However, higher energy structures are found in which the Be atom is located at the center of a Ge(n) (n = 7, 6) polyhedron. Examples of such structures are a centered C(2v) capped trigonal prismatic structure for Be@Ge(7)(2-), a centered D(5h) pentagonal bipyramidal structure for Be@Ge(7), a centered D(3h) trigonal prismatic structure for Be@Ge(6)(4-), and a centered octahedral structure for Be@Ge(6). Cluster buildup reactions of the type Be@Ge(n)(z) + Ge(2) → Be@Ge(n+2)(z) (n = 6, 8; z = -4, -2, 0, +2) are all predicted to be highly exothermic. This suggests that interstitial clusters having an endohedral atom inside a bare post transition element polyhedron with eight or fewer vertices are less than the optimum size. This is consistent with the experimental observation of several types of 10-vertex polyhedral bare post transition element clusters with interstitial atoms but the failure to observe such clusters with external polyhedra having eight or fewer vertices.

Point defect evolution in Ni, NiFe and NiCr alloys from atomistic simulations and irradiation experiments

DOE PAGES

Aidhy, Dilpuneet S.; Lu, Chenyang; Jin, Ke; ...

2015-08-08

Using molecular dynamics simulations, we elucidate irradiation-induced point defect evolution in fcc pure Ni, Ni 0.5Fe 0.5, and Ni 0.8Cr 0.2 solid solution alloys. We find that irradiation-induced interstitials form dislocation loops that are of 1/3 <111>{111}-type, consistent with our experimental results. While the loops are formed in all the three materials, the kinetics of formation is considerably slower in NiFe and NiCr than in pure Ni, indicating that defect migration barriers and extended defect formation energies could be higher in the alloys than pure Ni. As a result, while larger size clusters are formed in pure Ni, smaller andmore » more clusters are observed in the alloys. The vacancy diffusion occurs at relatively higher temperatures than interstitials, and their clustering leads to formation of stacking fault tetrahedra, also consistent with our experiments. The results also show that the surviving Frenkel pairs are composition-dependent and are largely Ni dominated.« less

[Analysis of Time-to-onset of Interstitial Lung Disease after the Administration of Small Molecule Molecularly-targeted Drugs].

PubMed

Komada, Fusao

2018-01-01

　The aim of this study was to investigate the time-to-onset of drug-induced interstitial lung disease (DILD) following the administration of small molecule molecularly-targeted drugs via the use of the spontaneous adverse reaction reporting system of the Japanese Adverse Drug Event Report database. DILD datasets for afatinib, alectinib, bortezomib, crizotinib, dasatinib, erlotinib, everolimus, gefitinib, imatinib, lapatinib, nilotinib, osimertinib, sorafenib, sunitinib, temsirolimus, and tofacitinib were used to calculate the median onset times of DILD and the Weibull distribution parameters, and to perform the hierarchical cluster analysis. The median onset times of DILD for afatinib, bortezomib, crizotinib, erlotinib, gefitinib, and nilotinib were within one month. The median onset times of DILD for dasatinib, everolimus, lapatinib, osimertinib, and temsirolimus ranged from 1 to 2 months. The median onset times of the DILD for alectinib, imatinib, and tofacitinib ranged from 2 to 3 months. The median onset times of the DILD for sunitinib and sorafenib ranged from 8 to 9 months. Weibull distributions for these drugs when using the cluster analysis showed that there were 4 clusters. Cluster 1 described a subgroup with early to later onset DILD and early failure type profiles or a random failure type profile. Cluster 2 exhibited early failure type profiles or a random failure type profile with early onset DILD. Cluster 3 exhibited a random failure type profile or wear out failure type profiles with later onset DILD. Cluster 4 exhibited an early failure type profile or a random failure type profile with the latest onset DILD.

Defect processes in Be12X (X = Ti, Mo, V, W)

NASA Astrophysics Data System (ADS)

Jackson, M. L.; Burr, P. A.; Grimes, R. W.

2017-08-01

The stability of intrinsic point defects in Be12X intermetallics (where X  =  Ti, V, Mo or W) are predicted using density functional theory simulations and discussed with respect to fusion energy applications. Schottky disorder is found to be the lowest energy complete disorder process, closely matched by Be Frenkel disorder in the cases of Be12V and Be12Ti. Antitisite and X Frenkel disorder are of significantly higher energy. Small clusters of point defects including Be divacancies, Be di-interstitials and accommodation of the X species on two Be sites were considered. Some di-interstitial, divacancy and X2Be combinations exhibit negative binding enthalpy (i.e. clustering is favourable), although this is orientationally dependent. None of the Be12X intermetallics are predicted to exhibit significant non-stoichiometry, ruling out non-stoichiometry as a mechanism for accommodating Be depletion due to neutron transmutation.

Kinetics of self-interstitial migration in bcc and fcc transition metals

NASA Astrophysics Data System (ADS)

Bukkuru, S.; Bhardwaj, U.; Srinivasa Rao, K.; Rao, A. D. P.; Warrier, M.; Valsakumar, M. C.

2018-03-01

Radiation damage is a multi-scale phenomenon. A thorough understanding of diffusivities and the migration energies of defects is a pre-requisite to quantify the after-effects of irradiation. We investigate the thermally activated mobility of self-interstitial atom (SIA) in bcc transition metals Fe, Mo, Nb and fcc transition metals Ag, Cu, Ni, Pt using molecular dynamics (MD) simulations. The self-interstitial diffusion involves various mechanisms such as interstitialcy, dumbbell or crowdion mechanisms. Max-Space Clustering (MSC) method has been employed to identify the interstitial and its configuration over a wide range of temperature. The self-interstitial diffusion is Arrhenius like, however, there is a slight deviation at high temperatures. The migration energies, pre-exponential factors of diffusion and jump-correlation factors, obtained from these simulations can be used as inputs to Monte Carlo simulations of defect transport. The jump-correlation factor shows the degree of preference of rectilinear or rotational jumps. We obtain the average jump-correlation factor of 1.4 for bcc metals and 0.44 for fcc metals. It indicates that rectilinear jumps are preferred in bcc metals and rotational jumps are preferred in fcc metals.

Short-range order in the Ca sub 1-x La sub x F sub 2+x solid solution: 1:0:3 or 1:0:4 clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laval, J.P.; Abaouz, A.; Frit, B.

1989-08-01

The defect structure of the Ca{sub 1-x}La{sub x}F{sub 2+x} solid solution (0 {le} x {le} 0.38) has been examined at room temperature by powder neutron diffraction. Two kinds of (xxx) interstitial anions, whose respective numbers increase linearly with increasing dopant cation concentration, have been found: one labeled F{sup 0} (x {approx} 0.41) is a true interstitial; the other labeled F{sup {prime}{double prime}} (x {approx} 0.31) can be considered a relaxed normal anion. Two 1:0:n defect clusters are compatible, within the experimental errors, with these results: the 1:0:3 (1V{sub F}, OF{prime}, 3F{sup {double prime}}, 2 La{sup 3+}) and the 1:0:4 (1V{submore » F}, OF{prime}, 4F{sup {double prime}}, 3La{sup 3+}) clusters. Charge balance considerations and comparisons with the homologous Ca{sub 1-x}M{sub x}{sup IV}F{sub 2+2x} solid solutions (M{sup IV} = Th, U) allow us to think that the less dense 1:0:3 cluster is present for the whole domain of both kinds of solid solutions.« less

Radiation-induced segregation and precipitation behaviours around cascade clusters under electron irradiation.

PubMed

Sueishi, Yuichiro; Sakaguchi, Norihito; Shibayama, Tamaki; Kinoshita, Hiroshi; Takahashi, Heishichiro

2003-01-01

We have investigated the formation of cascade clusters and structural changes in them by means of electron irradiation following ion irradiation in an austenitic stainless steel. Almost all of the cascade clusters, which were introduced by the ion irradiation, grew to form interstitial-type dislocation loops or vacancy-type stacking fault tetrahedra after electron irradiation at 623 K, whereas a few of the dot-type clusters remained in the matrix. It was possible to recognize the concentration of Ni and Si by radiation-induced segregation around the dot-type clusters. After electron irradiation at 773 K, we found that some cascade clusters became precipitates (delta-Ni2Si) due to radiation-induced precipitation. This suggests that the cascade clusters could directly become precipitation sites during irradiation.

Statistical model and first-principles simulation on concentration of HenV cluster and He bubble formation in α-Fe and W

NASA Astrophysics Data System (ADS)

Liu, Yue-Lin; Yu, Yang; Dai, Zhen-Hong

2015-01-01

Using first-principles calculations, we investigate the stabilities of He and Hen-vacancy (HenV) clusters in α-Fe and W. Vacancy formation energies are 2.08 eV in α-Fe and 3.11 eV in W, respectively. Single He in both α-Fe and W prefers to occupy the tetrahedral interstitial site. We recalculated the He solution energy considering the effect of zero-point energy (ZPE). The ZPEs of He in α-Fe and W at the tetrahedral (octahedral) interstitial site are 0.072 eV (0.031 eV) and 0.078 eV (0.034 eV), respectively. The trapping energies of single He at vacancy in α-Fe and W are -2.39 eV and -4.55 eV, respectively. By sequentially adding He into vacancy, a monovacancy trap up to 10 He atoms distributing in the vacancy vicinity. Based on the above results combined with statistical model, we evaluate the concentrations of all relevant HenV clusters as a function of He chemical potential. The critical HenV concentration is found to be ∼10-40 (atomic) at the critical temperature T = 600 K in α-Fe and T = 1600 K in W, respectively. Beyond the critical HenV concentrations, considerable HenV aggregate to form HenVm clusters. By further growing of HenVm, the HenVm clusters grow bigger resulting in the larger He bubble formation.

The multiple roles of small-angle tilt grain boundaries in annihilating radiation damage in SiC

DOE PAGES

Jiang, Hao; Wang, Xing; Szlufarska, Izabela

2017-02-09

Lattice defects generated by radiation damage can diffuse to grain boundaries (GBs) and be annihilated at GBs. However, the precise role of GBs in annihilating the segregated defects remains unclear. Here, we employed multi-scale models to determine how interstitials are annihilated at small-angle tilt GBs (STGBs) in SiC. First of all, we found the pipe diffusion of interstitials in STGBs is slower than bulk diffusion. This is because the increased interatomic distance at dislocation cores raises the migration barrier of interstitial dumbbells. Furthermore, we found both the annihilation of interstitials at jogs and jog nucleation from clusters are diffusion-controlled andmore » can occur under off-stoichiometric interstitial fluxes. Finally, a dislocation line model is developed to predict the role of STGBs in annihilating radiation damage. This model includes defect flux to GBs, pipe diffusion in STGBs, and the interaction of defects with jogs. The model predicts the role of STGBs in annihilating defects depends on the rate of defects segregation to and diffusion along STGBs. STGBs mainly serve as diffusion channel for defects to reach other sinks when defect diffusivity is high at boundaries. As a result, when defect diffusivity is low, most of the defects segregated to STGBs are annihilated by dislocation climb.« less

The multiple roles of small-angle tilt grain boundaries in annihilating radiation damage in SiC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Hao; Wang, Xing; Szlufarska, Izabela

Lattice defects generated by radiation damage can diffuse to grain boundaries (GBs) and be annihilated at GBs. However, the precise role of GBs in annihilating the segregated defects remains unclear. Here, we employed multi-scale models to determine how interstitials are annihilated at small-angle tilt GBs (STGBs) in SiC. First of all, we found the pipe diffusion of interstitials in STGBs is slower than bulk diffusion. This is because the increased interatomic distance at dislocation cores raises the migration barrier of interstitial dumbbells. Furthermore, we found both the annihilation of interstitials at jogs and jog nucleation from clusters are diffusion-controlled andmore » can occur under off-stoichiometric interstitial fluxes. Finally, a dislocation line model is developed to predict the role of STGBs in annihilating radiation damage. This model includes defect flux to GBs, pipe diffusion in STGBs, and the interaction of defects with jogs. The model predicts the role of STGBs in annihilating defects depends on the rate of defects segregation to and diffusion along STGBs. STGBs mainly serve as diffusion channel for defects to reach other sinks when defect diffusivity is high at boundaries. As a result, when defect diffusivity is low, most of the defects segregated to STGBs are annihilated by dislocation climb.« less

CENH3 morphogenesis reveals dynamic centromere associations during synaptonemal complex formation and the progression through male meiosis in hexaploid wheat.

PubMed

Sepsi, Adél; Higgins, James D; Heslop-Harrison, John S Pat; Schwarzacher, Trude

2017-01-01

During meiosis, centromeres in some species undergo a series of associations, but the processes and progression to homologous pairing is still a matter of debate. Here, we aimed to correlate meiotic centromere dynamics and early telomere behaviour to the progression of synaptonemal complex (SC) construction in hexaploid wheat (2n = 42) by triple immunolabelling of CENH3 protein marking functional centromeres, and SC proteins ASY1 (unpaired lateral elements) and ZYP1 (central elements in synapsed chromosomes). We show that single or multiple centromere associations formed in meiotic interphase undergo a progressive polarization (clustering) at the nuclear periphery in early leptotene, leading to formation of the telomere bouquet. Critically, immunolabelling shows the dynamics of these presynaptic centromere associations and a structural reorganization of the centromeric chromatin coinciding with key events of synapsis initiation from the subtelomeric regions. As short stretches of subtelomeric synapsis emerged at early zygotene, centromere clusters lost their strong polarization, gradually resolving as individual centromeres indicated by more than 21 CENH3 foci associated with unpaired lateral elements. Only following this centromere depolarization were homologous chromosome arms connected, as observed by the alignment and fusion of interstitial ZYP1 loci elongating at zygotene so synapsis at centromeres is a continuation of the interstitial synapsis. Our results thus reveal that centromere associations are a component of the timing and progression of chromosome synapsis, and the gradual release of the individual centromeres from the clusters correlates with the elongation of interstitial synapsis between the corresponding homologues. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

The effect of injected interstitials on void formation in self-ion irradiated nickel containing concentrated solid solution alloys

DOE PAGES

Yang, Tai-ni; Lu, Chenyang; Jin, Ke; ...

2017-02-21

Pure nickel and three nickel containing single-phase concentrated solid solution alloys (SP-CSAs) have been irradiated using 3 MeV Ni 2+ ions at 500 C to fluences of 1.5 x 10 16 and 5.0 x 10 16 cm 2. We characterized the radiation-induced voids using cross sectional transmission electron microscopy that distributions of voids and dislocation loops were presented as a function of depth. We also observed a various degree of void suppression on the tested samples and a defect clusters migration mechanism was proposed for NiCo. Furthermore, in order to sufficiently understand the defect dynamics in these SP-CSAs, the injectedmore » interstitial effect has been taken into account along with the 1-dimentional (1-D) and 3-dimentional (3-D) interstitial movement mechanisms.« less

Grain boundary resistance to amorphization of nanocrystalline silicon carbide

PubMed Central

Chen, Dong; Gao, Fei; Liu, Bo

2015-01-01

Under the C displacement condition, we have used molecular dynamics simulation to examine the effects of grain boundaries (GBs) on the amorphization of nanocrystalline silicon carbide (nc-SiC) by point defect accumulation. The results show that the interstitials are preferentially absorbed and accumulated at GBs that provide the sinks for defect annihilation at low doses, but also driving force to initiate amorphization in the nc-SiC at higher doses. The majority of surviving defects are C interstitials, as either C-Si or C-C dumbbells. The concentration of defect clusters increases with increasing dose, and their distributions are mainly observed along the GBs. Especially these small clusters can subsequently coalesce and form amorphous domains at the GBs during the accumulation of carbon defects. A comparison between displacement amorphized nc-SiC and melt-quenched single crystal SiC shows the similar topological features. At a dose of 0.55 displacements per atom (dpa), the pair correlation function lacks long range order, demonstrating that the nc-SiC is fully amorphilized. PMID:26558694

Grain boundary resistance to amorphization of nanocrystalline silicon carbide.

PubMed

Chen, Dong; Gao, Fei; Liu, Bo

2015-11-12

Under the C displacement condition, we have used molecular dynamics simulation to examine the effects of grain boundaries (GBs) on the amorphization of nanocrystalline silicon carbide (nc-SiC) by point defect accumulation. The results show that the interstitials are preferentially absorbed and accumulated at GBs that provide the sinks for defect annihilation at low doses, but also driving force to initiate amorphization in the nc-SiC at higher doses. The majority of surviving defects are C interstitials, as either C-Si or C-C dumbbells. The concentration of defect clusters increases with increasing dose, and their distributions are mainly observed along the GBs. Especially these small clusters can subsequently coalesce and form amorphous domains at the GBs during the accumulation of carbon defects. A comparison between displacement amorphized nc-SiC and melt-quenched single crystal SiC shows the similar topological features. At a dose of 0.55 displacements per atom (dpa), the pair correlation function lacks long range order, demonstrating that the nc-SiC is fully amorphilized.

Ab initio simulations of the structure, energetics and mobility of radiation-induced point defects in bcc Nb

NASA Astrophysics Data System (ADS)

Cerdeira, M. A.; Palacios, S. L.; González, C.; Fernández-Pello, D.; Iglesias, R.

2016-09-01

The formation, binding and migration energetics of helium clusters inside a niobium crystal have been analysed via ab initio simulations. The effect of placing several He atoms within an n-vacancy previously formed or as interstitials inside the initial perfect bulk matrix has been studied. DFT-based results show that He atoms prefer to aggregate forming small clusters at n-vacancy sites rather than at interstitial positions in the perfect crystal. The minimum formation energy is found when NHe is equal to the number of vacancies, n. It follows that vacancies act as almost perfect traps for He atoms, as is well known for other metals. The migration barriers of He atoms inside vacancies increase considerably when compared to what happens for vacancies alone. A secondary consequence is that the full set of energies obtained will be highly relevant as an input for new approaches to KMC simulations of defects in Nb.

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma

DTIC Science & Technology

2014-10-01

fibrosis, interstitial lung diseases 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...cadherin-11 in scleroderma patients with interstitial lung disease . We have been working with our collaborators at UTHSC to identify and sera that...83% female, avg age 49, avg disease duration 2.5 years, 59% with diffuse SSc, 28% with ILD and avg skin score of 16 at enrollment). Since there is

The energy and stability of helium-related cluster in nickel: A study of molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Gong, Hengfeng; Wang, Chengbin; Zhang, Wei; Xu, Jian; Huai, Ping; Deng, Huiqiu; Hu, Wangyu

2016-02-01

Using molecular dynamics simulation, we investigated the energy and stability of helium-related cluster in nickel. All the binding energies of the He-related clusters are demonstrated to be positive and increase with the cluster sizes. Due to the pre-existed self-interstitial nickel atom, the trapping capability of vacancy to defects becomes weak. Besides, the minimum energy configurations of He-related clusters exhibit the very high symmetry in the local atomistic environment. And for the HeN and HeNV1SIA1 clusters, the average length of He-He bonds shortens, but it elongates for the HeNV1 clusters with helium cluster sizes. The helium-to-vacancy ratio plays a decisive role on the binding energies of HeNVM cluster. These results can provide some excellent clues to insight the initial stage of helium bubbles nucleation and growth in the Ni-based alloys for the Generation-IV Molten Salt Reactor.

Interstitial loop transformations in FeCr

DOE PAGES

Béland, Laurent Karim; Osetsky, Yuri N.; Stoller, Roger E.; ...

2015-03-27

Here, we improve the Self-Evolving Atomistic Kinetic Monte Carlo (SEAKMC) algorithm by integrating the Activation Relaxation Technique nouveau (ARTn), a powerful open-ended saddle-point search method, into the algorithm. We use it to investigate the reaction of 37-interstitial 1/2[1 1 1] and 1/2[View the MathML source] loops in FeCr at 10 at.% Cr. They transform into 1/2[1 1 1], 1/2[View the MathML source], [1 0 0] and [0 1 0] 74-interstitial clusters with an overall barrier of 0.85 eV. We find that Cr decoration locally inhibits the rotation of crowdions, which dictates the final loop orientation. Moreover, the final loop orientationmore » depends on the details of the Cr decoration. Generally, a region of a given orientation is favored if Cr near its interface with a region of another orientation is able to inhibit reorientation at this interface more than the Cr present at the other interfaces. Also, we find that substitutional Cr atoms can diffuse from energetically unfavorable to energetically favorable sites within the interlocked 37-interstitial loops conformation with barriers of less than 0.35 eV.« less

Atomic origins of water-vapour-promoted alloy oxidation

NASA Astrophysics Data System (ADS)

Luo, Langli; Su, Mao; Yan, Pengfei; Zou, Lianfeng; Schreiber, Daniel K.; Baer, Donald R.; Zhu, Zihua; Zhou, Guangwen; Wang, Yanting; Bruemmer, Stephen M.; Xu, Zhijie; Wang, Chongmin

2018-06-01

The presence of water vapour, intentional or unavoidable, is crucial to many materials applications, such as in steam generators, turbine engines, fuel cells, catalysts and corrosion1-4. Phenomenologically, water vapour has been noted to accelerate oxidation of metals and alloys5,6. However, the atomistic mechanisms behind such oxidation remain elusive. Through direct in situ atomic-scale transmission electron microscopy observations and density functional theory calculations, we reveal that water-vapour-enhanced oxidation of a nickel-chromium alloy is associated with proton-dissolution-promoted formation, migration, and clustering of both cation and anion vacancies. Protons derived from water dissociation can occupy interstitial positions in the oxide lattice, consequently lowering vacancy formation energy and decreasing the diffusion barrier of both cations and anions, which leads to enhanced oxidation in moist environments at elevated temperatures. This work provides insights into water-vapour-enhanced alloy oxidation and has significant implications in other material and chemical processes involving water vapour, such as corrosion, heterogeneous catalysis and ionic conduction.

Atomic origins of water-vapour-promoted alloy oxidation.

PubMed

Luo, Langli; Su, Mao; Yan, Pengfei; Zou, Lianfeng; Schreiber, Daniel K; Baer, Donald R; Zhu, Zihua; Zhou, Guangwen; Wang, Yanting; Bruemmer, Stephen M; Xu, Zhijie; Wang, Chongmin

2018-06-01

The presence of water vapour, intentional or unavoidable, is crucial to many materials applications, such as in steam generators, turbine engines, fuel cells, catalysts and corrosion 1-4 . Phenomenologically, water vapour has been noted to accelerate oxidation of metals and alloys 5,6 . However, the atomistic mechanisms behind such oxidation remain elusive. Through direct in situ atomic-scale transmission electron microscopy observations and density functional theory calculations, we reveal that water-vapour-enhanced oxidation of a nickel-chromium alloy is associated with proton-dissolution-promoted formation, migration, and clustering of both cation and anion vacancies. Protons derived from water dissociation can occupy interstitial positions in the oxide lattice, consequently lowering vacancy formation energy and decreasing the diffusion barrier of both cations and anions, which leads to enhanced oxidation in moist environments at elevated temperatures. This work provides insights into water-vapour-enhanced alloy oxidation and has significant implications in other material and chemical processes involving water vapour, such as corrosion, heterogeneous catalysis and ionic conduction.

Effect of nickel on point defects diffusion in Fe – Ni alloys

DOE PAGES

Anento, Napoleon; Serra, Anna; Osetsky, Yury N.

2017-05-05

Iron-Nickel alloys are perspective alloys as nuclear energy structural materials because of their good radiation damage tolerance and mechanical properties. Understanding of experimentally observed features such as the effect of Ni content to radiation defects evolution is essential for developing predictive models of radiation. Recently an atomic-scale modelling study has revealed one particular mechanism of Ni effect related to the reduced mobility of clusters of interstitial atoms in Fe-Ni alloys. In this paper we present results of the microsecond-scale molecular dynamics study of point defects, i.e. vacancies and self-interstitial atoms, diffusion in Fe-Ni alloys. It is found that the additionmore » of Ni atoms affects diffusion processes: diffusion of vacancies is enhanced in the presence of Ni, whereas diffusion of interstitials is reduced and these effects increase at high Ni concentration and low temperature. As a result, the role of Ni solutes in radiation damage evolution in Fe-Ni alloys is discussed.« less

Damage structures in fission-neutron irradiated Ni-based alloys at high temperatures

NASA Astrophysics Data System (ADS)

Yamakawa, K.; Shimomura, Y.

1999-01-01

The defects formed in Ni based (Ni-Si, Ni-Cu and Ni-Fe) alloys which were irradiated with fission-neutrons were examined by electron microscopy. Irradiations were carried out at 473 K and 573 K. In the 473 K irradiated specimens, a high density of large interstitial loops and small vacancy clusters with stacking fault tetrahedra (SFT) were observed. The number densities of these two types of defects did not strongly depend on the amount of solute atoms in each alloy. The density of the loops in Ni-Si alloys was much higher than those in Ni-Cu and Ni-Fe alloys, while the density of SFT only slightly depended on the kind of solute. Also, the size of the loops depended on the kinds and amounts of solute. In 573 K irradiated Ni-Cu specimens, a high density of dislocation lines developed during the growth of interstitial loops. In Ni-Si alloys, the number density and size of the interstitial loops changed as a function of the amount of solute. Voids were formed in Ni-Cu alloys but scarcely formed in Ni-Si alloys. The number density of voids was one hundredth of that of SFT observed in 473 K irradiated Ni-Cu alloys. Possible formation processes of interstitial loops, SFT dislocation lines and voids are discussed.

Effect of dose and size on defect engineering in carbon cluster implanted silicon wafers

NASA Astrophysics Data System (ADS)

Okuyama, Ryosuke; Masada, Ayumi; Shigematsu, Satoshi; Kadono, Takeshi; Hirose, Ryo; Koga, Yoshihiro; Okuda, Hidehiko; Kurita, Kazunari

2018-01-01

Carbon-cluster-ion-implanted defects were investigated by high-resolution cross-sectional transmission electron microscopy toward achieving high-performance CMOS image sensors. We revealed that implantation damage formation in the silicon wafer bulk significantly differs between carbon-cluster and monomer ions after implantation. After epitaxial growth, small and large defects were observed in the implanted region of carbon clusters. The electron diffraction pattern of both small and large defects exhibits that from bulk crystalline silicon in the implanted region. On the one hand, we assumed that the silicon carbide structure was not formed in the implanted region, and small defects formed because of the complex of carbon and interstitial silicon. On the other hand, large defects were hypothesized to originate from the recrystallization of the amorphous layer formed by high-dose carbon-cluster implantation. These defects are considered to contribute to the powerful gettering capability required for high-performance CMOS image sensors.

Ground-state geometries and stability of impurity doped clusters: LinBe and LinMg (n=1-12)

NASA Astrophysics Data System (ADS)

Deshpande, M.; Dhavale, A.; Zope, R. R.; Chacko, S.; Kanhere, D. G.

2000-12-01

We have investigated the ground-state geometries of LinBe and LinMg (n=1-12) clusters using ab initio molecular dynamics. These divalent impurities Be and Mg induce different geometries and follow a different growth path for n>5. LinMg clusters are significantly different from the host geometries while LinBe clusters can be approximately viewed as Be occupying an interstitial site in the host. Our results indicate that Be gets trapped inside the Li cage, while Mg remains on the surface of the cluster. Mg-induced geometries become three-dimensional earlier at n=4 as compared to the Be system. In spite of a distinct arrangement of atoms in both cases the character of the wave functions in the d manifold is remarkably similar. In both cases an eight valence electron system has been found to be the most stable, in conformity with the spherical jellium model.

The interaction between atomic displacement cascades and tilt symmetrical grain boundaries in α-zirconium

NASA Astrophysics Data System (ADS)

Kapustin, P.; Svetukhin, V.; Tikhonchev, M.

2017-06-01

The atomic displacement cascade simulations near symmetric tilt grain boundaries (GBs) in hexagonal close packed-Zirconium were considered in this paper. Further defect structure analysis was conducted. Four symmetrical tilt GBs -∑14?, ∑14? with the axis of rotation [0 0 0 1] and ∑32?, ∑32? with the axis of rotation ? - were considered. The molecular dynamics method was used for atomic displacement cascades' simulation. A tendency of the point defects produced in the cascade to accumulate near the GB plane, which was an obstacle to the spread of the cascade, was discovered. The results of the point defects' clustering produced in the cascade were obtained. The clusters of both types were represented mainly by single point defects. At the same time, vacancies formed clusters of a large size (more than 20 vacancies per cluster), while self-interstitial atom clusters were small-sized.

Stochastic annealing simulations of defect interactions among subcascades

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heinisch, H.L.; Singh, B.N.

1997-04-01

The effects of the subcascade structure of high energy cascades on the temperature dependencies of annihilation, clustering and free defect production are investigated. The subcascade structure is simulated by closely spaced groups of lower energy MD cascades. The simulation results illustrate the strong influence of the defect configuration existing in the primary damage state on subsequent intracascade evolution. Other significant factors affecting the evolution of the defect distribution are the large differences in mobility and stability of vacancy and interstitial defects and the rapid one-dimensional diffusion of small, glissile interstitial loops produced directly in cascades. Annealing simulations are also performedmore » on high-energy, subcascade-producing cascades generated with the binary collision approximation and calibrated to MD results.« less

Clustering of Ca2+ transients in interstitial cells of Cajal defines slow wave duration

PubMed Central

Drumm, Bernard T.; Hennig, Grant W.; Battersby, Matthew J.; Sung, Tae Sik

2017-01-01

Interstitial cells of Cajal (ICC) in the myenteric plexus region (ICC-MY) of the small intestine are pacemakers that generate rhythmic depolarizations known as slow waves. Slow waves depend on activation of Ca2+-activated Cl− channels (ANO1) in ICC, propagate actively within networks of ICC-MY, and conduct to smooth muscle cells where they generate action potentials and phasic contractions. Thus, mechanisms of Ca2+ regulation in ICC are fundamental to the motor patterns of the bowel. Here, we characterize the nature of Ca2+ transients in ICC-MY within intact muscles, using mice expressing a genetically encoded Ca2+ sensor, GCaMP3, in ICC. Ca2+ transients in ICC-MY display a complex firing pattern caused by localized Ca2+ release events arising from multiple sites in cell somata and processes. Ca2+ transients are clustered within the time course of slow waves but fire asynchronously during these clusters. The durations of Ca2+ transient clusters (CTCs) correspond to slow wave durations (plateau phase). Simultaneous imaging and intracellular electrical recordings revealed that the upstroke depolarization of slow waves precedes clusters of Ca2+ transients. Summation of CTCs results in relatively uniform Ca2+ responses from one slow wave to another. These Ca2+ transients are caused by Ca2+ release from intracellular stores and depend on ryanodine receptors as well as amplification from IP3 receptors. Reduced extracellular Ca2+ concentrations and T-type Ca2+ channel blockers decreased the number of firing sites and firing probability of Ca2+ transients. In summary, the fundamental electrical events of small intestinal muscles generated by ICC-MY depend on asynchronous firing of Ca2+ transients from multiple intracellular release sites. These events are organized into clusters by Ca2+ influx through T-type Ca2+ channels to sustain activation of ANO1 channels and generate the plateau phase of slow waves. PMID:28592421

Computational Modeling of Radiation Phenomenon in SiC for Nuclear Applications

NASA Astrophysics Data System (ADS)

Ko, Hyunseok

Silicon carbide (SiC) material has been investigated for promising nuclear materials owing to its superior thermo-mechanical properties, and low neutron cross-section. While the interest in SiC has been increasing, the lack of fundamental understanding in many radiation phenomena is an important issue. More specifically, these phenomena in SiC include the fission gas transport, radiation induced defects and its evolution, radiation effects on the mechanical stability, matrix brittleness of SiC composites, and low thermal conductivities of SiC composites. To better design SiC and SiC composite materials for various nuclear applications, understanding each phenomenon and its significance under specific reactor conditions is important. In this thesis, we used various modeling approaches to understand the fundamental radiation phenomena in SiC for nuclear applications in three aspects: (a) fission product diffusion through SiC, (b) optimization of thermodynamic stable self-interstitial atom clusters, (c) interface effect in SiC composite and their change upon radiation. In (a) fission product transport work, we proposed that Ag/Cs diffusion in high energy grain boundaries may be the upper boundary in unirradiated SiC at relevant temperature, and radiation enhanced diffusion is responsible for fast diffusion measured in post-irradiated fuel particles. For (b) the self-interstitial cluster work, thermodynamically stable clusters are identified as a function of cluster size, shape, and compositions using a genetic algorithm. We found that there are compositional and configurational transitions for stable clusters as the cluster size increases. For (c) the interface effect in SiC composite, we investigated recently proposed interface, which is CNT reinforced SiC composite. The analytical model suggests that CNT/SiC composites have attractive mechanical and thermal properties, and these fortify the argument that SiC composites are good candidate materials for the cladding. We used grand canonical monte carlo to optimize the interface, as a part of the stepping stone for further study using the interface.

Usual interstitial pneumonia: typical, possible, and “inconsistent” patterns

PubMed Central

Torres, Pedro Paulo Teixeira e Silva; Rabahi, Marcelo Fouad; Moreira, Maria Auxiliadora Carmo; Meirelles, Gustavo de Souza Portes; Marchiori, Edson

2017-01-01

ABSTRACT Idiopathic pulmonary fibrosis is a severe and progressive chronic fibrosing interstitial lung disease, a definitive diagnosis being established by specific combinations of clinical, radiological, and pathological findings. According to current international guidelines, HRCT plays a key role in establishing a diagnosis of usual interstitial pneumonia (UIP). Current guidelines describe three UIP patterns based on HRCT findings: a typical UIP pattern; a pattern designated “possible UIP”; and a pattern designated “inconsistent with UIP”, each pattern having important diagnostic implications. A typical UIP pattern on HRCT is highly accurate for the presence of histopathological UIP, being currently considered to be diagnostic of UIP. The remaining patterns require further diagnostic investigation. Other known causes of a UIP pattern include drug-induced interstitial lung disease, chronic hypersensitivity pneumonitis, occupational diseases (e.g., asbestosis), and connective tissue diseases, all of which should be included in the clinical differential diagnosis. Given the importance of CT studies in establishing a diagnosis and the possibility of interobserver variability, the objective of this pictorial essay was to illustrate all three UIP patterns on HRCT. PMID:29160385

Bladder carcinoma in a transplant recipient: evidence to implicate the BK human polyomavirus as a causal transforming agent.

PubMed

Geetha, Duvuru; Tong, Betty C; Racusen, Lorraine; Markowitz, Jay S; Westra, William H

2002-06-27

The BK polyomavirus (BKV) infects most of the human population, but clinically relevant infections are mostly limited to individuals who are immunosuppressed. In transplant recipients, BKV has been associated with ureteral stenosis, interstitial nephritis, and hemorrhagic cystitis. The role of BKV in the development of human tumors is intriguing but uncertain. BKV has been identified in various tumor types including urothelial carcinoma, but the ubiquitous presence of BKV as a latent infection has confounded efforts to validate any causal role in cancer development. We report the case of a simultaneous pancreas and kidney transplant recipient who developed BKV interstitial nephritis and carcinoma of the bladder with widespread metastases. High level expression of BKV large T antigen in the primary and metastatic carcinoma, but not in the nonneoplastic urothelium, implicates BKV as an etiologic agent in the development of this tumor.

An observational and thermodynamic investigation of carbonate partial melting

NASA Astrophysics Data System (ADS)

Floess, David; Baumgartner, Lukas P.; Vonlanthen, Pierre

2015-01-01

Melting experiments available in the literature show that carbonates and pelites melt at similar conditions in the crust. While partial melting of pelitic rocks is common and well-documented, reports of partial melting in carbonates are rare and ambiguous, mainly because of intensive recrystallization and the resulting lack of criteria for unequivocal identification of melting. Here we present microstructural, textural, and geochemical evidence for partial melting of calcareous dolomite marbles in the contact aureole of the Tertiary Adamello Batholith. Petrographic observations and X-ray micro-computed tomography (X-ray μCT) show that calcite crystallized either in cm- to dm-scale melt pockets, or as an interstitial phase forming an interconnected network between dolomite grains. Calcite-dolomite thermometry yields a temperature of at least 670 °C, which is well above the minimum melting temperature of ∼600 °C reported for the CaO-MgO-CO2-H2O system. Rare-earth element (REE) partition coefficients (KDcc/do) range between 9-35 for adjacent calcite-dolomite pairs. These KD values are 3-10 times higher than equilibrium values between dolomite and calcite reported in the literature. They suggest partitioning of incompatible elements into a melt phase. The δ18O and δ13C isotopic values of calcite and dolomite support this interpretation. Crystallographic orientations measured by electron backscattered diffraction (EBSD) show a clustering of c-axes for dolomite and interstitial calcite normal to the foliation plane, a typical feature for compressional deformation, whereas calcite crystallized in pockets shows a strong clustering of c-axes parallel to the pocket walls, suggesting that it crystallized after deformation had stopped. All this together suggests the formation of partial melts in these carbonates. A Schreinemaker analysis of the experimental data for a CO2-H2O fluid-saturated system indeed predicts formation of calcite-rich melt between 650-880 °C, in agreement with our observations of partial melting. The presence of partial melts in crustal carbonates has important physical and chemical implications, including a drastic drop in rock viscosity and significant change in the dynamics and distribution of fluids within both the contact aureole and the intrusive body.

Role of Autoantibodies in the Diagnosis of Connective-Tissue Disease ILD (CTD-ILD) and Interstitial Pneumonia with Autoimmune Features (IPAF)

PubMed Central

Jee, Adelle S.; Adelstein, Stephen; Bleasel, Jane; Keir, Gregory J.; Nguyen, MaiAnh; Sahhar, Joanne; Youssef, Peter; Corte, Tamera J.

2017-01-01

The diagnosis of interstitial lung disease (ILD) requires meticulous evaluation for an underlying connective tissue disease (CTD), with major implications for prognosis and management. CTD associated ILD (CTD-ILD) occurs most commonly in the context of an established CTD, but can be the first and/or only manifestation of an occult CTD or occur in patients who have features suggestive of an autoimmune process, but not meeting diagnostic criteria for a defined CTD—recently defined as “interstitial pneumonia with autoimmune features” (IPAF). The detection of specific autoantibodies serves a critical role in the diagnosis of CTD-ILD, but there remains a lack of data to guide clinical practice including which autoantibodies should be tested on initial assessment and when or in whom serial testing should be performed. The implications of detecting autoantibodies in patients with IPAF on disease behaviour and management remain unknown. The evaluation of CTD-ILD is challenging due to the heterogeneity of presentations and types of CTD and ILD that may be encountered, and thus it is imperative that immunologic tests are interpreted in conjunction with a detailed rheumatologic history and examination and multidisciplinary collaboration between respiratory physicians, rheumatologists, immunologists, radiologists and pathologists. PMID:28471413

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jena, Puru; Kandalam, Anil K.; Christian, Theresa M.

Gallium phosphide bismide (GaP1-xBix) epilayers with bismuth fractions from 0.9% to 3.2%, as calculated from lattice parameter measurements, were studied with Rutherford backscattering spectrometry (RBS) to directly measure bismuth incorporation. The total bismuth fractions found by RBS were higher than expected from the lattice parameter calculations. Furthermore, in one analyzed sample grown by molecular beam epitaxy at 300 degrees C, 55% of incorporated bismuth was found to occupy interstitial sites. We discuss implications of this high interstitial incorporation fraction and its possible relationship to x-ray diffraction and photoluminescence measurements of GaP0.99Bi0.01.

Mental retardation in a boy with an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1: Implication for the MRX locus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muroya, Koji; Ogata, Tsutomu; Natsuo, Nobutake

Although genotype-phenotype correlations in male patients with various types of nullisomy for Xp22.3 have assigned a locus for X-linked mental retardation (MRX) to an approximately 3-Mb region between DXS31 and STS, the precise location has not been determined. In this paper, we describe a 14 7/12 year old Japanese boy with mental retardation and an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1, and compare the deletion map with that of previously reported three familial male patients with low-normal intelligence and a similar interstitial deletion at Xp22.3. The results suggest that the MRX gene is further localized to themore » roughly 1.5-Mb region between DXS1060 and DXS1139. 31 refs., 4 figs.« less

A tungsten-rhenium interatomic potential for point defect studies

DOE PAGES

Setyawan, Wahyu; Gao, Ning; Kurtz, Richard J.

2018-05-28

A tungsten-rhenium (W-Re) classical interatomic potential is developed within the embedded atom method (EAM) interaction framework. A force-matching method is employed to fit the potential to ab initio forces, energies, and stresses. Simulated annealing is combined with the conjugate gradient technique to search for an optimum potential from over 1000 initial trial sets. The potential is designed for studying point defects in W-Re systems. It gives good predictions of the formation energies of Re defects in W and the binding energies of W self-interstitial clusters with Re. The potential is further evaluated for describing the formation energy of structures inmore » the σ and χ intermetallic phases. The predicted convex-hulls of formation energy are in excellent agreement with ab initio data. In pure Re, the potential can reproduce the formation energies of vacancy and self-interstitial defects sufficiently accurately, and gives the correct ground state self-interstitial configuration. Furthermore, by including liquid structures in the fit, the potential yields a Re melting temperature (3130 K) that is close to the experimental value (3459 K).« less

A tungsten-rhenium interatomic potential for point defect studies

NASA Astrophysics Data System (ADS)

Setyawan, Wahyu; Gao, Ning; Kurtz, Richard J.

2018-05-01

A tungsten-rhenium (W-Re) classical interatomic potential is developed within the embedded atom method interaction framework. A force-matching method is employed to fit the potential to ab initio forces, energies, and stresses. Simulated annealing is combined with the conjugate gradient technique to search for an optimum potential from over 1000 initial trial sets. The potential is designed for studying point defects in W-Re systems. It gives good predictions of the formation energies of Re defects in W and the binding energies of W self-interstitial clusters with Re. The potential is further evaluated for describing the formation energy of structures in the σ and χ intermetallic phases. The predicted convex-hulls of formation energy are in excellent agreement with ab initio data. In pure Re, the potential can reproduce the formation energies of vacancies and self-interstitial defects sufficiently accurately and gives the correct ground state self-interstitial configuration. Furthermore, by including liquid structures in the fit, the potential yields a Re melting temperature (3130 K) that is close to the experimental value (3459 K).

A tungsten-rhenium interatomic potential for point defect studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Setyawan, Wahyu; Gao, Ning; Kurtz, Richard J.

A tungsten-rhenium (W-Re) classical interatomic potential is developed within the embedded atom method (EAM) interaction framework. A force-matching method is employed to fit the potential to ab initio forces, energies, and stresses. Simulated annealing is combined with the conjugate gradient technique to search for an optimum potential from over 1000 initial trial sets. The potential is designed for studying point defects in W-Re systems. It gives good predictions of the formation energies of Re defects in W and the binding energies of W self-interstitial clusters with Re. The potential is further evaluated for describing the formation energy of structures inmore » the σ and χ intermetallic phases. The predicted convex-hulls of formation energy are in excellent agreement with ab initio data. In pure Re, the potential can reproduce the formation energies of vacancy and self-interstitial defects sufficiently accurately, and gives the correct ground state self-interstitial configuration. Furthermore, by including liquid structures in the fit, the potential yields a Re melting temperature (3130 K) that is close to the experimental value (3459 K).« less

The stability of vacancy clusters and their effect on helium behaviors in 3C-SiC

NASA Astrophysics Data System (ADS)

Sun, Jingjing; Li, B. S.; You, Yu-Wei; Hou, Jie; Xu, Yichun; Liu, C. S.; Fang, Q. F.; Wang, Z. G.

2018-05-01

We have carried out systematical ab initio calculations to study the stability of vacancy clusters and their effect on helium behaviors in 3C-SiC. It is found that the formation energies of vacancy clusters containing only carbon vacancies are the lowest although the vacancies are not closest to each other, while the binding energies of vacancy clusters composed of both silicon and carbon vacancies in the closest neighbors to each other are the highest. Vacancy clusters can provide with free space for helium atoms to aggregate, while interstitial sites are not favorable for helium atoms to accumulate. The binding energies of vacancy clusters with helium atoms increase almost linearly with the ratio of helium to vacancy, n/m. The binding strength of vacancy cluster having the participation of the silicon vacancy with helium is relatively stronger than that without silicon vacancy. The vacancy clusters with more vacancies can trap helium atoms more tightly. With the presence of vacancy clusters in the material, the diffusivity of helium will be significantly reduced. Moreover, the three-dimension electron density is calculated to analyze the interplay of vacancy clusters with helium.

An analytical model to predict interstitial lubrication of cartilage in migrating contact areas.

PubMed

Moore, A C; Burris, D L

2014-01-03

For nearly a century, articular cartilage has been known for its exceptional tribological properties. For nearly as long, there have been research efforts to elucidate the responsible mechanisms for application toward biomimetic bearing applications. It is now widely accepted that interstitial fluid pressurization is the primary mechanism responsible for the unusual lubrication and load bearing properties of cartilage. Although the biomechanics community has developed elegant mathematical theories describing the coupling of solid and fluid (biphasic) mechanics and its role in interstitial lubrication, quantitative gaps in our understanding of cartilage tribology have inhibited our ability to predict how tribological conditions and material properties impact tissue function. This paper presents an analytical model of the interstitial lubrication of biphasic materials under migrating contact conditions. Although finite element and other numerical models of cartilage mechanics exist, they typically neglect the important role of the collagen network and are limited to a specific set of input conditions, which limits general applicability. The simplified approach taken in this work aims to capture the broader underlying physics as a starting point for further model development. In agreement with existing literature, the model indicates that a large Peclet number, Pe, is necessary for effective interstitial lubrication. It also predicts that the tensile modulus must be large relative to the compressive modulus. This explains why hydrogels and other biphasic materials do not provide significant interstitial pressure under high Pe conditions. The model quantitatively agrees with in-situ measurements of interstitial load support and the results have interesting implications for tissue engineering and osteoarthritis problems. This paper suggests that a low tensile modulus (from chondromalacia or local collagen rupture after impact, for example) may disrupt interstitial pressurization, increase shear stresses, and activate a condition of progressive surface damage as a potential precursor of osteoarthritis. © 2013 Elsevier Ltd. All rights reserved.

Electrical resistivity of V-Cr-Ti alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zinkle, S.J.; Gubbi, A.N.; Eatherly, W.S.

1997-04-01

Room temperature electrical resistivity measurements have been performed on vanadium alloys containing 3-6%Cr and 3-6%Ti in order to evaluate the microstructural stability of these alloys. A nonlinear dependence on Cr and Ti concentration was observed, which suggests that either short range ordering or solute precipitation (perhaps in concert with interstitial solute clustering) has occurred in V-6Cr-6Ti.

Comparative study of displacement cascades simulated with 'magnetic' potentials and Mendelev-type potential in α-Fe

NASA Astrophysics Data System (ADS)

Gao, Chan; Tian, Dongfeng; Li, Maosheng; Qian, Dazhi

2017-04-01

Different interatomic potentials produce displacement cascades with different features, and hence they significantly influence the results obtained from the displacement cascade simulations. The displacement cascade simulations in α-Fe have been carried out by molecular dynamics with three 'magnetic' potentials (MP) and Mendelev-type potential in this paper. Prior to the cascade simulations, the 'magnetic' potentials are hardened to suit for cascade simulations. We find that the peak time, maximum of defects, cascade volume and cascade density with 'magnetic' potentials are smaller than those with Mendelev-type potential. There is no significant difference within statistical uncertainty in the defect production efficiency with Mendelev-type potential and the second 'magnetic' potential at the same cascade energy, but remarkably smaller than those with the first and third 'magnetic' potential. Self interstitial atom (SIA) clustered fractions with 'magnetic' potentials are smaller than that with Mendelev-type potential, especially at the higher energy, due to the larger interstitial formation energies which result from the 'magnetic' potentials. The defect clustered fractions, which are input data for radiation damage accumulation models, may influence the prediction of microstructural evolution under radiation.

Simulation of defects in fusion plasma first wall materials

NASA Astrophysics Data System (ADS)

T, Troev; N, Nankov; T, Yoshiie

2014-06-01

Numerical calculations of radiation damages in beryllium, alpha-iron and tungsten irradiated by fusion neutrons were performed using molecular dynamics (MD) simulations. The displacement cascades efficiency has been calculated using the Norgett-Robinson-Torrens (NRT) formula, the universal pair-potential of Ziegler-Biersack-Littmark (ZBL) and the EAM inter-atomic potential. The pair potential overestimates the defects production by a factor of 2. The ZBL pair potential results and the EAM are comparable at higher primary knock-on atom (PKA) energies (E > 100 keV). We found that the most common types of defects are single vacancies, di-vacancies, interstitials and small number of interstitial clusters. On the bases of calculated results, the behavior of vacancies, empty nano-voids and nano-voids with hydrogen and helium were discussed.

Optimal doping control of magnetic semiconductors via subsurfactant epitaxy.

PubMed

Zeng, Changgan; Zhang, Zhenyu; van Benthem, Klaus; Chisholm, Matthew F; Weitering, Hanno H

2008-02-15

"Subsurfactant epitaxy" is established as a conceptually new approach for introducing manganese as a magnetic dopant into germanium. A kinetic pathway is devised in which the subsurface interstitial sites on Ge(100) are first selectively populated with Mn, while lateral diffusion and clustering on or underneath the surface are effectively suppressed. Subsequent Ge deposition as a capping layer produces a novel surfactantlike phenomenon as the interstitial Mn atoms float towards newly defined subsurface sites at the growth front. Furthermore, the Mn atoms that failed to float upwards are uniformly distributed within the Ge capping layer. The resulting doping levels of order 0.25 at. % would normally be considered too low for ferromagnetic ordering, but the Curie temperature exceeds room temperature by a comfortable margin. Subsurfactant epitaxy thus enables superior dopant control in magnetic semiconductors.

Tracing the `ninth sulfur' of the nitrogenase cofactor via a semi-synthetic approach

NASA Astrophysics Data System (ADS)

Tanifuji, Kazuki; Lee, Chi Chung; Sickerman, Nathaniel S.; Tatsumi, Kazuyuki; Ohki, Yasuhiro; Hu, Yilin; Ribbe, Markus W.

2018-05-01

The M-cluster is the [(homocitrate)MoFe7S9C] active site of nitrogenase that is derived from an 8Fe core assembled viacoupling and rearrangement of two [Fe4S4] clusters concomitant with the insertion of an interstitial carbon and a `ninth sulfur'. Combining synthetic [Fe4S4] clusters with an assembly protein template, here we show that sulfite can give rise to the ninth sulfur that is incorporated in the catalytically important belt region of the cofactor after the radical S-adenosyl-l-methionine-dependent carbide insertion and the concurrent 8Fe-core rearrangement have already taken place. Based on the differential reactivity of the formed cluster species, we also propose a new [Fe8S8C] cluster intermediate, the L*-cluster, which is similar to the [Fe8S9C] L-cluster, but lacks the ninth sulfur from sulfite. This work provides a semi-synthetic tool for protein reconstitution that could be widely applicable for the functional analysis of other FeS systems.

Tracing the 'ninth sulfur' of the nitrogenase cofactor via a semi-synthetic approach.

PubMed

Tanifuji, Kazuki; Lee, Chi Chung; Sickerman, Nathaniel S; Tatsumi, Kazuyuki; Ohki, Yasuhiro; Hu, Yilin; Ribbe, Markus W

2018-05-01

The M-cluster is the [(homocitrate)MoFe 7 S 9 C] active site of nitrogenase that is derived from an 8Fe core assembled viacoupling and rearrangement of two [Fe 4 S 4 ] clusters concomitant with the insertion of an interstitial carbon and a 'ninth sulfur'. Combining synthetic [Fe 4 S 4 ] clusters with an assembly protein template, here we show that sulfite can give rise to the ninth sulfur that is incorporated in the catalytically important belt region of the cofactor after the radical S-adenosyl-L-methionine-dependent carbide insertion and the concurrent 8Fe-core rearrangement have already taken place. Based on the differential reactivity of the formed cluster species, we also propose a new [Fe 8 S 8 C] cluster intermediate, the L*-cluster, which is similar to the [Fe 8 S 9 C] L-cluster, but lacks the ninth sulfur from sulfite. This work provides a semi-synthetic tool for protein reconstitution that could be widely applicable for the functional analysis of other FeS systems.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Field, Kevin G.; Yang, Ying; Busby, Jeremy T.

Radiation induced segregation (RIS) is a well-studied phenomena which occurs in many structurally relevant nuclear materials including austenitic stainless steels. RIS occurs due to solute atoms preferentially coupling to mobile point defect fluxes that migrate and interact with defect sinks. Here, a 304 stainless steel was neutron irradiated up to 47.1 dpa at 320 °C. Investigations into the RIS response at specific grain boundary types were utilized to determine the sink characteristics of different boundary types as a function of irradiation dose. A rate theory model built on the foundation of the modified inverse Kirkendall (MIK) model is proposed andmore » benchmarked to the experimental results. This model, termed the GiMIK model, includes alterations in the boundary conditions based on grain boundary structure and includes expressions for interstitial binding. This investigation, through experiment and modeling, found specific grain boundary structures exhibit unique defect sink characteristics depending on their local structure. Furthermore, such interactions were found to be consistent across all doses investigated and had larger global implications including precipitation of Ni-Si clusters near different grain boundary types.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Field, Kevin G.; Yang, Ying; Allen, Todd R.

Radiation induced segregation (RIS) is a well-studied phenomena which occurs in many structurally relevant nuclear materials including austenitic stainless steels. RIS occurs due to solute atoms preferentially coupling to mobile point defect fluxes that migrate and interact with defect sinks. Here, a 304 stainless steel was neutron irradiated up to 47.1 dpa at 320 °C. Investigations into the RIS response at specific grain boundary types were utilized to determine the sink characteristics of different boundary types as a function of irradiation dose. A rate theory model built on the foundation of the modified inverse Kirkendall (MIK) model is proposed andmore » benchmarked to the experimental results. This model, termed the GiMIK model, includes alterations in the boundary conditions based on grain boundary structure and includes expressions for interstitial binding. This investigation, through experiment and modeling, found specific grain boundary structures exhibit unique defect sink characteristics depending on their local structure. Such interactions were found to be consistent across all doses investigated and had larger global implications including precipitation of Ni-Si clusters near different grain boundary types.« less

Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases

PubMed Central

Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

2016-01-01

Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent. PMID:27200087

Structural Characterization of CO-Inhibited Mo-Nitrogenase by Combined Application of Nuclear Resonance Vibrational Spectroscopy, Extended X-ray Absorption Fine Structure, and Density Functional Theory: New Insights into the Effects of CO Binding and the Role of the Interstitial Atom

DOE PAGES

Scott, Aubrey D.; Pelmenschikov, Vladimir; Guo, Yisong; ...

2014-10-02

The properties of CO-inhibited Azotobacter vinelandii (Av) Mo-nitrogenase (N 2ase) have been examined by the combined application of nuclear resonance vibrational spectroscopy (NRVS), extended X-ray absorption fine structure (EXAFS), and density functional theory (DFT). Dramatic changes in the NRVS are seen under high-CO conditions, especially in a 188 cm –1 mode associated with symmetric breathing of the central cage of the FeMo-cofactor. Similar changes are reproduced with the α-H195Q N 2ase variant. In the frequency region above 450 cm –1, additional features are seen that are assigned to Fe-CO bending and stretching modes (confirmed by 13CO isotope shifts). The EXAFSmore » for wild-type N 2ase shows evidence for a significant cluster distortion under high-CO conditions, most dramatically in the splitting of the interaction between Mo and the shell of Fe atoms originally at 5.08 Å in the resting enzyme. A DFT model with both a terminal ₋CO and a partially reduced ₋CHO ligand bound to adjacent Fe sites is consistent with both earlier FT-IR experiments, and the present EXAFS and NRVS observations for the wild-type enzyme. Another DFT model with two terminal CO ligands on the adjacent Fe atoms yields Fe-CO bands consistent with the α-H195Q variant NRVS. The calculations also shed light on the vibrational “shake” modes of the interstitial atom inside the central cage, and their interaction with the Fe-CO modes. We discuss implications for the CO and N 2 reactivity of N 2ase.« less

Geographical variation in reporting Interstitial Lung Disease as an adverse drug reaction: findings from an European Medicines Agency analysis of reports in EudraVigilance.

PubMed

Pinheiro, Luis; Blake, Kevin; Januskiene, Justina; Yue, Qun-Ying; Arlett, Peter

2016-06-01

Clinically, interstitial lung disease (ILD) is a heterogeneous group of over 150 respiratory disorders. In the context of its signal evaluation work, the European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has seen geographic clustering of case reports of ILD from Japan. To explore this further, EudraVigilance (EV), the EMA's database of adverse drug reactions (ADRs), was analysed. The results have been used to inform on implications for pharmacovigilance including signal detection and evaluation activities. EV was queried for reports of respiratory ADRs coded using MedDRA for the period 1994-2014 for all medicinal products. Descriptive statistics and non-parametric (chi-square) independence tests were produced to compare reporting of ILD from Japan versus the rest of the world. As of 31 December 2014, there were 26 551 case reports of ILD in EV of which 17 526 (66%) originated in Japan. The reporting rate of ILD for Japan has been consistently higher over the period. The odds that a case report from Japan in EV refers to ILD is OR = 20.7, 95% CI 20.2, 21.3 (p < 0.001), compared to OR = 0.60, 95% CI 0.54, 0.67 (p < 0.001) for pulmonary fibrosis. A geographic imbalance between Japan and the rest of the world in reporting respiratory ADRs as ILD is confirmed. Consequently, the PRAC has developed approaches to address this in relation to signals of ILD it assesses to allow for more targeted risk minimisation including updates to the product information in the EU setting. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Genomic Organization of Repetitive DNA in Woodpeckers (Aves, Piciformes): Implications for Karyotype and ZW Sex Chromosome Differentiation

PubMed Central

Kretschmer, Rafael; Bertocchi, Natasha Avila; Degrandi, Tiago Marafiga; de Oliveira, Edivaldo Herculano Corrêa; Cioffi, Marcelo de Bello; Garnero, Analía del Valle; Gunski, Ricardo José

2017-01-01

Birds are characterized by a low proportion of repetitive DNA in their genome when compared to other vertebrates. Among birds, species belonging to Piciformes order, such as woodpeckers, show a relatively higher amount of these sequences. The aim of this study was to analyze the distribution of different classes of repetitive DNA—including microsatellites, telomere sequences and 18S rDNA—in the karyotype of three Picidae species (Aves, Piciformes)—Colaptes melanochloros (2n = 84), Colaptes campestris (2n = 84) and Melanerpes candidus (2n = 64)–by means of fluorescence in situ hybridization. Clusters of 18S rDNA were found in one microchromosome pair in each of the three species, coinciding to a region of (CGG)10 sequence accumulation. Interstitial telomeric sequences were found in some macrochromosomes pairs, indicating possible regions of fusions, which can be related to variation of diploid number in the family. Only one, from the 11 different microsatellite sequences used, did not produce any signals. Both species of genus Colaptes showed a similar distribution of microsatellite sequences, with some difference when compared to M. candidus. Microsatellites were found preferentially in the centromeric and telomeric regions of micro and macrochromosomes. However, some sequences produced patterns of interstitial bands in the Z chromosome, which corresponds to the largest element of the karyotype in all three species. This was not observed in the W chromosome of Colaptes melanochloros, which is heterochromatic in most of its length, but was not hybridized by any of the sequences used. These results highlight the importance of microsatellite sequences in differentiation of sex chromosomes, and the accumulation of these sequences is probably responsible for the enlargement of the Z chromosome. PMID:28081238

Structural characterization of CO-inhibited Mo-nitrogenase by combined application of nuclear resonance vibrational spectroscopy, extended X-ray absorption fine structure, and density functional theory: new insights into the effects of CO binding and the role of the interstitial atom.

PubMed

Scott, Aubrey D; Pelmenschikov, Vladimir; Guo, Yisong; Yan, Lifen; Wang, Hongxin; George, Simon J; Dapper, Christie H; Newton, William E; Yoda, Yoshitaka; Tanaka, Yoshihito; Cramer, Stephen P

2014-11-12

The properties of CO-inhibited Azotobacter vinelandii (Av) Mo-nitrogenase (N2ase) have been examined by the combined application of nuclear resonance vibrational spectroscopy (NRVS), extended X-ray absorption fine structure (EXAFS), and density functional theory (DFT). Dramatic changes in the NRVS are seen under high-CO conditions, especially in a 188 cm(-1) mode associated with symmetric breathing of the central cage of the FeMo-cofactor. Similar changes are reproduced with the α-H195Q N2ase variant. In the frequency region above 450 cm(-1), additional features are seen that are assigned to Fe-CO bending and stretching modes (confirmed by (13)CO isotope shifts). The EXAFS for wild-type N2ase shows evidence for a significant cluster distortion under high-CO conditions, most dramatically in the splitting of the interaction between Mo and the shell of Fe atoms originally at 5.08 Å in the resting enzyme. A DFT model with both a terminal -CO and a partially reduced -CHO ligand bound to adjacent Fe sites is consistent with both earlier FT-IR experiments, and the present EXAFS and NRVS observations for the wild-type enzyme. Another DFT model with two terminal CO ligands on the adjacent Fe atoms yields Fe-CO bands consistent with the α-H195Q variant NRVS. The calculations also shed light on the vibrational "shake" modes of the interstitial atom inside the central cage, and their interaction with the Fe-CO modes. Implications for the CO and N2 reactivity of N2ase are discussed.

Polyhydrido Copper Clusters: Synthetic Advances, Structural Diversity, and Nanocluster-to-Nanoparticle Conversion.

PubMed

Dhayal, Rajendra S; van Zyl, Werner E; Liu, C W

2016-01-19

Metal hydride clusters have historically been studied to unravel their aesthetically pleasing molecular structures and interesting properties, especially toward hydrogen related applications. Central to this work is the hydride ligand, H¯, the smallest closed-shell spherical anion known. Two new developments in polyhydrido nanocluster chemistry include the determination of heretofore unknown hydride coordination modes and novel structural constructs, and conversion from the molecular entities to rhombus-shaped copper nanoparticles (CuNPs). These advances, together with hydrogen evolution and catalysis, have provided both experimentalists and theorists with a rich scientific directive to further explore. The isolation of hexameric [{(Ph3P)CuH}6] (Stryker reagent) could be regarded as the springboard for the recent emergence of polyhydrido copper cluster chemistry due to its utilization in a variety of organic chemical transformations. The stability of clusters of various nuclearity was improved through phosphine, pyridine, and carbene type ligands. Our focus lies with the isolation of novel copper (poly)hydride clusters using mostly the phosphor-1,1-dithiolato type ligands. We found such chalcogen-stabilized clusters to be exceptionally air and moisture stable over a wide range of nuclearities (Cu7 to Cu32). In this Account, we (i) report on state-of-the-art copper hydride cluster chemistry, especially with regards to the diverse and novel structural types generally, and newly discovered hydride coordination modes in particular, (ii) demonstrate the indispensable power of neutron diffraction for the unambiguous assignment and location of hydride ligand(s) within a cluster, and (iii) prove unique transformations that can occur not only between well characterized high nuclearity clusters, but also how such clusters can transform to uniquely shaped nanoparticles of several nanometers in diameter through copper hydride reduction. The increase in the number of low- to high-nuclearity hydride clusters allows for different means by which they can be classified. We chose a classification based on the coordination mode of hydride ligand within the cluster. This includes copper clusters associated with bridging (μ2-H) and capping (μ3-H) hydride modes, followed by an interstitial (μ4-H) hydride mode that was introduced for the first time into octa- and hepta-nuclear copper clusters stabilized by dichalcogen-type ligands. This breakthrough provided a means to explore higher nuclearity polyhydrido nanoclusters, which contain both capping (μ3-H) and interstitial (μ(4-6)-H) hydrides. The presence of bidentate ligands having mixed S/P dative sites led to air- and moisture-stable copper hydride nanoclusters. The formation of rhombus-shaped nanoparticles (CuNPs) from copper polyhydrides in the presence of excess borohydrides suggests the presence of metal hydrides as intermediates during the formation of nanoparticles.

Renal myofibroblasts contract collagen I matrix lattices in vitro.

PubMed

Kelynack, K J; Hewitson, T D; Pedagogos, E; Nicholls, K M; Becker, G J

1999-01-01

Myofibroblasts, cells with both fibroblastic and smooth muscle cell features, have been implicated in renal scarring. In addition to synthetic properties, contractile features and integrin expression may allow myofibroblasts to rearrange and contract interstitial collagenous proteins. Myofibroblasts from normal rat kidneys were grown in cell-populated collagen lattices to measure cell generated contraction. Following detachment of cell populated collagen lattices, myofibroblasts progressively contracted collagen lattices, reducing lattice diameter by 42% at 24 h. Alignment of myofibroblasts, rearrangement of fibrils and beta(1) integrin expression were observed within lattices. We postulate that interstitial myofibroblasts contribute to renal scarring through manipulation of collagenous proteins. Copyright 1999 S. Karger AG, Basel

Visualization of T Cell-Regulated Monocyte Clusters Mediating Keratinocyte Death in Acquired Cutaneous Immunity.

PubMed

Liu, Zheng; Yang, Fei; Zheng, Hao; Fan, Zhan; Qiao, Sha; Liu, Lei; Tao, Juan; Luo, Qingming; Zhang, Zhihong

2018-06-01

It remains unclear how monocytes are mobilized to amplify inflammatory reactions in T cell-mediated adaptive immunity. Here, we investigate dynamic cellular events in the cascade of inflammatory responses through intravital imaging of a multicolor-labeled murine contact hypersensitivity model. We found that monocytes formed clusters around hair follicles in the contact hypersensitivity model. In this process, effector T cells encountered dendritic cells under regions of monocyte clusters and secreted IFN-γ, which mobilizes CCR2-dependent monocyte interstitial migration and CXCR2-dependent monocyte cluster formation. We showed that hair follicles shaped the inflammatory microenvironment for communication among the monocytes, keratinocytes, and effector T cells. After disrupting the T cell-mobilized monocyte clusters through CXCR2 antagonization, monocyte activation and keratinocyte apoptosis were significantly inhibited. Our study provides a new perspective on effector T cell-regulated monocyte behavior, which amplifies the inflammatory reaction in acquired cutaneous immunity. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Annealing in tellurium-nitrogen co-doped ZnO films: The roles of intrinsic zinc defects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Kun, E-mail: ktang@nju.edu.cn; Gu, Ran; Gu, Shulin, E-mail: slgu@nju.edu.cn

2015-04-07

In this article, the authors have conducted an extensive investigation on the roles of intrinsic zinc defects by annealing of a batch of Te-N co-doped ZnO films. The formation and annihilation of Zn interstitial (Zn{sub i}) clusters have been found in samples with different annealing temperatures. Electrical and Raman measurements have shown that the Zn{sub i} clusters are a significant compensation source to holes, and the Te co-doping has a notable effect on suppressing the Zn{sub i} clusters. Meanwhile, shallow acceptors have been identified in photoluminescence spectra. The N{sub O}-Zn-Te complex, zinc vacancy (V{sub Zn})-N{sub O} complex, and V{sub Zn}more » clusters are thought to be the candidates as the shallow acceptors. The evolution of shallow acceptors upon annealing temperature have been also studied. The clustering of V{sub Zn} at high annealing temperature is proposed to be a possible candidate as a stable acceptor in ZnO.« less

Fibroblasts and the extracellular matrix in right ventricular disease.

PubMed

Frangogiannis, Nikolaos G

2017-10-01

Right ventricular failure predicts adverse outcome in patients with pulmonary hypertension (PH), and in subjects with left ventricular heart failure and is associated with interstitial fibrosis. This review manuscript discusses the cellular effectors and molecular mechanisms implicated in right ventricular fibrosis. The right ventricular interstitium contains vascular cells, fibroblasts, and immune cells, enmeshed in a collagen-based matrix. Right ventricular pressure overload in PH is associated with the expansion of the fibroblast population, myofibroblast activation, and secretion of extracellular matrix proteins. Mechanosensitive transduction of adrenergic signalling and stimulation of the renin-angiotensin-aldosterone cascade trigger the activation of right ventricular fibroblasts. Inflammatory cytokines and chemokines may contribute to expansion and activation of macrophages that may serve as a source of fibrogenic growth factors, such as transforming growth factor (TGF)-β. Endothelin-1, TGF-βs, and matricellular proteins co-operate to activate cardiac myofibroblasts, and promote synthesis of matrix proteins. In comparison with the left ventricle, the RV tolerates well volume overload and ischemia; whether the right ventricular interstitial cells and matrix are implicated in these favourable responses remains unknown. Expansion of fibroblasts and extracellular matrix protein deposition are prominent features of arrhythmogenic right ventricular cardiomyopathies and may be implicated in the pathogenesis of arrhythmic events. Prevailing conceptual paradigms on right ventricular remodelling are based on extrapolation of findings in models of left ventricular injury. Considering the unique embryologic, morphological, and physiologic properties of the RV and the clinical significance of right ventricular failure, there is a need further to dissect RV-specific mechanisms of fibrosis and interstitial remodelling. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Synthesis and isolation of [Fe@Ge(10)](3-): a pentagonal prismatic Zintl ion cage encapsulating an interstitial iron atom.

PubMed

Zhou, Binbin; Denning, Mark S; Kays, Deborah L; Goicoechea, Jose M

2009-03-04

Reaction of an ethylenediamine (en) solution of the Zintl phase precursor K(4)Ge(9) with FeAr(2) (Ar = 2,6-Mes(2)C(6)H(3)) in the presence of 2,2,2-crypt (4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane) yielded the endohedral Zintl ion [Fe@Ge(10)](3-) (1) which was crystallographically characterized as a [K(2,2,2-crypt)](+) salt in [K(2,2,2-crypt)](3)[Fe@Ge(10)]*2en. This unprecedented Zintl ion exhibits a pentagonal prismatic 10-atom germanium cage with an interstitial iron atom in the central cavity. Confirmation of the existence of the cluster anion in solution was corroborated by positive and negative ion mode electrospray mass spectrometry.

Distribution of mast cell subtypes in interstitial cystitis: implications for novel diagnostic and therapeutic strategies?

PubMed

Malik, Shabana T; Birch, Brian R; Voegeli, David; Fader, Mandy; Foria, Vipul; Cooper, Alan J; Walls, Andrew F; Lwaleed, Bashir A

2018-05-15

To identify the presence and geographical distribution of mast cell (MC) subtypes: MC T (tryptase positive-chymase negative) and MC TC (tryptase positive-chymase positive) in bladder tissue. Bladder tissue was obtained from patients with painful bladder syndrome/interstitial cystitis (n=14) and normal histology from University Hospital Southampton tissue bank. Sequential tissue slices were immunohistochemically stained for MC subtypes using anti-MC tryptase (for MC T and MC TC ) and anti-MC chymase (for MC TC ). Stained sections were photographed, and positively stained MCs were quantified using ImageJ. Data were analysed using descriptive statistics and individual paired t-tests. There was a significant difference in the density of MCs between each layer of the disease bladder, with the greatest accumulation within the detrusor (p<0.001). There was a significant increase in MC TC subtype in the lamina (p=0.009) in painful bladder syndrome/interstitial cystitis. Our results suggest that mastocytosis is present within all layers of disease bladder, especially the muscle layer. The varying increase in MC subtypes in the lamina and mucosa may explain the variability in painful bladder syndrome/interstitial cystitis symptoms. A high influx of MC TC in the mucosa of individuals who also had ulceration noted within their diagnostic notes may be of the Hunner's ulcer subclassification. These findings suggest a relationship between the pathogenesis of MC subtypes and the clinical presentation of painful bladder syndrome/interstitial cystitis. A cohort study would further elucidate the diagnostic and/or therapeutic potential of MCs in patients with painful bladder syndrome/interstitial cystitis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Orthopyroxene oikocrysts in the MG1 chromitite layer of the Bushveld Complex: implications for cumulate formation and recrystallisation

NASA Astrophysics Data System (ADS)

Kaufmann, Felix E. D.; Vukmanovic, Zoja; Holness, Marian B.; Hecht, Lutz

2018-02-01

Two typical mineral textures of the MG 1 chromitite of the Bushveld Complex, South Africa, were observed; one characterised by abundant orthopyroxene oikocrysts, and the other by coarse-grained granular chromitite with only minor amounts of interstitial material. Oikocrysts form elongate clusters of several crystals aligned parallel to the layering, and typically have subhedral, almost chromite-free, core zones containing remnants of olivine. The core zones are surrounded by poikilitic aureoles overgrowing euhedral to subhedral chromite chadacrysts. Chromite grains show no preferred crystal orientation, whereas orthopyroxene grains forming clusters commonly share the same crystallographic orientation. Oikocryst core zones have lower Mg# and higher concentrations of incompatible trace elements compared to their poikilitic aureoles. Core zones are relatively enriched in REE compared to a postulated parental magma (B1) and did not crystallise in equilibrium with the surrounding minerals, whereas the composition of the poikilitic orthopyroxene is consistent with growth from the B1 magma. These observations cannot be explained by the classic cumulus and post-cumulus models of oikocryst formation. Instead, we suggest that the oikocryst core zones in the MG1 chromitite layer formed by peritectic replacement of olivine primocrysts by reaction with an upwards-percolating melt enriched in incompatible trace elements. Poikilitic overgrowth on oikocryst core zones occurred in equilibrium with a basaltic melt of B1 composition near the magma-crystal mush interface. Finally, adcumulus crystallisation followed by grain growth resulted in the surrounding granular chromitite.

Mapping strain rate dependence of dislocation-defect interactions by atomistic simulations

PubMed Central

Fan, Yue; Osetskiy, Yuri N.; Yip, Sidney; Yildiz, Bilge

2013-01-01

Probing the mechanisms of defect–defect interactions at strain rates lower than 106 s−1 is an unresolved challenge to date to molecular dynamics (MD) techniques. Here we propose an original atomistic approach based on transition state theory and the concept of a strain-dependent effective activation barrier that is capable of simulating the kinetics of dislocation–defect interactions at virtually any strain rate, exemplified within 10−7 to 107 s−1. We apply this approach to the problem of an edge dislocation colliding with a cluster of self-interstitial atoms (SIAs) under shear deformation. Using an activation–relaxation algorithm [Kushima A, et al. (2009) J Chem Phys 130:224504], we uncover a unique strain-rate–dependent trigger mechanism that allows the SIA cluster to be absorbed during the process, leading to dislocation climb. Guided by this finding, we determine the activation barrier of the trigger mechanism as a function of shear strain, and use that in a coarse-graining rate equation formulation for constructing a mechanism map in the phase space of strain rate and temperature. Our predictions of a crossover from a defect recovery at the low strain-rate regime to defect absorption behavior in the high strain-rate regime are validated against our own independent, direct MD simulations at 105 to 107 s−1. Implications of the present approach for probing molecular-level mechanisms in strain-rate regimes previously considered inaccessible to atomistic simulations are discussed. PMID:24114271

Observation of interstitial molecular hydrogen in clathrate hydrates.

PubMed

Grim, R Gary; Barnes, Brian C; Lafond, Patrick G; Kockelmann, Winfred A; Keen, David A; Soper, Alan K; Hiratsuka, Masaki; Yasuoka, Kenji; Koh, Carolyn A; Sum, Amadeu K

2014-09-26

The current knowledge and description of guest molecules within clathrate hydrates only accounts for occupancy within regular polyhedral water cages. Experimental measurements and simulations, examining the tert-butylamine + H2 + H2O hydrate system, now suggest that H2 can also be incorporated within hydrate crystal structures by occupying interstitial sites, that is, locations other than the interior of regular polyhedral water cages. Specifically, H2 is found within the shared heptagonal faces of the large (4(3)5(9)6(2)7(3)) cage and in cavities formed from the disruption of smaller (4(4)5(4)) water cages. The ability of H2 to occupy these interstitial sites and fluctuate position in the crystal lattice demonstrates the dynamic behavior of H2 in solids and reveals new insight into guest-guest and guest-host interactions in clathrate hydrates, with potential implications in increasing overall energy storage properties. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identifying self-interstitials of bcc and fcc crystals in molecular dynamics

NASA Astrophysics Data System (ADS)

Bukkuru, S.; Bhardwaj, U.; Warrier, M.; Rao, A. D. P.; Valsakumar, M. C.

2017-02-01

Identification of self-interstitials in molecular dynamics (MD) simulations is of critical importance. There exist several criteria for identifying the self-interstitial. Most of the existing methods use an assumed cut-off value for the displacement of an atom from its lattice position to identify the self-interstitial. The results obtained are affected by the chosen cut-off value. Moreover, these chosen cut-off values are independent of temperature. We have developed a novel unsupervised learning algorithm called Max-Space Clustering (MSC) to identify an appropriate cut-off value and its dependence on temperature. This method is compared with some widely used methods such as effective sphere (ES) method and nearest neighbor sphere (NNS) method. The cut-off radius obtained using our method shows a linear variation with temperature. The value of cut-off radius and its temperature dependence is derived for five bcc (Cr, Fe, Mo, Nb, W) and six fcc (Ag, Au, Cu, Ni, Pd, Pt) crystals. It is seen that the ratio of the cut-off values "r" to the lattice constant "a" lies between 0.23 and 0.3 at 300 K and this ratio is on an average smaller for the fcc crystals. Collision cascade simulations are carried out for Primary knock-on Atom (PKA) energies of 5 keV in Fe (at 300 K and 1000 K) and W (at 300 K and 2500 K) and the results are compared using the various methods.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Setyawan, Wahyu; Nandipati, Giridhar; Kurtz, Richard J.

The stability of tungsten self-interstitial atom (SIA) clusters is studied using first-principles methods. Clusters from one to seven SIAs are systematically explored from 1264 unique configurations. Finite-size effect of the simulation cell is corrected based on the scaling of formation energy versus inverse volume cell. Furthermore, the accuracy of the calculations is improved by treating the 5p semicore states as valence states. Configurations of the three most stable clusters in each cluster size n are presented, which consist of parallel [111] dumbbells. The evolution of these clusters leading to small dislocation loops is discussed. The binding energy of size-n clustersmore » is analyzed relative to an n → (n-1) + 1 dissociation and is shown to increase with size. Extrapolation for n > 7 is presented using a dislocation loop model. In addition, the interaction of these clusters with a substitutional Re, Os, or Ta solute is explored by replacing one of the dumbbells with the solute. Re and Os strongly attract these clusters, but Ta strongly repels. The strongest interaction is found when the solute is located on the periphery of the cluster rather than in the middle. The magnitude of this interaction decreases with cluster size. Empirical fits to describe the trend of the solute binding energy are presented.« less

Structure, stability and magnetism of cobalt doped (ZnO)n clusters.

PubMed

Yang, Jack; Zhang, Y B; Li, Sean

2011-03-01

Clusters of magnetic impurities are believed to play an important role in retaining ferromagnetism in diluted magnetic semiconductors (DMS), the origin of which has been a long debated issue. Controlling the dopant homogeneity in magnetic semiconductors is therefore a critical issue for the fabrication of high performance DMS. The current paper presents a first principle study on the stability and magnetic properties of Co doped (ZnO)n (n = 12 and 15) clusters using density functional theory. The results show that cobalt ions in these clusters tend to increase their stabilities by maximizing their co-ordination numbers to oxygen. This will likely to be the case for (ZnO)n clusters with n other than 12 and 15 in order for Co to reside in a stable local crystal field. Expansive (shrinkage) stress is introduced when cobalt resides in exohedral substitutional (endohedral interstitial) sites; such strain can be offset by the cluster deformation. Bidoped cluster is found to be unstable due to the increase of system strain energy. All the doped clusters were found to preserve 3 microg of magnetic moments from Co in the overall clusters, but with part of the local moments on cobalt re-distributed onto neighboring oxygen atoms. Current findings may provide a better understanding on the structural chemistry of magnetic dopants in nanocrystallined DMS materials.

An empirical potential for simulating vacancy clusters in tungsten.

PubMed

Mason, D R; Nguyen-Manh, D; Becquart, C S

2017-12-20

We present an empirical interatomic potential for tungsten, particularly well suited for simulations of vacancy-type defects. We compare energies and structures of vacancy clusters generated with the empirical potential with an extensive new database of values computed using density functional theory, and show that the new potential predicts low-energy defect structures and formation energies with high accuracy. A significant difference to other popular embedded-atom empirical potentials for tungsten is the correct prediction of surface energies. Interstitial properties and short-range pairwise behaviour remain similar to the Ackford-Thetford potential on which it is based, making this potential well-suited to simulations of microstructural evolution following irradiation damage cascades. Using atomistic kinetic Monte Carlo simulations, we predict vacancy cluster dissociation in the range 1100-1300 K, the temperature range generally associated with stage IV recovery.

Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD).

PubMed

O'Dwyer, David N; Armstrong, Michelle E; Cooke, Gordon; Dodd, Jonathan D; Veale, Douglas J; Donnelly, Seamas C

2013-10-01

Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD. © 2013.

High-Performance and Traditional Multicrystalline Silicon: Comparing Gettering Responses and Lifetime-Limiting Defects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castellanos, Sergio; Ekstrom, Kai E.; Autruffe, Antoine

2016-05-01

In recent years, high-performance multicrystalline silicon (HPMC-Si) has emerged as an attractive alternative to traditional ingot-based multicrystalline silicon (mc-Si), with a similar cost structure but improved cell performance. Herein, we evaluate the gettering response of traditional mc-Si and HPMC-Si. Microanalytical techniques demonstrate that HPMC-Si and mc-Si share similar lifetime-limiting defect types but have different relative concentrations and distributions. HPMC-Si shows a substantial lifetime improvement after P-gettering compared with mc-Si, chiefly because of lower area fraction of dislocation-rich clusters. In both materials, the dislocation clusters and grain boundaries were associated with relatively higher interstitial iron point-defect concentrations after diffusion, which ismore » suggestive of dissolving metal-impurity precipitates. The relatively fewer dislocation clusters in HPMC-Si are shown to exhibit similar characteristics to those found in mc-Si. Given similar governing principles, a proxy to determine relative recombination activity of dislocation clusters developed for mc-Si is successfully transferred to HPMC-Si.« less

Effect of solute atom concentration on vacancy cluster formation in neutron-irradiated Ni alloys

NASA Astrophysics Data System (ADS)

Sato, Koichi; Itoh, Daiki; Yoshiie, Toshimasa; Xu, Qiu; Taniguchi, Akihiro; Toyama, Takeshi

2011-10-01

The dependence of microstructural evolution on solute atom concentration in Ni alloys was investigated by positron annihilation lifetime measurements. The positron annihilation lifetimes in pure Ni, Ni-0.05 at.%Si, Ni-0.05 at.%Sn, Ni-Cu, and Ni-Ge alloys were about 400 ps even at a low irradiation dose of 3 × 10 -4 dpa, indicating the presence of microvoids in these alloys. The size of vacancy clusters in Ni-Si and Ni-Sn alloys decreased with an increase in the solute atom concentration at irradiation doses less than 0.1 dpa; vacancy clusters started to grow at an irradiation dose of about 0.1 dpa. In Ni-2 at.%Si, irradiation-induced segregation was detected by positron annihilation coincidence Doppler broadening measurements. This segregation suppressed one-dimensional (1-D) motion of the interstitial clusters and promoted mutual annihilation of point defects. The frequency and mean free path of the 1-D motion depended on the solute atom concentration and the amount of segregation.

The role of nickel in radiation damage of ferritic alloys

DOE PAGES

Osetsky, Y.; Anento, Napoleon; Serra, Anna; ...

2014-11-26

According to modern theory, damage evolution under neutron irradiation depends on the fraction of self-interstitial atoms (SIAs) produced in the form of one-dimensional glissile clusters. These clusters, having a low interaction cross-section with other defects, are absorbed mainly by grain boundaries and dislocations, creating the so-called production bias. It is known empirically that the addition of certain alloying elements influences many radiation effects, including swelling; however, the mechanisms are unknown in many cases. In this study, we report the results of an extensive multi-technique atomistic level modeling study of SIA clusters mobility in body-centered cubic Fe–Ni alloys. We have foundmore » that Ni interacts strongly with the periphery of clusters, affecting their mobility. The total effect is defined by the number of Ni atoms interacting with the cluster at the same time and can be significant, even in low-Ni alloys. Thus a 1 nm (37SIAs) cluster is practically immobile at T < 500 K in the Fe–0.8 at.% Ni alloy. Increasing cluster size and Ni content enhances cluster immobilization. Finally, this effect should have quite broad consequences in void swelling, matrix damage accumulation and radiation induced hardening and the results obtained help to better understand and predict the effects of radiation in Fe–Ni ferritic alloys.« less

Assessment and management of refractory breathlessness in interstitial lung disease.

PubMed

Speakman, Lucy; Walthall, Helen

2017-09-02

Interstitial lung disease (ILD) refers to a cluster of fibroinflammatory conditions. There are limited treatment options and most patients have severe dyspnoea. The prognosis is poor. This study aims to evaluate current literature on the assessment and management of refractory breathlessness in ILD. Few tools are available to assess dyspnoea in advanced respiratory disease. Holistic assessment requires a combination of tools but there are few disease specific tools. The role of opioids is well established in the reduction of breathlessness, but there is insufficient evidence that benzodiazepines are beneficial. Non-pharmcolological breathlessness intervention services can give patients mastery of their disease, reduced distress due to breathlessness and were more cost effective. More research on holistic interventions for use in advanced disease needs to be done. Patient-reported outcome measures could elicit valuable evidence to describe the benefit of breathlessness management services in advanced respiratory disease.

Velo-cardio-facial and partial DiGeorge phenotype in a child with interstitial deletion at 10p13 - implications for cytogenetics and molecular biology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lipson, A.; Sholler, G.; Issacs, D.

We report on a female with a interstitial deletion of 10p13 and a phenotype similar to that seen with the 22q deletion syndromes (DiGeorge/velo-cardio-facial). She had a posterior cleft palate, perimembranous ventricular septal defect, dyscoordinate swallowing, T-cell subset abnormalities, small ears, maxillary and mandibular hypoplasia, broad nasal bridge, deficient alae nasi, contractures of fingers and developmental delay. This could indicate homology of some developmental genes at 22q and 10p so that patients with the velocardiofacial phenotype who do not prove to be deleted on 22q are candidates for a 10p deletion. 58 refs., 3 figs.

Defect sink characteristics of specific grain boundary types in 304 stainless steels under high dose neutron environments

DOE PAGES

Field, Kevin G.; Yang, Ying; Busby, Jeremy T.; ...

2015-03-09

Radiation induced segregation (RIS) is a well-studied phenomena which occurs in many structurally relevant nuclear materials including austenitic stainless steels. RIS occurs due to solute atoms preferentially coupling to mobile point defect fluxes that migrate and interact with defect sinks. Here, a 304 stainless steel was neutron irradiated up to 47.1 dpa at 320 °C. Investigations into the RIS response at specific grain boundary types were utilized to determine the sink characteristics of different boundary types as a function of irradiation dose. A rate theory model built on the foundation of the modified inverse Kirkendall (MIK) model is proposed andmore » benchmarked to the experimental results. This model, termed the GiMIK model, includes alterations in the boundary conditions based on grain boundary structure and includes expressions for interstitial binding. This investigation, through experiment and modeling, found specific grain boundary structures exhibit unique defect sink characteristics depending on their local structure. Furthermore, such interactions were found to be consistent across all doses investigated and had larger global implications including precipitation of Ni-Si clusters near different grain boundary types.« less

The effect of interstitial pressure on tumor growth: coupling with the blood and lymphatic vascular systems

PubMed Central

Wu, Min; Frieboes, Hermann B.; McDougall, Steven R.; Chaplain, Mark A.J.; Cristini, Vittorio; Lowengrub, John

2013-01-01

The flow of interstitial fluid and the associated interstitial fluid pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of interstitial pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and interstitial hydraulic conductivities inside the tumor as well as diminished osmotic pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform distribution of oxygen, solid tumor pressure and a broad-based collapse of the tumor lymphatics. We also find that the rate that IFF is fluxed into the lymphatics and host tissue is largely controlled by an elevated vascular hydraulic conductivity in the tumor. We discuss the implications of these results on microenvironmental transport barriers, and the tumor invasive and metastatic potential. Our results suggest the possibility of developing strategies of targeting tumor cells based on the cues in the interstitial fluid. PMID:23220211

Radiation tolerance of nanocrystalline ceramics: insights from Yttria Stabilized Zirconia.

PubMed

Dey, Sanchita; Drazin, John W; Wang, Yongqiang; Valdez, James A; Holesinger, Terry G; Uberuaga, Blas P; Castro, Ricardo H R

2015-01-13

Materials for applications in hostile environments, such as nuclear reactors or radioactive waste immobilization, require extremely high resistance to radiation damage, such as resistance to amorphization or volume swelling. Nanocrystalline materials have been reported to present exceptionally high radiation-tolerance to amorphization. In principle, grain boundaries that are prevalent in nanomaterials could act as sinks for point-defects, enhancing defect recombination. In this paper we present evidence for this mechanism in nanograined Yttria Stabilized Zirconia (YSZ), associated with the observation that the concentration of defects after irradiation using heavy ions (Kr(+), 400 keV) is inversely proportional to the grain size. HAADF images suggest the short migration distances in nanograined YSZ allow radiation induced interstitials to reach the grain boundaries on the irradiation time scale, leaving behind only vacancy clusters distributed within the grain. Because of the relatively low temperature of the irradiations and the fact that interstitials diffuse thermally more slowly than vacancies, this result indicates that the interstitials must reach the boundaries directly in the collision cascade, consistent with previous simulation results. Concomitant radiation-induced grain growth was observed which, as a consequence of the non-uniform implantation, caused cracking of the nano-samples induced by local stresses at the irradiated/non-irradiated interfaces.

Radiation Tolerance of Nanocrystalline Ceramics: Insights from Yttria Stabilized Zirconia

PubMed Central

Dey, Sanchita; Drazin, John W.; Wang, Yongqiang; Valdez, James A.; Holesinger, Terry G.; Uberuaga, Blas P.; Castro, Ricardo H. R.

2015-01-01

Materials for applications in hostile environments, such as nuclear reactors or radioactive waste immobilization, require extremely high resistance to radiation damage, such as resistance to amorphization or volume swelling. Nanocrystalline materials have been reported to present exceptionally high radiation-tolerance to amorphization. In principle, grain boundaries that are prevalent in nanomaterials could act as sinks for point-defects, enhancing defect recombination. In this paper we present evidence for this mechanism in nanograined Yttria Stabilized Zirconia (YSZ), associated with the observation that the concentration of defects after irradiation using heavy ions (Kr+, 400 keV) is inversely proportional to the grain size. HAADF images suggest the short migration distances in nanograined YSZ allow radiation induced interstitials to reach the grain boundaries on the irradiation time scale, leaving behind only vacancy clusters distributed within the grain. Because of the relatively low temperature of the irradiations and the fact that interstitials diffuse thermally more slowly than vacancies, this result indicates that the interstitials must reach the boundaries directly in the collision cascade, consistent with previous simulation results. Concomitant radiation-induced grain growth was observed which, as a consequence of the non-uniform implantation, caused cracking of the nano-samples induced by local stresses at the irradiated/non-irradiated interfaces. PMID:25582769

Radiation tolerance of nanocrystalline ceramics: Insights from yttria stabilized zirconia

DOE PAGES

Dey, Sanchita; Drazin, John W.; Wang, Yongqiang; ...

2015-01-13

Materials for applications in hostile environments, such as nuclear reactors or radioactive waste immobilization, require extremely high resistance to radiation damage, such as resistance to amorphization or volume swelling. Nanocrystalline materials have been reported to present exceptionally high radiation-tolerance to amorphization. In principle, grain boundaries that are prevalent in nanomaterials could act as sinks for point-defects, enhancing defect recombination. In this paper we present evidence for this mechanism in nanograined Yttria Stabilized Zirconia (YSZ), associated with the observation that the concentration of defects after irradiation using heavy ions (Kr⁺, 400 keV) is inversely proportional to the grain size. HAADF imagesmore » suggest the short migration distances in nanograined YSZ allow radiation induced interstitials to reach the grain boundaries on the irradiation time scale, leaving behind only vacancy clusters distributed within the grain. Because of the relatively low temperature of the irradiations and the fact that interstitials diffuse thermally more slowly than vacancies, this result indicates that the interstitials must reach the boundaries directly in the collision cascade, consistent with previous simulation results. Concomitant radiation-induced grain growth was observed which, as a consequence of the non-uniform implantation, caused cracking of the nano-samples induced by local stresses at the irradiated/non-irradiated interfaces.« less

Smoking-related interstitial fibrosis combined with pulmonary emphysema: computed tomography-pathologic correlative study using lobectomy specimens.

PubMed

Otani, Hideji; Tanaka, Tomonori; Murata, Kiyoshi; Fukuoka, Junya; Nitta, Norihisa; Nagatani, Yukihiro; Sonoda, Akinaga; Takahashi, Masashi

2016-01-01

To evaluate the incidence and pathologic correlation of thin-section computed tomography (TSCT) findings in smoking-related interstitial fibrosis (SRIF) with pulmonary emphysema. Our study included 172 consecutive patients who underwent TSCT and subsequent lobectomy. TSCT findings including clustered cysts with visible walls (CCVW) and ground-glass attenuation with/without reticulation (GGAR) were evaluated and compared in nonsmokers and smokers and among lung locations. TSCT findings, especially CCVW, were also compared with histological findings using lobectomy specimens. The incidence of CCVW and GGAR was significantly higher in smokers than in nonsmokers (34.1% and 40.7%, respectively, vs 2.0% and 12.2%). CCVW and GGAR were frequently found in the lower and peripheral zones. Histologically, CCVW corresponded more often with SRIF with emphysema than usual interstitial pneumonia (UIP, 63.3% vs 30%). CCVW of irregular size and shape were seen in 19 of 20 SRIF with emphysema and in seven of nine UIP-manifested areas with similar round cysts. A less-involved subpleural parenchyma was observed more frequently in SRIF with emphysema. SRIF with emphysema is a more frequent pathological finding than UIP in patients with CCVW on TSCT. The irregular size and shape of CCVW and a less-involved subpleural parenchyma may be a clue suggesting the presence of SRIF with emphysema.

Anorectal and Pelvic Pain

PubMed Central

Bharucha, Adil E.; Lee, Tae Hee

2016-01-01

Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the three most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first two conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacologic, behavioral, and physical therapy. Opioids should not be avoided, and surgery has a limited role, primarily in refractory interstitial cystitis. PMID:27712641

Modeling viscous dissipation during vocal fold contact: the influence of tissue viscosity and thickness with implications for hydration.

PubMed

Erath, Byron D; Zañartu, Matías; Peterson, Sean D

2017-06-01

The mechanics of vocal fold contact during phonation is known to play a crucial role in both normal and pathological speech production, though the underlying physics is not well understood. Herein, a viscoelastic model of the stresses during vocal fold contact is developed. This model assumes the cover to be a poroelastic structure wherein interstitial fluid translocates in response to mechanical squeezing. The maximum interstitial fluid pressure is found to generally increase with decreasing viscous dissipation and/or decreasing tissue elasticity. A global minimum in the total contact stress, comprising interstitial fluid pressure and elastic stress in the tissue, is observed over the studied dimensionless parameter range. Interestingly, physiologically reasonable estimates for the governing parameters fall within this global minimum region. The model is validated against prior experimental and computational work, wherein the predicted contact stress magnitude and impact duration agree well with published results. Lastly, observations of the potential relationship between vocal fold hydration and increased risk of tissue damage are discussed based upon model predictions of stress as functions of cover layer thickness and viscosity.

An integrated approach in the diagnosis of smoking-related interstitial lung diseases.

PubMed

Caminati, Antonella; Cavazza, Alberto; Sverzellati, Nicola; Harari, Sergio

2012-09-01

Cigarette smoke consists of several chemical compounds with a variety of effects in many organs. In the lung, apart being the main cause of chronic obstructive pulmonary disease, carcinoma and idiopathic spontaneous pneumothorax, tobacco smoke is associated with interstitial lung diseases (ILDs), including respiratory bronchiolitis-associated ILD (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans' cell histiocytosis (PLCH), idiopathic pulmonary fibrosis, acute eosinophilic pneumonia, ILD in rheumatoid arthritis and pulmonary haemorrhage in Goodpasture syndrome. This review will focus on the diseases with a stronger epidemiological association with tobacco smoke, namely RB-ILD, DIP and PLCH. Although the exact pathogenetic evidence linking smoking with these disorders is still not completely understood, there is growing evidence that tobacco smoke targets the terminal or respiratory bronchioles in these diseases, and the differences are reflective of the degree of severity of small airway and parenchymal reaction to the smoke exposure. Despite considerable clinical, radiological and histological overlap between RB-ILD, DIP and PLCH, it is useful to retain the separate classifications for prognostic and therapeutic implications.

A Patient with Non-Hodgkin Lymphoma and Nonspecific Interstitial Pneumonia during Ibrutinib Therapy.

PubMed

Jungmann, Sven; Ludwig, Wolf-Dieter; Schönfeld, Nicolas; Blum, Torsten-Gerriet; Großwendt, Claudia; Boch, Christian; Rehbock, Beate; Griff, Sergej; Schmittel, Alexander; Bauer, Torsten T

2017-01-01

We present a 74-year-old male with nonspecific interstitial pneumonia (NSIP) during treatment with ibrutinib for mantle cell lymphoma. Previously, the patient had received six cycles of bendamustine and rituximab and six cycles of R-CHOP, followed by rituximab maintenance therapy. Respiratory tract complications of ibrutinib other than infectious pneumonia have not been mentioned in larger trials, but individual case reports hinted to a possible association with the development of pneumonitis. In our patient, the onset of alveolitis that progressed towards NSIP together with the onset of ibrutinib treatment suggests causality. One week after ibrutinib was discontinued, nasal symptoms resolved first. A follow-up CT showed a reduction in the reticular hyperdensities and ground-glass opacities, suggestive of restitution of the lung disease. To our knowledge, this is the first case showing a strong link between ibrutinib and interstitial lung disease, strengthening a previous report on subacute pneumonitis. Our findings have clinical implications because pulmonary side effects were reversible at this early stage. We, therefore, suggest close monitoring for respiratory side effects in patients receiving ibrutinib.

Co-located hAT transposable element and 5S rDNA in an interstitial telomeric sequence suggest the formation of Robertsonian fusion in armored catfish.

PubMed

Glugoski, Larissa; Giuliano-Caetano, Lucia; Moreira-Filho, Orlando; Vicari, Marcelo R; Nogaroto, Viviane

2018-04-15

Co-located 5S rDNA genes and interstitial telomeric sites (ITS) revealed the involvement of multiple 5S rDNA clusters in chromosome rearrangements of Loricariidae. Interstitial (TTAGGG)n vestiges, in addition to telomeric sites, can coincide with locations of chromosomal rearrangements, and they are considered to be hotspots for chromosome breaks. This study aimed the molecular characterization of 5S rDNA in two Rineloricaria latirostris populations and examination of roles of 5S rDNA in breakpoint sites and its in situ localization. Rineloricaria latirostris from Brazil's Das Pedras river (2n = 46 chromosomes) presented five pairs identified using a 5S rDNA probe, in addition to a pair bearing a co-located ITS/5S rDNA. Rineloricaria latirostris from the Piumhi river (2n = 48 chromosomes) revealed two pairs containing 5S rDNA, without ITS. A 702-bp amplified sequence, using 5S rDNA primers, revealed an insertion of the hAT transposable element (TE), referred to as a degenerate 5S rDNA. Double-FISH (fluorescence in situ hybridization) demonstrated co-localization of 5S rDNA/degenerate 5S rDNA, 5S rDNA/hAT and ITS/5S rDNA from the Das Pedras river population. Piumhi river isolates possessed only 5S rDNA sites. We suggest that the degenerate 5S rDNA was generated by unequal crossing over, which was driven by invasion of hAT, establishing a breakpoint region susceptible to chromosome breakage, non-homologous recombination and Robertsonian (Rb) fusion. Furthermore, the presence of clusters of 5S rDNA at fusion points in other armored catfish species suggests its re-use and that these regions represent hotspots for evolutionary rearrangements within Loricariidae genomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Architecture of the human renal inner medulla and functional implications

PubMed Central

Wei, Guojun; Rosen, Seymour; Dantzler, William H.

2015-01-01

The architecture of the inner stripe of the outer medulla of the human kidney has long been known to exhibit distinctive configurations; however, inner medullary architecture remains poorly defined. Using immunohistochemistry with segment-specific antibodies for membrane fluid and solute transporters and other proteins, we identified a number of distinctive functional features of human inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop descending thin limbs (DTLs) lie alongside descending and ascending vasa recta (DVR, AVR) within vascular bundles. These vascular bundles are continuations of outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at the margins of coalescing collecting duct (CD) clusters, thereby forming two regions, the vascular bundle region and the CD cluster region. Although AQP1 and urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR, respectively, their expression declines with depth below the outer medulla. Transcellular water and urea fluxes likely decline in these segments at progressively deeper levels. Smooth muscle myosin heavy chain protein is also expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated capillaries abut CDs along their entire length, paralleling ascending thin limbs (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however, in humans this architecture rarely occurs. Thus INSs are relatively infrequent in the human inner medulla, unlike in the rodent where they are abundant. UT-B is expressed within the papillary epithelium of the lower inner medulla, indicating a transcellular pathway for urea across this epithelium. PMID:26290371

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhayal, Rajendra S.; Liao, Jian-Hong; Kahlal, Samia

An air- and moisture-stable nanoscale polyhydrido copper cluster [Cu 32(H) 20{S 2P(O i Pr) 2 } 12 ] (1 H) was synthesized and structurally characterized. The molecular structure of 1 H exhibits a hexacapped pseudo-rhombohedral core of 14 Cu atoms sandwiched between two nestlike triangular cupola fragments of (2x9) Cu atoms in an elongated triangular gyrobicupola polyhedron. The discrete Cu 32 cluster is stabilized by 12 dithiophosphate ligands and a record number of 20 hydride ligands, which were found by high-resolution neutron diffraction to exhibit tri-, tetra-, and pentacoordinated hydrides in capping and interstitial modes. We conclude that this resultmore » was further supported by a density functional theory investigation on the simplified model [Cu 32(H) 20(S 2PH 2) 12].« less

Role of perinuclear mitochondria in the spatiotemporal dynamics of spontaneous Ca2+ waves in interstitial cells of Cajal-like cells of the rabbit urethra

PubMed Central

Hashiatni, Hikaru; Lang, Richard J; Suzuki, Hikaru

2010-01-01

BACKGROUND AND PURPOSE Although spontaneous Ca2+ waves in interstitial cells of Cajal (ICC)-like cells (ICC-LCs) primarily arise from endoplasmic reticulum (ER) Ca2+ release, the interactions among mitochondrial Ca2+ buffering, cellular energetics and ER Ca2+ release in determining the spatiotemporal dynamics of intracellular Ca2+ remain to be elucidated. EXPERIMENTAL APPROACH Spontaneous Ca2+ transients in freshly isolated ICC-LCs of the rabbit urethra were visualized using fluo-4 Ca2+ imaging, while the intracellular distribution of mitochondria was viewed with MitoTracker Red. KEY RESULTS Spontaneous Ca2+ waves invariably originated from the perinuclear region where clusters of mitochondria surround the nucleus. Perinuclear Ca2+ dynamics were characterized by a gradual rise in basal Ca2+ that preceded each regenerative Ca2+ transient. Caffeine evoked oscillatory Ca2+ waves originating from anywhere within ICC-LCs. Ryanodine or cyclopiazonic acid prevented Ca2+ wave generation with a rise in basal Ca2+, and subsequent caffeine evoked a single rudimentary Ca2+ transient. Inhibition of glycolysis with 2-deoxy-glucose or carbonyl cyanide 3-chlorophenylhydrazone, a mitochondrial protonophore, increased basal Ca2+ and abolished Ca2+ waves. However, caffeine still induced oscillatory Ca2+ transients. Mitochondrial Ca2+ uptake inhibition with RU360 attenuated Ca2+ wave amplitudes, while mitochondrial Ca2+ efflux inhibition with CGP37157 suppressed the initial Ca2+ rise to reduce Ca2+ wave frequency. CONCLUSIONS AND IMPLICATIONS Perinuclear mitochondria in ICC-LCs play a dominant role in the spatial regulation of Ca2+ wave generation and may regulate ER Ca2+ release frequency by buffering Ca2+ within microdomains between both organelles. Glycolysis inhibition reduced mitochondrial Ca2+ buffering without critically disrupting ER function. Perinuclear mitochondria may function as sensors of intracellular metabolites. PMID:20880405

Long-time atomistic dynamics through a new self-adaptive accelerated molecular dynamics method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, N.; Yang, L.; Gao, F.

2017-02-27

A self-adaptive accelerated molecular dynamics method is developed to model infrequent atomic- scale events, especially those events that occur on a rugged free-energy surface. Key in the new development is the use of the total displacement of the system at a given temperature to construct a boost-potential, which is slowly increased to accelerate the dynamics. The temperature is slowly increased to accelerate the dynamics. By allowing the system to evolve from one steady-state con guration to another by overcoming the transition state, this self-evolving approach makes it possible to explore the coupled motion of species that migrate on vastly differentmore » time scales. The migrations of single vacancy (V) and small He-V clusters, and the growth of nano-sized He-V clusters in Fe for times in the order of seconds are studied by this new method. An interstitial- assisted mechanism is rst explored for the migration of a helium-rich He-V cluster, while a new two-component Ostwald ripening mechanism is suggested for He-V cluster growth.« less

AB INITIO calculation of the electromigration wind valence of interstitial hydrogen in f.c.c metals

NASA Astrophysics Data System (ADS)

van Ek, J.; Lodder, A.

1990-02-01

Calculated electromigration wind valences, obtained within a KKR-Green function description, are presented. It is shown that the electromigration wind valence of hydrogen along different migration paths in Cu, Ag and Pd can be calculated including charge transfer effects in the impurity cluster. A nice procedure for retrieving the scalar character of the wind valence in an f.c.c metal introduces an explanation for the isotope effect in the wind valence.

Clinical phenotypes and survival of pre-capillary pulmonary hypertension in systemic sclerosis.

PubMed

Launay, David; Montani, David; Hassoun, Paul M; Cottin, Vincent; Le Pavec, Jérôme; Clerson, Pierre; Sitbon, Olivier; Jaïs, Xavier; Savale, Laurent; Weatherald, Jason; Sobanski, Vincent; Mathai, Stephen C; Shafiq, Majid; Cordier, Jean-François; Hachulla, Eric; Simonneau, Gérald; Humbert, Marc

2018-01-01

Pre-capillary pulmonary hypertension (PH) in systemic sclerosis (SSc) is a heterogeneous condition with an overall bad prognosis. The objective of this study was to identify and characterize homogeneous phenotypes by a cluster analysis in SSc patients with PH. Patients were identified from two prospective cohorts from the US and France. Clinical, pulmonary function, high-resolution chest tomography, hemodynamic and survival data were extracted. We performed cluster analysis using the k-means method and compared survival between clusters using Cox regression analysis. Cluster analysis of 200 patients identified four homogenous phenotypes. Cluster C1 included patients with mild to moderate risk pulmonary arterial hypertension (PAH) with limited or no interstitial lung disease (ILD) and low DLCO with a 3-year survival of 81.5% (95% CI: 71.4-88.2). C2 had pre-capillary PH due to extensive ILD and worse 3-year survival compared to C1 (adjusted hazard ratio [HR] 3.14; 95% CI 1.66-5.94; p = 0.0004). C3 had severe PAH and a trend towards worse survival (HR 2.53; 95% CI 0.99-6.49; p = 0.052). Cluster C4 and C1 were similar with no difference in survival (HR 0.65; 95% CI 0.19-2.27, p = 0.507) but with a higher DLCO in C4. PH in SSc can be characterized into distinct clusters that differ in prognosis.

A study of the effect of helium concentration and displacement damage on the microstructure of helium ion irradiated tungsten

NASA Astrophysics Data System (ADS)

Harrison, R. W.; Greaves, G.; Hinks, J. A.; Donnelly, S. E.

2017-11-01

Transmission electron microscopy (TEM) with in-situ He ion irradiation has been used to examine the damage microstructure of W when varying the helium concentration to displacement damage ratio, irradiation temperature and total dose. Irradiations employed 15, 60 or 85 keV He ions, at temperatures between 500 and 1000 °C up to doses of ∼3.0 DPA. Once nucleated and grown to an observable size in the TEM, bubble diameter as a function of irradiation dose did not measurably increase at irradiation temperatures of 500 °C between 1.0 and 3.0 DPA; this is attributed to the low mobility of vacancies and He/vacancy complexes at these temperatures. Bubble diameter increased slightly for irradiation temperatures of 750 °C and rapidly increased when irradiated at 1000 °C. Dislocation loops were observed at irradiation temperatures of 500 and 750 °C and no loops were observed at 1000 °C. Burgers vectors of the dislocations were determined to be b = ±½<111> type only and both vacancy and interstitial loops were observed. The proportion of interstitial loops increased with He-appm/DPA ratio and this is attributed to the concomitant increase in bubble areal density, which reduces the vacancy flux for both the growth of vacancy-type loops and the annihilation of interstitial clusters.

Smoking-related interstitial fibrosis combined with pulmonary emphysema: computed tomography-pathologic correlative study using lobectomy specimens

PubMed Central

Otani, Hideji; Tanaka, Tomonori; Murata, Kiyoshi; Fukuoka, Junya; Nitta, Norihisa; Nagatani, Yukihiro; Sonoda, Akinaga; Takahashi, Masashi

2016-01-01

Purpose To evaluate the incidence and pathologic correlation of thin-section computed tomography (TSCT) findings in smoking-related interstitial fibrosis (SRIF) with pulmonary emphysema. Patients and methods Our study included 172 consecutive patients who underwent TSCT and subsequent lobectomy. TSCT findings including clustered cysts with visible walls (CCVW) and ground-glass attenuation with/without reticulation (GGAR) were evaluated and compared in nonsmokers and smokers and among lung locations. TSCT findings, especially CCVW, were also compared with histological findings using lobectomy specimens. Results The incidence of CCVW and GGAR was significantly higher in smokers than in nonsmokers (34.1% and 40.7%, respectively, vs 2.0% and 12.2%). CCVW and GGAR were frequently found in the lower and peripheral zones. Histologically, CCVW corresponded more often with SRIF with emphysema than usual interstitial pneumonia (UIP, 63.3% vs 30%). CCVW of irregular size and shape were seen in 19 of 20 SRIF with emphysema and in seven of nine UIP-manifested areas with similar round cysts. A less-involved subpleural parenchyma was observed more frequently in SRIF with emphysema. Conclusion SRIF with emphysema is a more frequent pathological finding than UIP in patients with CCVW on TSCT. The irregular size and shape of CCVW and a less-involved subpleural parenchyma may be a clue suggesting the presence of SRIF with emphysema. PMID:27445472

Rare variants in RTEL1 are associated with familial interstitial pneumonia.

PubMed

Cogan, Joy D; Kropski, Jonathan A; Zhao, Min; Mitchell, Daphne B; Rives, Lynette; Markin, Cheryl; Garnett, Errine T; Montgomery, Keri H; Mason, Wendi R; McKean, David F; Powers, Julia; Murphy, Elissa; Olson, Lana M; Choi, Leena; Cheng, Dong-Sheng; Blue, Elizabeth Marchani; Young, Lisa R; Lancaster, Lisa H; Steele, Mark P; Brown, Kevin K; Schwarz, Marvin I; Fingerlin, Tasha E; Schwartz, David A; Lawson, William E; Loyd, James E; Zhao, Zhongming; Phillips, John A; Blackwell, Timothy S

2015-03-15

Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families. To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis. Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds. We identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected carriers of these rare variants had short telomeres (<10% for age) in peripheral blood mononuclear cells and increased T-circle formation, suggesting impaired RTEL1 function. Rare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis.

Anorectal and Pelvic Pain.

PubMed

Bharucha, Adil E; Lee, Tae Hee

2016-10-01

Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the 3 most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first 2 conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacological, behavioral, and physical therapy. Opioids should be avoided, and surgical treatment has a limited role, primarily in refractory interstitial cystitis. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Crystal orientation effects on helium ion depth distributions and adatom formation processes in plasma-facing tungsten

DOE PAGES

Hammond, Karl D.; Wirth, Brian D.

2014-10-09

Here, we present atomistic simulations that show the effect of surface orientation on helium depth distributions and surface feature formation as a result of low-energy helium plasma exposure. We find a pronounced effect of surface orientation on the initial depth of implanted helium ions, as well as a difference in reflection and helium retention across different surface orientations. Our results indicate that single helium interstitials are sufficient to induce the formation of adatom/substitutional helium pairs under certain highly corrugated tungsten surfaces, such as {1 1 1}-orientations, leading to the formation of a relatively concentrated layer of immobile helium immediately belowmore » the surface. The energies involved for helium-induced adatom formation on {1 1 1} and {2 1 1} surfaces are exoergic for even a single adatom very close to the surface, while {0 0 1} and {0 1 1} surfaces require two or even three helium atoms in a cluster before a substitutional helium cluster and adatom will form with reasonable probability. This phenomenon results in much higher initial helium retention during helium plasma exposure to {1 1 1} and {2 1 1} tungsten surfaces than is observed for {0 0 1} or {0 1 1} surfaces and is much higher than can be attributed to differences in the initial depth distributions alone. Lastly, the layer thus formed may serve as nucleation sites for further bubble formation and growth or as a source of material embrittlement or fatigue, which may have implications for the formation of tungsten “fuzz” in plasma-facing divertors for magnetic-confinement nuclear fusion reactors and/or the lifetime of such divertors.« less

Architecture of the human renal inner medulla and functional implications.

PubMed

Wei, Guojun; Rosen, Seymour; Dantzler, William H; Pannabecker, Thomas L

2015-10-01

The architecture of the inner stripe of the outer medulla of the human kidney has long been known to exhibit distinctive configurations; however, inner medullary architecture remains poorly defined. Using immunohistochemistry with segment-specific antibodies for membrane fluid and solute transporters and other proteins, we identified a number of distinctive functional features of human inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop descending thin limbs (DTLs) lie alongside descending and ascending vasa recta (DVR, AVR) within vascular bundles. These vascular bundles are continuations of outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at the margins of coalescing collecting duct (CD) clusters, thereby forming two regions, the vascular bundle region and the CD cluster region. Although AQP1 and urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR, respectively, their expression declines with depth below the outer medulla. Transcellular water and urea fluxes likely decline in these segments at progressively deeper levels. Smooth muscle myosin heavy chain protein is also expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated capillaries abut CDs along their entire length, paralleling ascending thin limbs (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however, in humans this architecture rarely occurs. Thus INSs are relatively infrequent in the human inner medulla, unlike in the rodent where they are abundant. UT-B is expressed within the papillary epithelium of the lower inner medulla, indicating a transcellular pathway for urea across this epithelium. Copyright © 2015 the American Physiological Society.

New gas phase inorganic ion cluster species and their atmospheric implications

NASA Technical Reports Server (NTRS)

Maerk, T. D.; Peterson, K. I.; Castleman, A. W., Jr.

1980-01-01

Recent experimental laboratory observations, with high-pressure mass spectroscopy, have revealed the existence of previously unreported species involving water clustered to sodium dimer ions, and alkali metal hydroxides clustered to alkali metal ions. The important implications of these results concerning the existence of such species are here discussed, as well as how from a practical aspect they confirm the stability of certain cluster species proposed by Ferguson (1978) to explain masses recently detected at upper altitudes using mass spectrometric techniques.

Studies of Point Defects and Defect Interactions in Metals Using Perturbed Gamma Gamma Angular Correlations

NASA Astrophysics Data System (ADS)

Shropshire, Steven Leslie

Point defects in plastically deformed Au, Pt, and Ni were studied with atomic-scale sensitivity using the perturbed gamma-gamma angular correlations (PAC) technique by monitoring formation and transformation of complexes of vacancy defects with very dilute ^{111}In/ ^{111}Cd solute probes. Three topics were investigated: (1) Production of vacancy defects during plastic deformation of Au was investigated to differentiate models of defect production. Concentrations of mono-, di-, and tri-vacancy species were measured in Au, and the ratio of mono- to di-vacancies was found to be independent of the amount of deformation. Results indicate that point defects are produced in correlated lattice locations, such as in "strings", as a consequence of dislocation interactions and not at random locations. (2) Hydrogen interactions with vacancy-solute complexes were studied in Pt. From thermal detrapping experiments, binding of hydrogen in complexes with mono-, di- and tri-vacancies was determined using a model for hydrogen diffusing in a medium with traps, with enthalpies all measured in the narrow range 0.23-0.28 eV, proving that the binding is insensitive to the precise structure of small vacancy clusters. Nuclear relaxation of the probe in a trivacancy complex in Pt was studied as a function of temperature, from which an activation energy of 0.34 eV was measured. This value is inconsistent with relaxation caused by diffusion or trapping of hydrogen, but explainable by dynamical hopping of the PAC probe atom in a cage of vacancies. (3) By observing transformations between vacancy-solute complexes induced by annihilation reactions, it was demonstrated that interstitials are produced during plastic deformation. The evolution of concentrations of the different vacancy complexes under an interstitial flux was measured and analyzed using a kinetic-rate model, from which interstitial capture cross-sections for the different vacancy complexes and the relative quantities of interstitial species in the flux were determined. Deformation of Au was found to produce only mono- and di-interstitial fluxes in a 1:2 ratio. Cross-sections increased rapidly with the number of vacancies, which is attributed to the amount of relaxation of lattice strains around solute-vacancy complexes.

Spatial Clustering of Aedes aegypti Related to Breeding Container Characteristics in Coastal Ecuador: Implications for Dengue Control

PubMed Central

Schafrick, Nathaniel H.; Milbrath, Meghan O.; Berrocal, Veronica J.; Wilson, Mark L.; Eisenberg, Joseph N. S.

2013-01-01

Mosquito management within households remains central to the control of dengue virus transmission. An important factor in these management decisions is the spatial clustering of Aedes aegypti. We measured spatial clustering of Ae. aegypti in the town of Borbón, Ecuador and assessed what characteristics of breeding containers influenced the clustering. We used logistic regression to assess the spatial extent of that clustering. We found strong evidence for juvenile mosquito clustering within 20 m and for adult mosquito clustering within 10 m, and stronger clustering associations for containers ≥ 40 L than those < 40 L. Aedes aegypti clusters persisted after adjusting for various container characteristics, suggesting that patterns are likely attributable to short dispersal distances rather than shared characteristics of containers in cluster areas. These findings have implications for targeting Ae. aegypti control efforts. PMID:24002483

Susceptibility of interstitial continuous glucose monitor performance to sleeping position.

PubMed

Mensh, Brett D; Wisniewski, Natalie A; Neil, Brian M; Burnett, Daniel R

2013-07-01

Developing a round-the-clock artificial pancreas requires accurate and stable continuous glucose monitoring. The most widely used continuous glucose monitors (CGMs) are percutaneous, with the sensor residing in the interstitial space. Inaccuracies in percutaneous CGM readings during periods of lying on the devices (e.g., in various sleeping positions) have been anecdotally reported but not systematically studied. In order to assess the impact of sleep and sleep position on CGM performance, we conducted a study in human subjects in which we measured the variability of interstitial CGM data at night as a function of sleeping position. Commercially available sensors were placed for 4 days in the abdominal subcutaneous tissue in healthy, nondiabetic volunteers (four sensors per person, two per side). Nocturnal sleeping position was determined from video recordings and correlated to sensor data. We observed that, although the median of the four sensor readings was typically 70-110 mg/dl during sleep, individual sensors intermittently exhibited aberrant glucose readings (>25 mg/dl away from median) and that these aberrant readings were strongly correlated with subjects lying on the sensors. We expected and observed that most of these aberrant sleep-position-related CGM readings were sudden decreases in reported glucose values, presumably due to local blood-flow decreases caused by tissue compression. Curiously, in rare cases, the aberrant CGM readings were elevated values. These findings highlight limitations in our understanding of interstitial fluid physiology in the subcutaneous space and have significant implications for the utilization of sensors in the construction of an artificial pancreas. © 2013 Diabetes Technology Society.

Analysis of pulmonary sounds for the diagnosis of interstitial lung diseases secondary to rheumatoid arthritis.

PubMed

Pancaldi, Fabrizio; Sebastiani, Marco; Cassone, Giulia; Luppi, Fabrizio; Cerri, Stefania; Della Casa, Giovanni; Manfredi, Andreina

2018-05-01

The diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis is fundamental to improving their survival rate. In particular, the average survival time of patients affected by rheumatoid arthritis with pulmonary implications is approximately 3 years. The gold standard for confirming the diagnosis of this disease is computer tomography. However, it is very difficult to raise diagnosis suspicion because the symptoms of the disease are extremely common in elderly people. The detection of the so-called velcro crackle in lung sounds can effectively raise the suspicion of an interstitial disease and speed up diagnosis. However, this task largely relies on the experience of physicians and has not yet been standardized in clinical practice. The diagnosis of interstitial lung diseases based on thorax auscultation still represents an underexplored field in the study of rheumatoid arthritis. In this study, we investigate the problem of the automatic detection of velcro crackle in lung sounds. In practice, the patient is auscultated using a digital stethoscope and the lung sounds are saved to a file. The acquired digital data are then analysed using a suitably developed algorithm. In particular, the proposed solution relies on the empirical observation that the audio bandwidth associated with velcro crackle is larger than that associated with healthy breath sounds. Experimental results from a database of 70 patients affected by rheumatoid arthritis demonstrate that the developed tool can outperform specialized physicians in terms of diagnosing pulmonary disorders. The overall accuracy of the proposed solution is 90.0%, with negative and positive predictive values of 95.0% and 83.3%, respectively, whereas the reliability of physician diagnosis is in the range of 60-70%. The devised algorithm represents an enabling technology for a novel approach to the diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future.

PubMed

Plog, Benjamin A; Nedergaard, Maiken

2018-01-24

The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here, we review the role of the glymphatic pathway in CNS physiology, the factors known to regulate glymphatic flow, and the pathologic processes in which a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, are also discussed.

The glymphatic system in CNS health and disease: past, present and future

PubMed Central

Plog, Benjamin A.; Nedergaard, Maiken

2018-01-01

The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudo-lymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here we review the role of the glymphatic pathway in CNS physiology, factors known to regulate glymphatic flow, and pathologic processes where a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, will also be discussed. PMID:29195051

First-principles calculations of niobium hydride formation in superconducting radio-frequency cavities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ford, Denise C.; Cooley, Lance D.; Seidman, David N.

Niobium hydride is suspected to be a major contributor to degradation of the quality factor of niobium superconducting radio-frequency (SRF) cavities. In this study, we connect the fundamental properties of hydrogen in niobium to SRF cavity performance and processing. We modeled several of the niobium hydride phases relevant to SRF cavities and present their thermodynamic, electronic, and geometric properties determined from calculations based on density-functional theory. We find that the absorption of hydrogen from the gas phase into niobium is exothermic and hydrogen becomes somewhat anionic. The absorption of hydrogen by niobium lattice vacancies is strongly preferred over absorption intomore » interstitial sites. A single vacancy can accommodate six hydrogen atoms in the symmetrically equivalent lowest-energy sites and additional hydrogen in the nearby interstitial sites affected by the strain field: this indicates that a vacancy can serve as a nucleation center for hydride phase formation. Small hydride precipitates may then occur near lattice vacancies upon cooling. Vacancy clusters and extended defects should also be enriched in hydrogen, potentially resulting in extended hydride phase regions upon cooling. We also assess the phase changes in the niobium-hydrogen system based on charge transfer between niobium and hydrogen, the strain field associated with interstitial hydrogen, and the geometry of the hydride phases. The results of this study stress the importance of not only the hydrogen content in niobium, but also the recovery state of niobium for the performance of SRF cavities.« less

An improved interatomic potential for xenon in UO2: a combined density functional theory/genetic algorithm approach.

PubMed

Thompson, Alexander E; Meredig, Bryce; Wolverton, C

2014-03-12

We have created an improved xenon interatomic potential for use with existing UO2 potentials. This potential was fit to density functional theory calculations with the Hubbard U correction (DFT + U) using a genetic algorithm approach called iterative potential refinement (IPR). We examine the defect energetics of the IPR-fitted xenon interatomic potential as well as other, previously published xenon potentials. We compare these potentials to DFT + U derived energetics for a series of xenon defects in a variety of incorporation sites (large, intermediate, and small vacant sites). We find the existing xenon potentials overestimate the energy needed to add a xenon atom to a wide set of defect sites representing a range of incorporation sites, including failing to correctly rank the energetics of the small incorporation site defects (xenon in an interstitial and xenon in a uranium site neighboring uranium in an interstitial). These failures are due to problematic descriptions of Xe-O and/or Xe-U interactions of the previous xenon potentials. These failures are corrected by our newly created xenon potential: our IPR-generated potential gives good agreement with DFT + U calculations to which it was not fitted, such as xenon in an interstitial (small incorporation site) and xenon in a double Schottky defect cluster (large incorporation site). Finally, we note that IPR is very flexible and can be applied to a wide variety of potential forms and materials systems, including metals and EAM potentials.

Rare Variants in RTEL1 Are Associated with Familial Interstitial Pneumonia

PubMed Central

Cogan, Joy D.; Zhao, Min; Mitchell, Daphne B.; Rives, Lynette; Markin, Cheryl; Garnett, Errine T.; Montgomery, Keri H.; Mason, Wendi R.; McKean, David F.; Powers, Julia; Murphy, Elissa; Olson, Lana M.; Choi, Leena; Cheng, Dong-Sheng; Blue, Elizabeth Marchani; Young, Lisa R.; Lancaster, Lisa H.; Steele, Mark P.; Brown, Kevin K.; Schwarz, Marvin I.; Fingerlin, Tasha E.; Schwartz, David A.; Lawson, William E.; Loyd, James E.; Zhao, Zhongming; Phillips, John A.; Blackwell, Timothy S.

2015-01-01

Rationale: Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families. Objectives: To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis. Methods: Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds. Measurements and Main Results: We identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected carriers of these rare variants had short telomeres (<10% for age) in peripheral blood mononuclear cells and increased T-circle formation, suggesting impaired RTEL1 function. Conclusions: Rare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis. PMID:25607374

Defect interactions with stepped CeO₂/SrTiO₃ interfaces: implications for radiation damage evolution and fast ion conduction.

PubMed

Dholabhai, Pratik P; Aguiar, Jeffery A; Misra, Amit; Uberuaga, Blas P

2014-05-21

Due to reduced dimensions and increased interfacial content, nanocomposite oxides offer improved functionalities in a wide variety of advanced technological applications, including their potential use as radiation tolerant materials. To better understand the role of interface structures in influencing the radiation damage tolerance of oxides, we have conducted atomistic calculations to elucidate the behavior of radiation-induced point defects (vacancies and interstitials) at interface steps in a model CeO2/SrTiO3 system. We find that atomic-scale steps at the interface have substantial influence on the defect behavior, which ultimately dictate the material performance in hostile irradiation environments. Distinctive steps react dissimilarly to cation and anion defects, effectively becoming biased sinks for different types of defects. Steps also attract cation interstitials, leaving behind an excess of immobile vacancies. Further, defects introduce significant structural and chemical distortions primarily at the steps. These two factors are plausible origins for the enhanced amorphization at steps seen in our recent experiments. The present work indicates that comprehensive examination of the interaction of radiation-induced point defects with the atomic-scale topology and defect structure of heterointerfaces is essential to evaluate the radiation tolerance of nanocomposites. Finally, our results have implications for other applications, such as fast ion conduction.

Thermal desorption behavior of helium in aged titanium tritide films

NASA Astrophysics Data System (ADS)

Cheng, G. J.; Shi, L. Q.; Zhou, X. S.; Liang, J. H.; Wang, W. D.; Long, X. G.; Yang, B. F.; Peng, S. M.

2015-11-01

The desorption behavior of helium in TiT(1.5∼1.8)-x3Hex film samples (x = 0.0022-0.22) was investigated by thermal desorption technique in vacuum condition in this paper. The thermal helium desorption spectrometry (THDS) of aging titanium tritide films prepared by electron beam evaporation revealed that, depending on the decayed 3He concentration in the samples, there are more than four states of helium existing in the films. The divided four zones in THDS based on helium states represent respectively: (1) the mobile single helium atoms with low activation energy in all aging samples resulted from the interstitial sites or dissociated from interstitial clusters, loops and dislocations, (2) helium bubbles inside the grain lattices, (3) helium bubbles in the grain boundaries and interconnected networks of dislocations in the helium concentration of 3Hegen/Ti > 0.0094, and (4) helium bubbles near or linked to the film surface by interconnected channel for later aging stage with 3Hegen/Ti > 0.18. The proportion of helium desorption in each zone was estimated, and dissociated energies of helium for different trapping states were given.

Detection of one-dimensional migration of single self-interstitial atoms in tungsten using high-voltage electron microscopy

PubMed Central

Amino, T.; Arakawa, K.; Mori, H.

2016-01-01

The dynamic behaviour of atomic-size disarrangements of atoms—point defects (self-interstitial atoms (SIAs) and vacancies)—often governs the macroscopic properties of crystalline materials. However, the dynamics of SIAs have not been fully uncovered because of their rapid migration. Using a combination of high-voltage transmission electron microscopy and exhaustive kinetic Monte Carlo simulations, we determine the dynamics of the rapidly migrating SIAs from the formation process of the nanoscale SIA clusters in tungsten as a typical body-centred cubic (BCC) structure metal under the constant-rate production of both types of point defects with high-energy electron irradiation, which must reflect the dynamics of individual SIAs. We reveal that the migration dimension of SIAs is not three-dimensional (3D) but one-dimensional (1D). This result overturns the long-standing and well-accepted view of SIAs in BCC metals and supports recent results obtained by ab-initio simulations. The SIA dynamics clarified here will be one of the key factors to accurately predict the lifetimes of nuclear fission and fusion materials. PMID:27185352

Displacement damage and predicted non-ionizing energy loss in GaAs

NASA Astrophysics Data System (ADS)

Gao, Fei; Chen, Nanjun; Hernandez-Rivera, Efrain; Huang, Danhong; LeVan, Paul D.

2017-03-01

Large-scale molecular dynamics (MD) simulations, along with bond-order interatomic potentials, have been applied to study the defect production for lattice atom recoil energies from 500 eV to 20 keV in gallium arsenide (GaAs). At low energies, the most surviving defects are single interstitials and vacancies, and only 20% of the interstitial population is contained in clusters. However, a direct-impact amorphization in GaAs occurs with a high degree of probability during the cascade lifetime for Ga PKAs (primary knock-on atoms) with energies larger than 2 keV. The results reveal a non-linear defect production that increases with the PKA energy. The damage density within a cascade core is evaluated, and used to develop a model that describes a new energy partition function. Based on the MD results, we have developed a model to determine the non-ionizing energy loss (NIEL) in GaAs, which can be used to predict the displacement damage degradation induced by space radiation on electronic components. The calculated NIEL predictions are compared with the available data, thus validating the NIEL model developed in this study.

Raman spectroscopic studies of defect structures and phase transition in hyper-stoichiometric UO(2+x).

PubMed

He, Heming; Shoesmith, David

2010-07-28

A method to determine the defect structures in hyper-stoichiometric UO(2+x) using a combination of XRD and Raman spectroscopy has been developed. A sequence of phase transitions, from cubic to tetragonal symmetry, occurs with increasing degree of non-stoichiometry. This sequence proceeds from a cubic phase through an intermediate t''-type tetragonal (axial ratio c/a = 1) phase to a final t-type tetragonal (c/a not = 1) phase. Four distinct structural defect regions can be identified in the stoichiometry range, UO(2) to U(3)O(7): (i) a random point defect structure (x (in UO(2+x)) < or = 0.05); (ii) a non-stoichiometry region (0.05 < or = x < or = 0.15) over which point defects are gradually eliminated and replaced by the Willis 2:2:2 cluster; (iii) a mixture of Willis and cuboctahedral clusters (0.15 < or = x < or = 0.23); (iv) the cuboctahedral cluster (x > or = 0.23). The geometry and steric arrangement of these defects is primarily determined by the concentration of the excess-oxygen interstitials.

Advances in the treatment of rheumatic interstitial lung disease.

PubMed

Vassallo, Robert; Thomas, Charles F

2004-05-01

Interstitial lung disease frequently complicates the rheumatic diseases. The purpose of this review is to outline recent advances and current concepts regarding the management of these interstitial lung diseases. Several histologic lesions cause interstitial lung disease in rheumatic diseases, including nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, lymphocytic interstitial pneumonia, desquamative interstitial pneumonia, and acute interstitial pneumonia. Although the relative frequency of occurrence of these histopathologic lesions is not definitively established, it seems that nonspecific interstitial pneumonia accounts for a large proportion of rheumatic disease-associated interstitial lung diseases. Although usual interstitial pneumonia generally responds poorly to corticosteroid therapy, other forms of interstitial pneumonia are often steroid responsive and have a more favorable long-term prognosis. Pulmonary hypertension is increasingly recognized as a complication of these interstitial lung diseases. Treatment of pulmonary hypertension in these patients provides clinical benefit and may suppress pulmonary inflammation and fibrosis. Lung transplantation is a treatment option for selected patients with severe pulmonary involvement and limited life expectancy. Interstitial lung disease is common in the rheumatic diseases, may be caused by a variety of lesions that respond differently to treatment, and may lead to the development of pulmonary hypertension. Whether the prognosis of interstitial lung disease associated with rheumatic disease is similar to that associated with the idiopathic interstitial pneumonias is not known. Treatment of these interstitial lung diseases should take into account the specific histologic lesion, the activity of the underlying rheumatic disease, and associated pulmonary hypertension, if present. The diagnosis of a rheumatic disease is no longer an absolute contraindication to lung transplantation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Chenyang; Niu, Liangliang; Chen, Nanjun

A grand challenge in material science is to understand the correlation between intrinsic properties and defect dynamics. Radiation tolerant materials are in great demand for safe operation and advancement of nuclear and aerospace systems. Unlike traditional approaches that rely on microstructural and nanoscale features to mitigate radiation damage, this study demonstrates enhancement of radiation tolerance with the suppression of void formation by two orders magnitude at elevated temperatures in equiatomic single-phase concentrated solid solution alloys, and more importantly, reveals its controlling mechanism through a detailed analysis of the depth distribution of defect clusters and an atomistic computer simulation. The enhancedmore » swelling resistance is attributed to the tailored interstitial defect cluster motion in the alloys from a long-range one-dimensional mode to a short-range three-dimensional mode, which leads to enhanced point defect recombination. Finally, the results suggest design criteria for next generation radiation tolerant structural alloys.« less

[Cu 32(H) 20{S 2P(O i Pr) 2 } 12 ]: The Largest Number of Hydrides Recorded in a Molecular Nanocluster by Neutron Diffraction

DOE PAGES

Dhayal, Rajendra S.; Liao, Jian-Hong; Kahlal, Samia; ...

2015-04-20

An air- and moisture-stable nanoscale polyhydrido copper cluster [Cu 32(H) 20{S 2P(O i Pr) 2 } 12 ] (1 H) was synthesized and structurally characterized. The molecular structure of 1 H exhibits a hexacapped pseudo-rhombohedral core of 14 Cu atoms sandwiched between two nestlike triangular cupola fragments of (2x9) Cu atoms in an elongated triangular gyrobicupola polyhedron. The discrete Cu 32 cluster is stabilized by 12 dithiophosphate ligands and a record number of 20 hydride ligands, which were found by high-resolution neutron diffraction to exhibit tri-, tetra-, and pentacoordinated hydrides in capping and interstitial modes. We conclude that this resultmore » was further supported by a density functional theory investigation on the simplified model [Cu 32(H) 20(S 2PH 2) 12].« less

The effect of primary recoil spectrum on radiation induced segregation in nickel-silicon alloys

NASA Astrophysics Data System (ADS)

Averback, R. S.; Rehn, L. E.; Wagner, W.; Ehrhart, P.

1983-08-01

Segregation of silicon to the surface of Ni-12.7 at% Si alloys during 2.0-MeV He and 3.25-MeV Kr irradiations was measured using Rutherford backscattering spectrometry. For equal calculated defect production rates the Kr irradiation was < 3 % as efficient as the He irradiation for promoting segregation in the temperature range, 450 °C-580 °C. It was further observed that Kr preirradiation of specimens dramatically reduced segregation during subsequent He irradiation. A model for cascade annealing in Ni-Si alloys is presented which qualitatively explains the segregation results. The model assumes that small interstitial-atom-clusters form in individual cascades and that these clusters become trapped at silicon solute atoms. The vacancy thereby becomes the more mobile defect. The model should also have relevance for the observation that void swelling in nickel is suppressed by the addition of silicon solute.

Enhancing radiation tolerance by controlling defect mobility and migration pathways in multicomponent single-phase alloys

NASA Astrophysics Data System (ADS)

Lu, Chenyang; Niu, Liangliang; Chen, Nanjun; Jin, Ke; Yang, Taini; Xiu, Pengyuan; Zhang, Yanwen; Gao, Fei; Bei, Hongbin; Shi, Shi; He, Mo-Rigen; Robertson, Ian M.; Weber, William J.; Wang, Lumin

2016-12-01

A grand challenge in material science is to understand the correlation between intrinsic properties and defect dynamics. Radiation tolerant materials are in great demand for safe operation and advancement of nuclear and aerospace systems. Unlike traditional approaches that rely on microstructural and nanoscale features to mitigate radiation damage, this study demonstrates enhancement of radiation tolerance with the suppression of void formation by two orders magnitude at elevated temperatures in equiatomic single-phase concentrated solid solution alloys, and more importantly, reveals its controlling mechanism through a detailed analysis of the depth distribution of defect clusters and an atomistic computer simulation. The enhanced swelling resistance is attributed to the tailored interstitial defect cluster motion in the alloys from a long-range one-dimensional mode to a short-range three-dimensional mode, which leads to enhanced point defect recombination. The results suggest design criteria for next generation radiation tolerant structural alloys.

Atomic-scale investigation of point defects and hydrogen-solute atmospheres on the edge dislocation mobility in alpha iron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhatia, M. A.; Solanki, K. N., E-mail: kiran.solanki@asu.edu; Groh, S.

2014-08-14

In this study, we present atomistic mechanisms of 1/2 [111](11{sup ¯}0) edge dislocation interactions with point defects (hydrogen and vacancies) and hydrogen solute atmospheres in body centered cubic (bcc) iron. In metals such as iron, increases in hydrogen concentration can increase dislocation mobility and/or cleavage-type decohesion. Here, we first investigate the dislocation mobility in the presence of various point defects, i.e., change in the frictional stress as the edge dislocation interacts with (a) vacancy, (b) substitutional hydrogen, (c) one substitutional and one interstitial hydrogen, (d) interstitial hydrogen, (e) vacancy and interstitial hydrogen, and (f) two interstitial hydrogen. Second, we examinemore » the role of a hydrogen-solute atmosphere on the rate of local dislocation velocity. The edge dislocation simulation with a vacancy in the compression side of the dislocation and an interstitial hydrogen atom at the tension side exhibit the strongest mechanical response, suggesting a higher potential barrier and hence, the higher frictional stress (i.e., ∼83% higher than the pure iron Peierls stress). In the case of a dislocation interacting with a vacancy on the compressive side, the vacancy binds with the edge dislocation, resulting in an increase in the friction stress of about 28% when compared with the Peierls stress of an edge dislocation in pure iron. Furthermore, as the applied strain increases, the vacancy migrates through a dislocation transportation mechanism by attaining a velocity of the same order as the dislocation velocity. For the case of the edge dislocation interacting with interstitial hydrogen on the tension side, the hydrogen atom jumps through one layer perpendicular to the glide plane during the pinning-unpinning process. Finally, our simulation of dislocation interactions with hydrogen show first an increase in the local dislocation velocity followed by a pinning of the dislocation core in the atmosphere, resulting in resistance to dislocation motion as the dislocation moves though the hydrogen-solute atmospheres. With this systematic, atomistic study of the edge dislocation with various point defects, we show significant increase in obstacle strengths in addition to an increase in the local dislocation velocity during interaction with solute atmospheres. The results have implications for constitutive development and modeling of the hydrogen effect on dislocation mobility and deformation in metals.« less

Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT

ClinicalTrials.gov

2018-06-08

Pulmonary Arterial Hypertension; Pulmonary Hypertension; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Respiratory Bronchiolitis Associated Interstitial Lung Disease; Desquamative Interstitial Pneumonia; Cryptogenic Organizing Pneumonia; Acute Interstitial Pneumonitis; Idiopathic Lymphoid Interstitial Pneumonia; Idiopathic Pleuroparenchymal Fibroelastosis

Inhibition of p38 MAPK attenuates renal atrophy and fibrosis in a murine renal artery stenosis model.

PubMed

Wang, Diping; Warner, Gina M; Yin, Ping; Knudsen, Bruce E; Cheng, Jingfei; Butters, Kim A; Lien, Karen R; Gray, Catherine E; Garovic, Vesna D; Lerman, Lilach O; Textor, Stephen C; Nath, Karl A; Simari, Robert D; Grande, Joseph P

2013-04-01

Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-β-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.

Serum metalloproteinases 1 and 7 in the diagnosis of idiopathic pulmonary fibrosis and other interstitial pneumonias.

PubMed

Morais, António; Beltrão, Marília; Sokhatska, Oksana; Costa, Diogo; Melo, Natalia; Mota, Patricia; Marques, Agostinho; Delgado, Luís

2015-08-01

Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) has important therapeutic and prognostic implications and would be greatly aided by reliable diagnostic biomarkers as IPF has sometimes overlapping features with other interstitial lung diseases (ILD). To explore the value of serum metalloproteinases (MMP) 1 and 7 levels in the differential diagnosis of IPF with other ILD. MMP-1/7 serum levels were measured using Luminex xMAP technology in 139 patients- 47 IPF, 36 non-IPF Usual Interstitial Pneumonia (UIP), 14 idiopathic Nonspecific Interstitial Pneumonia (iNSIP), 29 secondary NSIP (secNSIP), 13 stage IV sarcoidosis- and 20 healthy controls, and compared using the Mann-Whitney U test. MMP-1 was significantly higher in IPF than non-IPF UIP (P = .042) and sarcoidosis (P = .027). MMP-7 was significantly higher in IPF than controls (P < .001), non-IPF UIP (P = .003), secNSIP (P < .001), and sarcoidosis (P < .001). The Area Under the Curve for IPF versus other ILD was 0.63 (95%CI, 0.53-0.73) for MMP-1, 0.73 (95%CI, 0.65-0.81) for MMP-7, and 0.74 (95%CI, 0.66-0.82) for MMP-1/MMP-7 combined. Sensitivity and specificity for MMP-7 cutoff = 3.91 ng/mL was 72.3% and 66.3%, respectively, Positive Predictive Values = 52.3% and Negative Predictive Values = 82.4%. MMP-1 and particularly MMP-7 serum levels were significantly higher in IPF than in non-IPF UIP, the main entity in differential diagnosis. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF diagnosis needs to be considered and further explored. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review

PubMed Central

Iqbal, Kundan; Kelly, Clive

2015-01-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 0.5–1% of the worldwide population. Whilst predominantly causing chronic pain and inflammation in synovial joints, it is also associated with significant extra-articular manifestations in a large proportion of patients. Among the various pulmonary manifestations, interstitial lung disease (ILD), a progressive fibrotic disease of the lung parenchyma, is the commonest and most important, contributing significantly to increased morbidity and mortality. The most frequent patterns of RA-associated ILD (RA-ILD) are usual interstitial pneumonia and nonspecific interstitial pneumonia. New insights during the past several years have highlighted the epidemiological impact of RA-ILD and have begun to identify factors contributing to its pathogenesis. Risk factors include smoking, male sex, human leukocyte antigen haplotype, rheumatoid factor and anticyclic citrullinated protein antibodies (ACPAs). Combined with clinical information, chest examination and pulmonary function testing, high-resolution computed tomography of the chest forms the basis of investigation and allows assessment of subtype and disease extent. The management of RA-ILD is a challenge. Several therapeutic agents have been suggested in the literature but as yet no large randomized controlled trials have been undertaken to guide clinical management. Therapy is further complicated by commonly prescribed drugs of proven articular benefit such as methotrexate, leflunomide (LEF) and anti-tumour necrosis factor α agents having been implicated in both ex novo occurrence and acceleration of existing ILD. Agents that offer promise include immunomodulators such as mycophenolate and rituximab as well as newly studied antifibrotic agents. In this review, we discuss the current literature to evaluate recommendations for the management of RA-ILD and discuss key gaps in our knowledge of this important disease. PMID:26622326

Photoinduced Disaggregation of TiO2 Nanoparticles Enables Transdermal Penetration

PubMed Central

Bennett, Samuel W.; Zhou, Dongxu; Mielke, Randall; Keller, Arturo A.

2012-01-01

Under many aqueous conditions, metal oxide nanoparticles attract other nanoparticles and grow into fractal aggregates as the result of a balance between electrostatic and Van Der Waals interactions. Although particle coagulation has been studied for over a century, the effect of light on the state of aggregation is not well understood. Since nanoparticle mobility and toxicity have been shown to be a function of aggregate size, and generally increase as size decreases, photo-induced disaggregation may have significant effects. We show that ambient light and other light sources can partially disaggregate nanoparticles from the aggregates and increase the dermal transport of nanoparticles, such that small nanoparticle clusters can readily diffuse into and through the dermal profile, likely via the interstitial spaces. The discovery of photoinduced disaggregation presents a new phenomenon that has not been previously reported or considered in coagulation theory or transdermal toxicological paradigms. Our results show that after just a few minutes of light, the hydrodynamic diameter of TiO2 aggregates is reduced from ∼280 nm to ∼230 nm. We exposed pigskin to the nanoparticle suspension and found 200 mg kg−1 of TiO2 for skin that was exposed to nanoparticles in the presence of natural sunlight and only 75 mg kg−1 for skin exposed to dark conditions, indicating the influence of light on NP penetration. These results suggest that photoinduced disaggregation may have important health implications. PMID:23155401

Molecular dynamics simulations of the diffusion and coalescence of helium in tungsten

NASA Astrophysics Data System (ADS)

Zhou, Y. L.; Wang, J.; Hou, Q.; Deng, A. H.

2014-03-01

Molecular dynamics (MD) simulations are performed on the diffusion and coalescence of helium in tungsten. A new method for determining the effective capture radii (ECRs) and the dissociation energies of helium-related defects is proposed in this work. It is observed that the ECR of an interstitial helium atom trapping helium interstitials (denoted as He-Hen, n = 1-3) decreases with increasing temperature, except for He-He2 at T < 400 K. The traditional view that the ECR is approximately equal to the lattice constant, which has been widely used in kinetic Monte Carlo (KMC) and rate theory (RT) models, is only valid in some cases. However, the ECR between an interstitial helium atom and a substitutional helium atom (denoted as He-HeV) always approximates the third nearest-neighbor tetrahedral positions of the HeV. The diffusion coefficients Dn for helium clusters are also investigated. He2 migrates more quickly than a single He atom does at T < 400 K, whereas the diffusion path of He2 changes at higher temperatures. Another counterintuitive observation is that D5 > D3 > D4 at T < 500 K, which can be attributed to the disordered structure of He5. The Arrhenius relation describes the diffusion of Hen well in the temperature range from 300 K to 550 K, whereas the diffusion is not a standard thermally activated process at higher temperatures. Taken together, these results help elucidate the initial stage of helium bubble formation in tungsten as well as the requirements of long-term evolution methods such as KMC or RT models.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohori, N.P.; Sciurba, F.C.; Owens, G.R.

We report four cases of giant-cell interstitial pneumonia that occurred in association with exposure to hard metals. All patients presented with chronic interstitial lung disease and had open-lung biopsies that revealed marked interstitial fibrosis, cellular interstitial infiltrates, and prominent intraalveolar macrophages as well as giant cells displaying cellular cannibalism. We also review the literature to determine the sensitivity and specificity of giant-cell interstitial pneumonia for hard-metal pneumoconiosis. Although hard-metal pneumoconiosis may take the form of usual interstitial pneumonia, desquamative interstitial pneumonia, and giant-cell interstitial pneumonia, the finding of giant-cell interstitial pneumonia is almost pathognomonic of hard-metal disease and should provokemore » an investigation of occupational exposure. 25 references.« less

Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

PubMed

Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

2015-01-01

The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

The local pathology of interstitial edema: surface tension increases hydration potential in heat-damaged skin.

PubMed

McGee, Maria P; Morykwas, Michael J; Argenta, Louis C

2011-01-01

The local pathogenesis of interstitial edema in burns is incompletely understood. This ex vivo study investigates the forces mediating water-transfer in and out of heat-denatured interstitial matrix. Experimentally, full-thickness dermal samples are heated progressively to disrupt glycosaminoglycans, kill cells, and denature collagen under conditions that prevent water loss/gain; subsequently, a battery of complementary techniques including among others, high-resolution magnetic resonance imaging, equilibrium vapor pressure and osmotic stress are used to compare water-potential parameters of nonheated and heated dermis. The hydration potential (HP) determined by osmotic stress is a measure of the total water-potential defined empirically as the pressure at which no net water influx/efflux into/from the dermis is detected. Results show that after heat denaturation, the HP, the intensity of T2-weighed magnetic resonance images, and the vapor pressure increase indicating higher water activity and necessarily, smaller contributions from colloidosmotic forces to fluid influx in burned relative to healthy dermis. Concomitant increases in HP and in water activity implicate local changes in interfacial and metabolic energy as the source of excess fluid-transfer potential. These ex vivo findings also show that these additional forces contributing to abnormal fluid-transfer in burned skin develop independently of inflammatory and systemic hydrodynamic responses. © 2011 by the Wound Healing Society.

Personalized medicine in interstitial lung diseases.

PubMed

Spagnolo, Paolo; Oldham, Justin M; Jones, Mark G; Lee, Joyce S

2017-05-01

A number of recent studies have explored the possibility to apply personalized medicine to interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF), the most common and deadly of the idiopathic interstitial pneumonias. In our review, we summarize and discuss the most recent literature on personalized medicine in IPF as well as hypersensitivity pneumonitis and sarcoidosis, with emphasis on patient subgroups for which a personalized approach to disease prognostication and management may become a reality in the near future. Most of the studies that have explored the applicability of personalized medicine to ILDs have been conducted in patients with IPF. Such studies have suggested the existence of several distinct disease subgroups defined by similar genetic profiles, molecular pathways, exposures and individual lifestyles. Personalized medicine in hypersensitivity pneumonitis is in its infancy. The development and applicability of personalized medicine to sarcoidosis, on the other hand, remains problematic for several reasons, including the lack of a diagnostic gold standard, the highly variable and unpredictable disease course, particularly across patients of different ethnicities, the poor correlation between disease activity and disease severity and the lack of a validated management algorithm. A number of distinct patient subgroups have been identified in ILDs. Although available data need to be validated longitudinally, the possibility to study homogeneous groups of patients may allow prediction of disease behavior and response to treatment with dramatic clinical implications.

Seizure clusters: characteristics and treatment.

PubMed

Haut, Sheryl R

2015-04-01

Many patients with epilepsy experience 'clusters' or flurries of seizures, also termed acute repetitive seizures (ARS). Seizure clustering has a significant impact on health and quality of life. This review summarizes recent advances in the definition and neurophysiologic understanding of clustering, the epidemiology and risk factors for clustering and both inpatient and outpatient clinical implications. New treatments for seizure clustering/ARS are perhaps the area of greatest recent progress. Efforts have focused on creating a uniform definition of a seizure cluster. In neurophysiologic studies of refractory epilepsy, seizures within a cluster appear to be self-triggering. Clinical progress has been achieved towards a more precise prevalence of clustering, and consensus guidelines for epilepsy monitoring unit safety. The greatest recent advances are in the study of nonintravenous route of benzodiazepines as rescue medications for seizure clusters/ARS. Rectal benzodiazepines have been very effective but barriers to use exist. New data on buccal, intramuscular and intranasal preparations are anticipated to lead to a greater number of approved treatments. Progesterone may be effective for women who experience catamenial clusters. Seizure clustering is common, particularly in the setting of medically refractory epilepsy. Clustering worsens health and quality of life, and the field requires greater focus on clarifying of definition and clinical implications. Progress towards the development of nonintravenous routes of benzodiazepines has the potential to improve care in this area.

Diffusion and interactions of interstitials in hard-sphere interstitial solid solutions

NASA Astrophysics Data System (ADS)

van der Meer, Berend; Lathouwers, Emma; Smallenburg, Frank; Filion, Laura

2017-12-01

Using computer simulations, we study the dynamics and interactions of interstitial particles in hard-sphere interstitial solid solutions. We calculate the free-energy barriers associated with their diffusion for a range of size ratios and densities. By applying classical transition state theory to these free-energy barriers, we predict the diffusion coefficients, which we find to be in good agreement with diffusion coefficients as measured using event-driven molecular dynamics simulations. These results highlight that transition state theory can capture the interstitial dynamics in the hard-sphere model system. Additionally, we quantify the interactions between the interstitials. We find that, apart from excluded volume interactions, the interstitial-interstitial interactions are almost ideal in our system. Lastly, we show that the interstitial diffusivity can be inferred from the large-particle fluctuations alone, thus providing an empirical relationship between the large-particle fluctuations and the interstitial diffusivity.

Textural versus electrostatic exclusion-enrichment effects in the effective chemical transport within the cortical bone: a numerical investigation.

PubMed

Lemaire, T; Kaiser, J; Naili, S; Sansalone, V

2013-11-01

Interstitial fluid within bone tissue is known to govern the remodelling signals' expression. Bone fluid flow is generated by skeleton deformation during the daily activities. Due to the presence of charged surfaces in the bone porous matrix, the electrochemical phenomena occurring in the vicinity of mechanosensitive bone cells, the osteocytes, are key elements in the cellular communication. In this study, a multiscale model of interstitial fluid transport within bone tissues is proposed. Based on an asymptotic homogenization method, our modelling takes into account the physicochemical properties of bone tissue. Thanks to this multiphysical approach, the transport of nutrients and waste between the blood vessels and the bone cells can be quantified to better understand the mechanotransduction of bone remodelling. In particular, it is shown that the electrochemical tortuosity may have stronger implications in the mass transport within the bone than the purely morphological one. Copyright © 2013 John Wiley & Sons, Ltd.

First-principles investigation of diffusion and defect properties of Fe and Ni in Cr2O3

NASA Astrophysics Data System (ADS)

Rak, Zs.; Brenner, D. W.

2018-04-01

Diffusion of Fe and Ni and the energetics of Fe- and Ni-related defects in chromium oxide (α-Cr2O3) are investigated using first-principles Density Functional Theory calculations in combination with the climbing-image nudged elastic band method. The orientations of the spin magnetic moments of the migrating ions are taken into account and their effects on migration barriers are examined. Several possible diffusion pathways were explored through interstitial and vacancy mechanisms, and it was found that the principal mode of ion transport in Cr2O3 is via vacancies. Both interstitial- and vacancy-mediated diffusions are anisotropic, with diffusion being faster in the z-direction. The energetics of defect formation indicates that the Ni-related defects are less stable than the Fe-related ones. This is consistent with Ni-diffusion being faster than Fe-diffusion. The results are compared with previous theoretical and experimental data and possible implications in corrosion control are discussed.

Fluid resuscitation following a burn injury: implications of a mathematical model of microvascular exchange.

PubMed

Bert, J; Gyenge, C; Bowen, B; Reed, R; Lund, T

1997-03-01

A validated mathematical model of microvascular exchange in thermally injured humans has been used to predict the consequences of different forms of resuscitation and potential modes of action of pharmaceuticals on the distribution and transport of fluid and macromolecules in the body. Specially, for 10 and/or 50 per cent burn surface area injuries, predictions are presented for no resuscitation, resuscitation with the Parkland formula (a high fluid and low protein formulation) and resuscitation with the Evans formula (a low fluid and high protein formulation). As expected, Parkland formula resuscitation leads to interstitial accumulation of excess fluid, while use of the Evans formula leads to interstitial accumulation of excessive amounts of proteins. The hypothetical effects of pharmaceuticals on the transport barrier properties of the microvascular barrier and on the highly negative tissue pressure generated postburn in the injured tissue were also investigated. Simulations predict a relatively greater amelioration of the acute postburn edema through modulation of the postburn tissue pressure effects.

Two unrelated children with overlapping 6q25.3 deletions, motor speech disorders, and language delays.

PubMed

Peter, Beate; Lancaster, Hope; Vose, Caitlin; Fares, Amna; Schrauwen, Isabelle; Huentelman, Matthew

2017-10-01

Interstitial and terminal 6q25 deletions are associated with developmental delays, hypotonia, eye pathologies, craniofacial dysmorphologies, and structural brain anomalies. In most cases, speech and language deficits are not described in detail. We report on a case (Patient 1, age 7 years) with a de novo 6q25.3-qter deletion, 11.1 Mb long and encompassing 108 genes, and a case (Patient 2, age 5 years) with an inherited interstitial 6q25.3 deletion, located within Patient 1's deletion region and 403 kb long, the smallest 6q25 deletion reported to date. Both children have hypotonia, motor speech disorders, and expressive language delays. Patient 1's speech was characterized by childhood apraxia of speech (CAS) and dysarthria. Other findings include developmental delay, ataxic cerebral palsy, optic nerve dysplagia, and atypical brain morphologies regarding the corpus callosum and gyration patterns, a clinical profile that closely matches a previously reported case with a nearly identical deletion. Patient 2 had speech characterized by CAS and typical nonverbal processing abilities. His father, a carrier, had typical speech and language but showed difficulties with complex motor speech and hand motor tasks, similar to other adults with residual signs of CAS. The small deletion in this family contains the IGF2R-AIRN-SLC22A2-SLC22A3 gene cluster, which is associated with imprinting and maternal-specific expression of Igf2R, Slc22a2, and Slc22a3 in mice, whereas imprinting in humans is a polymorphic trait. The shared phenotypes in the two patients might be associated with the deletion of the gene cluster. © 2017 Wiley Periodicals, Inc.

Axial compartmentation of descending and ascending thin limbs of Henle's loops

PubMed Central

Westrick, Kristen Y.; Serack, Bradley; Dantzler, William H.

2013-01-01

In the inner medulla, radial organization of nephrons and blood vessels around collecting duct (CD) clusters leads to two lateral interstitial regions and preferential intersegmental fluid and solute flows. As the descending (DTLs) and ascending thin limbs (ATLs) pass through these regions, their transepithelial fluid and solute flows are influenced by variable transepithelial solute gradients and structure-to-structure interactions. The goal of this study was to quantify structure-to-structure interactions, so as to better understand compartmentation and flows of transepithelial water, NaCl, and urea and generation of the axial osmotic gradient. To accomplish this, we determined lateral distances of AQP1-positive and AQP1-negative DTLs and ATLs from their nearest CDs, so as to gauge interactions with intercluster and intracluster lateral regions and interactions with interstitial nodal spaces (INSs). DTLs express reduced AQP1 and low transepithelial water permeability along their deepest segments. Deep AQP1-null segments, prebend segments, and ATLs lie equally near to CDs. Prebend segments and ATLs abut CDs and INSs throughout much of their descent and ascent, respectively; however, the distal 30% of ATLs of the longest loops lie distant from CDs as they approach the outer medullary boundary and have minimal interaction with INSs. These relationships occur regardless of loop length. Finally, we show that ascending vasa recta separate intercluster AQP1-positive DTLs from descending vasa recta, thereby minimizing dilution of gradients that drive solute secretion. We hypothesize that DTLs and ATLs enter and exit CD clusters in an orchestrated fashion that is important for generation of the corticopapillary solute gradient by minimizing NaCl and urea loss. PMID:23195680

Axial compartmentation of descending and ascending thin limbs of Henle's loops.

PubMed

Westrick, Kristen Y; Serack, Bradley; Dantzler, William H; Pannabecker, Thomas L

2013-02-01

In the inner medulla, radial organization of nephrons and blood vessels around collecting duct (CD) clusters leads to two lateral interstitial regions and preferential intersegmental fluid and solute flows. As the descending (DTLs) and ascending thin limbs (ATLs) pass through these regions, their transepithelial fluid and solute flows are influenced by variable transepithelial solute gradients and structure-to-structure interactions. The goal of this study was to quantify structure-to-structure interactions, so as to better understand compartmentation and flows of transepithelial water, NaCl, and urea and generation of the axial osmotic gradient. To accomplish this, we determined lateral distances of AQP1-positive and AQP1-negative DTLs and ATLs from their nearest CDs, so as to gauge interactions with intercluster and intracluster lateral regions and interactions with interstitial nodal spaces (INSs). DTLs express reduced AQP1 and low transepithelial water permeability along their deepest segments. Deep AQP1-null segments, prebend segments, and ATLs lie equally near to CDs. Prebend segments and ATLs abut CDs and INSs throughout much of their descent and ascent, respectively; however, the distal 30% of ATLs of the longest loops lie distant from CDs as they approach the outer medullary boundary and have minimal interaction with INSs. These relationships occur regardless of loop length. Finally, we show that ascending vasa recta separate intercluster AQP1-positive DTLs from descending vasa recta, thereby minimizing dilution of gradients that drive solute secretion. We hypothesize that DTLs and ATLs enter and exit CD clusters in an orchestrated fashion that is important for generation of the corticopapillary solute gradient by minimizing NaCl and urea loss.

Density functional theory calculations of UO2 oxidation: evolution of UO(2+x), U4O(9-y), U3O7, and U3O8.

PubMed

Andersson, D A; Baldinozzi, G; Desgranges, L; Conradson, D R; Conradson, S D

2013-03-04

Formation of hyperstoichiometric uranium dioxide, UO2+x, derived from the fluorite structure was investigated by means of density functional theory (DFT) calculations. Oxidation was modeled by adding oxygen atoms to UO2 fluorite supercells. For each compound ab initio molecular dynamics simulations were performed to allow the ions to optimize their local geometry. A similar approach was used for studying the reduction of U3O8. In agreement with the experimental phase diagram we identify stable line compounds at the U4O9-y and U3O7 stoichiometries. Although the transition from fluorite to the layered U3O8 structure occurs at U3O7 (UO2.333) or U3O7.333 (UO2.444), our calculated low temperature phase diagram indicates that the fluorite derived compounds are favored up to UO2.5, that is, as long as the charge-compensation for adding oxygen atoms occurs via formation of U(5+) ions, after which the U3O8-y phase becomes more stable. The most stable fluorite UO2+x phases at low temperature (0 K) are based on ordering of split quad-interstitial oxygen clusters. Most existing crystallographic models of U4O9 and U3O7, however, apply the cuboctahedral cluster. To better understand these discrepancies, the new structural models are analyzed in terms of existing neutron diffraction data. DFT calculations were also performed on the experimental cuboctahedral based U4O9-y structure, which enable comparisons between the properties of this phase with the quad-interstitial ones in detail.

Oxygen-related vacancy-type defects in ion-implanted silicon

NASA Astrophysics Data System (ADS)

Pi, X. D.; Burrows, C. P.; Coleman, P. G.; Gwilliam, R. M.; Sealy, B. J.

2003-10-01

Czochralski silicon samples implanted to a dose of 5 × 1015 cm-2 with 0.5 MeV O and to a dose of 1016 cm-2 with 1 MeV Si, respectively, have been studied by positron annihilation spectroscopy. The evolution of divacancies to vacancy (V)-O complexes is out-competed by V-interstitial (I) recombination at 400 and 500 °C in the Si- and O-implanted samples; the higher oxygen concentration makes the latter temperature higher. The defective region shrinks as the annealing temperature increases as interstitials are injected from the end of the implantation range (Rp). VmOn (m> n) are formed in the shallow region most effectively at 700 °C for both Si and O implantation. VxOy (x< y) are produced near Rp by the annealing. At 800 °C, implanted Si ions diffuse and reduce m and implanted O ions diffuse and increase n in VmOn. All oxygen-related vacancy-type defects appear to begin to dissociate at 950 °C, with the probable formation of oxygen clusters. At 1100 °C, oxygen precipitates appear to form just before Rp in O-implanted silicon.

Neurokinin B-producing projection neurons in the lateral stripe of the striatum and cell clusters of the accumbens nucleus in the rat.

PubMed

Zhou, Ligang; Furuta, Takahiro; Kaneko, Takeshi

2004-12-06

Neurons producing preprotachykinin B (PPTB), the precursor of neurokinin B, constitute 5% of neurons in the dorsal striatum and project to the substantia innominata (SI) selectively. In the ventral striatum, PPTB-producing neurons are collected mainly in the lateral stripe of the striatum (LSS) and cell clusters of the accumbens nucleus (Acb). In the present study, we first examined the distribution of PPTB-immunoreactive neurons in rat ventral striatum and found that a large part of the PPTB-immunoreactive cell clusters was continuous to the LSS, but a smaller part was not. Thus, we divided the PPTB-immunoreactive cell clusters into the LSS-associated and non-LSS-associated ones. We next investigated the projection targets of the PPTB-producing ventral striatal neurons by combining immunofluorescence labeling and retrograde tracing. After injection of Fluoro-Gold into the basal component of the SI (SIb) and medial part of the interstitial nucleus of posterior limb of the anterior commissure, many PPTB-immunoreactive neurons were retrogradely labeled in the LSS-associated cell clusters and LSS, respectively. When the injection site included the ventral part of the sublenticular component of the SI(SIsl), retrogradely labeled neurons showed PPTB-immunoreactivity frequently in non-LSS-associated cell clusters. Furthermore, these PPTB-immunoreactive projections were confirmed by the double-fluorescence method after anterograde tracer injection into the ventral striatum containing the cell clusters. Since the dorsalmost part of the SIsl is known to receive strong inputs from PPTB-producing dorsal striatal neurons, the present results indicate that PPTB-producing ventral striatal neurons project to basal forebrain target regions in parallel with dorsal striatal neurons without significant convergence. 2004 Wiley-Liss, Inc.

Study of point- and cluster-defects in radiation-damaged silicon

NASA Astrophysics Data System (ADS)

Donegani, Elena M.; Fretwurst, Eckhart; Garutti, Erika; Klanner, Robert; Lindstroem, Gunnar; Pintilie, Ioana; Radu, Roxana; Schwandt, Joern

2018-08-01

Non-ionising energy loss of radiation produces point defects and defect clusters in silicon, which result in a significant degradation of sensor performance. In this contribution results from TSC (Thermally Stimulated Current) defect spectroscopy for silicon pad diodes irradiated by electrons to fluences of a few 1014 cm-2 and energies between 3.5 and 27 MeV for isochronal annealing between 80 and 280∘C, are presented. A method based on SRH (Shockley-Read-Hall) statistics is introduced, which assumes that the ionisation energy of the defects in a cluster depends on the fraction of occupied traps. The difference of ionisation energy of an isolated point defect and a fully occupied cluster, ΔEa, is extracted from the TSC data. For the VOi (vacancy-oxygen interstitial) defect ΔEa = 0 is found, which confirms that it is a point defect, and validates the method for point defects. For clusters made of deep acceptors the ΔEa values for different defects are determined after annealing at 80∘C as a function of electron energy, and for the irradiation with 15 MeV electrons as a function of annealing temperature. For the irradiation with 3.5 MeV electrons the value ΔEa = 0 is found, whereas for the electron energies of 6-27 MeV ΔEa > 0. This agrees with the expected threshold of about 5 MeV for cluster formation by electrons. The ΔEa values determined as a function of annealing temperature show that the annealing rate is different for different defects. A naive diffusion model is used to estimate the temperature dependencies of the diffusion of the defects in the clusters.

Nitric oxide activation by distal redox modulation in tetranuclear iron nitrosyl complexes.

PubMed

de Ruiter, Graham; Thompson, Niklas B; Lionetti, Davide; Agapie, Theodor

2015-11-11

A series of tetranuclear iron complexes displaying a site-differentiated metal center was synthesized. Three of the metal centers are coordinated to our previously reported ligand, based on a 1,3,5-triarylbenzene motif with nitrogen and oxygen donors. The fourth (apical) iron center is coordinatively unsaturated and appended to the trinuclear core through three bridging pyrazolates and an interstitial μ4-oxide moiety. Electrochemical studies of complex [LFe3(PhPz)3OFe][OTf]2 revealed three reversible redox events assigned to the Fe(II)4/Fe(II)3Fe(III) (-1.733 V), Fe(II)3Fe(III)/Fe(II)2Fe(III)2 (-0.727 V), and Fe(II)2Fe(III)2/Fe(II)Fe(III)3 (0.018 V) redox couples. Combined Mössbauer and crystallographic studies indicate that the change in oxidation state is exclusively localized at the triiron core, without changing the oxidation state of the apical metal center. This phenomenon is assigned to differences in the coordination environment of the two metal sites and provides a strategy for storing electron and hole equivalents without affecting the oxidation state of the coordinatively unsaturated metal. The presence of a ligand-binding site allowed the effect of redox modulation on nitric oxide activation by an Fe(II) metal center to be studied. Treatment of the clusters with nitric oxide resulted in binding of NO to the apical iron center, generating a {FeNO}(7) moiety. As with the NO-free precursors, the three reversible redox events are localized at the iron centers distal from the NO ligand. Altering the redox state of the triiron core resulted in significant change in the NO stretching frequency, by as much as 100 cm(-1). The increased activation of NO is attributed to structural changes within the clusters, in particular, those related to the interaction of the metal centers with the interstitial atom. The differences in NO activation were further shown to lead to differential reactivity, with NO disproportionation and N2O formation performed by the more electron-rich cluster.

A computer-aided differential diagnosis between UIP and NSIP using automated assessment of the extent and distribution of regional disease patterns at HRCT: comparison with the radiologist's decision

NASA Astrophysics Data System (ADS)

Kim, Namkug; Seo, Joon Beom; Park, Sang Ok; Lee, Youngjoo; Lee, Jeongjin

2009-02-01

To evaluate the accuracy of computer aided differential diagnosis (CADD) between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) at HRCT in comparison with that of a radiologist's decision. A computerized classification for six local disease patterns (normal, NL; ground-glass opacity, GGO; reticular opacity, RO; honeycombing, HC; emphysema, EM; and consolidation, CON) using texture/shape analyses and a SVM classifier at HRCT was used for pixel-by-pixel labeling on the whole lung area. The mode filter was applied on the results to reduce noise. Area fraction (AF) of each pattern, directional probabilistic density function (pdf) (dPDF: mean, SD, skewness of pdf /3 directions: superior-inferior, anterior-posterior, central-peripheral), regional cluster distribution pattern (RCDP: number, mean, SD of clusters, mean, SD of centroid of clusters) were automatically evaluated. Spatially normalized left and right lungs were evaluated separately. Disease division index (DDI) on every combination of AFs and asymmetric index (AI) between left and right lung ((left-right)/left) were also evaluated. To assess the accuracy of the system, fifty-four HRCT data sets in patients with pathologically diagnosed UIP (n=26) and NSIP (n=28) were used. For a classification procedure, a CADD-SVM classifier with internal parameter optimization, and sequential forward floating feature selection (SFFS) were employed. The accuracy was assessed by a 5-folding cross validation with 20- times repetition. For comparison, two thoracic radiologists reviewed the whole HRCT images without clinical information and diagnose each case either as UIP or NSIP. The accuracies of radiologists' decision were 0.75 and 0.87, respectively. The accuracies of the CADD system using the features of AF, dPDF, AI of dPDF, RDP, AI of RDP, DDI were 0.70, 0.79, 0.77, 0.80, 0.78, 0.81, respectively. The accuracy of optimized CADD using all features after SFFS was 0.91. We developed the CADD system to differentiate between UIP and NSIP using automated assessment of the extent and distribution of regional disease patterns at HRCT.

Energetics of halogen impurities in thorium dioxide

NASA Astrophysics Data System (ADS)

Kuganathan, Navaratnarajah; Ghosh, Partha S.; Arya, Ashok K.; Dey, Gautam K.; Grimes, Robin W.

2017-11-01

Defect energies for halogen impurity atoms (Cl, Br and I) in thoria are calculated using the generalized gradient approximation and projector augmented plane wave potentials under the framework of density functional theory. The energy to place a halogen atom at a pre-existing lattice site is the incorporation energy. Seven sites are considered: octahedral interstitial, O vacancy, Th vacancy, Th-O di-vacancy cluster (DV) and the three O-Th-O tri-vacancy cluster (NTV) configurations. For point defects and vacancy clusters, neutral and all possible defect charge states up to full formal charge are considered. The most favourable incorporation site for Cl is the singly charged positive oxygen vacancy while for Br and I it is the NTV1 cluster. By considering the energy to form the defect sites, solution energies are generated. These show that in both ThO2-x and ThO2 the most favourable solution equilibrium site for halides is the single positively charged oxygen vacancy (although in ThO2, I demonstrates the same solubility in the NTV1 and DV clusters). Solution energies are much lower in ThO2-x than in ThO2 indicating that stoichiometry is a significant factor in determining solubility. In ThO2, all three halogens are highly insoluble and in ThO2-x Br and I remain insoluble. Although ½Cl2 is soluble in ThO2-x alternative phases such as ZrCl4 exist which are of lower energy.

Modulating kidney transplant interstitial fibrosis and tubular atrophy: is the RAAS an important target?

PubMed

Amer, Hatem; Griffin, Matthew D

2014-02-01

In follow-up to a recently published randomized controlled clinical trial, Issa et al. provide evidence that systemic activity and physiological responsiveness of the renin aldosterone angiotensin system (RAAS) are well within normal limits in most kidney recipients during the first 5 years post-transplant. Implications of the results include the need to better understand intra-renal RAAS activity in transplanted kidneys and to identify patients in which the graft-protective effects of RAAS blockade are most relevant.

Clusterization Effects in III-V Nitrides: Nitrogen Vacancies, and Si and Mg Impurities in Aluminum Nitride and Gallium Nitride

NASA Astrophysics Data System (ADS)

Gubanov, V. A.; Pentaleri, E. A.; Boekema, C.; Fong, C. Y.; Klein, B. M.

1997-03-01

We have investigated clusterization of nitrogen vacancies and Si and Mg doping impurities in zinc-blende aluminum nitride (c-AlN) and gallium nitride (c-GaN) by the tight-binding LMTO technique. The calculations used 128-site supercells. Si and Mg atoms replacing ions in both the cation and anion sublattices of the host lattices of the host crystals have been considered. The Mg impurity at cation sites is found to form partially occupied states at the valence-band edge, and may result in p-type conductivity. When Si substitutes for Ga, the impurity band is formed at the conduction-band edge, resulting in n-type conductivity. Si impurities at cation sites, and Mg impurity at anion sites are able to form resonance states in the gap. The influence of impurity clusterization in the host lattice and interstitial sites on electronic properties of c-AlN and c-GaN crystals are modeled. The changes in vacancy- and impurity-state energies, bonding type, localization, density of states at the Fermi level in different host lattices, their dependence on impurity/vacancy concentration are analyzed and compared with the experimental data.

Hydrogen-enhanced clusterization of intrinsic defects and impurities in silicon

NASA Astrophysics Data System (ADS)

Mukashev, B. N.; Abdullin, Kh. A.; Gorelkinskii, Yu. V.; Tamendarov, M. F.; Tokmoldin, S. Zh

2001-01-01

Formation of intrinsic and impurity defect complexes in hydrogenated monocrystalline silicon is studied. Hydrogen was incorporated into samples by different ways: either by proton implantation at 80 and 300 K, or by annealing at 1250°C for 30-60 min in a sealed quartz ampoule containing ∼10 -3 ml of distilled water, or by treatment in hydrogen plasma. Radiation defects were incorporated either during the hydrogen implantation or by additional irradiation with protons or α-particles. The measurements were performed by electron paramagnetic resonance (EPR), deep level transient spectroscopy (DLTS) and infrared absorption (IR) methods. Essential differences of defect formation processes in hydrogenated samples as compared with reference samples were detected. The main reasons responsible for the differences are (i) hydrogen precipitation in a supersaturated solution during thermal treatment; (ii) interaction of hydrogen with defects and impurities and hydrogen-induced formation of defects; (iii) ability of hydrogen to play the role of accelerator of impurities precipitation. These factors result in the formation of vacancy-related, interstitial-related and impurity clusters which are observed only in the presence of hydrogen. The nature of the clusters and possible models of their structure are discussed.

Septicemia in a neonatal calf associated with Chromobacterium violaceum.

PubMed

Ajithdoss, D K; Porter, B F; Calise, D V; Libal, M C; Edwards, J F

2009-01-01

Chromobacterium violaceum infections are highly fatal and rarely reported in domestic animals. This report describes a fatal case of C. violaceum septicemia in a 7-day-old female beef calf. The calf had necrosuppurative omphalophlebitis, necrotizing interstitial pneumonia, necrosuppurative hepatitis and splenitis, anterior uveitis with hypopyon, suppurative polyarthritis, and disseminated hemorrhagic meningitis with multifocal necrotizing encephalitis. Histologically, clusters of gram-negative bacilli were found in many of the lesions. C. violaceum was isolated in high numbers from the lungs, liver, spleen, carpus, and in pure culture from the cerebrospinal fluid. To our knowledge, this is the first case report of chromobacteriosis in a calf.

Interstitial cystitis - resources

MedlinePlus

Resources - interstitial cystitis ... The following organizations are good resources for information on interstitial cystitis : Interstitial Cystitis Association -- www.ichelp.org National Institute of Diabetes and Digestive and Kidney Diseases -- www. ...

Analysis of Dissolved Organic Nutrients in the Interstitial Water of Natural Biofilms.

PubMed

Tsuchiya, Yuki; Eda, Shima; Kiriyama, Chiho; Asada, Tomoya; Morisaki, Hisao

2016-07-01

In biofilms, the matrix of extracellular polymeric substances (EPSs) retains water in the interstitial region of the EPS. This interstitial water is the ambient environment for microorganisms in the biofilms. The nutrient condition in the interstitial water may affect microbial activity in the biofilms. In the present study, we measured the concentrations of dissolved organic nutrients, i.e., saccharides and proteins, contained in the interstitial water of biofilms formed on the stones. We also analyzed the molecular weight distribution, chemical species, and availability to bacteria of some saccharides in the interstitial water. Colorimetric assays showed that the concentrations of saccharides and proteins in the biofilm interstitial water were significantly higher (ca. 750 times) than those in the surrounding lake waters (p < 0.05). Chromatographic analyses demonstrated that the saccharides in the interstitial waters were mainly of low molecular-weight saccharides such as glucose and maltose, while proteins in the interstitial water were high molecular-weight proteins (over 7000 Da). Bacterial growth and production of EPS occurred simultaneously with the decrease in the low molecular-weight saccharide concentrations when a small portion of biofilm suspension was inoculated to the collected interstitial water, suggesting that the dissolved saccharides in the interstitial water support bacterial growth and formation of biofilms.

Taenia crassiceps: infections of male mice lead to severe disruption of seminiferous tubule cells and increased apoptosis.

PubMed

Zepeda, Nadia; Copitin, Natalia; Solano, Sandra; González, Maricarmen; Fernández, Ana M; Tato, Patricia; Molinari, José L

2011-01-01

This research was carried out to study the effects of infection with Taenia crassiceps cysticerci on the seminiferous epithelium histoarchitecture in the testes of male mice. Our results showed a severe disruption of the histoarchitecture of the testis epithelium in infected mice. In these animals, a significant infiltration of macrophages within seminiferous tubules was observed (P < 0.001). Generalized apoptosis of germ cells within the seminiferous tubules was observed, as assessed by TUNEL assay and apoptotic nuclei were quantified. The total number of fluorescent objects (DNA) (including clusters, singles, and objects in clusters) was significantly higher in the infected cells than in the control group (P = 0.0286). Observation of the interstitial tissue showed disorder and deterioration of many Leydig cells of infected mice, as well as intense vacuolization and destruction of their inter-cellular junctions. Several ultrastructural abnormalities were observed through electron microscopy as well. The observed pathology could lead to a state of infertility. Copyright © 2010 Elsevier Inc. All rights reserved.

Icosahedral and decagonal quasicrystals of intermetallic compounds are multiple twins of cubic or orthorhombic crystals composed of very large atomic complexes with icosahedral point-group symmetry in cubic close packing or body-centered packing: Structure of decagonal Al6Pd

PubMed Central

Pauling, Linus

1989-01-01

A doubly icosahedral complex involves roughly spherical clusters of atoms with icosahedral point-group symmetry, which are themselves, in parallel orientation, icosahedrally packed. These complexes may form cubic crystallites; three structures of this sort have been identified. Analysis of electron diffraction photographs of the decagonal quasicrystal Al6Pd has led to its description as involving pentagonal twinning of an orthorhombic crystal with a = 51.6 Å, b = 37.6 Å, and c = 33.24 Å, with about 4202 atoms in the unit, comprising two 1980-atom doubly icosahedral complexes, each involving icosahedral packing of 45 44-atom icosahedral complexes (at 0 0 0 and 1/2 1/2 1/2) and 242 interstitial atoms. The complexes and clusters are oriented with one of their fivefold axes in the c-axis direction. Images PMID:16594092

Icosahedral and decagonal quasicrystals of intermetallic compounds are multiple twins of cubic or orthorhombic crystals composed of very large atomic complexes with icosahedral point-group symmetry in cubic close packing or body-centered packing: Structure of decagonal Al(6)Pd.

PubMed

Pauling, L

1989-12-01

A doubly icosahedral complex involves roughly spherical clusters of atoms with icosahedral point-group symmetry, which are themselves, in parallel orientation, icosahedrally packed. These complexes may form cubic crystallites; three structures of this sort have been identified. Analysis of electron diffraction photographs of the decagonal quasicrystal Al(6)Pd has led to its description as involving pentagonal twinning of an orthorhombic crystal with a = 51.6 A, b = 37.6 A, and c = 33.24 A, with about 4202 atoms in the unit, comprising two 1980-atom doubly icosahedral complexes, each involving icosahedral packing of 45 44-atom icosahedral complexes (at 0 0 0 and 1/2 1/2 1/2) and 242 interstitial atoms. The complexes and clusters are oriented with one of their fivefold axes in the c-axis direction.

Enhancing radiation tolerance by controlling defect mobility and migration pathways in multicomponent single-phase alloys

DOE PAGES

Lu, Chenyang; Niu, Liangliang; Chen, Nanjun; ...

2016-12-15

A grand challenge in material science is to understand the correlation between intrinsic properties and defect dynamics. Radiation tolerant materials are in great demand for safe operation and advancement of nuclear and aerospace systems. Unlike traditional approaches that rely on microstructural and nanoscale features to mitigate radiation damage, this study demonstrates enhancement of radiation tolerance with the suppression of void formation by two orders magnitude at elevated temperatures in equiatomic single-phase concentrated solid solution alloys, and more importantly, reveals its controlling mechanism through a detailed analysis of the depth distribution of defect clusters and an atomistic computer simulation. The enhancedmore » swelling resistance is attributed to the tailored interstitial defect cluster motion in the alloys from a long-range one-dimensional mode to a short-range three-dimensional mode, which leads to enhanced point defect recombination. Finally, the results suggest design criteria for next generation radiation tolerant structural alloys.« less

Adsorption behavior of Fe atoms on a naphthalocyanine monolayer on Ag(111) surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Ling -Hao; Wu, Rong -Ting; Bao, De -Liang

2015-05-29

Adsorption behavior of Fe atoms on a metal-free naphthalocyanine (H 2Nc) monolayer on Ag(111) surface at room temperature has been investigated using scanning tunneling microscopy combined with density functional theory (DFT) based calculations. We found that the Fe atoms adsorbed at the centers of H 2Nc molecules and formed Fe-H 2Nc complexes at low coverage. DFT calculations show that the configuration of Fe at the center of a molecule is the most stable site, in good agreement with the experimental observations. After an Fe-H 2Nc complex monolayer was formed, the extra Fe atoms self-assembled to Fe clusters of uniform sizemore » and adsorbed dispersively at the interstitial positions of Fe-H 2Nc complex monolayer. Furthermore, the H 2Nc monolayer grown on Ag(111) could be a good template to grow dispersed magnetic metal atoms and clusters at room temperature for further investigation of their magnetism-related properties.« less

Ethical implications of excessive cluster sizes in cluster randomised trials.

PubMed

Hemming, Karla; Taljaard, Monica; Forbes, Gordon; Eldridge, Sandra M; Weijer, Charles

2018-02-20

The cluster randomised trial (CRT) is commonly used in healthcare research. It is the gold-standard study design for evaluating healthcare policy interventions. A key characteristic of this design is that as more participants are included, in a fixed number of clusters, the increase in achievable power will level off. CRTs with cluster sizes that exceed the point of levelling-off will have excessive numbers of participants, even if they do not achieve nominal levels of power. Excessively large cluster sizes may have ethical implications due to exposing trial participants unnecessarily to the burdens of both participating in the trial and the potential risks of harm associated with the intervention. We explore these issues through the use of two case studies. Where data are routinely collected, available at minimum cost and the intervention poses low risk, the ethical implications of excessively large cluster sizes are likely to be low (case study 1). However, to maximise the social benefit of the study, identification of excessive cluster sizes can allow for prespecified and fully powered secondary analyses. In the second case study, while there is no burden through trial participation (because the outcome data are routinely collected and non-identifiable), the intervention might be considered to pose some indirect risk to patients and risks to the healthcare workers. In this case study it is therefore important that the inclusion of excessively large cluster sizes is justifiable on other grounds (perhaps to show sustainability). In any randomised controlled trial, including evaluations of health policy interventions, it is important to minimise the burdens and risks to participants. Funders, researchers and research ethics committees should be aware of the ethical issues of excessively large cluster sizes in cluster trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Aerosol partitioning in mixed-phase clouds at the Jungfraujoch (3580 m asl)

NASA Astrophysics Data System (ADS)

Henning, S.; Bojinski, S.; Diehl, K.; Ghan, S.; Nyeki, S.; Weingartner, E.; Wurzler, S.; Baltensperger, U.

2003-04-01

Field measurements on the partitioning between the interstitial and the liquid/ice phase in natural clouds were performed at the high-alpine research station Jungfraujoch (3580 m asl, Switzerland) during a summer and a winter campaign. The size distributions of the total and the interstitial aerosol were determined by means of a scanning mobility particle sizer (SMPS). From these, size resolved scavenging ratios were calculated. Simultaneously, cloud water content (CWC) and cloud particle size distributions along with meteorological data were obtained. In cold mixed phase clouds (existing of liquid droplets and ice crystals), strong differences were found in comparison to the warm summer clouds. In the warm cloud types all particles above a certain diameter were activated and thereby the scavenging ratio (number of activated particles divided by the total number concentration) above a certain threshold diameter approached 1. In the winter clouds, the scavenging ratio never reached the value of 1 and could be as low as 0. These observations are explained by the Bergeron-Findeisen process: Here, particles are also activated to droplets in the first step, but after the formation of the ice phase droplets evaporate while the ice crystals grow, due to difference in the saturation vapor pressure over water and ice. This release of aerosol particles to the interstitial aerosol has significant implications for the climate forcing: It can be expected that the number of CCN is of less importance as soon as ice crystals are formed.

Aerosol partitioning between the interstitial and the condensed phase in mixed-phase clouds

NASA Astrophysics Data System (ADS)

Verheggen, Bart; Cozic, Julie; Weingartner, Ernest; Bower, Keith; Mertes, Stephan; Connolly, Paul; Gallagher, Martin; Flynn, Michael; Choularton, Tom; Baltensperger, Urs

2007-12-01

The partitioning of aerosol particles between the cloud and the interstitial phase (i.e., unactivated aerosol) has been investigated during several Cloud and Aerosol Characterization Experiments (CLACE-3, CLACE-3? and CLACE-4) conducted in winter and summer 2004 and winter 2005 at the high alpine research station Jungfraujoch (3580 m altitude, Switzerland). Ambient air was sampled using different inlets in order to determine the activated fraction of aerosol particles, FN, defined as the fraction of the total aerosol number concentration (with particle diameter dp > 100 nm) that has been incorporated into cloud particles. The liquid and ice water content of mixed-phase clouds were characterized by analyzing multiple cloud probes. The dependence of the activated fraction on several environmental factors is discussed on the basis of more than 900 h of in-cloud observations and parameterizations for key variables are given. FN is found to increase with increasing liquid water content and to decrease with increasing particle number concentration in liquid clouds. FN also decreases with increasing cloud ice mass fraction and with decreasing temperature from 0 to -25°C. The Wegener-Bergeron-Findeisen process probably contributed to this trend, since the presence of ice crystals causes liquid droplets to evaporate, thus releasing the formerly activated particles back into the interstitial phase. Ice nucleation could also have prevented additional cloud condensation nuclei from activating. The observed activation behavior has significant implications for our understanding of the indirect effect of aerosols on climate.

De novo interstitial duplication of the 15q11.2-q14 PWS/AS region of maternal origin: Clinical description, array CGH analysis, and review of the literature.

PubMed

Kitsiou-Tzeli, Sophia; Tzetis, Maria; Sofocleous, Christalena; Vrettou, Christina; Xaidara, Athena; Giannikou, Krinio; Pampanos, Andreas; Mavrou, Ariadne; Kanavakis, E

2010-08-01

The 15q11-q13 PWS/AS critical region involves genes that are characterized by genomic imprinting. Multiple repeat elements within the region mediate rearrangements, including interstitial duplications, interstitial triplications, and supernumerary isodicentric marker chromosomes, as well as the deletions that cause Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Recently, duplications of maternal origin concerning the same critical region have been implicated in autism spectrum disorders (ASD). We present a 6-month-old girl carrying a de novo duplication of maternal origin of the 15q11.2-q14 PWS/AS region (17.73 Mb in size) [46,XX,dup(15)(q11.2-q14)] detected with a high-resolution microarray-based comparative genomic hybridization (array-CGH). The patient is characterized by severe hypotonia, obesity, microstomia, long eyelashes, hirsutism, microretrognathia, short nose, severe psychomotor retardation, and multiple episodes of drug-resistant epileptic seizures, while her brain magnetic resonance imaging (MRI) documented partial corpus callosum dysplasia. In our patient the duplicated region is quite large extending beyond the Prader-Willi-Angelman critical region (PWACR), containing a number of genes that have been shown to be involved in ASD, exhibiting a severe phenotype, beyond the typical PWS/AS clinical manifestations. Reporting of similar well-characterized clinical cases with clearly delineated breakpoints of the duplicated region will clarify the contribution of specific genes to the phenotype.

TRP channels in the digestive system

PubMed Central

Holzer, Peter

2011-01-01

Several of the 28 mammalian transient receptor potential (TRP) channel subunits are expressed throughout the alimentary canal where they play important roles in taste, chemo- and mechanosensation, thermoregulation, pain and hyperalgesia, mucosal function and homeostasis, control of motility by neurons, interstitial cells of Cajal and muscle cells, and vascular function. While the implications of some TRP channels, notably TRPA1, TRPC4, TRPM5, TRPM6, TRPM7, TRPV1, TRPV4, and TRPV6, have been investigated in much detail, the understanding of other TRP channels in their relevance to digestive function lags behind. The polymodal chemo- and mechanosensory function of TRPA1, TRPM5, TRPV1 and TRPV4 is particularly relevant to the alimentary canal whose digestive and absorptive function depends on the surveillance and integration of many chemical and physical stimuli. TRPV5 and TRPV6 as well as TRPM6 and TRPM7 appear to be essential for the absorption of Ca2+ and Mg2+, respectively, while TRPM7 appears to contribute to the pacemaker activity of the interstitial cells of Cajal, and TRPC4 transduces smooth muscle contraction evoked by muscarinic acetylcholine receptor activation. The implication of some TRP channels in pathological processes has raised enormous interest in exploiting them as a therapeutic target. This is particularly true for TRPV1, TRPV4 and TRPA1, which may be targeted for the treatment of several conditions of chronic abdominal pain. Consequently, blockers of these TRP channels have been developed, and their clinical usefulness has yet to be established. PMID:20932260

The hydraulic permeability of blood clots as a function of fibrin and platelet density.

PubMed

Wufsus, A R; Macera, N E; Neeves, K B

2013-04-16

Interstitial fluid flow within blood clots is a biophysical mechanism that regulates clot growth and dissolution. Assuming that a clot can be modeled as a porous medium, the physical property that dictates interstitial fluid flow is the hydraulic permeability. The objective of this study was to bound the possible values of the hydraulic permeability in clots formed in vivo and present relationships that can be used to estimate clot permeability as a function of composition. A series of clots with known densities of fibrin and platelets, the two major components of a clot, were formed under static conditions. The permeability was calculated by measuring the interstitial fluid velocity through the clots at a constant pressure gradient. Fibrin gels formed with a fiber volume fraction of 0.02-0.54 had permeabilities of 1.2 × 10(-1)-1.5 × 10(-4)μm(2). Platelet-rich clots with a platelet volume fraction of 0.01-0.61 and a fibrin volume fraction of 0.03 had permeabilities over a range of 1.1 × 10(-2)-1.5 × 10(-5)μm(2). The permeability of fibrin gels and of clots with platelet volume fraction of <0.2 were modeled as an array of disordered cylinders with uniform diameters. Clots with a platelet volume fraction of >0.2 were modeled as a Brinkman medium of coarse solids (platelets) embedded in a mesh of fine fibers (fibrin). Our data suggest that the permeability of clots formed in vivo can vary by up to five orders of magnitude, with pore sizes that range from 4 to 350 nm. These findings have important implications for the transport of coagulation zymogens/enzymes in the interstitial spaces during clot formation, as well as the design of fibrinolytic drug delivery strategies. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Longitudinal follow-up of fibrosing interstitial pneumonia: relationship between physiologic testing, computed tomography changes, and survival rate.

PubMed

Hwang, Jeong-Hwa; Misumi, Shigeki; Curran-Everett, Douglas; Brown, Kevin K; Sahin, Hakan; Lynch, David A

2011-08-01

The aim of this study was to evaluate the prognostic implications of computed tomography (CT) and physiologic variables at baseline and on sequential evaluation in patients with fibrosing interstitial pneumonia. We identified 72 patients with fibrosing interstitial pneumonia (42 with idiopathic disease, 30 with collagen vascular disease). Pulmonary function tests and CT were performed at the time of diagnosis and at a median follow-up of 12 months, respectively. Two chest radiologists scored the extent of specific abnormalities and overall disease on baseline and follow-up CT. Rate of survival was estimated using the Kaplan-Meier method. Three Cox proportional hazards models were constructed to evaluate the relationship between CT and physiologic variables and rate of survival: model 1 included only baseline variables, model 2 included only serial change variables, and model 3 included both baseline and serial change variables. On follow-up CT, the extent of mixed ground-glass and reticular opacities (P<0.001), pure reticular opacity (P=0.04), honeycombing (P=0.02), and overall extent of disease (P<0.001) was increased in the idiopathic group, whereas these variables remained unchanged in the collagen vascular disease group. Patients with idiopathic disease had a shorter rate of survival than those with collagen vascular disease (P=0.03). In model 1, the extent of honeycombing on baseline CT was the only independent predictor of mortality (P=0.02). In model 2, progression in honeycombing was the only predictor of mortality (P=0.005). In model 3, baseline extent of honeycombing and progression of honeycombing were the only independent predictors of mortality (P=0.001 and 0.002, respectively). Neither baseline nor serial change physiologic variables, nor the presence of collagen vascular disease, was predictive of rate of survival. The extent of honeycombing at baseline and its progression on follow-up CT are important determinants of rate of survival in patients with fibrosing interstitial pneumonia.

Novel actions of tissue-type plasminogen activator in chronic kidney disease: a paradigm shift

PubMed Central

Hu, Kebin; Mars, Wendy M.; Liu, Youhua

2009-01-01

Tissue-type plasminogen activator (tPA) is traditionally viewed as a simple serine protease whose main function is to convert plasminogen into biologically active plasmin. As a protease, tPA plays a crucial role in regulating blood fibrinolysis, in maintaining the homeostasis of extracellular matrix (ECM) and in modulating the post-translational activation of growth factors. However, emerging evidence indicates that tPA may also function as a cytokine that transmits its signal across the cell membrane, initiates a diverse array of intracellular signaling, and dictates gene expression in the nuclei. Structurally, tPA is a kringle-containing protein that shares significant similarity to other classic cytokines such as hepatocyte growth factor (HGF) and macrophage-stimulating protein (MSP). Although there is no dedicated receptor, tPA binds to the cell membrane low density lipoprotein (LDL) receptor-related protein-1 (LRP-1), triggers LRP-1 tyrosine phosphorylation, and activates various intracellular signaling. As a cytokine, tPA plays a pivotal role in the pathogenesis of renal interstitial fibrosis through diverse mechanisms. It induces matrix matelloproteinase-9 (MMP-9) gene expression in renal interstitial fibroblasts, which causes the destruction of the tubular basement membrane (TBM), thereby facilitating tubular epithelial to mesenchymal transition (EMT). tPA also potentiates myofibroblast activation from quiescent interstitial fibroblasts through LRP-1-mediated recruitment of β1 integrin signaling. Furthermore, tPA acts as a survival factor that protects renal interstitial fibroblasts/myofibroblasts from apoptosis, thereby resulting in an expansion of myofibroblast populations in diseased kidney. Together, a growing body of evidence has implicated tPA as a fibrogenic cytokine that promotes the progression of kidney diseases. These new findings have radically changed our conception of tPA in renal fibrogenesis and represent a paradigm shift towards uncovering its cytokine function. A better understanding of renal tPA biology will ultimately translate into more rational therapeutic remedies for patients with chronic kidney fibrosis. PMID:18508579

The Hydraulic Permeability of Blood Clots as a Function of Fibrin and Platelet Density

PubMed Central

Wufsus, A.R.; Macera, N.E.; Neeves, K.B.

2013-01-01

Interstitial fluid flow within blood clots is a biophysical mechanism that regulates clot growth and dissolution. Assuming that a clot can be modeled as a porous medium, the physical property that dictates interstitial fluid flow is the hydraulic permeability. The objective of this study was to bound the possible values of the hydraulic permeability in clots formed in vivo and present relationships that can be used to estimate clot permeability as a function of composition. A series of clots with known densities of fibrin and platelets, the two major components of a clot, were formed under static conditions. The permeability was calculated by measuring the interstitial fluid velocity through the clots at a constant pressure gradient. Fibrin gels formed with a fiber volume fraction of 0.02–0.54 had permeabilities of 1.2 × 10−1–1.5 × 10−4μm2. Platelet-rich clots with a platelet volume fraction of 0.01–0.61 and a fibrin volume fraction of 0.03 had permeabilities over a range of 1.1 × 10−2–1.5 × 10−5μm2. The permeability of fibrin gels and of clots with platelet volume fraction of <0.2 were modeled as an array of disordered cylinders with uniform diameters. Clots with a platelet volume fraction of >0.2 were modeled as a Brinkman medium of coarse solids (platelets) embedded in a mesh of fine fibers (fibrin). Our data suggest that the permeability of clots formed in vivo can vary by up to five orders of magnitude, with pore sizes that range from 4 to 350 nm. These findings have important implications for the transport of coagulation zymogens/enzymes in the interstitial spaces during clot formation, as well as the design of fibrinolytic drug delivery strategies. PMID:23601328

The X-ray structure of a galaxy cluster at z = 0.54 - Implications for cluster evolution and cosmology

NASA Technical Reports Server (NTRS)

White, S. D. M.; Silk, J.; Henry, J. P.

1981-01-01

High-resolution X-ray observations of the rich cluster 0016+16 at a redshift of 0.541 are presented. The emitting gas in this cluster is hot and extremely luminous, and its structure resembles that seen in the brightest nearby cluster sources. In most of its properties, 0016+16 resembles a richer version of the Coma cluster, and it offers little support to the hypothesis that clusters at z greater than 0.5 differ fundamentally from nearer objects.

Patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma.

PubMed

Mizuno, Ryuichi; Asano, Koichiro; Mikami, Shuji; Nagata, Hirohiko; Kaneko, Gou; Oya, Mototsugu

2012-05-01

To elucidate the patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma, we reviewed seven cases of everolimus-induced interstitial lung disease. Seven patients with metastatic renal cell carcinoma, which continued to progress despite treatment with sunitinib or sorafenib, developed interstitial lung disease after treatment with everolimus. Chest X-ray demonstrated diffuse infiltrates in lung fields, and chest computed tomography showed bilateral reticular and ground-glass opacities. Serum levels of lactate dehydrogenase (7/7), C-reactive protein (6/7), pulmonary surfactant associated protein D (1/7) and Krebs von den Lungen 6 (5/7) were elevated. The bronchoalveolar lavage fluid obtained from four patients with Grade 3 interstitial lung disease showed lymphocytosis. The transbronchial lung biopsy specimens showed interstitial lymphocytic infiltration and septal thickening of alveolar walls. In two cases with mild interstitial lung disease, the everolimus therapy was successfully continued. In four cases with Grade 3 interstitial lung disease, the drug was discontinued and steroid therapy was initiated. Pulmonary symptoms and radiological abnormalities resolved within 2 months. Serum Krebs von den Lungen 6 was elevated compared with baseline in all cases with interstitial lung disease. Some patients who developed mild interstitial lung disease during everolimus treatment could continue to receive the treatment. Even when severe interstitial lung disease developed, withdrawal of the drug and short-term use of high-dose steroids resulted in rapid recovery. Prompt recognition of interstitial lung disease exacerbation as well as exclusion of progressive disease or infection is of primary importance.

Changes in the interstitial fluid and the muscle water in rabbits in hemorrhagic shock.

PubMed Central

Wolcott, M W; Malinin, T I; Wu, N M

1976-01-01

Dynamics and changes in the biochemical composition in the interstitial fluid and the muscle water were studied in hemorrhagic shock. The interstitial fluid was collected from implanted perforated capsules. Muscle biopsies were examined with regard to their water content by the steady state magnetic nuclear resonance spectroscopy. The consistent and what appears to be the most significant changes were the fall in the interstitial fluid pressures, the quantitative reduction of muscle water, a sharp fall in the blood and interstitial blood pH, the moderate hyperkalemia and lack of change in blood an interstitial fluid sodium, and the rise in blood glucose levels not accompanied by a rise in the interstitial fluid glucose levels. PMID:11754

Tubular Epithelial NF-κB Activity Regulates Ischemic AKI

PubMed Central

Vigolo, Emilia; Hinze, Christian; Park, Joon-Keun; Roël, Giulietta; Balogh, András; Choi, Mira; Wübken, Anne; Cording, Jimmi; Blasig, Ingolf E.; Luft, Friedrich C.; Scheidereit, Claus; Schmidt-Ott, Kai M.; Schmidt-Ullrich, Ruth; Müller, Dominik N.

2016-01-01

NF-κB is a key regulator of innate and adaptive immunity and is implicated in the pathogenesis of AKI. The cell type–specific functions of NF-κB in the kidney are unknown; however, the pathway serves distinct functions in immune and tissue parenchymal cells. We analyzed tubular epithelial-specific NF-κB signaling in a mouse model of ischemia-reperfusion injury (IRI)–induced AKI. NF-κB reporter activity and nuclear localization of phosphorylated NF-κB subunit p65 analyses in mice revealed that IRI induced widespread NF-κB activation in renal tubular epithelia and in interstitial cells that peaked 2–3 days after injury. To genetically antagonize tubular epithelial NF-κB activity, we generated mice expressing the human NF-κB super-repressor IκBαΔN in renal proximal, distal, and collecting duct epithelial cells. Compared with control mice, these mice exhibited improved renal function, reduced tubular apoptosis, and attenuated neutrophil and macrophage infiltration after IRI-induced AKI. Furthermore, tubular NF-κB–dependent gene expression profiles revealed temporally distinct functional gene clusters for apoptosis, chemotaxis, and morphogenesis. Primary proximal tubular cells isolated from IκBαΔN-expressing mice and exposed to hypoxia-mimetic agent cobalt chloride exhibited less apoptosis and expressed lower levels of chemokines than cells from control mice did. Our results indicate that postischemic NF-κB activation in renal tubular epithelia aggravates tubular injury and exacerbates a maladaptive inflammatory response. PMID:26823548

Cytogenetic and Molecular Data Support the Occurrence of Three Gymnotus Species (Gymnotiformes: Gymnotidae) Used as Live Bait in Corumbá, Brazil: Implications for Conservation and Management of Professional Fishing.

PubMed

de Sousa, Tatiane Pires; Marques, Débora Karla Silvestre; Vitorino, Carla de Andrade; Faria, Karina de Cassia; Braga, Gisele da Silva Ferreira; Ferreira, Daniela Cristina; Venere, Paulo Cesar

2017-04-01

In the Pantanal of Mato Grosso do Sul, electric fish (Gymnotus spp.) are the primary source of live bait, accounting for more than three-quarters of total sales. Based on chromosomal and molecular markers, the present study attempted to identify the Gymnotus species used as bait in the region of Corumbá, Mato Grosso do Sul, Brazil. Three species were detected, based on their distinct karyotypes: G. paraguensis (2n = 54), G. sylvius (2n = 40), and G. pantanal (2n = 39-40, X 1 X 2 Y/X 1 X 1 X 2 X 2 ), with no evidence being found of interspecific hybrids. All three species presented a single nucleolar organizer regions (NOR) (heterochromatin CMA 3 + /DAPI - ) and pericentromeric heterochromatin in almost all chromosomes, with a few distal and/or interstitial blocks. G. sylvius and G. pantanal had one and two pairs of chromosomes with 5S rDNA sites, respectively, while G. paraguensis had 17 chromosome pairs with these markers. The three species formed well-defined clusters in the DNA barcoding analysis. The integrated analysis of the cytogenetic and DNA barcoding data confirmed that the diversity of Gymnotus species exploited as live bait in the study region has been underestimated. These findings indicate that the markers analyzed represent valuable tools for the conservation and fishery management of the Gymnotus stocks exploited.

[Airway-centered interstitial fibrosis related to exposure to fumes from cleaning products].

PubMed

Serrano, Mario; Molina-Molina, María; Ramírez, José; Sánchez, Marcelo; Xaubet, Antoni

2006-10-01

Airway-centered interstitial fibrosis is a little known clinical entity that has only recently been described in the literature. Its pathology is characterized by bronchial fibrosis and localized interstitial pulmonary fibrosis around the airways. The disease has been associated with inhalation of a variety of substances, environmental or occupational, organic or inorganic. Clinical signs, radiographic manifestations, and lung function in patients with airway-centered interstitial fibrosis are similar to those of patients with idiopathic interstitial pneumonia. We describe a case of airway-centered interstitial fibrosis related to exposure to fumes from cleaning products.

Seizure clustering.

PubMed

Haut, Sheryl R

2006-02-01

Seizure clusters, also known as repetitive or serial seizures, occur commonly in epilepsy. Clustering implies that the occurrence of one seizure may influence the probability of a subsequent seizure; thus, the investigation of the clustering phenomenon yields insights into both specific mechanisms of seizure clustering and more general concepts of seizure occurrence. Seizure clustering has been defined clinically as a number of seizures per unit time and, statistically, as a deviation from a random distribution, or interseizure interval dependence. This review explores the pathophysiology, epidemiology, and clinical implications of clustering, as well as other periodic patterns of seizure occurrence. Risk factors for experiencing clusters and potential precipitants of clustering are also addressed.

ASCA Temperature Maps for Several Interesting Clusters and Their Interpretations

NASA Technical Reports Server (NTRS)

Markevitch, M.; Sarazin, C.; Forman, W.; Vikhlinin, A.

1998-01-01

We present ASCA temperature maps for several galaxy clusters with strong mergers, as well as for several relaxed clusters selected for X-ray mass determination. From the merger temperature maps, we estimate velocities of the colliding subunits and discuss several implications of these estimates. For the relaxed clusters, we derive unprecedentedly accurate mass and gas fraction profiles out to radii of overdensity approximately 500.

Geologic implications of gas hydrates in the offshore of India: results of the National Gas Hydrate Program Expedition 01

USGS Publications Warehouse

Collett, Timothy S.; Boswell, Ray; Cochran, J.R.; Kumar, Pushpendra; Lall, Malcolm; Mazumdar, Aninda; Ramana, Mangipudi Venkata; Ramprasad, Tammisetti; Riedel, Michael; Sain, Kalachand; Sathe, Arun Vasant; Vishwanath, Krishna

2014-01-01

One of the specific objectives of this expedition was to test gas hydrate formation models and constrain model parameters, especially those that account for the formation of concentrated gas hydrate accumulations. The necessary data for characterizing the occurrence of in situ gas hydrate, such as interstitial water chlorinities, core-derived gas chemistry, physical and sedimentological properties, thermal images of the recovered cores, and downhole measured logging data (LWD and/or conventional wireline log data), were obtained from most of the drill sites established during NGHP-01. Almost all of the drill sites yielded evidence for the occurrence of gas hydrate; however, the inferred in situ concentration of gas hydrate varied substantially from site to site. For the most part, the interpretation of downhole logging data, core thermal images, interstitial water analyses, and pressure core images from the sites drilled during NGHP-01 indicate that the occurrence of concentrated gas hydrate is mostly associated with the presence of fractures in the sediments, and in some limited cases, by coarser grained (mostly sand-rich) sediments.

Dysregulated Functions of Lung Macrophage Populations in COPD.

PubMed

Kapellos, Theodore S; Bassler, Kevin; Aschenbrenner, Anna C; Fujii, Wataru; Schultze, Joachim L

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD.

Adherence of Myxobolus cerebralis myxospores to waders: Implications for disease dissemination

USGS Publications Warehouse

Gates, K.K.; Guy, C.S.; Zale, A.V.; Horton, T.B.

2008-01-01

The vectors involved in the spread of whirling disease, which is caused by Myxobolus cerebralis, are only partly understood. However, the parasite has rapidly become established in many regions, suggesting that it is easily disseminated. We gained insight into transport vectors by examining the surface porosity of common wading equipment materials and the adherence of M. cerebralis myxospores to them. Interstitial spaces within rubber, felt, lightweight nylon, and neoprene were measured on scanning electron microscope images. Myxospores were applied to each material, the material was rinsed, and the myxospores recovered to assess adherence. The mean interstitial space size of rubber was the smallest (2.0 ??m), whereas that of felt was the largest (31.3 ??m). The highest recovery rates were from rubber and the glass control. Percent myxospore recovery varied by material, the recovery from felt being lower than that from all other materials. The potential for felt to carry even small numbers of myxospores suggests that the introduction of M. cerebralis by felt-soled wading boots is possible. ?? Copyright by the American Fisheries Society 2008.

Dysregulated Functions of Lung Macrophage Populations in COPD

PubMed Central

Bassler, Kevin; Aschenbrenner, Anna C.

2018-01-01

Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. PMID:29670919

Molecular dynamics study of the role of symmetric tilt grain boundaries on the helium distribution in nickel

NASA Astrophysics Data System (ADS)

Torres, E.; Pencer, J.

2018-04-01

Helium impurities, from either direct implantation or transmutation reactions, have been associated with embrittlement in nickel-based alloys. Helium has very low solubility in nickel, and has been found to aggregate at lattice defects such as vacancies, dislocations, and grain boundaries. The retention and precipitation of helium in nickel-based alloys have deleterious effects on the material mechanical properties. However, the underlying mechanisms that lead to helium effects in the host metal are not fully understood. In the present work, we investigate the role of symmetric tilt grain boundary (STGB) structures on the distribution of helium in nickel using molecular dynamics simulations. We investigate the family of STGBs specific to the 〈 110 〉 tilt axis. The present results indicate that accumulation of helium at the grain boundary may be modulated by details of grain boundary geometry. A plausible correlation between the grain boundary energy and misorientation with the accumulation and mobility of helium is proposed. Small clusters with up to 6 helium atoms show significant interstitial mobility in the nickel bulk, but also become sites for nucleation and grow of more stable helium clusters. High-energy GBs are found mainly populated with small helium clusters. The high mobility of small clusters along the GBs indicates the role of these GBs as fast two-dimensional channels for diffusion. In contrast, the accumulation of helium in large helium clusters at low-energy STGB creates a favorable environment for the formation of large helium bubbles, indicating a potential role for low-energy STGB in promoting helium-induced GB embrittlement.

Interstitial space and collagen alterations of the developing rat diaphragm

NASA Technical Reports Server (NTRS)

Gosselin, L. E.; Martinez, D. A.; Vailas, A. C.; Sieck, G. C.

1993-01-01

The effect of growth on the relative interstitial space [%total cross-sectional area (CSA)] and collagen content of the rat diaphragm muscle was examined at postnatal ages of 0, 7, 14, and 21 days as well as in adult males. The proportion of interstitial space relative to total muscle CSA was determined by computerized image analysis of lectin-stained cross sections of diaphragm muscle. To assess collagen content and extent of collagen maturation (i.e., cross-linking), high-pressure liquid chromatography analysis was used to measure hydroxyproline concentration and the nonreducible collagen cross-link hydroxylysylpyridinoline (HP), respectively. At birth, interstitial space accounted for approximately 47% of total diaphragm muscle CSA. During postnatal growth, the relative contribution of interstitial space decreased such that by adulthood the interstitial space accounted for approximately 18% of total muscle CSA. The change in relative interstitial space occurred without a concomitant change in hydroxyproline concentration. However, the concentration of HP markedly increased with age such that the adult diaphragm contained approximately 17 times more HP than at birth. These results indicate that during development the relative CSA occupied by interstitial space decreases as muscle fiber size increases. However, the reduction in relative interstitial space is not associated with a change in collagen concentration. Thus collagen density in the interstitial space may increase with age. It is possible that the observed changes in relative interstitial space and collagen influence the passive length-force properties of the diaphragm.

Puncture-ejection of own egg by Least Bell's Vireo and potential implications for anti-parasitism defense

USGS Publications Warehouse

Sharp, Bryan L.; Peterson, Bonnie L.; Kus, Barbara E.

2005-01-01

A simple, papillary cystic adenocarcinoma of the mammary gland with metastases to the internal iliac and mesenteric lymph nodes, liver, and spleen was observed in a 12 to 13 year old female black-footed ferret (Mustela nigripes). Histologically, the tumor was aggressive, and lymphatic invasion was found. Attempts at virus isolation were negative. Other findings were bilateral infarcts in the kidneys, apparently resulting in acute renal shutdown and death, multiple thrombi in the right atrium, aortic arteriosclerosis, and focal interstitial pneumonia.

Study of irradiation induced surface pattern and structural changes in Inconel 718 alloy

NASA Astrophysics Data System (ADS)

Wan, Hao; Si, Naichao; Zhao, Zhenjiang; Wang, Jian; Zhang, Yifei

2018-05-01

Helium ions irradiation induced surface pattern and structural changes of Inconel 718 alloy were studied with the combined utilization of atomic force microscopy (AFM), x-ray diffraction (XRD) and transmission electron microscopy (TEM). In addition, SRIM-2013 software was used to calculate the sputtering yield and detailed collision events. The result shows that, irradiation dose play an important role in altering the pattern of the surface. Enhanced irradiation aggravated the surface etching and increased the surface roughness. In ion irradiated layer, large amount of interstitials, vacancies and defect sinks were produced. Moreover, in samples with increasing dose irradiation, the dependence of interplanar spacing variation due to point defects clustering on sink density was discussed.

Di-μ-cyanido-tetra-cyanido(5,5,7,12,12,14-hexa-methyl-1,4,8,11-tetra-aza-cyclo-tetra-decane)[N-(quinolin-8-yl)quinoline-2-carboxamidato]diiron(III)nickel(II) 2.07-hydrate.

PubMed

Yang, Yuqi; Zhou, Hongbo; Shen, Xiaoping

2013-05-01

The asymmetric unit of the title complex, [Fe2Ni(C19H12N3O)2(CN)6(C16H36N4)]·2.07H2O, contains one [Fe(qcq)(CN)3](-) anion, half a [Ni(teta)](2+) cation and two partially occupied inter-stitial water mol-ecules [qcq(-) is the N-(quinolin-8-yl)quinoline-2-carboxamidate anion and teta is 5,5,7,12,12,14-hexa-methyl-1,4,8,11-tetra-aza-cyclo-tetra-deca-ne]. In the complex mol-ecule, two [Fe(qcq)(CN)3](-) anions additionally coordinate the central [Ni(teta)](2+) cation through cyanide groups in a trans mode, resulting in a trinuclear structure with the Ni(2+) cation lying on an inversion centre. The two inter-stitial water mol-ecules are partially occupied, with occupancy factors of 0.528 (10) and 0.506 (9). O-H⋯O and O-H⋯N hydrogen bonding involving the two lattice water molecules and the carbonyl function and a teta N atom in an adjacent cluster leads to the formation of layers extending parallel to (010).

Synthesized interstitial lung texture for use in anthropomorphic computational phantoms

NASA Astrophysics Data System (ADS)

Becchetti, Marc F.; Solomon, Justin B.; Segars, W. Paul; Samei, Ehsan

2016-04-01

A realistic model of the anatomical texture from the pulmonary interstitium was developed with the goal of extending the capability of anthropomorphic computational phantoms (e.g., XCAT, Duke University), allowing for more accurate image quality assessment. Contrast-enhanced, high dose, thorax images for a healthy patient from a clinical CT system (Discovery CT750HD, GE healthcare) with thin (0.625 mm) slices and filtered back- projection (FBP) were used to inform the model. The interstitium which gives rise to the texture was defined using 24 volumes of interest (VOIs). These VOIs were selected manually to avoid vasculature, bronchi, and bronchioles. A small scale Hessian-based line filter was applied to minimize the amount of partial-volumed supernumerary vessels and bronchioles within the VOIs. The texture in the VOIs was characterized using 8 Haralick and 13 gray-level run length features. A clustered lumpy background (CLB) model with added noise and blurring to match CT system was optimized to resemble the texture in the VOIs using a genetic algorithm with the Mahalanobis distance as a similarity metric between the texture features. The most similar CLB model was then used to generate the interstitial texture to fill the lung. The optimization improved the similarity by 45%. This will substantially enhance the capabilities of anthropomorphic computational phantoms, allowing for more realistic CT simulations.

Prion protein- and cardiac troponin T-marked interstitial cells from the adult myocardium spontaneously develop into beating cardiomyocytes

PubMed Central

Omatsu-Kanbe, Mariko; Nishino, Yuka; Nozuchi, Nozomi; Sugihara, Hiroyuki; Matsuura, Hiroshi

2014-01-01

Atypically-shaped cardiomyocytes (ACMs) constitute a novel subpopulation of beating heart cells found in the cultures of cardiac myocyte-removed crude fraction cells obtained from adult mouse cardiac ventricles. Although ~500 beating ACMs are observed under microscope in the cell cultures obtained from the hearts of either male or female mice, the origin of these cells in cardiac tissue has yet to be elucidated due to the lack of exclusive markers. In the present study, we demonstrate the efficacy of cellular prion protein (PrP) as a surface marker of ACMs. Cells expressing PrP at the plasma membrane in the culture of the crude fraction cells were found to develop into beating ACMs by themselves or fuse with each other to become larger multinuclear beating ACMs. Combining PrP with a cardiac-specific contractile protein cardiac troponin T (cTnT) allowed us to identify native ACMs in the mouse cardiac ventricles as either clustered or solitary cells. PrP- and cTnT-marked cells were also found in the adult, even aged, human cardiac ventricles. These findings suggest that interstitial cells marked by PrP and cTnT, native ACMs, exhibit life-long survival in the cardiac ventricles of both mice and humans. PMID:25466571

Effect of W self-implantation and He plasma exposure on early-stage defect and bubble formation in tungsten

NASA Astrophysics Data System (ADS)

Thompson, M.; Drummond, D.; Sullivan, J.; Elliman, R.; Kluth, P.; Kirby, N.; Riley, D.; Corr, C. S.

2018-06-01

To determine the effect of pre-existing defects on helium-vacancy cluster nucleation and growth, tungsten samples were self-implanted with 1 MeV tungsten ions at varying fluences to induce radiation damage, then subsequently exposed to helium plasma in the MAGPIE linear plasma device. Positron annihilation lifetime spectroscopy was performed both immediately after self-implantation, and again after plasma exposure. After self-implantation vacancies clusters were not observed near the sample surface (<30 nm). At greater depths (30–150 nm) vacancy clusters formed, and were found to increase in size with increasing W-ion fluence. After helium plasma exposure in the MAGPIE linear plasma device at ~300 K with a fluence of 1023 He-m‑2, deep (30–150 nm) vacancy clusters showed similar positron lifetimes, while shallow (<30 nm) clusters were not observed. The intensity of positron lifetime signals fell for most samples after plasma exposure, indicating that defects were filling with helium. The absence of shallow clusters indicates that helium requires pre-existing defects in order to drive vacancy cluster growth at 300 K. Further samples that had not been pre-damaged with W-ions were also exposed to helium plasma in MAGPIE across fluences from 1  ×  1022 to 1.2  ×  1024 He-m‑2. Samples exposed to fluences up to 1  ×  1023 He-m‑2 showed no signs of damage. Fluences of 5  ×  1023 He-m‑2 and higher showed significant helium-cluster formation within the first 30 nm, with positron lifetimes in the vicinity 0.5–0.6 ns. The sample temperature was significantly higher for these higher fluence exposures (~400 K) due to plasma heating. This higher temperature likely enhanced bubble formation by significantly increasing the rate interstitial helium clusters generate vacancies, which is we suspect is the rate-limiting step for helium-vacancy cluster/bubble nucleation in the absence of pre-existing defects.

Differences Between Ward's and UPGMA Methods of Cluster Analysis: Implications for School Psychology.

ERIC Educational Resources Information Center

Hale, Robert L.; Dougherty, Donna

1988-01-01

Compared the efficacy of two methods of cluster analysis, the unweighted pair-groups method using arithmetic averages (UPGMA) and Ward's method, for students grouped on intelligence, achievement, and social adjustment by both clustering methods. Found UPGMA more efficacious based on output, on cophenetic correlation coefficients generated by each…

Paragenesis of multiple platinum-group mineral populations in Shetland ophiolite chromitite: 3D X-ray tomography and in situ Os isotopes

NASA Astrophysics Data System (ADS)

Prichard, H. M.; Barnes, Stephen J.; Dale, C. W.; Godel, B.; Fisher, P. C.; Nowell, G. M.

2017-11-01

Chromitite from the Harold's Grave locality in the mantle section of the Shetland ophiolite complex is extremely enriched in Ru, Os and Ir, at μg/g concentrations. High-resolution X-ray computed tomography on micro-cores from these chromitites was used to determine the location, size, distribution and morphology of the platinum-group minerals (PGM). There are five generations of PGM in these chromitites. Small (average 5 μm in equivalent sphere diameter, ESD) euhedral laurites, often with Os-Ir alloys, are totally enclosed in the chromite and are likely to have formed first by direct crystallisation from the magma as the chromite crystallised. Also within the chromitite there are clusters of larger (50 μm ESD) aligned elongate crystals of Pt-, Rh-, Ir-, Os- and Ru-bearing PGM that have different orientations in different chromite crystals. These may have formed either by exsolution, or by preferential nucleation of PGMs in boundary layers around particular growing chromite grains. Thirdly there is a generation of large (100 μm ESD) composite Os-Ir-Ru-rich PGM that are all interstitial to the chromite grains and sometimes form in clusters. It is proposed that Os, Ir and Ru in this generation were concentrated in base metal sulfide droplets that were then re-dissolved into a later sulfide-undersaturated magma, leaving PGM interstitial to the chromite grains. Fourthly there is a group of almost spherical large (80 μm ESD) laurites, hosting minor Os-Ir-Ru-rich PGM that form on the edge or enclosed in chromite grains occurring in a sheet crosscutting a chromitite layer. These may be hosted in an annealed late syn- or post magmatic fracture. Finally a few of the PGM have been deformed in localised shear zones through the chromitites. The vast majority of the PGM - including small PGM enclosed within chromite, larger interstitial PGM and elongate aligned PGM - have Os isotope compositions that give Re-depletion model ages approximately equal to the age of the ophiolite at ∼492 Ma. A number of other PGM - not confined to a single textural group - fall to more or less radiogenic values, with four PGM giving anomalously unradiogenic Os corresponding to an older age of ∼1050 Ma. The 187Os/188Os isotopic ratios for PGM from Cliff and Quoys, from the same ophiolite section, are somewhat more radiogenic than those at Harold's Grave. This may be due to a distinct mantle source history or possibly the assimilation of radiogenic crustal Os.

Interstitial nephritis.

PubMed

Papper, S

1980-01-01

There are many causes of interstitial nephritis other than pyelonephritis. The term interstitial nephritis does not connote a single etiologic or pathogenetic mechanism; it rather arbitrarily places together a wider variety of renal diseases that have a predilection for early and major involvement of the renal interstitium. The prototype of acute interstitial nephritis is acute pyelonephritis. In addition, there is a drug-related acute interstitial disease that is probably of immunological nature and usually reverses with discontinuance of the offending drug. Chronic interstitial nephritis includes many diverse illnesses. Nonobstructive pyelonephritis occurs but its prevalence is debated. Analgesic abuse nephropathy is not rare and is potentially reversible. Papillary necrosis has many causes and a wide spectrum of clinical presentations. Heavy metals, such as lead, cause interstitial nephritis. Balkan nephropathy occurs in an endemic area and although not bacterial in origin is of unknown cause.

Balance point characterization of interstitial fluid volume regulation.

PubMed

Dongaonkar, R M; Laine, G A; Stewart, R H; Quick, C M

2009-07-01

The individual processes involved in interstitial fluid volume and protein regulation (microvascular filtration, lymphatic return, and interstitial storage) are relatively simple, yet their interaction is exceedingly complex. There is a notable lack of a first-order, algebraic formula that relates interstitial fluid pressure and protein to critical parameters commonly used to characterize the movement of interstitial fluid and protein. Therefore, the purpose of the present study is to develop a simple, transparent, and general algebraic approach that predicts interstitial fluid pressure (P(i)) and protein concentrations (C(i)) that takes into consideration all three processes. Eight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for P(i) and C(i) as functions of parameters characterizing microvascular, interstitial, and lymphatic function. Equilibrium values of P(i) and C(i) arise as balance points from the graphical intersection of transmicrovascular and lymph flows (analogous to Guyton's classical cardiac output-venous return curves). This approach goes beyond describing interstitial fluid balance in terms of conservation of mass by introducing the concept of inflow and outflow resistances. Algebraic solutions demonstrate that P(i) and C(i) result from a ratio of the microvascular filtration coefficient (1/inflow resistance) and effective lymphatic resistance (outflow resistance), and P(i) is unaffected by interstitial compliance. These simple algebraic solutions predict P(i) and C(i) that are consistent with reported measurements. The present work therefore presents a simple, transparent, and general balance point characterization of interstitial fluid balance resulting from the interaction of microvascular, interstitial, and lymphatic function.

Implications of using thermocouple thermometry in 27 MHz capacitively coupled interstitial hyperthermia.

PubMed

Crezee, J; van der Koijk, J F; Kaatee, R S; Lagendijk, J J

1997-04-01

The 27 MHz Multi Electrode Current Source (MECS) interstitial hyperthermia system uses segmented electrodes, 10-20 mm long, to steer the 3D power deposition. This power control at a scale of 1-2 cm requires detailed and accurate temperature feedback data. To this end seven-point thermocouples are integrated into the probes. The aim of this work was to evaluate the feasibility and reliability of integrated thermometry in the 27 MHz MECS system, with special attention to the interference between electrode and thermometry and its effect on system performance. We investigated the impact of a seven-sensor thermocouple probe (outer diameter 150 microns) on the apparent impedance and power output of a 20 mm dual electrode (O.D. 1.5 mm) in a polyethylene catheter in a muscle equivalent medium (sigma 1 = 0.6 S m-1). The cross coupling between electrode and thermocouple was found to be small (1-2 pF) and to cause no problems in the dual-electrode mode, and only minimal problems in the single-electrode mode. Power loss into the thermometry system can be prevented using simple filters. The temperature readings are reliable and representative of the actual tissue temperature around the electrode. Self-heating effects, occurring in some catheter materials, are eliminated by sampling the temperature after a short power-off interval. We conclude that integrated thermocouple thermometry is compatible with 27 MHz capacitively coupled interstitial hyperthermia. The performance of the system is not affected and the temperatures measured are a reliable indication of the maximum tissue temperatures.

Transcapillary fluid shifts in head and neck tissues during and after simulated microgravity

NASA Technical Reports Server (NTRS)

Parazynski, S. E.; Hargens, Alan R.; Tucker, B.; Aratow, M.; Styf, J.; Crenshaw, A.

1991-01-01

To understand the mechanism, magnitude, and time course of facial puffiness that occurs in microgravity, seven male subjects were tilted 6 degrees head down for 8 hr, and all four Starling transcapillary pressures were directly measured before, during, and after tilt. Head-down tilt (HDT) caused facial edema and a significant elevation of microvascular pressures measured in the lower lip: capillary pressures increased from 27.2 +/- 5 mm Hg pre-HDT to 33.9 +/- 1.7 mm Hg by the end of tilt. Subcutaneous and intramuscular interstitial fluid pressures in the neck also increased as a result of HDT, while interstitial fluid colloid osmotic pressures remained unchanged. Plasma colloid osmotic pressures dropped significantly after 4 hr of HDT, suggesting a transition from fluid filtration to absorption in capillary beds between the heart and feet during HDT. After 4 hr of seated recovery from HDT, microvascular pressures remained significantly elevated by 5 to 8 mm Hg above baseline values, despite a significant HDT diuresis and the orthostatic challenge of an upright, seated posture. During the control (baseline) period, urine output was 46.7 ml/hr; during HDT, it was 126.5 ml/hr. These results indicate that facial edema resulting from HDT is primarily caused by elevated capillary pressures and decreased plasma colloid osmotic pressures. Elevation of cephalic capillary pressures sustained for 4 hr after HDT suggests that there is a compensatory vasodilation to maintain microvascular perfusion. The negativity of interstitial fluid pressures above heart level also has implications for the maintenance of tissue fluid balance in upright posture.

A case of acute kidney injury caused by granulomatous interstitial nephritis associated with sarcoidosis.

PubMed

Horino, Taro; Matsumoto, Tatsuki; Inoue, Kosuke; Ichii, Osamu; Terada, Yoshio

2018-05-01

Sarcoidosis affects multiple organs including lung, heart and kidney. Sarcoidosis causes hypercalcemia, hypergammaglobulinemia, and rarely, granulomatous interstitial nephritis, resulting in renal stromal damage. Granulomatous interstitial nephritis is characterized as interstitial nephritis with noncaseating epithelioid granulomas. Diagnosing granulomatous interstitial nephritis before patient's death is challenging; hence, only few cases proven by renal biopsy have been reported till date. We present a case of acute kidney injury caused by granulomatous interstitial nephritis as a renal manifestation of sarcoidosis proven by renal biopsy, which can be confirmed by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Glucocorticoid therapy was helpful for improving and maintaining her renal function over a 6-year period.

Lowest-energy structures of (C60)nX (X=Li+,Na+,K+,Cl-) and (C60)nYCl (Y=Li,Na,K) clusters for n

PubMed

Hernández-Rojas, J; Bretón, J; Gomez Llorente, J M; Wales, D J

2004-12-22

Basin-hopping global optimization is used to find likely candidates for the lowest minima on the potential energy surface of (C(60))(n)X (X=Li(+),Na(+),K(+),Cl(-)) and (C(60))(n)YCl (Y=Li,Na,K) clusters with n

Evolution of anisotropy in bcc Fe distorted by interstitial boron

NASA Astrophysics Data System (ADS)

Gölden, Dominik; Zhang, Hongbin; Radulov, Iliya; Dirba, Imants; Komissinskiy, Philipp; Hildebrandt, Erwin; Alff, Lambert

2018-01-01

The evolution of magnetic anisotropy in bcc Fe as a function of interstitial boron atoms was investigated in thin films grown by molecular beam epitaxy. The thermodynamic nonequilibrium conditions during film growth allowed one to stabilize an interstitial boron content of about 14 at .% accompanied by lattice tetragonalization. The c /a ratio scaled linearly with the boron content up to a maximum value of 1.05 at 300 °C substrate growth temperature, with a room-temperature magnetization of. In contrast to nitrogen interstitials, the magnetic easy axis remained in-plane with an anisotropy of approximately -5.1 ×106erg /cm3 . Density functional theory calculations using the measured lattice parameters confirm this value and show that boron local ordering indeed favors in-plane magnetization. Given the increased temperature stability of boron interstitials as compared to nitrogen interstitials, this study will help to find possible ways to manipulate boron interstitials into a more favorable local order.

Core-halo age gradients and star formation in the Orion Nebula and NGS 2024 young stellar clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Getman, Konstantin V.; Feigelson, Eric D.; Kuhn, Michael A.

2014-06-01

We analyze age distributions of two nearby rich stellar clusters, the NGC 2024 (Flame Nebula) and Orion Nebula cluster (ONC) in the Orion molecular cloud complex. Our analysis is based on samples from the MYStIX survey and a new estimator of pre-main sequence (PMS) stellar ages, Age{sub JX} , derived from X-ray and near-infrared photometric data. To overcome the problem of uncertain individual ages and large spreads of age distributions for entire clusters, we compute median ages and their confidence intervals of stellar samples within annular subregions of the clusters. We find core-halo age gradients in both the NGC 2024more » cluster and ONC: PMS stars in cluster cores appear younger and thus were formed later than PMS stars in cluster peripheries. These findings are further supported by the spatial gradients in the disk fraction and K-band excess frequency. Our age analysis is based on Age{sub JX} estimates for PMS stars and is independent of any consideration of OB stars. The result has important implications for the formation of young stellar clusters. One basic implication is that clusters form slowly and the apparent age spreads in young stellar clusters, which are often controversial, are (at least in part) real. The result further implies that simple models where clusters form inside-out are incorrect and more complex models are needed. We provide several star formation scenarios that alone or in combination may lead to the observed core-halo age gradients.« less

Chylothorax in dermatomyositis complicated with interstitial pneumonia.

PubMed

Isoda, Kentaro; Kiboshi, Takao; Shoda, Takeshi

2017-04-01

Chylothorax is a disease in which chyle leaks and accumulates in the thoracic cavity. Interstitial pneumonia and pneumomediastinum are common thoracic manifestations of dermatomyositis, but chylothorax complicated with dermatomyositis is not reported. We report a case of dermatomyositis with interstitial pneumonia complicated by chylothorax. A 77-year-old woman was diagnosed as dermatomyositis with Gottron's papules, skin ulcers, anti-MDA5 antibody and rapid progressive interstitial pneumonia. Treatment with betamethasone, tacrolimus and intravenous high-dose cyclophosphamide was initiated, and her skin symptoms and interstitial pneumonia improved once. However, right-sided chylothorax began to accumulate and gradually increase, and at the same time, her interstitial pneumonia began to exacerbate, and skin ulcers began to reappear on her fingers and auricles. Although her chylothorax improved by fasting and parenteral nutrition, she died due to further exacerbations of dermatomyositis and interstitial pneumonia in spite of steroid pulse therapy, increase in the betamethasone dosage, additional intravenous high-dose cyclophosphamide and plasma pheresis. An autopsy showed no lesions such as malignant tumors in the thoracic cavity. This is the first report of chylothorax complicated by dermatomyositis with interstitial pneumonia.

An Exome Sequencing Study to Assess the Role of Rare Genetic Variation in Pulmonary Fibrosis.

PubMed

Petrovski, Slavé; Todd, Jamie L; Durheim, Michael T; Wang, Quanli; Chien, Jason W; Kelly, Fran L; Frankel, Courtney; Mebane, Caroline M; Ren, Zhong; Bridgers, Joshua; Urban, Thomas J; Malone, Colin D; Finlen Copeland, Ashley; Brinkley, Christie; Allen, Andrew S; O'Riordan, Thomas; McHutchison, John G; Palmer, Scott M; Goldstein, David B

2017-07-01

Idiopathic pulmonary fibrosis (IPF) is an increasingly recognized, often fatal lung disease of unknown etiology. The aim of this study was to use whole-exome sequencing to improve understanding of the genetic architecture of pulmonary fibrosis. We performed a case-control exome-wide collapsing analysis including 262 unrelated individuals with pulmonary fibrosis clinically classified as IPF according to American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines (81.3%), usual interstitial pneumonia secondary to autoimmune conditions (11.5%), or fibrosing nonspecific interstitial pneumonia (7.2%). The majority (87%) of case subjects reported no family history of pulmonary fibrosis. We searched 18,668 protein-coding genes for an excess of rare deleterious genetic variation using whole-exome sequence data from 262 case subjects with pulmonary fibrosis and 4,141 control subjects drawn from among a set of individuals of European ancestry. Comparing genetic variation across 18,668 protein-coding genes, we found a study-wide significant (P < 4.5 × 10 -7 ) case enrichment of qualifying variants in TERT, RTEL1, and PARN. A model qualifying ultrarare, deleterious, nonsynonymous variants implicated TERT and RTEL1, and a model specifically qualifying loss-of-function variants implicated RTEL1 and PARN. A subanalysis of 186 case subjects with sporadic IPF confirmed TERT, RTEL1, and PARN as study-wide significant contributors to sporadic IPF. Collectively, 11.3% of case subjects with sporadic IPF carried a qualifying variant in one of these three genes compared with the 0.3% carrier rate observed among control subjects (odds ratio, 47.7; 95% confidence interval, 21.5-111.6; P = 5.5 × 10 -22 ). We identified TERT, RTEL1, and PARN-three telomere-related genes previously implicated in familial pulmonary fibrosis-as significant contributors to sporadic IPF. These results support the idea that telomere dysfunction is involved in IPF pathogenesis.

Smoking-related interstitial lung diseases.

PubMed

Caminati, A; Graziano, P; Sverzellati, N; Harari, S

2010-12-01

In pulmonary pathology, a wide spectrum of morphological changes is related to the consequences of smoking, and recognizing them on surgical specimens and on small transbronchial biopsies represents a challenge for the pathologist. Respiratory bronchiolitis, also referred to as smoker's bronchiolitis, is a common histologic feature found in the lung tissue of cigarette smokers. When identified as the sole histopathologic finding in the clinical setting of symptomatic interstitial lung disease, a diagnosis of respiratory bronchiolitis-interstitial lung disease is made. Since smoking is recognized to cause a variety of histologic patterns encompassing respiratory bronchiolitis, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia and pulmonary Langerhans cell hystiocytosis, smoking-related interstitial lung disease may be a useful concept to keep in mind for the pathologists. The relationship of smoking with each of these entities has been largely established on the basis of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. Recently, respiratory bronchiolitis-interstitial lung disease with fibrosis has been described and postulated that this is a smoking-related condition distinct from fibrotic non-specific interstitial pneumonia.

Proteomics detection of S100A6 in tumor tissue interstitial fluid and evaluation of its potential as a biomarker of cholangiocarcinoma.

PubMed

Onsurathum, Sudarat; Haonon, Ornuma; Pinlaor, Porntip; Pairojkul, Chawalit; Khuntikeo, Narong; Thanan, Raynoo; Roytrakul, Sittiruk; Pinlaor, Somchai

2018-04-01

Tumor interstitial fluid contains tumor-specific proteins that may be useful biomarkers for cancers. In this study, we identified proteins present in cholangiocarcinoma interstitial fluid. Proteins derived from three samples of tumor interstitial fluid and paired samples of adjacent normal interstitial fluid from cholangiocarcinoma patients were subjected to two-dimensional liquid chromatography with tandem mass spectrometry. Candidate proteins were selected based on a greater than twofold change in expression levels between tumor interstitial fluid and normal interstitial fluid. Upregulation of six proteins in tumor interstitial fluid, including S100 calcium binding protein A6 (S100A6), S100 calcium binding protein A9, aldo-keto reductase family 1 member C4, neuropilin-1, 14-3-3 zeta/delta, and triosephosphate isomerase was assessed by western blot and immunohistochemistry. Their potential as markers was evaluated in human cholangiocarcinoma tissue arrays, and in serum using enzyme-linked immunosorbent assay. Expression of S100A6 was higher in tumor interstitial fluid than in normal interstitial fluid and showed the highest positive rate (98.96%) in cholangiocarcinoma tissues. Serum levels of S100A6 did not differ between cholangitis and cholangiocarcinoma patients, but were significantly higher than in healthy individuals ( p < 0.0001). In cholangiocarcinoma cases, S100A6 level was associated with vascular invasion ( p = 0.007) and could distinguish cholangiocarcinoma patients from healthy individuals as effectively as the carbohydrate antigen 19-9. In addition, potential for drug treatment targeting S100A6 and other candidate proteins was also demonstrated using STITCH analysis. In conclusion, proteomics analysis of tumor interstitial fluid could be a new approach for biomarker discovery, and S100A6 is a potential risk marker for screening of cholangiocarcinoma.

Geographic Clustering of Cardiometabolic Risk Factors in Metropolitan Centres in France and Australia

PubMed Central

Paquet, Catherine; Chaix, Basile; Howard, Natasha J.; Coffee, Neil T.; Adams, Robert J.; Taylor, Anne W.; Thomas, Frédérique; Daniel, Mark

2016-01-01

Understanding how health outcomes are spatially distributed represents a first step in investigating the scale and nature of environmental influences on health and has important implications for statistical power and analytic efficiency. Using Australian and French cohort data, this study aimed to describe and compare the extent of geographic variation, and the implications for analytic efficiency, across geographic units, countries and a range of cardiometabolic parameters (Body Mass Index (BMI) waist circumference, blood pressure, resting heart rate, triglycerides, cholesterol, glucose, HbA1c). Geographic clustering was assessed using Intra-Class Correlation (ICC) coefficients in biomedical cohorts from Adelaide (Australia, n = 3893) and Paris (France, n = 6430) for eight geographic administrative units. The median ICC was 0.01 suggesting 1% of risk factor variance attributable to variation between geographic units. Clustering differed by cardiometabolic parameters, administrative units and countries and was greatest for BMI and resting heart rate in the French sample, HbA1c in the Australian sample, and for smaller geographic units. Analytic inefficiency due to clustering was greatest for geographic units in which participants were nested in fewer, larger geographic units. Differences observed in geographic clustering across risk factors have implications for choice of geographic unit in sampling and analysis, and highlight potential cross-country differences in the distribution, or role, of environmental features related to cardiometabolic health. PMID:27213423

Nursing home care quality: a cluster analysis.

PubMed

Grøndahl, Vigdis Abrahamsen; Fagerli, Liv Berit

2017-02-13

Purpose The purpose of this paper is to explore potential differences in how nursing home residents rate care quality and to explore cluster characteristics. Design/methodology/approach A cross-sectional design was used, with one questionnaire including questions from quality from patients' perspective and Big Five personality traits, together with questions related to socio-demographic aspects and health condition. Residents ( n=103) from four Norwegian nursing homes participated (74.1 per cent response rate). Hierarchical cluster analysis identified clusters with respect to care quality perceptions. χ 2 tests and one-way between-groups ANOVA were performed to characterise the clusters ( p<0.05). Findings Two clusters were identified; Cluster 1 residents (28.2 per cent) had the best care quality perceptions and Cluster 2 (67.0 per cent) had the worst perceptions. The clusters were statistically significant and characterised by personal-related conditions: gender, psychological well-being, preferences, admission, satisfaction with staying in the nursing home, emotional stability and agreeableness, and by external objective care conditions: healthcare personnel and registered nurses. Research limitations/implications Residents assessed as having no cognitive impairments were included, thus excluding the largest group. By choosing questionnaire design and structured interviews, the number able to participate may increase. Practical implications Findings may provide healthcare personnel and managers with increased knowledge on which to develop strategies to improve specific care quality perceptions. Originality/value Cluster analysis can be an effective tool for differentiating between nursing homes residents' care quality perceptions.

Energy spectra of X-ray clusters of galaxies

NASA Technical Reports Server (NTRS)

Avni, Y.

1976-01-01

A procedure for estimating the ranges of parameters that describe the spectra of X-rays from clusters of galaxies is presented. The applicability of the method is proved by statistical simulations of cluster spectra; such a proof is necessary because of the nonlinearity of the spectral functions. Implications for the spectra of the Perseus, Coma, and Virgo clusters are discussed. The procedure can be applied in more general problems of parameter estimation.

Initial conditions of formation of starburst clusters: constraints from stellar dynamics

NASA Astrophysics Data System (ADS)

Banerjee, Sambaran

2017-03-01

How starburst clusters form out of molecular clouds is still an open question. In this article, I highlight some of the key constraints in this regard, that one can get from the dynamical evolutionary properties of dense stellar systems. I particularly focus on secular expansion of massive star clusters and hierarchical merging of sub-clusters, and discuss their implications vis-á-vis the observed properties of young massive clusters. The analysis suggests that residual gas expulsion is necessary for shaping these clusters as we see them today, irrespective of their monolithic or hierarchical mode of formation.

Alveolar epithelial cells undergo epithelial-mesenchymal transition in acute interstitial pneumonia: a case report

PubMed Central

2014-01-01

Background Acute interstitial pneumonia is a rare interstitial lung disease that rapidly progresses to respiratory failure or death. Several studies showed that myofibroblast plays an important role in the evolution of diffuse alveolar damage, which is the typical feature of acute interstitial pneumonia. However, no evidence exists whether alveolar epithelial cells are an additional source of myofibroblasts via epithelial-mesenchymal transition in acute interstitial pneumonia. Case presentation In this report, we present a case of acute interstitial pneumonia in a previously healthy 28-year-old non-smoking woman. Chest high-resolution computed tomography scan showed bilateral and diffusely ground-glass opacification. The biopsy was performed on the fifth day of her hospitalization, and results showed manifestation of acute exudative phase of diffuse alveolar damage characterized by hyaline membrane formation. On the basis of the preliminary diagnosis of acute interstitial pneumonia, high-dose glucocorticoid was used. However, this drug showed poor clinical response and could improve the patient’s symptoms only during the early phase. The patient eventually died of respiratory dysfunction. Histological findings in autopsy were consistent with the late form of acute interstitial pneumonia. Conclusions The results in this study revealed that alveolar epithelial cells underwent epithelial-mesenchymal transition and may be an important origin of myofibroblasts in the progression of acute interstitial pneumonia. Conducting research on the transformation of alveolar epithelial cells into myofibroblasts in the lung tissue of patients with acute interstitial pneumonia may be beneficial for the treatment of this disease. However, to our knowledge, no research has been conducted on this topic. PMID:24755111

Fuzzy-C-Means Clustering Based Segmentation and CNN-Classification for Accurate Segmentation of Lung Nodules

PubMed

K, Jalal Deen; R, Ganesan; A, Merline

2017-07-27

Objective: Accurate segmentation of abnormal and healthy lungs is very crucial for a steadfast computer-aided disease diagnostics. Methods: For this purpose a stack of chest CT scans are processed. In this paper, novel methods are proposed for segmentation of the multimodal grayscale lung CT scan. In the conventional methods using Markov–Gibbs Random Field (MGRF) model the required regions of interest (ROI) are identified. Result: The results of proposed FCM and CNN based process are compared with the results obtained from the conventional method using MGRF model. The results illustrate that the proposed method can able to segment the various kinds of complex multimodal medical images precisely. Conclusion: However, in this paper, to obtain an exact boundary of the regions, every empirical dispersion of the image is computed by Fuzzy C-Means Clustering segmentation. A classification process based on the Convolutional Neural Network (CNN) classifier is accomplished to distinguish the normal tissue and the abnormal tissue. The experimental evaluation is done using the Interstitial Lung Disease (ILD) database. Creative Commons Attribution License

Fuzzy-C-Means Clustering Based Segmentation and CNN-Classification for Accurate Segmentation of Lung Nodules

PubMed Central

K, Jalal Deen; R, Ganesan; A, Merline

2017-01-01

Objective: Accurate segmentation of abnormal and healthy lungs is very crucial for a steadfast computer-aided disease diagnostics. Methods: For this purpose a stack of chest CT scans are processed. In this paper, novel methods are proposed for segmentation of the multimodal grayscale lung CT scan. In the conventional methods using Markov–Gibbs Random Field (MGRF) model the required regions of interest (ROI) are identified. Result: The results of proposed FCM and CNN based process are compared with the results obtained from the conventional method using MGRF model. The results illustrate that the proposed method can able to segment the various kinds of complex multimodal medical images precisely. Conclusion: However, in this paper, to obtain an exact boundary of the regions, every empirical dispersion of the image is computed by Fuzzy C-Means Clustering segmentation. A classification process based on the Convolutional Neural Network (CNN) classifier is accomplished to distinguish the normal tissue and the abnormal tissue. The experimental evaluation is done using the Interstitial Lung Disease (ILD) database. PMID:28749127

Factors Affecting Impact Toughness in Stabilized Intermediate Purity 21Cr Ferritic Stainless Steels and Their Simulated Heat-Affected Zones

NASA Astrophysics Data System (ADS)

Anttila, Severi; Alatarvas, Tuomas; Porter, David A.

2017-12-01

The correlation between simulated weld heat-affected zone microstructures and toughness parameters has been investigated in four intermediate purity 21Cr ferritic stainless steels stabilized with titanium and niobium either separately or in combination. Extensive Charpy V impact toughness testing was carried out followed by metallography including particle analysis using electron microscopy. The results confirmed that the grain size and the number density of particle clusters rich in titanium nitride and carbide with an equivalent circular diameter of 2 µm or more are statistically the most critical factors influencing the ductile-to-brittle transition temperature. Other inclusions and particle clusters, as well as grain boundary precipitates, are shown to be relatively harmless. Stabilization with niobium avoids large titanium-rich inclusions and also suppresses excessive grain growth in the heat-affected zone when reasonable heat inputs are used. Thus, in order to maximize the limited heat-affected zone impact toughness of 21Cr ferritic stainless steels containing 380 to 450 mass ppm of interstitials, the stabilization should be either titanium free or the levels of titanium and nitrogen should be moderated.

Endemic chronic kidney disease of unknown etiology in Sri Lanka: Correlation of pathology with clinical stages.

PubMed

Wijetunge, S; Ratnatunga, N V I; Abeysekera, T D J; Wazil, A W M; Selvarajah, M

2015-01-01

Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy.

Intravesical NGF Antisense Therapy Using Lipid Nanoparticle for Interstitial Cystitis

DTIC Science & Technology

2015-10-01

intravesical botulinum toxin type A injec- tions plus hydrodistention with hydrodis- tention alone for the treatment of refractory interstitial cystitis/ painful ...SUPPLEMENTARY NOTES 14. ABSTRACT Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating disorder characterized by persistent pelvic pain ...from an animal efficacy experiment conducted during the previous period. The project is ongoing. 15. SUBJECT TERMS Interstitial cystitis/ painful

Mammalian Fe-S cluster biogenesis and its implication in disease.

PubMed

Beilschmidt, Lena K; Puccio, Hélène M

2014-05-01

Iron-sulfur (Fe-S) clusters are inorganic cofactors that are ubiquitous and essential. Due to their chemical versatility, Fe-S clusters are implicated in a wide range of protein functions including mitochondrial respiration and DNA repair. Composed of iron and sulfur, they are sensible to oxygen and their biogenesis requires a highly conserved protein machinery that facilitates assembly of the cluster as well as its insertion into apoproteins. Mitochondria are the central cellular compartment for Fe-S cluster biogenesis in eukaryotic cells and the importance of proper function of this biogenesis for life is highlighted by a constantly increasing number of human genetic diseases that are associated with dysfunction of this Fe-S cluster biogenesis pathway. Although these disorders are rare and appear dissimilar, common aspects are found among them. This review will give an overview on what is known on mammalian Fe-S cluster biogenesis today, by putting it into the context of what is known from studies from lower model organisms, and focuses on the associated diseases, by drawing attention to the respective mutations. Finally, it outlines the importance of adequate cellular and murine models to uncover not only each protein function, but to resolve their role and requirement throughout the mammalian organism. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

In vivo interstitial glucose characterization and monitoring in the skin by ATR-FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Skrebova Eikje, Natalja

2011-03-01

Successful development of real-time non-invasive glucose monitoring would represent a major advancement not only in the treatment and management of patients with diabetes mellitus and carbohydrate metabolism disorders, but also for understanding in those biochemical, metabolic and (patho-)physiological processes of glucose at the molecular level in vivo. Here, ATR-FTIR spectroscopy technique has been challenged not only for in vivo measurement of interstitial glucose levels, but also for their non-invasive molecular qualitative and quantitative comparative characterization in the skin tissue. The results, based on calculated mean values of determined 5 glucose-specific peaks in the glucose-related 1000-1160 cm-1 region, showed intra- and inter-subject differences in interstitial glucose activity levels with their changes at different times and doses of OGTT, while raising questions about the relationships between interstitial and blood glucose levels. In conclusion, the introduction of ATR-FTIR spectroscopy technique has opened up an access to the interstitial fluid space in the skin tissue for interstitial glucose characterization and monitoring in vivo. Though interstitial versus blood glucose monitoring has different characteristics, it can be argued that accurate and precise measurements of interstitial glucose levels may be more important clinically.

New insights into canted spiro carbon interstitial in graphite

NASA Astrophysics Data System (ADS)

EL-Barbary, A. A.

2017-12-01

The self-interstitial carbon is the key to radiation damage in graphite moderator nuclear reactor, so an understanding of its behavior is essential for plant safety and maximized reactor lifetime. The density functional theory is applied on four different graphite unit cells, starting from of 64 carbon atoms up to 256 carbon atoms, using AIMPRO code to obtain the energetic, athermal and mechanical properties of carbon interstitial in graphite. This study presents first principles calculations of the energy of formation that prove its high barrier to athermal diffusion (1.1 eV) and the consequent large critical shear stress (39 eV-50 eV) necessary to shear graphite planes in its presence. Also, for the first time, the gamma surface of graphite in two dimensions is calculated and found to yield the critical shear stress for perfect graphite. Finally, in contrast to the extensive literature describing the interstitial of carbon in graphite as spiro interstitial, in this work the ground state of interstitial carbon is found to be canted spiro interstitial.

The APOA1/C3/A4/A5 cluster and markers of allostatic load in the Boston Puerto Rican Health Study

USDA-ARS?s Scientific Manuscript database

The APOA1/C3/A4/A5 cluster encodes key regulators of plasma lipids. Interactions between dietary factors and single nucleotide polymorphisms (SNPs) in the cluster have been reported. Allostatic load, or physiological dysregulation in response to stress, has been implicated in shaping health disparit...

Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

PubMed

Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

2016-04-01

Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis. Copyright © 2016 Elsevier Inc. All rights reserved.

UO(2) Oxidative Corrosion by Nonclassical Diffusion.

PubMed

Stubbs, Joanne E; Chaka, Anne M; Ilton, Eugene S; Biwer, Craig A; Engelhard, Mark H; Bargar, John R; Eng, Peter J

2015-06-19

Using x-ray scattering, spectroscopy, and density-functional theory, we determine the structure of the oxidation front when a UO(2) (111) surface is exposed to oxygen at ambient conditions. In contrast to classical diffusion and previously reported bulk UO(2+x) structures, we find oxygen interstitials order into a nanoscale superlattice with three-layer periodicity and uranium in three oxidation states: IV, V, and VI. This oscillatory diffusion profile is driven by the nature of the electron transfer process, and has implications for understanding the initial stages of oxidative corrosion in materials at the atomistic level.

Barrier-free subsurface incorporation of 3 d metal atoms into Bi(111) films

DOE PAGES

Klein, C.; Vollmers, N. J.; Gerstmann, U.; ...

2015-05-27

By combining scanning tunneling microscopy with density functional theory it is shown that the Bi(111) surface provides a well-defined incorporation site in the first bilayer that traps highly coordinating atoms such as transition metals (TMs) or noble metals. All deposited atoms assume exactly the same specific sevenfold coordinated subsurface interstitial site while the surface topography remains nearly unchanged. Notably, 3 d TMs show a barrier-free incorporation. The observed surface modification by barrier-free subsorption helps to suppress aggregation in clusters. Thus, it allows a tuning of the electronic properties not only for the pure Bi(111) surface, but may also be observedmore » for topological insulators formed by substrate-stabilized Bi bilayers.« less

Role of lipids in the progression of renal disease in systemic lupus erythematosus patients.

PubMed

Luzar, B; Ferluga, D

2000-08-25

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease marked by immune-complex mediated lesions in small blood vessels of various organs, especially the kidneys, although other factors may also be implicated in the pathogenesis of the disease. This article focuses on the role of lipids in the progression of glomerular, vascular and tubulo-interstitial lesions in two patients with lupus nephritis associated with pronounced hyper- and dyslipidemia. The pathogenesis of progressive glomerulosclerosis in both patients appears to be multifactorial. In addition to immune complex mediated lupus glomerulonephritis, progressively active in the first patient, severe nephrotic-range persistent proteinuria, arterial hypertension associated with hyperfiltration and hyperperfusion injuries and, to a minor extent, hyper- and dyslipidemia were observed. Immunological and non-immunological factors were shown to contribute to the development of tubulo-interstitial lesions. In both patients, in addition to local immune deposits, prominent tubulo-interstitial lipid deposits were probably causally related to both hyperlipidemia and the increased permeability of the glomerular filtration barrier. Tubular lesions were highlighted by intracytoplasmic lipid droplets as well as small cleft-like spaces found to be impacted in the tubular lumina. They were seen to penetrate tubular epithelial cells and eventually lodge in the interstitium, surrounded by mononuclear cell infiltrates and foam cells. In both patients, hypertensive angiopathy and extraglomerular vascular immune deposits were demonstrated. In addition, in the second patient, arteriolar and small arterial hyaline was found at the age of 28 years to be full of lipids and calcium precipitates, suggesting a peripheral atherosclerosis-like process which never occurs as a natural age-related condition. In conclusion, all parts of the nephron may be involved in the pathogenetic process causally related or influenced by hyper- or dyslipidemia. Associated either with endothelial cell injury and consequent insudation of lipids in the vascular walls, glomerular filtration barrier injury with hyperfiltration, or tubulo-interstitial lipid deposition, the mechanism of tissue damage by lipids in all parts of the nephron shares similarities with the pathogenesis of systemic atherosclerosis.

Lung volumes and emphysema in smokers with interstitial lung abnormalities.

PubMed

Washko, George R; Hunninghake, Gary M; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C; Estépar, Raúl San José; Lynch, David A; Brehm, John M; Andriole, Katherine P; Diaz, Alejandro A; Khorasani, Ramin; D'Aco, Katherine; Sciurba, Frank C; Silverman, Edwin K; Hatabu, Hiroto; Rosas, Ivan O

2011-03-10

Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P<0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).

Influence of aqueous chemistry on the chemical composition of fog water and interstitial aerosol in Fresno

NASA Astrophysics Data System (ADS)

Kim, Hwajin; Ge, Xinlei; Collier, Sonya; Xu, Jianzhong; Sun, Yele; Wang, Youliang; Herckes, Pierre; Zhang, Qi

2015-04-01

A measurement study was conducted in the Central Valley (Fresno) of California in January 2010, during which radiation fog events were frequently observed. Fog plays important roles in atmospheric chemistry by scavenging aerosol particles and trace gases and serving as a medium for various aqueous-phase reactions. Understanding the effects of fog on the microphysical and chemical processing of aerosol particles requires detailed information on their chemical composition. In this study, we characterized the chemical composition of fog water and interstitial aerosol particles to study the effects of fog processing on aerosol properties. Fog water samples were collected during the 2010 Fresno campaigns with a Caltech Active Strand Cloud water Collector (CASCC) while interstitial submicron aerosols were characterized in real time with an Aerodyne High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) and a scanning Mobility Particle Sizer (SMPS). The fog water samples were later analyzed using the HR-ToF-AMS, ion chromatography, and a total carbon analyzer. The chemical composition and characteristics of interstitial particles during the fog events were compared to those of dissolved inorganic and organic matter in fog waters. Compared to interstitial aerosols, fog water is composed of a higher fraction of ammonium nitrate and oxygenated organics, due to aqueous formation of secondary aerosol species as well as enhanced gas-to-particle partitioning of water soluble species under water rich conditions. Sulfate is formed most efficiently in fog water although its contribution to total dissolved mass is relatively low. The HR-ToF-AMS mass spectra of organic matter in fog water (FOM) are very similar to that of oxygenated organic aerosols (OOA) derived from positive matrix factorization (PMF) of the HR-ToF-AMS spectra of ambient aerosol (r2 = 0.96), but FOM appears to contain a large fraction of acidic functional groups than OOA. FOM is also enriched of organic nitrogen compounds, with an average N/C ratio ~3.8 times that of OOA. Most strikingly is the enhancement of the CxHyN2+ family ions in FOM spectra, indicating the presence of imidazole compounds, which commonly result from the aqueous phase reactions of tropospheric aldehyde such as glyoxal, formaldehyde or acetaldehyde with amino compounds. The results of this study demonstrate that aqueous phase reactions in fog water lead to the formation of some oxidized and nitrogen-containing compounds. Details and the environmental implications of results will be discussed.

Interstitial Lung Diseases

MedlinePlus

Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and ... is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among coal ...

Endemic chronic kidney disease of unknown etiology in Sri Lanka: Correlation of pathology with clinical stages

PubMed Central

Wijetunge, S.; Ratnatunga, N. V. I.; Abeysekera, T. D. J.; Wazil, A. W. M.; Selvarajah, M.

2015-01-01

Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy. PMID:26628792

Deficiency of interstitial cells of Cajal in the small intestine of patients with Crohn's disease.

PubMed

Porcher, Christophe; Baldo, Marjolaine; Henry, Monique; Orsoni, Pierre; Julé, Yvon; Ward, Sean M

2002-01-01

Interstitial cells of Cajal are critical for the generation of electrical slow waves that regulate the phasic contractile activity of the tunica muscularis of the GI tract. Under certain pathophysiological conditions loss of interstitial cells of Cajal may play a role in the generation of certain motility disorders. The aim of the present study was to determine if there is an abnormality in the density or distribution of interstitial cells of Cajal from patients with Crohn's disease. Small intestines from control subjects and patients with Crohn's disease were examined using immunohistochemistry and antibodies against the Kit receptor, which is expressed in interstitial cells of Cajal within the tunica muscularis of the GI tract. The density and distribution of interstitial cells of Cajal were assessed in the longitudinal and circular muscle layers and in the myenteric and deep muscular plexus regions of Crohn's and control tissues. Tissues from Crohn's disease patients showed an almost complete abolition of interstitial cells of Cajal within the longitudinal and circular muscle layers and a significant reduction in numbers at the level of the myenteric and deep muscular plexuses. In tissues from Crohn's disease patients, the density of interstitial cells of Cajal was reduced throughout the tunica muscularis in comparison to control small intestines. The disturbance of intestinal motility that occurs in patients with Crohn's disease may be a consequence of the loss of or defects in specific populations of interstitial cells of Cajal within the tunica muscularis.

Computed tomographic features of idiopathic fibrosing interstitial pneumonia: comparison with pulmonary fibrosis related to collagen vascular disease.

PubMed

Hwang, Jeong-Hwa; Misumi, Shigeki; Sahin, Hakan; Brown, Kevin K; Newell, John D; Lynch, David A

2009-01-01

To compare the computed tomographic (CT) features of idiopathic fibrosing interstitial pneumonia with those of pulmonary fibrosis related to collagen vascular disease (CVD). We reviewed the CT scans of 177 patients with diffuse interstitial pulmonary fibrosis, of which 97 had idiopathic fibrosing interstitial pneumonia and 80 had CVD. The CT images were systematically scored for the presence and extent of pulmonary and extrapulmonary abnormalities. Computed tomographic diagnosis of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was assigned. A CT pattern of UIP was identified in 59 (60.8%) of patients with idiopathic fibrosing interstitial pneumonia compared with 15 (18.7%) of those patients with CVD; conversely, the CT diagnosis of NSIP was made in 51 (64%) of patients with CVD compared with 36 (37%) of patients with idiopathic disease (P < 0.01). In 113 patients who had lung biopsy, the CT diagnoses of UIP and NSIP were concordant with the histologic diagnoses in 36 of 50 patients and 34 of 41 patients, respectively. Pleural effusions, esophageal dilation, and pericardial abnormalities were more frequent in patients with CVD than in patients with idiopathic fibrosing interstitial pneumonia. Compared with patients with CVD, those patients with an idiopathic fibrosing interstitial pneumonia showed a higher prevalence of a UIP pattern and lower prevalence of an NSIP pattern as determined by CT. Identification of coexisting extrapulmonary abnormalities on CT can support a diagnosis of CVD.

Neutrino masses, neutrino oscillations, and cosmological implications

NASA Technical Reports Server (NTRS)

Stecker, F. W.

1982-01-01

Theoretical concepts and motivations for considering neutrinos having finite masses are discussed and the experimental situation on searches for neutrino masses and oscillations is summarized. The solar neutrino problem, reactor, deep mine and accelerator data, tri decay experiments and double beta-decay data are considered and cosmological implications and astrophysical data relating to neutrino masses are reviewed. The neutrino oscillation solution to the solar neutrino problem, the missing mass problem in galaxy halos and galaxy cluster galaxy formation and clustering, and radiative neutrino decay and the cosmic ultraviolet background radiation are examined.

Dark matter and the equivalence principle

NASA Technical Reports Server (NTRS)

Frieman, Joshua A.; Gradwohl, Ben-Ami

1991-01-01

If the dark matter in galaxies and clusters is nonbaryonic, it can interact with additional long-range fields that are invisible to experimental tests of the equivalence principle. The astrophysical and cosmological implications of a long-range force coupled only to the dark matter are discussed and rather tight constraints on its strength are found. If the force is repulsive (attractive), the masses of galaxy groups and clusters (and the mean density of the universe inferred from them) have been systematically underestimated (overestimated). Such an interaction also has unusual implications for the growth of large-scale structure.

Implications of a possible clustering of highest-energy cosmic rays

PubMed Central

Sigl, Günter; Schramm, David N.; Lee, Sangjin; Hill, Christopher T.

1997-01-01

Recently, a possible clustering of a subset of observed ultra-high energy cosmic rays above ≃40 EeV (4 × 1019 eV) in pairs near the supergalactic plane was reported. We show that a confirmation of this effect would provide information on the origin and nature of these events and, in case of charged primaries, imply interesting constraints on the extragalactic magnetic field. Possible implications for the most common models of ultra-high energy cosmic ray production in the literature are discussed. PMID:11038576

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scott, Aubrey D.; Pelmenschikov, Vladimir; Guo, Yisong

The properties of CO-inhibited Azotobacter vinelandii (Av) Mo-nitrogenase (N 2ase) have been examined by the combined application of nuclear resonance vibrational spectroscopy (NRVS), extended X-ray absorption fine structure (EXAFS), and density functional theory (DFT). Dramatic changes in the NRVS are seen under high-CO conditions, especially in a 188 cm –1 mode associated with symmetric breathing of the central cage of the FeMo-cofactor. Similar changes are reproduced with the α-H195Q N 2ase variant. In the frequency region above 450 cm –1, additional features are seen that are assigned to Fe-CO bending and stretching modes (confirmed by 13CO isotope shifts). The EXAFSmore » for wild-type N 2ase shows evidence for a significant cluster distortion under high-CO conditions, most dramatically in the splitting of the interaction between Mo and the shell of Fe atoms originally at 5.08 Å in the resting enzyme. A DFT model with both a terminal ₋CO and a partially reduced ₋CHO ligand bound to adjacent Fe sites is consistent with both earlier FT-IR experiments, and the present EXAFS and NRVS observations for the wild-type enzyme. Another DFT model with two terminal CO ligands on the adjacent Fe atoms yields Fe-CO bands consistent with the α-H195Q variant NRVS. The calculations also shed light on the vibrational “shake” modes of the interstitial atom inside the central cage, and their interaction with the Fe-CO modes. We discuss implications for the CO and N 2 reactivity of N 2ase.« less

Induced Autologous Stem Cell Transplantation for Treatment of Rabbit Renal Interstitial Fibrosis

PubMed Central

Ruan, Guang-Ping; Xu, Fan; Li, Zi-An; Zhu, Guang-Xu; Pang, Rong-Qing; Wang, Jin-Xiang; Cai, Xue-Min; He, Jie; Yao, Xiang; Ruan, Guang-Hong; Xu, Xin-Ming; Pan, Xing-Hua

2013-01-01

Introduction Renal interstitial fibrosis (RIF) is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. Methods A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP). These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. Results Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05) were observed in serum creatinine (SCr) (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L) and blood urea nitrogen (BUN) (119 ± 22 µmol/L to 97 ± 13 µmol/L), indicating improvement in renal function. Conclusions We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function. PMID:24367598

Carbon, oxygen and their interaction with intrinsic point defects in solar silicon ribbon material: A speculative approach

NASA Technical Reports Server (NTRS)

Goesele, U.; Ast, D. G.

1983-01-01

Some background information on intrinsic point defects is provided and on carbon and oxygen in silicon in so far as it may be relevant for the efficiency of solar cells fabricated from EFG ribbon material. The co-precipitation of carbon and oxygen and especially of carbon and silicon self interstitials are discussed. A simple model for the electrical activity of carbon-self-interstitial agglomerates is presented. The self-interstitial content of these agglomerates is assumed to determine their electrical activity and that both compressive stresses (high self-interstitial content) and tensile stresses (low self-interstitial content) give rise to electrical activity of the agglomerates. The self-interstitial content of these carbon-related agglomerates may be reduced by an appropriate high temperature treatment and enhanced by a supersaturation of self-interstitials generated during formation of the p-n junction of solar cells. Oxygen present in supersaturation in carbon-rich silicon may be induced to form SiO, precipitates by self-interstitials generated during phosphorus diffusion. It is proposed that the SiO2-Si interface of the precipates gives rise to a continuum of donor stables and that these interface states are responsible for at least part of the light inhancement effects observed in oxygen containing EFG silicon after phosphorus diffusion.

Are Large Core Radius Clusters Merging Systems?

NASA Technical Reports Server (NTRS)

Forman, William R.

1997-01-01

We have analyzed observations for two lensing clusters of galaxies, A1689 and A2218. Our investigations have explored the implications of their X-ray properties for mass determinations both in X-rays and through both weak and strong gravitational lensing. The work on these two clusters is summarized below and copies of the two papers submitted to the Astrophysical Journal and accepted for publication are attached.

A Case of Clinically Amyopathic Dermatomyositis with Interstitial Pneumonia that Was Successfully Treated with Plasma Exchange.

PubMed

Yagishita, Mizuki; Kondo, Yuya; Terasaki, Toshihiko; Terasaki, Mayu; Shimizu, Masaru; Honda, Fumika; Oyama, Ayako; Takahashi, Hiroyuki; Yokosawa, Masahiro; Asashima, Hiromitsu; Hagiwara, Shinya; Tsuboi, Hiroto; Matsumoto, Isao; Sumida, Takayuki

2018-02-28

Patients with clinically amyopathic dermatomyositis (CADM), a subset of dermatomyositis characterized by a lack of muscle involvement, frequently develop rapidly progressive and treatment-resistant interstitial lung disease. We report the case of a 49-year-old man who was diagnosed with CADM. He developed interstitial pneumonia, which did not respond to combination therapy with methylprednisolone pulse therapy, cyclophosphamide, and cyclosporine. We therefore attempted plasma exchange. After 7 courses of therapeutic plasma exchange, the interstitial pneumonia gradually improved. This case suggests that plasma exchange might be an effective therapeutic option for patients with progressive interstitial lung disease in steroid- and immunosuppressive therapy-refractive CADM.

A Taxonomic Approach to the Gestalt Theory of Perls

ERIC Educational Resources Information Center

Raming, Henry E.; Frey, David H.

1974-01-01

This study applied content analysis and cluster analysis to the ideas of Fritz Perls to develop a taxonomy of Gestalt processes and goals. Summaries of the typal groups or clusters were written and the implications of taxonomic research in counseling discussed. (Author)

Active Galactic Nucleus Feedback with the Square Kilometre Array and Implications for Cluster Physics and Cosmology

NASA Astrophysics Data System (ADS)

Iqbal, Asif; Kale, Ruta; Majumdar, Subhabrata; Nath, Biman B.; Pandge, Mahadev; Sharma, Prateek; Malik, Manzoor A.; Raychaudhury, Somak

2017-12-01

Active Galactic Nuclei (AGN) feedback is regarded as an important non-gravitational process in galaxy clusters, providing useful constraints on large-scale structure formation. It modifies the structure and energetics of the intra-cluster medium (ICM) and hence its understanding is crucially needed in order to use clusters as high precision cosmological probes. In this context, particularly keeping in mind the upcoming high quality radio data expected from radio surveys like Square Kilometre Array (SKA) with its higher sensitivity, high spatial and spectral resolutions, we review our current understanding of AGN feedback, its cosmological implications and the impact that SKA can have in revolutionizing our understanding of AGN feedback in large-scale structures. Recent developments regarding the AGN outbursts and its possible contribution to excess entropy in the hot atmospheres of groups and clusters, its correlation with the feedback energy in ICM, quenching of cooling flows and the possible connection between cool core clusters and radio mini-halos, are discussed. We describe current major issues regarding modeling of AGN feedback and its impact on the surrounding medium. With regard to the future of AGN feedback studies, we examine the possible breakthroughs that can be expected from SKA observations. In the context of cluster cosmology, for example, we point out the importance of SKA observations for cluster mass calibration by noting that most of z>1 clusters discovered by eROSITA X-ray mission can be expected to be followed up through a 1000 hour SKA1-mid programme. Moreover, approximately 1000 radio mini halos and ˜ 2500 radio halos at z<0.6 can be potentially detected by SKA1 and SKA2 and used as tracers of galaxy clusters and determination of cluster selection function.

Molecular dynamics growth modeling of InAs1-xSbx-based type-II superlattice

NASA Astrophysics Data System (ADS)

Ciani, Anthony J.; Grein, Christoph H.; Irick, Barry; Miao, Maosheng; Kioussis, Nicholas

2017-09-01

Type-II strained-layer superlattices (T2SL) based on InAs1-xSbx are a promising photovoltaic detector material technology for thermal imaging; however, Shockley-Read-Hall recombination and generation rates are still too high for thermal imagers based on InAs1-xSbx T2SL to reach their ideal performance. Molecular dynamics simulations using the Stillinger-Weber (SW) empirical potentials are a useful tool to study the growth of tetrahedral coordinated crystals and the nonequilibrium formation of defects within them, including the long-range effects of strain. SW potentials for the possible atomic interactions among {Ga, In, As, Sb} were developed by fitting to ab initio calculations of elastically distorted zinc blende and diamond unit cells. The SW potentials were tested against experimental observations of molecular beam epitaxial (MBE) growth and then used to simulate the MBE growth of InAs/InAs0.5Sb0.5 T2SL on GaSb substrates over a range of processes parameters. The simulations showed and helped to explain Sb cross-incorporation into the InAs T2SL layers, Sb segregation within the InAsSb layers, and identified medium-range defect clusters involving interstitials and their induction of interstitial-vacancy pairs. Defect formation was also found to be affected by growth temperature and flux stoichiometry.

Angiotensin (1-7) and its receptor Mas are expressed in the human testis: implications for male infertility.

PubMed

Reis, Augusto B; Araújo, Fabiano C; Pereira, Virginia M; Dos Reis, Adelina M; Santos, Robson A; Reis, Fernando M

2010-02-01

The presence of classical components of the renin-angiotensin system has been demonstrated in the male reproductive tract, mainly in the testes and epididymis. The objective of this study was to verify the localization of angiotensin (Ang)-(1-7) and its receptor Mas in human testis. The study included 12 men with previously proven fertility submitted to orchiectomy for prostate cancer and 20 infertile men submitted to testicular biopsy for infertility work-up, comprising a subgroup with obstructive azoospermia/normal spermatogenesis (n = 8) and another with non-obstructive azoospermia and severely impaired spermatogenesis (n = 12). Testicular tissue samples were processed by immunohistochemistry and real time polymerase chain reaction. Ang-(1-7) was strongly expressed in the interstitial compartment, mainly in Leydig cells, with similar intensity in all groups evaluated. The peptide was also detected in the seminiferous tubules, but with much less intensity compared to interstitial cells. The receptor Mas was equally distributed between interstitial and tubular compartments and was found in all layers of the normal seminiferous epithelium. However, neither Ang-(1-7) nor Mas were detected in the seminiferous tubules of samples with impaired spermatogenesis. The testicular samples of infertile men with impaired spermatogenesis (non-obstructive azoospermia) expressed Mas and ACE2 mRNA at lower concentrations (fold change = 0.06 and 0.04, respectively, P < 0.05) than samples with full spermatogenesis (obstructive azoospermia). This shows, for the first time, the immunolocalization of Ang-(1-7) and its receptor Mas in testes of fertile and infertile men, and suggests that this system may be altered when spermatogenesis is severely impaired.

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities.

PubMed

Ho, Jennifer E; Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O; Hatabu, Hiroto; Latourelle, Jeanne C; Nishino, Mizuki; Dupuis, Josée; Washko, George R; O'Connor, George T; Hunninghake, Gary M

2016-07-01

Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8-2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6-1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3-2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49-4.76; P < 0.001). Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis.

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities

PubMed Central

Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O.; Hatabu, Hiroto; Latourelle, Jeanne C.; Nishino, Mizuki; Dupuis, Josée; Washko, George R.; O’Connor, George T.; Hunninghake, Gary M.

2016-01-01

Rationale: Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. Objectives: We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. Methods: We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Measurements and Main Results: Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8–2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6–1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3–2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49–4.76; P < 0.001). Conclusions: Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis. PMID:26771117

Cytokine expression in patients with bladder pain syndrome/interstitial cystitis ESSIC type 3C.

PubMed

Logadottir, Yr; Delbro, Dick; Fall, Magnus; Gjertsson, Inger; Jirholt, Pernilla; Lindholm, Catharina; Peeker, Ralph

2014-11-01

Bladder wall nitric oxide production in patients with bladder pain syndrome type 3C is increased compared to undetectable nitric oxide in patients with nonHunner bladder pain syndrome and healthy controls. However, the underlying mechanism/s of the increased nitric oxide production is largely unknown. We compared mRNA expression of a select group of cytokines in patients with bladder pain syndrome/interstitial cystitis type 3C and in pain-free controls. Cold cup biopsies from 7 patients with bladder pain syndrome type 3C and 6 healthy subjects were analyzed. mRNA expression of IL-4, 6, 10 and 17A, iNOS, TNF-α, TGF-β and IFN-γ was estimated by real-time polymerase chain reaction. IL-17 protein expression was determined by immunohistochemistry. Mast cells were labeled with tryptase to evaluate cell appearance and count. IL-6, 10 and 17A, and iNOS mRNA levels as well as the number of mast cells infiltrating the bladder mucosa were significantly increased in patients with bladder pain syndrome type 3C compared to healthy controls. TNF-α, TGF-β and IFN-γ mRNA levels were similar in patients and controls. IL-17A expression at the protein level was up-regulated and localized to inflammatory cells and urothelium in patients with bladder pain syndrome type 3C. Patients with bladder pain syndrome/interstitial cystitis had increased mRNA levels of IL-17A, 10 and 6, and iNOS. IL-17A might be important in the inflammatory process. To our knowledge the increase in IL-17A is a novel finding that may have new treatment implications. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Embedded Clusters

NASA Astrophysics Data System (ADS)

Ascenso, Joana

The past decade has seen an increase of star formation studies made at the molecular cloud scale, motivated mostly by the deployment of a wealth of sensitive infrared telescopes and instruments. Embedded clusters, long recognised as the basic units of coherent star formation in molecular clouds, are now seen to inhabit preferentially cluster complexes tens of parsecs across. This chapter gives an overview of some important properties of the embedded clusters in these complexes and of the complexes themselves, along with the implications of viewing star formation as a molecular-cloud scale process rather than an isolated process at the scale of clusters.

Fragile sites, dysfunctional telomere and chromosome fusions: What is 5S rDNA role?

PubMed

Barros, Alain Victor; Wolski, Michele Andressa Vier; Nogaroto, Viviane; Almeida, Mara Cristina; Moreira-Filho, Orlando; Vicari, Marcelo Ricardo

2017-04-15

Repetitive DNA regions are known as fragile chromosomal sites which present a high flexibility and low stability. Our focus was characterize fragile sites in 5S rDNA regions. The Ancistrus sp. species shows a diploid number of 50 and an indicative Robertsonian fusion at chromosomal pair 1. Two sequences of 5S rDNA were identified: 5S.1 rDNA and 5S.2 rDNA. The first sequence gathers the necessary structures to gene expression and shows a functional secondary structure prediction. Otherwise, the 5S.2 rDNA sequence does not contain the upstream sequences that are required to expression, furthermore its structure prediction reveals a nonfunctional ribosomal RNA. The chromosomal mapping revealed several 5S.1 and 5S.2 rDNA clusters. In addition, the 5S.2 rDNA clusters were found in acrocentric and metacentric chromosomes proximal regions. The pair 1 5S.2 rDNA cluster is co-located with interstitial telomeric sites (ITS). Our results indicate that its clusters are hotspots to chromosomal breaks. During the meiotic prophase bouquet arrangement, double strand breaks (DSBs) at proximal 5S.2 rDNA of acrocentric chromosomes could lead to homologous and non-homologous repair mechanisms as Robertsonian fusions. Still, ITS sites provides chromosomal instability, resulting in telomeric recombination via TRF2 shelterin protein and a series of breakage-fusion-bridge cycles. Our proposal is that 5S rDNA derived sequences, act as chromosomal fragile sites in association with some chromosomal rearrangements of Loricariidae. Copyright © 2017 Elsevier B.V. All rights reserved.

IL-33 mast cell axis is central in LL-37 induced bladder inflammation and pain in a murine interstitial cystitis model.

PubMed

Martin Jensen, M; Jia, Wanjian; Schults, Austin J; Ye, Xiangyang; Prestwich, Glenn D; Oottamasathien, Siam

2018-05-18

Interstitial cystitis (IC), also known as painful bladder syndrome (PBS), is a debilitating chronic condition that afflicts over 3 million women above the age of 18 in the U.S., and most patients fail to respond to current treatment options. Mast cells have previously been implicated as both a diagnostic and prognostic marker in IC/PBS. Patients with IC/PBS have been shown to have elevated levels of IL-33, a cytokine released in response to tissue insult, in their urine. We hypothesize that mast cell-mediated inflammation induced from IL-33 may play an important role in initiating pain and inflammation in IC/PBS. A human cathelicidin, LL-37, which is found at elevated levels in IC/PBS patients, was used to induce an IC/PBS-like state of inflammation and bladder pain in mast cell deficient C-kit (-/-) and wild type C57Bl/6 (WT) mice. Inflammation was quantified using myeloperoxidase (MPO) expression in bladder tissues measured via ELISA. Response rate to suprapubic stimulation from von Frey filaments was used to assess the relative pain and discomfort. Both types of mice increased IL-33 expression in response to LL-37 exposure. However, mast cell deficient mice demonstrated significantly lower levels of inflammation (p < 0.001) and reduced pain response (p < 0.001) compared to WT mice. These findings implicate an IL-33-mast cell dependent axis with a potential etiology of pain and inflammation in IC/PBS. Future therapeutics aimed at targeting the IL-33 - mast cell axis could potentially serve as useful targets for treating IC/PBS. Copyright © 2018. Published by Elsevier Ltd.

Casting core for a cooling arrangement for a gas turbine component

DOEpatents

Lee, Ching-Pang; Heneveld, Benjamin E

2015-01-20

A ceramic casting core, including: a plurality of rows (162, 166, 168) of gaps (164), each gap (164) defining an airfoil shape; interstitial core material (172) that defines and separates adjacent gaps (164) in each row (162, 166, 168); and connecting core material (178) that connects adjacent rows (170, 174, 176) of interstitial core material (172). Ends of interstitial core material (172) in one row (170, 174, 176) align with ends of interstitial core material (172) in an adjacent row (170, 174, 176) to form a plurality of continuous and serpentine shaped structures each including interstitial core material (172) from at least two adjacent rows (170, 174, 176) and connecting core material (178).

The prevalence and overlap of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome in men: results of the RAND Interstitial Cystitis Epidemiology male study.

PubMed

Suskind, Anne M; Berry, Sandra H; Ewing, Brett A; Elliott, Marc N; Suttorp, Marika J; Clemens, J Quentin

2013-01-01

As part of the RICE (RAND Interstitial Cystitis Epidemiology) study, we developed validated case definitions to identify interstitial cystitis/bladder pain syndrome in women and chronic prostatitis/chronic pelvic pain syndrome in men. Using population based screening methods, we applied these case definitions to determine the prevalence of these conditions in men. A total of 6,072 households were contacted by telephone to screen for men who had symptoms of interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome. An initial 296 men screened positive, of whom 149 met the inclusionary criteria and completed the telephone interview. For interstitial cystitis/bladder pain syndrome 2 case definitions were applied (1 with high sensitivity and 1 with high specificity), while for chronic prostatitis/chronic pelvic pain syndrome a single case definition (with high sensitivity and specificity) was used. These case definitions were used to classify subjects into groups based on diagnosis. The interstitial cystitis/bladder pain syndrome weighted prevalence estimates for the high sensitivity and high specificity definitions were 4.2% (3.1-5.3) and 1.9% (1.1-2.7), respectively. The chronic prostatitis/chronic pelvic pain syndrome weighted prevalence estimate was 1.8% (0.9-2.7). These values equate to 1,986,972 (95% CI 966,042-2,996,924) men with chronic prostatitis/chronic pelvic pain syndrome and 2,107,727 (95% CI 1,240,485-2,974,969) men with the high specificity definition of interstitial cystitis/bladder pain syndrome in the United States. The overlap between men who met the high specificity interstitial cystitis/bladder pain syndrome case definition or the chronic prostatitis/chronic pelvic pain syndrome case definition was 17%. Symptoms of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome are widespread among men in the United States. The prevalence of interstitial cystitis/bladder pain syndrome symptoms in men approaches that in women, suggesting that this condition may be underdiagnosed in the male population. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis.

PubMed

Towner, Rheal A; Wisniewski, Amy B; Wu, Dee H; Van Gordon, Samuel B; Smith, Nataliya; North, Justin C; McElhaney, Rayburt; Aston, Christopher E; Shobeiri, S Abbas; Kropp, Bradley P; Greenwood-Van Meerveld, Beverley; Hurst, Robert E

2016-03-01

Interstitial cystitis/bladder pain syndrome is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated as patients present with a wide range of symptoms, physical examination findings and clinical test responses. One hypothesis is that interstitial cystitis symptoms arise from increased bladder permeability to urine solutes. This study establishes the feasibility of using contrast enhanced magnetic resonance imaging to quantify bladder permeability in patients with interstitial cystitis. Permeability alterations in bladder urothelium were assessed by intravesical administration of the magnetic resonance imaging contrast agent Gd-DTPA (Gd-diethylenetriaminepentaacetic acid) in a small cohort of patients. Magnetic resonance imaging signal intensity in patient and control bladders was compared regionally and for entire bladders. Quantitative assessment of magnetic resonance imaging signal intensity indicated a significant increase in signal intensity in anterior bladder regions compared to posterior regions in patients with interstitial cystitis (p <0.01) and significant increases in signal intensity in anterior bladder regions (p <0.001). Kurtosis (shape of probability distribution) and skewness (measure of probability distribution asymmetry) were associated with contrast enhancement in total bladders in patients with interstitial cystitis vs controls (p <0.05). Regarding symptomatology interstitial cystitis cases differed significantly from controls on the SF-36®, PUF (Pelvic Pain and Urgency/Frequency) and ICPI (Interstitial Cystitis Problem Index) questionnaires with no overlap in the score range in each group. ICSI (Interstitial Cystitis Symptom Index) differed significantly but with a slight overlap in the range of scores. Data suggest that contrast enhanced magnetic resonance imaging provides an objective, quantifiable measurement of bladder permeability that could be used to stratify bladder pain patients and monitor therapy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Interstitial Features at Chest CT Enhance the Deleterious Effects of Emphysema in the COPDGene Cohort.

PubMed

Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Rahaghi, Farbod N; Sanchez-Ferrero, Gonzalo Vegas; Putman, Rachel K; Hunninghake, Gary M; Onieva, Jorge Onieva; Martinez, Fernando J; Choi, Augustine M; Bowler, Russell P; Lynch, David A; Hatabu, Hiroto; Bhatt, Surya P; Dransfield, Mark T; Wells, J Michael; Rosas, Ivan O; San Jose Estepar, Raul; Washko, George R

2018-06-05

Purpose To determine if interstitial features at chest CT enhance the effect of emphysema on clinical disease severity in smokers without clinical pulmonary fibrosis. Materials and Methods In this retrospective cohort study, an objective CT analysis tool was used to measure interstitial features (reticular changes, honeycombing, centrilobular nodules, linear scar, nodular changes, subpleural lines, and ground-glass opacities) and emphysema in 8266 participants in a study of chronic obstructive pulmonary disease (COPD) called COPDGene (recruited between October 2006 and January 2011). Additive differences in patients with emphysema with interstitial features and in those without interstitial features were analyzed by using t tests, multivariable linear regression, and Kaplan-Meier analysis. Multivariable linear and Cox regression were used to determine if interstitial features modified the effect of continuously measured emphysema on clinical measures of disease severity and mortality. Results Compared with individuals with emphysema alone, those with emphysema and interstitial features had a higher percentage predicted forced expiratory volume in 1 second (absolute difference, 6.4%; P < .001), a lower percentage predicted diffusing capacity of lung for carbon monoxide (DLCO) (absolute difference, 7.4%; P = .034), a 0.019 higher right ventricular-to-left ventricular (RVLV) volume ratio (P = .029), a 43.2-m shorter 6-minute walk distance (6MWD) (P < .001), a 5.9-point higher St George's Respiratory Questionnaire (SGRQ) score (P < .001), and 82% higher mortality (P < .001). In addition, interstitial features modified the effect of emphysema on percentage predicted DLCO, RVLV volume ratio, 6WMD, SGRQ score, and mortality (P for interaction < .05 for all). Conclusion In smokers, the combined presence of interstitial features and emphysema was associated with worse clinical disease severity and higher mortality than was emphysema alone. In addition, interstitial features enhanced the deleterious effects of emphysema on clinical disease severity and mortality. © RSNA, 2018 Online supplemental material is available for this article.

Numerical Modeling of Fluid Flow in Solid Tumors

PubMed Central

Soltani, M.; Chen, P.

2011-01-01

A mathematical model of interstitial fluid flow is developed, based on the application of the governing equations for fluid flow, i.e., the conservation laws for mass and momentum, to physiological systems containing solid tumors. The discretized form of the governing equations, with appropriate boundary conditions, is developed for a predefined tumor geometry. The interstitial fluid pressure and velocity are calculated using a numerical method, element based finite volume. Simulations of interstitial fluid transport in a homogeneous solid tumor demonstrate that, in a uniformly perfused tumor, i.e., one with no necrotic region, because of the interstitial pressure distribution, the distribution of drug particles is non-uniform. Pressure distribution for different values of necrotic radii is examined and two new parameters, the critical tumor radius and critical necrotic radius, are defined. Simulation results show that: 1) tumor radii have a critical size. Below this size, the maximum interstitial fluid pressure is less than what is generally considered to be effective pressure (a parameter determined by vascular pressure, plasma osmotic pressure, and interstitial osmotic pressure). Above this size, the maximum interstitial fluid pressure is equal to effective pressure. As a consequence, drugs transport to the center of smaller tumors is much easier than transport to the center of a tumor whose radius is greater than the critical tumor radius; 2) there is a critical necrotic radius, below which the interstitial fluid pressure at the tumor center is at its maximum value. If the tumor radius is greater than the critical tumor radius, this maximum pressure is equal to effective pressure. Above this critical necrotic radius, the interstitial fluid pressure at the tumor center is below effective pressure. In specific ranges of these critical sizes, drug amount and therefore therapeutic effects are higher because the opposing force, interstitial fluid pressure, is low in these ranges. PMID:21673952

Influence of interstitial Mn on magnetism in the room-temperature ferromagnet Mn 1 + δ Sb

DOE PAGES

Taylor, Alice E.; Berlijn, Tom; Hahn, Steven E.; ...

2015-06-15

We repormore » t elastic and inelastic neutron scattering measurements of the high-TC ferromagnet Mn 1 + δ Sb . Measurements were performed on a large, T C = 434 K, single crystal with interstitial Mn content of δ ≈ 0.13. The neutron diffraction results reveal that the interstitial Mn has a magnetic moment, and that it is aligned antiparallel to the main Mn moment. We perform density functional theory calculations including the interstitial Mn, and find the interstitial to be magnetic in agreement with the diffraction data. The inelastic neutron scattering measurements reveal two features in the magnetic dynamics: i) a spin-wave-like dispersion emanating from ferromagnetic Bragg positions (H K 2n), and ii) a broad, non-dispersive signal centered at forbidden Bragg positions (H K 2n+1). The inelastic spectrum cannot be modeled by simple linear spin-wave theory calculations, and appears to be significantly altered by the presence of the interstitial Mn ions. Finally, the results show that the influence of the interstitial Mn on the magnetic state in this system is more important than previously understood.« less

The pulmonary histopathology of anti-KS transfer RNA synthetase syndrome.

PubMed

Schneider, Frank; Aggarwal, Rohit; Bi, David; Gibson, Kevin; Oddis, Chester; Yousem, Samuel A

2015-01-01

The clinical spectrum of the antisynthetase syndromes (AS) has been poorly defined, although some frequently present with pulmonary manifestations. The anti-KS anti-asparaginyl-transfer RNA synthetase syndrome is one in which pulmonary interstitial lung disease is almost always present and yet the histopathologic spectrum is not well described. To define the morphologic manifestations of pulmonary disease in those patients with anti-KS antiasparaginyl syndrome. We reviewed the connective tissue disorder registry of the University of Pittsburgh and identified those patients with anti-KS autoantibodies who presented with interstitial lung disease and had surgical lung biopsies. The 5 patients with anti-KS antisynthetase syndrome were usually women presenting with dyspnea and without myositis, but with mechanic's hands (60%) and Raynaud phenomenon (40%). They most often presented with a usual interstitial pneumonia pattern of fibrosis (80%), with the final patient displaying organizing pneumonia. Pulmonary interstitial lung disease is a common presentation in patients with the anti-KS-antisynthetase syndrome, who are often women with rather subtle or subclinical connective tissue disease, whereas the literature emphasizes the nonspecific interstitial pneumonia pattern often diagnosed clinically. Usual interstitial pneumonia and organizing pneumonia patterns of interstitial injury need to be added to this clinical differential diagnosis.

Lung transplantation and interstitial lung disease.

PubMed

Alalawi, Raed; Whelan, Timothy; Bajwa, Ravinder S; Hodges, Tony N

2005-09-01

Interstitial lung disease includes a heterogeneous group of disorders that leads to respiratory insufficiency and death in a significant number of patients. Lung transplantation is a therapeutic option in select candidates. The indications, transplant procedure options, and outcomes continue to evolve. Various recipient comorbidities influence the choice of procedure in patients with interstitial lung disease. Single lung transplants are used as the procedure of choice and bilateral transplants are reserved for patients with suppurative lung disease and patients with pulmonary hypertension. Issues unique to patients with interstitial lung disease affect the morbidity, mortality and recurrence of the disease. Lung transplantation is an effective therapy for respiratory failure in interstitial lung disease with survival following transplant being similar to that achieved in transplant recipients with other diseases.

Segmenting Student Markets with a Student Satisfaction and Priorities Survey.

ERIC Educational Resources Information Center

Borden, Victor M. H.

1995-01-01

A market segmentation analysis of 872 university students compared 2 hierarchical clustering procedures for deriving market segments: 1 using matching-type measures and an agglomerative clustering algorithm, and 1 using the chi-square based automatic interaction detection. Results and implications for planning, evaluating, and improving academic…

The Implications of "Contamination" for Experimental Design in Education

ERIC Educational Resources Information Center

Rhoads, Christopher H.

2011-01-01

Experimental designs that randomly assign entire clusters of individuals (e.g., schools and classrooms) to treatments are frequently advocated as a way of guarding against contamination of the estimated average causal effect of treatment. However, in the absence of contamination, experimental designs that randomly assign intact clusters to…

Self-optimized construction of transition rate matrices from accelerated atomistic simulations with Bayesian uncertainty quantification

NASA Astrophysics Data System (ADS)

Swinburne, Thomas D.; Perez, Danny

2018-05-01

A massively parallel method to build large transition rate matrices from temperature-accelerated molecular dynamics trajectories is presented. Bayesian Markov model analysis is used to estimate the expected residence time in the known state space, providing crucial uncertainty quantification for higher-scale simulation schemes such as kinetic Monte Carlo or cluster dynamics. The estimators are additionally used to optimize where exploration is performed and the degree of temperature acceleration on the fly, giving an autonomous, optimal procedure to explore the state space of complex systems. The method is tested against exactly solvable models and used to explore the dynamics of C15 interstitial defects in iron. Our uncertainty quantification scheme allows for accurate modeling of the evolution of these defects over timescales of several seconds.

SARCOCYSTIS NEURONA-ASSOCIATED MENINGOENCEPHALITIS IN A PACIFIC WALRUS ( ODOBENDUS ROSMARUS DIVERGENS).

PubMed

Krol, Lana; Fravel, Vanessa; Procter, Diana G; Colegrove, Kathleen M

2017-12-01

A 21-yr-old intact male walrus ( Odobendus rosmarus divergens) presented with acute onset of shifting lameness, initially associated with breeding behaviors. Further clinical signs manifested, including muscle tremors, anorexia, hematuria, and coughing. Diagnostics were limited, as the animal would not offer behaviors for voluntary sample collection. Signs were addressed with anti-inflammatories, anticonvulsants, and antibiotics. The walrus developed cluster seizures and ultimately, respiratory and cardiac arrest. Postmortem lesions included meningoencephalitis with intra- and extracellular protozoal zoites and schizonts, as well as interstitial pneumonia with intraendothelial protozoa. Immunolabeling of the protozoal organisms revealed Sarcocystis neurona. Previous S. neurona infections in an odobenid have not been reported. Protozoal infection should be considered in all species of captive marine mammals with nonspecific orthopedic, neurological, and respiratory clinical signs.

Therapeutic Targeting of CC Ligand 21 or CC Chemokine Receptor 7 Abrogates Pulmonary Fibrosis Induced by the Adoptive Transfer of Human Pulmonary Fibroblasts to Immunodeficient Mice

PubMed Central

Pierce, Elizabeth M.; Carpenter, Kristin; Jakubzick, Claudia; Kunkel, Steven L.; Flaherty, Kevin R.; Martinez, Fernando J.; Hogaboam, Cory M.

2007-01-01

Idiopathic interstitial pneumonias (IIPs) are a collection of pulmonary fibrotic diseases of unknown etiopathogenesis. CC chemokine receptor 7 (CCR7) is expressed in IIP biopsies and primary fibroblast lines, but its role in pulmonary fibrosis was not previously examined. To study the in vivo role of CCR7 in a novel model of pulmonary fibrosis, 1.0 × 106 primary fibroblasts grown from idiopathic pulmonary fibrosis/usual interstitial pneumonia, nonspecific interstitial pneumonia, or histologically normal biopsies were injected intravenously into C.B-17 severe combined immunodeficiency (SCID)/beige (bg) mice. At days 35 and 63 after idiopathic pulmonary fibrosis/usual interstitial pneumonia fibroblast injection, patchy interstitial fibrosis and increased hydroxyproline were present in the lungs of immunodeficient mice. Adoptively transferred nonspecific interstitial pneumonia fibroblasts caused a more diffuse interstitial fibrosis and increased hydroxyproline levels at both times, but injected normal human fibroblasts did not induce interstitial remodeling changes in C.B-17SCID/bg mice. Systemic therapeutic immunoneutralization of either human CCR7 or CC ligand 21, its ligand, significantly attenuated the pulmonary fibrosis in groups of C.B-17SCID/bg mice that received either type of IIP fibroblasts. Thus, the present study demonstrates that pulmonary fibrosis is initiated by the intravenous introduction of primary human fibroblast lines into immunodeficient mice, and this fibrotic response is dependent on the interaction between CC ligand 21 and CCR7. PMID:17392156

Intercalation of P atoms in Fullerene-like CP x

NASA Astrophysics Data System (ADS)

Gueorguiev, G. K.; Czigány, Zs.; Furlan, A.; Stafström, S.; Hultman, L.

2011-01-01

The energy cost for P atom intercalation and corresponding structural implications during formation of Fullerene-like Phosphorus carbide (FL-CPx) were evaluated within the framework of Density Functional Theory. Single P atom interstitial defects in FL-CPx are energetically feasible and exhibit energy cost of 0.93-1.21 eV, which is comparable to the energy cost for experimentally confirmed tetragon defects and dangling bonds in CPx. A single P atom intercalation event in FL-CPx can increase the inter-sheet distance from 3.39-3.62 Å to 5.81-7.04 Å. These theoretical results are corroborated by Selected Area Electron Diffraction characterization of FL-CPx samples.

Unusual coexistence of opportunistic lung infections in a human immunodeficiency virus positive patient suffering from persistent Pneumocystis jirovecii pneumonia: a case report.

PubMed

Ponces Bento, D; Esteves, F; Matos, O; Miranda, A C; Ventura, F; Araújo, C; Mansinho, K

2013-01-01

It is well established that HIV patients are at high risk of opportunistic infections (OI), like the ones caused by Pneumocystis jirovecii, a worldwide pathogen implicated in interstitial pneumonia (PcP). We present a case of a newly diagnosed HIV-1 patient with multiple OI, including a persistent form of PcP, an invasive aspergillosis (IA), cytomegalovirus and Mycobacterium xenopi lung infection. We describe the combination of laboratorial screening, surgery and antimicrobial therapy that were crucial for patient recovery. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Multimorbidity and health-related quality of life (HRQoL) in a nationally representative population sample: implications of count versus cluster method for defining multimorbidity on HRQoL.

PubMed

Wang, Lili; Palmer, Andrew J; Cocker, Fiona; Sanderson, Kristy

2017-01-09

No universally accepted definition of multimorbidity (MM) exists, and implications of different definitions have not been explored. This study examined the performance of the count and cluster definitions of multimorbidity on the sociodemographic profile and health-related quality of life (HRQoL) in a general population. Data were derived from the nationally representative 2007 Australian National Survey of Mental Health and Wellbeing (n = 8841). The HRQoL scores were measured using the Assessment of Quality of Life (AQoL-4D) instrument. The simple count (2+ & 3+ conditions) and hierarchical cluster methods were used to define/identify clusters of multimorbidity. Linear regression was used to assess the associations between HRQoL and multimorbidity as defined by the different methods. The assessment of multimorbidity, which was defined using the count method, resulting in the prevalence of 26% (MM2+) and 10.1% (MM3+). Statistically significant clusters identified through hierarchical cluster analysis included heart or circulatory conditions (CVD)/arthritis (cluster-1, 9%) and major depressive disorder (MDD)/anxiety (cluster-2, 4%). A sensitivity analysis suggested that the stability of the clusters resulted from hierarchical clustering. The sociodemographic profiles were similar between MM2+, MM3+ and cluster-1, but were different from cluster-2. HRQoL was negatively associated with MM2+ (β: -0.18, SE: -0.01, p < 0.001), MM3+ (β: -0.23, SE: -0.02, p < 0.001), cluster-1 (β: -0.10, SE: 0.01, p < 0.001) and cluster-2 (β: -0.36, SE: 0.01, p < 0.001). Our findings confirm the existence of an inverse relationship between multimorbidity and HRQoL in the Australian population and indicate that the hierarchical clustering approach is validated when the outcome of interest is HRQoL from this head-to-head comparison. Moreover, a simple count fails to identify if there are specific conditions of interest that are driving poorer HRQoL. Researchers should exercise caution when selecting a definition of multimorbidity because it may significantly influence the study outcomes.

Effect of electron injection on defect reactions in irradiated silicon containing boron, carbon, and oxygen

NASA Astrophysics Data System (ADS)

Makarenko, L. F.; Lastovskii, S. B.; Yakushevich, H. S.; Moll, M.; Pintilie, I.

2018-04-01

Comparative studies employing Deep Level Transient Spectroscopy and C-V measurements have been performed on recombination-enhanced reactions between defects of interstitial type in boron doped silicon diodes irradiated with alpha-particles. It has been shown that self-interstitial related defects which are immobile even at room temperatures can be activated by very low forward currents at liquid nitrogen temperatures. Their activation is accompanied by the appearance of interstitial carbon atoms. It has been found that at rather high forward current densities which enhance BiOi complex disappearance, a retardation of Ci annealing takes place. Contrary to conventional thermal annealing of the interstitial boron-interstitial oxygen complex, the use of forward current injection helps to recover an essential part of charge carriers removed due to irradiation.

CT in the diagnosis of interstitial lung disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergin, C.J.; Mueller, N.L.

1985-09-01

The computed tomographic (CT) appearance of interstitial lung disease was assessed in 23 patients with known interstitial disease. These included seven patients with fibrosing alveolitis, six with silicosis, two with hypersensitivity pneumonitis, three with lymphangitic spread of tumor, two with sarcoidosis, one with rheumatoid lung disease, and two with neurofibromatosis. The CT appearance of the interstitial changes in the different disease entities was assessed. Nodules were a prominent CT feature in silicosis, sarcoidosis, and lymphangitic spread of malignancy. Distribution of nodules and associated interlobular septal thickening provided further distinguishing features in these diseases. Reticular densities were the predominant CT changemore » in fibrosing alveolitis, rheumatoid lung disease, and extrinsic allergic alveolitis. CT can be useful in the investigation of selected instances of interstitial pulmonary disease.« less

Numerical analysis of stress effects on Frank loop evolution during irradiation in austenitic Fe&z.sbnd;Cr&z.sbnd;Ni alloy

NASA Astrophysics Data System (ADS)

Tanigawa, Hiroyasu; Katoh, Yutai; Kohyama, Akira

1995-08-01

Effects of applied stress on early stages of interstitial type Frank loop evolution were investigated by both numerical calculation and irradiation experiments. The final objective of this research is to propose a comprehensive model of complex stress effects on microstructural evolution under various conditions. In the experimental part of this work, the microstructural analysis revealed that the differences in resolved normal stress caused those in the nucleation rates of Frank loops on {111} crystallographic family planes, and that with increasing external applied stress the total nucleation rate of Frank loops was increased. A numerical calculation was carried out primarily to evaluate the validity of models of stress effects on nucleation processes of Frank loop evolution. The calculation stands on rate equuations which describe evolution of point defects, small points defect clusters and Frank loops. The rate equations of Frank loop evolution were formulated for {111} planes, considering effects of resolved normal stress to clustering processes of small point defects and growth processes of Frank loops, separately. The experimental results and the predictions from the numerical calculation qualitatively coincided well with each other.

Respiratory herpesvirus infection in two Indian Ringneck parakeets.

PubMed

Lazic, Tatjana; Ackermann, Mark R; Drahos, Jo M; Stasko, Judith; Haynes, Joseph S

2008-03-01

A flock of Indian Ringneck parakeets (Psittacula krameri manillensis) was imported to the United States from Australia. Soon after, 1 parakeet suddenly died, and a second parakeet died after a 2-day course of illness, which consisted of anorexia, lethargy, emaciation, and dyspnea. At necropsy, the affected birds had diffuse consolidation and red discoloration of the lungs, as well as thickened, congested air sacs. The microscopic examination revealed multifocal, necrotizing bronchitis, parabronchitis, and interstitial pneumonia. The lumen of the affected airways contained numerous, large syncytial cells with up to 15 nuclei. The nuclei of these syncytial cells often contained large, eosinophilic inclusion bodies, consistent with herpesvirus. The epithelium of the trachea and air sacs was hypertrophied and contained syncytial cells with intranuclear inclusion bodies similar to the bronchi. In addition, a few intranuclear inclusion bodies were also present in the epithelial cells that line the air capillaries. On ultrastructural examination, the nuclei of degenerating epithelial cells contained clusters of viral nucleocapsid proteins and unenveloped, icosahedral, viral particles that were approximately 90 nm in diameter. In addition, some epithelial cells contained clusters of enveloped viral particles approximately 105 nm in diameter, within the cytocavitary network. These lesions are characteristic of those caused by respiratory herpesvirus of parakeets.

Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

PubMed

Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

2010-10-01

In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular) interstitial neurons in the postnatal and adult deep cerebral white matter (i.e. corpus callosum, anterior commissure, internal and external capsule and the corona radiata/centrum semiovale). Although these deep interstitial neurons are poorly developed or absent in the brains of rodents, they represent a prominent feature of the significantly enlarged white matter of human and non-human primate brains. © 2010 The Authors. Journal of Anatomy © 2010 Anatomical Society of Great Britain and Ireland.

Evaluation of phase II toxicity identification evaluation methods for freshwater whole sediment and interstitial water.

PubMed

Phillips, Bryn M; Anderson, Brian S; Hunt, John W; Clark, Sara L; Voorhees, Jennifer P; Tjeerdema, Ron S; Casteline, Jane; Stewart, Margaret

2009-02-01

Phase I whole sediment toxicity identification evaluation (TIE) methods have been developed to characterize the cause of toxicity as organic chemicals, metals, or ammonia. In Phase II identification treatments, resins added to whole sediment to reduce toxicity caused by metals and organics can be separated and eluted much like solid-phase extraction (SPE) columns are eluted for interstitial water. In this study, formulated reference sediments spiked with toxic concentrations of copper, fluoranthene, and nonylphenol were subjected to whole sediment and interstitial water TIE treatments to evaluate Phase I and II TIE procedures for identifying the cause of toxicity to Hyalella azteca. Phase I TIE treatments consisted of adding adsorbent resins to whole sediment, and using SPE columns to remove spiked chemicals from interstitial water. Phase II treatments consisted of eluting resins and SPE columns and the preparation and testing of eluates for toxicity and chemistry. Whole sediment resins and SPE columns significantly reduced toxicity, and the eluates from all treatments contained toxic concentrations of the spiked chemical except for interstitial water fluoranthene. Toxic unit analysis based on median lethal concentrations (LC50s) allowed for the comparison of chemical concentrations among treatments, and demonstrated that the bioavailability of some chemicals was reduced in some samples and treatments. The concentration of fluoranthene in the resin eluate closely approximated the original interstitial water concentration, but the resin eluate concentrations of copper and nonylphenol were much higher than the original interstitial water concentrations. Phase II whole sediment TIE treatments provided complementary lines of evidence to the interstitial water TIE results.

Making Sense of Cluster Analysis: Revelations from Pakistani Science Classes

ERIC Educational Resources Information Center

Pell, Tony; Hargreaves, Linda

2011-01-01

Cluster analysis has been applied to quantitative data in educational research over several decades and has been a feature of the Maurice Galton's research in primary and secondary classrooms. It has offered potentially useful insights for teaching yet its implications for practice are rarely implemented. It has been subject also to negative…

Endothelial necrosis at 1h post-burn predicts progression of tissue injury

PubMed Central

Hirth, Douglas; McClain, Steve A.; Singer, Adam J.; Clark, Richard A.F.

2013-01-01

Burn injury progression has not been well characterized at the cellular level. To define burn injury progression in terms of cell death, histopathologic spatiotemporal relationships of cellular necrosis and apoptosis were investigated in a validated porcine model of vertical burn injury progression. Cell necrosis was identified by High Mobility Group Box 1 protein and apoptosis by Caspase 3a staining of tissue samples taken 1h, 24h and 7 days post-burn. Level of endothelial cell necrosis at 1h was predictive of level of apoptosis at 24h (Pearson's r=0.87) and of level of tissue necrosis at 7 days (Pearson's r=0.87). Furthermore, endothelial cell necrosis was deeper than interstitial cell necrosis at 1h (p<0.001). Endothelial cell necrosis at 1h divided the zone of injury progression (Jackson's zone of stasis) into an upper subzone with necrotic endothelial cells and initially viable adnexal and interstitial cells at 1h that progressed to necrosis by 24h, and a lower zone with initially viable endothelial cells at 1h, but necrosis and apoptosis of all cell types by 24h. Importantly, this spatiotemporal series of events and rapid progression resembles myocardial infarction and stroke, and implicates mechanisms of these injuries, ischemia, ischemia reperfusion, and programmed cell death, in burn progression. PMID:23627744

Respiratory bronchiolitis-associated interstitial lung disease secondary to electronic nicotine delivery system use confirmed with open lung biopsy.

PubMed

Flower, Mark; Nandakumar, Lakshmy; Singh, Mahendra; Wyld, David; Windsor, Morgan; Fielding, David

2017-05-01

As a modern phenomenon, there is currently limited understanding of the possible toxic effects and broader implications of electronic nicotine delivery systems (ENDS). Large volumes of aerosolized particles are inhaled during "vaping" and there are now an increasing number of case reports demonstrating toxic effects of ENDS, as well as human studies demonstrating impaired lung function in users. This article presents a case of respiratory bronchiolitis interstitial lung disease (RB-ILD) precipitated by vaping in a 33-year-old male with 10 pack years of traditional cigarette and prior treatment for mixed germ cell tumour. The patient had started vaping 10-15 times per day while continuing to smoke 10 traditional cigarettes per day. After 3 months of exposure to e-cigarette vapour, chest computed tomography demonstrated multiple new poorly defined pulmonary nodules with fluffy parenchyma opacification centred along the terminal bronchovascular units. Video-assisted thoracoscopy with lung biopsy of the right upper and right middle lobes was undertaken. The microscopic findings were overall consistent with RB-ILD. This case demonstrates toxicity with use of ENDS on open lung biopsy with resolution of radiographic findings on cessation. We believe that this is the first case where open lung biopsy has demonstrated this and our findings are consistent with RB-ILD.

Coxiella burnetii, a hidden pathogen in interstitial lung disease?

PubMed

Melenotte, Cléa; Izaaryene, Jalal-Jean; Gomez, Carine; Delord, Marion; Prudent, Elsa; Lepidi, Hubert; Mediannikov, Oleg; Lacoste, Marion; Djossou, Felix; Mania, Alexandre; Bernard, Noelle; Huchot, Eric; Mège, Jean-Louis; Brégeon, Fabienne; Raoult, Didier

2018-04-06

We report 7 patients with interstitial lung disease (ILD) on CT-scan reviewing. C. burnetii was diagnosed in situ in one lung biopsy performed. All patients had advanced interstitial lung fibrosis and persistent C. burnetii infection. Q fever may be a cofactor of ILD, especially in endemic areas.

[Modern Views on Children's Interstitial Lung Disease].

PubMed

Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu

2015-01-01

Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article.

Studies of O18 impurity trapping at interstitial dislocation loops in ion implanted Fe (1 1 0) by ion channeling and ab initio calculations

NASA Astrophysics Data System (ADS)

Mathayan, Vairavel; Kothalamuthu, Saravanan; Gnanasekaran, Jaiganesh; Balakrishnan, Sundaravel; Panigrahi, Binaykumar

2018-01-01

The O18 and self ions are implanted at same depth in Fe (1 1 0) crystal and annealed to study the oxygen trapping under excess self interstitial defects. Rutherford backscattering spectrometry, nuclear reaction analysis and channeling measurements have been performed to determine the lattice site position of O18. The presence of dislocation loops is confirmed by energy-dependent dechanneling parameter measurements. From the tilt angular scans of Fe and O18 signals along 〈1 0 0〉, 〈1 1 0〉 axes, O18 is found to be displaced 0.2 Å from tetrahedral towards octahedral interstitial site in O18. Similar lattice site location of oxygen with the displacement of 0.37 Å is predicted by density functional theory calculations for the interaction of oxygen with 〈1 0 0〉 interstitial dislocation loop structure. Our results provide strong evidence on oxygen trapping at interstitial dislocation loops in the presence of excess interstitial defects in iron.

Feasibility of interstitial diffuse optical tomography using cylindrical diffusing fiber for prostate PDT

PubMed Central

Liang, Xing; Wang, Ken Kang-Hsin; Zhu, Timothy C.

2013-01-01

Interstitial diffuse optical tomography (DOT) has been used to characterize spatial distribution of optical properties for prostate photodynamic therapy (PDT) dosimetry. We have developed an interstitial DOT method using cylindrical diffuse fibers (CDFs) as light sources, so that the same light sources can be used for both DOT measurement and PDT treatment. In this novel interstitial CDF-DOT method, absolute light fluence per source strength (in unit of 1/cm2) is used to separate absorption and scattering coefficients. A mathematical phantom and a solid prostate phantom including anomalies with known optical properties were used, respectively, to test the feasibility of reconstructing optical properties using interstitial CDF-DOT. Three dimension spatial distributions of the optical properties were reconstructed for both scenarios. Our studies show that absorption coefficient can be reliably extrapolated while there are some cross talks between absorption and scattering properties. Even with the suboptimal reduced scattering coefficients, the reconstructed light fluence rate agreed with the measured values to within ±10%, thus the proposed CDF-DOT allows greatly improved light dosimetry calculation for interstitial PDT. PMID:23629149

Xenon Defects in Uranium Dioxide From First Principles and Interatomic Potentials

NASA Astrophysics Data System (ADS)

Thompson, Alexander

In this thesis, we examine the defect energetics and migration energies of xenon atoms in uranium dioxide (UO2) from first principles and interatomic potentials. We also parameterize new, accurate interatomic potentials for xenon and uranium dioxide. To achieve accurate energetics and provide a foundation for subsequent calculations, we address difficulties in finding consistent energetics within Hubbard U corrected density functional theory (DFT+U). We propose a method of slowly ramping the U parameter in order to guide the calculation into low energy orbital occupations. We find that this method is successful for a variety of materials. We then examine the defect energetics of several noble gas atoms in UO2 for several different defect sites. We show that the energy to incorporate large noble gas atoms into interstitial sites is so large that it is energetically favorable for a Schottky defect cluster to be created to relieve the strain. We find that, thermodynamically, xenon will rarely ever be in the interstitial site of UO2. To study larger defects associated with the migration of xenon in UO 2, we turn to interatomic potentials. We benchmark several previously published potentials against DFT+U defect energetics and migration barriers. Using a combination of molecular dynamics and nudged elastic band calculations, we find a new, low energy migration pathway for xenon in UO2. We create a new potential for xenon that yields accurate defect energetics. We fit this new potential with a method we call Iterative Potential Refinement that parameterizes potentials to first principles data via a genetic algorithm. The potential finds accurate energetics for defects with relatively low amounts of strain (xenon in defect clusters). It is important to find accurate energetics for these sorts of low-strain defects because they essentially represent small xenon bubbles. Finally, we parameterize a new UO2 potential that simultaneously yields accurate vibrational properties and defect energetics, important properties for UO2 because of the high temperature and defective reactor environment.. Previously published potentials could only yield accurate defect energetics or accurate phonons, but never both.

Sleep, Dietary, and Exercise Behavioral Clusters among Truck Drivers with Obesity: Implications for Interventions

PubMed Central

Olson, Ryan; Thompson, Sharon V.; Wipfli, Brad; Hanson, Ginger; Elliot, Diane L.; Anger, W. Kent; Bodner, Todd; Hammer, Leslie B.; Hohn, Elliot; Perrin, Nancy A.

2015-01-01

Objective Our objectives were to describe a sample of truck drivers, identify clusters of drivers with similar patterns in behaviors affecting energy balance (sleep, diet, and exercise), and test for cluster differences in health and psychosocial factors. Methods Participants’ (n=452, BMI M=37.2, 86.4% male) self-reported behaviors were dichotomized prior to hierarchical cluster analysis, which identified groups with similar behavior co-variation. Cluster differences were tested with generalized estimating equations. Results Five behavioral clusters were identified that differed significantly in age, smoking status, diabetes prevalence, lost work days, stress, and social support, but not in BMI. Cluster 2, characterized by the best sleep quality, had significantly lower lost workdays and stress than other clusters. Conclusions Weight management interventions for drivers should explicitly address sleep, and may be maximally effective after establishing socially supportive work environments that reduce stress exposures. PMID:26949883

Kinetics of carbon clustering in detonation of high explosives: Does theory match experiment?

NASA Astrophysics Data System (ADS)

Velizhanin, Kirill; Watkins, Erik; Dattelbaum, Dana; Gustavsen, Richard; Aslam, Tariq; Podlesak, David; Firestone, Millicent; Huber, Rachel; Ringstrand, Bryan; Willey, Trevor; Bagge-Hansen, Michael; Hodgin, Ralph; Lauderbach, Lisa; van Buuren, Tony; Sinclair, Nicholas; Rigg, Paulo; Seifert, Soenke; Gog, Thomas

2017-06-01

Chemical reactions in detonation of carbon-rich high explosives yield carbon clusters as major constituents of the products. Efforts to model carbon clustering as a diffusion-limited irreversible coagulation of carbon clusters go back to the seminal paper by Shaw and Johnson. However, first direct experimental observations of the kinetics of clustering yielded cluster growth one to two orders of magnitude slower than theoretical predictions. Multiple efforts were undertaken to test and revise the basic assumptions of the model in order to achieve better agreement with experiment. We discuss our very recent direct experimental observations of carbon clustering dynamics and demonstrate that these new results are in much better agreement with the modified Shaw-Johnson model. The implications of this much better agreement on our present understanding of detonation carbon clustering processes and possible ways to increase the agreement between theory and experiment even further are discussed.

Sleep, Dietary, and Exercise Behavioral Clusters Among Truck Drivers With Obesity: Implications for Interventions.

PubMed

Olson, Ryan; Thompson, Sharon V; Wipfli, Brad; Hanson, Ginger; Elliot, Diane L; Anger, W Kent; Bodner, Todd; Hammer, Leslie B; Hohn, Elliot; Perrin, Nancy A

2016-03-01

The objectives of the study were to describe a sample of truck drivers, identify clusters of drivers with similar patterns in behaviors affecting energy balance (sleep, diet, and exercise), and test for cluster differences in health safety, and psychosocial factors. Participants' (n = 452, body mass index M = 37.2, 86.4% male) self-reported behaviors were dichotomized prior to hierarchical cluster analysis, which identified groups with similar behavior covariation. Cluster differences were tested with generalized estimating equations. Five behavioral clusters were identified that differed significantly in age, smoking status, diabetes prevalence, lost work days, stress, and social support, but not in body mass index. Cluster 2, characterized by the best sleep quality, had significantly lower lost workdays and stress than other clusters. Weight management interventions for drivers should explicitly address sleep, and may be maximally effective after establishing socially supportive work environments that reduce stress exposures.

Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration.

PubMed

Fry, Brendan C; Edwards, Aurélie; Layton, Anita T

2015-05-01

The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2 (-)) and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and O2 (-) concentration in the OM and upper IM. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. The model further predicts that due to the nonlinear interactions among O2, NO, and O2 (-), the effects of NO and O2 (-) on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. An additional simulation suggests that a sufficiently large reduction in tubular transport efficiency may be the key contributing factor, more so than oxidative stress alone, to hypertension-induced medullary hypoxia. Moreover, model predictions suggest that urine Po2 could serve as a biomarker for medullary hypoxia and a predictor of the risk for hospital-acquired acute kidney injury. Copyright © 2015 the American Physiological Society.

Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration

PubMed Central

Edwards, Aurélie; Layton, Anita T.

2015-01-01

The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2−) and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and O2− concentration in the OM and upper IM. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. The model further predicts that due to the nonlinear interactions among O2, NO, and O2−, the effects of NO and O2− on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. An additional simulation suggests that a sufficiently large reduction in tubular transport efficiency may be the key contributing factor, more so than oxidative stress alone, to hypertension-induced medullary hypoxia. Moreover, model predictions suggest that urine Po2 could serve as a biomarker for medullary hypoxia and a predictor of the risk for hospital-acquired acute kidney injury. PMID:25651567

A characterization of the coupled evolution of grain fabric and pore space using complex networks: Pore connectivity and optimized flows in the presence of shear bands

NASA Astrophysics Data System (ADS)

Russell, Scott; Walker, David M.; Tordesillas, Antoinette

2016-03-01

A framework for the multiscale characterization of the coupled evolution of the solid grain fabric and its associated pore space in dense granular media is developed. In this framework, a pseudo-dual graph transformation of the grain contact network produces a graph of pores which can be readily interpreted as a pore space network. Survivability, a new metric succinctly summarizing the connectivity of the solid grain and pore space networks, measures material robustness. The size distribution and the connectivity of pores can be characterized quantitatively through various network properties. Assortativity characterizes the pore space with respect to the parity of the number of particles enclosing the pore. Multiscale clusters of odd parity versus even parity contact cycles alternate spatially along the shear band: these represent, respectively, local jamming and unjamming regions that continually switch positions in time throughout the failure regime. Optimal paths, established using network shortest paths in favor of large pores, provide clues on preferential paths for interstitial matter transport. In systems with higher rolling resistance at contacts, less tortuous shortest paths thread through larger pores in shear bands. Notably the structural patterns uncovered in the pore space suggest that more robust models of interstitial pore flow through deforming granular systems require a proper consideration of the evolution of in situ shear band and fracture patterns - not just globally, but also inside these localized failure zones.

Statistical study of defects caused by primary knock-on atoms in fcc Cu and bcc W using molecular dynamics

NASA Astrophysics Data System (ADS)

Warrier, M.; Bhardwaj, U.; Hemani, H.; Schneider, R.; Mutzke, A.; Valsakumar, M. C.

2015-12-01

We report on molecular Dynamics (MD) simulations carried out in fcc Cu and bcc W using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) code to study (i) the statistical variations in the number of interstitials and vacancies produced by energetic primary knock-on atoms (PKA) (0.1-5 keV) directed in random directions and (ii) the in-cascade cluster size distributions. It is seen that around 60-80 random directions have to be explored for the average number of displaced atoms to become steady in the case of fcc Cu, whereas for bcc W around 50-60 random directions need to be explored. The number of Frenkel pairs produced in the MD simulations are compared with that from the Binary Collision Approximation Monte Carlo (BCA-MC) code SDTRIM-SP and the results from the NRT model. It is seen that a proper choice of the damage energy, i.e. the energy required to create a stable interstitial, is essential for the BCA-MC results to match the MD results. On the computational front it is seen that in-situ processing saves the need to input/output (I/O) atomic position data of several tera-bytes when exploring a large number of random directions and there is no difference in run-time because the extra run-time in processing data is offset by the time saved in I/O.

Temporal and spatial variations in kinetics of alkaline phosphatase in sediments of a shallow Chinese eutrophic lake (Lake Donghu).

PubMed

Yiyong, Zhou; Jianqiu, Li; Min, Zhang

2002-04-01

Monthly sediment and interstitial water samples were collected in a shallow Chinese freshwater lake (Lake Donghu) from three areas to determine if alkaline phosphatase activity (APA) plays an important role, in phosphorus cycling in sediment. The seasonal variability in the kinetics of APA and other relevant parameters were investigated from 1995-1996. The phosphatase hydrolyzable phosphorus (PHP) fluctuated seasonally in interstitial water, peaking in the spring. A synchronous pattern was observed in chlorophyll a contents in surface water in general. The orthophosphate (o-P) concentrations in the interstitial water increased during the spring. An expected negative relationship between PHP and Vmax of APA is not evident in interstitial water. The most striking feature of the two variables is their co-occurring, which can be explained in terms of an induction mechanism. It is argued that phosphatase activity mainly contributes to the driving force of o-P regeneration from PHP in interstitial water, supporting the development of phytoplankton biomass in spring. The Vmax values in sediment increased during the summer, in conjunction with lower Km values in interstitial water that suggest a higher affinity for the substrate. The accumulation of organic matter in the sediment could be traced back to the breakdown of the algal spring bloom, which may stimulate APA with higher kinetic efficiency, by a combination of the higher Vmax in sediments plus lower Km values in interstitial water, in summer. In summary, a focus on phosphatase and its substrate in annual scale may provide a useful framework for the development of novel P cycling, possible explanations for the absence of a clear relationship between PHP and APA were PHP released from the sediment which induced APA, and the presence of kinetically higher APA both in sediment and interstitial water which permitted summer mineralization of organic matter derived from the spring bloom to occur. The study highlighted the need for distinguishing functionally distinct extracellular enzymes between the sediment and interstitial water of lakes.

Native interstitial defects in ZnGeN2

NASA Astrophysics Data System (ADS)

Skachkov, Dmitry; Lambrecht, Walter R. L.

2017-10-01

A density functional study is presented of the interstitial Zni, Gei, and Ni in ZnGeN2. Corrections to the band gap are included by means of the LDA+U method. The Zn and Ge interstitials are both found to strongly prefer the larger octahedral site compared to the two types of tetrahedral sites. The Zn interstitial is found to be a shallow double donor, but it has higher energy than previously studied antisite defects. It has a resonance in the conduction band that is Zn-s like. The Ge interstitial is an even higher energy of formation defect and also behaves as a shallow double donor, but it also has a deep level in the gap corresponding to a Ge-s orbital character while the Ge-p forms a resonance in the conduction band. The nitrogen interstitial forms a split-interstitial configuration, as also occurs in GaN. Its electronic levels can be related to that of a N2 molecule. The defect levels in the gap correspond to the πg-like lowest unoccupied molecular orbital of the molecule, which here becomes filled with three electrons in the defect's neutral charge state. They are found to prefer a high-spin configuration in the q =+1 state. The corresponding transition levels are obtained and show that this is an amphoteric trap level occurring in +2 , +1 , 0, and -1 charge states. The two possible sites for this split interstitial, on top of Zn or on top of Ge, differ slightly in N2 bond length. While the Ni defects have the lowest formation energy among the interstitials, it is still higher than that of the antisites. Hence they are not expected to occur in sufficient concentration to affect the intrinsic Fermi level position. In particular, they do not contribute to the unintentional n -type background doping.

Impurity and defect interactions during laser thermal annealing in Ge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milazzo, R., E-mail: ruggero.milazzo@unipd.it; De Salvador, D.; Carnera, A.

2016-01-28

The microscopic mechanisms involving dopants, contaminants, and defects in Ge during pulsed melting laser thermal annealing (LTA) are investigated in detail. Samples both un-implanted and implanted with As or B are processed by LTA as well as characterized in terms of chemical (1D and 3D), electrical, and strain profiling. The clustering of As is directly measured by 3D chemical profiling and correlated with its partial electrical activation along with a reduction of the lattice strain induced by As atoms. A semi-quantitative microscopic model involving the interaction with mobile As-vacancy (AsV) complexes is proposed to describe the clustering mechanism. Boron ismore » shown to follow different clustering behavior that changes with depth and marked by completely different strain levels. Oxygen penetrates from the surface into all the samples as a result of LTA and, only in un-implanted Ge, it occupies an interstitial position inducing also positive strain in the lattice. On the contrary, data suggest that the presence of As or B forces O to assume different configurations with negligible strain, through O-V or O-B interactions for the two dopant species, respectively. These data suggest that LTA does not inject a significant amount of vacancies in Ge, at variance with Si, unless As atoms or possibly other n-type dopants are present. These results have to be carefully considered for modeling the LTA process in Ge and its implementation in technology.« less

Lattice strain in irradiated materials unveils a prevalent defect evolution mechanism

NASA Astrophysics Data System (ADS)

Debelle, Aurélien; Crocombette, Jean-Paul; Boulle, Alexandre; Chartier, Alain; Jourdan, Thomas; Pellegrino, Stéphanie; Bachiller-Perea, Diana; Carpentier, Denise; Channagiri, Jayanth; Nguyen, Tien-Hien; Garrido, Frédérico; Thomé, Lionel

2018-01-01

Modification of materials using ion beams has become a widespread route to improve or design materials for advanced applications, from ion doping for microelectronic devices to emulation of nuclear reactor environments. Yet, despite decades of studies, major issues regarding ion/solid interactions are not solved, one of them being the lattice-strain development process in irradiated crystals. In this work, we address this question using a consistent approach that combines x-ray diffraction (XRD) measurements with both molecular dynamics (MD) and rate equation cluster dynamics (RECD) simulations. We investigate four distinct materials that differ notably in terms of crystalline structure and nature of the atomic bonding. We demonstrate that these materials exhibit a common behavior with respect to the strain development process. In fact, a strain build-up followed by a strain relaxation is observed in the four investigated cases. The strain variation is unambiguously ascribed to a change in the defect configuration, as revealed by MD simulations. Strain development is due to the clustering of interstitial defects into dislocation loops, while the strain release is associated with the disappearance of these loops through their integration into a network of dislocation lines. RECD calculations of strain depth profiles, which are in agreement with experimental data, indicate that the driving force for the change in the defect nature is the defect clustering process. This study paves the way for quantitative predictions of the microstructure changes in irradiated materials.

Interstitial-phase precipitation in iron-base alloys: a comparative study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pelton, A.R.

1982-06-01

Recent developments have elucidated the atomistic mechanisms of precipitation of interstitial elements in simple alloy systems. However, in the more technologically important iron base alloys, interstitial phase precipitation is generally not well understood. The present experimental study was therefore designed to test the applicability of these concepts to more complex ferrous alloys. Hence, a comparative study was made of interstitial phase precipitation in ferritic Fe-Si-C and in austenitic phosphorus-containing Fe-Cr-Ni steels. These systems were subjected to a variety of quench-age thermal treatments, and the microstructural development was subsequently characterized by transmission electron microscopy.

A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration

PubMed Central

Winter, Benjamin J.; O'Connell, Helen E.; Bowden, Scott; Carey, Marcus; Eisen, Damon P.

2015-01-01

Objectives To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis. Subjects and Methods A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR. Results Case patients were reflective of interstitial cystitis epidemiology with age range from 26–88 years (median 58) and female predominance (41/50 F). There was a significant increase in the frequency of polyomavirus shedding between cases and controls (p<0.02). Polyomavirus shedding, in particular BK viruria, was associated with vesical ulceration, a marker of disease severity, among interstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89–24.4). There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17–17.4). Conclusion The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation. PMID:26325074

Primary radiation damage of Zr-0.5%Nb binary alloy: atomistic simulation by molecular dynamics method

NASA Astrophysics Data System (ADS)

Tikhonchev, M.; Svetukhin, V.; Kapustin, P.

2017-09-01

Ab initio calculations predict high positive binding energy (˜1 eV) between niobium atoms and self-interstitial configurations in hcp zirconium. It allows the expectation of increased niobium fraction in self-interstitials formed under neutron irradiation in atomic displacement cascades. In this paper, we report the results of molecular dynamics simulation of atomic displacement cascades in Zr-0.5%Nb binary alloy and pure Zr at the temperature of 300 K. Two sets of n-body interatomic potentials have been used for the Zr-Nb system. We consider a cascade energy range of 2-20 keV. Calculations show close estimations of the average number of produced Frenkel pairs in the alloy and pure Zr. A high fraction of Nb is observed in the self-interstitial configurations. Nb is mainly detected in single self-interstitial configurations, where its fraction reaches tens of percent, i.e. more than its tenfold concentration in the matrix. The basic mechanism of this phenomenon is the trapping of mobile self-interstitial configurations by niobium. The diffusion of pure zirconium and mixed zirconium-niobium self-interstitial configurations in the zirconium matrix at 300 K has been simulated. We observe a strong dependence of the estimated diffusion coefficients and fractions of Nb in self-interstitials produced in displacement cascades on the potential.

Impact of Interstitial Ni on the Thermoelectric Properties of the Half-Heusler TiNiSn.

PubMed

Barczak, Sonia A; Buckman, Jim; Smith, Ronald I; Baker, Annabelle R; Don, Eric; Forbes, Ian; Bos, Jan-Willem G

2018-03-30

TiNiSn is an intensively studied half-Heusler alloy that shows great potential for waste heat recovery. Here, we report on the structures and thermoelectric properties of a series of metal-rich TiNi 1+y Sn compositions prepared via solid-state reactions and hot pressing. A general relation between the amount of interstitial Ni and lattice parameter is determined from neutron powder diffraction. High-resolution synchrotron X-ray powder diffraction reveals the occurrence of strain broadening upon hot pressing, which is attributed to the metastable arrangement of interstitial Ni. Hall measurements confirm that interstitial Ni causes weak n-type doping and a reduction in carrier mobility, which limits the power factor to 2.5-3 mW m -1 K -2 for these samples. The thermal conductivity was modelled within the Callaway approximation and is quantitively linked to the amount of interstitial Ni, resulting in a predicted value of 12.7 W m -1 K -1 at 323 K for stoichiometric TiNiSn. Interstitial Ni leads to a reduction of the thermal band gap and moves the peak ZT = 0.4 to lower temperatures, thus offering the possibility to engineer a broad ZT plateau. This work adds further insight into the impact of small amounts of interstitial Ni on the thermal and electrical transport of TiNiSn.

Impact of Interstitial Ni on the Thermoelectric Properties of the Half-Heusler TiNiSn

PubMed Central

Barczak, Sonia A.; Smith, Ronald I.; Baker, Annabelle R.; Don, Eric; Forbes, Ian

2018-01-01

TiNiSn is an intensively studied half-Heusler alloy that shows great potential for waste heat recovery. Here, we report on the structures and thermoelectric properties of a series of metal-rich TiNi1+ySn compositions prepared via solid-state reactions and hot pressing. A general relation between the amount of interstitial Ni and lattice parameter is determined from neutron powder diffraction. High-resolution synchrotron X-ray powder diffraction reveals the occurrence of strain broadening upon hot pressing, which is attributed to the metastable arrangement of interstitial Ni. Hall measurements confirm that interstitial Ni causes weak n-type doping and a reduction in carrier mobility, which limits the power factor to 2.5–3 mW m−1 K−2 for these samples. The thermal conductivity was modelled within the Callaway approximation and is quantitively linked to the amount of interstitial Ni, resulting in a predicted value of 12.7 W m−1 K−1 at 323 K for stoichiometric TiNiSn. Interstitial Ni leads to a reduction of the thermal band gap and moves the peak ZT = 0.4 to lower temperatures, thus offering the possibility to engineer a broad ZT plateau. This work adds further insight into the impact of small amounts of interstitial Ni on the thermal and electrical transport of TiNiSn. PMID:29601547

A systematic review of validated methods for identifying pulmonary fibrosis and interstitial lung disease using administrative and claims data.

PubMed

Jones, Natalie; Schneider, Gary; Kachroo, Sumesh; Rotella, Philip; Avetisyan, Ruzan; Reynolds, Matthew W

2012-01-01

The Food and Drug Administration's Mini-Sentinel pilot program initially aimed to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest (HOIs) from administrative and claims data. This paper summarizes the process and findings of the algorithm review of pulmonary fibrosis and interstitial lung disease. PubMed and Iowa Drug Information Service Web searches were conducted to identify citations applicable to the pulmonary fibrosis/interstitial lung disease HOI. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify pulmonary fibrosis and interstitial lung disease, including validation estimates of the coding algorithms. Our search revealed a deficiency of literature focusing on pulmonary fibrosis and interstitial lung disease algorithms and validation estimates. Only five studies provided codes; none provided validation estimates. Because interstitial lung disease includes a broad spectrum of diseases, including pulmonary fibrosis, the scope of these studies varied, as did the corresponding diagnostic codes used. Research needs to be conducted on designing validation studies to test pulmonary fibrosis and interstitial lung disease algorithms and estimating their predictive power, sensitivity, and specificity. Copyright © 2012 John Wiley & Sons, Ltd.

Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling

PubMed Central

2015-01-01

Hepatocellular carcinoma (HCC) is the most common form of liver cancer (~80%), and it is one of the few cancer types with rising incidence in the United States. This highly invasive cancer is very difficult to detect until its later stages, resulting in limited treatment options and low survival rates. There is a dearth of knowledge regarding the mechanisms associated with the effects of biomechanical forces such as interstitial fluid flow (IFF) on hepatocellular carcinoma invasion. We hypothesized that interstitial fluid flow enhanced hepatocellular carcinoma cell invasion through chemokine-mediated autologous chemotaxis. Utilizing a 3D in vitro invasion assay, we demonstrated that interstitial fluid flow promoted invasion of hepatocellular carcinoma derived cell lines. Furthermore, we showed that autologous chemotaxis influences this interstitial fluid flow-induced invasion of hepatocellular carcinoma derived cell lines via the C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12) signaling axis. We also demonstrated that mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling affects interstitial fluid flow-induced invasion; however, this pathway was separate from CXCR4/CXCL12 signaling. This study demonstrates, for the first time, the potential role of interstitial fluid flow in hepatocellular carcinoma invasion. Uncovering the mechanisms that control hepatocellular carcinoma invasion will aid in enhancing current liver cancer therapies and provide better treatment options for patients. PMID:26560447

Evaluation of antitumor efficiency of experimental interstitial photodynamic therapy on the model of M1 sarcoma.

PubMed

Skugareva, O A; Kaplan, M A; Malygina, A I; Mikhailovskaya, A A

2009-11-01

Antitumor efficiency of interstitial photodynamic therapy was evaluated in experiments on outbred albino rats with implanted M-1 sarcoma. Interstitial photodynamic therapy was carried out using one diffusor at different output power and duration of exposure. The percentage of complete regression of the tumors increased with increasing exposure parameters.

Clustering cancer gene expression data by projective clustering ensemble

PubMed Central

Yu, Xianxue; Yu, Guoxian

2017-01-01

Gene expression data analysis has paramount implications for gene treatments, cancer diagnosis and other domains. Clustering is an important and promising tool to analyze gene expression data. Gene expression data is often characterized by a large amount of genes but with limited samples, thus various projective clustering techniques and ensemble techniques have been suggested to combat with these challenges. However, it is rather challenging to synergy these two kinds of techniques together to avoid the curse of dimensionality problem and to boost the performance of gene expression data clustering. In this paper, we employ a projective clustering ensemble (PCE) to integrate the advantages of projective clustering and ensemble clustering, and to avoid the dilemma of combining multiple projective clusterings. Our experimental results on publicly available cancer gene expression data show PCE can improve the quality of clustering gene expression data by at least 4.5% (on average) than other related techniques, including dimensionality reduction based single clustering and ensemble approaches. The empirical study demonstrates that, to further boost the performance of clustering cancer gene expression data, it is necessary and promising to synergy projective clustering with ensemble clustering. PCE can serve as an effective alternative technique for clustering gene expression data. PMID:28234920

Role of Hydrophobic Clusters and Long-Range Contact Networks in the Folding of (α/β)8 Barrel Proteins

PubMed Central

Selvaraj, S.; Gromiha, M. Michael

2003-01-01

Analysis on the three dimensional structures of (α/β)8 barrel proteins provides ample light to understand the factors that are responsible for directing and maintaining their common fold. In this work, the hydrophobically enriched clusters are identified in 92% of the considered (α/β)8 barrel proteins. The residue segments with hydrophobic clusters have high thermal stability. Further, these clusters are formed and stabilized through long-range interactions. Specifically, a network of long-range contacts connects adjacent β-strands of the (α/β)8 barrel domain and the hydrophobic clusters. The implications of hydrophobic clusters and long-range networks in providing a feasible common mechanism for the folding of (α/β)8 barrel proteins are proposed. PMID:12609894

Effect of all-trans retinoic acid treatment on prohibitin and renin-angiotensin-aldosterone system expression in hypoxia-induced renal tubular epithelial cell injury.

PubMed

Zhou, Tian-Biao; Ou, Chao; Rong, Liang; Drummen, Gregor P C

2014-09-01

All-trans retinoic acid (ATRA) exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. Prohibitins (PHB), including prohibitin 1 (PHB1) and prohibitin 2 (PHB2), are evolutionary conserved and pleiotropic proteins implicated in various cellular functions, including proliferation, tumor suppression, apoptosis, transcription, and mitochondrial protein folding. The renin-angiotensin-aldosterone system plays a pivotal role in the regulation of blood pressure and volume homeostasis. All these factors and systems have been implicated in renal interstitial fibrosis. Therefore, the objective of this study was to investigate the effect of ATRA treatment on the renin-angiotensin-aldosterone system and expression of prohibitins to further understand its role in the processes leading to renal interstitial fibrosis. The hypoxic and oxidative stress conditions in obstructive renal disease were simulated in a hypoxia/reoxygenation model with renal tubular epithelial cells (RTEC) as a model system. Subsequently, the effect of ATRA on mRNA and protein expression levels was determined and correlations were established between factors involved in the renin-angiotensin-aldosterone system, the prohibitins, cellular redox status, renal interstitial fibrosis and ATRA treatment. Correlation analysis showed that both PHB1 and PHB2 protein levels were negatively correlated with angiotensin I, ACE1, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA (PHB1: r = -0.792, -0.834, -0.805, -0.795, -0.778, -0.798, -0.751, -0.682; PHB2: r = -0.872, -0.799, -0.838, -0.773, -0.769, -0.841, -0.794, -0.826; each p < 0.05), but positively correlated with ACE2, SOD, and GSH (PHB1: r = 0.796, 0.879, 0.824; PHB2: r = 0.785, 0.914, 0.849; each p < 0.05). ACE1 was positively correlated with angiotensin I, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA, and negatively correlated with ACE2, SOD, and GSH (each p < 0.05). ACE2 was negatively correlated with ACE1, angiotensin I, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA, and positively correlated with SOD and GSH (each p < 0.05). The results suggest that ATRA acts as a positive regulator of PHB1, PHB2 and ACE2, and as a negative regulator of ACE1, angiotensin I, and angiotensin II in a RTEC model system under hypoxia/reoxygenation conditions. © The Author(s) 2014.

Implications of Pearl, Gold, Silver (PGS) craft industrial cluster towards settlements region in Karang Pule Village, Sekarbela District Of Mataram City

NASA Astrophysics Data System (ADS)

Sushanti, I. R.; Fitri, I. S.

2017-06-01

The existence of industry clusters in Mataram City gave effect to the surrounding residential areas [1]. In accordance Spatial Plan of Mataram City in 2011-2031 PGS industry cluster in the village of Karang Pule, Sekarbela district established as shopping tourism area. Distribution of industrial locations were in four of seven environments in Karang Pule. Distribution of PGS industry is divided into three (3) groups: craftsmen, craftsmen who is also a seller, and the seller (merchant). The location of the craftsmen, craftsmen who are also businessmen and entrepreneurs are also used as a dwelling house or workshop and store. So most of the people living in settlements around clusters of industry that there is a link between industry cluster and settlements. This study aims to determine the implications or the impact of the presence of PGS industry clusters the surrounding residential areas. The method used in this research is descriptive qualitative with the collection of primary data through direct observation and questionnaires. Based on direct observation on the shopping tourism area there are inequality between the conditions of industry clusters and settlements area by the presence of slums. The results showed that the PGS industry cluster impact on social, economic and environment near settlements area. Impacts that occur are: 1) the social aspect, there is a significant change in the level of education, social welfare and social disparities but less significant to the formation of institutions, particularly in community participation, 2) the economic aspect of the change status of community work, and increased revenue and 3) the environmental aspects of the change to the condition of the building, the quality of public housing, the presence of slums, changes in infrastructure and the environmental pollution.

Assessment of thermal effects of interstitial laser phototherapy on mammary tumors using proton resonance frequency method

PubMed Central

Le, Kelvin; Li, Xiaosong; Figueroa, Daniel; Towner, Rheal A.; Garteiser, Philippe; Saunders, Debra; Smith, Nataliya; Liu, Hong; Hode, Tomas; Nordquist, Robert E.; Chen, Wei R.

2011-01-01

Laser immunotherapy (LIT) uses a synergistic approach to treat cancer systemically through local laser irradiation and immunological stimulation. Currently, LIT utilizes dye-assisted noninvasive laser irradiation to achieve selective photothermal interaction. However, LIT faces difficulties treating deeper tumors or tumors with heavily pigmented overlying skin. To circumvent these barriers, we use interstitial laser irradiation to induce the desired photothermal effects. The purpose of this study is to analyze the thermal effects of interstitial irradiation using proton resonance frequency (PRF). An 805-nm near-infrared laser with an interstitial cylindrical diffuser was used to treat rat mammary tumors. Different power settings (1.0, 1.25, and 1.5 W) were applied with an irradiation duration of 10 min. The temperature distributions of the treated tumors were measured by a 7 T magnetic resonance imager using PRF. We found that temperature distributions in tissue depended on both laser power and time settings, and that variance in tissue composition has a major influence in temperature elevation. The temperature elevations measured during interstitial laser irradiation by PRF and thermocouple were consistent, with some variations due to tissue composition and the positioning of the thermocouple's needle probes. Our results indicated that, for a tissue irradiation of 10 min, the elevation of rat tumor temperature ranged from 8 to 11°C for 1 W and 8 to 15°C for 1.5 W. This is the first time a 7 T magnetic resonance imager has been used to monitor interstitial laser irradiation via PRF. Our work provides a basic understanding of the photothermal interaction needed to control the thermal damage inside a tumor using interstitial laser treatment. Our work may lead to an optimal protocol for future cancer treatment using interstitial phototherapy in conjunction with immunotherapy. PMID:22191937

MicroRNA-17-92 cluster promotes the proliferation and the chemokine production of keratinocytes: implication for the pathogenesis of psoriasis.

PubMed

Zhang, Weigang; Yi, Xiuli; An, Yawen; Guo, Sen; Li, Shuli; Song, Pu; Chang, Yuqian; Zhang, Shaolong; Gao, Tianwen; Wang, Gang; Li, Chunying

2018-05-11

Keratinocytes are the main epidermal cell type that constitutes the skin barrier against environmental damages, which emphasizes the balance between the growth and the death of keratinocytes in maintaining skin homeostasis. Aberrant proliferation of keratinocytes and the secretion of inflammatory factors from keratinocytes are related to the formation of chronic inflammatory skin diseases like psoriasis. MicroRNA-17-92 (miRNA-17-92 or miR-17-92) is a miRNA cluster that regulates cell growth and immunity, but the role of miR-17-92 cluster in keratinocytes and its relation to skin diseases have not been well investigated. In the present study, we initially found that miR-17-92 cluster promoted the proliferation and the cell-cycle progression of keratinocytes via suppressing cyclin-dependent kinase inhibitor 2B (CDKN2B). Furthermore, miR-17-92 cluster facilitated the secretion of C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10) from keratinocytes by inhibiting suppressor of cytokine signaling 1 (SOCS1), which enhanced the chemotaxis for T lymphocytes formed by keratinocytes. In addition, we detected increased expression of miR-17-92 cluster in psoriatic lesions and the level of lesional miR-17-92 cluster was positively correlated with the disease severity in psoriasis patients. At last, miR-17-92 cluster was increased in keratinocytes by cytokines through the activation of signal transducers and activators of transcription 1 (STAT1) signaling pathway. Our findings demonstrate that cytokine-induced overexpression of miR-17-92 cluster can promote the proliferation and the immune function of keratinocytes, and thus may contribute to the development of inflammatory skin diseases like psoriasis, which implicates miR-17-92 cluster as a potential therapeutic target for psoriasis and other skin diseases with similar inflammatory pathogenesis.

Structural effects in the interstitial solid solution system (La,Ce)(Fe,Si)13Cx-H: Correlation with hydrogenation kinetics

NASA Astrophysics Data System (ADS)

Hai, X.; Porcher, F.; Mayer, C.; Miraglia, S.

2018-02-01

Steady state and in-situ neutron powder diffraction on selected compositions of the magneto-caloric (La,Ce)(Fe,Si)13CxHy compounds has been used to locate the sites accommodated by the interstitial species and to reveal the structural modifications (breathing) that occur upon metal substitution and/or interstitial insertion. The latter type of measurement in which the sequential filling of interstitial sites is followed allows one to extract some useful hydrogenation kinetics data. This structural investigation has allowed to precise the deformations undergone by the complex metallic alloys La(Fe,Si)13 when subjected to light interstitial insertion or rare earth substitution at the cation site of the NaZn13-structure type. We attempt to correlate hydrogenation kinetics variations (depression or enhancement of the hydrogen absorption rate) with a particular inhomogeneous cell variation (breathing) and bonding of the NaZn13 structure-type.

Interstitial granulomatous dermatitis with arthritis.

PubMed

Long, D; Thiboutot, D M; Majeski, J T; Vasily, D B; Helm, K F

1996-06-01

Interstitial granulomatous dermatitis with arthritis is an uncommon systemic disorder involving the cutaneous and musculoskeletal systems. The eruption may mimic other dermatoses including granuloma annulare, erythema chronicum migrans, and the inflammatory stage of morphea. Key histopathologic characteristics, along with clinical correlation, allow accurate diagnosis. We describe the clinical, serologic, and histologic features in three patients with interstitial granulomatous dermatitis with arthritis. Skin biopsy specimens were examined and correlated with the clinical and laboratory findings. Erythematous, annular, indurated plaques on the extremities were present in two women. An erythematous, papular eruption on the head and neck was present in a third patient. All patients had myalgia and migratory polyarthralgias of the extremities along with various serologic abnormalities. Histologic examination revealed a dense lymphohistiocytic interstitial infiltrate involving primarily the reticular dermis. Foci of necrobiotic collagen were present. Vasculitis was absent. Interstitial granulomatous dermatitis with arthritis is unique multisystem disease with variable cutaneous expression. Abnormal serologic findings indicate a possible connection to collagen vascular disease.

Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders

PubMed Central

Kaarteenaho, Riitta; Kinnula, Vuokko L.

2011-01-01

It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal. PMID:21637367

Sonority and Cross-Linguistic Acquisition of Initial S-Clusters

ERIC Educational Resources Information Center

Yavas, Mehmet; Ben-David, Avivit; Gerrits, Ellen; Kristoffersen, Kristian E.; Simonsen, Hanne G.

2008-01-01

This paper examines the findings and implications of the cross-linguistic acquisition of #sC clusters in relation to sonority patterns. Data from individual studies on English, Dutch, Norwegian, and Hebrew are compared for accuracy of production as well as the reductions with respect to potential differences across subtypes of #sC groups. In all…

[Time for cluster C personality disorders: state of the art].

PubMed

Hutsebaut, J; Willemsen, E M C; Van, H L

Compared to cluster B personality disorders, the assessment and treatment of people with obsessive-compulsive, dependent, and avoidant personality disorders (cluster C) is given little attention in the field of research and clinical practice. Presenting the current state of affairs in regard to cluster C personality disorders. A systematic literature search was conducted using the main data bases. Cluster C personality disorders are present in approximately 3-9% of the general population. In about half of the cases of mood, anxiety, and eating disorders, there is co-morbid cluster C pathology. This has a major influence on the progression of symptoms, treatment effectiveness and potential relapse. There are barely any well conducted randomized studies on the treatment of cluster-C in existence. Open cohort studies, however, show strong, lasting treatment effects. Given the frequent occurrence of cluster C personality disorders, the burden of disease, associated societal costs and the prognostic implications in case of a co-morbid cluster C personality disorder, early detection and treatment of these disorders is warranted.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Langli; Su, Mao; Yan, Pengfei

The presence of water vapor, intentional or unavoidable, is crucial to many materials applications, such as steam generator, turbine engine, fuel cell, catalyst, and corrosion 1-6. Phenomenologically, water vapor has been noticed to accelerate oxidation of metals/alloys 7,8, however, the atomistic mechanisms remain elusive. Herein, through direct in situ atomic-scale transmission electron microscopy observation and density functional theory calculation, we reveal that water vapor enhanced oxidation of Ni-Cr alloy is associated with proton dissolution promoted vacancy formation, migration and clustering. Protons derived from water dissociation occupy interstitial position in the oxide lattice, which consequently leads to the lowering of bothmore » vacancy formation energy and the cation diffusion barrier. The atomic scale observations reveal a water vapor derived proton mediated oxide growth mechanism, which provides insights for reckoning many technological processes concerning materials in moist environment at elevated temperatures.« less

Structure of the SnO2(110 ) -(4 ×1 ) Surface

NASA Astrophysics Data System (ADS)

Merte, Lindsay R.; Jørgensen, Mathias S.; Pussi, Katariina; Gustafson, Johan; Shipilin, Mikhail; Schaefer, Andreas; Zhang, Chu; Rawle, Jonathan; Nicklin, Chris; Thornton, Geoff; Lindsay, Robert; Hammer, Bjørk; Lundgren, Edvin

2017-09-01

Using surface x-ray diffraction (SXRD), quantitative low-energy electron diffraction (LEED), and density-functional theory (DFT) calculations, we have determined the structure of the (4 ×1 ) reconstruction formed by sputtering and annealing of the SnO2(110 ) surface. We find that the reconstruction consists of an ordered arrangement of Sn3O3 clusters bound atop the bulk-terminated SnO2(110 ) surface. The model was found by application of a DFT-based evolutionary algorithm with surface compositions based on SXRD, and shows excellent agreement with LEED and with previously published scanning tunneling microscopy measurements. The model proposed previously consisting of in-plane oxygen vacancies is thus shown to be incorrect, and our result suggests instead that Sn(II) species in interstitial positions are the more relevant features of reduced SnO2(110 ) surfaces.

Photo-induced transformation process at gold clusters-semiconductor interface: Implications for the complexity of gold clusters-based photocatalysis

NASA Astrophysics Data System (ADS)

Liu, Siqi; Xu, Yi-Jun

2016-03-01

The recent thrust in utilizing atomically precise organic ligands protected gold clusters (Au clusters) as photosensitizer coupled with semiconductors for nano-catalysts has led to the claims of improved efficiency in photocatalysis. Nonetheless, the influence of photo-stability of organic ligands protected-Au clusters at the Au/semiconductor interface on the photocatalytic properties remains rather elusive. Taking Au clusters-TiO2 composites as a prototype, we for the first time demonstrate the photo-induced transformation of small molecular-like Au clusters to larger metallic Au nanoparticles under different illumination conditions, which leads to the diverse photocatalytic reaction mechanism. This transformation process undergoes a diffusion/aggregation mechanism accompanied with the onslaught of Au clusters by active oxygen species and holes resulting from photo-excited TiO2 and Au clusters. However, such Au clusters aggregation can be efficiently inhibited by tuning reaction conditions. This work would trigger rational structural design and fine condition control of organic ligands protected-metal clusters-semiconductor composites for diverse photocatalytic applications with long-term photo-stability.

Interstitial deletion in the long arms of chromosome 1: 46,XY,del(1)(pter leads to q22::q25 leads to qter).

PubMed Central

de Pablo, C E; García Sagredo, J M; Ferro, M T; Ferrando, P; San Román, C

1980-01-01

A child was brought to us with multiple anomalies. On examination we found an interstitial deletion in the long arms of chromosome 1. We studied genetic and chromosome markers, comparing our clinical and cytogenetic findings with other reported cases of chromosome 1 interstitial deletion. Images PMID:6937620

ENTEROCOCCI IN THE WATER COLUMN AND SHORELINE INTERSTITIAL WATERS AT BEACHES ON THE GULF OF MEXICO AND SANTA ROSA SOUND, PENSACOLA, FLORIDA

EPA Science Inventory

Interstitial water in the swash zone, that area of a beach where waves continuously wash up on the sand, is suspected of accumulating microbes. If pathogens are concentrated in the interstitial water or if they grow, they may pose a health risk, especially for children. This st...

Interstitial pulmonary fibrosis and progressive massive fibrosis related to smoking methamphetamine with talc as filler.

PubMed

Baylor, Peter A; Sobenes, Juan R; Vallyathan, Val

2013-05-01

We present a case of interstitial pulmonary fibrosis accompanied by radiographic evidence of progressive massive fibrosis in a patient who had a 15-20 year history of almost daily recreational inhalation of methamphetamine. Mineralogical analysis confirmed the presence of talc on biopsy of the area of progressive massive fibrosis. The coexistence of interstitial pulmonary fibrosis and progressive massive fibrosis suggests that prolonged recreational inhalation of methamphetamine that has been "cut" with talc can result in sufficient amount of talc being inhaled to result in interstitial pulmonary fibrosis and progressive massive fibrosis in the absence of other causes.

Interstitial pneumonitis after acetylene welding: a case report.

PubMed

Brvar, Miran

2014-01-01

Acetylene is a colorless gas commonly used for welding. It acts mainly as a simple asphyxiant. In this paper, however, we present a patient who developed a severe interstitial pneumonitis after acetylene exposure during aluminum welding. A 44-year old man was welding with acetylene, argon and aluminum electrode sticks in a non-ventilated aluminum tank for 2 h. Four hours after welding dyspnea appeared and 22 h later he was admitted at the Emergency Department due to severe respiratory insufficiency with pO2 = 6.7 kPa. Chest X-ray showed diffuse interstitial infiltration. Pulmonary function and gas diffusion tests revealed a severe restriction (55% of predictive volume) and impaired diffusion capacity (47% of predicted capacity). Toxic interstitial pneumonitis was diagnosed and high-dose systemic corticosteroid methylprednisolone and inhalatory corticosteroid fluticasone therapy was started. Computed Tomography (CT) of the lungs showed a diffuse patchy ground-glass opacity with no signs of small airway disease associated with interstitial pneumonitis. Corticosteroid therapy was continued for the next 8 weeks gradually reducing the doses. The patient's follow-up did not show any deterioration of respiratory function. In conclusion, acetylene welding might result in severe toxic interstitial pneumonitis that improves after an early systemic and inhalatory corticosteroid therapy.

Interstitial Cells: Regulators of Smooth Muscle Function

PubMed Central

Sanders, Kenton M.; Ward, Sean M.; Koh, Sang Don

2014-01-01

Smooth muscles are complex tissues containing a variety of cells in addition to muscle cells. Interstitial cells of mesenchymal origin interact with and form electrical connectivity with smooth muscle cells in many organs, and these cells provide important regulatory functions. For example, in the gastrointestinal tract, interstitial cells of Cajal (ICC) and PDGFRα+ cells have been described, in detail, and represent distinct classes of cells with unique ultrastructure, molecular phenotypes, and functions. Smooth muscle cells are electrically coupled to ICC and PDGFRα+ cells, forming an integrated unit called the SIP syncytium. SIP cells express a variety of receptors and ion channels, and conductance changes in any type of SIP cell affect the excitability and responses of the syncytium. SIP cells are known to provide pacemaker activity, propagation pathways for slow waves, transduction of inputs from motor neurons, and mechanosensitivity. Loss of interstitial cells has been associated with motor disorders of the gut. Interstitial cells are also found in a variety of other smooth muscles; however, in most cases, the physiological and pathophysiological roles for these cells have not been clearly defined. This review describes structural, functional, and molecular features of interstitial cells and discusses their contributions in determining the behaviors of smooth muscle tissues. PMID:24987007

SU-F-19A-12: Split-Ring Applicator with Interstitial Needle for Improved Volumetric Coverage in HDR Brachytherapy for Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sherertz, T; Ellis, R; Colussi, V

2014-06-15

Purpose: To evaluate volumetric coverage of a Mick Radionuclear titanium Split-Ring applicator (SRA) with/without interstitial needle compared to an intracavitary Vienna applicator (VA), interstitial-intracavitary VA, and intracavitary ring and tandem applicator (RTA). Methods: A 57 year-old female with FIGO stage IIB cervical carcinoma was treated following chemoradiotherapy (45Gy pelvic and 5.4Gy parametrial boost) with highdose- rate (HDR) brachytherapy to 30Gy in 5 fractions using a SRA. A single interstitial needle was placed using the Ellis Interstitial Cap for the final three fractions to increase coverage of left-sided gross residual disease identified on 3T-MRI. High-risk (HR) clinical target volume (CTV) andmore » intermediate-risk (IR) CTV were defined using axial T2-weighted 2D and 3D MRI sequences (Philips PET/MRI unit). Organs-at-risks (OARs) were delineated on CT. Oncentra planning system was used for treatment optimization satisfying GEC-ESTRO guidelines for target coverage and OAR constraints. Retrospectively, treatment plans (additional 20 plans) were simulated using intracavitary SRA (without needle), intracavitary VA (without needle), interstitial-intracavitary VA, and intracavitary RTA with this same patient case. Plans were optimized for each fraction to maintain coverage to HR-CTV. Results: Interstitial-intracavitary SRA achieved the following combined coverage for external radiation and brachytherapy (EQD2): D90 HR-CTV =94.6Gy; Bladder-2cc =88.9Gy; Rectum-2cc =65.1Gy; Sigmoid-2cc =48.9Gy; Left vaginal wall (VW) =103Gy, Right VW =99.2Gy. Interstitial-intracavitary VA was able to achieve identical D90 HR-CTV =94.6Gy, yet Bladder-2cc =91.9Gy (exceeding GEC-ESTRO recommendations of 2cc<90Gy) and Left VW =120.8Gy and Right VW =115.5Gy. Neither the SRA nor VA without interstitial needle could cover HR-CTV adequately without exceeding dose to Bladder-2cc. Conventional RTA was unable to achieve target coverage for the HR-CTV >80Gy without severely overdosing OARs. Conclusion: The Ellis Interstitial Cap for the SRA offered superior dosimetric coverage as compared to the interstitialintracavitary VA. This represents the first reported use for this devise, and further investigation is warranted.« less

DISCOVERY OF A DISSOCIATIVE GALAXY CLUSTER MERGER WITH LARGE PHYSICAL SEPARATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dawson, William A.; Wittman, David; Jee, M. James

2012-03-10

We present DLSCL J0916.2+2951 (z = 0.53), a newly discovered major cluster merger in which the collisional cluster gas has become dissociated from the collisionless galaxies and dark matter (DM). We identified the cluster using optical and weak-lensing observations as part of the Deep Lens Survey. Our follow-up observations with Keck, Subaru, Hubble Space Telescope, and Chandra show that the cluster is a dissociative merger and constrain the DM self-interaction cross-section {sigma}{sub DM} m{sup -1}{sub DM} {approx}< 7 cm{sup 2} g{sup -1}. The system is observed at least 0.7 {+-} 0.2 Gyr since first pass-through, thus providing a picture ofmore » cluster mergers 2-5 times further progressed than similar systems observed to date. This improved temporal leverage has implications for our understanding of merging clusters and their impact on galaxy evolution.« less

Towards Effective Clustering Techniques for the Analysis of Electric Power Grids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hogan, Emilie A.; Cotilla Sanchez, Jose E.; Halappanavar, Mahantesh

2013-11-30

Clustering is an important data analysis technique with numerous applications in the analysis of electric power grids. Standard clustering techniques are oblivious to the rich structural and dynamic information available for power grids. Therefore, by exploiting the inherent topological and electrical structure in the power grid data, we propose new methods for clustering with applications to model reduction, locational marginal pricing, phasor measurement unit (PMU or synchrophasor) placement, and power system protection. We focus our attention on model reduction for analysis based on time-series information from synchrophasor measurement devices, and spectral techniques for clustering. By comparing different clustering techniques onmore » two instances of realistic power grids we show that the solutions are related and therefore one could leverage that relationship for a computational advantage. Thus, by contrasting different clustering techniques we make a case for exploiting structure inherent in the data with implications for several domains including power systems.« less

Profiles of behavioral problems in children who witness domestic violence.

PubMed

Spilsbury, James C; Kahana, Shoshana; Drotar, Dennis; Creeden, Rosemary; Flannery, Daniel J; Friedman, Steve

2008-01-01

Unlike previous investigations of shelter-based samples, our study examined whether profiles of adjustment problems occurred in a community-program-based sample of 175 school-aged children exposed to domestic violence. Cluster analysis revealed three stable profiles/clusters. The largest cluster (69%) consisted of children below clinical thresholds for any internalizing or externalizing problem. Children in the next largest cluster (18%) were characterized as having externalizing problems with or without internalizing problems. The smallest cluster (13%) consisted of children with internalizing problems only. Comparison across demographic and violence characteristics revealed that the profiles differed by child gender, mother's education, child's lifetime exposure to violence, and aspects of the event precipitating contact with the community program. Clinical and future research implications of study findings are discussed.

ASCA Temperature Maps for Merging and Relaxed Clusters and Physics of the Cluster Gas

NASA Technical Reports Server (NTRS)

Markevitch, M.; Sarazin, C.; Nevalainen, J.; Vikhlinin, A.; Forman, W.

1999-01-01

ASCA temperature maps for several galaxy clusters undergoing strong mergers will be presented. From these maps, it is possible to estimate velocities of the colliding subclusters. I will discuss several interesting implications of these estimates for the physics of the cluster gas and the shape of the gravitational potential. I will also present temperature maps and profiles for several relaxed clusters selected for X-ray mass determination, and present the mass values derived without the assumption of isothermality. The accurate mass-temperature and luminosity-temperature relations will be discussed. This talk will review how AXAF will revolutionize X-ray astronomy through its radically better imaging and spectroscopic resolution. Examples from many fields of astrophysics will be given.

Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin

PubMed Central

Liu, Qingdu; Binns, Thomas C.; Davidoff, Olena; Kapitsinou, Pinelopi P.; Pfaff, Andrew S.; Olauson, Hannes; Fogo, Agnes B.; Fong, Guo-Hua; Gross, Kenneth W.

2016-01-01

Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2–/– renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2–/– mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation. PMID:27088801

The role of interstitial binding in radiation induced segregation in W-Re alloys

NASA Astrophysics Data System (ADS)

Gharaee, Leili; Marian, Jaime; Erhart, Paul

2016-07-01

Due to their high strength and advantageous high-temperature properties, tungsten-based alloys are being considered as plasma-facing candidate materials in fusion devices. Under neutron irradiation, rhenium, which is produced by nuclear transmutation, has been found to precipitate in elongated precipitates forming thermodynamic intermetallic phases at concentrations well below the solubility limit. Recent measurements have shown that Re precipitation can lead to substantial hardening, which may have a detrimental effect on the fracture toughness of W alloys. This puzzle of sub-solubility precipitation points to the role played by irradiation induced defects, specifically mixed solute-W interstitials. Here, using first-principles calculations based on density functional theory, we study the energetics of mixed interstitial defects in W-Re, W-V, and W-Ti alloys, as well as the heat of mixing for each substitutional solute. We find that mixed interstitials in all systems are strongly attracted to each other with binding energies of -2.4 to -3.2 eV and form interstitial pairs that are aligned along parallel first-neighbor <111 > strings. Low barriers for defect translation and rotation enable defect agglomeration and alignment even at moderate temperatures. We propose that these elongated agglomerates of mixed-interstitials may act as precursors for the formation of needle-shaped intermetallic precipitates. This interstitial-based mechanism is not limited to radiation induced segregation and precipitation in W-Re alloys but is also applicable to other body-centered cubic alloys.

Immunephenotype of glomerular and interstitial infiltrating cells in protocol renal allograft biopsies and histological diagnosis.

PubMed

Moreso, F; Seron, D; O'Valle, F; Ibernon, M; Gomà, M; Hueso, M; Cruzado, J M; Bestard, O; Duarte, V; del Moral, R García; Grinyó, J M

2007-12-01

Patients with a protocol renal allograft biopsy simultaneously displaying interstitial fibrosis/tubular atrophy (IF/TA) and subclinical rejection (SCR) have a shortened graft survival than patients with a normal biopsy, or with a biopsy only displaying IF/TA or SCR. The poor outcome of these patients could be related with a more severe inflammation. We evaluate the immunophenotype of infiltrating cells in these diagnostic categories. Nonexhausted paraffin blocks from protocol biopsies done during the first year were stained with anti-CD45, CD3, CD20, CD68 and CD15 monoclonal antibodies. Glomerular and interstitial positive cells were counted. C4d deposition in peritubular capillaries was evaluated. Histological diagnoses were: normal (n = 80), SCR (n = 17), IF/TA (n = 42) and IF/TA + SCR (n = 17). Only interstitial CD20 positive cells were significantly increased in patients displaying IF/TA + SCR; normal (137 +/- 117), SCR (202 +/- 145), IF/TA (208 +/- 151) and IF/TA + SCR (307 +/- 180 cells/mm(2)), p < 0.01. The proportion of biopsies displaying C4d deposition was not different among groups. The upper tertile of CD20 positive interstitial cells was associated with a decreased death-censored graft survival (relative risk: 3.01, 95% confidence interval: 1.23-7.35; p = 0.015). These data suggest that B-cell interstitial infiltrates are associated with histological damage and outcome, but do not distinguish whether these infiltrates were the cause or the consequence of chronic tubulo-interstitial damage.

The safety and efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel in the treatment of non-small cell lung cancer patients with interstitial lung disease.

PubMed

Yasuda, Yuichiro; Hattori, Yoshihiro; Tohnai, Rie; Ito, Shoichi; Kawa, Yoshitaka; Kono, Yuko; Urata, Yoshiko; Nogami, Munenobu; Takenaka, Daisuke; Negoro, Shunichi; Satouchi, Miyako

2018-01-01

The optimal chemotherapy regimen for non-small cell lung cancer patients with interstitial lung disease is unclear. We therefore investigated the safety and efficacy of carboplatin plus nab-paclitaxel as a first-line regimen for non-small cell lung cancer in patients with interstitial lung disease. We retrospectively reviewed advanced non-small cell lung cancer patients with interstitial lung disease who received carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen at Hyogo Cancer Center between February 2013 and August 2016. interstitial lung disease was diagnosed according to the findings of pretreatment chest high-resolution computed tomography. Twelve patients were included (male, n = 11; female, n = 1). The overall response rate was 67% and the disease control rate was 100%. The median progression free survival was 5.1 months (95% CI: 2.9-8.3 months) and the median overall survival was 14.9 months (95% CI: 4.8-not reached). A chemotherapy-related acute exacerbation of interstitial lung disease was observed in one patient; the extent of this event was Grade 2. There were no treatment-related deaths. Carboplatin plus nab-paclitaxel, as a first-line chemotherapy regimen for non-small cell lung cancer, showed favorable efficacy and safety in patients with preexisting interstitial lung disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Age-related collagen turnover of the interstitial matrix and basement membrane: Implications of age- and sex-dependent remodeling of the extracellular matrix.

PubMed

Kehlet, Stephanie N; Willumsen, Nicholas; Armbrecht, Gabriele; Dietzel, Roswitha; Brix, Susanne; Henriksen, Kim; Karsdal, Morten A

2018-01-01

The extracellular matrix (ECM) plays a vital role in maintaining normal tissue function. Collagens are major components of the ECM and there is a tight equilibrium between degradation and formation of these proteins ensuring tissue health and homeostasis. As a consequence of tissue turnover, small collagen fragments are released into the circulation, which act as important biomarkers in the study of certain tissue-related remodeling factors in health and disease. The aim of this study was to establish an age-related collagen turnover profile of the main collagens of the interstitial matrix (type I and III collagen) and basement membrane (type IV collagen) in healthy men and women. By using well-characterized competitive ELISA-assays, we assessed specific fragments of degraded (C1M, C3M, C4M) and formed (PINP, Pro-C3, P4NP7S) type I, III and IV collagen in serum from 617 healthy men and women ranging in ages from 22 to 86. Subjects were divided into 5-year age groups according to their sex and age. Groups were compared using Kruskal-Wallis adjusted for Dunn's multiple comparisons test and Mann-Whitney t-test. Age-specific changes in collagen turnover was most profound for type I collagen. PINP levels decreased in men with advancing age, whereas in women, the level decreased in early adulthood followed by an increase around the age of menopause (age 40-60). Sex-specific changes in type I, III and IV collagen turnover was present at the age around menopause (age 40-60) with women having an increased turnover. In summary, collagen turnover is affected by age and sex with the interstitial matrix and the basement membrane being differently regulated. The observed changes needs to be accounted for when measuring ECM related biomarkers in clinical studies.

Physical and chemical changes in the foreshore of an estuarine beach: Implications for viability and development of horseshoe crab Limulus polyphemus eggs

USGS Publications Warehouse

Jackson, N.L.; Smith, D.R.; Nordstrom, K.F.

2008-01-01

Knowledge of conditions that favor development of eggs is important for management of species whose population growth is sensitive to early life history survival. Viability and development of the eggs of horseshoe crabs Limulus polyphemus on a sand and gravel beach were evaluated using data gathered on Delaware Bay, USA, from 18 May to 19 June 2004. Eggs were transplanted to pouches and buried in the foreshore for up to 6 wk. Viability and developmental stage were estimated as a function of oxygen and temperature gradients across the foreshore. These gradients were related to the characteristics of the intertidal foreshore sediments, beach water table changes, and frequency of inundation due to tide and swash/backwash processes. Results demonstrate the importance of interstitial temperature for development to larvae and the passive role of sediment characteristics on moisture retention and temperature. Percentage of eggs remaining in egg stage was similar across the foreshore, but more eggs developed to embryos at 0.45 of foreshore width, where moisture and gravel content were greater and interstitial temperature was lower. More eggs developed to larvae at 0.60 and 0.75 of foreshore width, where moisture and gravel content were less but interstitial temperature was higher. The beach above 0.75 of foreshore width came under the influence of wave action or full tidal inundation only during high wave heights or spring tides, and pouches at 0.75 of foreshore width were inundated only 19% of the time. Periodic wetting at this elevation did not reduce overall viability of the eggs. High wave energy events resulted in sediment activation depths to pouches at 0.30 of foreshore width, where loss of eggs due to wave activation was the most important control on the development of eggs. ?? Inter-Research 2008.

Water geochemistry of shallow lakes from the southeastern Pampa plain, Argentina and their implications on mollusk shells preservation.

PubMed

Cristini, Paula A; Tietze, Eleonor; De Francesco, Claudio G; Martínez, Daniel E

2017-12-15

A seasonal sampling of sediments, column and interstitial water for physico-chemical analysis were performed in littoral and open water areas in three freshwater shallow lakes (Nahuel Rucá, Las Mostazas and Los Carpinchos) from Southeastern Pampa plain, Argentina. The main objective of the present study is to evaluate how the characteristics of the depositional environments could be affecting mollusk shell preservation. These lakes are very shallow (2m) and are characterized by an extensive littoral area, dominated by the emergent macrophyte Schoenoplectus californicus, which forms a complete ring around the lake, and an open water area, in general free of vegetation. Five samples of sediments in each compartment were extracted for analysis of pH, moisture, organic matter and carbonates content using a gravity corer, while five samples from column and interstitial water were extracted for chemical analysis (pH, conductivity, major ions, minor ions and hardness). Besides, calcite and aragonite saturation indices and the redox potential were calculated for each lake. The results show the significant impact of water chemistry and redox conditions on the preservation potential of freshwater mollusk and consequently in the quality of paleonvironmental reconstruction based on the biological record from the study region. The higher concentration of organic matter and lower pH registered in the littoral area, mainly during warm months (autumn and summer), suggest worst environments for mollusk preservation, compared to open waters. Moreover, water geochemistry analysis showed aragonite and calcite indices near equilibrium or slightly subsaturated in interstitial water associated with more acid pHs, while column water is strongly oversaturated related to alkaline pHs. These results suggest that carbonate remains within sediments will be subject to dissolution affecting negatively their preservation potential. However, mollusk shells in contact with the column water are not expected to be dissolved. Copyright © 2017 Elsevier B.V. All rights reserved.

The Student-Teacher Relationship Quality of Abused Children

PubMed Central

Haskett, Mary E.; Hawkins, Amy L.

2016-01-01

Considering the association between children’s quality of relationships with teachers and their academic adjustment, information pertaining to how abused children are functioning in their relationships with teachers could be useful in promoting their academic success— yet there has been limited research in this area. The purpose of this study was to use cluster analyses to explore within-group differences in relational schemas and quality of student-teacher relationships for 70 abused children. Two clusters of abused children emerged, and as hypothesized, there were significant differences in student-teacher relationships for the two clusters. The cluster with more positive relational schemas had less conflict and less dependency reported by their teachers compared to the cluster with negative relational schemas. However, there were no differences between the clusters in terms of closeness with teachers. Implications for practice in schools is discussed. PMID:28713179

MCNP Parametric Studies of Plutonium Metal and Various Interstitial Moderating Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glazener, Natasha; Kamm, Ryan James

2017-03-31

Nuclear Criticality Safety (NCS) has performed calculations evaluating the effect of different interstitial materials on 5.0-kg of plutonium metal. As with all non-fissionable interstitials, the results here illustrate that it requires significant quantities of oil to be intimately mixed with plutonium, reflected by a thick layer of full-density water, to achieve the same reactivity as that of solid plutonium metal.

[Distribution characteristics and correlations of phosphorus in sediment and interstitial water of Nansi Lake, Shandong Province of East China in summer and winter].

PubMed

Li, Bao; Wang, Zhi-Qi; Wang, Qian-Suo; Cuan, Jing-Bo

2013-06-01

By using cylindrical sediment sampler and Peeper' s interstitial water sampler, the intact sediment and interstitial water were collected from different zones of Nansi Lake in Shandong Province in summer and winter. The distribution characteristics of the sediment phosphorus forms and of the phosphate (PO4(3-)-P) in interstitial water were analyzed, and their correlations were discussed. In the sediments of Nansi Lake, phosphorus was richer, and had a significant spatial differentiation, with an overall decreasing trend from north to south, which was related to the seriously polluted Northern Nansi Lake near Jining City. Among the phosphorous forms, inorganic phosphorus (IP) had the highest concentration, accounting for 52.3%-87.2% and 60.6%-88.3% of the total phosphorus (TP) in summer and winter, respectively. The TP concentrations in 5 cm surface sediment of four sub-lakes were all higher in summer than in winter, which could be related to the human activities such as exuberant aquaculture, more chemical fertilizers application around lake, and frequent tourism activities, etc. in summer. In vertical direction, the PO4(3-)-P concentration in interstitial water decreased after an initial increase in summer and winter, and was obviously higher in summer than in winter, suggesting that the phosphorous in sediment had a higher potential to release to the overlying water in summer. The organic phosphorus (OP) and IP in sediment had a significant correlation in summer but less correlation in winter, indicating that the transformation between sediment IP and OP was more active in summer than in winter. The iron and aluminum bound phosphorus (Fe/Al-P) and IP in sediment were significantly positively correlated with the PO4(3-)-P in interstitial water. In summer and winter, the average PO4(3-)-P concentration in interstitial water collected by Peeper' s interstitial water sampler was about 20%-50% higher than that collected by the conventional centrifugal method, suggesting that using Peeper' s interstitial water sampler could be more precise.

Pressure monitoring during lipofilling procedures.

PubMed

Klein, S M; Prantl, L; Geis, S; Eisenmann-Klein, M; Dolderer, J; Felthaus, O; Loibl, M; Heine, N

2014-01-01

Grafting of autologous lipoaspirate for various clinical applications has become a common procedure in clinical practice. With an estimated mortality rate of 10-15 percent, fat embolism is among the most severe complications to be expected after lipofilling therapies. The aim of this study was to determine the level of interstitial pressure after the injection of defined volumes of lipoaspirate into the subcutaneous tissue of female breasts. It was hypothesized, that interstitial pressure levels exceed the physiologic capillary pressure during lipofilling procedures and hence increase the potential risk for fat embolism. Further it was investigated if external tissue expansion has the potential to significantly reduce interstitial tissue pressure. Interstitial pressure was monitored in 36 female patients, that underwent autologous fat injections into the breast. Measurements were conducted with a sensor needle connected to a pressure transducer (LogiCal Pressure Monitoring Kit, Smiths medical int. Ltd., UK). Patients were divided into 4 subcohorts differing in their pre-treatment regimen or local tissue conditions. Pre-treatment consisted of tissue expansion, achieved with the Brava™ (Brava LLC Miami, Fla., USA) vacuum-chamber. The increase in interstitial pressure after injection volumes of 100 ml (p = 0.006), 200 ml (p = 0.000) and between 100 ml and 200 ml (p = 0.004) respectively, were significant in non-mastectomized patients without pre-treatment. Patients pre-treated with Brava™ did not show such statistically significant differences in interstitial pressures before and after the injection of 100 ml and 200 ml of lipoaspirate (p = 0.178). The difference in interstitial pressure in mastectomized patients between 0 ml and 100 ml (p = 0.003), as well as 0 ml and 200 ml (p = 0.028) was significant. The difference in pressures between pre-treated patients and patients without pre-treatment did not differ significantly in the mastectomized patient cohort. During lipofilling procedures interstitial pressures are reached that exceed pressure limits defined as hazardous for fat embolism. To date it is unknown what pressure levels need to be considered critical for complications in soft tissue interventions. Further the results indicate higher interstitial pressures for patients that had undergone mastectomy, whereas pre-treatment with external tissue expansion seemed to diminish pressure values.

Photo-induced transformation process at gold clusters-semiconductor interface: Implications for the complexity of gold clusters-based photocatalysis

PubMed Central

Liu, Siqi; Xu, Yi-Jun

2016-01-01

The recent thrust in utilizing atomically precise organic ligands protected gold clusters (Au clusters) as photosensitizer coupled with semiconductors for nano-catalysts has led to the claims of improved efficiency in photocatalysis. Nonetheless, the influence of photo-stability of organic ligands protected-Au clusters at the Au/semiconductor interface on the photocatalytic properties remains rather elusive. Taking Au clusters–TiO2 composites as a prototype, we for the first time demonstrate the photo-induced transformation of small molecular-like Au clusters to larger metallic Au nanoparticles under different illumination conditions, which leads to the diverse photocatalytic reaction mechanism. This transformation process undergoes a diffusion/aggregation mechanism accompanied with the onslaught of Au clusters by active oxygen species and holes resulting from photo-excited TiO2 and Au clusters. However, such Au clusters aggregation can be efficiently inhibited by tuning reaction conditions. This work would trigger rational structural design and fine condition control of organic ligands protected-metal clusters-semiconductor composites for diverse photocatalytic applications with long-term photo-stability. PMID:26947754

Large stability and high catalytic activities of sub-nm metal (0) clusters: implications into the nucleation and growth theory.

PubMed

Piñeiro, Yolanda; Buceta, David; Calvo, Javier; Huseyinova, Shahana; Cuerva, Miguel; Pérez, Ángel; Domínguez, Blanca; López-Quintela, M Arturo

2015-07-01

Clusters are stable catalytic species, which are produced during the synthesis of nanoparticles (NPs). Their existence contradicts the thermodynamic principles used to explain the formation of NPs by the classical nucleation and growth theories (NGTs). Using chemical and electrochemical methods we will show that depending on the experimental conditions one can produce either Ag clusters or Ag NPs. Moreover, using already prepared Ag clusters one can observe the disappearance of the usual induction period observed for the kinetics of NP formation, indicating that clusters catalyze the formation of NPs. Taking these data together with some previous examples of cluster-catalyzed anisotropic growth, we derived a qualitative approach to include the catalytic activities of clusters into the formation of NPs, which is incorporated into the NGT. Some qualitative conclusions about the main experimental parameters, which affect the formation of clusters versus NPs, as well as the catalytic mechanism versus the non-catalytic one, are also described. Copyright © 2015 Elsevier Inc. All rights reserved.

Kinetic Monte Carlo (kMC) simulation of carbon co-implant on pre-amorphization process.

PubMed

Park, Soonyeol; Cho, Bumgoo; Yang, Seungsu; Won, Taeyoung

2010-05-01

We report our kinetic Monte Carlo (kMC) study of the effect of carbon co-implant on the pre-amorphization implant (PAL) process. We employed BCA (Binary Collision Approximation) approach for the acquisition of the initial as-implant dopant profile and kMC method for the simulation of diffusion process during the annealing process. The simulation results implied that carbon co-implant suppresses the boron diffusion due to the recombination with interstitials. Also, we could compare the boron diffusion with carbon diffusion by calculating carbon reaction with interstitial. And we can find that boron diffusion is affected from the carbon co-implant energy by enhancing the trapping of interstitial between boron and interstitial.

Reactive Granulomatous Dermatitis: A Review of Palisaded Neutrophilic and Granulomatous Dermatitis, Interstitial Granulomatous Dermatitis, Interstitial Granulomatous Drug Reaction, and a Proposed Reclassification.

PubMed

Rosenbach, Misha; English, Joseph C

2015-07-01

The terms "palisaded neutrophilic and granulomatous dermatitis," "interstitial granulomatous dermatitis," and the subset "interstitial granulomatous drug reaction" are a source of confusion. There exists substantial overlap among the entities with few strict distinguishing features. We review the literature and highlight areas of distinction and overlap, and propose a streamlined diagnostic workup for patients presenting with this cutaneous reaction pattern. Because the systemic disease associations and requisite workup are similar, and the etiopathogenesis is poorly understood but likely similar among these entities, we propose the simplified unifying term "reactive granulomatous dermatitis" to encompass these entities. Copyright © 2015 Elsevier Inc. All rights reserved.

A Case of Transient Pulmonary Interstitial Lesions in Aquaporin-4-positive Neuromyelitis Optica Spectrum Disorder.

PubMed

Asato, Yuko; Kamitani, Toshiaki; Ootsuka, Kuniyuki; Kuramochi, Mizuki; Nakanishi, Kozo; Shimada, Tetsuya; Takahashi, Toshiyuki; Misu, Tatsuro; Aoki, Masashi; Fujihara, Kazuo; Kawabata, Yoshinori

2018-05-18

We herein report the case of a 76-year old man with aquaporin-4-Immunoglobulin-G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD), in whom transient interstitial pulmonary lesions developed at the early stage of the disease. Chest X-ray showed multiple infiltrative shadows in both upper lung fields, and computed tomography revealed abnormal shadows distributed randomly in the lungs. Surgical lung biopsy showed features of unclassifiable interstitial pneumonia, characterized by various types of air-space organization, which resulted in obscure lung structure. This is the first report to describe the pathological findings of interstitial pneumonia, which may represent a rare extra-central nervous system complication of NMOSD.

IMAGING DIAGNOSIS-SPONTANEOUS PNEUMOMEDIASTINUM SECONDARY TO PRIMARY PULMONARY PATHOLOGY IN A DALMATIAN DOG.

PubMed

Agut, Amalia; Talavera, Jesus; Buendia, Antonio; Anson, Agustina; Santarelli, Giorgia; Gomez, Serafin

2015-01-01

A 1.5-year-old, 23 kg intact male Dalmatian dog was evaluated for acute respiratory insufficiency without a previous history of trauma or toxic exposition. Imaging revealed pneumomediastinum, pneumothorax, diffuse unstructured interstitial pulmonary pattern, pulmonary interstitial emphysema, and pneumoretroperitoneum. Histopathological evaluation of the lungs revealed perivascular and peribronchial emphysema, mild lymphocytic interstitial pneumonia with atypical proliferation of type II pneumocytes in bronchioles and alveoli. A lung disease resembling fibrosing interstitial pneumonia in man and cats has been previously reported in Dalmatians and should be included as a differential diagnosis for Dalmatians with this combination of clinical and imaging characteristics. © 2014 American College of Veterinary Radiology.

The relationship between negative expressivity, anger, and PTSD symptom clusters.

PubMed

Claycomb, Meredith; Roley, Michelle E; Contractor, Ateka A; Armour, Cherie; Dranger, Paula; Wang, Li; Elhai, Jon D

2016-09-30

More investigation is needed to understand how specific posttraumatic stress disorder (PTSD) symptom clusters relate to the internal experience of anger and overt negative behaviors in response to anger (negative expressivity). We investigated whether anger mediated relations between PTSD symptom clusters and negative expressivity. Multiple regression revealed lower PTSD intrusion symptoms associated with higher levels of negative expressivity. Anger mediated this relationship. Higher avoidance symptoms related to higher negative expressivity. Clinical implications, limitations, and strengths are discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

X-radiation from clusters of galaxies: Spectral evidence for a hot evolved gas

NASA Technical Reports Server (NTRS)

Serlemitsos, P. J.; Smith, B. W.; Boldt, E. A.; Holt, S. S.; Swank, J. H.

1976-01-01

OSO-8 observations of the X-ray flux in the range 2-60 keV from the Virgo, Perseus, and Coma Clusters provide strong evidence for the thermal origin of the radiation, including iron line emission. The data are adequately described by emission from an isothermal plasma with an iron abundance in near agreement with cosmic levels. A power law description is generally less acceptable and is ruled out in the case of Perseus. Implications on the origin of the cluster gas are discussed.

Exploratory Cluster Analysis to Identify Patterns of Chronic Kidney Disease in the 500 Cities Project.

PubMed

Liu, Shelley H; Li, Yan; Liu, Bian

2018-05-17

Chronic kidney disease is a leading cause of death in the United States. We used cluster analysis to explore patterns of chronic kidney disease in 500 of the largest US cities. After adjusting for socio-demographic characteristics, we found that unhealthy behaviors, prevention measures, and health outcomes related to chronic kidney disease differ between cities in Utah and those in the rest of the United States. Cluster analysis can be useful for identifying geographic regions that may have important policy implications for preventing chronic kidney disease.

Cosmological Implications of the Effects of X-Ray Clusters on the Cosmic Microwave Background

NASA Technical Reports Server (NTRS)

Forman, William R.

1996-01-01

We have been carrying forward a program to confront X-ray observations of clusters and their evolution as derived from X-ray observatories with observations of the cosmic microwave background radiation (CMBR). In addition to the material covered in our previous reports (including three published papers), most recently we have explored the effects of a cosmological constant on the predicted Sunyaev-Zel'dovich effect from the ensemble of clusters. In this report we summarize that work from which a paper will be prepared.

Roles of Vacancy/Interstitial Diffusion and Segregation in the Microchemistry at Grain Boundaries of Irradiated Fe-Cr-Ni alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Ying; Field, Kevin G.; Allen, Todd R.

2016-02-23

A detailed analysis of the diffusion fluxes near and at grain boundaries of irradiated Fe–Cr–Ni alloys, induced by preferential atom-vacancy and atom-interstitial coupling, is presented. The diffusion flux equations were based on the Perks model formulated through the linear theory of the thermodynamics of irreversible processes. The preferential atom-vacancy coupling was described by the mobility model, whereas the preferential atom-interstitial coupling was described by the interstitial binding model. The composition dependence of the thermodynamic factor was modeled using the CALPHAD approach. The calculated fluxes up to 10 dpa suggested the dominant diffusion mechanism for chromium and iron is via vacancy,more » while that for nickel can swing from the vacancy to the interstitial dominant mechanism. The diffusion flux in the vicinity of a grain boundary was found to be greatly modified by the segregation induced by irradiation, leading to the oscillatory behavior of alloy compositions in this region.« less

Molecular dynamics and quasidynamics simulations of the annealing of bulk and near-surface interstitials formed in molecular-beam epitaxial Si due to low-energy particle bombardment during deposition

NASA Technical Reports Server (NTRS)

Kitabatake, M.; Fons, P.; Greene, J. E.

1991-01-01

The relaxation, diffusion, and annihilation of split and hexagonal interstitials resulting from 10 eV Si irradiation of (2x1)-terminated Si(100) are investigated. Molecular dynamics and quasidynamics simulations, utilizing the Tersoff many-body potential are used in the investigation. The interstitials are created in layers two through six, and stable atomic configurations and total potential energies are derived as a function of site symmetry and layer depth. The interstitial Si atoms are allowed to diffuse, and the total potential energy changes are calculated. Lattice configurations along each path, as well as the starting configurations, are relaxed, and minimum energy diffusion paths are derived. The results show that the minimum energy paths are toward the surface and generally involved tetrahedral sites. The calculated interstitial migration activation energies are always less than 1.4 eV and are much lower in the near-surface region than in the bulk.

Lithification opf gas-rich chondrite regolith breccias by grain boundary and localized shock melting

NASA Technical Reports Server (NTRS)

Bischoff, A.; Rubin, A. E.; Keil, K.; Stoeffler, D.

1983-01-01

The fine-grained matrices (less than 150 microns) of 14 gas-rich ordinary chondrile regolith breccias were studied in an attempt to decipher the nature of the lithification process that converted loose regolith material into consolidated breccias. It is found that there is a continuouos gradation in matrix textures from nearly completely clastic (class A) to highly cemented (class C) breccias in which the remining clasts are completely surrounded by interstitial, shock-melted material. It is concluded that this interstitial material is formed by shock melting in the porous regolith. In general, the abundances of solar-wind-implanted He-4 and Ne-20 are inversely correlated with the abundance of intenstitial, shock-melted, feldspathic material. Chondrites with the highest abundance of interstitial, melted material (class C) experienced the highest shock pressures and temperatures and suffered the most extensive degassing. It is this interstitial, feldspathic melt that lithifies and cements the breccias together; those breccias with very little interstitial melt (class A) are the most porous and least consolidated.

A review of recent advances in the assessment of bone porosity, permeability, and interstitial fluid flow

PubMed Central

Cardoso, Luis; Fritton, Susannah P.; Gailani, Gaffar; Benalla, Mohammed; Cowin, Stephen C.

2012-01-01

This contribution reviews recent research performed to assess the porosity and permeability of bone tissue with the objective of understanding interstitial fluid movement. Bone tissue mechanotransduction is considered to occur due to the passage of interstitial pore fluid adjacent to dendritic cell structures in the lacunar-canalicular porosity. The movement of interstitial fluid is also necessary for the nutrition of osteocytes. This review will focus on four topics related to improved assessment of bone interstitial fluid flow. First, the advantages and limitations of imaging technologies to visualize bone porosities and architecture at several length scales are summarized. Second, recent efforts to measure the vascular porosity and lacunar-canalicular microarchitecture are discussed. Third, studies associated with the measurement and estimation of the fluid pressure and permeability in the vascular and lacunar-canalicular domains are summarized. Fourth, the development of recent models to represent the interchange of fluids between the bone porosities is described. PMID:23174418

[New toxicity of fotemustine: diffuse interstitial lung disease].

PubMed

Bertrand, M; Wémeau-Stervinou, L; Gauthier, S; Auffret, M; Mortier, L

2012-04-01

Fotemustine is an alkylating cytostatic drug belonging to the nitrosourea family and is used in particular in the treatment of disseminated malignant melanoma. Herein, we report a case of interstitial lung disease associated with fotemustine. An 81-year-old man treated with fotemustine for metastatic melanoma presented acute interstitial lung disease 20 days after a fourth course of fotemustine monotherapy. The condition regressed spontaneously, with the patient returning to the clinical, radiological and blood gas status that had preceded fotemustine treatment. After other potential aetiologies had been ruled out, acute fotemustine-induced lung toxicity was considered and this treatment was definitively withdrawn. Other cytostatic agents belonging to the nitrosourea family can cause similar pictures, with a number of cases of interstitial lung disease thus being ascribed to fotemustine and dacarbazine. To our knowledge, this is the first case of interstitial lung disease induced by fotemustine monotherapy. This diagnosis should be considered where respiratory signs appear in melanoma patients undergoing fotemustine treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Lithium in a short-period tidally locked binary of M67: Implications for stellar evolution, Galactic Lithium evolution, and cosmology

NASA Technical Reports Server (NTRS)

Deliyannis, Constantine P.; King, Jeremy R.; Boesgaard, Ann M.; Ryan, Sean G.

1994-01-01

In open clusters, late-F stars exhibit a Li maximum (the Li 'peak' region) at lower abundance with age, which could be due either to stellar depletion or Galactic Li enrichment (or some other cause). We have observed a short-period tidally locked binary (SPTLB) on the Li peak region in the old cluster M67 to distinguish between alternatives. SPTLBs which synchronized in the early pre-main sequence would avoid the rotational mixing which, according to Yale models, may be responsible for depleting Li with age in open cluster dwarfs. We find that both components of the M67 SPTLB have a Li abundance lying about a factor of 2 or more above any other M67 single star and about a factor of 3 or more above the mean Li peak region abundance in M67. Our results suggest that the initial Li abundance in M67 is at least as high as approximately 3.0 = 12 + log (N(sub Li)/N(sub H)). Our high M67 SPTLB Li abundance and those in other clusters support the combination of Zahn's tidal circularization and the Yale rotational mixing theories and may indicate that the halo Li plateau (analogous to the cluster Li peak region) abundance has been depleted from a higher primordial value. Implications are discussed.

Laparoscopic management of interstitial pregnancy with automatic stapler

PubMed Central

Ahsan Akhtar, Muhammad; Izzat, Feras; Keay, Stephen D

2012-01-01

A 36-year-old woman was referred by general practitioner to the early pregnancy unit with pelvic pain in her seventh week of pregnancy. She had a transvaginal ultrasound. Unruptured live twin tubal ectopic pregnancy was diagnosed on. Diagnostic laparoscopy revealed an unruptured left interstitial ectopic pregnancy. The interstitial tubal pregnancy was removed by laparoscopic automatic stapler with minimal blood loss. The patient had an uneventful recovery to health. PMID:23093504

An Evaluation of the Corrosion and Mechanical Performance of Interstitially Surface Hardened Stainless Steel

DTIC Science & Technology

2013-05-10

Performance of Interstitially Surface Hardened Stainless Steel 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jones, Jennifer Lynn...interstitial carbon atoms into stainless steel surfaces without the formation of carbides. Surface hardening of machine elements such as impellors or...the corrosion resistance of the stainless steel is retained, rather than degraded, is of particular interest for marine applications. This project

Spatial distribution of end-stage renal disease (ESRD) and social inequalities in mixed urban and rural areas: a study in the Bretagne administrative region of France.

PubMed

Kihal-Talantikite, Wahida; Deguen, Séverine; Padilla, Cindy; Siebert, Muriel; Couchoud, Cécile; Vigneau, Cécile; Bayat, Sahar

2015-02-01

Several studies have investigated the implication of biological and environmental factors on geographic variations of end-stage renal disease (ESRD) incidence at large area scales, but none of them assessed the implication of neighbourhood characteristics (healthcare supply, socio-economic level and urbanization degree) on spatial repartition of ESRD. We evaluated the spatial implications of adjustment for neighbourhood characteristics on the spatial distribution of ESRD incidence at the smallest geographic unit in France. All adult patients living in Bretagne and beginning renal replacement therapy during the 2004-09 period were included. Their residential address was geocoded at the census block level. Each census block was characterized by socio-economic deprivation index, healthcare supply and rural/urban typology. Using a spatial scan statistic, we examined whether there were significant clusters of high risk of ESRD incidence. The ESRD incidence was non-randomly spatially distributed, with a cluster of high risk in the western Bretagne region (relative risk, RR = 1.28, P-value = 0.0003). Adjustment for sex, age and neighbourhood characteristics induced cluster shifts. After these adjustments, a significant cluster (P = 0.013) persisted. Our spatial analysis of ESRD incidence at a fine scale, across a mixed rural/urban area, indicated that, beyond age and sex, neighbourhood characteristics explained a great part of spatial distribution of ESRD incidence. However, to better understand spatial variation of ESRD incidence, it would be necessary to research and adjust for other determinants of ESRD.

[Experience in the treatment of interstitial cystitis: review of 17 cases].

PubMed

Flores-Carreras, Oscar; Martínez-Espinoza, Claudia J; González-Ruiz, María Isabel

2011-03-01

The Interstitial Cystitis (IC) has been considered in the past an uncommon pathology, however it has received a special attention during the last 20 years, (1678 scientific articles published since 1984 to 2009). There are many therapeutic options not at all satisfactory because there isn't consensus about diagnostic and treatment. To share our experiences in the treatment of interstitial cystitis, additionally, to comment on the therapeutic response of treatment used. Observational, retrospective an analytic study of 17 treated patients from 22 with diagnosis of IC and Bladder Painful Syndrome (IC/BPS) were managed in Urodifem de Occidente, S.C. a private Urogynecologic unit between January 2001 and April 2010. The diagnosis was done in agreement with the concepts of Interstitial Cystitis group from clinical and cystoscopic characteristics. The treatment was: Dimethyl sulfoxide (DIMSO) and Pentosan Polysulfate. The evaluation was measured by Interstitial Cystitis Symptomatic Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) both validated evaluation instruments, 82% of the patients had a significative improvement of symptomatology and quality of live The ICSI pre and post treatment was of 17.0 and 4.5 and the ICPI was of 14.8 and 4.1 respectively. We recommend the use of combine treatment of DIMSO and PPS in cases of I.C.

Novel Assessment of Interstitial Lung Disease Using the "Computer-Aided Lung Informatics for Pathology Evaluation and Rating" (CALIPER) Software System in Idiopathic Inflammatory Myopathies.

PubMed

Ungprasert, Patompong; Wilton, Katelynn M; Ernste, Floranne C; Kalra, Sanjay; Crowson, Cynthia S; Rajagopalan, Srinivasan; Bartholmai, Brian J

2017-10-01

To evaluate the correlation between measurements from quantitative thoracic high-resolution CT (HRCT) analysis with "Computer-Aided Lung Informatics for Pathology Evaluation and Rating" (CALIPER) software and measurements from pulmonary function tests (PFTs) in patients with idiopathic inflammatory myopathies (IIM)-associated interstitial lung disease (ILD). A cohort of patients with IIM-associated ILD seen at Mayo Clinic was identified from medical record review. Retrospective analysis of HRCT data and PFTs at baseline and 1 year was performed. The abnormalities in HRCT were quantified using CALIPER software. A total of 110 patients were identified. At baseline, total interstitial abnormalities as measured by CALIPER, both by absolute volume and by percentage of total lung volume, had a significant negative correlation with diffusing capacity for carbon monoxide (DLCO), total lung capacity (TLC), and oxygen saturation. Analysis by subtype of interstitial abnormality revealed significant negative correlations between ground glass opacities (GGO) and reticular density (RD) with DLCO and TLC. At one year, changes of total interstitial abnormalities compared with baseline had a significant negative correlation with changes of TLC and oxygen saturation. A negative correlation between changes of total interstitial abnormalities and DLCO was also observed, but it was not statistically significant. Analysis by subtype of interstitial abnormality revealed negative correlations between changes of GGO and RD and changes of DLCO, TLC, and oxygen saturation, but most of the correlations did not achieve statistical significance. CALIPER measurements correlate well with functional measurements in patients with IIM-associated ILD.

Is postural tremor size controlled by interstitial potassium concentration in muscle?

PubMed Central

Lakie, M; Hayes, N; Combes, N; Langford, N

2004-01-01

Objectives: To determine whether factors associated with postural tremor operate by altering muscle interstitial K+. Methods: An experimental approach was used to investigate the effects of procedures designed to increase or decrease interstitial K+. Postural physiological tremor was measured by conventional means. Brief periods of ischaemic muscle activity were used to increase muscle interstitial K+. Infusion of the ß2 agonist terbutaline was used to decrease plasma (and interstitial) K+. Blood samples were taken for the determination of plasma K+. Results: Ischaemia rapidly reduced tremor size, but only when the muscle was active. The ß2 agonist produced a slow and progressive rise in tremor size that was almost exactly mirrored by a slow and progressive decrease in plasma K+. Conclusions: Ischaemic reduction of postural tremor has been attributed to effects on muscle spindles or an unexplained effect on muscle. This study showed that ischaemia did not reduce tremor size unless there was accompanying muscular activity. An accumulation of K+ in the interstitium of the ischaemic active muscle may blunt the response of the muscle and reduce its fusion frequency, so that the force output becomes less pulsatile and tremor size decreases. When a ß2 agonist is infused, the rise in tremor mirrors the resultant decrease in plasma K+. Decreased plasma K+ reduces interstitial K+ concentration and may produce greater muscular force fluctuation (more tremor). Many other factors that affect postural tremor size may exert their effect by altering plasma K+ concentration, thereby changing the concentration of K+ in the interstitial fluid. PMID:15201362

The Objective Identification and Quantification of Interstitial Lung Abnormalities in Smokers.

PubMed

Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Putman, Rachel K; Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; Estepar, Raul San Jose; Washko, George R

2017-08-01

Previous investigation suggests that visually detected interstitial changes in the lung parenchyma of smokers are highly clinically relevant and predict outcomes, including death. Visual subjective analysis to detect these changes is time-consuming, insensitive to subtle changes, and requires training to enhance reproducibility. Objective detection of such changes could provide a method of disease identification without these limitations. The goal of this study was to develop and test a fully automated image processing tool to objectively identify radiographic features associated with interstitial abnormalities in the computed tomography scans of a large cohort of smokers. An automated tool that uses local histogram analysis combined with distance from the pleural surface was used to detect radiographic features consistent with interstitial lung abnormalities in computed tomography scans from 2257 individuals from the Genetic Epidemiology of COPD study, a longitudinal observational study of smokers. The sensitivity and specificity of this tool was determined based on its ability to detect the visually identified presence of these abnormalities. The tool had a sensitivity of 87.8% and a specificity of 57.5% for the detection of interstitial lung abnormalities, with a c-statistic of 0.82, and was 100% sensitive and 56.7% specific for the detection of the visual subtype of interstitial abnormalities called fibrotic parenchymal abnormalities, with a c-statistic of 0.89. In smokers, a fully automated image processing tool is able to identify those individuals who have interstitial lung abnormalities with moderate sensitivity and specificity. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

The deep muscular plexus of the pig duodenum: a histochemical and ultrastructural study with special reference to the interstitial cells.

PubMed

Henry, M; Porcher, C; Julé, Y

1998-06-10

The aim of the present study was to describe the deep muscular plexus of the pig duodenum and to characterize its cellular components. Numerous nerve varicosities have been detected in the deep muscular plexus using anti-synaptophysin antibodies. Nerve fibres were also detected here in the outer circular muscle layer, whereas no nerve fibres were observed in the inner circular muscle layer. In the deep muscular plexus, nerve fibres projected to interstitial cells which were characterized at the ultrastructural level. The interstitial cells were of two kinds: the interstitial fibroblastic-like cells (FLC) and the interstitial dense cells (IDC), both of which were interposed between nerve fibres and smooth muscle cells. The FLC were characterized by their elongated bipolar shape, the lack of basal lamina, a well-developed endoplasmic reticulum, a Golgi apparatus, and intermediate filaments. They were closely apposed to axon terminals containing small clear synaptic vesicles and/or dense-cored vesicles. They were frequently connected to each other and to smooth muscle cells of the inner and outer circular layer by desmosomes and more rarely by gap junctions. The IDC are myoid-like cells. They had a stellate appearance and were characterized by a dense cell body, numerous caveolae, and a discontinuous basal lamina. The IDC were always closely apposed to nerve fibres and were connected to smooth muscle cells by desmosomes and small gap junctions. The present results show the unique pattern of cellular organization of the deep muscular plexus of the pig small intestine. They suggest that the interstitial cells in the deep muscular plexus are involved in the integration and transmission of nervous inputs from myenteric neurons to the inner and outer circular muscle layers. The clear-cut distinction observed here between the two types of interstitial cells (fibroblastic and myoid-like) suggests that the interstitial cells of each type may also be involved in some other specific activity, which still remains to be determined.

The evolution of interaction between grain boundary and irradiation-induced point defects: Symmetric tilt GB in tungsten

NASA Astrophysics Data System (ADS)

Li, Hong; Qin, Yuan; Yang, Yingying; Yao, Man; Wang, Xudong; Xu, Haixuan; Phillpot, Simon R.

2018-03-01

Molecular dynamics method is used and scheme of calculational tests is designed. The atomic evolution view of the interaction between grain boundary (GB) and irradiation-induced point defects is given in six symmetric tilt GB structures of bcc tungsten with the energy of the primary knock-on atom (PKA) EPKA of 3 and 5 keV and the simulated temperature of 300 K. During the collision cascade with GB structure there are synergistic mechanisms to reduce the number of point defects: one is vacancies recombine with interstitials, and another is interstitials diffuse towards the GB with vacancies almost not move. The larger the ratio of the peak defect zone of the cascades overlaps with the GB region, the statistically relative smaller the number of surviving point defects in the grain interior (GI); and when the two almost do not overlap, vacancy-intensive area generally exists nearby GBs, and has a tendency to move toward GB with the increase of EPKA. In contrast, the distribution of interstitials is relatively uniform nearby GBs and is affected by the EPKA far less than the vacancy. The GB has a bias-absorption effect on the interstitials compared with vacancies. It shows that the number of surviving vacancies statistically has increasing trend with the increase of the distance between PKA and GB. While the number of surviving interstitials does not change much, and is less than the number of interstitials in the single crystal at the same conditions. The number of surviving vacancies in the GI is always larger than that of interstitials. The GB local extension after irradiation is observed for which the interstitials absorbed by the GB may be responsible. The designed scheme of calculational tests in the paper is completely applicable to the investigation of the interaction between other types of GBs and irradiation-induced point defects.

Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin

PubMed Central

Foster, Derek M.; Martin, Luke G.; Papich, Mark G.

2016-01-01

Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900% penetration to the airways. Despite high diffusion into the bronchi, the tulathromycin concentrations achieved were lower than the MIC of susceptible bacteria at most time points. PMID:26872361

[Medical management of interstitiel pregnancy by in situ methotrexate].

PubMed

Debras, E; Fernandez, H; Pourcelot, A-G; Houllier, M; Capmas, P

2016-09-01

Interstitial pregnancy accounts for 3 to 11% of ectopic pregnancy; these pregnancies are the more frequently non-tubal ectopic pregnancy. Medical treatment can be used in case of unruptured interstitial pregnancy and is used more and more frequently to avoid hemorrhagic risk and risk of conversion to radical surgery when a surgical management is decided. However, a larger use of methotrexate in interstitial pregnancy and conditions of use are not clearly defined. The aim of this study is to report a series of unruptured interstitial pregnancy managed by in situ injection of methotrexate. This retrospective observational study included women treated for an interstitial pregnancy between 2010 and 2013 in a teaching hospital. Medical management used was an in situ injection of methotrexate (1mg/kg) guided by vaginal sonography plus an intramuscular injection of methotrexate (1mg/kg) in the 48hours following in situ injection and 600mg of mifepristone when progesterone blood rate was more than 9ng/mL. A great decrease of serum hCG without surgery was considered a success. Fourteen women had an interstitial pregnancy during the study period. Six were managed surgically in 5 cases for suspicion of uterine rupture and one for pregnancy of unknown location. Eight women had a medical management and the success rate was 100%. Mean time for decrease of serum hCG until 2 UI/L was 54.4 days [34.0-74.8]. No uterine rupture or immediate complication was reported. Five women out of 8 had a spontaneous pregnancy after management of interstitial pregnancy. Medical management by in situ injection of methotrexate under sonographic guidance with an intramuscular injection within the 48hours following the in situ injection and mifepristone when ectopic pregnancy was active can be proposed in first-line therapy in case of unruptured interstitial pregnancy. This treatment has a great efficiency and low rate of complications. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Direct Observation of Defect Range and Evolution in Ion-Irradiated Single Crystalline Ni and Ni Binary Alloys.

PubMed

Lu, Chenyang; Jin, Ke; Béland, Laurent K; Zhang, Feifei; Yang, Taini; Qiao, Liang; Zhang, Yanwen; Bei, Hongbin; Christen, Hans M; Stoller, Roger E; Wang, Lumin

2016-02-01

Energetic ions have been widely used to evaluate the irradiation tolerance of structural materials for nuclear power applications and to modify material properties. It is important to understand the defect production, annihilation and migration mechanisms during and after collision cascades. In this study, single crystalline pure nickel metal and single-phase concentrated solid solution alloys of 50%Ni50%Co (NiCo) and 50%Ni50%Fe (NiFe) without apparent preexisting defect sinks were employed to study defect dynamics under ion irradiation. Both cross-sectional transmission electron microscopy characterization (TEM) and Rutherford backscattering spectrometry channeling (RBS-C) spectra show that the range of radiation-induced defect clusters far exceed the theoretically predicted depth in all materials after high-dose irradiation. Defects in nickel migrate faster than in NiCo and NiFe. Both vacancy-type stacking fault tetrahedra (SFT) and interstitial loops coexist in the same region, which is consistent with molecular dynamics simulations. Kinetic activation relaxation technique (k-ART) simulations for nickel showed that small vacancy clusters, such as di-vacancies and tri-vacancies, created by collision cascades are highly mobile, even at room temperature. The slower migration of defects in the alloy along with more localized energy dissipation of the displacement cascade may lead to enhanced radiation tolerance.

Features of primary damage by high energy displacement cascades in concentrated Ni-based alloys

DOE PAGES

Béland, Laurent Karim; Lu, Chenyang; Osetskiy, Yuri N.; ...

2016-02-25

Alloying of Ni with Fe or Co reduces primary damage production under ion irradiation. Similar results have been obtained from classical molecular dynamics simulations of 1, 10, 20, and 40 keV collision cascades in Ni, NiFe, and NiCo. In all cases, a mix of imperfect stacking fault tetrahedra, faulted loops with a 1/3 {111} Burgers vector, and glissile interstitial loops with a 1/2 {110} Burgers vector were formed, along with small sessile point defect complexes and clusters. Primary damage reduction occurs by three mechanisms. First, Ni-Co, Ni-Fe, Co-Co, and Fe-Fe short-distance repulsive interactions are stiffer than Ni-Ni interactions, which leadmore » to a decrease in damage formation during the transition from the supersonic ballistic regime to the sonic regime. This largely controls final defect production. Second, alloying decreases thermal conductivity, leading to a longer thermal spike lifetime. The associated annealing reduces final damage production. These two mechanisms are especially important at cascades energies less than 40 keV. Third, at the higher energies, the production of large defect clusters by subcascades is inhibited in the alloys. A number of challenges and limitations pertaining to predictive atomistic modeling of alloys under high-energy particle irradiation are discussed.« less

Achieving Radiation Tolerance through Non-Equilibrium Grain Boundary Structures.

PubMed

Vetterick, Gregory A; Gruber, Jacob; Suri, Pranav K; Baldwin, Jon K; Kirk, Marquis A; Baldo, Pete; Wang, Yong Q; Misra, Amit; Tucker, Garritt J; Taheri, Mitra L

2017-09-25

Many methods used to produce nanocrystalline (NC) materials leave behind non-equilibrium grain boundaries (GBs) containing excess free volume and higher energy than their equilibrium counterparts with identical 5 degrees of freedom. Since non-equilibrium GBs have increased amounts of both strain and free volume, these boundaries may act as more efficient sinks for the excess interstitials and vacancies produced in a material under irradiation as compared to equilibrium GBs. The relative sink strengths of equilibrium and non-equilibrium GBs were explored by comparing the behavior of annealed (equilibrium) and as-deposited (non-equilibrium) NC iron films on irradiation. These results were coupled with atomistic simulations to better reveal the underlying processes occurring on timescales too short to capture using in situ TEM. After irradiation, NC iron with non-equilibrium GBs contains both a smaller number density of defect clusters and a smaller average defect cluster size. Simulations showed that excess free volume contribute to a decreased survival rate of point defects in cascades occurring adjacent to the GB and that these boundaries undergo less dramatic changes in structure upon irradiation. These results suggest that non-equilibrium GBs act as more efficient sinks for defects and could be utilized to create more radiation tolerant materials in future.

Direct Observation of Defect Range and Evolution in Ion-Irradiated Single Crystalline Ni and Ni Binary Alloys

PubMed Central

Lu, Chenyang; Jin, Ke; Béland, Laurent K.; Zhang, Feifei; Yang, Taini; Qiao, Liang; Zhang, Yanwen; Bei, Hongbin; Christen, Hans M.; Stoller, Roger E.; Wang, Lumin

2016-01-01

Energetic ions have been widely used to evaluate the irradiation tolerance of structural materials for nuclear power applications and to modify material properties. It is important to understand the defect production, annihilation and migration mechanisms during and after collision cascades. In this study, single crystalline pure nickel metal and single-phase concentrated solid solution alloys of 50%Ni50%Co (NiCo) and 50%Ni50%Fe (NiFe) without apparent preexisting defect sinks were employed to study defect dynamics under ion irradiation. Both cross-sectional transmission electron microscopy characterization (TEM) and Rutherford backscattering spectrometry channeling (RBS-C) spectra show that the range of radiation-induced defect clusters far exceed the theoretically predicted depth in all materials after high-dose irradiation. Defects in nickel migrate faster than in NiCo and NiFe. Both vacancy-type stacking fault tetrahedra (SFT) and interstitial loops coexist in the same region, which is consistent with molecular dynamics simulations. Kinetic activation relaxation technique (k-ART) simulations for nickel showed that small vacancy clusters, such as di-vacancies and tri-vacancies, created by collision cascades are highly mobile, even at room temperature. The slower migration of defects in the alloy along with more localized energy dissipation of the displacement cascade may lead to enhanced radiation tolerance. PMID:26829570

A de novo 1q22q23.1 Interstitial Microdeletion in a Girl with Intellectual Disability and Multiple Congenital Anomalies Including Congenital Heart Defect.

PubMed

Aleksiūnienė, Beata; Preiksaitiene, Egle; Morkūnienė, Aušra; Ambrozaitytė, Laima; Utkus, Algirdas

2018-01-01

Many studies have shown that molecular karyotyping is an effective diagnostic tool in individuals with developmental delay/intellectual disability. We report on a de novo interstitial 1q22q23.1 microdeletion, 1.6 Mb in size, detected in a patient with short stature, microcephaly, hypoplastic corpus callosum, cleft palate, minor facial anomalies, congenital heart defect, camptodactyly of the 4-5th fingers, and intellectual disability. Chromosomal microarray analysis revealed a 1.6-Mb deletion in the 1q22q23.1 region, arr[GRCh37] 1q22q23.1(155630752_157193893)×1. Real-time PCR analysis confirmed its de novo origin. The deleted region encompasses 50 protein-coding genes, including the morbid genes APOA1BP, ARHGEF2, LAMTOR2, LMNA, NTRK1, PRCC, RIT1, SEMA4A, and YY1AP1. Although the unique phenotype observed in our patient can arise from the haploinsufficiency of the dosage-sensitive LMNA gene, the dosage imbalance of other genes implicated in the rearrangement could also contribute to the phenotype. Further studies are required for the delineation of the phenotype associated with this rare chromosomal alteration and elucidation of the critical genes for manifestation of the specific clinical features. © 2018 S. Karger AG, Basel.

An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas.

PubMed

Korsgren, Erik; Korsgren, Olle

2016-04-01

The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Adult and juvenile dermatomyositis: are the distinct clinical features explained by our current understanding of serological subgroups and pathogenic mechanisms?

PubMed Central

2013-01-01

Adult and juvenile dermatomyositis share the hallmark features of pathognomic skin rash and muscle inflammation, but are heterogeneous disorders with a range of additional disease features and complications. The frequency of important clinical features such as calcinosis, interstitial lung disease and malignancy varies markedly between adult and juvenile disease. These differences may reflect different disease triggers between children and adults, but whilst various viral and other environmental triggers have been implicated, results are so far conflicting. Myositis-specific autoantibodies can be detected in both adults and children with idiopathic inflammatory myopathies. They are associated with specific disease phenotypes and complications, and divide patients into clinically homogenous subgroups. Interestingly, whilst the same autoantibodies are found in both adults and children, the disease features remain different within autoantibody subgroups, particularly with regard to life-threatening disease associations, such as malignancy and rapidly progressive interstitial lung disease. Our understanding of the mechanisms that underlie these differences is limited by a lack of studies directly comparing adults and children. Dermatomyositis is an autoimmune disease, which is believed to develop as a result of an environmental trigger in a genetically predisposed individual. Age-specific host immune responses and muscle physiology may be additional complicating factors that have significant impact on disease presentation. Further study into this area may produce new insights into disease pathogenesis. PMID:23566358

Lung radiology and pulmonary function of children chronically exposed to air pollution.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Fordham, Lynn A; Chung, Charles J; Valencia-Salazar, Gildardo; Flores-Gómez, Silvia; Solt, Anna C; Gomez-del Campo, Alberto; Jardón-Torres, Ricardo; Henríquez-Roldán, Carlos; Hazucha, Milan J; Reed, William

2006-09-01

We analyzed the chest radiographs (CXRs) of 249 clinically healthy children, 230 from southwest Mexico City and 19 from Tlaxcala. In contrast to children from Tlaxcala, children from southwest Mexico City were chronically exposed to ozone levels exceeding the U.S. National Ambient Air Quality Standards for an average of 4.7 hr/day and to concentrations of particulate matter (PM) with aerodynamic diameters

A new glaucoma hypothesis: a role of glymphatic system dysfunction.

PubMed

Wostyn, Peter; Van Dam, Debby; Audenaert, Kurt; Killer, Hanspeter Esriel; De Deyn, Peter Paul; De Groot, Veva

2015-06-29

In a recent review article titled "A new look at cerebrospinal fluid circulation", Brinker et al. comprehensively described novel insights from molecular and cellular biology as well as neuroimaging research, which indicate that cerebrospinal fluid (CSF) physiology is much more complex than previously believed. The glymphatic system is a recently defined brain-wide paravascular pathway for CSF and interstitial fluid exchange that facilitates efficient clearance of interstitial solutes, including amyloid-β, from the brain. Although further studies are needed to substantiate the functional significance of the glymphatic concept, one implication is that glymphatic pathway dysfunction may contribute to the deficient amyloid-β clearance in Alzheimer's disease. In this paper, we review several lines of evidence suggesting that the glymphatic system may also have potential clinical relevance for the understanding of glaucoma. As a clinically acceptable MRI-based approach to evaluate glymphatic pathway function in humans has recently been developed, a unique opportunity now exists to investigate whether suppression of the glymphatic system contributes to the development of glaucoma. The observation of a dysfunctional glymphatic system in patients with glaucoma would provide support for the hypothesis recently proposed by our group that CSF circulatory dysfunction may play a contributory role in the pathogenesis of glaucomatous damage. This would suggest a new hypothesis for glaucoma, which, just like Alzheimer's disease, might be considered then as an imbalance between production and clearance of neurotoxins, including amyloid-β.

A model of fluid and solute exchange in the human: validation and implications.

PubMed

Bert, J L; Gyenge, C C; Bowen, B D; Reed, R K; Lund, T

2000-11-01

In order to understand better the complex, dynamic behaviour of the redistribution and exchange of fluid and solutes administered to normal individuals or to those with acute hypovolemia, mathematical models are used in addition to direct experimental investigation. Initial validation of a model developed by our group involved data from animal experiments (Gyenge, C.C., Bowen, B.D., Reed, R.K. & Bert, J.L. 1999b. Am J Physiol 277 (Heart Circ Physiol 46), H1228-H1240). For a first validation involving humans, we compare the results of simulations with a wide range of different types of data from two experimental studies. These studies involved administration of normal saline or hypertonic saline with Dextran to both normal and 10% haemorrhaged subjects. We compared simulations with data including the dynamic changes in plasma and interstitial fluid volumes VPL and VIT respectively, plasma and interstitial colloid osmotic pressures PiPL and PiIT respectively, haematocrit (Hct), plasma solute concentrations and transcapillary flow rates. The model predictions were overall in very good agreement with the wide range of experimental results considered. Based on the conditions investigated, the model was also validated for humans. We used the model both to investigate mechanisms associated with the redistribution and transport of fluid and solutes administered following a mild haemorrhage and to speculate on the relationship between the timing and amount of fluid infusions and subsequent blood volume expansion.

Conservation of the Nucleotide Excision Repair Pathway: Characterization of Hydra Xeroderma Pigmentosum Group F Homolog

PubMed Central

Barve, Apurva; Ghaskadbi, Saroj; Ghaskadbi, Surendra

2013-01-01

Hydra, one of the earliest metazoans with tissue grade organization and nervous system, is an animal with a remarkable regeneration capacity and shows no signs of organismal aging. We have for the first time identified genes of the nucleotide excision repair (NER) pathway from hydra. Here we report cloning and characterization of hydra homolog of xeroderma pigmentosum group F (XPF) gene that encodes a structure-specific 5′ endonuclease which is a crucial component of NER. In silico analysis shows that hydra XPF amino acid sequence is very similar to its counterparts from other animals, especially vertebrates, and shows all features essential for its function. By in situ hybridization, we show that hydra XPF is expressed prominently in the multipotent stem cell niche in the central region of the body column. Ectoderm of the diploblastic hydra was shown to express higher levels of XPF as compared to the endoderm by semi-quantitative RT-PCR. Semi-quantitative RT-PCR analysis also demonstrated that interstitial cells, a multipotent and rapidly cycling stem cell lineage of hydra, express higher levels of XPF mRNA than other cell types. Our data show that XPF and by extension, the NER pathway is highly conserved during evolution. The prominent expression of an NER gene in interstitial cells may have implications for the lack of senescence in hydra. PMID:23577191

Conservation of the nucleotide excision repair pathway: characterization of hydra Xeroderma Pigmentosum group F homolog.

PubMed

Barve, Apurva; Ghaskadbi, Saroj; Ghaskadbi, Surendra

2013-01-01

Hydra, one of the earliest metazoans with tissue grade organization and nervous system, is an animal with a remarkable regeneration capacity and shows no signs of organismal aging. We have for the first time identified genes of the nucleotide excision repair (NER) pathway from hydra. Here we report cloning and characterization of hydra homolog of xeroderma pigmentosum group F (XPF) gene that encodes a structure-specific 5' endonuclease which is a crucial component of NER. In silico analysis shows that hydra XPF amino acid sequence is very similar to its counterparts from other animals, especially vertebrates, and shows all features essential for its function. By in situ hybridization, we show that hydra XPF is expressed prominently in the multipotent stem cell niche in the central region of the body column. Ectoderm of the diploblastic hydra was shown to express higher levels of XPF as compared to the endoderm by semi-quantitative RT-PCR. Semi-quantitative RT-PCR analysis also demonstrated that interstitial cells, a multipotent and rapidly cycling stem cell lineage of hydra, express higher levels of XPF mRNA than other cell types. Our data show that XPF and by extension, the NER pathway is highly conserved during evolution. The prominent expression of an NER gene in interstitial cells may have implications for the lack of senescence in hydra.

Mathematical Modeling of Herpes Simplex Virus Distribution in Solid Tumors: Implications for Cancer Gene Therapy

PubMed Central

Mok, Wilson; Stylianopoulos, Triantafyllos; Boucher, Yves; Jain, Rakesh K.

2010-01-01

Purpose Although oncolytic viral vectors show promise for the treatment of various cancers, ineffective initial distribution and propagation throughout the tumor mass often limit the therapeutic response. A mathematical model is developed to describe the spread of herpes simplex virus from the initial injection site. Experimental Design The tumor is modeled as a sphere of radius R. The model incorporates reversible binding, interstitial diffusion, viral degradation, and internalization and physiologic parameters. Three species are considered as follows: free interstitial virus, virus bound to cell surfaces, and internalized virus. Results This analysis reveals that both rapid binding and internalization as well as hindered diffusion contain the virus to the initial injection volume, with negligible spread to the surrounding tissue. Unfortunately, increasing the dose to saturate receptors and promote diffusion throughout the tumor is not a viable option: the concentration necessary would likely compromise safety. However, targeted modifications to the virus that decrease the binding affinity have the potential to increase the number of infected cells by 1.5-fold or more. An increase in the effective diffusion coefficient can result in similar gains. Conclusions This analysis suggests criteria by which the potential response of a tumor to oncolytic herpes simplex virus therapy can be assessed. Furthermore, it reveals the potential of modifications to the vector delivery method, physicochemical properties of the virus, and tumor extracellular matrix composition to enhance efficacy. PMID:19318482

Understanding pain and coping in women with interstitial cystitis/bladder pain syndrome.

PubMed

Katz, Laura; Tripp, Dean A; Carr, Lesley K; Mayer, Robert; Moldwin, Robert M; Nickel, J Curtis

2017-08-01

To examine a self-regulation and coping model for interstitial cystitis/bladder pain syndrome (IC/BPS) that may help us understand the pain experience of patients with chronic IC/BPS. The model tested illness perceptions, illness-focused coping, emotional regulation, mental health and disability in a stepwise method using factor analysis and structural equation modelling. Step 1, explored the underlying constructs. Step 2, confirmed the measurement models to determine the structure/composition of the main constructs. Step 3, evaluated the model fit and specified pathways in the proposed IC/BPS self-regulation model. In all, 217 female patients with urologist diagnosed IC/BPS were recruited and diagnosed across tertiary care centres in North America. The data were collected through self-report questionnaires. An IC/BPS self-regulation model was supported. Physical disability was worsened by patient's negative perception of their illness, attempts to cope using illness-focused coping and poorer emotional regulation. Mental health was supported by perceptions that individuals could do something about their illness, using wellness-focused behavioural strategies and adaptive emotion regulation. The results clarify the complex and unique process of self-regulation in women with IC/BPS, implicating cognitive and coping targets, and highlighting emotional regulation. This knowledge should help clinicians understand and manage these patients' distress and disability. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Interactions of small platinum clusters with the TiC(001) surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao, Jianjun; Li, Shasha; Chu, Xingli

2015-11-14

Density functional theory calculations are used to elucidate the interactions of small platinum clusters (Pt{sub n}, n = 1–5) with the TiC(001) surface. The results are analyzed in terms of geometric, energetic, and electronic properties. It is found that a single Pt atom prefers to be adsorbed at the C-top site, while a Pt{sub 2} cluster prefers dimerization and a Pt{sub 3} cluster forms a linear structure on the TiC(001). As for the Pt{sub 4} cluster, the three-dimensional distorted tetrahedral structure and the two-dimensional square structure almost have equal stability. In contrast with the two-dimensional isolated Pt{sub 5} cluster, the adsorbed Pt{submore » 5} cluster prefers a three-dimensional structure on TiC(001). Substantial charge transfer takes place from TiC(001) surface to the adsorbed Pt{sub n} clusters, resulting in the negatively charged Pt{sub n} clusters. At last, the d-band centers of the absorbed Pt atoms and their implications in the catalytic activity are discussed.« less

COMPARATIVE ASSESSMENT OF THE COMPOSITION AND CHARGE STATE OF NITROGENASE FeMo-COFACTOR

PubMed Central

Harris, Travis V.; Szilagyi, Robert K.

2011-01-01

A significant limitation in our understanding of the molecular mechanism of biological nitrogen fixation is the uncertain composition of the FeMo-cofactor (FeMo-co) of nitrogenase. In this study we present a systematic, density functional theory-based evaluation of spin coupling schemes, iron oxidation states, ligand protonation states, and interstitial ligand composition using a wide range of experimental criteria. The employed functionals and basis sets were validated with molecular orbital information from X-ray absorption spectroscopic data of relevant iron-sulfur clusters. Independently from the employed level of theory, the electronic structure with the greatest number of antiferromagnetic interactions corresponds to the lowest energy state for a given charge and oxidation state distribution of the iron ions. The relative spin state energies of resting and oxidized FeMo-co already allowed the exclusion of certain iron oxidation state distributions and interstitial ligand compositions. Geometry optimized FeMo-co structures of several models further eliminated additional states and compositions, while reduction potentials indicated a strong preference for the most likely charge state of FeMo-co. Mössbauer and ENDOR parameter calculations were found to be remarkably dependent on the employed training set, density functional and basis set. Overall, we found that a more oxidized [MoIV-2FeII-5FeIII-9S2−-C4−] composition with a hydroxyl-protonated homocitrate ligand satisfies all of the available experimental criteria, and is thus favored over the currently preferred composition of [MoIV-4FeII-3FeIII-9S2−-N3−] from the literature. PMID:21545160

Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter

PubMed Central

Dantzler, William H.; Pannabecker, Thomas L.

2012-01-01

We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na+ or urea-Cl− cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na+ or urea- Cl− cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data. PMID:22088433

Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter.

PubMed

Layton, Anita T; Dantzler, William H; Pannabecker, Thomas L

2012-03-01

We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na(+) or urea-Cl(-) cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na(+) or urea- Cl(-) cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data.

The defect chemistry of UO2 ± x from atomistic simulations

NASA Astrophysics Data System (ADS)

Cooper, M. W. D.; Murphy, S. T.; Andersson, D. A.

2018-06-01

Control of the defect chemistry in UO2 ± x is important for manipulating nuclear fuel properties and fuel performance. For example, the uranium vacancy concentration is critical for fission gas release and sintering, while all oxygen and uranium defects are known to strongly influence thermal conductivity. Here the point defect concentrations in thermal equilibrium are predicted using defect energies from density functional theory (DFT) and vibrational entropies calculated using empirical potentials. Electrons and holes have been treated in a similar fashion to other charged defects allowing for structural relaxation around the localized electronic defects. Predictions are made for the defect concentrations and non-stoichiometry of UO2 ± x as a function of oxygen partial pressure and temperature. If vibrational entropy is omitted, oxygen interstitials are predicted to be the dominant mechanism of excess oxygen accommodation over only a small temperature range (1265 K-1350 K), in contrast to experimental observation. Conversely, if vibrational entropy is included oxygen interstitials dominate from 1165 K to 1680 K (Busker potential) or from 1275 K to 1630 K (CRG potential). Below these temperature ranges, excess oxygen is predicted to be accommodated by uranium vacancies, while above them the system is hypo-stoichiometric with oxygen deficiency accommodated by oxygen vacancies. Our results are discussed in the context of oxygen clustering, formation of U4O9, and issues for fuel behavior. In particular, the variation of the uranium vacancy concentrations as a function of temperature and oxygen partial pressure will underpin future studies into fission gas diffusivity and broaden the understanding of UO2 ± x sintering.

Studies in the X-Ray Emission of Clusters of Galaxies and Other Topics

NASA Technical Reports Server (NTRS)

Vrtilek, Jan; Thronson, Harley (Technical Monitor)

2001-01-01

The paper discusses the following: (1) X-ray study of groups of galaxies with Chandra and XMM. (2) X-ray properties of point sources in Chandra deep fields. (3) Study of cluster substructure using wavelet techniques. (4) Combined study of galaxy clusters with X-ray and the S-Z effect. Groups of galaxies are the fundamental building blocks of large scale structure in the Universe. X-ray study of the intragroup medium offers a powerful approach to addressing some of the major questions that still remain about almost all aspects of groups: their ages, origins, importance of composition of various galaxy types, relations to clusters, and origin and enrichment of the intragroup gas. Long exposures with Chandra have opened new opportunities for the study of X-ray background. The presence of substructure within clusters of galaxies has substantial implications for our understanding of cluster evolution as well as fundamental questions in cosmology.

Vitellogenesis in Archigetes sieboldi Leuckart, 1878 (Cestoda, Caryophyllidea, Caryophyllaeidae), an intestinal parasite of carp (Cyprinus carpio L.).

PubMed

Brunanská, M; Mackiewicz, J S; Nebesárová, J

2012-12-01

Vitellogenesis in the caryophyllidean tapeworm Archigetes sieboldi Leuckart, 1878, from carp Cyprinus carpio L. in Slovakia, has been examined using transmission electron microscopy and cytochemical staining with periodic acid-thiosemicarbazide-silver proteinate (PA-TSC-SP) for glycogen. Vitelline follicles extend in two lateral bands in the medullary parenchyma along both sides of the monozoic body. They are surrounded by an external basal lamina and contain vitellocytes and an interstitial tissue. The general pattern of vitellogenesis is essentially like that of other caryophyllideans. It involves four stages: immature, early maturing, advanced maturing cells and mature vitellocytes. During vitellogenesis, a continuous increase in cell volume is accompanied by an extensive development of cell components engaged in shell globule formation, e.g. granular endoplasmic reticulum and Golgi. Shell globule clusters are membrane-bound. Nuclear and nucleolar transformation are associated with formation and storage of large amounts of intranuclear glycogen, a very specific feature of the Caryophyllidea. For the first time, (a) additional vitelline material in Archigetes is represented by lamellar bodies and (b) lipid droplets are described in the mature vitellocytes from vitelline follicles and vitelloduct of the Caryophyllidea. Our results indicate that there may be a double origin of lamellar bodies: either from the endoplasmic reticulum or through transformation of shell globule/shell globule clusters. Lamellar body clusters and some single lamellar bodies appear to have a membrane. Other ultrastructural features of vitellogenesis and/or vitellocyte in A. sieboldi from its vertebrate (fish) and invertebrate (oligochaete) hosts are briefly compared and contrasted with those in other caryophyllideans and/or Neodermata.

Innervation of the anterior byssal retractor muscle in Mytilus edulis L. II. Ultrastructure of the glio-interstitial cells.

PubMed

Gilloteaux, J

1975-08-27

Studies on the intrinsic innervation of the anterior byssal retractor muscle (ABRM) in Mytilus edulis L. were continued at the ultrastructural level. Electron micrographs show nerve processes ensheathed by glio-interstitial cells running between muscle fibers. The glio-interstitial cells may represent all the types of osmiophilic cells previously described by the light microscopic ZIO technique in the anterior byssal retractor muscle.

Bismuth interstitial impurities and the optical properties of GaP 1- x - yBi xN y

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christian, Theresa M.; Beaton, Daniel A.; Perkins, John D.

Two distinctive regimes of behavior are observed from GaP 1-x-y Bi x N y alloys with x < 2.4%, y < 3.4% grown by molecular beam epitaxy. These regimes are correlated with abundant bismuth interstitial impurities that are encouraged or suppressed according to the sample growth temperature, with up to 55% of incorporated bismuth located interstitially. When bismuth interstitials are present, radiative recombination arises at near-band-edge localized states rather than from impurity bands and deep state luminescence. Finally, this change demonstrates a novel strategy for controlling luminescence in isoelectronic semiconductor alloys and is attributed to a disruption of carrier transfermore » processes.« less

Bismuth interstitial impurities and the optical properties of GaP 1- x - yBi xN y

DOE PAGES

Christian, Theresa M.; Beaton, Daniel A.; Perkins, John D.; ...

2017-10-10

Two distinctive regimes of behavior are observed from GaP 1-x-y Bi x N y alloys with x < 2.4%, y < 3.4% grown by molecular beam epitaxy. These regimes are correlated with abundant bismuth interstitial impurities that are encouraged or suppressed according to the sample growth temperature, with up to 55% of incorporated bismuth located interstitially. When bismuth interstitials are present, radiative recombination arises at near-band-edge localized states rather than from impurity bands and deep state luminescence. Finally, this change demonstrates a novel strategy for controlling luminescence in isoelectronic semiconductor alloys and is attributed to a disruption of carrier transfermore » processes.« less

Very Broad [O III] λλ4959, 5007 Emission from the NGC 4472 Globular Cluster RZ 2109 and Implications for the Mass of Its Black Hole X-Ray Source

NASA Astrophysics Data System (ADS)

Zepf, Stephen E.; Stern, Daniel; Maccarone, Thomas J.; Kundu, Arunav; Kamionkowski, Marc; Rhode, Katherine L.; Salzer, John J.; Ciardullo, Robin; Gronwall, Caryl

2008-08-01

We present Keck LRIS spectroscopy of the black hole-hosting globular cluster RZ 2109 in the Virgo elliptical galaxy NGC 4472. We find that this object has extraordinarily broad [O III] λ5007 and [O III] λ4959 emission lines, with velocity widths of approximately 2000 km s-1. This result has significant implications for the nature of this accreting black hole system and the mass of the globular cluster black hole. We show that the broad [O III] λ5007 emission must arise from material driven at high velocity from the black hole system. This is because the volume available near the black hole is too small by many orders of magnitude to have enough [O III]-emitting atoms to account for the observed L([O III] λ5007) at high velocities, even if this volume is filled with oxygen at the critical density for [O III] λ5007. The Balmer emission is also weak, indicating the observed [O III] is not due to shocks. We therefore conclude that the [O III] λλ4959, 5007 is produced by photoionization of material driven across the cluster. The only known way to drive significant material at high velocity is for a system accreting mass near or above its Eddington limit, which indicates a stellar-mass black hole. Since it is dynamically implausible to form an accreting stellar-mass black hole system in a globular cluster with an intermediate-mass black hole (IMBH), it appears this massive globular cluster does not have an IMBH. We discuss further tests of this conclusion, and its implications for the MBH - Mstellar and MBH - σ relations. Based on observations made at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

The Psychology of Yoga Practitioners: A Cluster Analysis.

PubMed

Genovese, Jeremy E C; Fondran, Kristine M

2017-11-01

Yoga practitioners (N = 261) completed the revised Expression of Spirituality Inventory (ESI) and the Multidimensional Body-Self Relations Questionnaire. Cluster analysis revealed three clusters: Cluster A scored high on all four spiritual constructs. They had high positive evaluations of their appearance, but a lower orientation towards their appearance. They tended to have a high evaluation of their fitness and health, and higher body satisfaction. Cluster B showed lower scores on the spiritual constructs. Like Cluster A, members of Cluster B tended to show high positive evaluations of appearance and fitness. They also had higher body satisfaction. Members of Cluster B had a higher fitness orientation and a higher appearance orientation than members of Cluster A. Members of Cluster C had low scores for all spiritual constructs. They had a low evaluation of, and unhappiness with, their appearance. They were unhappy with the size and appearance of their bodies. They tended to see themselves as overweight. There was a significant difference in years of practice between the three groups (Kruskall -Wallis, p = .0041). Members of Cluster A have the most years of yoga experience and members of Cluster B have more yoga experience than members of Cluster C. These results suggest the possible existence of a developmental trajectory for yoga practitioners. Such a developmental sequence may have important implications for yoga practice and instruction.

The Psychology of Yoga Practitioners: A Cluster Analysis.

PubMed

Genovese, Jeremy E C; Fondran, Kristine M

2017-03-30

Yoga practitioners (N = 261) completed the revised Expression of Spirituality Inventory (ESI) and the Multidimensional Body-Self Relations Questionnaire. Cluster analysis revealed three clusters: Cluster A scored high on all four spiritual constructs. They had high positive evaluations of their appearance, but a lower orientation towards their appearance. They tended to have a high evaluation of their fitness and health, and higher body satisfaction. Cluster B showed lower scores on the spiritual constructs. Like Cluster A, members of Cluster B tended to show high positive evaluations of appearance and fitness. They also had higher body satisfaction. Members of Cluster B had a higher fitness orientation and a higher appearance orientation than members of Cluster A. Members of Cluster C had low scores for all spiritual constructs. They had a low evaluation of, and unhappiness with, their appearance. They were unhappy with the size and appearance of their bodies. They tended to see themselves as overweight. There was a significant difference in years of practice between the three groups (Kruskall-Wallis, p = .0041). Members of Cluster A have the most years of yoga experience and members of Cluster B have more yoga experience than members of Cluster C. These results suggest the possible existence of a developmental trajectory for yoga practitioners. Such a developmental sequence may have important implications for yoga practice and instruction.

Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling

PubMed Central

Mattila, Pieta K.; Batista, Facundo D.

2016-01-01

Recent evidence implicates the actin cytoskeleton in the control of receptor signaling. This may be of particular importance in the context of immune receptors, such as the B cell receptor, where dysregulated signaling can result in autoimmunity and malignancy. Here, we discuss the role of the actin cytoskeleton in controlling receptor compartmentalization, dynamics, and clustering as a means to regulate receptor signaling through controlling the interactions with protein partners. We propose that the actin cytoskeleton is a point of integration for receptor cross talk through modulation of protein dynamics and clustering. We discuss the implication of this cross talk via the cytoskeleton for both ligand-induced and low-level constitutive (tonic) signaling necessary for immune cell survival. PMID:26833785

Radiation-sustained nanocluster metastability in oxide dispersion strengthened materials

NASA Astrophysics Data System (ADS)

Ribis, J.; Bordas, E.; Trocellier, P.; Serruys, Y.; de Carlan, Y.; Legris, A.

2015-12-01

ODS materials constitute a new promising class of structural materials for advanced fission and fusion energy application. These Fe-Cr based ferritic steels contain ultra-high density of dispersion-strengthening nanoclusters conferring excellent mechanical properties to the alloy. Hence, guarantee the nanocluster stability under irradiation remain a critical issue. Nanoclusters are non-equilibrium multicomponent compounds (YTiCrO) forming through a complex nucleation pathway during the elaboration process. In this paper, it is proposed to observe the response of these nanoclusters when the system is placed far from equilibrium by means of ion beam. The results indicate that the Y, Ti, O and Cr atoms self-organized so that nanoclusters coarsened but maintain their non-equilibrium chemical composition. It is discussed that the radiation-sustained nanocluster metastability emerges from cooperative effects: radiation-induced Ostwald ripening, permanent creation of vacancies in the clusters, and fast Cr diffusion mediated by interstitials.

Multi-scale Modeling of Radiation Damage: Large Scale Data Analysis

NASA Astrophysics Data System (ADS)

Warrier, M.; Bhardwaj, U.; Bukkuru, S.

2016-10-01

Modification of materials in nuclear reactors due to neutron irradiation is a multiscale problem. These neutrons pass through materials creating several energetic primary knock-on atoms (PKA) which cause localized collision cascades creating damage tracks, defects (interstitials and vacancies) and defect clusters depending on the energy of the PKA. These defects diffuse and recombine throughout the whole duration of operation of the reactor, thereby changing the micro-structure of the material and its properties. It is therefore desirable to develop predictive computational tools to simulate the micro-structural changes of irradiated materials. In this paper we describe how statistical averages of the collision cascades from thousands of MD simulations are used to provide inputs to Kinetic Monte Carlo (KMC) simulations which can handle larger sizes, more defects and longer time durations. Use of unsupervised learning and graph optimization in handling and analyzing large scale MD data will be highlighted.

Fe implantation effect in the 6H-SiC semiconductor investigated by Mössbauer spectrometry

NASA Astrophysics Data System (ADS)

Diallo, M. L.; Diallo, L.; Fnidiki, A.; Lechevallier, L.; Cuvilly, F.; Blum, I.; Viret, M.; Marteau, M.; Eyidi, D.; Juraszek, J.; Declémy, A.

2017-08-01

P-doped 6H-SiC substrates were implanted with 57Fe ions at 380 °C or 550 °C to produce a diluted magnetic semiconductor with an Fe homogeneous concentration of about 100 nm thickness. The magnetic properties were studied with 57Fe Conversion Electron Mössbauer Spectrometry at room temperature (RT). Results obtained by this technique on annealed samples prove that ferromagnetism in 57Fe-implanted SiC for Fe concentrations close to 2% and 4% is mostly due to Fe atoms diluted in the matrix. In contrast, for Fe concentrations close to 6%, it also comes from Fe in magnetic phase nano-clusters. This study allows quantifying the Fe amount in the interstitial and substitutional sites and the nanoparticles and shows that the majority of the diluted Fe atoms are substituted on Si sites inducing ferromagnetism up to RT.

Irradiation Creep in Graphite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ubic, Rick; Butt, Darryl; Windes, William

2014-03-13

An understanding of the underlying mechanisms of irradiation creep in graphite material is required to correctly interpret experimental data, explain micromechanical modeling results, and predict whole-core behavior. This project will focus on experimental microscopic data to demonstrate the mechanism of irradiation creep. High-resolution transmission electron microscopy should be able to image both the dislocations in graphite and the irradiation-induced interstitial clusters that pin those dislocations. The team will first prepare and characterize nanoscale samples of virgin nuclear graphite in a transmission electron microscope. Additional samples will be irradiated to varying degrees at the Advanced Test Reactor (ATR) facility and similarlymore » characterized. Researchers will record microstructures and crystal defects and suggest a mechanism for irradiation creep based on the results. In addition, the purchase of a tensile holder for a transmission electron microscope will allow, for the first time, in situ observation of creep behavior on the microstructure and crystallographic defects.« less

Atomic origins of water-vapour-promoted alloy oxidation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Langli; Su, Mao; Yan, Pengfei

The presence of water vapor, intentional or unavoidable, is crucial to many materials applications, such as steam generator, turbine engine, fuel cell, catalyst, and corrosion 1-6. Phenomenologically, water vapor has been noticed to accelerate oxidation of metals/alloys 7,8, however, the atomistic mechanisms remain elusive. Herein, through direct in situ atomic-scale transmission electron microscopy observation and density functional theory calculation, we reveal that water vapor enhanced oxidation of Ni-Cr alloy is associated with proton dissolution promoted vacancy formation, migration and clustering. Protons derived from water dissociation occupy interstitial position in the oxide lattice, which consequently leads to the lowering of bothmore » vacancy formation energy and the cation diffusion barrier. The atomic scale observations reveal a water vapor derived proton mediated oxide growth mechanism, which provides insights for reckoning many technological processes concerning materials in moist environment at elevated temperatures.« less

A defect model for UO2+x based on electrical conductivity and deviation from stoichiometry measurements

NASA Astrophysics Data System (ADS)

Garcia, Philippe; Pizzi, Elisabetta; Dorado, Boris; Andersson, David; Crocombette, Jean-Paul; Martial, Chantal; Baldinozzi, Guido; Siméone, David; Maillard, Serge; Martin, Guillaume

2017-10-01

Electrical conductivity of UO2+x shows a strong dependence upon oxygen partial pressure and temperature which may be interpreted in terms of prevailing point defects. A simulation of this property along with deviation from stoichiometry is carried out based on a model that takes into account the presence of impurities, oxygen interstitials, oxygen vacancies, holes, electrons and clusters of oxygen atoms. The equilibrium constants for each defect reaction are determined to reproduce the experimental data. An estimate of defect concentrations and their dependence upon oxygen partial pressure can then be determined. The simulations carried out for 8 different temperatures (973-1673 K) over a wide range of oxygen partial pressures are discussed and resulting defect equilibrium constants are plotted in an Arrhenius diagram. This provides an estimate of defect formation energies which may further be compared to other experimental data or ab-initio and empirical potential calculations.

Primary radiation damage of an FeCr alloy under pressure: Atomistic simulation

NASA Astrophysics Data System (ADS)

Tikhonchev, M. Yu.; Svetukhin, V. V.

2017-05-01

The primary radiation damage of a binary FeCr alloy deformed by applied mechanical loading is studied by an atomistic molecular dynamics simulation. Loading is simulated by specifying an applied pressure of 0.25, 1.0, and 2.5 GPa of both signs. Hydrostatic and uniaxial loading is considered along the [001], [111], [112], and [210] directions. The influence of loading on the energy of point defect formation and the threshold atomic displacement energy in single-component bcc iron is investigated. The 10-keV atomic displacement cascades in a "random" binary Fe-9 at % Cr alloy are simulated at an initial temperature of 300 K. The number of the point defects generated in a cascade is estimated, and the clustering of point defects and the spatial orientation of interstitial configurations are analyzed. Our results agree with the results of other researchers and supplement them.

Cyclic nocturnal awakening: a warning sign of a cluster bout.

PubMed

Martins, Isabel Pavão

2015-04-01

Cluster headache is an excruciating unilateral headache with autonomic symptoms whose periodic nocturnal activity, which interrupts sleep, has been attributed to a hypothalamic generator. We describe a patient with a longstanding episodic cluster headache who experienced, on two occasions, a period of nocturnal awakenings without pain or autonomic symptoms, lasting one week before the onset of a cluster bout. Awakenings occurred twice/night at the same hours of impending cluster attacks and had no apparent trigger, being unusual for this patient who had no previous sleep disturbances. Neurological examination and brain imaging were normal. This case documents two new aspects of cluster headache. It suggests that repeated nocturnal awakenings can be a warning sign of an impending cluster period, a finding that may have therapeutic implications, and also that hypothalamic activation may begin several days before trigemino-autonomic symptoms, thus behaving as a true bout generator. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release.

PubMed

Pesce, Luca; Calandrini, Vania; Marjault, Henri-Baptiste; Lipper, Colin H; Rossetti, Gulia; Mittler, Ron; Jennings, Patricia A; Bauer, Andreas; Nechushtai, Rachel; Carloni, Paolo

2017-11-30

The NEET proteins are a novel family of iron-sulfur proteins characterized by an unusual three cysteine and one histidine coordinated [2Fe-2S] cluster. Aberrant cluster release, facilitated by the breakage of the Fe-N bond, is implicated in a variety of human diseases, including cancer. Here, the molecular dynamics in the multi-microsecond timescale, along with quantum chemical calculations, on two representative members of the family (the human NAF-1 and mitoNEET proteins), show that the loss of the cluster is associated with a dramatic decrease in secondary and tertiary structure. In addition, the calculations provide a mechanism for cluster release and clarify, for the first time, crucial differences existing between the two proteins, which are reflected in the experimentally observed difference in the pH-dependent cluster reactivity. The reliability of our conclusions is established by an extensive comparison with the NMR data of the solution proteins, in part measured in this work.

Sensing Size through Clustering in Non-Equilibrium Membranes and the Control of Membrane-Bound Enzymatic Reactions

PubMed Central

Vagne, Quentin; Turner, Matthew S.; Sens, Pierre

2015-01-01

The formation of dynamical clusters of proteins is ubiquitous in cellular membranes and is in part regulated by the recycling of membrane components. We show, using stochastic simulations and analytic modeling, that the out-of-equilibrium cluster size distribution of membrane components undergoing continuous recycling is strongly influenced by lateral confinement. This result has significant implications for the clustering of plasma membrane proteins whose mobility is hindered by cytoskeletal “corrals” and for protein clustering in cellular organelles of limited size that generically support material fluxes. We show how the confinement size can be sensed through its effect on the size distribution of clusters of membrane heterogeneities and propose that this could be regulated to control the efficiency of membrane-bound reactions. To illustrate this, we study a chain of enzymatic reactions sensitive to membrane protein clustering. The reaction efficiency is found to be a non-monotonic function of the system size, and can be optimal for sizes comparable to those of cellular organelles. PMID:26656912

Interstitial lung disease induced by fluoxetine: Systematic review of literature and analysis of Vigiaccess, Eudravigilance and a national pharmacovigilance database.

PubMed

Deidda, Arianna; Pisanu, Claudia; Micheletto, Laura; Bocchetta, Alberto; Del Zompo, Maria; Stochino, Maria Erminia

2017-06-01

We investigated a pulmonary adverse drug reaction possibly induced by fluoxetine, the Interstitial Lung Disease, by performing a systematic review of published case reports on this subject, a review of the World Health Organization VigiAccess database, of the European EudraVigilance database and of a national Pharmacovigilance database (Italian Pharmacovigilance Network). The research found a total of seven cases linking fluoxetine to Interstitial Lung Disease in the literature. 36 cases of interstitial lung disease related to fluoxetine were retrieved from the VigiAccess database (updated to July 2016), and 36 reports were found in EudraVigilance database (updated to June 2016). In the Italian Pharmacovigilance database (updated to August 2016), we found only one case of Interstitial Lung Disease, codified as "pulmonary disease". Our investigation shows that fluoxetine might be considered as a possible cause of Interstitial Lung Disease. In particular, although here we do not discuss the assessment of benefits and harms of fluoxetine, since this antidepressant is widely used, our review suggests that fluoxetine-induced Interstitial Lung Disease should be considered in patients with dyspnea, associated or not with dry cough, who are treated with this drug. An early withdrawn of fluoxetine could be useful to obtain a complete remission of this adverse drug reaction and special attention should be particularly devoted to long-term therapy, and to female and elderly patients. Although the spontaneous reporting system is affected by important limitations, drug post- marketing surveillance represents an important tool to evaluate the real world effectiveness and safety of drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

PubMed Central

Atochina-Vasserman, Elena N.; Massa, Christopher B.; Birkelbach, Bastian; Guo, Chang-Jiang; Scott, Pamela; Haenni, Beat; Beers, Michael F.; Ochs, Matthias; Gow, Andrew J.

2015-01-01

Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd−/−) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd−/− mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd−/− mice. These changes were reduced in DiNOS, and compared with Sftpd−/− mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd−/−. Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces. PMID:26320150

Angiotensin II type 1 and 2 receptors and lymphatic vessels modulate lung remodeling and fibrosis in systemic sclerosis and idiopathic pulmonary fibrosis.

PubMed

Parra, Edwin Roger; Ruppert, Aline Domingos Pinto; Capelozzi, Vera Luiza

2014-01-01

To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis.

[Alternative treatments for interstitial cystitis].

PubMed

Gamé, X; Bart, S; Castel-Lacanal, E; De Sèze, M; Karsenty, G; Labat, J-J; Rigaud, J; Scheiber-Nogueira, M C; Ruffion, A

2009-06-01

Interstitial cystitis is the first cause of bladder pain. In case of failure of the usual treatments, several other modalities have been proposed. These therapeutic modalities are posterior sacral root neuromodulation, posterior tibial nerve stimulation, vanilloid agent intravesical instillation, intradetrusor botulinum toxin injections and surgery. A certain efficiency of each of these treatments in the interstitial cystitis has been reported. However, the evaluation of these treatments is limited and the level of evidence is too low to propose these treatments in routine.

Formation and Migration Energies of Interstitials in Silicon Under Strain Conditions

NASA Technical Reports Server (NTRS)

Halicioglu, Timur; Barnett, David M.

1999-01-01

Simulation calculations are conducted for Si substrates to analyze formation and diffusion energies of interstitials under strain condition using statics methods .based on a Stillinger-Weber type potential function. Defects in the vicinity of the surface region and in the bulk are examined, and the role played by compressive and tensile strains on the energetics of interstitials is investigated. Results indicate that strain alters defect energetics which, in turn, modifies their diffusion characteristics.

Rheb/mTORC1 Signaling Promotes Kidney Fibroblast Activation and Fibrosis

PubMed Central

Jiang, Lei; Xu, Lingling; Mao, Junhua; Li, Jianzhong; Fang, Li; Zhou, Yang; Liu, Wei; He, Weichun; Zhao, Allan Zijian

2013-01-01

Ras homolog enriched in brain (Rheb) is a small GTPase that regulates cell growth, differentiation, and survival by upregulating mammalian target of rapamycin complex 1 (mTORC1) signaling. The role of Rheb/mTORC1 signaling in the activation of kidney fibroblasts and the development of kidney fibrosis remains largely unknown. In this study, we found that Rheb/mTORC1 signaling was activated in interstitial myofibroblasts from fibrotic kidneys. Treatment of rat kidney interstitial fibroblasts (NRK-49F cell line) with TGFβ1 also activated Rheb/mTORC1 signaling. Blocking Rheb/mTORC1 signaling with rapamycin or Rheb small interfering RNA abolished TGFβ1-induced fibroblast activation. In a transgenic mouse, ectopic expression of Rheb activated kidney fibroblasts. These Rheb transgenic mice exhibited increased activation of mTORC1 signaling in both kidney tubular and interstitial cells as well as progressive interstitial renal fibrosis; rapamycin inhibited these effects. Similarly, mice with fibroblast-specific deletion of Tsc1, a negative regulator of Rheb, exhibited activated mTORC1 signaling in kidney interstitial fibroblasts and increased renal fibrosis, both of which rapamycin abolished. Taken together, these results suggest that Rheb/mTORC1 signaling promotes the activation of kidney fibroblasts and contributes to the development of interstitial fibrosis, possibly providing a therapeutic target for progressive renal disease. PMID:23661807

Voiding diary might serve as a useful tool to understand differences between bladder pain syndrome/interstitial cystitis and overactive bladder.

PubMed

Kim, Sung Han; Oh, Shin Ah; Oh, Seung-June

2014-02-01

To identify the voiding characteristics of bladder pain syndrome/interstitial cystitis and overactive bladder. Between September 2005 and June 2010, 3-day voiding diaries of 49 consecutive bladder pain syndrome/interstitial cystitis patients and 301 overactive bladder patients were prospectively collected at an outpatient clinic and retrospectively analyzed. The characteristics of the two groups were not significantly different. However, all voiding variables including volume and frequency were significantly different except for the total voided volume: patients with bladder pain syndrome/interstitial cystitis showed significantly higher voiding frequencies, smaller maximal and mean voided volume, and more constant and narrower ranges of voided volume compared with overactive bladder patients (P < 0.005). Furthermore, mean intervals between voiding in bladder pain syndrome/interstitial cystitis were shorter and more consistent during the day and night (P < 0.001), although mean night-time variances were greater than daytime variances. Logistic regression analysis showed that total night-time frequency, maximal night-time voided volume and mean variance of daytime voiding intervals most significantly differentiated the two groups. Some voiding characteristics of bladder pain syndrome/interstitial cystitis and overactive bladder patients differ significantly according to 3-day voiding diary records. These findings provide additional information regarding the differences between these two diseases in the outpatient clinical setting. © 2013 The Japanese Urological Association.

Interstitial copper defect induced reconstruction of a new ;CuO4; quadrilateral in CaCu3Ti4O12: A first-principles study

NASA Astrophysics Data System (ADS)

Xiao, Haibo; Xu, Linfang; Wang, Ruilong; Yang, Changping

2017-09-01

The geometric structure, electronic structure and formation energy of CaCu3Ti4O12 (CCTO) with interstitial copper atom have been studied using the density-functional method within the GGA approximation. Result of structural optimization shows that the interstitial Cu-atom (Cu7) prefers to occupy a special location which is symmetrical with an intrinsic copper atom (Cu13) deviated from the normal site. The mulliken analysis indicates the loss of electrons from interstitial atom (Cu7) and Cu13 are only half more of the losing in other copper atom, which reveals a characteristics of covalent bonding between Cu7/Cu13 and surrounding oxygen atoms respectively. Meanwhile, it is found from electron density difference (EDD) and orbital analysis that the introduction of interstitial Cu atom causes prominent structural reconstruction of a new ;CuO4; quadrilateral. Moreover, the new ;CuO4; planar leads to a corresponding electronic reconstruction in the hybridization between Cu7/Cu13 3d and O 2p at the vicinity of fermi surface, for which a new conductive filament channel comes into being. Besides, the formation energies of the interstitial defects in various charge states are corrected with the value of 2.18, -4.17 and -9.46 eV for charge of 0, 1+ and 2+, respectively.

Blood and interstitial flow in the hierarchical pore space architecture of bone tissue.

PubMed

Cowin, Stephen C; Cardoso, Luis

2015-03-18

There are two main types of fluid in bone tissue, blood and interstitial fluid. The chemical composition of these fluids varies with time and location in bone. Blood arrives through the arterial system containing oxygen and other nutrients and the blood components depart via the venous system containing less oxygen and reduced nutrition. Within the bone, as within other tissues, substances pass from the blood through the arterial walls into the interstitial fluid. The movement of the interstitial fluid carries these substances to the cells within the bone and, at the same time, carries off the waste materials from the cells. Bone tissue would not live without these fluid movements. The development of a model for poroelastic materials with hierarchical pore space architecture for the description of blood flow and interstitial fluid flow in living bone tissue is reviewed. The model is applied to the problem of determining the exchange of pore fluid between the vascular porosity and the lacunar-canalicular porosity in bone tissue due to cyclic mechanical loading and blood pressure. These results are basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of gravimetric techniques to estimate the microvascular filtration coefficient

PubMed Central

Dongaonkar, R. M.; Laine, G. A.; Stewart, R. H.

2011-01-01

Microvascular permeability to water is characterized by the microvascular filtration coefficient (Kf). Conventional gravimetric techniques to estimate Kf rely on data obtained from either transient or steady-state increases in organ weight in response to increases in microvascular pressure. Both techniques result in considerably different estimates and neither account for interstitial fluid storage and lymphatic return. We therefore developed a theoretical framework to evaluate Kf estimation techniques by 1) comparing conventional techniques to a novel technique that includes effects of interstitial fluid storage and lymphatic return, 2) evaluating the ability of conventional techniques to reproduce Kf from simulated gravimetric data generated by a realistic interstitial fluid balance model, 3) analyzing new data collected from rat intestine, and 4) analyzing previously reported data. These approaches revealed that the steady-state gravimetric technique yields estimates that are not directly related to Kf and are in some cases directly proportional to interstitial compliance. However, the transient gravimetric technique yields accurate estimates in some organs, because the typical experimental duration minimizes the effects of interstitial fluid storage and lymphatic return. Furthermore, our analytical framework reveals that the supposed requirement of tying off all draining lymphatic vessels for the transient technique is unnecessary. Finally, our numerical simulations indicate that our comprehensive technique accurately reproduces the value of Kf in all organs, is not confounded by interstitial storage and lymphatic return, and provides corroboration of the estimate from the transient technique. PMID:21346245

Blood and Interstitial flow in the hierarchical pore space architecture of bone tissue

PubMed Central

Cowin, Stephen C.; Cardoso, Luis

2015-01-01

There are two main types of fluid in bone tissue, blood and interstitial fluid. The chemical composition of these fluids varies with time and location in bone. Blood arrives through the arterial system containing oxygen and other nutrients and the blood components depart via the venous system containing less oxygen and reduced nutrition. Within the bone, as within other tissues, substances pass from the blood through the arterial walls into the interstitial fluid. The movement of the interstitial fluid carries these substances to the cells within the bone and, at the same time, carries off the waste materials from the cells. Bone tissue would not live without these fluid movements. The development of a model for poroelastic materials with hierarchical pore space architecture for the description of blood flow and interstitial fluid flow in living bone tissue is reviewed. The model is applied to the problem of determining the exchange of pore fluid between the vascular porosity and the lacunar-canalicular porosity in bone tissue due to cyclic mechanical loading and blood pressure. These results are basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. PMID:25666410

Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood-brain barrier: [17O]H2O JJVCPE MRI study.

PubMed

Huber, Vincent J; Igarashi, Hironaka; Ueki, Satoshi; Kwee, Ingrid L; Nakada, Tsutomu

2018-06-13

The blood-brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow-Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow-Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [O]H2O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [O]H2O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB.

MASGOMAS PROJECT, New automatic-tool for cluster search on IR photometric surveys

NASA Astrophysics Data System (ADS)

Rübke, K.; Herrero, A.; Borissova, J.; Ramirez-Alegria, S.; García, M.; Marin-Franch, A.

2015-05-01

The Milky Way is expected to contain a large number of young massive (few x 1000 solar masses) stellar clusters, borne in dense cores of gas and dust. Yet, their known number remains small. We have started a programme to search for such clusters, MASGOMAS (MAssive Stars in Galactic Obscured MAssive clusterS). Initially, we selected promising candidates by means of visual inspection of infrared images. In a second phase of the project we have presented a semi-automatic method to search for obscured massive clusters that resulted in the identification of new massive clusters, like MASGOMAS-1 (with more than 10,000 solar masses) and MASGOMAS-4 (a double-cored association of about 3,000 solar masses). We have now developped a new automatic tool for MASGOMAS that allows the identification of a large number of massive cluster candidates from the 2MASS and VVV catalogues. Cluster candidates fulfilling criteria appropriated for massive OB stars are thus selected in an efficient and objective way. We present the results from this tool and the observations of the first selected cluster, and discuss the implications for the Milky Way structure.

A new giant luminous arc gravitational lens associated with a z = 0.62 galaxy cluster, and the environments of distant radio galaxies

NASA Technical Reports Server (NTRS)

Dickinson, Mark

1993-01-01

In the course of a survey investigating the cluster environments of distant 3CR radio galaxies, I have identified a previously unknown 'giant luminous arc' gravitational lens. The lensing cluster is associated with the radio galaxy 3C 220.1 at z = 0.62 and is the most distant cluster now known to produce such arcs. I present imaging and spectroscopic observations of the cluster and the arc, and discuss the implications for the cluster mass. At z greater than 0.6 the cluster velocity dispersions implied by such giant arcs may provide an interesting constraint on theories of large scale structure formation. The parent investigation in which this arc was identified concerns galaxy clusters and radio galaxy environments at 0.35 less than z less than 0.8. At the present epoch, powerful FR 2 radio galaxies tend to be found in environments of poor or average galaxy density. In contrast, at the higher redshifts investigated here, richer group and cluster environments are common. I present additional data on other clusters from this survey, and discuss its extension to z greater than 1 through a program of near-infrared and optical imaging.

Kinetic Monte Carlo Simulation of Oxygen Diffusion in Ytterbium Disilicate

NASA Technical Reports Server (NTRS)

Good, Brian S.

2015-01-01

Ytterbium disilicate is of interest as a potential environmental barrier coating for aerospace applications, notably for use in next generation jet turbine engines. In such applications, the transport of oxygen and water vapor through these coatings to the ceramic substrate is undesirable if high temperature oxidation is to be avoided. In an effort to understand the diffusion process in these materials, we have performed kinetic Monte Carlo simulations of vacancy-mediated and interstitial oxygen diffusion in Ytterbium disilicate. Oxygen vacancy and interstitial site energies, vacancy and interstitial formation energies, and migration barrier energies were computed using Density Functional Theory. We have found that, in the case of vacancy-mediated diffusion, many potential diffusion paths involve large barrier energies, but some paths have barrier energies smaller than one electron volt. However, computed vacancy formation energies suggest that the intrinsic vacancy concentration is small. In the case of interstitial diffusion, migration barrier energies are typically around one electron volt, but the interstitial defect formation energies are positive, with the result that the disilicate is unlikely to exhibit experience significant oxygen permeability except at very high temperature.

Ab initio study of point defects near stacking faults in 3C-SiC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xi, Jianqi; Liu, Bin; Zhang, Yanwen

Interactions between point defects and stacking faults in 3C-SiC are studied using an ab initio method based on density functional theory. The results show that the discontinuity of the stacking sequence considerably affects the configurations and behavior of intrinsic defects, especially in the case of silicon interstitials. The existence of an intrinsic stacking fault (missing a C-Si bilayer) shortens the distance between the tetrahedral-center site and its second-nearest-neighboring silicon layer, making the tetrahedral silicon interstitial unstable. Instead of a tetrahedral configuration with four C neighbors, a pyramid-like interstitial structure with a defect state within the band gap becomes a stablemore » configuration. In addition, orientation rotation occurs in the split interstitials that has diverse effects on the energy landscape of silicon and carbon split interstitials in the stacking fault region. Moreover, our analyses of ionic relaxation and electronic structure of vacancies show that the built-in strain field, owing to the existence of the stacking fault, makes the local environment around vacancies more complex than that in the bulk.« less

Ab initio study of point defects near stacking faults in 3C-SiC

DOE PAGES

Xi, Jianqi; Liu, Bin; Zhang, Yanwen; ...

2016-07-02

Interactions between point defects and stacking faults in 3C-SiC are studied using an ab initio method based on density functional theory. The results show that the discontinuity of the stacking sequence considerably affects the configurations and behavior of intrinsic defects, especially in the case of silicon interstitials. The existence of an intrinsic stacking fault (missing a C-Si bilayer) shortens the distance between the tetrahedral-center site and its second-nearest-neighboring silicon layer, making the tetrahedral silicon interstitial unstable. Instead of a tetrahedral configuration with four C neighbors, a pyramid-like interstitial structure with a defect state within the band gap becomes a stablemore » configuration. In addition, orientation rotation occurs in the split interstitials that has diverse effects on the energy landscape of silicon and carbon split interstitials in the stacking fault region. Moreover, our analyses of ionic relaxation and electronic structure of vacancies show that the built-in strain field, owing to the existence of the stacking fault, makes the local environment around vacancies more complex than that in the bulk.« less

Investigations of lymphatic drainage from the interstitial space

NASA Astrophysics Data System (ADS)

Jayathungage Don, Tharanga; Richard Clarke Collaboration; John Cater Collaboration; Vinod Suresh Collaboration

2017-11-01

The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is important to treat several pathological conditions. The main focus of this study is to computationally model the lymphatic drainage from the interstitial space. The model has been developed to consider a 3D lymphatic network and uses biological data to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy's law in the interstitium and the Navier-Stokes equations in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradient. In addition, we have examined the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model. The computational results are in accordance with the available experimental measurements.

Chronic hypersensitivity pneumonitis: important considerations in the work-up of this fibrotic lung disease.

PubMed

Glazer, Craig S

2015-03-01

Chronic hypersensitivity pneumonitis is increasingly recognized as an important mimic of other fibrotic lung diseases. This review will summarize recent data regarding the importance and difficulty of determining causative exposures both for accurate diagnosis and prognosis, and describe the expanded pathologic spectrum of the disease, the effects of fibrosis on prognosis and challenges in the diagnostic evaluation. Several recent publications show the potential pathologic patterns induced by chronic hypersensitivity pneumonitis are broader than the classic triad of bronchiolitis, interstitial infiltrates and granulomas. Other pathologic patterns include nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, bronchiolitis and airway centric fibrosis. Detecting a causative antigen in fibrotic hypersensitivity pneumonitis is challenging but critically important both for accurate diagnosis and improved prognosis. The prognosis in hypersensitivity pneumonitis worsens in the presence of fibrosis, but it remains significantly better than idiopathic pulmonary fibrosis. Hypersensitivity pneumonitis is increasingly recognized as an important cause of fibrotic interstitial lung disease. Hypersensitivity pneumonitis demonstrates a remarkable tendency to mimic other idiopathic interstitial pneumonias. A detailed exposure history remains a cornerstone of diagnosis and management.

Therapeutic Effects of Human Amniotic Fluid-Derived Stem Cells on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

PubMed Central

Yin, Zhongcheng; Zhou, Xudong; Li, Xiaoju; Xiao, Aiguo

2013-01-01

Interstitial fibrosis is regarded as the main pathway for the progression of chronic kidney disease (CKD) and is often associated with severe renal dysfunction. Stem cell-based therapies may provide alternative approaches for the treatment of CKD. Human amniotic fluid-derived stem cells (hAFSCs) are a novel stem cell population, which exhibit both embryonic and mesenchymal stem cell characteristics. Herein, the present study investigated whether the transplantation of hAFSCs into renal tissues could improve renal interstitial fibrosis in a murine model of unilateral ureteral obstruction (UUO). We showed that hAFSCs provided a protective effect and alleviated interstitial fibrosis as reflected by an increase in microvascular density; additionally, hAFSCs treatment beneficially modulated protein levels of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1). Therefore, we hypothesize that hAFSCs could represent an alternative, readily available source of stem cells that can be applied for the treatment of renal interstitial fibrosis. PMID:23724119

020. Coexistence of lung adenocarcinoma and usual interstitial pneumonia: a case report

PubMed Central

Baliaka, Aggeliki; Papaemmanouil, Styliani; Spyratos, Dionysis; Zarogoulidis, Paul; Sakkas, Leonidas

2015-01-01

Background Usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause. The most common symptoms are progressively increased shortness of breath and dry cough. Some studies suggest an association between usual interstitial pneumonia and lung cancer through different pathogenetic mechanisms. Objective The case presentation of a patient with lung adenocarcinoma and UIP. Methods A 66-year-old male presented with persistent dry cough, hemoptysis and dyspnea. The chest radiographs revealed a mass in the lower lobe of the left lung, measuring 3 cm, as well as diffuse interstitial changes in the same lobe. Two partial lobectomies were performed. Results Histological examination of the mass showed moderately differentiated adenocarcinoma, focally with bronchoalveolar pattern (Immunohistochemical detection of EGFR: positive). The rest lung parenchyma presented histological appearance of UIP. Conclusions According to clinicopathological studies, the prevalence of lung cancer among patients with UIP/IPF varies between 4% and 9%. The overall median survival of IPF-Ca patients is seven months in comparison with IPF only patients (14 months).

Native defects in GaN: a hybrid functional study

NASA Astrophysics Data System (ADS)

Diallo, Ibrahima Castillo; Demchenko, Denis

Intrinsic defects play an important role in the performance of GaN-based devices. We present hybrid density functional calculations of the electronic and possible optical properties of interstitial N (Ni-Ni) , N antisite (NGa) , interstitial Ga (Gai) , Ga antisite (GaN) , Ga vacancy (VGa) , N vacancy (VN) and Ga-N divacancies (VGaVN) in GaN. Our results show that the vacancies display relatively low formation energies in certain samples, whereas antisites and interstitials are energetically less favorable. However, interstitials can be created by electron irradiation. For instance, in 2.5 MeV electron-irradiated GaN samples, a strong correlation between the frequently observed photoluminescence (PL) band centered around 0.85 eV accompanied with a rich phonon sideband of ~0.88 eV and the theoretical optical behavior of interstitial Ga is discussed. N vacancies are found to likely contribute to the experimentally obtained green luminescence band (GL2) peaking at 2.24 eV in high-resistivity undoped and Mg-doped GaN. National Science Foundation (DMR-1410125) and the Thomas F. and Kate Miller Jeffress Memorial Trust.

Interstitial telomeric sequences in vertebrate chromosomes: Origin, function, instability and evolution.

PubMed

Bolzán, Alejandro D

2017-07-01

By definition, telomeric sequences are located at the very ends or terminal regions of chromosomes. However, several vertebrate species show blocks of (TTAGGG)n repeats present in non-terminal regions of chromosomes, the so-called interstitial telomeric sequences (ITSs), interstitial telomeric repeats or interstitial telomeric bands, which include those intrachromosomal telomeric-like repeats located near (pericentromeric ITSs) or within the centromere (centromeric ITSs) and those telomeric repeats located between the centromere and the telomere (i.e., truly interstitial telomeric sequences) of eukaryotic chromosomes. According with their sequence organization, localization and flanking sequences, ITSs can be classified into four types: 1) short ITSs, 2) subtelomeric ITSs, 3) fusion ITSs, and 4) heterochromatic ITSs. The first three types have been described mainly in the human genome, whereas heterochromatic ITSs have been found in several vertebrate species but not in humans. Several lines of evidence suggest that ITSs play a significant role in genome instability and evolution. This review aims to summarize our current knowledge about the origin, function, instability and evolution of these telomeric-like repeats in vertebrate chromosomes. Copyright © 2017 Elsevier B.V. All rights reserved.

[Effect of rapamycin on proliferation of rat heart valve interstitial cells in vitro].

PubMed

Tan, Yan; Wang, Ji-Ye; Yi, Ren-Liang; Qiu, Jian

2016-04-01

To investigate the effect of rapamycin on the proliferation of rat valvular interstitial cells in primary culture. The interstitial cells isolated from rat aortic valves were cultured and treated with rapamycin, and the cell growth and cell cycle changes were analyzed using MTT assay and flow cytometry, respectively. RT-PCR was used to detect mRNA expression levels of S6 and P70S6K in cells, and the protein expressions level of S6, P70S6K, P-S6, and P-P70S6K were detected using Western blotting. Rat aortic valvular interstitial cells was isolated successfully. The rapamycin-treated cells showed a suppressed proliferative activity (P<0.05), but the cell cycle distribution remained unaffected. Rapamycin treatment resulted in significantly decreased S6 and P70S6K protein phosphorylation level in the cells (P<0.05). The mechanism by which rapamycin inhibits the proliferation of valvular interstitial cells probably involves suppression of mTOR to lower S6 and P70S6K phosphorylation level but not direct regulation of the cell cycle.

Reversal of a Neurospora Translocation by Crossing over Involving Displaced Rdna, and Methylation of the Rdna Segments That Result from Recombination

PubMed Central

Perkins, David D.; Metzenberg, Robert L.; Raju, Namboori B.; Selker, Eric U.; Barry, Edward G.

1986-01-01

In translocation OY321 of Neurospora crassa, the nucleolus organizer is divided into two segments, a proximal portion located interstitially in one interchange chromosome, and a distal portion now located terminally on another chromosome, linkage group I. In crosses of Translocation x Translocation, exceptional progeny are recovered nonselectively in which the chromosome sequence has apparently reverted to Normal. Genetic, cytological, and molecular evidence indicates that reversion is the result of meiotic crossing over between homologous displaced rDNA repeats. Marker linkages are wild type in these exceptional progeny. They differ from wild type, however, in retaining an interstitial block of rRNA genes which can be demonstrated cytologically by the presence of a second, small interstitial nucleolus and genetically by linkage of an rDNA restriction site polymorphism to the mating-type locus in linkage group I. The interstitial rDNA is more highly methylated than the terminal rDNA. The mechanism by which methylation enzymes distinguish between interstitial rDNA and terminal rDNA is unknown. Some hypotheses are considered. PMID:2947829

Modulation of invasive phenotype by interstitial pressure-driven convection in aggregates of human breast cancer cells.

PubMed

Tien, Joe; Truslow, James G; Nelson, Celeste M

2012-01-01

This paper reports the effect of elevated pressure on the invasive phenotype of patterned three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. We found that the directionality of the interstitial pressure profile altered the frequency of invasion by cells located at the surface of an aggregate. In particular, application of pressure at one end of an aggregate suppressed invasion at the opposite end. Experimental alteration of the configuration of cell aggregates and computational modeling of the resulting flow and solute concentration profiles revealed that elevated pressure inhibited invasion by altering the chemical composition of the interstitial fluid near the surface of the aggregate. Our data reveal a link between hydrostatic pressure, interstitial convection, and invasion.

The behaviour of stacking fault energy upon interstitial alloying.

PubMed

Lee, Jee-Yong; Koo, Yang Mo; Lu, Song; Vitos, Levente; Kwon, Se Kyun

2017-09-11

Stacking fault energy is one of key parameters for understanding the mechanical properties of face-centered cubic materials. It is well known that the plastic deformation mechanism is closely related to the size of stacking fault energy. Although alloying is a conventional method to modify the physical parameter, the underlying microscopic mechanisms are not yet clearly established. Here, we propose a simple model for determining the effect of interstitial alloying on the stacking fault energy. We derive a volumetric behaviour of stacking fault energy from the harmonic approximation to the energy-lattice curve and relate it to the contents of interstitials. The stacking fault energy is found to change linearly with the interstitial content in the usual low concentration domain. This is in good agreement with previously reported experimental and theoretical data.

Purse-string suture technique to enable laparoscopic management of the interstitial gestation of a heterotopic pregnancy.

PubMed

Aust, Thomas; O'Neill, Aoife; Cario, Gregory

2011-01-01

To describe the laparoscopic management of an interstitial gestation of a heterotopic pregnancy. Case report and technique description. Tertiary-level private practice. Woman with a 6-week gestation spontaneous heterotopic twin pregnancy: one twin intrauterine, one interstitial. A purse-string suture was applied to the proximal portion of the interstitial heterotopic pregnancy. To enable a cornual resection to be performed with minimal bleeding and without recourse to laparotomy. At 8 weeks gestation an ultrasound scan confirmed a viable singleton intrauterine pregnancy, but a scan at 12 weeks showed a missed miscarriage. The embedding of the suture into the uterine serosa prevents slipping of the ligature that could occur with a pretied loop. Copyright © 2011 American Society for Reproductive Medicine. All rights reserved.

The use of lung ultrasound images for the differential diagnosis of pulmonary and cardiac interstitial pathology.

PubMed

Soldati, Gino; Demi, Marcello

2017-06-01

In recent years, great advances have been made in the use of lung ultrasound to detect pulmonary edema and interstitial changes in the lung. However, it is clear that B-lines oversimplify the description of the physical phenomena associated with their presence. The artifactual images that ultrasounds provide in interstitial pulmonary pathology are merely the ultimate outcome of the complex interaction of a specific acoustic wave with a specific three-dimensional biological structure. This interaction lacks a solid physical interpretation of the acoustic signs to support it. The aim of this paper was to describe the differences between the sonographic interstitial syndrome related to lung diseases and that related to cardiogenic edema in the light of current knowledge regarding the pleural plane's response to ultrasound waves.

Adherens Junctions Revisualized: Organizing Cadherins as Nanoassemblies.

PubMed

Yap, Alpha S; Gomez, Guillermo A; Parton, Robert G

2015-10-12

This Perspective considers how classical cadherin cell-cell adhesion receptors are organized at the nanoscale to generate lateral clusters. Recent advances in optical microscopy reveal that clustering constitutes a general feature of cadherin organization, but one that takes diverse forms. Here we consider the molecular mechanisms responsible for cadherin clustering and their functional implications. We frame our discussion in light of what is known about how nanoscale organization is conferred upon the plasma membrane, through protein-protein interactions, regulation of the cortical actin cytoskeleton, and the lipid environment of the membrane. Copyright © 2015 Elsevier Inc. All rights reserved.

Hard X-ray emission from accretion shocks around galaxy clusters

NASA Astrophysics Data System (ADS)

Kushnir, Doron; Waxman, Eli

2010-02-01

We show that the hard X-ray (HXR) emission observed from several galaxy clusters is consistent with a simple model, in which the nonthermal emission is produced by inverse Compton scattering of cosmic microwave background photons by electrons accelerated in cluster accretion shocks: The dependence of HXR surface brightness on cluster temperature is consistent with that predicted by the model, and the observed HXR luminosity is consistent with the fraction of shock thermal energy deposited in relativistic electrons being lesssim0.1. Alternative models, where the HXR emission is predicted to be correlated with the cluster thermal emission, are disfavored by the data. The implications of our predictions to future HXR observations (e.g. by NuStar, Simbol-X) and to (space/ground based) γ-ray observations (e.g. by Fermi, HESS, MAGIC, VERITAS) are discussed.

Binary Black Hole Mergers from Globular Clusters: Implications for Advanced LIGO.

PubMed

Rodriguez, Carl L; Morscher, Meagan; Pattabiraman, Bharath; Chatterjee, Sourav; Haster, Carl-Johan; Rasio, Frederic A

2015-07-31

The predicted rate of binary black hole mergers from galactic fields can vary over several orders of magnitude and is extremely sensitive to the assumptions of stellar evolution. But in dense stellar environments such as globular clusters, binary black holes form by well-understood gravitational interactions. In this Letter, we study the formation of black hole binaries in an extensive collection of realistic globular cluster models. By comparing these models to observed Milky Way and extragalactic globular clusters, we find that the mergers of dynamically formed binaries could be detected at a rate of ∼100 per year, potentially dominating the binary black hole merger rate. We also find that a majority of cluster-formed binaries are more massive than their field-formed counterparts, suggesting that Advanced LIGO could identify certain binaries as originating from dense stellar environments.

The Mass Function of Young Star Clusters in the "Antennae" Galaxies.

PubMed

Zhang; Fall

1999-12-20

We determine the mass function of young star clusters in the merging galaxies known as the "Antennae" (NGC 4038/9) from deep images taken with the Wide Field Planetary Camera 2 on the refurbished Hubble Space Telescope. This is accomplished by means of reddening-free parameters and a comparison with stellar population synthesis tracks to estimate the intrinsic luminosity and age, and hence the mass, of each cluster. We find that the mass function of the young star clusters (with ages less, similar160 Myr) is well represented by a power law of the form psi&parl0;M&parr0;~M-2 over the range 104 less, similarM less, similar106 M middle dot in circle. This result may have important implications for our understanding of the origin of globular clusters during the early phases of galactic evolution.

Waiting-time distributions of magnetic discontinuities: clustering or Poisson process?

PubMed

Greco, A; Matthaeus, W H; Servidio, S; Dmitruk, P

2009-10-01

Using solar wind data from the Advanced Composition Explorer spacecraft, with the support of Hall magnetohydrodynamic simulations, the waiting-time distributions of magnetic discontinuities have been analyzed. A possible phenomenon of clusterization of these discontinuities is studied in detail. We perform a local Poisson's analysis in order to establish if these intermittent events are randomly distributed or not. Possible implications about the nature of solar wind discontinuities are discussed.

Language Acquisition and Machine Learning.

DTIC Science & Technology

1986-02-01

machine learning and examine its implications for computational models of language acquisition. As a framework for understanding this research, the authors propose four component tasks involved in learning from experience-aggregation, clustering, characterization, and storage. They then consider four common problems studied by machine learning researchers-learning from examples, heuristics learning, conceptual clustering, and learning macro-operators-describing each in terms of our framework. After this, they turn to the problem of grammar

Waiting-time distributions of magnetic discontinuities: Clustering or Poisson process?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greco, A.; Matthaeus, W. H.; Servidio, S.

2009-10-15

Using solar wind data from the Advanced Composition Explorer spacecraft, with the support of Hall magnetohydrodynamic simulations, the waiting-time distributions of magnetic discontinuities have been analyzed. A possible phenomenon of clusterization of these discontinuities is studied in detail. We perform a local Poisson's analysis in order to establish if these intermittent events are randomly distributed or not. Possible implications about the nature of solar wind discontinuities are discussed.

MULTI-K: accurate classification of microarray subtypes using ensemble k-means clustering

PubMed Central

Kim, Eun-Youn; Kim, Seon-Young; Ashlock, Daniel; Nam, Dougu

2009-01-01

Background Uncovering subtypes of disease from microarray samples has important clinical implications such as survival time and sensitivity of individual patients to specific therapies. Unsupervised clustering methods have been used to classify this type of data. However, most existing methods focus on clusters with compact shapes and do not reflect the geometric complexity of the high dimensional microarray clusters, which limits their performance. Results We present a cluster-number-based ensemble clustering algorithm, called MULTI-K, for microarray sample classification, which demonstrates remarkable accuracy. The method amalgamates multiple k-means runs by varying the number of clusters and identifies clusters that manifest the most robust co-memberships of elements. In addition to the original algorithm, we newly devised the entropy-plot to control the separation of singletons or small clusters. MULTI-K, unlike the simple k-means or other widely used methods, was able to capture clusters with complex and high-dimensional structures accurately. MULTI-K outperformed other methods including a recently developed ensemble clustering algorithm in tests with five simulated and eight real gene-expression data sets. Conclusion The geometric complexity of clusters should be taken into account for accurate classification of microarray data, and ensemble clustering applied to the number of clusters tackles the problem very well. The C++ code and the data sets tested are available from the authors. PMID:19698124

Gallium interstitial in irradiated germanium: Deep level transient spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolkovsky, Vl.; Petersen, M. Christian; Larsen, A. Nylandsted

Two electronic levels at 0.34 eV above the valence band and 0.32 eV below the conduction band, in gallium doped, p-type Ge irradiated with 2 MeV electrons have been studied by deep level transient spectroscopy (DLTS) with both majority- and minority-carrier injections, and Laplace DLTS spectroscopy. It is concluded that these levels, having donor and acceptor characters, respectively, are correlated with interstitial Ga atoms, formed by the Watkins-replacement mechanism via self-interstitials.

Gallium interstitial in irradiated germanium: Deep level transient spectroscopy

NASA Astrophysics Data System (ADS)

Kolkovsky, Vl.; Petersen, M. Christian; Mesli, A.; van Gheluwe, J.; Clauws, P.; Larsen, A. Nylandsted

2008-12-01

Two electronic levels at 0.34 eV above the valence band and 0.32 eV below the conduction band, in gallium doped, p -type Ge irradiated with 2 MeV electrons have been studied by deep level transient spectroscopy (DLTS) with both majority- and minority-carrier injections, and Laplace DLTS spectroscopy. It is concluded that these levels, having donor and acceptor characters, respectively, are correlated with interstitial Ga atoms, formed by the Watkins-replacement mechanism via self-interstitials.

Interstitial Lung Disease due to Siderosis in a Lathe Machine Worker.

PubMed

Gothi, D; Satija, B; Kumar, S; Kaur, Omkar

2015-01-01

Since its first description in 1936, siderosis of lung has been considered a benign pneumoconiosis due to absence of significant clinical symptoms or respiratory impairment. Subsequently, authors have questioned the non-fibrogenic property of iron. However, siderosis causing interstitial lung disease with usual interstitial pneumonia (UIP) pattern has not been described in the past. We report a case of UIP on high resolution computed tomography, proven to be siderosis on transbronchial lung biopsy in a lathe machine worker.

Comparison of Bladder Directed and Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain Syndrome

DTIC Science & Technology

2017-09-01

PROJECT NUMBER Kenneth M. Peters 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT...AWARD NUMBER: W81XWH-16-1-0307 TITLE: Comparison of Bladder-Directed and Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain...Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain Syndrome 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

HEAO-A2 observations of the X-ray spectra of the Centaurus and A1060 clusters of galaxies

NASA Technical Reports Server (NTRS)

Mitchell, R.; Mushotzky, R.

1979-01-01

The X-ray spectral observations of two low luminosity clusters of galaxies, Centaurus and A1060, are presented. An emission feature of the Centaurus cluster at 7.9 keV is detected at about one third of the strength of the 6.7 keV line. This higher energy line represents K sub beta emission from highly ionized iron. An isothermal model with an Fe emission line is discussed and it is shown that the model cannot fit the data of the Centaurus or the A1060 clusters. The implications of the two component nature of the continuum on the Fe abundance and the X-ray surface brightness distribution are discussed.

Motivational and emotional profiles in university undergraduates: a self-determination theory perspective.

PubMed

González, Antonio; Paoloni, Verónica; Donolo, Danilo; Rinaudo, Cristina

2012-11-01

Previous research has focused on specific forms of self-determined motivation or discrete class-related emotions, but few studies have simultaneously examined both constructs. The aim of this study on 472 undergraduates was twofold: to perform cluster analysis to identify homogeneous groups of motivation in the sample; and to determine the profile of each cluster for emotions and academic achievement. Cluster analysis configured four groups in terms of motivation: controlled, autonomous, both high, and both low. Each cluster revealed a distinct emotional profile, autonomous motivation being the most adaptable with high scores for academic achievement and pleasant emotions and low values for unpleasant emotions. The results are discussed in the light of their implications for academic adjustment.

Idiopathic Interstitial Pneumonias

MedlinePlus

... 50 More than 60% Pulmonary rehabilitation Lung transplantation Pirfenidone or nintedanib 50–70% die in 5 years. ... In This Article Generic Name Select Brand Names Pirfenidone ESBRIET nintedanib OFEV Interstitial Lung Diseases Overview of ...

Water Dynamics at Protein-Protein Interfaces: Molecular Dynamics Study of Virus-Host Receptor Complexes.

PubMed

Dutta, Priyanka; Botlani, Mohsen; Varma, Sameer

2014-12-26

The dynamical properties of water at protein-water interfaces are unlike those in the bulk. Here we utilize molecular dynamics simulations to study water dynamics in interstitial regions between two proteins. We consider two natural protein-protein complexes, one in which the Nipah virus G protein binds to cellular ephrin B2 and the other in which the same G protein binds to ephrin B3. While the two complexes are structurally similar, the two ephrins share only a modest sequence identity of ∼50%. X-ray crystallography also suggests that these interfaces are fairly extensive and contain exceptionally large amounts of waters. We find that while the interstitial waters tend to occupy crystallographic sites, almost all waters exhibit residence times of less than hundred picoseconds in the interstitial region. We also find that while the differences in the sequence of the two ephrins result in quantitative differences in the dynamics of interstitial waters, the trends in the shifts with respect to bulk values are similar. Despite the high wetness of the protein-protein interfaces, the dynamics of interstitial waters are considerably slower compared to the bulk-the interstitial waters diffuse an order of magnitude slower and have 2-3 fold longer hydrogen bond lifetimes and 2-1000 fold slower dipole relaxation rates. To understand the role of interstitial waters, we examine how implicit solvent models compare against explicit solvent models in producing ephrin-induced shifts in the G conformational density. Ephrin-induced shifts in the G conformational density are critical to the allosteric activation of another viral protein that mediates fusion. We find that in comparison with the explicit solvent model, the implicit solvent model predicts a more compact G-B2 interface, presumably because of the absence of discrete waters at the G-B2 interface. Simultaneously, we find that the two models yield strikingly different induced changes in the G conformational density, even for those residues whose conformational densities in the apo state are unaffected by the treatment of the bulk solvent. Together, these results show that the explicit treatment of interstitial water molecules is necessary for a proper description of allosteric transitions.

Multiscale mutation clustering algorithm identifies pan-cancer mutational clusters associated with pathway-level changes in gene expression

PubMed Central

Poole, William; Leinonen, Kalle; Shmulevich, Ilya

2017-01-01

Cancer researchers have long recognized that somatic mutations are not uniformly distributed within genes. However, most approaches for identifying cancer mutations focus on either the entire-gene or single amino-acid level. We have bridged these two methodologies with a multiscale mutation clustering algorithm that identifies variable length mutation clusters in cancer genes. We ran our algorithm on 539 genes using the combined mutation data in 23 cancer types from The Cancer Genome Atlas (TCGA) and identified 1295 mutation clusters. The resulting mutation clusters cover a wide range of scales and often overlap with many kinds of protein features including structured domains, phosphorylation sites, and known single nucleotide variants. We statistically associated these multiscale clusters with gene expression and drug response data to illuminate the functional and clinical consequences of mutations in our clusters. Interestingly, we find multiple clusters within individual genes that have differential functional associations: these include PTEN, FUBP1, and CDH1. This methodology has potential implications in identifying protein regions for drug targets, understanding the biological underpinnings of cancer, and personalizing cancer treatments. Toward this end, we have made the mutation clusters and the clustering algorithm available to the public. Clusters and pathway associations can be interactively browsed at m2c.systemsbiology.net. The multiscale mutation clustering algorithm is available at https://github.com/IlyaLab/M2C. PMID:28170390

Multiscale mutation clustering algorithm identifies pan-cancer mutational clusters associated with pathway-level changes in gene expression.

PubMed

Poole, William; Leinonen, Kalle; Shmulevich, Ilya; Knijnenburg, Theo A; Bernard, Brady

2017-02-01

Cancer researchers have long recognized that somatic mutations are not uniformly distributed within genes. However, most approaches for identifying cancer mutations focus on either the entire-gene or single amino-acid level. We have bridged these two methodologies with a multiscale mutation clustering algorithm that identifies variable length mutation clusters in cancer genes. We ran our algorithm on 539 genes using the combined mutation data in 23 cancer types from The Cancer Genome Atlas (TCGA) and identified 1295 mutation clusters. The resulting mutation clusters cover a wide range of scales and often overlap with many kinds of protein features including structured domains, phosphorylation sites, and known single nucleotide variants. We statistically associated these multiscale clusters with gene expression and drug response data to illuminate the functional and clinical consequences of mutations in our clusters. Interestingly, we find multiple clusters within individual genes that have differential functional associations: these include PTEN, FUBP1, and CDH1. This methodology has potential implications in identifying protein regions for drug targets, understanding the biological underpinnings of cancer, and personalizing cancer treatments. Toward this end, we have made the mutation clusters and the clustering algorithm available to the public. Clusters and pathway associations can be interactively browsed at m2c.systemsbiology.net. The multiscale mutation clustering algorithm is available at https://github.com/IlyaLab/M2C.