Quantitative analysis of interaction between the free troposphere and planetary boundary layer using multiple measurements and large eddy simulation model

NASA Astrophysics Data System (ADS)

Huang, Guanyu

We investigate the interaction between the free troposphere (FT) and planetary boundary layer (PBL) using multiple measurements and Dutch Atmospheric Large Eddy Simulation (DALES) coupled with a chemical module. A residual layer (RL) storing high ozone concentrations can significantly influence ground ozone concentration through the entrainment process whereby the RL aloft is incorporated into the growing convective boundary layer (CBL) during the morning transition. We use DALES model coupled with a chemical module to simultaneously study the dynamical and chemical impacts of a RL (200-1200 m above ground level (AGL)) on ground-level (0-200 m AGL) ozone concentrations. Four numerical experiments test these interactions: 1) a RL with high ozone (100 ppb); 2) a RL with low ozone (50 ppb); 3) no RL with high ozone above the NBL (100 ppb from 200-1200 m AGL); and 4) no RL with low ozone above the NBL (50 ppb). The results indicate that ozone stored in the RL can contribute up to 86% of the ozone concentration in the CBL during the following day in Case 1. Even in Case 2, 64% of the ozone in the developed CBL results from intrusions from the RL. Additionally, a RL also increases the enhancement rate of ozone in the CBL. Furthermore, we investigate the ozone diurnal variation on September 6, 2013 in Huntsville AL. The ozone variation in the CBL is mainly caused by local emissions due to the weather conditions being controlled by an anticyclonic system. The local chemical production contributes over 67% of the ozone enhancement in the CBL. The dynamical processes contribute the rest. The numerical experiments show good agreement with our ozone lidar observations. However, our simulation results and ozone lidar observations fail to reproduce a declining trend of surface ozone measured by an Environment Protection Agency (EPA) surface monitoring station that is 6 km south of our facilities, which is very likely due to the large ozone horizontal variation and the diurnal variation of ozone dry deposition under urban environment.

Investigating the Impact of Surface Heterogeneity on the Convective Boundary Layer Over Urban Areas Through Coupled Large-Eddy Simulation and Remote Sensing

NASA Technical Reports Server (NTRS)

Dominguez, Anthony; Kleissl, Jan P.; Luvall, Jeffrey C.

2011-01-01

Large-eddy Simulation (LES) was used to study convective boundary layer (CBL) flow through suburban regions with both large and small scale heterogeneities in surface temperature. Constant remotely sensed surface temperatures were applied at the surface boundary at resolutions of 10 m, 90 m, 200 m, and 1 km. Increasing the surface resolution from 1 km to 200 m had the most significant impact on the mean and turbulent flow characteristics as the larger scale heterogeneities became resolved. While previous studies concluded that scales of heterogeneity much smaller than the CBL inversion height have little impact on the CBL characteristics, we found that further increasing the surface resolution (resolving smaller scale heterogeneities) results in an increase in mean surface heat flux, thermal blending height, and potential temperature profile. The results of this study will help to better inform sub-grid parameterization for meso-scale meteorological models. The simulation tool developed through this study (combining LES and high resolution remotely sensed surface conditions) is a significant step towards future studies on the micro-scale meteorology in urban areas.

An equilibrium model for the coupled ocean-atmosphere boundary layer in the tropics

NASA Technical Reports Server (NTRS)

Sui, C.-H.; Lau, K.-M.; Betts, Alan K.

1991-01-01

An atmospheric convective boundary layer (CBL) model is coupled to an ocean mixed-layer (OML) model in order to study the equilibrium state of the coupled system in the tropics, particularly in the Pacific region. The equilibrium state of the coupled system is solved as a function of sea-surface temperature (SST) for a given surface wind and as a function of surface wind for a given SST. It is noted that in both cases, the depth of the CBL and OML increases and the upwelling below the OML decreases, corresponding to either increasing SST or increasing surface wind. The coupled ocean-atmosphere model is solved iteratively as a function of surface wind for a fixed upwelling and a fixed OML depth, and it is observed that SST falls with increasing wind in both cases. Realistic gradients of mixed-layer depth and upwelling are observed in experiments with surface wind and SST prescribed as a function of longitude.

A Physical Mechanism for the Asymmetry in Top-Down and Bottom-Up Diffusion.

NASA Astrophysics Data System (ADS)

Wyngaard, J. C.

1987-04-01

Recent large-eddy simulations of the vertical diffusion of a passive, conservative scalar through the convective boundary layer (CBL) show strikingly different eddy diffusivity profiles in the `top-down' and `bottom-up' cases. These results indicate that for a given turbulent velocity field and associated scalar flux, the mean change in scalar mixing ratio across the CBL is several times larger if the flux originates at the top of the boundary layer (i.e., in top-down diffusion) rather than at the bottom. The large-eddy simulation (LES) data show that this asymmetry is due to a breakdown of the eddy-diffusion concept.A simple updraft-downdraft model of the CBL reveals a physical mechanism that could cause this unexpected behavior. The large, positive skewness of the convectively driven vertical velocity gives an appreciably higher probability of downdrafts than updrafts; this excess probability of downdrafts, interacting with the time changes of the mean mixing ratio caused by the nonstationarity of the bottom-up and top-down diffusion processes, decreases the equilibrium value of mean mixing-ratio jump across the mixed layer in the bottom-up case and increases it in the top-down case. The resulting diffusion asymmetry agrees qualitatively with that found through LES.

Human convective boundary layer and its interaction with room ventilation flow.

PubMed

Licina, D; Melikov, A; Sekhar, C; Tham, K W

2015-02-01

This study investigates the interaction between the human convective boundary layer (CBL) and uniform airflow with different velocity and from different directions. Human body is resembled by a thermal manikin with complex body shape and surface temperature distribution as the skin temperature of an average person. Particle image velocimetry (PIV) and pseudocolor visualization (PCV) are applied to identify the flow around the manikin's body. The findings show that the direction and magnitude of the surrounding airflows considerably influence the airflow distribution around the human body. Downward flow with velocity of 0.175 m/s does not influence the convective flow in the breathing zone, while flow at 0.30 m/s collides with the CBL at the nose level reducing the peak velocity from 0.185 to 0.10 m/s. Transverse horizontal flow disturbs the CBL at the breathing zone even at 0.175 m/s. A sitting manikin exposed to airflow from below with velocity of 0.30 and 0.425 m/s assisting the CBL reduces the peak velocity in the breathing zone and changes the flow pattern around the body, compared to the assisting flow of 0.175 m/s or quiescent conditions. In this case, the airflow interaction is strongly affected by the presence of the chair. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An LES study on the spatial variability impact of surface sensible heat flux (SHF) on the convective boundary layer (CBL)

NASA Astrophysics Data System (ADS)

Kang, S. L.; Chun, J.; Kumar, A.

2015-12-01

We study the spatial variability impact of surface sensible heat flux (SHF) on the convective boundary layer (CBL), using the Weather Research and Forecasting (WRF) model in large eddy simulation (LES) mode. In order to investigate the response of the CBL to multi-scale feature of the surface SHF field over a local area of several tens of kilometers or smaller, an analytic surface SHF map is crated as a function of the chosen feature. The spatial variation in the SHF map is prescribed with a two-dimensional analytical perturbation field, which is generated by using the inverse transform technique of the Fourier series whose coefficients are controlled, of which spectrum to have a particular slope in the chosen range of wavelength. Then, the CBL responses to various SHF heterogeneities are summarized as a function of the spectral slope, in terms of mean structure, turbulence statistics and cross-scale processes. The range of feasible SHF heterogeneities is obtained from the SHF maps produced by a land surface model (LSM) of the WRF system. The LSM-derived SHF maps are a function of geographical data on various resolutions. Based on the numerical experiment results with the surface heterogeneities in the range, we will discuss the uncertainty in the SHF heterogeneity and its impact on the atmosphere in a numerical model. Also we will present the range of spatial scale of the surface SHF heterogeneity that significantly influence on the whole CBL. Lastly, we will report the test result of the hypothesis that the spatial variability of SHF is more representative of surface thermal heterogeneity than is the latent heat flux over the local area of several tens of kilometers or smaller.

Inner-outer interactions in the convective atmospheric boundary layer

NASA Astrophysics Data System (ADS)

Salesky, S.

2017-12-01

Recently, observational and numerical studies have revealed the existence of so-called large scale motions (LSMs) that populate the logarithmic layer of wall-bounded turbulent shear flows and modulate the amplitude and frequency of turbulence dynamics near the ground. Properties of LSMs are well understood in neutrally stratified flows over smooth and rough walls. However, the implications of previous studies for the convective atmospheric boundary layer (CBL) are not entirely clear, since the morphology of both small-scale and large-scale turbulent structures is known to be strongly affected by buoyancy [e.g. Salesky et al., Bound.-Layer Meteorol. 163:41-68 (2017)]. In the present study, inner-outer interactions in the CBL are investigated using a suite of large eddy simulations spanning neutral to highly convective conditions. Simulation results reveal that, as the atmosphere becomes increasingly unstable, the inclination angle of structures near the ground increases from 12-15° to nearly 90°. Furthermore, the scale separation between the inner and outer peaks in the premultiplied velocity spectra decreases until only a single peak remains (comparable in magnitude to the boundary layer depth). The extent to which the amplitude modulation of surface layer turbulence by outer layer structures changes with increasing instability will be considered, following the decoupling procedure proposed by Mathis et al. [J. Fluid Mech., vol 628, 311-337 (2009)]. Frequency modulation of surface layer turbulence also will be examined, following the wavelet analysis approach of Baars et al. [Exp. Fluids, 56:188, (2015)].

Estimate of Boundary-Layer Depth Over Beijing, China, Using Doppler Lidar Data During SURF-2015

NASA Astrophysics Data System (ADS)

Huang, Meng; Gao, Zhiqiu; Miao, Shiguang; Chen, Fei; LeMone, Margaret A.; Li, Ju; Hu, Fei; Wang, Linlin

2017-03-01

Planetary boundary-layer (PBL) structure was investigated using observations from a Doppler lidar and the 325-m Institute of Atmospheric Physics (IAP) meteorological tower in the centre of Beijing during the summer 2015 Study of Urban-impacts on Rainfall and Fog/haze (SURF-2015) field campaign. Using six fair-weather days of lidar and tower data under clear to cloudy skies, we evaluate the ability of the Doppler lidar to probe the urban boundary-layer structure, and then propose a composite method for estimating the diurnal cycle of the PBL depth using the Doppler lidar. For the convective boundary layer (CBL), a threshold method using vertical velocity variance (σ _w^2 >0.1 m2s^{-2}) is used, since it provides more reliable CBL depths than a conventional maximum wind-shear method. The nocturnal boundary-layer (NBL) depth is defined as the height at which σ _w^2 decreases to 10 % of its near-surface maximum minus a background variance. The PBL depths determined by combining these methods have average values ranging from ≈ 270 to ≈ 1500 m for the six days, with the greatest maximum depths associated with clear skies. Release of stored and anthropogenic heat contributes to the maintenance of turbulence until late evening, keeping the NBL near-neutral and deeper at night than would be expected over a natural surface. The NBL typically becomes more shallow with time, but grows in the presence of low-level nocturnal jets. While current results are promising, data over a broader range of conditions are needed to fully develop our PBL-depth algorithms.

Experimental Study of Aligned and Staggered Wind Farms in a Convective Boundary Layer

NASA Astrophysics Data System (ADS)

Markfort, Corey; Zhang, Wei; Porte-Agel, Fernando

2011-11-01

Wind farm-atmosphere interaction is complicated by turbine configuration and thermal effects on momentum and kinetic energy fluxes. Wind farms of finite length have been modeled as increased surface roughness or as a sparse canopy; however it is not clear which approach is more appropriate. Experiments were conducted in a thermally controlled boundary layer wind tunnel, using a custom x-wire/cold wire and surface heat flux sensors, to understand the effect of aligned versus staggered turbine configurations on momentum absorption and flow adjustment in a convective boundary layer (CBL). Results for experiments of a large farm show the span-wise averaged flow statistics exhibit similar turbulent transport properties to that of canopy flows. The wake adjusts within and grows over the farm more quickly for a staggered compared to an aligned farm. Using canopy flow scaling, we show that the flow equilibrates faster and the overall momentum absorption is higher in a staggered compared to an aligned farm. Wake recovery behind a single turbine is facilitated by buoyancy in a CBL (Zhang et al. under review). We find a similar effect in wind farms resulting in reduced effective roughness and momentum absorption. We also find a reduction of surface heat flux for both wind farms, but greater for the staggered farm.

Perturbations to the Spatial and Temporal Characteristics of the Diurnally-Varying Atmospheric Boundary Layer Due to an Extensive Wind Farm

NASA Astrophysics Data System (ADS)

Sharma, V.; Parlange, M. B.; Calaf, M.

2017-02-01

The effect of extensive terrestrial wind farms on the spatio-temporal structure of the diurnally-evolving atmospheric boundary layer is explored. High-resolution large-eddy simulations of a realistic diurnal cycle with an embedded wind farm are performed. Simulations are forced by a constant geostrophic velocity with time-varying surface boundary conditions derived from a selected period of the CASES-99 field campaign. Through analysis of the bulk statistics of the flow as a function of height and time, it is shown that extensive wind farms shift the inertial oscillations and the associated nocturnal low-level jet vertically upwards by approximately 200 m; cause a three times stronger stratification between the surface and the rotor-disk region, and as a consequence, delay the formation and growth of the convective boundary layer (CBL) by approximately 2 h. These perturbations are shown to have a direct impact on the potential power output of an extensive wind farm with the displacement of the low-level jet causing lower power output during the night as compared to the day. The low-power regime at night is shown to persist for almost 2 h beyond the morning transition due to the reduced growth of the CBL. It is shown that the wind farm induces a deeper entrainment region with greater entrainment fluxes. Finally, it is found that the diurnally-averaged effective roughness length for wind farms is much lower than the reference value computed theoretically for neutral conditions.

Directed Vertical Diffusion of Photovoltaic Active Layer Components into Porous ZnO-Based Cathode Buffer Layers.

PubMed

Kang, Jia-Jhen; Yang, Tsung-Yu; Lan, Yi-Kang; Wu, Wei-Ru; Su, Chun-Jen; Weng, Shih-Chang; Yamada, Norifumi L; Su, An-Chung; Jeng, U-Ser

2018-04-01

Cathode buffer layers (CBLs) can effectively further the efficiency of polymer solar cells (PSCs), after optimization of the active layer. Hidden between the active layer and cathode of the inverted PSC device configuration is the critical yet often unattended vertical diffusion of the active layer components across CBL. Here, a novel methodology of contrast variation with neutron and anomalous X-ray reflectivity to map the multicomponent depth compositions of inverted PSCs, covering from the active layer surface down to the bottom of the ZnO-based CBL, is developed. Uniquely revealed for a high-performance model PSC are the often overlooked porosity distributions of the ZnO-based CBL and the differential diffusions of the polymer PTB7-Th and fullerene derivative PC 71 BM of the active layer into the CBL. Interface modification of the ZnO-based CBL with fullerene derivative PCBEOH for size-selective nanochannels can selectively improve the diffusion of PC 71 BM more than that of the polymer. The deeper penetration of PC 71 BM establishes a gradient distribution of fullerene derivatives over the ZnO/PCBE-OH CBL, resulting in markedly improved electron mobility and device efficiency of the inverted PSC. The result suggests a new CBL design concept of progressive matching of the conduction bands. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Atmospheric Boundary Layer of a pasture site in Amazônia

NASA Astrophysics Data System (ADS)

Trindade de Araújo Tiburtino Neves, Theomar; Fisch, Gilberto; Raasch, Siegfried

2013-04-01

A great effort has been made by the community of micrometeorology and planetary boundary layer for a better description of the properties of the Atmospheric Boundary Layer (ABL), such as its height, thermodynamics characteristics and its time evolution. This work aims to give a review of the main characteristics of Atmospheric Boundary Layer over a pasture site in Amazonia. The measurements dataset was carried out from 3 different LBA field campaigns: RBLE 3 (during the dry season from 1993), RaCCI (during the dry-to-wet transition season from 2002) and WetAMC (during the wet season from 1999), collected with tethered balloon, radiosondes and eddy correlation method in a pasture site in the southwestern Amazonia. Different techniques and instruments were used to estimate the ABĹs properties. During the daytime, it was possible to observe that there is an abrupt growth of the Convective Boundary Layer (CBL) between 08 and 11 LT, with a stationary pattern between 14 and 17 LT. The maximum heights at late afternoon were around 1600 m during the dry season, whilst the wet season it only reached 1000 m. This is due to the lower surface turbulent sensible heat flux as the soil is wetter and the partition of energy is completely different between wet to the dry season. For the transition period (RaCCI 2002), it was possible to analyze and compare several estimates from different instruments and methods. It showed that the parcel method overestimates the heights of all measurements (mainly at 14 LT) due to the high incidence of solar radiation and superadiabatic gradients. The profile and Richardson number methods gave results very similar to estimate the height of the CBL. The onset of the Nocturnal Boundary Layer (NBL) occurs before the sunset (18 LT) and its height is reasonable stable during the night (typical values around 180-250 m). An alternative method (Vmax) which used the height of the maximum windspeed derived from a SODAR instrument during RaCCI 2002 was proposed and it showed to be satisfactory comparing with the others methods. Besides that, it has the advantage to have measurements each 30 min.

Boundary Layer Depth In Coastal Regions

NASA Astrophysics Data System (ADS)

Porson, A.; Schayes, G.

The results of earlier studies performed about sea breezes simulations have shown that this is a relevant feature of the Planetary Boundary Layer that still requires effort to be diagnosed properly by atmospheric models. Based on the observations made during the ESCOMPTE campaign, over the Mediterranean Sea, different CBL and SBL height estimation processes have been tested with a meso-scale model, TVM. The aim was to compare the critical points of the BL height determination computed using turbulent kinetic energy profile with some other standard evaluations. Moreover, these results have been analysed with different mixing length formulation. The sensitivity of formulation is also analysed with a simple coastal configuration.

Near-Surface Effects of Free Atmosphere Stratification in Free Convection

NASA Astrophysics Data System (ADS)

Mellado, Juan Pedro; van Heerwaarden, Chiel C.; Garcia, Jade Rachele

2016-04-01

The effect of a linear stratification in the free atmosphere on near-surface properties in a free convective boundary layer (CBL) is investigated by means of direct numerical simulation. We consider two regimes: a neutral stratification regime, which represents a CBL that grows into a residual layer, and a strong stratification regime, which represents the equilibrium (quasi-steady) entrainment regime. We find that the mean buoyancy varies as z^{-1/3}, in agreement with classical similarity theory. However, the root-mean-square (r.m.s.) of the buoyancy fluctuation and the r.m.s. of the vertical velocity vary as z^{-0.45} and ln z, respectively, both in disagreement with theory. These scaling laws are independent of the stratification regime, but the depth over which they are valid depends on the stratification. In the strong stratification regime, this depth is about 20 to 25 % of the CBL depth instead of the commonly used 10 %, which we only observe under neutral conditions. In both regimes, the near-surface flow structure can be interpreted as a hierarchy of circulations attached to the surface. Based on this structure, we define a new near-surface layer in free convection, the plume-merging layer, that is conceptually different from the constant-flux layer. The varying depth of the plume-merging layer depending on the stratification accounts for the varying depth of validity of the scaling laws. These findings imply that the buoyancy transfer law needed in mixed-layer and single-column models is well described by the classical similarity theory, independent of the stratification in the free atmosphere, even though other near-surface properties, such as the r.m.s. of the buoyancy fluctuation and the r.m.s. of the vertical velocity, are inconsistent with that theory.

Relation Between the Arc-Root Fluctuations, the Cold Boundary Layer Thickness and the Particle Thermal Treatment

NASA Astrophysics Data System (ADS)

Noguès, E.; Fauchais, P.; Vardelle, M.; Granger, P.

2007-12-01

In plasma spraying, the arc-root fluctuations, modifying the length and characteristics of the plasma jet, have an important influence on particle thermal treatment. These voltage fluctuations are strongly linked to the thickness of the cold boundary layer (CBL), surrounding the arc column. This thickness depends on the plasma spray parameters (composition and plasma forming gas mass flow rate, arc current, etc.) and the plasma torch design (anode-nozzle internal diameter and shape, etc.). In order to determine the influence of these different spray parameters on the CBL properties and voltage fluctuations, experiments were performed with two different plasma torches from Sulzer Metco. The first one is a PTF4 torch with a cylindrical anode-nozzle, working with Ar-H2 plasma gas mixtures and the second one is a 3MB torch with either a conical or a cylindrical anode-nozzle, working with N2-H2 plasma gas mixtures. Moreover, arc voltage fluctuations influence on particle thermal treatment was studied through the measurements of transient temperature and velocity of particles, issued from an yttria partially stabilized zirconia powder with a size distribution between 5 and 25 μm.

Effect of ring-shaped SiO2 current blocking layer thickness on the external quantum efficiency of high power light-emitting diodes

NASA Astrophysics Data System (ADS)

Zhou, Shengjun; Liu, Mengling; Hu, Hongpo; Gao, Yilin; Liu, Xingtong

2017-12-01

A ring-shaped SiO2 CBL underneath the p-electrode was employed to enhance current spreading of GaN-based light-emitting diodes (LEDs). Effects of ring-shaped SiO2 current blocking layer (CBL) thickness on optical and electrical characteristics of high power LEDs were investigated. A 190-nm-thick ring-shaped SiO2 CBL with inclined sidewalls was obtained using a combination of a thermally reflowed photoresist technique and an inductively coupled plasma (ICP) etching process, allowing for the deposition of conformal indium tin oxide (ITO) transparent conductive layer on sidewalls of ring-shaped SiO2 CBL. It was indicated that the external quantum efficiency (EQE) of high power LEDs increased with increasing thickness of ring-shaped SiO2 CBL. The EQE of high power LED with 190-nm-thick ring-shaped SiO2 CBL was 12.7% higher than that of high power LED without SiO2 CBL. Simulations performed with commercial SimuLED software package showed that the ring-shaped SiO2 CBL could significantly alleviate current crowding around p-electrode, resulting in enhanced current spreading over the entire high power LED structure.

Efficiency enhancement in DIBSQ:PC71BM organic photovoltaic cells by using Liq-doped Bphen as a cathode buffer layer

NASA Astrophysics Data System (ADS)

Chen, Guo; Si, Changfeng; Zhang, Pengpeng; Guo, Kunping; Pan, Saihu; Zhu, Wenqing; Wei, Bin

2017-09-01

We have improved the photovoltaic performance of 2,4-bis[4-(N,Ndiisobutylamino)- 2,6-dihydroxyphenyl] squaraine:[6,6]-phenyl C71-butyric acid methyl ester (DIBSQ:PC71BM) organic photovoltaic (OPV) cells via incorporating Liq-doped Bphen (Bphen-Liq) as a cathode buffer layer (CBL). Based on the Bphen-Liq CBL, a DIBSQ:PC71BM OPV cell possessed an optimal power conversion efficiency of 4.90%, which was 13% and 60% higher than those of the devices with neat Bphen as CBL and without CBL, respectively. The enhancement of the device performance could be attributed to the enhanced electron mobility and improved electrode/active layer contact and thus the improved photocurrent extraction by incorporating the Bphen-Liq CBL. Light-intensity dependent device performance analysis indicates that the incorporating of the Bphen-Liq CBL can remarkably improve the charge transport of the DIBSQ:PC71BM OPV cell and thus decrease the recombination losses of the device, resulting in enhanced device performance. Our finding indicates that the doped Bphen-Liq CBL has great potential for high-performance solution-processed small-molecule OPVs.

Characteristics of Water Vapor Turbulence Profiles in Convective Boundary Layers During the Dry and Wet Seasons Over Darwin

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

Osman, Mohammed K.; Turner, D. D.; Heus, T.

Here, this study explores water vapor turbulence in the convective boundary layer (CBL) using the Raman lidar observations from the Atmospheric Radiation Measurement site located at Darwin, Australia. An autocovariance technique was used to separate out the random instrument error from the atmospheric variability during time periods when the CBL is cloud–free, quasi–stationary, and well mixed. We identified 45 cases, comprising of 8 wet and 37 dry seasons events, over the 5–year data record period. The dry season in Darwin is known by warm and dry sunny days, while the wet season is characterized by high humidity and monsoonal rains.more » The inherent variability of the latter resulted in a more limited number of cases during the wet season. Profiles of the integral scale, variance, coefficient of the structure function, and skewness were analyzed and compared with similar observations from the Raman lidar at the Atmospheric Radiation Measurement Southern Great Plains (SGP) site. The wet season shows larger median variance profiles than the dry season, while the median profile of the variance from the dry season and the SGP site are found to be more comparable particularly between 0.4 and 0.75 z i. The variance and coefficient of the structure function show qualitatively the same vertical pattern. Furthermore, deeper CBL, larger gradient of water vapor mixing ratio at z i, and the strong correlation with the water vapor variance at z i are seen during the dry season. The median value in the skewness is mostly positive below 0.6 z i unlike the SGP site.« less

Characteristics of Water Vapor Turbulence Profiles in Convective Boundary Layers During the Dry and Wet Seasons Over Darwin

DOE PAGES

Osman, Mohammed K.; Turner, D. D.; Heus, T.; ...

2018-04-23

Here, this study explores water vapor turbulence in the convective boundary layer (CBL) using the Raman lidar observations from the Atmospheric Radiation Measurement site located at Darwin, Australia. An autocovariance technique was used to separate out the random instrument error from the atmospheric variability during time periods when the CBL is cloud–free, quasi–stationary, and well mixed. We identified 45 cases, comprising of 8 wet and 37 dry seasons events, over the 5–year data record period. The dry season in Darwin is known by warm and dry sunny days, while the wet season is characterized by high humidity and monsoonal rains.more » The inherent variability of the latter resulted in a more limited number of cases during the wet season. Profiles of the integral scale, variance, coefficient of the structure function, and skewness were analyzed and compared with similar observations from the Raman lidar at the Atmospheric Radiation Measurement Southern Great Plains (SGP) site. The wet season shows larger median variance profiles than the dry season, while the median profile of the variance from the dry season and the SGP site are found to be more comparable particularly between 0.4 and 0.75 z i. The variance and coefficient of the structure function show qualitatively the same vertical pattern. Furthermore, deeper CBL, larger gradient of water vapor mixing ratio at z i, and the strong correlation with the water vapor variance at z i are seen during the dry season. The median value in the skewness is mostly positive below 0.6 z i unlike the SGP site.« less

Idealised large-eddy-simulation of thermally driven flows over an isolated mountain range with multiple ridges

NASA Astrophysics Data System (ADS)

Lang, Moritz N.; Gohm, Alexander; Wagner, Johannes S.; Leukauf, Daniel; Posch, Christian

2014-05-01

Two dimensional idealised large-eddy-simulations are performed using the WRF model to investigate thermally driven flows during the daytime over complex terrain. Both the upslope flows and the temporal evolution of the boundary layer structure are studied with a constant surface heat flux forcing of 150 W m-2. In order to distinguish between different heating processes the flow is Reynold decomposed into its mean and turbulent part. The heating processes associated with the mean flow are a cooling through cold-air advection along the slopes and subsidence warming within the valleys. The turbulent component causes bottom-up heating near the ground leading to a convective boundary layer (CBL) inside the valleys. Overshooting potentially colder thermals cool the stably stratified valley atmosphere above the CBL. Compared to recent investigations (Schmidli 2013, J. Atmos. Sci., Vol. 70, No. 12: pp. 4041-4066; Wagner et al. 2014, manuscript submitted to Mon. Wea. Rev.), which used an idealised topography with two parallel mountain crests separated by a straight valley, this project focuses on multiple, periodic ridges and valleys within an isolated mountain range. The impact of different numbers of ridges on the flow structure is compared with the sinusoidal envelope-topography. The present simulations show an interaction between the smaller-scale upslope winds within the different valleys and the large-scale flow of the superimposed mountain-plain wind circulation. Despite a smaller boundary layer air volume in the envelope case compared to the multiple ridges case the volume averaged heating rates are comparable. The reason is a stronger advection-induced cooling along the slopes and a weaker warming through subsidence at the envelope-topography compared to the mountain range with multiple ridges.

Optimization of the Energy Level Alignment between the Photoactive Layer and the Cathode Contact Utilizing Solution-Processed Hafnium Acetylacetonate as Buffer Layer for Efficient Polymer Solar Cells.

PubMed

Yu, Lu; Li, Qiuxiang; Shi, Zhenzhen; Liu, Hao; Wang, Yaping; Wang, Fuzhi; Zhang, Bing; Dai, Songyuan; Lin, Jun; Tan, Zhan'ao

2016-01-13

The insertion of an appropriate interfacial buffer layer between the photoactive layer and the contact electrodes makes a great impact on the performance of polymer solar cells (PSCs). Ideal interfacial buffer layers could minimize the interfacial traps and the interfacial barriers caused by the incompatibility between the photoactive layer and the electrodes. In this work, we utilized solution-processed hafnium(IV) acetylacetonate (Hf(acac)4) as an effective cathode buffer layer (CBL) in PSCs to optimize the energy level alignment between the photoactive layer and the cathode contact, with the short-circuit current density (Jsc), open-circuit voltage (Voc), and fill factor (FF) all simultaneously improved with Hf(acac)4 CBL, leading to enhanced power conversion efficiencies (PCEs). Ultraviolet photoemission spectroscopy (UPS) and scanning Kelvin probe microscopy (SKPM) were performed to confirm that the interfacial dipoles were formed with the same orientation direction as the built-in potential between the photoactive layer and Hf(acac)4 CBL, benefiting the exciton separation and electron transport/extraction. In addition, the optical characteristics and surface morphology of the Hf(acac)4 CBL were also investigated.

Nested mesoscale-to-LES modeling of the atmospheric boundary layer in the presence of under-resolved convective structures

DOE PAGES

Mazzaro, Laura J.; Munoz-Esparza, Domingo; Lundquist, Julie K.; ...

2017-07-06

Multiscale atmospheric simulations can be computationally prohibitive, as they require large domains and fine spatiotemporal resolutions. Grid-nesting can alleviate this by bridging mesoscales and microscales, but one turbulence scheme must run at resolutions within a range of scales known as the terra incognita (TI). TI grid-cell sizes can violate both mesoscale and microscale subgrid-scale parametrization assumptions, resulting in unrealistic flow structures. Herein we assess the impact of unrealistic lateral boundary conditions from parent mesoscale simulations at TI resolutions on nested large eddy simulations (LES), to determine whether parent domains bias the nested LES. We present a series of idealized nestedmore » mesoscale-to-LES runs of a dry convective boundary layer (CBL) with different parent resolutions in the TI. We compare the nested LES with a stand-alone LES with periodic boundary conditions. The nested LES domains develop ~20% smaller convective structures, while potential temperature profiles are nearly identical for both the mesoscales and LES simulations. The horizontal wind speed and surface wind shear in the nested simulations closely resemble the reference LES. Heat fluxes are overestimated by up to ~0.01 K m s –1 in the top half of the PBL for all nested simulations. Overestimates of turbulent kinetic energy (TKE) and Reynolds stress in the nested domains are proportional to the parent domain's grid-cell size, and are almost eliminated for the simulation with the finest parent grid-cell size. Furthermore, based on these results, we recommend that LES of the CBL be forced by mesoscale simulations with the finest practical resolution.« less

Nested mesoscale-to-LES modeling of the atmospheric boundary layer in the presence of under-resolved convective structures

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

Mazzaro, Laura J.; Munoz-Esparza, Domingo; Lundquist, Julie K.

Multiscale atmospheric simulations can be computationally prohibitive, as they require large domains and fine spatiotemporal resolutions. Grid-nesting can alleviate this by bridging mesoscales and microscales, but one turbulence scheme must run at resolutions within a range of scales known as the terra incognita (TI). TI grid-cell sizes can violate both mesoscale and microscale subgrid-scale parametrization assumptions, resulting in unrealistic flow structures. Herein we assess the impact of unrealistic lateral boundary conditions from parent mesoscale simulations at TI resolutions on nested large eddy simulations (LES), to determine whether parent domains bias the nested LES. We present a series of idealized nestedmore » mesoscale-to-LES runs of a dry convective boundary layer (CBL) with different parent resolutions in the TI. We compare the nested LES with a stand-alone LES with periodic boundary conditions. The nested LES domains develop ~20% smaller convective structures, while potential temperature profiles are nearly identical for both the mesoscales and LES simulations. The horizontal wind speed and surface wind shear in the nested simulations closely resemble the reference LES. Heat fluxes are overestimated by up to ~0.01 K m s –1 in the top half of the PBL for all nested simulations. Overestimates of turbulent kinetic energy (TKE) and Reynolds stress in the nested domains are proportional to the parent domain's grid-cell size, and are almost eliminated for the simulation with the finest parent grid-cell size. Furthermore, based on these results, we recommend that LES of the CBL be forced by mesoscale simulations with the finest practical resolution.« less

On the link between potential evaporation and regional evaporation from a CBL perspective

NASA Astrophysics Data System (ADS)

Lhomme, J. P.; Guilioni, L.

2010-07-01

The relationship between potential evaporation and actual evaporation was first examined by Bouchet (Proc Berkeley Calif Symp IAHS Publ, 62:134-142, 1963) who considered potential evaporation as the consequence of regional evaporation due to atmospheric feedbacks. Using a heuristic approach, he derived a complementary relationship which, despite no real theoretical background, has proven to be very useful in interpreting many experimental data under various climatic conditions. Here, the relationship between actual and potential evaporation is reinterpreted in the context of the development of the convective boundary layer (CBL): first, with a closed-box approach, where the CBL has an impermeable lid; and then with an open system, where air is exchanged between the CBL and its external environment. By applying steady forcing to these systems, it is shown that an equilibrium state is reached, where potential evaporation has a specific equilibrium formulation as a function of two parameters: one representing large-scale advection and the other the feedback effect of regional evaporation on potential evaporation, i.e. a kind of “medium-scale advection”. It is also shown that the original form of Bouchet’s complementary relationship is not verified in the equilibrium state. This analysis leads us to propose a new and more rational approach of the relationship between potential and actual evaporation through the effective surface resistance of the region.

Enhanced lifetime for thin-dielectric microdischarge-arrays operating in DC

NASA Astrophysics Data System (ADS)

Dussart, Remi; Felix, Valentin; Overzet, Lawrence; Aubry, Olivier; Stolz, Arnaud; Lefaucheux, Philippe; Gremi-Univ Orleans-Cnrs Collaboration; University Of Texas At Dallas Collaboration

2016-09-01

Micro-hollow cathode discharge arrays using silicon as the cathode have a very limited lifetime because the silicon bubbles and initiates micro-arcing. To avoid this destructive behavior, the same configuration was kept but, another material was selected for the cathode. Using micro and nanotechnologies ordinarily used in microelectronic and MEMS device fabrication, we made arrays of cathode boundary layer (CBL)-type microreactors consisting of nickel electrodes separated by a 6 µm thick SiO2 layer. Microdischarges were ignited in arrays of 100 µm diameter holes at different pressures (200750 Torr) in different gases. Electrical and optical measurements were made to characterize the arrays. Unlike the microdischarges produced using silicon cathodes, the Ni cathode discharges remain very stable with essentially no micro-arcing. DC currents between 50 and 900 µA flowed through each microreactor with a discharge voltage of typically 200 V. Stable V-I characteristics showing both the normal and abnormal regimes were observed and are consistent with the spread of the plasma over the cathode area. Due to their stability and lifetime, new applications of these DC, CBL-type microreactors can now be envisaged.

Mesoscale circulation systems and ozone concentrations during ESCOMPTE: a case study from IOP 2b

NASA Astrophysics Data System (ADS)

Kalthoff, N.; Kottmeier, C.; Thürauf, J.; Corsmeier, U.; Saїd, F.; Fréjafon, E.; Perros, P. E.

2005-03-01

The main objective of 'Expérience sur Site pour COntraindre les Modèles de Pollution atmosphérique et de Transport d'Emissions' (ESCOMPTE) is to generate a relevant data set for testing and evaluating mesoscale chemistry-transport models (CTMs). During ESCOMPTE, measurements have been performed at numerous surface stations, by radars and lidars, and several aircraft in the planetary boundary layer. The data from these different sources have been merged to obtain a consistent description of the spatial distribution of wind, temperature, humidity, and ozone for the photosmog episode on June 25, 2001 (IOP 2b). On this day, moderate synoptic winds favour the evolution of different mesoscale circulation systems. During daytime, the sea breeze penetrates towards the north in the Rhône valley. As the winds above the sea breeze layer come from the east, polluted air from the metropolitan area of Marseille leads to an increase of ozone at elevated layers above the convective boundary layer (CBL). At the mountainous station of Luberon about 55 km north of Marseille around noon, when the CBL top surpasses the height of the mountain summit, polluted air with ozone concentrations of about 120 ppbv arrived from southerly directions, thus indicating the passage of the city plume of Marseille. At Cadarache and Vinon in the Durance valley, about 60 km inland, the ozone maximum at the surface and at flight level 920 m MSL appears between 14 and 15 UTC. At this time, southwesterly valley winds prevail in the valley, while southerly winds occur above. This finding highlights the height-dependent advection of ozone due to interacting mesoscale circulation systems. These dynamical processes need to be represented adequately in CTMs to deliver a realistic description of the ozone concentration fields.

Profiles of second- to third-order moments of turbulent temperature fluctuations in the convective boundary layer: first measurements with Rotational Raman Lidar

NASA Astrophysics Data System (ADS)

Behrendt, A.; Wulfmeyer, V.; Hammann, E.; Muppa, S. K.; Pal, S.

2014-11-01

The rotational Raman lidar of the University of Hohenheim (UHOH) measures atmospheric temperature profiles during daytime with high resolution (10 s, 109 m). The data contain low noise errors even in daytime due to the use of strong UV laser light (355 nm, 10 W, 50 Hz) and a very efficient interference-filter-based polychromator. In this paper, we present the first profiling of the second- to forth-order moments of turbulent temperature fluctuations as well as of skewness and kurtosis in the convective boundary layer (CBL) including the interfacial layer (IL). The results demonstrate that the UHOH RRL resolves the vertical structure of these moments. The data set which is used for this case study was collected in western Germany (50°53'50.56'' N, 6°27'50.39'' E, 110 m a.s.l.) within one hour around local noon on 24 April 2013 during the Intensive Observations Period (IOP) 6 of the HD(CP)2 Observational Prototype Experiment (HOPE), which is embedded in the German project HD(CP)2 (High-Definition Clouds and Precipitation for advancing Climate Prediction). First, we investigated profiles of the noise variance and compared it with estimates of the statistical temperature measurement uncertainty Δ T based on Poisson statistics. The agreement confirms that photon count numbers obtained from extrapolated analog signal intensities provide a lower estimate of the statistical errors. The total statistical uncertainty of a 20 min temperature measurement is lower than 0.1 K up to 1050 m a.g.l. at noontime; even for single 10 s temperature profiles, it is smaller than 1 K up to 1000 m a.g.l.. Then we confirmed by autocovariance and spectral analyses of the atmospheric temperature fluctuations that a temporal resolution of 10 s was sufficient to resolve the turbulence down to the inertial subrange. This is also indicated by the profile of the integral scale of the temperature fluctuations, which was in the range of 40 to 120 s in the CBL. Analyzing then profiles of the second-, third-, and forth-order moments, we found the largest values of all moments in the IL around the mean top of the CBL which was located at 1230 m a.g.l. The maximum of the variance profile in the IL was 0.40 K2 with 0.06 and 0.08 K2 for the sampling error and noise error, respectively. The third-order moment was not significantly different from zero inside the CBL but showed a negative peak in the IL with a minimum of -0.72 K3 and values of 0.06 and 0.14 K3 for the sampling and noise errors, respectively. The forth-order moment and kurtosis values throughout the CBL were quasi-normal.

Profiles of second- to fourth-order moments of turbulent temperature fluctuations in the convective boundary layer: first measurements with rotational Raman lidar

NASA Astrophysics Data System (ADS)

Behrendt, A.; Wulfmeyer, V.; Hammann, E.; Muppa, S. K.; Pal, S.

2015-05-01

The rotational Raman lidar (RRL) of the University of Hohenheim (UHOH) measures atmospheric temperature profiles with high resolution (10 s, 109 m). The data contain low-noise errors even in daytime due to the use of strong UV laser light (355 nm, 10 W, 50 Hz) and a very efficient interference-filter-based polychromator. In this paper, the first profiling of the second- to fourth-order moments of turbulent temperature fluctuations is presented. Furthermore, skewness profiles and kurtosis profiles in the convective planetary boundary layer (CBL) including the interfacial layer (IL) are discussed. The results demonstrate that the UHOH RRL resolves the vertical structure of these moments. The data set which is used for this case study was collected in western Germany (50°53'50.56'' N, 6°27'50.39'' E; 110 m a.s.l.) on 24 April 2013 during the Intensive Observations Period (IOP) 6 of the HD(CP)2 (High-Definition Clouds and Precipitation for advancing Climate Prediction) Observational Prototype Experiment (HOPE). We used the data between 11:00 and 12:00 UTC corresponding to 1 h around local noon (the highest position of the Sun was at 11:33 UTC). First, we investigated profiles of the total noise error of the temperature measurements and compared them with estimates of the temperature measurement uncertainty due to shot noise derived with Poisson statistics. The comparison confirms that the major contribution to the total statistical uncertainty of the temperature measurements originates from shot noise. The total statistical uncertainty of a 20 min temperature measurement is lower than 0.1 K up to 1050 m a.g.l. (above ground level) at noontime; even for single 10 s temperature profiles, it is smaller than 1 K up to 1020 m a.g.l. Autocovariance and spectral analyses of the atmospheric temperature fluctuations confirm that a temporal resolution of 10 s was sufficient to resolve the turbulence down to the inertial subrange. This is also indicated by the integral scale of the temperature fluctuations which had a mean value of about 80 s in the CBL with a tendency to decrease to smaller values towards the CBL top. Analyses of profiles of the second-, third-, and fourth-order moments show that all moments had peak values in the IL around the mean top of the CBL which was located at 1230 m a.g.l. The maximum of the variance profile in the IL was 0.39 K2 with 0.07 and 0.11 K2 for the sampling error and noise error, respectively. The third-order moment (TOM) was not significantly different from zero in the CBL but showed a negative peak in the IL with a minimum of -0.93 K3 and values of 0.05 and 0.16 K3 for the sampling and noise errors, respectively. The fourth-order moment (FOM) and kurtosis values throughout the CBL were not significantly different to those of a Gaussian distribution. Both showed also maxima in the IL but these were not statistically significant taking the measurement uncertainties into account. We conclude that these measurements permit the validation of large eddy simulation results and the direct investigation of turbulence parameterizations with respect to temperature.

Characterisation of boundary layer turbulent processes by the Raman lidar BASIL in the frame of HD(CP)2 Observational Prototype Experiment

NASA Astrophysics Data System (ADS)

Di Girolamo, Paolo; Cacciani, Marco; Summa, Donato; Scoccione, Andrea; De Rosa, Benedetto; Behrendt, Andreas; Wulfmeyer, Volker

2017-01-01

Measurements carried out by the University of Basilicata Raman lidar system (BASIL) are reported to demonstrate the capability of this instrument to characterise turbulent processes within the convective boundary layer (CBL). In order to resolve the vertical profiles of turbulent variables, high-resolution water vapour and temperature measurements, with a temporal resolution of 10 s and vertical resolutions of 90 and 30 m, respectively, are considered. Measurements of higher-order moments of the turbulent fluctuations of water vapour mixing ratio and temperature are obtained based on the application of autocovariance analyses to the water vapour mixing ratio and temperature time series. The algorithms are applied to a case study (11:30-13:30 UTC, 20 April 2013) from the High Definition Clouds and Precipitation for Climate Prediction (HD(CP)2) Observational Prototype Experiment (HOPE), held in western Germany in the spring 2013. A new correction scheme for the removal of the elastic signal crosstalk into the low quantum number rotational Raman signal is applied. The noise errors are small enough to derive up to fourth-order moments for both water vapour mixing ratio and temperature fluctuations.To the best of our knowledge, BASIL is the first Raman lidar with a demonstrated capability to simultaneously retrieve daytime profiles of water vapour turbulent fluctuations up to the fourth order throughout the atmospheric CBL. This is combined with the capability of measuring daytime profiles of temperature fluctuations up to the fourth order. These measurements, in combination with measurements from other lidar and in situ systems, are important for verifying and possibly improving turbulence and convection parameterisation in weather and climate models at different scales down to the grey zone (grid increment ˜ 1 km; Wulfmeyer et al., 2016).For the considered case study, which represents a well-mixed and quasi-stationary CBL, the mean boundary layer height is found to be 1290 ± 75 m above ground level (a.g.l.). Values of the integral scale for water vapour and temperature fluctuations at the top of the CBL are in the range of 70-125 and 75-225 s, respectively; these values are much larger than the temporal resolution of the measurements (10 s), which testifies that the temporal resolution considered for the measurements is sufficiently high to resolve turbulent processes down to the inertial subrange and, consequently, to resolve the major part of the turbulent fluctuations. Peak values of all moments are found in the interfacial layer in the proximity of the top of the CBL. Specifically, water vapour and temperature second-order moments (variance) have maximum values of 0.29 g2 kg-2 and 0.26 K2; water vapour and temperature third-order moments have peak values of 0.156 g3 kg-3 and -0.067 K3, while water vapour and temperature fourth-order moments have maximum values of 0.28 g4 kg-4 and 0.24 K4. Water vapour and temperature kurtosis have values of ˜ 3 in the upper portion of the CBL, which indicate normally distributed humidity and temperature fluctuations. Reported values of the higher-order moments are in good agreement with previous measurements at different locations, thus providing confidence in the possibility of using these measurements for turbulence parameterisation in weather and climate models.In the determination of the temperature profiles, particular care was dedicated to minimise potential effects associated with elastic signal crosstalk on the rotational Raman signals. For this purpose, a specific algorithm was defined and tested to identify and remove the elastic signal crosstalk and to assess the residual systematic uncertainty affecting temperature measurements after correction. The application of this approach confirms that, for the present Raman lidar system, the crosstalk factor remains constant with time; consequently an appropriate assessment of its constant value allows for a complete removal of the leaking elastic signal from the rotational Raman lidar signals at any time (with a residual error on temperature measurements after correction not exceeding 0.18 K).

Analysis of Doppler Lidar Data Acquired During the Pentagon Shield Field Campaign

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

Newsom, Rob K.

2011-04-14

Observations from two coherent Doppler lidars deployed during the Pentagon Shield field campaign are analyzed in conjunction with other sensors to characterize the overall boundary-layer structure, and identify the dominant flow characteristics during the entire two-week field campaign. Convective boundary layer (CBL) heights and cloud base heights (CBH) are estimated from an analysis of the lidar signal-to-noise-ratio (SNR), and mean wind profiles are computed using a modified velocity-azimuth-display (VAD) algorithm. Three-dimensional wind field retrievals are computed from coordinated overlapping volume scans, and the results are analyzed by visualizing the flow in horizontal and vertical cross sections. The VAD winds showmore » that southerly flows dominate during the two-week field campaign. Low-level jets (LLJ) were evident on all but two of the nights during the field campaign. The LLJs tended to form a couple hours after sunset and reach maximum strength between 03 and 07 UTC. The surface friction velocities show distinct local maxima during four nights when strong LLJs formed. Estimates of the convective boundary layer height and residual layer height are obtained through an analysis of the vertical gradient of the lidar signal-to-noise-ratio (SNR). Strong minimum in the SNR gradient often develops just above the surface after sunrise. This minimum is associated with the developing CBL, and increases rapidly during the early portion of the daytime period. On several days, this minimum continues to increase until about sunset. Secondary minima in the SNR gradient were also observed at higher altitudes, and are believed to be remnants of the CBL height from previous days, i.e. the residual layer height. The dual-Doppler analysis technique used in this study makes use of hourly averaged radial velocity data to produce three-dimensional grids of the horizontal velocity components, and the horizontal velocity variance. Visualization of horizontal and vertical cross sections of the dual-Doppler wind retrievals often indicated a jet-like flow feature over the Potomac River under southerly flow conditions. This linear flow feature is roughly aligned with the Potomac River corridor to the south of the confluence with the Anatostia River, and is most apparent at low levels (i.e. below ~150 m MSL). It is believed that this flow arises due to reduced drag over the water surface and when the large scale flow aligns with the Potomac River corridor. A so-called area-constrained VAD analysis generally confirmed the observations from the dual-Doppler analysis. When the large scale flow is southerly, wind speeds over the Potomac River are consistently larger than the at a site just to the west of the river for altitudes less than 100 m MSL. Above this level, the trend is somewhat less obvious. The data suggest that the depth of the wind speed maximum may be reduced by strong directional shear aloft.« less

Power Conversion Efficiency and Device Stability Improvement of Inverted Perovskite Solar Cells by Using a ZnO:PFN Composite Cathode Buffer Layer.

PubMed

Jia, Xiaorui; Zhang, Lianping; Luo, Qun; Lu, Hui; Li, Xueyuan; Xie, Zhongzhi; Yang, Yongzhen; Li, Yan-Qing; Liu, Xuguang; Ma, Chang-Qi

2016-07-20

We have demonstrated in this article that both power conversion efficiency (PCE) and performance stability of inverted planar heterojunction perovskite solar cells can be improved by using a ZnO:PFN nanocomposite (PFN: poly[(9,9-bis(3'-(N,N-dimethylamion)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctyl)-fluorene]) as the cathode buffer layer (CBL). This nanocomposite could form a compact and defect-less CBL film on the perovskite/PC61BM surface (PC61BM: phenyl-C61-butyric acid methyl ester). In addition, the high conductivity of the nanocomposite layer makes it works well at a layer thickness of 150 nm. Both advantages of the composite layer are helpful in reducing interface charge recombination and improving device performance. The power conversion efficiency (PCE) of the best ZnO:PFN CBL based device was measured to be 12.76%, which is higher than that of device without CBL (9.00%), or device with ZnO (7.93%) or PFN (11.30%) as the cathode buffer layer. In addition, the long-term stability is improved by using ZnO:PFN composite cathode buffer layer when compare to that of the reference cells. Almost no degradation of open circuit voltage (VOC) and fill factor (FF) was found for the device having ZnO:PFN, suggesting that ZnO:PFN is able to stabilize the interface property and consequently improve the solar cell performance stability.

Atmospheric Structure and Diurnal Variations at Low Altitudes in the Martian Tropics

NASA Astrophysics Data System (ADS)

Hinson, David P.; Spiga, A.; Lewis, S.; Tellmann, S.; Pätzold, M.; Asmar, S.; Häusler, B.

2013-10-01

We are using radio occultation measurements from Mars Express, Mars Reconnaissance Orbiter, and Mars Global Surveyor to characterize the diurnal cycle in the lowest scale height above the surface. We focus on northern spring and summer, using observations from 4 Martian years at local times of 4-5 and 15-17 h. We supplement the observations with results obtained from large-eddy simulations and through data assimilation by the UK spectral version of the LMD Mars Global Circulation Model. We previously investigated the depth of the daytime convective boundary layer (CBL) and its variations with surface elevation and surface properties. We are now examining unusual aspects of the temperature structure observed at night. Most important, predawn profiles in the Tharsis region contain an unexpected layer of neutral static stability at pressures of 200-300 Pa with a depth of 4-5 km. The mixed layer is bounded above by a midlevel temperature inversion and below by another strong inversion adjacent to the surface. The narrow temperature minimum at the base of the midlevel inversion suggests the presence of a water ice cloud layer, with the further implication that radiative cooling at cloud level can induce convective activity at lower altitudes. Conversely, nighttime profiles in Amazonis show no sign of a midlevel inversion or a detached mixed layer. These regional variations in the nighttime temperature structure appear to arise in part from large-scale variations in topography, which have several notable effects. First, the CBL is much deeper in the Tharsis region than in Amazonis, owing to a roughly 6-km difference in surface elevation. Second, large-eddy simulations show that daytime convection is not only deeper above Tharsis but also considerably more intense than it is in Amazonis. Finally, the daytime surface temperatures are comparable in the two regions, so that Tharsis acts as an elevated heat source throughout the CBL. These topographic effects are expected to enhance the vertical mixing of water vapor above elevated terrain, which might lead to the formation and regional confinement of nighttime clouds.

Temperature Inversions and Nighttime Convection in the Martian Tropics

NASA Astrophysics Data System (ADS)

Hinson, D. P.; Spiga, A.; Lewis, S.; Tellmann, S.; Paetzold, M.; Asmar, S. W.; Häusler, B.

2013-12-01

We are using radio occultation measurements from Mars Express, Mars Reconnaissance Orbiter, and Mars Global Surveyor to characterize the diurnal cycle in the lowest scale height above the surface. We focus on northern spring and summer, using observations from 4 Martian years at local times of 4-5 and 15-17 h. We supplement the observations with results obtained from large-eddy simulations and through data assimilation by the UK spectral version of the LMD Mars Global Circulation Model. We previously investigated the depth of the daytime convective boundary layer (CBL) and its variations with surface elevation and surface properties. We are now examining unusual aspects of the temperature structure observed at night. Most important, predawn profiles in the Tharsis region contain an unexpected layer of neutral static stability at pressures of 200-300 Pa with a depth of 4-5 km. The mixed layer is bounded above by a midlevel temperature inversion and below by another strong inversion adjacent to the surface. The sharp temperature minimum at the base of the midlevel inversion suggests the presence of a thin water ice cloud layer, with the further implication that radiative cooling at cloud level can induce convective activity at lower altitudes. Conversely, nighttime profiles in Amazonis show no sign of a midlevel inversion or a detached mixed layer. These regional variations in the nighttime temperature structure appear to arise in part from large-scale variations in topography, which have several notable effects. First, the CBL is much deeper in the Tharsis region than in Amazonis, owing to a roughly 6-km difference in surface elevation. Second, large-eddy simulations show that daytime convection is not only deeper above Tharsis but also considerably more intense than it is in Amazonis. Finally, the daytime surface temperatures are comparable in the two regions, so that Tharsis acts as an elevated heat source throughout the CBL. These topographic effects are expected to enhance the vertical mixing of water vapor above elevated terrain, which might lead to the formation and regional confinement of nighttime clouds.

Influence of Saharan dust outbreaks and atmospheric stability upon vertical profiles of size-segregated aerosols and water vapor

NASA Astrophysics Data System (ADS)

Giménez, Joaquín; Pastor, Carlos; Castañer, Ramón; Nicolás, José; Crespo, Javier; Carratalá, Adoración

2010-01-01

Vertical profiles of aerosols and meteorological parameters were obtained using a hot air balloon and motorized paraglider. They were studied under anticyclonic conditions in four different contexts. Three flights occurred near sunrise, and one took place in the central hours of the day. The effects of North African dust intrusions were analyzed, whose entrance to the study area took place above the Stable Boundary Layer (SBL) in flight 1 and below it in flight 2. These flights have been compared with a non-intrusion situation (flight 3). A fourth flight characterized the profiles in the central hours of the day with a well-formed Convective Boundary Layer (CBL). With respect to the particle number distribution, the results show that not all sizes increase within the presence of an intrusion; during the first flight the smallest particles were not affected. The particle sizes affected in the second flight fell within the 0.35-2.5 μm interval. Under situations of convective dynamics, the reduction percentage of the particle number concentration reduces with increasing altitude, independently of their size, with respect to stability conditions. The negative vertical gradient for aerosols and water vapor, characteristic of a highly stable SBL (flight 3) becomes a constant profile within a CBL (flight 4). There are two situations that seem to alter the negative vertical gradient of the water vapor mixing ratio within the SBL: the presence of an intrusion and the possible stratification of the SBL based on different degrees of stability.

High performance planar p-i-n perovskite solar cells with crown-ether functionalized fullerene and LiF as double cathode buffer layers

NASA Astrophysics Data System (ADS)

Liu, Xiaodong; Lei, Ming; Zhou, Yi; Song, Bo; Li, Yongfang

2015-08-01

Double cathode buffer layers (CBLs) composed of fullerene derivative functionalized with a crown-ether end group in its side chain (denoted as PCBC) and a LiF layer were introduced between the PCBM acceptor layer and the top cathode in planar p-i-n perovskite solar cells (pero-SCs) based on CH3NH3PbI3-XClX. The devices with the PCBC/LiF double CBLs showed significant improvements in power conversion efficiency (PCE) and long-term stability when compared to the device with LiF single CBL. Through optimizing the spin-coating speed of PCBC, a maximum PCE of 15.53% has been achieved, which is approximately 15% higher than that of the device with single LiF CBL. The remarkable improvement in PCE can be attributed to the formation of a better ohmic contact in the CBL between PCBC and LiF/Al electrode arising from the dipole moment of PCBC, leading to the enhanced fill factor and short-circuit current density (Jsc). Besides the PCE, the long-term stability of the devices with PCBC interlayer is also superior to that of the device with LiF single CBL, which is due to the more effective protection for the perovskite/PCBM interface.

Enhanced light extraction efficiency of GaN-based light-emittng diodes by nitrogen implanted current blocking layer

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

Kim, Yong Deok; Oh, Seung Kyu; Park, Min Joo

Highlights: • A nitrogen implanted current-blocking layer was successfully demonstrated. • Light-extraction efficiency and radiant intensity was increased by more than 20%. • Ion implantation was successfully implemented in GaN based light-emitting diodes. - Abstract: GaN-based light emitting diodes (LEDs) with a nitrogen implanted current-blocking layer (CBL) were successfully demonstrated for improving the light extraction efficiency (LEE) and radiant intensity. The LEE and radiant intensity of the LEDs with a shallow implanted CBL with nitrogen was greatly increased by more than 20% compared to that of a conventional LED without the CBL due to an increase in the effective currentmore » path, which reduces light absorption at the thick p-pad electrode. Meanwhile, deep implanted CBL with a nitrogen resulted in deterioration of the LEE and radiant intensity because of formation of crystal damage, followed by absorption of the light generated at the multi-quantum well(MQW). These results clearly suggest that ion implantation method, which is widely applied in the fabrication of Si based devices, can be successfully implemented in the fabrication of GaN based LEDs by optimization of implanted depth.« less

All-ion-implanted planar-gate current aperture vertical Ga2O3 MOSFETs with Mg-doped blocking layer

NASA Astrophysics Data System (ADS)

Wong, Man Hoi; Goto, Ken; Morikawa, Yoji; Kuramata, Akito; Yamakoshi, Shigenobu; Murakami, Hisashi; Kumagai, Yoshinao; Higashiwaki, Masataka

2018-06-01

A vertical β-Ga2O3 metal–oxide–semiconductor field-effect transistor featuring a planar-gate architecture is presented. The device was fabricated by an all-ion-implanted process without requiring trench etching or epitaxial regrowth. A Mg-ion-implanted current blocking layer (CBL) provided electrical isolation between the source and the drain except at an aperture opening through which drain current was conducted. Successful transistor action was realized by gating a Si-ion-implanted channel above the CBL. Thermal diffusion of Mg induced a large source–drain leakage current through the CBL, which resulted in compromised off-state device characteristics as well as a reduced peak extrinsic transconductance compared with the results of simulations.

High performance planar p-i-n perovskite solar cells with crown-ether functionalized fullerene and LiF as double cathode buffer layers

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

Liu, Xiaodong; Zhou, Yi, E-mail: yizhou@suda.edu.cn, E-mail: songbo@suda.edu.cn, E-mail: liyf@iccas.ac.cn; Song, Bo, E-mail: yizhou@suda.edu.cn, E-mail: songbo@suda.edu.cn, E-mail: liyf@iccas.ac.cn

2015-08-10

Double cathode buffer layers (CBLs) composed of fullerene derivative functionalized with a crown-ether end group in its side chain (denoted as PCBC) and a LiF layer were introduced between the PCBM acceptor layer and the top cathode in planar p-i-n perovskite solar cells (pero-SCs) based on CH{sub 3}NH{sub 3}PbI{sub 3−X}Cl{sub X}. The devices with the PCBC/LiF double CBLs showed significant improvements in power conversion efficiency (PCE) and long-term stability when compared to the device with LiF single CBL. Through optimizing the spin-coating speed of PCBC, a maximum PCE of 15.53% has been achieved, which is approximately 15% higher than thatmore » of the device with single LiF CBL. The remarkable improvement in PCE can be attributed to the formation of a better ohmic contact in the CBL between PCBC and LiF/Al electrode arising from the dipole moment of PCBC, leading to the enhanced fill factor and short-circuit current density (J{sub sc}). Besides the PCE, the long-term stability of the devices with PCBC interlayer is also superior to that of the device with LiF single CBL, which is due to the more effective protection for the perovskite/PCBM interface.« less

Low turbulence/high efficiency cyclone separators: Facility qualification results

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

Razgaitis, R.; Paul, D.D.; Bioarski, A.A.

1985-01-01

The objective of this work is to experimentally investigate the near-wall turbulent flow-fields characteristic of cyclone separators in order to determine the influence of wall-originating turbulence on the separation of fine particles. In particular, seven turbulence suppression concepts will be evaluated with reference to a well-established baseline condition. Concepts which appear attractive will be studied and characterized in more detail. The work accomplished to date is principally the design, construction, and qualification of two of the facilities that will be used to study the various concepts of turbulence suppression. The qualification of the primary facility, the Cyclonic Wind Tunnel (CWT),more » has required the development and adaptation of laser Doppler velocimetry (LDV) to perform simultaneous two-dimensional turbulence measurements in a highly swirling flow. A companion facility to the CWT is the Curvilinear Boundary Layer (CBL) apparatus. The purpose of the CBL is to provide a thick, visually-observable near-wall flow region under dynamically similar conditions to the CWT to that a physical understanding of the turbulence suppression process can be obtained. 9 refs., 15 figs.« less

A Novel Concept for Observing Land-Surface-Atmosphere Feedback Based on a Synergy of Scanning Lidar Systems

NASA Astrophysics Data System (ADS)

Wulfmeyer, V.; Turner, D. D.; Mauder, M.; Behrendt, A.; Ingwersen, J.; Streck, T.

2015-12-01

Improved simulations of land-surface-atmosphere interaction are fundamental for improving weather forecast and climate models. This requires observations of 2D fields of surface fluxes and the 3D structure of the atmospheric boundary layer simultaneously. A novel strategy is introduced for studying land-surface exchange and entrainment processes in the convective boundary layer (CBL) over complex terrain by means of a new generation of remote sensing systems. The sensor synergy consists of scanning Doppler lidar (DL), water-vapor differential absorption lidar (WVDIAL), and temperature rotational Raman lidar (TRRL) systems supported by surface in-situ measurements. The 2D measurements of surface fluxes are realized by the operation of a DL, a WVDIAL, and a TRRL along the same line-of-sight (LOS) in a range-height-indicator (RHI) mode whereas the other DL is performing a series of cross track RHI scans along this LOS. This new setup enables us to determine the friction velocity as well as surface sensible and latent heat fluxes by closing the complete set of Monin-Obukhov similarity relationships under a variety of surface layer stability conditions and different land cover and soil properties. As this closure is performed at all DL crossing points along the LOS, this is a strategy towards a 2D mapping of surface fluxes entirely based on remote sensing systems. Further details are presented at the conference. The second configuration is the simultaneous vertical profiling of vertical wind, humidity and temperature by DL, WVDIAL and TRRL so that latent heat and sensible heat flux profiles as well as a variety of different turbulent moments can be measured in the CBL. Consequently, by alternating of RHI scanning and vertical pointing modes, entrainment fluxes and surface fluxes can be measured almost simultaneously. This novel strategy has been realized for the first time during the Surface Atmospheric Boundary Layer Exchange (SABLE) campaign in the Kraichgau region, north of the Black Forest low mountain region, in Southern Germany in August 2014 (see https://klimawandel.uni-hohenheim.de/start?&L=1). A further refined design of this experiment is planned at the Atmospheric Radiation Measurement Program (ARM) Southern Great Plains (SGP) site in summer 2016.

Ca/Alq3 hybrid cathode buffer layer for the optimization of organic solar cells based on a planar heterojunction

NASA Astrophysics Data System (ADS)

El Jouad, Z.; Barkat, L.; Stephant, N.; Cattin, L.; Hamzaoui, N.; Khelil, A.; Ghamnia, M.; Addou, M.; Morsli, M.; Béchu, S.; Cabanetos, C.; Richard-Plouet, M.; Blanchard, P.; Bernède, J. C.

2016-11-01

Use of efficient anode cathode buffer layer (CBL) is crucial to improve the efficiency of organic photovoltaic cells. Here we show that using a double CBL, Ca/Alq3, allows improving significantly cell performances. The insertion of Ca layer facilitates electron harvesting and blocks hole collection, leading to improved charge selectivity and reduced leakage current, whereas Alq3 blocks excitons. After optimisation of this Ca/Alq3 CBL using CuPc as electron donor, it is shown that it is also efficient when SubPc is substituted to CuPc in the cells. In that case we show that the morphology of the SubPc layer, and therefore the efficiency of the cells, strongly depends on the deposition rate of the SubPc film. It is necessary to deposit slowly (0.02 nm/s) the SubPc films because at higher deposition rate (0.06 nm/s) the films are porous, which induces leakage currents and deterioration of the cell performances. The SubPc layers whose formations are kinetically driven at low deposition rates are more uniform, whereas those deposited faster exhibit high densities of pinholes.

Quantitative Assessment of Microstructural Changes of the Retina in Infants With Congenital Zika Syndrome.

PubMed

Aleman, Tomas S; Ventura, Camila V; Cavalcanti, Milena M; Serrano, Leona W; Traband, Anastasia; Nti, Akosua A; Gois, Adriana L; Bravo-Filho, Vasco; Martins, Thayze T; Nichols, Charles W; Maia, Mauricio; Belfort, Rubens

2017-10-01

A better pathophysiologic understanding of the neurodevelopmental abnormalities observed in neonates exposed in utero to Zika virus (ZIKV) is needed to develop treatments. The retina as an extension of the diencephalon accessible to in vivo microcopy with spectral-domain optical coherence tomography (SD-OCT) can provide an insight into the pathophysiology of congenital Zika syndrome (CZS). To quantify the microstructural changes of the retina in CZS and compare these changes with those of cobalamin C (cblC) deficiency, a disease with potential retinal maldevelopment. This case series included 8 infants with CZS and 8 individuals with cblC deficiency. All patients underwent ophthalmologic evaluation at 2 university teaching hospitals and SD-OCT imaging in at least 1 eye. Patients with cblC deficiency were homozygous or compound heterozygotes for mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Data were collected from January 1 to March 17, 2016, for patients with CZS and from May 4, 2015, to April 23, 2016, for patients with cblC deficiency. The SD-OCT cross-sections were segmented using automatic segmentation algorithms embedded in the SD-OCT systems. Each retinal layer thickness was measured at critical eccentricities using the position of the signal peaks and troughs on longitudinal reflectivity profiles. Eight infants with CZS (5 girls and 3 boys; age range, 3-5 months) and 8 patients with cblC deficiency (3 girls and 5 boys; age range, 4 months to 15 years) were included in the analysis. All 8 patients with CZS had foveal abnormalities in the analyzed eyes (8 eyes), including discontinuities of the ellipsoid zone, thinning of the central retina with increased backscatter, and severe structural disorganization, with 3 eyes showing macular pseudocolobomas. Pericentral retina with normal lamination showed a thinned (<30% of normal thickness) ganglion cell layer (GCL) that colocalized in 7 of 8 eyes with a normal photoreceptor layer. The inner nuclear layer was normal or had borderline thinning. The central retinal degeneration was similar to that of cblC deficiency. Congenital Zika syndrome showed a central retinal degeneration with severe GCL loss, borderline inner nuclear layer thinning, and less prominent photoreceptor loss. The findings provide the first, to date, in vivo evidence in humans for possible retinal maldevelopment with a predilection for retinal GCL loss in CZS, consistent with a murine model of the disease and suggestive of in utero depletion of this neuronal population as a consequence of Zika virus infection.

Characterization of Water Vapor Fluxes by the Raman Lidar System Basil and the Univeristy of Cologne Wind Lidar in the Frame of the HD(CP)2 Observational Prototype Experiment - Hope

NASA Astrophysics Data System (ADS)

Di Girolamo, Paolo; Summa, Donato; Stelitano, Dario; Cacciani, Marco; Scoccione, Andrea; Schween, Jan H.

2016-06-01

Measurements carried out by the Raman lidar system BASIL and the University of Cologne wind lidar are reported to demonstrate the capability of these instruments to characterize water vapour fluxes within the Convective Boundary Layer (CBL). In order to determine the water vapour flux vertical profiles, high resolution water vapour and vertical wind speed measurements, with a temporal resolution of 1 sec and a vertical resolution of 15-90, are considered. Measurements of water vapour flux profiles are based on the application of covariance approach to the water vapour mixing ratio and vertical wind speed time series. The algorithms are applied to a case study (IOP 11, 04 May 2013) from the HD(CP)2 Observational Prototype Experiment (HOPE), held in Central Germany in the spring 2013. For this case study, the water vapour flux profile is characterized by increasing values throughout the CBL with lager values (around 0.1 g/kg m/s) in the entrainment region. The noise errors are demonstrated to be small enough to allow the derivation of water vapour flux profiles with sufficient accuracy.

Lidar Measurements of Wind, Moisture and Boundary Layer Evolution in a Dryline During IHOP2002

NASA Technical Reports Server (NTRS)

Demoz, Belay; Evans, Keith; DiGirolamo, Paolo; Wang, Zhien; Whiteman, David; Schwemmer, Geary; Gentry, Bruce; Miller, David

2003-01-01

Variability in the convective boundary layer moisture, wind and temperature fields and their importance in the forecasting and understanding of storms have been discussed in the literature. These variations have been reported in relation to frontal zones, stationary boundaries and during horizontal convective rolls. While all three vary substantially in the convective boundary layer, moisture poses a particular challenge. Moisture or water vapor concentration (expressed as a mass mixing ratio, g/kg), is conserved in all meteorological processes except condensation and evaporation. The water vapor mixing ratio often remains distinct across an air -mass boundary even when the temperature difference is indistinct. These properties make it an ideal choice in visualizing and understanding many of the atmosphere's dynamic features. However, it also presents a unique measurement challenge because water vapor content can vary by more than three orders of magnitude in the troposphere. Characterization of the 3D-distribution of water vapor is also difficult as water vapor observations can suffer from large sampling errors and substantial variability both in the vertical and horizontal. This study presents groundbased measurements of wind, boundary layer structure and water vapor mixing ratio measurements observed by three co-located lidars. This presentation will focus on the evolution and variability of moisture and wind in the boundary layer during a dry line event that occurred on 22 May 2002. These data sets and analyses are unique in that they combine simultaneous measurements of wind, moisture and CBL structure to study the detailed thermal variability in and around clear air updrafts during a dryline event. It will quantify the variation caused by, in and around buoyant plumes and across a dryline. The data presented here were collected in the panhandle of Oklahoma as part of the International BO Project (IHOP-2002), a field experiment that took place over the Southern Great Plains (SGP) of the United States from 13 May to 30 June 2002. The chief goal of IHOP-2002 is to improve characterization of the four-dimensional (4-D) distribution of water vapor and its application to improving the understanding and prediction of convection

Lidar Measurements of Wind, Moisture, and Boundary Layer Evolution in a Dry Line during 1HOP 2002

NASA Technical Reports Server (NTRS)

Demoz, Belay; Evans, Keith; DiGirolamo, Paolo; Wang, Zhe-In; Whiteman, David; Schwemmer, Geary; Gentry, Bruce; Miller, David; Palm, Stephen

2002-01-01

Variability in the convective boundary layer moisture, wind and temperature fields and their importance in the forecasting and understanding of storms have been discussed in the literature. These . variations have been reported in relation to frontal zones, stationary boundaries and during horizontal convective rolls. While all three vary substantially in the convective boundary layer, moisture poses a particular challenge. Moisture or water vapor concentration (expressed as a mass mixing ratio, g/kg), is conserved in all meteorological processes except condensation and evaporation. The water vapor mixing ratio often remains distinct across an air-mass boundary even when the temperature difference is indistinct. These properties make it an ideal choice in visualizing and understanding many of the atmosphere's dynamic features. However, it also presents a unique measurement challenge because water vapor content can vary by more than three orders of magnitude in the troposphere. Characterization of the 3D-distribution of water vapor is also difficult as water vapor observations can suffer from large sampling errors and substantial variability both in the vertical and horizontal. This study presents ground-based measurements of wind, boundary layer structure and water vapor mixing ratio measurements observed by three co-located lidars. This presentation will focus on the evolution and variability of moisture and wind in the boundary layer during a dry line event that occurred on 22 May 2002. These data sets and analyses are unique in that they combine simultaneous measurements of wind, moisture and CBL structure to study the detailed thermal variability in and around clear air updrafts during a dryline event. It will quantify the variation caused by, in and around buoyant plumes and across a dryline. The data presented here were collected in the panhandle of Oklahoma as part of the International H2O Project (MOP-2002), a field experiment that took place over the Southern Great Plains (SGP) of the United States from 13 May to 30 June 2002. The chief goal of MOP-2002 is to improve characterization of the four-dimensional (4-D) distribution of water vapor and its application to improving the understanding and prediction of convection

Effects of current crowding on light extraction efficiency of conventional GaN-based light-emitting diodes.

PubMed

Cao, Bin; Li, Shuiming; Hu, Run; Zhou, Shengjun; Sun, Yi; Gan, Zhiying; Liu, Sheng

2013-10-21

Current crowding effects (CCEs) on light extraction efficiency (LEE) of conventional GaN-based light-emitting diodes (LEDs) are analyzed through Monte Carlo ray-tracing simulation. The non-uniform radiative power distribution of the active layer of the Monte Carlo model is obtained based on the current spreading theory and rate equation. The simulation results illustrate that CCE around n-pad (n-CCE) has little effect on LEE, while CCE around p-pad (p-CCE) results in a notable LEE droop due to the significant absorption of photons emitted under p-pad. LEE droop is alleviated by a SiO₂ current blocking layer (CBL) and reflective p-pad. Compared to the conventional LEDs without CBL, the simulated LEE of LEDs with CBL at 20 A/cm² and 70 A/cm² is enhanced by 7.7% and 19.0%, respectively. It is further enhanced by 7.6% and 11.4% after employing a reflective p-pad due to decreased absorption. These enhancements are in accordance with the experimental results. Output power of LEDs with CBL is enhanced by 8.7% and 18.2% at 20 A/cm² and 70 A/cm², respectively. And the reflective p-pad results in a further enhancement of 8.9% and 12.7%.

Automatic remote sensing detection of the convective boundary layer structure over flat and complex terrain using the novel PathfinderTURB algorithm

NASA Astrophysics Data System (ADS)

Poltera, Yann; Martucci, Giovanni; Hervo, Maxime; Haefele, Alexander; Emmenegger, Lukas; Brunner, Dominik; Henne, stephan

2016-04-01

We have developed, applied and validated a novel algorithm called PathfinderTURB for the automatic and real-time detection of the vertical structure of the planetary boundary layer. The algorithm has been applied to a year of data measured by the automatic LIDAR CHM15K at two sites in Switzerland: the rural site of Payerne (MeteoSwiss station, 491 m, asl), and the alpine site of Kleine Scheidegg (KSE, 2061 m, asl). PathfinderTURB is a gradient-based layer detection algorithm, which in addition makes use of the atmospheric variability to detect the turbulent transition zone that separates two low-turbulence regions, one characterized by homogeneous mixing (convective layer) and one above characterized by free tropospheric conditions. The PathfinderTURB retrieval of the vertical structure of the Local (5-10 km, horizontal scale) Convective Boundary Layer (LCBL) has been validated at Payerne using two established reference methods. The first reference consists of four independent human-expert manual detections of the LCBL height over the year 2014. The second reference consists of the values of LCBL height calculated using the bulk Richardson number method based on co-located radio sounding data for the same year 2014. Based on the excellent agreement with the two reference methods at Payerne, we decided to apply PathfinderTURB to the complex-terrain conditions at KSE during 2014. The LCBL height retrievals are obtained by tilting the CHM15K at an angle of 19 degrees with respect to the horizontal and aiming directly at the Sphinx Observatory (3580 m, asl) on the Jungfraujoch. This setup of the CHM15K and the processing of the data done by the PathfinderTURB allows to disentangle the long-transport from the local origin of gases and particles measured by the in-situ instrumentation at the Sphinx Observatory. The KSE measurements showed that the relation amongst the LCBL height, the aerosol layers above the LCBL top and the gas + particle concentration is all but trivial. Retrieving the structure of the LCBL along the line of sight connecting KSE to the Sphinx Observatory allows to monitor when the LCBL top reaches the altitude of the in-situ instrumentation at the Sphinx and to relate the measured gas + particle concentration with the locally-produced aerosols. On the other hand, when the LCBL top is lower than the Sphinx altitude, the measured concentration of gas + particle at the Sphinx is either due to long transport of aerosols (>100 km) or to the residual aerosol layer reaching the Sphinx's height or to non-local (> 5 km and <100 km) CBL aerosols advected at the Sphinx's height. Except when the aerosol layer is decoupled from the LCBL underneath, for all the other cases the CHM15K sees the probed layer as a continuous (not necessarily well-mixed) aerosol layer starting at the KSE surface. The depth of this continuous layer has been retrieved by the PathfinderTURB and related with the black carbon absorption coefficient measured at Sphinx. The result of the comparison shows clearly that the depth of the layer is well correlated with the absorption coefficient measured at the Sphinx. This is an important result that allows not only to retrieve real-time CBL heights in an automatic and trustworthy way, but also to adapt the retrievals to complex-terrain and complex-atmospheric conditions with customized tilted instrument settings.

Numerical Investigation of a Heated, Sheared Planetary Boundary Layer

NASA Astrophysics Data System (ADS)

Liou, Yu-Chieng

1996-01-01

A planetary boundary layer (PBL) developed on 11 July, 1987 during the First International Satellites Land Surface Climatology Project (ISLSCP) Field Experiment (FIFE) is investigated numerically by a two dimensional and a three dimensional large eddy simulation (LES) model. Most of the simulated mean and statistical properties are utilized to compare or verify against the observational results extracted from single Doppler lidar scans conducted by Gal-Chen et al. (1992) on the same day. Through the methods of field measurements and numerical simulations, it is found that this PBL, in contrast to the well-known convective boundary layer (CBL), is driven by not only buoyancy but also wind shear. Large eddies produced by the surface heating, as well as internal gravity waves excited by the convection, are both present in the boundary layer. The most unique feature is that in the stable layer, the momentum flux ({overlinerm u^' w^'}), transported by the gravity waves, is counter-gradient. The occurrence of this phenomenon is interpreted by Gal-Chen et al. (1992) using the theory of critical layer singularity, and is confirmed by the numerical simulations in this study. Qualitative agreements are achieved between the model-generated and lidar-derived results. However, quantitative comparisons are less satisfactory. The most serious discrepancy is that in the stable layer the magnitudes of the observed momentum flux ({overlinerm u^ ' w^'}) and vertical velocity variance ({overlinerm w^'^2}) are much larger than their simulated counterparts. Nevertheless, through the technique of numerical simulation, evidence is collected to show inconsistencies among the observations. Thus, the lidar measurements of {overline rm u^' w^'} and {overlinerm w^ '^2} seem to be doubtful. A Four Dimensional Data Assimilation (FDDA) experiment is performed in order to connect the evolution of the model integration with the observations. The results indicate that the dynamical relaxation (nudging) scheme appears to be an appropriate method by which the observed mean quantities such as mean wind ({overline u}) and potential temperature ({ overlinetheta}) can be assimilated into the model without causing data rejection.

Retinal Structure in Cobalamin C Disease: Mechanistic and Therapeutic Implications.

PubMed

Aleman, Tomas S; Brodie, Frank; Garvin, Christopher; Gewaily, Dina Y; Ficicioglu, Can H; Mills, Monte D; Forbes, Brian J; Maguire, Albert M; Davidson, Stefanie L

2015-01-01

To describe the retinal structure in a patient with cobalamin C (cblC) disease. A 13-year-old male patient diagnosed with cblC disease during a perinatal metabolic screening prompted by jaundice and hypotony underwent ophthalmic examinations, electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT). The patient carried a homozygous (c.271dupA) mutation in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. At age 3 months he had a normal eye exam. A pigmentary maculopathy progressed to chorioretinal atrophy from 5-10 months. ERG at 7 months was normal. A nystagmus remained stable since the age of 2 years. At age 13, visual acuity was 20/250 (right eye) and 20/400 (left eye), with a +5.00 D correction, a level of vision maintained since first measurable at age 5 years. SD-OCT showed bilateral macular coloboma-like lesions; there was also a thickened surface layer with ganglion cell layer thinning. Photoreceptor outer segment loss and thinning of the outer nuclear layer (ONL) transitioned to regions with no discernible ONL with a delaminated, thickened, inner retina. A thick surface layer near the optic nerve resembling an immature retina and an initially normal macula that rapidly developed coloboma-like lesions suggest there may be an interference with retinal/foveal development in cblC, a mechanism of maculopathy that may be shared by other early onset retinal degenerations. Photoreceptor loss and inner retinal remodeling confirm associated photoreceptor degeneration.

Interaction between turbulent flow and sea breeze front over urban-like coast in large-eddy simulation

NASA Astrophysics Data System (ADS)

Jiang, Ping; Wen, Zhiping; Sha, Weiming; Chen, Guixing

2017-05-01

Turbulent flow and its interaction with a sea breeze front (SBF) over an urban-like coast with a regular block array were investigated using a building-resolving computational fluid dynamics model. It was found that during daytime with an offshore ambient flow, streaky turbulent structures tended to grow within the convective boundary layer (CBL) over a warm urban surface ahead of the SBF. The structures were organized as streamwise streaks at an interval of a few hundred meters, which initiated at the rooftop level with strong wind shear and strengthens in the CBL with moderate buoyancy. The streaks then interacted with the onshore-propagating SBF as it made landfall. The SBF, which was initially characterized as a shallow and quasi-linear feature over the sea, developed three-dimensional structures with intensified updrafts at an elevated frontal head after landfall. Frontal updrafts were locally enhanced at intersections where the streaks merged with the SBF, which greatly increased turbulent fluxes at the front. The frontal line was irregular because of merging, tilting, and transformation effects of vorticity associated with streaky structures. Inland penetration of the SBF was slowed by the frictional effect of urban-like surfaces and turbulent flow on land. The overall SBF intensity weakened after the interaction with turbulent flow. These findings aid understanding of local weather over coastal cities during typical sea breeze conditions.

Loss of Cbl-PI3K interaction enhances osteoclast survival due to p21-Ras mediated PI3K activation independent of Cbl-b.

PubMed

Adapala, Naga Suresh; Barbe, Mary F; Tsygankov, Alexander Y; Lorenzo, Joseph A; Sanjay, Archana

2014-07-01

Cbl family proteins, Cbl and Cbl-b, are E3 ubiquitin ligases and adaptor proteins, which play important roles in bone-resorbing osteoclasts. Loss of Cbl in mice decreases osteoclast migration, resulting in delayed bone development where as absence of Cbl-b decreases bone volume due to hyper-resorptive osteoclasts. A major structural difference between Cbl and Cbl-b is tyrosine 737 (in YEAM motif) only on Cbl, which upon phosphorylation interacts with the p85 subunit of phosphatidylinositol-3 Kinase (PI3K). In contrast to Cbl(-/-) and Cbl-b(-/-) , mice lacking Cbl-PI3K interaction due to a Y737F (tyrosine to phenylalanine, YF) mutation showed enhanced osteoclast survival, but defective bone resorption. To investigate whether Cbl-PI3K interaction contributes to distinct roles of Cbl and Cbl-b in osteoclasts, mice bearing CblY737F mutation in the Cbl-b(-/-) background (YF/YF;Cbl-b(-/-) ) were generated. The differentiation and survival were augmented similarly in YF/YF and YF/YF;Cbl-b(-/-) osteoclasts, associated with enhanced PI3K signaling suggesting an exclusive role of Cbl-PI3K interaction, independent of Cbl-b. In addition to PI3K, the small GTPase Ras also regulates osteoclast survival. In the absence of Cbl-PI3K interaction, increased Ras GTPase activity and Ras-PI3K binding were observed and inhibition of Ras activation attenuated PI3K mediated osteoclast survival. In contrast to differentiation and survival, increased osteoclast activity observed in Cbl-b(-/-) mice persisted even after introduction of the resorption-defective YF mutation in YF/YF;Cbl-b(-/-) mice. Hence, Cbl and Cbl-b play mutually exclusive roles in osteoclasts. Whereas Cbl-PI3K interaction regulates differentiation and survival, bone resorption is predominantly regulated by Cbl-b in osteoclasts. © 2014 Wiley Periodicals, Inc.

A novel CBL-Bflox/flox mouse model allows tissue-selective fully conditional CBL/CBL-B double-knockout: CD4-Cre mediated CBL/CBL-B deletion occurs in both T-cells and hematopoietic stem cells

PubMed Central

Goetz, Benjamin; An, Wei; Mohapatra, Bhopal; Zutshi, Neha; Iseka, Fany; Storck, Matthew D.; Meza, Jane; Sheinin, Yuri; Band, Vimla; Band, Hamid

2016-01-01

CBL-family ubiquitin ligases are critical negative regulators of tyrosine kinase signaling, with a clear redundancy between CBL and CBL-B evident in the immune cell and hematopoietic stem cell studies. Since CBL and CBL-B are negative regulators of immune cell activation, elimination of their function to boost immune cell activities could be beneficial in tumor immunotherapy. However, mutations of CBL are associated with human leukemias, pointing to tumor suppressor roles of CBL proteins; hence, it is critical to assess the tumor-intrinsic roles of CBL and CBL-B in cancers. This has not been possible since the only available whole-body CBL-B knockout mice exhibit constitutive tumor rejection. We engineered a new CBL-Bflox/flox mouse, combined this with an existing CBLflox/flox mouse to generate CBLflox/flox; CBL-Bflox/flox mice, and tested the tissue-specific concurrent deletion of CBL and CBL-B using the widely-used CD4-Cre transgenic allele to produce a T-cell-specific double knockout. Altered T-cell development, constitutive peripheral T-cell activation, and a lethal multi-organ immune infiltration phenotype largely resembling the previous Lck-Cre driven floxed-CBL deletion on a CBL-B knockout background establish the usefulness of the new model for tissue-specific CBL/CBL-B deletion. Unexpectedly, CD4-Cre-induced deletion in a small fraction of hematopoietic stem cells led to expansion of certain non-T-cell lineages, suggesting caution in the use of CD4-Cre for T-cell-restricted gene deletion. The establishment of a new model of concurrent tissue-selective CBL/CBL-B deletion should allow a clear assessment of the tumor-intrinsic roles of CBL/CBL-B in non-myeloid malignancies and help test the potential for CBL/CBL-B inactivation in immunotherapy of tumors. PMID:27276677

The C-terminal domain of CblD interacts with CblC and influences intracellular cobalamin partitioning.

PubMed

Gherasim, Carmen; Hannibal, Luciana; Rajagopalan, Deepa; Jacobsen, Donald W; Banerjee, Ruma

2013-05-01

Mutations in cobalamin or B12 trafficking genes needed for cofactor assimilation and targeting lead to inborn errors of cobalamin metabolism. The gene corresponding to one of these loci, cblD, affects both the mitochondrial and cytoplasmic pathways for B12 processing. We have demonstrated that fibroblast cell lines from patients with mutations in CblD, can dealkylate exogenously supplied methylcobalamin (MeCbl), an activity catalyzed by the CblC protein, but show imbalanced intracellular partitioning of the cofactor into the MeCbl and 5'-deoxyadenosylcobalamin (AdoCbl) pools. These results confirm that CblD functions downstream of CblC in the cofactor assimilation pathway and that it plays an important role in controlling the traffic of the cofactor between the competing cytoplasmic and mitochondrial routes for MeCbl and AdoCbl synthesis, respectively. In this study, we report the interaction of CblC with four CblD protein variants with variable N-terminal start sites. We demonstrate that a complex between CblC and CblD can be isolated particularly under conditions that permit dealkylation of alkylcobalamin by CblC or in the presence of the corresponding dealkylated and oxidized product, hydroxocobalamin (HOCbl). A weak CblC·CblD complex is also seen in the presence of cyanocobalamin. Formation of the CblC·CblD complex is observed with all four CblD variants tested suggesting that the N-terminal 115 residues missing in the shortest variant are not essential for this interaction. Furthermore, limited proteolysis of the CblD variants indicates the presence of a stable C-terminal domain spanning residues ∼116-296. Our results are consistent with an adapter function for CblD, which in complex with CblC·HOCbl, or possibly the less oxidized CblC·cob(II)alamin, partitions the cofactor between AdoCbl and MeCbl assimilation pathways. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The C-terminal domain of CblD interacts with CblC and influences intracellular cobalamin partitioning☆

PubMed Central

Gherasim, Carmen; Hannibal, Luciana; Rajagopalan, Deepa; Jacobsen, Donald W.; Banerjee, Ruma

2013-01-01

Mutations in cobalamin or B12 trafficking genes needed for cofactor assimilation and targeting lead to inborn errors of cobalamin metabolism. The gene corresponding to one of these loci, cblD, affects both the mitochondrial and cytoplasmic pathways for B12 processing. We have demonstrated that fibroblast cell lines from patients with mutations in CblD, can dealkylate exogenously supplied methylcobalamin (MeCbl), an activity catalyzed by the CblC protein, but show imbalanced intracellular partitioning of the cofactor into the MeCbl and 5′-deoxyadenosylcobalamin (AdoCbl) pools. These results confirm that CblD functions downstream of CblC in the cofactor assimilation pathway and that it plays an important role in controlling the traffic of the cofactor between the competing cytoplasmic and mitochondrial routes for MeCbl and AdoCbl synthesis, respectively. In this study, we report the interaction of CblC with four CblD protein variants with variable N-terminal start sites. We demonstrate that a complex between CblC and CblD can be isolated particularly under conditions that permit dealkylation of alkylcobalamin by CblC or in the presence of the corresponding dealkylated and oxidized product, hydroxocobalamin (HOCbl). A weak CblC·CblD complex is also seen in the presence of cyanocobalamin. Formation of the CblC·CblD complex is observed with all four CblD variants tested suggesting that the N-terminal 115 residues missing in the shortest variant are not essential for this interaction. Furthermore, limited proteolysis of the CblD variants indicates the presence of a stable C-terminal domain spanning residues ~116–296. Our results are consistent with an adapter function for CblD, which in complex with CblC·HOCbl, or possibly the less oxidized CblC·cob(II)alamin, partitions the cofactor between AdoCbl and MeCbl assimilation pathways. PMID:23415655

Cbl-family ubiquitin ligases and their recruitment of CIN85 are largely dispensable for epidermal growth factor receptor endocytosis

PubMed Central

Ahmad, Gulzar; Mohapatra, Bhopal; Schulte, Nancy A.; Nadeau, Scott; Luan, Haitao; Zutshi, Neha; Tom, Eric; Ortega-Cava, Cesar; Tu, Chun; Sanada, Masashi; Ogawa, Seishi; Toews, Myron L.; Band, Vimla; Band, Hamid

2014-01-01

Members of the Casitas B-Lineage Lymphoma (Cbl) family (Cbl, Cbl-b and Cbl-c) of ubiquitin ligases serve as negative regulators of receptor tyrosine kinases (RTKs). An essential role of Cbl-family protein-dependent ubiquitination for efficient ligand-induced lysosomal targeting and degradation is now well-accepted. However, a more proximal role of Cbl and Cbl-b as adapters for CIN85-endophilin recruitment to mediate ligand-induced initial internalization of RTKs is supported by some studies but refuted by others. Overexpression and/or incomplete depletion of Cbl proteins in these studies is likely to have contributed to this dichotomy. To address the role of endogenous Cbl and Cbl-b in the internalization step of RTK endocytic traffic, we established Cbl/Cbl-b double-knockout (DKO) mouse embryonic fibroblasts (MEFs) and demonstrated that these cells lack the expression of both Cbl-family members as well as endophilin A, while they express CIN85. We show that ligand-induced ubiquitination of EGFR, as a prototype RTK, was abolished in DKO MEFs, and EGFR degradation was delayed. These traits were reversed by ectopic human Cbl expression. EGFR endocytosis, assessed using the internalization of 125I-labeled or fluorescent EGF, or of EGFR itself, was largely retained in Cbl/Cbl-b DKO compared to wild type MEFs. EGFR internalization was also largely intact in Cbl/Cbl-b depleted MCF-10A human mammary epithelial cell line. Inducible shRNA-mediated knockdown of CIN85 in wild type or Cbl/Cbl-b DKO MEFs had no impact on EGFR internalization. Our findings, establish that, at physiological expression levels, Cbl, Cbl-b and CIN85 are largely dispensable for EGFR internalization. Our results support the model that Cbl-CIN85-endophilin complex is not required for efficient internalization of EGFR, a prototype RTK. PMID:25449262

Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.

PubMed

Bonafede, Lucas; Ficicioglu, Can H; Serrano, Leona; Han, Grace; Morgan, Jessica I W; Mills, Monte D; Forbes, Brian J; Davidson, Stefanie L; Binenbaum, Gil; Kaplan, Paige B; Nichols, Charles W; Verloo, Patrick; Leroy, Bart P; Maguire, Albert M; Aleman, Tomas S

2015-12-01

To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.

Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

PubMed Central

Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

2015-01-01

Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

Loss of Cbl–PI3K Interaction Enhances Osteoclast Survival due to p21-Ras Mediated PI3K Activation Independent of Cbl-b

PubMed Central

Adapala, Naga Suresh; Barbe, Mary F.; Tsygankov, Alexander Y.; Lorenzo, Joseph A.; Sanjay, Archana

2015-01-01

Cbl family proteins, Cbl and Cbl-b, are E3 ubiquitin ligases and adaptor proteins, which play important roles in bone-resorbing osteoclasts. Loss of Cbl in mice decreases osteoclast migration, resulting in delayed bone development where as absence of Cbl-b decreases bone volume due to hyper-resorptive osteoclasts. A major structural difference between Cbl and Cbl-b is tyrosine 737 (in YEAM motif) only on Cbl, which upon phosphorylation interacts with the p85 subunit of phosphatidylinositol-3 Kinase (PI3K). In contrast to Cbl−/− and Cbl-b−/−, mice lacking Cbl–PI3K interaction due to a Y737F (tyrosine to phenylalanine, YF) mutation showed enhanced osteoclast survival, but defective bone resorption. To investigate whether Cbl–PI3K interaction contributes to distinct roles of Cbl and Cbl-b in osteoclasts, mice bearing CblY737F mutation in the Cbl-b−/− background (YF/YF;Cbl-b−/−) were generated. The differentiation and survival were augmented similarly in YF/YF and YF/YF;Cbl-b−/− osteoclasts, associated with enhanced PI3K signaling suggesting an exclusive role of Cbl–PI3K interaction, independent of Cbl-b. In addition to PI3K, the small GTPase Ras also regulates osteoclast survival. In the absence of Cbl–PI3K interaction, increased Ras GTPase activity and Ras–PI3K binding were observed and inhibition of Ras activation attenuated PI3K mediated osteoclast survival. In contrast to differentiation and survival, increased osteoclast activity observed in Cbl-b−/− mice persisted even after introduction of the resorption-defective YF mutation in YF/YF;Cbl-b−/− mice. Hence, Cbl and Cbl-b play mutually exclusive roles in osteoclasts. Whereas Cbl–PI3K interaction regulates differentiation and survival, bone resorption is predominantly regulated by Cbl-b in osteoclasts. PMID:24470255

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

Wulfmeyer, Volker; Turner, David

The Land-Atmosphere Feedback Experiment (LAFE; pronounced “la-fey”) deploys several state-of-the-art scanning lidar and remote sensing systems to the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility’s Southern Great Plains (SGP) site. These instruments will augment the ARM instrument suite in order to collect a data set for studying feedback processes between the land surface and the atmosphere. The novel synergy of remote-sensing systems will be applied for simultaneous measurements of land-surface fluxes and horizontal and vertical transport processes in the atmospheric convective boundary layer (CBL). The impact of spatial inhomogeneities of the soil-vegetation continuum on land-surface-atmospheremore » (LSA) feedback will be studied using the scanning capability of the instrumentation. The time period of the observations is August 2017, because large differences in surface fluxes between different fields and bare soil can be observed, e.g., pastures versus fields where the wheat has already been harvested. The remote sensing system synergy will consist of three components: 1) The SGP water vapor and temperature Raman lidar (SRL), the SGP Doppler lidar (SDL), and the National Center for Atmospheric Research (NCAR) water vapor differential absorption lidar (DIAL) (NDIAL) mainly in vertical staring modes to measure mean profiles and gradients of moisture, temperature, and horizontal wind. They will also measure profiles of higher-order turbulent moments in the water vapor and wind fields and profiles of the latent heat flux. 2) A novel scanning lidar system synergy consisting of the National Oceanic and Atmospheric Administration (NOAA) High-Resolution Doppler lidar (HRDL), the University of Hohenheim (UHOH) water-vapor differential absorption lidar (UDIAL), and the UHOH temperature Raman lidar (URL). These systems will perform coordinated range-height indicator (RHI) scans from just above the canopy level to the lower troposphere, including the interfacial layer of the CBL. The optimal azimuth is to the ENE of the SGP central facility, which takes advantage of both changes in the surface elevation and different crop types planted along that path. 3) The University of Wisconsin Space Science and Engineering Center Portable Atmospheric Research Center (SPARC) and the University of Oklahoma Collaborative Lower Atmospheric Mobile Profiling System (CLAMPS) operating two vertically pointing atmospheric emitted radiance interferometers (AERIs) and two Doppler lidar (DL) systems scanning cross track to the central RHI for determining the surface friction velocity and the horizontal variability of temperature, moisture, and wind. Thus, both the variability of surface fluxes and CBL dynamics and thermodynamics over the SGP site will be studied for the first time. The combination of these three components will enable us to estimate both the divergence of the latent heat profile and the advection of moisture. Thus, the moisture budget in the SGP domain can be studied. Furthermore, the simultaneous measurements of surface and entrainment fluxes as well as the daily cycle of the CBL thermodynamic state will provide a unique data set for characterizing LSA interaction in dependence of large-scale and local conditions such as soil moisture and the state of the vegetation. The measurements will also be applied for the development of improved parameterizations of surface fluxes and turbulence in the CBL. The latter is possible because mean profiles, gradients, higher-order moments, and fluxes are measured simultaneously. The results will be used for the verification of simulations of LSA feedback in large-eddy simulation (LES) and mesoscale models, which are planned for the SGP site. Due to the strong connection between the pre-convective state of the CBL and the formation of clouds and precipitation, this new generation of experiments will strongly contribute to the improvement of their representation in weather, climate, and earth system models.« less

Processing of alkylcobalamins in mammalian cells: a role for the MMACHC (cblC) gene product

PubMed Central

Hannibal, Luciana; Kim, Jihoe; Brasch, Nicola E.; Wang, Sihe; Rosenblatt, David S.; Banerjee, Ruma; Jacobsen, Donald W.

2009-01-01

The MMACHC gene product of the cblC complementation group, referred to as the cblC protein, catalyzes the in vitro and in vivo decyanation of cyanocobalamin (vitamin B12). We hypothesized that the cblC protein would also catalyze the dealkylation of newly internalized methylcobalamin (MeCbl) and 5′-deoxyadenosylcobalamin (AdoCbl), the naturally occurring alkylcobalamins that are present in the diet. The hypothesis was tested in cultured endothelial cells using [57Co]-AdoCbl and MeCbl analogs consisting of [57Co]-labeled straight-chain alkylcobalamins ranging from C2 (ethylcobalamin) to C6 (hexylcobalamin). [57Co]-AdoCbl was converted to [57Co]-MeCbl by cultured bovine aortic endothelial cells, suggesting that a dealkylation process likely involving the cblC protein removed the 5′-deoxyadenosyl alkyl group. Surprisingly, all of the straight-chain alkylcobalamins served as substrates for the biosynthesis of both AdoCbl and MeCbl. Dealkylation was then assessed in normal skin fibroblasts and fibroblasts derived from 3 patients with mutations in the MMACHC gene. While normal skin fibroblasts readily converted [57Co]-propylcobalamin to [57Co]-AdoCbl and [57Co]-MeCbl, there was little or no conversion in cblC mutant fibroblasts. These studies suggest that the CblC protein is responsible for early processing of both CNCbl (decyanation) and alkylcobalamins (dealkylation) in mammalian cells. PMID:19447654

Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product.

PubMed

Hannibal, Luciana; Kim, Jihoe; Brasch, Nicola E; Wang, Sihe; Rosenblatt, David S; Banerjee, Ruma; Jacobsen, Donald W

2009-08-01

The MMACHC gene product of the cblC complementation group, referred to as the cblC protein, catalyzes the in vitro and in vivo decyanation of cyanocobalamin (vitamin B(12)). We hypothesized that the cblC protein would also catalyze the dealkylation of newly internalized methylcobalamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl), the naturally occurring alkylcobalamins that are present in the diet. The hypothesis was tested in cultured endothelial cells using [(57)Co]-AdoCbl and MeCbl analogs consisting of [(57)Co]-labeled straight-chain alkylcobalamins ranging from C2 (ethylcobalamin) to C6 (hexylcobalamin). [(57)Co]-AdoCbl was converted to [(57)Co]-MeCbl by cultured bovine aortic endothelial cells, suggesting that a dealkylation process likely involving the cblC protein removed the 5'-deoxyadenosyl alkyl group. Surprisingly, all of the straight-chain alkylcobalamins served as substrates for the biosynthesis of both AdoCbl and MeCbl. Dealkylation was then assessed in normal skin fibroblasts and fibroblasts derived from three patients with mutations in the MMACHC gene. While normal skin fibroblasts readily converted [(57)Co]-propylcobalamin to [(57)Co]-AdoCbl and [(57)Co]-MeCbl, there was little or no conversion in cblC mutant fibroblasts. These studies suggest that the CblC protein is responsible for early processing of both CNCbl (decyanation) and alkylcobalamins (dealkylation) in mammalian cells.

Organometallic DNA-B12 Conjugates as Potential Oligonucleotide Vectors: Synthesis and Structural and Binding Studies with Human Cobalamin-Transport Proteins.

PubMed

Mutti, Elena; Hunger, Miriam; Fedosov, Sergey; Nexo, Ebba; Kräutler, Bernhard

2017-11-16

The synthesis and structural characterization of Co-(dN) 25 -Cbl (Cbl: cobalamin; dN: deoxynucleotide) and Co-(dN) 39 -Cbl, which are organometallic DNA-B 12 conjugates with single DNA strands consisting of 25 and 39 deoxynucleotides, respectively, and binding studies of these two DNA-Cbl conjugates to three homologous human Cbl transporting proteins, transcobalamin (TC), intrinsic factor (IF), and haptocorrin (HC), are reported. This investigation tests the suitability of such DNA-Cbls for the task of eventual in vivo oligonucleotide delivery. The binding of DNA-Cbl to TC, IF, and HC was investigated in competition with either a fluorescent Cbl derivative and Co-(dN) 25 -Cbl, or radiolabeled vitamin B 12 ( 57 Co-CNCbl) and Co-(dN) 25 -Cbl or Co-(dN) 39 -Cbl. Binding of the new DNA-Cbl conjugates was fast and tight with TC, but poorer with HC and IF, which extends a similar original finding with the simpler DNA-Cbl, Co-(dN) 18 -Cbl. The contrasting affinities of TC versus IF and HC for the DNA-Cbl conjugates are rationalized herein by a stepwise mechanism of Cbl binding. Critical contributions to overall affinity result from gradual conformational adaptations of the Cbl-binding proteins to the DNA-Cbl, which is first bound to the respective β domains. This transition is fast with TC, but slow with IF and HC, with which weaker binding results. The invariably tight interaction of the DNA-Cbl conjugates with TC makes the Cbl moiety a potential natural vector for the specific delivery of oligonucleotide loads from the blood into cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification and functional characterization of an Src homology domain 3 domain-binding site on Cbl.

PubMed

Sanjay, Archana; Miyazaki, Tsuyoshi; Itzstein, Cecile; Purev, Enkhtsetseg; Horne, William C; Baron, Roland

2006-12-01

Cbl is an adaptor protein and ubiquitin ligase that binds and is phosphorylated by the nonreceptor tyrosine kinase Src. We previously showed that the primary interaction between Src and Cbl is mediated by the Src homology domain 3 (SH3) of Src binding to proline-rich sequences of Cbl. The peptide Cbl RDLPPPPPPDRP(540-551), which corresponds to residues 540-551 of Cbl, inhibited the binding of a GST-Src SH3 fusion protein to Cbl, whereas RDLAPPAPPPDR(540-551) did not, suggesting that Src binds to this site on Cbl in a class I orientation. Mutating prolines 543-548 reduced Src binding to the Cbl 479-636 fragment significantly more than mutating the prolines in the PPVPPR(494-499) motif, which was previously reported to bind Src SH3. Mutating Cbl prolines 543-548 to alanines substantially reduced Src binding to Cbl, Src-induced phosphorylation of Cbl, and the inhibition of Src kinase activity by Cbl. Expressing the mutated Cbl in osteoclasts induced a moderate reduction in bone-resorbing activity and increased amounts of Src protein. In contrast, disabling the tyrosine kinase-binding domain of full-length Cbl by mutating glycine 306 to glutamic acid, and thereby preventing the previously described binding of the tyrosine kinase-binding domain to the Src phosphotyrosine 416, had no effect on Cbl phosphorylation, the inhibition of Src activity by full-length Cbl, or bone resorption. These data indicate that the Cbl RDLPPPP(540-546) sequence is a functionally important binding site for Src.

Cbl-b is a novel physiologic regulator of glycoprotein VI-dependent platelet activation.

PubMed

Daniel, James L; Dangelmaier, Carol A; Mada, Sripal; Buitrago, Lorena; Jin, Jianguo; Langdon, Wallace Y; Tsygankov, Alexander Y; Kunapuli, Satya P; Sanjay, Archana

2010-06-04

Cbl-b, a member of the Cbl family of E3 ubiquitin ligases, plays an important role in the activation of lymphocytes. However, its function in platelets remains unknown. We show that Cbl-b is expressed in human platelets along with c-Cbl, but in contrast to c-Cbl, it is not tyrosine-phosphorylated upon glycoprotein VI (GPVI) stimulation. Cbl-b, unlike c-Cbl, is not required for Syk ubiquitylation downstream of GPVI activation. Phospholipase Cgamma2 (PLCgamma2) and Bruton's tyrosine kinase (BTK) are constituently associated with Cbl-b. Cbl-b-deficient (Cbl-b(-/-)) platelets display an inhibition in the concentration-response curve for GPVI-specific agonist-induced aggregation, secretion, and Ca(2+) mobilization. A parallel inhibition is found for activation of PLCgamma2 and BTK. However, Syk activation is not affected by the absence of Cbl-b, indicating that Cbl-b acts downstream of Syk but upstream of BTK and PLCgamma2. When Cbl-b(-/-) mice were tested in the ferric chloride thrombosis model, occlusion time was increased and clot stability was reduced compared with wild type controls. These data indicate that Cbl-b plays a positive modulatory role in GPVI-dependent platelet signaling, which translates to an important regulatory role in hemostasis and thrombosis in vivo.

Numerical simulation of local atmospheric circulations in the pre-Alpine area between Lake Garda and Verona

NASA Astrophysics Data System (ADS)

Laiti, L.; Serafin, S.; Zardi, D.

2010-09-01

The pre-Alpine area between Lake Garda and Verona displays a very complex and heterogeneous territory, allowing the development of several interacting systems of thermally driven local winds, the major being the lake/land breeze system on the coasts of Lake Garda and the up/down-valley wind system between the plain and the river Adige Valley. In order to investigate the local wind patterns, a series of nested numerical simulations with a horizontal resolution of 500 m were carried out using the ARPS 5.2.9 model (Xue et al. 2000, 2001), considering a fair weather day suitable for a clear development of the expected circulations (15th July 2003). The simulated wind speed and direction, pressure, temperature and water vapour mixing ratio were compared to synoptic scale meteorological charts, to vertical profiles from radiosoundings taken at the major sounding stations of the alpine region and to local scale measurements performed at the surface station of Dolcè (at the inlet of the Adige Valley). Numerical results at all scales were found to be in very good agreement with the available sets of meteorological observations. The analysis of the diurnal evolution of the 3D fields of temperature, moisture content, wind and turbulent kinetic energy allowed the identification of a very shallow and clearly defined breeze front of cold and humid air moving from off-shore towards the Lake Garda coast, from the late morning (10:00 LST) until the evening (20:00 LST). The diurnal up-valley breeze was also well reproduced: the valley atmosphere displays a thick mixed layer dominated by shallow turbulent convection between 11:00 LST and 21:00 LST. Lateral slope winds were also recognized, as they created cross-valley convective cells. While no clear evidence of a nocturnal land breeze was found in the simulations, the nocturnal down-valley wind in the Adige Valley was clearly reproduced. Finally, a scalar transport equation was added to the ARPS model in order to simulate transport and diffusion processes for a passive tracer (ideally, a non-reactive pollutant). The cold and stable lake and down-valley breeze corps were found to act like pollutant concentrators at ground level, while the diurnal up-valley wind favours an almost homogenous dispersion of the tracer through the entire Convective Boundary Layer (CBL) thickness. The upper entrainment layer is found to effectively confine the ground-emitted pollutant inside the CBL, except for some occasional plumes that are first conveyed up-slope and then to the centre of the valley above the CBL by cross-valley circulation cells.

Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy.

PubMed

Adapala, Naga Suresh; Holland, Danielle; Scanlon, Vanessa; Barbe, Mary F; Langdon, Wallace Y; Tsygankov, Alexander Y; Lorenzo, Joseph A; Sanjay, Archana

2014-10-01

Cbl and Cbl-b are E3 ubiquitin ligases and adaptor proteins, which perform regulatory roles in bone remodeling. Cbl-/- mice have delayed bone development due to decreased osteoclast migration. Cbl-b-/- mice are osteopenic due to increased bone resorbing activity of osteoclasts. Unique to Cbl, but not present in Cbl-b, is tyrosine 737 in the YEAM motif, which upon phosphorylation provides a binding site for the regulatory p85 subunit of PI3K. Substitution of tyrosine 737 with phenylalanine (Y737F, CblYF/YF mice) prevents Y737 phosphorylation and abrogates the Cbl-PI3K interaction. We have previously reported that CblYF/YF mice had increased bone volume due to defective bone resorption and increased bone formation. Here we show that the lumbar vertebra from CblYF/YF mice did not have significant bone loss following ovariectomy. Our data also suggests that abrogation of Cbl-PI3K interaction in mice results in the loss of coupling between bone resorption and formation, since ovariectomized CblYF/YF mice did not show significant changes in serum levels of c-terminal telopeptide (CTX), whereas the serum levels of pro-collagen type-1 amino-terminal pro-peptide (P1NP) were decreased. In contrast, following ovariectomy, Cbl-/- and Cbl-b-/- mice showed significant bone loss in the tibiae and L2 vertebrae, concomitant with increased serum CTX and P1NP levels. These data indicate that while lack of Cbl or Cbl-b distinctly affects bone remodeling, only the loss of Cbl-PI3K interaction protects mice from significant bone loss following ovariectomy. Copyright © 2014 Elsevier Inc. All rights reserved.

Tissue distribution of oral vitamin B12 is influenced by B12 status and B12 form: an experimental study in rats.

PubMed

Kornerup, Linda S; Fedosov, Sergey N; Juul, Christian B; Greibe, Eva; Heegaard, Christian W; Nexo, Ebba

2018-06-01

Hydroxocobalamin (HOCbl) is the dominating Cbl form in food, whereas cyanocobalamin (CNCbl) is common in vitamin pills and oral supplements. This study compares single-dose absorption and distribution of oral HO[ 57 Co]Cbl and CN[ 57 Co]Cbl in Cbl-deficient and normal rats. Male Wistar rats (7 weeks) were fed a 14-day diet with (n = 15) or without (n = 15) Cbl. We compared the uptakes of HO[ 57 Co]Cbl (free or bound to bovine transcobalamin) and free CN[ 57 Co]Cbl administered by gastric gavage (n = 5 in each diet group). Rats were sacrificed after 24 h. Blood, liver, kidney, brain, heart, spleen, intestines, skeletal muscle, 24-h urine and faeces were collected, and the content of [ 57 Co]Cbl was measured. Endogenous Cbl in tissues and plasma was analysed by routine methods. Mean endogenous plasma-Cbl was sevenfold lower in deficient vs. normal rats (190 vs. 1330 pmol/L, p < 0.0001). Cbl depletion increased endogenous Cbl ratios (tissue/plasma = k in /k out ) in all organs except for the kidney, where the ratio decreased considerably. Twenty-four-hour accumulation of labelled Cbl showed that HOCbl > CNCbl (liver) and CNCbl > HOCbl (brain, muscle and plasma). The Cbl status of rats and the administered Cbl form influence 24-h Cbl accumulation in tissues and plasma.

Estimation of evaporation from equilibrium diurnal boundary layer humidity

NASA Astrophysics Data System (ADS)

Salvucci, G.; Rigden, A. J.; Li, D.; Gentine, P.

2017-12-01

Simplified conceptual models of the convective boundary layer as a well mixed profile of potential temperature (theta) and specific humidity (q) impinging on an initially stably stratified linear potential temperature profile have a long history in atmospheric sciences. These one dimensional representations of complex mixing are useful for gaining insights into land-atmosphere interactions and for prediction when state of the art LES approaches are infeasible. As previously shown (e.g. Betts), if one neglects the role of q in bouyancy, the framework yields a unique relation between mixed layer Theta, mixed layer height (h), and cumulative sensible heat flux (SH) throughout the day. Similarly assuming an initially q profile yields a simple relation between q, h, and cumulative latent heat flux (LH). The diurnal dynamics of theta and q are strongly dependent on SH and the initial lapse rates of theta (gamma_thet) and q (gamma q). In the estimation method proposed here, we further constrain these relations with two more assumptions: 1) The specific humidity is the same at the start of the period of boundary layer growth and at the collapse; and 2) Once the mixed layer reaches the LCL, further drying occurs proportionally to the deardorff convective velocity scale (omega) multiplied by q. Assumption (1) is based on the idea that below the cloud layer, there are no sinks of moisture within the mixed layer (neglecting lateral humidity divergence). Thus the net mixing of dry air aloft with evaporation from the surface must balance. Inclusion of the simple model of moisture loss above the LCL into the bulk-CBL model allows definition of an equilibrium humidity (q) condition at which the diurnal cycle of q repeats (i.e. additions of q from surface balance entrainment of dry air from above). Surprisingly, this framework allows estimation of LH from q, theta, and estimated net radiation by solving for the value of Evaporative Fraction (EF) for which the diurnal cycle of q repeats. Three parameters need specification: cloud area fraction, entrainment factor, and morning lapse rate. Surprisingly, a single set of values for these parameters are adequate to estimate EF at over 70 tested Ameriflux sites to within about 20%, though improvements are gained using a single regression model for gamma_thet that has been fitted to radiosonde data.

CBL enhances breast tumor formation by inhibiting tumor suppressive activity of TGF-β signaling.

PubMed

Kang, J M; Park, S; Kim, S J; Hong, H Y; Jeong, J; Kim, H-S; Kim, S-J

2012-12-13

Casitas B-lineage lymphoma (CBL) protein family functions as multifunctional adaptor proteins and E3 ubiquitin ligases that are implicated as regulators of signaling in various cell types. Recent discovery revealed mutations of proto-oncogenic CBL in the linker region and RING finger domain in human acute myeloid neoplasm, and these transforming mutations induced carcinogenesis. However, the adaptor function of CBL mediated signaling pathway during tumorigenesis has not been well characterized. Here, we show that CBL is highly expressed in breast cancer cells and significantly inhibits transforming growth factor-β (TGF-β) tumor suppressive activity. Knockdown of CBL expression resulted in the increased expression of TGF-β target genes, PAI-I and CDK inhibitors such as p15(INK4b) and p21(Cip1). Furthermore, we demonstrate that CBL is frequently overexpressed in human breast cancer tissues, and the loss of CBL decreases the tumorigenic activity of breast cancer cells in vivo. CBL directly binds to Smad3 through its proline-rich motif, thereby preventing Smad3 from interacting with Smad4 and blocking nuclear translocation of Smad3. CBL-b, one of CBL protein family, also interacted with Smad3 and knockdown of both CBL and CBL-b further enhanced TGF-β transcriptional activity. Our findings provide evidence for a previously undescribed mechanism by which oncogenic CBL can block TGF-β tumor suppressor activity.

Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy

PubMed Central

Adapala, Naga Suresh; Holland, Danielle; Piccuillo, Vanessa; Barbe, Mary F.; Langdon, Wallace Y.; Tsygankov, Alexander Y.; Lorenzo, Joseph A.; Sanjay, Archana

2014-01-01

Cbl and Cbl-b are E3 ubiquitin ligases and adaptor proteins, which perform regulatory roles in bone remodeling. Cbl−/− mice have delayed bone development due to decreased osteoclast migration. Cbl-b−/− mice are osteopenic due to increased bone resorbing activity of osteoclasts. Unique to Cbl, but not present in Cbl-b, is tyrosine 737 in the YEAM motif, which upon phosphorylation provides a binding site for the regulatory p85 subunit of PI3K. Substitution of tyrosine 737 with phenylalanine (Y737F, CblYF/YF mice) prevents Y737 phosphorylation and abrogates the Cbl-PI3K interaction. We have previously reported that CblYF/YF mice had increased bone volume due to defective bone resorption and increased bone formation. Here we show that the lumbar vertebra from CblYF/YF mice did not have significant bone loss following ovariectomy. Our data also suggests that abrogation of Cbl-PI3K interaction in mice results in the loss of coupling between bone resorption and formation, since ovariectomized CblYF/YF mice did not show significant changes in serum levels of c-terminal telopeptide (CTX), whereas the serum levels of pro-collagen type-1 amino-terminal pro-peptide (P1NP) were decreased. In contrast, following ovariectomy, Cbl−/− and Cbl-b−/− mice showed significant bone loss in tibiae and L2 vertebrae, concomitant with increased serum CTX and P1NP levels. These data indicate that while lack of Cbl or Cbl-b distinctly affects bone remodeling, only the loss of Cbl-PI3K interaction protects mice from significant bone loss following ovariectomy. PMID:24994594

Loss of Cbl and Cbl-b ubiquitin ligases abrogates hematopoietic stem cell quiescence and sensitizes leukemic disease to chemotherapy

PubMed Central

An, Wei; Nadeau, Scott A.; Mohapatra, Bhopal C.; Feng, Dan; Zutshi, Neha; Storck, Matthew D.; Arya, Priyanka; Talmadge, James E.; Meza, Jane L.; Band, Vimla; Band, Hamid

2015-01-01

Cbl and Cbl-b are tyrosine kinase-directed RING finger type ubiquitin ligases (E3s) that negatively regulate cellular activation pathways. E3 activity-disrupting human Cbl mutations are associated with myeloproliferative disorders (MPD) that are reproduced in mice with Cbl RING finger mutant knock-in or hematopoietic Cbl and Cbl-b double knockout. However, the role of Cbl proteins in hematopoietic stem cell (HSC) homeostasis, especially in the context of MPD is unclear. Here we demonstrate that HSC expansion and MPD development upon combined Cbl and Cbl-b deletion are dependent on HSCs. Cell cycle analysis demonstrated that DKO HSCs exhibit reduced quiescence associated with compromised reconstitution ability and propensity to undergo exhaustion. We show that sustained c-Kit and FLT3 signaling in DKO HSCs promotes loss of colony-forming potential, and c-Kit or FLT3 inhibition in vitro protects HSCs from exhaustion. In vivo, treatment with 5-fluorouracil hastens DKO HSC exhaustion and protects mice from death due to MPD. Our data reveal a novel and leukemia therapy-relevant role of Cbl and Cbl-b in the maintenance of HSC quiescence and protection against exhaustion, through negative regulation of tyrosine kinase-coupled receptor signaling. PMID:25871390

An essential role of ubiquitination in Cbl-mediated negative regulation of the Src-family kinase Fyn

PubMed Central

Rao, Navin; Ghosh, Amiya K.; Douillard, Patrice; Andoniou, Christopher E.; Zhou, Pengcheng; Band, Hamid

2009-01-01

SUMMARY The Cbl family of ubiquitin ligases function as negative regulators of activated receptor tyrosine kinases by facilitating their ubiquitination and subsequent lysosomal targeting. Here, we have investigated the role of Cbl ubiquitin ligase activity in the negative regulation of a non-receptor tyrosine kinase, the Src-family kinase Fyn. Using primary embryonic fibroblasts from Cbl+/+ and Cbl−/− mice, we demonstrate that endogenous Cbl mediates the ubiquitination of Fyn and dictates the rate of Fyn turnover. By analyzing CHO-TS20 cells with a temperature-sensitive ubiquitin activating enzyme, we demonstrate that intact cellular ubiquitin machinery is required for Cbl-induced degradation of Fyn. Analyses of Cbl mutants, with mutations in or near the RING finger domain, in 293T cells revealed that the ubiquitin ligase activity of Cbl is essential for Cbl-induced degradation of Fyn by the proteasome pathway. Finally, use of a SRE-luciferase reporter demonstrated that Cbl-dependent negative regulation of Fyn function requires the region of Cbl that mediates the ubiquitin ligase activity. Given the conservation of structure between various Src-family kinases and the ability of Cbl to interact with multiple members of this family, Cbl-dependent ubiquitination could serve a general role to negatively regulate activated Src-family kinases. PMID:19966925

High resolution crystal structure of the methylcobalamin analogues ethylcobalamin and butylcobalamin by X-ray synchrotron diffraction.

PubMed

Hannibal, Luciana; Smith, Clyde A; Smith, Jessica A; Axhemi, Armend; Miller, Abby; Wang, Sihe; Brasch, Nicola E; Jacobsen, Donald W

2009-07-20

The X-ray crystal structures of the methylcobalamin (MeCbl) analogues ethylcobalamin (EtCbl) and butylcobalamin (BuCbl) are reported. The X-ray crystal structures of EtCbl and BuCbl were obtained with some of the lowest crystallographic residuals ever achieved for cobalamins (R = 0.0468 and 0.0438, respectively). The Co-C bond distances for EtCbl and BuCbl are 2.023(2) and 2.028(4) A, whereas the Co-alpha-5,6-dimethylbenzimidazole (Co-N3B) bond distances were 2.232(1) and 2.244(1) A, respectively. Although EtCbl and BuCbl displayed a longer Co-N3B bond than that observed in the naturally occurring methylcobalamin, the orientation of the alpha-5,6-dimethylbenzimidazole moiety with respect to the corrin ring did not vary substantially among the structures. The lengthening of both Co-C and Co-N3B bonds in EtCbl and BuCbl can be attributed to the "inverse" trans influence exerted by the sigma-donating alkyl groups, typically observed in alkylcobalamins. Analysis of the molecular surface maps showed that the alkyl ligands in EtCbl and BuCbl are directed toward the hydrophobic side of the corrin ring. The corrin fold angles in EtCbl and BuCbl were determined to be 14.7 degrees and 13.1 degrees, respectively. A rough correlation exists between the corrin fold angle and the length of the Co-N3B bond, and both alkylcobalamins follow the same trend.

High Resolution Crystal Structure of the Methylcobalamin Analogs Ethylcobalamin and Butylcobalamin by X-ray Synchrotron Diffraction

PubMed Central

Hannibal, Luciana; Smith, Clyde A; Smith, Jessica A.; Axhemi, Armend; Miller, Abby; Wang, Sihe; Brasch, Nicola E.; Jacobsen, Donald W.

2009-01-01

The X-ray crystal structures of the methylcobalamin (MeCbl) analogs ethylcobalamin (EtCbl) and butylcobalamin (BuCbl) are reported. The X-ray crystal structures of EtCbl and BuCbl were obtained with some of the lowest crystallographic residuals ever achieved for cobalamins (R = 0.0468 and 0.0438, respectively). The Co-C bond distances for EtCbl and BuCbl are 2.023(2) and 2.028(4) Å, whereas the Co-α-5,6-dimethylbenzimidazole (Co-N3B) bond distances were 2.232(1) and 2.244(1) Å, respectively. Although EtCbl and BuCbl displayed a longer Co-N3B bond than that observed in the naturally occurring methylcobalamin, the orientation of the α-5,6-dimethylbenzimidazole moiety with respect to the corrin ring did not vary substantially amongst the structures. The lengthening of both Co-C and Co-N3B bonds in EtCbl and BuCbl can be attributed to the “inverse” trans influence exerted by the σ-donating alkyl groups, typically observed in alkylcobalamins. Analysis of the molecular surface maps showed that the alkyl ligands in EtCbl and BuCbl are directed towards the hydrophobic side of the corrin ring. The corrin fold angles in EtCbl and BuCbl were determined to be 14.7° and 13.1°, respectively. A rough correlation exists between the corrin fold angle and the length of the Co-N3B bond, and both alkylcobalamins follow the same trend. PMID:19545130

Enhancing active learning in microbiology through case based learning: experiences from an Indian medical school.

PubMed

Ciraj, A M; Vinod, P; Ramnarayan, K

2010-01-01

Case-based learning (CBL) is an interactive student-centered exploration of real life situations. This paper describes the use of CBL as an educational strategy for promoting active learning in microbiology. CBL was introduced in the microbiology curriculum for the second year medical students after an orientation program for faculty and students. After intervention, the average student scores in CBL topics were compared with scores obtained in lecture topics. An attempt was also made to find the effect of CBL on the academic performance. Student and faculty perception on CBL were also recorded. In a cross sectional survey conducted to assess the effectiveness of CBL, students responded that, apart from helping them acquire substantive knowledge in microbiology, CBL sessions enhanced their analytic, collaborative, and communication skills. The block examination scores in CBL topics were significantly higher than those obtained for lecture topics. Faculty rated the process to be highly effective in stimulating student interest and long term retention of microbiology knowledge. The student scores were significantly higher in the group that used CBL, compared to the group that had not used CBL as a learning strategy. Our experience indicated that CBL sessions enhanced active learning in microbiology. More frequent use of CBL sessions would not only help the student gain requisite knowledge in microbiology but also enhance their analytic and communication skills.

Structure of Human B12 Trafficking Protein CblD Reveals Molecular Mimicry and Identifies a New Subfamily of Nitro-FMN Reductases.

PubMed

Yamada, Kazuhiro; Gherasim, Carmen; Banerjee, Ruma; Koutmos, Markos

2015-12-04

In mammals, B12 (or cobalamin) is an essential cofactor required by methionine synthase and methylmalonyl-CoA mutase. A complex intracellular pathway supports the assimilation of cobalamin into its active cofactor forms and delivery to its target enzymes. MMADHC (the methylmalonic aciduria and homocystinuria type D protein), commonly referred to as CblD, is a key chaperone involved in intracellular cobalamin trafficking, and mutations in CblD cause methylmalonic aciduria and/or homocystinuria. Herein, we report the first crystal structure of the globular C-terminal domain of human CblD, which is sufficient for its interaction with MMADHC (the methylmalonic aciduria and homocystinuria type C protein), or CblC, and for supporting the cytoplasmic cobalamin trafficking pathway. CblD contains an α+β fold that is structurally reminiscent of the nitro-FMN reductase superfamily. Two of the closest structural relatives of CblD are CblC, a multifunctional enzyme important for cobalamin trafficking, and the activation domain of methionine synthase. CblD, CblC, and the activation domain of methionine synthase share several distinguishing features and, together with two recently described corrinoid-dependent reductive dehalogenases, constitute a new subclass within the nitro-FMN reductase superfamily. We demonstrate that CblD enhances oxidation of cob(II)alamin bound to CblC and that disease-causing mutations in CblD impair the kinetics of this reaction. The striking structural similarity of CblD to CblC, believed to be contiguous in the cobalamin trafficking pathway, suggests the co-option of molecular mimicry as a strategy for achieving its function. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Inferring the effects of compositional boundary layers on crystal nucleation, growth textures, and mineral chemistry in natural volcanic tephras through submicron-resolution imaging

NASA Astrophysics Data System (ADS)

Zellmer, Georg; Sakamoto, Naoya; Hwang, Shyh-Lung; Matsuda, Nozomi; Iizuka, Yoshiyuki; Moebis, Anja; Yurimoto, Hisayoshi

2016-09-01

Crystal nucleation and growth are first order processes captured in volcanic rocks and record important information about the rates of magmatic processes and chemical evolution of magmas during their ascent and eruption. We have studied glass-rich andesitic tephras from the Central Plateau of the Southern Taupo Volcanic Zone by electron- and ion-microbeam imaging techniques to investigate down to sub-micrometre scale the potential effects of compositional boundary layers (CBLs) of melt around crystals on the nucleation and growth of mineral phases and the chemistry of crystal growth zones. We find that CBLs may influence the types of mineral phases nucleating and growing, and growth textures such as the development of swallowtails. The chemistry of the CBLs also has the capacity to trigger intermittent overgrowths of nanometre-scale bands of different phases in rapidly growing crystals, resulting in what we refer to as cryptic phase zoning. The existence of cryptic phase zoning has implications for the interpretation of microprobe compositional data, and the resulting inferences made on the conditions of magmatic evolution. Identification of cryptic phase zoning may in future lead to more accurate thermobarometric estimates and thus geospeedometric constraints. In future, a more quantitative characterization of CBL formation and its effects on crystal nucleation and growth may contribute to a better understanding of melt rheology and magma ascent processes at the onset of explosive volcanic eruptions, and will likely be of benefit to hazard mitigation efforts.

E3 ubiquitin ligase Cbl-b in innate and adaptive immunity

PubMed Central

Liu, Qingjun; Zhou, Hong; Langdon, Wallace Y; Zhang, Jian

2014-01-01

Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b), a RING finger E3 ubiquitin-protein ligase, has been demonstrated to play a crucial role in establishing the threshold for T-cell activation and controlling peripheral T-cell tolerance via multiple mechanisms. Accumulating evidence suggests that Cbl-b also regulates innate immune responses and plays an important role in host defense to pathogens. Understanding the signaling pathways regulated by Cbl-b in innate and adaptive immune cells is therefore essential for efficient manipulation of Cbl-b in emerging immunotherapies for human disorders such as autoimmune diseases, allergic inflammation, infections, and cancer. In this article, we review the latest developments in the molecular structural basis of Cbl-b function, the regulation of Cbl-b expression, the signaling mechanisms of Cbl-b in immune cells, as well as the biological function of Cbl-b in physiological and pathological immune responses in animal models and human diseases. PMID:24875217

Tyrosine phosphorylated c-Cbl regulates platelet functional responses mediated by outside-in signaling

PubMed Central

Buitrago, Lorena; Langdon, Wallace Y.

2011-01-01

c-Cbl protein functions as an E3 ligase and scaffolding protein, where 3 residues, Y700, Y731, and Y774, upon phosphorylation, have been shown to initiate several signaling cascades. In this study, we investigated the role of these phospho-tyrosine residues in the platelet functional responses after integrin engagement. We observed that c-Cbl Y700, Y731 and Y774 undergo phosphorylation upon platelet adhesion to immobilized fibrinogen, which was inhibited in the presence of PP2, a pan-src family kinase (SFK) inhibitor, suggesting that c-Cbl is phosphorylated downstream of SFKs. However, OXSI-2, a Syk inhibitor, significantly reduced c-Cbl phosphorylation at residues Y774 and Y700, without affecting Y731 phosphorylation. Interestingly, PP2 inhibited both platelet-spreading on fibrinogen as well as clot retraction, whereas OXSI-2 blocked only platelet-spreading, suggesting a differential role of these tyrosine residues. The physiologic role of c-Cbl and Y731 was studied using platelets from c-Cbl KO and c-CblYF/YF knock-in mice. c-Cbl KO and c-CblYF/YF platelets had a significantly reduced spreading over immobilized fibrinogen. Furthermore, clot retraction with c-Cbl KO and c-CblYF/YF platelets was drastically delayed. These results indicate that c-Cbl and particularly its phosphorylated residue Y731 plays an important role in platelet outside-in signaling contributing to platelet-spreading and clot retraction. PMID:21967979

Role of Cystathionine β-Lyase in Catabolism of Amino Acids to Sulfur Volatiles by Genetic Variants of Lactobacillus helveticus CNRZ 32▿

PubMed Central

Lee, Won-Jae; Banavara, Dattatreya S.; Hughes, Joanne E.; Christiansen, Jason K.; Steele, James L.; Broadbent, Jeffery R.; Rankin, Scott A.

2007-01-01

Catabolism of sulfur-containing amino acids plays an important role in the development of cheese flavor. During ripening, cystathionine β-lyase (CBL) is believed to contribute to the formation of volatile sulfur compounds (VSCs) such as methanethiol and dimethyl disulfide. However, the role of CBL in the generation of VSCs from the catabolism of specific sulfur-containing amino acids is not well characterized. The objective of this study was to investigate the role of CBL in VSC formation by Lactobacillus helveticus CNRZ 32 using genetic variants of L. helveticus CNRZ 32 including the CBL-null mutant, complementation of the CBL-null mutant, and the CBL overexpression mutant. The formation of VSCs from methionine, cystathionine, and cysteine was determined in a model system using gas chromatography-mass spectrometry with solid-phase microextraction. With methionine as a substrate, CBL overexpression resulted in higher VSC production than that of wild-type L. helveticus CNRZ 32 or the CBL-null mutant. However, there were no differences in VSC production between the wild type and the CBL-null mutant. With cystathionine, methanethiol production was detected from the CBL overexpression variant and complementation of the CBL-null mutant, implying that CBL may be involved in the conversion of cystathionine to methanethiol. With cysteine, no differences in VSC formation were observed between the wild type and genetic variants, indicating that CBL does not contribute to the conversion of cysteine. PMID:17337535

Neuronal Cbl Controls Biosynthesis of Insulin-Like Peptides in Drosophila melanogaster

PubMed Central

Yu, Yue; Sun, Ying; He, Shengqi; Yan, Cheng; Rui, Liangyou; Li, Wenjun

2012-01-01

The Cbl family proteins function as both E3 ubiquitin ligases and adaptor proteins to regulate various cellular signaling events, including the insulin/insulin-like growth factor 1 (IGF1) and epidermal growth factor (EGF) pathways. These pathways play essential roles in growth, development, metabolism, and survival. Here we show that in Drosophila melanogaster, Drosophila Cbl (dCbl) regulates longevity and carbohydrate metabolism through downregulating the production of Drosophila insulin-like peptides (dILPs) in the brain. We found that dCbl was highly expressed in the brain and knockdown of the expression of dCbl specifically in neurons by RNA interference increased sensitivity to oxidative stress or starvation, decreased carbohydrate levels, and shortened life span. Insulin-producing neuron-specific knockdown of dCbl resulted in similar phenotypes. dCbl deficiency in either the brain or insulin-producing cells upregulated the expression of dilp genes, resulting in elevated activation of the dILP pathway, including phosphorylation of Drosophila Akt and Drosophila extracellular signal-regulated kinase (dERK). Genetic interaction analyses revealed that blocking Drosophila epidermal growth factor receptor (dEGFR)-dERK signaling in pan-neurons or insulin-producing cells by overexpressing a dominant-negative form of dEGFR abolished the effect of dCbl deficiency on the upregulation of dilp genes. Furthermore, knockdown of c-Cbl in INS-1 cells, a rat β-cell line, also increased insulin biosynthesis and glucose-stimulated secretion in an ERK-dependent manner. Collectively, these results suggest that neuronal dCbl regulates life span, stress responses, and metabolism by suppressing dILP production and the EGFR-ERK pathway mediates the dCbl action. Cbl suppression of insulin biosynthesis is evolutionarily conserved, raising the possibility that Cbl may similarly exert its physiological actions through regulating insulin production in β cells. PMID:22778134

Cbl downregulation increases RBP4 expression in adipocytes of female mice

PubMed Central

Ameen, Gulizar Issa

2018-01-01

Obesity leads to adipose tissue dysfunction, insulin resistance and diabetes. Adipose tissue produces adipokines that contribute to regulate insulin sensitivity. In turn, insulin stimulates the production and release of some adipokines. Casitas-b-lymphoma proteins (c-Cbl, Cbl-b and Cbl3) are intracellular adaptor signalling proteins that are rapidly phosphorylated by activation of tyrosine kinase receptors. c-Cbl is rapidly phosphorylated by insulin in adipocytes. Here, we tested the hypothesis that Cbl signalling regulates adipokine expression in adipose tissue. We determined the adipokine profile of WAT of Cbl−/− and Cbl+/+ mice in the C57BL6 background. Female Cbl−/− mice exhibited altered expression of adiponectin, leptin and RBP4 in visceral adipose tissue, while no significant changes were seen in male mice. TNFα and IL6 levels were unaffected by Cbl depletion. RBP4 expression was unchanged in liver. Adipose tissue of Cbl−/− animals showed increased basal activation of extracellular regulated kinases (ERK1/2) compared to Cbl+/+. c-Cbl knockdown in 3T3L1 adipocytes also increased basal ERK phosphorylation and RBP4 expression. Inhibition of ERK1/2 phosphorylation in Cbl-depleted 3T3L1 adipocytes or in adipose tissue explants of Cbl−/− mice reduced RBP4 mRNA. 17β-Estradiol increased RBP4 mRNA in adipocytes. Cbl depletion did not change ER expression but increased phosphorylation of ERα at S118, a target site for ERK1/2. ERK1/2 inhibition reduced phosphoER and RBP4 levels. These findings suggest that Cbl contributes to regulate RBP4 expression in adipose of female mice through ERK1/2-mediated activation of ERα. Since Cbl signalling is compromised in diabetes, these data highlight a novel mechanism that upregulates RBP4 locally. PMID:29114012

Naturally occurring cobalamins have antimalarial activity.

PubMed

Chemaly, Susan M; Chen, Chien-Teng; van Zyl, Robyn L

2007-05-01

The acquisition of resistance by malaria parasites towards existing antimalarials has necessitated the development of new chemotherapeutic agents. The effect of vitamin B(12) derivatives on the formation of beta-haematin (synthetic haemozoin) was determined under conditions similar to those in the parasitic food vacuole (using chloroquine, a known inhibitor of haemozoin formation for comparison). Adenosylcobalamin (Ado-cbl), methylcobalamin (CH(3)-cbl) and aquocobalamin (H(2)O-cbl) were approximately forty times more effective inhibitors of beta-haematin formation than chloroquine, cyanocobalamin (CN-cbl) was slightly more inhibitory than chloroquine, while dicyanocobinamide had no effect. It is proposed that the cobalamins exert their inhibitory effect on beta-haematin formation by pi-interactions of their corrin ring with the Fe(III)-protoporphyrin ring and by hydrogen-bonding using their 5,6-dimethylbenzimidazole/ribose/sugar side-chain. The antimalarial activity for the cobalamins (Ado-cbl>CH(3)-cbl>H(2)O-cbl>CN-cbl) was found to be less than that for chloroquine or quinine. Ado-cbl, CH(3)-cbl and CN-cbl do not accumulate in the parasite food vacuole by pH trapping, but H(2)O-cbl does. Unlike humans, the malaria parasite has only one enzyme that uses cobalamin as a cofactor, namely methionine synthase, which is important for growth and metabolism. Thus cobalamins in very small amounts are necessary for Plasmodium falciparum growth but in larger amounts they display antimalarial properties.

Oncogenic Signaling by Leukemia-Associated Mutant Cbl Proteins

PubMed Central

Nadeau, Scott; An, Wei; Palermo, Nick; Feng, Dan; Ahmad, Gulzar; Dong, Lin; Borgstahl, Gloria E. O.; Natarajan, Amarnath; Naramura, Mayumi; Band, Vimla; Band, Hamid

2013-01-01

Members of the Cbl protein family (Cbl, Cbl-b, and Cbl-c) are E3 ubiquitin ligases that have emerged as critical negative regulators of protein tyrosine kinase (PTK) signaling. This function reflects their ability to directly interact with activated PTKs and to target them as well as their associated signaling components for ubiquitination. Given the critical roles of PTK signaling in driving oncogenesis, recent studies in animal models and genetic analyses in human cancer have firmly established that Cbl proteins function as tumor suppressors. Missense mutations or small in-frame deletions within the regions of Cbl protein that are essential for its E3 activity have been identified in nearly 5% of leukemia patients with myelodysplastic/myeloproliferative disorders. Based on evidence from cell culture studies, in vivo models and clinical data, we discuss the potential signaling mechanisms of mutant Cbl-driven oncogenesis. Mechanistic insights into oncogenic Cbl mutants and associated animal models are likely to enhance our understanding of normal hematopoietic stem cell homeostasis and provide avenues for targeted therapy of mutant Cbl-driven cancers. PMID:23997989

Protein tyrosine kinase regulation by ubiquitination: Critical roles of Cbl-family ubiquitin ligases

PubMed Central

Mohapatra, Bhopal; Ahmad, Gulzar; Nadeau, Scott; Zutshi, Neha; An, Wei; Scheffe, Sarah; Dong, Lin; Feng, Dan; Goetz, Benjamin; Arya, Priyanka; Bailey, Tameka A.; Palermo, Nicholas; Borgstahl, Gloria E.O.; Natarajan, Amarnath; Raja, Srikumar M.; Naramura, Mayumi; Band, Vimla; Band, Hamid

2012-01-01

Protein tyrosine kinases (PTKs) coordinate a broad spectrum of cellular responses to extracellular stimuli and cell–cell interactions during development, tissue homeostasis, and responses to environmental challenges. Thus, an understanding of the regulatory mechanisms that ensure physiological PTK function and potential aberrations of these regulatory processes during diseases such as cancer are of broad interest in biology and medicine. Aside from the expected role of phospho-tyrosine phosphatases, recent studies have revealed a critical role of covalent modification of activated PTKs with ubiquitin as a critical mechanism of their negative regulation. Members of the Cbl protein family (Cbl, Cbl-b and Cbl-c in mammals) have emerged as dominant “activated PTK-selective” ubiquitin ligases. Structural, biochemical and cell biological studies have established that Cbl protein-dependent ubiquitination targets activated PTKs for degradation either by facilitating their endocytic sorting into lysosomes or by promoting their proteasomal degradation. This mechanism also targets PTK signaling intermediates that become associated with Cbl proteins in a PTK activation-dependent manner. Cellular and animal studies have established that the relatively broadly expressed mammalian Cbl family members Cbl and Cbl-b play key physiological roles, including their critical functions to prevent the transition of normal immune responses into autoimmune disease and as tumor suppressors; the latter function has received validation from human studies linking mutations in Cbl to human leukemia. These newer insights together with embryonic lethality seen in mice with a combined deletion of Cbl and Cbl-b genes suggest an unappreciated role of the Cbl family proteins, and by implication the ubiquitin-dependent control of activated PTKs, in stem/progenitor cell maintenance. Future studies of existing and emerging animal models and their various cell lineages should help test the broader implications of the evolutionarily-conserved Cbl family protein-mediated, ubiquitin-dependent, negative regulation of activated PTKs in physiology and disease. PMID:23085373

Student Response to Remote-Online Case-Based Learning: A Qualitative Study.

PubMed

Nicklen, Peter; Keating, Jennifer L; Maloney, Stephen

2016-03-22

Case-based learning (CBL) typically involves face-to-face interaction in small collaborative groups with a focus on self-directed study. To our knowledge, no published studies report an evaluation of Web conferencing in CBL. The primary aim of this study was to explore student perceptions and attitudes in response to a remote-online case-based learning (RO-CBL) experience. This study took place over a 2-week period in 2013 at Monash University, Victoria, Australia. A third year cohort (n=73) of physiotherapy students was invited to participate. Students were required to participate in 2 training sessions, followed by RO-CBL across 2 sessions. The primary outcome of interest was the student feedback on the quality of the learning experience during RO-CBL participation. This was explored with a focus group and a survey. Most students (68/73) completed the postintervention survey (nonparticipation rate 8%). RO-CBL was generally well received by participants, with 59% (40/68) of participates stating that they'd like RO-CBL to be used in the future and 78% (53/68) of participants believing they could meet the CBL's learning objectives via RO-CBL. The 4 key themes relevant to student response to RO-CBL that emerged from the focus groups and open-ended questions on the postintervention survey were how RO-CBL compared to expectations, key benefits of RO-CBL including flexibility and time and cost savings, communication challenges in the online environment compared to face-to-face, and implications of moving to an online platform. Web conferencing may be a suitable medium for students to participate in CBL. Participants were satisfied with the learning activity and felt they could meet the CBL's learning objectives. Further study should evaluate Web conferencing CBL across an entire semester in regard to student satisfaction, perceived depth of learning, and learning outcomes.

Fasudil, a clinically-safe ROCK Inhibitor, Decreases Disease Burden in a Cbl/Cbl-b Deficiency-Driven Murine Model of Myeloproliferative Disorders

PubMed Central

William, Basem M.; An, Wei; Feng, Dan; Nadeau, Scott; Mohapatra, Bhopal C; Storck, Matthew A.; Band, Vimla; Band, Hamid

2017-01-01

Objectives Mutations in Cbl or Cbl-b gene occur in 10% of MPD patients and are associated with poor prognosis. Hematopoietic Cbl/Cbl-b double knockout (DKO) leads to a disease in mice phenotypically similar to human MPDs. The aim of this study was to evaluate the anti-MPD activity of a clinical safe drug, Fasudil identified in an in vitro kinase inhibitor as an inhibitor of proliferation of DKO mouse hematopoietic stem/progenitor cells (HSPCs). Methods Fasudil exhibited relatively selective anti-proliferative activity against Cbl/Cbl-b DKO vs. control murine bone marrow HSPCs. We established a mouse model with uniform time of MPD onset by transplanting Cbl/Cbl-b DKO HSPCs into busulfan-conditioned NOD/SCID/gamma chain-deficient mice. Four weeks post-transplant, mice were treated with 100 mg/kg fasudil (13 mice) or water (control, 8 mice) daily by oral gavage, followed by blood cell count every two weeks. Results By two weeks of treatment, total white cell and monocyte counts were significantly lower in mice treated with fasudil. We observed a trend towards improved survival in fasudil-treated mice that didn’t reach statistical significance. Notably, prolonged survival beyond 27 weeks was observed in 2 fasudil-treated mice, nearly twice the 16-week average life-span in the Cbl/Cbl-b DKO MPD model. Conclusions Our results suggest a therapeutic potential for fasudil, a clinically-safe drug with promising results in vascular diseases, in the treatment of MPDs or other mutant Cbl-driven myeloid disorders. PMID:26177294

The loss of Cbl-phosphatidylinositol 3-kinase interaction perturbs RANKL-mediated signaling, inhibiting bone resorption and promoting osteoclast survival.

PubMed

Adapala, Naga Suresh; Barbe, Mary F; Langdon, Wallace Y; Nakamura, Mary C; Tsygankov, Alexander Y; Sanjay, Archana

2010-11-19

Cbl is an adaptor protein and an E3 ligase that plays both positive and negative roles in several signaling pathways that affect various cellular functions. Tyrosine 737 is unique to Cbl and is phosphorylated by Syk and Src family kinases. Phosphorylated Cbl Tyr(737) creates a binding site for the p85 regulatory subunit of PI3K, which also plays an important role in the regulation of bone resorption by osteoclasts. To investigate the role of Cbl-PI3K interaction in bone homeostasis, we examined the knock-in mice (Cbl(YF/YF)) in which the PI3K binding site in Cbl is ablated due to the mutation in the regulatory tyrosine. We report that in Cbl(YF/YF) mice, despite increased numbers of osteoclasts, bone volume is increased due to defective osteoclast function. Additionally, in ex vivo cultures, mature Cbl(YF/YF) osteoclasts showed an increased ability to survive in the presence of RANKL due to delayed onset of apoptosis. RANKL-mediated signaling is perturbed in Cbl(YF/YF) osteoclasts, and most interestingly, AKT phosphorylation is up-regulated, suggesting that the lack of PI3K sequestration by Cbl results in increased survival and decreased bone resorption. Cumulatively, these in vivo and in vitro results show that, on one hand, binding of Cbl to PI3K negatively regulates osteoclast differentiation, survival, and signaling events (e.g. AKT phosphorylation), whereas on the other hand it positively influences osteoclast function.

Characterization of turbulent processes by the Raman lidar system BASIL during the HD(CP)2 observational prototype experiment - HOPE

NASA Astrophysics Data System (ADS)

Di Girolamo, Paolo; Summa, Donato; Stelitano, Dario; Cacciani, Marco; Scoccione, Andrea; Behrendt, Andreas; Wulfmeyer, Volker

2017-02-01

Measurements carried out by the Raman lidar system BASIL are reported to demonstrate the capability of this instrument to characterize turbulent processes within the Convective Boundary Layer (CBL). In order to resolve the vertical profiles of turbulent variables, high resolution water vapour and temperature measurements, with a temporal resolution of 10 sec and a vertical resolution of 90 and 30 m, respectively, are considered. Measurements of higher-order moments of the turbulent fluctuations of water vapour mixing ratio and temperature are obtained based on the application of spectral and auto-covariance analyses to the water vapour mixing ratio and temperature time series. The algorithms are applied to a case study (IOP 5, 20 April 2013) from the HD(CP)2 Observational Prototype Experiment (HOPE), held in Central Germany in the spring 2013. The noise errors are demonstrated to be small enough to allow the derivation of up to fourth-order moments for both water vapour mixing ratio and temperature fluctuations with sufficient accuracy.

Calcineurin B-like 3 calcium sensor associates with and inhibits 5'-methylthioadenosine nucleosidase 2 in Arabidopsis.

PubMed

Ok, Sung Han; Cho, Joo Hyuk; Oh, Seung-Ick; Choi, Mi Na; Ma, Jae-Yeon; Shin, Jeong-Sheop; Kim, Kyung-Nam

2015-09-01

Calcineurin B-like (CBL) proteins constitute a unique family of calcium sensor relays in plants. It is well known that CBLs detect the calcium signals elicited by a variety of abiotic stresses and relay the information to a group of serine/threonine protein kinases called CBL-interacting protein kinases (CIPKs). In this study, we found that a few CBL members can also target another group of enzymes 5'-methylthioadenosine nucleosidases (MTANs), which are encoded by two genes in Arabidopsis, AtMTAN1 and AtMTAN2. In the yeast two-hybrid system, AtMTAN1 interacted with multiple CBL members such as CBL2, CBL3 and CBL6, whereas AtMTAN2 associated exclusively with CBL3. We further demonstrated that the CBL3-AtMTAN2 association occurs in a calcium-dependent manner, which results in a significant decrease in the enzyme activity of the AtMTAN2 protein. Taken together, these results clearly indicate that the CBL family can target at least two distinct groups of enzymes (CIPKs and MTANs), conferring an additional level of complexity on the CBL-mediated signaling networks. In addition, our finding also provides a novel molecular mechanism by which calcium signals are transduced to alter metabolite profiles in plants. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Salmonella enterica synthesizes 5,6-dimethylbenzimidazolyl-(DMB)-α-riboside. Why some Firmicutes do not require the canonical DMB activation system to synthesize adenosylcobalamin.

PubMed

Mattes, Theodoric A; Escalante-Semerena, Jorge C

2017-01-01

5,6-Dimethylbenzimidazolyl-(DMB)-α-ribotide [α-ribazole-5'-phosphate (α-RP)] is an intermediate in the biosynthesis of adenosylcobalamin (AdoCbl) in many prokaryotes. In such microbes, α-RP is synthesized by nicotinate mononucleotide (NaMN):DMB phosphoribosyltransferases (CobT in Salmonella enterica), in a reaction that is considered to be the canonical step for the activation of the base of the nucleotide present in adenosylcobamides. Some Firmicutes lack CobT-type enzymes but have a two-protein system comprised of a transporter (i.e., CblT) and a kinase (i.e., CblS) that can salvage exogenous α-ribazole (α-R) from the environment using CblT to take up α-R, followed by α-R phosphorylation by CblS. We report that Geobacillus kaustophilus CblT and CblS proteins restore α-RP synthesis in S. enterica lacking the CobT enzyme. We also show that a S. enterica cobT strain that synthesizes GkCblS ectopically makes only AdoCbl, even under growth conditions where the synthesis of pseudoCbl is favored. Our results indicate that S. enterica synthesizes α-R, a metabolite that had not been detected in this bacterium and that GkCblS has a strong preference for DMB-ribose over adenine-ribose as substrate. We propose that in some Firmicutes DMB is activated to α-RP via α-R using an as-yet-unknown route to convert DMB to α-R and CblS to convert α-R to α-RP. © 2016 John Wiley & Sons Ltd.

Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B12)-Defective Mice Is Subject to Maternal Influences

PubMed Central

Mottram, Lynda; Speak, Anneliese O.; Selek, Reza M.; Cambridge, Emma L.; McIntyre, Zoe; Kane, Leanne; Mukhopadhyay, Subhankar; Grove, Carolyn; Colin, Amy; Brandt, Cordelia; Duque-Correa, Maria A.; Forbester, Jessica; Nguyen, Tu Anh Pham; Hale, Christine; Vasilliou, George S.; Arends, Mark J.; Wren, Brendan W.; Dougan, Gordon

2016-01-01

ABSTRACT Mice harboring a mutation in the gene encoding gastric intrinsic factor (Gif), a protein essential for the absorption of vitamin B12/cobalamin (Cbl), have potential as a model to explore the role of vitamins in infection. The levels of Cbl in the blood of Giftm1a/tm1a mutant mice were influenced by the maternal genotype, with offspring born to heterozygous (high Cbl, F1) mothers exhibiting a significantly higher serum Cbl level than those born to homozygous (low Cbl, F2) equivalents. Low Cbl levels correlated with susceptibility to an infectious challenge with Salmonella enterica serovar Typhimurium or Citrobacter rodentium, and this susceptibility phenotype was moderated by Cbl administration. Transcriptional and metabolic profiling revealed that Cbl deficient mice exhibited a bioenergetic shift similar to a metabolic phenomenon commonly found in cancerous cells under hypoxic conditions known as the Warburg effect, with this metabolic effect being exacerbated further by infection. Our findings demonstrate a role for Cbl in bacterial infection, with potential general relevance to dietary deficiency and infection susceptibility. PMID:27329747

Case-based Learning in Microbiology: Observations from a North West Indian Medical College.

PubMed

Singhal, Anita

2017-12-01

Microbiology is usually taught by conventional lectures, and its retention and application is observed to be poor among medical graduates/practitioners. Introduction of case-based learning (CBL) in microbiology for second-year professional MBBS students. Students were divided into two groups of fifty each. Four clinical cases were used for CBL. One group had two CBL sessions whereas the other had didactic lectures (DLs) and then the groups were crossed over. Case scenario handouts were given to students a week before the session, and smaller groups were formed for discussions and presentations in CBL sessions. Posttest, in multiple choice questions format, was conducted in two phases: First, immediately after the completion of the four CBL and DL sessions, and second, 6 weeks after the first posttest. Student and faculty feedback was taken about CBL sessions. Hundred MBBS students of the fourth semester voluntarily participated in the CBL study. The CBL scores were significantly higher than DL session scores ( P = 0.015). This difference was more marked in scoring done after 6 weeks of session completion ( P < 0.001). Student reported satisfaction in being taught by CBL method in 5-point Likert scale feedback form. Faculty feedback was positive for CBL. CBL helped in retention of knowledge and its application better than DL in our observation. More sessions on commonly encountered case scenarios will be useful for students in recalling basic science knowledge in their later years as practitioners.

Coordination chemistry controls the thiol oxidase activity of the B12-trafficking protein CblC

PubMed Central

Li, Zhu; Shanmuganathan, Aranganathan; Ruetz, Markus; Yamada, Kazuhiro; Lesniak, Nicholas A.; Kräutler, Bernhard; Brunold, Thomas C.; Koutmos, Markos; Banerjee, Ruma

2017-01-01

The cobalamin or B12 cofactor supports sulfur and one-carbon metabolism and the catabolism of odd-chain fatty acids, branched-chain amino acids, and cholesterol. CblC is a B12-processing enzyme involved in an early cytoplasmic step in the cofactor-trafficking pathway. It catalyzes the glutathione (GSH)-dependent dealkylation of alkylcobalamins and the reductive decyanation of cyanocobalamin. CblC from Caenorhabditis elegans (ceCblC) also exhibits a robust thiol oxidase activity, converting reduced GSH to oxidized GSSG with concomitant scrubbing of ambient dissolved O2. The mechanism of thiol oxidation catalyzed by ceCblC is not known. In this study, we demonstrate that novel coordination chemistry accessible to ceCblC-bound cobalamin supports its thiol oxidase activity via a glutathionyl-cobalamin intermediate. Deglutathionylation of glutathionyl-cobalamin by a second molecule of GSH yields GSSG. The crystal structure of ceCblC provides insights into how architectural differences at the α- and β-faces of cobalamin promote the thiol oxidase activity of ceCblC but mute it in wild-type human CblC. The R161G and R161Q mutations in human CblC unmask its latent thiol oxidase activity and are correlated with increased cellular oxidative stress disease. In summary, we have uncovered key architectural features in the cobalamin-binding pocket that support unusual cob(II)alamin coordination chemistry and enable the thiol oxidase activity of ceCblC. PMID:28442570

Expression Patterns and Identified Protein-Protein Interactions Suggest That Cassava CBL-CIPK Signal Networks Function in Responses to Abiotic Stresses.

PubMed

Mo, Chunyan; Wan, Shumin; Xia, Youquan; Ren, Ning; Zhou, Yang; Jiang, Xingyu

2018-01-01

Cassava is an energy crop that is tolerant of multiple abiotic stresses. It has been reported that the interaction between Calcineurin B-like (CBL) protein and CBL-interacting protein kinase (CIPK) is implicated in plant development and responses to various stresses. However, little is known about their functions in cassava. Herein, 8 CBL ( MeCBL ) and 26 CIPK ( MeCIPK ) genes were isolated from cassava by genome searching and cloning of cDNA sequences of Arabidopsis CBL s and CIPK s. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that the expression levels of MeCBL and MeCIPK genes were different in different tissues throughout the life cycle. The expression patterns of 7 CBL and 26 CIPK genes in response to NaCl, PEG, heat and cold stresses were analyzed by quantitative real-time PCR (qRT-PCR), and it was found that the expression of each was induced by multiple stimuli. Furthermore, we found that many pairs of CBLs and CIPKs could interact with each other via investigating the interactions between 8 CBL and 25 CIPK proteins using a yeast two-hybrid system. Yeast cells co-transformed with cassava MeCIPK24, MeCBL10 , and Na + /H + antiporter MeSOS1 genes exhibited higher salt tolerance compared to those with one or two genes. These results suggest that the cassava CBL-CIPK signal network might play key roles in response to abiotic stresses.

c-Cbl regulates αPix-mediated cell migration and invasion

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

Seong, Min Woo; Park, Ji Ho; Yoo, Hee Min

2014-12-12

Highlights: • c-Cbl ubiquitinates αPix for proteasome-mediated degradation. • C6 and A172 glioma cells lack c-Cbl, which leads to stabilization of αPix. • The accumulated αPix promotes migration and invasion of the cancer cells. • The lack of c-Cbl in the cells appears responsible for their malignant behavior. - Abstract: c-Cbl, a RING-type ubiquitin E3 ligase, down-regulates receptor tyrosine kinases, including EGF receptor, and inhibits cell proliferation. Moreover, c-Cbl mutations are frequently found in patients with myeloid neoplasm. Therefore, c-Cbl is known as a tumor suppressor. αPix is expressed only in highly proliferative and mobile cells, including immune cells, andmore » up-regulated in certain invasive tumors, such as glioblastoma multiforme. Here, we showed that c-Cbl serves as an ubiquitin E3 ligase for proteasome-mediated degradation of αPix, but not βPix. Remarkably, the rat C6 and human A172 glioma cells were unable to express c-Cbl, which leads to a dramatic accumulation of αPix. Depletion of αPix by shRNA markedly reduced the ability of the glioma cells to migrate and invade, whereas complementation of shRNA-insensitive αPix promoted it. These results indicate that c-Cbl negatively regulates αPix-mediated cell migration and invasion and the lack of c-Cbl in the C6 and A172 glioma cells is responsible for their malignant behavior.« less

Mutations of E3 Ubiquitin Ligase Cbl Family Members Constitute a Novel Common Pathogenic Lesion in Myeloid Malignancies

PubMed Central

Makishima, Hideki; Cazzolli, Heather; Szpurka, Hadrian; Dunbar, Andrew; Tiu, Ramon; Huh, Jungwon; Muramatsu, Hideki; O'Keefe, Christine; Hsi, Eric; Paquette, Ronald L.; Kojima, Seiji; List, Alan F.; Sekeres, Mikkael A.; McDevitt, Michael A.; Maciejewski, Jaroslaw P.

2009-01-01

Purpose Acquired somatic uniparental disomy (UPD) is commonly observed in myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative neoplasms (MDS/MPN), or secondary acute myelogenous leukemia (sAML) and may point toward genes harboring mutations. Recurrent UPD11q led to identification of homozygous mutations in c-Cbl, an E3 ubiquitin ligase involved in attenuation of proliferative signals transduced by activated receptor tyrosine kinases. We examined the role and frequency of Cbl gene family mutations in MPN and related conditions. Methods We applied high-density SNP-A karyotyping to identify loss of heterozygosity of 11q in 442 patients with MDS, MDS/MPN, MPN, sAML evolved from these conditions, and primary AML. We sequenced c-Cbl, Cbl-b, and Cbl-c in patients with or without corresponding UPD or deletions and correlated mutational status with clinical features and outcomes. Results We identified c-Cbl mutations in 5% and 9% of patients with chronic myelomonocytic leukemia (CMML) and sAML, and also in CML blast crisis and juvenile myelomonocytic leukemia (JMML). Most mutations were homozygous and affected c-Cbl; mutations in Cbl-b were also found in patients with similar clinical features. Patients with Cbl family mutations showed poor prognosis, with a median survival of 5 months. Pathomorphologic features included monocytosis, monocytoid blasts, aberrant expression of phosphoSTAT5, and c-kit overexpression. Serial studies showed acquisition of c-Cbl mutations during malignant evolution. Conclusion Mutations in the Cbl family RING finger domain or linker sequence constitute important pathogenic lesions associated with not only preleukemic CMML, JMML, and other MPN, but also progression to AML, suggesting that impairment of degradation of activated tyrosine kinases constitutes an important cancer mechanism. PMID:19901108

Assembly of the intrinsic factor domains and oligomerization of the protein in the presence of cobalamin.

PubMed

Fedosov, Sergey N; Fedosova, Natalya U; Berglund, Lars; Moestrup, Søren K; Nexø, Ebba; Petersen, Torben E

2004-11-30

Human intrinsic factor (IF) was purified from the recombinant plant Arabidopsis thaliana by affinity chromatography. Cobalamin (Cbl) saturated protein was separated by gel filtration into peaks I and II, which contained according to SDS electrophoresis the 50 kDa full-length protein IF(50) and a mixture of two fragments, respectively. Two components of peak II were identified as the 30 kDa N-terminal peptide IF(30) and the 20 kDa C-terminal glycopeptide IF(20). Measurements of M(w) under the nondenaturing conditions were conducted by static light scattering. They revealed 100 kDa IF dimers in peak I, whereas 50 kDa cleaved monomers were found in peak II. The protein devoid of Cbl dissociated to the elementary units incapable of association in the absence of Cbl. The individual proteolytic fragments bound Cbl at high concentration of the ligand; however, neither IF(30).Cbl nor IF(20).Cbl oligomerized. A mixture of two fragments IF(30) + IF(20) and Cbl produced a firm complex, IF(30+20).Cbl, which could not associate to dimers. In contrast to IF(30+20).Cbl, the saturated full-length monomers IF(50).Cbl dimerized with K(d) approximately 1 microM. We suggest a two-domain organization of the full-length protein, where two distant units, IF(30) and IF(20), can be assembled only by Cbl. They are connected by a protease-sensitive link, whose native structure is likely to be important for dimerization. However, linkage between two domains is not compulsory for Cbl binding. Advantages of the two-domain structure of IF are discussed.

Maintenance of Epithelial Stem Cells by Cbl Proteins

DTIC Science & Technology

2013-09-01

our research findings during the entire grant period (Sept. 2010 – Aug. 2013). 1. Analysis of Cbl functions in progenitor-type mammary epithelial...catenin pathway, but further investigation is required to establish this. 2. Analysis of Cbl functions in vivo using gene mutant mouse models We...Nandwani N, Gu H, Band V, Band H. Rapidly fatal myeloproliferative disorders in mice with deletion of Casitas B-cell lymphoma (Cbl) and Cbl-b in

Student Response to Remote-Online Case-Based Learning: A Qualitative Study

PubMed Central

2016-01-01

Background Case-based learning (CBL) typically involves face-to-face interaction in small collaborative groups with a focus on self-directed study. To our knowledge, no published studies report an evaluation of Web conferencing in CBL. Objective The primary aim of this study was to explore student perceptions and attitudes in response to a remote-online case-based learning (RO-CBL) experience. Methods This study took place over a 2-week period in 2013 at Monash University, Victoria, Australia. A third year cohort (n=73) of physiotherapy students was invited to participate. Students were required to participate in 2 training sessions, followed by RO-CBL across 2 sessions. The primary outcome of interest was the student feedback on the quality of the learning experience during RO-CBL participation. This was explored with a focus group and a survey. Results Most students (68/73) completed the postintervention survey (nonparticipation rate 8%). RO-CBL was generally well received by participants, with 59% (40/68) of participates stating that they’d like RO-CBL to be used in the future and 78% (53/68) of participants believing they could meet the CBL’s learning objectives via RO-CBL. The 4 key themes relevant to student response to RO-CBL that emerged from the focus groups and open-ended questions on the postintervention survey were how RO-CBL compared to expectations, key benefits of RO-CBL including flexibility and time and cost savings, communication challenges in the online environment compared to face-to-face, and implications of moving to an online platform. Conclusions Web conferencing may be a suitable medium for students to participate in CBL. Participants were satisfied with the learning activity and felt they could meet the CBL’s learning objectives. Further study should evaluate Web conferencing CBL across an entire semester in regard to student satisfaction, perceived depth of learning, and learning outcomes. PMID:27731852

Remote-online case-based learning: A comparison of remote-online and face-to-face, case-based learning - a randomized controlled trial.

PubMed

Nicklen, Peter; Keating, Jenny L; Paynter, Sophie; Storr, Michael; Maloney, Stephen

2016-01-01

Case-based learning (CBL) is an educational approach where students work in small, collaborative groups to solve problems. Computer assisted learning (CAL) is the implementation of computer technology in education. The purpose of this study was to compare the effects of a remote-online CBL (RO-CBL) with traditional face-to-face CBL on learning the outcomes of undergraduate physiotherapy students. Participants were randomized to either the control (face-to-face CBL) or to the CAL intervention (RO-CBL). The entire 3rd year physiotherapy cohort (n = 41) at Monash University, Victoria, Australia, were invited to participate in the randomized controlled trial. Outcomes included a postintervention multiple-choice test evaluating the knowledge gained from the CBL, a self-assessment of learning based on examinable learning objectives and student satisfaction with the CBL. In addition, a focus group was conducted investigating perceptions and responses to the online format. Thirty-eight students (control n = 19, intervention n = 19) participated in two CBL sessions and completed the outcome assessments. CBL median scores for the postintervention multiple-choice test were comparable (Wilcoxon rank sum P = 0.61) (median/10 [range] intervention group: 9 [8-10] control group: 10 [7-10]). Of the 15 examinable learning objectives, eight were significantly in favor of the control group, suggesting a greater perceived depth of learning. Eighty-four percent of students (16/19) disagreed with the statement "I enjoyed the method of CBL delivery." Key themes identified from the focus group included risks associated with the implementation of, challenges of communicating in, and flexibility offered, by web-based programs. RO-CBL appears to provide students with a comparable learning experience to traditional CBL. Procedural and infrastructure factors need to be addressed in future studies to counter student dissatisfaction and decreased perceived depth of learning.

X-ray structural characterization of imidazolylcobalamin and histidinylcobalamin: cobalamin models for aquacobalamin bound to the B12 transporter protein transcobalamin.

PubMed

Hannibal, Luciana; Bunge, Scott D; van Eldik, Rudi; Jacobsen, Donald W; Kratky, Christoph; Gruber, Karl; Brasch, Nicola E

2007-04-30

The X-ray structures of imidazolylcobalamin (ImCbl) and histidinylcobalamin (HisCbl) are reported. These structures are of interest given that the recent structures of human and bovine transcobalamin prepared in their holo forms from aquacobalamin show a histidine residue of the metalloprotein bound at the beta-axial site of the cobalamin (Wuerges, J. et al. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 4386-4391). The beta-axial Co-N bond distances for ImCbl and HisCbl are 1.94(1) and 1.951(7) A, respectively. The alpha-axial Co-N bond distances to the 5,6-dimethylbenzimidazole are 2.01(1) and 1.979(8) A for ImCbl and HisCbl, respectively, and are typical for cobalamins with weak sigma-donor ligands at the beta-axial site. The corrin fold angles of 11.8(3) degrees (ImCbl) and 12.0(3) degrees (HisCbl) are smaller than those typically observed for cobalamins.

Structural Basis of Multifunctionality in a Vitamin B[subscript 12]-processing Enzyme

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

Koutmos, Markos; Gherasim, Carmen; Smith, Janet L.

An early step in the intracellular processing of vitamin B{sub 12} involves CblC, which exhibits dual reactivity, catalyzing the reductive decyanation of cyanocobalamin (vitamin B{sub 12}), and the dealkylation of alkylcobalamins (e.g. methylcobalamin; MeCbl). Insights into how the CblC scaffold supports this chemical dichotomy have been unavailable despite it being the most common locus of patient mutations associated with inherited cobalamin disorders that manifest in both severe homocystinuria and methylmalonic aciduria. Herein, we report structures of human CblC, with and without bound MeCbl, which provide novel biochemical insights into its mechanism of action. Our results reveal that CblC is themore » most divergent member of the NADPH-dependent flavin reductase family and can use FMN or FAD as a prosthetic group to catalyze reductive decyanation. Furthermore, CblC is the first example of an enzyme with glutathione transferase activity that has a sequence and structure unrelated to the GST superfamily. CblC thus represents an example of evolutionary adaptation of a common structural platform to perform diverse chemistries. The CblC structure allows us to rationalize the biochemical basis of a number of pathological mutations associated with severe clinical phenotypes.« less

Cbl-phosphatidylinositol 3 kinase interaction differentially regulates macrophage colony-stimulating factor-mediated osteoclast survival and cytoskeletal reorganization.

PubMed

Adapala, Naga Suresh; Barbe, Mary F; Langdon, Wallace Y; Tsygankov, Alexander Y; Sanjay, Archana

2010-03-01

The Cbl protein is a key player in macrophage colony-stimulating factor (M-CSF)-induced signaling. To examine the role of Cbl in M-CSF-mediated cellular events, we used Cbl(YF/YF) knockin mice in which the regulatory tyrosine 737, which when phosphorylated binds to the p85 subunit of phosphatidylinositol 3 kinase (PI3K), is substituted to phenylalanine. In ex vivo cultures, M-CSF and receptor activator of nuclear factor-kappaB ligand-mediated differentiation of bone marrow precursors from Cbl(YF/YF) mice generated increased number of osteoclasts; however, osteoclast numbers in Cbl(YF/YF) cultures were unchanged with increasing doses of M-CSF. We found that Cbl(YF/YF) osteoclasts have enhanced intrinsic ability to survive, and this response was further augmented upon exposure to M-CSF. Treatment of osteoclasts with M-CSF-induced actin reorganization and lamellipodia formation in wild-type osteoclasts; however, in Cbl(YF/YF) osteoclasts lamellipodia formation was compromised. Collectively, these results indicate that abrogation of the Cbl-PI3K interaction, although not affecting M-CSF-induced proliferation and differentiation of precursors, is required for regulation of survival and actin cytoskeletal reorganization of mature osteoclasts.

Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex.

PubMed

Myers, Margaret D; Sosinowski, Tomasz; Dragone, Leonard L; White, Carmen; Band, Hamid; Gu, Hua; Weiss, Arthur

2006-01-01

The adaptor molecule SLAP and E3 ubiquitin ligase c-Cbl each regulate expression of T cell receptor (TCR)-CD3 on thymocytes. Here we provide genetic and biochemical evidence that both molecules function in the same pathway. TCR-CD3 expression was similar in the absence of SLAP and/or c-Cbl. SLAP and c-Cbl were found to interact, and their expression together downregulated CD3epsilon. This required multiple domains in SLAP and the ring finger of c-Cbl. Furthermore, expression of SLAP and c-Cbl together induced TCRzeta ubiquitination and degradation, preventing the accumulation of fully assembled recycling TCR complexes. These studies indicate that SLAP links the E3 ligase activity of c-Cbl to the TCR, allowing for stage-specific regulation of TCR expression.

Carbon Balance at Landscape Level inferred fromTower CO2 Concentration Measurements

NASA Astrophysics Data System (ADS)

Chen, J. M.; Chen, B.; Higuchi, K.; Chan, D.; Shashkov, A.; Lin, H.; Liu, J.

2003-04-01

Terrestrial carbon sinks are considerable in the global carbon budget, but the accumulation of carbon in terrestrial ecosystems is very small (~0.2% per year) relative to the total carbon stocks in forests. Currently, eddy-covariance instruments mounted on towers are the only reliable means to measure carbon balance of a land surface, albeit limited to small areas and not free of caveats. In our quest of understanding the collective performance of ecosystems under the changing climate, it is highly desirable to have the ability to acquire carbon cycle information for large areas (landscape) consisting of patches of different ecosystems. For this purpose we explored methodologies of inferring carbon cycle information from tower CO2 concentration measurements affected by large areas (100-10000 km2). An ecosystem model named Boreal Ecosystem Productivity Simulator (BEPS) is coupled with a carbon-specific Vertical Diffusion Scheme (VDS) in order to decipher temporal variations in CO2 for landscape-level photosynthesis and respiration information. The coupled BEPS-VDS is applied to a unique 9-year (1990-2000 with 1997-8 missing data) 5-minute CO2 record measured on a 40-m tower over boreal forests near Fraserdale, Ontario, Canada. Over the period, the mean diurnal amplitude of the measured CO2 at 40 m increased by 5.58 ppmv, or 28% in the growing season. The increase in nighttime ecosystem respiration, causing the increase in the daily maximum CO2 concentration, was responsible for 65% of the increase in the diurnal amplitude, i.e., 3.61 ppmv, corresponding to an increase in the mean daily air temperature by about 2.77 degC and precipitation by 5% over the same period. The rest (35%) is explained by the increase in ecosystem daytime photosynthesis, causing the decrease in the daily minimum CO2 concentration. As the nighttime stable boundary layer (SBL) (270-560 m) was much shallower than the daytime convective boundary layer (CBL) (1000-1600 m), the increase in nighttime respiration was actually smaller than the increase in daytime photosynthesis according simulations using BEPS-VDS. This is because the same amount of change in ppmv at 40 m required a larger change in the surface flux in CBL than in SBL, i.e. CBL was able to dilute the surface effects in a higher air column than was SBL. As a consequence, we found that the boreal landscape in the vicinity of the tower up to 100 km, consisting of mostly black spruce forests with small fractions of aspen and wetland, acted as a carbon sink in the 1990-2000 period. The absolute magnitude of the sink requires modeling for 50-100 years, but we infer from the short CO2 record that the sink magnitude increased by 0.44 gC/(m2.y) on average, i.e., the accumulated effect over the 11 years was 4.8 gC/m2. Our model simulations indicate that improved nutrient mineralization in soil at higher temperatures was the main cause for enhanced photosynthesis. Although uncertainties exist in these estimates, the results suggest the usefulness of air CO2 records at high frequencies (at least hourly) for long periods.

Regulation of CTP Synthase Filament Formation During DNA Endoreplication in Drosophila.

PubMed

Wang, Pei-Yu; Lin, Wei-Cheng; Tsai, Yi-Cheng; Cheng, Mei-Ling; Lin, Yu-Hung; Tseng, Shu-Heng; Chakraborty, Archan; Pai, Li-Mei

2015-12-01

CTP synthase (CTPsyn) plays an essential role in DNA, RNA, and lipid synthesis. Recent studies in bacteria, yeast, and Drosophila all reveal a polymeric CTPsyn structure, which dynamically regulates its enzymatic activity. However, the molecular mechanism underlying the formation of CTPsyn polymers is not completely understood. In this study, we found that reversible ubiquitination regulates the dynamic assembly of the filamentous structures of Drosophila CTPsyn. We further determined that the proto-oncogene Cbl, an E3 ubiquitin ligase, controls CTPsyn filament formation in endocycles. While the E3 ligase activity of Cbl is required for CTPsyn filament formation, Cbl does not affect the protein levels of CTPsyn. It remains unclear whether the regulation of CTPsyn filaments by Cbl is through direct ubiquitination of CTPsyn. In the absence of Cbl or with knockdown of CTPsyn, the progression of the endocycle-associated S phase was impaired. Furthermore, overexpression of wild-type, but not enzymatically inactive CTPsyn, rescued the endocycle defect in Cbl mutant cells. Together, these results suggest that Cbl influences the nucleotide pool balance and controls CTPsyn filament formation in endocycles. This study links Cbl-mediated ubiquitination to the polymerization of a metabolic enzyme and reveals a role for Cbl in endocycles during Drosophila development. Copyright © 2015 by the Genetics Society of America.

Anticipated and Actual Implementation of Case-Based Learning by Dental Faculty Members During and After Training.

PubMed

Behar-Horenstein, Linda S; Catalanotto, Frank A; Nascimento, Marcelle M

2015-09-01

The aims of this study were to describe the processes used to train dental faculty members in case-based learning (CBL) and to determine their beliefs about the anticipated implementation of CBL and perceptions of actual implementation following use of the CBL approach. Participants were dental faculty members at the University of Florida who received a four-day intensive training course in the use of CBL. Two focus groups were conducted. The first occurred during training to assess how the participants anticipated using CBL. The second was conducted during the faculty members' implementation of CBL. All 19 trainees participated in focus group 1 (100%). During the course of the study, two faculty members left the school; of the remaining 17, 12 participated in focus group 2 (participation rate of 71%). The findings showed that initially the faculty members were hesitant and uncertain about using CBL. Following implementation, those issues dissipated, as the participants began to consider how to optimize the effectiveness of CBL as a legitimate method for fostering student ownership of learning and active participation. Understanding what CBL means for individual educators at varying stages of change will likely allow the dental education community to better anticipate and address tensions and challenges that faculty members are likely to experience.

Inherited selective intestinal cobalamin malabsorption and cobalamin deficiency in dogs.

PubMed

Fyfe, J C; Giger, U; Hall, C A; Jezyk, P F; Klumpp, S A; Levine, J S; Patterson, D F

1991-01-01

Inherited selective intestinal malabsorption of cobalamin (Cbl) was observed in a family of giant schnauzer dogs. Family studies and breeding experiments demonstrated simple autosomal recessive inheritance of this disease. Affected puppies exhibited chronic inappetence and failure to thrive beginning between 6 and 12 wk of age. Neutropenia with hypersegmentation, anemia with anisocytosis and poikilocytosis, and megaloblastic changes of the bone marrow were present. Serum Cbl concentrations were low, and methylmalonic aciduria and homocysteinemia were present. Parenteral, but not oral, cyanocobalamin administration rapidly eliminated all signs of Cbl deficiency except for low serum Cbl concentrations. Cbl malabsorption in affected dogs was documented by oral administration of [57Co]cyanocobalamin with or without simultaneous oral administration of intrinsic factor or normal dog gastric juice. Quantitation and function studies of intrinsic factor and transcobalamin-II from affected dogs revealed no abnormality. Other gastrointestinal functions and ileal morphology were normal, indicating a selective defect of Cbl absorption at the level of the ileal enterocyte. Immunoelectron microscopy of ileal biopsies showed that the receptor for intrinsic factor-Cbl complex was absent from the apical brush border microvillus pits of affected dogs. This canine disorder resembles inherited selective intestinal Cbl malabsorption (Imerslund-Gräsbeck syndrome) in humans, and is a spontaneously occurring animal model of early onset Cbl deficiency.

Expression Patterns and Identified Protein-Protein Interactions Suggest That Cassava CBL-CIPK Signal Networks Function in Responses to Abiotic Stresses

PubMed Central

Mo, Chunyan; Wan, Shumin; Xia, Youquan; Ren, Ning; Zhou, Yang; Jiang, Xingyu

2018-01-01

Cassava is an energy crop that is tolerant of multiple abiotic stresses. It has been reported that the interaction between Calcineurin B-like (CBL) protein and CBL-interacting protein kinase (CIPK) is implicated in plant development and responses to various stresses. However, little is known about their functions in cassava. Herein, 8 CBL (MeCBL) and 26 CIPK (MeCIPK) genes were isolated from cassava by genome searching and cloning of cDNA sequences of Arabidopsis CBLs and CIPKs. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that the expression levels of MeCBL and MeCIPK genes were different in different tissues throughout the life cycle. The expression patterns of 7 CBL and 26 CIPK genes in response to NaCl, PEG, heat and cold stresses were analyzed by quantitative real-time PCR (qRT-PCR), and it was found that the expression of each was induced by multiple stimuli. Furthermore, we found that many pairs of CBLs and CIPKs could interact with each other via investigating the interactions between 8 CBL and 25 CIPK proteins using a yeast two-hybrid system. Yeast cells co-transformed with cassava MeCIPK24, MeCBL10, and Na+/H+ antiporter MeSOS1 genes exhibited higher salt tolerance compared to those with one or two genes. These results suggest that the cassava CBL-CIPK signal network might play key roles in response to abiotic stresses. PMID:29552024

Case-Based Web Learning Versus Face-to-Face Learning: A Mixed-Method Study on University Nursing Students.

PubMed

Chan, Aileen Wai-Kiu; Chair, Sek-Ying; Sit, Janet Wing-Hung; Wong, Eliza Mi-Ling; Lee, Diana Tze-Fun; Fung, Olivia Wai-Man

2016-03-01

Case-based learning (CBL) is an effective educational method for improving the learning and clinical reasoning skills of students. Advances in e-learning technology have supported the development of the Web-based CBL approach to teaching as an alternative or supplement to the traditional classroom approach. This study aims to examine the CBL experience of Hong Kong students using both traditional classroom and Web-based approaches in undergraduate nursing education. This experience is examined in terms of the perceived self-learning ability, clinical reasoning ability, and satisfaction in learning of these students. A mixture of quantitative and qualitative approaches was adopted. All Year-3 undergraduate nursing students were recruited. CBL was conducted using the traditional classroom approach in Semester 1, and the Web-based approach was conducted in Semester 2. Student evaluations were collected at the end of each semester using a self-report questionnaire. In-depth, focus-group interviews were conducted at the end of Semester 2. One hundred twenty-two students returned their questionnaires. No difference between the face-to-face and Web-based approaches was found in terms of self-learning ability (p = .947), clinical reasoning ability (p = .721), and satisfaction (p = .083). Focus group interview findings complemented survey findings and revealed five themes that reflected the CBL learning experience of Hong Kong students. These themes were (a) the structure of CBL, (b) the learning environment of Web-based CBL, (c) critical thinking and problem solving, (d) cultural influence on CBL learning experience, and (e) student-centered and teacher-centered learning. The Web-based CBL approach was comparable but not superior to the traditional classroom CBL approach. The Web-based CBL experience of these students sheds light on the impact of Chinese culture on student learning behavior and preferences.

Cobalamin Concentrations in Fetal Liver Show Gender Differences: A Result from Using a High-Pressure Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry as an Ultratrace Cobalt Speciation Method.

PubMed

Bosle, Janine; Goetz, Sven; Raab, Andrea; Krupp, Eva M; Scheckel, Kirk G; Lombi, Enzo; Meharg, Andrew A; Fowler, Paul A; Feldmann, Jörg

2016-12-20

Maternal diet and lifestyle choices may affect placental transfer of cobalamin (Cbl) to the fetus. Fetal liver concentration of Cbl reflects nutritional status with regards to vitamin B12, but at these low concentration current Cbl measurement methods lack robustness. An analytical method based on enzymatic extraction with subsequent reversed-phase-high-pressure liquid chromatography (RP-HPLC) separation and parallel ICPMS and electrospray ionization (ESI)-Orbitrap-MS to determine specifically Cbl species in liver samples of only 10-50 mg was developed using 14 pig livers. Subsequently 55 human fetal livers were analyzed. HPLC-ICPMS analysis for cobalt (Co) and Cbl gave detection limits of 0.18 ng/g and 0.88 ng/g d.m. in liver samples, respectively, with a recovery of >95%. Total Co (Co t ) concentration did not reflect the amount of Cbl or vitamin B12 in the liver. Cbl bound Co contributes only 45 ± 15% to Co t . XRF mapping and μXANES analysis confirmed the occurrence of non-Cbl cobalt in pig liver hot spots indicating particular Co. No correlations of total cobalt nor Cbl with fetal weight or weeks of gestation were found for the human fetal livers. Although no gender difference could be identified for total Co concentration, female livers were significantly higher in Cbl concentration (24.1 ± 7.8 ng/g) than those from male fetuses (19.8 ± 7.1 ng/g) (p = 0.04). This HPLC-ICPMS method was able to quantify total Co t and Cbl in fetus liver, and it was sensitive and precise enough to identify this gender difference.

Fasting time and vitamin B12 levels in a community-based population.

PubMed

Orton, Dennis J; Naugler, Christopher; Sadrzadeh, S M Hossein

2016-07-01

Vitamin B12, also known as cobalamin (Cbl), is an essential vitamin that manifests with numerous severe but non-specific symptoms in cases of deficiency. Assessing Cbl status often requires fasting, although this requirement is not standard between institutions. This study evaluated the impact of fasting on Cbl levels in a large community-based cohort in an effort to promote standardization of Cbl testing between sites. Laboratory data for Cbl, fasting time, patient age and sex were obtained from laboratory information service from Calgary Laboratory Services (CLS) for the period of April 2011 to June 2015. CLS is the sole supplier of laboratory services in the Southern Alberta region in Canada (population, approximately 1.4 million). To investigate potential sex-specific effects of fasting on Cbl levels, males and females were analyzed separately using linear regression models. A total of 346,957 individual patient results (196,849 females, 146,085 males) were obtained. The mean plasma Cbl level was 386.5 (±195.6) pmol/L and 412.0 (±220.8) pmol/L for males and females, respectively. Linear regression analysis showed fasting had no significant association with Cbl levels in females; however a statistically significant decrease of 0.9pmol/L/hour fasting (p<0.001) was noted in males. The broad population variance in Cbl suggests the slight gender-specific differences noted in this study are insignificant. Despite this, fasting has the potential to contribute to higher rates of Cbl deficiency in men. Together, these data suggest fasting should be excluded as a requirement for evaluating plasma Cbl. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of a Novel Tc-99m Labelled Vitamin B12 Derivative for Targeting Escherichia coli and Staphylococcus aureus In Vitro and in an Experimental Foreign-Body Infection Model.

PubMed

Baldoni, Daniela; Waibel, Robert; Bläuenstein, Peter; Galli, Filippo; Iodice, Violetta; Signore, Alberto; Schibli, Roger; Trampuz, Andrej

2015-12-01

Vitamin B12 (cyanocobalamin, Cbl) is accumulated by rapidly replicating prokaryotic and eukaryotic cells. We investigated the potential of a Tc-99m labelled Cbl derivative ([(99m)Tc]PAMA(4)-Cbl) for targeting infections caused by Escherichia coli and Staphylococcus aureus. In vitro binding assays were followed by biodistribution studies in a mouse model of foreign body infection. E. coli (ATCC 25922) and S. aureus (ATCC 43335) were used as test strains. [(57)Co]Cbl, [(67)Ga]citrate and [(99m)Tc]DTPA served as reference compounds. The in vitro competitive binding of [(57)Co]Cbl or [(99m)Tc]PAMA(4)-Cbl, and unlabeled Cbl, to viable or killed bacteria, was evaluated at 37 and 4 °C. A cage mouse model of infection was used for biodistribution of intravenous [(57)Co]Cbl and [(99m)Tc]PAMA(4)-Cbl in cage and dissected tissues of infected and non-infected mice. Maximum binding (mean ± SD) of [(57)Co]Cbl to viable E. coli was 81.7 ± 2.6 % and to S. aureus 34.0 ± 6.7 %, at 37 °C; no binding occurred to heat-killed bacteria. Binding to both test strains was displaced by 100- to 1000-fold excess of unlabeled Cbl. The in vitro binding of [(99m)Tc]PAMA(4)-Cbl was 100-fold and 3-fold lower than the one of [(57)Co]Cbl for E. coli and S. aureus, respectively. In vivo, [(99m)Tc]PAMA(4)-Cbl showed peak percentage of injected dose (% ID) values between 1.33 and 2.3, at 30 min post-injection (p.i.). Significantly higher retention occurred in cage fluids infected with S. aureus at 4 h and with E. coli at 8 h p.i. than in non-infected animals. Accumulation into infected cages was also higher than the one of [(99m)Tc]DTPA, which showed similar biodistribution in infected and sterile mice. [(57)Co]Cbl gradually accumulated in cages with peaks % ID between 3.58 and 4.83 % achieved from 24 to 48 h. Discrimination for infection occurred only in E. coli-infected mice, at 72 h p.i. [(67)Ga]citrate, which showed a gradual accumulation into cage fluids during 12 h, was discriminative for infection from 48 to 72 h p.i. (P < 0.05). Cbl displayed rapid and specific in vitro binding to test strains. [(99m)Tc]PAMA(4)-Cbl was rapidly cleared from most tissues and discriminated between sterile and infected cages, being a promising candidate for imaging infections in humans.

The influence of undergraduate education on professional practice transition: a comparative descriptive study.

PubMed

Williams, Bev; Richard, Liz; Al Sayah, Fatima

2015-03-01

Graduates from Problem/Context Based Learning (CBL) undergraduate nursing programs often express concern that they may not be as well prepared for transition to graduate nursing practice as their colleagues from more traditional lecture-based programs. To determine if there is a difference in how graduates from CBL and non-CBL programs describe their transition to graduate practice within the first 2 years of graduation. This was a comparative descriptive study that involved the use of a web-based survey. A convenience sample of 163 graduate nurses with 1 to 2 years of experience consented to be part of the study. They completed a researcher-designed questionnaire, which consisted of 26 items based on entry to practice competencies identified by the provincial professional nursing organization. There was no significant difference in the transition experience of graduates from CBL and traditional education programs within their first 2 years following graduation. These results confirm the findings of authors who compared transition among CBL and non-CBL graduates who had graduated anywhere from six months to several years following graduation. It is clear that CBL programs do prepare graduates to successfully transition into graduate nurse practice. Graduates from both CBL and non-CBL programs indicated a need for more formal agency sponsored orientation and transition assistance programs at the beginning of their initial employment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Does the Use of Case-Based Learning Impact the Retention of Key Concepts in Undergraduate Biochemistry?

ERIC Educational Resources Information Center

Kulak, Verena; Newton, Genevieve; Sharma, Rahul

2017-01-01

Objective: Enhanced knowledge retention and a preference towards a deep learning approach are desirable pedagogical outcomes of case-based learning (CBL). The CBL literature is sparse with respect to these outcomes, and this is especially so in the area of biochemistry. The present study determined the effect of CBL vs. non CBL on knowledge…

Suppression of NF-κB Survival Signaling by Nitrosylcobalamin Sensitizes Neoplasms to the Anti-tumor Effects of Apo2L/TRAIL*

PubMed Central

Chawla-Sarkar, Mamta; Bauer, Joseph A.; Lupica, Joseph A.; Morrison, Bei H.; Tang, Zhuo; Oates, Rhonda K.; Almasan, Alex; DiDonato, Joseph A.; Borden, Ernest C.; Lindner, Daniel J.

2007-01-01

We have previously demonstrated the anti-tumor activity of nitrosylcobalamin (NO-Cbl), an analog of vitamin B12 that delivers nitric oxide (NO) and increases the expression of tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) and its receptors in human tumors. The specific aim of this study was to examine whether NO-Cbl could sensitize drug-resistant melanomas to Apo2L/TRAIL. Antiproliferative effects of NO-Cbl and Apo2L/TRAIL were assessed in malignant melanomas and non-tumorigenic melanocyte and fibro-blast cell lines. Athymic nude mice bearing human melanoma A375 xenografts were treated with NO-Cbl and Apo2L/TRAIL. Apoptosis was measured by TUNEL and confirmed by examining levels and activity of key mediators of apoptosis. The activation status of NF-κB was established by assaying DNA binding, luciferase reporter activity, the phosphorylation status of IκBα, and in vitro IKK activity. NO-Cbl sensitized Apo2L/TRAIL-resistant melanoma cell lines to growth inhibition by Apo2L/TRAIL but had minimal effect on normal cell lines. NO-Cbl and Apo2L/TRAIL exerted synergistic anti-tumor activity against A375 xenografts. Treatment with NO-Cbl followed by Apo2L/TRAIL induced apoptosis in Apo2L/TRAIL-resistant tumor cells, characterized by cleavage of caspase-3, caspase-8, and PARP. NO-Cbl inhibited IKK activation, characterized by decreased phosphorylation of IκBα and inhibition of NF-κB DNA binding activity. NO-Cbl suppressed Apo2L/TRAIL- and TNF-α-mediated activation of a transfected NF-κB-driven luciferase reporter. XIAP, an inhibitor of apoptosis, was inactivated by NO-Cbl. NO-Cbl treatment rendered Apo2L/TRAIL-resistant malignancies sensitive to the anti-tumor effects of Apo2L/TRAIL in vitro and in vivo. The use of NO-Cbl and Apo2L/TRAIL capitalizes on the tumor-specific properties of both agents and represents a promising anti-cancer combination. PMID:12881518

CD2-associated Protein (CD2AP) Enhances Casitas B Lineage Lymphoma-3/c (Cbl-3/c)-mediated Ret Isoform-specific Ubiquitination and Degradation via Its Amino-terminal Src Homology 3 Domains*

PubMed Central

Calco, Gina N.; Stephens, Olivia R.; Donahue, Laura M.; Tsui, Cynthia C.; Pierchala, Brian A.

2014-01-01

Ret is the receptor tyrosine kinase for the glial cell line-derived neurotrophic factor (GDNF) family of neuronal growth factors. Upon activation by GDNF, Ret is rapidly polyubiquitinated and degraded. This degradation process is isoform-selective, with the longer Ret51 isoform exhibiting different degradation kinetics than the shorter isoform, Ret9. In sympathetic neurons, Ret degradation is induced, at least in part, by a complex consisting of the adaptor protein CD2AP and the E3-ligase Cbl-3/c. Knockdown of Cbl-3/c using siRNA reduced the GDNF-induced ubiquitination and degradation of Ret51 in neurons and podocytes, suggesting that Cbl-3/c was a predominant E3 ligase for Ret. Coexpression of CD2AP with Cbl-3/c augmented the ubiquitination of Ret51 as compared with the expression of Cbl-3/c alone. Ret51 ubiquitination by the CD2AP·Cbl-3/c complex required a functional ring finger and TKB domain in Cbl-3/c. The SH3 domains of CD2AP were sufficient to drive the Cbl-3/c-dependent ubiquitination of Ret51, whereas the carboxyl-terminal coiled-coil domain of CD2AP was dispensable. Interestingly, activated Ret induced the degradation of CD2AP, but not Cbl-3/c, suggesting a potential inhibitory feedback mechanism. There were only two major ubiquitination sites in Ret51, Lys1060 and Lys1107, and the combined mutation of these lysines almost completely eliminated both the ubiquitination and degradation of Ret51. Ret9 was not ubiquitinated by the CD2AP·Cbl-3/c complex, suggesting that Ret9 was down-regulated by a fundamentally different mechanism. Taken together, these results suggest that only the SH3 domains of CD2AP were necessary to enhance the E3 ligase activity of Cbl-3/c toward Ret51. PMID:24425877

Comparative experimental and simulation studies of high-power AlGaN-based 353 nm ultraviolet flip-chip and top-emitting LEDs

NASA Astrophysics Data System (ADS)

Liu, Mengling; Zhou, Shengjun; Liu, Xingtong; Gao, Yilin; Ding, Xinghuo

2018-03-01

Experimental and simulation studies of high-power AlGaN-based 353 nm ultraviolet (UV) flip-chip (FC) and top-emitting (TE) light-emitting diodes (LEDs) are performed here. To improve the optical and electrical properties of ultraviolet LEDs, we fabricate high-power FC-UV LEDs with Ta2O5/SiO2 distributed Bragg reflectors (DBRs) and a strip-shaped SiO2 current blocking layer (CBL). The reflectance of fourteen pairs of Ta2O5/SiO2 DBRs is 96.4% at 353 nm. The strip-shaped SiO2 CBL underneath the strip-shaped p-electrode can prevent the current concentrating in regions immediately adjacent to the p-electrode where the overlying opaque p-electrode metal layer absorbs the emitted UV light. Moreover, two-level metallization electrodes are used to improve current spreading. Our numerical results show that FC-UV LED has a more favorable current spreading uniformity than TE-UV LED. The light output power of 353 nm FC-UV LED was 23.22 mW at 350 mA, which is 24.7% higher than that of TE-UV LED.

The proto-oncogene product p120CBL and the adaptor proteins CRKL and c-CRK link c-ABL, p190BCR/ABL and p210BCR/ABL to the phosphatidylinositol-3' kinase pathway.

PubMed

Sattler, M; Salgia, R; Okuda, K; Uemura, N; Durstin, M A; Pisick, E; Xu, G; Li, J L; Prasad, K V; Griffin, J D

1996-02-15

Chronic myelogenous leukemia (CML) and some acute lymphoblastic leukemias (ALL) are caused by the t(9;22) chromosome translocation, which produces the constitutively activated BCR/ABL tyrosine kinase. When introduced into factor dependent hematopoietic cell lines, BCR/ABL induces the tyrosine phosphorylation of many cellular proteins. One prominent BCR/ABL substrate is p120CBL, the cellular homolog of the v-Cbl oncoprotein. In an effort to understand the possible contribution of p120CBL to transformation by BCR/ABL, we looked for cellular proteins which associate with p120CBL in hematopoietic cell lines transformed by BCR/ABL. In addition to p210BCR/ABL and c-ABL, p120CBL coprecipitated with an 85 kDa phosphoprotein, which was identified as the p85 subunit of PI3K. Anti-p120CBL immunoprecipitates from BCR/ABL-transformed, but not from untransformed, cell lines contained PI3K lipid kinase activity. Interestingly, the adaptor proteins CRKL and c-CRK were also found in these complexes. In vitro binding studies indicated that the SH2 domains of CRKL and c-CRK bound directly to p120CBL, while the SH3 domains of c-CRK and CRKL bound to BCR/ABL and c-ABL. The N-terminal and the C-terminal SH2 and the SH3 domain of p85PI3K bound directly in vitro to p120CBL. The ABL-SH2, but not ABL-SH3, could also bind to p120CBL. These data suggest that BCR/ABL may induce the formation of multimeric complexes of signaling proteins which include p120CBL, PI3K, c-CRK or CRKL, c-ABL and BCR/ABL itself.

Identification and comprehensive analyses of the CBL and CIPK gene families in wheat (Triticum aestivum L.).

PubMed

Sun, Tao; Wang, Yan; Wang, Meng; Li, Tingting; Zhou, Yi; Wang, Xiatian; Wei, Shuya; He, Guangyuan; Yang, Guangxiao

2015-11-04

Calcineurin B-like (CBL) proteins belong to a unique group of calcium sensors in plant that decode the Ca(2+) signature by interacting with CBL-interacting protein kinases (CIPKs). Although CBL-CIPK complexes have been shown to play important roles in the responses to various stresses in plants, little is known about their functions in wheat. A total of seven TaCBL and 20 TaCIPK genes were amplified from bread wheat, Triticum aestivum cv. Chinese Spring. Reverse-transcriptase-polymerase chain reaction (RT-PCR) and in silico expression analyses showed that TaCBL and TaCIPK genes were expressed at different levels in different tissues, or maintained at nearly constant expression levels during the whole life cycle of the wheat plant. Some TaCBL and TaCIPK genes showed up- or down-regulated expressions during seed germination. Preferential interactions between TaCBLs and TaCIPKs were observed in yeast two-hybrid and bimolecular fluorescence complementation experiments. Analyses of a deletion series of TaCIPK proteins with amino acid variations at the C-terminus provided new insights into the specificity of the interactions between TaCIPKs and TaCBLs, and indicated that the TaCBL-TaCIPK signaling pathway is very complex in wheat because of its hexaploid genome. The expressions of many TaCBLs and TaCIPKs were responsive to abiotic stresses (salt, cold, and simulated drought) and abscisic acid treatment. Transgenic Arabidopsis plants overexpressing TaCIPK24 exhibited improved salt tolerance through increased Na(+) efflux and an enhanced reactive oxygen species scavenging capacity. These results contribute to our understanding of the functions of CBL-CIPK complexes and provide the basis for selecting appropriate genes for in-depth functional studies of CBL-CIPK in wheat.

Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner.

PubMed

Dragone, Leonard L; Myers, Margaret D; White, Carmen; Gadwal, Shyam; Sosinowski, Tomasz; Gu, Hua; Weiss, Arthur

2006-11-28

Src-like adaptor protein (SLAP) and c-Cbl recently have been shown to cooperate in regulating T cell receptor (TCR) levels in developing T cells. SLAP also is expressed in developing B cells, and its deficiency leads to alterations in B cell receptor (BCR) levels and B cell development. Hence, we hypothesized that SLAP and c-Cbl may cooperate during B cell development to regulate BCR levels. In mice deficient in both SLAP and c-Cbl, we found that B cell development is altered, suggesting that they function through intersecting pathways. To study the mechanism by which SLAP and c-Cbl alter BCR levels, we coexpressed them in a mature mouse B cell line (Bal-17). First we determined that SLAP associates with proximal components of the BCR complex after stimulation and internalization. Coexpression of SLAP and c-Cbl in Bal-17 led to decreased surface and total BCR levels. This decrease in BCR levels depended on intact Src homology 2 (SH2) and C-terminal domains of SLAP. In addition, a mutation in the SH2 domain of SLAP blocked its colocalization with c-Cbl and the BCR complex, whereas deletion of the C terminus did not affect its localization. Last, coexpression of SLAP and c-Cbl altered BCR complex recycling. This alteration in BCR complex recycling depended on enzymatically active c-Cbl and Src family kinases, as well as the intact SH2 and C-terminal domains of SLAP. These data suggest that SLAP has a conserved function in B and T cells by adapting c-Cbl to the antigen-receptor complex and targeting it for degradation.

Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner

PubMed Central

Dragone, Leonard L.; Myers, Margaret D.; White, Carmen; Gadwal, Shyam; Sosinowski, Tomasz; Gu, Hua; Weiss, Arthur

2006-01-01

Src-like adaptor protein (SLAP) and c-Cbl recently have been shown to cooperate in regulating T cell receptor (TCR) levels in developing T cells. SLAP also is expressed in developing B cells, and its deficiency leads to alterations in B cell receptor (BCR) levels and B cell development. Hence, we hypothesized that SLAP and c-Cbl may cooperate during B cell development to regulate BCR levels. In mice deficient in both SLAP and c-Cbl, we found that B cell development is altered, suggesting that they function through intersecting pathways. To study the mechanism by which SLAP and c-Cbl alter BCR levels, we coexpressed them in a mature mouse B cell line (Bal-17). First we determined that SLAP associates with proximal components of the BCR complex after stimulation and internalization. Coexpression of SLAP and c-Cbl in Bal-17 led to decreased surface and total BCR levels. This decrease in BCR levels depended on intact Src homology 2 (SH2) and C-terminal domains of SLAP. In addition, a mutation in the SH2 domain of SLAP blocked its colocalization with c-Cbl and the BCR complex, whereas deletion of the C terminus did not affect its localization. Last, coexpression of SLAP and c-Cbl altered BCR complex recycling. This alteration in BCR complex recycling depended on enzymatically active c-Cbl and Src family kinases, as well as the intact SH2 and C-terminal domains of SLAP. These data suggest that SLAP has a conserved function in B and T cells by adapting c-Cbl to the antigen-receptor complex and targeting it for degradation. PMID:17110436

Timed Release of Cerebrolysin Using Drug-Loaded Titanate Nanospheres Reduces Brain Pathology and Improves Behavioral Functions in Parkinson's Disease.

PubMed

Ozkizilcik, Asya; Sharma, Aruna; Muresanu, Dafin F; Lafuente, José V; Tian, Z Ryan; Patnaik, Ranjana; Mössler, Herbert; Sharma, Hari S

2018-01-01

Previous studies from our laboratory show that intraperitoneal injections of 1-metyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP, 20 mg/kg) daily within 2-h intervals for 5 days in mice induce Parkinson's disease (PD)-like symptoms on the 8th day. A significant decrease in dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) along with a marked decrease in the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta (SNpc) and striatum (STr) confirms the validity of this model for studying PD. Since cerebrolysin (CBL) is a well-balanced composition of several neurotrophic factors and active peptide fragments, in the present investigation we examined the timed release of CBL using titanate nanospheres (TiNS) in treating PD in our mouse model. Our observations show that TiNS-CBL (in a dose of 3 ml/kg, i.v.) given after 2 days of MPTP administration for 5 days resulted in a marked increase in TH-positive cells in the SNpc and STr as compared to normal CBL. Also, TiNS-CBL resulted in significantly higher levels of DA, DOPAC, and HVA in SNpc and STr on the 8th day as compared to normal CBL therapy. TiNS-CBL also thwarted increased α-synuclein levels in the brain and in the cerebrospinal fluid (CSF) as well as neuronal nitric oxide synthase (nNOS) in the in PD brain as compared to untreated group. Behavioral function was also significantly improved in MPTP-treated animals that received TiNS-CBL. These observations are the first to demonstrate that timed release of TiNS-CBL has far more superior neuroprotective effects in PD than normal CBL.

Cell Type-Specific Modulation of Cobalamin Uptake by Bovine Serum

PubMed Central

Zhao, Hua; Ruberu, Kalani; Li, Hongyun; Garner, Brett

2016-01-01

Tracking cellular 57Co-labelled cobalamin (57Co-Cbl) uptake is a well-established method for studying Cbl homeostasis. Previous studies established that bovine serum is not generally permissive for cellular Cbl uptake when used as a supplement in cell culture medium, whereas supplementation with human serum promotes cellular Cbl uptake. The underlying reasons for these differences are not fully defined. In the current study we address this question. We extend earlier observations by showing that fetal calf serum inhibits cellular 57Co-Cbl uptake by HT1080 cells (a fibrosarcoma-derived fibroblast cell line). Furthermore, we discovered that a simple heat-treatment protocol (95°C for 10 min) ameliorates this inhibitory activity for HT1080 cell 57Co-Cbl uptake. We provide evidence that the very high level of haptocorrin in bovine serum (as compared to human serum) is responsible for this inhibitory activity. We suggest that bovine haptocorrin competes with cell-derived transcobalamin for Cbl binding, and that cellular Cbl uptake may be minimised in the presence of large amounts of bovine haptocorrin that are present under routine in vitro cell culture conditions. In experiments conducted with AG01518 cells (a neonatal foreskin-derived fibroblast cell line), overall cellular 57Co-Cbl uptake was 86% lower than for HT1080 cells, cellular TC production was below levels detectable by western blotting, and heat treatment of fetal calf serum resulted in only a modest increase in cellular 57Co-Cbl uptake. We recommend a careful assessment of cell culture protocols should be conducted in order to determine the potential benefits that heat-treated bovine serum may provide for in vitro studies of mammalian cell lines. PMID:27893837

VAV1-Cre mediated hematopoietic deletion of CBL and CBL-B leads to JMML-like aggressive early-neonatal myeloproliferative disease

PubMed Central

An, Wei; Mohapatra, Bhopal C.; Zutshi, Neha; Bielecki, Timothy A.; Goez, Benjamin T.; Luan, Haitao; Iseka, Fany; Mushtaq, Insha; Storck, Matthew D.; Band, Vimla; Band, Hamid

2016-01-01

CBL and CBL-B ubiquitin ligases play key roles in hematopoietic stem cell homeostasis and their aberrations are linked to leukemogenesis. Mutations of CBL, often genetically-inherited, are particularly common in Juvenile Myelomonocytic Leukemia (JMML), a disease that manifests early in children. JMML is fatal unless corrected by bone marrow transplant, which is effective in only half of the recipients, stressing the need for animal models that recapitulate the key clinical features of this disease. However, mouse models established so far only develop hematological malignancy in adult animals. Here, using VAV1-Cre-induced conditional CBL/CBL-B double knockout (DKO) in mice, we established an animal model that exhibits a neonatal myeloproliferative disease (MPD). VAV1-Cre induced DKO mice developed a strong hematological phenotype at postnatal day 10, including severe leukocytosis and hepatomegaly, bone marrow cell hypersensitivity to cytokines including GM-CSF, and rapidly-progressive disease and invariable lethality. Interestingly, leukemic stem cells were most highly enriched in neonatal liver rather than bone marrow, which, along with the spleen and thymus, were hypo-cellular. Nonetheless, transplantation assays showed that both DKO bone marrow and liver cells can initiate leukemic disease in the recipient mice with seeding of both spleen and bone marrow. Together, our results support the usefulness of the new hematopoietic-specific CBL/CBL-B double KO animal model to study JMML-related pathogenesis and to further understand the function of CBL family proteins in regulating fetal and neonatal hematopoiesis. To our knowledge, this is the first mouse model that exhibits neonatal MPD in infancy, by day 10 of postnatal life. PMID:27449297

αPIX Is a Trafficking Regulator that Balances Recycling and Degradation of the Epidermal Growth Factor Receptor

PubMed Central

Kortüm, Fanny; Harms, Frederike Leonie; Hennighausen, Natascha; Rosenberger, Georg

2015-01-01

Endosomal sorting is an essential control mechanism for signaling through the epidermal growth factor receptor (EGFR). We report here that the guanine nucleotide exchange factor αPIX, which modulates the activity of Rho-GTPases, is a potent bimodal regulator of EGFR trafficking. αPIX interacts with the E3 ubiquitin ligase c-Cbl, an enzyme that attaches ubiquitin to EGFR, thereby labelling this tyrosine kinase receptor for lysosomal degradation. We show that EGF stimulation induces αPIX::c-Cbl complex formation. Simultaneously, αPIX and c-Cbl protein levels decrease, which depends on both αPIX binding to c-Cbl and c-Cbl ubiquitin ligase activity. Through interaction αPIX sequesters c-Cbl from EGFR and this results in reduced EGFR ubiquitination and decreased EGFR degradation upon EGF treatment. However, quantitatively more decisive for cellular EGFR distribution than impaired EGFR degradation is a strong stimulating effect of αPIX on EGFR recycling to the cell surface. This function depends on the GIT binding domain of αPIX but not on interaction with c-Cbl or αPIX exchange activity. In summary, our data demonstrate a previously unappreciated function of αPIX as a strong promoter of EGFR recycling. We suggest that the novel recycling regulator αPIX and the degradation factor c-Cbl closely cooperate in the regulation of EGFR trafficking: uncomplexed αPIX and c-Cbl mediate a positive and a negative feedback on EGFR signaling, respectively; αPIX::c-Cbl complex formation, however, results in mutual inhibition, which may reflect a stable condition in the homeostasis of EGF-induced signal flow. PMID:26177020

Characterization of Turbulent Processes by the Raman Lidar System Basil in the Frame of the HD(CP)2 Observational Prototype Experiment - Hope

NASA Astrophysics Data System (ADS)

Di Girolamo, Paolo; Summa, Donato; Stelitano, Dario; Cacciani, Marco; Scoccione, Andrea; Behrendt, Andreas; Wulfmeyer, Volker

2016-06-01

Measurements carried out by the Raman lidar system BASIL are reported to demonstrate the capability of this instrument to characterize turbulent processes within the Convective Boundary Layer (CBL). In order to resolve the vertical profiles of turbulent variables, high resolution water vapour and temperature measurements, with a temporal resolution of 10 sec and a vertical resolution of 90 and 210 m, respectively, are considered. Measurements of higher-order moments of the turbulent fluctuations of water vapour mixing ratio and temperature are obtained based on the application of spectral and auto-covariance analyses to the water vapour mixing ratio and temperature time series. The algorithms are applied to a case study (IOP 5, 20 April 2013) from the HD(CP)2 Observational Prototype Experiment (HOPE), held in Central Germany in the spring 2013. The noise errors are demonstrated to be small enough to allow the derivation of up to fourth-order moments for both water vapour mixing ratio and temperature fluctuations with sufficient accuracy.

Dynamin Forms a Src Kinase–sensitive Complex with Cbl and Regulates Podosomes and Osteoclast Activity

PubMed Central

Bruzzaniti, Angela; Neff, Lynn; Sanjay, Archana; Horne, William C.; De Camilli, Pietro; Baron, Roland

2005-01-01

Podosomes are highly dynamic actin-containing adhesion structures found in osteoclasts, macrophages, and Rous sarcoma virus (RSV)-transformed fibroblasts. After integrin engagement, Pyk2 recruits Src and the adaptor protein Cbl, forming a molecular signaling complex that is critical for cell migration, and deletion of any molecule in this complex disrupts podosome ring formation and/or decreases osteoclast migration. Dynamin, a GTPase essential for endocytosis, is also involved in actin cytoskeleton remodeling and is localized to podosomes where it has a role in actin turnover. We found that dynamin colocalizes with Cbl in the actin-rich podosome belt of osteoclasts and that dynamin forms a complex with Cbl in osteoclasts and when overexpressed in 293VnR or SYF cells. The association of dynamin with Cbl in osteoclasts was decreased by Src tyrosine kinase activity and we found that destabilization of the dynamin-Cbl complex involves the recruitment of Src through the proline-rich domain of Cbl. Overexpression of dynamin increased osteoclast bone resorbing activity and migration, whereas overexpression of dynK44A decreased osteoclast resorption and migration. These studies suggest that dynamin, Cbl, and Src coordinately participate in signaling complexes that are important in the assembly and remodeling of the actin cytoskeleton, leading to changes in osteoclast adhesion, migration, and resorption. PMID:15872089

Analysis of Dust Devils on Mars using CFD

NASA Astrophysics Data System (ADS)

Lange, C. F.; Chen, K.; Davis, J. A.; Gheynani, B. T.

2009-05-01

Recent Mars missions have reported evidence of the existence of dust devils. A detailed study of vortex dynamics will provide a better understanding of this swirling flow of the Martian atmosphere. Further, it is believed that there is a relationship between dust devils and water transport. Recently, the Phoenix Mars mission, designed to investigate ice water and natural events on Mars, has successfully finished. The Phoenix Surface Stereo Imager (SSI) camera captured images of the passage of dust devils over or close to the lander. Additionally, dustless devils, which have similar vortex characteristics but insufficient strength to raise dust from the surface, have been detected in the lander's pressure measurements. It was found that dust devils occur mainly in the early afternoon. Because of this, numerical models of a vortex generator are used to study the physics of this complex swirling flow and the effect of dust devils on the transport of water vapour from the regolith. Characteristic parameters such as core radius and swirl ratio are being explored for scaling factors. Scaling factors will be studied and tested, comparing the small and large scales of numerically generated vortices and laboratory generated vortices. Small scale of numerical models of atmospheric vortices are studied using a commercial software package, ANSYS/CFX11.0 with finite volume method (FVM). Large eddy simulations (LES) of planetary boundary layers are based on NCAR LES code to simulate convective vertical vortices that naturally form in quiescent convective boundary layers (CBL) over homogeneous flat surfaces. This will help to find the approximate location and physical characteristics of the vortices on the surface. The numerical models of atmospheric vortices and the experimental vortex generator validations will help to define the water vapour cycle on Mars.

Observations of precipitable water vapor fluctuations in convective boundary layer via microwave interferometry

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

Shao, X.M.; Carlos, R.C.; Kirkland, M.W.

1999-07-01

At microwave frequencies, each centimeter of precipitable water vapor (PWV) causes about 6.45 cm of extra electrical path length relative to the {open_quotes}dry{close_quotes} air. The fluctuations of the water vapor dominate the changes of the effective path length through the atmosphere in a relatively short time period of a few hours. In this paper we describe a microwave interferometer developed for water vapor investigations and present the observation results. The interferometer consists of 10 antennas along two orthogonal 400-m arms that form many baselines (antenna pairs) ranging from 100 to 400 m. All the antennas receive a common CW signalmore » (11.7 GHz) from a geostationary television satellite, and phase differences between pairs of antennas are measured. The phase differences reflect the column-integrated water vapor differences from the top of the atmosphere to the spatially separated antennas at the ground. The interferometric, baseline-differential measurements allow us to study the statistical properties of the PWV fluctuations, as well as the turbulent activity of the convective boundary layer (CBL). Structure function analysis of the interferometer measurements shows good agreement with results obtained from the Very Large Array (VLA) and with a theoretical model developed for radio astronomical very long baseline interferometry (VLBI), reported previously by other investigators. The diurnally varying structure constant correlates remarkably well with the combination of the latent and sensible heat fluxes measured simultaneously from a 10-m meteorological tower. The average drift velocity of the PWV over the interferometer was also derived from the measurements. The derived velocity agrees well during the morning hours with the wind measured by an anemometer at the center of the interferometer. {copyright} 1999 American Geophysical Union« less

The Coupled Boundary Layers and Air-Sea Transfer (CBLAST) Experiments at the Martha's Vineyard Coastal Observatory

NASA Astrophysics Data System (ADS)

Edson, J. B.

2001-12-01

The Woods Hole Oceanographic Institution (WHOI) completed the initial phase of the Martha's Vineyard Coastal Observatory (MVCO) in July of 2001. The MVCO is being using to monitor coastal atmospheric and oceanic processes. Specifically, the observatory is expected to: - Provide continuous long-term observations for climate studies. - Provide a reliable system and rugged sensors that allow opportunistic sampling of extreme events. - Provide a local climatology for intensive, short duration field campaigns. - Further facilitate regional studies of coastal processes by providing infrastructure that supports easy access to power and data. This talk provides an example of the last two objectives using the low wind component of the Office of Naval Research's (ONR) Coupled Boundary Layers and Air-Sea Transfer (CBLAST) program. CBLAST-LOW has been designed to investigate air-sea interaction and coupled atmospheric and oceanic boundary layer dynamics at low wind speeds where the dynamic processes are driven and/or strongly modulated by thermal forcing. This effort is being carried out by scientists at WHOI, NPS, NOAA, NRL, Rutgers, UW/APL, JH/APL, OSU, NCAR, and other institutions, and includes observational and modeling components. The MVCO is providing observations and infrastructure in support of several intensive operating periods in the summers of 2001, 2002, and possibly 2003. During these periods, the observational network around the observatory was and will be greatly expanded using traditional oceanographic moorings and bottom mounted instrumentation, innovative 2- and 3-D moored and drifting arrays, survey ships, AUVs, satellite remote sensing, and heavily instrumented aircraft. In addition, the MVCO cabled components will be extended out to the 20-m isobath where we plan to deploy a 35-m tower. The tower will be instrumented from 15-m above the ocean surface to the ocean bottom with instruments capable of directly measuring the momentum, heat, and radiative fluxes in the atmospheric, oceanic, and bottom boundary layers. This tower will be directly connected to shore via the existing node at the MVCO using an additional fiber-optic-power cable. All of these measurements will be combined to obtain direct measurements of vertical fluxes (transfer) of momentum, heat and mass across the coupled boundary layers (CBLs); to map the 3-D structure of the CBLs over a range of spatial and temporal scales; to identify the processes that drive the fluxes and CBL structure; to develop and evaluate parameterizations of the flux-producing processes; and to test the mean and variance budgets for momentum, heat, mass, and kinetic energy. These measurements will also be used to evaluate and improve mesoscale models, large eddy simulations (LES), and direct numerical simulations (DNS) that will, in-turn, provide nowcasts, forecasts, and simulations of these processes to help interpret the observations. >http://www.whoi.edu/science/AOPE/dept/CBLAST/lowwind.html

A Stability-Indicating HPLC Method for the Determination of Nitrosylcobalamin (NO-Cbl), a Novel Vitamin B12 Analog.

PubMed

Dunphy, Michael J; Sysel, Annette M; Lupica, Joseph A; Griffith, Kristie; Sherrod, Taylor; Bauer, Joseph A

2014-04-01

Nitrosylcobalamin (NO-Cbl), a novel vitamin B 12 analog and anti-tumor agent, functions as a biologic 'Trojan horse', utilizing the vitamin B 12 transcobalamin II transport protein and cell surface receptor to specifically target cancer cells. a stability-indicating HPLC method was developed for the detection of NO-Cbl during forced degradation studies. This method utilized an ascentis ® RP-amide (150 mm × 4.6 mm, 5 μm) column at 35 °C with a mobile phase (1.0 mL min -1 ) combining a gradient of methanol and an acetate buffer at pH 6.0. Detection wavelengths of 450 and 254 nm were used to detect corrin and non-corrin-based products, respectively. NO-Cbl, synthesized from hydroxocobalamin and pure nitric oxide gas, was subjected to degradative stress conditions including oxidation, hydrolysis and thermal and radiant energy challenge. The method was validated by assessing linearity, accuracy, precision, detection and quantitation limits and robustness. The method was applied successfully for purity assessment of synthesized NO-Cbl and for the determination of NO-Cbl during kinetic studies in aqueous solution and in solid-state degradation assessments. This HPLC method is suitable for the separation of cobalamins in aqueous and methanolic solutions, for routine detection of NO-Cbl and for purity assessment of synthesized NO-Cbl. additionally, this method has potential application in identification and monitoring of diseases involving altered nitric oxide homeostasis where vitamin B 12 therapy is utilized to scavenge excess nitric oxide, subsequently resulting in the in vivo production of NO-Cbl.

A Stability-Indicating HPLC Method for the Determination of Nitrosylcobalamin (NO-Cbl), a Novel Vitamin B12 Analog

PubMed Central

Dunphy, Michael J.; Sysel, Annette M.; Lupica, Joseph A.; Griffith, Kristie; Sherrod, Taylor

2014-01-01

Nitrosylcobalamin (NO-Cbl), a novel vitamin B12 analog and anti-tumor agent, functions as a biologic ‘Trojan horse’, utilizing the vitamin B12 transcobalamin II transport protein and cell surface receptor to specifically target cancer cells. a stability-indicating HPLC method was developed for the detection of NO-Cbl during forced degradation studies. This method utilized an ascentis® RP-amide (150 mm × 4.6 mm, 5 μm) column at 35 °C with a mobile phase (1.0 mL min−1) combining a gradient of methanol and an acetate buffer at pH 6.0. Detection wavelengths of 450 and 254 nm were used to detect corrin and non-corrin-based products, respectively. NO-Cbl, synthesized from hydroxocobalamin and pure nitric oxide gas, was subjected to degradative stress conditions including oxidation, hydrolysis and thermal and radiant energy challenge. The method was validated by assessing linearity, accuracy, precision, detection and quantitation limits and robustness. The method was applied successfully for purity assessment of synthesized NO-Cbl and for the determination of NO-Cbl during kinetic studies in aqueous solution and in solid-state degradation assessments. This HPLC method is suitable for the separation of cobalamins in aqueous and methanolic solutions, for routine detection of NO-Cbl and for purity assessment of synthesized NO-Cbl. additionally, this method has potential application in identification and monitoring of diseases involving altered nitric oxide homeostasis where vitamin B12 therapy is utilized to scavenge excess nitric oxide, subsequently resulting in the in vivo production of NO-Cbl. PMID:24855323

The tomato calcium sensor Cbl10 and its interacting protein kinase Cipk6 define a signaling pathway in plant immunity.

PubMed

de la Torre, Fernando; Gutiérrez-Beltrán, Emilio; Pareja-Jaime, Yolanda; Chakravarthy, Suma; Martin, Gregory B; del Pozo, Olga

2013-07-01

Ca(2+) signaling is an early and necessary event in plant immunity. The tomato (Solanum lycopersicum) kinase Pto triggers localized programmed cell death (PCD) upon recognition of Pseudomonas syringae effectors AvrPto or AvrPtoB. In a virus-induced gene silencing screen in Nicotiana benthamiana, we independently identified two components of a Ca(2+)-signaling system, Cbl10 (for calcineurin B-like protein) and Cipk6 (for calcineurin B-like interacting protein kinase), as their silencing inhibited Pto/AvrPto-elicited PCD. N. benthamiana Cbl10 and Cipk6 are also required for PCD triggered by other plant resistance genes and virus, oomycete, and nematode effectors and for host susceptibility to two P. syringae pathogens. Tomato Cipk6 interacts with Cbl10 and its in vitro kinase activity is enhanced in the presence of Cbl10 and Ca(2+), suggesting that tomato Cbl10 and Cipk6 constitute a Ca(2+)-regulated signaling module. Overexpression of tomato Cipk6 in N. benthamiana leaves causes accumulation of reactive oxygen species (ROS), which requires the respiratory burst homolog RbohB. Tomato Cbl10 and Cipk6 interact with RbohB at the plasma membrane. Finally, Cbl10 and Cipk6 contribute to ROS generated during effector-triggered immunity in the interaction of P. syringae pv tomato DC3000 and N. benthamiana. We identify a role for the Cbl/Cipk signaling module in PCD, establishing a mechanistic link between Ca(2+) and ROS signaling in plant immunity.

Loss of Cbl-PI3K interaction modulates the periosteal response to fracture by enhancing osteogenic commitment and differentiation.

PubMed

Scanlon, Vanessa; Walia, Bhavita; Yu, Jungeun; Hansen, Marc; Drissi, Hicham; Maye, Peter; Sanjay, Archana

2017-02-01

The periosteum contains multipotent skeletal progenitors that contribute to bone repair. The signaling pathways regulating the response of periosteal cells to fracture are largely unknown. Phosphatidylinositol-3 Kinase (PI3K), a prominent lipid kinase, is a major signaling protein downstream of several factors that regulate osteoblast differentiation. Cbl is an E3 ubiquitin ligase and a major adaptor protein that binds to the p85 regulatory subunit and modulates PI3K activity. Substitution of tyrosine 737 to phenylalanine (Y737F) in Cbl abolishes the interaction between Cbl and p85 subunit without affecting the Cbl's ubiquitin ligase function. Here, we investigated the role of PI3K signaling during the very early stages of fracture healing using Osterix RFP reporter mice. We found that the absence of PI3K regulation by Cbl resulted in robust periosteal thickening, with increased proliferation of periosteal cells. While the multipotent properties of periosteal progenitors to differentiate into chondrocytes and adipocytes did not change, osteogenic differentiation in the absence of Cbl-PI3K interaction was highly augmented. The increased stability and nuclear localization of Osterix observed in periosteal cells lacking Cbl-PI3K interaction may explain this enhanced osteogenic differentiation since the expression of Osterix transcriptional target genes including osteocalcin and BSP are increased in YF cells. Overall, our findings highlight a hitherto unexplored and novel role for Cbl and PI3K in modulating the osteogenic response of periosteal cells during the early stages of fracture repair. Copyright © 2016 Elsevier Inc. All rights reserved.

Decreased pulmonary c-Cbl expression and tyrosine phosphorylation in the nitrofen-induced rat model of congenital diaphragmatic hernia.

PubMed

Friedmacher, Florian; Gosemann, Jan-Hendrik; Takahashi, Hiromizu; Corcionivoschi, Nicolae; Puri, Prem

2013-01-01

The high morbidity of newborn infants with congenital diaphragmatic hernia (CDH) is attributed to pulmonary hypoplasia (PH), which is characterized by a failure of alveolar development. The nitrofen-induced CDH model has been widely used to investigate the pathogenesis of PH in CDH. It has previously been shown that the fibroblast growth factor receptor (FGFR) pathway, which is essential for a proper lung development, is disrupted during late gestation of nitrofen-induced CDH. Casitas B-lineage lymphoma (c-Cbl) proteins are known regulators of signal transduction through FGFRs, indicating their important role during alveolarization in developing lungs. Furthermore, it has been demonstrated that tyrosine phosphorylation of c-Cbl proteins has a pivotal role for their physiological function and activity during fetal lung development. We designed this study to test the hypothesis that pulmonary c-Cbl expression and tyrosine phosphorylation status are decreased in the nitrofen-induced CDH model. Timed-pregnant rats received either 100 mg nitrofen or vehicle on gestation day 9 (D9). Fetuses were harvested on D18 and D21, and lungs were divided into two groups: control and hypoplastic lungs with CDH (CDH(+)) (n = 10 at each time-point, respectively). Pulmonary gene expression levels of c-Cbl were analyzed by quantitative real-time polymerase chain reaction. Western blotting combined with densitometry analysis was used for semi-quantification of protein levels of pulmonary c-Cbl and tyrosine phosphorylation status. Confocal-immunofluorescence staining was performed to evaluate c-Cbl protein expression and distribution. Relative mRNA expression levels of pulmonary c-Cbl were significantly decreased in CDH(+) on D18 and D21 compared to controls. Western blotting showed markedly decreased protein levels of pulmonary c-Cbl and tyrosine phosphorylation status in CDH(+) on D18 and D21. Confocal-immunofluorescence analysis confirmed decreased c-Cbl expression in CDH(+) on D18 and D21 mainly in the distal alveolar epithelium compared to controls. Decreased pulmonary c-Cbl gene and protein expression accompanied by a decreased tyrosine phosphorylation status during the late stages of fetal lung development may result in reduced c-Cbl activity, and thus interfere with the FGFR-mediated alveolarization in the nitrofen-induced CDH model.

Germline mutation of CBL is associated with moyamoya disease in a child with juvenile myelomonocytic leukemia and Noonan syndrome-like disorder.

PubMed

Hyakuna, Nobuyuki; Muramatsu, Hideki; Higa, Takeshi; Chinen, Yasutsugu; Wang, Xinan; Kojima, Seiji

2015-03-01

Germline mutations in CBL have been identified in patients with Noonan syndrome-like phenotypes, while juvenile myelomonocytic leukemia (JMML) harbors duplication of a germline CBL, resulting in acquired isodisomy. The association between moyamoya disease and Noonan syndrome carrying a PTPN11 mutation has recently been reported. We present a patient with JMML who developed moyamoya disease and neovascular glaucoma. Our patient exhibited a Noonan syndrome-like phenotype. Genetic analysis revealed acquired isodisomy and a germline heterozygous mutation in CBL. This is a rare case of CBL mutation associated with moyamoya disease. Prolonged RAS pathway signaling may cause disruption of cerebrovascular development. © 2014 Wiley Periodicals, Inc.

CBL family E3 ubiquitin ligases control JAK2 ubiquitination and stability in hematopoietic stem cells and myeloid malignancies

PubMed Central

Lv, Kaosheng; Jiang, Jing; Donaghy, Ryan; Riling, Christopher R.; Cheng, Ying; Chandra, Vemika; Rozenova, Krasimira; An, Wei; Mohapatra, Bhopal C.; Goetz, Benjamin T.; Pillai, Vinodh; Han, Xu; Todd, Emily A.; Jeschke, Grace R.; Langdon, Wallace Y.; Kumar, Suresh; Hexner, Elizabeth O.

2017-01-01

Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (CBL) family E3 ubiquitin ligases down-regulate JAK2 stability and signaling via the adaptor protein LNK/SH2B3. We demonstrated that depletion of CBL/CBL-B or LNK abrogated JAK2 ubiquitination, extended JAK2 half-life, and enhanced JAK2 signaling and cell growth in human cell lines as well as primary murine HSPCs. Built on these findings, we showed that JAK inhibitor (JAKi) significantly reduced aberrant HSPCs and mitigated leukemia development in a mouse model of aggressive myeloid leukemia driven by loss of Cbl and Cbl-b. Importantly, primary human CBL mutated (CBLmut) leukemias exhibited increased JAK2 protein levels and signaling and were hypersensitive to JAKi. Loss-of-function mutations in CBL E3 ubiquitin ligases are found in a wide range of myeloid malignancies, which are diseases without effective treatment options. Hence, our studies reveal a novel signaling axis that regulates JAK2 in normal and malignant HSPCs and suggest new therapeutic strategies for treating CBLmut myeloid malignancies. PMID:28611190

EphrinA2 Regulates Clathrin Mediated KSHV Endocytosis in Fibroblast Cells by Coordinating Integrin-Associated Signaling and c-Cbl Directed Polyubiquitination

PubMed Central

Dutta, Dipanjan; Chakraborty, Sayan; Bandyopadhyay, Chirosree; Valiya Veettil, Mohanan; Ansari, Mairaj Ahmed; Singh, Vivek Vikram; Chandran, Bala

2013-01-01

Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with human dermal endothelial cell surface tyrosine kinase EphrinA2 (EphA2) and integrins (α3β1 and αVβ3) in the lipid raft (LR) region, and EphA2 regulates macropinocytic virus entry by coordinating integrin-c-Cbl associated signaling. In contrast, KSHV enters human foreskin fibroblast (HFF) cells by LR-independent clathrin mediated endocytosis. The present studies conducted to identify the key molecules regulating KSHV entry in HFF cells showed that KSHV induces association with integrins (αVβ5, αVβ3 and α3β1) and EphA2 in non-LR regions early during infection and activates EphA2, which in turn associates with phosphorylated c-Cbl, myosin IIA, FAK, Src, and PI3-K, as well as clathrin and its adaptor AP2 and effector Epsin-15 proteins. EphA2 knockdown significantly reduced these signal inductions, virus internalization and gene expression. c-Cbl knockdown ablated the c-Cbl mediated K63 type polyubiquitination of EphA2 and clathrin association with EphA2 and KSHV. Mutations in EphA2's tyrosine kinase domain (TKD) or sterile alpha motif (SAM) abolished its interaction with c-Cbl. Mutations in tyrosine kinase binding (TKB) or RING finger (RF) domains of c-Cbl resulted in very poor association of c-Cbl with EphA2 and decreased EphA2 polyubiquitination. These studies demonstrated the contributions of these domains in EphA2 and c-Cbl association, EphA2 polyubiquitination and virus-EphA2 internalization. Collectively, these results revealed for the first time that EphA2 influences the tyrosine phosphorylation of clathrin, the role of EphA2 in clathrin mediated endocytosis of a virus, and c-Cbl mediated EphA2 polyubiquitination directing KSHV entry in HFF cells via coordinated signal induction and progression of endocytic events, all of which suggest that targeting EphA2 and c-Cbl could block KSHV entry and infection. PMID:23874206

The MMACHC proteome: hallmarks of functional cobalamin deficiency in humans.

PubMed

Hannibal, Luciana; DiBello, Patricia M; Yu, Michelle; Miller, Abby; Wang, Sihe; Willard, Belinda; Rosenblatt, David S; Jacobsen, Donald W

2011-07-01

Cobalamin (Cbl, B(12)) is an essential micronutrient required to fulfill the enzymatic reactions of cytosolic methylcobalamin-dependent methionine synthase and mitochondrial adenosylcobalamin-dependent methylmalonyl-CoA mutase. Mutations in the MMACHC gene (cblC complementation group) disrupt processing of the upper-axial ligand of newly internalized cobalamins, leading to functional deficiency of the vitamin. Patients with cblC disease present with both hyperhomocysteinemia and methylmalonic acidemia, cognitive dysfunction, and megaloblastic anemia. In the present study we show that cultured skin fibroblasts from cblC patients export increased levels of both homocysteine and methylmalonic acid compared to control skin fibroblasts, and that they also have decreased levels of total intracellular folates. This is consistent with the clinical phenotype of functional cobalamin deficiency in vivo. The protein changes that accompany human functional Cbl deficiency are unknown. The proteome of control and cblC fibroblasts was quantitatively examined by two dimensional difference in-gel electrophoresis (2D-DIGE) and liquid chromatography-electrospray ionization-mass spectrometry (LC/ESI/MS). Major changes were observed in the expression levels of proteins involved in cytoskeleton organization and assembly, the neurological system and cell signaling. Pathway analysis of the differentially expressed proteins demonstrated strong associations with neurological disorders, muscular and skeletal disorders, and cardiovascular diseases in the cblC mutant cell lines. Supplementation of the cell cultures with hydroxocobalamin did not restore the cblC proteome to the patterns of expression observed in control cells. These results concur with the observed phenotype of patients with the cblC disorder and their sometimes poor response to treatment with hydroxocobalamin. Our findings could be valuable for designing alternative therapies to alleviate the clinical manifestation of the cblC disorder, as some of the protein changes detected in our study are common hallmarks of known pathologies such as Alzheimer's and Parkinson's diseases as well as muscular dystrophies. Copyright © 2011 Elsevier Inc. All rights reserved.

THE MMACHC PROTEOME: HALLMARKS OF FUNCTIONAL COBALAMIN DEFICIENCY IN HUMANS

PubMed Central

Hannibal, Luciana; DiBello, Patricia M.; Yu, Michelle; Miller, Abby; Wang, Sihe; Willard, Belinda; Rosenblatt, David S.; Jacobsen, Donald W.

2011-01-01

Cobalamin (Cbl, B12) is an essential micronutrient required to fulfill the enzymatic reactions of cytosolic methylcobalamin-dependent methionine synthase and mitochondrial adenosylcobalamin-dependent methylmalonyl-CoA mutase. Mutations in the MMACHC gene (cblC complementation group) disrupt processing of the upper-axial ligand of newly internalized cobalamins, leading to functional deficiency of the vitamin. Patients with cblC disease present with both hyperhomocysteinemia and methylmalonic acidemia, cognitive dysfunction, and megaloblastic anemia. In the present study we show that cultured skin fibroblasts from cblC patients export increased levels of both homocysteine and methylmalonic acid compared to control skin fibroblasts, and that they also have decreased levels of total intracellular folates. This is consistent with the clinical phenotype of functional cobalamin deficiency in vivo. The protein changes that accompany human functional Cbl deficiency are unknown. The proteome of control and cblC fibroblasts was quantitatively examined by two dimensional in-gel electrophoresis (2D-DIGE) and liquid chromatography-electrospray ionization-mass spectrometry (LC/ESI/MS). Major changes were observed in the expression levels of proteins involved in cytoskeleton organization and assembly, the neurological system and cell signaling. Pathway analysis of the differentially expressed proteins demonstrated strong associations with neurological disorders, muscular and skeletal disorders, and cardiovascular diseases in the cblC mutant cell lines. Supplementation of the cell cultures with hydroxocobalamin did not restore the cblC proteome to the patterns of expression observed in control cells. These results concur with the observed phenotype of patients with the cblC disorder and their sometimes poor response to treatment with hydroxocobalamin. Our findings could be valuable for designing alternative therapies to alleviate the clinical manifestation of the cblC disorder, as some of the protein changes detected in our study are common hallmarks of known pathologies such as Alzheimer’s and Parkinson's diseases as well as muscular dystrophies. PMID:21497120

Combination of vitamin B12 active forms improved fetal growth in Wistar rats through up-regulation of placental miR-16 and miR-21 levels.

PubMed

Shah, Tejas; Mishra, Sanjay; More, Amol; Otiv, Suhas; Apte, Kishori; Joshi, Kalpana

2017-12-15

Epidemiological studies have indicated importance of folate and vitamin (B12) during pregnancy. Also available evidence on efficacy of B12 forms viz. Cyanocobalamin (Cbl), Methylcobalamin (MeCbl), Adenosylcobalamin (AdCbl) and Hydroxycobalamin (HCbl) in preventing or treating cobalamin deficiency is limited. The present study examines the effect of various forms of B12 in combination with folate during pregnancy and their effect on gestational outcomes. In the present study, we examined the effect of various vitamin B12 forms in presence of recommended folate (RFol: 400μg/day) and high folate (HFol: 5mg/day) on gestational outcomes in female Wistar rats. Dams dosed with excessive folate (HFol group) delivered low birth weight (LBW) offsprings (p<0.01) as compared to RFol dams. Plasma homocysteine levels were found to be significantly higher (p<0.05) in dams of HFol group and were reduced after vitamin B12 supplementation. Excessive folate supplementation and homocysteine levels showed inverse association with placental weight (p<0.01) and placental efficiency (p<0.05). B12 supplementation significantly up-regulated placental miR-16 and miR-21, associated with fetal growth which in turn reflected in improved birthweights. Supplementation with vitamin B12 forms, especially combination of active forms of cobalamins: MeCbl+AdCbl significantly increased birth weights (p<0.05) and modulated gestational outcomes in RFol as well as HFol supplemented dams. Our results indicated supplementing vitamin B12 along with folate during pregnancy had positive impact on the gestational outcomes. We have shown for the first time that combination of active forms of vitamin B12: MeCbl+AdCbl has better efficacy as compared to Cbl, MeCbl, AdCbl and HCbl alone. Copyright © 2017 Elsevier Inc. All rights reserved.

Methylcobalamin promotes proliferation and migration and inhibits apoptosis of C2C12 cells via the Erk1/2 signaling pathway

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

Okamoto, Michio; Tanaka, Hiroyuki, E-mail: tanahiro-osk@umin.ac.jp; Okada, Kiyoshi

2014-01-17

Highlights: •Methylcobalamin activated the Erk1/2 signaling pathway in C2C12 cells. •Methylcobalamin promoted the proliferation and migration in C2C12 cells. •C2C12 cell apoptosis during differentiation was inhibited by methylcobalamin. -- Abstract: Methylcobalamin (MeCbl) is a vitamin B12 analog that has some positive effects on peripheral nervous disorders. Although some previous studies revealed the effects of MeCbl on neurons, its effect on the muscle, which is the final target of motoneuron axons, remains to be elucidated. This study aimed to determine the effect of MeCbl on the muscle. We found that MeCbl promoted the proliferation and migration of C2C12 myoblasts in vitromore » and that these effects are mediated by the Erk1/2 signaling pathway without affecting the activity of the Akt signaling pathway. We also demonstrated that MeCbl inhibits C2C12 cell apoptosis during differentiation. Our results suggest that MeCbl has beneficial effects on the muscle in vitro. MeCbl administration may provide a novel therapeutic approach for muscle injury or degenerating muscle after denervation.« less

Cbl Associates with Pyk2 and Src to Regulate Src Kinase Activity, αvβ3 Integrin-Mediated Signaling, Cell Adhesion, and Osteoclast Motility

PubMed Central

Sanjay, Archana; Houghton, Adam; Neff, Lynn; DiDomenico, Emilia; Bardelay, Chantal; Antoine, Evelyne; Levy, Joan; Gailit, James; Bowtell, David; Horne, William C.; Baron, Roland

2001-01-01

The signaling events downstream of integrins that regulate cell attachment and motility are only partially understood. Using osteoclasts and transfected 293 cells, we find that a molecular complex comprising Src, Pyk2, and Cbl functions to regulate cell adhesion and motility. The activation of integrin αvβ3 induces the [Ca2+]i-dependent phosphorylation of Pyk2 Y402, its association with Src SH2, Src activation, and the Src SH3-dependent recruitment and phosphorylation of c-Cbl. Furthermore, the PTB domain of Cbl is shown to bind to phosphorylated Tyr-416 in the activation loop of Src, the autophosphorylation site of Src, inhibiting Src kinase activity and integrin-mediated adhesion. Finally, we show that deletion of c Src or c-Cbl leads to a decrease in osteoclast migration. Thus, binding of αvβ3 integrin induces the formation of a Pyk2/Src/Cbl complex in which Cbl is a key regulator of Src kinase activity and of cell adhesion and migration. These findings may explain the osteopetrotic phenotype in the Src−/− mice. PMID:11149930

c-Cbl promotes T cell receptor-induced thymocyte apoptosis by activating the phosphatidylinositol 3-kinase/Akt pathway.

PubMed

Thien, Christine B F; Dagger, Samantha A; Steer, James H; Koentgen, Frank; Jansen, Elisa S; Scott, Clare L; Langdon, Wallace Y

2010-04-02

The ability of thymocytes to assess T cell receptor (TCR) signaling strength and initiate the appropriate downstream response is crucial for determining their fate. We have previously shown that a c-Cbl RING finger mutant knock-in mouse, in which the E3 ubiquitin ligase activity of c-Cbl is inactivated, is highly sensitive to TCR-induced death signals that cause thymic deletion. This high intensity signal involves the enhanced tyrosine phosphorylation of the mutant c-Cbl protein promoting a marked increase in the activation of Akt. Here we show that this high intensity signal in c-Cbl RING finger mutant thymocytes also promotes the enhanced induction of two mediators of TCR-directed thymocyte apoptosis, Nur77 and the pro-apoptotic Bcl-2 family member, Bim. In contrast, a knock-in mouse harboring a mutation at Tyr-737, the site in c-Cbl that activates phosphatidylinositol 3-kinase, shows reduced TCR-mediated responses including suppression of Akt activation, a reduced induction of Nur77 and Bim, and greater resistance to thymocyte death. These findings identify tyrosine-phosphorylated c-Cbl as a critical sensor of TCR signal strength that regulates the engagement of death-promoting signals.

E3 Ubiquitin Ligase c-cbl Inhibits Microglia Activation After Chronic Constriction Injury.

PubMed

Xue, Pengfei; Liu, Xiaojuan; Shen, Yiming; Ju, Yuanyuan; Lu, Xiongsong; Zhang, Jinlong; Xu, Guanhua; Sun, Yuyu; Chen, Jiajia; Gu, Haiyan; Cui, Zhiming; Bao, Guofeng

2018-06-22

E3 ubiquitin ligase c-Caritas B cell lymphoma (c-cbl) is associated with negative regulation of receptor tyrosine kinases, signal transduction of antigens and cytokine receptors, and immune response. However, the expression and function of c-cbl in the regulation of neuropathic pain after chronic constriction injury (CCI) are unknown. In rat CCI model, c-cbl inhibited the activation of spinal cord microglia and the release of pro-inflammatory factors including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), which alleviated mechanical and heat pain through down-regulating extracellular signal-regulated kinase (ERK) pathway. Additionally, exogenous TNF-α inhibited c-cbl protein level vice versa. In the primary microglia transfected with c-cbl siRNA, when treated with TNF-α or TNF-α inhibitor, the corresponding secretion of IL-1β and IL-6 did not change. In summary, CCI down-regulated c-cbl expression and induced the activation of microglia, then activated microglia released inflammatory factors via ERK signaling to cause pain. Our data might supply a novel molecular target for the therapy of CCI-induced neuropathic pain.

Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B12)-Defective Mice Is Subject to Maternal Influences.

PubMed

Mottram, Lynda; Speak, Anneliese O; Selek, Reza M; Cambridge, Emma L; McIntyre, Zoe; Kane, Leanne; Mukhopadhyay, Subhankar; Grove, Carolyn; Colin, Amy; Brandt, Cordelia; Duque-Correa, Maria A; Forbester, Jessica; Nguyen, Tu Anh Pham; Hale, Christine; Vasilliou, George S; Arends, Mark J; Wren, Brendan W; Dougan, Gordon; Clare, Simon

2016-06-21

Mice harboring a mutation in the gene encoding gastric intrinsic factor (Gif), a protein essential for the absorption of vitamin B12/cobalamin (Cbl), have potential as a model to explore the role of vitamins in infection. The levels of Cbl in the blood of Gif(tm1a/tm1a) mutant mice were influenced by the maternal genotype, with offspring born to heterozygous (high Cbl, F1) mothers exhibiting a significantly higher serum Cbl level than those born to homozygous (low Cbl, F2) equivalents. Low Cbl levels correlated with susceptibility to an infectious challenge with Salmonella enterica serovar Typhimurium or Citrobacter rodentium, and this susceptibility phenotype was moderated by Cbl administration. Transcriptional and metabolic profiling revealed that Cbl deficient mice exhibited a bioenergetic shift similar to a metabolic phenomenon commonly found in cancerous cells under hypoxic conditions known as the Warburg effect, with this metabolic effect being exacerbated further by infection. Our findings demonstrate a role for Cbl in bacterial infection, with potential general relevance to dietary deficiency and infection susceptibility. Malnutrition continues to be a major public health problem in countries with weak infrastructures. In communities with a high prevalence of poor diet, malnourishment and infectious disease can impact vulnerable individuals such as pregnant women and children. Here, we describe a highly flexible murine model for monitoring maternal and environmental influences of vitamin B12 metabolism. We also demonstrate the potential importance of vitamin B12 in controlling susceptibility to bacterial pathogens such as C. rodentium and S Typhimurium. We postulate that this model, along with similarly vitamin deficient mice, could be used to further explore the mechanisms associated with micronutrients and susceptibility to diseases, thereby increasing our understanding of disease in the malnourished. Copyright © 2016 Mottram et al.

A guide to using case-based learning in biochemistry education.

PubMed

Kulak, Verena; Newton, Genevieve

2014-01-01

Studies indicate that the majority of students in undergraduate biochemistry take a surface approach to learning, associated with rote memorization of material, rather than a deep approach, which implies higher cognitive processing. This behavior relates to poorer outcomes, including impaired course performance and reduced knowledge retention. The use of case-based learning (CBL) into biochemistry teaching may facilitate deep learning by increasing student engagement and interest. Abundant literature on CBL exists but clear guidance on how to design and implement case studies is not readily available. This guide provides a representative review of CBL uses in science and describes the process of developing CBL modules to be used in biochemistry. Included is a framework to implement a directed CBL assisted with lectures in a content-driven biochemistry course regardless of class size. Moreover, this guide can facilitate adopting CBL to other courses. Consequently, the information presented herein will be of value to undergraduate science educators with an interest in active learning pedagogies. © 2014 The International Union of Biochemistry and Molecular Biology.

Functional analysis of MeCIPK23 and MeCBL1/9 in cassava defense response against Xanthomonas axonopodis pv. manihotis.

PubMed

Yan, Yu; He, Xinyi; Hu, Wei; Liu, Guoyin; Wang, Peng; He, Chaozu; Shi, Haitao

2018-06-01

MeCIPK23 interacts with MeCBL1/9, and they confer improved defense response, providing potential genes for further genetic breeding in cassava. Cassava (Manihot esculenta) is an important food crop in tropical area, but its production is largely affected by cassava bacterial blight. However, the information of defense-related genes in cassava is very limited. Calcium ions play essential roles in plant development and stress signaling pathways. Calcineurin B-like proteins (CBLs) and CBL-interacting protein kinases (CIPKs) are crucial components of calcium signals. In this study, systematic expression profile of 25MeCIPKs in response to Xanthomonas axonopodis pv. manihotis (Xam) infection was examined, by which seven candidate MeCIPKs were chosen for functional investigation. Through transient expression in Nicotiana benthamiana leaves, we found that six MeCIPKs (MeCIPK5, MeCIPK8, MeCIPK12, MeCIPK22, MeCIPK23 and MeCIPK24) conferred improved defense response, via regulating the transcripts of several defense-related genes. Notably, we found that MeCIPK23 interacted with MeCBL1 and MeCBL9, and overexpression of these genes conferred improved defense response. On the contrary, virus-induced gene silencing of either MeCIPK23 or MeCBL1/9 or both genes resulted in disease sensitive in cassava. To our knowledge, this is the first study identifying MeCIPK23 as well as MeCBL1 and MeCBL9 that confer enhanced defense response against Xam.

Deficient tyrosine phosphorylation of c-Cbl and associated proteins in phorbol ester-resistant EL4 mouse thymoma cells.

PubMed

Luo, X; Sando, J J

1997-05-02

Two tyrosine phosphoproteins in phorbol ester-sensitive EL4 (S-EL4) mouse thymoma cells have been identified as the p120 c-Cbl protooncogene product and the p85 subunit of phosphatidylinositol 3-kinase. Tyrosine phosphorylation of p120 and p85 increased rapidly after phorbol ester stimulation. Phorbol ester-resistant EL4 (R-EL4) cells expressed comparable amounts of c-Cbl and phosphatidylinositol 3-kinase protein but greatly diminished tyrosine phosphorylation. Co-immunoprecipitation experiments revealed complexes of c-Cbl with p85, and of p85 with the tyrosine kinase Lck in phorbol ester-stimulated S-EL4 but not in unstimulated S-EL4 or in R-EL4 cells. In vitro binding of c-Cbl with Lck SH2 or SH3 domains was detected in both S-EL4 and R-EL4 cells, suggesting that c-Cbl, p85, and Lck may form a ternary complex. In vitro kinase assays revealed phosphorylation of p85 by Lck only in phorbol ester-stimulated S-EL4 cells. Collectively, these results suggest that Cbl-p85 and Lck-p85 complexes may form in unstimulated S-EL4 and R-EL4 cells but were not detected due to absence of tyrosine phosphorylation of p85. Greatly decreased tyrosine phosphorylation of c-Cbl and p85 in the complexes may contribute to the failure of R-EL4 cells to respond to phorbol ester.

E3 Ubiquitin Ligase Cbl-b Prevents Tumor Metastasis by Maintaining the Epithelial Phenotype in Multiple Drug-Resistant Gastric and Breast Cancer Cells.

PubMed

Xu, Ling; Zhang, Ye; Qu, Xiujuan; Che, Xiaofang; Guo, Tianshu; Cai, Ying; Li, Aodi; Li, Danni; Li, Ce; Wen, Ti; Fan, Yibo; Hou, Kezuo; Ma, Yanju; Hu, Xuejun; Liu, Yunpeng

2017-04-01

Multiple drug resistance (MDR) and metastasis are two major factors that contribute to the failure of cancer treatment. However, the relationship between MDR and metastasis has not been characterized. Additionally, the role of the E3 ubiquitin ligase Cbl-b in metastasis of MDR gastric and breast cancer is not well known. In the present study, we found that MDR gastric and breast cancer cells possess a typical mesenchymal phenotype and enhanced cell migration capacity. Additionally, Cbl-b is poorly expressed in MDR gastric and breast cancer cells. In MDR gastric adenocarcinoma tissues, gastric cancer patients with low Cbl-b expression were more likely to have tumor invasion (P=.016) and lymph node metastasis (P=.007). Moreover, overexpression of Cbl-b reduced cell migration in MDR cell cultures both in vitro and in vivo. Cbl-b overexpression also prevented EMT by inducing ubiquitination and degradation of EGFR, leading to inhibition of the EGFR-ERK/Akt-miR-200c-ZEB1 axis. However, further overexpression of EGFR on a background of Cbl-b overexpression restored both the mesenchymal phenotype and cell migration capacity of MDR gastric and breast cancer cells. These results suggest that Cbl-b is an important factor for maintenance of the epithelial phenotype and inhibition of cell migration in MDR gastric and breast cancer cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Challenges for Collaborative Blended Learning in Undergraduate Students

ERIC Educational Resources Information Center

Monteiro, Elisa; Morrison, Keith

2014-01-01

This study reports a quasi-experiment in collaborative blended learning (CBL) with undergraduate students who, despite being in a world-leading, enriched digital environment, were new to collaboration and CBL. The mixed-methods research found that only small improvements to students' CBL took place over time, and explanations for this are…

Modulation of Immune Cell Functions by the E3 Ligase Cbl-b

PubMed Central

Lutz-Nicoladoni, Christina; Wolf, Dominik; Sopper, Sieghart

2015-01-01

Maintenance of immunological tolerance is a critical hallmark of the immune system. Several signaling checkpoints necessary to balance activating and inhibitory input to immune cells have been described so far, among which the E3 ligase Cbl-b appears to be a central player. Cbl-b is expressed in all leukocyte subsets and regulates several signaling pathways in T cells, NK cells, B cells, and different types of myeloid cells. In most cases, Cbl-b negatively regulates activation signals through antigen or pattern recognition receptors and co-stimulatory molecules. In line with this function, cblb-deficient immune cells display lower activation thresholds and cblb knockout mice spontaneously develop autoimmunity and are highly susceptible to experimental autoimmunity. Interestingly, genetic association studies link CBLB-polymorphisms with autoimmunity also in humans. Vice versa, the increased activation potential of cblb-deficient cells renders them more potent to fight against malignancies or infections. Accordingly, several reports have shown that cblb knockout mice reject tumors, which mainly depends on cytotoxic T and NK cells. Thus, targeting Cbl-b may be an interesting strategy to enhance anti-cancer immunity. In this review, we summarize the findings on the molecular function of Cbl-b in different cell types and illustrate the potential of Cbl-b as target for immunomodulatory therapies. PMID:25815272

The effects of different learning environments on students' motivation for learning and their achievement.

PubMed

Baeten, Marlies; Dochy, Filip; Struyven, Katrien

2013-09-01

Research in higher education on the effects of student-centred versus lecture-based learning environments generally does not take into account the psychological need support provided in these learning environments. From a self-determination theory perspective, need support is important to study because it has been associated with benefits such as autonomous motivation and achievement. The purpose of the study is to investigate the effects of different learning environments on students' motivation for learning and achievement, while taking into account the perceived need support. First-year student teachers (N= 1,098) studying a child development course completed questionnaires assessing motivation and perceived need support. In addition, a prior knowledge test and case-based assessment were administered. A quasi-experimental pre-test/post-test design was set up consisting of four learning environments: (1) lectures, (2) case-based learning (CBL), (3) alternation of lectures and CBL, and (4) gradual implementation with lectures making way for CBL. Autonomous motivation and achievement were higher in the gradually implemented CBL environment, compared to the CBL environment. Concerning achievement, two additional effects were found; students in the lecture-based learning environment scored higher than students in the CBL environment, and students in the gradually implemented CBL environment scored higher than students in the alternated learning environment. Additionally, perceived need support was positively related to autonomous motivation, and negatively to controlled motivation. The study shows the importance of gradually introducing students to CBL, in terms of their autonomous motivation and achievement. Moreover, the study emphasizes the importance of perceived need support for students' motivation. © 2012 The British Psychological Society.

Loss of Cbl-PI3K Interaction Modulates the Periosteal Response to Fracture by Enhancing Osteogenic Commitment and Differentiation

PubMed Central

Scanlon, Vanessa; Walia, Bhavita; Yu, Jungeun; Hansen, Marc; Drissi, Hicham; Maye, Peter; Sanjay, Archana

2018-01-01

The periosteum contains multipotent skeletal progenitors that contribute to bone repair. The signaling pathways regulating the response of periosteal cells to fracture are largely unknown. Phosphatidylinositol-3 Kinase (PI3K), a prominent lipid kinase, is a major signaling protein downstream of several factors that regulate osteoblast differentiation. Cbl is an E3 ubiquitin ligase and a major adaptor protein that binds to the p85 regulatory subunit and modulates PI3K activity. Substitution of tyrosine 737 to phenylalanine (Y737F) in Cbl abolishes the interaction between Cbl and the p85 subunit without affecting the Cbl’s ubiquitin ligase function. Here, we investigated the role of PI3K signaling during the very early stages of fracture healing using OsterixRFP reporter mice. We found that the absence of PI3K regulation by Cbl resulted in robust periosteal thickening, with increased proliferation of periosteal cells. While the multipotent properties of periosteal progenitors to differentiate into chondrocytes and adipocytes did not change, osteogenic differentiation in the absence of Cbl-PI3K interaction was highly augmented. The increased stability and nuclear localization of Osterix observed in periosteal cells lacking Cbl-PI3K interaction may explain this enhanced osteogenic differentiation since the expression of Osterix transcriptional target genes including osteocalcin and BSP are increased in YF cells. Overall, our findings highlight a hitherto unexplored and novel role for Cbl and PI3K in modulating the osteogenic response of periosteal cells during the early stages of fracture repair. PMID:27884787

Applying Challenge-Based Learning in the (Feminist) Communication Classroom: Positioning Students as Knowledgeable Change Agents

ERIC Educational Resources Information Center

Cruger, Katherine M.

2018-01-01

This article explores the potential of challenge-based learning (CBL) for feminist pedagogy. In a qualitative case study of an introductory mass communication and social theory course, students were more likely to indicate sophisticated, intersectional understandings of course concepts following the CBL project. Before the CBL project, students…

Proteomics of vitamin B12 processing.

PubMed

Hannibal, Luciana; DiBello, Patricia M; Jacobsen, Donald W

2013-03-01

The causes of cobalamin (B12, Cbl) deficiency are multifactorial. Whether nutritional due to poor dietary intake, or functional due to impairments in absorption or intracellular processing and trafficking events, the major symptoms of Cbl deficiency include megaloblastic anemia, neurological deterioration and in extreme cases, failure to thrive and death. The common biomarkers of Cbl deficiency (hyperhomocysteinemia and methylmalonic acidemia) are extremely valuable diagnostic indicators of the condition, but little is known about the changes that occur at the protein level. A mechanistic explanation bridging the physiological changes associated with functional B12 deficiency with its intracellular processers and carriers is lacking. In this article, we will cover the effects of B12 deficiency in a cblC-disrupted background (also referred to as MMACHC) as a model of functional Cbl deficiency. As will be shown, major protein changes involve the cytoskeleton, the neurological system as well as signaling and detoxification pathways. Supplementation of cultured MMACHC-mutant cells with hydroxocobalamin (HOCbl) failed to restore these variants to the normal phenotype, suggesting that a defective Cbl processing pathway produces irreversible changes at the protein level.

Hemolytic uremic syndrome (HUS) secondary to cobalamin C (cblC) disorder.

PubMed

Sharma, Ajay P; Greenberg, Cheryl R; Prasad, Asuri N; Prasad, Chitra

2007-12-01

Diarrhea-positive hemolytic uremic syndrome (HUS) is a common cause of acute renal failure in children. Diarrhea-negative (D-), or atypical HUS, is etiologically distinct. A Medline search identified seven previously reported D- cases of HUS secondary to cobalamin C (cblC) disease presenting in infancy. An infantile presentation is reported to be associated with a high mortality rate (6/7 cases). We describe the results of a 5-year longitudinal follow-up in a child diagnosed with D- HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene. We briefly review the published experience in cblC-associated HUS to highlight the clinical characteristics of this uncommon, but potentially treatable, condition.

Development of a functional food or drug against unloading-mediated muscle atrophy

NASA Astrophysics Data System (ADS)

Nikawa, Takeshi; Nakao, Reiko; Kagawa, Sachiko; Yamada, Chiharu; Abe, Manami; Tamura, Seiko; Kohno, Shohei; Sukeno, Akiko; Hirasaka, Katsuya; Okumura, Yuushi; Ishidoh, Kazumi

The ubiquitin-proteasome pathway is a primary regulator of muscle protein turnover, providing a mechanism for selective degradation of regulatory and structural proteins. This pathway is constitutively active in muscle fibers and mediates both intracellular signaling events and normal muscle protein turnover. However, conditions of decreased muscle use, so called unloading, remarkably stimulate activity of this pathway, resulting in loss of muscle protein. In fact, we previously reported that expression of several ubiquitin ligase genes, such as MuRF-1, Cbl-b, and Siah-1A, which are rate-limiting enzymes of the ubiquitin-proteasome proteolytic pathway, are significantly up-regulated in rat skeletal muscle during spaceflight. Moreover, we found that Cbl-b-mediated ubiquitination and degradation of IRS-1, an important intermediates of IGF-1 signal transduction, contributes to muscle atrophy during unloading. Therefore, we hypothesized that inhibition of Cbl-b-mediated ubiquitination and degradation of IRS-1 leads to prevention of muscle atrophy during unloading. In this study, we aimed to evaluate oligopeptide as an inhibitor against ubiquitination of IRS-1 by Cbl-b. We synthesized various oligopeptides that may competitively inhibit the binding of Cbl-b to IRS-1 on the basis of their structures and screened inhibitory effects of these synthesized oligopeptides on Cbl-b-mediated ubiquitination of IRS-1 using in vitro ubiquitination systems. We found that two synthetic oligopeptides with specific amino acid sequences effectively inhibited interaction with Cbl-b and IRS-1, resulting in decreased ubiquitination and degradation of IRS-1 (Patent pending). In contrast, we also found inhibitory activity against Cbl-b-mediated ubiquitination of IRS-1 in soy protein-derived oligopeptides, whereas their inhibitory effects were weaker than those of synthetic oligopeptides. Our results suggest that specific oligopeptides may be available as a functional food against the muscle atrophy, especially through downregulation of the Cbl-b-mediated IRS-1 degradation.

Effect of cerebrolysin on gross motor function of children with cerebral palsy: a clinical trial.

PubMed

Nasiri, Jafar; Safavifar, Faezeh

2017-06-01

Gross motor dysfunction is considered as the most challenging problem in cerebral palsy (CP). It is proven that improvement of gross motor function could reduce CP-related disabilities and provide better quality of life in this group of patients. Therefore, the aim of this trial is to evaluate the effectiveness of cerebrolysin (CBL) on gross motor function of children with CP who are undergoing treatment. In this clinical trial study, paediatric patients aged 18-75 months with spastic diplegic or quadriplegic cerebral palsy, who were under rehabilitation therapy, were selected and randomly allocated in control and CBL groups. Patients in CBL group underwent treatment with standard rehabilitation therapy plus CBL. The latter was administrated intramuscularly as a single daily dose of 0.1 cc/kg for 10 days and then continued weekly for 4 months. Gross motor function of participants in the two studied groups, before and after trial, was evaluated and compared using the validated Persian version of gross motor function classification system-expanded and revised (GMFCS-E&R). During this trial, 108 patients with CP were evaluated for eligibility. From these, 50 patients were enrolled and randomly allocated in the CBL and control groups. Four months after trial, the mean level of GMFCS decreased significantly in the two groups (P < 0.05). However, it was significantly lower in the CBL group than in the control group (2.1 vs. 3.16, P < 0.05). The results of this trial indicated that CBL could improve gross motor function in patients with CP. This finding is consistent with neurotrophic and neuroprotective effects of CBL, which have been reported in various clinical trials in other neurological disorders. Further studies are recommended to establish the value of continued neuroprotection and to determine the pharmacokinetics/dynamics of CBL in this group of patients.

Reactive oxygen species upregulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells.

PubMed

Uchida, Takayuki; Sakashita, Yoshihiro; Kitahata, Kanako; Yamashita, Yui; Tomida, Chisato; Kimori, Yuki; Komatsu, Akio; Hirasaka, Katsuya; Ohno, Ayako; Nakao, Reiko; Higashitani, Atsushi; Higashibata, Akira; Ishioka, Noriaki; Shimazu, Toru; Kobayashi, Takeshi; Okumura, Yuushi; Choi, Inho; Oarada, Motoko; Mills, Edward M; Teshima-Kondo, Shigetada; Takeda, Shin'ichi; Tanaka, Eiji; Tanaka, Keiji; Sokabe, Masahiro; Nikawa, Takeshi

2018-06-01

Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of muscle volume (Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T. Mol Cell Biol 29: 4798-4811, 2009). However, the pathological role of ROS production associated with unloading-mediated muscle atrophy still remains unknown. Here, we showed that the ROS-mediated signal transduction caused by microgravity or its simulation contributes to Cbl-b expression. In L6 myotubes, the assessment of redox status revealed that oxidized glutathione was increased under microgravity conditions, and simulated microgravity caused a burst of ROS, implicating ROS as a critical upstream mediator linking to downstream atrophic signaling. ROS generation activated the ERK1/2 early-growth response protein (Egr)1/2-Cbl-b signaling pathway, an established contributing pathway to muscle volume loss. Interestingly, antioxidant treatments such as N-acetylcysteine and TEMPOL, but not catalase, blocked the clinorotation-mediated activation of ERK1/2. The increased ROS induced transcriptional activity of Egr1 and/or Egr2 to stimulate Cbl-b expression through the ERK1/2 pathway in L6 myoblasts, since treatment with Egr1/2 siRNA and an ERK1/2 inhibitor significantly suppressed clinorotation-induced Cbl-b and Egr expression, respectively. Promoter and gel mobility shift assays revealed that Cbl-b was upregulated via an Egr consensus oxidative responsive element at -110 to -60 bp of the Cbl-b promoter. Together, this indicates that under microgravity conditions, elevated ROS may be a crucial mechanotransducer in skeletal muscle cells, regulating muscle mass through Cbl-b expression activated by the ERK-Egr signaling pathway.

Evaluation of Computer-aided Strategies for Teaching Medical Students Prenatal Ultrasound Diagnostic Skills.

PubMed

Amesse, Lawrence S; Callendar, Ealena; Pfaff-Amesse, Teresa; Duke, Janice; Herbert, William N P

2008-09-24

To evaluate whether computer-based learning (CBL) improves newly acquired knowledge and is an effective strategy for teaching prenatal ultrasound diagnostic skills to third-year medical students when compared with instruction by traditional paper-based methods (PBM). We conducted a randomized, prospective study involving volunteer junior (3(rd) year) medical students consecutively rotating through the Obstetrics and Gynecology clerkship during six months of the 2005-2006 academic year. The students were randomly assigned to permuted blocks and divided into two groups. Half of the participants received instruction in prenatal ultrasound diagnostics using an interactive CBL program; the other half received instruction using equivalent material by the traditional PBM. Outcomes were evaluated by comparing changes in pre-tutorial and post instruction examination scores. All 36 potential participants (100%) completed the study curriculum. Students were divided equally between the CBL (n = 18) and PBM (n = 18) groups. Pre-tutorial exam scores (mean+/-s.d.) were 44%+/-11.1% for the CBL group and 44%+/-10.8% for the PBL cohort, indicating no statistically significant differences (p>0.05) between the two groups. After instruction, post-tutorial exam scores (mean+/-s.d.) were increased from the pre-tutorial scores, 74%+/-11% and 67%+/-12%, for students in the CBL and the PBM groups, respectively. The improvement in post-tutorial exam scores from the pre-test scores was considered significant (p<0.05). When post-test scores for the tutorial groups were compared, the CBL subjects achieved a score that was, on average, 7 percentage points higher than their PBM counterparts, a statistically significant difference (p < 0.05). Instruction by either CBL or PBM strategies is associated with improvements in newly acquired knowledge as reflected by increased post-tutorial examination scores. Students that received CBL had significantlyhigher post-tutorial exam scores than those in the PBM group, indicating that CBL is an effective instruction strategy in this setting.

Combined Application of Study Design and Case-Based Learning Comprehensive Model in Epidemiology Teaching

ERIC Educational Resources Information Center

Shi, Xiuquan; Zhou, Yanna; Wang, Haiyan; Wang, Tao; Nie, Chan; Shi, Shangpeng

2017-01-01

This paper aims to conduct the SD-CBL (study design with the case based learning, SD-CBL) in Epidemiology teaching and evaluate its effect. Students from five classes were recruited, and a combined comprehensive teaching model of SD-CBL was used in the "Injury Epidemiology" chapter, while other chapters in "Epidemiology"…

Abrogation of Cbl-PI3K interaction increases bone formation and osteoblast proliferation.

PubMed

Brennan, Tracy; Adapala, Naga Suresh; Barbe, Mary F; Yingling, Vanessa; Sanjay, Archana

2011-11-01

Cbl is an adaptor protein and E3 ligase that plays both positive and negative roles in several signaling pathways that affect various cellular functions. Tyrosine 737 is unique to Cbl and phosphorylated by Src family kinases. Phosphorylated CblY737 creates a binding site for the p85 regulatory subunit of phosphatidylinositol 3 kinase (PI3K) that also plays an important role in the regulation of bone homeostasis. To investigate the role of Cbl-PI3K interaction in bone homeostasis, we examined knock-in mice in which the PI3K binding site on Cbl was ablated due to the substitution of tyrosine 737 to phenylalanine (Cbl(YF/YF), YF mice). We previously reported that bone volume in these mice is increased due to decreased osteoclast function (Adapala et al., J Biol Chem 285:36745-36758, 19). Here, we report that YF mice also have increased bone formation and osteoblast numbers. In ex vivo cultures bone marrow-derived YF osteoblasts showed increased Col1A expression and their proliferation was also significantly augmented. Moreover, proliferation of MC3T3-E1 cells was increased after treatment with conditioned medium generated by culturing YF bone marrow stromal cells. Expression of stromal derived factor-1 (SDF-1) was increased in YF bone marrow stromal cells compared to wild type. Increased immunostaining of SDF-1 and CXCR4 was observed in YF bone marrow stromal cells compared to wild type. Treatment of YF condition medium with neutralizing anti-SDF-1 and anti-CXCR4 antibodies attenuated MC3T3-E1 cell proliferation. Cumulatively, these results show that abrogation of Cbl-PI3K interaction perturbs bone homeostasis, affecting both osteoclast function and osteoblast proliferation.

Exploring Student Preconceptions of Readiness for Remote-Online Case-Based Learning: A Case Study

PubMed Central

2016-01-01

Background Case-based learning (CBL) is an educational approach where students work in small, collaborative groups to solve problems. Web-conferencing software provides a platform to present information and share concepts that are vital to CBL. Previous studies have found that participants were resistant to change associated with implementing e-learning; however, strategies to reduce this resistance have not been explored. Objective This study was designed to explore student preconceptions and understanding of remote-online case-based learning (RO-CBL). Methods The study took place during the Bachelor of Physiotherapy program at Monash University, Victoria, Australia, in 2013. The entire third-year cohort (n=73) was invited to participate. The primary outcome of interest was students’ preconceptions of RO-CBL, collected via pre- and posttraining surveys. Results Of the 73 students, 66 completed both surveys (attrition rate 9.6%). Three key themes relevant to student preconceptions of RO-CBL emerged: flexibility in time and location of CBL, readiness or hesitation to change to a Web-based format, and the value of training in RO-CBL that included a demonstration and trial run. Thirty-four percent of the participants were hesitant to move to an online format. Conclusions This study explored students’ preconceptions of Web-based learning and evaluated the change in students’ attitudes after training. The results suggest that educational designers should not assume that students are confident and competent in applying these technologies to professional educational activities. By identifying students’ needs before implementation, training sessions can be designed to target these needs, and improve the understanding of RO-CBL and how it works in practice. This may reduce resistance to change, enhance students’ satisfaction, and ultimately improve the learning experience. PMID:27731854

Exploring Student Preconceptions of Readiness for Remote-Online Case-Based Learning: A Case Study.

PubMed

Nicklen, Peter; Keating, Jennifer L; Maloney, Stephen

2016-04-28

Case-based learning (CBL) is an educational approach where students work in small, collaborative groups to solve problems. Web-conferencing software provides a platform to present information and share concepts that are vital to CBL. Previous studies have found that participants were resistant to change associated with implementing e-learning; however, strategies to reduce this resistance have not been explored. This study was designed to explore student preconceptions and understanding of remote-online case-based learning (RO-CBL). The study took place during the Bachelor of Physiotherapy program at Monash University, Victoria, Australia, in 2013. The entire third-year cohort (n=73) was invited to participate. The primary outcome of interest was students' preconceptions of RO-CBL, collected via pre- and posttraining surveys. Of the 73 students, 66 completed both surveys (attrition rate 9.6%). Three key themes relevant to student preconceptions of RO-CBL emerged: flexibility in time and location of CBL, readiness or hesitation to change to a Web-based format, and the value of training in RO-CBL that included a demonstration and trial run. Thirty-four percent of the participants were hesitant to move to an online format. This study explored students' preconceptions of Web-based learning and evaluated the change in students' attitudes after training. The results suggest that educational designers should not assume that students are confident and competent in applying these technologies to professional educational activities. By identifying students' needs before implementation, training sessions can be designed to target these needs, and improve the understanding of RO-CBL and how it works in practice. This may reduce resistance to change, enhance students' satisfaction, and ultimately improve the learning experience.

Effect of case-based learning on the development of graduate nurses' problem-solving ability.

PubMed

Yoo, Moon-Sook; Park, Jin-Hee

2014-01-01

Case-based learning (CBL) is a teaching strategy which promotes clinical problem-solving ability. This research was performed to investigate the effects of CBL on problem-solving ability of graduate nurses. This research was a quasi-experimental design using pre-test, intervention, and post-test with a non-synchronized, non-equivalent control group. The study population was composed of 190 new graduate nurses from university hospital A in Korea. Results of the research indicate that there was a statistically significant difference in objective problem-solving ability scores of CBL group demonstrating higher scores. Subjective problem-solving ability was also significantly higher in CBL group than in the lecture-based group. These results may suggest that CBL is a beneficial and effective instructional method of training graduate nurses to improve their clinical problem-solving ability. Copyright © 2013 Elsevier Ltd. All rights reserved.

CBL-CIPK network for calcium signaling in higher plants

NASA Astrophysics Data System (ADS)

Luan, Sheng

Plants sense their environment by signaling mechanisms involving calcium. Calcium signals are encoded by a complex set of parameters and decoded by a large number of proteins including the more recently discovered CBL-CIPK network. The calcium-binding CBL proteins specifi-cally interact with a family of protein kinases CIPKs and regulate the activity and subcellular localization of these kinases, leading to the modification of kinase substrates. This represents a paradigm shift as compared to a calcium signaling mechanism from yeast and animals. One example of CBL-CIPK signaling pathways is the low-potassium response of Arabidopsis roots. When grown in low-K medium, plants develop stronger K-uptake capacity adapting to the low-K condition. Recent studies show that the increased K-uptake is caused by activation of a specific K-channel by the CBL-CIPK network. A working model for this regulatory pathway will be discussed in the context of calcium coding and decoding processes.

32 CFR 623.4 - Accounting procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... or O) indicating which loan of the day is first; e.g., A-first, B-second, etc. 51 “M”. 52-53 “G4” for... commercial bills of lading (CBL). Freight charges will be paid by the borrower. The CBL will cite proper project codes. NOTE: In emergencies where use of CBL would delay shipment, government bills of lading (GBL...

32 CFR 623.4 - Accounting procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... or O) indicating which loan of the day is first; e.g., A-first, B-second, etc. 51 “M”. 52-53 “G4” for... commercial bills of lading (CBL). Freight charges will be paid by the borrower. The CBL will cite proper project codes. NOTE: In emergencies where use of CBL would delay shipment, government bills of lading (GBL...

Development and Evaluation of a Longitudinal Case-Based Learning (CBL) Experience for a Geriatric Medicine Rotation

ERIC Educational Resources Information Center

Struck, Bryan D.; Teasdale, Thomas A.

2008-01-01

The DWR Department of Geriatric Medicine at OUHSC and the OKC VA Medical Center began a mandatory third-year geriatric medicine clerkship in 2003. As part of the didactic sessions, the Department created a longitudinal Case-Based Learning (CBL) experience. The purpose of this paper is to describe the CBL experience, report student satisfaction…

Comparison of collimated blue-light generation in 85Rb atoms via the D1 and D2 lines

NASA Astrophysics Data System (ADS)

Prajapati, Nikunj; Akulshin, Alexander M.; Novikova, Irina

2018-05-01

We experimentally studied the characteristics of the collimated blue light (CBL) produced in ${}^{85}$Rb vapor by two resonant laser fields exciting atoms into the $5D_{3/2}$ state, using either the $5P_{1/2}$ or the $5P_{3/2}$ intermediate state. We compared the CBL output at different values of frequency detunings, powers, and polarizations of the pump lasers in these two cases, and confirmed the observed trends using a simple theoretical model. We also demonstrated that the addition of the repump laser, preventing the accumulation of atomic population in the uncoupled hyperfine ground state, resulted in nearly an order of magnitude increase in CBL power output. Overall, we found that the $5S_{1/2} - 5P_{1/2} - 5D_{3/2}$ excitation pathway results in stronger CBL generation, as we detected up to $4.25~\\mu$W using two pumps of the same linear polarization. The optimum CBL output for the $5S_{1/2} - 5P_{3/2} - 5D_{3/2}$ excitation pathway required the two pump lasers to have the same circular polarization, but resulted only in a maximum CBL power of $450$~nW.

Kinetic studies on the reaction of cob(II)alamin with hypochlorous acid: Evidence for one electron oxidation of the metal center and corrin ring destruction.

PubMed

Dassanayake, Rohan S; Farhath, Mohamed M; Shelley, Jacob T; Basu, Soumitra; Brasch, Nicola E

2016-10-01

Kinetic and mechanistic studies on the reaction of a major intracellular vitamin B 12 form, cob(II)alamin (Cbl(II)), with hypochlorous acid/hypochlorite (HOCl/OCl - ) have been carried out. Cbl(II) (Co(II)) is rapidly oxidized by HOCl to predominately aquacobalamin/hydroxycobalamin (Cbl(III), Co(III)) with a second-order rate constant of 2.4×10 7 M -1 s -1 (25.0°C). The stoichiometry of the reaction is 1:1. UHPLC/HRMS analysis of the product mixture of the reaction of Cbl(II) with 0.9mol equiv. HOCl provides support for HOCl being initially reduced to Cl and subsequent H atom abstraction from the corrin macrocycle occurring, resulting in small amounts of corrinoid species with two or four H atoms fewer than the parent cobalamin. Upon the addition of excess (H)OCl further slower reactions are observed. Finally, SDS-PAGE experiments show that HOCl-induced damage to bovine serum albumin does not occur in the presence of Cbl(II), providing support for Cbl(II) being an efficient HOCl trapping agent. Copyright © 2016 Elsevier Inc. All rights reserved.

Retrospective Cohort Study of 4,591 Straumann Implants Placed in 2,060 Patients in Private Practice with up to 10-Year Follow-up: The Relationship Between Crestal Bone Level and Soft Tissue Condition.

PubMed

French, David; Cochran, David L; Ofec, Ronen

The purpose of this report is to describe the crestal bone level (CBL) around implants of various designs, describe the peri-implant soft tissue condition, and evaluate the relationship between the two over time. This retrospective cohort study reports on 2,060 patients with 4,591 implants evaluated after 3 months; 1, 3, 5, and 7 years; and up to 10 years. Periapical radiographs were used to evaluate changes in CBL. The peri-implant soft tissue was evaluated using a modified Bleeding Index termed the Implant Mucosal Index (IMI) where: 0 = no bleeding; 1 = minimal, single-point bleeding; 2 = moderate, multipoint bleeding; 3 = profuse, multipoint bleeding; and 4 = suppuration. At 3 months, the mean CBL was 0.06 ± 0.22 mm; by 8 to 10 years, it had increased to 0.44 ± 0.81 mm. The median CBL remained stable throughout the study at < 0.1 mm. At 8 to 10 years, 15% of implants exhibited a CBL > 1.02 mm, and 5% exhibited a CBL > 2.28 mm. More than 50% of patients experienced some bleeding, as seen by an IMI ≥ 1 during follow-up. A positive correlation was found between IMI and CBL, as shown by a mean CBL after 4 years of 0.33 mm, 0.71 mm, and 1.52 mm for IMI = 2, 3, and 4, respectively. One exception was between IMI = 0 and IMI = 1, where no significant difference was found and bone loss was minimal. Bone loss, as measured by changes in CBL during the first 10 years of implant life spans, was minimal for most implants. Nevertheless, it is not unusual to observe implants with advanced bone loss. The soft tissue condition is a good indicator of bone loss. Time alone and minimal bleeding did not correlate with bone loss, but care should be taken for implants with profuse bleeding or suppuration.

A Rich Man, Poor Man Story of S-Adenosylmethionine and Cobalamin Revisited.

PubMed

Bridwell-Rabb, Jennifer; Grell, Tsehai A J; Drennan, Catherine L

2018-06-20

S-adenosylmethionine (AdoMet) has been referred to as both "a poor man's adenosylcobalamin (AdoCbl)" and "a rich man's AdoCbl," but today, with the ever-increasing number of functions attributed to each cofactor, both appear equally rich and surprising. The recent characterization of an organometallic species in an AdoMet radical enzyme suggests that the line that differentiates them in nature will be constantly challenged. Here, we compare and contrast AdoMet and cobalamin (Cbl) and consider why Cbl-dependent AdoMet radical enzymes require two cofactors that are so similar in their reactivity. We further carry out structural comparisons employing the recently determined crystal structure of oxetanocin-A biosynthetic enzyme OxsB, the first three-dimensional structural data on a Cbl-dependent AdoMet radical enzyme. We find that the structural motifs responsible for housing the AdoMet radical machinery are largely conserved, whereas the motifs responsible for binding additional cofactors are much more varied.

Juvenile selective vitamin B₁₂ malabsorption: 50 years after its description-10 years of genetic testing.

PubMed

Gräsbeck, Ralph; Tanner, Stephan M

2011-09-01

Fifty years have passed since the description of juvenile selective malabsorption of cobalamin (Cbl). Quality of life improvements have dramatically reduced the incidence of parasite-induced or nutritional Cbl deficiency. Consequently, inherited defects have become a leading cause of Cbl deficiency in children, which is not always expressed as anemia. Unfortunately, the gold standard for clinical diagnosis, the Schilling test, has increasingly become unavailable, and replacement tests are only in their infancy. Genetic testing is complicated by genetic heterogeneity and differential diagnosis. This review documents the history, research, and advances in genetics that have elucidated the causes of juvenile Cbl malabsorption. Genetic research has unearthed many cases in the past decade, mostly in Europe and North America, often among immigrants from the Middle East or North Africa. Lack of suitable clinical testing potentially leaves many patients inadequately diagnosed. The consequences of suboptimal Cbl levels for neurological development are well documented. By raising awareness, we wish to push for fast track development of better clinical tools and suitable genetic testing. Clinical awareness must include attention to ethnicity, a sensitive topic but effective for fast diagnosis. The treatment with monthly parenteral Cbl for life offers a simple and cost-effective solution once proper diagnosis is made.

[The effects of case-based learning using video on clinical decision making and learning motivation in undergraduate nursing students].

PubMed

Yoo, Moon-Sook; Park, Jin-Hee; Lee, Si-Ra

2010-12-01

The purpose of this study was to examine the effects of case-base learning (CBL) using video on clinical decision-making and learning motivation. This research was conducted between June 2009 and April 2010 as a nonequivalent control group non-synchronized design. The study population was 44 third year nursing students who enrolled in a college of nursing, A University in Korea. The nursing students were divided into the CBL and the control group. The intervention was the CBL with three cases using video. The controls attended a traditional live lecture on the same topics. With questionnaires objective clinical decision-making, subjective clinical decision-making, and learning motivation were measured before the intervention, and 10 weeks after the intervention. Significant group differences were observed in clinical decision-making and learning motivation. The post-test scores of clinical decision-making in the CBL group were statistically higher than the control group. Learning motivation was also significantly higher in the CBL group than in the control group. These results indicate that CBL using video is effective in enhancing clinical decision-making and motivating students to learn by encouraging self-directed learning and creating more interest and curiosity in learning.

Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody.

PubMed

Lee, J M; Kim, B; Lee, S B; Jeong, Y; Oh, Y M; Song, Y-J; Jung, S; Choi, J; Lee, S; Cheong, K H; Kim, D U; Park, H W; Han, Y K; Kim, G W; Choi, H; Song, P H; Kim, K A

2014-01-02

The Met receptor tyrosine kinase, found to be constitutively activated in many tumors, has become a leading target for cancer therapy. Disruptions in Met downregulation have been associated with aggressive tumor progression with several therapeutic strategies addressing this aspect of Met biology. Castias B-lineage lymphoma (Cbl) E3 ligase-mediated degradation, which attenuates Met signaling via ligand-dependent Met internalization, is a major negative regulator of Met expression. It is believed that one of the mechanisms by which the therapeutic anti-Met antibodies induce cancer cell death in Met overexpressing tumors is via internalization and subsequent degradation of Met from the cell surface. However, a previously reported Met-targeting antibody demonstrated intrinsic agonistic activity while being capable of inducing Cbl-mediated degradation of Met, suggesting that Cbl-mediated degradation requires receptor activation and impedes therapeutic application. We have developed a potent and selective bivalent Met-targeting antibody (SAIT301) that invokes Met degradation using an alternative regulator LRIG1. In this report, we demonstrate that LRIG1 mediates degradation of Met by SAIT301 and this degradation does not require Met activation. Furthermore, SAIT301 was able to downregulate Met and dramatically inhibit growth of tumors with low or no Cbl expression, as well as tumors with Met exon 14 deletion that prevents Met binding to Cbl. In summary, we demonstrate the enhanced therapeutic potential of a novel tumor-inhibiting anti-Met antibody, SAIT301, which utilizes a Cbl-independent, LRIG1-mediated Met degradation pathway and thereby avoids the agonism that limits the effectiveness of previously reported anti-Met antibodies.

Anergic CD4+ T cells form mature immunological synapses with enhanced accumulation of c-Cbl and Cbl-b1

PubMed Central

Doherty, Melissa; Osborne, Douglas G.; Browning, Diana L.; Parker, David C.; Wetzel, Scott A.

2010-01-01

CD4+ T cell recognition of MHC:peptide complexes in the context of a costimulatory signal results in the large-scale redistribution of molecules at the T-APC interface to form the immunological synapse. The immunological synapse is the location of sustained TCR signaling and delivery of a subset of effector functions. T cells activated in the absence of costimulation are rendered anergic and are hyporesponsive when presented with antigen in the presence of optimal costimulation. Several previous studies have looked at aspects of immunological synapses formed by anergic T cells, but it remains unclear whether there are differences in the formation or composition of anergic immunological synapses. In this study we anergized primary murine CD4+ T cells by incubation of costimulation-deficient, transfected fibroblast APC. Using a combination of TCR, MHC:peptide, and ICAM-1 staining, we found that anergic T cells make mature immunological synapses with characteristic cSMAC and pSMAC domains that were indistinguishable from control synapses. There were small increases in total phosphotyrosine at the anergic synapse along with significant decreases in phosphorylated ERK 1/2 accumulation. Most striking, there was specific accumulation of c-Cbl and Cbl-b to the anergic synapses. Cbl-b, previously shown to be essential in anergy induction, was found in both the pSMAC and the cSMAC of the anergic synapse. This Cbl-b (and c-Cbl) accumulation at the anergic synapse may play an important role in anergy maintenance and/or induction. PMID:20207996

Detection of L265P MYD-88 mutation in a series of clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ).

PubMed

Kalpadakis, Christina; Pangalis, Gerassimos A; Vassilakopoulos, Theodoros P; Roumelioti, Maria; Sachanas, Sotirios; Korkolopoulou, Penelope; Koulieris, Efstathios; Moschogiannis, Maria; Yiakoumis, Xanthi; Tsirkinidis, Pantelis; Pontikoglou, Charalampos; Rondoyianni, Dimitra; Papadaki, Helen A; Panayiotidis, Panayiotidis; Angelopoulou, Maria K

2017-12-01

Clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ) is a recently described entity characterized by the presence of clonal B cells in the blood and/or bone marrow (BM) with morphologic and immunophenotypic features consistent with marginal zone derivation in otherwise healthy individuals. CBL-MZ is commonly associated with paraproteinemia, usually immunoglobulin M (IgM), raising diagnostic difficulties from Waldenstrom macroglobulinemia (WM). The aim of the present study was to determine the presence of MYD-88 L265P mutation in a well-characterized series of CBL-MZ to identify cases that may in fact represent WM. Fifty-three CBL-MZ cases were retrospectively evaluated. MYD-88 L265P mutation was determined by allele-specific polymerase chain reaction in blood and/or BM mononuclear cells. Almost half of the CBL-MZ cases (49%) were associated with paraproteinemia mainly of the IgM type (65%). MYD-88 L265P mutation was identified in 10 cases (19%). These cases may truly represent WM, whereas 43 cases (81%) are still classified as CBL-MZ. Mutated cases were all associated with paraproteinemia compared with 37% of the nonmutated ones (P < .0001). In addition, mutated cases displayed more frequently CD38 and CD25 positivity (P = .002 and P = .005, respectively). Moreover, cases without paraproteinemia presented more frequently with lymphocytosis, irrespective of the presence of the MYD-88 mutation (P = .02). The present study demonstrates that MYD-88 L265P mutation may represent the only sensitive marker for the differentiation of CBL-MZ from probable WM. However, further studies are warranted to better define the biological significance of MYD-88 L265P mutation and to clarify whether the presence of the mutation establishes WM diagnosis or that it can also be present in borderline cases associated with paraproteinemia. Copyright © 2016 John Wiley & Sons, Ltd.

Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease.

PubMed

Ubhi, Kiren; Rockenstein, Edward; Vazquez-Roque, Ruben; Mante, Michael; Inglis, Chandra; Patrick, Christina; Adame, Anthony; Fahnestock, Margaret; Doppler, Edith; Novak, Philip; Moessler, Herbert; Masliah, Eliezer

2013-02-01

Alzheimer's disease (AD) is characterized by degeneration of neocortex, limbic system, and basal forebrain, accompanied by accumulation of amyloid-β and tangle formation. Cerebrolysin (CBL), a peptide mixture with neurotrophic-like effects, is reported to improve cognition and activities of daily living in patients with AD. Likewise, CBL reduces synaptic and behavioral deficits in transgenic (tg) mice overexpressing the human amyloid precursor protein (hAPP). The neuroprotective effects of CBL may involve multiple mechanisms, including signaling regulation, control of APP metabolism, and expression of neurotrophic factors. We investigate the effects of CBL in the hAPP tg model of AD on levels of neurotrophic factors, including pro-nerve growth factor (NGF), NGF, brain-derived neurotrophic factor (BDNF), neurotropin (NT)-3, NT4, and ciliary neurotrophic factor (CNTF). Immunoblot analysis demonstrated that levels of pro-NGF were increased in saline-treated hAPP tg mice. In contrast, CBL-treated hAPP tg mice showed levels of pro-NGF comparable to control and increased levels of mature NGF. Consistently with these results, immunohistochemical analysis demonstrated increased NGF immunoreactivity in the hippocampus of CBL-treated hAPP tg mice. Protein levels of other neurotrophic factors, including BDNF, NT3, NT4, and CNTF, were unchanged. mRNA levels of NGF and other neurotrophins were also unchanged. Analysis of neurotrophin receptors showed preservation of the levels of TrKA and p75(NTR) immunoreactivity per cell in the nucleus basalis. Cholinergic cells in the nucleus basalis were reduced in the saline-treated hAPP tg mice, and treatment with CBL reduced these cholinergic deficits. These results suggest that the neurotrophic effects of CBL might involve modulation of the pro-NGF/NGF balance and a concomitant protection of cholinergic neurons. Copyright © 2012 Wiley Periodicals, Inc.

Supplementing lactating dairy cows with a vitamin B12 precursor, 5,6-dimethylbenzimidazole, increases the apparent ruminal synthesis of vitamin B12.

PubMed

Brito, A; Chiquette, J; Stabler, S P; Allen, R H; Girard, C L

2015-01-01

Cobalamin (CBL), the biologically active form of vitamin B12, and its analogs, are produced by bacteria only if cobalt supply is adequate. The analogs differ generally by the nucleotide moiety of the molecule. In CBL, 5,6-dimethylbenzimidazole (5,6-DMB) is the base in the nucleotide moiety. The present study aimed to determine if a supplement of 5,6-DMB could increase utilization of dietary cobalt for synthesis of CBL and change ruminal fermentation, nutrient digestibility, omasal flow of nutrients and ruminal protozoa counts. Eight ruminally cannulated multiparous Holstein cows (mean±standard deviation=238±21 days in milk and 736±47 kg of BW) were used in a crossover design. Cows were randomly assigned to a daily supplement of a gelatin capsule containing 1.5 g of 5,6-DMB via the rumen cannula or no supplement. Each period lasted 29 days and consisted of 21 days for treatment adaptation and 8 days for data and samples collection. Five corrinoids, CBL and four cobamides were detected in the total mixed ration and the omasal digesta from both treatments. The dietary supplement of 5,6-DMB increased (P=0.02) apparent ruminal synthesis of CBL from 14.6 to 19.6 (s.e.m. 0.8) mg/day but had no effect (P>0.1) on apparent ruminal synthesis of the four analogs. The supplement of 5,6-DMB had no effect (P>0.1) on milk production and composition, or on protozoal count, ruminal pH and concentrations of volatile fatty acids and ammonia nitrogen in rumen content. The supplement had also no effect (P>0.1) on intake, omasal flow and apparent ruminal digestibility of dry matter, organic matter, NDF, ADF and nitrogenous fractions. Plasma concentration of CBL was not affected by treatments (P=0.98). Providing a preformed part of the CBL molecule, that is, 5,6-DMB, increased by 34% the apparent ruminal synthesis of CBL by ruminal bacteria but had no effect on ruminal fermentation or protozoa count and it was not sufficient to increase plasma concentrations of the vitamin. Even though the efficiency of cobalt utilization for apparent synthesis of CBL was increased from 2.0% to 2.7% by the 5,6-DMB supplement, this improved efficiency was still very low. Further research is needed to identify the factors affecting efficiency of utilization of cobalt for synthesis of CBL by the bacterial populations in rumen.

The return of the Scarlet Pimpernel: cobalamin in inflammation II — cobalamins can both selectively promote all three nitric oxide synthases (NOS), particularly iNOS and eNOS, and, as needed, selectively inhibit iNOS and nNOS

PubMed Central

Wheatley, Carmen

2007-01-01

The up-regulation of transcobalamins [hitherto posited as indicating a central need for cobalamin (Cbl) in inflammation], whose expression, like inducible nitric oxide synthase (iNOS), is Sp1- and interferondependent, together with increased intracellular formation of glutathionylcobalamin (GSCbl), adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), may be essential for the timely promotion and later selective inhibition of iNOS and concordant regulation of endothelial and neuronal NOS (eNOS/nNOS.) Cbl may ensure controlled high output of nitric oxide (NO) and its safe deployment, because: (1) Cbl is ultimately responsible for the synthesis or availability of the NOS substrates and cofactors heme, arginine, BH4 flavin adenine dinucleotide/flavin mononucleotide (FAD/FMN) and NADPH, via the far-reaching effects of the two Cbl coenzymes, methionine synthase (MS) and methylmalonyl CoA mutase (MCoAM) in, or on, the folate, glutathione, tricarboxylic acid (TCA) and urea cycles, oxidative phosphorylation, glycolysis and the pentose phosphate pathway. Deficiency of any of theNOS substrates and cofactors results in ‘uncoupled’ NOS reactions, decreasedNO production and increased or excessive O2−, H2O2, ONOO− and other reactive oxygen species (ROS), reactive nitric oxide species (RNIS) leading to pathology. (2) Cbl is also the overlooked ultimate determinant of positive glutathione status, which favours the formation of more benign NO species, s-nitrosothiols, the predominant form in which NO is safely deployed. Cbl status may consequently act as a ‘back-up disc’ that ensures the active status of antioxidant systems, as well as reversing and modulating the effects of nitrosylation in cell signal transduction.New evidence shows that GSCbl can significantly promote iNOS/ eNOS NO synthesis in the early stages of inflammation, thus lowering high levels of tumour necrosis factor-a that normally result in pathology, while existing evidence shows that in extreme nitrosative and oxidative stress, GSCbl can regenerate the activity of enzymes important for eventual resolution, such as glucose 6 phosphate dehydrogenase, which ensures NADPH supply, lactate dehydrogenase, and more; with human clinical case studies of OHCbl for cyanide poisoning, suggesting Cbl may regenerate aconitase and cytochrome c oxidase in the TCA cycle and oxidative phosphorylation. Thus, Cbl may simultaneously promote a strong inflammatory response and the means to resolve it. PMID:18836533

What Are We Looking for in Computer-Based Learning Interventions in Medical Education? A Systematic Review.

PubMed

Taveira-Gomes, Tiago; Ferreira, Patrícia; Taveira-Gomes, Isabel; Severo, Milton; Ferreira, Maria Amélia

2016-08-01

Computer-based learning (CBL) has been widely used in medical education, and reports regarding its usage and effectiveness have ranged broadly. Most work has been done on the effectiveness of CBL approaches versus traditional methods, and little has been done on the comparative effects of CBL versus CBL methodologies. These findings urged other authors to recommend such studies in hopes of improving knowledge about which CBL methods work best in which settings. In this systematic review, we aimed to characterize recent studies of the development of software platforms and interventions in medical education, search for common points among studies, and assess whether recommendations for CBL research are being taken into consideration. We conducted a systematic review of the literature published from 2003 through 2013. We included studies written in English, specifically in medical education, regarding either the development of instructional software or interventions using instructional software, during training or practice, that reported learner attitudes, satisfaction, knowledge, skills, or software usage. We conducted 2 latent class analyses to group articles according to platform features and intervention characteristics. In addition, we analyzed references and citations for abstracted articles. We analyzed 251 articles. The number of publications rose over time, and they encompassed most medical disciplines, learning settings, and training levels, totaling 25 different platforms specifically for medical education. We uncovered 4 latent classes for educational software, characteristically making use of multimedia (115/251, 45.8%), text (64/251, 25.5%), Web conferencing (54/251, 21.5%), and instructional design principles (18/251, 7.2%). We found 3 classes for intervention outcomes: knowledge and attitudes (175/212, 82.6%), knowledge, attitudes, and skills (11.8%), and online activity (12/212, 5.7%). About a quarter of the articles (58/227, 25.6%) did not hold references or citations in common with other articles. The number of common references and citations increased in articles reporting instructional design principles (P=.03), articles measuring online activities (P=.01), and articles citing a review by Cook and colleagues on CBL (P=.04). There was an association between number of citations and studies comparing CBL versus CBL, independent of publication date (P=.02). Studies in this field vary highly, and a high number of software systems are being developed. It seems that past recommendations regarding CBL interventions are being taken into consideration. A move into a more student-centered model, a focus on implementing reusable software platforms for specific learning contexts, and the analysis of online activity to track and predict outcomes are relevant areas for future research in this field.

On the Influence of Surface Heterogeneities onto Roll Convection

NASA Astrophysics Data System (ADS)

Gryschka, M.; Drüe, C.; Raasch, S.; Etling, D.

2009-04-01

Roll convection is a common phenomenon in atmospheric convective boundary layers (CBL) with background wind. Roll convection is observed both over land and over sea for different synoptic situations. There is still some debate about the different types of roll convection and their causes or rather the necessary conditions for their appearance. The stability parameter ζ = -zi•L (zi: boundary layer height, L: Monin-Obukhov stability length) is widely used as a predictor for roll convection, since numerous studies suggest that convective rolls only appear when 0 < ζ < 20. In other words, roll development becomes unlikely for strong surface heating and weak vertical wind shear. In contrast to those studies the presence of roll convection in almost any polar cold air outbreak (as can be seen in numerous satellite images as cloud streets) reveals that even for large ζ roll convection can develop. Some studies report roll convection in cold air outbreaks for ζ = 250. Our large eddy simulations (LES) on roll convection suggests that the contrasting results concerning the dependency of roll convection on ζ are due to two different types of roll convection: One type which develops purely by self organization if ζ < 20 ("free rolls") and another type which is triggered by heterogeneities in surface temperature and develops also for large ζ ("forced rolls"). We think that most of the cloud streets observed in polar cold air outbreaks over open water are due to rolls of forced type which are tied to upstream located heterogeneities in the sea-ice distribution. The results of this study suggests that the omission of surface inhomogeneities in previous LES is the reason for the absence of rolls in all LES with strong surface heating and weak vertical wind shear so far. In this contribution we will present a large eddy simulation which successfully represents forced rolls under such conditions.

Paracellular transport of avidin saturated or not with biotinylated cobalamin through Caco-2 cell epithelium monolayer.

PubMed

Guy, M; Pons, L; Namour, F; de Nonancourt, M; Michalski, J C; Hatier, R; Guéant, J L

2001-01-01

The cationic charge of molecules may promote their uptake across epithelia, which are rich in brush border anionic sites. The transport of unsaturated avidin and avidin saturated with a biotinylated compound was investigated across Caco-2 adenocarcinoma cell with fetal enterocyte phenotype. The unsaturated avidin and avidin saturated with either biotin or a biotinyl-cobalamin conjugate (biotinyl-Cbl) were iodinated to follow their transport through the cell monolayer. Their apparent permeability coefficient (Papp) and transepithelial pathway were determined and compared to those for control radiolabeled markers [3H]-mannitol, [125I]-beta-lactoglobulin and [57Co]-cobalamin/intrinsic factor (Cbl/IF). The Papp of [125I]-avidin estimated at 2.8 x 10(-7) +/- 0.08 cm/s was close to that for mannitol that uses paracellular pathway. The binding of biotin or biotin conjugate to avidin enhanced its tetrameric conformation. The Papp for [125I]-avidin/biotin and [125I]- avidin/biotinyl-Cbl were respectively increased by 2-fold, compared to that for [125I]-avidin and 4-fold, compared to that for [125I]-beta-lactoglobulin and [54Co]-Cbl/IF. The protein was not accumulated in the cell and was found in intact form in the basolateral side, after its transport across the monolayer. Chloroquine (0.66 micromol/ml) did not significantly decrease the Papp for [125I]-avidin/biotinyl-Cbl. Conversely it decreased by 80% the Papp for Cbl/IF, that uses transepithelial pathway. Avidin (either saturated or not with biotin and biotinyl-Cbl) was able to cross the monolayer of Caco-2 cell line through a paracellular pathway. This study pointed out the interest for using this protein as a shuttle for increasing the transport rate of biotinylated compounds through fetal epithelial barriers. Copyright 2001 S. Karger AG, Basel

Benefits of Case-Based versus Traditional Lecture-Based Instruction in a Preclinical Removable Prosthodontics Course.

PubMed

Samuelson, David B; Divaris, Kimon; De Kok, Ingeborg J

2017-04-01

This study compared the acceptability and relative effectiveness of case-based learning (CBL) versus traditional lecture-based (LB) instruction in a preclinical removable prosthodontics course in the University of North Carolina at Chapel Hill School of Dentistry DDS curriculum. The entire second-year class (N=82) comprised this crossover study's sample. Assessments of baseline comprehension and confidence in removable partial denture (RPD) treatment planning were conducted at the beginning of the course. Near the end of the course, half of the class received CBL and LB instruction in an RPD module in alternating sequence, with students serving as their own control group. Assessments of perceived RPD treatment planning efficacy, comprehension, and instruction method preference were administered directly after students completed the RPD module and six months later. Analyses of variance accounting for period, carryover, and sequence effects were used to determine the relative effects of each approach using a p<0.05 statistical significance threshold. The results showed that the students preferred CBL (81%) over LB instruction (9%), a pattern that remained unchanged after a six-month period. Despite notable period and carryover effects, CBL was also associated with higher gains in RPD treatment planning comprehension (p=0.04) and perceived efficacy (p=0.01) compared to LB instruction. These gains diminished six months after the course-a finding based on a 49% follow-up response rate. Overall, the students overwhelmingly preferred CBL to LB instruction, and the findings suggest small albeit measurable educational benefits associated with CBL. This study's findings support the introduction and further testing of CBL in the preclinical dental curriculum, in anticipation of possible future benefits evident during clinical training.

TD-DFT Insight into Photodissociation of Co-C Bond in Coenzyme B12

NASA Astrophysics Data System (ADS)

Kozlowski, Pawel; Liu, Hui; Kornobis, Karina; Lodowski, Piotr; Jaworska, Maria

2013-12-01

Coenzyme B12 (AdoCbl) is one of the most biologically active forms of vitamin B12, and continues to be a topic of active research interest. The mechanism of Co-C bond cleavage in AdoCbl, and the corresponding enzymatic reactions are however, not well understood at the molecular level. In this work, time-dependent density functional theory (TD-DFT) has been applied to investigate the photodissociation of coenzyme B12. To reduce computational cost, while retaining the major spectroscopic features of AdoCbl, a truncated model based on ribosylcobalamin (RibCbl) was used to simulate Co-C photodissociation. Equilibrium geometries of RibCbl were obtained by optimization at the DFT/BP86/TZVP level of theory, and low-lying excited states were calculated by TD-DFT using the same functional and basis set. The calculated singlet states, and absorption spectra were simulated in both the gas phase, and water, using the polarizable continuum model (PCM). Both spectra were in reasonable agreement with experimental data, and potential energy curves based on vertical excitations were plotted to explore the nature of Co-C bond dissociation. It was found that a repulsive 3(σCo-C → σ*Co-C) triplet state became dissociative at large Co-C bond distance, similar to a previous observation for methylcobalamin (MeCbl). Furthermore, potential energy surfaces (PESs) obtained as a function of both Co-CRib and Co-NIm distances, identify the S1 state as a key intermediate generated during photoexcitation of RibCbl, attributed to a mixture of a MLCT (metal-to-ligand charge transfer) and a σ bonding-ligand charge transfer (SBLCT) states.

A Ca(2)+ signaling pathway regulates a K(+) channel for low-K response in Arabidopsis.

PubMed

Li, Legong; Kim, Beom-Gi; Cheong, Yong Hwa; Pandey, Girdhar K; Luan, Sheng

2006-08-15

Nutrient sensing is critical for plant adaptation to the environment. Because of extensive farming and erosion, low content of mineral nutrients such as potassium (K(+)) in soils becomes a limiting factor for plant growth. In response to low-K conditions, plants enhance their capability of K(+) uptake through an unknown signaling mechanism. Here we report the identification of a Ca(2+)-dependent pathway for low-K response in Arabidopsis. We are not aware of any other example of a molecular pathway for a nutrient response in plants. Earlier genetic analyses revealed three genes encoding two Ca(2+) sensors (CBL1 and CBL9) and their target protein kinase (CIPK23) to be critical for plant growth on low-K media and for stomatal regulation, indicating that these calcium signaling components participate in the low-K response and turgor regulation. In this study, we show that the protein kinase CIPK23 interacted with, and phosphorylated, a voltage-gated inward K(+) channel (AKT1) required for K(+) acquisition in Arabidopsis. In the Xenopus oocyte system, our studies showed that interacting calcium sensors (CBL1 and CBL9) together with target kinase CIPK23, but not either component alone, activated the AKT1 channel in a Ca(2+)-dependent manner, connecting the Ca(2+) signal to enhanced K(+) uptake through activation of a K(+) channel. Disruption of both CBL1 and CBL9 or CIPK23 gene in Arabidopsis reduced the AKT1 activity in the mutant roots, confirming that the Ca(2+)-CBL-CIPK pathway functions to orchestrate transporting activities in planta according to external K(+) availability.

Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation.

PubMed

Emdal, Kristina B; Pedersen, Anna-Kathrine; Bekker-Jensen, Dorte B; Tsafou, Kalliopi P; Horn, Heiko; Lindner, Sven; Schulte, Johannes H; Eggert, Angelika; Jensen, Lars J; Francavilla, Chiara; Olsen, Jesper V

2015-04-28

SH-SY5Y neuroblastoma cells respond to nerve growth factor (NGF)-mediated activation of the tropomyosin-related kinase A (TrkA) with neurite outgrowth, thereby providing a model to study neuronal differentiation. We performed a time-resolved analysis of NGF-TrkA signaling in neuroblastoma cells using mass spectrometry-based quantitative proteomics. The combination of interactome, phosphoproteome, and proteome data provided temporal insights into the molecular events downstream of NGF binding to TrkA. We showed that upon NGF stimulation, TrkA recruits the E3 ubiquitin ligase Cbl-b, which then becomes phosphorylated and ubiquitylated and decreases in abundance. We also found that recruitment of Cbl-b promotes TrkA ubiquitylation and degradation. Furthermore, the amount of phosphorylation of the kinase ERK and neurite outgrowth increased upon Cbl-b depletion in several neuroblastoma cell lines. Our findings suggest that Cbl-b limits NGF-TrkA signaling to control the length of neurites. Copyright © 2015, American Association for the Advancement of Science.

Cbl-b-regulated extracellular signal-regulated kinase signaling is involved in the shikonin-induced apoptosis of lung cancer cells in vitro

PubMed Central

QU, DAN; CHEN, YU; XU, XIAO-MAN; ZHANG, MENG; ZHANG, YI; LI, SHENG-QI

2015-01-01

Shikonin (SK), a naturally occurring naphthoquinone, exhibits antitumor activity. However, its precise mechanisms of action are unknown. In the present study, the effects of SK on NCI-H460 human lung cancer cells were investigated. It was found that SK reduced cell viability and induced apoptosis in the NCI-H460 cells. Additionally, SK inhibited extracellular signal-regulated kinase (ERK) activity, which indicates that inhibition of the ERK pathway is probably one of the mechanisms by which SK induced NCI-H460 cell apoptosis. The expression of Cbl-b was significantly increased by treatment with SK for 4 h, and gradually increased to a maximal level at 24 h; the time taken for the upregulation of Cbl-b protein was in accordance to that required for the downregulation of phospho (p)-ERK protein. The Cbl inhibitor Ps341 reversed the SK-induced downregulation of p-ERK and apoptosis of NCI-H460 cells. These results indicate that Cbl-b potentiates the apoptotic action of SK by inhibiting the ERK pathway in lung cancer cells. PMID:25780420

A B12-dependent radical SAM enzyme involved in Oxetanocin-A biosynthesis

PubMed Central

Bridwell-Rabb, Jennifer; Zhong, Aoshu; Sun, He G.; Drennan, Catherine L.; Liu, Hung-wen

2017-01-01

Summary Oxetanocin-A (OXT-A, 1) is a potent antitumor, antiviral, and antibacterial compound. Biosynthesis of OXT-A has been linked to a plasmid-borne, Bacillus megaterium gene cluster that contains four genes, oxsA, oxsB, oxrA, and oxrB. Here, we show that the oxsA and oxsB genes are both required for the production of OXT-A. Biochemical analysis of the encoded proteins, a cobalamin (Cbl)-dependent S-adenosylmethionine (AdoMet) radical enzyme, OxsB, and an HD-domain phosphohydrolase, OxsA, revealed that OXT-A is derived from 2′-deoxyadenosine phosphate in an OxsB-catalyzed ring contraction reaction initiated by H-atom abstraction from C2′. Hence, OxsB represents the first biochemically characterized non-methylating Cbl-dependent AdoMet radical enzyme. X-ray analysis of OxsB reveals the fold of a Cbl-dependent AdoMet radical enzyme for which there are an estimated 7000 members. Overall, this work provides a framework for understanding the interplay of AdoMet and Cbl cofactors and expands the catalytic repertoire of Cbl-dependent AdoMet radical enzymes. PMID:28346939

What Are We Looking for in Computer-Based Learning Interventions in Medical Education? A Systematic Review

PubMed Central

Ferreira, Patrícia; Taveira-Gomes, Isabel; Severo, Milton; Ferreira, Maria Amélia

2016-01-01

Background Computer-based learning (CBL) has been widely used in medical education, and reports regarding its usage and effectiveness have ranged broadly. Most work has been done on the effectiveness of CBL approaches versus traditional methods, and little has been done on the comparative effects of CBL versus CBL methodologies. These findings urged other authors to recommend such studies in hopes of improving knowledge about which CBL methods work best in which settings. Objective In this systematic review, we aimed to characterize recent studies of the development of software platforms and interventions in medical education, search for common points among studies, and assess whether recommendations for CBL research are being taken into consideration. Methods We conducted a systematic review of the literature published from 2003 through 2013. We included studies written in English, specifically in medical education, regarding either the development of instructional software or interventions using instructional software, during training or practice, that reported learner attitudes, satisfaction, knowledge, skills, or software usage. We conducted 2 latent class analyses to group articles according to platform features and intervention characteristics. In addition, we analyzed references and citations for abstracted articles. Results We analyzed 251 articles. The number of publications rose over time, and they encompassed most medical disciplines, learning settings, and training levels, totaling 25 different platforms specifically for medical education. We uncovered 4 latent classes for educational software, characteristically making use of multimedia (115/251, 45.8%), text (64/251, 25.5%), Web conferencing (54/251, 21.5%), and instructional design principles (18/251, 7.2%). We found 3 classes for intervention outcomes: knowledge and attitudes (175/212, 82.6%), knowledge, attitudes, and skills (11.8%), and online activity (12/212, 5.7%). About a quarter of the articles (58/227, 25.6%) did not hold references or citations in common with other articles. The number of common references and citations increased in articles reporting instructional design principles (P=.03), articles measuring online activities (P=.01), and articles citing a review by Cook and colleagues on CBL (P=.04). There was an association between number of citations and studies comparing CBL versus CBL, independent of publication date (P=.02). Conclusions Studies in this field vary highly, and a high number of software systems are being developed. It seems that past recommendations regarding CBL interventions are being taken into consideration. A move into a more student-centered model, a focus on implementing reusable software platforms for specific learning contexts, and the analysis of online activity to track and predict outcomes are relevant areas for future research in this field. PMID:27480053

Role of HIV-2 envelope in Lv2-mediated restriction

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

Reuter, Sandra; Kaumanns, Patrick; Buschhorn, Sabine B.

2005-02-05

We have characterized envelope protein pseudotyped HIV-2 particles derived from two HIV-2 isolates termed prCBL23 and CBL23 in order to define the role of the envelope protein for the Lv2-mediated restriction to infection. Previously, it has been described that the primary isolate prCBL23 is restricted to infection of several human cell types, whereas the T cell line adapted isolate CBL23 is not restricted in these cell types. Molecular cloning of the two isolates revealed that the env and the gag gene are responsible for the observed phenotype and that this restriction is mediated by Lv2, which is distinct from Ref1/Lv1more » (Schmitz, C., Marchant, D., Neil, S.J., Aubin, K., Reuter, S., Dittmar, M.T., McKnight, A., Kizhatil, K., Albritton, L.M., 2004. Lv2, a novel postentry restriction, is mediated by both capsid and envelope. J. Virol. 78 (4), 2006-2016). We generated pseudotyped viruses consisting of HIV-2 (ROD-A{delta}env-GFP, ROD-A{delta}env-RFP, or ROD-A{delta}env-REN) and the prCBL23 or CBL23 envelope proteins as well as chimeric proteins between these envelopes. We demonstrate that a single amino acid exchange at position 74 in the surface unit of CBL23-Env confers restriction to infection. This single point mutation causes tighter CD4 binding, resulting in a less efficient fusion into the cytosol of the restricted cell line. Prevention of endosome formation and prevention of endosome acidification enhance infectivity of the restricted particles for GHOST/X4 cells indicating a degradative lysosomal pathway as a cause for the reduced cytosolic entry. The described restriction to infection of the primary isolate prCBL23 is therefore largely caused by an entry defect. A remaining restriction to infection (19-fold) is preserved when endosomal acidification is prevented. This restriction to infection is also dependent on the presence of the point mutation at position 74 (G74E)« less

A simple biota removal algorithm for 35 GHz cloud radar measurements

NASA Astrophysics Data System (ADS)

Kalapureddy, Madhu Chandra R.; Sukanya, Patra; Das, Subrata K.; Deshpande, Sachin M.; Pandithurai, Govindan; Pazamany, Andrew L.; Ambuj K., Jha; Chakravarty, Kaustav; Kalekar, Prasad; Krishna Devisetty, Hari; Annam, Sreenivas

2018-03-01

Cloud radar reflectivity profiles can be an important measurement for the investigation of cloud vertical structure (CVS). However, extracting intended meteorological cloud content from the measurement often demands an effective technique or algorithm that can reduce error and observational uncertainties in the recorded data. In this work, a technique is proposed to identify and separate cloud and non-hydrometeor echoes using the radar Doppler spectral moments profile measurements. The point and volume target-based theoretical radar sensitivity curves are used for removing the receiver noise floor and identified radar echoes are scrutinized according to the signal decorrelation period. Here, it is hypothesized that cloud echoes are observed to be temporally more coherent and homogenous and have a longer correlation period than biota. That can be checked statistically using ˜ 4 s sliding mean and standard deviation value of reflectivity profiles. The above step helps in screen out clouds critically by filtering out the biota. The final important step strives for the retrieval of cloud height. The proposed algorithm potentially identifies cloud height solely through the systematic characterization of Z variability using the local atmospheric vertical structure knowledge besides to the theoretical, statistical and echo tracing tools. Thus, characterization of high-resolution cloud radar reflectivity profile measurements has been done with the theoretical echo sensitivity curves and observed echo statistics for the true cloud height tracking (TEST). TEST showed superior performance in screening out clouds and filtering out isolated insects. TEST constrained with polarimetric measurements was found to be more promising under high-density biota whereas TEST combined with linear depolarization ratio and spectral width perform potentially to filter out biota within the highly turbulent shallow cumulus clouds in the convective boundary layer (CBL). This TEST technique is promisingly simple in realization but powerful in performance due to the flexibility in constraining, identifying and filtering out the biota and screening out the true cloud content, especially the CBL clouds. Therefore, the TEST algorithm is superior for screening out the low-level clouds that are strongly linked to the rainmaking mechanism associated with the Indian Summer Monsoon region's CVS.

Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms.

PubMed

Paul, Cristiana; Brady, David M

2017-02-01

Three natural forms of vitamin B 12 are commercially available: methylcobalamin (MeCbl), adenosylcobalamin (AdCbl), and hydroxycobalamin (OHCbl), all of which have been shown in clinical studies to improve vitamin B 12 status. They are bioidentical to the B 12 forms occurring in human physiology and animal foods. In contrast, cyanocobalamin (CNCbl), a synthetic B 12 compound used for food fortification and in some supplements, occurs only in trace amounts in human tissues as a result of cyanide intake from smoking or other sources. This study had 3 objectives: (1) To summarize and compare assimilation pathways for 4 B 12 forms; (2) to determine whether supplementation with a particular B 12 form (or combination of forms) presents any advantages for the general population or for individuals with single nucleotide polymorphisms (SNPs) in B 12 -related pathways; and (3) to address misconceptions regarding B 12 forms, methylation pathways, and various SNPs reported in commercially available tests. PubMed was systematically searched for articles published up to June 2016 using specific key words. Human, animal, and in vitro studies that were published in English, French, and German were included. Other studies considered were found by selecting in PubMed the suggested "related studies" and also some referenced studies. The study occurred in Los Angeles, CA, USA. The studies reviewed provide evidence that all supplemental or food-derived B 12 forms are reduced to a core cobalamin molecule, which converts to the intracellular active forms: MeCbl and AdCbl, in a ratio not influenced by the form of B 12 ingested. The methyl and adenosyl components of supplemental MeCbl and AdCbl are cleaved inside cells and are not used in the synthesis of intracellular MeCbl and AdCbl, respectively. However, the overall bioavailability of each form of supplemental B 12 may be influenced by many factors such as gastrointestinal pathologies, age, and genetics. Polymorphisms on B 12 -related pathways may affect the efficiency of absorption, blood transport, cellular uptake, and intracellular transformations. Supplementing with any of the nature bioidentical forms of B 12 (MeCbl, OHCbl, and/or AdCbl) is preferred instead of the use of CNCbl, owing to their superior bioavailability and safety. For the majority of the population, all B 12 forms may likely have similar bioavailabilities and physiological effects; thus, it makes sense to employ the least-expensive form of B 12 , such as MeCbl. Individuals with particular single nucleotide polymorphisms (SNPs) affecting B 12 assimilation may raise their B 12 status more efficiently with 1 or more particular forms of vitamin B 12 . However, because those types of SNPs are not currently reported in commercial tests, individuals may require either a trial-and-error approach by supplementing with 1 particular form of B 12 at a time, or they might simply use a supplement with a combination of all 3 naturally occurring forms of B 12 that are commercially available for a better chance of achieving faster clinical results. That approach may or may not offset genetic polymorphisms involving B 12 metabolism and related pathways.

Mean shear flow in recirculating turbulent urban convection and the plume-puff eddy structure below stably stratified inversion layers

NASA Astrophysics Data System (ADS)

Fan, Yifan; Hunt, Julian; Yin, Shi; Li, Yuguo

2018-03-01

The mean and random components of the velocity field at very low wind speeds in a convective boundary layer (CBL) over a wide urban area are dominated by large eddy structures—either turbulent plumes or puffs. In the mixed layer at either side of the edges of urban areas, local mean recirculating flows are generated by sharp horizontal temperature gradients. These recirculation regions also control the mean shear profile and the bent-over plumes across the mixed layer, extending from the edge to the center of the urban area. A simplified physical model was proposed to calculate the mean flow speed at the edges of urban areas. Water tank experiments were carried out to study the mean recirculating flow and turbulent plume structures. The mean speed at urban edges was measured by the particle image velocimetry (PIV), and the plume structures were visualized by the thermalchromic liquid crystal (TLC) sheets. The horizontal velocity calculated by the physical model at the urban edge agrees well with that measured in the water tank experiments, with a root mean square of 0.03. The experiments also show that the pattern of the mean flow over the urban area changes significantly if the shape of the heated area changes or if the form of the heated urban area becomes sub-divided, for example by the creation of nearby but separated "satellite cities." The convective flow over the square urban area is characterized as the diagonal inflow at the lower level and the side outflow at the upper level. The outflow of the small city can be drawn into the inflow region of the large city in the "satellite city" case. A conceptual analysis shows how these changes significantly affect the patterns of dispersion of pollutants in different types of urban areas.

The Os-AKT1 Channel Is Critical for K+ Uptake in Rice Roots and Is Modulated by the Rice CBL1-CIPK23 Complex[W][OPEN

PubMed Central

Li, Juan; Long, Yu; Qi, Guo-Ning; Li, Juan; Xu, Zi-Jian; Wu, Wei-Hua; Wang, Yi

2014-01-01

Potassium (K+) is one of the essential nutrient elements for plant growth and development. Plants absorb K+ ions from the environment via root cell K+ channels and/or transporters. In this study, the Shaker K+ channel Os-AKT1 was characterized for its function in K+ uptake in rice (Oryza sativa) roots, and its regulation by Os-CBL1 (Calcineurin B-Like protein1) and Os-CIPK23 (CBL-Interacting Protein Kinase23) was investigated. As an inward K+ channel, Os-AKT1 could carry out K+ uptake and rescue the low-K+-sensitive phenotype of Arabidopsis thaliana akt1 mutant plants. Rice Os-akt1 mutant plants showed decreased K+ uptake and displayed an obvious low-K+-sensitive phenotype. Disruption of Os-AKT1 significantly reduced the K+ content, which resulted in inhibition of plant growth and development. Similar to the AKT1 regulation in Arabidopsis, Os-CBL1 and Os-CIPK23 were identified as the upstream regulators of Os-AKT1 in rice. The Os-CBL1-Os-CIPK23 complex could enhance Os-AKT1-mediated K+ uptake. A phenotype test confirmed that Os-CIPK23 RNAi lines exhibited similar K+-deficient symptoms as the Os-akt1 mutant under low K+ conditions. These findings demonstrate that Os-AKT1-mediated K+ uptake in rice roots is modulated by the Os-CBL1-Os-CIPK23 complex. PMID:25096783

Promotion of higher order of cognition in undergraduate medical students using case-based approach.

PubMed

Dubey, Suparna; Dubey, Ashok Kumar

2017-01-01

The curriculum of pathology is conventionally "taught" in a series of didactic lectures, which promotes learning by rote. In this study, case-based learning (CBL) was introduced to assess its effect on higher order cognition and problem-solving skills in undergraduate medical students. The prescribed syllabus of hepatobiliary system was delivered to the undergraduate medical students of the fourth semester by conventional didactic lectures. A pretest, which contained questions designed to test both analysis and recall, was administered, followed by CBL sessions, in the presence of a facilitator, encouraging active discussion among students. Students were then assessed using a similar posttest. The perceptions of the students and the faculty were gathered by means of feedback questionnaires. The scores obtained by the students in the pre- and post-test were compared by paired t -test. Eighty-one students participated in CBL sessions, with 95.06% expressing a desire for more such sessions, preferably in all the topics. The faculty members also felt that CBL would be beneficial for the students but opined that it should be restricted to some topics. CBL was found to cause a highly significant ( P < 0.0001) improvement in the students' higher levels of cognition, whereas the lower orders of cognition remained unaffected ( P = 0.2048). CBL promotes active learning and helps in the development of critical thinking and analysis in undergraduate medical students. Although it is resource-intensive, an attempt should be made to incorporate it along with lectures in clinically important topics.

Daytime turbulent exchange between the Amazon forest and the atmosphere

NASA Technical Reports Server (NTRS)

Fitzjarrald, David R.; Moore, Kathleen E.; Cabral, Osvaldo M. R.; Scolar, Jose; Manzi, Antonio O.; Deabreusa, Leonardo D.

1989-01-01

Detailed observations of turbulence just above and below the crown of the Amazon rain forest during the wet season are presented. The forest canopy is shown to remove high frequency turbulent fluctuations while passing lower frequencies. Filter characteristics of turbulent transfer into the Amazon rain forest canopy are quantified. Simple empirical relations that relate observed turbulent heat fluxes to horizontal wind variance are presented. Changes in the amount of turbulent coupling between the forest and the boundary layer associated with deep convective clouds are presented both as statistical averages and as a series of case studies. These convective processes during the rainy season are shown to alter the diurnal course of turbulent fluxes. In wake of giant coastal systems, no significant heat or moisture fluxes occur for up to a day after the event. Radar data is used to demonstrate that even small raining clouds are capable of evacuating the canopy of substances normally trapped by persistent static stability near the forest floor. Recovery from these events can take more than an hour, even during mid-day. In spite of the ubiquitous presence of clouds and frequent rain during this season, the average horizontal wind speed spectrum is well described by dry CBL similarity hypotheses originally found to apply in flat terrain.

Daytime turbulent exchange between the Amazon forest and the atmosphere

NASA Technical Reports Server (NTRS)

Fitzjarrald, David R.; Moore, Kathleen E.; Cabral, Osvaldo M. R.; Scolar, Jose; Manzi, Antonio

1990-01-01

Detailed observations of turbulence just above and below the crown of the Amazon rain forest during the wet season are presented. The forest canopy is shown to remove high frequency turbulent fluctuations while passing lower frequencies. Filter characteristics of turbulent transfer into the Amazon rain forest canopy are quantified. Simple empirical relations that relate observed turbulent heat fluxes to horizontal wind variance are presented. Changes in the amount of turbulent coupling between the forest and the boundary layer associated with deep convective clouds are presented both as statistical averages and as a series of case studies. These convective processes during the rainy season are shown to alter the diurnal course of turbulent fluxes. In wake of giant coastal systems, no significant heat or moisture fluxes occur for up to a day after the event. Radar data is used to demonstrate that even small raining clouds are capable of evacuating the canopy of substances normally trapped by persistent static stability near the forest floor. Recovery from these events can take more than an hour, even during mid-day. In spite of the ubiquitous presence of clouds and frequent rain during this season, the average horizontal wind speed spectrum is well described by dry CBL similarity hypotheses originally found to apply in flat terrain.

δ-Catenin Increases the Stability of EGFR by Decreasing c-Cbl Interaction and Enhances EGFR/Erk1/2 Signaling in Prostate Cancer.

PubMed

Shrestha, Nensi; Shrestha, Hridaya; Ryu, Taeyong; Kim, Hangun; Simkhada, Shishli; Cho, Young-Chang; Park, So-Yeon; Cho, Sayeon; Lee, Kwang-Youl; Lee, Jae-Hyuk; Kim, Kwonseop

2018-04-30

δ-Catenin, a member of the p120-catenin subfamily of armadillo proteins, reportedly increases during the late stage of prostate cancer. Our previous study demonstrates that δ-catenin increases the stability of EGFR in prostate cancer cell lines. However, the molecular mechanism behind δ-catenin-mediated enhanced stability of EGFR was not explored. In this study, we hypothesized that δ-catenin enhances the protein stability of EGFR by inhibiting its lysosomal degradation that is mediated by c-casitas b-lineage lymphoma (c-Cbl), a RING domain E3 ligase. c-Cbl monoubiquitinates EGFR and thus facilitates its internalization, followed by lysosomal degradation. We observed that δ-catenin plays a key role in EGFR stability and downstream signaling. δ-Catenin competes with c-Cbl for EGFR binding, which results in a reduction of binding between c-Cbl and EGFR and thus decreases the ubiquitination of EGFR. This in turn increases the expression of membrane bound EGFR and enhances EGFR/Erk1/2 signaling. Our findings add a new perspective on the role of δ-catenin in enhancing EGFR/Erk1/2 signaling-mediated prostate cancer.

Transcellular transport of cobalamin in aortic endothelial cells.

PubMed

Hannibal, Luciana; Bolisetty, Keerthana; Axhemi, Armend; DiBello, Patricia M; Quadros, Edward V; Fedosov, Sergey; Jacobsen, Donald W

2018-05-09

Cobalamin [Cbl (or B 12 )] deficiency causes megaloblastic anemia and a variety of neuropathies. However, homeostatic mechanisms of cyanocobalamin (CNCbl) and other Cbls by vascular endothelial cells are poorly understood. Herein, we describe our investigation into whether cultured bovine aortic endothelial cells (BAECs) perform transcytosis of B 12 , namely, the complex formed between serum transcobalamin and B 12 , designated as holo-transcobalamin (holo-TC). We show that cultured BAECs endocytose [ 57 Co]-CNCbl-TC (source material) via the CD320 receptor. The bound Cbl is transported across the cell both via exocytosis in its free form, [ 57 Co]-CNCbl, and via transcytosis as [ 57 Co]-CNCbl-TC. Transcellular mobilization of Cbl occurred in a bidirectional manner. A portion of the endocytosed [ 57 Co]-CNCbl was enzymatically processed by methylmalonic aciduria combined with homocystinuria type C (cblC) with subsequent formation of hydroxocobalamin, methylcobalamin, and adenosylcobalamin, which were also transported across the cell in a bidirectional manner. This demonstrates that transport mechanisms for Cbl in vascular endothelial cells do not discriminate between various β-axial ligands of the vitamin. Competition studies with apoprotein- and holo-TC and holo-intrinsic factor showed that only holo-TC was effective at inhibiting transcellular transport of Cbl. Incubation of BAECs with a blocking antibody against the extracellular domain of the CD320 receptor inhibited uptake and transcytosis by ∼40%. This study reveals that endothelial cells recycle uncommitted intracellular Cbl for downstream usage by other cell types and suggests that the endothelium is self-sufficient for the specific acquisition and subsequent distribution of circulating B 12 via the CD320 receptor. We posit that the endothelial lining of the vasculature is an essential component for the maintenance of serum-tissue homeostasis of B 12 .-Hannibal, L., Bolisetty, K., Axhemi, A., DiBello, P. M., Quadros, E. V., Fedosov, S., Jacobsen, D. W. Transcellular transport of cobalamin in aortic endothelial cells.

MicroRNA-29b-2-5p inhibits cell proliferation by directly targeting Cbl-b in pancreatic ductal adenocarcinoma.

PubMed

Li, Ce; Dong, Qian; Che, Xiaofang; Xu, Ling; Li, Zhi; Fan, Yibo; Hou, Kezuo; Wang, Shuo; Qu, Jinglei; Xu, Lu; Wen, Ti; Yang, Xianghong; Qu, Xiujuan; Liu, Yunpeng

2018-06-25

MicroRNAs can be used in the prognosis of malignancies; however, their regulatory mechanisms are unknown, especially in pancreatic ductal adenocarcinoma (PDAC). In 120 PDAC specimens, miRNA levels were assessed by quantitative real time polymerase chain reaction (qRT-PCR). Then, the role of miR-29b-2-5p in cell proliferation was evaluated both in vitro (Trypan blue staining and cell cycle analysis in the two PDAC cell lines SW1990 and Capan-2) and in vivo using a xenograft mouse model. Next, bioinformatics methods, a luciferase reporter assay, Western blot, and immunohistochemistry (IHC) were applied to assess the biological effects of Cbl-b inhibition by miR-29b-2-5p. Moreover, the relationship between Cbl-b and p53 was evaluated by immunoprecipitation (IP), Western blot, and immunofluorescence. From the 120 PDAC patients who underwent surgical resection, ten patients with longest survival and ten with shortest survival were selected. We found that high miR-29b-2-5p expression was associated with good prognosis (p = 0.02). The validation cohort confirmed miR-29b-2-5p as an independent prognostic factor in PDAC (n = 100, 95% CI = 0.305-0.756, p = 0.002). Furthermore, miR-29b-2-5p inhibited cell proliferation, induced cell cycle arrest, and promoted apoptosis both in vivo and in vitro. Interestingly, miR-29b-2-5p directly bound the Cbl-b gene, down-regulating its expression and reducing Cbl-b-mediated degradation of p53. Meanwhile, miR-29b-2-5p expression was negatively correlated with Cbl-b in PDAC tissues (r = - 0.33, p = 0.001). Taken together, these findings indicated that miR-29b-2-5p improves prognosis in PDAC by targeting Cbl-b to promote p53 expression, and would constitute an important prognostic factor in PDAC.

Experiencing community psychology through community-based learning class projects: reflections from an American University in the Middle East.

PubMed

Amer, Mona M; Mohamed, Salma N; Ganzon, Vincent

2013-01-01

Many introductory community psychology courses do not incorporate community-based learning (CBL), and when they do, it is most often in the form of individualized volunteer hours. We present an alternative model for CBL in which the entire class collaborates on an experiential project that promotes community action. We believe that such an approach better embodies the values and methods of the discipline and has a more powerful impact on the students and stakeholders. It may be especially effective in developing countries that do not have an established network of service infrastructures; in such nations the onus is on the teachers and learners of community psychology to contribute to transformative change. In this article practical guidelines are provided by the instructor regarding how to structure and implement this CBL model. Additionally, two students describe how the CBL experience solidified their learning of course concepts and significantly impacted them personally.

The E3 ligase c-Cbl regulates dendritic cell activation

PubMed Central

Chiou, Shin-Heng; Shahi, Payam; Wagner, Ryan T; Hu, Hongbo; Lapteva, Natalia; Seethammagari, Mamatha; Sun, Shao-Cong; Levitt, Jonathan M; Spencer, David M

2011-01-01

The activation of innate and adaptive immunity is always balanced by inhibitory signalling mechanisms to maintain tissue integrity. We have identified the E3 ligase c-Cbl––known for its roles in regulating lymphocyte signalling––as a modulator of dendritic cell activation. In c-Cbl-deficient dendritic cells, Toll-like receptor-induced expression of proinflammatory factors, such as interleukin-12, is increased, correlating with a greater potency of dendritic-cell-based vaccines against established tumours. This proinflammatory phenotype is accompanied by an increase in nuclear factor (NF)-κB activity. In addition, c-Cbl deficiency reduces both p50 and p105 levels, which have been shown to modulate the stimulatory function of NF-κB. Our data indicate that c-Cbl has a crucial, RING-domain-dependent role in regulating dendritic cell maturation, probably by facilitating the regulatory function of p105 and/or p50. PMID:21799517

Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms

PubMed Central

Paul, Cristiana; Brady, David M.

2017-01-01

Context Three natural forms of vitamin B12 are commercially available: methylcobalamin (MeCbl), adenosylcobalamin (AdCbl), and hydroxycobalamin (OHCbl), all of which have been shown in clinical studies to improve vitamin B12 status. They are bioidentical to the B12 forms occurring in human physiology and animal foods. In contrast, cyanocobalamin (CNCbl), a synthetic B12 compound used for food fortification and in some supplements, occurs only in trace amounts in human tissues as a result of cyanide intake from smoking or other sources. Objective This study had 3 objectives: (1) To summarize and compare assimilation pathways for 4 B12 forms; (2) to determine whether supplementation with a particular B12 form (or combination of forms) presents any advantages for the general population or for individuals with single nucleotide polymorphisms (SNPs) in B12-related pathways; and (3) to address misconceptions regarding B12 forms, methylation pathways, and various SNPs reported in commercially available tests. Design PubMed was systematically searched for articles published up to June 2016 using specific key words. Human, animal, and in vitro studies that were published in English, French, and German were included. Other studies considered were found by selecting in PubMed the suggested “related studies” and also some referenced studies. Setting The study occurred in Los Angeles, CA, USA. Results The studies reviewed provide evidence that all supplemental or food-derived B12 forms are reduced to a core cobalamin molecule, which converts to the intracellular active forms: MeCbl and AdCbl, in a ratio not influenced by the form of B12 ingested. The methyl and adenosyl components of supplemental MeCbl and AdCbl are cleaved inside cells and are not used in the synthesis of intracellular MeCbl and AdCbl, respectively. However, the overall bioavailability of each form of supplemental B12 may be influenced by many factors such as gastrointestinal pathologies, age, and genetics. Polymorphisms on B12-related pathways may affect the efficiency of absorption, blood transport, cellular uptake, and intracellular transformations. Conclusions Supplementing with any of the nature bioidentical forms of B12 (MeCbl, OHCbl, and/or AdCbl) is preferred instead of the use of CNCbl, owing to their superior bioavailability and safety. For the majority of the population, all B12 forms may likely have similar bioavailabilities and physiological effects; thus, it makes sense to employ the least-expensive form of B12, such as MeCbl. Individuals with particular single nucleotide polymorphisms (SNPs) affecting B12 assimilation may raise their B12 status more efficiently with 1 or more particular forms of vitamin B12. However, because those types of SNPs are not currently reported in commercial tests, individuals may require either a trial-and-error approach by supplementing with 1 particular form of B12 at a time, or they might simply use a supplement with a combination of all 3 naturally occurring forms of B12 that are commercially available for a better chance of achieving faster clinical results. That approach may or may not offset genetic polymorphisms involving B12 metabolism and related pathways. PMID:28223907

The CBL-Interacting Protein Kinase CIPK23 Regulates HAK5-Mediated High-Affinity K+ Uptake in Arabidopsis Roots.

PubMed

Ragel, Paula; Ródenas, Reyes; García-Martín, Elena; Andrés, Zaida; Villalta, Irene; Nieves-Cordones, Manuel; Rivero, Rosa M; Martínez, Vicente; Pardo, Jose M; Quintero, Francisco J; Rubio, Francisco

2015-12-01

Plant growth and development requires efficient acquisition of essential elements. Potassium (K(+)) is an important macronutrient present in the soil solution at a wide range of concentrations. Regulation of the K(+) uptake systems in the roots is essential to secure K(+) supply. It has been shown in Arabidopsis (Arabidopsis thaliana) that when the external K(+) concentration is very low (<10 µm), K(+) nutrition depends exclusively on the high-affinity K(+) transporter5 (HAK5). Low-K(+)-induced transcriptional activation of the gene encoding HAK5 has been previously reported. Here, we show the posttranscriptional regulation of HAK5 transport activity by phosphorylation. Expression in a heterologous system showed that the Ca(2+) sensors calcineurin B-like (CBL1), CBL8, CBL9, and CBL10, together with CBL-interacting protein kinase23 (CIPK23), activated HAK5 in vivo. This activation produced an increase in the affinity and the Vmax of K(+) transport. In vitro experiments show that the N terminus of HAK5 is phosphorylated by CIPK23. This supports the idea that phosphorylation of HAK5 induces a conformational change that increases its affinity for K(+). Experiments of K(+) (Rb(+)) uptake and growth measurements in low-K(+) medium with Arabidopsis single mutants hak5, akt1, and cipk23, double mutants hak5 akt1, hak5 cipk23, and akt1 cipk23, and the triple mutant hak5 akt1 cipk23 confirmed the regulatory role of CIPK23 in planta. © 2015 American Society of Plant Biologists. All Rights Reserved.

Spectroscopic and computational studies of cobalamin species with variable lower axial ligation: implications for the mechanism of Co-C bond activation by class I cobalamin-dependent isomerases.

PubMed

Conrad, Karen S; Jordan, Christopher D; Brown, Kenneth L; Brunold, Thomas C

2015-04-20

5'-deoxyadenosylcobalamin (coenzyme B12, AdoCbl) serves as the cofactor for several enzymes that play important roles in fermentation and catabolism. All of these enzymes initiate catalysis by promoting homolytic cleavage of the cofactor's Co-C bond in response to substrate binding to their active sites. Despite considerable research efforts, the role of the lower axial ligand in facilitating Co-C bond homolysis remains incompletely understood. In the present study, we characterized several derivatives of AdoCbl and its one-electron reduced form, Co(II)Cbl, by using electronic absorption and magnetic circular dichroism spectroscopies. To complement our experimental data, we performed computations on these species, as well as additional Co(II)Cbl analogues. The geometries of all species investigated were optimized using a quantum mechanics/molecular mechanics method, and the optimized geometries were used to compute absorption spectra with time-dependent density functional theory. Collectively, our results indicate that a reduction in the basicity of the lower axial ligand causes changes to the cofactor's electronic structure in the Co(II) state that replicate the effects seen upon binding of Co(II)Cbl to Class I isomerases, which replace the lower axial dimethylbenzimidazole ligand of AdoCbl with a protein-derived histidine (His) residue. Such a reduction of the basicity of the His ligand in the enzyme active site may be achieved through proton uptake by the catalytic triad of conserved residues, DXHXGXK, during Co-C bond homolysis.

Correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography and clinical presentations in patients with low cobalamin status.

PubMed

Tu, Min-Chien; Lo, Chung-Ping; Chen, Ching-Yuan; Huang, Ching-Feng

2015-12-03

Cobalamin (Cbl) deficiency has been associated with various neuropsychiatric symptoms of different severities. While some studies dedicated in structural neuroimaging credibly address negative impact of low Cbl status, functional imaging reports are limited. We herein retrospectively review the correlation of Tc-99 m ethyl cysteinate dimer single-photon emission computed tomography (Tc-99 m-ECD SPECT) and clinical presentations among patients with low serum cobalamin (Cbl) status (<250 pg/ml). Twelve symptomatic patients with low serum Cbl status were enrolled. Clinical presentations, Tc-99 m-ECD SPECT, and neuropsychological tests were reviewed. Dysexecutive syndrome (67 %), forgetfulness (50 %), attention deficits (42 %), and sleep disorders (33 %) constituted the major clinical presentations. All patients (100 %) had temporal hypoperfusion on the Tc-99 m-ECD SPECT. Five patients (42 %) had hypoperfusion restricted within temporal regions and deep nuclei; seven patients (58 %) had additional frontal hypoperfusion. In patients with hypoperfusion restricted within temporal regions and deep nuclei, psychiatric symptoms with spared cognition were their main presentations. Among patients with additional frontal hypoperfusion, six of seven patients (86 %) showed impaired cognitive performances (two of them were diagnosed as having dementia). Among ten patients who finished neuropsychological tests, abstract thinking (70 %) was the most commonly affected, followed by verbal fluency (60 %), short-term memory (50 %), and attention (50 %). Anxiety and sleep problems were the major clinically remarkable psychiatric features (33 % both). Four Tc-99 m-ECD SPECT follow-up studies were available; the degree and extent of signal reversal correlated with cognitive changes after Cbl replacement therapy. Our TC-99 m-ECD SPECT observations provide pivotal information of neurobiological changes within basal ganglia and fronto-temporal regions in conjunction with disease severity among patients with Cbl deficiency. Hypoperfusion within thalamus/basal ganglia and temporal regions may be seen in the earlier state of Cbl deficiency, when psychiatric symptoms predominate. Hypoperfusion beyond thalamus/basal ganglia and involving frontal regions appears when cognitive problems, mostly dysexecutive syndrome, are manifested. Symmetric hypofrontality of SPECT in the context of dysexcutive syndrome serves as a distinguishing feature of non-amnestic mild cognitive impairment attributed to Cbl deficiency. Concordant with TC-99 m-ECD SPECT findings, the psychiatric symptoms and dysexcutive syndrome undergird impaired limbic and dorsolateral prefrontal circuits originating from basal ganglia respectively.

C-Cbl reverses HER2-mediated tamoxifen resistance in human breast cancer cells.

PubMed

Li, Wei; Xu, Ling; Che, Xiaofang; Li, Haizhou; Zhang, Ye; Song, Na; Wen, Ti; Hou, Kezuo; Yang, Yi; Zhou, Lu; Xin, Xing; Xu, Lu; Zeng, Xue; Shi, Sha; Liu, Yunpeng; Qu, Xiujuan; Teng, Yuee

2018-05-02

Tamoxifen is a frontline therapy for estrogen receptor (ER)-positive breast cancer in premenopausal women. However, many patients develop resistance to tamoxifen, and the mechanism underlying tamoxifen resistance is not well understood. Here we examined whether ER-c-Src-HER2 complex formation is involved in tamoxifen resistance. MTT and colony formation assays were used to measure cell viability and proliferation. Western blot was used to detect protein expression and protein complex formations were detected by immunoprecipitation and immunofluorescence. SiRNA was used to examine the function of HER2 in of BT474 cells. An in vivo xenograft animal model was established to examine the role of c-Cbl in tumor growth. MTT and colony formation assay showed that BT474 cells are resistant to tamoxifen and T47D cells are sensitive to tamoxifen. Immunoprecipitation experiments revealed ER-c-Src-HER2 complex formation in BT474 cells but not in T47D cells. However, ER-c-Src-HER2 complex formation was detected after overexpressing HER2 in T47D cells and these cells were more resistant to tamoxifen. HER2 knockdown by siRNA in BT474 cells reduced ER-c-Src-HER2 complex formation and reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was also disrupted and tamoxifen resistance was reversed in BT474 cells by the c-Src inhibitor PP2 and HER2 antibody trastuzumab. Nystatin, a lipid raft inhibitor, reduced ER-c-Src-HER2 complex formation and partially reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was disrupted by overexpression of c-Cbl but not by the c-Cbl ubiquitin ligase mutant. In addition, c-Cbl could reverse tamoxifen resistance in BT474 cells, but the ubiquitin ligase mutant had no effect. The effect of c-Cbl was validated in BT474 tumor-bearing nude mice in vivo. Immunofluorescence also revealed ER-c-Src-HER2 complex formation was reduced in tumor tissues of nude mice with c-Cbl overexpression. Our results suggested that c-Cbl can reverse tamoxifen resistance in HER2-overexpressing breast cancer cells by inhibiting the formation of the ER-c-Src-HER2 complex.

The effectiveness of case-based learning in health professional education. A BEME systematic review: BEME Guide No. 23.

PubMed

Thistlethwaite, Jill Elizabeth; Davies, David; Ekeocha, Samilia; Kidd, Jane M; MacDougall, Colin; Matthews, Paul; Purkis, Judith; Clay, Diane

2012-01-01

Case-based learning (CBL) is a long established pedagogical method, which is defined in a number of ways depending on the discipline and type of 'case' employed. In health professional education, learning activities are commonly based on patient cases. Basic, social and clinical sciences are studied in relation to the case, are integrated with clinical presentations and conditions (including health and ill-health) and student learning is, therefore, associated with real-life situations. Although many claims are made for CBL as an effective learning and teaching method, very little evidence is quoted or generated to support these claims. We frame this review from the perspective of CBL as a type of inquiry-based learning. To explore, analyse and synthesise the evidence relating to the effectiveness of CBL as a means of achieving defined learning outcomes in health professional prequalification training programmes. We focused the review on CBL for prequalification health professional programmes including medicine, dentistry, veterinary science, nursing and midwifery, social care and the allied health professions (physiotherapy, occupational therapy, etc.). Papers were required to have outcome data on effectiveness. The search covered the period from 1965 to week 4 September 2010 and the following databases: ASSIA, CINAHL, EMBASE, Education Research, Medline and Web of Knowledge (WoK). Two members of the topic review group (TRG) independently reviewed the 173 abstracts retrieved from Medline and compared findings. As there was good agreement on inclusion, one went onto review the WoK and ASSIA EndNote databases and the other the Embase, CINAHL and Education Research databases to decide on papers to submit for coding. Coding and data analysis: The TRG modified the standard best evidence medical education coding sheet to fit our research questions and assessed each paper for quality. After a preliminary reliability exercise, each full paper was read and graded by one reviewer with the papers scoring 3-5 (of 5) for strength of findings being read by a second reviewer. A summary of each completed coding form was entered into an Excel spread sheet. The type of data in the papers was not amenable to traditional meta-analysis because of the variability in interventions, information given, student numbers (and lack of) and timings. We, therefore, adopted a narrative synthesis method to compare, contrast, synthesise and interpret the data, working within a framework of inquiry-based learning. The final number of coded papers for inclusion was 104. The TRG agreed that 23 papers would be classified as of higher quality and significance (22%). There was a wide diversity in the type, timing, number and length of exposure to cases and how cases were defined. Medicine was the most commonly included profession. Numbers of students taking part in CBL varied from below 50 to over 1000. The shortest interventions were two hours, and one case, whereas the longest was CBL through a whole year. Group sizes ranged from students working alone to over 30, with the majority between 2 and 15 students per group. The majority of studies involved single cohorts of students (61%), with 29% comparing multiple groups, 8% involving different year groups and 2% with historical controls. The outcomes evaluation was either carried out postintervention only (78 papers; 75%), preintervention and postintervention (23 papers; 22%) or during and postintervention (3 papers; <3%). Our analysis provided the basis for discussion of definitions of CBL, methods used and advocated, topics and learning outcomes and whether CBL is effective based on the evaluation data. Overwhelmingly, students enjoy CBL and think that it enhances their learning. The empirical data taken as a whole are inconclusive as to the effects on learning compared with other types of activity. Teachers enjoy CBL, partly because it engages, and is perceived to motivate, students. CBL seems to foster learning in small groups though whether this is the case delivery or the group learning effect is unclear.

CompuLung: a multimedia CBL on pulmonary auscultation.

PubMed Central

Mangione, S.; Dennis, S.

1992-01-01

Cardio-pulmonary auscultation, a time honored art, is suffering a declining interest caused by competing diagnostic technology and inadequate training of physicians. Overreliance on diagnostic technology is expensive, not cost-effective and bound to lead to loss of our clinical heritage. We need novel methods to teach and revive this art. Computer-Based Learning (CBL), particularly multimedia supporting graphics plus sound-and-motion pictures, appears to be ideally suited for teaching and sharpening this skill. We present in this paper a multimedia CBL ("CompuLung"), that provides the user with a comprehensive and interactive tutorial on pulmonary auscultation. PMID:1482999

The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T-mediated virulence.

PubMed

Balachandran, Priya; Dragone, Leonard; Garrity-Ryan, Lynne; Lemus, Armando; Weiss, Arthur; Engel, Joanne

2007-02-01

Pseudomonas aeruginosa, an important cause of opportunistic infections in humans, delivers bacterial cytotoxins by type III secretion directly into the host cell cytoplasm, resulting in disruption of host cell signaling and host innate immunity. However, little is known about the fate of the toxins themselves following injection into the host cytosol. Here, we show by both in vitro and in vivo studies that the host ubiquitin ligase Cbl-b interacts with the type III-secreted effector exotoxin T (ExoT) and plays a key role in vivo in limiting bacterial dissemination mediated by ExoT. We demonstrate that, following polyubiquitination, ExoT undergoes regulated proteasomal degradation in the host cell cytosol. ExoT interacts with the E3 ubiquitin ligase Cbl-b and Crk, the substrate for the ExoT ADP ribosyltransferase (ADPRT) domain. The efficiency of degradation is dependent upon the activity of the ADPRT domain. In mouse models of acute pneumonia and systemic infection, Cbl-b is specifically required to limit the dissemination of ExoT-producing bacteria whereas c-Cbl plays no detectable role. To the best of our knowledge, this represents the first identification of a mammalian gene product that is specifically required for in vivo resistance to disease mediated by a type III-secreted effector.

The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T–mediated virulence

PubMed Central

Balachandran, Priya; Dragone, Leonard; Garrity-Ryan, Lynne; Lemus, Armando; Weiss, Arthur; Engel, Joanne

2007-01-01

Pseudomonas aeruginosa, an important cause of opportunistic infections in humans, delivers bacterial cytotoxins by type III secretion directly into the host cell cytoplasm, resulting in disruption of host cell signaling and host innate immunity. However, little is known about the fate of the toxins themselves following injection into the host cytosol. Here, we show by both in vitro and in vivo studies that the host ubiquitin ligase Cbl-b interacts with the type III–secreted effector exotoxin T (ExoT) and plays a key role in vivo in limiting bacterial dissemination mediated by ExoT. We demonstrate that, following polyubiquitination, ExoT undergoes regulated proteasomal degradation in the host cell cytosol. ExoT interacts with the E3 ubiquitin ligase Cbl-b and Crk, the substrate for the ExoT ADP ribosyltransferase (ADPRT) domain. The efficiency of degradation is dependent upon the activity of the ADPRT domain. In mouse models of acute pneumonia and systemic infection, Cbl-b is specifically required to limit the dissemination of ExoT-producing bacteria whereas c-Cbl plays no detectable role. To the best of our knowledge, this represents the first identification of a mammalian gene product that is specifically required for in vivo resistance to disease mediated by a type III–secreted effector. PMID:17235393

Arabidopsis CALCINEURIN B-LIKE10 Functions Independently of the SOS Pathway during Reproductive Development in Saline Conditions1[OPEN

PubMed Central

Smith, Steven E.; Schumaker, Karen S.

2016-01-01

The accumulation of sodium in soil (saline conditions) negatively affects plant growth and development. The Salt Overly Sensitive (SOS) pathway in Arabidopsis (Arabidopsis thaliana) functions to remove sodium from the cytosol during vegetative development preventing its accumulation to toxic levels. In this pathway, the SOS3 and CALCINEURIN B-LIKE10 (CBL10) calcium sensors interact with the SOS2 protein kinase to activate sodium/proton exchange at the plasma membrane (SOS1) or vacuolar membrane. To determine if the same pathway functions during reproductive development in response to salt, fertility was analyzed in wild type and the SOS pathway mutants grown in saline conditions. In response to salt, CBL10 functions early in reproductive development before fertilization, while SOS1 functions mostly after fertilization when seed development begins. Neither SOS2 nor SOS3 function in reproductive development in response to salt. Loss of CBL10 function resulted in reduced anther dehiscence, shortened stamen filaments, and aborted pollen development. In addition, cbl10 mutant pistils could not sustain the growth of wild-type pollen tubes. These results suggest that CBL10 is critical for reproductive development in the presence of salt and that it functions in different pathways during vegetative and reproductive development. PMID:26979332

Primordial-like enzymes from bacteria with reduced genomes.

PubMed

Ferla, Matteo P; Brewster, Jodi L; Hall, Kelsi R; Evans, Gary B; Patrick, Wayne M

2017-08-01

The first cells probably possessed rudimentary metabolic networks, built using a handful of multifunctional enzymes. The promiscuous activities of modern enzymes are often assumed to be relics of this primordial era; however, by definition these activities are no longer physiological. There are many fewer examples of enzymes using a single active site to catalyze multiple physiologically-relevant reactions. Previously, we characterized the promiscuous alanine racemase (ALR) activity of Escherichia coli cystathionine β-lyase (CBL). Now we have discovered that several bacteria with reduced genomes lack alr, but contain metC (encoding CBL). We characterized the CBL enzymes from three of these: Pelagibacter ubique, the Wolbachia endosymbiont of Drosophila melanogaster (wMel) and Thermotoga maritima. Each is a multifunctional CBL/ALR. However, we also show that CBL activity is no longer required in these bacteria. Instead, the wMel and T. maritima enzymes are physiologically bi-functional alanine/glutamate racemases. They are not highly active, but they are clearly sufficient. Given the abundance of the microorganisms using them, we suggest that much of the planet's biochemistry is carried out by enzymes that are quite different from the highly-active exemplars usually found in textbooks. Instead, primordial-like enzymes may be an essential part of the adaptive strategy associated with streamlining. © 2017 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd.

The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells.

PubMed

Paolino, Magdalena; Choidas, Axel; Wallner, Stephanie; Pranjic, Blanka; Uribesalgo, Iris; Loeser, Stefanie; Jamieson, Amanda M; Langdon, Wallace Y; Ikeda, Fumiyo; Fededa, Juan Pablo; Cronin, Shane J; Nitsch, Roberto; Schultz-Fademrecht, Carsten; Eickhoff, Jan; Menninger, Sascha; Unger, Anke; Torka, Robert; Gruber, Thomas; Hinterleitner, Reinhard; Baier, Gottfried; Wolf, Dominik; Ullrich, Axel; Klebl, Bert M; Penninger, Josef M

2014-03-27

Tumour metastasis is the primary cause of mortality in cancer patients and remains the key challenge for cancer therapy. New therapeutic approaches to block inhibitory pathways of the immune system have renewed hopes for the utility of such therapies. Here we show that genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage lymphoma-b) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumours. The TAM tyrosine kinase receptors Tyro3, Axl and Mer (also known as Mertk) were identified as ubiquitylation substrates for Cbl-b. Treatment of wild-type NK cells with a newly developed small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing anti-metastatic NK cell activity in vivo. Oral or intraperitoneal administration using this TAM inhibitor markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. We further report that the anticoagulant warfarin exerts anti-metastatic activity in mice via Cbl-b/TAM receptors in NK cells, providing a molecular explanation for a 50-year-old puzzle in cancer biology. This novel TAM/Cbl-b inhibitory pathway shows that it might be possible to develop a 'pill' that awakens the innate immune system to kill cancer metastases.

Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women.

PubMed

Barbosa, P R; Stabler, S P; Machado, A L K; Braga, R C; Hirata, R D C; Hirata, M H; Sampaio-Neto, L F; Allen, R H; Guerra-Shinohara, E M

2008-08-01

To examine the association between methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), methionine synthase (MTR) A2756G and methionine synthase reductase (MTRR) A66G gene polymorphisms and total homocysteine (tHcy), methylmalonic acid (MMA) and S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) levels; and to evaluate the potential interactions with folate or cobalamin (Cbl) status. Two hundred seventy-five healthy women at labor who delivered full-term normal babies. Cbl, folate, tHcy, MMA, SAM and SAH were measured in serum specimens. The genotypes for polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP). Serum folate, MTHFR 677T allele and MTR 2756AA genotypes were the predictors of tHcy levels in pregnant women. Serum Cbl and creatinine were the predictors of SAM/SAH ratio and MMA levels, respectively. The gene polymorphisms were not determinants for MMA levels and SAM/SAH ratios. Low levels of serum folate were associated with elevated tHcy in pregnant women, independently of the gene polymorphisms. In pregnant women carrying MTHFR 677T allele, or MTHFR 1298AA or MTRR 66AA genotypes, lower Cbl levels were associated with higher levels of tHcy. Lower SAM/SAH ratio was found in MTHFR 677CC or MTRR A2756AA genotypes carriers when Cbl levels were lower than 142 pmol/l. Serum folate and MTHFR C677T and MTR A2576G gene polymorphisms were the determinants for tHcy levels. The interaction between low levels of serum Cbl and MTHFR (C677T or A1298C) or MTRR A66G gene polymorphisms was associated with increased tHcy.

Case based learning: a method for better understanding of biochemistry in medical students.

PubMed

Nair, Sandhya Pillai; Shah, Trushna; Seth, Shruti; Pandit, Niraj; Shah, G V

2013-08-01

Health professionals need to develop analytic and diagnostic thinking skills and not just a mere accumulation of large amount of facts. Hence, Case Based Learning (CBL) has been used in the medical curriculum for this reason, so that the students are exposed to the real medical problems, which helps them in develop analysing abilities. This also helps them in interpreting and solving the problems and in the course of doing this, they develop interest. In addition to didactic lectures, CBL was used as a learning method. This study was conducted in the Department of Biochemistry, S.B.K.S.M.I and R.C, Sumandeep Vidyapeeth ,Piparia, Gujarat, India. A group of 100 students were selected and they were divided into two groups as the control group and the study group. A total of 50 students were introduced to case based learning, which formed the study group and 50 students who attended didactic lectures formed the control group. A very significant improvement (p<0.0001) was observed among the students after the CBL sessions and they were also motivated by these sessions. A 4 point Likert scale questionnaire which contained 8 questions was administered to the students, to know their perception on the usefulness of the CBL. 98% of the students reported that they found the CBL sessions to be an interesting method of gaining knowledge. 84% of them felt that they exposed them to an experience of logical application of the knowledge which was gained in cracking cases, which would be of great help in the future also. Case Based Learning (CBL) was used and it is effective in the medical curriculum for a better understanding of Biochemistry among the medical students.

Crestal bone loss around submerged and nonsubmerged dental implants: A systematic review.

PubMed

Al Amri, Mohammad D

2016-05-01

To my knowledge, there is no systematic review of crestal bone loss (CBL) around submerged and nonsubmerged dental implants. The purpose of this review was to systematically assess CBL around submerged and nonsubmerged dental implants. The addressed focused question was, "Does crestal and subcrestal placement of dental implants influence crestal bone levels?" Databases were searched from 1986 through October 2015 using different combinations of the following keywords: crestal, sub-crestal, bone loss, dental implant, submerged, and nonsubmerged. Reference lists of potentially relevant original and review articles were hand-searched to identify any further studies. Letters to the editor, case reports, commentaries, studies on platform-switched implants, and studies published in languages other than English were excluded. In total, 13 studies (6 human and 7 animal), which were performed at universities, were included. In the human studies, the number of participants ranged from 8 to 84 individuals. The follow-up period ranged from 1 to 5 years. CBL at the test sites ranged from 0.17 mm to 0.9 mm and at control sites from 0.02 mm to 1.4 mm. Five human studies reported no significant difference in CBL around implants placed at the test and control sites. All animal studies were performed in dogs with a mean age ranging from 1 to approximately 2 years. The follow-up period ranged from 2 to 6 months. Four animal studies reported no significant difference in CBL around submerged and nonsubmerged implants. No significant difference in CBL was found around submerged and nonsubmerged dental implants. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Three-dimensional turbulent boundary layers; Proceedings of the Symposium, Berlin, West Germany, March 29-April 1, 1982

NASA Astrophysics Data System (ADS)

Fernholz, H. H.; Krause, E.

Papers are presented on recent research concerning three-dimensional turbulent boundary layers. Topics examined include experimental techniques in three-dimensional turbulent boundary layers, turbulence measurements in ship-model flow, measurements of Reynolds-stress profiles in the stern region of a ship model, the effects of crossflow on the vortex-layer-type three-dimensional flow separation, and wind tunnel investigations of some three-dimensional separated turbulent boundary layers. Also examined are three-dimensional boundary layers in turbomachines, the boundary layers on bodies of revolution spinning in axial flows, the effect on a developed turbulent boundary layer of a sudden local wall motion, three-dimensional turbulent boundary layer along a concave wall, the numerical computation of three-dimensional boundary layers, a numerical study of corner flows, three-dimensional boundary calculations in design aerodynamics, and turbulent boundary-layer calculations in design aerodynamics. For individual items see A83-47012 to A83-47036

"Egg-Streme" Egg Crashes

ERIC Educational Resources Information Center

Ward, Lauren; Lyden, Sarah; Fitzallen, Noleine

2016-01-01

Context based learning (CBL) is a powerful tool that utilises areas of student interest framed in meaningful contexts to foster development of new skills and understanding. For middle school students, engineering activities that relate to real-world problems provide suitable CBL contexts for acquiring conceptual scientific and mathematical…

Indispensable roles of mammalian Cbl family proteins as negative regulators of protein tyrosine kinase signaling

PubMed Central

Band, Vimla

2011-01-01

All higher eukaryotes utilize protein tyrosine kinases (PTKs) as molecular switches to control a variety of cellular signals. Notably, many PTKs have been identified as proto-oncogenes whose aberrant expression, mutations or co-option by pathogens can lead to human malignancies. Thus, it is obvious that PTK functions must be precisely regulated in order to maintain homeostasis of an organism. Investigations over the past fifteen years have revealed that members of the Cbl family proteins can serve as negative regulators of PTK signaling, and biochemical and cell biological studies have unraveled the mechanistic basis of this regulation. Yet, it is only recently that the field has begun to appreciate the real significance of this novel regulatory apparatus in shaping PTK-mediated signaling in organismic contexts and in human diseases. Here, we discuss recent progress in murine models that are beginning to provide insights into the critical roles of Cbl proteins in physiological pathways, with important implications in understanding how aberrations of Cbl proteins contribute to oncogenesis. PMID:21655429

Catfish (Clarias batrachus) serum lectin recognizes polyvalent Tn [alpha-D-GalpNAc1-Ser/Thr], Talpha [beta-D-Galp-(1-->3)-alpha-D-GalpNAc1-Ser/Thr], and II [beta-D-Galp(1-->4)-beta-D-GlcpNAc1-] mammalian glycotopes.

PubMed

Singha, Biswajit; Adhya, Mausumi; Chatterjee, Bishnu P

2008-09-22

A new calcium dependent GalNAc/Gal specific lectin was isolated from the serum of Indian catfish, Clarias batrachus and designated as C. batrachus lectin (CBL). It is a disulfide-linked homodecameric lectin of 74.65kDa subunits and the oligomeric form is essential for its activity. Binding specificity of CBL was investigated by enzyme-linked lectin-sorbent assay using a series of simple sugars, polysaccharides, and glycoproteins. GalNAc was more potent inhibitor than Gal; and alpha glycosides of both were more inhibitory than their beta counterparts. CBL showed maximum affinity for human tumor-associated Tn-antigens (GalNAcalpha1-Ser/Thr) at the molecular level and was 3.5 times higher than GalNAc. CBL interacted strongly with polyvalent Tn and Talpha (Galbeta1,3GalNAcalpha1-) as well as multivalent-II (Galbeta1,4GlcNAcbeta1-) antigens containing glycoproteins and intensity of inhibition was 10(3)-10(5) times more than monovalent ones. The overall specificity of CBL lies in the order of polyvalent Tn, Talpha and II>monovalent Tn > or = Me-alphaGalNAc>monovalent Talpha> Me-betaGalNAc>Me-alphaGal>monovalent T>GalNAc>monovalent F>monovalent II>Me-betaGal>Gal.

Neuro-peptide treatment with Cerebrolysin improves the survival of neural stem cell grafts in an APP transgenic model of Alzheimer disease.

PubMed

Rockenstein, Edward; Desplats, Paula; Ubhi, Kiren; Mante, Michael; Florio, Jazmin; Adame, Anthony; Winter, Stefan; Brandstaetter, Hemma; Meier, Dieter; Masliah, Eliezer

2015-07-01

Neural stem cells (NSCs) have been considered as potential therapy in Alzheimer's disease (AD) but their use is hampered by the poor survival of grafted cells. Supply of neurotrophic factors to the grafted cells has been proposed as a way to augment survival of the stem cells. In this context, we investigated the utility of Cerebrolysin (CBL), a peptidergic mixture with neurotrophic-like properties, as an adjunct to stem cell therapy in an APP transgenic (tg) model of AD. We grafted murine NSCs into the hippocampus of non-tg and APP tg that were treated systemically with CBL and analyzed after 1, 3, 6 and 9months post grafting. Compared to vehicle-treated non-tg mice, in the vehicle-treated APP tg mice there was considerable reduction in the survival of the grafted NSCs. Whereas, CBL treatment enhanced the survival of NSCs in both non-tg and APP tg with the majority of the surviving NSCs remaining as neuroblasts. The NSCs of the CBL treated mice displayed reduced numbers of caspase-3 and TUNEL positive cells and increased brain derived neurotrophic factor (BDNF) and furin immunoreactivity. These results suggest that CBL might protect grafted NSCs and as such be a potential adjuvant therapy when combined with grafting. Copyright © 2015. Published by Elsevier B.V.

Role of Cbl-PI3K Interaction during Skeletal Remodeling in a Murine Model of Bone Repair.

PubMed

Scanlon, Vanessa; Soung, Do Yu; Adapala, Naga Suresh; Morgan, Elise; Hansen, Marc F; Drissi, Hicham; Sanjay, Archana

2015-01-01

Mice in which Cbl is unable to bind PI3K (YF mice) display increased bone volume due to enhanced bone formation and repressed bone resorption during normal bone homeostasis. We investigated the effects of disrupted Cbl-PI3K interaction on fracture healing to determine whether this interaction has an effect on bone repair. Mid-diaphyseal femoral fractures induced in wild type (WT) and YF mice were temporally evaluated via micro-computed tomography scans, biomechanical testing, histological and histomorphometric analyses. Imaging analyses revealed no change in soft callus formation, increased bony callus formation, and delayed callus remodeling in YF mice compared to WT mice. Histomorphometric analyses showed significantly increased osteoblast surface per bone surface and osteoclast numbers in the calluses of YF fractured mice, as well as increased incorporation of dynamic bone labels. Furthermore, using laser capture micro-dissection of the fracture callus we found that cells lacking Cbl-PI3K interaction have higher expression of Osterix, TRAP, and Cathepsin K. We also found increased expression of genes involved in propagating PI3K signaling in cells isolated from the YF fracture callus, suggesting that the lack of Cbl-PI3K interaction perhaps results in enhanced PI3K signaling, leading to increased bone formation, but delayed remodeling in the healing femora.

The Efficacy of Three Learning Methods Collaborative, Context-Based Learning and Traditional, on Learning, Attitude and Behaviour of Undergraduate Nursing Students: Integrating Theory and Practice.

PubMed

Hasanpour-Dehkordi, Ali; Solati, Kamal

2016-04-01

Communication skills training, responsibility, respect, and self-awareness are important indexes of changing learning behaviours in modern approaches. The aim of this study was to investigate the efficacy of three learning approaches, collaborative, context-based learning (CBL), and traditional, on learning, attitude, and behaviour of undergraduate nursing students. This study was a clinical trial with pretest and post-test of control group. The participants were senior nursing students. The samples were randomly assigned to three groups; CBL, collaborative, and traditional. To gather data a standard questionnaire of students' behaviour and attitude was administered prior to and after the intervention. Also, the rate of learning was investigated by a researcher-developed questionnaire prior to and after the intervention in the three groups. In CBL and collaborative training groups, the mean score of behaviour and attitude increased after the intervention. But no significant association was obtained between the mean scores of behaviour and attitude prior to and after the intervention in the traditional group. However, the mean learning score increased significantly in the CBL, collaborative, and traditional groups after the study in comparison to before the study. Both CBL and collaborative approaches were useful in terms of increased respect, self-awareness, self-evaluation, communication skills and responsibility as well as increased motivation and learning score in comparison to traditional method.

Case-based learning in endocrine physiology: an approach toward self-directed learning and the development of soft skills in medical students.

PubMed

Gade, Shubhada; Chari, Suresh

2013-12-01

The Medical Council of India, in the recent Vision 2015 document, recommended curricular reforms for undergraduates. Case-based learning (CBL) is one method where students are motivated toward self-directed learning and to develop analytic and problem-solving skills. An overview of thyroid physiology was given in a didactic lecture. A paper-based case scenario of multinodular goiter was given to phase I Bachelor of Medicine, Bachelor of Surgery students in two sessions. An attitude survey of the students and teachers was done using a Likert scale ranging from strongly disagrees to strongly agree. A pretest and posttest were conducted. The students opined that CBL helped them to better their understanding of a particular topic, gave them better retention of knowledge, helped them to relate clinical conditions to basic sciences, improved soft skills such as communication skills and group dynamics, and promoted a better teacher-student relationship. There was significant improvement in student's performance when pre- and posttest scores were compared (P = 0.018). Furthermore, faculty members opined that CBL promoted self-study and problem-solving abilities of the students. In conclusion, CBL motivates students toward self-directed learning and to develop analytic and problem-solving skills; thus, CBL could be beneficial for students' entry into clinical departments and, finally, in managing patients.

Adaptable Interactive CBL Design Tools for Education.

ERIC Educational Resources Information Center

Chandra, Peter

The design team approach to the development of computer based learning (CBL) courseware relies heavily on the effective communication between different members of the team, including up-to-date paperwork and documentation. This is important for the accurate and efficient overall coordination of the courseware design, and for future maintenance of…

Validating Variance Similarity Functions in the Entrainment Zone

NASA Astrophysics Data System (ADS)

Osman, M.; Turner, D. D.; Heus, T.; Newsom, R. K.

2017-12-01

In previous work, the water vapor variance in the entrainment zone was proposed to be proportional to the convective velocity scale, gradient water vapor mixing ratio and the Brunt-Vaisala frequency in the interfacial layer, while the variance of the vertical wind at in the entrainment zone was defined in terms of the convective velocity scale. The variances in the entrainment zone have been hypothesized to depend on two distinct functions, which also depend on the Richardson number. To the best of our knowledge, these hypotheses have never been tested observationally. Simultaneous measurements of the Eddy correlation surface flux, wind shear profiles from wind profilers, and variance profile measurements of vertical motions and water vapor by Doppler and Raman lidars, respectively, provide a unique opportunity to thoroughly examine the functions used in defining the variances and validate them. These observations were made over the Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) site. We have identified about 30 cases from 2016 during which the convective boundary layer (CBL) is quasi-stationary and well mixed for at least 2 hours. The vertical profiles of turbulent fluctuations of the vertical wind and water vapor have been derived using an auto covariance technique to separate out the instrument random error to a set of 2-h period time series. The error analysis of the lidars observations demonstrates that the lidars are capable of resolving the vertical structure of turbulence around the entrainment zone. Therefore, utilizing this unique combination of observations, this study focuses on extensively testing the hypotheses that the second-order moments are indeed proportional to the functions which also depend on Richardson number. The coefficients that are used in defining the functions will also be determined observationally and compared against with the values suggested by Large eddy simulation (LES) studies.

Discussion of boundary-layer characteristics near the casing of an axial-flow compressor

NASA Technical Reports Server (NTRS)

Mager, Artur; Mahoney, John J; Budinger, Ray E

1951-01-01

Boundary-layer velocity profiles on the casing of an axial-flow compressor behind the guide vanes and rotor were measured and resolved into two components: along the streamline of the flow and perpendicular to it. Boundary-layer thickness and the deflection of the boundary layer at the wall were the generalizing parameters. By use of these results and the momentum-integral equations, the characteristics of boundary on the walls of axial-flow compressor are qualitatively discussed. Important parameters concerning secondary flow in the boundary layer appear to be turning of the flow and the product of boundary-layer thickness and streamline curvature outside the boundary layer. Two types of separation are shown to be possible in three dimensional boundary layer.

A review of evaluative studies of computer-based learning in nursing education.

PubMed

Lewis, M J; Davies, R; Jenkins, D; Tait, M I

2001-01-01

Although there have been numerous attempts to evaluate the learning benefits of computer-based learning (CBL) packages in nursing education, the results obtained have been equivocal. A literature search conducted for this review found 25 reports of the evaluation of nursing CBL packages since 1966. Detailed analysis of the evaluation methods used in these reports revealed that most had significant design flaws, including the use of too small a sample group, the lack of a control group, etc. Because of this, the conclusions reached were not always valid. More effort is required in the design of future evaluation studies of nursing CBL packages. Copyright 2001 Harcourt Publishers Ltd.

Students' Experiences of Clinic-Based Learning during a Final Year Veterinary Internship Programme

ERIC Educational Resources Information Center

Matthew, Susan M.; Taylor, Rosanne M.; Ellis, Robert A.

2010-01-01

This study investigated veterinary students' experiences of clinic-based learning (CBL) during a comprehensive final year internship programme. Open-ended surveys (n = 93) were used to gather qualitative data about students' conceptions of what is learned during CBL and their approaches to learning in clinics. Phenomenography was used for detailed…

Community-Based Learning. Adding Value to Programs Involving Service Agencies and Schools.

ERIC Educational Resources Information Center

Cumming, Jim

Community-based learning (CBL) is a structured approach to learning and teaching that connects meaningful community experience with intellectual development, personal growth, and active citizenship. Enthusiasm for CBL is emerging in Australia and elsewhere because it is seen as the following: strategy for whole-school reform, especially in…

One Happy Union: Infusing Community-Based Learning Projects through Online Instruction

ERIC Educational Resources Information Center

Lee, Jason W.; Kane, Jennifer; Cavanaugh, Terence

2015-01-01

Both community-based learning (CBL) and online learning are popular pedagogical practices, with distinct benefits and issues for teaching and learning. The integration of these practices may seem challenging, but they can be compatible. This article seeks to provide effective examples and support for conducting CBL projects in online courses while…

Case-based learning in education of Traditional Chinese Medicine: a systematic review.

PubMed

Chen, Ji; Li, Ying; Tang, Yong; Zeng, Fang; Wu, Xi; Liang, Fanrong

2013-10-01

To assess the effect of case-based learning (CBL) in the education of Traditional Chinese Medicine (TCM). The studies concerning TCM courses designed with CBL were included by searching the databases of EBSCO, Pubmed, Science Citation Index, China National Knowledge Infrastructure, Chongqing VIP database. The valid data was extracted in accordance with the included criteria. The quality of the studies was assessed with Gemma Flores-Masteo. A total of 22 articles were retrieved that met the selection criteria: one was of high quality; two were of low quality; the rest were categorized as moderate quality. The majority of the studies demonstrated the better effect produced by CBL, while a few studies showed no difference, compared with the didactic format. All included studies confirmed the favorable effect on learners' attitude, skills and ability. CBL showed the desirable results in achieving the goal of learning. Compared to didactic approach, it played a more active role in promoting students' competency. Since the quality of the articles on which the study was based was not so high, the findings still need further research to become substantiated.

Targeted brain activation using an MR-compatible wrist torque measurement device and isometric motor tasks during functional magnetic resonance imaging.

PubMed

Vlaar, Martijn P; Mugge, Winfred; Groot, Paul F C; Sharifi, Sarvi; Bour, Lo J; van der Helm, Frans C T; van Rootselaar, Anne-Fleur; Schouten, Alfred C

2016-07-01

Dedicated pairs of isometric wrist flexion tasks, with and without visual feedback of the exerted torque, were designed to target activation of the CBL and BG in healthy subjects during functional magnetic resonance imaging (fMRI). Selective activation of the cerebellum (CBL) and basal ganglia (BG), often implicated in movement disorders such as tremor and dystonia, may help identify pathological changes and expedite diagnosis. A prototyped MR-compatible wrist torque measurement device, free of magnetic and conductive materials, allowed safe execution of tasks during fMRI without causing artifacts. A significant increase of activity in CBL and BG was found in healthy volunteers during a constant torque task with visual feedback compared to a constant torque task without visual feedback. This study shows that specific pairs of motor tasks using MR-compatible equipment at the wrist allow for targeted activation of CBL and BG, paving a new way for research into the pathophysiology of movement disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Antiamnesic Effect of Broccoli (Brassica oleracea var. italica) Leaves on Amyloid Beta (Aβ)1-42-Induced Learning and Memory Impairment.

PubMed

Park, Seon Kyeong; Ha, Jeong Su; Kim, Jong Min; Kang, Jin Yong; Lee, Du Sang; Guo, Tian Jiao; Lee, Uk; Kim, Dae-Ok; Heo, Ho Jin

2016-05-04

To examine the antiamnesic effects of broccoli (Brassica oleracea var. italica) leaves, we performed in vitro and in vivo tests on amyloid beta (Aβ)-induced neurotoxicity. The chloroform fraction from broccoli leaves (CBL) showed a remarkable neuronal cell-protective effect and an inhibition against acetylcholinesterase (AChE). The ameliorating effect of CBL on Aβ1-42-induced learning and memory impairment was evaluated by Y-maze, passive avoidance, and Morris water maze tests. The results indicated improving cognitive function in the CBL group. After the behavioral tests, antioxidant effects were detected by superoxide dismutase (SOD), oxidized glutathione (GSH)/total GSH, and malondialdehyde (MDA) assays, and inhibition against AChE was also presented in the brain. Finally, oxo-dihydroxy-octadecenoic acid (oxo-DHODE) and trihydroxy-octadecenoic acid (THODE) as main compounds were identified by quadrupole time-of-flight ultraperformance liquid chromatography (Q-TOF UPLC-MS) analysis. Therefore, our studies suggest that CBL could be used as a natural resource for ameliorating Aβ1-42-induced learning and memory impairment.

The Efficacy of Three Learning Methods Collaborative, Context-Based Learning and Traditional, on Learning, Attitude and Behaviour of Undergraduate Nursing Students: Integrating Theory and Practice

PubMed Central

Hasanpour-Dehkordi, Ali

2016-01-01

Introduction Communication skills training, responsibility, respect, and self-awareness are important indexes of changing learning behaviours in modern approaches. Aim The aim of this study was to investigate the efficacy of three learning approaches, collaborative, context-based learning (CBL), and traditional, on learning, attitude, and behaviour of undergraduate nursing students. Materials and Methods This study was a clinical trial with pretest and post-test of control group. The participants were senior nursing students. The samples were randomly assigned to three groups; CBL, collaborative, and traditional. To gather data a standard questionnaire of students’ behaviour and attitude was administered prior to and after the intervention. Also, the rate of learning was investigated by a researcher-developed questionnaire prior to and after the intervention in the three groups. Results In CBL and collaborative training groups, the mean score of behaviour and attitude increased after the intervention. But no significant association was obtained between the mean scores of behaviour and attitude prior to and after the intervention in the traditional group. However, the mean learning score increased significantly in the CBL, collaborative, and traditional groups after the study in comparison to before the study. Conclusion Both CBL and collaborative approaches were useful in terms of increased respect, self-awareness, self-evaluation, communication skills and responsibility as well as increased motivation and learning score in comparison to traditional method. PMID:27190926

CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia

PubMed Central

Makishima, Hideki; Jankowska, Anna M.; McDevitt, Michael A.; O'Keefe, Christine; Dujardin, Simon; Cazzolli, Heather; Przychodzen, Bartlomiej; Prince, Courtney; Nicoll, John; Siddaiah, Harish; Shaik, Mohammed; Szpurka, Hadrian; Hsi, Eric; Advani, Anjali; Paquette, Ronald

2011-01-01

Progression of chronic myelogenous leukemia (CML) to accelerated (AP) and blast phase (BP) is because of secondary molecular events, as well as additional cytogenetic abnormalities. On the basis of the detection of JAK2, CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations in myelodysplastic/myeloproliferative neoplasms, we hypothesized that they may also contribute to progression in CML. We screened these genes for mutations in 54 cases with CML (14 with chronic phase, 14 with AP, 20 with myeloid, and 6 with nonmyeloid BP). We identified 1 CBLB and 2 TET2 mutations in AP, and 1 CBL, 1 CBLB, 4 TET2, 2 ASXL1, and 2 IDH family mutations in myeloid BP. However, none of these mutations were found in chronic phase. No cases with JAK2V617F mutations were found. In 2 cases, TET2 mutations were found concomitant with CBLB mutations. By single nucleotide polymorphism arrays, uniparental disomy on chromosome 5q, 8q, 11p, and 17p was found in AP and BP but not involving 4q24 (TET2) or 11q23 (CBL). Microdeletions on chromosomes 17q11.2 and 21q22.12 involved tumor associated genes NF1 and RUNX1, respectively. Our results indicate that CBL family, TET2, ASXL1, and IDH family mutations and additional cryptic karyotypic abnormalities can occur in advanced phase CML. PMID:21346257

Comparison of Methods for Determining Boundary Layer Edge Conditions for Transition Correlations

NASA Technical Reports Server (NTRS)

Liechty, Derek S.; Berry, Scott A.; Hollis, Brian R.; Horvath, Thomas J.

2003-01-01

Data previously obtained for the X-33 in the NASA Langley Research Center 20-Inch Mach 6 Air Tunnel have been reanalyzed to compare methods for determining boundary layer edge conditions for use in transition correlations. The experimental results were previously obtained utilizing the phosphor thermography technique to monitor the status of the boundary layer downstream of discrete roughness elements via global heat transfer images of the X-33 windward surface. A boundary layer transition correlation was previously developed for this data set using boundary layer edge conditions calculated using an inviscid/integral boundary layer approach. An algorithm was written in the present study to extract boundary layer edge quantities from higher fidelity viscous computational fluid dynamic solutions to develop transition correlations that account for viscous effects on vehicles of arbitrary complexity. The boundary layer transition correlation developed for the X-33 from the viscous solutions are compared to the previous boundary layer transition correlations. It is shown that the boundary layer edge conditions calculated using an inviscid/integral boundary layer approach are significantly different than those extracted from viscous computational fluid dynamic solutions. The present results demonstrate the differences obtained in correlating transition data using different computational methods.

Repeated restraint stress-induced atrophy of glutamatergic pyramidal neurons and decreases in glutamatergic efflux in the rat amygdala are prevented by the antidepressant agomelatine.

PubMed

Grillo, C A; Risher, M; Macht, V A; Bumgardner, A L; Hang, A; Gabriel, C; Mocaër, E; Piroli, G G; Fadel, J R; Reagan, L P

2015-01-22

Major depressive illness is among the most prevalent neuropsychiatric disorders and is associated with neuroplasticity deficits in limbic structures such as the amygdala. Since exposure to stressful life events is proposed to contribute to depressive illness, our recent studies examined the effects of stress on amygdalar neuroplasticity. These studies determined that repeated stress elicits deficits in glutamatergic activity in the amygdala, neuroplasticity deficits that can be prevented by some but not all antidepressants. In view of these observations, the goal of the current study was to determine the effects of repeated restraint stress (RRS) on the dendritic architecture of pyramidal neurons in the rat basolateral nucleus of the amygdala (CBL), as well as glutamate efflux in the CBL and central nucleus of the amygdala (CMX) via in vivo microdialysis. We also examined the ability of the antidepressant agomelatine to prevent RRS-induced neuroplasticity deficits. Compared with control rats, rats subjected to RRS exhibited atrophy of CBL pyramidal neurons, including decreases in total dendritic length, branch points, and dendritic complexity index. In addition, glutamate efflux was significantly reduced in the CMX of rats subjected to RRS, thereby identifying a potential neurochemical consequence of stress-induced dendritic atrophy of CBL pyramidal neurons. Lastly, an acute stress challenge increased corticosterone (CORT) levels in the CBL, suggesting that stress-induced increases in CORT levels may contribute to the neuroanatomical and neurochemical effects of RRS in the CBL. Importantly, these RRS-induced changes were prevented by daily agomelatine administration. These results demonstrate that the neuroanatomical and neurochemical properties of glutamatergic neurons in the rat amygdala are adversely affected by repeated stress and suggest that the therapeutic effects of agomelatine may include protection of structural and neurochemical plasticity in limbic structures like the amygdala. Published by Elsevier Ltd.

6-Formylindolo(3,2-b)Carbazole (FICZ) Modulates the Signalsome Responsible for RA-Induced Differentiation of HL-60 Myeloblastic Leukemia Cells

PubMed Central

Bunaciu, Rodica P.; LaTocha, Dorian H.; Varner, Jeffrey D.; Yen, Andrew

2015-01-01

6-Formylindolo(3,2-b)carbazole (FICZ) is a photoproduct of tryptophan and an endogenous high affinity ligand for aryl hydrocarbon receptor (AhR). It was previously reported that, in patient-derived HL-60 myeloblastic leukemia cells, retinoic acid (RA)-induced differentiation is driven by a signalsome containing c-Cbl and AhR. FICZ enhances RA-induced differentiation, assessed by expression of the membrane differentiation markers CD38 and CD11b, cell cycle arrest and the functional differentiation marker, inducible oxidative metabolism. Moreover, FICZ augments the expression of a number of the members of the RA-induced signalsome, such as c-Cbl, Vav1, Slp76, PI3K, and the Src family kinases Fgr and Lyn. Pursuing the molecular signaling responsible for RA-induced differentiation, we characterized, using FRET and clustering analysis, associations of key molecules thought to drive differentiation. Here we report that, assayed by FRET, AhR interacts with c-Cbl upon FICZ plus RA-induced differentiation, whereas AhR constitutively interacts with Cbl-b. Moreover, correlation analysis based on the flow cytometric assessment of differentiation markers and western blot detection of signaling factors reveal that Cbl-b, p-p38α and pT390-GSK3β, are not correlated with other known RA-induced signaling components or with a phenotypic outcome. We note that FICZ plus RA elicited signaling responses that were not typical of RA alone, but may represent alternative differentiation-driving pathways. In clusters of signaling molecules seminal to cell differentiation, FICZ co-administered with RA augments type and intensity of the dynamic changes induced by RA. Our data suggest relevance for FICZ in differentiation-induction therapy. The mechanism of action includes modulation of a SFK and MAPK centered signalsome and c-Cbl-AhR association. PMID:26287494

Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs.

PubMed

Bauer, Joseph A; Frye, Gerald; Bahr, Anne; Gieg, Jennifer; Brofman, Peter

2010-10-01

Given the limited options available to treat canine cancers, the use of companion animals for evaluating new drugs may identify better therapies for veterinary and human oncology. The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12-based carrier of nitric oxide (NO), was evaluated in four dogs with spontaneous cancer. (1) A 13 year-old female spayed Giant Schnauzer with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 year-old male neutered Golden Retriever with a malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old neutered male Bichon Frise with apocrine gland anal sac adenocarcinoma (AGACA). (4) A 7 year-old female spayed Labrador mix with spinal meningioma following partial surgical resection. Tumor regression was measured by physical exam and verified using ultrasound (case 1) and MRI (case 2-4). Serum chemistries and hematologic parameters were monitored throughout the studies. (1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume after ten weeks of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 53% reduction in tumor volume after 15 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of an iliac lymph node measured by MRI after 15 months of treatment. After 61 months, the dog currently has stable disease, normal liver enzymes, CBC analysis, and no evidence of toxicity. (4) The Labrador demonstrated complete regression of the residual tumor after 6 months of treatment. We have shown previously that NO-Cbl is endocytosed by malignant cells, resulting in intra-tumoral NO release. In this study, we have shown that daily long-term use of NO-Cbl induced responses in all dogs without any signs of toxicity. The use of NO-Cbl capitalizes on the tumor-specific properties of the vitamin B12 receptor and represents a promising anti-cancer therapy.

The basic amino acids in the coiled-coil domain of CIN85 regulate its interaction with c-Cbl and phosphatidic acid during epidermal growth factor receptor (EGFR) endocytosis.

PubMed

Zheng, Xiudan; Zhang, Jing; Liao, Kan

2014-07-08

During EGFR internalization CIN85 bridges EGFR-Cbl complex, endocytic machinery and fusible membrane through the interactions of CIN85 with c-Cbl, endophilins and phosphatidic acid. These protein-protein and protein-lipid interactions are mediated or regulated by the positively charged C-terminal coiled-coil domain of CIN85. However, the details of CIN85-lipid interaction remain unknown. The present study suggested a possible electric interaction between the negative charge of phosphatidic acid and the positive charge of basic amino acids in coiled-coil domain. Mutations of the basic amino acids in the coiled-coil domain, especially K645, K646, R648 and R650, into neutral amino acid alanine completely blocked the interaction of CIN85 with c-Cbl or phosphatidic acid. However, they did not affect CIN85-endophilin interaction. In addition, CIN85 was found to associate with the internalized EGFR endosomes. It interacted with several ESCRT (Endosomal Sorting Complex Required for Transport) component proteins for ESCRT assembly on endosomal membrane. Mutations in the coiled-coil domain (deletion of the coiled-coil domain or point mutations of the basic amino acids) dissociated CIN85 from endosomes. These mutants bound the ESCRT components in cytoplasm to prevent them from assembly on endosomal membrane and inhibited EGFR sorting for degradation. As an adaptor protein, CIN85 interacts with variety of partners through several domains. The positive charges of basic amino acids in the coiled-coil domain are not only involved in the interaction with phosphatidic acid, but also regulate the interaction of CIN85 with c-Cbl. CIN85 also interacts with ESCRT components for protein sorting in endosomes. These CIN85-protein and CIN85-lipid interactions enable CIN85 to link EGFR-Cbl endocytic complex with fusible membrane during EGFR endocytosis and subsequently to facilitate ESCRT formation on endosomal membrane for EGFR sorting and degradation.

Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer's Disease.

PubMed

Sharma, Hari Shanker; Muresanu, Dafin Fior; Lafuente, José Vicente; Patnaik, Ranjana; Tian, Z Ryan; Ozkizilcik, Asya; Castellani, Rudy J; Mössler, Herbert; Sharma, Aruna

2018-01-01

Neprilysin (NPL), the rate-limiting enzyme for amyloid beta peptide (AβP), appears to play a crucial role in the pathogenesis of Alzheimer's disease (AD). Since mesenchymal stem cells (MSCs) and/or cerebrolysin (CBL, a combination of neurotrophic factors and active peptide fragments) have neuroprotective effects in various CNS disorders, we examined nanowired delivery of MSCs and CBL on NPL content and brain pathology in AD using a rat model. AD-like symptoms were produced by intraventricular (i.c.v.) administration of AβP (1-40) in the left lateral ventricle (250 ng/10 μl, once daily) for 4 weeks. After 30 days, the rats were examined for NPL and AβP concentrations in the brain and related pathology. Co-administration of TiO2-nanowired MSCs (10 6 cells) with 2.5 ml/kg CBL (i.v.) once daily for 1 week after 2 weeks of AβP infusion significantly increased the NPL in the hippocampus (400 pg/g) from the untreated control group (120 pg/g; control 420 ± 8 pg/g brain) along with a significant decrease in the AβP deposition (45 pg/g from untreated control 75 pg/g; saline control 40 ± 4 pg/g). Interestingly, these changes were much less evident when the MSCs or CBL treatment was given alone. Neuronal damages, gliosis, and myelin vesiculation were also markedly reduced by the combined treatment of TiO2, MSCs, and CBL in AD. These observations are the first to show that co-administration of TiO2-nanowired CBL and MSCs has superior neuroprotective effects in AD probably due to increasing the brain NPL level effectively, not reported earlier.

Job requirements compared to dental school education: impact of a case-based learning curriculum.

PubMed

Keeve, Philip L; Gerhards, Ute; Arnold, Wolfgang A; Zimmer, Stefan; Zöllner, Axel

2012-01-01

Case-based learning (CBL) is suggested as a key educational method of knowledge acquisition to improve dental education. The purpose of this study was to assess graduates from a patient-oriented, case-based learning (CBL)-based curriculum as regards to key competencies required at their professional activity. 407 graduates from a patient-oriented, case-based learning (CBL) dental curriculum who graduated between 1990 and 2006 were eligible for this study. 404 graduates were contacted between 2007 and 2008 to self-assess nine competencies as required at their day-to-day work and as taught in dental school on a 6-point Likert scale. Baseline demographics and clinical characteristics were presented as mean ± standard deviation (SD) for continuous variables. To determine whether dental education sufficiently covers the job requirements of physicians, we calculated the mean difference ∆ between the ratings of competencies as required in day-to-day work and as taught in medical school by subtracting those from each other (negative mean difference ∆ indicates deficit; positive mean difference ∆ indicates surplus). Spearman's rank correlation coefficient was calculated to reveal statistical significance (statistical significance p<0.05). 41.6% recipients of the questionnaire responded (n=168 graduates). A homogeneous distribution quantity of the graduate groups concerning gender, graduation date, professional experience and average examination grade was achieved.Comparing competencies required at work and taught in medical school, CBL was associated with benefits in "Research competence" (∆+0.6) "Interdisciplinary thinking" (∆+0.47), "Dental medical knowledge" (∆+0.43), "Practical dental skills" (∆+0.21), "Team work" (∆+0.16) and "Independent learning/working" (∆+0.08), whereas "Problem-solving skills" (∆-0.07), "Psycho-social competence" (∆-0.66) and "Business competence" (∆-2.86) needed improvement in the CBL-based curriculum. CBL demonstrated benefits with regard to competencies which were highly required in the job of dentists. Psycho-social and business competence deserve closer attention in future curricular development.

Combination of blood flow asymmetry in the cerebral and cerebellar hemispheres on brain perfusion SPECT predicts 5-year outcome in patients with symptomatic unilateral major cerebral artery occlusion.

PubMed

Nomura, Jun-ichi; Ogasawara, Kuniaki; Saito, Hideo; Terasaki, Kazunori; Matsumoto, Yoshiyasu; Takahashi, Yoshihiro; Ogasawara, Yasushi; Saura, Hiroaki; Yoshida, Koji; Sato, Yuiko; Kubo, Yoshitaka; Ogawa, Akira

2014-03-01

Misery perfusion increases the risk of stroke recurrence in patients with symptomatic major cerebral artery occlusion. The ratio of brain perfusion contralateral-to-affected asymmetry in the cerebellar hemisphere to brain perfusion affected-to-contralateral asymmetry in the cerebral hemisphere (CblPR/CbrPR) indicates affected-to-contralateral asymmetry of oxygen extraction fraction (OEF) in the cerebral hemisphere. The purpose of the present study was to determine whether the CblPR/CbrPR on brain perfusion single-photon emission computed tomography (SPECT) predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the middle cerebral artery (MCA) or internal carotid artery (ICA). Brain perfusion was assessed using N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) SPECT in 70 patients. A region of interest (ROI) was manually placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres, and the CblPR/CbrPR was calculated. All patients were prospectively followed for 5 years. The primary end points were stroke recurrence or death. A total of 17 patients exhibited the primary end points, 11 of whom experienced subsequent ipsilateral strokes. Multivariate analysis revealed that only high CblPR/CbrPR was significantly associated with the development of the primary end point or subsequent ipsilateral strokes (95% confidential limits [CIs], 1.130-3.145; P  =  0.0114 or 95% CIs, 2.558-5.140; P  =  0.0045, respectively). The CblPR/CbrPR provided 65% (11/17) or 91% (10/11) sensitivity and 88% (47/53) or 88% (52/59) specificity in predicting the primary end point or subsequent ipsilateral strokes, respectively. The CblPR/CbrPR on brain perfusion SPECT predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the MCA or ICA.

Separation behavior of boundary layers on three-dimensional wings

NASA Technical Reports Server (NTRS)

Stock, H. W.

1981-01-01

An inverse boundary layer procedure for calculating separated, turbulent boundary layers at infinitely long, crabbing wing was developed. The procedure was developed for calculating three dimensional, incompressible turbulent boundary layers was expanded to adiabatic, compressible flows. Example calculations with transsonic wings were made including viscose effects. In this case an approximated calculation method described for areas of separated, turbulent boundary layers, permitting calculation of this displacement thickness. The laminar boundary layer development was calculated with inclined ellipsoids.

Summary of experimentally determined facts concerning the behavior of the boundary layer and performance of boundary layer measurements. [considering sailing flight

NASA Technical Reports Server (NTRS)

Vanness, W.

1978-01-01

A summary report of boundary layer studies is presented. Preliminary results of experimental measurements show that: (1) A very thin layer (approximately 0.4 mm) of the boundary layer seems to be accelerated; (2) the static pressure of the outer flow does not remain exactly constant through the boundary layer; and (3) an oncoming boundary layer which is already turbulent at the suction point can again become laminar behind this point without being completely sucked off.

Orbiter Entry Aeroheating Working Group Viscous CFD Boundary Layer Transition Trailblazer Solutions

NASA Technical Reports Server (NTRS)

Wood, William A.; Erickson, David W.; Greene, Francis A.

2007-01-01

Boundary layer transition correlations for the Shuttle Orbiter have been previously developed utilizing a two-layer boundary layer prediction technique. The particular two-layer technique that was used is limited to Mach numbers less than 20. To allow assessments at Mach numbers greater than 20, it is proposed to use viscous CFD to the predict boundary layer properties. This report addresses if the existing Orbiter entry aeroheating viscous CFD solutions, which were originally intended to be used for heat transfer rate predictions, adequately resolve boundary layer edge properties and if the existing two-layer results could be leveraged to reduce the number of needed CFD solutions. The boundary layer edge parameters from viscous CFD solutions are extracted along the wind side centerline of the Space Shuttle Orbiter at reentry conditions, and are compared with results from the two-layer boundary layer prediction technique. The differences between the viscous CFD and two-layer prediction techniques vary between Mach 6 and 18 flight conditions and Mach 6 wind tunnel conditions, and there is not a straightforward scaling between the viscous CFD and two-layer values. Therefore: it is not possible to leverage the existing two-layer Orbiter flight boundary layer data set as a substitute for a viscous CFD data set; but viscous CFD solutions at the current grid resolution are sufficient to produce a boundary layer data set suitable for applying edge-based boundary layer transition correlations.

Teachers' Thoughts on Student Decision Making during Engineering Design Lessons

ERIC Educational Resources Information Center

Meyer, Helen

2018-01-01

In this paper, I share the results of a study of teachers' ideas about student decision-making at entry into a professional development program to integrate engineering into their instruction. The framework for the Engineering Design Process (EDP) was based on a Challenge-Based Learning (CBL) model. The EDP embedded within the CBL model suggests…

Calculation methods for compressible turbulent boundary layers, 1976

NASA Technical Reports Server (NTRS)

Bushnell, D. M.; Cary, A. M., Jr.; Harris, J. E.

1977-01-01

Equations and closure methods for compressible turbulent boundary layers are discussed. Flow phenomena peculiar to calculation of these boundary layers were considered, along with calculations of three dimensional compressible turbulent boundary layers. Procedures for ascertaining nonsimilar two and three dimensional compressible turbulent boundary layers were appended, including finite difference, finite element, and mass-weighted residual methods.

A general integral form of the boundary-layer equation for incompressible flow with an application to the calculation of the separation point of turbulent boundary layers

NASA Technical Reports Server (NTRS)

Tetervin, Neal; Lin, Chia Chiao

1951-01-01

A general integral form of the boundary-layer equation, valid for either laminar or turbulent incompressible boundary-layer flow, is derived. By using the experimental finding that all velocity profiles of the turbulent boundary layer form essentially a single-parameter family, the general equation is changed to an equation for the space rate of change of the velocity-profile shape parameter. The lack of precise knowledge concerning the surface shear and the distribution of the shearing stress across turbulent boundary layers prevented the attainment of a reliable method for calculating the behavior of turbulent boundary layers.

Microgravity Effects on Plant Boundary Layers

NASA Technical Reports Server (NTRS)

Stutte, Gary; Monje, Oscar

2005-01-01

The goal of these series of experiment was to determine the effects of microgravity conditions on the developmental boundary layers in roots and leaves and to determine the effects of air flow on boundary layer development. It is hypothesized that microgravity induces larger boundary layers around plant organs because of the absence of buoyancy-driven convection. These larger boundary layers may affect normal metabolic function because they may reduce the fluxes of heat and metabolically active gases (e.g., oxygen, water vapor, and carbon dioxide. These experiments are to test whether there is a change in boundary layer associated with microgravity, quantify the change if it exists, and determine influence of air velocity on boundary layer thickness under different gravity conditions.

Boundary layer friction of solvate ionic liquids as a function of potential.

PubMed

Li, Hua; Rutland, Mark W; Watanabe, Masayoshi; Atkin, Rob

2017-07-01

Atomic force microscopy (AFM) has been used to investigate the potential dependent boundary layer friction at solvate ionic liquid (SIL)-highly ordered pyrolytic graphite (HOPG) and SIL-Au(111) interfaces. Friction trace and retrace loops of lithium tetraglyme bis(trifluoromethylsulfonyl)amide (Li(G4) TFSI) at HOPG present clearer stick-slip events at negative potentials than at positive potentials, indicating that a Li + cation layer adsorbed to the HOPG lattice at negative potentials which enhances stick-slip events. The boundary layer friction data for Li(G4) TFSI shows that at HOPG, friction forces at all potentials are low. The TFSI - anion rich boundary layer at positive potentials is more lubricating than the Li + cation rich boundary layer at negative potentials. These results suggest that boundary layers at all potentials are smooth and energy is predominantly dissipated via stick-slip events. In contrast, friction at Au(111) for Li(G4) TFSI is significantly higher at positive potentials than at negative potentials, which is comparable to that at HOPG at the same potential. The similarity of boundary layer friction at negatively charged HOPG and Au(111) surfaces indicates that the boundary layer compositions are similar and rich in Li + cations for both surfaces at negative potentials. However, at Au(111), the TFSI - rich boundary layer is less lubricating than the Li + rich boundary layer, which implies that anion reorientations rather than stick-slip events are the predominant energy dissipation pathways. This is confirmed by the boundary friction of Li(G4) NO 3 at Au(111), which shows similar friction to Li(G4) TFSI at negative potentials due to the same cation rich boundary layer composition, but even higher friction at positive potentials, due to higher energy dissipation in the NO 3 - rich boundary layer.

Turbulent Combustion Study of Scramjet Problem

DTIC Science & Technology

2015-08-01

boundary layer model for 2D simulations of a supersonic flat plate boundary layer . The inflow O2 has an average density of...flow above the flat plate has a transition from a laminar boundary layer to a turbulent boundary layer at a position downstream from the inlet. The...δ. Chapman [13] estimated the number of cells need to resolve the outer layer is proportional to Re0.4 for flat plat boundary layer and

The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells

PubMed Central

Ibabao, Christopher N.; Bunaciu, Rodica P.; Schaefer, Deanna M.W.; Yen, Andrew

2015-01-01

In binary cell-fate decisions, driving one lineage and suppressing the other are conjoined. We have previously reported that aryl hydrocarbon receptor (AhR) promotes retinoic acid (RA)-induced granulocytic differentiation of lineage bipotent HL-60 myeloblastic leukemia cells. VAF347, an AhR agonist, impairs the development of CD14+CD11b+ monocytes from granulo-monocytic (GM) stage precursors. We thus hypothesized that VAF347 propels RA-induced granulocytic differentiation and impairs D3-induced monocytic differentiation of HL-60 cells. Our results show that VAF347 enhanced RA-induced cell cycle arrest, CD11b integrin expression and neutrophil respiratory burst. Granulocytic differentiation is known to be driven by MAPK signaling events regulated by Fgr and Lyn Src-family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c-Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome. We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47phox. Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn. Thus, we report that, while VAF347 impedes monocytic differentiation induced by 1,25-dihydroxyvitamin D3, VAF347 promotes RA-induced differentiation. This effect seems to involve but not to be limited to Lyn, Vav1, c-Cbl, AhR, and Fgr. PMID:25941627

The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells.

PubMed

Ibabao, Christopher N; Bunaciu, Rodica P; Schaefer, Deanna M W; Yen, Andrew

2015-01-01

In binary cell-fate decisions, driving one lineage and suppressing the other are conjoined. We have previously reported that aryl hydrocarbon receptor (AhR) promotes retinoic acid (RA)-induced granulocytic differentiation of lineage bipotent HL-60 myeloblastic leukemia cells. VAF347, an AhR agonist, impairs the development of CD14(+)CD11b(+) monocytes from granulo-monocytic (GM) stage precursors. We thus hypothesized that VAF347 propels RA-induced granulocytic differentiation and impairs D3-induced monocytic differentiation of HL-60 cells. Our results show that VAF347 enhanced RA-induced cell cycle arrest, CD11b integrin expression and neutrophil respiratory burst. Granulocytic differentiation is known to be driven by MAPK signaling events regulated by Fgr and Lyn Src-family kinases, the CD38 cell membrane receptor, the Vav1 GEF, the c-Cbl adaptor, as well as AhR, all of which are embodied in a putative signalsome. We found that the VAF347 AhR ligand regulates the signalsome. VAF347 augments RA-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47(phox). Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn. Thus, we report that, while VAF347 impedes monocytic differentiation induced by 1,25-dihydroxyvitamin D3, VAF347 promotes RA-induced differentiation. This effect seems to involve but not to be limited to Lyn, Vav1, c-Cbl, AhR, and Fgr.

Heterozygous Germline Mutations in the CBL Tumor-Suppressor Gene Cause a Noonan Syndrome-like Phenotype

PubMed Central

Martinelli, Simone; De Luca, Alessandro; Stellacci, Emilia; Rossi, Cesare; Checquolo, Saula; Lepri, Francesca; Caputo, Viviana; Silvano, Marianna; Buscherini, Francesco; Consoli, Federica; Ferrara, Grazia; Digilio, Maria C.; Cavaliere, Maria L.; van Hagen, Johanna M.; Zampino, Giuseppe; van der Burgt, Ineke; Ferrero, Giovanni B.; Mazzanti, Laura; Screpanti, Isabella; Yntema, Helger G.; Nillesen, Willy M.; Savarirayan, Ravi; Zenker, Martin; Dallapiccola, Bruno; Gelb, Bruce D.; Tartaglia, Marco

2010-01-01

RAS signaling plays a key role in controlling appropriate cell responses to extracellular stimuli and participates in early and late developmental processes. Although enhanced flow through this pathway has been established as a major contributor to oncogenesis, recent discoveries have revealed that aberrant RAS activation causes a group of clinically related developmental disorders characterized by facial dysmorphism, a wide spectrum of cardiac disease, reduced growth, variable cognitive deficits, ectodermal and musculoskeletal anomalies, and increased risk for certain malignancies. Here, we report that heterozygous germline mutations in CBL, a tumor-suppressor gene that is mutated in myeloid malignancies and encodes a multivalent adaptor protein with E3 ubiquitin ligase activity, can underlie a phenotype with clinical features fitting or partially overlapping Noonan syndrome (NS), the most common condition of this disease family. Independent CBL mutations were identified in two sporadic cases and two families from among 365 unrelated subjects who had NS or suggestive features and were negative for mutations in previously identified disease genes. Phenotypic heterogeneity and variable expressivity were documented. Mutations were missense changes altering evolutionarily conserved residues located in the RING finger domain or the linker connecting this domain to the N-terminal tyrosine kinase binding domain, a known mutational hot spot in myeloid malignancies. Mutations were shown to affect CBL-mediated receptor ubiquitylation and dysregulate signal flow through RAS. These findings document that germline mutations in CBL alter development to cause a clinically variable condition that resembles NS and that possibly predisposes to malignancies. PMID:20619386

A method of developing and introducing case-based learning to a preclinical veterinary curriculum.

PubMed

Crowther, Emma; Baillie, Sarah

2016-01-01

Case-based learning (CBL) has been introduced as part of a major review of the veterinary curriculum at the University of Bristol. The initial aim was to improve integration between all first year subjects, i.e., basic science disciplines (anatomy, physiology, and biochemistry), animal management, and professional studies, while highlighting the relevance by providing clinical context. The CBL was delivered as whole class sessions in a lecture theatre, as small group teaching facilities were not readily available, co-facilitated by two to four basic scientists and clinicians. Active learning tasks were included by using an audience response system and encouraging discussion. A case template was developed in PowerPoint and then populated by basic science and clinical staff in an iterative design process. Comments from a student focus group informed the design of the case sessions. Feedback collected from students via a survey after the first three cases suggested that CBL was well received and assisted students in integrating material taught in the first year units and was used to further improve the ongoing case design. The project team developed eight cases for Year 1 and is implementing CBL in various formats throughout the curriculum. There was a considerable time commitment in developing each case; however, the use of readily available software and the large group format overcame limitations, including resourcing small group sessions. This article reports a model that could be successfully adapted by other institutions wishing to use CBL to provide clinical context and promote integration of the basic sciences. © 2015 American Association of Anatomists.

Graphing Calculators, the CBL2[TM] and TI-Interactive[TM] in High School Science.

ERIC Educational Resources Information Center

Molnar, Bill

This collection of activities is designed to show how TI-Interactive[TM] and Calculator-based Laboratories (CBL) can be used to explore topics in high school science. The activities address such topics as specific heat, Boyle's Law, Newton's Law of Cooling, and Antarctic Ozone Levels. Teaching notes and calculator instructions are included as are…

Assessment in the Use of Excel Competency for Problem Solving Using the Approach of Expert and Novice Theory

ERIC Educational Resources Information Center

Gallardo, Katherina Edith; González, Jaime Ricardo Valenzuela

2014-01-01

The assessment of Competency-­Based Learning (CBL) generally lacks a foundation to guide the construction of instruments that accords the nature and goals of this educational model. The measurement instruments normally used in CBL only provide a numerical score with limited information about the levels of competencies reached. This research aims…

Promoting Graphical Thinking: Using Temperature and a Graphing Calculator to Teach Kinetics Concepts

ERIC Educational Resources Information Center

Cortes-Figueroa, Jose E.; Moore-Russo, Deborah A.

2004-01-01

A combination of graphical thinking with chemical and physical theories in the classroom is encouraged by using the Calculator-Based Laboratory System (CBL) with a temperature sensor and graphing calculator. The theory of first-order kinetics is logically explained with the aid of the cooling or heating of the metal bead of the CBL's temperature…

The Effectiveness of CBL Model to Improve Analytical Thinking Skills the Students of Sport Science

ERIC Educational Resources Information Center

Sudibyo, Elok; Jatmiko, Budi; Widodo, Wahono

2016-01-01

Sport science undergraduate education, one of which purposes is to produce an analyst in sport. However, generally analytical thinking skills of sport science's students is still relatively very low in the context of sport. This study aimed to describe the effectiveness of Physics Learning Model in Sport Context, Context Based Learning (CBL)…

Comparison of Expert-Based and Empirical Evaluation Methodologies in the Case of a CBL Environment: The ''Orestis'' Experience

ERIC Educational Resources Information Center

Karoulis, Athanasis; Demetriadis, Stavros; Pombortsis, Andreas

2006-01-01

This paper compares several interface evaluation methods applied in the case of a computer based learning (CBL) environment, during a longitudinal study performed in three European countries, Greece, Germany, and Holland, and within the framework of an EC funded Leonardo da Vinci program. The paper firstly considers the particularities of the CBL…

Investigative cases and student outcomes in an upper-division cell and molecular biology laboratory course at a minority-serving institution.

PubMed

Knight, Jonathan D; Fulop, Rebecca M; Márquez-Magaña, Leticia; Tanner, Kimberly D

2008-01-01

Active-learning strategies are increasingly being integrated into college-level science courses to make material more accessible to all students and to improve learning outcomes. One active-learning pedagogy, case-based learning (CBL), was developed as a way to both enhance engagement in the material and to accommodate diverse learning styles. Yet, adoption of CBL approaches in undergraduate biology courses has been piecemeal, in part because of the perceived investment of time required. Furthermore, few CBL lesson plans have been developed specifically for upper-division laboratory courses. Here, we describe four cases that we developed and implemented for a senior cell and molecular biology laboratory course at San Francisco State University, a minority-serving institution. To evaluate the effectiveness of these modules, we used both written and verbal assessments to gauge learning outcomes and attitudinal responses of students over two semesters. Students responded positively to the new approach and seemed to meet the learning goals for the course. Most said they would take a course using CBL again. These case modules are readily adaptable to a variety of classroom settings.

Investigative Cases and Student Outcomes in an Upper-Division Cell and Molecular Biology Laboratory Course at a Minority-serving Institution

PubMed Central

Fulop, Rebecca M.; Márquez-Magaña, Leticia; Tanner, Kimberly D.

2008-01-01

Active-learning strategies are increasingly being integrated into college-level science courses to make material more accessible to all students and to improve learning outcomes. One active-learning pedagogy, case-based learning (CBL), was developed as a way to both enhance engagement in the material and to accommodate diverse learning styles. Yet, adoption of CBL approaches in undergraduate biology courses has been piecemeal, in part because of the perceived investment of time required. Furthermore, few CBL lesson plans have been developed specifically for upper-division laboratory courses. Here, we describe four cases that we developed and implemented for a senior cell and molecular biology laboratory course at San Francisco State University, a minority-serving institution. To evaluate the effectiveness of these modules, we used both written and verbal assessments to gauge learning outcomes and attitudinal responses of students over two semesters. Students responded positively to the new approach and seemed to meet the learning goals for the course. Most said they would take a course using CBL again. These case modules are readily adaptable to a variety of classroom settings. PMID:19047425

Adsorption of 1-naphthyl methyl carbamate in water by utilizing a surface molecularly imprinted polymer

NASA Astrophysics Data System (ADS)

So, Juhyok; Pang, Cholho; Dong, Hongxing; Jang, Paeksan; U, Juhyok; Ri, Kumchol; Yun, Cholyong

2018-05-01

Surface molecularly imprinting polymer (SMIP) was utilized in the removal of a residual pesticide (carbaryl (CBL)) in water and simulated fruit juice. Being the crosslinking agent, ethylene glycol dimethacrylate (EGDMA) was copolymerized with the monomer, methacrylic acid (MAA) and CBL as the template molecules on the surface of the silica gel particles to produce the SMIP adsorbents. The SMIP adsorbents showed good selectivity and good adsorption capacity for CBL in the competitive adsorptions with two structurally related carbamate pesticides. The effect of the pretreatment solvents on the adsorption capacity of the SMIP adsorbent was investigated with the results of the numerical simulations. The adsorption isotherms and the adsorption kinetics were well described by the Freundlich equilibrium model and the pseudo-second-order kinetic model, respectively. Scatchard plot analysis revealed that there were two classes of binding sites populated in the SMIP adsorbents. In addition, the good selective adsorption of CBL by the SMIP adsorbent in a simulated fruit juice containing vitamin C and fructose indicated the great potential of the SMIP adsorbents to remove residual pesticide in food industry and processing industry for agricultural products.

MMACHC gene mutation in familial hypogonadism with neurological symptoms.

PubMed

Shi, Changhe; Shang, Dandan; Sun, Shilei; Mao, Chengyuan; Qin, Jie; Luo, Haiyang; Shao, Mingwei; Chen, Zhengguang; Liu, Yutao; Liu, Xinjing; Song, Bo; Xu, Yuming

2015-12-15

Recent studies have convincingly documented that hypogonadism is a component of various hereditary disorders and is often recognized as an important clinical feature in combination with various neurological symptoms, yet, the causative genes in a few related families are still unknown. High-throughput sequencing has become an efficient method to identify causative genes in related complex hereditary disorders. In this study, we performed exome sequencing in a family presenting hypergonadotropic hypogonadism with neurological presentations of mental retardation, epilepsy, ataxia, and leukodystrophy. After bioinformatic analysis and Sanger sequencing validation, we identified compound heterozygous mutations: c.482G>A (p.R161Q) and c.609G>A (p.W203X) in MMACHC gene in this pedigree. MMACHC was previously confirmed to be responsible for methylmalonic aciduria (MMA) combined with homocystinuria, cblC type (cblC disease), a hereditary vitamin B12 metabolic disorder. Biochemical and gas chromatography-mass spectrometry (GC-MS) examinations in this pedigree further supported the cblC disease diagnosis. These results indicated that hypergonadotropic hypogonadism may be a novel clinical manifestation of cblC disease, but more reports on additional patients are needed to support this hypothesis. Copyright © 2015 Elsevier B.V. All rights reserved.

Free-stream disturbance, continuous Eigenfunctions, boundary-layer instability and transition

NASA Technical Reports Server (NTRS)

Grosch, C. E.

1980-01-01

A rational foundation is presented for the application of the linear shear flows to transition prediction, and an explicit method is given for carrying out the necessary calculations. The expansions used are shown to be complete. Sample calculations show that a typical boundary layer is very sensitive to vorticity disturbances in the inner boundary layer, near the critical layer. Vorticity disturbances three or four boundary layer thicknesses above the boundary are nearly uncoupled from the boundary layer in that the amplitudes of the discrete Tollmien-Schlicting waves are an extremely small fraction of the amplitude of the disturbance.

Amelioration of CCl4 induced liver injury in swiss albino mice by antioxidant rich leaf extract of Croton bonplandianus Baill.

PubMed

Dutta, Somit; Chakraborty, Arnab Kumar; Dey, Priyankar; Kar, Pallab; Guha, Pokhraj; Sen, Subhajit; Kumar, Anoop; Sen, Arnab; Chaudhuri, Tapas Kumar

2018-01-01

The progress in industrialization has blessed mankind with a technologically superior lifestyle but poor management of industrial waste has in turn poisoned nature. One such chemical is carbon tetra chloride (CCl4), which is a potent environmental toxin emitted from chemical industries and its presence in the atmosphere is increasing at an alarming rate. Presence of CCl4 in human body is reported to cause liver damage through free radical mediated inflammatory processes. Kupffer cells present in the liver are potentially more sensitive to oxidative stress than hepatocytes. Kuffer cells produced tumor necrosis factor-α (TNF-α) in response to reactive oxygen species (ROS), that might further cause inflammation or apoptosis. In this study hepatoprotective capacity of antioxidant rich extract of Croton bonplandianus Baill. (CBL) was evaluated on CCl4 induced acute hepatotoxicity in murine model. Hydro-methanolic extract of C. bonplandianus leaf was used for evaluation of free radical scavenging activity. Liver cells of experimental mice were damaged using CCl4 and subsequently hepatoprotective potential of the plant extract was evaluated using series of in-vivo and in-vitro studies. In the hepatoprotective study, silymarin was used as a positive control. Antioxidant enzymes, pro-inflammatory markers, liver enzymatic and biochemical parameters were studied to evaluate hepatoprotective activity of Croton bonplandianus leaf extract. Free radical scavenging activity of CBL extract was also observed in WRL-68 cell line. The phytochemicals identified by GCMS analysis were scrutinized using in-silico molecular docking procedure. The results showed that CBL extract have potent free radical scavenging capacity. The biochemical parameters were over expressed due to CCl4 administration, which were significantly normalized by CBL extract treatment. This finding was also supported by histopathological evidences showing less hepatocellularnecrosis, inflammation and fibrosis in CBL and silymarin treated group, compared to CCl4 group. ROS generated due to H2O2 in WRL-68 cell line were normalize in the highest group (200 μg/ml) when compared with control and negative control (CCl4) group. After molecular docking analysis, it was observed that the compound α-amyrin present in the leaf extract of C. bonplandianus has better potentiality to protect hepatocellular damages than the standard drug Silymarin. The present study provided supportive evidence that CBL extract possesses potent hepatoprotective capacity by ameliorating haloalkane induced liver injury in the murine model. The antioxidant and anti-inflammatory activities also affirm the same. The synergistic effects of the phytochemicals present in CBL are to be credited for all the hepatoprotective activity claimed above.

Amelioration of CCl4 induced liver injury in swiss albino mice by antioxidant rich leaf extract of Croton bonplandianus Baill.

PubMed Central

Dutta, Somit; Chakraborty, Arnab Kumar; Dey, Priyankar; Kar, Pallab; Guha, Pokhraj; Sen, Subhajit; Kumar, Anoop; Sen, Arnab

2018-01-01

The progress in industrialization has blessed mankind with a technologically superior lifestyle but poor management of industrial waste has in turn poisoned nature. One such chemical is carbon tetra chloride (CCl4), which is a potent environmental toxin emitted from chemical industries and its presence in the atmosphere is increasing at an alarming rate. Presence of CCl4 in human body is reported to cause liver damage through free radical mediated inflammatory processes. Kupffer cells present in the liver are potentially more sensitive to oxidative stress than hepatocytes. Kuffer cells produced tumor necrosis factor-α (TNF-α) in response to reactive oxygen species (ROS), that might further cause inflammation or apoptosis. In this study hepatoprotective capacity of antioxidant rich extract of Croton bonplandianus Baill. (CBL) was evaluated on CCl4 induced acute hepatotoxicity in murine model. Hydro-methanolic extract of C. bonplandianus leaf was used for evaluation of free radical scavenging activity. Liver cells of experimental mice were damaged using CCl4 and subsequently hepatoprotective potential of the plant extract was evaluated using series of in-vivo and in-vitro studies. In the hepatoprotective study, silymarin was used as a positive control. Antioxidant enzymes, pro-inflammatory markers, liver enzymatic and biochemical parameters were studied to evaluate hepatoprotective activity of Croton bonplandianus leaf extract. Free radical scavenging activity of CBL extract was also observed in WRL-68 cell line. The phytochemicals identified by GCMS analysis were scrutinized using in-silico molecular docking procedure. The results showed that CBL extract have potent free radical scavenging capacity. The biochemical parameters were over expressed due to CCl4 administration, which were significantly normalized by CBL extract treatment. This finding was also supported by histopathological evidences showing less hepatocellularnecrosis, inflammation and fibrosis in CBL and silymarin treated group, compared to CCl4 group. ROS generated due to H2O2 in WRL-68 cell line were normalize in the highest group (200 μg/ml) when compared with control and negative control (CCl4) group. After molecular docking analysis, it was observed that the compound α-amyrin present in the leaf extract of C. bonplandianus has better potentiality to protect hepatocellular damages than the standard drug Silymarin. The present study provided supportive evidence that CBL extract possesses potent hepatoprotective capacity by ameliorating haloalkane induced liver injury in the murine model. The antioxidant and anti-inflammatory activities also affirm the same. The synergistic effects of the phytochemicals present in CBL are to be credited for all the hepatoprotective activity claimed above. PMID:29709010

Analysis of turbulent free-convection boundary layer on flat plate

NASA Technical Reports Server (NTRS)

Eckert, E R G; Jackson, Thomas W

1950-01-01

A calculation was made for the flow and heat transfer in the turbulent free-convection boundary layer on a vertical flat plate. Formulas for the heat-transfer coefficient, boundary layer thickness, and the maximum velocity in the boundary layer were obtained.

Observations of the magnetopause current layer: Cases with no boundary layer and tests of recent models

NASA Technical Reports Server (NTRS)

Eastman, Timothy E.

1995-01-01

Evidence for the probable existence of magnetospheric boundary layers was first presented by Hones, et al. (1972), based on VELA satellite plasma observations (no magnetic field measurements were obtained). This magnetotail boundary layer is now known to be the tailward extension of the high-latitude boundary layer or plasma mantle (first uniquely identified using HEOS 2 plasma and field observations by Rosenbauer et al., 1975) and the low-latitude boundary layer (first uniquely identified using IMP 6 plasma and field observations by Eastman et al., 1976). The magnetospheric boundary layer is the region of magnetosheath-like plasma located Earthward of, but generally contiguous with the magnetopause. This boundary layer is typically identified by comparing low-energy (less than 10 keV) ion spectra across the magnetopause. Low-energy electron measurements are also useful for identifying the boundary layer because the shocked solar wind or magnetosheath has a characteristic spectral signature for electrons as well. However, there are magnetopause crossings where low-energy electrons might suggest a depletion layer outside the magnetopause even though the traditional field-rotation signature indicates that this same region is a boundary layer Earthward of the current layer. Our analyses avoided crossings which exhibit such ambiguities. Pristine magnetopause crossings are magnetopause crossings for which the current layer is well defined and for which there is no adjoining magnetospheric boundary layer as defined above. Although most magnetopause models to date apply to such crossings, few comparisons between such theory and observations of pristine magnetopause crossings have been made because most crossings have an associated magnetospheric boundary layer which significantly affects the applicable boundary conditions for the magnetopause current layer. Furthermore, almost no observational studies of magnetopause microstructure have been done even though key theoretical issues have been discussed for over two decades. This is because plasma instruments deployed prior to the ISEE and AMPTE missions did not have the required time resolution and most ISEE investigations to-date have focused on tests of MHD plasma models, especially reconnection. More recently, many phenomenological and theoretical models have been developed to explain the existence and characteristics of the magnetospheric boundary layers with only limited success to date. The cases with no boundary layer treated in this study provide a contrary set of conditions to those observed with a boundary layer. For the measured parameters of such cases, a successful boundary layer model should predict no plasma penetration across the magnetopause. Thus, this research project provides the first direct observational tests of magnetopause models using pristine magnetopause crossings and provides important new results on magnetopause microstructure and associated kinetic processes.

Is Case-Based Learning an Effective Teaching Strategy to Challenge Students' Alternative Conceptions regarding Chemical Kinetics?

ERIC Educational Resources Information Center

Yalcinkaya, Eylem; Tastan-Kirik, Ozgecan; Boz, Yezdan; Yildiran, Demet

2012-01-01

Background: Case-based learning (CBL) is simply teaching the concept to the students based on the cases. CBL involves a case, which is a scenario based on daily life, and study questions related to the case, which allows students to discuss their ideas. Chemical kinetics is one of the most difficult concepts for students in chemistry. Students…

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

Schumaker, Karen S

The long-term goal of our experiments was to understand mechanisms that regulate energy coupling by ion currents in plants. Activities of living organisms require chemical, mechanical, osmotic or electrical work, the energy for which is supplied by metabolism. Adenosine triphosphate (ATP) has long been recognized as the universal energy currency, with metabolism supporting the synthesis of ATP and the hydrolysis of ATP being used for the subsequent work. However, ATP is not the only energy currency in living organisms. A second and very different energy currency links metabolism to work by the movement of ions passing from one side ofmore » a membrane to the other. These ion currents play a major role in energy capture and they support a range of physiological processes from the active transport of nutrients to the spatial control of growth and development. In Arabidopsis thaliana (Arabidopsis), the activity of a plasma membrane Na+/H+ exchanger, SALT OVERLY SENSITIVE1 (SOS1), is essential for regulation of sodium ion homeostasis during plant growth in saline conditions. Mutations in SOS1 result in severely reduced seedling growth in the presence of salt compared to the growth of wild type. SOS1 is a secondary active transporter coupling movement of sodium ions out of the cell using energy stored in the transplasma membrane proton gradient, thereby preventing the build-up of toxic levels of sodium in the cytosol. SOS1 is regulated by complexes containing the SOS2 and CALCINEURIN B-LIKE10 (CBL10) or SOS3 proteins. CBL10 and SOS3 (also identified as CBL4) encode EF-hand calcium sensors that interact physically with and activate SOS2, a serine/threonine protein kinase. The CBL10/SOS2 or SOS3/SOS2 complexes then activate SOS1 Na+/H+ exchange activity. We completed our studies to understand how SOS1 activity is regulated. Specifically, we asked: (1) how does CBL10 regulate SOS1 activity? (2) What role do two putative CBL10-interacting proteins play in SOS1 regulation? (3) Are there differences in the regulation and/or activity of SOS1 in plants differing in their adaptation to salinity?« less

The basic amino acids in the coiled-coil domain of CIN85 regulate its interaction with c-Cbl and phosphatidic acid during epidermal growth factor receptor (EGFR) endocytosis

PubMed Central

2014-01-01

Background During EGFR internalization CIN85 bridges EGFR-Cbl complex, endocytic machinery and fusible membrane through the interactions of CIN85 with c-Cbl, endophilins and phosphatidic acid. These protein-protein and protein-lipid interactions are mediated or regulated by the positively charged C-terminal coiled-coil domain of CIN85. However, the details of CIN85-lipid interaction remain unknown. The present study suggested a possible electric interaction between the negative charge of phosphatidic acid and the positive charge of basic amino acids in coiled-coil domain. Results Mutations of the basic amino acids in the coiled-coil domain, especially K645, K646, R648 and R650, into neutral amino acid alanine completely blocked the interaction of CIN85 with c-Cbl or phosphatidic acid. However, they did not affect CIN85-endophilin interaction. In addition, CIN85 was found to associate with the internalized EGFR endosomes. It interacted with several ESCRT (Endosomal Sorting Complex Required for Transport) component proteins for ESCRT assembly on endosomal membrane. Mutations in the coiled-coil domain (deletion of the coiled-coil domain or point mutations of the basic amino acids) dissociated CIN85 from endosomes. These mutants bound the ESCRT components in cytoplasm to prevent them from assembly on endosomal membrane and inhibited EGFR sorting for degradation. Conclusions As an adaptor protein, CIN85 interacts with variety of partners through several domains. The positive charges of basic amino acids in the coiled-coil domain are not only involved in the interaction with phosphatidic acid, but also regulate the interaction of CIN85 with c-Cbl. CIN85 also interacts with ESCRT components for protein sorting in endosomes. These CIN85-protein and CIN85-lipid interactions enable CIN85 to link EGFR-Cbl endocytic complex with fusible membrane during EGFR endocytosis and subsequently to facilitate ESCRT formation on endosomal membrane for EGFR sorting and degradation. PMID:25005938

Measurements and Modeling of the Mean and Turbulent Flow Structure in High-Speed Rough-Wall Non-Equilibrium Boundary Layers

DTIC Science & Technology

2010-01-25

study builds on three basic bodies of knowledge: (1) supersonic rough wall boundary layers, (2) distorted supersonic turbulent boundary layers, and...with the boundary layer turbulence . The present study showed that secondary distortions associated with such waves significantly affect the transport...38080 14. ABSTRACT The response of a supersonic high Reynolds number turbulent boundary layer flow subjected to mechanical distortions was

Understanding the Fundamental Roles of Momentum and Vorticity Injections in Flow Control

DTIC Science & Technology

2016-09-02

production by pitched and skewed jets in a turbulent boundary layer . AIAA Journal 30, 640–647. DISTRIBUTION A: Distribution approved for public release...adverse pressure gradient along the suction surface, which ultimately results in a separated boundary layer . Such behavior of the boundary layer can... boundary layer either directly or by utilizing free stream momentum to energize the boundary layer (Gad-el-Hak, 2000a). Directly adding momentum to the

Effect of an isolated semi-arid pine forest on the boundary layer height

NASA Astrophysics Data System (ADS)

Brugger, Peter; Banerjee, Tirtha; Kröniger, Konstantin; Preisler, Yakir; Rotenberg, Eyal; Tatarinov, Fedor; Yakir, Dan; Mauder, Matthias

2017-04-01

Forests play an important role for earth's climate by influencing the surface energy balance and CO2 concentrations in the atmosphere. Semi-arid forests and their effects on the local and regional climate are studied within the CliFF project (Climate Feedbacks and benefits of semi-arid Forests). This requires understanding of the atmospheric boundary layer over semi-arid forests, because it links the surface and the free atmosphere and determines the exchange of momentum, heat and trace gases. Our study site, Yatir, is a semi-arid isolated pine forest in the Negev desert in Israel. Higher roughness and lower albedo compared to the surrounding shrubland make it interesting to study the influences of the semi-arid Yatir forest on the boundary layer. Previous studies of the forest focused on the energy balance and secondary circulations. This study focuses on the boundary layer structure above the forest, in particular the boundary layer height. The boundary layer height is an essential parameter for many applications (e.g. construction of convective scaling parameters or air pollution modeling). We measured the boundary layer height upwind, over and downwind of the forest. In addition we measured at two sites wind profiles within the boundary layer and turbulent fluxes at the surface. This allows us to quantify the effects of the forest on boundary layer compared to the surrounding shrubland. Results show that the forest increases the boundary layer height in absence of a strong boundary layer top inversion. A model of the boundary layer height based on eddy-covariance data shows some agreement to the measurements, but fails during anticyclonic conditions and the transition to the nocturnal boundary layer. More complex models accounting for large scale influences are investigated. Further influences of the forest and surrounding shrubland on the turbulent transport of energy are discussed in a companion presentation (EGU2017-2219).

Spatial Linear Instability of Confluent Wake/Boundary Layers

NASA Technical Reports Server (NTRS)

Liou, William W.; Liu, Feng-Jun; Rumsey, C. L. (Technical Monitor)

2001-01-01

The spatial linear instability of incompressible confluent wake/boundary layers is analyzed. The flow model adopted is a superposition of the Blasius boundary layer and a wake located above the boundary layer. The Orr-Sommerfeld equation is solved using a global numerical method for the resulting eigenvalue problem. The numerical procedure is validated by comparing the present solutions for the instability of the Blasius boundary layer and for the instability of a wake with published results. For the confluent wake/boundary layers, modes associated with the boundary layer and the wake, respectively, are identified. The boundary layer mode is found amplified as the wake approaches the wall. On the other hand, the modes associated with the wake, including a symmetric mode and an antisymmetric mode, are stabilized by the reduced distance between the wall and the wake. An unstable mode switching at low frequency is observed where the antisymmetric mode becomes more unstable than the symmetric mode when the wake velocity defect is high.

A nonperturbing boundary-layer transition detection

NASA Astrophysics Data System (ADS)

Ohare, J. E.

1985-01-01

A laser interferometer technique is being applied to the characterization of boundary-layer conditions on models in supersonic and hypersonic wind tunnels in the von Karman Facility at Arnold Engineering Development Center (AEDC). The Boundary-Layer Transition Detector (BLTD), based on lateral interferometry, is applicable for determining the turbulence frequency spectrum of boundary layers in compressible flow. The turbulence, in terms of air density fluctuations, is detected by monitoring interferometric fringe phase shifts (in real time) formed by one beam which passes through the boundary layer and a reference beam which is outside the boundary layer. This technique is nonintrusive to the flow field unlike other commonly used methods such as pitot tube probing and hot-wire anemometry. Model boundary-layer data are presented at Mach 8 and compared with data recorded using other methods during boundary-layer transition from laminar to turbulent flow. Spectra from the BLTD reveal the presence of a high-frequency peak during transition, which is characteristic of spectra obtained with hot wires. The BLTD is described along with operational requirements and limitations.

A Nonperturbing Boundary-Layer Transition Detector

NASA Astrophysics Data System (ADS)

O'Hare, J. E.

1986-01-01

A laser interferometer technique is being applied to the characterization of boundary-layer conditions on models in supersonic and hypersonic wind tunnels in the von Kaman Facility at Arnold Engineering Development Center (AEDC). The Boundary-Layer Transition Detector (BLTD), based on lateral interferometry, is applicable for determining the turbulence frequency spectrum of boundary layers in compressible flow. The turbulence, in terms of air density fluctuations, is detected by monitoring interferometric fringe phase shifts (in real time) formed by one beam which passes through the boundary layer and a reference beam which is outside the boundary layer. This technique is nonintrusive to the flow field unlike other commonly used methods such as pitot tube probing and hot-wire anemometry. Model boundary-layer data are presented at Mach 8 and compared with data recorded using other methods during boundary-layer transition from laminar to turbulent flow. Spectra from the BLTD reveal the presence of a high-frequency peak during transition, which is characteristic of spectra obtained with hot wires. The BLTD is described along with operational requirements and limitations.

Comparison of theoretical and experimental boundary-layer development in a Mach 2.5 mixed-compression inlet

NASA Technical Reports Server (NTRS)

Hingst, W. R.; Towne, C. E.

1974-01-01

An analytical investigation was made of the boundary layer flow in an axisymmetric Mach 2.5 mixed compression inlet, and the results were compared with experimental measurements. The inlet tests were conducted in the Lewis 10- by 10-foot supersonic wind tunnel at a unit Reynolds number of 8.2 million/m. The inlet incorporated porous bleed regions for boundary layer control, and the effect of this bleed was taken into account in the analysis. The experimental boundary layer data were analyzed by using similarity laws from which the skin friction coefficient was obtained. The boundary layer analysis included predictions of laminar and turbulent boundary layer growth, transition, and the effects of the shock boundary layer interactions. In addition, the surface static pressures were compared with those obtained from an inviscid characteristics program. The results of investigation showed that the analytical techniques gave satisfactory predictions of the boundary layer flow except in regions that were badly distorted by the terminal shock.

Boundary layers in centrifugal compressors. [application of boundary layer theory to compressor design

NASA Technical Reports Server (NTRS)

Dean, R. C., Jr.

1974-01-01

The utility of boundary-layer theory in the design of centrifugal compressors is demonstrated. Boundary-layer development in the diffuser entry region is shown to be important to stage efficiency. The result of an earnest attempt to analyze this boundary layer with the best tools available is displayed. Acceptable prediction accuracy was not achieved. The inaccuracy of boundary-layer analysis in this case would result in stage efficiency prediction as much as four points low. Fluid dynamic reasons for analysis failure are discussed with support from flow data. Empirical correlations used today to circumnavigate the weakness of the theory are illustrated.

Reduced ratio of protective versus proinflammatory cytokine responses to commensal bacteria in HLA-B27 transgenic rats

PubMed Central

DIELEMAN, L A; HOENTJEN, F; QIAN, B-F; SPRENGERS, D; TJWA, E; TORRES, M F; TORRICE, C D; SARTOR, R B; TONKONOGY, S L

2004-01-01

Germ-free HLA-B27 transgenic (TG) rats do not develop colitis, but colonization with specific pathogen-free (SPF) bacteria induces colitis accompanied by immune activation. To study host-dependent immune responses to commensal caecal bacteria we investigated cytokine profiles in mesenteric lymph node (MLN) cells from HLA-B27 TG versus nontransgenic (non-TG) littermates after in vitro stimulation with caecal bacterial lysates (CBL). Supernatants from CBL-stimulated unseparated T- or B- cell-depleted MLN cells from HLA-B27 TG and non-TG littermates were analysed for IFN-γ, IL-12, TNF, IL-10 and TGF-β production. Our results show that unfractionated TG MLN cells stimulated with CBL produced more IFN-γ, IL-12 and TNF than did non-TG MLN cells. In contrast, CBL-stimulated non-TG MLN cells produced more IL-10 and TGF-β. T cell depletion abolished IFN-γ and decreased IL-12 production, but did not affect IL-10 and TGF-β production. Conversely, neither IL-10 nor TGF-β was produced in cultures of B cell-depleted MLN. In addition, CD4+ T cells enriched from MLN of HLA-B27 TG but not from non-TG rats produced IFN-γ when cocultured with CBL-pulsed antigen presenting cells from non-TG rats. Interestingly, IL-10 and TGF-β, but not IFN-γ, IL-12 and TNF were produced by MLN cells from germ-free TG rats. These results indicate that the colitis that develops in SPF HLA-B27 TG rats is accompanied by activation of IFN-γ-producing CD4+ T cells that respond to commensal bacteria. However, B cell cytokine production in response to components of commensal intestinal microorganisms occurs in the absence of intestinal inflammation. PMID:15030511

Morphometric assessment of normal human ciliary body using ultrasound biomicroscopy.

PubMed

Okamoto, Yoshifumi; Okamoto, Fumiki; Nakano, Shinichiro; Oshika, Tetsuro

2017-12-01

To quantitatively assess the biometry of the ciliary body in normal human eyes using ultrasound biomicroscopy. We evaluated 85 eyes of 85 normal subjects (35 men and 50 women), whose age ranged from 11 to 86 years (mean ± SD, 56.8 ± 20.4 years). The eyes were assessed along the 3-, 6-, 9-, and 12-o'clock meridians relative to the center of the cornea. Clinical data were collected, including age, axial length, ciliary body length (CBL), ciliary body thickness (CBT), anterior chamber depth, iris root thickness, trabecular-iris angle, and scleral-ciliary process angle. Axial length was measured using A-scan ultrasonography. CBL and CBT tended to be larger in the superior than in the inferior quadrant, but the differences among the four quadrants were not statistically significant. The average CBL showed a significant positive correlation with the average CBT (r = 0.40, P < 0.001). Average CBL and CBT were significantly correlated with axial length (r = 0.33, P = 0.031; r = 0.46, P < 0.01 respectively). In addition, the average CBL was significantly correlated with anterior chamber depth (r = 0.23, P < 0.05), trabecular-iris angle (r = 0.29, P = 0.01), and scleral-ciliary process angle (r = 0.40, P < 0.001). Ultrasound biomicroscopic imaging demonstrated that the ciliary body is similar in size in all circumferences, and eyes with longer axial length have an elongated and thicker ciliary body. The values obtained in the present study may serve as standard clinical references.

Characterization of the complex between native and reduced bovine serum albumin with aquacobalamin and evidence of dual tetrapyrrole binding.

PubMed

Dereven'kov, Ilia A; Hannibal, Luciana; Makarov, Sergei V; Makarova, Anna S; Molodtsov, Pavel A; Koifman, Oskar I

2018-05-02

Serum albumin binds to a variety of endogenous ligands and drugs. Human serum albumin (HSA) binds to heme via hydrophobic interactions and axial coordination of the iron center by protein residue Tyr161. Human serum albumin binds to another tetrapyrrole, cobalamin (Cbl), but the structural and functional properties of this complex are poorly understood. Herein, we investigate the reaction between aquacobalamin (H 2 OCbl) and bovine serum albumin (BSA, the bovine counterpart of HSA) using Ultraviolet-Visible and fluorescent spectroscopy, and electron paramagnetic resonance. The reaction between H 2 OCbl and BSA led to the formation of a BSA-Cbl(III) complex consistent with N-axial ligation (amino). Prior to the formation of this complex, the reactants participate in an additional binding event that has been examined by fluorescence spectroscopy. Binding of BSA to Cbl(III) reduced complex formation between the bound cobalamin and free cyanide to form cyanocobalamin (CNCbl), suggesting that the β-axial position of the cobalamin may be occupied by an amino acid residue from the protein. Reaction of BSA containing reduced disulfide bonds with H 2 OCbl produces cob(II)alamin and disulfide with intermediate formation of thiolate Cbl(III)-BSA complex and its decomposition. Finally, in vitro studies showed that cobalamin binds to BSA only in the presence of an excess of protein, which is in contrast to heme binding to BSA that involves a 1:1 stoichiometry. In vitro formation of BSA-Cbl(III) complex does not preclude subsequent heme binding, which occurs without displacement of H 2 OCbl bound to BSA. These data suggest that the two tetrapyrroles interact with BSA in different binding pockets.

Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1

PubMed Central

Tefferi, A

2010-01-01

Myeloproliferative neoplasms (MPNs) originate from genetically transformed hematopoietic stem cells that retain the capacity for multilineage differentiation and effective myelopoiesis. Beginning in early 2005, a number of novel mutations involving Janus kinase 2 (JAK2), Myeloproliferative Leukemia Virus (MPL), TET oncogene family member 2 (TET2), Additional Sex Combs-Like 1 (ASXL1), Casitas B-lineage lymphoma proto-oncogene (CBL), Isocitrate dehydrogenase (IDH) and IKAROS family zinc finger 1 (IKZF1) have been described in BCR-ABL1-negative MPNs. However, none of these mutations were MPN specific, displayed mutual exclusivity or could be traced back to a common ancestral clone. JAK2 and MPL mutations appear to exert a phenotype-modifying effect and are distinctly associated with polycythemia vera, essential thrombocythemia and primary myelofibrosis; the corresponding mutational frequencies are ∼99, 55 and 65% for JAK2 and 0, 3 and 10% for MPL mutations. The incidence of TET2, ASXL1, CBL, IDH or IKZF1 mutations in these disorders ranges from 0 to 17% these latter mutations are more common in chronic (TET2, ASXL1, CBL) or juvenile (CBL) myelomonocytic leukemias, mastocytosis (TET2), myelodysplastic syndromes (TET2, ASXL1) and secondary acute myeloid leukemia, including blast-phase MPN (IDH, ASXL1, IKZF1). The functional consequences of MPN-associated mutations include unregulated JAK-STAT (Janus kinase/signal transducer and activator of transcription) signaling, epigenetic modulation of transcription and abnormal accumulation of oncoproteins. However, it is not clear as to whether and how these abnormalities contribute to disease initiation, clonal evolution or blastic transformation. PMID:20428194

Berberine Inhibits Proliferation and Down-Regulates Epidermal Growth Factor Receptor through Activation of Cbl in Colon Tumor Cells

PubMed Central

Wang, Lihong; Cao, Hailong; Lu, Ning; Liu, Liping; Wang, Bangmao; Hu, Tianhui; Israel, Dawn A.; Peek, Richard M.; Polk, D. Brent; Yan, Fang

2013-01-01

Berberine, an isoquinoline alkaloid, is an active component of Ranunculaceae and Papaveraceae plant families. Berberine has been found to suppress growth of several tumor cell lines in vitro through the cell-type-dependent mechanism. Expression and activation of epidermal growth factor receptor (EGFR) is increased in colonic precancerous lesions and tumours, thus EGFR is considered a tumour promoter. The aim of this study was to investigate the effects and mechanisms of berberine on regulation of EGFR activity and proliferation in colonic tumor cell lines and in vivo. We reported that berberine significantly inhibited basal level and EGF-stimulated EGFR activation and proliferation in the immorto Min mouse colonic epithelial (IMCE) cells carrying the APC min mutation and human colonic carcinoma cell line, HT-29 cells. Berberine acted to inhibit proliferation through inducing G1/S and G2/M cell cycle arrest, which correlated with regulation of the checkpoint protein expression. In this study, we also showed that berberine stimulated ubiquitin ligase Cbl activation and Cbl's interaction with EGFR, and EGFR ubiquitinylation and down-regulation in these two cell lines in the presence or absence of EGF treatment. Knock-down Cbl expression blocked the effects of berberine on down-regulation of EGFR and inhibition of proliferation. Furthermore, berberine suppressed tumor growth in the HT-29 cell xenograft model. Cell proliferation and EGFR expression level was decreased by berberine treatment in this xenograft model and in colon epithelial cells of APC min/+ mice. Taken together, these data indicate that berberine enhances Cbl activity, resulting in down-regulation of EGFR expression and inhibition of proliferation in colon tumor cells. PMID:23457600

Boundary-Layer Bypass Transition Over Large-Scale Bodies

DTIC Science & Technology

2016-12-16

shape of the streamwise velocity profile compared to the flat- plate boundary layer. The research showed that the streamwise wavenumber plays a key role...many works on the suppression of the transitional boundary layer. Most of the results in the literature are for the flat- plate boundary layer but the...behaviour of the velocity and pressure changes with the curvature. This work aims to extend the results of the flat- plate boundary layer to a Rankine

An experimental investigation of a two and a three-dimensional low speed turbulent boundary layer

NASA Technical Reports Server (NTRS)

Winkelmann, A. E.; Melnik, W. L.

1976-01-01

Experimental studies of a two and a three-dimensional low speed turbulent boundary layer were conducted on the side wall of a boundary layer wind tunnel. The 20 ft. long test section, with a rectangular cross section measuring 17.5 in. x 46 in., produced a 3.5 in. thick turbulent boundary layer at a free stream Reynolds number. The three-dimensional turbulent boundary layer was produced by a 30 deg swept wing-like model faired into the side wall of the test section. Preliminary studies in the two-dimensional boundary layer indicated that the flow was nonuniform on the 46 in. wide test wall. The nonuniform boundary layer is characterized by transverse variations in the wall shear stress and is primarily caused by nonuniformities in the inlet damping screens.

Widening Paths to Success, Improving the Environment, and Moving Toward Lessons Learned from the Experiences of Powre and Cbl Awardees

NASA Astrophysics Data System (ADS)

Rosser, Sue V.; Daniels, Jane Z.

To better understand the barriers and discouragements encountered by female faculty members in science and engineering, this article compares the experience of National Science Foundation - funded Professional Opportunities for Women in Research and Education (POWRE) awardees and Clare Boothe Luce (CBL) Professorship recipients. Because most POWRE awardees work at research institutions, and many CBL professors teach at small liberal arts colleges, this study helps in understanding the experiences of female faculty members across a broad spectrum of academic settings. Their experiences suggest positive changes in institutional policies or practices to increase the satisfaction, retention, and success of female faculty members infields in which they are the least well represented. The retention of female faculty members becomes critical for attracting undergraduate students as they consider the wisdom of choosing careers in academia.

Interaction of Atmospheric Turbulence with Blade Boundary Layer Dynamics on a 5MW Wind Turbine using Blade-Boundary-Layer-Resolved CFD with hybrid URANS-LES.

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

Vijayakumar, Ganesh; Brasseur, James; Lavely, Adam

We describe the response of the NREL 5 MW wind turbine blade boundary layer to the passage of atmospheric turbulence using blade-boundary-layer-resolved computational fluid dynamics with hybrid URANS-LES modeling.

Semiconductor P-I-N detector

DOEpatents

Sudharsanan, Rengarajan; Karam, Nasser H.

2001-01-01

A semiconductor P-I-N detector including an intrinsic wafer, a P-doped layer, an N-doped layer, and a boundary layer for reducing the diffusion of dopants into the intrinsic wafer. The boundary layer is positioned between one of the doped regions and the intrinsic wafer. The intrinsic wafer can be composed of CdZnTe or CdTe, the P-doped layer can be composed of ZnTe doped with copper, and the N-doped layer can be composed of CdS doped with indium. The boundary layers is formed of an undoped semiconductor material. The boundary layer can be deposited onto the underlying intrinsic wafer. The doped regions are then typically formed by a deposition process or by doping a section of the deposited boundary layer.

Practical calculation of laminar and turbulent bled-off boundary layers

NASA Technical Reports Server (NTRS)

Eppler, R.

1978-01-01

Bleed-off of boundary layer material is shown to be an effective means for reducing drag by conserving the laminar boundary layer and preventing separation of the turbulent boundary layer. The case in which the two effects of bleed-off overlap is examined. Empirical methods are extended to the case of bleed-off. Laminar and turbulent boundary layers are treated simultaneously and the approximation differential equations are solved without an uncertain error. The case without bleed-off is also treated.

Tables for correcting airfoil data obtained in the Langley 0.3-meter transonic cryogenic tunnel for sidewall boundary-layer effects

NASA Technical Reports Server (NTRS)

Jenkins, R. V.; Adcock, J. B.

1986-01-01

Tables for correcting airfoil data taken in the Langley 0.3-meter Transonic Cryogenic Tunnel for the presence of sidewall boundary layer are presented. The corrected Mach number and the correction factor are minutely altered by a 20 percent change in the boundary layer virtual origin distance. The sidewall boundary layer displacement thicknesses measured for perforated sidewall inserts and without boundary layer removal agree with the values calculated for solid sidewalls.

Interaction of antimicrobial preservatives with blow-fill-seal packs: correlating sorption with solubility parameters.

PubMed

Amin, Aeshna; Dare, Manish; Sangamwar, Abhay; Bansal, Arvind Kumar

2012-01-01

The aim of this work was to study the interaction of four commonly used ophthalmic antimicrobial preservatives [benzyl alcohol (BA), chlorbutol (CBL), benzalkonium chloride (BKC), and chlorhexidine gluconate (CG)] with Blow-Fill-Seal (BFS) packs. Effect of packaging material [low-density polyethylene (LDPE), polypropylene (PP)], humidity (25% RH, 75% RH) and concentration (0.5, 1.0, 2.0 mM BA/CBL in LDPE) was studied. BKC and CG gave negligible loss (<4%) in BFS packs over a period of 3 months. BA and CBL, however, gave marked losses in LDPE (ca. 70-90%) and PP (ca. 7-25%) packs. Humidity did not have any effect on the sorption loss of any preservative. Loss of BA switched from Case II to anomalous behavior with increasing initial concentration. A two-stage sorption behavior was inherent at all concentrations. Loss of CBL followed anomalous behavior with biphasic kinetics of loss. It was concluded that all the four preservatives were appropriate for use in PP BFS packs. However, only BKC and CG were amenable to be used in LDPE BFS packs. Lastly, an empirical expression consisting of the "solubility parameter distance" and "molar volume" of preservatives was developed to correlate the preservative loss in LDPE with the physicochemical properties of the preservatives.

Soy Glycinin Contains a Functional Inhibitory Sequence against Muscle-Atrophy-Associated Ubiquitin Ligase Cbl-b

PubMed Central

Yama, Tomonari; Ochi, Arisa; Suto, Takuro; Hirasaka, Katsuya; Teshima-Kondo, Shigetada; Okumura, Yuushi; Oarada, Motoko; Choi, Inho; Mukai, Rie; Terao, Junji

2013-01-01

Background. Unloading stress induces skeletal muscle atrophy. We have reported that Cbl-b ubiquitin ligase is a master regulator of unloading-associated muscle atrophy. The present study was designed to elucidate whether dietary soy glycinin protein prevents denervation-mediated muscle atrophy, based on the presence of inhibitory peptides against Cbl-b ubiquitin ligase in soy glycinin protein. Methods. Mice were fed either 20% casein diet, 20% soy protein isolate diet, 10% glycinin diet containing 10% casein, or 20% glycinin diet. One week later, the right sciatic nerve was cut. The wet weight, cross sectional area (CSA), IGF-1 signaling, and atrogene expression in hindlimb muscles were examined at 1, 3, 3.5, or 4 days after denervation. Results. 20% soy glycinin diet significantly prevented denervation-induced decreases in muscle wet weight and myofiber CSA. Furthermore, dietary soy protein inhibited denervation-induced ubiquitination and degradation of IRS-1 in tibialis anterior muscle. Dietary soy glycinin partially suppressed the denervation-mediated expression of atrogenes, such as MAFbx/atrogin-1 and MuRF-1, through the protection of IGF-1 signaling estimated by phosphorylation of Akt-1. Conclusions. Soy glycinin contains a functional inhibitory sequence against muscle-atrophy-associated ubiquitin ligase Cbl-b. Dietary soy glycinin protein significantly prevented muscle atrophy after denervation in mice. PMID:23762056

Discussion of Boundary-Layer Characteristics Near the Wall of an Axial-Flow Compressor

NASA Technical Reports Server (NTRS)

Mager, Artur; Mohoney, John J; Budinger, Ray E

1952-01-01

The boundary-layer velocity profiles in the tip region of an axial-flow compressor downstream of the guide vanes and downstream of the rotor were measured by use of total-pressure and claw-type yaw probes. These velocities were resolved into two components: one along the streamline of the flow outside the boundary layer, and the other perpendicular to it. The affinity among all profiles was thus demonstrated with the boundary-layer thickness and the deflection of the boundary layer at the wall as the generalizing parameters. By use of these results and the momentum-integral equations, boundary-layer characteristics on the walls of an axial-flow compressor were qualitatively evaluated.

Prediction of turbulent shear layers in turbomachines

NASA Technical Reports Server (NTRS)

Bradshaw, P.

1974-01-01

The characteristics of turbulent shear layers in turbomachines are compared with the turbulent boundary layers on airfoils. Seven different aspects are examined. The limits of boundary layer theory are investigated. Boundary layer prediction methods are applied to analysis of the flow in turbomachines.

Study of boundary-layer transition using transonic-cone preston tube data

NASA Technical Reports Server (NTRS)

Reed, T. D.; Moretti, P. M.

1980-01-01

The laminar boundary layer on a 10 degree cone in a transonic wind tunnel was studied. The inviscid flow and boundary layer development were simulated by computer programs. The effects of pitch and yaw angles on the boundary layer were examined. Preston-tube data, taken on the boundary-layer-transition cone in the NASA Ames 11 ft transonic wind tunnel, were used to develope a correlation which relates the measurements to theoretical values of laminar skin friction. The recommended correlation is based on a compressible form of the classical law-of-the-wall. The computer codes successfully simulates the laminar boundary layer for near-zero pitch and yaw angles. However, in cases of significant pitch and/or yaw angles, the flow is three dimensional and the boundary layer computer code used here cannot provide a satisfactory model. The skin-friction correlation is thought to be valid for body geometries other than cones.

Stability of boundary layer flow based on energy gradient theory

NASA Astrophysics Data System (ADS)

Dou, Hua-Shu; Xu, Wenqian; Khoo, Boo Cheong

2018-05-01

The flow of the laminar boundary layer on a flat plate is studied with the simulation of Navier-Stokes equations. The mechanisms of flow instability at external edge of the boundary layer and near the wall are analyzed using the energy gradient theory. The simulation results show that there is an overshoot on the velocity profile at the external edge of the boundary layer. At this overshoot, the energy gradient function is very large which results in instability according to the energy gradient theory. It is found that the transverse gradient of the total mechanical energy is responsible for the instability at the external edge of the boundary layer, which induces the entrainment of external flow into the boundary layer. Within the boundary layer, there is a maximum of the energy gradient function near the wall, which leads to intensive flow instability near the wall and contributes to the generation of turbulence.

Wind and boundary layers in Rayleigh-Bénard convection. II. Boundary layer character and scaling.

PubMed

van Reeuwijk, Maarten; Jonker, Harm J J; Hanjalić, Kemo

2008-03-01

The scaling of the kinematic boundary layer thickness lambda(u) and the friction factor C(f) at the top and bottom walls of Rayleigh-Bénard convection is studied by direct numerical simulation (DNS). By a detailed analysis of the friction factor, a new parameterisation for C(f) and lambda(u) is proposed. The simulations were made of an L/H=4 aspect-ratio domain with periodic lateral boundary conditions at Ra=(10(5), 10(6), 10(7), 10(8)) and Pr=1. The continuous spectrum, as well as significant forcing due to Reynolds stresses, clearly indicates a turbulent character of the boundary layer, while viscous effects cannot be neglected, judging from the scaling of classical integral boundary layer parameters with Reynolds number. Using a conceptual wind model, we find that the friction factor C(f) should scale proportionally to the thermal boundary layer thickness as C(f) proportional variant lambda(Theta)/H, while the kinetic boundary layer thickness lambda(u) scales inversely proportionally to the thermal boundary layer thickness and wind Reynolds number lambda(u)/H proportional variant (lambda(Theta)/H)(-1)Re(-1). The predicted trends for C(f) and lambda(u) are in agreement with DNS results.

Unsteady transonic viscous-inviscid interaction using Euler and boundary-layer equations

NASA Technical Reports Server (NTRS)

Pirzadeh, Shahyar; Whitfield, Dave

1989-01-01

The Euler code is used extensively for computation of transonic unsteady aerodynamics. The boundary layer code solves the 3-D, compressible, unsteady, mean flow kinetic energy integral boundary layer equations in the direct mode. Inviscid-viscous coupling is handled using porosity boundary conditions. Some of the advantages and disadvantages of using the Euler and boundary layer equations for investigating unsteady viscous-inviscid interaction is examined.

Inventory of File gfs.t06z.smartguam00.tm00.grib2

Science.gov Websites

boundary layer WDIR analysis Wind Direction (from which blowing) [degtrue] 013 planetary boundary layer WIND analysis Wind Speed [m/s] 014 planetary boundary layer RH analysis Relative Humidity [%] 015 planetary boundary layer DIST analysis Geometric Height [m] 016 surface 4LFTX analysis Best (4 layer) Lifted

Observations of the Summertime Boundary Layer over the Ross Ice Shelf, Antarctica Using SUMO UAVs

NASA Astrophysics Data System (ADS)

Nigro, M. A.; Cassano, J. J.; Jolly, B.; McDonald, A.

2014-12-01

During January 2014 Small Unmanned Meteorological Observer (SUMO) unmanned aerial vehicles (UAVs) were used to observe the boundary layer over the Ross Ice Shelf, Antarctica. A total of 41 SUMO flights were completed during a 9-day period with a maximum of 11 flights during a single day. Flights occurred as frequently as every 1.5 hours so that the time evolution of the boundary layer could be documented. On almost all of the flights the boundary layer was well mixed from the surface to a depth of less than 50 m to over 350 m. The depth of the well-mixed layer was observed to both increase and decrease over the course of an individual day suggesting that processes other than entrainment were altering the boundary layer depth. The well-mixed layer was observed to both warm and cool during the field campaign indicating that advective processes as well as surface fluxes were acting to control the temporal evolution of the boundary layer temperature. Only a small number of weakly stably stratified boundary layers were observed. Strong, shallow inversions, of up to 6 K, were observed above the top of the boundary layer. Observations from a 30 m automatic weather station and two temporary automatic weather stations 10 km south and west of the main field campaign location provide additional data for understanding the boundary layer evolution observed by the SUMO UAVs during this 9-day period. This presentation will discuss the observed evolution of the summertime boundary layer as well as comment on lessons learned operating the SUMO UAVs at a remote Antarctic field camp.

INDIVIDUAL TURBULENT CELL INTERACTION: BASIS FOR BOUNDARY LAYER ESTABLISHMENT

EPA Science Inventory

Boundary layers are important in determining the forces on objects in flowing fluids, mixing characteristics, and other phenomena. For example, benthic boundary layers are frequently active resuspension layers that determine bottom turbidity and transniissivity. Traditionally, bo...

Skin-Friction Measurements at Subsonic and Transonic Mach Numbers with Embedded-Wire Gages

DTIC Science & Technology

1981-01-01

Model ................................... 17 9. Boundary-Layer Rake Installation on EBOR Model...boundary-layer total pressure rake eliminates this bulky mechanism and the long data acquisition time, but it introduces interferences which affect the...its construction. Further, boundary-layer rakes are restricted to measurements in thick boundary layers. Surface pressure probes such as Stanton tubes

Mechanics of Boundary Layer Transition. Part 5: Boundary Layer Stability theory in incompressible and compressible flow

NASA Technical Reports Server (NTRS)

Mack, L. M.

1967-01-01

The fundamentals of stability theory, its chief results, and the physical mechanisms at work are presented. The stability theory of the laminar boundary determines whether a small disturbance introduced into the boundary layer will amplify or damp. If the disturbance damps, the boundary layer remains laminar. If the disturbance amplifies, and by a sufficient amount, then transition to turbulence eventually takes place. The stability theory establishes those states of the boundary layer which are most likely to lead to transition, identifys those frequencies which are the most dangerous, and indicates how the external parameters can best be changed to avoid transition.

Three dimensional flow field inside compressor rotor, including blade boundary layers

NASA Technical Reports Server (NTRS)

Galmes, J. M.; Pouagere, M.; Lakshminarayana, B.

1982-01-01

The Reynolds stress equation, pressure strain correlation, and dissipative terms and diffusion are discussed in relation to turbulence modelling using the Reynolds stress model. Algebraic modeling of Reynolds stresses and calculation of the boundary layer over an axial cylinder are examined with regards to the kinetic energy model for turbulence modelling. The numerical analysis of blade and hub wall boundary layers, and an experimental study of rotor blade boundary layer in an axial flow compressor rotor are discussed. The Patankar-Spalding numerical method for two dimensional boundary layers is included.

Boundary-layer effects in composite laminates. I - Free-edge stress singularities. II - Free-edge stress solutions and basic characteristics

NASA Technical Reports Server (NTRS)

Wang, S. S.; Choi, I.

1982-01-01

The fundamental nature of the boundary-layer effect in fiber-reinforced composite laminates is formulated in terms of the theory of anisotropic elasticity. The basic structure of the boundary-layer field solution is obtained by using Lekhnitskii's stress potentials (1963). The boundary-layer stress field is found to be singular at composite laminate edges, and the exact order or strength of the boundary layer stress singularity is determined using an eigenfunction expansion method. A complete solution to the boundary-layer problem is then derived, and the convergence and accuracy of the solution are analyzed, comparing results with existing approximate numerical solutions. The solution method is demonstrated for a symmetric graphite-epoxy composite.

Modification in drag of turbulent boundary layers resulting from manipulation of large-scale structures

NASA Technical Reports Server (NTRS)

Corke, T. C.; Guezennec, Y.; Nagib, H. M.

1981-01-01

The effects of placing a parallel-plate turbulence manipulator in a boundary layer are documented through flow visualization and hot wire measurements. The boundary layer manipulator was designed to manage the large scale structures of turbulence leading to a reduction in surface drag. The differences in the turbulent structure of the boundary layer are summarized to demonstrate differences in various flow properties. The manipulator inhibited the intermittent large scale structure of the turbulent boundary layer for at least 70 boundary layer thicknesses downstream. With the removal of the large scale, the streamwise turbulence intensity levels near the wall were reduced. The downstream distribution of the skin friction was also altered by the introduction of the manipulator.

Validation of High-Speed Turbulent Boundary Layer and Shock-Boundary Layer Interaction Computations with the OVERFLOW Code

NASA Technical Reports Server (NTRS)

Oliver, A. B.; Lillard, R. P.; Blaisdell, G. A.; Lyrintizis, A. S.

2006-01-01

The capability of the OVERFLOW code to accurately compute high-speed turbulent boundary layers and turbulent shock-boundary layer interactions is being evaluated. Configurations being investigated include a Mach 2.87 flat plate to compare experimental velocity profiles and boundary layer growth, a Mach 6 flat plate to compare experimental surface heat transfer,a direct numerical simulation (DNS) at Mach 2.25 for turbulent quantities, and several Mach 3 compression ramps to compare computations of shock-boundary layer interactions to experimental laser doppler velocimetry (LDV) data and hot-wire data. The present paper describes outlines the study and presents preliminary results for two of the flat plate cases and two small-angle compression corner test cases.

The influence of free-stream turbulence on turbulent boundary layers with mild adverse pressure gradients

NASA Technical Reports Server (NTRS)

Hoffmann, J. A.; Kassir, S. M.; Larwood, S. M.

1989-01-01

The influence of near isotropic free-stream turbulence on the shape factors and skin friction coefficients of turbulent boundary layers is presented for the cases of zero and mild adverse pressure gradients. With free-stream turbulence, improved fluid mixing occurs in boundary layers with adverse pressure gradients relative to the zero pressure gradient condition, with the same free-stream turbulence intensity and length scale. Stronger boundary layers with lower shape factors occur as a result of a lower ratio of the integral scale of turbulence to the boundary layer thickness, and to vortex stretching of the turbulent eddies in the free-stream, both of which act to improve the transmission of momentum from the free-stream to the boundary layers.

Using a CBL Unit, a Temperature Sensor, and a Graphing Calculator to Model the Kinetics of Consecutive First-Order Reactions as Safe In-Class Demonstrations

ERIC Educational Resources Information Center

Moore-Russo, Deborah A.; Cortes-Figueroa, Jose E.; Schuman, Michael J.

2006-01-01

The use of Calculator-Based Laboratory (CBL) technology, the graphing calculator, and the cooling and heating of water to model the behavior of consecutive first-order reactions is presented, where B is the reactant, I is the intermediate, and P is the product for an in-class demonstration. The activity demonstrates the spontaneous and consecutive…

Increased Jet Noise Due to a "Nominally Laminar" State of Nozzle Exit Boundary Layer

NASA Technical Reports Server (NTRS)

Zaman, K. B. M. Q.

2017-01-01

A set of 2-in. diameter nozzles is used to investigate the effect of varying exit boundary layer state on the radiated noise from high-subsonic jets. It is confirmed that nozzles involving turbulent boundary layers are the quietest while nozzles involving a "nominally laminar" boundary layer are loud especially on the high-frequency side of the sound pressure level spectrum. The latter boundary layer state involves a "Blasius-like" mean velocity profile but higher turbulence intensities compared to those in the turbulent state. The higher turbulence in the initial region of the jet shear layer leads to increased high-frequency noise. The results strongly suggest that an anomaly noted with subsonic jet noise databases in the literature is due to a similar effect of differences in the initial boundary layer state.

Increased Jet Noise Due to a "Nominally Laminar" State of Nozzle Exit Boundary Layer

NASA Technical Reports Server (NTRS)

Zaman, K. B. M. Q.

2017-01-01

A set of 2-inch diameter nozzles is used to investigate the effect of varying exit boundary layer state on the radiated noise from high-subsonic jets. It is confirmed that nozzles involving turbulent boundary layers are the quietest while nozzles involving a nominally-laminar boundary layer are loud especially on the high-frequency side of the sound pressure level spectrum. The latter boundary layer state involves a Blasius-like mean velocity profile but higher turbulence intensities compared to those in the turbulent state. The higher turbulence in the initial region of the jet shear layer leads to increased high-frequency noise. The results strongly suggest that an anomaly noted with subsonic jet noise databases in the literature is due to a similar effect of differences in the initial boundary layer state.

ANGULAR MOMENTUM TRANSPORT BY ACOUSTIC MODES GENERATED IN THE BOUNDARY LAYER. I. HYDRODYNAMICAL THEORY AND SIMULATIONS

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

Belyaev, Mikhail A.; Rafikov, Roman R.; Stone, James M., E-mail: rrr@astro.princeton.edu

The nature of angular momentum transport in the boundary layers of accretion disks has been one of the central and long-standing issues of accretion disk theory. In this work we demonstrate that acoustic waves excited by supersonic shear in the boundary layer serve as an efficient mechanism of mass, momentum, and energy transport at the interface between the disk and the accreting object. We develop the theory of angular momentum transport by acoustic modes in the boundary layer, and support our findings with three-dimensional hydrodynamical simulations, using an isothermal equation of state. Our first major result is the identification ofmore » three types of global modes in the boundary layer. We derive dispersion relations for each of these modes that accurately capture the pattern speeds observed in simulations to within a few percent. Second, we show that angular momentum transport in the boundary layer is intrinsically nonlocal, and is driven by radiation of angular momentum away from the boundary layer into both the star and the disk. The picture of angular momentum transport in the boundary layer by waves that can travel large distances before dissipating and redistributing angular momentum and energy to the disk and star is incompatible with the conventional notion of local transport by turbulent stresses. Our results have important implications for semianalytical models that describe the spectral emission from boundary layers.« less

Outer layer effects in wind-farm boundary layers: Coriolis forces and boundary layer height

NASA Astrophysics Data System (ADS)

Allaerts, Dries; Meyers, Johan

2015-11-01

In LES studies of wind-farm boundary layers, scale separation between the inner and outer region of the atmospheric boundary layer (ABL) is frequently assumed, i.e., wind turbines are presumed to fall within the inner layer and are not affected by outer layer effects. However, modern wind turbine and wind farm design tends towards larger rotor diameters and farm sizes, which means that outer layer effects will become more important. In a prior study, it was already shown for fully-developed wind farms that the ABL height influences the power performance. In this study, we use the in-house LES code SP-Wind to investigate the importance of outer layer effects on wind-farm boundary layers. In a suite of LES cases, the ABL height is varied by imposing a capping inversion with varying inversion strengths. Results indicate the growth of an internal boundary layer (IBL), which is limited in cases with low inversion layers. We further find that flow deceleration combined with Coriolis effects causes a change in wind direction throughout the farm. This effect increases with decreasing boundary layer height, and can result in considerable turbine wake deflection near the end of the farm. The authors are supported by the ERC (ActiveWindFarms, grant no: 306471). Computations were performed on VSC infrastructiure (Flemish Supercomputer Center), funded by the Hercules Foundation and the Flemish Government-department EWI.

Nonequilibrium chemistry boundary layer integral matrix procedure

NASA Technical Reports Server (NTRS)

Tong, H.; Buckingham, A. C.; Morse, H. L.

1973-01-01

The development of an analytic procedure for the calculation of nonequilibrium boundary layer flows over surfaces of arbitrary catalycities is described. An existing equilibrium boundary layer integral matrix code was extended to include nonequilibrium chemistry while retaining all of the general boundary condition features built into the original code. For particular application to the pitch-plane of shuttle type vehicles, an approximate procedure was developed to estimate the nonequilibrium and nonisentropic state at the edge of the boundary layer.

Differential analysis for the turbulent boundary layer on a compressor blade element (including boundary-layer separation)

NASA Technical Reports Server (NTRS)

Schmidt, J. F.; Todd, C. A.

1974-01-01

A two-dimensional differential analysis is developed to approximate the turbulent boundary layer on a compressor blade element with strong adverse pressure gradients, including the separated region with reverse flow. The predicted turbulent boundary layer thicknesses and velocity profiles are in good agreement with experimental data for a cascade blade, even in the separated region.

Similarity theory of the buoyantly interactive planetary boundary layer with entrainment

NASA Technical Reports Server (NTRS)

Hoffert, M. I.; Sud, Y. C.

1976-01-01

A similarity model is developed for the vertical profiles of turbulent flow variables in an entraining turbulent boundary layer of arbitrary buoyant stability. In the general formulation the vertical profiles, internal rotation of the velocity vector, discontinuities or jumps at a capping inversion and bulk aerodynamic coefficients of the boundary layer are given by solutions to a system of ordinary differential equations in the similarity variable. To close the system, a formulation for buoyantly interactive eddy diffusivity in the boundary layer is introduced which recovers Monin-Obukhov similarity near the surface and incorporates a hypothesis accounting for the observed variation of mixing length throughout the boundary layer. The model is tested in simplified versions which depend only on roughness, surface buoyancy, and Coriolis effects by comparison with planetary-boundary-layer wind- and temperature-profile observations, measurements of flat-plate boundary layers in a thermally stratified wind tunnel and observations of profiles of terms in the turbulent kinetic-energy budget of convective planetary boundary layers. On balance, the simplified model reproduced the trend of these various observations and experiments reasonably well, suggesting that the full similarity formulation be pursued further.

Assessment of a 3-D boundary layer code to predict heat transfer and flow losses in a turbine

NASA Technical Reports Server (NTRS)

Anderson, O. L.

1984-01-01

Zonal concepts are utilized to delineate regions of application of three-dimensional boundary layer (DBL) theory. The zonal approach requires three distinct analyses. A modified version of the 3-DBL code named TABLET is used to analyze the boundary layer flow. This modified code solves the finite difference form of the compressible 3-DBL equations in a nonorthogonal surface coordinate system which includes coriolis forces produced by coordinate rotation. These equations are solved using an efficient, implicit, fully coupled finite difference procedure. The nonorthogonal surface coordinate system is calculated using a general analysis based on the transfinite mapping of Gordon which is valid for any arbitrary surface. Experimental data is used to determine the boundary layer edge conditions. The boundary layer edge conditions are determined by integrating the boundary layer edge equations, which are the Euler equations at the edge of the boundary layer, using the known experimental wall pressure distribution. Starting solutions along the inflow boundaries are estimated by solving the appropriate limiting form of the 3-DBL equations.

Effects of boundary layer on flame propagation generated by forced ignition behind an incident shock wave

NASA Astrophysics Data System (ADS)

Ishihara, S.; Tamura, S.; Ishii, K.; Kataoka, H.

2016-09-01

To study the effects of the boundary layer on the deflagration to detonation transition (DDT) process, the mixture behind an incident shock wave was ignited using laser breakdown. Ignition timing was controlled so that the interaction of the resulting flame with a laminar or turbulent boundary layer could be examined. In the case of the interaction with a laminar boundary layer, wrinkling of the flame was observed after the flame reached the corner of the channel. On the other hand, interaction with the turbulent boundary layer distorted the flame front and increased the spreading rate of the flame followed by prompt DDT. The inner structure of the turbulent boundary layer plays an important role in the DDT process. The region that distorted the flame within the turbulent boundary layer was found to be the intermediate region 0.01< y/δ < 0.4, where y is the distance from the wall and δ is the boundary layer thickness. The flame disturbance by the turbulent motions is followed by the flame interaction with the inner layer near the wall, which in turn generates a secondary-ignition kernel that produced a spherical accelerating flame, which ultimately led to the onset of detonation. After the flame reached the intermediate region, the time required for DDT was independent of the ignition position. The effect of the boundary layer on the propagating flame, thus, became relatively small after the accelerating flame was generated.

Turbulent boundary layer in high Rayleigh number convection in air.

PubMed

du Puits, Ronald; Li, Ling; Resagk, Christian; Thess, André; Willert, Christian

2014-03-28

Flow visualizations and particle image velocimetry measurements in the boundary layer of a Rayleigh-Bénard experiment are presented for the Rayleigh number Ra=1.4×1010. Our visualizations indicate that the appearance of the flow structures is similar to ordinary (isothermal) turbulent boundary layers. Our particle image velocimetry measurements show that vorticity with both positive and negative sign is generated and that the smallest flow structures are 1 order of magnitude smaller than the boundary layer thickness. Additional local measurements using laser Doppler velocimetry yield turbulence intensities up to I=0.4 as in turbulent atmospheric boundary layers. From our observations, we conclude that the convective boundary layer becomes turbulent locally and temporarily although its Reynolds number Re≈200 is considerably smaller than the value 420 underlying existing phenomenological theories. We think that, in turbulent Rayleigh-Bénard convection, the transition of the boundary layer towards turbulence depends on subtle details of the flow field and is therefore not universal.

Experimental Study of Fillets to Reduce Corner Effects in an Oblique Shock-Wave/Boundary Layer Interaction

NASA Technical Reports Server (NTRS)

Hirt, Stefanie M.

2015-01-01

A test was conducted in the 15 cm x 15 cm supersonic wind tunnel at NASA Glenn Research Center that focused on corner effects of an oblique shock-wave/boundary-layer interaction. In an attempt to control the interaction in the corner region, eight corner fillet configurations were tested. Three parameters were considered for the fillet configurations: the radius, the fillet length, and the taper length from the square corner to the fillet radius. Fillets effectively reduced the boundary-layer thickness in the corner; however, there was an associated penalty in the form of increased boundary-layer thickness at the tunnel centerline. Larger fillet radii caused greater reductions in boundary-layer thickness along the corner bisector. To a lesser, but measureable, extent, shorter fillet lengths resulted in thinner corner boundary layers. Overall, of the configurations tested, the largest radius resulted in the best combination of control in the corner, evidenced by a reduction in boundary-layer thickness, coupled with minimal impacts at the tunnel centerline.

Relaxation of the accelerating-gas boundary layer to the test-gas boundary layer on a flat plate in an expansion tube

NASA Technical Reports Server (NTRS)

Gupta, R. N.; Trimpi, R. L.

1973-01-01

An analytic investigation of the relaxation of the accelerating-gas boundary layer to the test-gas boundary layer over a flat plate mounted in an expansion tube has been conducted. In this treatment, nitrogen has been considered as the test gas and helium as the accelerating gas. The problem is analyzed in two conically similar limits: (1) when the time lag between the arrival of the shock and the interface at the leading edge of the plate is very large, and (2) when this time lag is negligible. The transient laminar boundary-layer equations of a perfect binary-gas mixture are taken as the flow governing equations. These coupled equations have been solved numerically by Gauss-Seidel line-relaxation method. The results predict the transient behavior as well as the time required for an all-helium accelerating-gas boundary layer to relax to an all-nitrogen boundary layer.

Generating Inviscid and Viscous Fluid Flow Simulations over a Surface Using a Quasi-simultaneous Technique

NASA Technical Reports Server (NTRS)

Sturdza, Peter (Inventor); Martins-Rivas, Herve (Inventor); Suzuki, Yoshifumi (Inventor)

2014-01-01

A fluid-flow simulation over a computer-generated surface is generated using a quasi-simultaneous technique. The simulation includes a fluid-flow mesh of inviscid and boundary-layer fluid cells. An initial fluid property for an inviscid fluid cell is determined using an inviscid fluid simulation that does not simulate fluid viscous effects. An initial boundary-layer fluid property a boundary-layer fluid cell is determined using the initial fluid property and a viscous fluid simulation that simulates fluid viscous effects. An updated boundary-layer fluid property is determined for the boundary-layer fluid cell using the initial fluid property, initial boundary-layer fluid property, and an interaction law. The interaction law approximates the inviscid fluid simulation using a matrix of aerodynamic influence coefficients computed using a two-dimensional surface panel technique and a fluid-property vector. An updated fluid property is determined for the inviscid fluid cell using the updated boundary-layer fluid property.

A nonperturbing boundary-layer transition detector

NASA Astrophysics Data System (ADS)

Ohare, J. E.

1985-11-01

A laser interferometer technique is being applied to the characterization of boundary-layer conditions on models in supersonic and hypersonic wind tunnels. The boundary-layer transition detector (BLTD), based on lateral interferometry, is applicable for determining the turbulence frequency spectrum of boundary layers in compressible flow. The turbulence, in terms of air density fluctuations, is detected by monitoring interferometric fringe phase shifts (in real time) formed by one beam which passes through the boundary layer and a reference beam which is outside the boundary layer. This technique is nonintrusive to the flow field unlike other commonly used methods such as pitot tube probing and hot-wire anemometry. Data which depict boundary-layer transition from laminar to turbulent flow are presented to provide comparisons of the BLTD with other measurement methods. Spectra from the BLTD reveals the presence of a high-frequency peak during transition which is characteristic of spectra obtained with hot wires. The BLTD is described along with operational requirements and limitations.

Mean velocity and turbulence measurements in a 90 deg curved duct with thin inlet boundary layer

NASA Technical Reports Server (NTRS)

Crawford, R. A.; Peters, C. E.; Steinhoff, J.; Hornkohl, J. O.; Nourinejad, J.; Ramachandran, K.

1985-01-01

The experimental database established by this investigation of the flow in a large rectangular turning duct is of benchmark quality. The experimental Reynolds numbers, Deans numbers and boundary layer characteristics are significantly different from previous benchmark curved-duct experimental parameters. This investigation extends the experimental database to higher Reynolds number and thinner entrance boundary layers. The 5% to 10% thick boundary layers, based on duct half-width, results in a large region of near-potential flow in the duct core surrounded by developing boundary layers with large crossflows. The turbulent entrance boundary layer case at R sub ed = 328,000 provides an incompressible flowfield which approaches real turbine blade cascade characteristics. The results of this investigation provide a challenging benchmark database for computational fluid dynamics code development.

Compressible Boundary Layer Investigation for Ramjet/scramjet Inlets and Nozzles

NASA Astrophysics Data System (ADS)

Goldfeld, M. A.; Starov, A. V.; Semenova, Yu. V.

2005-02-01

The results of experimental investigation of a turbulent boundary layer on compression and expansion surfaces are presented. They include the study of the shock wave and/or expansion fan action upon the boundary layer, boundary layer separation and its relaxation. Complex events of paired interactions and the flow on compression convex-concave surfaces were studied [M. Goldfeld, 1993]. The possibility and conditions of the boundary layer relaminarization behind the expansion fan and its effect on the relaxation length are presented. Different model configurations for wide range conditions were investigated. Comparison of results for different interactions was carried out.

Heat transfer through turbulent boundary layers - The effects of introduction of and recovery from convex curvature

NASA Technical Reports Server (NTRS)

Simon, T. W.; Moffat, R. J.

1979-01-01

Measurements have been made of the heat transfer through a turbulent boundary layer on a convexly curved isothermal wall and on a flat plate following the curved section. Data were taken for one free-stream velocity and two different ratios of boundary layer thickness to radius of curvature delta/R = 0.051 and delta/R = 0.077. Only small differences were observed in the distribution of heat transfer rates for the two boundary layer thicknesses tested, although differences were noted in the temperature distributions within the boundary layer

F-16XL ship #1 - CAWAP boundary layer rakes and hot film on left wing

NASA Technical Reports Server (NTRS)

1996-01-01

This photo shows the boundary layer hot film and the boundary layer rakes on the left wing of NASA's single-seat F-16XL (ship #1) used for the Cranked-Arrow Wing Aerodynamic Project (CAWAP) at Dryden Flight Research Center, Edwards, California. The modified airplane features a delta 'cranked-arrow' wing with strips of tubing along the leading edge to the trailing edge to sense static on the wing and obtain pressure distribution data. The right wing receives data on pressure distribution and the left wing has three types of instrumentation - preston tubes to measure local skin friction, boundary layer rakes to measure boundary layer profiles (the layer where the air interacts with the surfaces of a moving aircraft), and hot films to determine boundary layer transition locations. The first flight of CAWAP occurred on November 21, 1995, and the test program ended in April 1996.

An Experimental Investigation of the Confluent Boundary Layer on a High-Lift System

NASA Technical Reports Server (NTRS)

Thomas, F. O.; Nelson, R. C.

1997-01-01

This paper describes a fundamental experimental investigation of the confluent boundary layer generated by the interaction of a leading-edge slat wake with the boundary layer on the main element of a multi-element airfoil model. The slat and airfoil model geometry are both fully two-dimensional. The research reported in this paper is performed in an attempt to investigate the flow physics of confluent boundary layers and to build an archival data base on the interaction of the slat wake and the main element wall layer. In addition, an attempt is made to clearly identify the role that slat wake / airfoil boundary layer confluence has on lift production and how this occurs. Although complete LDV flow surveys were performed for a variety of slat gap and overhang settings, in this report the focus is on two cases representing both strong and weak wake boundary layer confluence.

Towards Natural Transition in Compressible Boundary Layers

DTIC Science & Technology

2016-06-29

AFRL-AFOSR-CL-TR-2016-0011 Towards natural transition in compressible boundary layers Marcello Faraco de Medeiros FUNDACAO PARA O INCREMENTO DA...to 29-03-2016 Towards natural transition in compressible boundary layers FA9550-11-1-0354 Marcello A. Faraco de Medeiros Germán Andrés Gaviria...unlimited. 109 Final report Towards natural transition in compressible boundary layers Principal Investigator: Marcello Augusto Faraco de Medeiros

Inventory of File nam.t00z.smartconus00.tm00.grib2

Science.gov Websites

(Eta model reduction) [Pa] 014 planetary boundary layer WDIR analysis Wind Direction (from which blowing) [degtrue] 015 planetary boundary layer WIND analysis Wind Speed [m/s] 016 planetary boundary layer RH analysis Relative Humidity [%] 017 planetary boundary layer DIST analysis Geometric Height [m

Evaluation of Aerosol Pollution Determination From MODIS Satellite Retrievals for Semi-Arid Reno, NV, USA with In-Situ Measurements

NASA Astrophysics Data System (ADS)

Loria-Salazar, S. Marcela

The aim of the present work is to carry out a detailed analysis of ground and columnar aerosol properties obtained by in-situ Photoacoustic and Integrated Nephelometer (PIN), Cimel CE-318 sunphotometer and MODIS instrument onboard Aqua and Terra satellites, for semi-arid Reno, Nevada, USA in the local summer months of 2012. Satellite determination of local aerosol pollution is desirable because of the potential for broad spatial and temporal coverage. However, retrieval of quantitative measures of air pollution such as Aerosol Optical Depth (AOD) from satellite measurements is challenging because of the underlying surface albedo being heterogeneous in space and time. Therefore, comparisons of satellite retrievals with measurements from ground-based sun photometers are crucial for validation, testing, and further development of instruments and retrieval algorithms. Ground-based sunphotometry and in-situ ground observations show that seasonal weather changes and fire plumes have great influence on the atmosphere aerosol optics. The Apparent Optical Height (AOH) follows the shape of the development of the Convective Boundary Layer (CBL) when fire conditions were not present. However, significant fine particle optical depth was inferred beyond the CBL thereby complicating the use of remote sensing measurements for near-ground aerosol pollution measurements. A meteorological analysis was performed to help diagnose the nature of the aerosols above Reno. The calculation of a Zephyr index and back trajectory analysis demonstrated that a local circulation often induces aerosol transport from Northern CA over the Sierra Nevada Mountains that doubles the Aerosol Optical Depth (AOD) at 500 nm. Sunphotometer measurements were used as a `ground truth' for satellite retrievals to evaluate the current state of the science retrievals in this challenging location. Satellite retrieved for AOD showed the presence of wild fires in Northern CA during August. AOD retrieved using the "dark-target algorithm" may be unrealistically high over the Great Basin. Low correlation was found between AERONET AOD and dark-target algorithm AOD retrievals from Aqua and Terra during June and July. During fire conditions the dark-target algorithm AOD values correlated better with AERONET measurements in August. Use of the Deep-blue algorithm for MODIS data to retrieve AOD did not provide enough points to compare with AERONET in June and July. In August, AOD from deep-blue and AERONET retrievals exhibited low correlation. AEE from MODIS products and AERONET exhibited low correlation during every month. Apparently satellite AOD retrievals need much improvement for areas like semi-arid Reno.

Asymmetric simple exclusion process with position-dependent hopping rates: Phase diagram from boundary-layer analysis.

PubMed

Mukherji, Sutapa

2018-03-01

In this paper, we study a one-dimensional totally asymmetric simple exclusion process with position-dependent hopping rates. Under open boundary conditions, this system exhibits boundary-induced phase transitions in the steady state. Similarly to totally asymmetric simple exclusion processes with uniform hopping, the phase diagram consists of low-density, high-density, and maximal-current phases. In various phases, the shape of the average particle density profile across the lattice including its boundary-layer parts changes significantly. Using the tools of boundary-layer analysis, we obtain explicit solutions for the density profile in different phases. A detailed analysis of these solutions under different boundary conditions helps us obtain the equations for various phase boundaries. Next, we show how the shape of the entire density profile including the location of the boundary layers can be predicted from the fixed points of the differential equation describing the boundary layers. We discuss this in detail through several examples of density profiles in various phases. The maximal-current phase appears to be an especially interesting phase where the boundary layer flows to a bifurcation point on the fixed-point diagram.

Asymmetric simple exclusion process with position-dependent hopping rates: Phase diagram from boundary-layer analysis

NASA Astrophysics Data System (ADS)

Mukherji, Sutapa

2018-03-01

In this paper, we study a one-dimensional totally asymmetric simple exclusion process with position-dependent hopping rates. Under open boundary conditions, this system exhibits boundary-induced phase transitions in the steady state. Similarly to totally asymmetric simple exclusion processes with uniform hopping, the phase diagram consists of low-density, high-density, and maximal-current phases. In various phases, the shape of the average particle density profile across the lattice including its boundary-layer parts changes significantly. Using the tools of boundary-layer analysis, we obtain explicit solutions for the density profile in different phases. A detailed analysis of these solutions under different boundary conditions helps us obtain the equations for various phase boundaries. Next, we show how the shape of the entire density profile including the location of the boundary layers can be predicted from the fixed points of the differential equation describing the boundary layers. We discuss this in detail through several examples of density profiles in various phases. The maximal-current phase appears to be an especially interesting phase where the boundary layer flows to a bifurcation point on the fixed-point diagram.

Boundary Layer

NASA Technical Reports Server (NTRS)

Loitsianskii. L. G.

1956-01-01

The fundamental, practically the most important branch of the modern mechanics of a viscous fluid or a gas, is that branch which concerns itself with the study of the boundary layer. The presence of a boundary layer accounts for the origin of the resistance and lift force, the breakdown of the smooth flow about bodies, and other phenomena that are associated with the motion of a body in a real fluid. The concept of boundary layer was clearly formulated by the founder of aerodynamics, N. E. Joukowsky, in his well-known work "On the Form of Ships" published as early as 1890. In his book "Theoretical Foundations of Air Navigation," Joukowsky gave an account of the most important properties of the boundary layer and pointed out the part played by it in the production of the resistance of bodies to motion. The fundamental differential equations of the motion of a fluid in a laminar boundary layer were given by Prandtl in 1904; the first solutions of these equations date from 1907 to 1910. As regards the turbulent boundary layer, there does not exist even to this day any rigorous formulation of this problem because there is no closed system of equations for the turbulent motion of a fluid. Soviet scientists have done much toward developing a general theory of the boundary layer, and in that branch of the theory which is of greatest practical importance at the present time, namely the study of the boundary layer at large velocities of the body in a compressed gas, the efforts of the scientists of our country have borne fruit in the creation of a new theory which leaves far behind all that has been done previously in this direction. We shall herein enumerate the most important results by Soviet scientists in the development of the theory of the boundary layer.

Hypersonic Boundary Layer Transition Measurements Using NO2 approaches NO Photo-dissociation Tagging Velocimetry

NASA Technical Reports Server (NTRS)

Bathel, Brett F.; Johansen, Craig T.; Danehy, Paul M.; Inman, Jennifer A.; Jones, Stephen B.; Goyne, Christopher P.

2011-01-01

Measurements of instantaneous and mean streamwise velocity profiles in a hypersonic laminar boundary layer as well as a boundary layer undergoing laminar-to-turbulent transition were obtained over a 10-degree half-angle wedge model. A molecular tagging velocimetry technique consisting of a NO2 approaches?NO photo-dissociation reaction and two subsequent excitations of NO was used. The measurement of the transitional boundary layer velocity profiles was made downstream of a 1-mm tall, 4-mm diameter cylindrical trip along several lines lying within a streamwise measurement plane normal to the model surface and offset 6-mm from the model centerline. For laminar and transitional boundary layer measurements, the magnitudes of streamwise velocity fluctuations are compared. In the transitional boundary layer the fluctuations were, in general, 2-4 times larger than those in the laminar boundary layer. Of particular interest were fluctuations corresponding to a height of approximately 50% of the laminar boundary layer thickness having a magnitude of nearly 30% of the mean measured velocity. For comparison, the measured fluctuations in the laminar boundary layer were approximately 5% of the mean measured velocity at the same location. For the highest 10% signal-to-noise ratio data, average single-shot uncertainties using a 1 ?Es and 50 ?Es interframe delay were 115 m/s and 3 m/s, respectively. By averaging single-shot measurements of the transitional boundary layer, uncertainties in mean velocity as low as 39 m/s were obtained in the wind tunnel. The wall-normal and streamwise spatial resolutions were 0.14-mm (2 pixel) and 0.82-mm (11 pixels), respectively. These measurements were performed in the 31-inch Mach 10 Air Wind Tunnel at the NASA Langley Research Center.

Laminar-turbulent transition tripped by step on transonic compressor profile

NASA Astrophysics Data System (ADS)

Flaszynski, Pawel; Doerffer, Piotr; Szwaba, Ryszard; Piotrowicz, Michal; Kaczynski, Piotr

2018-02-01

The shock wave boundary layer interaction on the suction side of transonic compressor blade is one of the main objectives of TFAST project (Transition Location Effect on Shock Wave Boundary Layer Interaction). The experimental and numerical results for the flow structure investigations are shown for the flow conditions as the existing ones on the suction side of the compressor profile. The two cases are investigated: without and with boundary layer tripping device. In the first case, boundary layer is laminar up to the shock wave, while in the second case the boundary layer is tripped by the step. Numerical results carried out by means of Fine/Turbo Numeca with Explicit Algebraic Reynolds Stress Model including transition modeling are compared with schlieren, Temperature Sensitive Paint and wake measurements. Boundary layer transition location is detected by Temperature Sensitive Paint.

Sound-turbulence interaction in transonic boundary layers

NASA Astrophysics Data System (ADS)

Lelostec, Ludovic; Scalo, Carlo; Lele, Sanjiva

2014-11-01

Acoustic wave scattering in a transonic boundary layer is investigated through a novel approach. Instead of simulating directly the interaction of an incoming oblique acoustic wave with a turbulent boundary layer, suitable Dirichlet conditions are imposed at the wall to reproduce only the reflected wave resulting from the interaction of the incident wave with the boundary layer. The method is first validated using the laminar boundary layer profiles in a parallel flow approximation. For this scattering problem an exact inviscid solution can be found in the frequency domain which requires numerical solution of an ODE. The Dirichlet conditions are imposed in a high-fidelity unstructured compressible flow solver for Large Eddy Simulation (LES), CharLESx. The acoustic field of the reflected wave is then solved and the interaction between the boundary layer and sound scattering can be studied.

Pitot-probe displacement in a supersonic turbulent boundary layer

NASA Technical Reports Server (NTRS)

Allen, J. M.

1972-01-01

Eight circular pitot probes ranging in size from 2 to 70 percent of the boundary-layer thickness were tested to provide experimental probe displacement results in a two-dimensional turbulent boundary layer at a nominal free-stream Mach number of 2 and unit Reynolds number of 8 million per meter. The displacement obtained in the study was larger than that reported by previous investigators in either an incompressible turbulent boundary layer or a supersonic laminar boundary layer. The large probes indicated distorted Mach number profiles, probably due to separation. When the probes were small enough to cause no appreciable distortion, the displacement was constant over most of the boundary layer. The displacement in the near-wall region decreased to negative displacement in some cases. This near-wall region was found to extend to about one probe diameter from the test surface.

Flat Plate Boundary Layer Stimulation Using Trip Wires and Hama Strips

NASA Astrophysics Data System (ADS)

Peguero, Charles; Henoch, Charles; Hrubes, James; Fredette, Albert; Roberts, Raymond; Huyer, Stephen

2017-11-01

Water tunnel experiments on a flat plate at zero angle of attack were performed to investigate the effect of single roughness elements, i.e., trip wires and Hama strips, on the transition to turbulence. Boundary layer trips are traditionally used in scale model testing to force a boundary layer to transition from laminar to turbulent flow at a single location to aid in scaling of flow characteristics. Several investigations of trip wire effects exist in the literature, but there is a dearth of information regarding the influence of Hama strips on the flat plate boundary layer. The intent of this investigation is to better understand the effects of boundary layer trips, particularly Hama strips, and to investigate the pressure-induced drag of both styles of boundary layer trips. Untripped and tripped boundary layers along a flat plate at a range of flow speeds were characterized with multiple diagnostic measurements in the NUWC/Newport 12-inch water tunnel. A wide range of Hama strip and wire trip thicknesses were used. Measurements included dye flow visualization, direct skin friction and parasitic drag force, boundary layer profiles using LDV, wall shear stress fluctuations using hot film anemometry, and streamwise pressure gradients. Test results will be compared to the CFD and boundary layer model results as well as the existing body of work. Conclusions, resulting in guidance for application of Hama strips in model scale experiments and non-dimensional predictions of pressure drag will be presented.

Year-Long Vertical Velocity Statistics Derived from Doppler Lidar Data for the Continental Convective Boundary Layer

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

Berg, Larry K.; Newsom, Rob K.; Turner, David D.

One year of Coherent Doppler Lidar (CDL) data collected at the U.S. Department of Energy’s Atmospheric Radiation Measurement (ARM) site in Oklahoma is analyzed to provide profiles of vertical velocity variance, skewness, and kurtosis for cases of cloud-free convective boundary layers. The variance was scaled by the Deardorff convective velocity scale, which was successful when the boundary layer depth was stationary but failed in situations when the layer was changing rapidly. In this study the data are sorted according to time of day, season, wind direction, surface shear stress, degree of instability, and wind shear across the boundary-layer top. Themore » normalized variance was found to have its peak value near a normalized height of 0.25. The magnitude of the variance changes with season, shear stress, and degree of instability, but was not impacted by wind shear across the boundary-layer top. The skewness was largest in the top half of the boundary layer (with the exception of wintertime conditions). The skewness was found to be a function of the season, shear stress, wind shear across the boundary-layer top, with larger amounts of shear leading to smaller values. Like skewness, the vertical profile of kurtosis followed a consistent pattern, with peak values near the boundary-layer top (also with the exception of wintertime data). The altitude of the peak values of kurtosis was found to be lower when there was a large amount of wind shear at the boundary-layer top.« less

Towards a Viscous Wall Model for Immersed Boundary Methods

NASA Technical Reports Server (NTRS)

Brehm, Christoph; Barad, Michael F.; Kiris, Cetin C.

2016-01-01

Immersed boundary methods are frequently employed for simulating flows at low Reynolds numbers or for applications where viscous boundary layer effects can be neglected. The primary shortcoming of Cartesian mesh immersed boundary methods is the inability of efficiently resolving thin turbulent boundary layers in high-Reynolds number flow application. The inefficiency of resolving the thin boundary is associated with the use of constant aspect ratio Cartesian grid cells. Conventional CFD approaches can efficiently resolve the large wall normal gradients by utilizing large aspect ratio cells near the wall. This paper presents different approaches for immersed boundary methods to account for the viscous boundary layer interaction with the flow-field away from the walls. Different wall modeling approaches proposed in previous research studies are addressed and compared to a new integral boundary layer based approach. In contrast to common wall-modeling approaches that usually only utilize local flow information, the integral boundary layer based approach keeps the streamwise history of the boundary layer. This allows the method to remain effective at much larger y+ values than local wall modeling approaches. After a theoretical discussion of the different approaches, the method is applied to increasingly more challenging flow fields including fully attached, separated, and shock-induced separated (laminar and turbulent) flows.

Investigations on entropy layer along hypersonic hyperboloids using a defect boundary layer

NASA Technical Reports Server (NTRS)

Brazier, J. P.; Aupoix, B.; Cousteix, J.

1992-01-01

A defect approach coupled with matched asymptotic expansions is used to derive a new set of boundary layer equations. This method ensures a smooth matching of the boundary layer with the inviscid solution. These equations are solved to calculate boundary layers over hypersonic blunt bodies involving the entropy gradient effect. Systematic comparisons are made for both axisymmetric and plane flows in several cases with different Mach and Reynolds numbers. After a brief survey of the entropy layer characteristics, the defect boundary layer results are compared with standard boundary layer and full Navier-Stokes solutions. The entropy gradient effects are found to be more important in the axisymmetric case than in the plane one. The wall temperature has a great influence on the results through the displacement effect. Good predictions can be obtained with the defect approach over a cold wall in the nose region, with a first order solution. However, the defect approach gives less accurate results far from the nose on axisymmetric bodies because of the thinning of the entropy layer.

Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death

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

Hemendinger, Richelle A., E-mail: richelle.hemendinger@carolinashealthcare.org; Armstrong, Edward J.; Brooks, Benjamin Rix

Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC{sub 50} (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolatemore » (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC{sub 50} (concentration at which 50% of maximal cell death is inhibited) of 0.6 {mu}M and 0.4 {mu}M, respectively. In contrast, MTHF (up to 10 {mu}M) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.« less

Coastal change analysis of Lovells Island using high resolution ground based LiDAR imagery

NASA Astrophysics Data System (ADS)

Ly, Jennifer K.

Many methods have been employed to study coastline change. These methods range from historical map analysis to GPS surveys to modern airborne LiDAR and satellite imagery. These previously used methods can be time consuming, labor intensive, and expensive and have varying degrees of accuracy and temporal coverage. Additionally, it is often difficult to apply such techniques in direct response to an isolated event within an appropriate temporal framework. Here we utilize a new ground based Canopy Biomass LiDAR (CBL) system built at The University of Massachusetts Boston (in collaboration with the Rochester Institute of Technology) in order to identify and analyze coastal change on Lovells Island, Boston Harbor. Surveys of a bluff developing in an eroding drumlin and beach cusps on a high-energy cobble beach on Lovells Island were conducted in June, September and December of 2013. At each site for each survey, the CBL was set up and multiple scans of each feature were taken on a predetermined transect that was established parallel to the high-water mark at distances relative to the scale of the bluff and cusps. The scans from each feature were compiled, integrated and visualized using Meshlab. Results from our surveys indicate that the highly portable and easy to deploy CBL system produces images of exceptional clarity, with the capacity to resolve small-scale changes to coastal features and systems. The CBL, while still under development (and coastal surveying protocols with it are just being established), appears to be an ideal tool for analyzing coastal geological features and is anticipated to prove to be a useful tool for the observation and analysis of coastal change. Furthermore, there is significant potential for utilizing the low cost ultra-portable CBL in frequent deployments to develop small-scale erosion rate and sediment budget analyses.

Inventory of File gfs.t06z.smartguam15.tm00.grib2

Science.gov Websites

hour fcst Visibility [m] 014 planetary boundary layer WDIR 15 hour fcst Wind Direction (from which blowing) [degtrue] 015 planetary boundary layer WIND 15 hour fcst Wind Speed [m/s] 016 planetary boundary layer RH 15 hour fcst Relative Humidity [%] 017 planetary boundary layer DIST 15 hour fcst Geometric

Physical modeling of the atmospheric boundary layer in the UNH Flow Physics Facility

NASA Astrophysics Data System (ADS)

Taylor-Power, Gregory; Gilooly, Stephanie; Wosnik, Martin; Klewicki, Joe; Turner, John

2016-11-01

The Flow Physics Facility (FPF) at UNH has test section dimensions W =6.0m, H =2.7m, L =72m. It can achieve high Reynolds number boundary layers, enabling turbulent boundary layer, wind energy and wind engineering research with exceptional spatial and temporal instrument resolution. We examined the FPF's ability to experimentally simulate different types of the atmospheric boundary layer (ABL) using upstream roughness arrays. The American Society for Civil Engineers defines standards for simulating ABLs for different terrain types, from open sea to dense city areas (ASCE 49-12). The standards require the boundary layer to match a power law shape, roughness height, and power spectral density criteria. Each boundary layer type has a corresponding power law exponent and roughness height. The exponent and roughness height both increase with increasing roughness. A suburban boundary layer was chosen for simulation and a roughness element fetch was created. Several fetch lengths were experimented with and the resulting boundary layers were measured and compared to standards in ASCE 49-12: Wind Tunnel Testing for Buildings and Other Structures. Pitot tube and hot wire anemometers were used to measure average and fluctuating flow characteristics. Velocity profiles, turbulence intensity and velocity spectra were found to compare favorably.

Effect of Pulsed Plasma Jets on the Recovering Boundary Layer Downstream of a Reflected Shock Interaction

NASA Astrophysics Data System (ADS)

Greene, Benton; Clemens, Noel; Magari, Patrick; Micka, Daniel; Ueckermann, Mattheus

2015-11-01

Shock-induced turbulent boundary layer separation can have many detrimental effects in supersonic inlets including flow distortion and instability, structural fatigue, poor pressure recovery, and unstart. The current study investigates the effect of pulsed plasma jets on the recovering boundary layer downstream of a reflected shock wave-boundary layer interaction. The effects of pitch and skew angle of the jet as well as the heating parameter and discharge time scale are tested using several pulsing frequencies. In addition, the effect of the plasma jets on the undisturbed boundary layer at 6 mm and 11 mm downstream of the jets is measured. A pitot-static pressure probe is used to measure the velocity profile of the boundary layer 35 mm downstream of the plasma jets, and the degree of boundary layer distortion is compared between the different models and run conditions. Additionally, the effect of each actuator configuration on the shape of the mean separated region is investigated using surface oil flow visualization. Previous studies with lower energy showed a weak effect on the downstream boundary layer. The current investigation will attempt to increase this effect using a higher-energy discharge. Funded by AFRL through and SBIR in collaboration with Creare, LLC.

Optimal Control of Shock Wave Turbulent Boundary Layer Interactions Using Micro-Array Actuation

NASA Technical Reports Server (NTRS)

Anderson, Bernhard H.; Tinapple, Jon; Surber, Lewis

2006-01-01

The intent of this study on micro-array flow control is to demonstrate the viability and economy of Response Surface Methodology (RSM) to determine optimal designs of micro-array actuation for controlling the shock wave turbulent boundary layer interactions within supersonic inlets and compare these concepts to conventional bleed performance. The term micro-array refers to micro-actuator arrays which have heights of 25 to 40 percent of the undisturbed supersonic boundary layer thickness. This study covers optimal control of shock wave turbulent boundary layer interactions using standard micro-vane, tapered micro-vane, and standard micro-ramp arrays at a free stream Mach number of 2.0. The effectiveness of the three micro-array devices was tested using a shock pressure rise induced by the 10 shock generator, which was sufficiently strong as to separate the turbulent supersonic boundary layer. The overall design purpose of the micro-arrays was to alter the properties of the supersonic boundary layer by introducing a cascade of counter-rotating micro-vortices in the near wall region. In this manner, the impact of the shock wave boundary layer (SWBL) interaction on the main flow field was minimized without boundary bleed.

Generalization of Boundary-Layer Momentum-Integral Equations to Three-Dimensional Flows Including Those of Rotating System

NASA Technical Reports Server (NTRS)

Mager, Arthur

1952-01-01

The Navier-Stokes equations of motion and the equation of continuity are transformed so as to apply to an orthogonal curvilinear coordinate system rotating with a uniform angular velocity about an arbitrary axis in space. A usual simplification of these equations as consistent with the accepted boundary-layer theory and an integration of these equations through the boundary layer result in boundary-layer momentum-integral equations for three-dimensional flows that are applicable to either rotating or nonrotating fluid boundaries. These equations are simplified and an approximate solution in closed integral form is obtained for a generalized boundary-layer momentum-loss thickness and flow deflection at the wall in the turbulent case. A numerical evaluation of this solution carried out for data obtained in a curving nonrotating duct shows a fair quantitative agreement with the measures values. The form in which the equations are presented is readily adaptable to cases of steady, three-dimensional, incompressible boundary-layer flow like that over curved ducts or yawed wings; and it also may be used to describe the boundary-layer flow over various rotating surfaces, thus applying to turbomachinery, propellers, and helicopter blades.

Modeling marine boundary-layer clouds with a two-layer model: A one-dimensional simulation

NASA Technical Reports Server (NTRS)

Wang, Shouping

1993-01-01

A two-layer model of the marine boundary layer is described. The model is used to simulate both stratocumulus and shallow cumulus clouds in downstream simulations. Over cold sea surfaces, the model predicts a relatively uniform structure in the boundary layer with 90%-100% cloud fraction. Over warm sea surfaces, the model predicts a relatively strong decoupled and conditionally unstable structure with a cloud fraction between 30% and 60%. A strong large-scale divergence considerably limits the height of the boundary layer and decreases relative humidity in the upper part of the cloud layer; thus, a low cloud fraction results. The efffects of drizzle on the boundary-layer structure and cloud fraction are also studied with downstream simulations. It is found that drizzle dries and stabilizes the cloud layer and tends to decouple the cloud from the subcloud layer. Consequently, solid stratocumulus clouds may break up and the cloud fraction may decrease because of drizzle.

Calculation of sidewall boundary-layer parameters from rake measurements for the Langley 0.3-meter transonic cryogenic tunnel

NASA Technical Reports Server (NTRS)

Murthy, A. V.

1987-01-01

Correction of airfoil data for sidewall boundary-layer effects requires a knowledge of the boundary-layer displacement thickness and the shape factor with the tunnel empty. To facilitate calculation of these quantities under various test conditions for the Langley 0.3 m Transonic Cryogenic Tunnel, a computer program was written. This program reads the various tunnel parameters and the boundary-layer rake total head pressure measurements directly from the Engineering Unit tapes to calculate the required sidewall boundary-layer parameters. Details of the method along with the results for a sample case are presented.

Studies on the influence on flexural wall deformations on the development of the flow boundary layer

NASA Technical Reports Server (NTRS)

Schilz, W.

1978-01-01

Flexural wave-like deformations can be used to excite boundary layer waves which in turn lead to the onset of turbulence in the boundary layer. The investigations were performed with flow velocities between 5 m/s and 40 m/s. With four different flexural wave transmissions a frequency range from 0.2 kc/s to 1.5 kc/s and a phase velocity range from 3.5 m/s to 12 m/s was covered. The excitation of boundary layer waves becomes most effective if the phase velocity of the flexural wave coincides with the phase velocity region of unstable boundary layer waves.

Viscous flow drag reduction; Symposium, Dallas, Tex., November 7, 8, 1979, Technical Papers

NASA Technical Reports Server (NTRS)

Hough, G. R.

1980-01-01

The symposium focused on laminar boundary layers, boundary layer stability analysis of a natural laminar flow glove on the F-111 TACT aircraft, drag reduction of an oscillating flat plate with an interface film, electromagnetic precipitation and ducting of particles in turbulent boundary layers, large eddy breakup scheme for turbulent viscous drag reduction, blowing and suction, polymer additives, and compliant surfaces. Topics included influence of environment in laminar boundary layer control, generation rate of turbulent patches in the laminar boundary layer of a submersible, drag reduction of small amplitude rigid surface waves, and hydrodynamic drag and surface deformations generated by liquid flows over flexible surfaces.

Effect of aspect ratio on sidewall boundary-layer influence in two-dimensional airfoil testing

NASA Technical Reports Server (NTRS)

Murthy, A. V.

1986-01-01

The effect of sidewall boundary layers in airfoil testing in two-dimensional wind tunnels is investigated. The non-linear crossflow velocity variation induced because of the changes in the sidewall boundary-layer thickness is represented by the flow between a wavy wall and a straight wall. Using this flow model, a correction for the sidewall boundary-layer effects is derived in terms of the undisturbed sidewall boundary-layer properties, the test Mach number and the airfoil aspect ratio. Application of the proposed correction to available experimental data showed good correlation for the shock location and pressure distribution on airfoils.

Boundary-field-driven control of discontinuous phase transitions on hyperbolic lattices

NASA Astrophysics Data System (ADS)

Lee, Yoju; Verstraete, Frank; Gendiar, Andrej

2016-08-01

The multistate Potts models on two-dimensional hyperbolic lattices are studied with respect to various boundary effects. The free energy is numerically calculated using the corner transfer matrix renormalization group method. We analyze phase transitions of the Potts models in the thermodynamic limit with respect to contracted boundary layers. A false phase transition is present even if a couple of the boundary layers are contracted. Its significance weakens, as the number of the contracted boundary layers increases, until the correct phase transition (deep inside the bulk) prevails over the false one. For this purpose, we derive a thermodynamic quantity, the so-called bulk excess free energy, which depends on the contracted boundary layers and memorizes additional boundary effects. In particular, the magnetic field is imposed on the outermost boundary layer. While the boundary magnetic field does not affect the second-order phase transition in the bulk if suppressing all the boundary effects on the hyperbolic lattices, the first-order (discontinuous) phase transition is significantly sensitive to the boundary magnetic field. Contrary to the phase transition on the Euclidean lattices, the discontinuous phase transition on the hyperbolic lattices can be continuously controlled (within a certain temperature coexistence region) by varying the boundary magnetic field.

Numerical investigation of an internal layer in turbulent flow over a curved hill

NASA Technical Reports Server (NTRS)

Kim, S-W.

1989-01-01

The development of an internal layer in a turbulent boundary layer flow over a curved hill is investigated numerically. The turbulence field of the boundary layer flow over the curved hill is compared with that of a turbulent flow over a symmetric airfoil (which has the same geometry as the curved hill except that the leading and trailing edge plates were removed) to study the influence of the strongly curved surface on the turbulence field. The turbulent flow equations are solved by a control-volume based finite difference method. The turbulence is described by a multiple-time-scale turbulence model supplemented with a near-wall turbulence model. Computational results for the mean flow field (pressure distributions on the walls, wall shearing stresses and mean velocity profiles), the turbulence structure (Reynolds stress and turbulent kinetic energy profiles), and the integral parameters (displacement and momentum thicknesses) compared favorably with the measured data. Computational results show that the internal layer is a strong turbulence field which is developed beneath the external boundary layer and is located very close to the wall. Development of the internal layer was more obviously observed in the Reynolds stress profiles and in the turbulent kinetic energy profiles than in the mean velocity profiles. In this regard, the internal layers is significantly different from wall-bounded simple shear layers in which the mean velocity profile characterizes the boundary layer most distinguishably. Development of such an internal layer, characterized by an intense turbulence field, is attributed to the enormous mean flow strain rate caused by the streamline curvature and the strong pressure gradient. In the turbulent flow over the curved hill, the internal layer begin to form near the forward corner of the hill, merges with the external boundary layer, and develops into a new fully turbulent boundary layer as the fluid flows in the downstream direction. For the flow over the symmetric airfoil, the boundary layer began to form from almost the same location as that of the curved hill, grew in its strength, and formed a fully turbulent boundary layer from mid-part of the airfoil and in the downstream region. Computational results also show that the detailed turbulence structure in the region very close to the wall of the curved hill is almost the same as that of the airfoil in most of the curved regions except near the leading edge. Thus the internal layer of the curved hill and the boundary layer of the airfoil were also almost the same. Development of the wall shearing stress and separation of the boundary layer at the rear end of the curved hill mostly depends on the internal layer and is only slightly influenced by the external boundary layer flow.

The influence of free-stream turbulence on turbulent boundary layers with mild adverse pressure gradients

NASA Technical Reports Server (NTRS)

Hoffmann, Jon A.

1988-01-01

The influence of near isotropic free-stream turbulence on the shape factors and skin friction coefficients of turbulent bounday layers is presented for the cases of zero and mild adverse pressure gradients. With free-stream turbulence, improved fluid mixing occurs in boundary layers with adverse pressure gradients relative to the zero pressure gradient condition, with the same free-stream turbulence intensity and length scale. Stronger boundary layers with lower shape factors occur as a result of a lower ratio of the integral scale of turbulence to the boundary layer thickness, and to vortex stretching of the turbulent eddies in the free stream, both of which act to improve the transmission of momentum from the free stream to the boundary layers.

Observing the Vertical Extent of the Urban Boundary Layer Over Jersey City, NJ: A Diurnal and Seasonal Analysis

NASA Astrophysics Data System (ADS)

Dempsey, M. J.; Booth, J.; Arend, M.; Melecio-Vazquez, D.; Gonzalez, J.

2015-12-01

The atmospheric boundary remains one of the more difficult components of the climate system to classify. One of the most important characteristics is the boundary layer height, especially in urban settings. The current study examines the boundary layer height using the the New York City Meteorological Network or NYCMetNet. NYCMetNet is a network of weather stations, which report meteorological conditions in and around New York City, as part of the Optical Remote Sensing Laboratory of The City College of New York (ORSL). Of interest to this study is the data obtained from wind profiler station LSC01. The 915 MHz wind profiler is located 30m above the ground on the roof of the Liberty Science Center in Jersey City, NJ. It is a Vaisala Wind Profiler LAP 3000 with a wavelength of ~34cm, which means that the instrument responds primarily to Bragg backscattering. Can a seasonal urban boundary layer climatology be extrapolated from the data obtained from the wind profiler? What is the timing of boundary layer evolution and collapse over Jersey City? How effective is the profiler under cloudy skies and even in light rain or snow? This study examines the entire time period covered by the wind profile (2007 to present) and selects a series of clear days and a series of cloudy days. The top of the urban boundary layer is subjectively located from each half hour time stamp of signal to noise values. The urban boundary layer heights are recorded for clear and then cloudy days. Then the days are sorted seasonally (DJF, MAM, JJA, SON). A seasonal mean is calculated for every half hour time step. Finally a time series of seasonal urban boundary layer heights is constructed, and the timing of the urban boundary layer height maximum and time evolution and collapse of the boundary layer are generalized. A comparison is made against urban boundary layer heights obtained from Modern-Era Retrospective Analysis For Research And Applications (MERRA).

Foliar trichomes, boundary layers, and gas exchange in 12 species of epiphytic Tillandsia (Bromeliaceae).

PubMed

Benz, Brett W; Martin, Craig E

2006-04-01

We examined the relationships between H2O and CO2 gas exchange parameters and leaf trichome cover in 12 species of Tillandsia that exhibit a wide range in trichome size and trichome cover. Previous investigations have hypothesized that trichomes function to enhance boundary layers around Tillandsioid leaves thereby buffering the evaporative demand of the atmosphere and retarding transpirational water loss. Data presented herein suggest that trichome-enhanced boundary layers have negligible effects on Tillandsia gas exchange, as indicated by the lack of statistically significant relationships in regression analyses of gas exchange parameters and trichome cover. We calculated trichome and leaf boundary layer components, and their associated effects on H2O and CO2 gas exchange. The results further indicate trichome-enhanced boundary layers do not significantly reduce transpirational water loss. We conclude that although the trichomes undoubtedly increase the thickness of the boundary layer, the increase due to Tillandsioid trichomes is inconsequential in terms of whole leaf boundary layers, and any associated reduction in transpirational water loss is also negligible within the whole plant gas exchange pathway.

Hydrodynamic structure of the boundary layers in a rotating cylindrical cavity with radial inflow

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

Herrmann-Priesnitz, Benjamín, E-mail: bherrman@ing.uchile.cl; Torres, Diego A.; Advanced Mining Technology Center, Universidad de Chile, Av. Tupper 2007, Santiago

A flow model is formulated to investigate the hydrodynamic structure of the boundary layers of incompressible fluid in a rotating cylindrical cavity with steady radial inflow. The model considers mass and momentum transfer coupled between boundary layers and an inviscid core region. Dimensionless equations of motion are solved using integral methods and a space-marching technique. As the fluid moves radially inward, entraining boundary layers develop which can either meet or become non-entraining. Pressure and wall shear stress distributions, as well as velocity profiles predicted by the model, are compared to numerical simulations using the software OpenFOAM. Hydrodynamic structure of themore » boundary layers is governed by a Reynolds number, Re, a Rossby number, Ro, and the dimensionless radial velocity component at the periphery of the cavity, U{sub o}. Results show that boundary layers merge for Re < < 10 and Ro > > 0.1, and boundary layers become predominantly non-entraining for low Ro, low Re, and high U{sub o}. Results may contribute to improve the design of technology, such as heat exchange devices, and turbomachinery.« less

Control of boundary layer transition location and plate vibration in the presence of an external acoustic field

NASA Technical Reports Server (NTRS)

Maestrello, L.; Grosveld, F. W.

1991-01-01

The experiment is aimed at controlling the boundary layer transition location and the plate vibration when excited by a flow and an upstream sound source. Sound has been found to affect the flow at the leading edge and the response of a flexible plate in a boundary layer. Because the sound induces early transition, the panel vibration is acoustically coupled to the turbulent boundary layer by the upstream radiation. Localized surface heating at the leading edge delays the transition location downstream of the flexible plate. The response of the plate excited by a turbulent boundary layer (without sound) shows that the plate is forced to vibrate at different frequencies and with different amplitudes as the flow velocity changes indicating that the plate is driven by the convective waves of the boundary layer. The acoustic disturbances induced by the upstream sound dominate the response of the plate when the boundary layer is either turbulent or laminar. Active vibration control was used to reduce the sound induced displacement amplitude of the plate.

A Marine Boundary Layer Water Vapor Climatology Derived from Microwave and Near-Infrared Imagery

NASA Astrophysics Data System (ADS)

Millan Valle, L. F.; Lebsock, M. D.; Teixeira, J.

2017-12-01

The synergy of the collocated Advanced Microwave Scanning Radiometer (AMSR) and the Moderate Resolution Imaging Spectroradiometer (MODIS) provides daily global estimates of partial marine planetary boundary layer water vapor. AMSR microwave radiometry provides the total column water vapor, while MODIS near-infrared imagery provides the water vapor above the cloud layers. The difference between the two gives the vapor between the surface and the cloud top, which may be interpreted as the boundary layer water vapor. Comparisons against radiosondes, and GPS-Radio occultation data demonstrate the robustness of these boundary layer water vapor estimates. We exploit the 14 years of AMSR-MODIS synergy to investigate the spatial, seasonal, and inter-annual variations of the boundary layer water vapor. Last, it is shown that the measured AMSR-MODIS partial boundary layer water vapor can be generally prescribed using sea surface temperature, cloud top pressure and the lifting condensation level. The multi-sensor nature of the analysis demonstrates that there exists more information on boundary layer water vapor structure in the satellite observing system than is commonly assumed when considering the capabilities of single instruments. 2017 California Institute of Technology. U.S. Government sponsorship acknowledged.

The Regulation of Lactogenic Differentiation in Mammary Epithelial Cells by Ras-Dependent and -Independent Signal Transduction

DTIC Science & Technology

2006-01-06

binding site on EGFR/ErbB (Ohta, 2004). Therapeutic antibodies that target ErbB2 are, therefore, hypothesized to allow c-Cbl recruitment and c-Cbl...electrophoresed for 2 h at 200 V, the gels were dried and autoradiographed. For antibody supershift assays, nuclear extracts were pre- incubated with...Stat5b C17 antibody (Santa Cruz) for 20 min prior to the addition of the labeled probe. Northern blots Total RNA was extracted using TriPure reagent

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

A postdoctoral position is available in the Bioorganic Chemistry Section of the Chemical Biology Laboratory (CBL), NCI-Frederick, under the mentorship of Dr. Terrence Burke. Research will involve developing small molecule inhibitors of HIV integrase and RNase H. The fellowship has an initial duration of two years, with the potential to extend a third year. Salary and benefit package are highly competitive. The CBL is equipped with state-of-the-art instrumentation and is located on the campus of the National Cancer Institute at Frederick, Frederick, MD.

Maintenance of Epithelial Stem Cells by Cbl Proteins

DTIC Science & Technology

2012-09-01

may be a potential mechanism behind inhibition of MEC differentiation in the absence of Cbl.   7   Figure 1. Flow cytometry analysis of hTERT...results in tumors at the implant site as well as distant metastases To assess whether ErbB2-dependent MPPS1 cells retain their oncogenic potential ...the levels of ErbB2 are not lost in this cell line during culture [ ]. This in itself suggested the potential dependence of oncogenic traits of MPPS1

Boundary layers in cataclysmic variables: The HEAO-1 X-ray constraints

NASA Technical Reports Server (NTRS)

Jensen, K. A.

1983-01-01

The predictions of the boundary layer model for the X-ray emission from novae are summarized. A discrepancy between observations and theory in the X-ray observations is found. Constraints on the nature of the boundary layers in novae, based on the lack of detections of novae in the HEAO-1 soft X-ray survey are provided. Temperature and column densities for optically thick boundary layers in novae are estimated.

Turbulent boundary layers with secondary flow

NASA Technical Reports Server (NTRS)

Grushwitz, E.

1984-01-01

An experimental analysis of the boundary layer on a plane wall, along which the flow occurs, whose potential flow lines are curved in plane parallel to the wall is discussed. According to the equation frequently applied to boundary layers in a plane flow, which is usually obtained by using the pulse law, a generalization is derived which is valid for boundary layers with spatial flow. The wall shear stresses were calculated with this equation.

Investigation of blown boundary layers with an improved wall jet system. Ph.D. Thesis. Final Technical Report, 1 Jul. 1978 - Dec. 1979; [to prevent turbulent boundary layer separation

NASA Technical Reports Server (NTRS)

Saripalli, K. R.; Simpson, R. L.

1979-01-01

The behavior of two dimensional incompressible turbulent wall jets submerged in a boundary layer when they are used to prevent boundary layer separation on plane surfaces is investigated. The experimental set-up and instrumentation are described. Experimental results of zero pressure gradient flow and adverse pressure gradient flow are presented. Conclusions are given and discussed.

Three-dimensional boundary layers approaching separation

NASA Technical Reports Server (NTRS)

Williams, J. C., III

1976-01-01

The theory of semi-similar solutions of the laminar boundary layer equations is applied to several flows in which the boundary layer approaches a three-dimensional separation line. The solutions obtained are used to deduce the nature of three-dimensional separation. It is shown that in these cases separation is of the "ordinary" type. A solution is also presented for a case in which a vortex is embedded within the three-dimensional boundary layer.

Inventory of File gfs.t06z.smartguam24.tm00.grib2

Science.gov Websites

boundary layer WDIR 24 hour fcst Wind Direction (from which blowing) [degtrue] 016 planetary boundary layer WIND 24 hour fcst Wind Speed [m/s] 017 planetary boundary layer RH 24 hour fcst Relative Humidity [%] 018 planetary boundary layer DIST 24 hour fcst Geometric Height [m] 019 surface 4LFTX 24 hour fcst

Destiny of earthward streaming plasma in the plasmasheet boundary layer

NASA Technical Reports Server (NTRS)

Green, J. L.; Horwitz, J. L.

1986-01-01

The dynamics of the earth's magnetotail have been investigated, and it has become clear that the plasmasheet boundary layer field lines map into the Region I Field-Aligned Currents (FAC) of the auroral zone. It is pointed out that the role of earthward streaming ions in the plasmasheet boundary layer may be of fundamental importance in the understanding of magnetotail dynamics, auroral zone physics, and especially for ionospheric-magnetospheric interactions. The present paper has the objective to evaluate propagation characteristics for the earthward streaming ions observed in the plasmasheet boundary layer. An investigation is conducted of the propagation characteristics of protons in the plasmasheet boundary layer using independent single particle dynamics, and conclusions are discussed. The density of earthward streaming ions found in the plasmasheet boundary layer should include the ring current as well as the auroral zone precipitaiton and inner plasmasheet regions of the magnetosphere.

On optical imaging through aircraft turbulent boundary layers

NASA Technical Reports Server (NTRS)

Sutton, G. W.

1980-01-01

Optical resolution quality as affected by aircraft turbulent boundary layers is analyzed. Wind-tunnel data was analyzed to obtained the variation of boundary layer turbulence scale length and mass density rms fluctuations with Mach number. The data gave good agreement with a mass density fluctuation turbulence spectrum that is either isotropic of orthogonally anisotropic. The data did not match an isotropic turbulence velocity spectrum which causes an anisotropic non-orthogonal mass density fluctuation spectrum. The results indicate that the average mass density rms fluctuation is about 10% of the maximum mass density across the boundary layer and that the transverse turbulence scale size is about 10% of the boundary layer thickness. The results indicate that the effect of the turbulent boundary layer is large angle scattering which decreases contrast but not resolution. Using extinction as a criteria the range of acceptable aircraft operating conditions are given.

Application of the E - Turbulence Closure Model to the Neutral and Stable Atmospheric Boundary Layer.

NASA Astrophysics Data System (ADS)

Duynkerke, P. G.

1988-03-01

In the E - turbulence model an eddy-exchange coefficient is evaluated from the turbulent kinetic energy E and viscous dissipation . In this study we will apply the E - model to the stable and neutral atmospheric boundary layer. A discussion is given on the equation for , which terms should be included and how we have evaluated the constants. Constant cooling rate results for the stable atmospheric boundary layer are compared with a second-order closure study. For the neutral atmospheric boundary layer a comparison is made with observations, large-eddy simulations and a second-order closure study. It is shown that a small stability effect can change the neutral atmospheric boundary layer quite drastically, and therefore, it will be difficult to observe a neutral boundary layer in the atmosphere.

a Fractal Permeability Model Coupling Boundary-Layer Effect for Tight Oil Reservoirs

NASA Astrophysics Data System (ADS)

Wang, Fuyong; Liu, Zhichao; Jiao, Liang; Wang, Congle; Guo, Hu

A fractal permeability model coupling non-flowing boundary-layer effect for tight oil reservoirs was proposed. Firstly, pore structures of tight formations were characterized with fractal theory. Then, with the empirical equation of boundary-layer thickness, Hagen-Poiseuille equation and fractal theory, a fractal torturous capillary tube model coupled with boundary-layer effect was developed, and verified with experimental data. Finally, the parameters influencing effective liquid permeability were quantitatively investigated. The research results show that effective liquid permeability of tight formations is not only decided by pore structures, but also affected by boundary-layer distributions, and effective liquid permeability is the function of fluid type, fluid viscosity, pressure gradient, fractal dimension, tortuosity fractal dimension, minimum pore radius and maximum pore radius. For the tight formations dominated with nanoscale pores, boundary-layer effect can significantly reduce effective liquid permeability, especially under low pressure gradient.

A review of turbulent-boundary-layer heat transfer research at Stanford, 1958-1983

NASA Technical Reports Server (NTRS)

Moffat, R. J.; Kays, W. M.

1984-01-01

For the past 25 years, there has existed in the Thermosciences Laboratory of the Mechanical Engineering Department of Stanford University a research program, primarily experimental, concerned with heat transfer through turbulent boundary layers. In the early phases of the program, the topics considered were the simple zero-pressure-gradient turbulent boundary layer with constant and with varying surface temperature, and the accelerated boundary layer. Later equilibrium boundary layers were considered along with factors affecting the boundary layer, taking into account transpired flows, flows with axial pressure gradients, transpiration, acceleration, deceleration, roughness, full-coverage film cooling, surface curvature, free convection, and mixed convection. A description is provided of the apparatus and techniques used, giving attention to the smooth plate rig, the rough plate rig, the full-coverage film cooling rig, the curvature rig, the concave wall rig, the mixed convection tunnel, and aspects of data reduction and uncertainty analysis.

Interaction of solar wind with the magnetopause-boundary layer and generation of magnetic impulse events

NASA Technical Reports Server (NTRS)

Lee, L. C.; Wei, C. Q.

1993-01-01

The transport of mass, momentum, energy and waves from the solar wind to the Earth's magnetosphere takes place in the magnetopause-boundary layer region. Various plasma processes that may occur in this region have been proposed and studied. In this paper, we present a brief review of the plasma processes in the dayside magnetopause-boundary layer. These processes include (1) flux transfer events at the dayside magnetopause, (2) formation of plasma vortices in the low-latitude boundary layer by the Kelvin-Helmholtz instability and coupling to the polar ionosphere, (3) the response of the magnetopause to the solar wind dynamic pressure pulses, and (4) the impulsive penetration of solar wind plasma filaments through the dayside magnetopause into the magnetospheric boundary layer. Through the coupling of the magnetopause-boundary layer to the polar ionosphere, those above processes may lead to occurrence of magnetic impulse events observed in the high-latitude stations.

F-16XL ship #1 - CAWAP boundary layer rakes and hot film on left wing

NASA Technical Reports Server (NTRS)

1996-01-01

This photo shows the boundary layer hot film and the boundary layer rakes on the left wing of NASA's single-seat F-16XL (ship #1) used for the Cranked-Arrow Wing Aerodynamic Project (CAWAP) at Dryden Flight Research Center, Edwards, California. The modified airplane features a delta 'cranked-arrow' wing with strips of tubing along the leading edge to the trailing edge to sense static on the wing and obtain pressure distribution data. The right wing receives data on pressure distribution and the left wing has three types of instrumentation - preston tubes to measure local skin friction, boundary layer rakes to measure boundary layer profiles (the layer where the air interacts with the surfaces of a moving aircraft), and hot films to determine boundary layer transition locations. The program also gathered aero data on two wing planforms for NASA's High Speed Research Program. The first flight of CAWAP occurred on November 21, 1995, and the test program ended in April 1996.

Boundary-Layer Characteristics Over a Coastal Megacity

NASA Astrophysics Data System (ADS)

Melecio-Vazquez, D.; Ramamurthy, P.; Arend, M.; Moshary, F.; Gonzalez, J.

2017-12-01

Boundary-layer characteristics over New York City are analyzed for various local and synoptic conditions over several seasons. An array of vertical profilers, including a Doppler LiDAR, a micro-pulse LiDAR and a microwave radiometer are used to observe the structure and evolution of the boundary-layer. Additionally, an urbanized Weather Research and Forecasting (uWRF) model coupled to a high resolution landcover/land-use database is used to study the spatial variability in boundary layer characteristics. The summer daytime averaged potential temperature profile from the microwave radiometer shows the presence of a thermal internal boundary layer wherein a superadiabatic layer lies underneath a stable layer instead of a mixed-layer. Both the winter daytime and nighttime seasonal averages show that the atmosphere remains unstable near the surface and does not reach stable conditions during the nighttime. The mixing ratio seasonal averages show peaks in humidity near 200-m and 1100-m, above instrument level, which could result from sea breeze and anthropogenic sources. Ceilometer measurements show a high degree of variability in boundary layer height depending on wind direction. Comparison with uWRF results show that the model tends to overestimate convective efficiency for selected summer and winter cases and therefore shows a much deeper thermal boundary layer than the observed profiles. The model estimates a less humid atmosphere than seen in observations.

Vorticity interaction effects on blunt bodies. [hypersonic viscous shock layers

NASA Technical Reports Server (NTRS)

Anderson, E. C.; Wilcox, D. C.

1977-01-01

Numerical solutions of the viscous shock layer equations governing laminar and turbulent flows of a perfect gas and radiating and nonradiating mixtures of perfect gases in chemical equilibrium are presented for hypersonic flow over spherically blunted cones and hyperboloids. Turbulent properties are described in terms of the classical mixing length. Results are compared with boundary layer and inviscid flowfield solutions; agreement with inviscid flowfield data is satisfactory. Agreement with boundary layer solutions is good except in regions of strong vorticity interaction; in these flow regions, the viscous shock layer solutions appear to be more satisfactory than the boundary layer solutions. Boundary conditions suitable for hypersonic viscous shock layers are devised for an advanced turbulence theory.

The Atmospheric Boundary Layer

ERIC Educational Resources Information Center

Tennekes, Hendrik

1974-01-01

Discusses some important parameters of the boundary layer and effects of turbulence on the circulation and energy dissipation of the atmosphere. Indicates that boundary-layer research plays an important role in long-term forecasting and the study of air-pollution meteorology. (CC)

Internal and external 2-d boundary layer flows

NASA Technical Reports Server (NTRS)

Crawford, M. E.; Kays, W. M.

1978-01-01

Computer program computes general two dimensional turbulent boundary-layer flow using finite-difference techniques. Structure allows for user modification to accommodate unique problems. Program should prove useful in many applications where accurate boundary-layer flow calculations are required.

The turbulent plasmasphere boundary layer and the outer radiation belt boundary

NASA Astrophysics Data System (ADS)

Mishin, Evgeny; Sotnikov, Vladimir

2017-12-01

We report on observations of enhanced plasma turbulence and hot particle distributions in the plasmasphere boundary layer formed by reconnection-injected hot plasma jets entering the plasmasphere. The data confirm that the electron pressure peak is formed just outward of the plasmapause in the premidnight sector. Free energy for plasma wave excitation comes from diamagnetic ion currents near the inner edge of the boundary layer due to the ion pressure gradient, electron diamagnetic currents in the entry layer near the electron plasma sheet boundary, and anisotropic (sometimes ring-like) ion distributions revealed inside, and further inward of, the inner boundary. We also show that nonlinear parametric coupling between lower oblique resonance and fast magnetosonic waves significantly contributes to the VLF whistler wave spectrum in the plasmasphere boundary layer. These emissions represent a distinctive subset of substorm/storm-related VLF activity in the region devoid of substorm injected tens keV electrons and could be responsible for the alteration of the outer radiation belt boundary during (sub)storms.

[Application of case-based learning in clinical internship teaching of conservative dentistry and endodontics].

PubMed

Liu, Sheng-bo; Peng, Bin; Song, Ya-ling; Xu, Qing-an

2013-12-01

To investigate the education effect of case-based learning (CBL) pattern on clinical internship of conservative dentistry and endodontics. Forty-one undergraduates were randomly assigned into CBL group and traditional teaching group. After clinical internship in the department of conservative dentistry and endodontics for 11 weeks, each student in the 2 groups underwent comprehensive examinations including medical record writing, case analysis, academic knowledge, professional skills and the ability of winning the trust of the patients. The scores were compared between the 2 groups using SPSS 13.0 software package. There was no significant difference between the 2 groups with regard to the scores of academic knowledge and profession skills (P>0.05). However, the results of medical record writing, case analysis and the ability of winning the trust of the patients showed significant difference between the 2 groups(P<0.05). Proper application of CBL in clinical internship of conservative dentistry and endodontics contributes to improve students' ability of clinical thinking, synthetical analysis and adaptability to different patients.

Picomolar quantitation of free sulfite in foods by means of [57Co]hydroxocobalamin and radiometric chromatography of [57Co]sulfitocobalamin. Method, applications and significance of coexisting sulfides.

PubMed

Beck, R A; Anes, J M; Savini, L M; Mateer, R A

2000-06-09

The concentration dependent reaction of sulfite with 57Co-labeled hydroxocobalamin (OH57CoCbl) to produce a sulfitocobalamin (SO(3)57CoCbl) adduct served as a quantification strategy for foodborne sulfite residues freely extracted into pH 5.2, 0.05 M acetate buffer. SO(3)57CoCbl was then resolved using SP-Sephadex C-25 gel chromatography and its radiometric detection allowed calculation of a standard logit plot from which unknown sulfite concentrations could be determined. The sulfite detection range was 6.0 nM-0.3 pM with respective relative standard deviations of 4.4-29.4% for 50-microl samples. Individual incidences of foodborne sulfite intolerances provoked by L-cysteine or sulfite additive use in bakery products, which remained undetected using conventional sulfite analytical methods, underscored the quantitative value of the method. The analytical significance and occurrences of detectable sulfides coexisting with foodborne sulfite residues was also addressed.

Nursing Students' and Faculty Members' Experiences of Comfort during Transition to Context-Based Learning.

PubMed

Puplampu, Vivian

2017-07-28

There is evidence supporting student-centered learning (SCL) as an effective pedagogy to prepare professionals to work in the evolving health care system of the twenty-first century. SCL has many benefits, among them that it helps students to learn to work in teams and develop problem-solving, critical thinking and communication skills. The focus on the student means that the teacher's power is decreased. This, along with openness of the approach, can make the transition to SCL a challenge. This study used an exploratory descriptive qualitative design to explore how comfortable nursing students and faculty members were in a context-based learning (CBL) program, a version of SCL. Nursing students and faculty discussed common challenges of trusting the CBL process. They also discussed the emphasis on self-directed learning and how it could mean that tutors are not as involved with students. To enhance a smooth transition, recommendations have been made, including clarifying the CBL philosophy at orientation, and mentoring and reassuring students.

Comparison of Theoretical and Experimental Heat-Transfer Characteristics of Bodies of Revolution at Supersonic Speeds

NASA Technical Reports Server (NTRS)

Scherrer, Richard

1951-01-01

An investigation of the three important factors that determine convective heat-transfer characteristics at supersonic speeds, location boundary-layer transition, recovery factor, and heat-transfer parameter has been performed at Mach numbers from 1.49 to 1.18. The bodies of revolution that were tested had, in most cases, laminar boundary layers, and the test results have been compared with available theory. Boundary-layer transition was found to be affected by heat transfer. Adding heat to a laminar boundary layer caused transition to move forward on the test body, while removing heat caused transition to move rearward. These experimental results and the implications of boundary-layer-stability theory are in qualitative agreement.

Study of the Effect of Free-Stream Turbulence upon Disturbances in the Pre-Transitional Laminar Boundary Layer. Part I. Laminar Boundary Layer Distortion by Surface Roughness; Effect upon Stability. Part II.

DTIC Science & Technology

1982-04-01

Boundary Layer Near a Plate." NACA Rept. 562, 1936. 5) A. A. Hall and G. S. Hislop , "Experiments on the Transition of the Laminar Boundary Layer on a...Cylinder." Proc. 5th Inter. Congr. Appl. Math, 1938. 7) G. S. Hislop , "The Transition of a Laminar Boundary Layer in a Wind Tunnel." Ph.D. Thesis...Small Vertical Cylinder Attached to a Flat Plate", h Fa- Elul"s, Vol. 23, Part 1, pp. 221-223, Jan. 1980 . 9. A. Von Doenhoff and E. A. Horton, "A Low

Electron distributions in the plasma sheet boundary layer - Time-of-flight effects

NASA Technical Reports Server (NTRS)

Onsager, T. G.; Thomsen, M. F.; Gosling, J. T.; Bame, S. J.

1990-01-01

The electron edge of the plasma sheet boundary layer lies lobeward of the ion edge. Measurements obtained near the electron edge of the boundary layer reveal low-speed cutoffs for earthward and tailward-flowing electrons. These cutoffs progress to lower speeds with deeper penetration into the boundary layer, and are consistently lower for the earthward-directed electrons than for the tailward-direction electrons. The cutoffs and their variation with distance from the edge of the boundary layer can be consistently interpreted in terms of a time-of-flight effect on recently reconnected magnetic field lines. The observed cutoff speeds are used to estimate the downtail location of the reconnection site.

Goertler instability in compressible boundary layers along curved surfaces with suction and cooling

NASA Technical Reports Server (NTRS)

El-Hady, N.; Verma, A. K.

1982-01-01

The Goertler instability of the laminar compressible boundary layer flows along concave surfaces is investigated. The linearized disturbance equations for the three-dimensional, counter-rotating streamwise vortices in two-dimensional boundary layers are presented in an orthogonal curvilinear coordinate. The basic approximation of the disturbance equations, that includes the effect of the growth of the boundary layer, is considered and solved numerically. The effect of compressibility on critical stability limits, growth rates, and amplitude ratios of the vortices is evaluated for a range of Mach numbers for 0 to 5. The effect of wall cooling and suction of the boundary layer on the development of Goertler vortices is investigated for different Mach numbers.

A review of quasi-coherent structures in a numerically simulated turbulent boundary layer

NASA Technical Reports Server (NTRS)

Robinson, S. K.; Kline, S. J.; Spalart, P. R.

1989-01-01

Preliminary results of a comprehensive study of the structural aspects of a numerically simulated number turbulent boundary layer are presented. A direct Navier-Stokes simulation of a flat-plate, zero pressure gradient boundary layer at Re0 = 670 was used. Most of the known nonrandom, coherent features of turbulent boundary layers are confirmed in the simulation, and several new aspects of their spatial character are reported. The spatial relationships between many of the various structures are described, forming the basis for a more complete kinematical picture of boundary layer physics than has been previously known. In particular, the importance of vortex structures of various forms to the generation of Reynolds shear stress is investigated.

Computer graphic visualization of orbiter lower surface boundary-layer transition

NASA Technical Reports Server (NTRS)

Throckmorton, D. A.; Hartung, L. C.

1984-01-01

Computer graphic techniques are applied to the processing of Shuttle Orbiter flight data in order to create a visual presentation of the extent and movement of the boundary-layer transition front over the orbiter lower surface during entry. Flight-measured surface temperature-time histories define the onset and completion of the boundary-layer transition process at any measurement location. The locus of points which define the spatial position of the boundary-layer transition front on the orbiter planform is plotted at each discrete time for which flight data are available. Displaying these images sequentially in real-time results in an animated simulation of the in-flight boundary-layer transition process.

Sublayer of Prandtl Boundary Layers

NASA Astrophysics Data System (ADS)

Grenier, Emmanuel; Nguyen, Toan T.

2018-03-01

The aim of this paper is to investigate the stability of Prandtl boundary layers in the vanishing viscosity limit {ν \\to 0} . In Grenier (Commun Pure Appl Math 53(9):1067-1091, 2000), one of the authors proved that there exists no asymptotic expansion involving one of Prandtl's boundary layer, with thickness of order {√{ν}} , which describes the inviscid limit of Navier-Stokes equations. The instability gives rise to a viscous boundary sublayer whose thickness is of order {ν^{3/4}} . In this paper, we point out how the stability of the classical Prandtl's layer is linked to the stability of this sublayer. In particular, we prove that the two layers cannot both be nonlinearly stable in L^∞. That is, either the Prandtl's layer or the boundary sublayer is nonlinearly unstable in the sup norm.

Methods and results of boundary layer measurements on a glider

NASA Technical Reports Server (NTRS)

Nes, W. V.

1978-01-01

Boundary layer measurements were carried out on a glider under natural conditions. Two effects are investigated: the effect of inconstancy of the development of static pressure within the boundary layer and the effect of the negative pressure difference in a sublaminar boundary layer. The results obtained by means of an ion probe in parallel connection confirm those results obtained by means of a pressure probe. Additional effects which have occurred during these measurements are briefly dealt with.

A study of juncture flow in the NASA Langley 0.3-meter transonic cryogenic tunnel

NASA Technical Reports Server (NTRS)

Chokani, Ndaona

1992-01-01

A numerical investigation of the interaction between a wind tunnel sidewall boundary layer and a thin low-aspect-ratio wing has been performed for transonic speeds and flight Reynolds numbers. A three-dimensional Navier-Stokes code was applied to calculate the flow field. The first portion of the investigation examined the capability of the code to calculate the flow around the wing, with no sidewall boundary layer present. The second part of the research examined the effect of modeling the sidewall boundary layer. The results indicated that the sidewall boundary layer had a strong influence on the flow field around the wing. The viscous sidewall computations accurately predicted the leading edge suction peaks, and the strong adverse pressure gradients immediately downstream of the leading edge. This was in contrast to the consistent underpredictions of the free-air computations. The low momentum of the sidewall boundary layer resulted in higher pressures in the juncture region, which decreased the favorable spanwise pressure gradient. This significantly decreased the spanwise migration of the wing boundary layer. The computations indicated that the sidewall boundary layer remained attached for all cases examined. Weak vortices were predicted in both the upper and lower surface juncture regions. These vortices are believed to have been generated by lateral skewing of the streamlines in the approaching boundary layer.

Approach to Modeling Boundary Layer Ingestion Using a Fully Coupled Propulsion-RANS Model

NASA Technical Reports Server (NTRS)

Gray, Justin S.; Mader, Charles A.; Kenway, Gaetan K. W.; Martins, Joaquim R. R. A.

2017-01-01

Airframe-propulsion integration concepts that use boundary layer ingestion have the potential to reduce aircraft fuel burn. One concept that has been recently explored is NASA's Starc-ABL aircraft configuration, which offers the potential for 12% mission fuel burn reduction by using a turbo-electric propulsion system with an aft-mounted electrically driven boundary layer ingestion propulsor. This large potential for improved performance motivates a more detailed study of the boundary layer ingestion propulsor design, but to date, analyses of boundary layer ingestion have used uncoupled methods. These methods account for only aerodynamic effects on the propulsion system or propulsion system effects on the aerodynamics, but not both simultaneously. This work presents a new approach for building fully coupled propulsive-aerodynamic models of boundary layer ingestion propulsion systems. A 1D thermodynamic cycle analysis is coupled to a RANS simulation to model the Starc-ABL aft propulsor at a cruise condition and the effects variation in propulsor design on performance are examined. The results indicates that both propulsion and aerodynamic effects contribute equally toward the overall performance and that the fully coupled model yields substantially different results compared to uncoupled. The most significant finding is that boundary layer ingestion, while offering substantial fuel burn savings, introduces throttle dependent aerodynamics effects that need to be accounted for. This work represents a first step toward the multidisciplinary design optimization of boundary layer ingestion propulsion systems.

Effect of Protuberance Shape and Orientation on Space Shuttle Orbiter Boundary-Layer Transition

NASA Technical Reports Server (NTRS)

King, RUdolph A.; Berry, Scott A.; Kegerise, Michael A.

2008-01-01

This document describes an experimental study conducted to examine the effects of protuberances on hypersonic boundary-layer transition. The experiment was conducted in the Langley 20-Inch Mach 6 Tunnel on a series of 0.9%-scale Shuttle Orbiter models. The data were acquired to complement the existing ground-based boundary-layer transition database that was used to develop Version 1.0 of the boundary-layer transition RTF (return-to-flight) tool. The existing ground-based data were all acquired on 0.75%-scale Orbiter models using diamond-shaped ( pizza-box ) trips. The larger model scale facilitated in manufacturing higher fidelity protuberances. The end use of this experimental database will be to develop a technical basis (in the form of a boundary-layer transition correlation) to assess representative protrusion shapes, e.g., gap fillers and protrusions resulting from possible tile repair concepts. The primary objective of this study is to investigate the effects of protuberance-trip location and geometry on Shuttle Orbiter boundary-layer transition. Secondary goals are to assess the effects of gap-filler orientation and other protrusion shapes on boundary-layer transition. Global heat-transfer images using phosphor thermography of the Orbiter windward surface and the corresponding streamwise and spanwise heating distributions were used to infer the state of the boundary layer, i.e., laminar, transitional, or turbulent.

Boundary-layer exchange by bubble: A novel method for generating transient nanofluidic layers

NASA Astrophysics Data System (ADS)

Jennissen, Herbert P.

2005-10-01

Unstirred layers (i.e., Nernst boundary layers) occur on every dynamic solid-liquid interface, constituting a diffusion barrier, since the velocity of a moving liquid approaches zero at the surface (no slip). If a macromolecule-surface reaction rate is higher than the diffusion rate, the Nernst layer is solute depleted and the reaction rate becomes mass-transport limited. The thickness of a Nernst boundary layer (δN) generally lies between 5 and 50μm. In an evanescent wave rheometer, measuring fibrinogen adsorption to fused silica, we made the fundamental observation that an air bubble preceding the sample through the flow cell abolishes the mass-transport limitation of the Nernst diffusion layer. Instead exponential kinetics are found. Experimental and simulation studies strongly indicate that these results are due to the elimination of the Nernst diffusion layer and its replacement by a dynamic nanofluidic layer (δν) maximally 200-300nm thick. It is suggested that the air bubble leads to a transient boundary-layer separation into a novel nanoboundary layer on the surface and the bulk fluid velocity profile separated by a vortex sheet with an estimated lifetime of 30-60s. A bubble-induced boundary-layer exchange from the Nernst to the nanoboundary layer and back is obtained, giving sufficient time for the measurement of unbiased exponential surface kinetics. Noteworthy is that the nanolayer can exist at all and displays properties such as (i) a long persistence and resistance to dissipation by the bulk liquid (boundary-layer-exchange-hysteresis) and (ii) a lack of solute depletion in spite of boundary-layer separation. The boundary-layer-exchange by bubble (BLEB) method therefore appears ideal for enhancing the rates of all types of diffusion-limited macromolecular reactions on surfaces with contact angles between 0° and 90° and only appears limited by slippage due to nanobubbles or an air gap beneath the nanofluidic layer on very hydrophobic surfaces. The possibility of producing nanoboundary layers without any nanostructuring or nanomachining should also be useful for fundamental physical studies in nanofluidics.

Response of Moist Convection to Multi-scale Surface Flux Heterogeneity

NASA Astrophysics Data System (ADS)

Kang, S. L.; Ryu, J. H.

2015-12-01

We investigate response of moist convection to multi-scale feature of the spatial variation of surface sensible heat fluxes (SHF) in the afternoon evolution of the convective boundary layer (CBL), utilizing a mesoscale-domain large eddy simulation (LES) model. The multi-scale surface heterogeneity feature is analytically created as a function of the spectral slope in the wavelength range from a few tens of km to a few hundreds of m in the spectrum of surface SHF on a log-log scale. The response of moist convection to the κ-3 - slope (where κ is wavenumber) surface SHF field is compared with that to the κ-2 - slope surface, which has a relatively weak mesoscale feature, and the homogeneous κ0 - slope surface. Given the surface energy balance with a spatially uniform available energy, the prescribed SHF has a 180° phase lag with the latent heat flux (LHF) in a horizontal domain of (several tens of km)2. Thus, warmer (cooler) surface is relatively dry (moist). For all the cases, the same observation-based sounding is prescribed for the initial condition. For all the κ-3 - slope surface heterogeneity cases, early non-precipitating shallow clouds further develop into precipitating deep thunderstorms. But for all the κ-2 - slope cases, only shallow clouds develop. We compare the vertical profiles of domain-averaged fluxes and variances, and the contribution of the mesoscale and turbulence contributions to the fluxes and variances, between the κ-3 versus κ-2 slope cases. Also the cross-scale processes are investigated.

N-myristoylated ubiquitin ligase Cbl-b inhibitor prevents on glucocorticoid-induced atrophy in mouse skeletal muscle.

PubMed

Ochi, Arisa; Abe, Tomoki; Nakao, Reiko; Yamamoto, Yoriko; Kitahata, Kanako; Takagi, Marina; Hirasaka, Katsuya; Ohno, Ayako; Teshima-Kondo, Shigetada; Taesik, Gwag; Choi, Inho; Kawamura, Tomoyuki; Nemoto, Hisao; Mukai, Rie; Terao, Junji; Nikawa, Takeshi

2015-03-15

A DGpYMP peptide mimetic of tyrosine(608)-phosphorylated insulin receptor substrate-1 (IRS-1), named Cblin, was previously shown to significantly inhibit Cbl-b-mediated IRS-1 ubiquitination. In the present study, we developed N-myristoylated Cblin and investigated whether it was effective in preventing glucocorticoid-induced muscle atrophy. Using HEK293 cells overexpressing Cbl-b, IRS-1 and ubiquitin, we showed that the 50% inhibitory concentrations of Cbl-b-mediated IRS-1 ubiquitination by N-myristoylated Cblin and Cblin were 30 and 120 μM, respectively. Regarding the DEX-induced atrophy of C2C12 myotubes, N-myristoylated Cblin was more effective than Cblin for inhibiting the DEX-induced decreases in C2C12 myotube diameter and IRS-1 degradation. The inhibitory efficacy of N-myristoylated Cblin on IRS-1 ubiquitination in C2C12 myotubes was approximately fourfold larger than that of Cblin. Furthermore, N-myristoylation increased the incorporation of Cblin into HEK293 cells approximately 10-folds. Finally, we demonstrated that N-myristoylated Cblin prevented the wet weight loss, IRS-1 degradation, and MAFbx/atrogin-1 and MuRF-1 expression in gastrocnemius muscle of DEX-treated mice approximately fourfold more effectively than Cblin. Taken together, these results suggest that N-myristoylated Cblin prevents DEX-induced skeletal muscle atrophy in vitro and in vivo, and that N-myristoylated Cblin more effectively prevents muscle atrophy than unmodified Cblin. Copyright © 2015 Elsevier Inc. All rights reserved.

Contribution of the Cerebellum in Cue-Dependent Force Changes During an Isometric Precision Grip Task.

PubMed

Kutz, Dieter F; Schmid, Barbara C; Meindl, Tobias; Timmann, Dagmar; Kolb, Florian P

2016-08-01

The "raspberry task" represents a precision grip task that requires continuous adjustment of grip forces and pull forces. During this task, subjects use a specialised grip rod and have to increase the pull force linearly while the rod is locked. The positions of the fingers are unrestrained and freely selectable. From the finger positions and the geometry of the grip rod, a physical lever was derived which is a comprehensive measurement of the subject's grip behaviour. In this study, the involvement of the cerebellum in establishing cued force changes (CFC) was examined. The auditory stimulus was associated with a motor behaviour that has to be readjusted during an ongoing movement that already started. Moreover, cerebellar involvement on grip behaviour was examined. The results show that patients presenting with degenerating cerebellar disease (CBL) were able to elicit CFC and were additionally able to optimise grip behaviour by minimising the lever. Comparison of the results of CBL with a control group of healthy subjects showed, however, that the CFC incidence was significantly lower and the reduction of the lever was less in CBL. Hence, the cerebellum is involved not only in the classical conditioning of reflexes but also in the association of sensory stimuli with complex changes in motor behaviour. Furthermore, the cerebellum is involved in the optimisation of grip behaviour during ongoing movements. Recent studies lead to the assumption that the cerebello-reticulo-spinal pathway might be important for the reduced optimisation of grip behaviour in CBL.

Nutritional Quality and Physicochemical Characteristics of Defatted Bovine Liver Treated by Supercritical Carbon Dioxide and Organic Solvent

PubMed Central

Kang, Sung-Won; Kim, Hye-Min; Rahman, M. Shafiur; Kim, Ah-Na; Yang, Han-Sul

2017-01-01

Defatted bovine liver (DBL) is a potential source of protein and minerals. Supercritical carbon dioxide (SC-CO2) and a traditional organic solvent method were used to remove lipid from bovine liver, and the quality characteristics of a control bovine liver (CBL), bovine liver defatted by SC-CO2 (DBLSC-CO2) at different pressures, and bovine liver defatted by organic solvent (DBL-OS) were compared. The DBLSC-CO2 samples had significantly higher (p<0.05) protein, amino acid, carbohydrate, and fiber contents than CBL and DBL-OS. There was a higher yield of lipid from CBL when using SC-CO2 than the organic solvent method. SDS-PAGE analysis demonstrated that the CBL and DBLSC-CO2 had protein bands of a similar intensity and area, whereas DBL-OS appeared extremely poor bands or no bands due to the degradation of proteins, particularly in the 50 to 75 kDa and 20 to 25 kDa molecular weight ranges. In addition, DBLSC-CO2 was shown to have superior functional properties in terms of total soluble content, water and oil absorption, and foaming and emulsification properties. Therefore, SC-CO2 treatment offers a nutritionally and environmentally friendly approach for the removal of lipid from high protein food sources. In addition, SC-CO2 may be a better substitute of traditional organic solvent extraction for producing more stable and high quality foods with high-protein, fat-free, and low calorie contents. PMID:28316468

Nutritional Quality and Physicochemical Characteristics of Defatted Bovine Liver Treated by Supercritical Carbon Dioxide and Organic Solvent.

PubMed

Kang, Sung-Won; Kim, Hye-Min; Rahman, M Shafiur; Kim, Ah-Na; Yang, Han-Sul; Choi, Sung-Gil

2017-01-01

Defatted bovine liver (DBL) is a potential source of protein and minerals. Supercritical carbon dioxide (SC-CO 2 ) and a traditional organic solvent method were used to remove lipid from bovine liver, and the quality characteristics of a control bovine liver (CBL), bovine liver defatted by SC-CO 2 (DBLSC-CO 2 ) at different pressures, and bovine liver defatted by organic solvent (DBL-OS) were compared. The DBLSC-CO 2 samples had significantly higher ( p <0.05) protein, amino acid, carbohydrate, and fiber contents than CBL and DBL-OS. There was a higher yield of lipid from CBL when using SC-CO 2 than the organic solvent method. SDS-PAGE analysis demonstrated that the CBL and DBLSC-CO 2 had protein bands of a similar intensity and area, whereas DBL-OS appeared extremely poor bands or no bands due to the degradation of proteins, particularly in the 50 to 75 kDa and 20 to 25 kDa molecular weight ranges. In addition, DBLSC-CO 2 was shown to have superior functional properties in terms of total soluble content, water and oil absorption, and foaming and emulsification properties. Therefore, SC-CO 2 treatment offers a nutritionally and environmentally friendly approach for the removal of lipid from high protein food sources. In addition, SC-CO 2 may be a better substitute of traditional organic solvent extraction for producing more stable and high quality foods with high-protein, fat-free, and low calorie contents.

Comparison of case-based and lecture-based learning in dental education using the SOLO taxonomy.

PubMed

Ilgüy, Mehmet; Ilgüy, Dilhan; Fişekçioğlu, Erdoğan; Oktay, Inci

2014-11-01

The aim of this study was to compare the impact of case-based learning (CBL) and lecture-based learning (LBL) on fourth-year dental students' clinical decision making by using the Structure of Observed Learning Outcome (SOLO) taxonomy. Participants in the study were fourth-year dental students (n=55) in academic year 2012-13 taught in a large-group LBL context and fourth-year dental students (n=54) in academic year 2013-14 taught with the CBL methodology; both took place in the oral diseases course at Yeditepe University Faculty of Dentistry, Istanbul, Turkey. All eligible students participated, for a 100 percent response rate. A real case was presented to the students in both groups to assess their clinical decision making on the topic of oral diseases. Their performance was evaluated with the SOLO taxonomy. Student t-test was used for statistical evaluation, and significance was set at the p<0.05 level. A statistically significant difference was found between the mean scores of the relational and extended abstract categories of the CBL and LBL groups (p<0.05). Students who were taught with CBL had higher scores at the top two levels of the SOLO taxonomy than students taught with LBL. These findings suggest that an integrated case-based curriculum may be effective in promoting students' deep learning and it holds promise for better integration of clinical cases likely to be encountered during independent practice.

Relationship of leaf oxygen and carbon isotopic composition with transpiration efficiency in the C4 grasses Setaria viridis and Setaria italica.

PubMed

Ellsworth, Patrick Z; Ellsworth, Patrícia V; Cousins, Asaph B

2017-06-15

Leaf carbon and oxygen isotope ratios can potentially provide a time-integrated proxy for stomatal conductance (gs) and transpiration rate (E), and can be used to estimate transpiration efficiency (TE). In this study, we found significant relationships of bulk leaf carbon isotopic signature (δ13CBL) and bulk leaf oxygen enrichment above source water (Δ18OBL) with gas exchange and TE in the model C4 grasses Setaria viridis and S. italica. Leaf δ13C had strong relationships with E, gs, water use, biomass, and TE. Additionally, the consistent difference in δ13CBL between well-watered and water-limited plants suggests that δ13CBL is effective in separating C4 plants with different availability of water. Alternatively, the use of Δ18OBL as a proxy for E and TE in S. viridis and S. italica was problematic. First, the oxygen isotopic composition of source water, used to calculate leaf water enrichment (Δ18OLW), was variable with time and differed across water treatments. Second, water limitations changed leaf size and masked the relationship of Δ18OLW and Δ18OBL with E. Therefore, the data collected here suggest that δ13CBL but not Δ18OBL may be an effective proxy for TE in C4 grasses. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Structure of the low-latitude boundary layer. [in magnetopause

NASA Technical Reports Server (NTRS)

Sckopke, N.; Paschmann, G.; Haerendel, G.; Sonnerup, B. U. OE.; Bame, S. J.; Forbes, T. G.; Hones, E. W., Jr.; Russell, C. T.

1981-01-01

High temporal resolution observations of the frontside magnetopause and plasma boundary layer made with the fast plasma analyzer aboard the ISEE 1 and 2 spacecraft are reported. The data are found to be compatible with a boundary layer that is always attached to the magnetopause but where the layer thickness has a large-scale spatial modulation pattern which travels tailward past the spacecraft. Periods are included when the thickness is essentially zero and others when it is of the order of 1 earth radius. The duration of these periods is highly variable but is typically in the range of 2-5 min corresponding to a distance along the magnetopuase of approximately 3-8 earth radii. The observed boundary layer features include a steep density gradient at the magnetopause with an approximately constant boundary layer plasma density amounting to about 25% of the magnetosheath density, and a second abrupt density decrease at the inner edge of the layer.

Computation of the shock-wave boundary layer interaction with flow separation

NASA Technical Reports Server (NTRS)

Ardonceau, P.; Alziary, T.; Aymer, D.

1980-01-01

The boundary layer concept is used to describe the flow near the wall. The external flow is approximated by a pressure displacement relationship (tangent wedge in linearized supersonic flow). The boundary layer equations are solved in finite difference form and the question of the presence and unicity of the solution is considered for the direct problem (assumed pressure) or converse problem (assumed displacement thickness, friction ratio). The coupling algorithm presented implicitly processes the downstream boundary condition necessary to correctly define the interacting boundary layer problem. The algorithm uses a Newton linearization technique to provide a fast convergence.

The behavior of a compressible turbulent boundary layer in a shock-wave-induced adverse pressure gradient. Ph.D. Thesis - Washington Univ., Seattle, Aug. 1972

NASA Technical Reports Server (NTRS)

Rose, W. C.

1973-01-01

The results of an experimental investigation of the mean- and fluctuating-flow properties of a compressible turbulent boundary layer in a shock-wave-induced adverse pressure gradient are presented. The turbulent boundary layer developed on the wall of an axially symmetric nozzle and test section whose nominal free-stream Mach number and boundary-layer thickness Reynolds number were 4 and 100,000, respectively. The adverse pressure gradient was induced by an externally generated conical shock wave. Mean and time-averaged fluctuating-flow data, including the complete experimental Reynolds stress tensor and experimental turbulent mass- and heat-transfer rates are presented for the boundary layer and external flow, upstream, within and downstream of the pressure gradient. The mean-flow data include distributions of total temperature throughout the region of interest. The turbulent mixing properties of the flow were determined experimentally with a hot-wire anemometer. The calibration of the wires and the interpretation of the data are discussed. From the results of the investigation, it is concluded that the shock-wave - boundary-layer interaction significantly alters the turbulent mixing characteristics of the boundary layer.

Response of a hypersonic boundary layer to freestream pulse acoustic disturbance.

PubMed

Wang, Zhenqing; Tang, Xiaojun; Lv, Hongqing

2014-01-01

The response of hypersonic boundary layer over a blunt wedge to freestream pulse acoustic disturbance was investigated. The stability characteristics of boundary layer for freestream pulse wave and continuous wave were analyzed comparatively. Results show that freestream pulse disturbance changes the thermal conductivity characteristics of boundary layer. For pulse wave, the number of main disturbance clusters decreases and the frequency band narrows along streamwise. There are competition and disturbance energy transfer among different modes in boundary layer. The dominant mode of boundary layer has an inhibitory action on other modes. Under continuous wave, the disturbance modes are mainly distributed near fundamental and harmonic frequencies, while under pulse wave, the disturbance modes are widely distributed in different modes. For both pulse and continuous waves, most of disturbance modes slide into a lower-growth or decay state in downstream, which is tending towards stability. The amplitude of disturbance modes in boundary layer under continuous wave is considerably larger than pulse wave. The growth rate for the former is also considerably larger than the later the disturbance modes with higher growth are mainly distributed near fundamental and harmonic frequencies for the former, while the disturbance modes are widely distributed in different frequencies for the latter.

Response of a Hypersonic Boundary Layer to Freestream Pulse Acoustic Disturbance

PubMed Central

Wang, Zhenqing; Tang, Xiaojun; Lv, Hongqing

2014-01-01

The response of hypersonic boundary layer over a blunt wedge to freestream pulse acoustic disturbance was investigated. The stability characteristics of boundary layer for freestream pulse wave and continuous wave were analyzed comparatively. Results show that freestream pulse disturbance changes the thermal conductivity characteristics of boundary layer. For pulse wave, the number of main disturbance clusters decreases and the frequency band narrows along streamwise. There are competition and disturbance energy transfer among different modes in boundary layer. The dominant mode of boundary layer has an inhibitory action on other modes. Under continuous wave, the disturbance modes are mainly distributed near fundamental and harmonic frequencies, while under pulse wave, the disturbance modes are widely distributed in different modes. For both pulse and continuous waves, most of disturbance modes slide into a lower-growth or decay state in downstream, which is tending towards stability. The amplitude of disturbance modes in boundary layer under continuous wave is considerably larger than pulse wave. The growth rate for the former is also considerably larger than the later the disturbance modes with higher growth are mainly distributed near fundamental and harmonic frequencies for the former, while the disturbance modes are widely distributed in different frequencies for the latter. PMID:24737993

Wind tunnel study of a vertical axis wind turbine in a turbulent boundary layer flow

NASA Astrophysics Data System (ADS)

Rolin, Vincent; Porté-Agel, Fernando

2015-04-01

Vertical axis wind turbines (VAWTs) are in a relatively infant state of development when compared to their cousins the horizontal axis wind turbines. Very few studies have been carried out to characterize the wake flow behind VAWTs, and virtually none to observe the influence of the atmospheric boundary layer. Here we present results from an experiment carried out at the EPFL-WIRE boundary-layer wind tunnel and designed to study the interaction between a turbulent boundary layer flow and a VAWT. Specifically we use stereoscopic particle image velocimetry to observe and quantify the influence of the boundary layer flow on the wake generated by a VAWT, as well as the effect the VAWT has on the boundary layer flow profile downstream. We find that the wake behind the VAWT is strongly asymmetric, due to the varying aerodynamic forces on the blades as they change their position around the rotor. We also find that the wake adds strong turbulence levels to the flow, particularly on the periphery of the wake where vortices and strong velocity gradients are present. The boundary layer is also shown to cause greater momentum to be entrained downwards rather than upwards into the wake.

Wind turbine wakes in forest and neutral plane wall boundary layer large-eddy simulations

NASA Astrophysics Data System (ADS)

Schröttle, Josef; Piotrowski, Zbigniew; Gerz, Thomas; Englberger, Antonia; Dörnbrack, Andreas

2016-09-01

Wind turbine wake flow characteristics are studied in a strongly sheared and turbulent forest boundary layer and a neutral plane wall boundary layer flow. The reference simulations without wind turbine yield similar results as earlier large-eddy simulations by Shaw and Schumann (1992) and Porte-Agel et al. (2000). To use the fields from the homogeneous turbulent boundary layers on the fly as inflow fields for the wind turbine wake simulations, a new and efficient methodology was developed for the multiscale geophysical flow solver EULAG. With this method fully developed turbulent flow fields can be achieved upstream of the wind turbine which are independent of the wake flow. The large-eddy simulations reproduce known boundary-layer statistics as mean wind profile, momentum flux profile, and eddy dissipation rate of the plane wall and the forest boundary layer. The wake velocity deficit is more asymmetric above the forest and recovers faster downstream compared to the velocity deficit in the plane wall boundary layer. This is due to the inflection point in the mean streamwise velocity profile with corresponding turbulent coherent structures of high turbulence intensity in the strong shear flow above the forest.

Inventory of File nam.t00z.smartpr00.tm00.grib2

Science.gov Websites

layer WDIR analysis Wind Direction (from which blowing) [degtrue] 016 planetary boundary layer WIND analysis Wind Speed [m/s] 017 planetary boundary layer RH analysis Relative Humidity [%] 018 planetary boundary layer DIST analysis Geometric Height [m] 019 surface 4LFTX analysis Best (4 layer) Lifted Index [K

Inventory of File nam.t00z.smartak00.tm00.grib2

Science.gov Websites

layer WDIR analysis Wind Direction (from which blowing) [degtrue] 016 planetary boundary layer WIND analysis Wind Speed [m/s] 017 planetary boundary layer RH analysis Relative Humidity [%] 018 planetary boundary layer DIST analysis Geometric Height [m] 019 surface 4LFTX analysis Best (4 layer) Lifted Index [K

Inventory of File nam.t00z.smarthi00.tm00.grib2

Science.gov Websites

layer WDIR analysis Wind Direction (from which blowing) [degtrue] 016 planetary boundary layer WIND analysis Wind Speed [m/s] 017 planetary boundary layer RH analysis Relative Humidity [%] 018 planetary boundary layer DIST analysis Geometric Height [m] 019 surface 4LFTX analysis Best (4 layer) Lifted Index [K

Modeling large wind farms in conventionally neutral atmospheric boundary layers under varying initial conditions

NASA Astrophysics Data System (ADS)

Allaerts, Dries; Meyers, Johan

2014-05-01

Atmospheric boundary layers (ABL) are frequently capped by an inversion layer limiting the entrainment rate and boundary layer growth. Commonly used analytical models state that the entrainment rate is inversely proportional to the inversion strength. The height of the inversion turns out to be a second important parameter. Conventionally neutral atmospheric boundary layers (CNBL) are ABLs with zero surface heat flux developing against a stratified free atmosphere. In this regime the inversion-filling process is merely driven by the downward heat flux at the inversion base. As a result, CNBLs are strongly dependent on the heating history of the boundary layer and strong inversions will fail to erode during the course of the day. In case of large wind farms, the power output of the farm inside a CNBL will depend on the height and strength of the inversion above the boundary layer. On the other hand, increased turbulence levels induced by wind farms may partially undermine the rigid lid effect of the capping inversion, enhance vertical entrainment of air into the farm, and increase boundary layer growth. A suite of large eddy simulations (LES) is performed to investigate the effect of the capping inversion on the conventionally neutral atmospheric boundary layer and on the wind farm performance under varying initial conditions. For these simulations our in-house pseudo-spectral LES code SP-Wind is used. The wind turbines are modelled using a non-rotating actuator disk method. In the absence of wind farms, we find that a decrease in inversion strength corresponds to a decrease in the geostrophic angle and an increase in entrainment rate and geostrophic drag. Placing the initial inversion base at higher altitudes further reduces the effect of the capping inversion on the boundary layer. The inversion can be fully neglected once it is situated above the equilibrium height that a truly neutral boundary layer would attain under the same external conditions such as geostrophic wind speed and surface roughness. Wind farm simulations show the expected increase in boundary layer height and growth rate with respect to the case without wind farms. Raising the initial strength of the capping inversion in these simulations dampens the turbulent growth of the boundary layer above the farm, decreasing the farms energy extraction. The authors acknowledge support from the European Research Council (FP7-Ideas, grant no. 306471). Simulations were performed on the computing infrastructure of the VSC Flemish Supercomputer Center, funded by the Hercules Foundation and the Flemish Government.

Numerical investigation of the boundary layer separation in chemical oxygen iodine laser

NASA Astrophysics Data System (ADS)

Huai, Ying; Jia, Shuqin; Wu, Kenan; Jin, Yuqi; Sang, Fengting

2017-11-01

Large eddy simulation is carried out to model the flow process in a supersonic chemical oxygen iodine laser. Unlike the common approaches relying on the tensor representation theory only, the model in the present work is an explicit anisotropy-resolving algebraic Subgrid-scale scalar flux formulation. With an accuracy in capturing the unsteady flow behaviours in the laser. Boundary layer separation initiated by the adverse pressure gradient is identified using Large Eddy Simulation. To quantify the influences of flow boundary layer on the laser performance, the fluid computations coupled with a physical optics loaded cavity model is developed. It has been found that boundary layer separation has a profound effect on the laser outputs due to the introduced shock waves. The F factor of the output beam decreases to 10% of the original one when the boundary transit into turbulence for the setup depicted in the paper. Because the pressure is always greater on the downstream of the boundary layer, there will always be a tendency of boundary separation in the laser. The results inspire designs of the laser to apply positive/passive control methods avoiding the boundary layer perturbation.

Understanding Micro-Ramp Control for Shock Boundary Layer Interactions

DTIC Science & Technology

2008-02-07

micro-ramps on a supersonic boundary layer at M=3.0 was investigated using monotone integrated Large Eddy Simulations (MILES) and Reynolds Averaged Navier... Supersonic boundary layer flow with micro-ramp and no shock wave 3.2 SBLI with no micro-ramp 3.3 SBLI with micro-ramp 3.4 Micro-ramp size and location IV . C...ramps on a supersonic boundary layer at M=3.0 was investigated using monotone integrated Large Eddy Simulations (MILES) and Reynolds Averaged Navier

The Effects of Rotation on Boundary Layers in Turbomachine Rotors

NASA Technical Reports Server (NTRS)

Johnston, J. P.

1974-01-01

The boundary layers in turbomachine rotors are subject to Coriolis forces which can (1) contribute directly to the development of secondary flows and (2) indirectly influence the behavior of boundary layers by augmentation and/or suppression of turbulence production in the boundary layers on blades. Both these rotation-induced phenomena are particularly important in the development of understanding of flow and loss mechanisms in centrifugal and mixed flow machines. The primary objective of this paper is to review the information available on these effects.

Boundary layers in cataclysmic variables - The HEAO 1 X-ray constraints

NASA Technical Reports Server (NTRS)

Jensen, K. A.

1984-01-01

The predictions of the boundary layer model for the X-ray emission from novae are summarized. A discrepancy between observations and theory in the X-ray observations is found. Constraints on the nature of the boundary layers in novae, based on the lack of detections of novae in the HEAO-1 soft X-ray survey are provided. Temperature and column densities for optically thick boundary layers in novae are estimated. Previously announced in STAR as N84-13046

Some Features of Artificially Thickened Fully Developed Turbulent Boundary Layers with Zero Pressure Gradient

NASA Technical Reports Server (NTRS)

Klebanoff, P S; Diehl, Z W

1952-01-01

Report gives an account of an investigation conducted to determine the feasibility of artificially thickening a turbulent boundary layer on a flat plate. A description is given of several methods used to thicken artificially the boundary layer. It is shown that it is possible to do substantial thickening and obtain a fully developed turbulent boundary layer, which is free from any distortions introduced by the thickening process, and, as such, is a suitable medium for fundamental research.

Measurements in a synthetic turbulent boundary layer

NASA Astrophysics Data System (ADS)

Arakeri, J. H.; Coles, D. E.

Some measurements in a synthetic turbulent boundary layer (SBL) are reported. The main diagnostic tool is an X-wire probe. The velocity of the large eddies is determined to be 0.842 times the freestream velocity. The mean properties of the SBL are reasonably close to those of a natural turbulent boundary layer. The large eddy in the SBL appears to be a pair of counterrotating eddies in the stream direction, inclined at a shallow angle and occupying much of the boundary-layer thickness.

Boundary layer transition observations on a body of revolution with surface heating and cooling in water

NASA Astrophysics Data System (ADS)

Arakeri, V. H.

1980-04-01

Boundary layer flow visualization in water with surface heat transfer was carried out on a body of revolution which had the predicted possibility of laminar separation under isothermal conditions. Flow visualization was by in-line holographic technique. Boundary layer stabilization, including elimination of laminar separation, was observed to take place on surface heating. Conversely, boundary layer destabilization was observed on surface cooling. These findings are consistent with the theoretical predictions of Wazzan et al. (1970).

Re-Innovating Recycling for Turbulent Boundary Layer Simulations

NASA Astrophysics Data System (ADS)

Ruan, Joseph; Blanquart, Guillaume

2017-11-01

Historically, turbulent boundary layers along a flat plate have been expensive to simulate numerically, in part due to the difficulty of initializing the inflow with ``realistic'' turbulence, but also due to boundary layer growth. The former has been resolved in several ways, primarily dedicating a region of at least 10 boundary layer thicknesses in width to rescale and recycle flow or by extending the region far enough downstream to allow a laminar flow to develop into turbulence. Both of these methods are relatively costly. We propose a new method to remove the need for an inflow region, thus reducing computational costs significantly. Leveraging the scale similarity of the mean flow profiles, we introduce a coordinate transformation so that the boundary layer problem can be solved as a parallel flow problem with additional source terms. The solutions in the new coordinate system are statistically homogeneous in the downstream direction and so the problem can be solved with periodic boundary conditions. The present study shows the stability of this method, its implementation and its validation for a few laminar and turbulent boundary layer cases.

Observations of Strong Surface Radar Ducts over the Persian Gulf.

NASA Astrophysics Data System (ADS)

Brooks, Ian M.; Goroch, Andreas K.; Rogers, David P.

1999-09-01

Ducting of microwave radiation is a common phenomenon over the oceans. The height and strength of the duct are controlling factors for radar propagation and must be determined accurately to assess propagation ranges. A surface evaporation duct commonly forms due to the large gradient in specific humidity just above the sea surface; a deeper surface-based or elevated duct frequently is associated with the sudden change in temperature and humidity across the boundary layer inversion.In April 1996 the U.K. Meteorological Office C-130 Hercules research aircraft took part in the U.S. Navy Ship Antisubmarine Warfare Readiness/Effectiveness Measuring exercise (SHAREM-115) in the Persian Gulf by providing meteorological support and making measurements for the study of electromagnetic and electro-optical propagation. The boundary layer structure over the Gulf is influenced strongly by the surrounding desert landmass. Warm dry air flows from the desert over the cooler waters of the Gulf. Heat loss to the surface results in the formation of a stable internal boundary layer. The layer evolves continuously along wind, eventually forming a new marine atmospheric boundary layer. The stable stratification suppresses vertical mixing, trapping moisture within the layer and leading to an increase in refractive index and the formation of a strong boundary layer duct. A surface evaporation duct coexists with the boundary layer duct.In this paper the authors present aircraft- and ship-based observations of both the surface evaporation and boundary layer ducts. A series of sawtooth aircraft profiles map the boundary layer structure and provide spatially distributed estimates of the duct depth. The boundary layer duct is found to have considerable spatial variability in both depth and strength, and to evolve along wind over distances significant to naval operations (100 km). The depth of the evaporation duct is derived from a bulk parameterization based on Monin-Obukhov similarity theory using near-surface data taken by the C-130 during low-level (30 m) flight legs and by ship-based instrumentation. Good agreement is found between the two datasets. The estimated evaporation ducts are found to be generally uniform in depth; however, localized regions of greatly increased depth are observed on one day, and a marked change in boundary layer structure resulting in merging of the surface evaporation duct with the deeper boundary layer duct was observed on another. Both of these cases occurred within exceptionally shallow boundary layers (100 m), where the mean evaporation duct depths were estimated to be between 12 and 17 m. On the remaining three days the boundary layer depth was between 200 and 300 m, and evaporation duct depths were estimated to be between 20 and 35 m, varying by just a few meters over ranges of up to 200 km.The one-way radar propagation factor is modeled for a case with a pronounced change in duct depth. The case is modeled first with a series of measured profiles to define as accurately as possible the refractivity structure of the boundary layer, then with a single profile collocated with the radar antenna and assuming homogeneity. The results reveal large errors in the propagation factor when derived from a single profile.

Effects of resolved boundary layer turbulence on near-ground rotation in simulated quasi-linear convective systems (QLCSs)

NASA Astrophysics Data System (ADS)

Nowotarski, C. J.

2017-12-01

Though most strong to violent tornadoes are associated with supercell thunderstorms, quasi-linear convective systems (QLCSs) pose a risk of tornadoes, often at times and locations where supercell tornadoes are less common. Because QLCS low-level mesocyclones and tornado signatures tend to be less coherent, forecasting such tornadoes remains particularly difficult. The majority of simulations of such storms rely on horizontally homogeneous base states lacking resolved boundary layer turbulence and surface fluxes. Previous work has suggested that heterogeneities associated with boundary layer turbulence in the form of horizontal convective rolls can influence the evolution and characteristics of low-level mesocyclones in supercell thunderstorms. This study extends methods for generating boundary layer convection to idealized simulations of QLCSs. QLCS simulations with resolved boundary layer turbulence will be compared against a control simulation with a laminar boundary layer. Effects of turbulence, the resultant heterogeneity in the near-storm environment, and surface friction on bulk storm characteristics and the intensity, morphology, and evolution of low-level rotation will be presented. Although maximum surface vertical vorticity values are similar, when boundary layer turbulence is included, a greater number of miso- and meso-scale vortices develop along the QLCS gust front. The source of this vorticity is analyzed using Eulerian decomposition of vorticity tendency terms and trajectory analysis to delineate the relative importance of surface friction and baroclinicity in generating QLCS vortices. The role of anvil shading in suppressing boundary layer turbulence in the near-storm environment and subsequent effects on QLCS vortices will also be presented. Finally, implications of the results regarding inclusion of more realistic boundary layers in future idealized simulations of deep convection will be discussed.

Impact of the Diurnal Cycle of the Atmospheric Boundary Layer on Wind-Turbine Wakes: A Numerical Modelling Study

NASA Astrophysics Data System (ADS)

Englberger, Antonia; Dörnbrack, Andreas

2018-03-01

The wake characteristics of a wind turbine for different regimes occurring throughout the diurnal cycle are investigated systematically by means of large-eddy simulation. Idealized diurnal cycle simulations of the atmospheric boundary layer are performed with the geophysical flow solver EULAG over both homogeneous and heterogeneous terrain. Under homogeneous conditions, the diurnal cycle significantly affects the low-level wind shear and atmospheric turbulence. A strong vertical wind shear and veering with height occur in the nocturnal stable boundary layer and in the morning boundary layer, whereas atmospheric turbulence is much larger in the convective boundary layer and in the evening boundary layer. The increased shear under heterogeneous conditions changes these wind characteristics, counteracting the formation of the night-time Ekman spiral. The convective, stable, evening, and morning regimes of the atmospheric boundary layer over a homogeneous surface as well as the convective and stable regimes over a heterogeneous surface are used to study the flow in a wind-turbine wake. Synchronized turbulent inflow data from the idealized atmospheric boundary-layer simulations with periodic horizontal boundary conditions are applied to the wind-turbine simulations with open streamwise boundary conditions. The resulting wake is strongly influenced by the stability of the atmosphere. In both cases, the flow in the wake recovers more rapidly under convective conditions during the day than under stable conditions at night. The simulated wakes produced for the night-time situation completely differ between heterogeneous and homogeneous surface conditions. The wake characteristics of the transitional periods are influenced by the flow regime prior to the transition. Furthermore, there are different wake deflections over the height of the rotor, which reflect the incoming wind direction.

Bristled shark skin: a microgeometry for boundary layer control?

PubMed

Lang, A W; Motta, P; Hidalgo, P; Westcott, M

2008-12-01

There exists evidence that some fast-swimming shark species may have the ability to bristle their scales during fast swimming. Experimental work using a water tunnel facility has been performed to investigate the flow field over and within a bristled shark skin model submerged within a boundary layer to deduce the possible boundary layer control mechanisms being used by these fast-swimming sharks. Fluorescent dye flow visualization provides evidence of the formation of embedded cavity vortices within the scales. Digital particle image velocimetry (DPIV) data, used to evaluate the cavity vortex formation and boundary layer characteristics close to the surface, indicate increased momentum in the slip layer forming above the scales. This increase in flow velocity close to the shark's skin is indicative of boundary layer control mechanisms leading to separation control and possibly transition delay for the bristled shark skin microgeometry.

Experimental study of the separating confluent boundary-layer. Volume 2: Experimental data

NASA Technical Reports Server (NTRS)

Braden, J. A.; Whipkey, R. R.; Jones, G. S.; Lilley, D. E.

1983-01-01

An experimental low speed study of the separating confluent boundary layer on a NASA GAW-1 high lift airfoil is described. The airfoil was tested in a variety of high lift configurations comprised of leading edge slat and trailing edge flap combinations. The primary test instrumentation was a two dimensional laser velocimeter (LV) system operating in a backscatter mode. Surface pressures and corresponding LV derived boundary layer profiles are given in terms of velocity components, turbulence intensities and Reynolds shear stresses as characterizing confluent boundary layer behavior up to and beyond stall. LV derived profiles and associated boundary layer parameters and those obtained from more conventional instrumentation such as pitot static transverse, Preston tube measurements and hot-wire surveys are compared.

Boundary-layer transition and displacement thickness effects on zero-lift drag of a series of power-law bodies at Mach 6

NASA Technical Reports Server (NTRS)

Ashby, G. C., Jr.; Harris, J. E.

1974-01-01

Wave and skin-friction drag have been numerically calculated for a series of power-law bodies at a Mach number of 6 and Reynolds numbers, based on body length, from 1.5 million to 9.5 million. Pressure distributions were computed on the nose by the inverse method and on the body by the method of characteristics. These pressure distributions and the measured locations of boundary-layer transition were used in a nonsimilar-boundary-layer program to determine viscous effects. A coupled iterative approach between the boundary-layer and pressure-distribution programs was used to account for boundary-layer displacement-thickness effects. The calculated-drag coefficients compared well with previously obtained experimental data.

Stability characteristics of compressible boundary layers over thermo-mechanically compliant walls

NASA Astrophysics Data System (ADS)

Dettenrieder, Fabian; Bodony, Daniel

2017-11-01

Transition prediction at hypersonic flight conditions continues to be a challenge and results in conservative safety factors that increase vehicle weight. The weight and thus cost reduction of the outer skin panels promises significant impact; however, fluid-structure interaction due to unsteady perturbations in the laminar boundary layer regime has not been systematically studied at conditions relevant for reusable, hypersonic flight. In this talk, we develop and apply convective and global stability analyses for compressible boundary layers over thermo-mechanically compliant panels. This compliance is shown to change the convective stability of the boundary layer modes, with both stabilization and destabilization observed. Finite panel lengths are shown to affect the global stability properties of the boundary layer.

Boundary Layer Flow Over a Moving Wavy Surface

NASA Astrophysics Data System (ADS)

Hendin, Gali; Toledo, Yaron

2016-04-01

Boundary Layer Flow Over a Moving Wavy Surface Gali Hendin(1), Yaron Toledo(1) January 13, 2016 (1)School of Mechanical Engineering, Tel-Aviv University, Israel Understanding the boundary layer flow over surface gravity waves is of great importance as various atmosphere-ocean processes are essentially coupled through these waves. Nevertheless, there are still significant gaps in our understanding of this complex flow behaviour. The present work investigates the fundamentals of the boundary layer air flow over progressive, small-amplitude waves. It aims to extend the well-known Blasius solution for a boundary layer over a flat plate to one over a moving wavy surface. The current analysis pro- claims the importance of the small curvature and the time-dependency as second order effects, with a meaningful impact on the similarity pattern in the first order. The air flow over the ocean surface is modelled using an outer, inviscid half-infinite flow, overlaying the viscous boundary layer above the wavy surface. The assumption of a uniform flow in the outer layer, used in former studies, is now replaced with a precise analytical solution of the potential flow over a moving wavy surface with a known celerity, wavelength and amplitude. This results in a conceptual change from former models as it shows that the pressure variations within the boundary layer cannot be neglected. In the boundary layer, time-dependent Navier-Stokes equations are formulated in a curvilinear, orthogonal coordinate system. The formulation is done in an elaborate way that presents additional, formerly neglected first-order effects, resulting from the time-varying coordinate system. The suggested time-dependent curvilinear orthogonal coordinate system introduces a platform that can also support the formulation of turbulent problems for any surface shape. In order to produce a self-similar Blasius-type solution, a small wave-steepness is assumed and a perturbation method is applied. Consequently, a novel self-similar solution is obtained from the first order set of equations. A second order solution is also obtained, stressing the role of small curvature on the boundary layer flow. The proposed model and solution for the boundary layer problem overlaying a moving wavy surface can also be used as a base flow for stability problems that can develop in a boundary layer, including phases of transitional states.

A perspective on coherent structures and conceptual models for turbulent boundary layer physics

NASA Technical Reports Server (NTRS)

Robinson, Stephen K.

1990-01-01

Direct numerical simulations of turbulent boundary layers have been analyzed to develop a unified conceptual model for the kinematics of coherent motions in low Reynolds number canonical turbulent boundary layers. All classes of coherent motions are considered in the model, including low-speed streaks, ejections and sweeps, vortical structures, near-wall and outer-region shear layers, sublayer pockets, and large-scale outer-region eddies. The model reflects the conclusions from the study of the simulated boundary layer that vortical structures are directly associated with the production of turbulent shear stresses, entrainment, dissipation of turbulence kinetic energy, and the fluctuating pressure field. These results, when viewed from the perspective of the large body of published work on the subject of coherent motions, confirm that vortical structures may be considered the central dynamic element in the maintenance of turbulence in the canonical boundary layer. Vortical structures serve as a framework on which to construct a unified picture of boundary layer structure, providing a means to relate the many known structural elements in a consistent way.

An experimental investigation of turbulent boundary layers along curved surfaces

NASA Technical Reports Server (NTRS)

So, R. M. C.; Mellor, G. L.

1972-01-01

A curved wall tunnel was designed, and an equilibrium turbulent boundary layer was set up on the straight section preceding the curved test section. Turbulent boundary layer flows with uniform and adverse pressure distributions along convex and concave walls were investigated. Hot-wire measurements along the convex surface indicated that turbulent mixing between fluid layers was very much reduced. However, the law of the wall held and the skin friction, thus determined, correlated well with other measurements. Hot-wire measurements along the concave test wall revealed a system of longitudinal vortices inside the boundary layer and confirmed that concave curvature enhances mixing. A self-consistent set of turbulent boundary layer equations for flows along curved surfaces was derived together with a modified eddy viscosity. Solution of these equations together with the modified eddy viscosity gave results that correlated well with the present data on flows along the convex surface with arbitrary pressure distribution. However, it could only be used to predict the mean characteristics of the flow along concave walls because of the existence of the system of longitudinal vortices inside the boundary layer.

Turbulent boundary layer heat transfer experiments: Convex curvature effects, including introduction and recovery

NASA Technical Reports Server (NTRS)

Simon, T. W.; Moffat, R. J.; Johnston, J. P.; Kays, W. M.

1980-01-01

Heat transfer rates were measured through turbulent and transitional boundary layers on an isothermal, convexly curved wall and downstream flat plate. The effect of convex curvature on the fully turbulent boundary layer was a reduction of the local Stanton numbers 20-50% below those predicted for a flat wall under the same circumstances. The recovery of the heat transfer rates on the downstream flat wall was extremely slow. After 60 cm of recovery length, the Stanton number was still typically 15-20% below the flat wall predicted value. Various effects important in the modeling of curved flows were studied separately. These are: (1) the effect of initial boundary layer thickness; (2) the effect of freestream velocity; (3) the effect of freestream acceleration; (4) the effect of unheated starting length; and (5) the effect of the maturity of the boundary layer. Regardless of the initial state, curvature eventually forced the boundary layer into an asymptotic curved condition. The slope, minus one, is believed to be significant.

Influence of bulk turbulence and entrance boundary layer thickness on the curved duct flow field

NASA Technical Reports Server (NTRS)

Crawford, R. A.

1988-01-01

The influence of bulk turbulence and boundary layer thickness on the secondary flow development in a square, 90 degree turning duct was investigated. A three-dimensional laser velocimetry system was utilized to measure the mean and fluctuating components of velocity at six cross-planes in the duct. The results from this investigation, with entrance boundary layer thickness of 20 percent, were compared with the thin boundary layer results documented in NASA CR-174811. The axial velocity profiles, cross-flow velocities, and turbulence intensities were compared and evaluated with regard to the influence of bulk turbulence intensity and boundary layer thickness, and the influence was significant. The results of this investigation expand the 90 degree curved duct experimental data base to higher turbulence levels and thicker entrance boundary layers. The experimental results provide a challenging benchmark data base for computational fluid dynamics code development and validation. The variation of inlet bulk turbulence intensity provides additional information to aid in turbulence model evaluation.

Exact Calculation of Laminar Boundary Layer in Longitudinal Flow over a Flat Plate with Homogeneous Suction

NASA Technical Reports Server (NTRS)

Iglisch, Rudolf

1949-01-01

Lately it has been proposed to reduce the friction drag of a body in a flow for the technically important large Reynolds numbers by the following expedient: the boundary layer, normally turbulent, is artificially kept laminar up to high Reynolds numbers by suction. The reduction in friction drag thus obtained is of the order of magnitude of 60 to 80 percent of the turbulent friction drag, since the latter, for large Reynolds numbers, is several times the laminar friction drag. In considering the idea mentioned one has first to consider whether suction is a possible means of keeping the boundary layer laminar. This question can be answered by a theoretical investigation of the stability of the laminar boundary layer with suction. A knowledge, as accurate as possible, of the velocity distribution in the laminar boundary layer with suction forms the starting point for the stability investigation. E. Schlichting recently gave a survey of the present state of calculation of the laminar boundary layer with suction.

Dynamic behavior of an unsteady trubulent boundary layer

NASA Technical Reports Server (NTRS)

Parikh, P. G.; Reynolds, W. C.; Jayaramen, R.; Carr, L. W.

1981-01-01

Experiments on an unsteady turbulent boundary layer are reported in which the upstream portion of the flow is steady (in the mean) and in the downstream region, the boundary layer sees a linearly decreasing free stream velocity. This velocity gradient oscillates in time, at frequencies ranging from zero to approximately the bursting frequency. For the small amplitude, the mean velocity and mean turbulence intensity profiles are unaffected by the oscillations. The amplitude of the periodic velocity component, although as much as 70% greater than that in the free stream for very low frequencies, becomes equal to that in the free stream at higher frequencies. At high frequencies, both the boundary layer thickness and the Reynolds stress distribution across the boundary layer become frozen. The behavior at higher amplitude is quite similar. At sufficiently high frequencies, the boundary layer thickness remains frozen at the mean value over the oscillation cycle, even though flow reverses near the wall during a part of the cycle.

The Western North American Cretaceous-Tertiary (K-T) boundary interval and its content of shock-metamorphosed minerals: Implications concerning the K-T boundary impact-extinction theory

NASA Technical Reports Server (NTRS)

Izett, G. A.

1988-01-01

At 20 sites in the Raton Basin of Colorado and New Mexico, and at several other sites in Wyoming, Montana, and Canada, a pair of claystone units, an Ir abundance anomaly, and a concentration of shock-metamorphosed minerals mark the palynological K-T boundary. The K-T boundary claystone, which is composed of kaolinite and small amounts of illite/smectite mixed-layer clay, is similar in most respects to kaolinite tonstein layers in coal beds. At some, but not all, K-T boundary localities, the boundary claystone contains solid kaolinite and hollow and solid goyazite spherules, 0.05 to 1.2 mm in diameter. The upper unit, the K-T boundary impact layer, consists chiefly of kaolinite and various amounts of illite/smectite mixed-layer clay. The impact layer and boundary claystone are similar chemically, except that the former has slightly more Fe, K, Ba, Cr, Cu, Li, V, and Zn than the latter. The facts that the boundary claystone and impact layer contain anomalous amounts of Ir, comprise a stratigraphic couplet at Western North American sites, and form thin, discrete layers, similar to air-fall units (volcanic or impact), suggest that the claystone units are of impact origin. Significantly, the impact layer contains as much as 2 percent clastic mineral grains, about 30 percent of which contain multiple sets of shock lamellae. Only one such concentration of shocked minerals has been found near the K-T boundary. The type of K-T boundary shock-metamorphosed materials (quartzite and metaquartzite) in the impact layer and the lack of shock lamellae in quartz and feldspar of pumice lapilli and granitic xenoliths in air-fall pumice units of silicic tuffs, such as the Bishop Tuff, eliminate the possibility that the shock-metamorphosed minerals in the K-T impact layer are of volcanic origin. The global size distribution and abundance of shock-metamorphosed mineral grains suggest that the K-T impact occurred in North America.

Analysis and Modeling of Boundary Layer Separation Method (BLSM).

PubMed

Pethő, Dóra; Horváth, Géza; Liszi, János; Tóth, Imre; Paor, Dávid

2010-09-01

Nowadays rules of environmental protection strictly regulate pollution material emission into environment. To keep the environmental protection laws recycling is one of the useful methods of waste material treatment. We have developed a new method for the treatment of industrial waste water and named it boundary layer separation method (BLSM). We apply the phenomena that ions can be enriched in the boundary layer of the electrically charged electrode surface compared to the bulk liquid phase. The main point of the method is that the boundary layer at correctly chosen movement velocity can be taken out of the waste water without being damaged, and the ion-enriched boundary layer can be recycled. Electrosorption is a surface phenomenon. It can be used with high efficiency in case of large electrochemically active surface of electrodes. During our research work two high surface area nickel electrodes have been prepared. The value of electrochemically active surface area of electrodes has been estimated. The existence of diffusion part of the double layer has been experimentally approved. The electrical double layer capacity has been determined. Ion transport by boundary layer separation has been introduced. Finally we have tried to estimate the relative significance of physical adsorption and electrosorption.

Dynamic Turbulence Modelling in Large-eddy Simulations of the Cloud-topped Atmospheric Boundary Layer

NASA Technical Reports Server (NTRS)

Kirkpatrick, M. P.; Mansour, N. N.; Ackerman, A. S.; Stevens, D. E.

2003-01-01

The use of large eddy simulation, or LES, to study the atmospheric boundary layer dates back to the early 1970s when Deardor (1972) used a three-dimensional simulation to determine velocity and temperature scales in the convective boundary layer. In 1974 he applied LES to the problem of mixing layer entrainment (Deardor 1974) and in 1980 to the cloud-topped boundary layer (Deardor 1980b). Since that time the LES approach has been applied to atmospheric boundary layer problems by numerous authors. While LES has been shown to be relatively robust for simple cases such as a clear, convective boundary layer (Mason 1989), simulation of the cloud-topped boundary layer has proved more of a challenge. The combination of small length scales and anisotropic turbulence coupled with cloud microphysics and radiation effects places a heavy burden on the turbulence model, especially in the cloud-top region. Consequently, over the past few decades considerable effort has been devoted to developing turbulence models that are better able to parameterize these processes. Much of this work has involved taking parameterizations developed for neutral boundary layers and deriving corrections to account for buoyancy effects associated with the background stratification and local buoyancy sources due to radiative and latent heat transfer within the cloud (see Lilly 1962; Deardor 1980a; Mason 1989; MacVean & Mason 1990, for example). In this paper we hope to contribute to this effort by presenting a number of turbulence models in which the model coefficients are calculated dynamically during the simulation rather than being prescribed a priori.

Modeling the urban boundary layer

NASA Technical Reports Server (NTRS)

Bergstrom, R. W., Jr.

1976-01-01

A summary and evaluation is given of the Workshop on Modeling the Urban Boundary Layer; held in Las Vegas on May 5, 1975. Edited summaries from each of the session chairpersons are also given. The sessions were: (1) formulation and solution techniques, (2) K-theory versus higher order closure, (3) surface heat and moisture balance, (4) initialization and boundary problems, (5) nocturnal boundary layer, and (6) verification of models.

The Interactions of a Flame and Its Self-Induced Boundary Layer

NASA Technical Reports Server (NTRS)

Ott, James D.; Oran, Elaine S.; Anderson, John D.

1999-01-01

The interaction of a laminar flame with its self-generated boundary layer in a rectangular channel was numerically simulated using the two-dimensional, reacting, Navier-Stokes equations. A two species chemistry model was implemented which simulates the stoichiometric reaction of acetylene and air. Calculations were performed to investigate the effects of altering the boundary condition of the wall temperature, the Lewis number, the dynamic viscosity, and the ignition method. The purpose of this study was to examine the fundamental physics of the formation of the boundary layer and the interaction of the flame as it propagates into the boundary layer that its own motion has created.

Influence of the characteristics of atmospheric boundary layer on the vertical distribution of air pollutant in China's Yangtze River Delta

NASA Astrophysics Data System (ADS)

Wang, Chenggang; Cao, Le

2016-04-01

Air pollution occurring in the atmospheric boundary layer is a kind of weather phenomenon which decreases the visibility of the atmosphere and results in poor air quality. Recently, the occurrence of the heavy air pollution events has become more frequent all over Asia, especially in Mid-Eastern China. In December 2015, the most severe air pollution in recorded history of China occurred in the regions of Yangtze River Delta and Beijing-Tianjin-Hebei. More than 10 days of severe air pollution (Air Quality Index, AQI>200) appeared in many large cities of China such as Beijing, Tianjin, Shijiazhuang and Baoding. Thus, the research and the management of the air pollution has attracted most attentions in China. In order to investigate the formation, development and dissipation of the air pollutions in China, a field campaign has been conducted between January 1, 2015 and January 28, 2015 in Yangtze River Delta of China, aiming at a intensive observation of the vertical structure of the air pollutants in the atmospheric boundary layer during the time period with heavy pollution. In this study, the observation data obtained in the field campaign mentioned above is analyzed. The characteristics of the atmospheric boundary layer and the vertical distribution of air pollutants in the city Dongshan located in the center of Lake Taihu are shown and discussed in great detail. It is indicated that the stability of the boundary layer is the strongest during the nighttime and the early morning of Dongshan. Meanwhile, the major air pollutants, PM2.5 and PM10 in the boundary layer, reach their maximum values, 177.1μg m-3 and 285μg m-3 respectively. The convective boundary layer height in the observations ranges from approximately 700m to 1100m. It is found that the major air pollutants tend to be confined in a relatively shallow boundary layer, which represents that the boundary layer height is the dominant factor for controlling the vertical distribution of the air pollutants. In the observations, several strong temperature inversion layers are also found in the surface layer and the middle part of the boundary layer, which lead to the suppression of the vertical mixing of the air pollutants. The jet stream occurring in the boundary layer also contributes to the prevention of the vertical dissipation of the air pollutants. It is also observed that the temporal and spatial evolution of the air pollutants and the hygroscopic growth of the aerosols in the boundary layer are heavily dependent on the humidity of the air.

Lear jet boundary layer/shear layer laser propagation experiments

NASA Technical Reports Server (NTRS)

Gilbert, K.

1980-01-01

Optical degradations of aircraft turbulent boundary layers with shear layers generated by aerodynamic fences are analyzed. A collimated 2.5 cm diameter helium-neon laser (0.63 microns) traversed the approximate 5 cm thick natural aircraft boundary layer in double pass via a reflective airfoil. In addition, several flights examined shear layer-induced optical degradation. Flight altitudes ranged from 1.5 to 12 km, while Mach numbers were varied from 0.3 to 0.8. Average line spread function (LSF) and Modulation Transfer Function (MTF) data were obtained by averaging a large number of tilt-removed curves. Fourier transforming the resulting average MTF yields an LSF, thus affording a direct comparison of the two optical measurements. Agreement was good for the aerodynamic fence arrangement, but only fair in the case of a turbulent boundary layer. Values of phase variance inferred from the LSF instrument for a single pass through the random flow and corrected for a large aperture ranged from 0.08 to 0.11 waves (lambda = .63 microns) for the boundary layer. Corresponding values for the fence vary from 0.08 to 0.16 waves. Extrapolation of these values to 10.6 microns suggests negligible degradation for a CO2 laser transmitted through a 5 cm thick, subsonic turbulent boundary layer.

An experimental investigation of the effect of boundary layer refraction on the noise from a high-speed propeller

NASA Technical Reports Server (NTRS)

Dittmar, J. H.; Burns, R. J.; Leciejewski, D. J.

1984-01-01

Models of supersonic propellers were previously tested for acoustics in the Lewis 8- by 6-Foot Wind Tunnel using pressure transducers mounted in the tunnel ceiling. The boundary layer on the tunnel ceiling is believed to refract some of the propeller noise away from the measurement transducers. Measurements were made on a plate installed in the wind tunnel which had a thinner boundary layer than the ceiling boundary layer. The plate was installed in two locations for comparison with tunnel ceiling noise data and with fuselage data taken on the NASA Dryden Jetstar airplane. Analysis of the data indicates that the refraction increases with: increasing boundary layer thickness; increasing free stream Mach number; increasing frequency; and decreasing sound radiation angle (toward the inlet axis). At aft radiation angles greater than about 100 deg there was little or no refraction. Comparisons with the airplane data indicated that not only is the boundary layer thickness important but also the shape of the velocity profile. Comparisons with an existing two-dimensional theory, using an idealized shear layer to approximate the boundary layer, showed that the theory and data had the same trends. Analysis of the data taken in the tunnel at two different distances from the propeller indicates a decay with distance in the wind tunnel at high Mach numbers but the decay at low Mach numbers is not as clear.

F-16XL ship #1 wing close-up showing boundary layer detection Preston tubes

NASA Technical Reports Server (NTRS)

1995-01-01

This photo shows the boundary layer Preston tubes mounted on the left wing of NASA's single-seat F-16XL (ship #1) used for the Cranked-Arrow Wing Aerodynamic Project (CAWAP) at Dryden Flight Research Center, Edwards, California. The modified airplane features a delta 'cranked-arrow' wing with strips of tubing along the leading edge to the trailing edge to sense static on the wing and obtain pressure distribution data. The right wing receives data on pressure distribution and the left wing has three types of instrumentation - preston tubes to measure local skin friction, boundary layer rakes to measure boundary layer profiles (the layer where the air interacts with the surfaces of a moving aircraft), and hot films to determine boundary layer transition locations. The first flight of CAWAP occurred on November 21, 1995, and the test program ended in April 1996.

On the Existence of the Logarithmic Surface Layer in the Inner Core of Hurricanes

DTIC Science & Technology

2012-01-01

characteristics of eyewall boundary layer of Hurricane Hugo (1989). Mon. Wea. Rev., 139, 1447-1462. Zhang, JA, Montgomery MT. 2012 Observational...the inner core of hurricanes Roger K. Smitha ∗and Michael T. Montgomeryb a Meteorological Institute, University of Munich, Munich, Germany b Dept. of...logarithmic surface layer”, or log layer, in the boundary layer of the rapidly-rotating core of a hurricane . One such study argues that boundary-layer

The boundary layer as a means of controlling the flow of liquids and gases

NASA Technical Reports Server (NTRS)

Schrenk, Oskar

1930-01-01

According to one of the main propositions of the boundary layer theory the scarcely noticeable boundary layer may, under certain conditions, have a decisive influence on the form of the external flow by causing it to separate from the wing surface. These phenomena are known to be caused by a kind of stagnation of the boundary layer at the point of separation. The present report deals with similar phenomena. It is important to note that usually the cause (external interference) directly affects only the layer close to the wall, while its indirect effect extends to a large portion of the external flow.

Application of a transonic similarity rule to correct the effects of sidewall boundary layers in two-dimensional transonic wind tunnels. M.S. Thesis - George Washington Univ.

NASA Technical Reports Server (NTRS)

Sewall, W. G.

1982-01-01

A transonic similarity rule which accounts for the effects of attached sidewall boundary layers is presented and evaluated by comparison with the characteristics of airfoils tested in a two dimensional transonic tunnel with different sidewall boundary layer thicknesses. The rule appears valid provided the sidewall boundary layer both remains attached in the vicinity of the model and occupies a small enough fraction of the tunnel width to preserve sufficient two dimensionality in the tunnel.

Comparative Measurements of Total Temperature in a Supersonic Turbulent Boundary Layer Using a Conical Equilibrium and Combined Temperature-Pressure Probe

DTIC Science & Technology

1974-07-01

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Vortex/boundary layer interactions

NASA Technical Reports Server (NTRS)

Cutler, A. D.; Bradshaw, P.

1989-01-01

Detailed and high quality measurements with hot-wires and pressure probes are presented for two different interactions between a vortex pair with common flow down and a turbulent boundary layer. The interactions studied have larger values of the vortex circulation parameter than those studied previously. The results indicate that the boundary layer under the vortex pair is thinned by lateral divergence and that boundary layer fluid is entrained into the vortex. The effect of the interaction on the vortex core (other than the inviscid effect of the image vortices behind the surface) is small.

An eddy-viscosity treatment of the unsteady turbulent boundary layer on a flat plate in an expansion tube

NASA Technical Reports Server (NTRS)

Gupta, R. N.; Trimpi, R. L.

1974-01-01

An analysis is presented for the relaxation of a turbulent boundary layer on a semiinfinite flat plate after passage of a shock wave and a trailing driver gas-driven gas interface. The problem has special application to expansion tube flows. The flow-governing equations have been transformed into the Lamcrocco variables. The numerical results indicate that a fully turbulent boundary layer relaxes faster to the final steady-state values of heat transfer and skin-friction than a fully laminar boundary layer.

Notes on the Prediction of Shock-induced Boundary-layer Separation

NASA Technical Reports Server (NTRS)

Lange, Roy H.

1953-01-01

The present status of available information relative to the prediction of shock-induced boundary-layer separation is discussed. Experimental results showing the effects of Reynolds number and Mach number on the separation of both laminar and turbulent boundary layer are given and compared with available methods for predicting separation. The flow phenomena associated with separation caused by forward-facing steps, wedges, and incident shock waves are discussed. Applications of the flat-plate data to problems of separation on spoilers, diffusers, and scoop inlets are indicated for turbulent boundary layers.

Structure of turbulence in three-dimensional boundary layers

NASA Technical Reports Server (NTRS)

Subramanian, Chelakara S.

1993-01-01

This report provides an overview of the three dimensional turbulent boundary layer concepts and of the currently available experimental information for their turbulence modeling. It is found that more reliable turbulence data, especially of the Reynolds stress transport terms, is needed to improve the existing modeling capabilities. An experiment is proposed to study the three dimensional boundary layer formed by a 'sink flow' in a fully developed two dimensional turbulent boundary layer. Also, the mean and turbulence field measurement procedure using a three component laser Doppler velocimeter is described.

An Estimation of Turbulent Kinetic Energy and Energy Dissipation Rate Based on Atmospheric Boundary Layer Similarity Theory

NASA Technical Reports Server (NTRS)

Han, Jongil; Arya, S. Pal; Shaohua, Shen; Lin, Yuh-Lang; Proctor, Fred H. (Technical Monitor)

2000-01-01

Algorithms are developed to extract atmospheric boundary layer profiles for turbulence kinetic energy (TKE) and energy dissipation rate (EDR), with data from a meteorological tower as input. The profiles are based on similarity theory and scalings for the atmospheric boundary layer. The calculated profiles of EDR and TKE are required to match the observed values at 5 and 40 m. The algorithms are coded for operational use and yield plausible profiles over the diurnal variation of the atmospheric boundary layer.

A novel concept for subsonic inlet boundary-layer control

NASA Technical Reports Server (NTRS)

Miller, B. A.

1977-01-01

A self-bleeding method for boundary layer control is described and tested for a subsonic inlet designed to operate in the flowfield generated by high angles of attack. Naturally occurring surface static pressure gradients are used to remove the boundary layer from a separation-prone region of the inlet and to reinject it at a less critical location with a net performance gain. The results suggest that this self-bleeding method for boundary-layer control might be successfully applied to other inlets operating at extreme aerodynamic conditions.

The atmospheric boundary layer — advances in knowledge and application

NASA Astrophysics Data System (ADS)

Garratt, J. R.; Hess, G. D.; Physick, W. L.; Bougeault, P.

1996-02-01

We summarise major activities and advances in boundary-layer knowledge in the 25 years since 1970, with emphasis on the application of this knowledge to surface and boundary-layer parametrisation schemes in numerical models of the atmosphere. Progress in three areas is discussed: (i) the mesoscale modelling of selected phenomena; (ii) numerical weather prediction; and (iii) climate simulations. Future trends are identified, including the incorporation into models of advanced cloud schemes and interactive canopy schemes, and the nesting of high resolution boundary-layer schemes in global climate models.

Boundary-layer cumulus over land: Some observations and conceptual models

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

Stull, R.B.

1993-09-01

Starting in 1980, the Boundary Layer Research Team at the University of Wisconsin has been systematically studying the formation and evolution of nonprecipitating boundary-layer cumulus clouds (BLCu) in regions of fair weather (anticyclones) over land (Stull, 1980). Our approach is to quantify the average statistical characteristics of the surface, thermals, boundary layer, and clouds over horizontal regions of roughly 20 km in diameter. Within such a region over land, there is typically quite a variation in land use, and associated variations in surface albedo and moisture.

An investigation of the effects of the propeller slipstream of a laminar wing boundary layer

NASA Technical Reports Server (NTRS)

Howard, R. M.; Miley, S. J.; Holmes, B. J.

1985-01-01

A research program is in progress to study the effects of the propeller slipstream on natural laminar flow. Flight and wind tunnel measurements of the wing boundary layer have been made using hot-film velocity sensor probes. The results show the boundary layer, at any given point, to alternate between laminar and turbulent states. This cyclic behavior is due to periodic external flow turbulence originating from the viscous wake of the propeller blades. Analytic studies show the cyclic laminar/turbulent boundary layer to result in a significantly lower wing section drag than a fully turbulent boundary layer. The application of natural laminar flow design philosophy yields drag reduction benefits in the slipstream affected regions of the airframe, as well as the unaffected regions.

Calculations of unsteady turbulent boundary layers with flow reversal

NASA Technical Reports Server (NTRS)

Nash, J. F.; Patel, V. C.

1975-01-01

The results are presented of a series of computational experiments aimed at studying the characteristics of time-dependent turbulent boundary layers with embedded reversed-flow regions. A calculation method developed earlier was extended to boundary layers with reversed flows for this purpose. The calculations were performed for an idealized family of external velocity distributions, and covered a range of degrees of unsteadiness. The results confirmed those of previous studies in demonstrating that the point of flow reversal is nonsingular in a time-dependent boundary layer. A singularity was observed to develop downstream of reversal, under certain conditions, accompanied by the breakdown of the boundary-layer approximations. A tentative hypothesis was advanced in an attempt to predict the appearance of the singularity, and is shown to be consistent with the calculated results.

Energy efficient engine, low-pressure turbine boundary layer program

NASA Technical Reports Server (NTRS)

Gardner, W. B.

1981-01-01

A study was conducted to investigate development of boundary layers under the influence of velocity distributions simulating the suction side of two state-of-the-art turbine airfoils: a forward loaded airfoil (squared-off design) and an aft loaded airfoil (aft-loaded design). These velocity distributions were simulated in a boundary layer wind tunnel. Detailed measurements of boundary layer mean velocity and turbulence intensity profiles were obtained for an inlet turbulence level of 2.4 percent and an exit Reynolds number of 800,000. Flush-mounted hot film probes identified the boundary layer transition regimes in the adverse pressure gradient regions for both velocity distributions. Wall intermittency data showed good agreement with the correlations of Dhawan and Narasimha for the intermittency factor distribution in transitional flow regimes.

Experimental measurements of unsteady turbulent boundary layers near separation

NASA Technical Reports Server (NTRS)

Simpson, R. L.

1982-01-01

Investigations conducted to document the behavior of turbulent boundary layers on flat surfaces that separate due to adverse pressure gradients are reported. Laser and hot wire anemometers measured turbulence and flow structure of a steady free stream separating turbulent boundary layer produced on the flow of a wind tunnel section. The effects of sinusoidal and unsteadiness of the free stream velocity on this separating turbulent boundary layer at a reduced frequency were determined. A friction gage and a thermal tuft were developed and used to measure the surface skin friction and the near wall fraction of time the flow moves downstream for several cases. Abstracts are provided of several articles which discuss the effects of the periodic free stream unsteadiness on the structure or separating turbulent boundary layers.

Computation of turbulent boundary layers on curved surfaces, 1 June 1975 - 31 January 1976

NASA Technical Reports Server (NTRS)

Wilcox, D. C.; Chambers, T. L.

1976-01-01

An accurate method was developed for predicting effects of streamline curvature and coordinate system rotation on turbulent boundary layers. A new two-equation model of turbulence was developed which serves as the basis of the study. In developing the new model, physical reasoning is combined with singular perturbation methods to develop a rational, physically-based set of equations which are, on the one hand, as accurate as mixing-length theory for equilibrium boundary layers and, on the other hand, suitable for computing effects of curvature and rotation. The equations are solved numerically for several boundary layer flows over plane and curved surfaces. For incompressible boundary layers, results of the computations are generally within 10% of corresponding experimental data. Somewhat larger discrepancies are noted for compressible applications.

Effect of Sub-Boundary Layer Vortex Generations on Incident Turbulence

NASA Technical Reports Server (NTRS)

Casper, J.; Lin, J. C.; Yao, C. S.

2003-01-01

Sub-boundary layer vortex generators were tested in a wind tunnel to assess their effect on the velocity field within the wake region of a turbulent boundary layer. Both mean flow quantities and turbulence statistics were measured. Although very small relative to the boundary layer thickness, these so-called micro vortex generators were found to have a measurable effect on the power spectra and integral length scales of the turbulence at a distance many times the height of the devices themselves. In addition, the potential acoustic impact of these devices is also discussed. Measured turbulence spectra are used as input to an acoustic formulation in a manner that compares predicted sound pressure levels that result from the incident boundary-layer turbulence, with and without the vortex generators in the flow.

Hypersonic three-dimensional nonequilibrium boundary-layer equations in generalized curvilinear coordinates

NASA Technical Reports Server (NTRS)

Lee, Jong-Hun

1993-01-01

The basic governing equations for the second-order three-dimensional hypersonic thermal and chemical nonequilibrium boundary layer are derived by means of an order-of-magnitude analysis. A two-temperature concept is implemented into the system of boundary-layer equations by simplifying the rather complicated general three-temperature thermal gas model. The equations are written in a surface-oriented non-orthogonal curvilinear coordinate system, where two curvilinear coordinates are non-orthogonial and a third coordinate is normal to the surface. The equations are described with minimum use of tensor expressions arising from the coordinate transformation, to avoid unnecessary confusion for readers. The set of equations obtained will be suitable for the development of a three-dimensional nonequilibrium boundary-layer code. Such a code could be used to determine economically the aerodynamic/aerothermodynamic loads to the surfaces of hypersonic vehicles with general configurations. In addition, the basic equations for three-dimensional stagnation flow, of which solution is required as an initial value for space-marching integration of the boundary-layer equations, are given along with the boundary conditions, the boundary-layer parameters, and the inner-outer layer matching procedure. Expressions for the chemical reaction rates and the thermodynamic and transport properties in the thermal nonequilibrium environment are explicitly given.

Boundary layer effects on liners for aircraft engines

NASA Astrophysics Data System (ADS)

Gabard, Gwénaël

2016-10-01

The performance of acoustic treatments installed on aircraft engines is strongly influenced by the boundary layer of the grazing flow on the surface of the liner. The parametric study presented in this paper illustrates the extent of this effect and identifies when it is significant. The acoustic modes of a circular duct with flow are calculated using a finite difference method. The parameters are representative of the flow conditions, liners and sound fields found in current turbofan engines. Both the intake and bypass ducts are considered. Results show that there is a complex interplay between the boundary layer thickness, the direction of propagation and the liner impedance and that the boundary layer can have a strong impact on liner performance for typical configurations (including changes of the order of 30 dB on the attenuation of modes associated with tonal fan noise). A modified impedance condition including the effect of a small but finite boundary layer thickness is considered and compared to the standard Myers condition based on an infinitely thin boundary layer. We show how this impedance condition can be implemented in a mode calculation method by introducing auxiliary variables. This condition is able to capture the trends associated with the boundary layer effects and in most cases provides improved predictions of liner performance.

Effects of Periodic Unsteady Wake Flow and Pressure Gradient on Boundary Layer Transition Along the Concave Surface of a Curved Plate. Part 3

NASA Technical Reports Server (NTRS)

Schobeiri, M. T.; Radke, R. E.

1996-01-01

Boundary layer transition and development on a turbomachinery blade is subjected to highly periodic unsteady turbulent flow, pressure gradient in longitudinal as well as lateral direction, and surface curvature. To study the effects of periodic unsteady wakes on the concave surface of a turbine blade, a curved plate was utilized. On the concave surface of this plate, detailed experimental investigations were carried out under zero and negative pressure gradient. The measurements were performed in an unsteady flow research facility using a rotating cascade of rods positioned upstream of the curved plate. Boundary layer measurements using a hot-wire probe were analyzed by the ensemble-averaging technique. The results presented in the temporal-spatial domain display the transition and further development of the boundary layer, specifically the ensemble-averaged velocity and turbulence intensity. As the results show, the turbulent patches generated by the wakes have different leading and trailing edge velocities and merge with the boundary layer resulting in a strong deformation and generation of a high turbulence intensity core. After the turbulent patch has totally penetrated into the boundary layer, pronounced becalmed regions were formed behind the turbulent patch and were extended far beyond the point they would occur in the corresponding undisturbed steady boundary layer.

An experimental study of the turbulent boundary layer on a transport wing in subsonic and transonic flow

NASA Technical Reports Server (NTRS)

Spaid, Frank W.; Roos, Frederick W.; Hicks, Raymond M.

1990-01-01

The upper surface boundary layer on a transport wing model was extensively surveyed with miniature yaw probes at a subsonic and a transonic cruise condition. Additional data were obtained at a second transonic test condition, for which a separated region was present at mid-semispan, aft of mid-chord. Significant variation in flow direction with distance from the surface was observed near the trailing edge except at the wing root and tip. The data collected at the transonic cruise condition show boundary layer growth associated with shock wave/boundary layer interaction, followed by recovery of the boundary layer downstream of the shock. Measurements of fluctuating surface pressure and wingtip acceleration were also obtained. The influence of flow field unsteadiness on the boundary layer data is discussed. Comparisons among the data and predictions from a variety of computational methods are presented. The computed predictions are in reasonable agreement with the experimental data in the outboard regions where 3-D effects are moderate and adverse pressure gradients are mild. In the more highly loaded mid-span region near the trailing edge, displacement thickness growth was significantly underpredicted, except when unrealistically severe adverse pressure gradients associated with inviscid calculations were used to perform boundary layer calculations.

Measurements of tropospheric nitric acid over the Western United States and Northeastern Pacific Ocean

NASA Technical Reports Server (NTRS)

Lebel, P. J.; Huebert, B. J.; Schiff, H. I.; Vay, S. A.; Vanbramer, S. E.; Hastie, D. R.

1990-01-01

Over 240 measurements of nitric acid (HNO3) were made in the free troposphere as well as in the boundary layer. Marine HNO3 measurement results were strikingly similar to results from GAMETAG and other past atmospheric field experiments. The marine boundary layer HNO3 average, 62 parts-per-trillion by volume (pptv), was 1/3 lower than the marine free tropospheric average, 108 pptv, suggesting that the boundary layer is a sink for tropospheric nitric acid, probably by dry deposition. Nitric acid measurements on a nighttime continental flight gave a free tropospheric average of 218 pptv, substantially greater than the daytime continental free tropospheric 5-flight average of 61 pptv. However, the nighttime results may be influenced by highly convective conditions that existed from thunderstorms in the vicinity during that night flight. The continental boundary layer HNO3 average of 767 pptv is an order of magnitude greater than the free tropospheric average, indicating that the boundary layer is a source of free tropospheric HNO3. The distribution of continental boundary layer HNO3 data, from averages of 123 over rural Nevada and Utah to 1057 pptv in the polluted San Joaquin Valley of California suggest a close tie between boundary layer HNO3 and anthropogenic activity.

Steady Boundary Layer Disturbances Created By Two-Dimensional Surface Ripples

NASA Astrophysics Data System (ADS)

Kuester, Matthew

2017-11-01

Multiple experiments have shown that surface roughness can enhance the growth of Tollmien-Schlichting (T-S) waves in a laminar boundary layer. One of the common observations from these studies is a ``wall displacement'' effect, where the boundary layer profile shape remains relatively unchanged, but the origin of the profile pushes away from the wall. The objective of this work is to calculate the steady velocity field (including this wall displacement) of a laminar boundary layer over a surface with small, 2D surface ripples. The velocity field is a combination of a Blasius boundary layer and multiple disturbance modes, calculated using the linearized Navier-Stokes equations. The method of multiple scales is used to include non-parallel boundary layer effects of O (Rδ- 1) ; the non-parallel terms are necessary, because a wall displacement is mathematically inconsistent with a parallel boundary layer assumption. This technique is used to calculate the steady velocity field over ripples of varying height and wavelength, including cases where a separation bubble forms on the leeward side of the ripple. In future work, the steady velocity field will be the input for stability calculations, which will quantify the growth of T-S waves over rough surfaces. The author would like to acknowledge the support of the Kevin T. Crofton Aerospace & Ocean Engineering Department at Virginia Tech.