Spherical harmonic analysis of a model-generated climatology

NASA Technical Reports Server (NTRS)

Christidis, Z. D.; Spar, J.

1981-01-01

Monthly mean fields of 850 mb temperature (T850), 500 mb geopotential height (G500) and sea level pressure (SLP) were generated in the course of a five-year climate simulation run with a global general circulation model. Both the model-generated climatology and an observed climatology were subjected to spherical harmonic analysis, with separate analyses of the globe and the Northern Hemisphere. Comparison of the dominant harmonics of the two climatologies indicates that more than 95% of the area-weighted spatial variance of G500 and more than 90% of that of T850 are explained by fewer than three components, and that the model adequately simulates these large-scale characteristics. On the other hand, as many as 25 harmonics are needed to explain 95% of the observed variance of SLP, and the model simulation of this field is much less satisfactory. The model climatology is also evaluated in terms of the annual cycles of the dominant harmonics.

Ross sea ice motion, area flux, and deformation

NASA Technical Reports Server (NTRS)

kwok, Ron

2005-01-01

The sea ice motion, area export, and deformation of the Ross Sea ice cover are examined with satellite passive microwave and RADARSAT observations. The record of high-resolution synthetic aperture radar (SAR) data, from 1998 and 2000, allows the estimation of the variability of ice deformation at the small scale (10 km) and to assess the quality of the longer record of passive microwave ice motion. Daily and subdaily deformation fields and RADARSAT imagery highlight the variability of motion and deformation in the Ross Sea. With the passive microwave ice motion, the area export at a flux gate positioned between Cape Adare and Land Bay is estimated. Between 1992 and 2003, a positive trend can be seen in the winter (March-November) ice area flux that has a mean of 990 x 103 km2 and ranges from a low of 600 x 103 km2 in 1992 to a peak of 1600 x 103 km2 in 2001. In the mean, the southern Ross Sea produces almost twice its own area of sea ice during the winter. Cross-gate sea level pressure (SLP) gradients explain 60% of the variance in the ice area flux. A positive trend in this gradient, from reanalysis products, suggests a 'spinup' of the Ross Sea Gyre over the past 12 yr. In both the NCEP-NCAR and ERA-40 surface pressure fields, longer-term trends in this gradient and mean SLP between 1979 and 2002 are explored along with positive anomalies in the monthly cross-gate SLP gradient associated with the positive phase of the Southern Hemisphere annular mode and the extrapolar Southern Oscillation.

Physics Constrained Stochastic-Statistical Models for Extended Range Environmental Prediction

DTIC Science & Technology

2014-09-30

pressure ( SLP ), respectively]. A major finding of this work, illustrated in Figure 1, is that the North Pacific patterns identified in [1] are part of...Figure II 1. Reconstruction of sea ice concentration, SST, and SLP anomalies in the arctic using NLSA reemergence modes during an active phase of...to reemerge. The geostrophic winds associated with the annular SLP pattern in the right-hand column are cold Northerlies (warm Southerlies) in the

Statistical Downscaling in Multi-dimensional Wave Climate Forecast

NASA Astrophysics Data System (ADS)

Camus, P.; Méndez, F. J.; Medina, R.; Losada, I. J.; Cofiño, A. S.; Gutiérrez, J. M.

2009-04-01

Wave climate at a particular site is defined by the statistical distribution of sea state parameters, such as significant wave height, mean wave period, mean wave direction, wind velocity, wind direction and storm surge. Nowadays, long-term time series of these parameters are available from reanalysis databases obtained by numerical models. The Self-Organizing Map (SOM) technique is applied to characterize multi-dimensional wave climate, obtaining the relevant "wave types" spanning the historical variability. This technique summarizes multi-dimension of wave climate in terms of a set of clusters projected in low-dimensional lattice with a spatial organization, providing Probability Density Functions (PDFs) on the lattice. On the other hand, wind and storm surge depend on instantaneous local large-scale sea level pressure (SLP) fields while waves depend on the recent history of these fields (say, 1 to 5 days). Thus, these variables are associated with large-scale atmospheric circulation patterns. In this work, a nearest-neighbors analog method is used to predict monthly multi-dimensional wave climate. This method establishes relationships between the large-scale atmospheric circulation patterns from numerical models (SLP fields as predictors) with local wave databases of observations (monthly wave climate SOM PDFs as predictand) to set up statistical models. A wave reanalysis database, developed by Puertos del Estado (Ministerio de Fomento), is considered as historical time series of local variables. The simultaneous SLP fields calculated by NCEP atmospheric reanalysis are used as predictors. Several applications with different size of sea level pressure grid and with different temporal domain resolution are compared to obtain the optimal statistical model that better represents the monthly wave climate at a particular site. In this work we examine the potential skill of this downscaling approach considering perfect-model conditions, but we will also analyze the suitability of this methodology to be used for seasonal forecast and for long-term climate change scenario projection of wave climate.

Predictive Factors for Visual Field Conversion: Comparison of Scanning Laser Polarimetry and Optical Coherence Tomography.

PubMed

Diekmann, Theresa; Schrems-Hoesl, Laura M; Mardin, Christian Y; Laemmer, Robert; Horn, Folkert K; Kruse, Friedrich E; Schrems, Wolfgang A

2018-02-01

The purpose of this study was to compare the ability of scanning laser polarimetry (SLP) and spectral-domain optical coherence tomography (SD-OCT) to predict future visual field conversion of subjects with ocular hypertension and early glaucoma. All patients were recruited from the Erlangen glaucoma registry and examined using standard automated perimetry, 24-hour intraocular pressure profile, and optic disc photography. Peripapillary retinal nerve fiber layer thickness (RNFL) measurements were obtained by SLP (GDx-VCC) and SD-OCT (Spectralis OCT). Positive and negative predictive values (PPV, NPV) were calculated for morphologic parameters of SLP and SD-OCT. Kaplan-Meier survival curves were plotted and log-rank tests were performed to compare the survival distributions. Contingency tables and Venn-diagrams were calculated to compare the predictive ability. The study included 207 patients-75 with ocular hypertension, 85 with early glaucoma, and 47 controls. Median follow-up was 4.5 years. A total of 29 patients (14.0%) developed visual field conversion during follow-up. SLP temporal-inferior RNFL [0.667; 95% confidence interval (CI), 0.281-0.935] and SD-OCT temporal-inferior RNFL (0.571; 95% CI, 0.317-0.802) achieved the highest PPV; nerve fiber indicator (0.923; 95% CI, 0.876-0.957) and SD-OCT mean (0.898; 95% CI, 0.847-0.937) achieved the highest NPV of all investigated parameters. The Kaplan-Meier curves confirmed significantly higher survival for subjects within normal limits of measurements of both devices (P<0.001). Venn diagrams tested with McNemar test statistics showed no significant difference for PPV (P=0.219) or NPV (P=0.678). Both GDx-VCC and SD-OCT demonstrate comparable results in predicting future visual field conversion if taking typical scans for GDx-VCC. In addition, the likelihood ratios suggest that GDx-VCC's nerve fiber indicator<30 may be the most useful parameter to confirm future nonconversion. (http://www.ClinicalTrials.gov number, NTC00494923; Erlangen Glaucoma Registry).

Glaucoma Progression Detection by Retinal Nerve Fiber Layer Measurement Using Scanning Laser Polarimetry: Event and Trend Analysis

PubMed Central

Moon, Byung Gil; Cho, Jung Woo; Kang, Sung Yong; Yun, Sung-Cheol; Na, Jung Hwa; Lee, Youngrok; Kook, Michael S.

2012-01-01

Purpose To evaluate the use of scanning laser polarimetry (SLP, GDx VCC) to measure the retinal nerve fiber layer (RNFL) thickness in order to evaluate the progression of glaucoma. Methods Test-retest measurement variability was determined in 47 glaucomatous eyes. One eye each from 152 glaucomatous patients with at least 4 years of follow-up was enrolled. Visual field (VF) loss progression was determined by both event analysis (EA, Humphrey guided progression analysis) and trend analysis (TA, linear regression analysis of the visual field index). SLP progression was defined as a reduction of RNFL exceeding the predetermined repeatability coefficient in three consecutive exams, as compared to the baseline measure (EA). The slope of RNFL thickness change over time was determined by linear regression analysis (TA). Results Twenty-two eyes (14.5%) progressed according to the VF EA, 16 (10.5%) by VF TA, 37 (24.3%) by SLP EA and 19 (12.5%) by SLP TA. Agreement between VF and SLP progression was poor in both EA and TA (VF EA vs. SLP EA, k = 0.110; VF TA vs. SLP TA, k = 0.129). The mean (±standard deviation) progression rate of RNFL thickness as measured by SLP TA did not significantly differ between VF EA progressors and non-progressors (-0.224 ± 0.148 µm/yr vs. -0.218 ± 0.151 µm/yr, p = 0.874). SLP TA and EA showed similar levels of sensitivity when VF progression was considered as the reference standard. Conclusions RNFL thickness as measurement by SLP was shown to be capable of detecting glaucoma progression. Both EA and TA of SLP showed poor agreement with VF outcomes in detecting glaucoma progression. PMID:22670073

Glaucoma progression detection by retinal nerve fiber layer measurement using scanning laser polarimetry: event and trend analysis.

PubMed

Moon, Byung Gil; Sung, Kyung Rim; Cho, Jung Woo; Kang, Sung Yong; Yun, Sung-Cheol; Na, Jung Hwa; Lee, Youngrok; Kook, Michael S

2012-06-01

To evaluate the use of scanning laser polarimetry (SLP, GDx VCC) to measure the retinal nerve fiber layer (RNFL) thickness in order to evaluate the progression of glaucoma. Test-retest measurement variability was determined in 47 glaucomatous eyes. One eye each from 152 glaucomatous patients with at least 4 years of follow-up was enrolled. Visual field (VF) loss progression was determined by both event analysis (EA, Humphrey guided progression analysis) and trend analysis (TA, linear regression analysis of the visual field index). SLP progression was defined as a reduction of RNFL exceeding the predetermined repeatability coefficient in three consecutive exams, as compared to the baseline measure (EA). The slope of RNFL thickness change over time was determined by linear regression analysis (TA). Twenty-two eyes (14.5%) progressed according to the VF EA, 16 (10.5%) by VF TA, 37 (24.3%) by SLP EA and 19 (12.5%) by SLP TA. Agreement between VF and SLP progression was poor in both EA and TA (VF EA vs. SLP EA, k = 0.110; VF TA vs. SLP TA, k = 0.129). The mean (±standard deviation) progression rate of RNFL thickness as measured by SLP TA did not significantly differ between VF EA progressors and non-progressors (-0.224 ± 0.148 µm/yr vs. -0.218 ± 0.151 µm/yr, p = 0.874). SLP TA and EA showed similar levels of sensitivity when VF progression was considered as the reference standard. RNFL thickness as measurement by SLP was shown to be capable of detecting glaucoma progression. Both EA and TA of SLP showed poor agreement with VF outcomes in detecting glaucoma progression.

Simulated decadal modes of the NH atmospheric circulation arising from intra-decadal variability, external forcing and slow-decadal climate processes

NASA Astrophysics Data System (ADS)

Lou, Jiale; Zheng, Xiaogu; Frederiksen, Carsten S.; Liu, Haibo; Grainger, Simon; Ying, Kairan

2017-04-01

A decadal variance decomposition method is applied to the Northern Hemisphere (NH) 500-hPa geopotential height (GPH) and the sea level pressure (SLP) taken from the last millennium (850-1850 AD) experiment with the coupled climate model CCSM4, to estimate the contribution of the intra-decadal variability to the inter-decadal variability. By removing the intra-decadal variability from the total inter-decadal variability, the residual variability is more likely to be associated with slowly varying external forcings and slow-decadal climate processes, and therefore is referred to as slow-decadal variability. The results show that the (multi-)decadal changes of the NH 500-hPa GPH are primarily dominated by slow-decadal variability, whereas the NH SLP field is primarily dominated by the intra-decadal variability. At both pressure levels, the leading intra-decadal modes each have features related to the El Niño-southern oscillation, the intra-decadal variability of the Pacific decadal oscillation (PDO) and the Arctic oscillation (AO); while the leading slow-decadal modes are associated with external radiative forcing (mostly with volcanic aerosol loadings), the Atlantic multi-decadal oscillation and the slow-decadal variability of AO and PDO. Moreover, the radiative forcing has much weaker effect to the SLP than that to the 500-hPa GPH.

Impacts of Potential Aircraft Observations on Forecasts of Tropical Cyclones Over the Western North Pacific

DTIC Science & Technology

2014-12-01

anticyclone. Vertical wind shear was low, while a moderate level of upper level diffluence existed. The minimum sea level pressure ( SLP ) was estimated...pre-Sinlaku disturbance. At this time, JTWC estimated maximum surface level winds to be 15 to 20 kt, with a SLP near 1005 hPa. 17 Figure 11...poleward side of the circulation. Surface winds had increased to near 23 kt as the SLP continued to fall to 1004 hPa. JTWC forecasters upgraded the

Visible and Thermal Imaging of Sea Ice and Open Water from Coast Guard Arctic Domain Awareness Flights

DTIC Science & Technology

2014-09-30

dropsondes, micro- aircraft), cloud top/base heights Arctic Ocean Surface Temperature project Steele Buoy drops for SLP , SST, SSS, & surface velocity...Colón & Vancas (NIC) Drop buoys for SLP , temperature and surface velocity Waves & Fetch in the MIZ Thompson SWIFTS buoys measuring wave energy...Expendable CTD, AXCP= Air Expendable Current Profiler, SLP = Sea Level atmospheric Pressure, SST= Seas Surface Temperature, A/C= aircraft, FSD= Floe Size Distribution, SIC=Sea Ice Concentration

Some mean atmospheric characteristics for snowfall occurrences in southern Brazil

NASA Astrophysics Data System (ADS)

Mintegui, Jéssica Melo; Puhales, Franciano Scremin; Boiaski, Nathalie Tissot; Nascimento, Ernani de Lima; Anabor, Vagner

2018-01-01

Snowfall is considered a natural disaster in southern Brazil, where a little infrastructure exists up to prevent against the damage it induces, making snowfall forecast a matter of great interest in this region. The present article aims to describe the mean behavior of low, mid, and high atmospheric levels during snowfall occurrences in southern Brazil. Sea-level pressure (SLP), 1000-500 hPa atmospheric thickness, geopotential height at 500 hPa, and wind speed at 200 hPa have been analyzed. One hundred and ninety-six snowfall records from the conventional surface meteorological stations have been selected for the period from 1979 to 2015. The surface synoptic pattern associated with snowfall occurrences has been obtained from ERA-Interim reanalysis data with horizontal spatial resolution of 0.75° × 0.75° and temporal resolution of 12 h. SLP fields show a high-pressure transient system displacement from the Pacific Ocean to northeastern Argentina. In addition, it is possible to relate snowfall with displacement of a low-pressure system on the coast of southern Brazil. Thickness fields indicate shallow cold air mass intrusions one day before snowfall. Such a cold air continues moving towards low latitudes during consecutive snowfall days and it may be responsible for frost events in climatologically warm regions. Finally, mid and high atmospheric levels show an eastward propagating wave amplified by the Andes.

Diagnostic capability of scanning laser polarimetry with and without enhanced corneal compensation and optical coherence tomography.

PubMed

Benítez-del-Castillo, Javier; Martinez, Antonio; Regi, Teresa

2011-01-01

To compare the abilities of the current commercially available versions of scanning laser polarimetry (SLP) and optical coherence tomography (OCT), SLP-variable corneal compensation (VCC), SLP-enhanced corneal compensation (ECC), and high-definition (HD) OCT, in discriminating between healthy eyes and those with early-to-moderate glaucomatous visual field loss. Healthy volunteers and patients with glaucoma who met the eligibility criteria were consecutively enrolled in this prospective, cross-sectional, observational study. Subjects underwent complete eye examination, automated perimetry, SLP-ECC, SLP-VCC, and HD-OCT. Scanning laser polarimetry parameters were recalculated in 90-degree segments (quadrants) in the calculation circle to be compared. Areas under the receiver operating characteristic curve (AUROCs) were calculated for every parameter in order to compare the ability of each imaging modality to differentiate between normal and glaucomatous eyes. Fifty-five normal volunteers (mean age 59.1 years) and 33 patients with glaucoma (mean age 63.8 years) were enrolled. Average visual field mean deviation was -6.69 dB (95% confidence interval -8.07 to -5.31) in the glaucoma group. The largest AUROCs were associated with nerve fiber indicator (0.880 and 0.888) for the SLP-VCC and SLP-ECC, respectively, and with the average thickness in the HD-OCT (0.897). The best performing indices for the SLP-VCC, SLP-ECC, and HD OCT gave similar AUROCs, showing moderate diagnostic accuracy in patients with early to moderate glaucoma. Further studies are needed to evaluate the ability of these technologies to discriminate between normal and glaucomatous eyes.

Assessing Northern Hemisphere Land-Atmosphere Hotspots Using Dynamical Adjustment

NASA Astrophysics Data System (ADS)

Merrifield, Anna; Lehner, Flavio; Deser, Clara; Xie, Shang-Ping

2017-04-01

Understanding the influence of soil moisture on surface air temperature (SAT) is made more challenging by large-scale, internal atmospheric variability present in the midlatitude summer atmosphere. In this study, dynamical adjustment is used to characterize and remove summer SAT variability associated with large-scale circulation patterns in the Community Earth System Model large ensemble (CESM-LE). The adjustment is performed over North America and Europe with two different circulation indicators: sea level pressure (SLP) and 500mb height (Z500). The removal of dynamical "noise" leaves residual SAT variability in the central U.S. and Mediterranean regions identified as hotspots of land-atmosphere interaction (e.g. Koster et al. 2004, Seneviratne et al. 2006). The residual SAT variability "signal" is not clearly related to modes of sea surface temperature (SST) variability, but is related to local soil moisture, evaporative fraction, and radiation availability. These local relationships suggest that residual SAT variability is representative of the aggregate land surface signal. SLP dynamical adjustment removes ˜15% more variability in the central U.S. hotspot region than Z500 dynamical adjustment. Similar amounts of variability are removed by SLP and Z500 in the Mediterranean region. Differences in SLP and Z500 signal magnitude in the central U.S. are likely due to the modification of SLP by local land surface conditions, while the proximity of European hotspots to the Mediterranean sea mitigates the land surface influence. Variations in the Z500 field more closely resemble large-scale midlatitude circulation patterns and therefore Z500 may be a more suitable circulation indicator for summer dynamical adjustment. Changes in the residual SAT variability signal under increased greenhouse gas forcing will also be explored.

Purification, characterization and immunomodulatory activity of polysaccharides from stem lettuce.

PubMed

Nie, Chenzhipeng; Zhu, Peilei; Ma, Shuping; Wang, Mingchun; Hu, Youdong

2018-05-15

Stem lettuce has a long history of cultivation in China and possesses high nutritional and medicinal value. In our previous studies, extraction optimization, characterization, and bioactivities of stem lettuce polysaccharides (SLP) were investigated. In this study, SLP were further separated into two purified polysaccharides, SLP-1 and SLP-2, by anion exchange chromatography followed by size exclusion chromatography. SLP-1, with a molecular weight of 90 KDa, was mainly composed of galacturonic acid, galactose and arabinose in a molar ratio of 17.6:41.7:33.9. SLP-2, with a molecular weight of 44 KDa, was mainly composed of mannose, galacturonic acid, galactose and arabinose in a molar ratio of 11.5:69.5:9.3:8.2. In addition, both purified polysaccharides contain sulphate radicals, have triple helical structures and can promote macrophage proliferation without cytotoxicity. SLP-2 was better able to stimulate phagocytic and nitric oxide production than SLP-1. The results suggest that polysaccharides from stem lettuce could be explored as immunomodulatory agents in the field of pharmaceuticals and functional foods. Copyright © 2018 Elsevier Ltd. All rights reserved.

Energy absorption by a magnetic nanoparticle suspension in a rotating field

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

Raikher, Yu. L.; Stepanov, V. I., E-mail: stepanov@icmm.ru

Heat generation by viscous dissipation in a dilute suspension of single-domain ferromagnetic particles in a rotating magnetic field is analyzed by assuming that the suspended particles have a high magnetic rigidity. The problem is solved by using a kinetic approach based on a rotational diffusion equation. Behavior of specific loss power (SLP) as a function of field strength H and frequency {omega} is examined at constant temperature. SLP increases as either of these parameters squared when the other is constant, eventually approaching a saturation value. The function SLP(H, {omega}) can be used to determine optimal and admissible ranges of magneticallymore » induced heating.« less

A daily Azores-Iceland North Atlantic Oscillation index back to 1850.

PubMed

Cropper, Thomas; Hanna, Edward; Valente, Maria Antónia; Jónsson, Trausti

2015-07-01

We present the construction of a continuous, daily (09:00 UTC), station-based (Azores-Iceland) North Atlantic Oscillation (NAO) Index back to 1871 which is extended back to 1850 with additional daily mean data. The constructed index more than doubles the length of previously existing, widely available, daily NAO time series. The index is created using entirely observational sea-level pressure (SLP) data from Iceland and 73.5% of observational SLP data from the Azores - the remainder being filled in via reanalysis (Twentieth Century Reanalysis Project and European Mean Sea Level Pressure) SLP data. Icelandic data are taken from the Southwest Iceland pressure series. We construct and document a new Ponta Delgada SLP time series based on recently digitized and newly available data that extend back to 1872. The Ponta Delgada time series is created by splicing together several fractured records (from Ponta Delgada, Lajes, and Santa Maria) and filling in the major gaps (pre-1872, 1888-1905, and 1940-1941) and occasional days (145) with reanalysis data. Further homogeneity corrections are applied to the Azores record, and the daily (09:00 UTC) NAO index is then calculated. The resulting index, with its extended temporal length and daily resolution, is the first reconstruction of daily NAO back into the 19th Century and therefore is useful for researchers across multiple disciplines.

Comparison of Mid-latitude Cyclones in Sea Level Pressure, Gepotential Height and Vorticity Fields

NASA Astrophysics Data System (ADS)

Raible, Christoph C.; Blender, Richard; Fraedrich, Klaus

2013-04-01

The mid-latitudes are dominated by diurnal variability, which is related to traveling high- and low-pressure systems. The lows or cyclones are a major source of natural hazards. This has led to growing interest in the scientific community to develop Eulerian and Lagrangian measures and to analyze the atmospheric high-frequency variability. One important issue is that there is no straight forward definition of cyclones resulting in a large variety of so-called cyclone detection and tracking methods. Each of these methods relies on different input fields which are related to specific features of a cyclone, e.g., sea level pressure (SLP), which specifically focuses on the mass aspect of the velocity field. Recently, the available methods have been compared with respect to climatology and life cycles using the ERA interim data set (Neu et al. 2013). Based on this study we investigate different fields as input for one specific method. We focus on the three mostly used input data, sea level pressure (SLP), 1000-hPa gepotential height (Z1000) and 850-hPa vorticity (850VOR). The cyclone detection and tracking method developed by Blender et al. (1997) is used and we apply it to ERA interim data in the 1.5 x 1.5 resolution. The method was mainly applied for Z1000 and the Northern Hemisphere (e.g., Blender et al. 1997; Raible et al. 2008). To compare the tracks and cyclone characteristics obtained from the different input data we need to adapt critical parameters of the method in such a way that comparable numbers of cyclone centers are identified in either field. The target is set to the number of cyclone centers in northern hemispheric winter. This enables us to assess the seasonal and hemispheric dependence. Preliminary results show that the agreement between cyclones based on SLP and Z1000 varies between roughly 70 to 80% depending on the season and the hemisphere. Spatially, most of the differences are found around orographic features like Greenland. An interesting finding is that the number of cyclones based on Z1000 is increased comparing the winter and summer season as the number of heat lows increases in summer. However, the behavior is vice versa for cyclones based on SLP. References: Blender R., K. Fraedrich, and F. Lunkeit, 1997: Identification of cyclone-track regimes in the North Atlantic. Quart. J. Roy. Meteor. Soc., 123, 727-741. Neu, U., M. G. Akperov, N. Bellenbaum, R. Benestad, R. Blender, R. Caballero, A. Cocozza, H. F. Dacre, Y. Feng, K. Fraedrich, J. Grieger, S. Gulev, J. Hanley, T. Hewson, M. Inatsu, K. Keay, S. F. Kew, I. Kindem, G. C. Leckebusch, M. L. R. Liberato, P. Lionello, I. I. Mokhov, J. G. Pinto, C. C. Raible, M. Reale, I. Rudeva, M. Schuster, I. Simmonds, M. Sinclair, M. Sprenger, N. D. Tilinina, I. F. Trigo, S. Ulbrich, U. Ulbrich, X. L. Wang, H. Wernli, 2012: IMILAST - a community effort to intercompare extratropical cyclone detection and tracking algorithms: assessing method-related uncertainties, Bulletin of the American Meteorological Society, in press. Raible, C. C., P. Della-Marta, C. Schwierz, H. Wernli, and R. Blender, 2008: Northern Hemisphere extratropical cyclones: A comparison of detection and tracking methods and different reanalyses, Mon. Wea. Rev., 136 880-897.

Modulation of Bjerknes feedback on the decadal variations in ENSO predictability

NASA Astrophysics Data System (ADS)

Zheng, Fei; Fang, Xiang-Hui; Zhu, Jiang; Yu, Jin-Yi; Li, Xi-Chen

2016-12-01

Clear decadal variations exist in the predictability of the El Niño-Southern Oscillation (ENSO), with the most recent decade having the lowest ENSO predictability in the past six decades. The Bjerknes Feedback (BF) intensity, which dominates the development of ENSO, has been proposed to determine ENSO predictability. Here we demonstrate that decadal variations in BF intensity are largely a result of the sensitivity of the zonal winds to the zonal sea level pressure (SLP) gradient in the equatorial Pacific. Furthermore, the results show that during low-ENSO predictability decades, zonal wind anomalies over the equatorial Pacific are more linked to SLP variations in the off-equatorial Pacific, which can then transfer this information into surface temperature and precipitation fields through the BF, suggesting a weakening in the ocean-atmosphere coupling in the tropical Pacific. This result indicates that more attention should be paid to off-equatorial processes in the prediction of ENSO.

Comparison of sea level pressure reconstructions from western North American tree rings with a proxy record of winter severity in Japan

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

Gordon, G.A.; Lough, J.M.; Fritts, H.C.

Reconstructions of winter (December-February) sea level pressure (SLP) from western North American tree-ring chronologies are compared with a proxy record of winter severity in Japan derived from the historically documented freeze dates of Lake Suwa. The SLP reconstructions extend from 1602 to 1961 and freeze dates from 1443 to 1954. The instrumental and reconstructed SLP for the 20th century reveal two distinct circulation regimes (teleconnection patterns) over the North Pacific that appear to be associated with severe and mild winters and, consequently, with early and late freezing of the lake. The reconstructed SLPO anomaly map for severe winters prior tomore » 1683 shows a pattern similar to those in the instrumental and reconstructed records of the 20th century. The analysis reveals that the reliability of the reconstruction may vary with the configuration of the actual SLP pattern as the mild winter pattern is not as well reconstructed as the severe winter pattern. That result illustrates the importance of testing the reliability of a reconstruction within the context of the intended interpretation. This analysis demonstrates how different types of proxy climate data can be compared and verified.« less

Interannual variability of Indian monsoon rainfall

NASA Technical Reports Server (NTRS)

Paolino, D. A.; Shukla, J.

1984-01-01

The interannual variability of the Indian summer monsoon and its relationships with other atmospheric fluctuations were studied in hopes of gaining some insight into the predicability of the rainfall. Rainfall data for 31 meteorological subdivisions over India were provided by the India Meteorological Department (IMD). Fifty-three years of seasonal mean anomaly sea-level pressure (SLP) fields were used to determine if any relationships could be detected between fluctuations in Northern Hemisphere surface pressure and Indian monsoon rainfall. Three month running mean sea-level pressure anomalies at Darwin (close to one of the centers of the Southern Oscillation) were compiled for months preceding and following extreme years for rainfall averaged over all of India. Anomalies are small before the monsoon, but are quite large in months following the summer season. However, there is a large decrease in Darwin pressure for months preceding a heavy monsoon, while a deficient monsoon is preceded by a sharp increase in Darwin pressure. If a time series is constructed of the tendency of Darwin SLP between the Northern Hemisphere winter (DJF) and spring (MAM) and a correlation coefficient is computed between it and 81 years of rainfall average over all of India, one gets a C. C. of -.46, which is higher than any other previously computed predictor of the monsoon rainfall. This relationship can also be used to make a qualitative forecast for rainfall over the whole of India by considering the sign of the tendency in extreme monsoon years.

Joint impact of North and South Pacific extratropical atmospheric variability on the onset of ENSO events

NASA Astrophysics Data System (ADS)

Ding, Ruiqiang; Li, Jianping; Tseng, Yu-heng; Sun, Cheng; Xie, Fei

2017-01-01

Previous studies have indicated that boreal winter subtropical and extratropical sea surface pressure (SLP) anomalies over both the North and South Pacific are significantly related to the El Niño-Southern Oscillation (ENSO) state in the following boreal winter. Here we use observational data and model simulations to show that the ability of the boreal winter North Pacific SLP anomalies to initiate ENSO events a year later may strongly depend on the state of the simultaneous South Pacific SLP anomalies and vice versa. When the boreal winter North Pacific SLP anomalies are of the opposite sign to the simultaneous South Pacific anomalies, the correlation of the North or South Pacific anomalies with the following ENSO state becomes much weaker, and the strength of the ENSO events also tends to be weaker. One possible reason for this is that when the boreal winter North and South Pacific SLP anomalies have the opposite sign, the westerly anomalies over the western-central equatorial Pacific during the following boreal summer are greatly reduced by the interference between the antecedent North and South Pacific SLP anomalies, thereby not favoring the development of ENSO events. Further analysis indicates that a combination of North and South Pacific precursor signals may serve to enhance the ENSO prediction skill.

Investigating the Influence of Anthropogenic Forcing on Observed Mean and Extreme Sea Level Pressure Trends over the Mediterranean Region

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

Barkhordarian, Armineh

We investigate whether the observed mean sea level pressure (SLP) trends over the Mediterranean region in the period from 1975 to 2004 are significantly consistent with what 17 models projected as response of SLP to anthropogenic forcing (greenhouse gases and sulphate aerosols, GS). Obtained results indicate that the observed trends in mean SLP cannot be explained by natural (internal) variability. Externally forced changes are detectable in all seasons, except spring. The large-scale component (spatial mean) of the GS signal is detectable in all the 17 models in winter and in 12 of the 17 models in summer. However, the small-scalemore » component (spatial anomalies about the spatial mean) of GS signal is only detectable in winter within 11 of the 17 models. We also show that GS signal has a detectable influence on observed decreasing (increasing) tendency in the frequencies of extremely low (high) SLP days in winter and that these changes cannot be explained by internal climate variability. While the detection of GS forcing is robust in winter and summer, there are striking inconsistencies in autumn, where analysis points to the presence of an external forcing, which is not GS forcing.« less

Investigating the Influence of Anthropogenic Forcing on Observed Mean and Extreme Sea Level Pressure Trends over the Mediterranean Region

DOE PAGES

Barkhordarian, Armineh

2012-01-01

We investigate whether the observed mean sea level pressure (SLP) trends over the Mediterranean region in the period from 1975 to 2004 are significantly consistent with what 17 models projected as response of SLP to anthropogenic forcing (greenhouse gases and sulphate aerosols, GS). Obtained results indicate that the observed trends in mean SLP cannot be explained by natural (internal) variability. Externally forced changes are detectable in all seasons, except spring. The large-scale component (spatial mean) of the GS signal is detectable in all the 17 models in winter and in 12 of the 17 models in summer. However, the small-scalemore » component (spatial anomalies about the spatial mean) of GS signal is only detectable in winter within 11 of the 17 models. We also show that GS signal has a detectable influence on observed decreasing (increasing) tendency in the frequencies of extremely low (high) SLP days in winter and that these changes cannot be explained by internal climate variability. While the detection of GS forcing is robust in winter and summer, there are striking inconsistencies in autumn, where analysis points to the presence of an external forcing, which is not GS forcing.« less

Surface layer protein from Lactobacillus acidophilus NCFM inhibit intestinal pathogen-induced apoptosis in HT-29 cells.

PubMed

Meng, Jun; Zhang, Qiu-Xiang; Lu, Rong-Rong

2017-03-01

Intestinal pathogens have been proposed to adhere to epithelial cells and cause apoptosis. This study was to investigate the inhibitory effects of surface layer protein (SLP, 46kDa) from Lactobacillus acidophilus NCFM on Escherichia coli and Salmonella-induced apoptosis in HT-29 cells and the mechanism of the inhibition was also studied. The SLP could alleviate the chromatin condensation caused by intestinal pathogens as observed under fluorescent microscope. Flow cytometry analysis showed that the SLP decreased E. coli and Salmonella-induced apoptosis by 46% and 48%, respectively. The SLP could also inhibit the mitochondrial membrane potential reduction and Ca 2+ level increase in HT-29 cells. Furthermore, the activation of caspase-9 and caspase-3 induced by E. coli and Salmonella was significantly decreased by the addition of SLP. These results suggested that L. acidophilus NCFM SLP could protect HT-29 cells against intestinal pathogen-induced apoptosis through a mitochondria-mediated pathway. These findings may reveal a new method for the treatment of intestinal infection and provide a theoretical basis for the practical application of SLP in food, biological and pharmaceutical fields. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlation between local glaucomatous visual field defects and loss of nerve fiber layer thickness measured with polarimetry and spectral domain OCT.

PubMed

Horn, Folkert K; Mardin, Christian Y; Laemmer, Robert; Baleanu, Delia; Juenemann, Anselm M; Kruse, Friedrich E; Tornow, Ralf P

2009-05-01

To study the correlation between local perimetric field defects and glaucoma-induced thickness reduction of the nerve layer measured in the peripapillary area with scanning laser polarimetry (SLP) and spectral domain optical coherence tomography (SOCT) and to compare the results with those of a theoretical model. The thickness of the retinal nerve fiber layer was determined in 32 sectors (11.25 degrees each) by using SLP with variable cornea compensation (GDxVCC; Laser Diagnostics, San Diego, CA) and the newly introduced high-resolution SOCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany). Eighty-eight healthy subjects served as control subjects, to determine the thickness deviation in patients with glaucoma. The relationship between glaucomatous nerve fiber reduction and visual field losses was calculated in six nerve fiber bundle-related areas. Sixty-four patients at different stages of open-angle glaucoma and 26 patients with ocular hypertension underwent perimetry (Octopus G1; Haag-Streit, Köniz, Switzerland) and measurements with the two morphometric techniques. Sector-shaped analyses between local perimetric losses and reduction of the retinal nerve fiber layer thickness showed a significant association for corresponding areas except for the central visual field in SLP. Correlation coefficients were highest in the area of the nasal inferior visual field (SOCT, -0.81; SLP, -0.57). A linear model describes the association between structural and functional damage. Localized perimetric defects can be explained by reduced nerve fiber layer thickness. The data indicate that the present SOCT is useful for determining the functional-structural relationship in peripapillary areas and that association between perimetric defects and corresponding nerve fiber losses is stronger for SOCT than for the present SLP. (ClinicalTrials.gov number, NCT00494923.).

The use of a calculus-based cyclone identification method for generating storm statistics

NASA Astrophysics Data System (ADS)

Benestad, R. E.; Chen, D.

2006-08-01

Maps of 12 hr sea-level pressure (SLP) from the former National Meteotrological Center (NMC) and 24 hr SLP maps from the European Centre for Medium-range Weather Forecasts (ECMWF) 40 yr re-analysis (ERA40) were used to identify extratropical cyclones in the North Atlantic region. A calculus-based cyclone identification (CCI) method is introduced and evaluated, where a multiple regression against a truncated series of sinusoids was used to obtain a Fourier approximation of the north-south and east-west SLP profiles, providing a basis for analytical expressions of the derivatives. Local SLP minima were found from the zero-crossing points of the first-order derivatives for the SLP gradients where the second-order derivatives were greater than zero. Evaluation of cyclone counts indicates a good correspondence with storm track maps and independent monthly large-scale SLP anomalies. The results derived from ERA40 also revealed that the central storm pressure sometimes could be extremely deep in the re-analysis product, and it is not clear whether such outliers are truly representative of the actual events. The position and the depth of the cyclones were subjects for a study of long-term trends in cyclone number for various regions around the North Atlantic. Noting that the re-analyses may contain time-dependent biases due to changes in the observing practises, a tentative positive linear trend, statistically significant at the 10% level, was found in the number of intense storms over the Nordic countries over the period 1955-1994 in both the NMC and the ERA40 data. However, there was no significant trend in the western parts of the North Atlantic where trend analysis derived from NMC and ERA40 yielded different results. The choice of data set had a stronger influence on the results than choices such as the number of harmonics to include or spatial resolution of interpolation.

Atmospheric signature of the Agulhas current

NASA Astrophysics Data System (ADS)

Stela Nkwinkwa Njouodo, Arielle; Koseki, Shunya; Rouault, Mathieu; Keenlyside, Noel

2017-04-01

Satellite observation and Climate Forecast System Reanalysis (CFSR) are used to map the influence of the Agulhas current on local annual precipitation in Southern Africa. The pressure adjustment mechanism is applied over the Agulhas current region. Results unfold that the narrow band of precipitation above the Agulhas Current is collocated with surface wind convergence, sea surface temperature (SST) Laplacian and sea level pressure (SLP) Laplacian. Relationship between SLP Laplacian and wind convergence is found, with 0.54 correlation coefficient statistically significant. In the free troposphere, the band of precipitation above the Agulhas current is collocated with the wind divergence and the upward motion of wind velocity. The warm waters from the Agulhas current can influence local precipitation.

Experimental determination of the frequency and field dependence of Specific Loss Power in Magnetic Fluid Hyperthermia

NASA Astrophysics Data System (ADS)

Cobianchi, M.; Guerrini, A.; Avolio, M.; Innocenti, C.; Corti, M.; Arosio, P.; Orsini, F.; Sangregorio, C.; Lascialfari, A.

2017-12-01

Magnetic nanoparticles are promising systems for biomedical applications and in particular for Magnetic Fluid Hyperthermia, a therapy that utilizes the heat released by such systems to damage tumor cells. We present an experimental study of the physical properties that influences the capability of heat release, i.e. the Specific Loss Power, SLP, of three biocompatible ferrofluid samples having a magnetic core of maghemite with different diameter d = 10.2, 14.6 and 19.7 nm. The SLP was measured as a function of frequency f and intensity H of the applied alternating magnetic field, and it turned out to depend on the core diameter, as expected. The results allowed us to highlight experimentally that the physical mechanism responsible for the heating is size-dependent and to establish, at applied constant frequency, the phenomenological functional relationship SLP = c·Hx, with 2 ≤ x<3 for all samples. The x-value depends on sample size and field frequency, here chosen in the typical range of operating magnetic hyperthermia devices. For the smallest sample, the effective relaxation time τeff ≈ 19.5 ns obtained from SLP data is in agreement with the value estimated from magnetization data, thus confirming the validity of the Linear Response Theory model for this system at properly chosen field intensity and frequency.

An Analysis of the 2013 Program Evaluation Proposals for the School Leadership Preparation Program

ERIC Educational Resources Information Center

Sanzo, Karen

2016-01-01

This article presents a content analysis of the 2013 School Leadership Program (SLP) grants. SLP projects provide a unique opportunity for participants in the field to explore innovative leadership preparation and development and their impact on program participants, schools, school districts, and students. The article begins with an overview of…

Circulation patterns governing October snowfalls in southern Siberia

NASA Astrophysics Data System (ADS)

Bednorz, Ewa; Wibig, Joanna

2017-04-01

This study is focused on early fall season in southern Siberia (50-60 N) and is purposed as a contribution to the discussion on the climatic relevance of October Eurasian snow cover. Analysis is based on the daily snow depth data from 43 stations from years 1980-2012, available in the database of All-Russian Research Institute of Hydrometeorological Information—World Data Centre. The snow cover season in southern Siberia starts in early autumn and the number of days with snowfall varies from less than 5 days in the southernmost zone along the parallel 50 N to more than 25 days in the northeastern part of the analyzed area. October snowfall in southern Siberia is associated with occurrence of negative anomalies of sea level pressure (SLP), usually spreading right over the place of recorded intense snowfall or extending eastward from it. Negative anomalies of air temperature at the 850 hPa geopotential level (T850) occurring with increased cyclonic activity are also observed. Negative T850 anomalies are located west or northwest of the SLP depressions. Counterclockwise circulation around low-pressure systems transports cold Arctic air from the north or even colder Siberian polar air from the east, to the west, and northwest parts of cyclones, and induces negative anomalies of temperature. The pattern of T850 anomalies during heavy snowfalls in the eastern part of the southern Siberia is shifted counterclockwise in regard to SLP anomalies: the strongest negative T850 anomalies are located west or northwest of the SLP depressions.

Inter-annual variability and long term predictability of exchanges through the Strait of Gibraltar

NASA Astrophysics Data System (ADS)

Boutov, Dmitri; Peliz, Álvaro; Miranda, Pedro M. A.; Soares, Pedro M. M.; Cardoso, Rita M.; Prieto, Laura; Ruiz, Javier; García-Lafuente, Jesus

2014-03-01

Inter-annual variability of calculated barotropic (netflow) and simulated baroclinic (inflow and outflow) exchanges through the Strait of Gibraltar is analyzed and their response to the main modes of atmospheric variability is investigated. Time series of the outflow obtained by high resolution simulations and estimated from in-situ Acoustic Doppler Current Profiler (ADCP) current measurements are compared. The time coefficients (TC) of the leading empirical orthogonal function (EOF) modes that describe zonal atmospheric circulation in the vicinity of the Strait (1st and 3rd of Sea-Level Pressure (SLP) and 1st of the wind) show significant covariance with the inflow and outflow. Based on these analyses, a regression model between these SLP TCs and outflow of the Mediterranean Water was developed. This regression outflow time series was compared with estimates based on current meter observations and the predictability and reconstruction of past exchange variability based on atmospheric pressure fields are discussed. The simple regression model seems to reproduce the outflow evolution fairly reasonably, with the exception of the year 2008, which is apparently anomalous without available physical explanation yet. The exchange time series show a reduced inter-annual variability (less than 1%, 2.6% and 3.1% of total 2-day variability, for netflow, inflow and outflow, respectively). From a statistical point of view no clear long-term tendencies were revealed. Anomalously high baroclinic fluxes are reported for the years of 2000-2001 that are coincident with strong impact on the Alboran Sea ecosystem. The origin of the anomalous flow is associated with a strong negative anomaly (~ - 9 hPa) in atmospheric pressure fields settled north of Iberian Peninsula and extending over the central Atlantic, favoring an increased zonal circulation in winter 2000/2001. These low pressure fields forced intense and durable westerly winds in the Gulf of Cadiz-Alboran system. The signal of this anomaly is also seen in time coefficients of the most significant EOF modes. The predictability of the exchanges for future climate is discussed.

The role of the Southern Hemisphere semiannual oscillation in the development of a precursor to central and eastern Pacific Southern Oscillation warm events

NASA Astrophysics Data System (ADS)

Meehl, Gerald A.; van Loon, Harry; Arblaster, Julie M.

2017-07-01

The semiannual oscillation (SAO) is a twice-yearly northward movement (in May-June-July (MJJ) and November-December-January (NDJ)) of the circumpolar trough of sea level pressure (SLP) in the Southern Hemisphere with effects throughout the troposphere. During MJJ the second harmonic of SLP, describing the SAO, has low values of SLP north of 50°S in the subtropical South Pacific, while the first harmonic, which is dominant over the Australian sector, increases to its peak. This once-a-year peak in negative SLP gradients (decreasing to the east) between Australia and the ocean to its east extends to the equatorial Pacific. Southern Oscillation warm events since 1950, with an intensification of this seasonal cycle, have larger-amplitude SST anomalies in the eastern equatorial Pacific in MJJ and during the following mature phase in NDJ. Weak amplification of the seasonal cycle in MJJ tends to be followed by larger-amplitude SST anomalies in the central equatorial Pacific during NDJ.

Scanning laser polarimetry in glaucoma

PubMed Central

Dada, Tanuj; Sharma, Reetika; Angmo, Dewang; Sinha, Gautam; Bhartiya, Shibal; Mishra, Sanjay K; Panda, Anita; Sihota, Ramanjit

2014-01-01

Glaucoma is an acquired progressive optic neuropathy which is characterized by changes in the optic nerve head and retinal nerve fiber layer (RNFL). White-on-white perimetry is the gold standard for the diagnosis of glaucoma. However, it can detect defects in the visual field only after the loss of as many as 40% of the ganglion cells. Hence, the measurement of RNFL thickness has come up. Optical coherence tomography and scanning laser polarimetry (SLP) are the techniques that utilize the evaluation of RNFL for the evaluation of glaucoma. SLP provides RNFL thickness measurements based upon the birefringence of the retinal ganglion cell axons. We have reviewed the published literature on the use of SLP in glaucoma. This review elucidates the technological principles, recent developments and the role of SLP in the diagnosis and monitoring of glaucomatous optic neuropathy, in the light of scientific evidence so far. PMID:25494244

Scanning laser polarimetry in glaucoma.

PubMed

Dada, Tanuj; Sharma, Reetika; Angmo, Dewang; Sinha, Gautam; Bhartiya, Shibal; Mishra, Sanjay K; Panda, Anita; Sihota, Ramanjit

2014-11-01

Glaucoma is an acquired progressive optic neuropathy which is characterized by changes in the optic nerve head and retinal nerve fiber layer (RNFL). White-on-white perimetry is the gold standard for the diagnosis of glaucoma. However, it can detect defects in the visual field only after the loss of as many as 40% of the ganglion cells. Hence, the measurement of RNFL thickness has come up. Optical coherence tomography and scanning laser polarimetry (SLP) are the techniques that utilize the evaluation of RNFL for the evaluation of glaucoma. SLP provides RNFL thickness measurements based upon the birefringence of the retinal ganglion cell axons. We have reviewed the published literature on the use of SLP in glaucoma. This review elucidates the technological principles, recent developments and the role of SLP in the diagnosis and monitoring of glaucomatous optic neuropathy, in the light of scientific evidence so far.

Adopting public health approaches to communication disability: challenges for the education of speech-language pathologists.

PubMed

Wylie, Karen; McAllister, Lindy; Davidson, Bronwyn; Marshall, Julie; Law, James

2014-01-01

Public health approaches to communication disability challenge the profession of speech-language pathology (SLP) to reconsider both frames of reference for practice and models of education. This paper reviews the impetus for public health approaches to communication disability and considers how public health is, and could be, incorporated into SLP education, both now and in the future. The paper describes tensions between clinical services, which have become increasingly specialized, and public health approaches that offer a broader view of communication disability and communication disability prevention. It presents a discussion of these tensions and asserts that public health approaches to communication are themselves a specialist field, requiring specific knowledge and skills. The authors suggest the use of the term 'communication disability public health' to refer to this type of work and offer a preliminary definition in order to advance discussion. Examples from three countries are provided of how some SLP degree programmes are integrating public health into the SLP curriculum. Alternative models of training for communication disability public health that may be relevant in the future in different contexts and countries are presented, prompting the SLP profession to consider whether communication disability public health is a field of practice for speech-language pathologists or whether it has broader workforce implications. The paper concludes with some suggestions for the future which may advance thinking, research and practice in communication disability public health. © 2015 S. Karger AG, Basel.

Slp1 and Slp2-a Localize to the Plasma Membrane of CTL and Contribute to Secretion from the Immunological Synapse

PubMed Central

Holt, Oliver; Kanno, Eiko; Bossi, Giovanna; Booth, Sarah; Daniele, Tiziana; Santoro, Alessandra; Arico, Maurizio; Saegusa, Chika; Fukuda, Mitsunori; Griffiths, Gillian M

2008-01-01

Rab27a is required for polarized secretion of lysosomes from cytotoxic T lymphocytes (CTLs) at the immunological synapse. A series of Rab27a-interacting proteins have been identified; however, only Munc13-4 has been found to be expressed in CTL. In this study, we screened for expression of the synaptotagmin-like proteins (Slps): Slp1/JFC1, Slp2-a/exophilin4, Slp3-a, Slp4/granuphilin, Slp5 and rabphilin in CTL. We found that both Slp1 and Slp2-a are expressed in CTL. Isoforms of Slp2-a in CTL showed variation of the linker region but conserved the C2A and C2B and Slp homology (SHD) domains. Both Slp1 and Slp2-a interact with Rab27a in CTL, and Slp2-a, but not Slp1, is rapidly degraded when Rab27a is absent. Slp2-a contains PEST-like sequences within its linker region, which render it susceptible to degradation. Both Slp1 and Slp2-a localize predominantly to the plasma membrane of both human and mouse CTLs, and we show that Slp2-a can focus tightly at the immunological synapse formed with a target cell. Individual knockouts of either Slp2-a or Slp1 fail to impair CTL-mediated killing of targets; however, overexpression of a dominant-negative construct consisting of the SHD of Slp2-a, which is 56% identical to that of Slp1, reduces target cell death, suggesting that both Slp1 and Slp2-a contribute to secretory lysosome exocytosis from CTL. These results suggest that both Slp1 and Slp2-a may form part of a docking complex, capturing secretory lysosomes at the immunological synapse. PMID:18266782

Time evolution of atmospheric parameters and their influence on sea level pressure over the head Bay of Bengal

NASA Astrophysics Data System (ADS)

Patra, Anindita; Bhaskaran, Prasad K.; Jose, Felix

2018-06-01

A zonal dipole in the observed trends of wind speed and significant wave height over the Head Bay of Bengal region was recently reported in the literature attributed due to the variations in sea level pressure (SLP). The SLP in turn is governed by prevailing atmospheric conditions such as local temperature, humidity, rainfall, atmospheric pressure, wind field distribution, formation of tropical cyclones, etc. The present study attempts to investigate the inter-annual variability of atmospheric parameters and its role on the observed zonal dipole trend in sea level pressure, surface wind speed and significant wave height. It reports on the aspects related to linear trend as well as its spatial variability for several atmospheric parameters: air temperature, geopotential height, omega (vertical velocity), and zonal wind, over the head Bay of Bengal, by analyzing National Centers for Environmental Prediction (NCEP) Reanalysis 2 dataset covering a period of 38 years (1979-2016). Significant warming from sea level to 200 mb pressure level and thereafter cooling above has been noticed during all the seasons. Warming within the troposphere exhibits spatial difference between eastern and western side of the domain. This led to fall in lower tropospheric geopotential height and its east-west variability, exhibiting a zonal dipole pattern across the Head Bay. In the upper troposphere, uplift in geopotential height was found as a result of cooling in higher levels (10-100 mb). Variability in omega also substantiated the observed variations in geopotential height. The study also finds weakening in the upper level westerlies and easterlies. Interestingly, a linear trend in lower tropospheric u-wind component also reveals an east-west dipole pattern over the study region. Further, the study corroborates the reported dipole in trends of sea level pressure, wind speed and significant wave height by evaluating the influence of atmospheric variability on these parameters.

Contribution of Black Carbon Aerosol to Drying of the Mediterranean

NASA Astrophysics Data System (ADS)

Tang, T.; Shindell, D. T.; Samset, B. H.; Boucher, O.; Forster, P.; Hodnebrog, Ø.; Myhre, G.; Sillmann, J.; Voulgarakis, A.; Andrews, T.; Faluvegi, G.; Fläschner, D.; Iverson, T.; Kasoar, M.; Kharin, V. V.; Kirkevag, A.; Lamarque, J. F.; Olivié, D.; Richardson, T.; Stjern, C.; Takemura, T.; Zwiers, F. W.

2017-12-01

Atmospheric aerosols affect cloud properties, radiative balance and thus, the hydrological cycle. Many studies have reported that precipitation has decreased in the Mediterranean since the mid-20th century, and investigated possible mechanisms. So far, however, the effects of aerosol forcing on Mediterranean precipitation remain largely unknown. Here we compare observed Mediterranean precipitation trends during 1951-2010 with responses to individual forcing in a set of state-of-the-art global climate models. Our analyses suggest that nearly one-third (30%) of the observed precipitation decrease may be attributable to black carbon forcing. The remainder is most strongly linked to forcing of well-mixed greenhouse gases (WMGHGs), with scattering sulfate aerosols having negligible impacts. Black carbon caused an enhanced positive North Atlantic Oscillation (NAO)/Arctic Oscillation (AO)-like sea level pressure (SLP) pattern, characterized by higher SLP at mid-latitudes and lower SLP at high-latitudes. This SLP change diverted the jet stream and storm tracks further northward, reducing precipitation in the Mediterranean while increasing precipitation in Northern Europe. The results from this study suggest that future black carbon emissions may significantly affect regional water resources, agricultural practices, ecosystems, and economy in the Mediterranean region.

A new climate index controlling winter wave activity along the Atlantic coast of Europe: The West Europe Pressure Anomaly

NASA Astrophysics Data System (ADS)

Castelle, Bruno; Dodet, Guillaume; Masselink, Gerd; Scott, Tim

2017-02-01

A pioneering and replicable method based on a 66-year numerical weather and wave hindcast is developed to optimize a climate index based on the sea level pressure (SLP) that best explains winter wave height variability along the coast of western Europe, from Portugal to UK (36-52°N). The resulting so-called Western Europe Pressure Anomaly (WEPA) is based on the sea level pressure gradient between the stations Valentia (Ireland) and Santa Cruz de Tenerife (Canary Islands). The WEPA positive phase reflects an intensified and southward shifted SLP difference between the Icelandic low and the Azores high, driving severe storms that funnel high-energy waves toward western Europe southward of 52°N. WEPA outscores by 25-150% the other leading atmospheric modes in explaining winter-averaged significant wave height, and even by a largest amount the winter-averaged extreme wave heights. WEPA is also the only index capturing the 2013/2014 extreme winter that caused widespread coastal erosion and flooding in western Europe.

Northern Winter Climate Change: Assessment of Uncertainty in CMIP5 Projections Related to Stratosphere-Troposphere Coupling

NASA Technical Reports Server (NTRS)

Manzini, E.; Karpechko, A.Yu.; Anstey, J.; Shindell, Drew Todd; Baldwin, M.P.; Black, R.X.; Cagnazzo, C.; Calvo, N.; Charlton-Perez, A.; Christiansen, B.;

Analysis of the 1877-78 ENSO episode and comparison with 1982-83

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

Kiladis, G.N.; Diaz, H.F.

A comparison of the 1877-78 and 1982-83 El Nino/Southern Oscillation (ENSO) events was made using monthly and seasonal values of sea surface temperature (SST) and station pressure in the tropics, sea level pressure (SLP) in North America and the North Atlantic, temperature in North America and precipitation in several key areas around the globe. SST anomalies in the eastern tropical Pacific, heavy rains in coastal Peru and extreme pressure anomalies across the Pacific and Indian Oceans during 1877-78 indicate an ENSO event of comparable magnitude to that during 1982-83. Both events were also associated with drought conditions in the Indonesianmore » region, India, South Africa, northeastern Brazil and Hawaii. Wintertime teleconnections in the midlatitudes of the Northern Hemisphere were similar in terms of SLP from the North Pacific to Europe, resulting in significantly higher than normal temperatures over most of the US and extreme rains in California.« less

Links of the significant wave height distribution in the Mediterranean sea with the Northern Hemisphere teleconnection patterns

NASA Astrophysics Data System (ADS)

Lionello, P.; Galati, M. B.

2008-06-01

This study analyzes the link between the SWH (Significant Wave Height) distribution in the Mediterranean Sea during the second half of the 20th century and the Northern Hemisphere SLP (Sea Level Pressure) teleconnection patterns. The SWH distribution is computed using the WAM (WAve Model) forced by the surface wind fields provided by the ERA-40 reanalysis for the period 1958-2001. The time series of mid-latitude teleconnection patterns are downloaded from the NOAA web site. This study shows that several mid-latitude patterns are linked to the SWH field in the Mediterranean, especially in its western part during the cold season: East Atlantic Pattern (EA), Scandinavian Pattern (SCA), North Atlantic Oscillation (NAO), East Atlantic/West Russia Pattern (EA/WR) and East Pacific/ North Pacific Pattern (EP/NP). Though the East Atlantic pattern exerts the largest influence, it is not sufficient to characterize the dominant variability. NAO, though relevant, has an effect smaller than EA and comparable to other patterns. Some link results from possibly spurious structures. Patterns which have a very different global structure are associated to similar spatial features of the wave variability in the Mediterranean Sea. These two problems are, admittedly, shortcomings of this analysis, which shows the complexity of the response of the Mediterranean SWH to global scale SLP teleconnection patterns.

Measuring Ventilatory Activity with Structured Light Plethysmography (SLP) Reduces Instrumental Observer Effect and Preserves Tidal Breathing Variability in Healthy and COPD

PubMed Central

Niérat, Marie-Cécile; Dubé, Bruno-Pierre; Llontop, Claudia; Bellocq, Agnès; Layachi Ben Mohamed, Lila; Rivals, Isabelle; Straus, Christian; Similowski, Thomas; Laveneziana, Pierantonio

2017-01-01

The use of a mouthpiece to measure ventilatory flow with a pneumotachograph (PNT) introduces a major perturbation to breathing (“instrumental/observer effect”) and suffices to modify the respiratory behavior. Structured light plethysmography (SLP) is a non-contact method of assessment of breathing pattern during tidal breathing. Firstly, we validated the SLP measurements by comparing timing components of the ventilatory pattern obtained by SLP vs. PNT under the same condition; secondly, we compared SLP to SLP+PNT measurements of breathing pattern to evaluate the disruption of breathing pattern and breathing variability in healthy and COPD subjects. Measurements were taken during tidal breathing with SLP alone and SLP+PNT recording in 30 COPD and healthy subjects. Measurements included: respiratory frequency (Rf), inspiratory, expiratory, and total breath time/duration (Ti, Te, and Tt). Passing-Bablok regression analysis was used to evaluate the interchangeability of timing components of the ventilatory pattern (Rf, Ti, Te, and Tt) between measurements performed under the following experimental conditions: SLP vs. PNT, SLP+PNT vs. SLP, and SLP+PNT vs. PNT. The variability of different ventilatory variables was assessed through their coefficients of variation (CVs). In healthy: according to Passing-Bablok regression, Rf, TI, TE and TT were interchangeable between measurements obtained under the three experimental conditions (SLP vs. PNT, SLP+PNT vs. SLP, and SLP+PNT vs. PNT). All the CVs describing “traditional” ventilatory variables (Rf, Ti, Te, Ti/Te, and Ti/Tt) were significantly smaller in SLP+PNT condition. This was not the case for more “specific” SLP-derived variables. In COPD: according to Passing-Bablok regression, Rf, TI, TE, and TT were interchangeable between measurements obtained under SLP vs. PNT and SLP+PNT vs. PNT, whereas only Rf, TE, and TT were interchangeable between measurements obtained under SLP+PNT vs. SLP. However, most discrete variables were significantly different between the SLP and SLP+PNT conditions and CVs were significantly lower when COPD patients were assessed in the SLP+PNT condition. Measuring ventilatory activity with SLP preserves resting tidal breathing variability, reduces instrumental observer effect and avoids any disruptions in breathing pattern induced by the use of PNT-mouthpiece-nose-clip combination. PMID:28572773

Measuring Ventilatory Activity with Structured Light Plethysmography (SLP) Reduces Instrumental Observer Effect and Preserves Tidal Breathing Variability in Healthy and COPD.

PubMed

Niérat, Marie-Cécile; Dubé, Bruno-Pierre; Llontop, Claudia; Bellocq, Agnès; Layachi Ben Mohamed, Lila; Rivals, Isabelle; Straus, Christian; Similowski, Thomas; Laveneziana, Pierantonio

2017-01-01

The use of a mouthpiece to measure ventilatory flow with a pneumotachograph (PNT) introduces a major perturbation to breathing ("instrumental/observer effect") and suffices to modify the respiratory behavior. Structured light plethysmography (SLP) is a non-contact method of assessment of breathing pattern during tidal breathing. Firstly, we validated the SLP measurements by comparing timing components of the ventilatory pattern obtained by SLP vs. PNT under the same condition; secondly, we compared SLP to SLP+PNT measurements of breathing pattern to evaluate the disruption of breathing pattern and breathing variability in healthy and COPD subjects. Measurements were taken during tidal breathing with SLP alone and SLP+PNT recording in 30 COPD and healthy subjects. Measurements included: respiratory frequency (R f ), inspiratory, expiratory, and total breath time/duration (Ti, Te, and Tt). Passing-Bablok regression analysis was used to evaluate the interchangeability of timing components of the ventilatory pattern (R f , Ti, Te, and Tt) between measurements performed under the following experimental conditions: SLP vs. PNT, SLP+PNT vs. SLP, and SLP+PNT vs. PNT. The variability of different ventilatory variables was assessed through their coefficients of variation (CVs). In healthy: according to Passing-Bablok regression, Rf, TI, TE and TT were interchangeable between measurements obtained under the three experimental conditions (SLP vs. PNT, SLP+PNT vs. SLP, and SLP+PNT vs. PNT). All the CVs describing "traditional" ventilatory variables (R f , Ti, Te, Ti/Te, and Ti/Tt) were significantly smaller in SLP+PNT condition. This was not the case for more "specific" SLP-derived variables. In COPD: according to Passing-Bablok regression, Rf, TI, TE, and TT were interchangeable between measurements obtained under SLP vs. PNT and SLP+PNT vs. PNT, whereas only Rf, TE, and TT were interchangeable between measurements obtained under SLP+PNT vs. SLP. However, most discrete variables were significantly different between the SLP and SLP+PNT conditions and CVs were significantly lower when COPD patients were assessed in the SLP+PNT condition. Measuring ventilatory activity with SLP preserves resting tidal breathing variability, reduces instrumental observer effect and avoids any disruptions in breathing pattern induced by the use of PNT-mouthpiece-nose-clip combination.

A possible recovery of the near-surface wind speed in Eastern China during winter after 2000 and the potential causes

NASA Astrophysics Data System (ADS)

Zha, Jinlin; Wu, Jian; Zhao, Deming; Tang, Jianping

2018-04-01

A lasting decrease in the near-surface wind speed (SWS) in China has been revealed, but a following short-term strengthening in the SWS was rarely noted. In this paper, the daily mean SWS observed datasets from 328 measurement stations in Eastern China during the period 1981-2011 were used to investigate the facts and causes of the observed short-term strengthening in winter SWS in recent decades. The major results are summarized as follows: the SWS showed a significant decrease in the last 30 years, but a short-term strengthening in SWS was observed during the winter since 2000 in Eastern China. The SWS in Eastern China showed a significant decrease of - 0.11 m s-1 decade-1 from 1981 to 1999, followed by a weak increase of 0.0008 m s-1 decade-1 from 2000 to 2011. The short-term strengthening in the SWS since 2000 was mainly induced by the changes of the pressure-gradient force (PGF), which could be attributed to the changes of the sea-level pressure (SLP) in the region (51°-69.75° N, 51.75°-111.75° E). Furthermore, the changes of the PGF during the two periods of 1981-1999 and 2000-2011 were consistent with those of the SLP in the region (51°-69.75° N, 51.75°-111.75° E). The correlation coefficient between PGF and SLP was 0.32 and 0.66 during the period 1981-1999 and 2000-2011, respectively. Therefore, the effects of the changes in SLP over the region (51°-69.75° N, 51.75°-111.75° E) on changes of SWS in the Eastern China should be significant.

The relationship between the Asian dust and Arctic Oscillation: An observational investigation

NASA Astrophysics Data System (ADS)

Lee, Y.; Kim, J.; Cho, H.

2009-12-01

The Arctic Oscillation (AO) represents the leading empirical orthogonal function of winter sea level pressure (SLP) fields, which resembles North Atlantic Oscillation, but has a more zonally symmetric structure (Thompson and Wallace, 1998; Wallace, 2000; Wu and Wang, 2002). This primary mode of the internal dynamics in the atmosphere predominates the Extratropical Northern Hemisphere circulation from surface to the lower stratosphere showing an equivalent barotropic structure during cold season(November-April) (Thompson and Wallace, 2000). Also, the Asian dust storms show strong interannual variation (Sun et al., 2001; Yoshino, 2002; Zhao et al., 2006; Hara et al., 2006), which are suggested to be associated with climate indices. Therefore, the purpose of this study is to identify the possible connection for the AO and the Asian dust emission during periods from late winter to spring, based on the observational investigations. In order to examine these complex associations closely, the Aerosol Index (AI) from Total Ozone Mapping Spectrometer (TOMS) are used starting from November 1978 to December 1999, except for data pause from May 1993 to August 1996. SLP and geopotential height at 500hPa (Z500) monthly fields are derived from the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalyses (1958-2001). Also, source regions of Asian dust are mainly focused on three source areas, including the Taklimakan Desert (R1), Badain Jaran Desert (R2), and Mongolia (R3) in this study. In composite study during different phases of AO, the AO exhibits a “negative phase” with relatively high pressure over the polar region and low pressure at mid-latitudes (about 45 degrees North). In strong “negative phase” of AO, decrease of AO is found to be associated with decreases of local tropospheric temperature, U-wind, and geopotential height and strong north-south gradients over the source regions of Asian dust. Therefore, we also notice that a negative index phase in the spring AO results in the strengthened East Asian Trough at 500hPa and a significant pressure decrease in the lower atmosphere, which is favorable for producing the stronger Asian dust emission.

Sea ice and polar climate in the NCAR CSM

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

Weatherly, J.W.; Briegleb, B.P.; Large, W.G.

The Climate System Model (CSM) consists of atmosphere, ocean, land, and sea-ice components linked by a flux coupler, which computes fluxes of energy and momentum between components. The sea-ice component consists of a thermodynamic formulation for ice, snow, and leads within the ice pack, and ice dynamics using the cavitating-fluid ice rheology, which allows for the compressive strength of ice but ignores shear viscosity. The results of a 300-yr climate simulation are presented, with the focus on sea ice and the atmospheric forcing over sea ice in the polar regions. The atmospheric model results are compared to analyses from themore » European Centre for Medium-Range Weather Forecasts and other observational sources. The sea-ice concentrations and velocities are compared to satellite observational data. The atmospheric sea level pressure (SLP) in CSM exhibits a high in the central Arctic displaced poleward from the observed Beaufort high. The Southern Hemisphere SLP over sea ice is generally 5 mb lower than observed. Air temperatures over sea ice in both hemispheres exhibit cold biases of 2--4 K. The precipitation-minus-evaporation fields in both hemispheres are greatly improved over those from earlier versions of the atmospheric GCM.« less

The natural oscillation of two types of ENSO events based on analyses of CMIP5 model control runs

NASA Astrophysics Data System (ADS)

Xu, Kang; Su, Jingzhi; Zhu, Congwen

2014-07-01

The eastern- and central-Pacific El Niño-Southern Oscillation (EP- and CP-ENSO) have been found to be dominant in the tropical Pacific Ocean, and are characterized by interannual and decadal oscillation, respectively. In the present study, we defined the EP- and CP-ENSO modes by singular value decomposition (SVD) between SST and sea level pressure (SLP) anomalous fields. We evaluated the natural features of these two types of ENSO modes as simulated by the pre-industrial control runs of 20 models involved in phase five of the Coupled Model Intercomparison Project (CMIP5). The results suggested that all the models show good skill in simulating the SST and SLP anomaly dipolar structures for the EP-ENSO mode, but only 12 exhibit good performance in simulating the tripolar CP-ENSO modes. Wavelet analysis suggested that the ensemble principal components in these 12 models exhibit an interannual and multi-decadal oscillation related to the EP- and CP-ENSO, respectively. Since there are no changes in external forcing in the pre-industrial control runs, such a result implies that the decadal oscillation of CP-ENSO is possibly a result of natural climate variability rather than external forcing.

Implementation of High-resolution Manometry in the Clinical Practice of Speech Language Pathology

PubMed Central

Thibeault, Susan; McCulloch, Timothy M.

2014-01-01

Visual imaging modalities, videofluoroscopic swallow study (VFSS) and fiberoptic endoscopic evaluation of swallow, for assessment of oropharyngeal dysphagia have been part of the speech language pathologist’s (SLPs) armamentarium for the diagnosis and treatment of dysphagia for decades. Recently, the addition of high-resolution manometry (HRM) has enabled the SLP to evaluate pharyngeal pressures and upper esophageal sphincter relaxation. Taken together, the use of visual imaging modalities with HRM can improve interpretation of swallowing physiology and facilitate more effective treatment planning. The goal of this article is to describe a clinical paradigm using HRM as an adjunct to VFSS, by the SLP, in the assessment of complex dysphagia. Moreover, in three cases described, the value of manometric measurements in elucidating swallowing imaging studies and documenting physiologic change in response to treatment is highlighted. As technology in this area is evolving, so will the clinical use of HRM by the SLP. Limitations of current HRM systems and applications are discussed. PMID:24233810

Scanning laser polarimetry and spectral domain optical coherence tomography for the detection of retinal changes in Parkinson's disease.

PubMed

Stemplewitz, Birthe; Keserü, Matthias; Bittersohl, Diana; Buhmann, Carsten; Skevas, Christos; Richard, Gisbert; Hassenstein, Andrea

2015-12-01

Whether retinal degeneration is part of the degenerative processes in patients with Parkinson's disease (PD) is still unclear. This cross-sectional study was undertaken to compare the retinal morphology of patients with PD and healthy controls using spectral domain optical coherence tomography (SD-OCT) and scanning laser polarimetry (SLP). Both eyes of patients with PD (n = 108) and healthy controls (n = 165) were examined using SD-OCT and SLP on the same day. Data on the thickness of the retinal nerve fibre layer (RNFL) of all quadrants and the macular area were acquired by OCT (Cirrus, Zeiss). The SLP device (Glaucoma diagnostics (GDx), Zeiss) measured the RNFL and calculated the nerve fibre index (NFI). All patients and probands were checked for concomitant ocular disorders by an ophthalmologist. Visual acuity, intraocular pressure (IOP), objective refraction and the anterior and posterior segment were assessed. Patients with PD showed a reduced macular volume and a reduced central subfield thickness in OCT examinations. The RNFL in the different quadrants did not differ significantly from that of controls. SLP data showed a reduced average RNFL thickness, a decreased thickness of the inferior quadrant and an increase of the NFI in patients with PD. PD may be associated with reduced thickness and volume of the macula and a reduced thickness of the RNFL in the inferior quadrant of the retina. Investigations using SD-OCT and SLP revealed distinct but significant differences between patients with PD and healthy controls. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

The effect of Ocean resolution, and external forcing in the correlation between SLP and Sea Ice Concentration in the Pre-PRIMAVERA GCMs

NASA Astrophysics Data System (ADS)

Fuentes-Franco, Ramon; Koenigk, Torben

2017-04-01

Recently, an observational study has shown that sea ice variations in Barents Sea seem to be important for the sign of the following winter NAO (Koenigk et al. 2016). It has also been found that amplitude and extension of the Sea Level Pressure (SLP) patterns are modulated by Greenland and Labrador Seas ice areas. Therefore, Earth System Models participating in the PRIMAVERA Project are used to study the impact of resolution in ocean models in reproducing the previously mentioned observed correlation patterns between Sea Ice Concentration (SIC) and the SLP. When using ensembles of high ocean resolution (0.25 degrees) and low ocean resolution (1 degree) simulations, we found that the correlation sign between sea ice concentration over the Central Arctic, the Barents/Kara Seas and the Northern Hemisphere is similar to observations in the higher ocean resolution ensemble, although the amplitude is underestimated. In contrast, the low resolution ensemble shows opposite correlation patterns compared to observations. In general, high ocean resolution simulations show more similar results to observations than the low resolution simulations. Similarly, in order to study the mentioned observed SIC-SLP relationship reported by Koenigk et al (2016), we analyzed the impact of the use of pre-industrial and historical external forcing in the simulations. When using same forcing ensembles, we found that the correlation sign between SIC and SLP does not show a systematic behavior dependent on the use of different external forcing (pre-industrial or present day) as it does when using different ocean resolutions.

Interannual climate variations in Arctic as driven by the Global atmosphere oscillation

NASA Astrophysics Data System (ADS)

Serykh, Ilya; Byshev, Vladimir; Neiman, Victor; Sidorova, Alexandra; Sonechkin, Dmitry

2015-04-01

The present-day global climate change affects the Arctic basin substantially more because of the sea ice cover extinction and the permafrost melting. But there are essential variations of these effects from year to year. We believe that these variations might be a regional manifestation of a planetary-scale phenomenon named the Global atmospheric oscillation (GAO). GAO includes the well-known El Niño - Southern Oscillation (ENSO) process and similar processes in equatorial Atlantic and Indian Oceans within itself. The goal of this report is to present some arguments to support this point of view. For this goal, we have studied some interrelations between the above-mentioned Arctic anomalies and GAO as seen in global re-analyses of the sea level pressure (SLP) and near surface temperature (NST) for the period of 1920-2013. The mean global fields of SLP and NST have been computed for all El Niño events falling into this time period, and separately, for all and La Niña events. As a result, two (for SLP and NST as well) global fields of the mean El Niño/La Niña difference were obtained. Statistical significance of the non-zero values of these fields, i.e. the reality of GAO, was evaluated with the t-Student's test. It turned out that the main spatial structures of GAO, presented specifically by El Niño and La Niña events in Pacific region, exist at a very high level (up to 99%, t>4) of the significance. Therefore, one can conclude that the interannual-scale dynamics of GAO is actually reflected in the climate features of different regions of the Earth, including the Russian Arctic. In particular, when the boreal winter season coincides with an El Niño event GAO is indicative by a negative anomaly of NST (about -1°C) and a positive anomaly of SLP over the Arctic basin. In contrary, significant (about +1°C) positive anomaly of NST along with reduced SLP over the whole Arctic region is typical for any La Niña event (up to 95%, t>2). To control the reliability of GAO, numerical modeling of the hydrophysical variability of the Barents Sea was carried out for the period of the strongest El Niño event during 1997-98. A complex analysis of the modeling results corroborated that: - the shortage of the transportation of relatively warm and saline North-Atlantic water along with intensification of the encounter water flow of the Polar origin; - a lowering of overall heat content of water, and a strengthening of vertical convection; -a weakening of the water dynamic in the system of the general cyclonic gyre take place during the El Niño event. It is appropriate mention here that the winter of 1997-98 accompanied by an enlargement of Barents Sea ice cover. Thus, a certain deviation from the mean climatic conditions within the marine area under investigation seems to be connected with GAO.

Audiology and speech-language pathology practice in Saudi Arabia.

PubMed

Alanazi, Ahmad A

2017-01-01

Audiology and speech-language pathology (SLP) are relatively new professions in Saudi Arabia. The idea of establishing new audiology and SLP programs in some education facilities has become popular across Saudi Arabia; yet, only four undergraduate and graduate programs are currently available. This study aimed to explore the fields of audiology and SLP in Saudi Arabia, obtain demography of audiologists and Speech-language pathologists (SLPs), understand their current practices, and identify their perspective on what both professions need to improve. A cross-sectional mixed methods study design was used to address the aim of this study. Two online surveys were prepared and distributed to reach a large number of audiologists and SLPs. Both surveys consisted of close- and open-ended questions and primarily focused on three categories demography, audiology or SLP practices, and audiologists' or SLPs' perspective on their professions in Saudi Arabia. A total of 23 audiologists and 37 SLPs completed the surveys (age range = 21-50 years). The majority of respondents were from Riyadh with different academic qualifications and working experiences. Various practices were noticed among audiologists and SLPs who mainly worked in hospitals. Several suggestions regarding the development of audiology and SLP education and practice in Saudi Arabia are discussed. This study provides useful information about audiology and SLP education and practices in Saudi Arabia. Collaborative work between stakeholders to achieve high-quality educational and practical standards is critical. National database, clinical guidelines and policies should be developed, employed, and supervised. Further research is needed to improve education and practice of both professions in Saudi Arabia.

T cell costimulation via the integrin VLA-4 inhibits the actin-dependent centralization of signaling microclusters containing the adaptor SLP-76.

PubMed

Nguyen, Ken; Sylvain, Nicholas R; Bunnell, Stephen C

2008-06-01

Antigen-dependent T cell activation drives the formation of signaling microclusters containing the adaptor SLP-76. Costimulatory integrins regulate SLP-76 phosphorylation and could influence SLP-76 microclusters in the integrin-rich periphery of the immune synapse. We report that costimulation by the integrin VLA-4 (alpha4beta1) required SLP-76 domains implicated in microcluster assembly. Pro-adhesive ligands enlarged the contact and increased the number of SLP-76 microclusters regardless of their costimulatory potential. Costimulatory VLA-4 ligands also prevented the centralization of SLP-76, promoted microcluster persistence, prolonged lateral interactions between SLP-76 and its upstream kinase, ZAP-70, and retained SLP-76 in tyrosine-phosphorylated peripheral structures. SLP-76 centralization was driven by dynamic actin polymerization and was correlated with inward actin flows. VLA-4 ligation retarded these flows, even in the absence of SLP-76. These data suggest a widely applicable model of costimulation, in which integrins promote sustained signaling by attenuating cytoskeletal movements that drive the centralization and inactivation of SLP-76 microclusters.

Disruption of SLP-76 interaction with Gads inhibits dynamic clustering of SLP-76 and FcepsilonRI signaling in mast cells.

PubMed

Silverman, Michael A; Shoag, Jonathan; Wu, Jennifer; Koretzky, Gary A

2006-03-01

We developed a confocal real-time imaging approach that allows direct observation of the subcellular localization pattern of proteins involved in proximal FcepsilonRI signaling in RBL cells and primary bone marrow-derived mast cells. The adaptor protein Src homology 2 (SH2) domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) is critical for FcepsilonRI-induced calcium flux, degranulation, and cytokine secretion. In this study, we imaged SLP-76 and found it in the cytosol of unstimulated cells. Upon FcepsilonRI cross-linking, SLP-76 translocates to the cell membrane, forming clusters that colocalize with the FcepsilonRI, the tyrosine kinase Syk, the adaptor LAT, and phosphotyrosine. The disruption of the SLP-76 interaction with its constitutive binding partner, Gads, through the mutation of SLP-76 or the expression of the Gads-binding region of SLP-76, inhibits the translocation and clustering of SLP-76, suggesting that the interaction of SLP-76 with Gads is critical for appropriate subcellular localization of SLP-76. We further demonstrated that the expression of the Gads-binding region of SLP-76 in bone marrow-derived mast cells inhibits FcepsilonRI-induced calcium flux, degranulation, and cytokine secretion. These studies revealed, for the first time, that SLP-76 forms signaling clusters following FcepsilonRI stimulation and demonstrated that the Gads-binding region of SLP-76 regulates clustering of SLP-76 and FcepsilonRI-induced mast cell responses.

Downscaling of Global Climate Change Estimates to Regional Scales: An Application to Iberian Rainfall in Wintertime.

NASA Astrophysics Data System (ADS)

von Storch, Hans; Zorita, Eduardo; Cubasch, Ulrich

1993-06-01

A statistical strategy to deduct regional-scale features from climate general circulation model (GCM) simulations has been designed and tested. The main idea is to interrelate the characteristic patterns of observed simultaneous variations of regional climate parameters and of large-scale atmospheric flow using the canonical correlation technique.The large-scale North Atlantic sea level pressure (SLP) is related to the regional, variable, winter (DJF) mean Iberian Peninsula rainfall. The skill of the resulting statistical model is shown by reproducing, to a good approximation, the winter mean Iberian rainfall from 1900 to present from the observed North Atlantic mean SLP distributions. It is shown that this observed relationship between these two variables is not well reproduced in the output of a general circulation model (GCM).The implications for Iberian rainfall changes as the response to increasing atmospheric greenhouse-gas concentrations simulated by two GCM experiments are examined with the proposed statistical model. In an instantaneous `2 C02' doubling experiment, using the simulated change of the mean North Atlantic SLP field to predict Iberian rainfall yields, there is an insignificant increase of area-averaged rainfall of 1 mm/month, with maximum values of 4 mm/month in the northwest of the peninsula. In contrast, for the four GCM grid points representing the Iberian Peninsula, the change is 10 mm/month, with a minimum of 19 mm/month in the southwest. In the second experiment, with the IPCC scenario A ("business as usual") increase Of C02, the statistical-model results partially differ from the directly simulated rainfall changes: in the experimental range of 100 years, the area-averaged rainfall decreases by 7 mm/month (statistical model), and by 9 mm/month (GCM); at the same time the amplitude of the interdecadal variability is quite different.

Relevance Vector Machine and Support Vector Machine Classifier Analysis of Scanning Laser Polarimetry Retinal Nerve Fiber Layer Measurements

PubMed Central

Bowd, Christopher; Medeiros, Felipe A.; Zhang, Zuohua; Zangwill, Linda M.; Hao, Jiucang; Lee, Te-Won; Sejnowski, Terrence J.; Weinreb, Robert N.; Goldbaum, Michael H.

2010-01-01

Purpose To classify healthy and glaucomatous eyes using relevance vector machine (RVM) and support vector machine (SVM) learning classifiers trained on retinal nerve fiber layer (RNFL) thickness measurements obtained by scanning laser polarimetry (SLP). Methods Seventy-two eyes of 72 healthy control subjects (average age = 64.3 ± 8.8 years, visual field mean deviation =−0.71 ± 1.2 dB) and 92 eyes of 92 patients with glaucoma (average age = 66.9 ± 8.9 years, visual field mean deviation =−5.32 ± 4.0 dB) were imaged with SLP with variable corneal compensation (GDx VCC; Laser Diagnostic Technologies, San Diego, CA). RVM and SVM learning classifiers were trained and tested on SLP-determined RNFL thickness measurements from 14 standard parameters and 64 sectors (approximately 5.6° each) obtained in the circumpapillary area under the instrument-defined measurement ellipse (total 78 parameters). Tenfold cross-validation was used to train and test RVM and SVM classifiers on unique subsets of the full 164-eye data set and areas under the receiver operating characteristic (AUROC) curve for the classification of eyes in the test set were generated. AUROC curve results from RVM and SVM were compared to those for 14 SLP software-generated global and regional RNFL thickness parameters. Also reported was the AUROC curve for the GDx VCC software-generated nerve fiber indicator (NFI). Results The AUROC curves for RVM and SVM were 0.90 and 0.91, respectively, and increased to 0.93 and 0.94 when the training sets were optimized with sequential forward and backward selection (resulting in reduced dimensional data sets). AUROC curves for optimized RVM and SVM were significantly larger than those for all individual SLP parameters. The AUROC curve for the NFI was 0.87. Conclusions Results from RVM and SVM trained on SLP RNFL thickness measurements are similar and provide accurate classification of glaucomatous and healthy eyes. RVM may be preferable to SVM, because it provides a Bayesian-derived probability of glaucoma as an output. These results suggest that these machine learning classifiers show good potential for glaucoma diagnosis. PMID:15790898

Hiding the Source Based on Limited Flooding for Sensor Networks.

PubMed

Chen, Juan; Lin, Zhengkui; Hu, Ying; Wang, Bailing

2015-11-17

Wireless sensor networks are widely used to monitor valuable objects such as rare animals or armies. Once an object is detected, the source, i.e., the sensor nearest to the object, generates and periodically sends a packet about the object to the base station. Since attackers can capture the object by localizing the source, many protocols have been proposed to protect source location. Instead of transmitting the packet to the base station directly, typical source location protection protocols first transmit packets randomly for a few hops to a phantom location, and then forward the packets to the base station. The problem with these protocols is that the generated phantom locations are usually not only near the true source but also close to each other. As a result, attackers can easily trace a route back to the source from the phantom locations. To address the above problem, we propose a new protocol for source location protection based on limited flooding, named SLP. Compared with existing protocols, SLP can generate phantom locations that are not only far away from the source, but also widely distributed. It improves source location security significantly with low communication cost. We further propose a protocol, namely SLP-E, to protect source location against more powerful attackers with wider fields of vision. The performance of our SLP and SLP-E are validated by both theoretical analysis and simulation results.

77 FR 63406 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

... Liquidity Provider (``SLP'') for all assigned SLP securities in the aggregate (including shares of both a SLP proprietary trading unit (``SLP-Prop'') and a SLP market maker (``SLMM'') of the same member... per share price of $1.00 or more, if the SLP (i) meets the 10% average or more quoting requirement in...

Scanning Laser Polarimetry with Variable and Enhanced Corneal Compensation in Normal and Glaucomatous Eyes

PubMed Central

Sehi, Mitra; Guaqueta, Delia C.; Feuer, William J.; Greenfield, David S.

2007-01-01

Purpose To investigate whether correction for atypical birefringence pattern (ABP) using scanning laser polarimetry with enhanced corneal compensation (SLP-ECC) reduces the severity of ABP compared with variable corneal compensation (SLP-VCC), and improves the correlation with visual function. Design Prospective observational study. Methods Normal and glaucomatous eyes enrolled from 4 clinical sites underwent complete examination, automated perimetry, SLP-ECC and SLP-VCC. Eyes were characterized in 3 groups based upon the typical scan score (TSS): normal birefringence pattern (NBP) was defined as TSS 80, mild ABP as TSS 61–79, moderate-severe ABP as TSS 60. For each of 4 SLP parameters the area under the ROC curve (AUROC) was calculated to compare the ability of SLP-ECC and SLP-VCC to discriminate between normal and glaucomatous eyes. Results Eighty-four normal volunteers and 45 glaucoma patients were enrolled. Mean TSS was significantly (p<0.001) greater using SLP-ECC (98.0 ± 6.6) compared to SLP-VCC (83.4 ± 22.5). The frequency of moderate-severe ABP images was significantly (p<0.001, McNemar test) higher using SLP-VCC (18 of 129, 14%) compared to SLP-ECC (1 of 129, 0.8%). Two SLP-ECC parameters (TSNIT average and inferior average) had significantly (p=0.01, p<0.001) higher correlation (r=0.45, r=0.50 respectively) with MD compared to SLP-VCC (r=0.34, r=0.37). Among eyes with moderate-severe ABP (N = 18), inferior average obtained using SLP-ECC had significantly (p=0.03) greater AUROC (0.91 ± 0.07) compared with SLP-VCC (0.78 ± 0.11). Conclusions SLP-ECC significantly reduces the frequency and severity of ABP compared to SLP-VCC and improves the correlation between RNFL measures and visual function. PMID:17157800

Relationship between Scanning Laser Polarimetry with Enhanced Corneal Compensation and with Variable Corneal Compensation

PubMed Central

Kim, Kyung Hoon; Choi, Jaewan; Lee, Chang Hwan; Cho, Beom-Jin; Kook, Michael S.

2008-01-01

Purpose To evaluate the structure-function relationships between retinal sensitivity measured by Humphrey visual field analyzer (HVFA) and the retinal nerve fiber layer (RNFL) thickness measured by scanning laser polarimetry (SLP) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC) in glaucomatous and healthy eyes. Methods Fifty-three eyes with an atypical birefringence pattern (ABP) based on SLP-VCC (28 glaucomatous eyes and 25 normal healthy eyes) were enrolled in this cross-sectional study. RNFL thickness was measured by both VCC and ECC techniques, and the visual field was examined by HVFA with 24-2 full-threshold program. The relationships between RNFL measurements in superior and inferior sectors and corresponding retinal mean sensitivity were sought globally and regionally with linear regression analysis in each group. Coefficients of the determination were calculated and compared between VCC and ECC techniques. Results In eyes with ABP, R2 values for the association between SLP parameters and retinal sensitivity were 0.06-0.16 with VCC, whereas they were 0.21-0.48 with ECC. The association of RNFL thickness with retinal sensitivity was significantly better with ECC than with VCC in 5 out of 8 regression models between SLP parameters and HVF parameters (P<0.05). Conclusions The strength of the structure-function association was higher with ECC than with VCC in eyes with ABP, which suggests that the ECC algorithm is a better approach for evaluating the structure-function relationship in eyes with ABP. PMID:18323701

Attenuation of T cell receptor signaling by serine phosphorylation-mediated lysine 30 ubiquitination of SLP-76 protein.

PubMed

Wang, Xiaohong; Li, Ju-Pi; Chiu, Li-Li; Lan, Joung-Liang; Chen, Der-Yuan; Boomer, Jonathan; Tan, Tse-Hua

2012-10-05

SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa) is an adaptor protein that is essential for T cell development and T cell receptor (TCR) signaling activation. Previous studies have identified an important negative feedback regulation of SLP-76 by HPK1 (hematopoietic progenitor kinase 1; MAP4K1)-induced Ser-376 phosphorylation. Ser-376 phosphorylation of SLP-76 mediates 14-3-3 binding, resulting in the attenuation of SLP-76 activation and downstream signaling; however, the underlying mechanism of this action remains unknown. Here, we report that phosphorylated SLP-76 is ubiquitinated and targeted for proteasomal degradation during TCR signaling. SLP-76 ubiquitination is mediated by Ser-376 phosphorylation. Furthermore, Lys-30 is identified as a ubiquitination site of SLP-76. Loss of Lys-30 ubiquitination of SLP-76 results in enhanced anti-CD3 antibody-induced ERK and JNK activation. These results reveal a novel regulation mechanism of SLP-76 by ubiquitination and proteasomal degradation of activated SLP-76, which is mediated by Ser-376 phosphorylation, leading to down-regulation of TCR signaling.

The adapter protein SLP-76 mediates "outside-in" integrin signaling and function in T cells.

PubMed

Baker, R G; Hsu, C J; Lee, D; Jordan, M S; Maltzman, J S; Hammer, D A; Baumgart, T; Koretzky, G A

2009-10-01

The adapter protein SH2 domain-containing leukocyte protein of 76 kDa (SLP-76) is an essential mediator of signaling from the T-cell antigen receptor (TCR). We report here that SLP-76 also mediates signaling downstream of integrins in T cells and that SLP-76-deficient T cells fail to support adhesion to integrin ligands. In response to both TCR and integrin stimulation, SLP-76 relocalizes to surface microclusters that colocalize with phosphorylated signaling proteins. Disruption of SLP-76 recruitment to the protein named LAT (linker for activation of T cells) inhibits SLP-76 clustering downstream of the TCR but not downstream of integrins. Conversely, an SLP-76 mutant unable to bind ADAP (adhesion and degranulation-promoting adapter protein) forms clusters following TCR but not integrin engagement and fails to support T-cell adhesion to integrin ligands. These findings demonstrate that SLP-76 relocalizes to integrin-initiated signaling complexes by a mechanism different from that employed during TCR signaling and that SLP-76 relocalization corresponds to SLP-76-dependent integrin function in T cells.

Attenuation of T Cell Receptor Signaling by Serine Phosphorylation-mediated Lysine 30 Ubiquitination of SLP-76 Protein*

PubMed Central

Wang, Xiaohong; Li, Ju-Pi; Chiu, Li-Li; Lan, Joung-Liang; Chen, Der-Yuan; Boomer, Jonathan; Tan, Tse-Hua

2012-01-01

SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa) is an adaptor protein that is essential for T cell development and T cell receptor (TCR) signaling activation. Previous studies have identified an important negative feedback regulation of SLP-76 by HPK1 (hematopoietic progenitor kinase 1; MAP4K1)-induced Ser-376 phosphorylation. Ser-376 phosphorylation of SLP-76 mediates 14-3-3 binding, resulting in the attenuation of SLP-76 activation and downstream signaling; however, the underlying mechanism of this action remains unknown. Here, we report that phosphorylated SLP-76 is ubiquitinated and targeted for proteasomal degradation during TCR signaling. SLP-76 ubiquitination is mediated by Ser-376 phosphorylation. Furthermore, Lys-30 is identified as a ubiquitination site of SLP-76. Loss of Lys-30 ubiquitination of SLP-76 results in enhanced anti-CD3 antibody-induced ERK and JNK activation. These results reveal a novel regulation mechanism of SLP-76 by ubiquitination and proteasomal degradation of activated SLP-76, which is mediated by Ser-376 phosphorylation, leading to down-regulation of TCR signaling. PMID:22902619

SLP-2 overexpression could serve as a prognostic factor in node positive and HER2 negative breast cancer.

PubMed

Cao, Wenfeng; Zhang, Bin; Li, Jin; Liu, Yanxue; Liu, Zhihua; Sun, Baocun

2011-12-01

This study aimed to evaluate the utility as a prognostic factor of SLP-2 on the outcome of breast cancer patients. We performed immunohistochemical analysis to examine the SLP-2 expression in a large panel of invasive breast cancer samples. Of the 496 samples, 261 showed overexpression of SLP-2. Importantly, there were significant associations between SLP-2 overexpression and tumour size (p = 0.002), lymph node/distant metastases, clinical stage (p < 0.001), HER2/neu expression (p = 0.003). In addition, there were obvious differences in levels of SLP-2 expression within four molecular subtypes of breast cancer (p = 0.011). High level SLP-2 expression was shown in tumour samples of HER2 and luminal B subtypes, and low level SLP-2 expression was shown in luminal A and triple negative subtypes, suggesting that overexpression of SLP-2 was closely correlated with HER2/neu expression, and that both SLP-2 and HER2/neu can play a role in lymph node/distant metastases of breast cancers. Thus lymph node status, HER2/neu and SLP-2 high-level expression can act as independent prognostic factors. There is an obvious link between SLP-2 and HER2/neu expression. Overexpression of SLP-2 is associated with poorer total survival, especially in lymph node positive coupled with HER2/neu negative patients.

Baseline predictability of daily east Asian summer monsoon circulation indices

NASA Astrophysics Data System (ADS)

Ai, Shucong; Chen, Quanliang; Li, Jianping; Ding, Ruiqiang; Zhong, Quanjia

2017-05-01

The nonlinear local Lyapunov exponent (NLLE) method is adopted to quantitatively determine the predictability limit of East Asian summer monsoon (EASM) intensity indices on a synoptic timescale. The predictability limit of EASM indices varies widely according to the definitions of indices. EASM indices defined by zonal shear have a limit of around 7 days, which is higher than the predictability limit of EASM indices defined by sea level pressure (SLP) difference and meridional wind shear (about 5 days). The initial error of EASM indices defined by SLP difference and meridional wind shear shows a faster growth than indices defined by zonal wind shear. Furthermore, the indices defined by zonal wind shear appear to fluctuate at lower frequencies, whereas the indices defined by SLP difference and meridional wind shear generally fluctuate at higher frequencies. This result may explain why the daily variability of the EASM indices defined by zonal wind shear tends be more predictable than those defined by SLP difference and meridional wind shear. Analysis of the temporal correlation coefficient (TCC) skill for EASM indices obtained from observations and from NCEP's Global Ensemble Forecasting System (GEFS) historical weather forecast dataset shows that GEFS has a higher forecast skill for the EASM indices defined by zonal wind shear than for indices defined by SLP difference and meridional wind shear. The predictability limit estimated by the NLLE method is shorter than that in GEFS. In addition, the June-September average TCC skill for different daily EASM indices shows significant interannual variations from 1985 to 2015 in GEFS. However, the TCC for different types of EASM indices does not show coherent interannual fluctuations.

Are H-reflex and M-wave recruitment curve parameters related to aerobic capacity?

PubMed

Piscione, Julien; Grosset, Jean-François; Gamet, Didier; Pérot, Chantal

2012-10-01

Soleus Hoffmann reflex (H-reflex) amplitude is affected by a training period and type and level of training are also well known to modify aerobic capacities. Previously, paired changes in H-reflex and aerobic capacity have been evidenced after endurance training. The aim of this study was to investigate possible links between H- and M-recruitment curve parameters and aerobic capacity collected on a cohort of subjects (56 young men) that were not involved in regular physical training. Maximal H-reflex normalized with respect to maximal M-wave (H(max)/M(max)) was measured as well as other parameters of the H- or M-recruitment curves that provide information about the reflex or direct excitability of the motoneuron pool, such as thresholds of stimulus intensity to obtain H or M response (H(th) and M(th)), the ascending slope of H-reflex, or M-wave recruitment curves (H(slp) and M(slp)) and their ratio (H(slp)/M(slp)). Aerobic capacity, i.e., maximal oxygen consumption and maximal aerobic power (MAP) were, respectively, estimated from a running field test and from an incremental test on a cycle ergometer. Maximal oxygen consumption was only correlated with M(slp), an indicator of muscle fiber heterogeneity (p < 0.05), whereas MAP was not correlated with any of the tested parameters (p > 0.05). Although higher H-reflex are often described for subjects with a high aerobic capacity because of endurance training, at a basic level (i.e., without training period context) no correlation was observed between maximal H-reflex and aerobic capacity. Thus, none of the H-reflex or M-wave recruitment curve parameters, except M(slp), was related to the aerobic capacity of young, untrained male subjects.

Increased levels of SLP-2 correlate with poor prognosis in gastric cancer.

PubMed

Liu, Dongning; Zhang, Lei; Shen, Zhiyong; Tan, Fei; Hu, Yanfeng; Yu, Jiang; Li, Guoxin

2013-10-01

Stomatin-like protein 2 (SLP-2) is a member of the highly conserved stomatin protein family whose homologues span from Archaea to humans and include stomatin, SLP-1, and SLP-3. Several studies have indicated that overexpression of SLP-2 is strongly associated with adhesion and migration in several human cancers. The aim of the present study was to evaluate SLP-2 expression at the mRNA and protein level in patients with gastric cancer (GC) and to examine the relationships between SLP-2 expression, clinicopathological features, and prognosis. We investigated SLP-2 expression in primary GC and paired normal gastric tissue by real-time PCR (RT-PCR; n = 16) and Western blot analysis (n = 32). Additionally, we performed immunohistochemistry (IHC) on 113 paraffin-embedded GC specimens, 30 matched normal specimens, and 30 paired metastatic lymph node samples. SLP-2 is overexpressed in GC compared with the adjacent normal gastric epithelium (p < 0.001), and high-level SLP-2 expression is significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis, and American Joint Committee on Cancer (AJCC) stage. Furthermore, elevated SLP-2 expression is an independent prognostic factor in multivariate analysis using the Cox regression model (p = 0.005). Overexpression of SLP-2 may contribute to the progression and poor prognosis of GC.

SLP-76 couples Syk to the osteoclast cytoskeleton.

PubMed

Reeve, Jennifer L; Zou, Wei; Liu, Yuli; Maltzman, Jonathan S; Ross, F Patrick; Teitelbaum, Steven L

2009-08-01

The capacity of the osteoclast (OC) to resorb bone is dictated by cytoskeletal organization, which in turn emanates from signals derived from the alpha(v)beta(3) integrin and c-Fms. Syk is key to these signals and, in other cells, this tyrosine kinase exerts its effects via intermediaries including the SLP adaptors, SLP-76 and BLNK (B cell linker). Thus, we asked whether these two SLP proteins regulate OC function. We find BLNK-deficient OCs are normal, whereas cytoskeletal organization of those lacking SLP-76 is delayed, thus modestly reducing bone resorption in vitro. Cytoskeletal organization and bone resorption are more profoundly arrested in cultured OCs deficient in BLNK and SLP-76 double knockout (DKO) phenotypes. In contrast, stimulated bone resorption in vivo is inhibited approximately 40% in either SLP-76(-/-) or DKO mice. This observation, taken with the fact that DKO OCs are rescued by retroviral transduction of only SLP-76, indicates that SLP-76 is the dominant SLP family member in the resorptive process. We also find SLP-76 is phosphorylated in a Syk-dependent manner. Furthermore, in the absence of the adaptor protein, integrin-mediated phosphorylation of Vav3, the OC cytoskeleton-organizing guanine nucleotide exchange factor, is abrogated. In keeping with a central role of SLP-76/Vav3 association in osteoclastic resorption, retroviral transduction of SLP-76, in which the Vav binding site is disrupted (3YF), fails to normalize the cytoskeleton of DKO OCs and the resorptive capacity of the cells. Finally, c-Fms-activated Syk also exerts its OC cytoskeleton-organizing effect in a SLP-76/Vav3-dependent manner.

SLP-65 signal transduction requires Src homology 2 domain-mediated membrane anchoring and a kinase-independent adaptor function of Syk.

PubMed

Abudula, Abulizi; Grabbe, Annika; Brechmann, Markus; Polaschegg, Christian; Herrmann, Nadine; Goldbeck, Ingo; Dittmann, Kai; Wienands, Jürgen

2007-09-28

The family of SLPs (Src homology 2 domain-containing leukocyte adaptor proteins) are cytoplasmic signal effectors of lymphocyte antigen receptors. A main function of SLP is to orchestrate the assembly of Ca(2+)-mobilizing enzymes at the inner leaflet of the plasma membrane. For this purpose, SLP-76 in T cells utilizes the transmembrane adaptor LAT, but the mechanism of SLP-65 membrane anchoring in B cells remains an enigma. We now employed two genetic reconstitution systems to unravel structural requirements of SLP-65 for the initiation of Ca(2+) mobilization and subsequent activation of gene transcription. First, mutational analysis of SLP-65 in DT40 B cells revealed that its C-terminal Src homology 2 domain controls efficient tyrosine phosphorylation by the kinase Syk, plasma membrane recruitment, as well as downstream signaling to NFAT activation. Second, we dissected these processes by expressing SLP-65 in SLP-76-deficient T cells and found that a kinase-independent adaptor function of Syk is required to link phosphorylated SLP-65 to Ca(2+) mobilization. These approaches unmask a mechanistic complexity of SLP-65 activation and coupling to signaling cascades in that Syk is upstream as well as downstream of SLP-65. Moreover, membrane anchoring of the SLP-65-assembled Ca(2+) initiation complex, which appears to be fundamentally different from that of closely related SLP-76, does not necessarily involve a B cell-specific component.

SH2 domain containing leukocyte phosphoprotein of 76-kDa (SLP-76) feedback regulation of ZAP-70 microclustering.

PubMed

Liu, Hebin; Purbhoo, Marco A; Davis, Daniel M; Rudd, Christopher E

2010-06-01

T cell receptor (TCR) signaling involves CD4/CD8-p56lck recruitment of ZAP-70 to the TCR receptor, ZAP-70 phosphorylation of LAT that is followed by LAT recruitment of the GADS-SLP-76 complex. Back regulation of ZAP-70 by SLP-76 has not been documented. In this paper, we show that anti-CD3 induced ZAP-70 cluster formation is significantly reduced in the absence of SLP-76 (i.e., J14 cells) and in the presence of a mutant of SLP-76 (4KE) in Jurkat and primary T cells. Both the number of cells with clusters and the number of clusters per cell were reduced. This effect was not mediated by SLP-76 SH2 domain binding to ZAP-70 because SLP-76 failed to precipitate ZAP-70 and an inactivating SH2 domain mutation (i.e., R448L) on SLP-76 4KE did not reverse the inhibition of ZAP-70 clustering. Mutation of R448 on WT SLP-76 still supported ZAP-70 clustering. Intriguingly, by contrast, LAT clustering occurred normally in the absence of SLP-76, or the presence of 4KE SLP-76 indicating that this transmembrane adaptor can operate independently of ZAP-70-GADS-SLP-76. Our findings reconfigure the TCR signaling pathway by showing SLP-76 back-regulation of ZAP-70, an event that could ensure that signaling components are in balance for optimal T cell activation.

The SCP2-thiolase-like protein (SLP) of Trypanosoma brucei is an enzyme involved in lipid metabolism.

PubMed

Harijan, Rajesh K; Mazet, Muriel; Kiema, Tiila R; Bouyssou, Guillaume; Alexson, Stefan E H; Bergmann, Ulrich; Moreau, Patrick; Michels, Paul A M; Bringaud, Frédéric; Wierenga, Rik K

2016-08-01

Bioinformatics studies have shown that the genomes of trypanosomatid species each encode one SCP2-thiolase-like protein (SLP), which is characterized by having the YDCF thiolase sequence fingerprint of the Cβ2-Cα2 loop. SLPs are only encoded by the genomes of these parasitic protists and not by those of mammals, including human. Deletion of the Trypanosoma brucei SLP gene (TbSLP) increases the doubling time of procyclic T. brucei and causes a 5-fold reduction of de novo sterol biosynthesis from glucose- and acetate-derived acetyl-CoA. Fluorescence analyses of EGFP-tagged TbSLP expressed in the parasite located the TbSLP in the mitochondrion. The crystal structure of TbSLP (refined at 1.75 Å resolution) confirms that TbSLP has the canonical dimeric thiolase fold. In addition, the structures of the TbSLP-acetoacetyl-CoA (1.90 Å) and TbSLP-malonyl-CoA (2.30 Å) complexes reveal that the two oxyanion holes of the thiolase active site are preserved. TbSLP binds malonyl-CoA tightly (Kd 90 µM), acetoacetyl-CoA moderately (Kd 0.9 mM) and acetyl-CoA and CoA very weakly. TbSLP possesses low malonyl-CoA decarboxylase activity. Altogether, the data show that TbSLP is a mitochondrial enzyme involved in lipid metabolism. Proteins 2016; 84:1075-1096. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fetal hemorrhage and platelet dysfunction in SLP-76–deficient mice

PubMed Central

Clements, James L.; Lee, Jong Ran; Gross, Barbara; Yang, Baoli; Olson, John D.; Sandra, Alexander; Watson, Stephen P.; Lentz, Steven R.; Koretzky, Gary A.

1999-01-01

The adapter protein SLP-76 is expressed in T lymphocytes and hematopoietic cells of the myeloid lineage, and is known to be a substrate of the protein tyrosine kinases that are activated after ligation of the T-cell antigen receptor. Transient overexpression of SLP-76 in a T-cell line potentiates transcriptional activation after T-cell receptor ligation, while loss of SLP-76 expression abrogates several T-cell receptor–dependent signaling pathways. Mutant mice that lack SLP-76 manifest a severe block at an early stage of thymocyte development, implicating SLP-76 in signaling events that promote thymocyte maturation. While it is clear that SLP-76 plays a key role in development and activation of T lymphocytes, relatively little is understood regarding its role in transducing signals initiated after receptor ligation in other hematopoietic cell types. In this report, we describe fetal hemorrhage and perinatal mortality in SLP-76–deficient mice. Although megakaryocyte and platelet development proceeds normally in the absence of SLP-76, collagen-induced platelet aggregation and granule release is markedly impaired. Furthermore, treatment of SLP-76–deficient platelets with collagen fails to elicit tyrosine phosphorylation of phospholipase C-γ2 (PLC-γ2), suggesting that SLP-76 functions upstream of PLC-γ2 activation. These data provide one potential mechanism for the fetal hemorrhage observed in SLP-76–deficient mice and reveal that SLP-76 expression is required for optimal receptor-mediated signal transduction in platelets as well as T lymphocytes. PMID:9884330

Remarkable link between projected uncertainties of Arctic sea-ice decline and winter Eurasian climate

NASA Astrophysics Data System (ADS)

Cheung, Hoffman H. N.; Keenlyside, Noel; Omrani, Nour-Eddine; Zhou, Wen

2018-01-01

We identify that the projected uncertainty of the pan-Arctic sea-ice concentration (SIC) is strongly coupled with the Eurasian circulation in the boreal winter (December-March; DJFM), based on a singular value decomposition (SVD) analysis of the forced response of 11 CMIP5 models. In the models showing a stronger sea-ice decline, the Polar cell becomes weaker and there is an anomalous increase in the sea level pressure (SLP) along 60°N, including the Urals-Siberia region and the Iceland low region. There is an accompanying weakening of both the midlatitude westerly winds and the Ferrell cell, where the SVD signals are also related to anomalous sea surface temperature warming in the midlatitude North Atlantic. In the Mediterranean region, the anomalous circulation response shows a decreasing SLP and increasing precipitation. The anomalous SLP responses over the Euro-Atlantic region project on to the negative North Atlantic Oscillation-like pattern. Altogether, pan-Arctic SIC decline could strongly impact the winter Eurasian climate, but we should be cautious about the causality of their linkage.

Extreme cyclone events in the Arctic: Wintertime variability and trends

NASA Astrophysics Data System (ADS)

Rinke, A.; Maturilli, M.; Graham, R. M.; Matthes, H.; Handorf, D.; Cohen, L.; Hudson, S. R.; Moore, J. C.

2017-12-01

Extreme cyclone events often occur during Arctic winters, and are of concern as they transport heat and moisture into the Arctic, which is associated with mixed-phase clouds and increased longwave downward radiation, and can cause temperatures to rise above freezing resulting in wintertime sea-ice melting or retarded sea-ice growth. With Arctic amplification and associated reduced sea-ice cover and warmer sea surface temperatures, the occurrence of extreme cyclones events could be a plausible scenario. We calculate the spatial patterns, and changes and trends of the number of extreme cyclone events in the Arctic based on ERA-Interim six-hourly sea level pressure (SLP) data for winter (November-February) 1979-2015. Further, we analyze the SLP data from the Ny-Ålesund station for the same 37 year period. We define an extreme cyclone event by an extreme low central pressure (SLP below 985 hPa, which is the 5th percentile of the Ny-Ålesund/N-ICE2015 SLP data). Typically 20-40 extreme cyclone events (sometimes called `weather bombs') occur in the Arctic North Atlantic per winter season, with an increasing trend of 6 events/decade, according to the Ny-Ålesund data. This increased frequency of extreme cyclones drive considerable warming in that region, consistent with the observed significant winter warming of 3 K/decade. The positive winter trend in extreme cyclones is dominated by a positive monthly trend of about 3-4 events/decade in November-December, due mainly to an increasing persistence of extreme cyclone events. A negative trend in January opposes this, while there is no significant trend in February. We relate the regional patterns of the trend in extreme cyclones to anomalously low sea-ice conditions in recent years, together with associated large-scale atmospheric circulation changes such as "blocking-like" circulation patterns (e.g. Scandinavian blocking in December and Ural blocking during January-February).

Two groups of S-layer proteins, SLP1s and SLP2s, in Bacillus thuringiensis co-exist in the S-layer and in parasporal inclusions.

PubMed

Zhou, Zhou; Peng, Donghai; Zheng, Jinshui; Guo, Gang; Tian, Longjun; Yu, Ziniu; Sun, Ming

2011-05-01

We screened four B. thuringiensis strains whose parasporal inclusions contained the S-layer protein (SLP), and cloned two slp genes from each strain. Phylogenetic analysis indicated these SLPs could be divided into two groups, SLP1s and SLP2s. To confirm whether SLPs were present in the S-layer or as a parasporal inclusion, strains CTC and BMB1152 were chosen for further study. Western blots with whole-cell associated proteins from strains CTC and BMB1152 in the vegetative phase showed that SLP1s and SLP2s were constituents of the S-layer. Immunofluorescence utilizing spore-inclusion mixtures of strains CTC and BMB1152 in the sporulation phase showed that SLP1s and SLP2s were also constituents of parasporal inclusions. When heterogeneously expressed in the crystal negative strain BMB171, four SLPs from strains CTC and BMB1152 could also form parasporal inclusions. This temporal and spatial expression is not an occasional phenomenon but ubiquitous in B. thuringiensis strains.

[Expression of SLP-2 protein in esophageal squamous cell carcinoma is associated with cancer invasion].

PubMed

Cao, Wen-feng; Zhang, Li-yong; Zhang, Bin; Wang, Yue-qi; Liu, Zhi-hua; Sun, Bao-cun

2010-11-01

To study the expression of stomatin-like protein-2 (SLP-2) in esophageal squamous cell carcinoma (ESCC), and analyze the correlation between SLP-2 expression and clinicopathological features. The expression of SLP-2 protein in ESCC tissues (18 and 220 cases respectively) was detected by Western blot and IHC. The association between SLP-2 expression and clinicopathological features was analyzed. Compared with normal epithelium, 13 cases of ESCC tissues showed a higher expression of SLP-2 on the protein level (72.2%, 13/18). IHC analysis on tissue microarray revealed that the expression rate of SLP-2 protein in ESCC was 54.1% and in normal esophageal mucosa was 3.6%, showing a significant difference (P < 0.001). SLP-2 high-level expression correlates with the extent of ESCC invasion (P = 0.033), but not with other clinicopathologic characteristics (P > 0.05). SLP-2 as a novel cancer-related gene may play an important role in tumorigenesis of ESCC. The overexpression of SLP-2 may be closely associated with the invasion of esophageal cancer.

Two dimensional Blue Native-/SDS-PAGE analysis of SLP family adaptor protein complexes.

PubMed

Swamy, Mahima; Kulathu, Yogesh; Ernst, Sandra; Reth, Michael; Schamel, Wolfgang W A

2006-04-15

SH2 domain containing leukocyte protein (SLP) adaptor proteins serve a central role in the antigen-mediated activation of lymphocytes by organizing multiprotein signaling complexes. Here, we use two dimensional native-/SDS-gel electrophoresis to study the number, size and relative abundance of protein complexes containing SLP family proteins. In non-stimulated T cells all SLP-76 proteins are in a approximately 400 kDa complex with the small adaptor protein Grb2-like adaptor protein downstream of Shc (Gads), whereas half of Gads is monomeric. This constitutive SLP-76/Gads complex could be reconstituted in Drosophila S2 cells expressing both components, suggesting that it might not contain additional subunits. In contrast, in B cells SLP-65 exists in a 180 kDa complex as well as in monomeric form. Since the complex was not found in S2 cells expressing only SLP-65, it was not di/trimeric SLP-65. Upon antigen-stimulation only the complexed SLP-65 was phosphorylated. Surprisingly, stimulation-induced alteration of SLP complexes could not be detected, suggesting that active signaling complexes form only transiently, and are of low abundance.

Tidal breathing parameters measured using structured light plethysmography in healthy children and those with asthma before and after bronchodilator.

PubMed

Hmeidi, Hamzah; Motamedi-Fakhr, Shayan; Chadwick, Edward; Gilchrist, Francis J; Lenney, Warren; Iles, Richard; Wilson, Rachel C; Alexander, John

2017-03-01

Structured light plethysmography (SLP) is a light-based, noncontact technique that measures tidal breathing by monitoring displacements of the thoracoabdominal (TA) wall. We used SLP to measure tidal breathing parameters and their within-subject variability (v) in 30 children aged 7-16 years with asthma and abnormal spirometry (forced expiratory volume in 1 sec [FEV1] <80% predicted) during a routine clinic appointment. As part of standard care, the reversibility of airway obstruction was assessed by repeating spirometry after administration of an inhaled bronchodilator. In this study, SLP was performed before and after bronchodilator administration, and also once in 41 age-matched controls. In the asthma group, there was a significant increase in spirometry-assessed mean FEV1 after administration of bronchodilator. Of all measured tidal breathing parameters, the most informative was the inspiratory to expiratory TA displacement ratio (IE50 SLP , calculated as TIF50 SLP /TEF50 SLP , where TIF50 SLP is tidal inspiratory TA displacement rate at 50% of inspiratory displacement and TEF50 SLP is tidal expiratory TA displacement rate at 50% of expiratory displacement). Median (m) IE50 SLP and its variability (vIE50 SLP ) were both higher in children with asthma (prebronchodilator) compared with healthy children (mIE50 SLP : 1.53 vs. 1.22, P  <   0.001; vIE50 SLP : 0.63 vs. 0.47, P  <   0.001). After administration of bronchodilators to the asthma group, mIE50 SLP decreased from 1.53 to 1.45 ( P  =   0.01) and vIE50 SLP decreased from 0.63 to 0.60 ( P  =   0.04). SLP-measured tidal breathing parameters could differentiate between children with and without asthma and indicate a response to bronchodilator. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

77 FR 67431 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-09

..., and adds liquidity to the Exchange as a Supplemental Liquidity Provider (``SLP'') for all assigned SLP securities in the aggregate (including shares of both an SLP proprietary trading unit (``SLP- Prop'') and an SLP market maker (``SLMM'') of the same member organization) of more than 0.25% of NYSE CADV. The...

Downregulation of a mitochondria associated protein SLP-2 inhibits tumor cell motility, proliferation and enhances cell sensitivity to chemotherapeutic reagents.

PubMed

Wang, Yueqi; Cao, Wenfeng; Yu, Zaicheng; Liu, Zhihua

2009-09-01

Results from tissue microarray in this study and our previous reports revealed that stomatin-like protein 2 (SLP-2) is notably associated with tumorigenesis and metastasis. Many members of stomatin family are involved in tumor as mitochondrial component, and recent study has revealed that SLP-2 may also function in mitochondria. To further investigate the function of SLP-2, we used siRNA target SLP-2. Data showed that knock-down of SLP-2 potently inhibited cell motility, proliferation and slightly altered cell cycle without any significant change of apoptosis. Moreover, by combined application with different chemotherapeutic reagents, we observed the enhancement of cell chemosensitivity by SLP-2 depletion. We also confirmed that, SLP-2 localizes in mitochondria, affects mitochondrial membrane potential (MMP) and ATP production. We conclude that, SLP-2 is a mitochondrial protein and therefore, functions in energy process by MMP maintenance, and subsequently affecting cell motility, proliferation and chemosensitivity.

SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in pulmonary squamous cell carcinoma.

PubMed

Chang, Dong; Ma, Kai; Gong, Min; Cui, Yong; Liu, Zhi-hua; Zhou, Xiao-ge; Zhou, Chuan-nong; Wang, Tian-you

2010-03-01

To investigate the role of stomatin-like protein 2 (SLP-2), a novel cancer-related gene, in pulmonary squamous cell carcinoma (PSCC) and its implications. Immunohistochemical detection of SLP-2 was performed on 96 cases of PSCC with a tissue microarray. SLP-2 was overexpressed in lung cancer compared with normal lung tissue (p <0.001). High-level SLP-2 expression was significantly correlated with distant metastasis (p = 0.025), decreased overall survival (p = 0.018) and disease-free survival (p = 0.017). SLP-2 overexpression was an independent prognostic factor in multivariate analysis using the Cox regression model (p <0.05). SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in PSCC. SLP-2 could be regarded as a new significant prognostic biomarker for patients with PSCC.

The adaptor protein SLP-76 regulates HIV-1 release and cell to cell transmission in T-cells

PubMed Central

Nagaraja, Tirumuru; Anand, Appakkudal R.; Zhao, Helong; Ganju, Ramesh K.

2014-01-01

HIV-1 infection in T-cells is regulated by T-cell receptor (TCR) activation. However, the cellular proteins of the TCR pathway that regulate HIV-1 infection are poorly characterized. Here, we elucidated the role of SLP-76, a key adaptor protein of the TCR signaling complex, in HIV-1 infection. We observed a significant reduction of HIV-1 virus production in SLP-76-deficient Jurkat T-cells compared to wild-type and SLP-76-reconstituted Jurkat T-cells. We further confirmed the role of SLP-76 in HIV-1 infection by siRNA-mediated knockdown in MT4 cells and PBMCs. Structural-functional analysis revealed that the amino-terminal domain of SLP-76 was important for regulating HIV-1 infection. Further mechanistic studies revealed that lack of SLP-76 impaired virus release, but did not affect viral entry, integration and transcription. We also showed that SLP-76 plays a critical role in cell-to-cell transmission of HIV-1. Signaling studies revealed that SLP-76 associated with viral Nef protein and multiple signaling molecules during HIV-1 infection. Furthermore, SLP-76 facilitated the association of Nef and F-actin, suggesting that SLP-76 mediates the formation of a signaling complex that may regulate viral release via cytoskeletal changes. Taken together, our studies demonstrate a novel role for the adaptor molecule, SLP-76 in regulating HIV-1 infection in T-cells with potential to develop innovative strategies against HIV-1. PMID:22323535

Expression of SLP-2 was associated with invasion of esophageal squamous cell carcinoma.

PubMed

Cao, Wenfeng; Zhang, Bin; Ding, Fang; Zhang, Weiran; Sun, Baocun; Liu, Zhihua

2013-01-01

Stomatin-like protein 2 (SLP-2), a member of the Stomatin superfamily, has been identified as an oncogenic-related protein and found to be up-regulated in multi-cancers. Nonetheless, the expression pattern and regulation of SLP-2 in human esophageal squamous cell carcinoma (ESCC) remain unexplored. Immunohistochemistry and immunofluorescence staining analysis were performed to show SLP-2 expression and location. RNAi method was used to inhibit specific protein expression. Transwell assay was done to investigate cells invasive capability. RT-PCR and Western blot analysis were used to detect mRNA and protein expression levels. Immunohistochemical analysis showed that up-regulation of SLP-2 was found in invasive front compared with cancer central tissue in ESCC. Inhibition of SLP-2 by SLP-2 siRNA can decrease ESCC cells invasive capability through MMP-2 dependent manner. Up-regulation of SLP-2 was effectively abrogated by the ERK1/2 inhibitors either PD98059 or U0126, but no effect was showed by the treatment of AKT inhibitors either LY294002 or MK-2206. So the regulation of SLP-2 was involved in activation of the MAPK/ERK pathway. We found that PMA/EGF could induce the up-regulated expression of SLP-2 probably through activating ERK signalling. The current study suggests that SLP-2 may represent an important molecular hallmark that is clinically relevant to the invasion of ESCC.

Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival.

PubMed

Sun, Fei; Ding, Wen; He, Jie-Hua; Wang, Xiao-Jing; Ma, Ze-Biao; Li, Yan-Fang

2015-10-20

Stomatin-like protein 2 (SLP-2, also known as STOML2) is a stomatin homologue of uncertain function. SLP-2 overexpression has been suggested to be associated with cancer progression, resulting in adverse clinical outcomes in patients. Our study aim to investigate SLP-2 expression in epithelial ovarian cancer cells and its correlation with patient survival. SLP-2 mRNA and protein expression levels were analysed in five epithelial ovarian cancer cell lines and normal ovarian epithelial cells using real-time PCR and western blotting analysis. SLP-2 expression was investigated in eight matched-pair samples of epithelial ovarian cancer and adjacent noncancerous tissues from the same patients. Using immunohistochemistry, we examined the protein expression of paraffin-embedded specimens from 140 patients with epithelial ovarian cancer, 20 cases with borderline ovarian tumours, 20 cases with benign ovarian tumours, and 20 cases with normal ovarian tissues. Statistical analyses were applied to evaluate the clinicopathological significance of SLP-2 expression. SLP-2 mRNA and protein expression levels were significantly up-regulated in epithelial ovarian cancer cell lines and cancer tissues compared with normal ovarian epithelial cells and adjacent noncancerous ovarian tissues. Immunohistochemistry analysis revealed that the relative overexpression of SLP-2 was detected in 73.6 % (103/140) of the epithelial ovarian cancer specimens, 45.0 % (9/20) of the borderline ovarian specimens, 30.0 % (6/20) of the benign ovarian specimens and none of the normal ovarian specimens. SLP-2 protein expression in epithelial ovarian cancer was significantly correlated with the tumour stage (P < 0.001). Epithelial ovarian cancer patients with higher SLP-2 protein expression levels had shorter progress free survival and overall survival times compared to patients with lower SLP-2 protein expression levels. Multivariate analyses showed that SLP-2 expression levels were an independent prognostic factor for survival in epithelial ovarian cancer patients. SLP-2 mRNA and proteins were overexpressed in epithelial ovarian cancer tissues. SLP-2 protein overexpression was associated with advanced stage disease. Patients with higher SLP-2 protein expression had shorter progress free survival and poor overall survival times. Thus, SLP-2 protein expression was an independent prognostic factor for patients with epithelial ovarian cancer.

Stationary Light Pulses in Cold Atomic Media and without Bragg Gratings

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

Lin, Y.-W.; Liao, W.-T.; Peters, Thorsten

We study the creation of stationary light pulses (SLPs), i.e., light pulses without motion, based on the effect of electromagnetically induced transparency with two counterpropagating coupling fields in cold atoms. We show that the Raman excitations created by counterpropagating probe and coupling fields prohibit the formation of SLPs in media of cold and stationary atoms such as laser-cooled atom clouds, Bose condensates or color-center crystals. A method is experimentally demonstrated to suppress these Raman excitations and SLPs are realized in laser-cooled atoms. Furthermore, we report the first experimental observation of a bichromatic SLP at wavelengths for which no Bragg gratingmore » can be established. Our work advances the understanding of SLPs and opens a new avenue to SLP studies for few-photon nonlinear interactions.« less

Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function.

PubMed

Bubeck Wardenburg, J; Fu, C; Jackman, J K; Flotow, H; Wilkinson, S E; Williams, D H; Johnson, R; Kong, G; Chan, A C; Findell, P R

1996-08-16

Two families of tyrosine kinases, the Src and Syk families, are required for T-cell receptor activation. While the Src kinases are responsible for phosphorylation of receptor-encoded signaling motifs and for up-regulation of ZAP-70 activity, the downstream substrates of ZAP-70 are unknown. Evidence is presented herein that the Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP-76) is a substrate of ZAP-70. Phosphorylation of SLP-76 is diminished in T cells that express a catalytically inactive ZAP-70. Moreover, SLP-76 is preferentially phosphorylated by ZAP-70 in vitro and in heterologous cellular systems. In T cells, overexpression of wild-type SLP-76 results in a hyperactive receptor, while expression of a SLP-76 molecule that is unable to be tyrosine-phosphorylated attenuates receptor function. In addition, the SH2 domain of SLP-76 is required for T-cell receptor function, although its role is independent of the ability of SLP-76 to undergo tyrosine phosphorylation. As SLP-76 interacts with both Grb2 and phospholipase C-gamma1, these data indicate that phosphorylation of SLP-76 by ZAP-70 provides an important functional link between the T-cell receptor and activation of ras and calcium pathways.

The unique N-terminal zinc finger of synaptotagmin-like protein 4 reveals FYVE structure.

PubMed

Miyamoto, Kazuhide; Nakatani, Arisa; Saito, Kazuki

2017-12-01

Synaptotagmin-like protein 4 (Slp4), expressed in human platelets, is associated with dense granule release. Slp4 is comprised of the N-terminal zinc finger, Slp homology domain, and C2 domains. We synthesized a compact construct (the Slp4N peptide) corresponding to the Slp4 N-terminal zinc finger. Herein, we have determined the solution structure of the Slp4N peptide by nuclear magnetic resonance (NMR). Furthermore, experimental, chemical modification of Cys residues revealed that the Slp4N peptide binds two zinc atoms to mediate proper folding. NMR data showed that eight Cys residues coordinate zinc atoms in a cross-brace fashion. The Simple Modular Architecture Research Tool database predicted the structure of Slp4N as a RING finger. However, the actual structure of the Slp4N peptide adopts a unique C 4 C 4 -type FYVE fold and is distinct from a RING fold. To create an artificial RING finger (ARF) with specific ubiquitin-conjugating enzyme (E2)-binding capability, cross-brace structures with eight zinc-ligating residues are needed as the scaffold. The cross-brace structure of the Slp4N peptide could be utilized as the scaffold for the design of ARFs. © 2017 The Protein Society.

The SLP-76 Src homology 2 domain is required for T cell development and activation.

PubMed

Burns, Jeremy C; Corbo, Evann; Degen, Janine; Gohil, Mercy; Anterasian, Christine; Schraven, Burkart; Koretzky, Gary A; Kliche, Stefanie; Jordan, Martha S

2011-11-01

The adapter protein Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP-76) is critical for multiple aspects of T cell development and function. Through its protein-binding domains, SLP-76 serves as a platform for the assembly of multiple enzymes and adapter proteins that function together to activate second messengers required for TCR signal propagation. The N terminus of SLP-76, which contains three tyrosines that serve as docking sites for SH2 domain-containing proteins, and the central proline-rich region of SLP-76 have been well studied and are known to be important for both thymocyte selection and activation of peripheral T cells. Less is known about the function of the C-terminal SH2 domain of SLP-76. This region inducibly associates with ADAP and HPK1. Combining regulated deletion of endogenous SLP-76 with transgenic expression of a SLP-76 SH2 domain mutant, we demonstrate that the SLP-76 SH2 domain is required for peripheral T cell activation and positive selection of thymocytes, a function not previously attributed to this region. This domain is also important for T cell proliferation, IL-2 production, and phosphorylation of protein kinase D and IκB. ADAP-deficient T cells display similar, but in some cases less severe, defects despite phosphorylation of a negative regulatory site on SLP-76 by HPK1, a function that is lost in SLP-76 SH2 domain mutant T cells.

The adaptor protein SLP-76 regulates HIV-1 release and cell-to-cell transmission in T cells.

PubMed

Nagaraja, Tirumuru; Anand, Appakkudal R; Zhao, Helong; Ganju, Ramesh K

2012-03-15

HIV-1 infection in T cells is regulated by TCR activation. However, the cellular proteins of the TCR pathway that regulate HIV-1 infection are poorly characterized. In this study, in HIV-1 infection, we observed a significant reduction of HIV-1 virus production in Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76)-deficient Jurkat T cells compared with wild-type and SLP-76-reconstituted Jurkat T cells. We further confirmed the role of SLP-76 in HIV-1 infection by small interfering RNA-mediated knockdown in MT4 cells and PBMCs. Structural-functional analysis revealed that the N-terminal domain of SLP-76 was important for regulating HIV-1 infection. Further mechanistic studies revealed that lack of SLP-76 impaired virus release, but did not affect viral entry, integration, and transcription. We also showed that SLP-76 plays a critical role in cell-to-cell transmission of HIV-1. Signaling studies revealed that SLP-76 associated with viral negative regulatory factor protein and multiple signaling molecules during HIV-1 infection. Furthermore, SLP-76 facilitated the association of negative regulatory factor and F-actin, suggesting that SLP-76 mediates the formation of a signaling complex that may regulate viral release via cytoskeletal changes. Taken together, our studies demonstrate a novel role for the adaptor molecule SLP-76 in regulating HIV-1 infection in T cells with the potential to develop innovative strategies against HIV-1.

Expression of SLP-2 Was Associated with Invasion of Esophageal Squamous Cell Carcinoma

PubMed Central

Cao, Wenfeng; Zhang, Bin; Ding, Fang; Zhang, Weiran; Sun, Baocun; Liu, Zhihua

2013-01-01

Introduction Stomatin-like protein 2 (SLP-2), a member of the Stomatin superfamily, has been identified as an oncogenic-related protein and found to be up-regulated in multi-cancers. Nonetheless, the expression pattern and regulation of SLP-2 in human esophageal squamous cell carcinoma (ESCC) remain unexplored. Methods Immunohistochemistry and immunofluorescence staining analysis were performed to show SLP-2 expression and location. RNAi method was used to inhibit specific protein expression. Transwell assay was done to investigate cells invasive capability. RT-PCR and Western blot analysis were used to detect mRNA and protein expression levels. Results Immunohistochemical analysis showed that up-regulation of SLP-2 was found in invasive front compared with cancer central tissue in ESCC. Inhibition of SLP-2 by SLP-2 siRNA can decrease ESCC cells invasive capability through MMP-2 dependent manner. Up-regulation of SLP-2 was effectively abrogated by the ERK1/2 inhibitors either PD98059 or U0126, but no effect was showed by the treatment of AKT inhibitors either LY294002 or MK-2206. So the regulation of SLP-2 was involved in activation of the MAPK/ERK pathway. Conclusions We found that PMA/EGF could induce the up-regulated expression of SLP-2 probably through activating ERK signalling. The current study suggests that SLP-2 may represent an important molecular hallmark that is clinically relevant to the invasion of ESCC. PMID:23667687

Clinicopathological significance of SLP-2 overexpression in human gallbladder cancer.

PubMed

Wang, Wei-Xin; Lin, Qing-Feng; Shen, Dong; Liu, Shao-Ping; Mao, Wei-Dong; Ma, Gui; Qi, Wei-Dong

2014-01-01

Several studies have indicated that overexpression of stomatin-like protein 2 (SLP-2) has been identified in several types of cancer. However, its role and clinical relevance in gallbladder cancer (GBC) is unknown. The purpose of this study was to reveal the prognostic significance of SLP-2 in GBC. The SLP-2 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (qRT-PCR), and immunohistochemistry in GBC tissues and adjacent noncancerous tissues. Statistical analyses were applied to test the associations between SLP-2 expression, clinicopathologic factors, and prognosis. Immunohistochemistry and qRT-PCR showed that the protein and mRNA expression levels of SLP-2 were both significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that SLP-2 expression was significantly correlated with histological grade (P <0.001), pathologic T stage (P = 0.019), clinical stage (P = 0.001), and lymph node metastasis (P = 0.026). The Kaplan-Meier survival curves indicated that patients with high expression of SLP-2 had shorter overall survival than those with low expression (P <0.001). Meanwhile, the Cox multivariate analysis indicated that high expressions of SLP-2 were an independent prognostic factor for patients with GBC. These data showed that SLP-2 may play an important role in human GBC tumorigenesis, and SLP-2 might serve as a novel prognostic marker in human GBC.

Multipoint Binding of the SLP-76 SH2 Domain to ADAP Is Critical for Oligomerization of SLP-76 Signaling Complexes in Stimulated T Cells

PubMed Central

Coussens, Nathan P.; Hayashi, Ryo; Brown, Patrick H.; Balagopalan, Lakshmi; Balbo, Andrea; Akpan, Itoro; Houtman, Jon C. D.; Barr, Valarie A.; Schuck, Peter; Appella, Ettore

2013-01-01

The adapter molecules SLP-76 and LAT play central roles in T cell activation by recruiting enzymes and other adapters into multiprotein complexes that coordinate highly regulated signal transduction pathways. While many of the associated proteins have been characterized, less is known concerning the mechanisms of assembly for these dynamic and potentially heterogeneous signaling complexes. Following T cell receptor (TCR) stimulation, SLP-76 is found in structures called microclusters, which contain many signaling complexes. Previous studies showed that a mutation to the SLP-76 C-terminal SH2 domain nearly abolished SLP-76 microclusters, suggesting that the SH2 domain facilitates incorporation of signaling complexes into microclusters. S. C. Bunnell, A. L. Singer, D. I. Hong, B. H. Jacque, M. S. Jordan, M. C. Seminario, V. A. Barr, G. A. Koretzky, and L. E. Samelson, Mol. Cell. Biol., 26:7155–7166, 2006). Using biophysical methods, we demonstrate that the adapter, ADAP, contains three binding sites for SLP-76, and that multipoint binding to ADAP fragments oligomerizes the SLP-76 SH2 domain in vitro. These results were complemented with confocal imaging and functional studies of cells expressing ADAP with various mutations. Our results demonstrate that all three binding sites are critical for SLP-76 microcluster assembly, but any combination of two sites will partially induce microclusters. These data support a model whereby multipoint binding of SLP-76 to ADAP facilitates the assembly of SLP-76 microclusters. This model has implications for the regulation of SLP-76 and LAT microclusters and, as a result, T cell signaling. PMID:23979596

Stomatin-like protein 2 is overexpressed in cervical cancer and involved in tumor cell apoptosis

PubMed Central

Deng, Huan; Deng, Yongjian; Liu, Feiye; Chen, Jie; Li, Zheng; Zhao, Kelei; Guan, Xiaoqian; Liang, Weijiang

2017-01-01

Stomatin-like protein 2 (SLP-2) is overexpressed in numerous types of human cancer and previous studies revealed that SLP-2 may function in mitochondria. The purpose of the present study was to evaluate the expression of SLP-2 in cervical cancer and the association between SLP-2 expression and clinical features, in addition to investigating the role of SLP-2 in the apoptosis of cervical cancer cells. The expression profile of SLP-2 was determined by quantitative polymerase chain reaction, western blotting and immunohistochemical staining. The effect of SLP-2 on cell apoptosis induced by chemotherapeutics in cervical cancer cells was evaluated using Annexin V staining and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assays. The results indicated that SLP-2 expression in cervical cancer was significantly upregulated at the mRNA and protein levels, compared with that in normal cervical tissues. Immunohistochemical analysis revealed significant correlation between SLP-2 protein expression and clinical characteristics, including the squamous cell carcinoma antigen (P=0.003), deep stromal invasion (P=0.021), lymphovascular space involvement (P=0.044) and pelvic lymph node metastasis (P<0.001), which served as independent prognostic factors for predicting the shortening of overall survival time in patients with early-stage cervical cancer. In addition, TUNEL and Annexin V binding assays revealed that silencing SLP-2 expression significantly enhanced the sensitivity of cervical cancer cells to apoptosis induced by chemotherapeutics. Taken together, the results of the present study suggest that SLP-2 may be a progressive gene in the development of cervical cancer. Overexpression of SLP-2 serves an important role in the apoptosis of human cervical cancer cells. PMID:29181097

[Expression of SLP-2 mRNA in endometrial cancer and its significance].

PubMed

Feng, Wang-qin; Cui, Zhu-mei; Feng, Feng-zhi; Qi, Xiu-juan; Ding, Fang; Li, Wen-dong; Liu, Zhi-hua

2005-08-01

To characterize the differential expression of SLP-2 in endometrial cancer, and to study the effect of human SLP-2 gene on human endometrial cancer cell line. The expression of SLP-2 gene in 32 cases of endometrial cancer and 28 cases of normal endometrial tissues was examined by semi-quantitative RT-PCR. Eukaryotic expression vectors of sense and antisense SLP-2 were constructed and transfected into HEC-1B cell line using lipofectamine 2000 respectively. The morphological changes of the cell were observed by phase contrast microscopy. The cell growth was detected by methyl thiazolyl tetrazolium (MTT) assay, and the cell cycles were analyzed by flow cytometry. The expression of SLP-2 mRNA in endometrial cancer tissues was higher than that in normal endometrial tissues (1.6 +/- 0.7 vs 0.7 +/- 0.3, P < 0.05). Sense and antisense human SLP-2 constructs were transfected into HEC-1B cell line respectively. After being transfected with sense SLP-2, the expression of SLP-2 mRNA in HEC-1B cell line was increased by about 2.4 times that of the control group, the cell growth was accelerated, and the number of cells in G(1) phase was decreased by 12.5%, S phase was increased by 8.0%. After being transfected with antisense SLP-2, the expression of SLP-2 mRNA was declined 50%. The transfected cells showed slower growth, and the number of cells in G(1) phase was significantly increased by 10.5%, and S phase was declined by 9.8%. SLP-2 mRNA shows up-regulation in endometrial cancer tissues, and it may have some relationship with carcinogenesis of endometrial cancer.

Dual role of SLP-76 in mediating T cell receptor-induced activation of phospholipase C-gamma1.

PubMed

Beach, Dvora; Gonen, Ronnie; Bogin, Yaron; Reischl, Ilona G; Yablonski, Deborah

2007-02-02

Phospholipase C-gamma1 (PLC-gamma1) activation depends on a heterotrimeric complex of adaptor proteins composed of LAT, Gads, and SLP-76. Upon T cell receptor stimulation, a portion of PLC-gamma1 is recruited to a detergent-resistant membrane fraction known as the glycosphingolipid-enriched membrane microdomains (GEMs), or lipid rafts, to which LAT is constitutively localized. In addition to LAT, PLC-gamma1 GEM recruitment depended on SLP-76, and, in particular, required the Gads-binding domain of SLP-76. The N-terminal tyrosine phosphorylation sites and P-I region of SLP-76 were not required for PLC-gamma1 GEM recruitment, but were required for PLC-gamma1 phosphorylation at Tyr(783). Thus, GEM recruitment can be insufficient for full activation of PLC-gamma1 in the absence of a second SLP-76-mediated event. Indeed, a GEM-targeted derivative of PLC-gamma1 depended on SLP-76 for T cell receptor-induced phosphorylation at Tyr783 and subsequent NFAT activation. On a biochemical level, SLP-76 inducibly associated with both Vav and catalytically active ITK, which efficiently phosphorylated a PLC-gamma1 fragment at Tyr783 in vitro. Both associations were disrupted upon mutation of the N-terminal tyrosine phosphorylation sites of SLP-76. The P-I region deletion disrupted Vav association and reduced SLP-76-associated kinase activity. A smaller deletion within the P-I region, which does not impair PLC-gamma1 activation, did not impair the association with Vav, but reduced SLP-76-associated kinase activity. These results provide new insight into the multiple roles of SLP-76 and the functional importance of its interactions with other signaling proteins.

Multipoint binding of the SLP-76 SH2 domain to ADAP is critical for oligomerization of SLP-76 signaling complexes in stimulated T cells.

PubMed

Coussens, Nathan P; Hayashi, Ryo; Brown, Patrick H; Balagopalan, Lakshmi; Balbo, Andrea; Akpan, Itoro; Houtman, Jon C D; Barr, Valarie A; Schuck, Peter; Appella, Ettore; Samelson, Lawrence E

2013-11-01

The adapter molecules SLP-76 and LAT play central roles in T cell activation by recruiting enzymes and other adapters into multiprotein complexes that coordinate highly regulated signal transduction pathways. While many of the associated proteins have been characterized, less is known concerning the mechanisms of assembly for these dynamic and potentially heterogeneous signaling complexes. Following T cell receptor (TCR) stimulation, SLP-76 is found in structures called microclusters, which contain many signaling complexes. Previous studies showed that a mutation to the SLP-76 C-terminal SH2 domain nearly abolished SLP-76 microclusters, suggesting that the SH2 domain facilitates incorporation of signaling complexes into microclusters. S. C. Bunnell, A. L. Singer, D. I. Hong, B. H. Jacque, M. S. Jordan, M. C. Seminario, V. A. Barr, G. A. Koretzky, and L. E. Samelson, Mol. Cell. Biol., 26:7155-7166, 2006). Using biophysical methods, we demonstrate that the adapter, ADAP, contains three binding sites for SLP-76, and that multipoint binding to ADAP fragments oligomerizes the SLP-76 SH2 domain in vitro. These results were complemented with confocal imaging and functional studies of cells expressing ADAP with various mutations. Our results demonstrate that all three binding sites are critical for SLP-76 microcluster assembly, but any combination of two sites will partially induce microclusters. These data support a model whereby multipoint binding of SLP-76 to ADAP facilitates the assembly of SLP-76 microclusters. This model has implications for the regulation of SLP-76 and LAT microclusters and, as a result, T cell signaling.

Identification of SlpB, a Cytotoxic Protease from Serratia marcescens.

PubMed

Shanks, Robert M Q; Stella, Nicholas A; Hunt, Kristin M; Brothers, Kimberly M; Zhang, Liang; Thibodeau, Patrick H

2015-07-01

The Gram-negative bacterium and opportunistic pathogen Serratia marcescens causes ocular infections in healthy individuals. Secreted protease activity was characterized from 44 ocular clinical isolates, and a higher frequency of protease-positive strains was observed among keratitis isolates than among conjunctivitis isolates. A positive correlation between protease activity and cytotoxicity to human corneal epithelial cells in vitro was determined. Deletion of prtS in clinical keratitis isolate K904 reduced, but did not eliminate, cytotoxicity and secreted protease production. This indicated that PrtS is necessary for full cytotoxicity to ocular cells and implied the existence of another secreted protease(s) and cytotoxic factors. Bioinformatic analysis of the S. marcescens Db11 genome revealed three additional open reading frames predicted to code for serralysin-like proteases noted here as slpB, slpC, and slpD. Induced expression of prtS and slpB, but not slpC and slpD, in strain PIC3611 rendered the strain cytotoxic to a lung carcinoma cell line; however, only prtS induction was sufficient for cytotoxicity to a corneal cell line. Strain K904 with deletion of both prtS and slpB genes was defective in secreted protease activity and cytotoxicity to human cell lines. PAGE analysis suggests that SlpB is produced at lower levels than PrtS. Purified SlpB demonstrated calcium-dependent and AprI-inhibited protease activity and cytotoxicity to airway and ocular cell lines in vitro. Lastly, genetic analysis indicated that the type I secretion system gene, lipD, is required for SlpB secretion. These genetic data introduce SlpB as a new cytotoxic protease from S. marcescens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Identification of SlpB, a Cytotoxic Protease from Serratia marcescens

PubMed Central

Stella, Nicholas A.; Hunt, Kristin M.; Brothers, Kimberly M.; Zhang, Liang; Thibodeau, Patrick H.

2015-01-01

The Gram-negative bacterium and opportunistic pathogen Serratia marcescens causes ocular infections in healthy individuals. Secreted protease activity was characterized from 44 ocular clinical isolates, and a higher frequency of protease-positive strains was observed among keratitis isolates than among conjunctivitis isolates. A positive correlation between protease activity and cytotoxicity to human corneal epithelial cells in vitro was determined. Deletion of prtS in clinical keratitis isolate K904 reduced, but did not eliminate, cytotoxicity and secreted protease production. This indicated that PrtS is necessary for full cytotoxicity to ocular cells and implied the existence of another secreted protease(s) and cytotoxic factors. Bioinformatic analysis of the S. marcescens Db11 genome revealed three additional open reading frames predicted to code for serralysin-like proteases noted here as slpB, slpC, and slpD. Induced expression of prtS and slpB, but not slpC and slpD, in strain PIC3611 rendered the strain cytotoxic to a lung carcinoma cell line; however, only prtS induction was sufficient for cytotoxicity to a corneal cell line. Strain K904 with deletion of both prtS and slpB genes was defective in secreted protease activity and cytotoxicity to human cell lines. PAGE analysis suggests that SlpB is produced at lower levels than PrtS. Purified SlpB demonstrated calcium-dependent and AprI-inhibited protease activity and cytotoxicity to airway and ocular cell lines in vitro. Lastly, genetic analysis indicated that the type I secretion system gene, lipD, is required for SlpB secretion. These genetic data introduce SlpB as a new cytotoxic protease from S. marcescens. PMID:25939509

SRC homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) N-terminal tyrosine residues regulate a dynamic signaling equilibrium involving feedback of proximal T-cell receptor (TCR) signaling.

PubMed

Ji, Qinqin; Ding, Yiyuan; Salomon, Arthur R

2015-01-01

SRC homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) is a cytosolic adaptor protein that plays an important role in the T-cell receptor-mediated T-cell signaling pathway. SLP-76 links proximal receptor stimulation to downstream effectors through interaction with many signaling proteins. Previous studies showed that mutation of three tyrosine residues, Tyr(112), Tyr(128), and Tyr(145), in the N terminus of SLP-76 results in severely impaired phosphorylation and activation of Itk and PLCγ1, which leads to defective calcium mobilization, Erk activation, and NFAT activation. To expand our knowledge of the role of N-terminal phosphorylation of SLP-76 from these three tyrosine sites, we characterized nearly 1000 tyrosine phosphorylation sites via mass spectrometry in SLP-76 reconstituted wild-type cells and SLP-76 mutant cells in which three tyrosine residues were replaced with phenylalanines (Y3F mutant). Mutation of the three N-terminal tyrosine residues of SLP-76 phenocopied SLP-76-deficient cells for the majority of tyrosine phosphorylation sites observed, including feedback on proximal T-cell receptor signaling proteins. Meanwhile, reversed phosphorylation changes were observed on Tyr(192) of Lck when we compared mutants to the complete removal of SLP-76. In addition, N-terminal tyrosine sites of SLP-76 also perturbed phosphorylation of Tyr(440) of Fyn, Tyr(702) of PLCγ1, Tyr(204), Tyr(397), and Tyr(69) of ZAP-70, revealing new modes of regulation on these sites. All these findings confirmed the central role of N-terminal tyrosine sites of SLP-76 in the pathway and also shed light on novel signaling events that are uniquely regulated by SLP-76 N-terminal tyrosine residues. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Retinoic acid induces expression of SLP-76: expression with c-FMS enhances ERK activation and retinoic acid-induced differentiation/G0 arrest of HL-60 cells.

PubMed

Yen, Andrew; Varvayanis, Susi; Smith, James L; Lamkin, Thomas J

2006-02-01

Retinoic acid (RA) is known to cause MAPK signaling which propels G0 arrest and myeloid differentiation of HL-60 human myeloblastic leukemia cells. The present studies show that RA up-regulated expression of SLP-76 (Src-homology 2 domain-containing leukocyte-specific phospho-protein of 76 kDa), which became a prominent tyrosine-phosphorylated protein in RA-treated cells. SLP-76 is a known adaptor molecule associated with T-cell receptor and MAPK signaling. To characterize functional effects of SLP-76 expression in RA-induced differentiation and G0 arrest, HL-60 cells were stably transfected with SLP-76. Expression of SLP-76 had no discernable effect on RA-induced ERK activation, subsequent functional differentiation, or the rate of RA-induced G0 arrest. To determine the effects of SLP-76 in the presence of a RA-regulated receptor, SLP-76 was stably transfected into HL-60 cells already overexpressing the colony stimulating factor-1 (CSF-1) receptor, c-FMS, from a previous stable transfection. SLP-76 now enhanced RA-induced ERK activation, compared to parental c-FMS transfectants. It also enhanced RA-induced differentiation, evidenced by enhanced paxillin expression, inducible oxidative metabolism and superoxide production. RA-induced RB tumor suppressor protein hypophosphorylation was also enhanced, as was RA-induced G0 cell cycle arrest. A triple Y to F mutant SLP-76 known to be a dominant negative in T-cell receptor signaling failed to enhance RA-induced paxillin expression, but enhanced RA-induced ERK activation, differentiation and G0 arrest essentially as well as wild-type SLP-76. Thus, SLP-76 overexpression in the presence of c-FMS, a RA-induced receptor, had the effect of enhancing RA-induced cell differentiation. This is the first indication to our knowledge that RA induces the expression of an adapter molecule to facilitate induced differentiation via co-operation between c-FMS and SLP-76.

SRC Homology 2 Domain-containing Leukocyte Phosphoprotein of 76 kDa (SLP-76) N-terminal Tyrosine Residues Regulate a Dynamic Signaling Equilibrium Involving Feedback of Proximal T-cell Receptor (TCR) Signaling*

PubMed Central

Ji, Qinqin; Ding, Yiyuan; Salomon, Arthur R.

2015-01-01

SRC homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) is a cytosolic adaptor protein that plays an important role in the T-cell receptor–mediated T-cell signaling pathway. SLP-76 links proximal receptor stimulation to downstream effectors through interaction with many signaling proteins. Previous studies showed that mutation of three tyrosine residues, Tyr112, Tyr128, and Tyr145, in the N terminus of SLP-76 results in severely impaired phosphorylation and activation of Itk and PLCγ1, which leads to defective calcium mobilization, Erk activation, and NFAT activation. To expand our knowledge of the role of N-terminal phosphorylation of SLP-76 from these three tyrosine sites, we characterized nearly 1000 tyrosine phosphorylation sites via mass spectrometry in SLP-76 reconstituted wild-type cells and SLP-76 mutant cells in which three tyrosine residues were replaced with phenylalanines (Y3F mutant). Mutation of the three N-terminal tyrosine residues of SLP-76 phenocopied SLP-76-deficient cells for the majority of tyrosine phosphorylation sites observed, including feedback on proximal T-cell receptor signaling proteins. Meanwhile, reversed phosphorylation changes were observed on Tyr192 of Lck when we compared mutants to the complete removal of SLP-76. In addition, N-terminal tyrosine sites of SLP-76 also perturbed phosphorylation of Tyr440 of Fyn, Tyr702 of PLCγ1, Tyr204, Tyr397, and Tyr69 of ZAP-70, revealing new modes of regulation on these sites. All these findings confirmed the central role of N-terminal tyrosine sites of SLP-76 in the pathway and also shed light on novel signaling events that are uniquely regulated by SLP-76 N-terminal tyrosine residues. PMID:25316710

The chemokine CXCL12 generates costimulatory signals in T cells to enhance phosphorylation and clustering of the adaptor protein SLP-76.

PubMed

Smith, Xin; Schneider, Helga; Köhler, Karsten; Liu, Hebin; Lu, Yuning; Rudd, Christopher E

2013-07-30

The CXC chemokine CXCL12 mediates the chemoattraction of T cells and enhances the stimulation of T cells through the T cell receptor (TCR). The adaptor SLP-76 [Src homology 2 (SH2) domain-containing leukocyte protein of 76 kD] has two key tyrosine residues, Tyr(113) and Tyr(128), that mediate signaling downstream of the TCR. We investigated the effect of CXCL12 on SLP-76 phosphorylation and the TCR-dependent formation of SLP-76 microclusters. Although CXCL12 alone failed to induce SLP-76 cluster formation, it enhanced the number, stability, and phosphorylation of SLP-76 microclusters formed in response to stimulation of the TCR by an activating antibody against CD3, a component of the TCR complex. Addition of CXCL12 to anti-CD3-stimulated cells resulted in F-actin polymerization that stabilized SLP-76 microclusters in the cells' periphery at the interface with antibody-coated coverslips and increased the interaction between SLP-76 clusters and those containing ZAP-70, the TCR-associated kinase that phosphorylates SLP-76, as well as increased TCR-dependent gene expression. Costimulation with CXCL12 and anti-CD3 increased the extent of phosphorylation of SLP-76 at Tyr(113) and Tyr(128), but not that of other TCR-proximal components, and mutation of either one of these residues impaired the CXCL12-dependent effect on SLP-76 microcluster formation, F-actin polymerization, and TCR-dependent gene expression. The effects of CXCL12 on SLP-76 microcluster formation were dependent on the coupling of its receptor CXCR4 to G(i)-family G proteins (heterotrimeric guanine nucleotide-binding proteins). Thus, we identified a costimulatory mechanism by which CXCL12 and antigen converge at SLP-76 microcluster formation to enhance T cell responses.

The Candida albicans stress response gene Stomatin-Like Protein 3 is implicated in ROS-induced apoptotic-like death of yeast phase cells

PubMed Central

Salcedo, Eugenia C.

2018-01-01

The ubiquitous presence of SPFH (Stomatin, Prohibitin, Flotillin, HflK/HflC) proteins in all domains of life suggests that their function would be conserved. However, SPFH functions are diverse with organism-specific attributes. SPFH proteins play critical roles in physiological processes such as mechanosensation and respiration. Here, we characterize the stomatin ORF19.7296/SLP3 in the opportunistic human pathogen Candida albicans. Consistent with the localization of stomatin proteins, a Slp3p-Yfp fusion protein formed visible puncta along the plasma membrane. We also visualized Slp3p within the vacuolar lumen. Slp3p primary sequence analyses identified four putative S-palmitoylation sites, which may facilitate membrane localization and are conserved features of stomatins. Plasma membrane insertion sequences are present in mammalian and nematode SPFH proteins, but are absent in Slp3p. Strikingly, Slp3p was present in yeast cells, but was absent in hyphal cells, thus categorizing it as a yeast-phase specific protein. Slp3p membrane fluorescence significantly increased in response to cellular stress caused by plasma membrane, cell wall, oxidative, or osmotic perturbants, implicating SLP3 as a general stress-response gene. A slp3Δ/Δ homozygous null mutant had no detected phenotype when slp3Δ/Δ mutants were grown in the presence of a variety of stress agents. Also, we did not observe a defect in ion accumulation, filamentation, endocytosis, vacuolar structure and function, cell wall structure, or cytoskeletal structure. However, SLP3 over-expression triggered apoptotic-like death following prolonged exposure to oxidative stress or when cells were induced to form hyphae. Our findings reveal the cellular localization of Slp3p, and for the first time associate Slp3p function with the oxidative stress response. PMID:29389961

A novel pathway down-modulating T cell activation involves HPK-1-dependent recruitment of 14-3-3 proteins on SLP-76.

PubMed

Di Bartolo, Vincenzo; Montagne, Benjamin; Salek, Mogjiborahman; Jungwirth, Britta; Carrette, Florent; Fourtane, Julien; Sol-Foulon, Nathalie; Michel, Frédérique; Schwartz, Olivier; Lehmann, Wolf D; Acuto, Oreste

2007-03-19

The SH2 domain-containing leukocyte protein of 76 kD (SLP-76) is a pivotal element of the signaling machinery controlling T cell receptor (TCR)-mediated activation. Here, we identify 14-3-3epsilon and zeta proteins as SLP-76 binding partners. This interaction was induced by TCR ligation and required phosphorylation of SLP-76 at serine 376. Ribonucleic acid interference and in vitro phosphorylation experiments showed that serine 376 is the target of the hematopoietic progenitor kinase 1 (HPK-1). Interestingly, either S376A mutation or HPK-1 knockdown resulted in increased TCR-induced tyrosine phosphorylation of SLP-76 and phospholipase C-gamma1. Moreover, an SLP-76-S376A mutant induced higher interleukin 2 gene transcription than wild-type SLP-76. These data reveal a novel negative feedback loop involving HPK-1-dependent serine phosphorylation of SLP-76 and 14-3-3 protein recruitment, which tunes T cell activation.

SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis

PubMed Central

Lightfoot, Yaíma L; Selle, Kurt; Yang, Tao; Goh, Yong Jun; Sahay, Bikash; Zadeh, Mojgan; Owen, Jennifer L; Colliou, Natacha; Li, Eric; Johannssen, Timo; Lepenies, Bernd; Klaenhammer, Todd R; Mohamadzadeh, Mansour

2015-01-01

Intestinal immune regulatory signals govern gut homeostasis. Breakdown of such regulatory mechanisms may result in inflammatory bowel disease (IBD). Lactobacillus acidophilus contains unique surface layer proteins (Slps), including SlpA, SlpB, SlpX, and lipoteichoic acid (LTA), which interact with pattern recognition receptors to mobilize immune responses. Here, to elucidate the role of SlpA in protective immune regulation, the NCK2187 strain, which solely expresses SlpA, was generated. NCK2187 and its purified SlpA bind to the C-type lectin SIGNR3 to exert regulatory signals that result in mitigation of colitis, maintenance of healthy gastrointestinal microbiota, and protected gut mucosal barrier function. However, such protection was not observed in Signr3−/− mice, suggesting that the SlpA/SIGNR3 interaction plays a key regulatory role in colitis. Our work presents critical insights into SlpA/SIGNR3-induced responses that are integral to the potential development of novel biological therapies for autoinflammatory diseases, including IBD. PMID:25666591

SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis.

PubMed

Lightfoot, Yaíma L; Selle, Kurt; Yang, Tao; Goh, Yong Jun; Sahay, Bikash; Zadeh, Mojgan; Owen, Jennifer L; Colliou, Natacha; Li, Eric; Johannssen, Timo; Lepenies, Bernd; Klaenhammer, Todd R; Mohamadzadeh, Mansour

2015-04-01

Intestinal immune regulatory signals govern gut homeostasis. Breakdown of such regulatory mechanisms may result in inflammatory bowel disease (IBD). Lactobacillus acidophilus contains unique surface layer proteins (Slps), including SlpA, SlpB, SlpX, and lipoteichoic acid (LTA), which interact with pattern recognition receptors to mobilize immune responses. Here, to elucidate the role of SlpA in protective immune regulation, the NCK2187 strain, which solely expresses SlpA, was generated. NCK2187 and its purified SlpA bind to the C-type lectin SIGNR3 to exert regulatory signals that result in mitigation of colitis, maintenance of healthy gastrointestinal microbiota, and protected gut mucosal barrier function. However, such protection was not observed in Signr3(-/-) mice, suggesting that the SlpA/SIGNR3 interaction plays a key regulatory role in colitis. Our work presents critical insights into SlpA/SIGNR3-induced responses that are integral to the potential development of novel biological therapies for autoinflammatory diseases, including IBD. © 2015 The Authors.

Evaluation of respiratory dynamics by volumetric capnography during submaximal exercise protocol of six minutes on treadmill in cystic fibrosis patients.

PubMed

Parazzi, Paloma L F; Marson, Fernando A L; Ribeiro, Maria A G O; Schivinski, Camila I S; Ribeiro, José D

2017-11-29

Volumetric capnography provides the standard CO 2 elimination by the volume expired per respiratory cycle and is a measure to assess pulmonary involvement. Thus, the objective of this study was to evaluate the respiratory dynamics of healthy control subjects and those with cystic fibrosis in a submaximal exercise protocol for six minutes on the treadmill, using volumetric capnography parameters (slope 3 [Slp3], Slp3/tidal volume [Slp3/TV], and slope 2 [Slp2]). This was a cross-sectional study with 128 subjects (cystic fibrosis, 64 subjects; controls, 64 subjects]. Participants underwent volumetric capnography before, during, and after six minutes on the treadmill. Statistical analysis was performed using the Friedman, Mann-Whitney, and Kruskal-Wallis tests, considering age and sex. An alpha=0.05 was considered. Six minutes on the treadmill evaluation: in cystic fibrosis, volumetric capnography parameters were different before, during, and after six minutes on the treadmill; the same was observed for the controls, except for Slp2. Regarding age, an Slp3 difference was observed in cystic fibrosis patients regardless of age, at all moments, and in controls for age≥12 years; a difference in Slp3/TV was observed in cystic fibrosis and controls, regardless of age; and an Slp2 difference in the cystic fibrosis, regardless of age. Regarding sex, Slp3 and Slp3/TV differences were observed in cystic fibrosis regardless of sex, and in controls in male participants; an Slp2 difference was observed in the cystic fibrosis and female participants. The analysis between groups (cystic fibrosis and controls) indicated that Slp3 and Slp3/TV has identified the CF, regardless of age and sex, while the Slp2 showed the CF considering age. Cystic fibrosis showed greater values of the parameters before, during, and after exercise, even when stratified by age and sex, which may indicate ventilation inhomogeneity in the peripheral pathways in the cystic fibrosis. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Incorporating TPC observed parameters and QuikSCAT surface wind observations into hurricane initialization using 4D-VAR approaches

NASA Astrophysics Data System (ADS)

Park, Kyungjeen

This study aims to develop an objective hurricane initialization scheme which incorporates not only forecast model constraints but also observed features such as the initial intensity and size. It is based on the four-dimensional variational (4D-Var) bogus data assimilation (BDA) scheme originally proposed by Zou and Xiao (1999). The 4D-Var BDA consists of two steps: (i) specifying a bogus sea level pressure (SLP) field based on parameters observed by the Tropical Prediction Center (TPC) and (ii) assimilating the bogus SLP field under a forecast model constraint to adjust all model variables. This research focuses on improving the specification of the bogus SLP indicated in the first step. Numerical experiments are carried out for Hurricane Bonnie (1998) and Hurricane Gordon (2000) to test the sensitivity of hurricane track and intensity forecasts to specification of initial vortex. Major results are listed below: (1) A linear regression model is developed for determining the size of initial vortex based on the TPC observed radius of 34kt. (2) A method is proposed to derive a radial profile of SLP from QuikSCAT surface winds. This profile is shown to be more realistic than ideal profiles derived from Fujita's and Holland's formulae. (3) It is found that it takes about 1 h for hurricane prediction model to develop a conceptually correct hurricane structure, featuring a dominant role of hydrostatic balance at the initial time and a dynamic adjustment in less than 30 minutes. (4) Numerical experiments suggest that track prediction is less sensitive to the specification of initial vortex structure than intensity forecast. (5) Hurricane initialization using QuikSCAT-derived initial vortex produced a reasonably good forecast for hurricane landfall, with a position error of 25 km and a 4-h delay at landfalling. (6) Numerical experiments using the linear regression model for the size specification considerably outperforms all the other formulations tested in terms of the intensity prediction for both Hurricanes. For examples, the maximum track error is less than 110 km during the entire three-day forecasts for both hurricanes. The simulated Hurricane Gordon using the linear regression model made a nearly perfect landfall, with no position error and only 1-h error in landfalling time. (7) Diagnosis of model output indicates that the initial vortex specified by the linear regression model produces larger surface fluxes of sensible heat, latent heat and moisture, as well as stronger downward angular momentum transport than all the other schemes do. These enhanced energy supplies offset the energy lost caused by friction and gravity wave propagation, allowing for the model to maintain a strong and realistic hurricane during the entire forward model integration.

Loss of SLP-76 expression within myeloid cells confers resistance to neutrophil-mediated tissue damage while maintaining effective bacterial killing.

PubMed

Clemens, Regina A; Lenox, Laurie E; Kambayashi, Taku; Bezman, Natalie; Maltzman, Jonathan S; Nichols, Kim E; Koretzky, Gary A

2007-04-01

The Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) is an adaptor molecule critical for immunoreceptor and integrin signaling in multiple hemopoietic lineages. We showed previously that SLP-76 is required for neutrophil function in vitro, including integrin-induced adhesion and production of reactive oxygen intermediates, and to a lesser extent, FcgammaR-induced calcium flux and reactive oxygen intermediate production. It has been difficult to determine whether SLP-76 regulates neutrophil responses in vivo, because Slp-76(-/-) mice exhibit marked defects in thymocyte and vascular development, as well as platelet and mast cell function. To circumvent these issues, we generated mice with targeted loss of SLP-76 expression within myeloid cells. Neutrophils obtained from these animals failed to respond to integrin activation in vitro, similar to Slp-76(-/-) cells. Despite these abnormalities, SLP-76-deficient neutrophils migrated normally in vivo in response to Staphylococcus aureus infection and efficiently cleared micro-organisms. Interestingly, SLP-76-deficient neutrophils did not induce a robust inflammatory response in the localized Shwartzman reaction. Collectively, these data suggest that disruption of integrin signaling via loss of SLP-76 expression differentially impairs neutrophil functions in vivo, with preservation of migration and killing of S. aureus but reduction in LPS-induced tissue damage and vascular injury.

The SLP-76 SH2 domain is required for T cell development and activation

PubMed Central

Burns, Jeremy C.; Corbo, Evann; Degen, Janine; Gohil, Mercy; Anterasian, Christine; Schraven, Burkart; Koretzky, Gary A.; Kliche, Stefanie; Jordan, Martha S.

2011-01-01

The adaptor protein Src homology 2 (SH2) domain containing leukocyte protein of 76 kDa (SLP-76) is critical for multiple aspects of T cell development and function. Through its protein-binding domains, SLP-76 serves as a platform for the assembly of multiple enzymes and adaptor proteins that function together to activate second messengers required for TCR signal propagation. The N-terminus of SLP-76, which contains three tyrosines that serve as docking sites for SH2 domain-containing proteins, and the central proline-rich region of SLP-76 have been well studied and are known to be important for both thymocyte selection and activation of peripheral T cells. Less is known about the function of the C-terminal SH2 domain of SLP-76. This region inducibly associates with the adhesion- and degranulation-promoting adaptor protein (ADAP) and hematopoietic progenitor kinase 1 (HPK1). Combining regulated deletion of endogenous SLP-76 with transgenic expression of a SLP-76 SH2 domain mutant, we demonstrate that the SLP-76 SH2 domain is required for peripheral T cell activation and positive selection of thymocytes, a function not previously attributed to this region. This domain is also important for T cell proliferation, IL-2 production and phosphorylation of protein kinase D (PKD) and IκB. ADAP-deficient T cells display similar, but in some cases less severe, defects despite phosphorylation of a negative regulatory site on SLP-76 by HPK1, a function that is lost in SLP-76 SH2 domain mutant T cells. PMID:21949020

The effect of the magnetic nanoparticle's size dependence of the relaxation time constant on the specific loss power of magnetic nanoparticle hyperthermia

NASA Astrophysics Data System (ADS)

Harabech, Mariem; Leliaert, Jonathan; Coene, Annelies; Crevecoeur, Guillaume; Van Roost, Dirk; Dupré, Luc

2017-03-01

Magnetic nanoparticle hyperthermia is a cancer treatment in which magnetic nanoparticles (MNPs) are subjected to an alternating magnetic field to induce heat in the tumor. The generated heat of MNPs is characterized by the specific loss power (SLP) due to relaxation phenomena of the MNP. Up to now, several models have been proposed to predict the SLP, one of which is the Linear Response Theory. One parameter in this model is the relaxation time constant. In this contribution, we employ a macrospin model based on the Landau-Lifshitz-Gilbert equation to investigate the relation between the Gilbert damping parameter and the relaxation time constant. This relaxation time has a pre-factor τ0 which is often taken as a fixed value ranging between 10-8 and 10-12 s. However, in reality it has small size dependence. Here, the influence of this size dependence on the calculation of the SLP is demonstrated, consequently improving the accuracy of this estimate.

77 FR 33203 - Notice of Submission for OMB Review; Office of Innovation and Improvement; School Leadership...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-05

...; School Leadership Program (SLP) Annual Performance Report SUMMARY: The School Leadership Program (SLP... to this notice will be considered public records. Title of Collection: School Leadership Program (SLP... Leadership Program. There are two GPRA performance objectives and six performance measures for SLP grantees...

Downscaling of global climate change estimates to regional scales: An application to Iberian rainfall in wintertime

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

von Storch, H.; Zorita, E.; Cubasch, U.

A statistical strategy to deduct regional-scale features from climate general circulation model (GCM) simulations has been designed and tested. The main idea is to interrelate the characteristic patterns of observed simultaneous variations of regional climate parameters and of large-scale atmospheric flow using the canonical correlation technique. The large-scale North Atlantic sea level pressure (SLP) is related to the regional, variable, winter (DJF) mean Iberian Peninsula rainfall. The skill of the resulting statistical model is shown by reproducing, to a good approximation, the winter mean Iberian rainfall from 1900 to present from the observed North Atlantic mean SLP distributions. It ismore » shown that this observed relationship between these two variables is not well reproduced in the output of a general circulation model (GCM). The implications for Iberian rainfall changes as the response to increasing atmospheric greenhouse-gas concentrations simulated by two GCM experiments are examined with the proposed statistical model. In an instantaneous [open quotes]2 CO[sub 2][close quotes] doubling experiment, using the simulated change of the mean North Atlantic SLP field to predict Iberian rainfall yields, there is an insignificant increase of area-averaged rainfall of I mm/month, with maximum values of 4 mm/month in the northwest of the peninsula. In contrast, for the four GCM grid points representing the lberian Peninsula, the change is - 10 mm/month, with a minimum of - 19 mm/month in the southwest. In the second experiment, with the IPCC scenario A ([open quotes]business as usual[close quotes]) increase of CO[sub 2], the statistical-model results partially differ from the directly simulated rainfall changes: in the experimental range of 100 years, the area-averaged rainfall decreases by 7 mm/month (statistical model), and by 9 mm/month (GCM); at the same time the amplitude of the interdecadal variability is quite different. 17 refs., 10 figs.« less

A 10-aa-long sequence in SLP-76 upstream of the Gads binding site is essential for T cell development and function.

PubMed

Kumar, Lalit; Feske, Stefan; Rao, Anjana; Geha, Raif S

2005-12-27

The adapter SLP-76 is essential for T cell development and function. SLP-76 binds to the src homology 3 domain of Lck in vitro. This interaction depends on amino acids 185-194 of SLP-76. To examine the role of the Lck-binding region of SLP-76 in T cell development and function, SLP-76(-/-) mice were reconstituted with an SLP-76 mutant that lacks amino acids 185-194. Double and single positive thymocytes from reconstituted mice were severely reduced in numbers and exhibited impaired positive selection and increased apoptosis. Peripheral T cells were also reduced in numbers, exhibited impaired phospholipase C-gamma1 and Erk phosphorylation, and failed to flux calcium, secrete IL-2, and proliferate in response to T cell antigen receptor ligation. Delayed cutaneous hypersensitivity responses and Ab responses to T cell-dependent antigen were severely impaired. These results indicate that the Lck binding region of SLP-76 is essential for T cell antigen receptor signaling and normal T cell development and function.

Quantitative Phosphoproteomics Reveals SLP-76 Dependent Regulation of PAG and Src Family Kinases in T Cells

PubMed Central

Cao, Lulu; Ding, Yiyuan; Hung, Norris; Yu, Kebing; Ritz, Anna; Raphael, Benjamin J.; Salomon, Arthur R.

2012-01-01

The SH2-domain-containing leukocyte protein of 76 kDa (SLP-76) plays a critical scaffolding role in T cell receptor (TCR) signaling. As an adaptor protein that contains multiple protein-binding domains, SLP-76 interacts with many signaling molecules and links proximal receptor stimulation to downstream effectors. The function of SLP-76 in TCR signaling has been widely studied using the Jurkat human leukaemic T cell line through protein disruption or site-directed mutagenesis. However, a wide-scale characterization of SLP-76-dependant phosphorylation events is still lacking. Quantitative profiling of over a hundred tyrosine phosphorylation sites revealed new modes of regulation of phosphorylation of PAG, PI3K, and WASP while reconfirming previously established regulation of Itk, PLCγ, and Erk phosphorylation by SLP-76. The absence of SLP-76 also perturbed the phosphorylation of Src family kinases (SFKs) Lck and Fyn, and subsequently a large number of SFK-regulated signaling molecules. Altogether our data suggests unique modes of regulation of positive and negative feedback pathways in T cells by SLP-76, reconfirming its central role in the pathway. PMID:23071622

Quantitative phosphoproteomics reveals SLP-76 dependent regulation of PAG and Src family kinases in T cells.

PubMed

Cao, Lulu; Ding, Yiyuan; Hung, Norris; Yu, Kebing; Ritz, Anna; Raphael, Benjamin J; Salomon, Arthur R

2012-01-01

The SH2-domain-containing leukocyte protein of 76 kDa (SLP-76) plays a critical scaffolding role in T cell receptor (TCR) signaling. As an adaptor protein that contains multiple protein-binding domains, SLP-76 interacts with many signaling molecules and links proximal receptor stimulation to downstream effectors. The function of SLP-76 in TCR signaling has been widely studied using the Jurkat human leukaemic T cell line through protein disruption or site-directed mutagenesis. However, a wide-scale characterization of SLP-76-dependant phosphorylation events is still lacking. Quantitative profiling of over a hundred tyrosine phosphorylation sites revealed new modes of regulation of phosphorylation of PAG, PI3K, and WASP while reconfirming previously established regulation of Itk, PLCγ, and Erk phosphorylation by SLP-76. The absence of SLP-76 also perturbed the phosphorylation of Src family kinases (SFKs) Lck and Fyn, and subsequently a large number of SFK-regulated signaling molecules. Altogether our data suggests unique modes of regulation of positive and negative feedback pathways in T cells by SLP-76, reconfirming its central role in the pathway.

Winter temperatures over the Korean Peninsula and East Asia: development of a new index and its application to seasonal forecast

NASA Astrophysics Data System (ADS)

Kim, Seon Tae; Sohn, Soo-Jin; Kug, Jong-Seong

2017-09-01

This study proposes a new index for monitoring and predicting winter temperatures of the Korean Peninsula based on the dominant atmospheric winter teleconnection patterns. The utilization of this index is further extended to the East Asian Winter Monsoon (EAWM) index because the new index is found to well represent the main feature of the EAWM circulation. Among the teleconnection patterns, the East Atlantic (EA) and Western Pacific (WP) patterns are found to be most strongly correlated with winter temperatures via their partial association with changes in sea level pressure (SLP) around the Korean Peninsula, i.e., the EA and WP patterns are associated with SLP variation over the Siberian High region and the Kuroshio extension region to the east of Japan, respectively. On the basis of this relationship, the two regions representing the northwest-to-southeast SLP gradients are determined to define the new index. It is found that the new index can represent the Korean winter temperatures consistently well regardless of their considerable decadal changes. When compared with the existing SLP-based EAWM indices, the new index shows the best performance in delineating winter air temperatures, not only in the Korean Peninsula but also in the entire East Asian region. We also assess the prediction skill of the new index with seasonal coupled forecast models of the APEC Climate Center of Korea and its capability to predict winter temperatures. This assessment shows that the new index has potential for operationally predicting and monitoring winter temperatures in Korea and the whole of East Asia.

Storm surge along the Pacific coast of North America

NASA Astrophysics Data System (ADS)

Bromirski, Peter D.; Flick, Reinhard E.; Miller, Arthur J.

2017-01-01

Storm surge is an important factor that contributes to coastal flooding and erosion. Storm surge magnitude along eastern North Pacific coasts results primarily from low sea level pressure (SLP). Thus, coastal regions where high surge occurs identify the dominant locations where intense storms make landfall, controlled by storm track across the North Pacific. Here storm surge variability along the Pacific coast of North America is characterized by positive nontide residuals at a network of tide gauge stations from southern California to Alaska. The magnitudes of mean and extreme storm surge generally increase from south to north, with typically high amplitude surge north of Cape Mendocino and lower surge to the south. Correlation of mode 1 nontide principal component (PC1) during winter months (December-February) with anomalous SLP over the northeast Pacific indicates that the dominant storm landfall region is along the Cascadia/British Columbia coast. Although empirical orthogonal function spatial patterns show substantial interannual variability, similar correlation patterns of nontide PC1 over the 1948-1975 and 1983-2014 epochs with anomalous SLP suggest that, when considering decadal-scale time periods, storm surge and associated tracks have generally not changed appreciably since 1948. Nontide PC1 is well correlated with PC1 of both anomalous SLP and modeled wave height near the tide gauge stations, reflecting the interrelationship between storms, surge, and waves. Weaker surge south of Cape Mendocino during the 2015-2016 El Niño compared with 1982-1983 may result from changes in Hadley circulation. Importantly from a coastal impacts perspective, extreme storm surge events are often accompanied by high waves.

Clinical significance of SLP-2 in hepatocellular carcinoma tissues and its regulation in cancer cell proliferation, migration, and EMT

PubMed Central

Lin, Xiaoqi; Lin, Qingjun; Han, Ming; Guo, Guohu

2017-01-01

Stomatin-like protein 2 (SLP-2) gene was significantly upregulated in a variety of tumor tissues and found to be involved in proliferation and metastasis. However, its functional role in hepatocellular carcinoma (HCC) remains unknown. Our study was to investigate the function of SLP-2 in cell proliferation, migration, invasion, cell apoptosis, and the process of epithelial–mesenchymal transition (EMT) in HCC. SLP-2 mRNA and protein expression in HCC were assessed by qRT-PCR and immunohistochemical staining. In vitro, we determined cell proliferation, migration, invasion, and cell apoptosis by CCK-8, transwell, and flow cytometry assays, respectively. SLP-2 was found to be upregulated at both mRNA and protein levels in HCC tissues, and its aberrant overexpression was linked with poor prognosis in patients with HCC. SLP-2 downregulation by siRNAs significantly suppressed cell proliferation, migration, invasion, anti-apoptosis abilities, and inhibited EMT process in vitro. In conclusion, the present study demonstrated the overexpression of SLP-2 in HCC tissues for the first time. As an effective regulator involved in cell proliferation, migration, invasion, cell apoptosis, and EMT, SLP-2 could be a novel therapeutic target for patients with HCC who express high levels of SLP-2. PMID:29033585

Role of two adaptor molecules SLP-76 and LAT in the PI3K signaling pathway in activated T cells.

PubMed

Shim, Eun Kyung; Jung, Seung Hee; Lee, Jong Ran

2011-03-01

Previously, we identified p85, a subunit of PI3K, as one of the molecules that interacts with the N-terminal region of Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76). We also demonstrated that tyrosine phosphorylation either at the 113 and/or 128 position is sufficient for the association of SLP-76 with the Src homology 2 domain near the N terminus of p85. The present study further examines the role of the association of these two molecules on the activation of PI3K signaling cascade. Experiments were done to determine the role of SLP-76, either wild-type, tyrosine mutants, or membrane-targeted forms of various SLP-76 constructs, on the membrane localization and phosphorylation of Akt, which is an event downstream of PI3K activation. Reconstitution studies with these various SLP-76 constructs in a Jurkat variant cell line that lacks SLP-76 or linker for activation of T cells (LAT) show that the activation of PI3K pathway following TCR ligation requires both SLP-76 and LAT adaptor proteins. The results suggest that SLP-76 associates with p85 after T cell activation and that LAT recruits this complex to the membrane, leading to Akt activation.

Clinical significance of SLP-2 in hepatocellular carcinoma tissues and its regulation in cancer cell proliferation, migration, and EMT.

PubMed

Huang, Yijie; Chen, Yexi; Lin, Xiaoqi; Lin, Qingjun; Han, Ming; Guo, Guohu

2017-01-01

Stomatin-like protein 2 ( SLP-2 ) gene was significantly upregulated in a variety of tumor tissues and found to be involved in proliferation and metastasis. However, its functional role in hepatocellular carcinoma (HCC) remains unknown. Our study was to investigate the function of SLP-2 in cell proliferation, migration, invasion, cell apoptosis, and the process of epithelial-mesenchymal transition (EMT) in HCC. SLP-2 mRNA and protein expression in HCC were assessed by qRT-PCR and immunohistochemical staining. In vitro, we determined cell proliferation, migration, invasion, and cell apoptosis by CCK-8, transwell, and flow cytometry assays, respectively. SLP-2 was found to be upregulated at both mRNA and protein levels in HCC tissues, and its aberrant overexpression was linked with poor prognosis in patients with HCC. SLP-2 downregulation by siRNAs significantly suppressed cell proliferation, migration, invasion, anti-apoptosis abilities, and inhibited EMT process in vitro. In conclusion, the present study demonstrated the overexpression of SLP-2 in HCC tissues for the first time. As an effective regulator involved in cell proliferation, migration, invasion, cell apoptosis, and EMT, SLP-2 could be a novel therapeutic target for patients with HCC who express high levels of SLP-2.

Two ancient bacterial-like PPP family phosphatases from Arabidopsis are highly conserved plant proteins that possess unique properties.

PubMed

Uhrig, R Glen; Moorhead, Greg B

2011-12-01

Protein phosphorylation, catalyzed by the opposing actions of protein kinases and phosphatases, is a cornerstone of cellular signaling and regulation. Since their discovery, protein phosphatases have emerged as highly regulated enzymes with specificity that rivals their counteracting kinase partners. However, despite years of focused characterization in mammalian and yeast systems, many protein phosphatases in plants remain poorly or incompletely characterized. Here, we describe a bioinformatic, biochemical, and cellular examination of an ancient, Bacterial-like subclass of the phosphoprotein phosphatase (PPP) family designated the Shewanella-like protein phosphatases (SLP phosphatases). The SLP phosphatase subcluster is highly conserved in all plants, mosses, and green algae, with members also found in select fungi, protists, and bacteria. As in other plant species, the nucleus-encoded Arabidopsis (Arabidopsis thaliana) SLP phosphatases (AtSLP1 and AtSLP2) lack genetic redundancy and phylogenetically cluster into two distinct groups that maintain different subcellular localizations, with SLP1 being chloroplastic and SLP2 being cytosolic. Using heterologously expressed and purified protein, the enzymatic properties of both AtSLP1 and AtSLP2 were examined, revealing unique metal cation preferences in addition to a complete insensitivity to the classic serine/threonine PPP protein phosphatase inhibitors okadaic acid and microcystin. The unique properties and high conservation of the plant SLP phosphatases, coupled to their exclusion from animals, red algae, cyanobacteria, archaea, and most bacteria, render understanding the function(s) of this new subclass of PPP family protein phosphatases of particular interest.

Measurement of retinal nerve fiber layer thickness in eyes with optic disc swelling by using scanning laser polarimetry and optical coherence tomography.

PubMed

Hata, Masayuki; Miyamoto, Kazuaki; Oishi, Akio; Kimura, Yugo; Nakagawa, Satoko; Horii, Takahiro; Yoshimura, Nagahisa

2014-01-01

The retinal nerve fiber layer thickness (RNFLT) in patients with optic disc swelling of different etiologies was compared using scanning laser polarimetry (SLP) and spectral-domain optical coherence tomography (OCT). Forty-seven patients with optic disc swelling participated in the cross-sectional study. Both GDx SLP (enhanced corneal compensation) and Spectralis spectral-domain OCT measurements of RNFLT were made in 19 eyes with papilledema (PE), ten eyes with optic neuritis (ON), and 18 eyes with nonarteritic anterior ischemic optic neuropathy (NAION) at the neuro-ophthalmology clinic at Kyoto University Hospital. Differences in SLP (SLP-RNFLT) and OCT (OCT-RNFLT) measurements among different etiologies were investigated. No statistical differences in average OCT-RNFLT among PE, ON, and NAION patients were noted. Average SLP-RNFLT in NAION patients was smaller than in PE (P<0.01) or ON (P=0.02) patients. When RNFLT in each retinal quadrant was compared, no difference among etiologies was noted on OCT, but on SLP, the superior quadrant was thinner in NAION than in PE (P<0.001) or ON (P=0.001) patients. Compared with age-adjusted normative data of SLP-RNFLT, average SLP-RNFLT in PE (P<0.01) and ON (P<0.01) patients was greater. Superior SLP-RNFLT in NAION patients was smaller (P=0.026). The ratio of average SLP-RNFLT to average OCT-RNFLT was smaller in NAION than in PE (P=0.001) patients. In the setting of RNFL thickening, despite increased light retardance in PE and ON eyes, SLP revealed that NAION eyes have less retardance, possibly associated with ischemic axonal loss.

Measurement of retinal nerve fiber layer thickness in eyes with optic disc swelling by using scanning laser polarimetry and optical coherence tomography

PubMed Central

Hata, Masayuki; Miyamoto, Kazuaki; Oishi, Akio; Kimura, Yugo; Nakagawa, Satoko; Horii, Takahiro; Yoshimura, Nagahisa

2014-01-01

Background The retinal nerve fiber layer thickness (RNFLT) in patients with optic disc swelling of different etiologies was compared using scanning laser polarimetry (SLP) and spectral-domain optical coherence tomography (OCT). Methods Forty-seven patients with optic disc swelling participated in the cross-sectional study. Both GDx SLP (enhanced corneal compensation) and Spectralis spectral-domain OCT measurements of RNFLT were made in 19 eyes with papilledema (PE), ten eyes with optic neuritis (ON), and 18 eyes with nonarteritic anterior ischemic optic neuropathy (NAION) at the neuro-ophthalmology clinic at Kyoto University Hospital. Differences in SLP (SLP-RNFLT) and OCT (OCT-RNFLT) measurements among different etiologies were investigated. Results No statistical differences in average OCT-RNFLT among PE, ON, and NAION patients were noted. Average SLP-RNFLT in NAION patients was smaller than in PE (P<0.01) or ON (P=0.02) patients. When RNFLT in each retinal quadrant was compared, no difference among etiologies was noted on OCT, but on SLP, the superior quadrant was thinner in NAION than in PE (P<0.001) or ON (P=0.001) patients. Compared with age-adjusted normative data of SLP-RNFLT, average SLP-RNFLT in PE (P<0.01) and ON (P<0.01) patients was greater. Superior SLP-RNFLT in NAION patients was smaller (P=0.026). The ratio of average SLP-RNFLT to average OCT-RNFLT was smaller in NAION than in PE (P=0.001) patients. Conclusion In the setting of RNFL thickening, despite increased light retardance in PE and ON eyes, SLP revealed that NAION eyes have less retardance, possibly associated with ischemic axonal loss. PMID:24379653

Extreme cyclone events in the Arctic during wintertime: Variability and Trends

NASA Astrophysics Data System (ADS)

Rinke, Annette; Maturilli, Marion; Graham, Robert; Matthes, Heidrun; Handorf, Doerthe; Cohen, Lana; Hudson, Stephen; Moore, John

2017-04-01

Extreme cyclone events are of significant interest as they can transport much heat, moisture, and momentum poleward. Associated impacts are warming and sea-ice breakup. Recently, several examples of such extreme weather events occurred in winter (e.g. during the N-ICE2015 campaign north of Svalbard and the Frank North Atlantic storm during the end of December 2015). With Arctic amplification and associated reduced sea-ice cover and warmer sea surface temperatures, the occurrence of extreme cyclones events could be a plausible scenario. We calculate the spatial patterns, and changes and trends of the number of extreme cyclone events in the Arctic based on ERA-Interim six-hourly sea level pressure (SLP) data for winter (November-February) 1979-2015. Further, we analyze the SLP data from the Ny Alesund station for the same 37 year period. We define an extreme cyclone event by a extreme low central pressure (SLP below 985 hPa, which is the 5th percentile of the Ny Alesund/N-ICE2015 SLP data) and a deepening of at least 6 hPa/6 hours. Areas of highest frequency of occurrence of extreme cyclones are south/southeast of Greenland (corresponding to the Islandic low), between Norway and Svalbard and in the Barents/Kara Seas. The time series of the number of occurrence of extreme cyclone events for Ny Alesund/N-ICE show considerable interannual variability. The trend is not consistent through the winter, but we detect an increase in early winter and a slight decrease in late winter. The former is due to the increased occurrence of longer events at the expense of short events. Furthermore, the difference patterns of the frequency of events for months following the September with high and low Arctic sea-ice extent ("Low minus high sea ice") conforms with the change patterns of extreme cyclones numbers (frequency of events "2000-2015 minus 1979-1994") and with the trend patterns. This indicates that the changes in extreme cyclone occurrence in early winter are associated with sea-ice changes (regional feedback). In contrast, different mechanisms via large-scale circulation changes/teleconnections seem to play a role in late winter.

SLP-76 mediates and maintains activation of the Tec family kinase ITK via the T cell antigen receptor-induced association between SLP-76 and ITK.

PubMed

Bogin, Yaron; Ainey, Carmit; Beach, Dvora; Yablonski, Deborah

2007-04-17

ITK (IL-2-inducible T cell kinase), a Tec family protein tyrosine kinase (PTK), is one of three PTKs required for T cell antigen receptor (TCR)-induced activation of phospholipase C-gamma1 (PLC-gamma1). Like Src and Abl family PTKs, ITK adopts an inactive, "closed" conformation, and its conversion to the active conformation is not well understood, nor have its direct substrates been identified. In a side-by-side comparison of ITK and ZAP-70 (zeta chain-associated protein kinase of 70 kDa), ITK efficiently phosphorylated Y(783) and Y(775) of PLC-gamma1, two phosphorylation sites that are critical for its activation, whereas ZAP-70 did not. SLP-76 (SH2-domain-containing leukocyte protein of 76 kDa), an adaptor required for TCR-induced activation of PLC-gamma1, was required for the phosphorylation of both PLC-gamma1 sites in intact cells. Furthermore, this event depended on the N-terminal tyrosines of SLP-76. Likewise, SLP-76, particularly its N-terminal tyrosines, was required for TCR-induced tyrosine phosphorylation and activation of ITK but was not required for the phosphorylation or activation of ZAP-70. Both ZAP-70 and ITK phosphorylated SLP-76 in vitro; thus, both PTKs are potential regulators of SLP-76, but only ITK is regulated by SLP-76. Upon TCR stimulation, a small fraction of ITK bound to SLP-76. This fraction, however, encompassed most of the catalytically active ITK. Catalytic activity was lost upon mild elution of ITK from the SLP-76-nucleated complex but was restored upon reconstitution of the complex. We propose that SLP-76 is required for ITK activation; furthermore, an ongoing physical interaction between SLP-76 and ITK is required to maintain ITK in an active conformation.

77 FR 54939 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

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Coordination of receptor signaling in multiple hematopoietic cell lineages by the adaptor protein SLP-76.

PubMed

Jordan, Martha S; Koretzky, Gary A

2010-04-01

The adaptor protein SLP-76 is expressed in multiple hematopoietic lineages including T cells, platelets, and neutrophils. SLP-76 mediated signaling is dependent on its multiple protein interaction domains, as it creates a scaffold on which key signaling complexes are built. SLP-76 is critical for supporting signaling downstream of both immunoreceptors and integrins. The signaling molecules used both upstream and downstream of SLP-76 are similar among these receptors and across cell types; however, important differences exist. Appreciating how SLP-76 coordinates signal transduction across different cell and receptor types provides insights into the complex interplay of pathways critical for activation of cells of the immune system that are essential for host defense.

HBV-Derived Synthetic Long Peptide Can Boost CD4+ and CD8+ T-Cell Responses in Chronic HBV Patients Ex Vivo

PubMed Central

Dou, Yingying; van Montfoort, Nadine; van den Bosch, Aniek; de Man, Robert A; Zom, Gijs G; Krebber, Willem-Jan; Melief, Cornelis J M; Buschow, Sonja I; Woltman, Andrea M

2018-01-01

Abstract Background Vaccination with synthetic long peptides (SLP) is a promising new treatment strategy for chronic hepatitis B virus (CHB). SLP can induce broad T-cell responses for all HLA types. Here we investigated the ability of a prototype HBV-core (HBc)-sequence-derived SLP to boost HBV-specific T cells in CHB patients ex vivo. Methods HBc-SLP was used to assess cross-presentation by monocyte-derived dendritic cells (moDC) and BDCA1+ blood myeloid DC (mDC) to engineered HBV-specific CD8+ T cells. Autologous SLP-loaded and toll-like receptor (TLR)-stimulated DC were used to activate patient HBc-specific CD8+ and CD4+ T cells. Results HBV-SLP was cross-presented by moDC, which was further enhanced by adjuvants. Patient-derived SLP-loaded moDC significantly increased autologous HBcAg18-27-specific CD8+ T cells and CD4+ T cells ex vivo. HBV-specific T cells were functional as they synthesized tumor necrosis factor-alpha and interferon-gamma. In 6/7 of patients blockade of PD-L1 further increased SLP effects. Also, importantly, patient-derived BDCA1+ mDC cross-presented and activated autologous T-cell responses ex vivo. Conclusions As a proof of concept, we showed a prototype HBc-SLP can boost T-cell responses in patients ex vivo. These results pave the way for the development of a therapeutic SLP-based vaccine to induce effective HBV-specific adaptive immune responses in CHB patients. PMID:29220492

Mitochondrial and Plasma Membrane Pools of Stomatin-Like Protein 2 Coalesce at the Immunological Synapse during T Cell Activation

PubMed Central

Christie, Darah A.; Kirchhof, Mark G.; Vardhana, Santosh; Dustin, Michael L.; Madrenas, Joaquín

2012-01-01

Stomatin-like protein 2 (SLP-2) is a member of the stomatin – prohibitin – flotillin – HflC/K (SPFH) superfamily. Recent evidence indicates that SLP-2 is involved in the organization of cardiolipin-enriched microdomains in mitochondrial membranes and the regulation of mitochondrial biogenesis and function. In T cells, this role translates into enhanced T cell activation. Although the major pool of SLP-2 is associated with mitochondria, we show here that there is an additional pool of SLP-2 associated with the plasma membrane of T cells. Both plasma membrane-associated and mitochondria-associated pools of SLP-2 coalesce at the immunological synapse (IS) upon T cell activation. SLP-2 is not required for formation of IS nor for the re-localization of mitochondria to the IS because SLP-2-deficient T cells showed normal re-localization of these organelles in response to T cell activation. Interestingly, upon T cell activation, we found the surface pool of SLP-2 mostly excluded from the central supramolecular activation complex, and enriched in the peripheral area of the IS where signalling TCR microclusters are located. Based on these results, we propose that SLP-2 facilitates the compartmentalization not only of mitochondrial membranes but also of the plasma membrane into functional microdomains. In this latter location, SLP-2 may facilitate the optimal assembly of TCR signalosome components. Our data also suggest that there may be a net exchange of membrane material between mitochondria and plasma membrane, explaining the presence of some mitochondrial proteins in the plasma membrane. PMID:22623988

Evidence for the requirement of ITAM domains but not SLP-76/Gads interaction for integrin signaling in hematopoietic cells.

PubMed

Abtahian, Farhad; Bezman, Natalie; Clemens, Regina; Sebzda, Eric; Cheng, Lan; Shattil, Sanford J; Kahn, Mark L; Koretzky, Gary A

2006-09-01

Syk tyrosine kinase and Src homology 2 (SH2) domain-containing leukocyte-specific phosphoprotein of 76 kDa (SLP-76) are signaling mediators activated downstream of immunoreceptor tyrosine-based activation motif (ITAM)-containing immunoreceptors and integrins. While the signaling cascades descending from integrins are similar to immunoreceptors, the mechanism of Syk activation and SLP-76 recruitment remains unclear. We used an in vivo structure-function approach to study the requirements for the domains of Syk and SLP-76 in immunoreceptor and integrin signaling. We found that both SH2 domains and the kinase domain of Syk are required for immunoreceptor-dependent signaling and cellular response via integrins. While the Gads-binding domain of SLP-76 is needed for immunoreceptor signaling, it appears dispensable for integrin signaling. Syk and SLP-76 also are required for initiating and/or maintaining separation between the blood and lymphatic vasculature. Therefore, we correlated the signaling requirement of the various domains of Syk and SLP-76 to their requirement in regulating vascular separation. Our data suggest ITAMs are required in Syk-dependent integrin signaling, demonstrate the separation of the structural features of SLP-76 to selectively support immunoreceptor versus integrin signaling, and provide evidence that the essential domains of SLP-76 for ITAM signals are those which most efficiently support separation between lymphatic and blood vessels.

SlpE is a calcium-dependent cytotoxic metalloprotease associated with clinical isolates of Serratia marcescens.

PubMed

Stella, Nicholas A; Callaghan, Jake D; Zhang, Liang; Brothers, Kimberly M; Kowalski, Regis P; Huang, Jean J; Thibodeau, Patrick H; Shanks, Robert M Q

Serralysin-like proteases are found in a wide variety of bacteria. These metalloproteases are frequently implicated in virulence and are members of the widely conserved RTX-toxin family. We identified a serralysin-like protease in the genome of a clinical isolate of Serratia marcescens that is highly similar to the canonical serralysin protein, PrtS. This gene was named serralysin-like protease E, SlpE, and was found in the majority (67%) of tested clinical isolates, but was absent from most tested non-clinical isolates including the insect pathogen and reference S. marcescens strain Db11. Purified recombinant SlpE exhibited calcium-dependent protease activity similar to metalloproteases PrtS and SlpB. Induction of slpE in the low-protease-producing S. marcescens strain PIC3611 highly elevated extracellular protease activity, and extracellular secretion required the lipD type 1 secretion system gene. Transcription of slpE was highly reduced in an eepR transcription factor mutant. Mutation of the slpE gene in a highly proteolytic clinical isolate reduced its protease activity, and evidence suggests that SlpE confers cytotoxicity of S. marcescens to the A549 airway carcinoma cell line. Together, these data reveal SlpE to be an EepR-regulated cytotoxic metalloprotease associated with clinical isolates of an important opportunistic pathogen. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Atmospheric conditions during the spring and fall transitions in the coastal ocean off western United States

NASA Technical Reports Server (NTRS)

Strub, P. Ted; James, Corinne

1988-01-01

Atmospheric events which force the spring and fall oceanic transitions in the coastal ocean off the west coast of North America were examined by analyzing the records of adjusted sea level (ASL), coastal wind stress, sea level atmospheric pressure (SLP), and 500-mbar heights for the years 1971-1975 and 1980-1983. The records cover periods of 91 days, centered on the dates of the spring and fall transitions as determined from coastal ASL data. It was found that the dominant mode of the ASL and coastal wind stress are similar around the times of both the spring and fall transitions, and that the time series for these modes are highly correlated with one another. Principal estimator patterns show the spatial patterns of SLP which force the ASL and coastal wind stress during the transitions.

78 FR 48526 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

... Liquidity Provider (``SLP'') credits in its Price List. The Exchange proposes to implement the fee change... Statutory Basis for, the Proposed Rule Change 1. Purpose The Exchange proposes to amend one of the SLP... credit is determined by the ``tier'' that the SLP qualifies for, which is generally based on the SLP's...

78 FR 36281 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... change effective June 1, 2013. An SLP is a member organization that electronically enters orders or... quoting requirement'').\\3\\ In addition, for all assigned SLP securities, an SLP is required to satisfy a... forth in the Exchange's Price List.\\4\\ \\3\\ See Rule 107B(a). An SLP can either be a proprietary trading...

77 FR 47471 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-08

...\\ The amount of the credit is currently determined by the ``tier'' that the SLP qualifies for, which is based on the SLP's level of quoting and the average daily volume (``ADV'') \\4\\ of liquidity added by the SLP in assigned securities. \\3\\ SLP credits are not applicable to executions of securities with a per...

Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-gamma production.

PubMed

Hidano, Shinya; Sasanuma, Hiroki; Ohshima, Keiko; Seino, Ken-ichiro; Kumar, Lalit; Hayashi, Katsuhiko; Hikida, Masaki; Kurosaki, Tomohiro; Taniguchi, Masaru; Geha, Raif S; Kitamura, Daisuke; Goitsuka, Ryo

2008-03-01

Activation of NK cells is triggered by multiple receptors. We demonstrate here that SLP-76 is required for CD16- and NKG2D-mediated NK cell cytotoxicity, while MIST negatively regulates these responses in an SLP-76-dependent manner. Exceptionally, MIST acts as a positive regulator of cytotoxicity against YAC-1 cells, although SLP-76 plays a more key role. SLP-76 acts as a dominant positive regulator for both NKG2D-mediated and YAC-1 cell-triggered IFN-gamma production. Although NKG2D-mediated IFN-gamma production depends on phospholipase C (PLC) gamma 2, YAC-1 cell-triggered IFN-gamma production is PLC gamma 2- and Syk/ZAP-70 independent and nuclear factor-kappa B mediated. SLP-76 is required for this process in the presence of MIST but is dispensable in the absence of MIST. Thus, YAC-1 cell-triggered NKG2D-independent IFN-gamma production appears to be regulated by SLP-76-dependent and -independent pathways, in which the latter is negatively regulated by MIST. Taken together, these results suggest that SLP-76 and MIST distinctly but interactively regulate NK cell cytotoxicity and IFN-gamma production.

SLP-2 negatively modulates mitochondrial sodium-calcium exchange.

PubMed

Da Cruz, Sandrine; De Marchi, Umberto; Frieden, Maud; Parone, Philippe A; Martinou, Jean-Claude; Demaurex, Nicolas

2010-01-01

Mitochondria play a major role in cellular calcium homeostasis. Despite decades of studies, the molecules that mediate and regulate the transport of calcium ions in and out of the mitochondrial matrix remain unknown. Here, we investigate whether SLP-2, an inner membrane mitochondrial protein of unknown function, modulates the activity of mitochondrial Ca(2+) transporters. In HeLa cells depleted of SLP-2, the amplitude and duration of mitochondrial Ca(2+) elevations evoked by agonists were decreased compared to control cells. SLP-2 depletion increased the rates of calcium extrusion from mitochondria. This effect disappeared upon Na(+) removal or addition of CGP-37157, an inhibitor of the mitochondrial Na(+)/Ca(2+) exchanger, and persisted in permeabilized cells exposed to a fixed cytosolic Na(+) and Ca(2+) concentration. The rates of mitochondrial Ca(2+) extrusion were prolonged in SLP-2 over-expressing cells, independently of the amplitude of mitochondrial Ca(2+) elevations. The amplitude of cytosolic Ca(2+) elevations was increased by SLP-2 depletion and decreased by SLP-2 over-expression. These data show that SLP-2 modulates mitochondrial calcium extrusion, thereby altering the ability of mitochondria to buffer Ca(2+) and to shape cytosolic Ca(2+) signals. 2009 Elsevier Ltd. All rights reserved.

Purification of Lactobacillus acidophilus surface-layer protein and its immunomodulatory effects on RAW264.7 cells.

PubMed

Zhang, Dandan; Wu, Mengting; Guo, Yuxing; Xun, Mingyue; Wang, Wenwen; Wu, Zhen; Pan, Daodong

2017-09-01

Surface-layer proteins (SLP) have been found in the outermost layer of the cell wall in many types of lactobacillus are considered to be an important factor with respect to intestinal immunity. The present study compared the effects of SLP extracted by different concentrations of LiCl and carbamide, and subsequently identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, circular dichroism and differential scanning calorimetry. Furthermore, RAW 264.7 cells were used to evaluate the immunomodulatory effects of SLP. SLP were derived from Lactobacillus acidophilus CICC6074 with a molecular weight of 46 kDa, and consisted of 16.9% α-helix, 42.3% β-sheet, 20.8% β-turns and 22.5% random coils. SLP promoted NO secretion and higher quantities of NO were produced as the SLP concentrations increased. SLP concentrations over 50 µg mL -1 significantly decreased the amount of tumor necrosis factor-α secreted by RAW264.7 cells. SLP can trigger immunomodulatory effects in RAW 264.7 cells. This provides crucial information that will enable the further use of L. acidophilus in food, medicine and other products. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

SLP-2 interacts with prohibitins in the mitochondrial inner membrane and contributes to their stability.

PubMed

Da Cruz, Sandrine; Parone, Philippe A; Gonzalo, Philippe; Bienvenut, Willy V; Tondera, Daniel; Jourdain, Alexis; Quadroni, Manfredo; Martinou, Jean-Claude

2008-05-01

Stomatin is a member of a large family of proteins including prohibitins, HflK/C, flotillins, mechanoreceptors and plant defense proteins, that are thought to play a role in protein turnover. Using different proteomic approaches, we and others have identified SLP-2, a member of the stomatin gene family, as a component of the mitochondria. In this study, we show that SLP-2 is strongly associated with the mitochondrial inner membrane and that it interacts with prohibitins. Depleting HeLa cells of SLP-2 lead to increased proteolysis of prohibitins and of subunits of the respiratory chain complexes I and IV. Further supporting the role of SLP-2 in regulating the stability of specific mitochondrial proteins, we found that SLP-2 is up-regulated under conditions of mitochondrial stress leading to increased protein turnover. These data indicate that SLP-2 plays a role in regulating the stability of mitochondrial proteins including prohibitins and subunits of respiratory chain complexes.

Climate change projections for winter precipitation over Tropical America using statistical downscaling

NASA Astrophysics Data System (ADS)

Palomino-Lemus, Reiner; Córdoba-Machado, Samir; Quishpe-Vásquez, César; García-Valdecasas-Ojeda, Matilde; Raquel Gámiz-Fortis, Sonia; Castro-Díez, Yolanda; Jesús Esteban-Parra, María

2017-04-01

In this study the Principal Component Regression (PCR) method has been used as statistical downscaling technique for simulating boreal winter precipitation in Tropical America during the period 1950-2010, and then for generating climate change projections for 2071-2100 period. The study uses the Global Precipitation Climatology Centre (GPCC, version 6) data set over the Tropical America region [30°N-30°S, 120°W-30°W] as predictand variable in the downscaling model. The mean monthly sea level pressure (SLP) from the National Center for Environmental Prediction - National Center for Atmospheric Research (NCEP-NCAR reanalysis project), has been used as predictor variable, covering a more extended area [30°N-30°S, 180°W-30°W]. Also, the SLP outputs from 20 GCMs, taken from the Coupled Model Intercomparison Project (CMIP5) have been used. The model data include simulations with historical atmospheric concentrations and future projections for the representative concentration pathways RCP2.6, RCP4.5, and RCP8.5. The ability of the different GCMs to simulate the winter precipitation in the study area for present climate (1971-2000) was analyzed by calculating the differences between the simulated and observed precipitation values. Additionally, the statistical significance at 95% confidence level of these differences has been estimated by means of the bilateral rank sum test of Wilcoxon-Mann-Whitney. Finally, to project winter precipitation in the area for the period 2071-2100, the downscaling model, recalibrated for the total period 1950-2010, was applied to the SLP outputs of the GCMs under the RCP2.6, RCP4.5, and RCP8.5 scenarios. The results show that, generally, for present climate the statistical downscaling shows a high ability to faithfully reproduce the precipitation field, while the simulations performed directly by using not downscaled outputs of GCMs strongly distort the precipitation field. For future climate, the projected predictions under the RCP4.5 and RCP8.5 scenarios show large areas with significant changes. For the RCP2.6 scenario, projected results present a predominance of very moderate decreases in rainfall, although significant in some models. Keywords: climate change projections, precipitation, Tropical America, statistical downscaling. Acknowledgements: This work has been financed by the projects P11-RNM-7941 (Junta de Andalucía-Spain) and CGL2013-48539-R (MINECO-Spain, FEDER).

75 FR 54407 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-07

... the ability for an SLP to earn a rebate if it maintains a quote at the National Best Bid (``NBB'') or National Best Offer (``NBO'') an average of 3% in an assigned SLP security. Instead, an SLP would be... Exchange also proposes to clarify which mnemonics that a member organization may use for the SLP trading...

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Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

... adding liquidity to the NYSE.\\21\\ The amount of the credit is determined by the ``tier'' that the SLP qualifies for, which is based on the SLP's level of quoting and the ADV of liquidity added by the SLP in....0005 less than the current credit, which, going forward, would be applicable to the SLP's other...

[Relationship between SLP-2 expression and prognosis in laryngeal squamous cell carcinoma and mammary invasive carcinoma].

PubMed

Cao, Wen-feng; Zhang, Li-yong; Zhang, Bin; Liu, Ming-bo; Liu, Zhi-hua; Sun, Bao-cun

2010-05-01

To study the expression of stomatin like protein-2 (SLP-2) at mRNA and protein levels in two kinds of malignant epithelial tumors, including laryngeal squamous cell carcinoma (LSCC) and invasive breast cancer, and to study the relations of SLP-2 expression and clinicopathologic parameters with the prognosis. RT-PCR and Western blot were used to detect the expression of SLP-2 mRNA and protein in LSCC and their normal counterparts (46 and 10 pair, respectively). Immunohistochemistry was carried on tissue array constructed from LSCC (104 cases) and breast cancer (263 cases), respectively. The association between SLP-2 expression and clinicopathologic parameters was analyzed. LSCC showed a higher expression of SLP-2 than that of their normal counterparts (negative expression) at mRNA (83%, 38/46) and protein (7/10) level. Immunohistochemical analysis of LSCC showed that compared with negative expression in normal laryngeal epithelium (0/20), a higher SLP-2 expression was detected in LSCC (36/104, P=0.000) and associated with the advanced clinical stage (P<0.01) and lymph node metastasis (P=0.003). Immunohistochemical study of invasive breast cancer demonstrated that compared with negative expression in normal breast tissue (0/10), more than one half of the cases showed a high SLP-2 expression (52.5%, 138/263, P=0.000) in breast cancer, which correlated with the tumor size (P=0.020), lymph node metastasis (P<0.01), advanced clinical stage (P<0.01), distant metastasis (P=0.002) and HER2/neu protein expression (P=0.037). Survival analysis showed a shorter overall survival probability in patients with a high SLP-2 expression. It was considered that lymph node metastasis, positive HER2/neu expression, and high-level SLP-2 expression may act as the independent prognostic factors for those tumors. A high expression level of SLP-2 may be associating with the development of invasion and metastasis in LSCC and breast cancer, and SLP-2 is also considered working as an independent factor indicating a poor prognosis clinically in breast cancer.

Structure, organization and expression of common carp (Cyprinus carpio L.) SLP-76 gene.

PubMed

Huang, Rong; Sun, Xiao-Feng; Hu, Wei; Wang, Ya-Ping; Guo, Qiong-Lin

2008-05-01

SLP-76 is an important member of the SLP-76 family of adapters, and it plays a key role in TCR signaling and T cell function. Partial cDNA sequence of SLP-76 of common carp (Cyprinus carpio L.) was isolated from thymus cDNA library by the method of suppression subtractive hybridization (SSH). Subsequently, the full length cDNA of carp SLP-76 was obtained by means of 3' RACE and 5' RACE, respectively. The full length cDNA of carp SLP-76 was 2007 bp, consisting of a 5'-terminal untranslated region (UTR) of 285 bp, a 3'-terminal UTR of 240 bp, and an open reading frame of 1482 bp. Sequence comparison showed that the deduced amino acid sequence of carp SLP-76 had an overall similarity of 34-73% to that of other species homologues, and it was composed of an NH2-terminal domain, a central proline-rich domain, and a C-terminal SH2 domain. Amino acid sequence analysis indicated the existence of a Gads binding site R-X-X-K, a 10-aa-long sequence which binds to the SH3 domain of LCK in vitro, and three conserved tyrosine-containing sequence in the NH2-terminal domain. Then we used PCR to obtain a genomic DNA which covers the entire coding region of carp SLP-76. In the 9.2k-long genomic sequence, twenty one exons and twenty introns were identified. RT-PCR results showed that carp SLP-76 was expressed predominantly in hematopoietic tissues, and was upregulated in thymus tissue of four-month carp compared to one-year old carp. RT-PCR and virtual northern hybridization results showed that carp SLP-76 was also upregulated in thymus tissue of GH transgenic carp at the age of four-months. These results suggest that the expression level of SLP-76 gene may be related to thymocyte development in teleosts.

The regulatory role of SLP-2 and mechanism on CCBE1 gene expression in rectal carcinoma and adjacent lymphatic tube tissues.

PubMed

Guo, R-L; Wang, X-R; Wang, Q-G; Li, Z; Lu, X; Miao, R-Z; Chang, H

2018-01-01

  The incidence of rectal carcinoma (RC) has been increasing recently, and becomes the second most common digestive tumors besides gastric cancer, with a rise in the incidence of RC in younger populations. The early diagnosis and treatment are thus critical for the improvement of survival rate and life quality of patients. Stomatin-like protein 2 (SLP-2) is a type of membrane factor, which is generally found highly expressed in various tumors. Collagen and calcium-binding EGF domain (CCBE1) belongs to lymphatic tube genesis factor. The regulatory role of SLP-2 gene on CCBE1 expression in RC tumor and adjacent lymphatic tube tissues, however, has not been studied. 52 RC patients were recruited, and tumor and adjacent lymphatic tube tissues were collected. Real-time PCR, western blotting and immunohistochemistry (IHC) staining were used to analyze SLP-2 and CCBE1 expressions. Human lymphatic endothelial cells (LECs) were cultured in vitro and were assigned to control, scramble, and SLP-2 siRNA group. MTT assay was used to detect cell proliferation, while caspase 3 activity was detected. SLP-2 and CCBE1 levels were significantly elevated in tumor lymphatic tissues, compared to that in adjacent tissues. Statistically positive correlation between SLP-1 and CCBE2 was found (p<0.05). The downregulation of SLP-2 by siRNA inhibited cell proliferation, elevated caspase3 activity, and decreased CCBE1 expression (p<0.05 compared to control group). SLP-2 is up-regulated in RC lymphatic tissues, and is positively correlated with the level of CCBE1, which provides the academic the basis for the development of medicine targeting SLP-2 in the anti-rectal carcinoma therapy.

Knowledge about, attitude toward, and practice of skin lightening products use and its social correlates among university students in five Association of Southeast Asian Nations (ASEAN) countries.

PubMed

Peltzer, Karl; Pengpid, Supa

2017-03-01

The aim of this study was to investigate the knowledge about, attitude toward, and use of skin lightening products (SLP) and its social and psychological correlates among university students from five Association of Southeast Asian Nations (ASEAN) countries. In a cross sectional survey, 3259 undergraduate university students (Mean age = 20.5 years, SD = 1.6) from five ASEAN countries responded to an anonymous questionnaire. Multivariate logistic regression analysis was used to identify associations between sociodemographic characteristics, knowledge, attitude, poor mental health, and SLP use. Overall, 79.1% of the students were aware that the use of SLP can harm the skin, and 30.1% knew the active ingredients of SLP. Most students had a positive perception of having a lighter skin tone and SLP. Overall, the prevalence of SLP use over the past 12 months was 30.7%, 16.7% of male, and 30.0% of female students, ranging from 13.4% in Myanmar to 69.4% in Thailand. In multivariate logistic regression analysis, among women, older age, coming from a poorer family, residing in an upper middle income country, awareness of active skin lightening ingredients, and poor mental health were associated with SLP, while among men, not aware of the negative effects of SLP and awareness of active skin lightening ingredients and poor mental health were associated with SLP use. A high prevalence of SLP use was found in a large sample of ASEAN university students, and several social and mental health-related risk factors were found that may help in guiding interventions. © 2017 The International Society of Dermatology.

Lactobacillus acidophilus CP23 with weak immunomodulatory activity lacks anchoring structure for surface layer protein.

PubMed

Yanagihara, Sae; Kato, Shinji; Ashida, Nobuhisa; Yamamoto, Naoyuki

2015-05-01

To determine the reason for the low levels of Surface layer protein A (SlpA) on CP23 cells, which might play a crucial role in the immunomodulatory effect of Lactobacillus acidophilus, the DNA sequence of the slpA gene of CP23 and L-92 strains, including the upstream region, were analyzed. Unexpectedly, there was no significant difference in the predicted amino acid sequence of the C-terminus needed for cell anchoring, and only an additional Ala-Val-Ala sequence inserted in the N-terminal region of the mature CP23 protein. Therefore, anchoring of SlpA on the cell wall of CP23 and L-92 was evaluated by a reconstitution assay, which showed that SlpA released by LiCl treatment from both CP23 and L-92 was successfully anchored on LiCl-treated L-92 cells, but not on LiCl-treated CP23 cells. Moreover, quantitative analysis of SlpA protein in the culture medium of CP23 and L-92 by ELISA revealed higher levels of SlpA secretion in CP23 cells than in L-92 cells. Collectively, these results suggest that the lower levels of SlpA on the surface of CP23 cells might be caused by less cell wall capacity for SlpA anchoring, leading to an accumulation of SlpA in the culture medium of CP23 cells. The present study supports the importance of cell surface structure of L. acidophilus L-92 for SlpA anchoring on the cell surface needed for immunomodulatory effect. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

SLP-76 sterile α motif (SAM) and individual H5 α helix mediate oligomer formation for microclusters and T-cell activation.

PubMed

Liu, Hebin; Thaker, Youg Raj; Stagg, Loren; Schneider, Helga; Ladbury, John E; Rudd, Christopher E

2013-10-11

Despite the importance of the immune adaptor SLP-76 in T-cell immunity, it has been unclear whether SLP-76 directly self-associates to form higher order oligomers for T-cell activation. In this study, we show that SLP-76 self-associates in response to T-cell receptor ligation as mediated by the N-terminal sterile α motif (SAM) domain. SLP-76 co-precipitated alternately tagged SLP-76 in response to anti-CD3 ligation. Dynamic light scattering and fluorescent microscale thermophoresis of the isolated SAM domain (residues 1-78) revealed evidence of dimers and tetramers. Consistently, deletion of the SAM region eliminated SLP-76 co-precipitation of itself, concurrent with a loss of microcluster formation, nuclear factor of activated T-cells (NFAT) transcription, and interleukin-2 production in Jurkat or primary T-cells. Furthermore, the H5 α helix within the SAM domain contributed to self-association. Retention of H5 in the absence of H1-4 sufficed to support SLP-76 self-association with smaller microclusters that nevertheless enhanced anti-CD3-driven AP1/NFAT transcription and IL-2 production. By contrast, deletion of the H5 α helix impaired self-association and anti-CD3 induced AP1/NFAT transcription. Our data identified for the first time a role for the SAM domain in mediating SLP-76 self-association for T-cell function.

Complementary phosphorylation sites in the adaptor protein SLP-76 promote synergistic activation of natural killer cells.

PubMed

Kim, Hun Sik; Long, Eric O

2012-07-10

The cytotoxic effects of natural killer (NK) cells and their ability to secrete cytokines require synergistic signals from specific pairs of co-activation receptors, such as CD314 (also known as NKG2D) and CD244 (2B4), which bind to distinct ligands present on target cells. These signals are required to overcome inhibition mediated by the E3 ubiquitin ligase c-Cbl of the guanine nucleotide exchange factor Vav1, which promotes activation of NK cells. Here, we showed that the adaptor protein SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons) was required for this synergy and that distinct tyrosine residues in SLP-76 were phosphorylated by each member of a pair of synergistic receptors. Selective phosphorylation of tyrosine 113 or tyrosine 128 in SLP-76 enabled binding of SLP-76 to Vav1. Selective phosphorylation of SLP-76 at these residues was restricted to receptors that stimulated ligand-dependent target cell killing; antibody-dependent stimulation of the Fc receptor CD16 promoted phosphorylation at both sites. Knockdown and reconstitution experiments with SLP-76 mutant proteins showed the distinct role of each tyrosine in the synergistic mobilization of Ca2+, revealing an unexpected degree of selectivity in the phosphorylation of SLP-76 by NK cell co-activation receptors. Together, these data suggest that combined phosphorylation of separate tyrosine residues in SLP-76 forms the basis of synergistic NK cell activation.

SLP-76 Sterile α Motif (SAM) and Individual H5 α Helix Mediate Oligomer Formation for Microclusters and T-cell Activation*

PubMed Central

Liu, Hebin; Thaker, Youg Raj; Stagg, Loren; Schneider, Helga; Ladbury, John E.; Rudd, Christopher E.

2013-01-01

Despite the importance of the immune adaptor SLP-76 in T-cell immunity, it has been unclear whether SLP-76 directly self-associates to form higher order oligomers for T-cell activation. In this study, we show that SLP-76 self-associates in response to T-cell receptor ligation as mediated by the N-terminal sterile α motif (SAM) domain. SLP-76 co-precipitated alternately tagged SLP-76 in response to anti-CD3 ligation. Dynamic light scattering and fluorescent microscale thermophoresis of the isolated SAM domain (residues 1–78) revealed evidence of dimers and tetramers. Consistently, deletion of the SAM region eliminated SLP-76 co-precipitation of itself, concurrent with a loss of microcluster formation, nuclear factor of activated T-cells (NFAT) transcription, and interleukin-2 production in Jurkat or primary T-cells. Furthermore, the H5 α helix within the SAM domain contributed to self-association. Retention of H5 in the absence of H1–4 sufficed to support SLP-76 self-association with smaller microclusters that nevertheless enhanced anti-CD3-driven AP1/NFAT transcription and IL-2 production. By contrast, deletion of the H5 α helix impaired self-association and anti-CD3 induced AP1/NFAT transcription. Our data identified for the first time a role for the SAM domain in mediating SLP-76 self-association for T-cell function. PMID:23935094

The pipeline training program in maternal and child health: interdisciplinary preparation of undergraduate students from underrepresented groups.

PubMed

Pizur-Barnekow, Kris; Rhyner, Paula M; Lund, Shelley

2010-05-01

The Preparing Academically Successful Students in Maternal and Child Health (MCH PASS) training program provided financial support and specialized training to occupational therapy (OT) and speech-language pathology (SLP) undergraduate students from underrepresented groups in maternal and child health. The project assisted undergraduate trainees to matriculate into graduate programs in their respective fields and facilitated application into long-term maternal and child health training programs. Sixteen trainees (8 OT and 8 SLP) participated in an undergraduate training program with an emphasis on interdisciplinary teaming, family mentoring, leadership development, public health and population-based research. Instruction occurred in community and classroom settings through didactic instruction and small group discussions. Fifteen of the trainees applied to and were accepted in graduate programs in their respective fields. Two trainees applied to a long-term MCH training program. Students reported increased knowledge about programs that serve women and children, the effects of poverty on health, interdisciplinary teaming and the daily routines of families who have a child with a special health care need. The MCH PASS program provided a unique opportunity for undergraduate students in OT and SLP to learn about public health with an emphasis on maternal and child health. The specialized preparation enabled students to understand better the health concerns of underserved families whose children have special health care needs.

Monodispersed magnetite nanoparticles optimized for magnetic fluid hyperthermia: Implications in biological systems

NASA Astrophysics Data System (ADS)

Khandhar, Amit P.; Ferguson, R. Matthew; Krishnan, Kannan M.

2011-04-01

Magnetite (Fe3O4) nanoparticles (MNPs) are suitable materials for Magnetic Fluid Hyperthermia (MFH), provided their size is carefully tailored to the applied alternating magnetic field (AMF) frequency. Since aqueous synthesis routes produce polydisperse MNPs that are not tailored for any specific AMF frequency, we have developed a comprehensive protocol for synthesizing highly monodispersed MNPs in organic solvents, specifically tailored for our field conditions (f = 376 kHz, H0 = 13.4 kA/m) and subsequently transferred them to water using a biocompatible amphiphilic polymer. These MNPs (σavg. = 0.175) show truly size-dependent heating rates, indicated by a sharp peak in the specific loss power (SLP, W/g Fe3O4) for 16 nm (diameter) particles. For broader size distributions (σavg. = 0.266), we observe a 30% drop in overall SLP. Furthermore, heating measurements in biological medium [Dulbecco's modified Eagle medium (DMEM) + 10% fetal bovine serum] show a significant drop for SLP (˜30% reduction in 16 nm MNPs). Dynamic Light Scattering (DLS) measurements show particle hydrodynamic size increases over time once dispersed in DMEM, indicating particle agglomeration. Since the effective magnetic relaxation time of MNPs is determined by fractional contribution of the Neel (independent of hydrodynamic size) and Brownian (dependent on hydrodynamic size) components, we conclude that agglomeration in biological medium modifies the Brownian contribution and thus the net heating capacity of MNPs.

High-level SLP-2 expression and HER-2/neu protein expression are associated with decreased breast cancer patient survival.

PubMed

Cao, Wenfeng; Zhang, Bin; Liu, Yanxue; Li, Hongtao; Zhang, Shiwu; Fu, Li; Niu, Yun; Ning, Liansheng; Cao, Xuchen; Liu, Zhihua; Sun, Baocun

2007-09-01

There is sufficient evidence that human stomatin-like protein 2 (SLP-2) is a novel cancer-related gene. Its protein is overexpressed in many human cancers. SLP-2 can contribute to the promotion of cell growth, cell adhesion, and tumorigenesis in esophageal squamous cell carcinoma and lymph node metastasis in laryngeal squamous cell carcinoma. Immunohistochemical detection of SLP-2, estrogen and progesterone receptors, and HER-2/neu were performed on 263 cases of primary invasive breast cancer with a tissue microarray. Of 263 cases, 138 (52.5%) showed high expression of SLP-2 protein, and 125 (47.5%) showed low or absent expression. In addition, there were significant positive associations between tumor stage and size (P = .020), lymph node metastasis (P < .001), clinical stage (P < .001), distant metastasis (P = .002), and HER-2/neu protein expression (P = .037) and high-level SLP-2 expression. High-level SLP-2 expression was associated with decreased overall survival (P = .011) and was more often found in patients with tumors larger than 20 mm, lymph node metastasis, advanced clinical stage, distant metastasis, and HER-2/neu protein-positive expression. More important, lymph node metastasis, HER-2/neu-positive expression, and high-level SLP-2 expression were associated with significantly decreased survival.

On the application of the Principal Component Analysis for an efficient climate downscaling of surface wind fields

NASA Astrophysics Data System (ADS)

Chavez, Roberto; Lozano, Sergio; Correia, Pedro; Sanz-Rodrigo, Javier; Probst, Oliver

2013-04-01

With the purpose of efficiently and reliably generating long-term wind resource maps for the wind energy industry, the application and verification of a statistical methodology for the climate downscaling of wind fields at surface level is presented in this work. This procedure is based on the combination of the Monte Carlo and the Principal Component Analysis (PCA) statistical methods. Firstly the Monte Carlo method is used to create a huge number of daily-based annual time series, so called climate representative years, by the stratified sampling of a 33-year-long time series corresponding to the available period of the NCAR/NCEP global reanalysis data set (R-2). Secondly the representative years are evaluated such that the best set is chosen according to its capability to recreate the Sea Level Pressure (SLP) temporal and spatial fields from the R-2 data set. The measure of this correspondence is based on the Euclidean distance between the Empirical Orthogonal Functions (EOF) spaces generated by the PCA (Principal Component Analysis) decomposition of the SLP fields from both the long-term and the representative year data sets. The methodology was verified by comparing the selected 365-days period against a 9-year period of wind fields generated by dynamical downscaling the Global Forecast System data with the mesoscale model SKIRON for the Iberian Peninsula. These results showed that, compared to the traditional method of dynamical downscaling any random 365-days period, the error in the average wind velocity by the PCA's representative year was reduced by almost 30%. Moreover the Mean Absolute Errors (MAE) in the monthly and daily wind profiles were also reduced by almost 25% along all SKIRON grid points. These results showed also that the methodology presented maximum error values in the wind speed mean of 0.8 m/s and maximum MAE in the monthly curves of 0.7 m/s. Besides the bulk numbers, this work shows the spatial distribution of the errors across the Iberian domain and additional wind statistics such as the velocity and directional frequency. Additional repetitions were performed to prove the reliability and robustness of this kind-of statistical-dynamical downscaling method.

An Analysis of Numerical Weather Prediction of the Diabatic Rossby Vortex

DTIC Science & Technology

2014-06-01

Forecast SLP Mean and Spread ...............................................................................................148   2.   DRV02 72 Hour...ECMWF Ensemble Forecast SLP Mean and Spread ...............................................................................................149   3...DRV03 72 Hour ECMWF Ensemble Forecast SLP Mean and Spread

Cutting edge: rescue of pre-TCR but not mature TCR signaling in mice expressing membrane-targeted SLP-76.

PubMed

Bezman, Natalie A; Baker, Rebecca G; Lenox, Laurie E; Jordan, Martha S; Koretzky, Gary A

2009-05-01

SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa) organizes signaling from immunoreceptors, including the platelet collagen receptor, the pre-TCR, and the TCR, and is required for T cell development. In this study we examine a mouse in which wild-type SLP-76 is replaced with a mutant constitutively targeted to the cell membrane. Membrane-targeted SLP-76 (MTS) supports ITAM signaling in platelets and from the pre-TCR. Signaling from the mature TCR, however, is defective in MTS thymocytes, resulting in failed T cell differentiation. Defective thymic selection by MTS is not rescued by a SLP-76 mutant whose localization is restricted to the cytosol. Thus, fixed localization of SLP-76 reveals differential requirements for the subcellular localization of signaling complexes downstream of the pre-TCR vs mature TCR.

Non-linear principal component analysis applied to Lorenz models and to North Atlantic SLP

NASA Astrophysics Data System (ADS)

Russo, A.; Trigo, R. M.

2003-04-01

A non-linear generalisation of Principal Component Analysis (PCA), denoted Non-Linear Principal Component Analysis (NLPCA), is introduced and applied to the analysis of three data sets. Non-Linear Principal Component Analysis allows for the detection and characterisation of low-dimensional non-linear structure in multivariate data sets. This method is implemented using a 5-layer feed-forward neural network introduced originally in the chemical engineering literature (Kramer, 1991). The method is described and details of its implementation are addressed. Non-Linear Principal Component Analysis is first applied to a data set sampled from the Lorenz attractor (1963). It is found that the NLPCA approximations are more representative of the data than are the corresponding PCA approximations. The same methodology was applied to the less known Lorenz attractor (1984). However, the results obtained weren't as good as those attained with the famous 'Butterfly' attractor. Further work with this model is underway in order to assess if NLPCA techniques can be more representative of the data characteristics than are the corresponding PCA approximations. The application of NLPCA to relatively 'simple' dynamical systems, such as those proposed by Lorenz, is well understood. However, the application of NLPCA to a large climatic data set is much more challenging. Here, we have applied NLPCA to the sea level pressure (SLP) field for the entire North Atlantic area and the results show a slight imcrement of explained variance associated. Finally, directions for future work are presented.%}

Forecasting ENSO events: A neural network-extended EOF approach

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

Tangang, F.T.; Tang, B.; Monahan, A.H.

The authors constructed neural network models to forecast the sea surface temperature anomalies (SSTA) for three regions: Nino 4. Nino 3.5, and Nino 3, representing the western-central, the central, and the eastern-central parts of the equatorial Pacific Ocean, respectively. The inputs were the extended empirical orthogonal functions (EEOF) of the sea level pressure (SLP) field that covered the tropical Indian and Pacific Oceans and evolved for a duration of 1 yr. The EEOFs greatly reduced the size of the neural networks from those of the authors` earlier papers using EOFs. The Nino 4 region appeared to be the best forecastedmore » region, with useful skills up to a year lead time for the 1982-93 forecast period. By network pruning analysis and spectral analysis, four important inputs were identified: modes 1, 2, and 6 of the SLP EEOFs and the SSTA persistence. Mode 1 characterized the low-frequency oscillation (LFO, with 4-5-yr period), and was seen as the typical ENSO signal, while mode 2, with a period of 2-5 yr, characterized the quasi-biennial oscillation (QBO) plus the LFO. Mode 6 was dominated by decadal and interdecadal variations. Thus, forecasting ENSO required information from the QBO, and the decadal-interdecadal oscillations. The nonlinearity of the networks tended to increase with lead time and to become stronger for the eastern regions of the equatorial Pacific Ocean. 35 refs., 14 figs., 4 tabs.« less

Bragg peak prediction from quantitative proton computed tomography using different path estimates

PubMed Central

Wang, Dongxu; Mackie, T Rockwell

2015-01-01

This paper characterizes the performance of the straight-line path (SLP) and cubic spline path (CSP) as path estimates used in reconstruction of proton computed tomography (pCT). The GEANT4 Monte Carlo simulation toolkit is employed to simulate the imaging phantom and proton projections. SLP, CSP and the most-probable path (MPP) are constructed based on the entrance and exit information of each proton. The physical deviations of SLP, CSP and MPP from the real path are calculated. Using a conditional proton path probability map, the relative probability of SLP, CSP and MPP are calculated and compared. The depth dose and Bragg peak are predicted on the pCT images reconstructed using SLP, CSP, and MPP and compared with the simulation result. The root-mean-square physical deviations and the cumulative distribution of the physical deviations show that the performance of CSP is comparable to MPP while SLP is slightly inferior. About 90% of the SLP pixels and 99% of the CSP pixels lie in the 99% relative probability envelope of the MPP. Even at an imaging dose of ~0.1 mGy the proton Bragg peak for a given incoming energy can be predicted on the pCT image reconstructed using SLP, CSP, or MPP with 1 mm accuracy. This study shows that SLP and CSP, like MPP, are adequate path estimates for pCT reconstruction, and therefore can be chosen as the path estimation method for pCT reconstruction, which can aid the treatment planning and range prediction of proton radiation therapy. PMID:21212472

Seasonal Sea-Level Variations in San Francisco Bay in Response to Atmospheric Forcing, 1980

USGS Publications Warehouse

Wang, Jingyuan; Cheng, R.T.; Smith, P.C.

1997-01-01

The seasonal response of sea level in San Francisco Bay (SFB) to atmospheric forcing during 1980 is investigated. The relations between sea-level data from the Northern Reach, Central Bay and South Bay, and forcing by local wind stresses, sea level pressure (SLP), runoff and the large scale sea level pressure field are examined in detail. The analyses show that the sea-level elevations and slopes respond to the along-shore wind stress T(V) at most times of the year, and to the cross-shore wind stress T(N) during two transition periods in spring and autumn. River runoff raises the sea-level elevation during winter. It is shown that winter precipitation in the SFB area is mainly attributed to the atmospheric circulation associated with the Alcutian Low, which transports the warm, moist air into the Bay area. A multiple linear regression model is employed to estimate the independent contributions of barometric pressure and wind stress to adjusted sea level. These calculations have a simple dynamical interpretation which confirms the importance of along-shore wind to both sea level and north-south slope within the Bay.

Modeling of current characteristics of segmented Langmuir probe on DEMETER

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

Imtiaz, Nadia; Marchand, Richard; Lebreton, Jean-Pierre

We model the current characteristics of the DEMETER Segmented Langmuir probe (SLP). The probe is used to measure electron density and temperature in the ionosphere at an altitude of approximately 700 km. It is also used to measure the plasma flow velocity in the satellite frame of reference. The probe is partitioned into seven collectors: six electrically insulated spherical segments and a guard electrode (the rest of the sphere and the small post). Comparisons are made between the predictions of the model and DEMETER measurements for actual ionospheric plasma conditions encountered along the satellite orbit. Segment characteristics are computed numericallymore » with PTetra, a three-dimensional particle in cell simulation code. In PTetra, space is discretized with an unstructured tetrahedral mesh, thus, enabling a good representation of the probe geometry. The model also accounts for several physical effects of importance in the interaction of spacecraft with the space environment. These include satellite charging, photoelectron, and secondary electron emissions. The model is electrostatic, but it accounts for the presence of a uniform background magnetic field. PTetra simulation results show different characteristics for the different probe segments. The current collected by each segment depends on its orientation with respect to the ram direction, the plasma composition, the magnitude, and the orientation of the magnetic field. It is observed that the presence of light H{sup +} ions leads to a significant increase in the ion current branch of the I-V curves of the negatively polarized SLP. The effect of the magnetic field is demonstrated by varying its magnitude and direction with respect to the reference magnetic field. It is found that the magnetic field appreciably affects the electron current branch of the I-V curves of certain segments on the SLP, whereas the ion current branch remains almost unaffected. PTetra simulations are validated by comparing the computed characteristics and their angular anisotropy with the DEMETER measurements, as simulation results are found to be in good agreement with the measurements.« less

Human SLP-65 isoforms contribute differently to activation and apoptosis of B lymphocytes.

PubMed

Grabbe, Annika; Wienands, Jürgen

2006-12-01

The SH2 domain-containing leukocyte adaptor protein of 65 kDa (SLP-65) is the key effector for signaling downstream of the B-cell antigen receptor (BCR). SLP-65 controls not only B lymphopoiesis and humoral immunity but also possesses a yet poorly defined tumor suppressor activity that is lost in many cases of acute lymphoblastic leukemia. We found that the 2 isoforms of human SLP-65 are differentially involved in positive and negative B-cell signaling. Reconstitution experiments revealed that an atypical SH3 domain-binding motif, which is present in the long but not in the short SLP-65 isoform, mediates association to Grb2 and suppresses activation of mitogen-activated protein kinases p38 and JNK as well as up-regulation of c-Fos expression. In turn, the short isoform activates not only AP1-driven but also NF-kappaB-driven gene transcription more potently than the long isoform. Conversely, the long rather than the short SLP-65 isoform promotes BCR-induced B-cell apoptosis. Our data further delineate the structural requirements of positive and negative SLP-65 signal transduction in normal and neoplastic cells.

Functional hierarchy of the N-terminal tyrosines of SLP-76.

PubMed

Jordan, Martha S; Sadler, Jeffrey; Austin, Jessica E; Finkelstein, Lisa D; Singer, Andrew L; Schwartzberg, Pamela L; Koretzky, Gary A

2006-02-15

The adaptor protein Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) plays a central role in T cell activation and T cell development. SLP-76 has three functional modules: an acidic domain with three key tyrosines, a central proline-rich domain, and a C-terminal Src homology 2 domain. Of these, mutation of the three N-terminal tyrosines (Y112, Y128, and Y145) results in the most profound effects on T cell development and function. Y112 and Y128 associate with Vav and Nck, two proteins shown to be important for TCR-induced phosphorylation of proximal signaling substrates, Ca(2+) flux, and actin reorganization. Y145 has been shown to be important for optimal association of SLP-76 with inducible tyrosine kinase, a key regulator of T cell function. To investigate further the role of the phosphorylatable tyrosines of SLP-76 in TCR signaling, cell lines and primary T cells expressing SLP-76 with mutations in individual or paired tyrosine residues were analyzed. These studies show that Tyr(145) of SLP-76 is the most critical tyrosine for both T cell function in vitro and T cell development in vivo.

Treatment of Social Competence in Military Veterans, Service Members, and Civilians with Traumatic Brain Injury

DTIC Science & Technology

2015-08-01

Morey, MA, CCC- SLP 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING...Competence Problems after Traumatic Brain Injury: a Civilian and Military/Veteran Cohort Authors: Clare Morey, MA, CCC- SLP Lenore Hawley, MSSW, LCSW...Jody Newman, MA, CCC- SLP Angela Philippus, BA Cynthia Braden, MA, CCC- SLP Melissa Hofmann, MSPT Cynthia Harrison-Felix, PhD Please direct all

Prevention and Mitigation of Acute Radiation Syndrome in Mice by Synthetic Lipopeptide Agonists of Toll-Like Receptor 2 (TLR2)

PubMed Central

Shakhov, Alexander N.; Singh, Vijay K.; Bone, Frederick; Cheney, Alec; Kononov, Yevgeniy; Krasnov, Peter; Bratanova-Toshkova, Troitza K.; Shakhova, Vera V.; Young, Jason; Weil, Michael M.; Panoskaltsis-Mortari, Angela; Orschell, Christie M.; Baker, Patricia S.; Gudkov, Andrei; Feinstein, Elena

2012-01-01

Bacterial lipoproteins (BLP) induce innate immune responses in mammals by activating heterodimeric receptor complexes containing Toll-like receptor 2 (TLR2). TLR2 signaling results in nuclear factor-kappaB (NF-κB)-dependent upregulation of anti-apoptotic factors, anti-oxidants and cytokines, all of which have been implicated in radiation protection. Here we demonstrate that synthetic lipopeptides (sLP) that mimic the structure of naturally occurring mycoplasmal BLP significantly increase mouse survival following lethal total body irradiation (TBI) when administered between 48 hours before and 24 hours after irradiation. The TBI dose ranges against which sLP are effective indicate that sLP primarily impact the hematopoietic (HP) component of acute radiation syndrome. Indeed, sLP treatment accelerated recovery of bone marrow (BM) and spleen cellularity and ameliorated thrombocytopenia of irradiated mice. sLP did not improve survival of irradiated TLR2-knockout mice, confirming that sLP-mediated radioprotection requires TLR2. However, sLP was radioprotective in chimeric mice containing TLR2-null BM on a wild type background, indicating that radioprotection of the HP system by sLP is, at least in part, indirect and initiated in non-BM cells. sLP injection resulted in strong transient induction of multiple cytokines with known roles in hematopoiesis, including granulocyte colony-stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin-6 (IL-6). sLP-induced cytokines, particularly G-CSF, are likely mediators of the radioprotective/mitigative activity of sLP. This study illustrates the strong potential of LP-based TLR2 agonists for anti-radiation prophylaxis and therapy in defense and medical scenarios. PMID:22479357

Bruton's tyrosine kinase and SLP-65 regulate pre-B cell differentiation and the induction of Ig light chain gene rearrangement.

PubMed

Kersseboom, Rogier; Ta, Van B T; Zijlstra, A J Esther; Middendorp, Sabine; Jumaa, Hassan; van Loo, Pieter Fokko; Hendriks, Rudolf W

2006-04-15

Bruton's tyrosine kinase (Btk) and the adapter protein SLP-65 (Src homology 2 domain-containing leukocyte-specific phosphoprotein of 65 kDa) transmit precursor BCR (pre-BCR) signals that are essential for efficient developmental progression of large cycling into small resting pre-B cells. We show that Btk- and SLP-65-deficient pre-B cells have a specific defect in Ig lambda L chain germline transcription. In Btk/SLP-65 double-deficient pre-B cells, both kappa and lambda germline transcripts are severely reduced. Although these observations point to an important role for Btk and SLP-65 in the initiation of L chain gene rearrangement, the possibility remained that these signaling molecules are only required for termination of pre-B cell proliferation or for pre-B cell survival, whereby differentiation and L chain rearrangement is subsequently initiated in a Btk/SLP-65-independent fashion. Because transgenic expression of the antiapoptotic protein Bcl-2 did not rescue the developmental arrest of Btk/SLP-65 double-deficient pre-B cells, we conclude that defective L chain opening in Btk/SLP-65-deficient small resting pre-B cells is not due to their reduced survival. Next, we analyzed transgenic mice expressing the constitutively active Btk mutant E41K. The expression of E41K-Btk in Ig H chain-negative pro-B cells induced 1) surface marker changes that signify cellular differentiation, including down-regulation of surrogate L chain and up-regulation of CD2, CD25, and MHC class II; and 2) premature rearrangement and expression of kappa and lambda light chains. These findings demonstrate that Btk and SLP-65 transmit signals that induce cellular maturation and Ig L chain rearrangement independently of their role in termination of pre-B cell expansion.

SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila.

PubMed

Zanon, Alessandra; Kalvakuri, Sreehari; Rakovic, Aleksandar; Foco, Luisa; Guida, Marianna; Schwienbacher, Christine; Serafin, Alice; Rudolph, Franziska; Trilck, Michaela; Grünewald, Anne; Stanslowsky, Nancy; Wegner, Florian; Giorgio, Valentina; Lavdas, Alexandros A; Bodmer, Rolf; Pramstaller, Peter P; Klein, Christine; Hicks, Andrew A; Pichler, Irene; Seibler, Philip

2017-07-01

Mutations in the Parkin gene (PARK2) have been linked to a recessive form of Parkinson's disease (PD) characterized by the loss of dopaminergic neurons in the substantia nigra. Deficiencies of mitochondrial respiratory chain complex I activity have been observed in the substantia nigra of PD patients, and loss of Parkin results in the reduction of complex I activity shown in various cell and animal models. Using co-immunoprecipitation and proximity ligation assays on endogenous proteins, we demonstrate that Parkin interacts with mitochondrial Stomatin-like protein 2 (SLP-2), which also binds the mitochondrial lipid cardiolipin and functions in the assembly of respiratory chain proteins. SH-SY5Y cells with a stable knockdown of Parkin or SLP-2, as well as induced pluripotent stem cell-derived neurons from Parkin mutation carriers, showed decreased complex I activity and altered mitochondrial network morphology. Importantly, induced expression of SLP-2 corrected for these mitochondrial alterations caused by reduced Parkin function in these cells. In-vivo Drosophila studies showed a genetic interaction of Parkin and SLP-2, and further, tissue-specific or global overexpression of SLP-2 transgenes rescued parkin mutant phenotypes, in particular loss of dopaminergic neurons, mitochondrial network structure, reduced ATP production, and flight and motor dysfunction. The physical and genetic interaction between Parkin and SLP-2 and the compensatory potential of SLP-2 suggest a functional epistatic relationship to Parkin and a protective role of SLP-2 in neurons. This finding places further emphasis on the significance of Parkin for the maintenance of mitochondrial function in neurons and provides a novel target for therapeutic strategies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Structural basis for recognition of the T cell adaptor protein SLP-76 by the SH3 domain of phospholipase Cgamma1.

PubMed

Deng, Lu; Velikovsky, C Alejandro; Swaminathan, Chittoor P; Cho, Sangwoo; Mariuzza, Roy A

2005-09-09

The enzyme phospholipase Cgamma1 (PLCgamma1) is essential for T cell signaling and activation. Following T cell receptor ligation, PLCgamma1 interacts through its SH2 and SH3 domains with the adaptors LAT and SLP-76, respectively, to form a multiprotein signaling complex that leads to activation of PLCgamma1 by Syk tyrosine kinases. To identify the binding site for PLCgamma1 in SLP-76, we used isothermal titration calorimetry to measure affinities for the interaction of PLCgamma1-SH3 with a set of overlapping peptides spanning the central proline-rich region of SLP-76. PLCgamma1-SH3 bound with high specificity to the SLP-76 motif 186PPVPPQRP193, which represents the minimal binding site. To understand the basis for selective recognition, we determined the crystal structures of PLCgamma1-SH3 in free form, and bound to a 10-mer peptide containing this site, to resolutions of 1.60 A and 1.81 A, respectively. The structures reveal that several key contacting residues of the SH3 shift toward the SLP-76 peptide upon complex formation, optimizing the fit and strengthening hydrophobic interactions. Selectivity results mainly from strict shape complementarity between protein and peptide, rather than sequence-specific hydrogen bonding. In addition, Pro193 of SLP-76 assists in positioning Arg192 into the compass pocket of PLCgamma1-SH3, which coordinates the compass residue through an unusual aspartate. The PLCgamma1-SH3/SLP-76 structure provides insights into ligand binding by SH3 domains related to PLCgamma1-SH3, as well as into recognition by PLCgamma1 of signaling partners other than SLP-76.

Impaired thymic selection in mice expressing altered levels of the SLP-76 adaptor protein.

PubMed

Ramsey, Kimberley; Luckashenak, Nancy; Koretzky, Gary A; Clements, James L

2008-02-01

Intracellular signaling initiated by ligation of the TCR influences cell fate at multiple points during the lifespan of a T cell. This is especially evident during thymic selection, where the nature of TCR-dependent signaling helps to establish a MHC-restricted, self-tolerant T cell repertoire. The Src homology 2 domain-containing leukocyte-specific phosphoprotein of 76 kDa (SLP-76) adaptor protein is a required intermediate in multiple signaling pathways triggered by TCR engagement, several of which have been implicated in dictating the outcome of thymic selection (e.g., intracellular calcium flux and activation of ERK family MAPKs). To determine if thymocyte maturation and selection at later stages of development are sensitive to perturbations in SLP-76 levels, we analyzed these crucial events using several transgenic (Tg) lines of mice expressing altered levels of SLP-76 in the thymus. In Tg mice expressing low levels of SLP-76 in preselection thymocytes, the CD4:CD8 ratio in the thymus and spleen was skewed in a manner consistent with impaired selection and/or maturation of CD4+ thymocytes. Low SLP-76 expression also correlated with reduced CD5 expression on immature thymocytes, consistent with reduced TCR signaling potential. In contrast, reconstitution of SLP-76 at higher levels resulted in normal thymic CD5 expression and CD4:CD8 ratios in the thymus and periphery. It is curious that thymic deletion of TCR-Tg (HY) thymocytes was markedly impaired in both lines of Tg-reconstituted SLP-76-/- mice. Studies using chimeric mice indicate that the defect in deletion of HY+ thymocytes is intrinsic to the developing thymocyte, suggesting that maintenance of sufficient SLP-76 expression from the endogenous locus is a key element in the selection process.

SLP-76 is required for high-affinity IgE receptor- and IL-3 receptor-mediated activation of basophils.

PubMed

Hidano, Shinya; Kitamura, Daisuke; Kumar, Lalit; Geha, Raif S; Goitsuka, Ryo

2012-11-01

Basophils have been reported to play a critical role in allergic inflammation by secreting IL-4 in response to IL-3 or high-affinity IgE receptor (FcεRI)-cross-linking. However, the signaling pathways downstream of FcεRI and the IL-3 receptor in basophils have yet to be determined. In the present study, we used mice deficient in SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76kDa) to demonstrate critical functions of this adaptor molecule in transducing FcεRI- and IL-3 receptor-mediated signals that induce basophil activation. Although SLP-76 was dispensable for in vivo differentiation, as well as IL-3-induced in vitro proliferation of basophils, IL-4 production induced by both stimuli was completely ablated by SLP-76 deficiency. Biochemical analyses revealed that IL-3-induced phosphorylation of phospholipase C (PLC) γ2 and Akt, but not STAT5, was severely reduced in SLP-76-deficient basophils, whereas FcεRI cross-linking phosphorylation of PLCγ2, but not Akt, was abrogated by SLP-76 deficiency, suggesting important differences in the requirement of SLP-76 for Akt activation between FcεRI- and IL-3 receptor-mediated signaling pathways in basophils. Because IL-3-induced IL-4 production was sensitive to calcineurin inhibitors and an intracellular calcium chelator, in addition to PI3K inhibitors, SLP-76 appears to regulate FcεRI- and IL-3 receptor-induced IL-4 production via mediating PLCγ2 activation in basophils. Taken together, these findings indicate that SLP-76 is an essential signaling component for basophil activation downstream of both FcεRI and the IL-3 receptor.

Prevention and mitigation of acute radiation syndrome in mice by synthetic lipopeptide agonists of Toll-like receptor 2 (TLR2).

PubMed

Shakhov, Alexander N; Singh, Vijay K; Bone, Frederick; Cheney, Alec; Kononov, Yevgeniy; Krasnov, Peter; Bratanova-Toshkova, Troitza K; Shakhova, Vera V; Young, Jason; Weil, Michael M; Panoskaltsis-Mortari, Angela; Orschell, Christie M; Baker, Patricia S; Gudkov, Andrei; Feinstein, Elena

2012-01-01

Bacterial lipoproteins (BLP) induce innate immune responses in mammals by activating heterodimeric receptor complexes containing Toll-like receptor 2 (TLR2). TLR2 signaling results in nuclear factor-kappaB (NF-κB)-dependent upregulation of anti-apoptotic factors, anti-oxidants and cytokines, all of which have been implicated in radiation protection. Here we demonstrate that synthetic lipopeptides (sLP) that mimic the structure of naturally occurring mycoplasmal BLP significantly increase mouse survival following lethal total body irradiation (TBI) when administered between 48 hours before and 24 hours after irradiation. The TBI dose ranges against which sLP are effective indicate that sLP primarily impact the hematopoietic (HP) component of acute radiation syndrome. Indeed, sLP treatment accelerated recovery of bone marrow (BM) and spleen cellularity and ameliorated thrombocytopenia of irradiated mice. sLP did not improve survival of irradiated TLR2-knockout mice, confirming that sLP-mediated radioprotection requires TLR2. However, sLP was radioprotective in chimeric mice containing TLR2-null BM on a wild type background, indicating that radioprotection of the HP system by sLP is, at least in part, indirect and initiated in non-BM cells. sLP injection resulted in strong transient induction of multiple cytokines with known roles in hematopoiesis, including granulocyte colony-stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin-6 (IL-6). sLP-induced cytokines, particularly G-CSF, are likely mediators of the radioprotective/mitigative activity of sLP. This study illustrates the strong potential of LP-based TLR2 agonists for anti-radiation prophylaxis and therapy in defense and medical scenarios.

Biomechanical Analysis of Locust Jumping in a Physically Realistic Virtual Environment

NASA Astrophysics Data System (ADS)

Cofer, David; Cymbalyuk, Gennady; Heitler, William; Edwards, Donald

2008-03-01

The biomechanical and neural components that underlie locust jumping have been extensively studied. Previous research suggested that jump energy is stored primarily in the extensor apodeme, and in a band of cuticle called the semi-lunar process (SLP). As it has thus far proven impossible to experimentally alter the SLP without rendering a locust unable to jump, it has not been possible to test whether the energy stored in the SLP has a significant impact on the jump. To address problems such as this we have developed a software toolkit, AnimatLab, which allows researchers to build and test virtual organisms. We used this software to build a virtual locust, and then asked how the SLP is utilized during jumping. The results show that without the SLP the jump distance was reduced by almost half. Further, the simulations were also able to show that loss of the SLP had a significant impact on the final phase of the jump. We are currently working on postural control mechanisms for targeted jumping in locust.

Insights into the Membrane Interactions of the Saposin-Like Proteins Na-SLP-1 and Ac-SLP-1 from Human and Dog Hookworm

PubMed Central

Willis, Charlene; Wang, Conan K.; Osman, Asiah; Simon, Anne; Pickering, Darren; Mulvenna, Jason; Riboldi-Tunicliffe, Alan; Jones, Malcolm K.; Loukas, Alex; Hofmann, Andreas

2011-01-01

Saposin-like proteins (SAPLIPs) from soil-transmitted helminths play pivotal roles in host-pathogen interactions and have a high potential as targets for vaccination against parasitic diseases. We have identified two non-orthologous SAPLIPs from human and dog hookworm, Na-SLP-1 and Ac-SLP-1, and solved their three-dimensional crystal structures. Both proteins share the property of membrane binding as monitored by liposome co-pelleting assays and monolayer adsorption. Neither SAPLIP displayed any significant haemolytic or bactericidal activity. Based on the structural information, as well as the results from monolayer adsorption, we propose models of membrane interactions for both SAPLIPs. Initial membrane contact of the monomeric Na-SLP-1 is most likely by electrostatic interactions between the membrane surface and a prominent basic surface patch. In case of the dimeric Ac-SLP-1, membrane interactions are most likely initiated by a unique tryptophan residue that has previously been implicated in membrane interactions in other SAPLIPs. PMID:21991310

Insights into the membrane interactions of the saposin-like proteins Na-SLP-1 and Ac-SLP-1 from human and dog hookworm.

PubMed

Willis, Charlene; Wang, Conan K; Osman, Asiah; Simon, Anne; Pickering, Darren; Mulvenna, Jason; Riboldi-Tunicliffe, Alan; Jones, Malcolm K; Loukas, Alex; Hofmann, Andreas

2011-01-01

Saposin-like proteins (SAPLIPs) from soil-transmitted helminths play pivotal roles in host-pathogen interactions and have a high potential as targets for vaccination against parasitic diseases. We have identified two non-orthologous SAPLIPs from human and dog hookworm, Na-SLP-1 and Ac-SLP-1, and solved their three-dimensional crystal structures. Both proteins share the property of membrane binding as monitored by liposome co-pelleting assays and monolayer adsorption. Neither SAPLIP displayed any significant haemolytic or bactericidal activity. Based on the structural information, as well as the results from monolayer adsorption, we propose models of membrane interactions for both SAPLIPs. Initial membrane contact of the monomeric Na-SLP-1 is most likely by electrostatic interactions between the membrane surface and a prominent basic surface patch. In case of the dimeric Ac-SLP-1, membrane interactions are most likely initiated by a unique tryptophan residue that has previously been implicated in membrane interactions in other SAPLIPs.

Conditional deletion of SLP-76 in mature T cells abrogates peripheral immune responses1

PubMed Central

Wu, Gregory F.; Corbo, Evann; Schmidt, Michelle; Smith-Garvin, Jennifer E.; Riese, Matthew J.; Jordan, Martha S.; Laufer, Terri M.; Brown, Eric J.; Maltzman, Jonathan S.

2011-01-01

SUMMARY The adaptor protein Src homology 2 domain-containing leukocyte-specific protein of 76 kDa (SLP-76) is central to the organization of intracellular signaling downstream of the T cell receptor (TCR). Evaluation of its role in mature, primary T cells has been hampered by developmental defects that occur in the absence of wild-type SLP-76 protein in thymocytes. Following tamoxifen-regulated conditional deletion of SLP-76, mature, antigen-inexperienced T cells maintain normal TCR surface expression but fail to transduce TCR generated signals. Conditionally deficient T cells fail to proliferate in response to antigenic stimulation or a lymphopenic environment. Mice with induced deletion of SLP-76 are resistant to induction of the CD4+ T cell mediated autoimmune disease experimental autoimmune encephalomyelitis. Our findings demonstrate the critical role of SLP-76-mediated signaling in initiating T cell-directed immune responses both in vitro and in vivo and highlight the ability to analyze signaling processes in mature T cells in the absence of developmental defects. PMID:21469089

Conditional deletion reveals a cell-autonomous requirement of SLP-76 for thymocyte selection.

PubMed

Maltzman, Jonathan S; Kovoor, Lisa; Clements, James L; Koretzky, Gary A

2005-10-03

The SH2 domain containing leukocyte phosphoprotein of 76 kD (SLP-76) is critical for pre-TCR-mediated maturation to the CD4+CD8+ double positive (DP) stage in the thymus. The absolute block in SLP-76null mice at the CD4-CD8-CD44-CD25+ (double-negative 3, DN3) stage has hindered our understanding of the role of this adaptor in alphabeta TCR-mediated signal transduction in primary thymocytes and peripheral T lymphocytes. To evaluate the requirements for SLP-76 in these events, we used a cre-loxP approach to generate mice that conditionally delete SLP-76 after the DN3 checkpoint. These mice develop DP thymocytes that express the alphabeta TCR on the surface, but lack SLP-76 at the genomic DNA and protein levels. The DP compartment has reduced cellularity in young mice and fails to undergo positive selection to CD4+ or CD8+ single positive (SP) cells in vivo or activation-induced cell death in vitro. A small number of CD4+SP thymocytes are generated, but these cells fail to flux calcium in response to an alphabeta TCR-generated signal. Peripheral T cells are reduced in number, lack SLP-76 protein, and have an abnormal surface phenotype. These studies show for the first time that SLP-76 is required for signal transduction through the mature alphabeta TCR in primary cells of the T lineage.

Surface active stabilizer Tyloxapol in colloidal dispersions exerts cytostatic effects and apoptotic dismissal of cells

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

Kristl, Julijana; Teskac, Karmen; Milek, Miha

Solid lipid nanoparticles (SLN) have been praised for their advantageous drug delivery properties such as biocompatibility, controlled release and passive drug targeting. However, the cytotoxicity of SLN and their ingredients, especially over a longer time period, has not been investigated in detail. We examined the critical issues regarding the use of a surface active stabilizer Tyloxapol (Tyl) for the preparation of solid lipid particles (SLP) and their effects on cellular functions and viability. SLP composed of behenate, phospholipids and a stabilizer, Tyloxapol or Lutrol (Lut), were prepared by the lipid melt method, labeled with a fluorescent dye and tested onmore » Jurkat or HEK293 cells. The nano-sized particles were rapidly internalized and exhibited cytoplasmic localization. Incubation of cells with SLP-Tyl resulted in a dose- and time-dependent cytostatic effect, and also caused moderate and delayed cytotoxicity. Tyloxapol solution or SLP-Tyl dispersion caused the detachment of HEK293 cells, a decrease in cell proliferation and alterations in cellular morphology. Cell cycle analysis revealed that, while the unfavourable effects of SLP-Tyl and Tyloxapol solution are similar initially, longer incubation results in partial recovery of cells incubated with the dispersion of SLP-Tyl, whereas the presence of Tyloxapol solution induces apoptotic cell death. These findings indicate that Tyloxapol is an unfavourable stabilizer of SLP used for intracellular delivery and reinforce the role of stabilizers in a design of SLP with minimal cytotoxic properties.« less

Complementary Phosphorylation Sites in the Adaptor Protein SLP-76 Promote Synergistic Activation of Natural Killer Cells

PubMed Central

Kim, Hun Sik; Long, Eric O.

2013-01-01

The cytotoxic effects of natural killer (NK) cells and their ability to secrete cytokines require the induction of synergistic signals from co-activation receptors, such as CD314 (NKG2D) and CD244 (2B4), which bind to ligands expressed on target cells. Synergy is required to overcome inhibition of the guanine nucleotide exchange factor (GEF) Vav1, a central regulator of NK cell activation, by the E3 ubiquitin ligase c-Cbl. However, the molecular basis for this synergy is unknown. Here, we showed that the adaptor protein Src homology 2 (SH2) domain–containing leukocyte phosphoprotein of 76 kD (SLP-76) was required for this synergy, and that distinct tyrosine residues in SLP-76 were phosphorylated by each receptor of a synergistic pair. Selective phosphorylation of tyrosine 113 or tyrosine 128 in SLP-76, each of which enables binding of SLP-76 to Vav1, was unique to receptors that stimulate ligand-dependent target cell killing, because antibody-dependent stimulation by Fc receptor CD16 promoted phosphorylation at both sites. Knockdown and reconstitution experiments with SLP-76 showed the distinct role of each tyrosine in the synergistic mobilization of Ca2+, revealing an unexpected degree of selectivity in the phosphorylation of SLP-76 by NK cell co-activation receptors. Together, these data suggest that complementation of separate phospho-tyrosine targets in SLP-76 forms the basis of synergistic NK cell activation. PMID:22786724

Stomatin-Like Protein 2 Is Required for In Vivo Mitochondrial Respiratory Chain Supercomplex Formation and Optimal Cell Function

PubMed Central

Mitsopoulos, Panagiotis; Chang, Yu-Han; Wai, Timothy; König, Tim; Dunn, Stanley D.; Langer, Thomas

2015-01-01

Stomatin-like protein 2 (SLP-2) is a mainly mitochondrial protein that is widely expressed and is highly conserved across evolution. We have previously shown that SLP-2 binds the mitochondrial lipid cardiolipin and interacts with prohibitin-1 and -2 to form specialized membrane microdomains in the mitochondrial inner membrane, which are associated with optimal mitochondrial respiration. To determine how SLP-2 functions, we performed bioenergetic analysis of primary T cells from T cell-selective Slp-2 knockout mice under conditions that forced energy production to come almost exclusively from oxidative phosphorylation. These cells had a phenotype characterized by increased uncoupled mitochondrial respiration and decreased mitochondrial membrane potential. Since formation of mitochondrial respiratory chain supercomplexes (RCS) may correlate with more efficient electron transfer during oxidative phosphorylation, we hypothesized that the defect in mitochondrial respiration in SLP-2-deficient T cells was due to deficient RCS formation. We found that in the absence of SLP-2, T cells had decreased levels and activities of complex I-III2 and I-III2-IV1-3 RCS but no defects in assembly of individual respiratory complexes. Impaired RCS formation in SLP-2-deficient T cells correlated with significantly delayed T cell proliferation in response to activation under conditions of limiting glycolysis. Altogether, our findings identify SLP-2 as a key regulator of the formation of RCS in vivo and show that these supercomplexes are required for optimal cell function. PMID:25776552

Dynamical adjustment of Scandinavian glacier mass-balance time series

NASA Astrophysics Data System (ADS)

Bonan, D.; Christian, J. E.; Christianson, K. A.

2017-12-01

Glacier mass wastage is often cited as one of the most visible manifestations of anthropogenic climate change. Annual glacier mass-balance is related to local climate and atmospheric circulation, as it is defined as the yearly sum of accumulation and ablation—processes that are strongly influenced by year-to-year fluctuations in precipitation and temperature. Glacier response to a climatic trend can, however, be masked by internal variability in atmospheric circulation, and by non-climatic factors (such as topographic control, wind deposition, and incident solar radiation). Thus, unambiguous attribution of a negative glacier mass-balance trend to anthropogenic forcing remains challenging. Maritime glacier mass-balance records may be especially difficult to interpret due to the high winter balances from decadal-scale climate oscillations and the relatively short time series. Here we examine the influence of climate and atmospheric circulation variability on 14 Norwegian glaciers that span 20° of latitude, from southern Norway to Svalbard. We use dynamical adjustment—a statistical method based on partial least squares regression—to identify the components of variability within the mass-balance records that are associated with the time-varying sea level pressure (SLP) and sea surface temperature (SST) fields. We find that 30-50% of the variance in the winter mass-balance records of the glaciers in southern Norway is explained by using sea level pressure as a predictor. The leading SLP predictor pattern mimics the spatial signature of the North Atlantic Oscillation (NAO), indicating that winter balance is strongly influenced by the NAO. Moreover, the adjusted mass-balance records indicate a geographic trend: the southern Norwegian glaciers have significant negative trends in the summer balance that remain negative after adjustment, while the more northern glaciers have negative winter balance trends that only become significant after adjustment. We look into anthropogenic warming to explain the trends after dynamical adjustment.

Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling.

PubMed

Bertozzi, Cara C; Schmaier, Alec A; Mericko, Patricia; Hess, Paul R; Zou, Zhiying; Chen, Mei; Chen, Chiu-Yu; Xu, Bin; Lu, Min-min; Zhou, Diane; Sebzda, Eric; Santore, Matthew T; Merianos, Demetri J; Stadtfeld, Matthias; Flake, Alan W; Graf, Thomas; Skoda, Radek; Maltzman, Jonathan S; Koretzky, Gary A; Kahn, Mark L

2010-07-29

Although platelets appear by embryonic day 10.5 in the developing mouse, an embryonic role for these cells has not been identified. The SYK-SLP-76 signaling pathway is required in blood cells to regulate embryonic blood-lymphatic vascular separation, but the cell type and molecular mechanism underlying this regulatory pathway are not known. In the present study we demonstrate that platelets regulate lymphatic vascular development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2 (CLEC-2) receptors. PODOPLANIN (PDPN), a transmembrane protein expressed on the surface of lymphatic endothelial cells, is required in nonhematopoietic cells for blood-lymphatic separation. Genetic loss of the PDPN receptor CLEC-2 ablates PDPN binding by platelets and confers embryonic lymphatic vascular defects like those seen in animals lacking PDPN or SLP-76. Platelet factor 4-Cre-mediated deletion of Slp-76 is sufficient to confer lymphatic vascular defects, identifying platelets as the cell type in which SLP-76 signaling is required to regulate lymphatic vascular development. Consistent with these genetic findings, we observe SLP-76-dependent platelet aggregate formation on the surface of lymphatic endothelial cells in vivo and ex vivo. These studies identify a nonhemostatic pathway in which platelet CLEC-2 receptors bind lymphatic endothelial PDPN and activate SLP-76 signaling to regulate embryonic vascular development.

Service lifetime prediction for encapsulated photovoltaic cells/minimodules

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

Czanderna, A.W.; Jorgensen, G.J.

The overall purposes of this paper are to elucidate the crucial importance of predicting the service lifetime (SLP) for photovoltaics (PV) modules and to present an outline for developing a SLP methodology for encapsulated PV cells and minimodules. The specific objectives are (a) to illustrate the generic nature of SLP for several types of solar energy conversion or conversion devices, (b) to summarize the major durability issues concerned with these devices, (c) to justify using SLP in the triad of cost, performance, and durability instead of only durability, (d) to define and explain the seven major elements that comprise amore » generic SLP methodology, (e) to provide background about implementing the SLP methodology for PV cells and minimodules including the complexity of the encapsulation problems, (f) to summarize briefly the past focus of our task for improving and/or replacing ethylene vinyl acetate (EVA) as a PV pottant, and (g) to provide an outline of our present and future studies using encapsulated PV cells and minimodules for improving the encapsulation of PV cells and predicting a service lifetime for them using the SLP methodology outlined in objective (d). By using this methodology, our major conclusion is that predicting the service lifetime of PV cells and minimodules is possible. {copyright} {ital 1997 American Institute of Physics.}« less

Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells

PubMed Central

Sela, Meirav; Bogin, Yaron; Beach, Dvora; Oellerich, Thomas; Lehne, Johanna; Smith-Garvin, Jennifer E; Okumura, Mariko; Starosvetsky, Elina; Kosoff, Rachelle; Libman, Evgeny; Koretzky, Gary; Kambayashi, Taku; Urlaub, Henning; Wienands, Jürgen; Chernoff, Jonathan; Yablonski, Deborah

2011-01-01

Cooperatively assembled signalling complexes, nucleated by adaptor proteins, integrate information from surface receptors to determine cellular outcomes. In T and mast cells, antigen receptor signalling is nucleated by three adaptors: SLP-76, Gads and LAT. Three well-characterized SLP-76 tyrosine phosphorylation sites recruit key components, including a Tec-family tyrosine kinase, Itk. We identified a fourth, evolutionarily conserved SLP-76 phosphorylation site, Y173, which was phosphorylated upon T-cell receptor stimulation in primary murine and Jurkat T cells. Y173 was required for antigen receptor-induced phosphorylation of phospholipase C-γ1 (PLC-γ1) in both T and mast cells, and for consequent downstream events, including activation of the IL-2 promoter in T cells, and degranulation and IL-6 production in mast cells. In intact cells, Y173 phosphorylation depended on three, ZAP-70-targeted tyrosines at the N-terminus of SLP-76 that recruit and activate Itk, a kinase that selectively phosphorylated Y173 in vitro. These data suggest a sequential mechanism whereby ZAP-70-dependent priming of SLP-76 at three N-terminal sites triggers reciprocal regulatory interactions between Itk and SLP-76, which are ultimately required to couple active Itk to its substrate, PLC-γ1. PMID:21725281

In vivo disruption of T cell development by expression of a dominant-negative polypeptide designed to abolish the SLP-76/Gads interaction.

PubMed

Jordan, Martha S; Maltzman, Jonathan S; Kliche, Stefanie; Shabason, Jacob; Smith, Jennifer E; Obstfeld, Amrom; Schraven, Burkhart; Koretzky, Gary A

2007-10-01

Multi-molecular complexes nucleated by adaptor proteins play a central role in signal transduction. In T cells, one central axis consists of the assembly of several signaling proteins linked together by the adaptors linker of activated T cells (LAT), Src homology 2 domain-containing leukocyte-specific phosphoprotein of 76 kDa (SLP-76), and Grb2-related adaptor downstream of Shc (Gads). Each of these adaptors has been shown to be important for normal T cell development, and their proper sub-cellular localization is critical for optimal function in cell lines. We previously demonstrated in Jurkat T cells and a rat basophilic leukemic cell line that expression of a 50-amino acid polypeptide identical to the site on SLP-76 that binds to Gads blocks proper localization of SLP-76 and SLP-76-dependent signaling events. Here we extend these studies to investigate the ability of this polypeptide to inhibit TCR-induced integrin activity in Jurkat cells and to inhibit in vivo thymocyte development and primary T cell function. These data provide evidence for the in vivo function of a dominant-negative peptide based upon the biology of SLP-76 action and suggest the possibility of therapeutic potential of targeting the SLP-76/Gads interaction.

Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells.

PubMed

Sela, Meirav; Bogin, Yaron; Beach, Dvora; Oellerich, Thomas; Lehne, Johanna; Smith-Garvin, Jennifer E; Okumura, Mariko; Starosvetsky, Elina; Kosoff, Rachelle; Libman, Evgeny; Koretzky, Gary; Kambayashi, Taku; Urlaub, Henning; Wienands, Jürgen; Chernoff, Jonathan; Yablonski, Deborah

2011-07-01

Cooperatively assembled signalling complexes, nucleated by adaptor proteins, integrate information from surface receptors to determine cellular outcomes. In T and mast cells, antigen receptor signalling is nucleated by three adaptors: SLP-76, Gads and LAT. Three well-characterized SLP-76 tyrosine phosphorylation sites recruit key components, including a Tec-family tyrosine kinase, Itk. We identified a fourth, evolutionarily conserved SLP-76 phosphorylation site, Y173, which was phosphorylated upon T-cell receptor stimulation in primary murine and Jurkat T cells. Y173 was required for antigen receptor-induced phosphorylation of phospholipase C-γ1 (PLC-γ1) in both T and mast cells, and for consequent downstream events, including activation of the IL-2 promoter in T cells, and degranulation and IL-6 production in mast cells. In intact cells, Y173 phosphorylation depended on three, ZAP-70-targeted tyrosines at the N-terminus of SLP-76 that recruit and activate Itk, a kinase that selectively phosphorylated Y173 in vitro. These data suggest a sequential mechanism whereby ZAP-70-dependent priming of SLP-76 at three N-terminal sites triggers reciprocal regulatory interactions between Itk and SLP-76, which are ultimately required to couple active Itk to its substrate, PLC-γ1.

Molecular cloning, expression and adhesion analysis of silent slpB of Lactobacillus acidophilus NCFM.

PubMed

Guo, Yuxing; Li, Xiangyue; Yang, Yao; Wu, Zhen; Zeng, Xiaoqun; Nadari, Fawze; Pan, Daodong

2018-06-23

The slpB gene of Lactobacillus acidophilus NCFM, which differs from the slpA gene and is silent under normal conditions, was successfully amplified and ligated to the corresponding available sites on a recombinant pET-28a vector. Then the pET-28a-slpB vector was transformed into Escherichia coli DH (DE3) and the fusion His-slpB protein was expressed by induction with 1 mM IPTG for 14 h at 37 °C. The resulting His-slpB protein (S B ) had a relative molecular weight of 48 kDa. It was purified using a Ni-NTA column and was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot contrastive analysis. The slpA protein (S A ) from L. acidophilus NCFM was extracted and purified. It had a relative molecular weight of 46 kDa. Circular dichroism measurements suggested that the two S-layer proteins had a high β-sheet content and a low α-helix structure content. In an adhesion experiment, S A displayed higher adhesive capability towards Caco-2 cells than did S B . The results suggest that these two S-layer proteins could have biotechnological applications.

Specific loss power in superparamagnetic hyperthermia: nanofluid versus composite

NASA Astrophysics Data System (ADS)

Osaci, M.; Cacciola, M.

2017-01-01

Currently, the magnetic hyperthermia induced by nanoparticles is of great interest in biomedical applications. In the literature, we can find a lot of models for magnetic hyperthermia, but many of them do not give importance to a significant detail, such as the geometry of nanoparticle positions in the system. Usually, a nanofluid is treated by considering random positions of the nanoparticles, geometry that is actually characteristic to the composite nanoparticles. To assess the error which is frequently made, in this paper we propose a comparative analysis between the specific loss power (SLP) in case of a nanofluid and the SLP in case of a composite with magnetic nanoparticles. We are going to use a superparamagnetic hyperthermia model based on the improved model for calculating the Néel relaxation time in a magnetic field oblique to the nanoparticle magnetic anisotropy axes, and on the improved theoretical model LRT (linear response theory) for SLP. To generate the nanoparticle geometry in the system, we are going to apply a Monte Carlo method to a nanofluid, by minimising the interaction potentials in liquid medium and, for a composite environment, a method for generating random positions of the nanoparticles in a given volume.

Analysis of the Origin of Atypical Scanning Laser Polarimetry Patterns by Polarization-Sensitive Optical Coherence Tomography

PubMed Central

Götzinger, Erich; Pircher, Michael; Baumann, Bernhard; Hirn, Cornelia; Vass, Clemens; Hitzenberger, Christoph K.

2010-01-01

Purpose To analyze the physical origin of atypical scanning laser polarimetry (SLP) patterns. To compare polarization-sensitive optical coherence tomography (PS-OCT) scans to SLP images. To present a method to obtain pseudo-SLP images by PS-OCT that are free of atypical artifacts. Methods Forty-one eyes of healthy subjects, subjects with suspected glaucoma, and patients with glaucoma were imaged by SLP (GDx VCC) and a prototype spectral domain PS-OCT system. The PS-OCT system acquires three-dimensional (3D) datasets of intensity, retardation, and optic axis orientation simultaneously within 3 seconds. B-scans of intensity and retardation and en face maps of retinal nerve fiber layer (RNFL) retardation were derived from the 3D PS-OCT datasets. Results were compared with those obtained by SLP. Results Twenty-two eyes showed atypical retardation patterns, and 19 eyes showed normal patterns. From the 22 atypical eyes, 15 showed atypical patterns in both imaging modalities, five were atypical only in SLP images, and two were atypical only in PS-OCT images. In most (15 of 22) atypical cases, an increased penetration of the probing beam into the birefringent sclera was identified as the source of atypical patterns. In such cases, the artifacts could be eliminated in PS-OCT images by depth segmentation and exclusion of scleral signals. Conclusions PS-OCT provides deeper insight into the contribution of different fundus layers to SLP images. Increased light penetration into the sclera can distort SLP retardation patterns of the RNFL. PMID:19036999

Influence of occupational factors on regional differences in sick leave: A prospective population study.

PubMed

Sterud, Tom; Johannessen, Håkon A

2018-05-01

Number of sick leave days vary by county, but little is known about the extent to which this gradient may be explained by differences pertaining to occupational composition and occupational exposure. A randomly drawn cohort from the general population in Norway, aged 18-69 years, was interviewed by telephone in the second half of 2009 ( n=12,255; response at baseline=60.9%) and followed up in national registries to the end of 2010. Eligible respondents were registered with an active employee relationship in 2009 and 2010 ( n=8275). Information on counties ( n=19) was based on the administrative register. The outcome of interest was the number of physician-certified sick-leave days divided by scheduled man-days during 2010 (i.e. sick-leave percentage (SLP)). The average SLP during 2010 was 5.2%. The between-county variation in SLP ranged from 4.0% to 7.2%. Compared to the age- and gender-adjusted model, adjustment for occupation, economic sector and self-reported occupational exposure reduced the median difference in SLP between the county with the lowest SLP (reference county) and the SLP in the other counties by 1.08 percentage points (i.e. a 58% reduction). The impact of occupational composition and occupational exposure on the total between-county variance in SLP was a 16% reduction. Occupational composition and self-reported occupational exposure help to explain a significant part of the difference in SLP between counties, and appear to be more important explanatory factors than demographic variables, self-reported health and smoking.

Crystal structure of the C-terminal SH3 domain of the adaptor protein GADS in complex with SLP-76 motif peptide reveals a unique SH3-SH3 interaction.

PubMed

Dimasi, Nazzareno

2007-01-01

The Grb2-like adaptor protein GADS is essential for tyrosine kinase-dependent signaling in T lymphocytes. Following T cell receptor ligation, GADS interacts through its C-terminal SH3 domain with the adaptors SLP-76 and LAT, to form a multiprotein signaling complex that is crucial for T cell activation. To understand the structural basis for the selective recognition of GADS by SLP-76, herein is reported the crystal structure at 1.54 Angstrom of the C-terminal SH3 domain of GADS bound to the SLP-76 motif 233-PSIDRSTKP-241, which represents the minimal binding site. In addition to the unique structural features adopted by the bound SLP-76 peptide, the complex structure reveals a unique SH3-SH3 interaction. This homophilic interaction, which is observed in presence of the SLP-76 peptide and is present in solution, extends our understanding of the molecular mechanisms that could be employed by modular proteins to increase their signaling transduction specificity.

Conditional deletion of SLP-76 in mature T cells abrogates peripheral immune responses.

PubMed

Wu, Gregory F; Corbo, Evann; Schmidt, Michelle; Smith-Garvin, Jennifer E; Riese, Matthew J; Jordan, Martha S; Laufer, Terri M; Brown, Eric J; Maltzman, Jonathan S

2011-07-01

The adaptor protein Src homology 2 domain-containing leukocyte-specific protein of 76 kDa (SLP-76) is central to the organization of intracellular signaling downstream of the T-cell receptor (TCR). Evaluation of its role in mature, primary T cells has been hampered by developmental defects that occur in the absence of WT SLP-76 protein in thymocytes. Here, we show that following tamoxifen-regulated conditional deletion of SLP-76, mature, antigen-inexperienced T cells maintain normal TCR surface expression but fail to transduce TCR-generated signals. Conditionally deficient T cells fail to proliferate in response to antigenic stimulation or a lymphopenic environment. Mice with induced deletion of SLP-76 are resistant to induction of the CD4+ T-cell-mediated autoimmune disease experimental autoimmune encephalomyelitis. Altogether, our findings demonstrate the critical role of SLP-76-mediated signaling in initiating T-cell-directed immune responses both in vitro and in vivo and highlight the ability to analyze signaling processes in mature T cells in the absence of developmental defects. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Trichostatin A down-regulates ZAP-70, LAT and SLP-76 content in Jurkat T cells.

PubMed

Januchowski, Radosław; Jagodzinski, Paweł P

2007-02-01

We exploited Jurkat leukemia T cell clone E6-1 as a model of Trichostatin A (TSA) effect on cellular levels of ZAP-70, LAT and SLP-76 molecules involved in the signal transduction pathway from T cell receptor to nucleus. Using reverse transcription real-time quantitative PCR and Western blotting analysis we observed that TSA resulted in ZAP-70, LAT and SLP-76 transcript and protein down-regulation in Jurkat leukemia T cells. We also found that TSA reduced half-life of ZAP-70, LAT and SLP-76 mRNAs from 4.8, 3.5, and 4.8 to approximately 2.3, 1.9 and 1.7 h, respectively. Employing the protein biosynthesis inhibitor cycloheximide, we demonstrated the involvement of RNase and/or mRNA stabilization protein in ZAP-70, LAT and SLP-76 mRNAs stabilization. The effect of TSA on ZAP-70, LAT and SLP-76 content in T cells confirms an immunosuppressive effect by TSA, and the usefulness of this histone deacetylase inhibitor in the treatment of autoimmune diseases.

Stationary light pulse in solids with long-lived spin coherence

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

Zhang Xiaojun; Wang Haihua; Wang Lei

We present a detailed analysis of stationary light pulses (SLP's) for the case of inhomogeneous broadening in both optical and spin transitions, which is normally found in solid materials with long-lived spin coherence. By solving the Langevin equations of motion for the density matrix elements under the integral over the entire range of the inhomogeneous broadenings, the necessary conditions for creating the SLP in a solid are obtained. Then the decay and diffusion processes that the SLP undergoes are analyzed. The characteristics of such processes are studied based on the analytic solution of the SLP with a slowly varying envelope.more » The dependence of SLP lifetime on inhomogeneous broadenings of spin and optical transitions, which can be regarded as the laser linewidth in the repump scheme, has been discussed.« less

Stomatin-Like Protein 2 Binds Cardiolipin and Regulates Mitochondrial Biogenesis and Function▿

PubMed Central

Christie, Darah A.; Lemke, Caitlin D.; Elias, Isaac M.; Chau, Luan A.; Kirchhof, Mark G.; Li, Bo; Ball, Eric H.; Dunn, Stanley D.; Hatch, Grant M.; Madrenas, Joaquín

2011-01-01

Stomatin-like protein 2 (SLP-2) is a widely expressed mitochondrial inner membrane protein of unknown function. Here we show that human SLP-2 interacts with prohibitin-1 and -2 and binds to the mitochondrial membrane phospholipid cardiolipin. Upregulation of SLP-2 expression increases cardiolipin content and the formation of metabolically active mitochondrial membranes and induces mitochondrial biogenesis. In human T lymphocytes, these events correlate with increased complex I and II activities, increased intracellular ATP stores, and increased resistance to apoptosis through the intrinsic pathway, ultimately enhancing cellular responses. We propose that the function of SLP-2 is to recruit prohibitins to cardiolipin to form cardiolipin-enriched microdomains in which electron transport complexes are optimally assembled. Likely through the prohibitin functional interactome, SLP-2 then regulates mitochondrial biogenesis and function. PMID:21746876

Mediterranean summer climate and the monsoon regimes

NASA Astrophysics Data System (ADS)

Baldi, M.; Crisci, A.; Dalu, G. A.; Maracchi, G.; Meneguzzo, F.; Pasqui, M.

2003-04-01

The Authors examine the general features of climate of the Mediterranean Region, i.e. its variability and trends in the last 40 years, and the teleconnections between Mediterranean climate and the global climate, using zonal and global indices. In particular they focus the attention on the analysis of the summer Mediterranean climate, and its variability and connection with the summer monsoon regimes. Several subregions can be distinguished in the Mediterranean for each season, and the occurrence of Mediterranean Oscillation is evident between West and East sub-basins. Precipitation and SLP fields in the Eastern basin are shown to be correlated with Mediterranean Oscillation. A total decrease of precipitation has been detected in last few years, although there are some very intense. During winter a fundamental role is played by NAO index, which, influencing the storm tracks coming from the Atlantic and passing over the Mediterranean and North Europe, it has a major role in the precipitation patterns over the Region. Moreover, temperature analysis over the last 40 years in the Mediterranean shows a distinct warming, in agreement with the pattern over North Emisphere and NAO index fluctuations. During summer the Hadley cell extend further northwards, influencing the Mediterranean climate, and there is evidence of a possible teleconnection with the Asian Monsoon, and the Sahel precipitation (and related Hadley cell): the SLP field in the Eastern Mediterranean is inversely correlated with those two precipitation indices, while it is positively correlated with the pressure in the Western Mediterranean. Leading mechanisms of interaction between Mediterranean summer rainfall and SLP patterns and precipitation indices associated with monsoon regimes are stressed out and investigated, as well as the influence of the position and strength of the Hadley cell, by means of both statistical and dynamical analytical arguments. A modeling study has been carried out in order to study the variations and the anomalies in the recent Mediterranean summer precipitation patterns, consisting of two main phases. In the first phase, a numerical regional atmospheric model has been used to downscale the NCEP/NCAR reanalyses, showing a good agreement between model simulations and observations, proving the capability of the modeling tool. During the second phase, following and extending recent experiences the numerical model has been used to identify the features and extent of the impacts of the location and strength of the West Africa summer monsoon - therefore the regional Hadley cell - to the Mediterranean climate, by selectively modifying the main forcing of that tropical circulation, i.e. the Gulf of Guinea sea surface temperatures.

Speech-language pathology care and short- and long-term outcomes of oropharyngeal cancer treatment in the elderly.

PubMed

Webster, Kimberly T; Tippett, Donna; Simpson, Marissa; Abrams, Rina; Pietsch, Kristine; Herbert, Robert J; Eisele, David W; Gourin, Christine G

2018-06-01

To examine associations between speech-language pathology (SLP) care and pretreatment variables, short-term and long-term swallowing and airway impairment, and survival in elderly patients treated for oropharyngeal squamous cell cancer (SCCA). Retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data. We evaluated longitudinal data from 666 patients diagnosed with oropharyngeal SCCA from 2004 to 2007 using cross-tabulations, multivariate logistic regression, and survival analysis. SLP care was documented in 25% of patients. High-volume hospital care (odds ratio (OR) = 3.2 [1.0-10.0]) and dysphagia during treatment (OR = 13.0 [3.6-47.1]) were the only significant predictors of SLP care during the initial treatment period. SLP care was significantly more likely during the first year (OR = 5.3 [3.1-9.1]) and second year (OR = 4.5 [2.4-8.2]) following initial treatment. Subsequent dysphagia (OR = 32.5 [16.9-62.4]), stricture (OR = 2.2 [1.2-4.0]), gastrostomy (OR = 1.7 [1.1-2.7]), and tracheostomy tube use (OR = 2.4 [1.2-4.8]) were significantly associated with long-term SLP care. After controlling for patient, tumor, and treatment-related variables, SLP care was associated with significant relative attenuation of the OR for dysphagia (93%), stricture (35%), weight loss (8%), and airway obstruction (34%). Survival analysis, controlling for all other variables, demonstrated improved survival for patients under SLP care (hazard ratio = 0.73 [0.57-0.95]). SLP care is underutilized in elderly oropharyngeal SCCA patients and largely utilized after the onset of impaired airway and swallowing function, but is associated with improved outcomes. These data suggest a need for treatment guidelines that incorporate the routine use of SLP care in this population during the initial treatment period and beyond. 2c. Laryngoscope, 128:1403-1411, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

An inter-decadal increase in summer sea level pressure over the Mongolian region around the early 1990s

NASA Astrophysics Data System (ADS)

Zhang, Haiyan; Wen, Zhiping; Wu, Renguang; Li, Xiuzhen; Chen, Ruidan

2018-05-01

The East Asian summer monsoon is affected by processes in the mid-high latitudes in addition to various tropical and subtropical systems. The present study investigates the summer sea level pressure (SLP) variability over northern East Asia (NEA) and emphasizes the closed active center over the Mongolian region. It is found that the seasonal mean Mongolian SLP (MSLP) anomaly is closely connected with the variability of summertime regional synoptic extra-tropical cyclones on longer time scales. A significant inter-decadal increase in the MSLP around the early 1990s has been detected, which is accompanied by a weakening in the activity of regional extra-tropical cyclones. Recent warming over NEA may have a contribution to the inter-decadal change, which features evidently meridional inhomogeneity around 45°N. The inhomogeneous air temperature anomaly distribution results in decreased vertical wind shear, reduced atmospheric baroclinicity over the Mongolian region, and thus inactive regional cyclones and increased MSLP in the latter decade. The associated temperature anomaly distribution may be partly attributed to regional inhomogeneity in cloud and radiation anomalies, and it is further maintained by two positive feedback mechanisms associated with atmospheric internal processes: one via adiabatic heating and the other via horizontal temperature advection.

The stomatin-like protein SLP-1 and Cdk2 interact with the F-Box protein Fbw7-γ.

PubMed

Zhang, Wei; MacDonald, Elizabeth M; Koepp, Deanna M

2012-01-01

Control of cellular proliferation is critical to cell viability. The F-box protein Fbw7 (hAgo/hCdc4/FBXW7) functions as a specificity factor for the Skp1-Cul1-F-box protein (SCF) ubiquitin ligase complex and targets several proteins required for cellular proliferation for ubiquitin-mediated destruction. Fbw7 exists as three splice variants but the mechanistic role of each is not entirely clear. We examined the regulation of the Fbw7-γ isoform, which has been implicated in the degradation of c-Myc. We show here that Fbw7-γ is an unstable protein and that its turnover is proteasome-dependent in transformed cells. Using a two-hybrid screen, we identified a novel interaction partner, SLP-1, which binds the N-terminal domain of Fbw7-γ. Overexpression of SLP-1 inhibits the degradation of Fbw7-γ, suggesting that this interaction can happen in vivo. When Fbw7-γ is stabilized by overexpression of SLP-1, c-Myc protein abundance decreases, suggesting that the SCF(Fbw7-γ) complex maintains activity. We demonstrate that Cdk2 also binds the N-terminal domain of Fbw7-γ as well as SLP-1. Interestingly, co-expression of Cdk2 and SLP-1 does not inhibit Fbw7-γ degradation, suggesting that Cdk2 and SLP-1 may have opposing functions.

Murine natural killer immunoreceptors use distinct proximal signaling complexes to direct cell function

PubMed Central

May, Rebecca M.; Okumura, Mariko; Hsu, Chin-Jung; Bassiri, Hamid; Yang, Enjun; Rak, Gregory; Mace, Emily M.; Philip, Naomi H.; Zhang, Weiguo; Baumgart, Tobias; Orange, Jordan S.; Nichols, Kim E.

2013-01-01

Signaling pathways leading to natural killer (NK)–cell effector function are complex and incompletely understood. Here, we investigated the proximal signaling pathways downstream of the immunotyrosine-based activation motif (ITAM) bearing activating receptors. We found that the adaptor molecule SH2 domain-containing leukocyte protein of 76 kD (SLP-76) is recruited to microclusters at the plasma membrane in activated NK cells and that this is required for initiation of downstream signaling and multiple NK-cell effector functions in vitro and in vivo. Surprisingly, we found that 2 types of proximal signaling complexes involving SLP-76 were formed. In addition to the canonical membrane complex formed between SLP-76 and linker for activation of T cells (LAT) family members, a novel LAT family–independent SLP-76–dependent signaling pathway was identified. The LAT family–independent pathway involved the SH2 domain of SLP-76 and adhesion and degranulation-promoting adaptor protein (ADAP). Both the LAT family–dependent and ADAP-dependent pathway contributed to interferon-gamma production and cytotoxicity; however, they were not essential for other SLP-76–dependent events, including phosphorylation of AKT and extracellular signal–related kinase and cellular proliferation. These results demonstrate that NK cells possess an unexpected bifurcation of proximal ITAM-mediated signaling, each involving SLP-76 and contributing to optimal NK-cell function. PMID:23407547

76 FR 82328 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of a...

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... to the aeroplane has two load paths, a Primary Load Path (PLP) and a Secondary Load Path (SLP), which is only engaged in case of PLP failure. Following the design intent, engagement of the SLP leads to... representative flights have demonstrated that, when the SLP is engaged, it does not systematically jam the THSA...

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... Change The Exchange proposes to extend the operation of its Supplemental Liquidity Providers Pilot (``SLP... operation of its SLP Pilot,\\4\\ currently scheduled to expire on July 31, 2012, until the earlier of... No. 58877 (October 29, 2008), 73 FR 65904 (November 5, 2008) (SR-NYSE-2008-108) (establishing the SLP...

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... to the aeroplane has two load paths, a Primary Load Path (PLP) and a Secondary Load Path (SLP), which is only engaged in case of PLP failure. Following the design intent, engagement of the SLP leads to... representative flights have demonstrated that, when the SLP is engaged, it does not systematically jam the THSA...

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The role of atmospheric circulation patterns on short-term sea-level fluctuations along the eastern seaboard of the US

NASA Astrophysics Data System (ADS)

Sheridan, S. C.; Lee, C. C.; Pirhalla, D.; Ransi, V.

2017-12-01

Sea-level fluctuations over time are a product of short-term weather events, as well as long-term secular trends in sea-level rise. With sea-levl rise, these fluctuations increasingly have substantial impacts upon coastal ecosystems and impact society through coastal flooding events. In this research, we assess the impact of short-term events, combined with sea-level rise, through synoptic climatological analysis, exploring whether circulation pattern identification can be used to enhance probabilistic forecasts of flood likelihood. Self-organizing maps (SOMs) were created for two discrete atmospheric variables: 700-hPa geopotential height (700z) and sea-level pressure (SLP). For each variable, a SOM array of patterns was created based on data spanning 25°-50°N and 60°-90°W for the period 1979-2014. Sea-level values were derived from tidal gauges between Cape May, New Jersey and Charleston, South Carolina, along the mid-Atlantic coast of the US. Both anomalous sea-level values, as well as nuisance flood occurrence (defined using the local gauge threshold), were assessed. Results show the impacts of both the inverted barometer effect as well as surface wind forcing on sea levels. With SLP, higher sea levels are associated with either patterns that were indicative of on-shore flow or cyclones. At 700z, ridges situated along the east coast are associated with higher sea levels. As the SOM matrix arranges atmospheric patterns in a continuum, the nodes of each SOM show a clear spatial pattern in terms of anomalous sea level, including some significant sea-level anomalies associated with relatively ambiguous pressure patterns. Further, multi-day transitions are also analyzed, showing rapidly deepening cyclones, or persistent onshore flow, can be associated with the greatest likelihood of nuisance floods. Results are weaker with 700z than SLP; however, in some cases, it is clear that the mid-tropospheric circulation can modulate the connection between sea-level anomalies and surface circulation.

An extreme Arctic cyclone in August 2016 and its predictability on medium-range timescales

NASA Astrophysics Data System (ADS)

Yamagami, Akio; Matsueda, Mio; Tanaka, Hiroshi

2017-04-01

An extremely strong Arctic cyclone (AC) developed in August 2016. The AC exhibited a minimum sea level pressure (SLP) of 967.2 hPa and covered the entire Pacific sector of the Arctic Ocean at 0000UTC on 16 August. At this time the AC was comparable to the strong AC observed in August 2012, in terms of horizontal extent, position, and intensity as measured by SLP. Two processes contributed to the explosive development of the AC: growth due to baroclinic instability, similar to extratropical cyclones, during the early part of the development stage, and later nonlinear development via the merging of upper warm cores. The AC was maintained for more than one month through multiple mergings with cyclones both generated in the Arctic and migrating northward from lower latitudes, as a result of the high cyclone activity in summer 2016. This study also investigated the predictability of the AC using operational medium-range ensemble forecasts: CMC (Canada), ECMWF (EU), JMA (Japan), NCEP (USA), and UKMO (UK), available at the The Interactive Grand Global Ensemble (TIGGE) database. The minimum SLP of the AC at 0000UTC on 16 August was well predicted by ECMWF 6-day, NCEP and UKMO 5-day, CMC 4-day, and JMA 3-day in advance. The predictability of the minimum SLP of the AC in August 2016 was much higher than that of the AC in 2012 August. Whereas most of the members well predicted the cyclogenesis of the AC, the growth due to baroclinic instability was weaker in some members. Even if the baroclinic growth was predicted well, predicted AC did not develop when the nonlinear development via the merging was not predict accurately. The accurate prediction of the processes in both early and later parts of the development stage was important for the accurate prediction of the development of the AC.

Activated Cdc42-associated kinase 1 (ACK1) binds the sterile α motif (SAM) domain of the adaptor SLP-76 and phosphorylates proximal tyrosines.

PubMed

Thaker, Youg R; Recino, Asha; Raab, Monika; Jabeen, Asma; Wallberg, Maja; Fernandez, Nelson; Rudd, Christopher E

2017-04-14

The adaptor protein Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) plays a crucial role in T cell activation by linking antigen receptor (T cell receptor, TCR) signals to downstream pathways. At its N terminus, SLP-76 has three key tyrosines (Tyr-113, Tyr-128, and Tyr-145, "3Y") as well as a sterile α motif (SAM) domain whose function is unclear. We showed previously that the SAM domain has two binding regions that mediate dimer and oligomer formation. In this study, we have identified SAM domain-carrying non-receptor tyrosine kinase, activated Cdc42-associated tyrosine kinase 1 (ACK1; also known as Tnk2, tyrosine kinase non-receptor 2) as a novel binding partner of SLP-76. Co-precipitation, laser-scanning confocal microscopy, and in situ proximity analysis confirmed the binding of ACK1 to SLP-76. Further, the interaction was induced in response to the anti-TCR ligation and abrogated by the deletion of SLP-76 SAM domain (ΔSAM) or mutation of Tyr-113, Tyr-128, and Tyr-145 to phenylalanine (3Y3F). ACK1 induced phosphorylation of the SLP-76 N-terminal tyrosines (3Y) dependent on the SAM domain. Further, ACK1 promoted calcium flux and NFAT-AP1 promoter activity and decreased the motility of murine CD4 + primary T cells on ICAM-1-coated plates, an event reversed by a small molecule inhibitor of ACK1 (AIM-100). These findings identify ACK1 as a novel SLP-76-associated protein-tyrosine kinase that modulates early activation events in T cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Expression of SLP-2 gene and CCBE1 are associated with prognosis of rectal cancer.

PubMed

Zhang, L; Liu, F-J

2017-03-01

This study aims to investigate the clinical significance of SLP-2 gene for patients with rectal cancer. To analyze the effect of CCBE1 (Collagen and calcium-binding EGF domain-containing protein 1) on rectal cancer tissue and lymph vessels of para-carcinoma tissue. A total of 50 samples of rectal cancer tissues were enrolled in the experimental group, confirmed by pathological examination. 50 samples of para-carcinoma normal tissues were collected as control group. Protein expression of SLP-2 and CCBE1 was examined with immunohistochemical staining. mRNA expression of SLP-2 was examined with RT-PCR. Lymphatic vessel density (LVD) was evaluated with LYVE-1 immunohistochemical staining. Correlation analysis was performed to assess the relationship between patient survival data and clinical pathological features of rectal cancer. Immunohistochemical staining showed that, compared with the control group, a positive expression rate of SLP-2 in the experimental group was significantly higher (68.0% vs. 24.0%, p<0.05), and mRNA of SLP-2 was also significantly increased (p<0.05). Compared with the control group, protein expression of CCBE1 in the experimental group was significantly higher (p<0.05). Moreover, the expression level of SLP-2 was remarkably associated with TNM classification and lymphatic metastasis. Further analysis demonstrated that a positive expression of CCBE1 was associated with lymphatic metastasis, LVD and Ducks classification, and had a negative correlation with survival rate. Increased expression of SLP-2 promoted the formation of lymph vessels and exacerbated lymphatic metastasis of rectal cancer via up-regulating CCBE1. As a risk factor related to lymphatic metastasis, CCBE1 could be a novel biomarker for diagnosis and prognosis of rectal cancer.

Activated Cdc42-associated kinase 1 (ACK1) binds the sterile α motif (SAM) domain of the adaptor SLP-76 and phosphorylates proximal tyrosines

PubMed Central

Thaker, Youg R.; Recino, Asha; Raab, Monika; Jabeen, Asma; Wallberg, Maja; Fernandez, Nelson; Rudd, Christopher E.

2017-01-01

The adaptor protein Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) plays a crucial role in T cell activation by linking antigen receptor (T cell receptor, TCR) signals to downstream pathways. At its N terminus, SLP-76 has three key tyrosines (Tyr-113, Tyr-128, and Tyr-145, “3Y”) as well as a sterile α motif (SAM) domain whose function is unclear. We showed previously that the SAM domain has two binding regions that mediate dimer and oligomer formation. In this study, we have identified SAM domain-carrying non-receptor tyrosine kinase, activated Cdc42-associated tyrosine kinase 1 (ACK1; also known as Tnk2, tyrosine kinase non-receptor 2) as a novel binding partner of SLP-76. Co-precipitation, laser-scanning confocal microscopy, and in situ proximity analysis confirmed the binding of ACK1 to SLP-76. Further, the interaction was induced in response to the anti-TCR ligation and abrogated by the deletion of SLP-76 SAM domain (ΔSAM) or mutation of Tyr-113, Tyr-128, and Tyr-145 to phenylalanine (3Y3F). ACK1 induced phosphorylation of the SLP-76 N-terminal tyrosines (3Y) dependent on the SAM domain. Further, ACK1 promoted calcium flux and NFAT-AP1 promoter activity and decreased the motility of murine CD4+ primary T cells on ICAM-1-coated plates, an event reversed by a small molecule inhibitor of ACK1 (AIM-100). These findings identify ACK1 as a novel SLP-76-associated protein-tyrosine kinase that modulates early activation events in T cells. PMID:28188290

Surface Display of the Receptor-Binding Region of the Lactobacillus brevis S-Layer Protein in Lactococcus lactis Provides Nonadhesive Lactococci with the Ability To Adhere to Intestinal Epithelial Cells

PubMed Central

Åvall-Jääskeläinen, Silja; Lindholm, Agneta; Palva, Airi

2003-01-01

Lactobacillus brevis is a promising lactic acid bacterium for use as a probiotic dietary adjunct and a vaccine vector. The N-terminal region of the S-layer protein (SlpA) of L. brevis ATCC 8287 was recently shown to mediate adhesion to various human cell lines in vitro. In this study, a surface display cassette was constructed on the basis of this SlpA receptor-binding domain, a proteinase spacer, and an autolysin anchor. The cassette was expressed under control of the nisA promoter in Lactococcus lactis NZ9000. Western blot assay of lactococcal cell wall extracts with anti-SlpA antibodies confirmed that the SlpA adhesion domain of the fusion protein was expressed and located within the cell wall layer. Whole-cell enzyme-linked immunosorbent assay and immunofluorescence microscopy verified that the SlpA adhesion-mediating region was accessible on the lactococcal cell surface. In vitro adhesion assays with the human intestinal epithelial cell line Intestine 407 indicated that the recombinant lactococcal cells had gained an ability to adhere to Intestine 407 cells significantly greater than that of wild-type L. lactis NZ9000. Serum inhibition assay further confirmed that adhesion of recombinant lactococci to Intestine 407 cells was indeed mediated by the N terminus-encoding part of the slpA gene. The ability of the receptor-binding region of SlpA to adhere to fibronectin was also confirmed with this lactococcal surface display system. These results show that, with the aid of the receptor-binding region of the L. brevis SlpA protein, the ability to adhere to gut epithelial cells can indeed be transferred to another, nonadhesive, lactic acid bacterium. PMID:12676705

Surface display of the receptor-binding region of the Lactobacillus brevis S-layer protein in Lactococcus lactis provides nonadhesive lactococci with the ability to adhere to intestinal epithelial cells.

PubMed

Avall-Jääskeläinen, Silja; Lindholm, Agneta; Palva, Airi

2003-04-01

Lactobacillus brevis is a promising lactic acid bacterium for use as a probiotic dietary adjunct and a vaccine vector. The N-terminal region of the S-layer protein (SlpA) of L. brevis ATCC 8287 was recently shown to mediate adhesion to various human cell lines in vitro. In this study, a surface display cassette was constructed on the basis of this SlpA receptor-binding domain, a proteinase spacer, and an autolysin anchor. The cassette was expressed under control of the nisA promoter in Lactococcus lactis NZ9000. Western blot assay of lactococcal cell wall extracts with anti-SlpA antibodies confirmed that the SlpA adhesion domain of the fusion protein was expressed and located within the cell wall layer. Whole-cell enzyme-linked immunosorbent assay and immunofluorescence microscopy verified that the SlpA adhesion-mediating region was accessible on the lactococcal cell surface. In vitro adhesion assays with the human intestinal epithelial cell line Intestine 407 indicated that the recombinant lactococcal cells had gained an ability to adhere to Intestine 407 cells significantly greater than that of wild-type L. lactis NZ9000. Serum inhibition assay further confirmed that adhesion of recombinant lactococci to Intestine 407 cells was indeed mediated by the N terminus-encoding part of the slpA gene. The ability of the receptor-binding region of SlpA to adhere to fibronectin was also confirmed with this lactococcal surface display system. These results show that, with the aid of the receptor-binding region of the L. brevis SlpA protein, the ability to adhere to gut epithelial cells can indeed be transferred to another, nonadhesive, lactic acid bacterium.

Fission yeast APC/C activators Slp1 and Fzr1 sequentially trigger two consecutive nuclear divisions during meiosis.

PubMed

Chikashige, Yuji; Yamane, Miho; Okamasa, Kasumi; Osakada, Hiroko; Tsutsumi, Chihiro; Nagahama, Yuki; Fukuta, Noriko; Haraguchi, Tokuko; Hiraoka, Yasushi

2017-04-01

In meiosis, two rounds of nuclear division occur consecutively without DNA replication between the divisions. We isolated a fission yeast mutant in which the nucleus divides only once to generate two spores, as opposed to four, in meiosis. In this mutant, we found that the initiation codon of the slp1 + gene is converted to ATA, producing a reduced amount of Slp1. As a member of the Fizzy family of anaphase-promoting complex/cyclosome (APC/C) activators, Slp1 is essential for vegetative growth; however, the mutant allele shows a phenotype only in meiosis. Slp1 insufficiency delays degradation of maturation-promoting factor at the first meiotic division, and another APC/C activator, Fzr1, which acts late in meiosis, terminates meiosis immediately after the delayed first division to produce two viable spores. © 2017 Federation of European Biochemical Societies.

Preparing Speech Language Pathology Students to Work in Early Childhood

ERIC Educational Resources Information Center

Barton, Erin E.; Moore, Heather W.; Squires, Jane K.

2012-01-01

The shortage of highly qualified speech language pathologists (SLPs) with specialized training in early intervention and early childhood special education (EI/ECSE) is a pressing issue facing the field and dramatically impacts young children's social and academic success. SLP personnel preparation programs focused on training specialists in…

76 FR 1653 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-11

... adding liquidity to the Exchange in NYSE-listed securities, based on an SLP's ADV in added liquidity in... NYSE-listed securities, based on an SLP's ADV in added liquidity in the applicable month. Under the proposal, SLPs that meet the SLP 10% quoting requirement will receive a credit per share per transaction...

76 FR 82342 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-30

... Liquidity Providers Pilot (``SLP Pilot'' or ``Pilot'') (See Rule 107B), currently scheduled to expire on...-108) (establishing the SLP Pilot). See also Securities Exchange Act Release Nos. 59869 (May 6, 2009), 74 FR 22796 (May 14, 2009) (SR- NYSE-2009-46) (extending the operation of the SLP Pilot to October 1...

77 FR 42024 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-17

...\\ SLPs in the original class (``SLP-Props'') are eligible for credits when adding liquidity on the Exchange. The amount of the credit is determined by the ``tier'' for which the SLP-Prop qualifies, which is based on (i) whether the SLP-Prop meets the 10% average or more quoting requirement in all assigned...

77 FR 1769 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-11

... liquidity on the Exchange. Currently, under a tiered structure of credits, a SLP that meets the 10% average... 50529 (August 15, 2011) (SR-NYSE-2011-39). $0.0020 credit per share per transaction if the SLP adds... all assigned SLP securities; and \\4\\ Consolidated ADV is equal to the volume reported by all exchanges...

76 FR 612 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

... Change The Exchange proposes to extend the operation of its Supplemental Liquidity Providers Pilot (``SLP... (October 29, 2008), 73 FR 65904 (November 5, 2008) (SR-NYSE-2008-108) (establishing the SLP Pilot). See...-2009-46) (extending the operation of the SLP Pilot to October 1, 2009); 60756 (October 1, 2009), 74 FR...

75 FR 20401 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing of Proposed Rule Change, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-19

... Nasdaq Securities within the existing DMM and SLP framework used to trade its listed securities. The... substantially similar to the Exchange's current SLP procedures in Rule 107B--NYSE Amex Equities. See proposed..., reassign one or more Nasdaq Securities to a different DMM Unit or to a different SLP or SLPs. a. Assignment...

75 FR 2180 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-14

... (``SLP'') program.\\4\\ The Exchange proposes to establish a system of credits payable to SLPs when they... add liquidity to the Exchange in securities with a per share price of $1.00 or more, if the SLP meets... the SLP does not meet the 3% average or more quoting requirement in an assigned security pursuant to...

77 FR 22624 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-16

... proposes to amend its Price List to raise the Supplemental Liquidity Provider (``SLP'') rebate and raise..., the Proposed Rule Change 1. Purpose The Exchange proposes to amend its Price List to raise the SLP rebate and raise the NYSE CSII rate and fee cap. The Exchange proposes to raise the SLP rebate from $0...

Policies and Practices regarding Students with Accents in Speech-Language Pathology Training Programs

ERIC Educational Resources Information Center

Levy, Erika S.; Crowley, Catherine J.

2012-01-01

Speech-language pathology (SLP) training programs are the initial gateway for nonnative speakers of English to join the SLP profession. An anonymous web-based survey in New York State examined policies and practices implemented when SLP students have foreign accents in English or in other languages. Responses were elicited from 530 students and 28…

76 FR 50529 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-15

... or more, to include criteria based on an SLP's Average Daily Volume (``ADV'') in added liquidity in... liquidity in the applicable month for all assigned SLP securities, as follows: \\5\\ \\5\\ See Securities... is more than 10 million shares but not more than 20 million shares.\\6\\ \\6\\ For all other SLP...

Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury

PubMed Central

Block, Helena; Herter, Jan M.; Rossaint, Jan; Stadtmann, Anika; Kliche, Stefanie; Lowell, Clifford A.

2012-01-01

Neutrophils trigger inflammation-induced acute kidney injury (AKI), a frequent and potentially lethal occurrence in humans. Molecular mechanisms underlying neutrophil recruitment to sites of inflammation have proved elusive. In this study, we demonstrate that SLP-76 (SH2 domain–containing leukocyte phosphoprotein of 76 kD) and ADAP (adhesion and degranulation promoting adaptor protein) are involved in E-selectin–mediated integrin activation and slow leukocyte rolling, which promotes ischemia-reperfusion–induced AKI in mice. By using genetically engineered mice and transduced Slp76−/− primary leukocytes, we demonstrate that ADAP as well as two N-terminal–located tyrosines and the SH2 domain of SLP-76 are required for downstream signaling and slow leukocyte rolling. The Tec family kinase Bruton tyrosine kinase is downstream of SLP-76 and, together with ADAP, regulates PI3Kγ (phosphoinositide 3-kinase–γ)- and PLCγ2 (phospholipase Cγ2)-dependent pathways. Blocking both pathways completely abolishes integrin affinity and avidity regulation. Thus, SLP-76 and ADAP are involved in E-selectin–mediated integrin activation and neutrophil recruitment to inflamed kidneys, which may underlie the development of life-threatening ischemia-reperfusion–induced AKI in humans. PMID:22291096

Macromolecular assembly of the adaptor SLP-65 at intracellular vesicles in resting B cells.

PubMed

Engelke, Michael; Pirkuliyeva, Sona; Kühn, Julius; Wong, Leo; Boyken, Janina; Herrmann, Nadine; Becker, Stefan; Griesinger, Christian; Wienands, Jürgen

2014-08-19

The traditional view of how intracellular effector proteins are recruited to the B cell antigen receptor (BCR) complex at the plasma membrane is based on the occurrence of direct protein-protein interactions, as exemplified by the recruitment of the tyrosine kinase Syk (spleen tyrosine kinase) to phosphorylated motifs in BCR signaling subunits. By contrast, the subcellular targeting of the cytosolic adaptor protein SLP-65 (Src homology 2 domain-containing leukocyte adaptor protein of 65 kD), which serves as a proximal Syk substrate, is unclear. We showed that SLP-65 activation required its association at vesicular compartments in resting B cells. A module of ~50 amino acid residues located at the amino terminus of SLP-65 anchored SLP-65 to the vesicles. Nuclear magnetic resonance spectroscopy showed that the SLP-65 amino terminus was structurally disordered in solution but could bind in a structured manner to noncharged lipid components of cellular membranes. Our finding that preformed vesicular signaling scaffolds are required for B cell activation indicates that vesicles may deliver preassembled signaling cargo to sites of BCR activation. Copyright © 2014, American Association for the Advancement of Science.

Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury.

PubMed

Block, Helena; Herter, Jan M; Rossaint, Jan; Stadtmann, Anika; Kliche, Stefanie; Lowell, Clifford A; Zarbock, Alexander

2012-02-13

Neutrophils trigger inflammation-induced acute kidney injury (AKI), a frequent and potentially lethal occurrence in humans. Molecular mechanisms underlying neutrophil recruitment to sites of inflammation have proved elusive. In this study, we demonstrate that SLP-76 (SH2 domain-containing leukocyte phosphoprotein of 76 kD) and ADAP (adhesion and degranulation promoting adaptor protein) are involved in E-selectin-mediated integrin activation and slow leukocyte rolling, which promotes ischemia-reperfusion-induced AKI in mice. By using genetically engineered mice and transduced Slp76(-/-) primary leukocytes, we demonstrate that ADAP as well as two N-terminal-located tyrosines and the SH2 domain of SLP-76 are required for downstream signaling and slow leukocyte rolling. The Tec family kinase Bruton tyrosine kinase is downstream of SLP-76 and, together with ADAP, regulates PI3Kγ (phosphoinositide 3-kinase-γ)- and PLCγ2 (phospholipase Cγ2)-dependent pathways. Blocking both pathways completely abolishes integrin affinity and avidity regulation. Thus, SLP-76 and ADAP are involved in E-selectin-mediated integrin activation and neutrophil recruitment to inflamed kidneys, which may underlie the development of life-threatening ischemia-reperfusion-induced AKI in humans.

Empty nano and micro-structured lipid carriers of virgin coconut oil for skin moisturisation.

PubMed

Noor, Norhayati Mohamed; Khan, Abid Ali; Hasham, Rosnani; Talib, Ayesha; Sarmidi, Mohamad Roji; Aziz, Ramlan; Aziz, Azila Abd

2016-08-01

Virgin coconut oil (VCO) is the finest grade of coconut oil, rich in phenolic content, antioxidant activity and contains medium chain triglycerides (MCTs). In this work formulation, characterisation and penetration of VCO-solid lipid particles (VCO-SLP) have been studied. VCO-SLP were prepared using ultrasonication of molten stearic acid and VCO in an aqueous solution. The electron microscopy imaging revealed that VCO-SLP were solid and spherical in shape. Ultrasonication was performed at several power intensities which resulted in particle sizes of VCO-SLP ranged from 0.608 ± 0.002 µm to 44.265 ± 1.870 µm. The particle size was directly proportional to the applied power intensity of ultrasonication. The zeta potential values of the particles were from -43.2 ± 0.28 mV to -47.5 ± 0.42 mV showing good stability. The cumulative permeation for the smallest sized VCO-SLP (0.608 µm) was 3.83 ± 0.01 µg/cm(2) whereas for larger carriers it was reduced (3.59 ± 0.02 µg/cm(2)). It is concluded that SLP have the potential to be exploited as a micro/nano scale cosmeceutical carrying vehicle for improved dermal delivery of VCO.

Src Homology 2-Domain Containing Leukocyte-Specific Phosphoprotein of 76 kDa (SLP-76) Is Required for Optimal CXCR4-Stimulated T Lymphocyte Firm Arrest to ICAM-1 Under Shear Flow

PubMed Central

Lee, Dooyoung; Kim, Jiyeon; Baker, Rebecca G.; Koretzky, Gary A.; Hammer, Daniel A.

2014-01-01

Summary Rapid arrest of T cells at target sites upon engagement of chemokine receptors is crucial to the proper functioning of the immune system. Although T cell arrest always occurs under hydrodynamic forces in vivo, most studies investigating the molecular mechanisms of arrest have been performed under static conditions. While the requirement of the adaptor protein SLP-76 in TCR-induced integrin activation has been demonstrated, its role in chemokine-triggered T cell adhesion is unknown. Using a flow chamber system, we show that SLP-76 plays an important role in regulating the transition from tethering and rolling to firm adhesion of T cells under physiological shear flow in response to CXCL12α SDF-1α); SLP-76-deficient primary T cells exhibited defective adhesion with a significant decrease in the number of firmly arrested cells. We further demonstrate the N-terminal phosphotyrosines of SLP-76 play a critical role in this T cell adhesion under flow. These findings reveal a novel role for SLP-76 in CXCR4-mediated T lymphocyte trafficking. PMID:22806433

Web-based Reanalysis Intercomparison Tools (WRIT): Comparing Reanalyses and Observational data.

NASA Astrophysics Data System (ADS)

Compo, G. P.; Smith, C. A.; Hooper, D. K.

2014-12-01

While atmospheric reanalysis datasets are widely used in climate science, many technical issues hinder comparing them to each other and to observations. The reanalysis fields are stored in diverse file architectures, data formats, and resolutions, with metadata, such as variable name and units, that also differ. Individual users have to download the fields, convert them to a common format, store them locally, change variable names, re-grid if needed, and convert units. Comparing reanalyses with observational datasets is difficult for similar reasons. Even if a dataset can be read via Open-source Project for a Network Data Access Protocol (OPeNDAP) or a similar protocol, most of this work is still needed. All of these tasks take time, effort, and money. To overcome some of the obstacles in reanalysis intercomparison, our group at the Cooperative Institute for Research in the Environmental Sciences (CIRES) at the University of Colorado and affiliated colleagues at National Oceanic and Atmospheric Administration's (NOAA's) Earth System Research Laboratory Physical Sciences Division (ESRL/PSD) have created a set of Web-based Reanalysis Intercomparison Tools (WRIT) at http://www.esrl.noaa.gov/psd/data/writ/. WRIT allows users to easily plot and compare reanalysis and observational datasets, and to test hypotheses. Currently, there are tools to plot monthly mean maps and vertical cross-sections, timeseries, and trajectories for standard pressure level and surface variables. Users can refine dates, statistics, and plotting options. Reanalysis datasets currently available include the NCEP/NCAR R1, NCEP/DOE R2, MERRA, ERA-Interim, NCEP CFSR and the 20CR. Observational datasets include those containing precipitation (e.g. GPCP), temperature (e.g. GHCNCAMS), winds (e.g. WASWinds), precipitable water (e.g. NASA NVAP), SLP (HadSLP2), and SST (NOAA ERSST). WRIT also facilitates the mission of the Reanalyses.org website as a convenient toolkit for studying the reanalysis datasets.

North Atlantic Oscillation and pollutants variability in Europe: model analysis and measurements intercomparison

NASA Astrophysics Data System (ADS)

Pausata, F.; Pozzoli, L.; Van Dingenen, R.; Vignati, E.; Cavalli, F.; Dentener, F. J.

2013-12-01

Ozone pollution and particulate matter (PM) represent a serious health and environmental problem. While ozone pollution is mostly produced by photochemistry in summer, PM is of main concern during winter. Both pollutants can be influenced nt only by local scale processes but also by long range transport driven by the atmospheric circulation and stratospheric ozone intrusions. We analyze the role of large scale atmospheric circulation variability in the North Atlantic basin in determining surface ozone and PM concentrations over Europe. Here, we show, using ground station measurements and a coupled atmosphere-chemistry model simulation for the period 1980-2005, that with regard to ozone the North Atlantic Oscillation (NAO) does affect surface ozone concentrations - on a monthly timescale, over 10 ppbv in southwestern, central and northern Europe - during all seasons except fall. We find that the first Principal Component, computed from the time variation of the sea level pressure (SLP) field, detects the atmosphere circulation/ozone relationship not only in winter and spring but also during summer, when the atmospheric circulation weakens and regional photochemical processes peak. Given the NAO forecasting skill at intraseasonal time scale, the first Principal Component of the SLP field could be used as an indicator to identify areas more exposed to forthcoming ozone pollution events. Finally, our results suggest that the increasing baseline ozone in western and northern Europe during the 1990s could be related to the prevailing positive phase of the NAO in that period. With regard to PM, our study shows that in winter the NAO modulates surface PM concentrations accounting in average up to 30% of the total PM variability. During positive NAO phases, positive PM anomalies occur over southern Europe, and negative anomalies in central-northern Europe. A positve shift of the NAO mean states, hence, leads to an increase in cardiac and resipratory morbidity related to PM exposure in the Mediterranean countries with up to over 5000 more deaths per 20 million people for a 2000 emission inventory.

Extreme summer temperatures in Iberia: health impacts and associated synoptic conditions

NASA Astrophysics Data System (ADS)

García-Herrera, R.; Díaz, J.; Trigo, R. M.; Hernández, E.

2005-02-01

This paper examines the effect of extreme summer temperatures on daily mortality in two large cities of Iberia: Lisbon (Portugal) and Madrid (Spain). Daily mortality and meteorological variables are analysed using the same methodology based on Box-Jenkins models. Results reveal that in both cases there is a triggering effect on mortality when maximum daily temperature exceeds a given threshold (34°C in Lisbon and 36°C in Madrid). The impact of most intense heat events is very similar for both cities, with significant mortality values occurring up to 3 days after the temperature threshold has been surpassed. This impact is measured as the percentual increase of mortality associated to a 1°C increase above the threshold temperature. In this respect, Lisbon shows a higher impact, 31%, as compared with Madrid at 21%. The difference can be attributed to demographic and socio-economic factors. Furthermore, the longer life span of Iberian women is critical to explain why, in both cities, females are more susceptible than males to heat effects, with an almost double mortality impact value. The analysis of Sea Level Pressure (SLP), 500hPa geopotential height and temperature fields reveals that, despite being relatively close to each other, Lisbon and Madrid have relatively different synoptic circulation anomalies associated with their respective extreme summer temperature days. The SLP field reveals higher anomalies for Lisbon, but extending over a smaller area. Extreme values in Madrid seem to require a more western location of the Azores High, embracing a greater area over Europe, even if it is not as deep as for Lisbon. The origin of the hot and dry air masses that usually lead to extreme heat days in both cities is located in Northern Africa. However, while Madrid maxima require wind blowing directly from the south, transporting heat from Southern Spain and Northern Africa, Lisbon maxima occur under more easterly conditions, when Northern African air flows over the central Iberian plateau, which had been previously heated.

Simulation of the modern arctic climate by the NCAR CCM1

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

Bromwich, D.H.; Tzeng, R.Y.; Parish, T.R.

The NCAR CCM1's simulation of the modern arctic climate is evaluated by comparing a five-year seasonal cycle simulation with the ECMWF global analyses. The sea level pressure (SLP), storm tracks, vertical cross section of height, 500-hPa height, total energy budget, and moisture budget are analyzed to investigate the biases in the simulated arctic climate. The results show that the model simulates anomalously low SLP, too much activity, and anomalously strong baroclinicity to the west of Greenland and vice versa to the east of Greenland. This bias is mainly attributed to the model's topographic representation of Greenland. First, the broadened Greenlandmore » topography in the model distorts the path of cyclone waves over the North Atlantic Ocean. Second, the model oversimulates the ridge over Greenland, which intensifies its blocking effect and steers the cyclone waves clockwise around it and hence produces an artificial [open quotes]circum-Greenland[close quotes] trough. These biases are significantly alleviated when the horizontal resolution increases to T42. Over the Arctic basin, the modal simulates large amounts of low-level (stratus) clouds in winter and almost no stratus in summer, which is opposite to the observations. This bias is mainly due to the location of the simulated SLP features and the negative anomaly of storm activity, which prevent the transport of moisture into this region during summer but favor this transport in winter. 26 refs., 14 figs., 42 tabs.« less

Slp-76 is a critical determinant of NK-cell mediated recognition of missing-self targets.

PubMed

Lampe, Kristin; Endale, Mehari; Cashman, Siobhan; Fang, Hao; Mattner, Jochen; Hildeman, David; Hoebe, Kasper

2015-07-01

Absence of MHC class I expression is an important mechanism by which NK cells recognize a variety of target cells, yet the pathways underlying "missing-self" recognition, including the involvement of activating receptors, remain poorly understood. Using ethyl-N-nitrosourea mutagenesis in mice, we identified a germline mutant, designated Ace, with a marked defect in NK cell mediated recognition and elimination of "missing-self" targets. The causative mutation was linked to chromosome 11 and identified as a missense mutation (Thr428Ile) in the SH2 domain of Slp-76-a critical adapter molecule downstream of ITAM-containing surface receptors. The Slp-76 Ace mutation behaved as a hypomorphic allele-while no major defects were observed in conventional T-cell development/function, a marked defect in NK cell mediated elimination of β2-microglobulin (β2M) deficient target cells was observed. Further studies revealed Slp-76 to control NK-cell receptor expression and maturation; however, activation of Slp-76(ace/ace) NK cells through ITAM-containing NK-cell receptors or allogeneic/tumor target cells appeared largely unaffected. Imagestream analysis of the NK-β2M(-/-) target cell synapse revealed a specific defect in actin recruitment to the conjugate synapse in Slp-76(ace/ace) NK cells. Overall these studies establish Slp-76 as a critical determinant of NK-cell development and NK cell mediated elimination of missing-self target cells in mice. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular Characterization of Mosquitocidal Toxin (Surface Layer Protein, SLP) from Bacillus cereus VCRC B540.

PubMed

Mani, Chinnasamy; Selvakumari, Jeyaperumal; Han, YeonSoo; Jo, YongHun; Thirugnanasambantham, Krishnaraj; Sundarapandian, Somaiah; Poopathi, Subbiah

2018-04-01

A marine Bacillus cereus (VCRC B540) with mosquitocidal effect was recently reported from red snapper fish (Lutjanus sanguineous) gut and surface layer protein (S-layer protein, SLP) was reported to be mosquito larvicidal factor. In this present study, the gene encoding the surface layer protein was amplified from the genomic DNA and functionally characterized. Amplification of SLP-encoding gene revealed 1,518 bp PCR product, and analysis of the sequence revealed the presence of 1482 bp open reading frame with coding capacity for a polypeptide of 493 amino acids. Phylogenetic analysis revealed with homology among closely related Bacillus cereus groups of organisms as well as Bacillus strains. Removal of nucleotides encoding signaling peptide revealed the functional cloning fragment of length 1398 bp. Theoretical molecular weight (51.7 kDa) and isoelectric point (5.99) of the deduced functional SLP protein were predicted using ProtParam. The amplified PCR product was cloned into a plasmid vector (pGEM-T), and the open reading frame free off signaling peptide was subsequently cloned inpET-28a(+) and expressed in Escherichia coli BL21 (DE3). The isopropyl-β-D-thiogalactopyranoside (IPTG)-induced recombinant SLP was confirmed using western blotting, and functional SLP revealed mosquito larvicidal property. Therefore, the major findings revealed that SLP is a factor responsible for mosquitocidal activity, and the molecular characterization of this toxin was extensively studied.

Slp-76 is a critical determinant of NK cell-mediated recognition of missing-self targets

PubMed Central

Lampe, Kristin; Endale, Mehari; Cashman, Siobhan; Fang, Hao; Mattner, Jochen; Hildeman, David; Hoebe, Kasper

2015-01-01

Absence of MHC class I expression is an important mechanism by which NK cells recognize a variety of target cells, yet the pathways underlying “missing-self” recognition, including the involvement of activating receptors, remain poorly understood. Using ENU mutagenesis in mice, we identified a germline mutant, designated Ace, with a marked defect in NK cell-mediated recognition and elimination of “missing-self” targets. The causative mutation was linked to chromosome 11 and identified as a missense mutation [Thr428Ile] in the SH2 domain of Slp-76—a critical adapter molecule downstream of ITAM-containing surface receptors. The Slp-76 Ace mutation behaved as a hypomorphic allele—while no major defects were observed in conventional T cell development/function, a marked defect in NK cell-mediated elimination of β2-Microglobulin (β2M)-deficient target cells was observed. Further studies revealed Slp-76 to control NK cell receptor expression and maturation, however, activation of Slp-76ace/ace NK cells through ITAM-containing NK cell receptors or allogeneic/tumor target cells appeared largely unaffected. Imagestream analysis of the NK-β2M−/− target cell synapse, revealed a specific defect in actin recruitment to the conjugate synapse in Slp-76ace/ace NK cells. Overall these studies establish Slp-76 as a critical determinant of NK cell development and NK cell-mediated elimination of missing-self target cells. PMID:25929249

76 FR 1656 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-11

... Exchange-listed securities priced at $1.00 or more. For such transactions in which the SLP also meets the 5... requirement''), the credit per share for the SLP will increase from the current rate of $0.0020 to $0.0027. For such transactions in which the SLP does not meet the 5% quoting requirement, the credit per share...

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Federal Register 2010, 2011, 2012, 2013, 2014

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... Exchange proposes to trade Nasdaq Securities within the existing DMM and SLP framework used to trade its... member organization will not be permitted to be registered as both the DMM Unit and an SLP for the same... Nasdaq Securities to a different DMM Unit or to a different SLP or SLPs. \\5\\ A representative of NYSE...

Magnetic fluid hyperthermia probed by both calorimetric and dynamic hysteresis measurements

NASA Astrophysics Data System (ADS)

Guibert, Clément; Fresnais, Jérôme; Peyre, Véronique; Dupuis, Vincent

2017-01-01

In this paper, we report an investigation of magnetic fluid hyperthermia (MFH) using combined calorimetric and newly implemented dynamic hysteresis measurements for two sets of well characterized size-sorted maghemite nanoparticles (with diameters of about 10 nm and 20 nm) dispersed in water and in glycerol. Our primary goal was to assess the influence of viscosity on the heating efficiency of magnetic nanoparticles described in terms of specific loss power (SLP or specific absorption rate, SAR) and dynamic hysteresis. In particular, we aimed to investigate how this SLP depends on the transition from Néelian to Brownian behavior of nanoparticles expected to occur between 10 nm and 20 nm (for maghemite) and dependent on the viscosity. While we observed a good agreement between calorimetric and dynamic hysteresis measurements, we found that the SLP measured for the different systems do not depend noticeably on the viscosity of solvent. Calculations performed according to Rosensweig's linear model [1] allow us to quantitatively reproduce our results at low field intensities, provided we use a value for the magnetic anisotropy constant much smaller than the one commonly used in the literature. This raises the question of the temperature dependance of the magnetic anisotropy constant and its relevance for a quantitative description of MFH.

Assessment of Retinal Nerve Fiber Layer Using Optical Coherence Tomography and Scanning Laser Polarimetry in Progressive Glaucomatous Optic Neuropathy

PubMed Central

Sehi, Mitra; Greenfield, David S.

2006-01-01

Purpose To describe a case of progressive glaucomatous optic neuropathy using scanning laser polarimetry with fixed (SLP-FCC) and variable corneal compensation (SLP-VCC) and optical coherence tomography (OCT). Design Observational case report. Methods A 21-year-old male with juvenile primary open-angle glaucoma developed progression because of noncompliance with therapy. The patient underwent dilated stereoscopic examination and photography of the optic disk, standard automated perimetry (SAP), OCT, and SLP imaging with FCC and VCC at the baseline examination and after four years of follow-up. Results Optic disk, retinal nerve fiber layer (RNFL) atrophy, and SAP progression was observed. Reduction in mean RNFL thickness (average, superior, inferior) was 18, 18, and 27 microns (OCT); 22, 40, and 17 microns (SLP-FCC); and 6, 12, and 12 microns (SLP-VCC), respectively. Conclusions This case demonstrates that digital imaging of the peripapillary RNFL is capable of documentation and measurement of progressive glaucomatous RNFL atrophy. PMID:17157591

77 FR 74034 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-12

... (``NYSE CADV'') or of September 2012 Adding ADV (``SLP Baseline ADV''). If the Exchange did not exclude...% of NYSE CADV that relates to the SLP credit of $0.0023 (or $0.0018 if a Non-Displayed Reserve Order) per share; The thresholds of ADV of 0.22% of NYSE CADV and 0.18% of SLP Baseline ADV, as well as the...

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Stochastic Dynamic Mixed-Integer Programming (SD-MIP)

DTIC Science & Technology

2015-05-05

stochastic linear programming ( SLP ) problems. By using a combination of ideas from cutting plane theory of deterministic MIP (especially disjunctive...developed to date. b) As part of this project, we have also developed tools for very large scale Stochastic Linear Programming ( SLP ). There are...several reasons for this. First, SLP models continue to challenge many of the fastest computers to date, and many applications within the DoD (e.g

Ultra-Wideband Harmonic Radar for Locating Radio-Frequency Electronics

DTIC Science & Technology

2015-03-01

13  Fig. A-1 Measured S-parameters for the MiniCircuits SLP ...MiniCircuits SLP -1000+ lowpass filters. The relatively weak signal at f0 is increased by 40 dB by the Amplifier Research AR4W1000 power amplifier. The...Fig. A-1 Measured S-parameters for the MiniCircuits SLP -1000+ lowpass filter pair Fig. A-2 Measured S-parameters for the Amplifier Research

Retinal degeneration in progressive supranuclear palsy measured by optical coherence tomography and scanning laser polarimetry.

PubMed

Stemplewitz, Birthe; Kromer, Robert; Vettorazzi, Eik; Hidding, Ute; Frings, Andreas; Buhmann, Carsten

2017-07-13

This cross-sectional study compared the retinal morphology between patients with progressive supranuclear palsy (PSP) and healthy controls. (The retinal nerve fiber layer (RNFL) around the optic disc and the retina in the macular area of 22 PSP patients and 151 controls were investigated by spectral domain optical coherence tomography (SD-OCT). Additionally, the RNFL and the nerve fiber index (NFI) were measured by scanning laser polarimetry (SLP). Results of RNFL measurements with SD-OCT and SLP were compared to assess diagnostic discriminatory power. Applying OCT, PSP patients showed a smaller RNFL thickness in the inferior nasal and inferior temporal areas. The macular volume and the thickness of the majority of macular sectors were reduced compared to controls. SLP data showed a thinner RNFL thickness and an increase in the NFI in PSP patients. Sensitivity and specificity to discriminate PSP patients from controls were higher applying SLP than SD-OCT. Retinal changes did not correlate with disease duration or severity in any OCT or SLP measurement. PSP seems to be associated with reduced thickness and volume of the macula and reduction of the RNFL, independent of disease duration or severity. Retinal imaging with SD-OCT and SLP might become an additional tool in PSP diagnosis.

The Immune Adaptor SLP-76 Binds to SUMO-RANGAP1 at Nuclear Pore Complex Filaments to Regulate Nuclear Import of Transcription Factors in T Cells

PubMed Central

Liu, Hebin; Schneider, Helga; Recino, Asha; Richardson, Christine; Goldberg, Martin W.; Rudd, Christopher E.

2015-01-01

Summary While immune cell adaptors regulate proximal T cell signaling, direct regulation of the nuclear pore complex (NPC) has not been reported. NPC has cytoplasmic filaments composed of RanGAP1 and RanBP2 with the potential to interact with cytoplasmic mediators. Here, we show that the immune cell adaptor SLP-76 binds directly to SUMO-RanGAP1 of cytoplasmic fibrils of the NPC, and that this interaction is needed for optimal NFATc1 and NF-κB p65 nuclear entry in T cells. Transmission electron microscopy showed anti-SLP-76 cytoplasmic labeling of the majority of NPCs in anti-CD3 activated T cells. Further, SUMO-RanGAP1 bound to the N-terminal lysine 56 of SLP-76 where the interaction was needed for optimal RanGAP1-NPC localization and GAP exchange activity. While the SLP-76-RanGAP1 (K56E) mutant had no effect on proximal signaling, it impaired NF-ATc1 and p65/RelA nuclear entry and in vivo responses to OVA peptide. Overall, we have identified SLP-76 as a direct regulator of nuclear pore function in T cells. PMID:26321253

SLP-76 is required for optimal CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow.

PubMed

Lee, Dooyoung; Kim, Jiyeon; Baker, Rebecca G; Koretzky, Gary A; Hammer, Daniel A

2012-10-01

Rapid arrest of T cells at target sites upon engagement of chemokine receptors is crucial to the proper functioning of the immune system. Although T-cell arrest always occurs under hydrodynamic forces in vivo, most studies investigating the molecular mechanisms of arrest have been performed under static conditions. While the requirement of the adapter protein SLP-76 (Src homology 2-domain containing leukocyte-specific phosphoprotein of 76 kDa) in TCR-induced integrin activation has been demonstrated, its role in chemokine-triggered T-cell adhesion is unknown. Using a flow chamber system, we show that SLP-76 plays an important role in regulating the transition from tethering and rolling to firm adhesion of T cells under physiological shear flow in response to CXCL12α (stromal cell-derived factor-1α); SLP-76-deficient primary T cells exhibited defective adhesion with a significant decrease in the number of firmly arrested cells. We further demonstrate the N-terminal phosphotyrosines of SLP-76 play a critical role in T-cell adhesion under flow. These findings reveal a novel role for SLP-76 in CXCR4-mediated T lymphocyte trafficking. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficient T-cell receptor signaling requires a high-affinity interaction between the Gads C-SH3 domain and the SLP-76 RxxK motif.

PubMed

Seet, Bruce T; Berry, Donna M; Maltzman, Jonathan S; Shabason, Jacob; Raina, Monica; Koretzky, Gary A; McGlade, C Jane; Pawson, Tony

2007-02-07

The relationship between the binding affinity and specificity of modular interaction domains is potentially important in determining biological signaling responses. In signaling from the T-cell receptor (TCR), the Gads C-terminal SH3 domain binds a core RxxK sequence motif in the SLP-76 scaffold. We show that residues surrounding this motif are largely optimized for binding the Gads C-SH3 domain resulting in a high-affinity interaction (K(D)=8-20 nM) that is essential for efficient TCR signaling in Jurkat T cells, since Gads-mediated signaling declines with decreasing affinity. Furthermore, the SLP-76 RxxK motif has evolved a very high specificity for the Gads C-SH3 domain. However, TCR signaling in Jurkat cells is tolerant of potential SLP-76 crossreactivity, provided that very high-affinity binding to the Gads C-SH3 domain is maintained. These data provide a quantitative argument that the affinity of the Gads C-SH3 domain for SLP-76 is physiologically important and suggest that the integrity of TCR signaling in vivo is sustained both by strong selection of SLP-76 for the Gads C-SH3 domain and by a capacity to buffer intrinsic crossreactivity.

In vivo significance of ITK-SLP-76 interaction in cytokine production.

PubMed

Grasis, Juris A; Guimond, David M; Cam, Nicholas R; Herman, Krystal; Magotti, Paola; Lambris, John D; Tsoukas, Constantine D

2010-07-01

In vitro data have suggested that activation of the inducible T-cell kinase (ITK) requires an interaction with the adaptor protein SLP-76. One means for this interaction involves binding of the ITK SH3 domain to the polyproline-rich (PR) region of SLP-76. However, the biological significance of this association in live cells and the consequences of its disruption have not been demonstrated. Here, we utilized a polyarginine-rich, cell-permeable peptide that represents the portion of the SLP-76 PR region that interacts with the ITK SH3 domain as a competitive inhibitor to disrupt the association between ITK and SLP-76 in live cells. We demonstrate that treatment of cells with this peptide, by either in vitro incubation or intraperitoneal injection of the peptide in mice, inhibits the T-cell receptor (TCR)-induced association between ITK and SLP-76, recruitment and transphosphorylation of ITK, actin polarization at the T-cell contact site, and expression of Th2 cytokines. The inhibition is specific, as indicated by lack of effects by the polyarginine vehicle alone or a scrambled sequence of the cargo peptide. In view of the role of ITK as a regulator of Th2 cytokine expression, the data underscore the significance of ITK as a target for pharmacological intervention.

The Immune Adaptor SLP-76 Binds to SUMO-RANGAP1 at Nuclear Pore Complex Filaments to Regulate Nuclear Import of Transcription Factors in T Cells.

PubMed

Liu, Hebin; Schneider, Helga; Recino, Asha; Richardson, Christine; Goldberg, Martin W; Rudd, Christopher E

2015-09-03

While immune cell adaptors regulate proximal T cell signaling, direct regulation of the nuclear pore complex (NPC) has not been reported. NPC has cytoplasmic filaments composed of RanGAP1 and RanBP2 with the potential to interact with cytoplasmic mediators. Here, we show that the immune cell adaptor SLP-76 binds directly to SUMO-RanGAP1 of cytoplasmic fibrils of the NPC, and that this interaction is needed for optimal NFATc1 and NF-κB p65 nuclear entry in T cells. Transmission electron microscopy showed anti-SLP-76 cytoplasmic labeling of the majority of NPCs in anti-CD3 activated T cells. Further, SUMO-RanGAP1 bound to the N-terminal lysine 56 of SLP-76 where the interaction was needed for optimal RanGAP1-NPC localization and GAP exchange activity. While the SLP-76-RanGAP1 (K56E) mutant had no effect on proximal signaling, it impaired NF-ATc1 and p65/RelA nuclear entry and in vivo responses to OVA peptide. Overall, we have identified SLP-76 as a direct regulator of nuclear pore function in T cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of Laser Scanning Diagnostic Devices for Early Glaucoma Detection.

PubMed

Schulze, Andreas; Lamparter, Julia; Pfeiffer, Norbert; Berisha, Fatmire; Schmidtmann, Irene; Hoffmann, Esther M

2015-08-01

To compare the diagnostic accuracy and to evaluate the correlation of optic nerve head and retinal nerve fiber layer thickness values between Fourier-Domain optical coherence tomography (FD-OCT), confocal scanning laser ophthalmoscopy (CSLO), and scanning laser polarimetry (SLP) for early glaucoma detection. Ninety-three patients with early open-angle glaucoma, 58 patients with ocular hypertension, and 60 healthy control subjects were included in this observational, cross-sectional study. All study participants underwent FD-OCT (RTVue-100), CSLO (HRT3), and SLP (GDx VCC) imaging of the optic nerve head and the retinal nerve fiber layer. Area under the receiver operating characteristic curves (AUROC) and Bland-Altman analysis were performed. The parameters with the highest diagnostic accuracy were found for FD-OCT cup-to-disc ratio (AUROC=0.841), for SLP NFI (AUROC=0.835), and for CSLO cup-to-disc ratio (AUROC=0.789). Diagnostic accuracy of the best CSLO and SLP parameter was similar (P=0.259). There was a small statistically significant difference between the best CSLO and FD-OCT parameters for differentiating between glaucoma and healthy eyes (P=0.047). FD-OCT and SLP have a similarly good diagnostic ability to distinguish between early glaucoma and healthy subjects. The diagnostic accuracy of CSLO was comparable with SLP and marginally lower compared with FD-OCT.

"It's not everyday that parents get a chance to talk like this": Exploring parents' perceptions and expectations of speech-language pathology services for children with intellectual disability.

PubMed

Carroll, Clare

2010-08-01

Tailoring the delivery of disability services to the preferences and requirements of service users allows for more effective partnerships. The aim of this research was to explore parents' perceptions and the expectations of their child's speech-language pathology (SLP) within an intellectual disability service. Parents of school-aged children with intellectual disability who received a SLP service in Ireland participated in the research: 17 parents participated in focus groups and 103 parents answered questionnaires. The core themes from the focus groups, which subsequently informed the questionnaire design, were: experience of the SLP service, communication difficulties, expectations of the SLP service, and future developments. The key questionnaire results indicated that parents viewed their SLP as the "expert" and viewed school-based and clinic-based services differently. Parents were more likely to believe that their child would always need therapy if they received a school-based service. Whereas, parents were more likely to think that their child's speech was improving as they got older and were more likely to be aware of therapy activities if therapy was clinic-based. The findings have implications for the delivery of SLP services suggesting that clarification of parents' roles and expectations are required.

Ablation of SLP-76 signaling after T cell priming generates memory CD4 T cells impaired in steady-state and cytokine-driven homeostasis.

PubMed

Bushar, Nicholas D; Corbo, Evann; Schmidt, Michelle; Maltzman, Jonathan S; Farber, Donna L

2010-01-12

The intracellular signaling mechanisms regulating the generation and long-term persistence of memory T cells in vivo remain unclear. In this study, we used mouse models with conditional deletion of the key T cell receptor (TCR)-coupled adaptor molecule SH2-domain-containing phosphoprotein of 76 kDa (SLP-76), to analyze signaling mechanisms for memory CD4 T cell generation, maintenance, and homeostasis. We found that ablation of SLP-76 expression after T cell priming did not inhibit generation of phenotypic effector or memory CD4 T cells; however, the resultant SLP-76-deficient memory CD4 T cells could not produce recall cytokines in response to TCR-mediated stimulation and showed decreased persistence in vivo. In addition, SLP-76-deficient memory CD4 T cells exhibited reduced steady-state homeostasis and were impaired in their ability to homeostatically expand in vivo in response to the gamma(c) cytokine IL-7, despite intact proximal signaling through the IL-7R-coupled JAK3/STAT5 pathway. Direct in vivo deletion of SLP-76 in polyclonal memory CD4 T cells likewise led to impaired steady-state homeostasis as well as impaired homeostatic responses to IL-7. Our findings demonstrate a dominant role for SLP-76-dependent TCR signals in regulating turnover and perpetuation of memory CD4 T cells and their responses to homeostatic cytokines, with implications for the selective survival of memory CD4 T cells following pathogen exposure, vaccination, and aging.

Vav1-mediated scaffolding interactions stabilize SLP-76 microclusters and contribute to antigen-dependent T cell responses.

PubMed

Sylvain, Nicholas R; Nguyen, Ken; Bunnell, Stephen C

2011-03-08

The guanine nucleotide exchange factor (GEF) Vav1 synergizes with the adaptor protein SLP-76 (Src homology 2 domain--containing leukocyte phosphoprotein of 76 kD) to support T cell development and activation. In response to ligation of the T cell receptor (TCR), SLP-76 is assembled into microclusters that provide an essential platform for the signaling events that drive T cell activation. We found that Vav1 selectively entered SLP-76 microclusters, rather than TCR microclusters, influencing their stability and function. The carboxyl terminus of Vav1, which consists of Src homology domains, was both necessary and sufficient for the entry of Vav1 into SLP-76 microclusters; however, this fragment of Vav1 was insufficient to stabilize the microclusters, and it potently suppressed T cell activation. This indicated that the amino terminus of Vav1, which has the GEF domain, also contributed to the integrity of SLP-76 microclusters and thereby to T cell activation. These microcluster-stabilizing functions were independent of the GEF activity in the amino terminus of Vav1 and were unaffected if the GEF function of Vav1 was either inactivated or constitutively activated by mutation. In contrast, Vav1 deletion mutants lacking either the calponin homology domain or the catalytic core of the GEF exhibited mild scaffolding defects, but they differentially affected TCR-dependent calcium ion (Ca²+) responses. We conclude that multiple GEF-independent scaffolding functions distributed throughout the amino terminus of Vav1 contribute to the activation of T cells by acting synergistically to increase the stability and function of SLP-76 microclusters.

Electron transport chain in a thermotolerant yeast.

PubMed

Mejía-Barajas, Jorge A; Martínez-Mora, José A; Salgado-Garciglia, Rafael; Noriega-Cisneros, Ruth; Ortiz-Avila, Omar; Cortés-Rojo, Christian; Saavedra-Molina, Alfredo

2017-04-01

Yeasts capable of growing and surviving at high temperatures are regarded as thermotolerant. For appropriate functioning of cellular processes and cell survival, the maintenance of an optimal redox state is critical of reducing and oxidizing species. We studied mitochondrial functions of the thermotolerant Kluyveromyces marxianus SLP1 and the mesophilic OFF1 yeasts, through the evaluation of its mitochondrial membrane potential (ΔΨ m ), ATPase activity, electron transport chain (ETC) activities, alternative oxidase activity, lipid peroxidation. Mitochondrial membrane potential and the cytoplasmic free Ca 2+ ions (Ca 2+ cyt) increased in the SLP1 yeast when exposed to high temperature, compared with the mesophilic yeast OFF1. ATPase activity in the mesophilic yeast diminished 80% when exposed to 40° while the thermotolerant SLP1 showed no change, despite an increase in the mitochondrial lipid peroxidation. The SLP1 thermotolerant yeast exposed to high temperature showed a diminution of 33% of the oxygen consumption in state 4. The uncoupled state 3 of oxygen consumption did not change in the mesophilic yeast when it had an increase of temperature, whereas in the thermotolerant SLP1 yeast resulted in an increase of 2.5 times when yeast were grown at 30 o , while a decrease of 51% was observed when it was exposed to high temperature. The activities of the ETC complexes were diminished in the SLP1 when exposed to high temperature, but also it was distinguished an alternative oxidase activity. Our results suggest that the mitochondria state, particularly ETC state, is an important characteristic of the thermotolerance of the SLP1 yeast strain.

Responses of summer Asian-Pacific zonal thermal contrast and associated evolutions of atmospheric circulation to transient orbital change during the Holocene

NASA Astrophysics Data System (ADS)

Xiao, D.; Zhao, P.

2016-12-01

This study investigates the response of large-scale atmospheric circulation over the Asian-Pacific sector and precipitation over eastern China to the transient orbital changes during the Holocene summer. Corresponding to a variation of the incoming solar radiation, eddy sea level pressure (SLP) presented an out-of-phase relationship between the North Pacific and the Eurasian landmass, which is similar to the present-day Asia-Pacific Oscillation (APO) pattern and defined as the paleo-APO. Its index presented an increasing trend, which implies an enhancement of the zonal thermal contrast between Asia and North Pacific. Associated with the strengthening of thermal contrast was the westward shift of North Pacific high pressure. Accordingly, there were less summer precipitation over both the middle reach of the Yangtze River and Southwest China and more precipitation over North China during. The high-resolution stalagmite δ18O records further support this decrease in the simulated precipitation. From the negative phase of paleo-APO during the early Holocene to the recent positive phase, the eddy SLP anomalies show a decreasing/increasing trend over the Eurasian landmass/the North Pacific, with a phase change around 4.5 ka BP, and they both move westward. Meanwhile, less rainfall belt over East China shows a northward propagation from southern China.

On the relationship between tropospheric conditions and widespread hot days in Iran

NASA Astrophysics Data System (ADS)

Asakereh, Hossein; Shadman, Hassan

2018-01-01

The present study investigated how the tropospheric conditions relate to the occurrence of widespread hot days (WHD) in Iran using the data of maximum daily temperature and other tropospheric variables. To better understand the tropospheric conditions during WHD, different patterns of tropospheric circulation were examined systematically. Four tropospheric types were identified based on sea level pressure (SLP). SLP, 500 hPa height, anomaly patterns, and warm advection maps were constructed for typical days of each group. The tropospheric conditions associated with hot days occurred simultaneously with a low-pressure system at sea level, a ridge at middle troposphere over Iran, and a pronounced trough over the Mediterranean Sea at 500 hPa. These conditions caused air mass from subtropical regions toward Iran. That is, northward, northeastward, and even eastward winds injected heat with warm origins toward the country. Hot days compounded by drought conditions have affected many parts of the country in different ways such as decrease in the agricultural products in numerous areas and significant discharge reduction in many rivers. The society is also very likely to face considerable challenges to cope with hot days. The findings of the study can be utilized in climate modeling and climate prediction of hot days in the country. Accordingly, water and electricity consumption can be planned with further precision and water consumption can be managed in crises.

Seasonal mean pressure reconstruction for the North Atlantic (1750 1850) based on early marine data

NASA Astrophysics Data System (ADS)

Gallego, D.; Garcia-Herrera, R.; Ribera, P.; Jones, P. D.

2005-12-01

Measurements of wind strength and direction abstracted from European ships' logbooks during the recently finished CLIWOC project have been used to produce the first gridded Sea Level Pressure (SLP) reconstruction for the 1750-1850 period over the North Atlantic based solely on marine data. The reconstruction is based on a spatial regression analysis calibrated by using data taken from the ICOADS database. An objective methodology has been developed to select the optimal calibration period and spatial domain of the reconstruction by testing several thousands of possible models. The finally selected area, limited by the performance of the regression equations and by the availability of data, covers the region between 28° N and 52° N close to the European coast and between 28° N and 44° N in the open Ocean. The results provide a direct measure of the strength and extension of the Azores High during the 101 years of the study period. The comparison with the recent land-based SLP reconstruction by Luterbacher et al. (2002) indicates the presence of a common signal. The interannual variability of the CLIWOC reconstructions is rather high due to the current scarcity of abstracted wind data in the areas with best response in the regression. Guidelines are proposed to optimize the efficiency of future abstraction work.

Seasonal mean pressure reconstruction for the North Atlantic (1750 1850) based on early marine data

NASA Astrophysics Data System (ADS)

Gallego, D.; Garcia-Herrera, R.; Ribera, P.; Jones, P. D.

2005-08-01

Measures of wind strength and direction abstracted from European ships' logbooks during the recently finished CLIWOC project have been used to produce the first gridded Sea Level Pressure (SLP) reconstruction for the 1750-1850 period over the North Atlantic based solely on marine data. The reconstruction is based on a spatial regression analysis calibrated by using data taken from the ICOADS database. An objective methodology has been developed to select the optimal calibration period and spatial domain of the reconstruction by testing several thousands of possible models. The finally selected area, limited by the performance of the regression equations and by the availability of data, covers the region between 28°N and 52°N close to the European coast and between 28°N and 44°N in the open Ocean. The results provide a direct measure of the strength and extension of the Azores High during the 101 years of the study period. The comparison with the recent land-based SLP reconstruction by Luterbacher et al. (2002) indicates the presence of a common signal. The interannual variability of the CLIWOC reconstructions is rather high due to the current scarcity of abstracted wind data in the areas with best response in the regression. Guidelines are proposed to optimize the efficiency of future abstraction work.

A mutation within the SH2 domain of slp-76 regulates the tissue distribution and cytokine production of iNKT cells in mice.

PubMed

Danzer, Claudia; Koller, Anna; Baier, Julia; Arnold, Harald; Giessler, Claudia; Opoka, Robert; Schmidt, Stephanie; Willers, Maike; Mihai, Sidonia; Parsch, Hans; Wirtz, Stefan; Daniel, Christoph; Reinhold, Annegret; Engelmann, Swen; Kliche, Stefanie; Bogdan, Christian; Hoebe, Kasper; Mattner, Jochen

2016-09-01

TCR ligation is critical for the selection, activation, and integrin expression of T lymphocytes. Here, we explored the role of the TCR adaptor protein slp-76 on iNKT-cell biology. Compared to B6 controls, slp-76(ace/ace) mice carrying a missense mutation (Thr428Ile) within the SH2-domain of slp-76 showed an increase in iNKT cells in the thymus and lymph nodes, but a decrease in iNKT cells in spleens and livers, along with reduced ADAP expression and cytokine response. A comparable reduction in iNKT cells was observed in the livers and spleens of ADAP-deficient mice. Like ADAP(-/-) iNKT cells, slp-76(ace/ace) iNKT cells were characterized by enhanced CD11b expression, correlating with an impaired induction of the TCR immediate-early gene Nur77 and a decreased adhesion to ICAM-1. Furthermore, CD11b-intrinsic effects inhibited cytokine release, concanavalin A-mediated inflammation, and iNKT-cell accumulation in the liver. Unlike B6 and ADAP(-/-) mice, the expression of the transcription factors Id3 and PLZF was reduced, whereas NP-1-expression was enhanced in slp-76(ace/ace) mice. Blockade of NP-1 decreased the recovery of iNKT cells from peripheral lymph nodes, identifying NP-1 as an iNKT-cell-specific adhesion factor. Thus, slp-76 contributes to the regulation of the tissue distribution, PLZF, and cytokine expression of iNKT cells via ADAP-dependent and -independent mechanisms. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

HIV-1 Nef limits communication between linker of activated T cells and SLP-76 to reduce formation of SLP-76-signaling microclusters following TCR stimulation.

PubMed

Abraham, Libin; Bankhead, Peter; Pan, Xiaoyu; Engel, Ulrike; Fackler, Oliver T

2012-08-15

Signal initiation by engagement of the TCR triggers actin rearrangements, receptor clustering, and dynamic organization of signaling complexes to elicit and sustain downstream signaling. Nef, a pathogenicity factor of HIV, disrupts early TCR signaling in target T cells. To define the mechanism underlying this Nef-mediated signal disruption, we employed quantitative single-cell microscopy following surface-mediated TCR stimulation that allows for dynamic visualization of distinct signaling complexes as microclusters (MCs). Despite marked inhibition of actin remodeling and cell spreading, the induction of MCs containing TCR-CD3 or ZAP70 was not affected significantly by Nef. However, Nef potently inhibited the subsequent formation of MCs positive for the signaling adaptor Src homology-2 domain-containing leukocyte protein of 76 kDa (SLP-76) to reduce MC density in Nef-expressing and HIV-1-infected T cells. Further analyses suggested that Nef prevents formation of SLP-76 MCs at the level of the upstream adaptor protein, linker of activated T cells (LAT), that couples ZAP70 to SLP-76. Nef did not disrupt pre-existing MCs positive for LAT. However, the presence of the viral protein prevented de novo recruitment of active LAT into MCs due to retargeting of LAT to an intracellular compartment. These modulations in MC formation and composition depended on Nef's ability to simultaneously disrupt both actin remodeling and subcellular localization of TCR-proximal machinery. Nef thus employs a dual mechanism to disturb early TCR signaling by limiting the communication between LAT and SLP-76 and preventing the dynamic formation of SLP-76-signaling MCs.

Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1

PubMed Central

Dios-Esponera, Ana; Isern de Val, Soledad; Sevilla-Movilla, Silvia; García-Verdugo, Rosa; García-Bernal, David; Arellano-Sánchez, Nohemí; Cabañas, Carlos; Teixidó, Joaquin

2015-01-01

Stimulation by chemokines of integrin α4β1–dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase–inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76–, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation. PMID:26202465

Methylene blue stimulates substrate-level phosphorylation catalysed by succinyl-CoA ligase in the citric acid cycle.

PubMed

Komlódi, T; Tretter, L

2017-09-01

Methylene blue (MB), a potential neuroprotective agent, is efficient in various neurodegenerative disease models. Beneficial effects of MB have been attributed to improvements in mitochondrial functions. Substrate-level phosphorylation (SLP) results in the production of ATP independent from the ATP synthase (ATP-ase). In energetically compromised mitochondria, ATP produced by SLP can prevent the reversal of the adenine nucleotide translocase and thus the hydrolysis of glycolytic ATP. The aim of the present study was to investigate the effect of MB on mitochondrial SLP catalysed by succinyl-CoA ligase. Measurements were carried out on isolated guinea pig cortical mitochondria respiring on α-ketoglutarate, glutamate, malate or succinate. The mitochondrial functions and parameters like ATP synthesis, oxygen consumption, membrane potential, and NAD(P)H level were followed online, in parallel with the redox state of MB. SLP-mediated ATP synthesis was measured in the presence of inhibitors for ATP-ase and adenylate kinase. In the presence of the ATP-ase inhibitor oligomycin MB stimulated respiration with all of the respiratory substrates. However, the rate of ATP synthesis increased only with substrates α-ketoglutarate and glutamate (forming succinyl-CoA). MB efficiently stimulated SLP and restored the membrane potential in mitochondria also with the combined inhibition of Complex I and ATP synthase. ATP formed by SLP alleviated the energetic insufficiency generated by the lack of oxidative phosphorylation. Thus, the MB-mediated stimulation of SLP might be important in maintaining the energetic competence of mitochondria and in preventing the mitochondrial hydrolysis of glycolytic ATP. The mitochondrial effects of MB are explained by the ability to accept electrons from reducing equivalents and transfer them to cytochrome c bypassing the respiratory Complexes I and III. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Relative Frequency of Rossby Wave Train Triggering Mechanisms Associated with Downstream Development Over Europe

DTIC Science & Technology

2014-06-01

subsequent to the beginning of the transformation stage. Means ± standard deviation of SLP are listed for each step of transformation, and for the...labeled every 6 dam, and solid contours are SLP every 4 hPa (unpublished figure provided by H. Archambault...53.  A 1-day SLP anomaly (color shading, hPa) from the NCEP operational dataset for 31 Oct 2010. (Image provided by the NOAA/ESRL Physical Sciences

Defining a Technical Basis for Comparing and Contrasting Emerging Dynamic Discovery Protocols

DTIC Science & Technology

2001-05-02

UPnP, SLP, Bluetooth , and HAVi • Projected specific UML models for Jini, UPnP, and SLP • Completed a Rapide Model of Jini structure, function, and...narrow application focus but targeting a different application domain. (e.g., HAVi, Salutation Consortium, and Bluetooth Service Discovery) • Sun has...Our General Approach? 1/31/2002 7 Particulars of Our Approach Define a Generic UML Model that Encompasses Jini, UPnP, SLP, HAVi, and Bluetooth

SLP-76-ADAP adaptor module regulates LFA-1 mediated costimulation and T cell motility.

PubMed

Wang, Hongyan; Wei, Bin; Bismuth, Georges; Rudd, Christopher E

2009-07-28

Although adaptor ADAP (FYB) and its binding to SLP-76 has been implicated in TcR-induced "inside-out" signaling for LFA-1 activation in T cells, little is known regarding its role in LFA-1-mediated "outside-in" signaling. In this study, we demonstrate that ADAP and SLP-76-ADAP binding are coupled to LFA-1 costimulation of IL-2 production, F-actin clustering, cell polarization, and T cell motility. LFA-1 enhancement of anti-CD3-induced IL-2 production was completely dependent on SLP-76-ADAP binding. Further, anti-CD3 was found to require CD11a ligation by antibody or ICAM1 to cause T cell polarization. ADAP augmented this polarization induced by anti-CD3/CD11a, but not by anti-CD3 alone. ADAP expression with LFA-1 ligation alone was sufficient to polarize T cells directly and to increase T cell motility whereas the loss of ADAP in ADAP-/- primary T cells reduced motility. A mutant lacking SLP-76-binding sites (M12) blocked LFA-1 costimulation of IL-2 production, polarization, and motility. LFA-1-ADAP polarization was also dependent on src kinases, Rho GTPases, phospholipase C, and phosphoinositol 3-kinase. Our findings provide evidence of an obligatory role for the SLP-76-ADAP module in LFA-1-mediated costimulation in T cells.

GrpL, a Grb2-related Adaptor Protein, Interacts with SLP-76 to Regulate Nuclear Factor of Activated T Cell Activation

PubMed Central

Law, Che-Leung; Ewings, Maria K.; Chaudhary, Preet M.; Solow, Sasha A.; Yun, Theodore J.; Marshall, Aaron J.; Hood, Leroy; Clark, Edward A.

1999-01-01

Propagation of signals from the T cell antigen receptor (TCR) involves a number of adaptor molecules. SH2 domain–containing protein 76 (SLP-76) interacts with the guanine nucleotide exchange factor Vav to activate the nuclear factor of activated cells (NF-AT), and its expression is required for normal T cell development. We report the cloning and characterization of a novel Grb2-like adaptor molecule designated as Grb2-related protein of the lymphoid system (GrpL). Expression of GrpL is restricted to hematopoietic tissues, and it is distinguished from Grb2 by having a proline-rich region. GrpL can be coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jurkat cell lysates. In contrast, Grb2 can be coimmunoprecipitated with Sos1 and Sos2 but not with SLP-76. Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL. These data reveal the presence of distinct complexes involving GrpL and Grb2 in T cells. A functional role of the GrpL–SLP-76 complex is suggested by the ability of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in Jurkat T cells. PMID:10209041

Seasonal prediction of US summertime ozone using statistical analysis of large scale climate patterns.

PubMed

Shen, Lu; Mickley, Loretta J

2017-03-07

We develop a statistical model to predict June-July-August (JJA) daily maximum 8-h average (MDA8) ozone concentrations in the eastern United States based on large-scale climate patterns during the previous spring. We find that anomalously high JJA ozone in the East is correlated with these springtime patterns: warm tropical Atlantic and cold northeast Pacific sea surface temperatures (SSTs), as well as positive sea level pressure (SLP) anomalies over Hawaii and negative SLP anomalies over the Atlantic and North America. We then develop a linear regression model to predict JJA MDA8 ozone from 1980 to 2013, using the identified SST and SLP patterns from the previous spring. The model explains ∼45% of the variability in JJA MDA8 ozone concentrations and ∼30% variability in the number of JJA ozone episodes (>70 ppbv) when averaged over the eastern United States. This seasonal predictability results from large-scale ocean-atmosphere interactions. Warm tropical Atlantic SSTs can trigger diabatic heating in the atmosphere and influence the extratropical climate through stationary wave propagation, leading to greater subsidence, less precipitation, and higher temperatures in the East, which increases surface ozone concentrations there. Cooler SSTs in the northeast Pacific are also associated with more summertime heatwaves and high ozone in the East. On average, models participating in the Atmospheric Model Intercomparison Project fail to capture the influence of this ocean-atmosphere interaction on temperatures in the eastern United States, implying that such models would have difficulty simulating the interannual variability of surface ozone in this region.

Exploring the combined effects of the Arctic Oscillation and ENSO on the wintertime climate over East Asia using self-organizing maps

NASA Astrophysics Data System (ADS)

Huang, Wenyu; Chen, Ruyan; Yang, Zifan; Wang, Bin; Ma, Wenqian

2017-09-01

To examine the combined effects of the different spatial patterns of the Arctic Oscillation (AO)-related sea level pressure (SLP) anomalies and the El Niño-Southern Oscillation (ENSO)-related sea surface temperature (SST) anomalies on the wintertime surface temperature anomalies over East Asia, a nonlinear method based on self-organizing maps is employed. Investigation of identified regimes reveals that the AO can affect East Asian temperature anomalies when there are significant SLP anomalies over the Arctic Ocean and northern parts of Eurasian continent. Analogously, ENSO is found to affect East Asian temperature anomalies when significant SST anomalies are present over the tropical central Pacific. The regimes with the warmest and coldest temperature anomalies over East Asia are both associated with the negative phase of the AO. The ENSO-activated, Pacific-East Asian teleconnection pattern could affect the higher latitude continental regions when the impact of the AO is switched off. When the spatial patterns of the AO and ENSO have significant, but opposite, impacts on the coastal winds, no obvious temperature anomalies can be observed over south China. Further, the circulation state with nearly the same AO and Niño3 indices may drive rather different responses in surface temperature over East Asia. The well-known continuous weakening (recovery) of the East Asian winter monsoon that occurred around 1988 (2009) can be attributed to the transitions of the spatial patterns of the SLP anomalies over the Arctic Ocean and Eurasian continent, through their modulation on the occurrences of the Ural and central Siberian blocking events.

High-resolution boreal winter precipitation projections over tropical America from CMIP5 models

NASA Astrophysics Data System (ADS)

Palomino-Lemus, Reiner; Córdoba-Machado, Samir; Gámiz-Fortis, Sonia Raquel; Castro-Díez, Yolanda; Esteban-Parra, María Jesús

2017-11-01

Climate-change projections for boreal winter precipitation in Tropical America has been addressed by statistical downscaling (SD) using the principal component regression with sea-level pressure (SLP) as the predictor variable. The SD model developed from the reanalysis of SLP and gridded precipitation GPCC data, has been applied to SLP outputs from 20 CGMS of CMIP5, both from the present climate (1971-2000) and for the future (2071-2100) under the RCP2.6, RCP4.5, and RCP8.5 scenarios. The SD model shows a suitable performance over large regions, presenting a strong bias only in small areas characterized by very dry climate conditions or poor data coverage. The difference in percentage between the projected SD precipitation and the simulated SD precipitation for present climate, ranges from moderate to intense changes in rainfall (positive or negative, depending on the region and the SD GCM model considered), as the radiative forcing increases from the RCP2.6 to RCP8.5. The disparity in the GCMs outputs seems to be the major source of uncertainty in the projected changes, while the scenario considered appears less decisive. Mexico and eastern Brazil are the areas showing the most coherent decreases between SD GCMs, while northwestern and southeastern South America show consistently significant increases. This coherence is corroborated by the results of the ensemble mean which projects positive changes from 10°N towards the south, with exceptions such as eastern Brazil, northern Chile and some smaller areas, such as the center of Colombia, while projected negative changes are the majority found in the northernmost part.

Seasonal prediction of US summertime ozone using statistical analysis of large scale climate patterns

PubMed Central

Mickley, Loretta J.

2017-01-01

We develop a statistical model to predict June–July–August (JJA) daily maximum 8-h average (MDA8) ozone concentrations in the eastern United States based on large-scale climate patterns during the previous spring. We find that anomalously high JJA ozone in the East is correlated with these springtime patterns: warm tropical Atlantic and cold northeast Pacific sea surface temperatures (SSTs), as well as positive sea level pressure (SLP) anomalies over Hawaii and negative SLP anomalies over the Atlantic and North America. We then develop a linear regression model to predict JJA MDA8 ozone from 1980 to 2013, using the identified SST and SLP patterns from the previous spring. The model explains ∼45% of the variability in JJA MDA8 ozone concentrations and ∼30% variability in the number of JJA ozone episodes (>70 ppbv) when averaged over the eastern United States. This seasonal predictability results from large-scale ocean–atmosphere interactions. Warm tropical Atlantic SSTs can trigger diabatic heating in the atmosphere and influence the extratropical climate through stationary wave propagation, leading to greater subsidence, less precipitation, and higher temperatures in the East, which increases surface ozone concentrations there. Cooler SSTs in the northeast Pacific are also associated with more summertime heatwaves and high ozone in the East. On average, models participating in the Atmospheric Model Intercomparison Project fail to capture the influence of this ocean–atmosphere interaction on temperatures in the eastern United States, implying that such models would have difficulty simulating the interannual variability of surface ozone in this region. PMID:28223483

An improved non-uniformity correction algorithm and its GPU parallel implementation

NASA Astrophysics Data System (ADS)

Cheng, Kuanhong; Zhou, Huixin; Qin, Hanlin; Zhao, Dong; Qian, Kun; Rong, Shenghui

2018-05-01

The performance of SLP-THP based non-uniformity correction algorithm is seriously affected by the result of SLP filter, which always leads to image blurring and ghosting artifacts. To address this problem, an improved SLP-THP based non-uniformity correction method with curvature constraint was proposed. Here we put forward a new way to estimate spatial low frequency component. First, the details and contours of input image were obtained respectively by minimizing local Gaussian curvature and mean curvature of image surface. Then, the guided filter was utilized to combine these two parts together to get the estimate of spatial low frequency component. Finally, we brought this SLP component into SLP-THP method to achieve non-uniformity correction. The performance of proposed algorithm was verified by several real and simulated infrared image sequences. The experimental results indicated that the proposed algorithm can reduce the non-uniformity without detail losing. After that, a GPU based parallel implementation that runs 150 times faster than CPU was presented, which showed the proposed algorithm has great potential for real time application.

Apraxia-Kids

MedlinePlus

... About Apraxia Apraxia-KIDS Library Family Start Guide SLP Start Guide Apraxia Information Downloads Research Symposium Videos ... to Help How to Get Listed In Our SLP Directory Events CASANA Sponsored Events Educational Events Conferences ...

Experimental Demonstration of Quantum Stationary Light Pulses in an Atomic Ensemble

NASA Astrophysics Data System (ADS)

Park, Kwang-Kyoon; Cho, Young-Wook; Chough, Young-Tak; Kim, Yoon-Ho

2018-04-01

We report an experimental demonstration of the nonclassical stationary light pulse (SLP) in a cold atomic ensemble. A single collective atomic excitation is created and heralded by detecting a Stokes photon in the spontaneous Raman scattering process. The heralded single atomic excitation is converted into a single stationary optical excitation or the single-photon SLP, whose effective group velocity is zero, effectively forming a trapped single-photon pulse within the cold atomic ensemble. The single-photon SLP is then released from the atomic ensemble as an anti-Stokes photon after a specified trapping time. The second-order correlation measurement between the Stokes and anti-Stokes photons reveals the nonclassical nature of the single-photon SLP. Our work paves the way toward quantum nonlinear optics without a cavity.

Arctic circulation regimes

PubMed Central

Proshutinsky, Andrey; Dukhovskoy, Dmitry; Timmermans, Mary-Louise; Krishfield, Richard; Bamber, Jonathan L.

2015-01-01

Between 1948 and 1996, mean annual environmental parameters in the Arctic experienced a well-pronounced decadal variability with two basic circulation patterns: cyclonic and anticyclonic alternating at 5 to 7 year intervals. During cyclonic regimes, low sea-level atmospheric pressure (SLP) dominated over the Arctic Ocean driving sea ice and the upper ocean counterclockwise; the Arctic atmosphere was relatively warm and humid, and freshwater flux from the Arctic Ocean towards the subarctic seas was intensified. By contrast, during anticylonic circulation regimes, high SLP dominated driving sea ice and the upper ocean clockwise. Meanwhile, the atmosphere was cold and dry and the freshwater flux from the Arctic to the subarctic seas was reduced. Since 1997, however, the Arctic system has been under the influence of an anticyclonic circulation regime (17 years) with a set of environmental parameters that are atypical for this regime. We discuss a hypothesis explaining the causes and mechanisms regulating the intensity and duration of Arctic circulation regimes, and speculate how changes in freshwater fluxes from the Arctic Ocean and Greenland impact environmental conditions and interrupt their decadal variability. PMID:26347536

Multi-time-scale hydroclimate dynamics of a regional watershed and links to large-scale atmospheric circulation: Application to the Seine river catchment, France

NASA Astrophysics Data System (ADS)

Massei, N.; Dieppois, B.; Hannah, D. M.; Lavers, D. A.; Fossa, M.; Laignel, B.; Debret, M.

2017-03-01

In the present context of global changes, considerable efforts have been deployed by the hydrological scientific community to improve our understanding of the impacts of climate fluctuations on water resources. Both observational and modeling studies have been extensively employed to characterize hydrological changes and trends, assess the impact of climate variability or provide future scenarios of water resources. In the aim of a better understanding of hydrological changes, it is of crucial importance to determine how and to what extent trends and long-term oscillations detectable in hydrological variables are linked to global climate oscillations. In this work, we develop an approach associating correlation between large and local scales, empirical statistical downscaling and wavelet multiresolution decomposition of monthly precipitation and streamflow over the Seine river watershed, and the North Atlantic sea level pressure (SLP) in order to gain additional insights on the atmospheric patterns associated with the regional hydrology. We hypothesized that: (i) atmospheric patterns may change according to the different temporal wavelengths defining the variability of the signals; and (ii) definition of those hydrological/circulation relationships for each temporal wavelength may improve the determination of large-scale predictors of local variations. The results showed that the links between large and local scales were not necessarily constant according to time-scale (i.e. for the different frequencies characterizing the signals), resulting in changing spatial patterns across scales. This was then taken into account by developing an empirical statistical downscaling (ESD) modeling approach, which integrated discrete wavelet multiresolution analysis for reconstructing monthly regional hydrometeorological processes (predictand: precipitation and streamflow on the Seine river catchment) based on a large-scale predictor (SLP over the Euro-Atlantic sector). This approach basically consisted in three steps: 1 - decomposing large-scale climate and hydrological signals (SLP field, precipitation or streamflow) using discrete wavelet multiresolution analysis, 2 - generating a statistical downscaling model per time-scale, 3 - summing up all scale-dependent models in order to obtain a final reconstruction of the predictand. The results obtained revealed a significant improvement of the reconstructions for both precipitation and streamflow when using the multiresolution ESD model instead of basic ESD. In particular, the multiresolution ESD model handled very well the significant changes in variance through time observed in either precipitation or streamflow. For instance, the post-1980 period, which had been characterized by particularly high amplitudes in interannual-to-interdecadal variability associated with alternating flood and extremely low-flow/drought periods (e.g., winter/spring 2001, summer 2003), could not be reconstructed without integrating wavelet multiresolution analysis into the model. In accordance with previous studies, the wavelet components detected in SLP, precipitation and streamflow on interannual to interdecadal time-scales could be interpreted in terms of influence of the Gulf-Stream oceanic front on atmospheric circulation.

Characterizing and understanding the climatic determinism of high- to low-frequency variations in precipitation in northwestern France using a coupled wavelet multiresolution/statistical downscaling approach

NASA Astrophysics Data System (ADS)

Massei, Nicolas; Dieppois, Bastien; Hannah, David; Lavers, David; Fossa, Manuel; Laignel, Benoit; Debret, Maxime

2017-04-01

Geophysical signals oscillate over several time-scales that explain different amount of their overall variability and may be related to different physical processes. Characterizing and understanding such variabilities in hydrological variations and investigating their determinism is one important issue in a context of climate change, as these variabilities can be occasionally superimposed to long-term trend possibly due to climate change. It is also important to refine our understanding of time-scale dependent linkages between large-scale climatic variations and hydrological responses on the regional or local-scale. Here we investigate such links by conducting a wavelet multiresolution statistical dowscaling approach of precipitation in northwestern France (Seine river catchment) over 1950-2016 using sea level pressure (SLP) and sea surface temperature (SST) as indicators of atmospheric and oceanic circulations, respectively. Previous results demonstrated that including multiresolution decomposition in a statistical downscaling model (within a so-called multiresolution ESD model) using SLP as large-scale predictor greatly improved simulation of low-frequency, i.e. interannual to interdecadal, fluctuations observed in precipitation. Building on these results, continuous wavelet transform of simulated precipiation using multiresolution ESD confirmed the good performance of the model to better explain variability at all time-scales. A sensitivity analysis of the model to the choice of the scale and wavelet function used was also tested. It appeared that whatever the wavelet used, the model performed similarly. The spatial patterns of SLP found as the best predictors for all time-scales, which resulted from the wavelet decomposition, revealed different structures according to time-scale, showing possible different determinisms. More particularly, some low-frequency components ( 3.2-yr and 19.3-yr) showed a much wide-spread spatial extentsion across the Atlantic. Moreover, in accordance with other previous studies, the wavelet components detected in SLP and precipitation on interannual to interdecadal time-scales could be interpreted in terms of influence of the Gulf-Stream oceanic front on atmospheric circulation. Current works are now conducted including SST over the Atlantic in order to get further insights into this mechanism.

S-layer glycoprotein from Lactobacillus kefiri CIDCA 8348 enhances macrophages response to LPS in a Ca+2-dependent manner.

PubMed

Malamud, Mariano; Carasi, Paula; Freire, Teresa; Serradell, María de Los Angeles

2018-01-01

The S-layer is a (glyco)-proteinaceous envelope constituted by self-assembled subunits that form a two-dimensional lattice covering the surface of different species of Bacteria and Archaea. It could be considered as one of the most abundant biopolymers in our planet. Because of their unique self-assembly features, exhibiting repetitive identical physicochemical properties down to the subnanometer scale, as well as their involvement in specific interactions with host cells, the S-layer proteins (SLPs) show a high potential application in different areas of biotechnology, including the development of antigen carriers or new adjuvants. The presence of a glycosylated SLP on potentially probiotic Lactobacillus kefiri strains was previously described by our research group. In this study, we aim to investigate the role of carbohydrates present in the SLP from L. kefiri CIDCA 8348 (SLP-8348) in their internalization by murine macrophages, as well as to analyze their immunomodulatory capacity and their effect on LPS-stimulated macrophages. RAW 264.7 cells internalized the SLP-8348 in a process that was mediated by carbohydrate-receptor interactions since it was inhibited by glucose, mannose or EGTA, a Ca +2 chelating agent. These results correlated with the recognition of SLP-8348 by ConA lectin. We further show that while SLP-8348 was not able to induce the activation of macrophages by itself, it favored the LPS-induced response, since there was a significant increase in the expression of surface cell markers MHC-II, CD86 and CD40, as well as in IL-6 and IL-10 expression at both transcript and protein levels, in comparison with LPS-stimulated cells. The presence of EGTA completely abrogated this synergistic effect. Taken together, these results strongly suggest the involvement of both glycosidic residues and Ca +2 ions in the recognition of SLP-8348 by cellular receptors on murine macrophages. Moreover, these results suggest the potentiality of the SLP-8348 for the development of new adjuvants capable of stimulating antigen presenting cells by interaction with glycan receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

Structured Light Plethysmography (SLP): Management and follow up of a paediatric patient with pneumonia.

PubMed

Ghezzi, Michele; Tenero, Laura; Piazza, Michele; Bodini, Alessandro; Piacentini, Giorgio

2017-01-01

Structured Light Plethysmography (SLP) is a non-invasive method to study chest and abdominal movement during breathing and can identify abnormal contributions of the different regions of the chest. M.D hospitalized for pneumonia, underwent SLP and spirometry at admission (T0), after 48 hours (T1), and after one month (T2). SLP parameters showed expiratory flow limitation, information consistent with the spirometric parameters collected, and reduced motion in the area effected by pneumonia, with improvement and normalization at T1 and T2. This method gave useful information about the contribution to the respiratory movement of the lung area affected by pneumonia so we can speculate a possible use in the follow-up of children affected by pneumonia or other respiratory diseases, and who are not able to perform a spirometric test.

Cooperative interactions at the SLP-76 complex are critical for actin polymerization.

PubMed

Barda-Saad, Mira; Shirasu, Naoto; Pauker, Maor H; Hassan, Nirit; Perl, Orly; Balbo, Andrea; Yamaguchi, Hiroshi; Houtman, Jon C D; Appella, Ettore; Schuck, Peter; Samelson, Lawrence E

2010-07-21

T-cell antigen receptor (TCR) engagement induces formation of multi-protein signalling complexes essential for regulating T-cell functions. Generation of a complex of SLP-76, Nck and VAV1 is crucial for regulation of the actin machinery. We define the composition, stoichiometry and specificity of interactions in the SLP-76, Nck and VAV1 complex. Our data reveal that this complex can contain one SLP-76 molecule, two Nck and two VAV1 molecules. A direct interaction between Nck and VAV1 is mediated by binding between the C-terminal SH3 domain of Nck and the VAV1 N-terminal SH3 domain. Disruption of the VAV1:Nck interaction deleteriously affected actin polymerization. These novel findings shed new light on the mechanism of actin polymerization after T-cell activation.

The personality of past, present and future speech-language pathology students.

PubMed

Byrne, Nicole

2018-03-01

As allied health professions change over time to keep up with and reflect a rapidly changing society, it is quite possible that the people attracted to the profession may also change. If this is the case, then knowing this could be critical for future workforce marketing, training and planning. The aim was to investigate whether the personality of students entering a speech-language pathology (SLP) program had changed over time and whether there were generational differences in personality. The study used the Big Five personality inventory to consider whether there were differences in the personality in speech-language pathology (SLP) students enrolled in the same regional university in Australia in 2005 and 2016. The results showed there were significant differences between the two groups on the Agreeableness and Extroversion scales. The students who were more Conscientious were also more Confident in their ability to perform as an SLP. Generational differences across the two cohorts were also considered. SLP is a dynamic profession that is reflected through an evolving scope of practice, increasing utilization of technology and specialization. As careers evolve it is logical that the people attracted to those careers may also shift; as demonstrated here via changes in the personality of SLP students. Understanding the personality of current SLP students and future Generation Z students may assist universities to identify specific skills and experiences students need to be successful in the workforce. © 2017 Royal College of Speech and Language Therapists.

Response of the Kuroshio Extension path state to near-term global warming in CMIP5 experiments with MIROC4h

NASA Astrophysics Data System (ADS)

Li, Rui; Jing, Zhao; Chen, Zhaohui; Wu, Lixin

2017-04-01

In this study, responses of the Kuroshio Extension (KE) path state to near-term (2006-2035) global warming are investigated using a Kuroshio-resolving atmosphere-ocean coupled model. Under the representative concentration pathway 4.5 (RCP4.5) forcing, the KE system is intensified and its path state tends to move northward and becomes more stable. It is suggested that the local anticyclonic wind stress anomalies in the KE region favor the spin-up of the southern recirculation gyre, and the remote effect induced by the anticyclonic wind stress anomalies over the central and eastern midlatitude North Pacific also contributes to the stabilization of the KE system substantially. The dominant role of wind stress forcing on KE variability under near-term global warming is further confirmed by adopting a linear 1.5 layer reduced-gravity model forced by wind stress curl field from the present climate model. It is also found that the main contributing longitudinal band for KE index (KEI) moves westward in response to the warmed climate. This results from the northwestward expansion of the large-scale sea level pressure (SLP) field.

Quantitative reduction of the TCR adapter protein SLP-76 unbalances immunity and immune regulation.

PubMed

Siggs, Owen M; Miosge, Lisa A; Daley, Stephen R; Asquith, Kelly; Foster, Paul S; Liston, Adrian; Goodnow, Christopher C

2015-03-15

Gene variants that disrupt TCR signaling can cause severe immune deficiency, yet less disruptive variants are sometimes associated with immune pathology. Null mutations of the gene encoding the scaffold protein Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76), for example, cause an arrest of T cell positive selection, whereas a synthetic membrane-targeted allele allows limited positive selection but is associated with proinflammatory cytokine production and autoantibodies. Whether these and other enigmatic outcomes are due to a biochemical uncoupling of tolerogenic signaling, or simply a quantitative reduction of protein activity, remains to be determined. In this study we describe a splice variant of Lcp2 that reduced the amount of wild-type SLP-76 protein by ~90%, disrupting immunogenic and tolerogenic pathways to different degrees. Mutant mice produced excessive amounts of proinflammatory cytokines, autoantibodies, and IgE, revealing that simple quantitative reductions of SLP-76 were sufficient to trigger immune dysregulation. This allele reveals a dose-sensitive threshold for SLP-76 in the balance of immunity and immune dysregulation, a common disturbance of atypical clinical immune deficiencies. Copyright © 2015 by The American Association of Immunologists, Inc.

Accelerated Life Testing and Service Lifetime Prediction for PV Technologies in the Twenty-First Century

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

Czanderna, A. W.; Jorgensen, G. J.

The purposes of this paper are to (1) discuss the necessity for conducting accelerated life testing (ALT) in the early stages of developing new photovoltaic (PV) technologies, (2) elucidate the crucial importance for combining ALT with real-time testing (RTT) in terrestrial environments for promising PV technologies for the 21st century, and (3) outline the essential steps for making a service lifetime prediction (SLP) for any PV technology. The specific objectives are to (a) illustrate the essential need for ALT of complete, encapsulated multilayer PV devices, (b) indicate the typical causes of degradation in PV stacks, (c) elucidate the complexity associatedmore » with quantifying the durability of the devices, (d) explain the major elements that constitute a generic SLP methodology, (e) show how the introduction of the SLP methodology in the early stages of new device development can reduce the cost of technology development, and (f) outline the procedure for combining the results of ALT and RTT, establishing degradation mechanisms, using sufficient numbers of samples, and applying the SLP methodology to produce a SLP for existing or new PV technologies.« less

Structures, properties, and energy-storage mechanisms of the semi-lunar process cuticles in locusts.

PubMed

Wan, Chao; Hao, Zhixiu; Feng, Xiqiao

2016-10-17

Locusts have excellent jumping and kicking abilities to survive in nature, which are achieved through the energy storage and release processes occurring in cuticles, especially in the semi-lunar processes (SLP) at the femorotibial joints. As yet, however, the strain energy-storage mechanisms of the SLP cuticles remain unclear. To decode this mystery, we investigated the microstructure, material composition, and mechanical properties of the SLP cuticle and its remarkable strain energy-storage mechanisms for jumping and kicking. It is found that the SLP cuticle of adult Locusta migratoria manilensis consists of five main parts that exhibit different microstructural features, material compositions, mechanical properties, and biological functions in storing strain energy. The mechanical properties of these five components are all transversely isotropic and strongly depend on their water contents. Finite element simulations indicate that the two parts of the core region of the SLP cuticle likely make significant contributions to its outstanding strain energy-storage ability. This work deepens our understanding of the locomotion behaviors and superior energy-storage mechanisms of insects such as locusts and is helpful for the design and fabrication of strain energy-storage devices.

Structures, properties, and energy-storage mechanisms of the semi-lunar process cuticles in locusts

PubMed Central

Wan, Chao; Hao, Zhixiu; Feng, Xiqiao

2016-01-01

Locusts have excellent jumping and kicking abilities to survive in nature, which are achieved through the energy storage and release processes occurring in cuticles, especially in the semi-lunar processes (SLP) at the femorotibial joints. As yet, however, the strain energy-storage mechanisms of the SLP cuticles remain unclear. To decode this mystery, we investigated the microstructure, material composition, and mechanical properties of the SLP cuticle and its remarkable strain energy-storage mechanisms for jumping and kicking. It is found that the SLP cuticle of adult Locusta migratoria manilensis consists of five main parts that exhibit different microstructural features, material compositions, mechanical properties, and biological functions in storing strain energy. The mechanical properties of these five components are all transversely isotropic and strongly depend on their water contents. Finite element simulations indicate that the two parts of the core region of the SLP cuticle likely make significant contributions to its outstanding strain energy-storage ability. This work deepens our understanding of the locomotion behaviors and superior energy-storage mechanisms of insects such as locusts and is helpful for the design and fabrication of strain energy-storage devices. PMID:27748460

Structures, properties, and energy-storage mechanisms of the semi-lunar process cuticles in locusts

NASA Astrophysics Data System (ADS)

Wan, Chao; Hao, Zhixiu; Feng, Xiqiao

2016-10-01

Locusts have excellent jumping and kicking abilities to survive in nature, which are achieved through the energy storage and release processes occurring in cuticles, especially in the semi-lunar processes (SLP) at the femorotibial joints. As yet, however, the strain energy-storage mechanisms of the SLP cuticles remain unclear. To decode this mystery, we investigated the microstructure, material composition, and mechanical properties of the SLP cuticle and its remarkable strain energy-storage mechanisms for jumping and kicking. It is found that the SLP cuticle of adult Locusta migratoria manilensis consists of five main parts that exhibit different microstructural features, material compositions, mechanical properties, and biological functions in storing strain energy. The mechanical properties of these five components are all transversely isotropic and strongly depend on their water contents. Finite element simulations indicate that the two parts of the core region of the SLP cuticle likely make significant contributions to its outstanding strain energy-storage ability. This work deepens our understanding of the locomotion behaviors and superior energy-storage mechanisms of insects such as locusts and is helpful for the design and fabrication of strain energy-storage devices.

Your Starting Guide To Childhood Apraxia of Speech

MedlinePlus

... About Apraxia Apraxia-KIDS Library Family Start Guide SLP Start Guide Apraxia Information Downloads Research Symposium Videos ... About Apraxia Apraxia-KIDS Library Family Start Guide SLP Start Guide Research Symposium Videos On-Demand Webinars ...

Finding fixed satellite service orbital allotments with a k-permutation algorithm

NASA Technical Reports Server (NTRS)

Reilly, Charles H.; Mount-Campbell, Clark A.; Gonsalvez, David J. A.

1990-01-01

A satellite system synthesis problem, the satellite location problem (SLP), is addressed. In SLP, orbital locations (longitudes) are allotted to geostationary satellites in the fixed satellite service. A linear mixed-integer programming model is presented that views SLP as a combination of two problems: the problem of ordering the satellites and the problem of locating the satellites given some ordering. A special-purpose heuristic procedure, a k-permutation algorithm, has been developed to find solutions to SLPs. Solutions to small sample problems are presented and analyzed on the basis of calculated interferences.

The Siberian High and precipitation over Cyprus

NASA Astrophysics Data System (ADS)

Lingis, P.; Michaelides, S. C.

2009-04-01

The aim of this study is to find possible teleconnection patterns associated with the Siberian High (SH) and precipitation in Cyprus. In this respect, the study examines the impacts that the SH exerts on local climate in areas far beyond the area of its domination; in particular, the relation of the teleconnection patterns derived from the SH Sea Level Pressure (SLP) characteristics and precipitation over Cyprus are examined. Four indices are used describing the characteristics of the SH (strength and geographical displacement). In an attempt to identify possible relations between precipitation, on the one hand, and the SH indices, on the other hand, a network of 32 rain gauge stations in Cyprus, both coastal and inland, was carefully selected to cover the whole island. Precipitation in Cyprus is mainly the result of baroclinic depressions traveling in the eastern Mediterranean Basin. SH as one of the dominant centers of action in the northern hemisphere, acts as one of the regulators of the preferred paths of these frontal depressions. The overall effect of the SH on these depressions is connected to characteristics and behavior of the SH, such as its intensity and location, as it may act as a blocking system preventing the propagation of migratory depressions eastwards or diverting them towards the North or South. The depressions arriving or forming over the island have a short lifespan and they are not frequent. The mean monthly sea-level pressure (SLP) was obtained from the dataset of the Climatic Research Unit of the University of East Anglia, with horizontal analysis of 5 degree latitude and 10 degree longitude grid. The 5 degree resolution global mean monthly temperature anomaly values taken were also taken from the same source. Monthly total precipitation amounts from 32 rain gauges in Cyprus were obtained from the Cyprus Meteorological Service for the period 1961 - 2000. Finally, use has been made of the reanalysis data at 2.5x2.5 degree resolution of global monthly mean SLP and precipitation rate from the National Centers for Environmental Prediction (NCEP). Principal Component Analysis (PCA) for the gridded SLP dataset for each month was performed. From this analysis, the first four Principal Components (PC) were obtained, explaining for the winter months 89-90% of the total variance and for all months 81- 90%. From the PCA and for each of the four Principal Components (hereafter denoted as PC1, PC2, PC3 and PC4), graphs of the loading distributions and the respective time series resulting from the scores of each PC were constructed. The scores were used as indices for further calculations. Susequently, the correlation coefficients between the PC scores and mean SLP for each month were calculated. The data from the 32 rain gauges were used to calculate the monthly mean precipitation over Cyprus. Extrapolation using distance weighted average algorithm was used to plot the spatial distribution of precipitation of each month over the island. Correlation coefficients were calculated between the four PC indices and the precipitation at each one of the rain gauge stations; these correlation coefficients were subsequently plotted on geographical maps in an attempt to visualize any recognizable patterns. Also, to investigate the overall effect of the four indices (i.e. PC1 to PC4) on precipitation over Cyprus, multiple correlation analysis was employed between these four indices and the total amount of precipitation of each month (the sum of all rain gauges used for each month).

The influence of north Pacific atmospheric circulation on streamflow in the west

USGS Publications Warehouse

Cayan, Daniel R.; Peterson, David H.

1989-01-01

The annual cycle and nonseasonal variability of streamflow over western North America and Hawaii is studied in terms of atmospheric forcing elements. This study uses several decades of monthly average streamflow beginning as early as the late 1800's over a network of 38 stations. In addition to a strong annual cycle in mean streamflow and its variance at most of the stations, there is also a distinct annual cycle in the autocorrelation of anomalies that is related to the interplay between the annual cycles of temperature and precipitation. Of particular importance to these lag effects is the well-known role of water stored as snow pack, which controls the delay between peak precipitation and peak flow and also introduces persistence into the nonseasonal streamflow anomalies, with time scales from 1 month to over 1 year. The degree to which streamflow is related to winter atmospheric circulation over the North Pacific and western North America is tested using correlations with time averaged, gridded sea level pressure (SLP), which begins in 1899. Streamflow fluctuations show significant large-scale correlations for the winter (December through February) mean SLP anomaly patterns over the North Pacific with maximum correlations ranging from 0.3 to about 0.6. For streams along the west coast corridor the circulation pattern associated with positive streamflow anomalies is low pressure centered off the coast to the west or northwest, indicative of increased winter storms and an anomalous westerly-to-southwesterly wind component. For streams in the interior positive streamflow anomalies are associated with a positive SLP anomaly stationed remotely over the central North Pacific, and with negative but generally weaker SLP anomalies locally. One important influence on streamflow variability is the strength of the Aleutian Low in winter. This is represented by the familiar Pacific-North America (PNA) index and also by an index defined herein the “CNP” (Central North Pacific). This index, beginning in 1899, is taken to be the average of the SLP anomaly south of the Aleutians and the western Gulf of Alaska. Correlations between PNA or CNP and regional anomalies reflect streamflow the alternations in strength and position of the mean North Pacific storm track entering North America as well as shifts in the trade winds over the subtropical North Pacific. Regions whose streamflow is best tuned to the PNA or CNP include coastal Alaska, the northwestern United States, and Hawaii; the latter two regions have the opposite sign anomaly as the former. The pattern of streamflow variations associated with El Niño is similar, but the El Niño signal also includes a tendency for greater than normal streamflow in the southwestern United States. These indices are significantly correlated with streamflow at one to two seasons in advance of the December–August period, which may allow modestly skillful forecasts. It is important to note that streamflow variability in some areas, such as British Columbia and California, does not respond consistently to these broad scale Pacific atmospheric circulation indices, but is related to regional atmospheric anomaly features over the eastern North Pacific. Spatially, streamflow anomalies are fairly well correlated over scales of several hundred kilometers. Inspection of the spatial anomalies of stream-flow in this study suggest an asymmetry in the spatial pattern of positive versus negative streamflow anomalies in the western United States: dry patterns have tended to be larger and more spatially coherent than wet patterns.

Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1.

PubMed

Dios-Esponera, Ana; Isern de Val, Soledad; Sevilla-Movilla, Silvia; García-Verdugo, Rosa; García-Bernal, David; Arellano-Sánchez, Nohemí; Cabañas, Carlos; Teixidó, Joaquin

2015-09-15

Stimulation by chemokines of integrin α4β1-dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase-inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76-, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation. © 2015 Dios-Esponera, Isern de Val, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Rab27a regulates epithelial sodium channel (ENaC) activity through synaptotagmin-like protein (SLP-5) and Munc13-4 effector mechanism

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

Saxena, Sunil K.; Horiuchi, Hisanori; Fukuda, Mitsunori

Liddle's syndrome (excessive absorption of sodium ions) and PHA-1 (pseudohypoaldosteronism type 1) with decreased sodium absorption are caused by the mutations in the amiloride-sensitive epithelial sodium channel ENaC. Rab proteins are small GTPases involved in vesicle transport, docking, and fusion. Earlier, we reported that Rab27a inhibits ENaC-mediated currents through protein-protein interaction in HT-29 cells. We hereby report that Rab27a-dependent inhibition is associated with the GTP/GDP status as constitutively active or GTPase-deficient mutant Q78L inhibits amiloride-sensitive currents whereas GDP-locked inactive mutant T23N showed no effect. In order to further explore the molecular mechanism of this regulation, we performed competitive assays withmore » two Rab27a-binding proteins: synaptotagmin-like protein (SLP-5) and Munc13-4 (a putative priming factor for exocytosis). Both proteins eliminate negative modulation of Rab27a on ENaC function. The SLP-5 reversal of Rab27a effect was restricted to C-terminal C2A/C2B domains assigned for putative phospholipids-binding function while the Rab27a-binding SHD motif imparted higher inhibition. The ENaC-mediated currents remain unaffected by Rab27a though SLP-5 appears to strongly bind it. The immunoprecipitation experiments suggest that in the presence of excessive Munc13-4 and SLP-5 proteins, Rab27a interaction with ENaC is diminished. Munc13-4 and SLP-5 limit the Rab27a availability to ENaC, thus minimizing its effect on channel function. These observations decisively prove that Rab27a inhibits ENaC function through a complex mechanism that involves GTP/GDP status, and protein-protein interactions involving Munc13-4 and SLP-5 effector proteins.« less

The Bcr-Abl kinase regulates the actin cytoskeleton via a GADS/Slp-76/Nck1 adaptor protein pathway.

PubMed

Preisinger, Christian; Kolch, Walter

2010-05-01

Bcr-Abl is the transforming principle underlying chronic myelogenous leukaemia (CML). Here, we use a functional interaction proteomics approach to map pathways by which Bcr-Abl regulates defined cellular processes. The results show that Bcr-Abl regulates the actin cytoskeleton and non-apoptotic membrane blebbing via a GADS/Slp-76/Nck1 adaptor protein pathway. The binding of GADS to Bcr-Abl requires Bcr-Abl tyrosine kinase activity and is sensitive to the Bcr-Abl inhibitor imatinib, while the GADS/Slp-76 and Slp-76/Nck interactions are tyrosine phosphorylation independent. All three adaptor proteins co-localize with cortical actin in membrane blebs. Downregulation of each adaptor protein disrupts the actin cytoskeleton and membrane blebbing in a similar fashion and similar to imatinib. These findings highlight the importance of protein interaction dependent adaptor protein pathways in oncogenic kinase signaling. 2010 Elsevier Inc. All rights reserved.

Sustained ligand-activated preconditioning via δ-opioid receptors.

PubMed

Peart, Jason N; Hoe, Louise E See; Gross, Garrett J; Headrick, John P

2011-01-01

We have previously described novel cardioprotection in response to sustained morphine exposure, efficacious in young to aged myocardium and mechanistically distinct from conventional opioid or preconditioning (PC) responses. We further investigate opioid-dependent sustained ligand-activated preconditioning (SLP), assessing duration of protection, opioid receptor involvement, additivity with conventional responses, and signaling underlying preischemic induction of the phenotype. Male C57BL/6 mice were treated with morphine (75-mg subcutaneous pellet) for 5 days followed by morphine-free periods (0, 3, 5, or 7 days) before ex vivo assessment of myocardial tolerance to 25-min ischemia/45-min reperfusion. SLP substantially reduced infarction (by ∼50%) and postischemic contractile dysfunction (eliminating contracture, doubling force development). Cardioprotection persisted for 5 to 7 days after treatment. SLP was induced specifically by δ-receptor and not κ- or μ-opioid receptor agonism, was eliminated by δ-receptor and nonselective antagonism, and was additive with adenosinergic but not acute morphine- or PC-triggered protection. Cotreatment during preischemic morphine exposure with the phosphoinositide-3 kinase (PI3K) inhibitor wortmannin, but not the protein kinase A (PKA) inhibitor myristoylated PKI-(14-22)-amide, prevented induction of SLP. This was consistent with shifts in total and phospho-Akt during the induction period. In summary, data reveal that SLP triggers sustained protection from ischemia for up to 7 days after stimulus, is δ-opioid receptor mediated, is induced in a PI3K-dependent/PKA-independent manner, and augments adenosinergic protection. Mechanisms underlying SLP may be useful targets for manipulation of ischemic tolerance in young or aged myocardium.

Src homology 2-domain containing leukocyte-specific phosphoprotein of 76 kDa is mandatory for TCR-mediated inside-out signaling, but dispensable for CXCR4-mediated LFA-1 activation, adhesion, and migration of T cells.

PubMed

Horn, Jessica; Wang, Xiaoqian; Reichardt, Peter; Stradal, Theresia E; Warnecke, Nicole; Simeoni, Luca; Gunzer, Matthias; Yablonski, Deborah; Schraven, Burkhart; Kliche, Stefanie

2009-11-01

Engagement of the TCR or of chemokine receptors such as CXCR4 induces adhesion and migration of T cells via so-called inside-out signaling pathways. The molecular processes underlying inside-out signaling events are as yet not completely understood. In this study, we show that TCR- and CXCR4-mediated activation of integrins critically depends on the membrane recruitment of the adhesion- and degranulation-promoting adapter protein (ADAP)/Src kinase-associated phosphoprotein of 55 kDa (SKAP55)/Rap1-interacting adapter protein (RIAM)/Rap1 module. We further demonstrate that the Src homology 2 domain containing leukocyte-specific phosphoprotein of 76 kDa (SLP76) is crucial for TCR-mediated inside-out signaling and T cell/APC interaction. Besides facilitating membrane recruitment of ADAP, SKAP55, and RIAM, SLP76 regulates TCR-mediated inside-out signaling by controlling the activation of Rap1 as well as Rac-mediated actin polymerization. Surprisingly, however, SLP76 is not mandatory for CXCR4-mediated inside-out signaling. Indeed, both CXCR4-induced T cell adhesion and migration are not affected by loss of SLP76. Moreover, after CXCR4 stimulation, the ADAP/SKAP55/RIAM/Rap1 module is recruited to the plasma membrane independently of SLP76. Collectively, our data indicate a differential requirement for SLP76 in TCR- vs CXCR4-mediated inside-out signaling pathways regulating T cell adhesion and migration.

Evolution of bacterial-like phosphoprotein phosphatases in photosynthetic eukaryotes features ancestral mitochondrial or archaeal origin and possible lateral gene transfer.

PubMed

Uhrig, R Glen; Kerk, David; Moorhead, Greg B

2013-12-01

Protein phosphorylation is a reversible regulatory process catalyzed by the opposing reactions of protein kinases and phosphatases, which are central to the proper functioning of the cell. Dysfunction of members in either the protein kinase or phosphatase family can have wide-ranging deleterious effects in both metazoans and plants alike. Previously, three bacterial-like phosphoprotein phosphatase classes were uncovered in eukaryotes and named according to the bacterial sequences with which they have the greatest similarity: Shewanella-like (SLP), Rhizobiales-like (RLPH), and ApaH-like (ALPH) phosphatases. Utilizing the wealth of data resulting from recently sequenced complete eukaryotic genomes, we conducted database searching by hidden Markov models, multiple sequence alignment, and phylogenetic tree inference with Bayesian and maximum likelihood methods to elucidate the pattern of evolution of eukaryotic bacterial-like phosphoprotein phosphatase sequences, which are predominantly distributed in photosynthetic eukaryotes. We uncovered a pattern of ancestral mitochondrial (SLP and RLPH) or archaeal (ALPH) gene entry into eukaryotes, supplemented by possible instances of lateral gene transfer between bacteria and eukaryotes. In addition to the previously known green algal and plant SLP1 and SLP2 protein forms, a more ancestral third form (SLP3) was found in green algae. Data from in silico subcellular localization predictions revealed class-specific differences in plants likely to result in distinct functions, and for SLP sequences, distinctive and possibly functionally significant differences between plants and nonphotosynthetic eukaryotes. Conserved carboxyl-terminal sequence motifs with class-specific patterns of residue substitutions, most prominent in photosynthetic organisms, raise the possibility of complex interactions with regulatory proteins.

75 FR 63232 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

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2010-10-14

... (``SLPs''), the Exchange is modifying language referencing the SLP quoting requirement to reflect a recent... modifying language referencing the SLP quoting requirement to reflect a recent rule filing that changed the...

75 FR 64368 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

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2010-10-19

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Oral Care for the Patient with ALS: A Guide for the Caregiver

MedlinePlus

... with ALS by Kathleen H. Kaminski, MA, CCC-SLP As ALS progresses, daily routines frequently change for ... thanks and acknowledges Kathleen H. Kaminski, MA, CCC-SLP for sharing her time and expertise on this ...

Influence of testosterone on synaptic transmission in the rat medial vestibular nuclei: estrogenic and androgenic effects.

PubMed

Grassi, S; Frondaroli, A; Di Mauro, M; Pettorossi, V E

2010-12-15

In brainstem slices of young male rat, we investigated the influence of the neuroactive steroid testosterone (T) on the synaptic responses by analyzing the field potential evoked in the medial vestibular nucleus (MVN) by vestibular afferent stimulation. T induced three distinct and independent long-term synaptic changes: fast long-lasting potentiation (fLP), slow long-lasting potentiation (sLP) and long-lasting depression (LD). The fLP was mediated by 17β-estradiol (E(2)) since it was abolished by blocking the estrogen receptors (ERs) or the enzyme converting T to E(2). Conversely, sLP and LD were mediated by 5α-dihydrotestosterone (DHT) since they were prevented by blocking the androgen receptors (ARs) or the enzyme converting T to DHT. Therefore, the synaptic effects of T were mediated by its androgenic or estrogenic metabolites. The pathways leading to estrogenic and androgenic conversion of T might be co-localized since, the occurrence of fLP under block of androgenic pathway, and that of sLP and LD under estrogenic block, were higher than those observed without blocks. In case of co-localization, the effect on synaptic transmission should depend on the prevailing enzymatic activity. We conclude that circulating and neuronal T can remarkably influence synaptic responses of the vestibular neurons in different and opposite ways, depending on its conversion to estrogenic or androgenic metabolites. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

75 FR 41912 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-19

..., Division of Trading and Markets, Commission, dated July 12, 2010. v. SLP Credits The Exchange proposes different credits for SLP transactions in Nasdaq Securities contingent upon SLPs meeting their quoting requirements in [[Page 41913

77 FR 46144 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

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2012-08-02

... share credit per transaction when adding liquidity, if the SLP meets quoting requirements pursuant to... an equity per share credit per transaction when adding liquidity, if the SLP does not meet the...

75 FR 2176 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-14

...) whether the SLP has met the 3% average or more quoting requirement (the ``Quoting Requirement'') in Rule... amending it to specify that the current SLP liquidity credits apply only to transactions in securities with...

A k-permutation algorithm for Fixed Satellite Service orbital allotments

NASA Technical Reports Server (NTRS)

Reilly, Charles H.; Mount-Campbell, Clark A.; Gonsalvez, David J. A.

1988-01-01

A satellite system synthesis problem, the satellite location problem (SLP), is addressed in this paper. In SLP, orbital locations (longitudes) are allotted to geostationary satellites in the Fixed Satellite Service. A linear mixed-integer programming model is presented that views SLP as a combination of two problems: (1) the problem of ordering the satellites and (2) the problem of locating the satellites given some ordering. A special-purpose heuristic procedure, a k-permutation algorithm, that has been developed to find solutions to SLPs formulated in the manner suggested is described. Solutions to small example problems are presented and analyzed.

Using Hierarchical Linear Modeling to Examine How Individual SLPs Differentially Contribute to Children's Language and Literacy Gains in Public Schools.

PubMed

Farquharson, Kelly; Tambyraja, Sherine R; Logan, Jessica; Justice, Laura M; Schmitt, Mary Beth

2015-08-01

The purpose of this study was twofold: (a) to determine the unique contributions in children's language and literacy gains, over 1 academic year, that are attributable to the individual speech-language pathologist (SLP) and (b) to explore possible child- and SLP-level factors that may further explain SLPs' contributions to children's language and literacy gains. Participants were 288 kindergarten and 1st-grade children with language impairment who were currently receiving school-based language intervention from SLPs. Using hierarchical linear modeling, we partitioned the variance in children's gains in language (i.e., grammar, vocabulary) and literacy (i.e., word decoding) that could be attributed to their individual SLP. Results revealed a significant contribution of individual SLPs to children's gains in grammar, vocabulary, and word decoding. Children's fall language scores and grade were significant predictors of SLPs' contributions, although no SLP-level predictors were significant. The present study makes a first step toward incorporating implementation science and suggests that, for children receiving school-based language intervention, variance in child language and literacy gains in an academic year is at least partially attributable to SLPs. Continued work in this area should examine the possible SLP-level characteristics that may further explicate the relative contributions of SLPs.

Effect of magnetic dipolar interactions on nanoparticle heating efficiency: Implications for cancer hyperthermia

PubMed Central

Branquinho, Luis C.; Carrião, Marcus S.; Costa, Anderson S.; Zufelato, Nicholas; Sousa, Marcelo H.; Miotto, Ronei; Ivkov, Robert; Bakuzis, Andris F.

2013-01-01

Nanostructured magnetic systems have many applications, including potential use in cancer therapy deriving from their ability to heat in alternating magnetic fields. In this work we explore the influence of particle chain formation on the normalized heating properties, or specific loss power (SLP) of both low- (spherical) and high- (parallelepiped) anisotropy ferrite-based magnetic fluids. Analysis of ferromagnetic resonance (FMR) data shows that high particle concentrations correlate with increasing chain length producing decreasing SLP. Monte Carlo simulations corroborate the FMR results. We propose a theoretical model describing dipole interactions valid for the linear response regime to explain the observed trends. This model predicts optimum particle sizes for hyperthermia to about 30% smaller than those previously predicted, depending on the nanoparticle parameters and chain size. Also, optimum chain lengths depended on nanoparticle surface-to-surface distance. Our results might have important implications to cancer treatment and could motivate new strategies to optimize magnetic hyperthermia. PMID:24096272

77 FR 28912 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-16

... credit per transaction when adding liquidity, if the SLP meets quoting requirements pursuant to Rule 107B... $0.0030 equity per share credit per transaction when adding liquidity, if the SLP does not meet the...

Rainfall Prediction of Indian Peninsula: Comparison of Time Series Based Approach and Predictor Based Approach using Machine Learning Techniques

NASA Astrophysics Data System (ADS)

Dash, Y.; Mishra, S. K.; Panigrahi, B. K.

2017-12-01

Prediction of northeast/post monsoon rainfall which occur during October, November and December (OND) over Indian peninsula is a challenging task due to the dynamic nature of uncertain chaotic climate. It is imperative to elucidate this issue by examining performance of different machine leaning (ML) approaches. The prime objective of this research is to compare between a) statistical prediction using historical rainfall observations and global atmosphere-ocean predictors like Sea Surface Temperature (SST) and Sea Level Pressure (SLP) and b) empirical prediction based on a time series analysis of past rainfall data without using any other predictors. Initially, ML techniques have been applied on SST and SLP data (1948-2014) obtained from NCEP/NCAR reanalysis monthly mean provided by the NOAA ESRL PSD. Later, this study investigated the applicability of ML methods using OND rainfall time series for 1948-2014 and forecasted up to 2018. The predicted values of aforementioned methods were verified using observed time series data collected from Indian Institute of Tropical Meteorology and the result revealed good performance of ML algorithms with minimal error scores. Thus, it is found that both statistical and empirical methods are useful for long range climatic projections.

Comparison of seven techniques for typing international epidemic strains of Clostridium difficile: restriction endonuclease analysis, pulsed-field gel electrophoresis, PCR-ribotyping, multilocus sequence typing, multilocus variable-number tandem-repeat analysis, amplified fragment length polymorphism, and surface layer protein A gene sequence typing.

PubMed

Killgore, George; Thompson, Angela; Johnson, Stuart; Brazier, Jon; Kuijper, Ed; Pepin, Jacques; Frost, Eric H; Savelkoul, Paul; Nicholson, Brad; van den Berg, Renate J; Kato, Haru; Sambol, Susan P; Zukowski, Walter; Woods, Christopher; Limbago, Brandi; Gerding, Dale N; McDonald, L Clifford

2008-02-01

Using 42 isolates contributed by laboratories in Canada, The Netherlands, the United Kingdom, and the United States, we compared the results of analyses done with seven Clostridium difficile typing techniques: multilocus variable-number tandem-repeat analysis (MLVA), amplified fragment length polymorphism (AFLP), surface layer protein A gene sequence typing (slpAST), PCR-ribotyping, restriction endonuclease analysis (REA), multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). We assessed the discriminating ability and typeability of each technique as well as the agreement among techniques in grouping isolates by allele profile A (AP-A) through AP-F, which are defined by toxinotype, the presence of the binary toxin gene, and deletion in the tcdC gene. We found that all isolates were typeable by all techniques and that discrimination index scores for the techniques tested ranged from 0.964 to 0.631 in the following order: MLVA, REA, PFGE, slpAST, PCR-ribotyping, MLST, and AFLP. All the techniques were able to distinguish the current epidemic strain of C. difficile (BI/027/NAP1) from other strains. All of the techniques showed multiple types for AP-A (toxinotype 0, binary toxin negative, and no tcdC gene deletion). REA, slpAST, MLST, and PCR-ribotyping all included AP-B (toxinotype III, binary toxin positive, and an 18-bp deletion in tcdC) in a single group that excluded other APs. PFGE, AFLP, and MLVA grouped two, one, and two different non-AP-B isolates, respectively, with their AP-B isolates. All techniques appear to be capable of detecting outbreak strains, but only REA and MLVA showed sufficient discrimination to distinguish strains from different outbreaks.

Analytical three-dimensional neutron transport benchmarks for verification of nuclear engineering codes. Final report

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

Ganapol, B.D.; Kornreich, D.E.

Because of the requirement of accountability and quality control in the scientific world, a demand for high-quality analytical benchmark calculations has arisen in the neutron transport community. The intent of these benchmarks is to provide a numerical standard to which production neutron transport codes may be compared in order to verify proper operation. The overall investigation as modified in the second year renewal application includes the following three primary tasks. Task 1 on two dimensional neutron transport is divided into (a) single medium searchlight problem (SLP) and (b) two-adjacent half-space SLP. Task 2 on three-dimensional neutron transport covers (a) pointmore » source in arbitrary geometry, (b) single medium SLP, and (c) two-adjacent half-space SLP. Task 3 on code verification, includes deterministic and probabilistic codes. The primary aim of the proposed investigation was to provide a suite of comprehensive two- and three-dimensional analytical benchmarks for neutron transport theory applications. This objective has been achieved. The suite of benchmarks in infinite media and the three-dimensional SLP are a relatively comprehensive set of one-group benchmarks for isotropically scattering media. Because of time and resource limitations, the extensions of the benchmarks to include multi-group and anisotropic scattering are not included here. Presently, however, enormous advances in the solution for the planar Green`s function in an anisotropically scattering medium have been made and will eventually be implemented in the two- and three-dimensional solutions considered under this grant. Of particular note in this work are the numerical results for the three-dimensional SLP, which have never before been presented. The results presented were made possible only because of the tremendous advances in computing power that have occurred during the past decade.« less

H2O incorporation in the phosphorene/a-SiO2 interface: a first-principles study

NASA Astrophysics Data System (ADS)

Scopel, Wanderlã L.; Souza, Everson S.; Miwa, R. H.

2017-02-01

Based on first-principles calculations, we investigate (i) the energetic stability and electronic properties of single-layer phosphorene (SLP) adsorbed on an amorphous SiO2 surface (SLP/a-SiO2), and (ii) the further incorporation of water molecules at the phosphorene/a-SiO2 interface. In (i), we find that the phosphorene sheet binds to a-SiO2 through van der Waals interactions, even in the presence of oxygen vacancies on the surface. The SLP/a-SiO2 system presents a type-I band alignment, with the valence (conduction) band maximum (minimum) of the phosphorene lying within the energy gap of the a-SiO2 substrate. The structure and the surface-potential corrugations promote the formation of electron-rich and electron-poor regions on the phosphorene sheet and at the SLP/a-SiO2 interface. Such charge density puddles are strengthened by the presence of oxygen vacancies in a-SiO2. In (ii), because of the amorphous structure of the surface, we consider a number of plausible geometries for H2O embedded in the SLP/a-SiO2 interface. There is an energetic preference for the formation of hydroxyl (OH) groups on the a-SiO2 surface. Meanwhile, in the presence of oxygenated water or interstitial oxygen in the phosphorene sheet, we observe the formation of metastable OH bonded to the phosphorene, and the formation of energetically stable P-O-Si chemical bonds at the SLP/a-SiO2 interface. Further x-ray absorption spectra simulations are performed, which aim to provide additional structural/electronic information on the oxygen atoms forming hydroxyl groups or P-O-Si chemical bonds at the interface region.

H2O incorporation in the phosphorene/a-SiO2 interface: a first-principles study.

PubMed

Scopel, Wanderlã L; Souza, Everson S; Miwa, R H

2017-02-22

Based on first-principles calculations, we investigate (i) the energetic stability and electronic properties of single-layer phosphorene (SLP) adsorbed on an amorphous SiO 2 surface (SLP/a-SiO 2 ), and (ii) the further incorporation of water molecules at the phosphorene/a-SiO 2 interface. In (i), we find that the phosphorene sheet binds to a-SiO 2 through van der Waals interactions, even in the presence of oxygen vacancies on the surface. The SLP/a-SiO 2 system presents a type-I band alignment, with the valence (conduction) band maximum (minimum) of the phosphorene lying within the energy gap of the a-SiO 2 substrate. The structure and the surface-potential corrugations promote the formation of electron-rich and electron-poor regions on the phosphorene sheet and at the SLP/a-SiO 2 interface. Such charge density puddles are strengthened by the presence of oxygen vacancies in a-SiO 2 . In (ii), because of the amorphous structure of the surface, we consider a number of plausible geometries for H 2 O embedded in the SLP/a-SiO 2 interface. There is an energetic preference for the formation of hydroxyl (OH) groups on the a-SiO 2 surface. Meanwhile, in the presence of oxygenated water or interstitial oxygen in the phosphorene sheet, we observe the formation of metastable OH bonded to the phosphorene, and the formation of energetically stable P-O-Si chemical bonds at the SLP/a-SiO 2 interface. Further x-ray absorption spectra simulations are performed, which aim to provide additional structural/electronic information on the oxygen atoms forming hydroxyl groups or P-O-Si chemical bonds at the interface region.

Linkages Between the Great Arctic Cyclone of August 2012 and Tropopause Polar Vortices

NASA Astrophysics Data System (ADS)

Biernat, K.; Keyser, D.; Bosart, L. F.

2017-12-01

Coherent vortices in the vicinity of the tropopause, referred to as tropopause polar vortices (TPVs), are common features in the Arctic. TPVs may interact with and strengthen jet streams, as well as act as precursor disturbances for the development of Arctic cyclones. Arctic cyclones may be associated with strong surface winds and poleward advection of warm, moist air, contributing to reductions in Arctic sea-ice extent. Also, heavy precipitation, strong surface winds, and large waves accompanying Arctic cyclones may pose hazards to ships moving through open passageways in the Arctic Ocean. The Great Arctic Cyclone of August 2012 (hereafter AC12) is an example of an intense Arctic cyclone. AC12 formed on 2 August 2012 over central Siberia and attained a minimum sea level pressure (SLP) of 964 hPa on 6 August 2012 over the Arctic. Strong surface winds associated with AC12 led to reductions in Arctic sea-ice extent during a time in which sea ice was thin. Two TPVs are hypothesized to play a role in the life cycle of AC12. The purpose of this study is to investigate the linkages between AC12 and the two TPVs. The ERA-Interim dataset was utilized to examine the linkages between AC12 and the two TPVs. The two TPVs, TPV 1 and TPV 2, were tracked objectively using a TPV tracking algorithm. AC12 was tracked manually by following the locations of minimum SLP. During early August 2012, as TPV 1 approached and interacted with AC12 in a region of strong baroclinicity, it likely played an important role in the subsequent intensification of AC12. In addition, TPV-jet interactions involving both TPV 1 and TPV 2 likely contributed to the formation of a dual-jet configuration and jet coupling over AC12. The presence of warm, moist air and relatively strong lower-tropospheric ascent in the region of jet coupling and the subsequent interaction between both TPVs likely facilitated the intensification of AC12. After attaining its minimum SLP, AC12 moved slowly over the Arctic, where its expansive surface wind field contributed to reductions of Arctic sea-ice extent over a prolonged period. This study illustrates that TPVs, along with associated TPV-jet and TPV-TPV interactions, may play important roles in the life cycles of Arctic cyclones, which may lead to reductions in Arctic sea-ice extent.

Expression, refolding and crystallizations of the Grb2-like (GADS) C-terminal SH3 domain complexed with a SLP-76 motif peptide

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

Faravelli, Alessandro; Dimasi, Nazzareno, E-mail: ndimasi@gmail.com

Several crystals of the Grb2-like C-terminal SH3 domain in complex with a motif peptide from the SLP-76 protein were obtained and characterized. The Grb2-like adaptor protein GADS is composed of an N-terminal SH3 domain, an SH2 domain, a proline-rich region and a C-terminal SH3 domain. GADS interacts through its C-terminal SH3 domain with the adaptor protein SLP-76, thus recruiting this protein and other associated molecules to the linker for activation of T-cell (LAT) protein. The DNA encoding the C-terminal SH3 domain of GADS (GADS-cSH3) was assembled synthetically using a recursive PCR technique and the protein was overexpressed in Escherichia coli,more » refolded and purified. Several crystals of this domain in complex with the SLP-76 peptide were obtained and characterized.« less

Classification of reflected signals from cavitated tooth surfaces using an artificial intelligence technique incorporating a fiber optic displacement sensor

NASA Astrophysics Data System (ADS)

Rahman, Husna Abdul; Harun, Sulaiman Wadi; Arof, Hamzah; Irawati, Ninik; Musirin, Ismail; Ibrahim, Fatimah; Ahmad, Harith

2014-05-01

An enhanced dental cavity diameter measurement mechanism using an intensity-modulated fiber optic displacement sensor (FODS) scanning and imaging system, fuzzy logic as well as a single-layer perceptron (SLP) neural network, is presented. The SLP network was employed for the classification of the reflected signals, which were obtained from the surfaces of teeth samples and captured using FODS. Two features were used for the classification of the reflected signals with one of them being the output of a fuzzy logic. The test results showed that the combined fuzzy logic and SLP network methodology contributed to a 100% classification accuracy of the network. The high-classification accuracy significantly demonstrates the suitability of the proposed features and classification using SLP networks for classifying the reflected signals from teeth surfaces, enabling the sensor to accurately measure small diameters of tooth cavity of up to 0.6 mm. The method remains simple enough to allow its easy integration in existing dental restoration support systems.

The structure of the S-layer of Clostridium difficile.

PubMed

Bradshaw, William J; Roberts, April K; Shone, Clifford C; Acharya, K Ravi

2018-03-01

The nosocomially acquired pathogen Clostridium difficile is the primary causative agent of antibiotic associated diarrhoea and causes tens of thousands of deaths globally each year. C. difficile presents a paracrystalline protein array on the surface of the cell known as an S-layer. S-layers have been demonstrated to possess a wide range of important functions, which, combined with their inherent accessibility, makes them a promising drug target. The unusually complex S-layer of C. difficile is primarily comprised of the high- and low- molecular weight S-layer proteins, HMW SLP and LMW SLP, formed from the cleavage of the S-layer precursor protein, SlpA, but may also contain up to 28 SlpA paralogues. A model of how the S-layer functions as a whole is required if it is to be exploited in fighting the bacterium. Here, we provide a summary of what is known about the S-layer of C. difficile and each of the paralogues and, considering some of the domains present, suggest potential roles for them.

Characterizing speech and language pathology outcomes in stroke rehabilitation.

PubMed

Hatfield, Brooke; Millet, Deborah; Coles, Janice; Gassaway, Julie; Conroy, Brendan; Smout, Randall J

2005-12-01

Hatfield B, Millet D, Coles J, Gassaway J, Conroy B, Smout RJ. Characterizing speech and language pathology outcomes in stroke rehabilitation. To describe a subset of speech-language pathology (SLP) patients in the Post-Stroke Rehabilitation Outcomes Project and to examine outcomes for patients with low admission FIM levels of auditory comprehension and verbal expression. Observational cohort study. Five inpatient rehabilitation hospitals. Patients (N=397) receiving post-stroke SLP with admission FIM cognitive components at levels 1 through 5. Not applicable. Increase in comprehension and expression FIM scores from admission to discharge. Cognitively and linguistically complex SLP activities (problem-solving and executive functioning skills) were associated with greater likelihood of success in low- to mid-level functioning communicators in the acute post-stroke rehabilitation period. The results challenge common clinical practice by suggesting that use of high-level cognitively and linguistically complex SLP activities early in a patient's stay may result in more efficient practice and better outcomes regardless of the patient's functional communication severity level on admission.

Classification of reflected signals from cavitated tooth surfaces using an artificial intelligence technique incorporating a fiber optic displacement sensor.

PubMed

Rahman, Husna Abdul; Harun, Sulaiman Wadi; Arof, Hamzah; Irawati, Ninik; Musirin, Ismail; Ibrahim, Fatimah; Ahmad, Harith

2014-05-01

An enhanced dental cavity diameter measurement mechanism using an intensity-modulated fiber optic displacement sensor (FODS) scanning and imaging system, fuzzy logic as well as a single-layer perceptron (SLP) neural network, is presented. The SLP network was employed for the classification of the reflected signals, which were obtained from the surfaces of teeth samples and captured using FODS. Two features were used for the classification of the reflected signals with one of them being the output of a fuzzy logic. The test results showed that the combined fuzzy logic and SLP network methodology contributed to a 100% classification accuracy of the network. The high-classification accuracy significantly demonstrates the suitability of the proposed features and classification using SLP networks for classifying the reflected signals from teeth surfaces, enabling the sensor to accurately measure small diameters of tooth cavity of up to 0.6 mm. The method remains simple enough to allow its easy integration in existing dental restoration support systems.

Managing the language and learning needs of the communication-impaired preschool child. A proactive approach.

PubMed

Prelock, P A

1993-01-01

If a proactive approach to assessment and intervention had been used in the case study presented at the beginning of this article, the following might have occurred: The SLP would have asked the parents and brother of the 3 1/2-year-old child referred for a communication evaluation to participate in the assessment activities. The parents would have been asked to prioritize their expectations for their daughter's communication, behavior, and school success. They would have been told the SLP would do the same based on her knowledge of performance expectations in these areas for a 3 1/2-year old. Both the parents and the SLP would have agreed to consider describing the child's communication, behavior, and potential for school success in more than a single setting or context. The child would have been seen in her home as well as in a preschool setting. The clinician would have observed the child's play with both familiar and unfamiliar children and adults. The parents would have kept a log of their child's communication successes and failures for one week. The clinician would have used those situations the parents identified as successful and unsuccessful to specify the child's strengths and weaknesses. The parents would have been asked to write down ideas they had on the type of intervention, if any, they felt their daughter needed to meet the expectations they set. The clinician would do the same and would have consulted with an educational specialist and a psychologist to obtain their perspective on the educational and cognitive needs of a preschooler. The speech-language pathologist would have asked other professionals to assist in assessment of this child. The psychologist would have completed some testing in the home with the SLP providing help in interpreting the child's responses. The educational specialist would have invited the SLP to observe the child in a diagnostic preschool setting to assess the child's ability to understand and communicate in an unfamiliar environment with peers. The team, including the parents, the SLP, psychologist, and educational specialist would have met to share the information they had gathered about the child's communication, behavior, and potential for success in school. The SLP would have acted as a case manager and listed the strengths and weaknesses each participant identified for the child. When the list was complete, the SLP would have presented consistent areas of strength and weakness reported across contexts. The team members would have developed statements of their performance expectations for the child.(ABSTRACT TRUNCATED AT 400 WORDS)

Arctic Ocean Circulation Patterns Revealed by GRACE

NASA Astrophysics Data System (ADS)

Peralta-Ferriz, Cecilia; Morison, James H.; Wallace, John M.; Bonin, Jennifer A.; Zhang, Jinlun

2013-04-01

EOF analysis of non-seasonal, month-to-month variations in GRACE derived Arctic Ocean bottom pressure (OBP) yield three dominant modes. The first mode is a wintertime basin wide variation in mass associated with high atmospheric pressure (SLP) over Scandinavia. The second mode is a shift of mass from the central Arctic Ocean to the Siberian shelves due to low pressure over the basins, associated with the strength of the Arctic Oscillation. The third mode is a shift in mass between the Eastern and Western Siberian shelves, related to strength of the Beaufort High mainly in summer, and to eastward alongshore winds on the Barents Sea in winter. The PIOMAS and ECCO2 modeled OBP are consistent with the form of these modes and provide context in terms of variations in sea surface height. The models are used to investigate the ocean dynamics associated with each mode of OBP variability.

Neuromechanical simulation of the locust jump

PubMed Central

Cofer, D.; Cymbalyuk, G.; Heitler, W. J.; Edwards, D. H.

2010-01-01

The neural circuitry and biomechanics of kicking in locusts have been studied to understand their roles in the control of both kicking and jumping. It has been hypothesized that the same neural circuit and biomechanics governed both behaviors but this hypothesis was not testable with current technology. We built a neuromechanical model to test this and to gain a better understanding of the role of the semi-lunar process (SLP) in jump dynamics. The jumping and kicking behaviors of the model were tested by comparing them with a variety of published data, and were found to reproduce the results from live animals. This confirmed that the kick neural circuitry can produce the jump behavior. The SLP is a set of highly sclerotized bands of cuticle that can be bent to store energy for use during kicking and jumping. It has not been possible to directly test the effects of the SLP on jump performance because it is an integral part of the joint, and attempts to remove its influence prevent the locust from being able to jump. Simulations demonstrated that the SLP can significantly increase jump distance, power, total energy and duration of the jump impulse. In addition, the geometry of the joint enables the SLP force to assist leg flexion when the leg is flexed, and to assist extension once the leg has begun to extend. PMID:20228342

HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion.

PubMed

Patzak, Irene M; Königsberger, Sebastian; Suzuki, Akira; Mak, Tak W; Kiefer, Friedemann

2010-11-01

The hematopoietic progenitor kinase 1 (HPK1) signals into MAPK and NFκB pathways downstream of immunoreceptors, but enigmatically is a negative regulator of leukocytes. Here, we report a novel role for HPK1 in regulating the activation of the adhesion molecule leukocyte function-associated antigen-1 (LFA-1). Upon TCR stimulation, mediated by binding of adhesion and degranulation promoting adaptor protein (ADAP) to SLP-76, a ternary complex composed of ADAP/55-kDa src kinase associated phosphoprotein (SKAP-55) and RIAM translocates to the membrane and causes membrane recruitment of the active small GTPase Ras-related protein 1 (Rap1). Active Rap1, via its binding to RapL (regulator for cell adhesion and polarization enriched in lymphoid tissues), mediates LFA-1 integrin activation. We show here that HPK1, which also binds SLP-76, compete with ADAP for SLP-76 binding. In addition, HPK1 dampens Rap1 activation, resulting in decreased LFA-1 activity. Analysis of HPK1-deficient T cells revealed increased ADAP recruitment to SLP-76 and elevated Rap1 activation in those cells, leading to increased adhesion to ICAM-1 and cell spreading. Altogether, these results describe a novel function for HPK1 in linking TCR signaling to cell adhesion regulation and provide a mechanistic explanation for the negative regulatory role of HPK1 in T-cell biology.

Genetic structure of the populations migrating from San Luis Potosi and Zacatecas to Nuevo León in Mexico.

PubMed

Cerda-Flores, R M; Kshatriya, G K; Barton, S A; Leal-Garza, C H; Garza-Chapa, R; Schull, W J; Chakraborty, R

1991-06-01

The Mexicans residing in the Monterrey metropolitan area in Nuevo León, Mexico, were grouped by generation and birthplace [Monterrey Metropolitan Area (MMA), San Luis Potosi (SLP), and Zacatecas (ZAC)] of the four grandparents to determine the extent of genetic variation within this population and the genetic differences, if any, between the natives living in the MMA and the immigrant populations from SLP and ZAC. Nine genetic marker systems were analyzed. The genetic distance analysis indicates that SLP and ZAC are similar to the MMA, irrespective of birthplace and generation. Gene diversity analysis (GST) suggests that more than 96% of the total gene diversity (HT) can be attributed to individual variation within the population. The genetic admixture analysis suggests that the Mexicans of the MMA, SLP, and ZAC, stratified by birthplace and generation, have received a predominantly Spanish contribution (78.5%), followed by a Mexican Indian contribution (21.5%). Similarly, admixture analysis, conducted on the population of Nuevo León and stratified by generation, indicates a substantial contribution from the MMA (64.6%), followed by ZAC (22.1%) and SLP (13.3%). Finally, we demonstrate that there is no nonrandom association of alleles among the genetic marker systems (i.e., no evidence of gametic disequilibrium) despite the Mestizo origin of this population.

Contribution of atmospheric circulation to recent off-shore sea-level variations in the Baltic Sea and the North Sea

NASA Astrophysics Data System (ADS)

Karabil, Sitar; Zorita, Eduardo; Hünicke, Birgit

2018-01-01

The main purpose of this study is to quantify the contribution of atmospheric factors to recent off-shore sea-level variability in the Baltic Sea and the North Sea on interannual timescales. For this purpose, we statistically analysed sea-level records from tide gauges and satellite altimetry and several climatic data sets covering the last century. Previous studies had concluded that the North Atlantic Oscillation (NAO) is the main pattern of atmospheric variability affecting sea level in the Baltic Sea and the North Sea in wintertime. However, we identify a different atmospheric circulation pattern that is more closely connected to sea-level variability than the NAO. This circulation pattern displays a link to sea level that remains stable through the 20th century, in contrast to the much more variable link between sea level and the NAO. We denote this atmospheric variability mode as the Baltic Sea and North Sea Oscillation (BANOS) index. The sea-level pressure (SLP) BANOS pattern displays an SLP dipole with centres of action located over (5° W, 45° N) and (20° E, 70° N) and this is distinct from the standard NAO SLP pattern in wintertime. In summertime, the discrepancy between the SLP BANOS and NAO patterns becomes clearer, with centres of action of the former located over (30° E, 45° N) and (20° E, 60° N). This index has a stronger connection to off-shore sea-level variability in the study area than the NAO in wintertime for the period 1993-2013, explaining locally up to 90 % of the interannual sea-level variance in winter and up to 79 % in summer. The eastern part of the Gulf of Finland is the area where the BANOS index is most sensitive to sea level in wintertime, whereas the Gulf of Riga is the most sensitive region in summertime. In the North Sea region, the maximum sea-level sensitivity to the BANOS pattern is located in the German Bight for both winter and summer seasons. We investigated, and when possible quantified, the contribution of several physical mechanisms which may explain the link between the sea-level variability and the atmospheric pattern described by the BANOS index. These mechanisms include the inverse barometer effect (IBE), freshwater balance, net energy surface flux and wind-induced water transport. We found that the most important mechanism is the IBE in both wintertime and summertime. Assuming a complete equilibration of seasonal sea level to the SLP gradients over this region, the IBE can explain up to 88 % of the sea-level variability attributed to the BANOS index in wintertime and 34 % in summertime. The net energy flux at the surface is found to be an important factor for the variation of sea level, explaining 35 % of sea-level variance in wintertime and a very small amount in summer. The freshwater flux could only explain 27 % of the variability in summertime and a negligible part in winter. In contrast to the NAO, the direct wind forcing associated with the SLP BANOS pattern does not lead to transport of water from the North Sea into the Baltic Sea in wintertime.

Simulation of Extreme Arctic Cyclones in IPCC AR5 Experiments

NASA Astrophysics Data System (ADS)

Vavrus, S. J.

2012-12-01

Although impending Arctic climate change is widely recognized, a wild card in its expression is how extreme weather events in this region will respond to greenhouse warming. Intense polar cyclones represent one type of high-latitude phenomena falling into this category, including very deep synoptic-scale cyclones and mesoscale polar lows. These systems inflict damage through high winds, heavy precipitation, and wave action along coastlines, and their impact is expected to expand in the future, when reduced sea ice cover allows enhanced wave energy. The loss of a buffering ice pack could greatly increase the rate of coastal erosion, which has already been increasing in the Arctic. These and related threats may amplify if extreme Arctic cyclones become more frequent and/or intense in a warming climate with much more open water to fuel them. This possibility has merit on the basis of GCM experiments, which project that greenhouse forcing causes lower mean sea level pressure (SLP) in the Arctic and a strengthening of the deepest storms over boreal high latitudes. In this study, the latest Coupled Model Intercomparison Project (CMIP5) climate model output is used to investigate the following questions: (1) What are the spatial and seasonal characteristics of extreme Arctic cyclones? (2) How well do GCMs simulate these phenomena? (3) Are Arctic cyclones already showing the expected response to greenhouse warming in climate models? To address these questions, a retrospective analysis is conducted of the transient 20th century simulations among the CMIP5 GCMs (spanning years 1850-2005). The results demonstrate that GCMs are able to reasonably represent extreme Arctic cyclones and that the simulated characteristics do not depend significantly on model resolution. Consistent with observational evidence, climate models generate these storms primarily during winter and within the climatological Aleutian and Icelandic Low regions. Occasionally the cyclones remain very intense over the Arctic Ocean. The historical tendency in Arctic SLP varies considerably among the GCMs, but the intermodel average trend exhibits a lowering of mean-annual pressure over the Arctic during the past 150 years and an increase in extreme cyclones in the vicinity of the Aleutian and Icelandic Lows. However, only weak trends in extreme cyclones are simulated through 2005 over the Arctic Ocean, where simulations of future climate change produce the largest SLP falls.

Neuromodulation and Neurorehabilitation for Treatment of Functional Deficits after mTBI plus PTSD

DTIC Science & Technology

2016-10-01

What individuals have worked on the project? Name: Brett Blabas, MS No Change Name: Ann Guernon, MS, CCC- SLP , CCRC No Change Name...Theresa Pape, DrPH, MA, CCC- SLP Project Role: PI Nearest person month worked: 1 Contribution to Project: Dr. Pape has overseen protocol

Program Intensity and Service Delivery Models in the Schools: SLP Survey Results

ERIC Educational Resources Information Center

Brandel, Jayne; Loeb, Diane Frome

2011-01-01

Purpose: School-based speech-language pathologists (SLPs) routinely work with team members to make recommendations regarding an intervention program's intensity and method of service delivery for children with speech and language impairments. In this study, student, SLP, and workplace characteristics that may influence SLPs' recommendations were…

rTMS: A Treatment to Restore Function After Severe TBI

DTIC Science & Technology

2015-10-01

with the preparation of Hines VA and Northwestern IRB amendments as well as SCVMC’s initial IRB submission packet. Name: Ann Guernon, MS, CCC- SLP ...submissions to HRPO and interface with HRPO to address needed amendments. Name: Theresa Pape, DrPH, MA, CCC- SLP Project Role: PI Nearest

77 FR 16540 - Notice of Proposed Information Collection Requests; Office of Innovation and Improvement; School...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-21

... and Improvement; School Leadership Program (SLP) Annual Performance Report SUMMARY: Information in the School Leadership Program (SLP) Annual Performance Report (APR) is collected in compliance with the... Leadership Program. DATES: Interested persons are invited to submit comments on or before May 21, 2012...

Variable corneal compensation improves discrimination between normal and glaucomatous eyes with the scanning laser polarimeter.

PubMed

Tannenbaum, Dana P; Hoffman, Douglas; Lemij, Hans G; Garway-Heath, David F; Greenfield, David S; Caprioli, Joseph

2004-02-01

The presently available scanning laser polarimeter (SLP) has a fixed corneal compensator (FCC) that neutralizes corneal birefringence only in eyes with birefringence that matches the population mode. A prototype variable corneal compensator (VCC) provides neutralization of individual corneal birefringence based on individual macular retardation patterns. The aim of this study was to evaluate the relative ability of the SLP with the FCC and with the VCC to discriminate between normal and glaucomatous eyes. Prospective, nonrandomized, comparative case series. Algorithm-generating set consisting of 56 normal eyes and 55 glaucomatous eyes and an independent data set consisting of 83 normal eyes and 56 glaucomatous eyes. Sixteen retardation measurements were obtained with the SLP with the FCC and the VCC from all subjects. Dependency of parameters on age, gender, ethnic origin, and eye side was sought. Logistic regression was used to evaluate how well the various parameters could detect glaucoma. Discriminant functions were generated, and the area under the receiver operating characteristic (ROC) curve was determined. Discrimination between normal and glaucomatous eyes on the basis of single parameters was significantly better with the VCC than with the FCC for 6 retardation parameters: nasal average (P = 0.0003), superior maximum (P = 0.0003), ellipse average (P = 0.002), average thickness (P = 0.003), superior average (P = 0.010), and inferior average (P = 0.010). Discriminant analysis identified the optimal combination of parameters for the FCC and for the VCC. When the discriminant functions were applied to the independent data set, areas under the ROC curve were 0.84 for the FCC and 0.90 for the VCC (P<0.021). When the discriminant functions were applied to a subset of patients with early visual field loss, areas under the ROC curve were 0.82 for the FCC and 0.90 for the VCC (P<0.016). Individual correction for corneal birefringence with the VCC significantly improved the ability of the SLP to distinguish between normal and glaucomatous eyes and enabled detection of patients with early glaucoma.

Circulation types related to lightning activity over Catalonia and the Principality of Andorra

NASA Astrophysics Data System (ADS)

Pineda, N.; Esteban, P.; Trapero, L.; Soler, X.; Beck, C.

In the present study, we use a Principal Component Analysis (PCA) to characterize the surface 6-h circulation types related to substantial lightning activity over the Catalonia area (north-eastern Iberia) and the Principality of Andorra (eastern Pyrenees) from January 2003 to December 2007. The gridded data used for classification of the circulation types is the NCEP Final Analyses of the Global Tropospheric Analyses at 1° resolution over the region 35°N-48°N by 5°W-8°E. Lightning information was collected by the SAFIR lightning detection system operated by the Meteorological Service of Catalonia (SMC), which covers the region studied. We determined nine circulation types on the basis of the S-mode orthogonal rotated Principal Component Analysis. The “extreme scores” principle was used previous to the assignation of all cases, to obtain the number of final types and their centroids. The distinct differences identified in the resulting mean Sea Level Pressure (SLP) fields enabled us to group the types into three main patterns, taking into account their scale/dynamical origin. The first group of types shows the different distribution of the centres of action at synoptic scale associated with the occurrence of lightning. The second group is connected to mesoscale dynamics, mainly induced by the relief of the Pyrenees. The third group shows types with low gradient SLP patterns in which the lightning activity is a consequence of thermal dynamics (coastal and mountain breezes). Apart from reinforcing the consistency of the groups obtained, analysis of the resulting classification improves our understanding of the geographical distribution and genesis factors of thunderstorm activity in the study area, and provides complementary information for supporting weather forecasting. Thus, the catalogue obtained will provide advances in different climatological and meteorological applications, such as nowcasting products or detection of climate change trends.

Empowered Commanders: The Cornerstone to Agile, Flexible Command and Control

DTIC Science & Technology

2015-02-01

Feb/ SLP -Wilsbach-Lyle.pdf. 4. Gilmary Michael Hostage III and Larry R. Broadwell Jr., "Resilient Command and Control: The Need for Distributed Control...www.au.af.mil / au/ afri/aspj/digital/pdf/ articles/ 2014-Jul-Aug/ SLP -Deptula.pdf. 18. Gen Hawk Carlisle, multiple speeches, November 2012-September

Employment Myths and Realities in Speech and Language Pathology.

ERIC Educational Resources Information Center

Chan, T. C.; Curran, Theresa; Deskin, Caroline

This study compared the professional expectations of graduate students in speech and language pathology (SLP) with the employment realities offered by the profession. A total of 89 graduate students enrolled in the SLP program at Valdosta State University (VSU) in Georgia during 1995-97 completed a seven-item questionnaire on employment prospects.…

Providing Effective Speech-Language Pathology Group Treatment in the Comprehensive Inpatient Rehabilitation Setting.

PubMed

Baron, Christine; Holcombe, Molly; van der Stelt, Candace

2018-02-01

Group treatment is an integral part of speech-language pathology (SLP) practice. The majority of SLP literature concerns group treatment provided in outpatient settings. This article describes the goals, procedures, and benefits of providing quality SLP group therapy in the comprehensive inpatient rehabilitation (CIR) setting. Effective CIR groups must be designed with attention to type and severity of communication impairment, as well physical stamina of group members. Group leaders need to target individualized patient goals while creating a challenging, complex, and dynamic group context that supports participation by all group members. Direct patient-to-patient interaction is fostered as much as possible. Peer feedback supports goal acquisition by fellow group members. The rich, complex group context fosters improved insight, initiation, social connectedness, and generalization of communication skills. Group treatment provides a unique type of treatment not easily replicated with individual treatment. SLP group treatment in a CIR is an essential component of an intensive, high-quality program. Continued advocacy for group therapy provision and research into its efficacy and effectiveness are warranted. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Synaptotagmin-Like Proteins Control Formation of a Single Apical Membrane Domain in Epithelial Cells

PubMed Central

Gálvez-Santisteban, Manuel; Rodriguez-Fraticelli, Alejo E.; Bryant, David M.; Vergarajauregui, Silvia; Yasuda, Takao; Bañón-Rodríguez, Inmaculada; Bernascone, Ilenia; Datta, Anirban; Spivak, Natalie; Young, Kitty; Slim, Christiaan L.; Brakeman, Paul R.; Fukuda, Mitsunori; Mostov, Keith E.; Martín-Belmonte, Fernando

2012-01-01

SUMMARY The formation of epithelial tissues requires both the generation of apical-basal polarity and the co-ordination of this polarity between neighboring cells to form a central lumen. During de novo lumen formation, vectorial membrane transport contributes to formation of a singular apical membrane, resulting in contribution of each cell to only a single lumen. Here, from a functional screen for genes required for 3D epithelial architecture we identify key roles for Synaptotagmin-like proteins 2-a and 4-a (Slp2-a/4-a) in generation of a single apical surface per cell. Slp2-a localizes to the luminal membrane in a PI(4,5)P2-dependent manner, where it targets Rab27-loaded vesicles to initiate a single lumen. Vesicle tethering and fusion is controlled by Slp4-a, in conjunction with Rab27/Rab3/Rab8 and the SNARE Syntaxin-3. Together, Slp2-a/4-a co-ordinate the spatiotemporal organization of vectorial apical transport to ensure only a single apical surface, and thus formation of a single lumen, occurs per cell. PMID:22820376

A PLC-γ1 Feedback Pathway Regulates Lck Substrate Phosphorylation at the T-Cell Receptor and SLP-76 Complex.

PubMed

Belmont, Judson; Gu, Tao; Mudd, Ashley; Salomon, Arthur R

2017-08-04

Phospholipase C gamma 1 (PLC-γ1) occupies a critically important position in the T-cell signaling pathway. While its functions as a regulator of both Ca 2+ signaling and PKC-family kinases are well characterized, PLC-γ1's role in the regulation of early T-cell receptor signaling events is incompletely understood. Activation of the T-cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from SLP-76 to the apical kinase in the pathway, Lck. To determine if PLC-γ1 contributes to the regulation of these feedback networks, we performed a quantitative phosphoproteomic analysis of PLC-γ1-deficient T cells. These data revealed a previously unappreciated role for PLC-γ1 in the positive regulation of Zap-70 and T-cell receptor tyrosine phosphorylation. Conversely, PLC-γ1 negatively regulated the phosphorylation of SLP-76-associated proteins, including previously established Lck substrate phosphorylation sites within this complex. While the positive and negative regulatory phosphorylation sites on Lck were largely unchanged, Tyr 192 phosphorylation was elevated in Jgamma1. The data supports a model wherein Lck's targeting, but not its kinase activity, is altered by PLC-γ1, possibly through Lck Tyr 192 phosphorylation and increased association of the kinase with protein scaffolds SLP-76 and TSAd.

Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes

PubMed Central

Fasbender, Frank; Claus, Maren; Wingert, Sabine; Sandusky, Mina; Watzl, Carsten

2017-01-01

In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway. This direct ITAM/SYK/SLP-76 signaling pathway therefore differs from previously described ITAM signaling. However, the SYK-family kinase ZAP70 required the additional co-expression of the Src-family kinases Fyn or Lck to efficiently phosphorylate SLP-76 in S2 cells. This difference in Src-family kinase dependency of SYK versus ZAP70-mediated ITAM-based signaling was further demonstrated in human lymphocytes. ITAM signaling in ZAP70-expressing T cells was dependent on the activity of Src-family kinases. In contrast, Src-family kinases were partially dispensable for ITAM signaling in SYK-expressing B cells or in natural killer cells, which express SYK and ZAP70. This demonstrates that SYK can signal using a Src-kinase independent ITAM-based signaling pathway, which may be involved in calibrating the threshold for lymphocyte activation. PMID:28736554

The Amino-Terminus of Vav1 Regulates TCR-Induced SLP-76 Microclusters via the Calponin Homology Domain and Non-Catalytic Surfaces within the GEF Module

PubMed Central

Sylvain, Nicholas R.; Nguyen, Ken; Bunnell, Stephen C.

2013-01-01

The guanine nucleotide exchange factor (GEF) Vav1 synergizes with the adapter SLP-76 to support T cell development and activation. Here, we demonstrate that Vav1 controls the stability and movement T cell receptor-induced SLP-76 microclusters. The SH2 domain enables the recruitment of Vav1 into SLP-76 microclusters, whereas the SH3 domains of Vav1 cooperate to enhance microcluster stability and function. Although the amino-terminus of Vav1 is essential for downstream signaling, it possesses novel scaffolding functions that are unaffected by the inactivation of the Vav1 GEF or by the constitutive GEF activation that accompanies the mutation of the regulatory tyrosine residues 142, 160, and 174. In contrast, GEF-inactivating point mutations predicted to perturb the structural integrity of the Vav1 GEF abolish these scaffolding functions. Paradoxically, the excision of catalytic Dbl-homology (DH) / pleckstrin homology (PH) cassette produces a relatively mild scaffolding defect, indicating that the L213A and L278Q point mutations antagonize scaffolding functions mediated by adjacent domains. A deletion mutant lacking the CH domain potently inhibits calcium responses, but also exhibits mild scaffolding defects. We conclude multiple GEF-independent scaffolding functions contained within the amino-terminus of Vav1 contribute to T cell activation by acting synergistically to increase the stability and functionality of SLP-76 microclusters. PMID:21386095

Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes.

PubMed

Fasbender, Frank; Claus, Maren; Wingert, Sabine; Sandusky, Mina; Watzl, Carsten

2017-01-01

In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway. This direct ITAM/SYK/SLP-76 signaling pathway therefore differs from previously described ITAM signaling. However, the SYK-family kinase ZAP70 required the additional co-expression of the Src-family kinases Fyn or Lck to efficiently phosphorylate SLP-76 in S2 cells. This difference in Src-family kinase dependency of SYK versus ZAP70-mediated ITAM-based signaling was further demonstrated in human lymphocytes. ITAM signaling in ZAP70-expressing T cells was dependent on the activity of Src-family kinases. In contrast, Src-family kinases were partially dispensable for ITAM signaling in SYK-expressing B cells or in natural killer cells, which express SYK and ZAP70. This demonstrates that SYK can signal using a Src-kinase independent ITAM-based signaling pathway, which may be involved in calibrating the threshold for lymphocyte activation.

Speech sound disorders in a community study of preschool children.

PubMed

McLeod, Sharynne; Harrison, Linda J; McAllister, Lindy; McCormack, Jane

2013-08-01

To undertake a community (nonclinical) study to describe the speech of preschool children who had been identified by parents/teachers as having difficulties "talking and making speech sounds" and compare the speech characteristics of those who had and had not accessed the services of a speech-language pathologist (SLP). Stage 1: Parent/teacher concern regarding the speech skills of 1,097 4- to 5-year-old children attending early childhood centers was documented. Stage 2a: One hundred forty-three children who had been identified with concerns were assessed. Stage 2b: Parents returned questionnaires about service access for 109 children. The majority of the 143 children (86.7%) achieved a standard score below the normal range for the percentage of consonants correct (PCC) on the Diagnostic Evaluation of Articulation and Phonology (Dodd, Hua, Crosbie, Holm, & Ozanne, 2002). Consonants produced incorrectly were consistent with the late-8 phonemes ( Shriberg, 1993). Common phonological patterns were fricative simplification (82.5%), cluster simplification (49.0%)/reduction (19.6%), gliding (41.3%), and palatal fronting (15.4%). Interdental lisps on /s/ and /z/ were produced by 39.9% of the children, dentalization of other sibilants by 17.5%, and lateral lisps by 13.3%. Despite parent/teacher concern, only 41/109 children had contact with an SLP. These children were more likely to be unintelligible to strangers, to express distress about their speech, and to have a lower PCC and a smaller consonant inventory compared to the children who had no contact with an SLP. A significant number of preschool-age children with speech sound disorders (SSD) have not had contact with an SLP. These children have mild-severe SSD and would benefit from SLP intervention. Integrated SLP services within early childhood communities would enable earlier identification of SSD and access to intervention to reduce potential educational and social impacts affiliated with SSD.

Electrochemical noise measurements of sustained microbially influenced pitting corrosion in a laboratory flow loop system

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

Lin, Y.; Frank, J.R.; St. Martin, E.J.

Because of the chaotic nature of the corrosion process and the complexity of the electrochemical noise signals that are generated, there is no generally accepted method of measuring and interpreting these signals that allows the consistent detection and identification of sustained localized pitting (SLP) as compared to general corrosion. The authors have reexamined electrochemical noise analysis (ENA) of localized corrosion using different hardware, signal collection, and signal processing designs than those used in conventional ENA techniques. The new data acquisition system was designed to identify and monitor the progress of SLP by analyzing the power spectral density (PSD) of themore » trend of the corrosion current noise level (CNL) and potential noise level (PNL). Each CNL and PNL data point was calculated from the root-mean-square value of the ac components of current and potential fluctuation signals, which were measured simultaneously during a short time period. The PSD analysis results consistently demonstrated that the trends of PNL and CNL contain information that can be used to differentiate between SLP and general corrosion mechanisms. The degree of linear slope in the low-frequency portion of the PSD analysis was correlated with the SLP process. Laboratory metal coupons as well as commercial corrosion probes were tested to ensure the reproducibility and consistency of the results. The on-line monitoring capability of this new ENA method was evaluated in a bench-scale flow-loop system, which simulated microbially influenced corrosion (MIC) activity. The conditions in the test flow-loop system were controlled by the addition of microbes and different substrates to favor accelerated corrosion. The ENA results demonstrated that this in-situ corrosion monitoring system could effectively identify SLP corrosion associated with MIC, compared to a more uniform general corrosion mechanism. A reduction in SLP activity could be clearly detected by the ENA monitoring system when a corrosion inhibitor was added into one of the test loops during the corrosion testing.« less

Electrochemical noise measurements of sustained microbially influenced pitting corrosion in a laboratory flow loop system.

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

Lin, Y. J.

Because of the chaotic nature of the corrosion process and the complexity of the electrochemical noise signals that are generated, there is no generally accepted method of measuring and interpreting these signals that allows the consistent detection and identification of sustained localized pitting (SLP) as compared to general corrosion. We have reexamined electrochemical noise analysis (ENA) of localized corrosion using different hardware, signal collection, and signal processing designs than those used in conventional ENA techniques. The new data acquisition system was designed to identify and monitor the progress of SLP by analyzing the power spectral density (PSD) of the trendmore » of the corrosion current noise level (CNL) and potential noise level (PNL). Each CNL and PNL data point was calculated from the root-mean- square value of the ac components of current and potential fluctuation signals, which were measured simultaneously during a short time period. The PSD analysis results consistently demonstrated that the trends of PNL and CNL contain information that can be used to differentiate between SLP and general corrosion mechanisms. The degree of linear slope in the low-frequency portion of the PSD analysis was correlated with the SLP process. Laboratory metal coupons as well as commercial corrosion probes were tested to ensure the reproducibility and consistency of the results. The on-line monitoring capability of this new ENA method was evaluated in a bench-scale flow-loop system, which simulated microbially influenced corrosion (MIC) activity. The conditions in the test flow-loop system were controlled by the addition of microbes and different substrates to favor accelerated corrosion. The ENA results demonstrated that this in-situ corrosion monitoring system could effectively identify SLP corrosion associated with MIC, compared to a more uniform general corrosion mechanism. A reduction in SLP activity could be clearly detected by the ENA monitoring system when a corrosion inhibitor was added into one of the test loops during the corrosion testing.« less

Association of a Proactive Swallowing Rehabilitation Program With Feeding Tube Placement in Patients Treated for Pharyngeal Cancer.

PubMed

Ajmani, Gaurav S; Nocon, Cheryl C; Brockstein, Bruce E; Campbell, Nicholas P; Kelly, Amy B; Allison, Jamie; Bhayani, Mihir K

2018-04-19

A proactive speech and language pathology (SLP) program is an important component of the multidisciplinary care of patients with head and neck squamous cell carcinoma (HNSCC). Swallowing rehabilitation can reduce the rate of feeding tube placement, thereby significantly improving quality of life. To evaluate the initiation of a proactive SLP rehabilitation program at a single institution and its association with rates of feeding tube placement and dietary intake in patients with HNSCC. Cohort study at a tertiary care and referral center for patients with HNSCC serving the northern Chicago region. Patients were treated for squamous cell carcinomas of the hypopharynx, oropharynx, and nasopharynx from 2004 to 2015 with radiation or chemoradiation therapy in the definitive or adjuvant setting. Patients who received less than 5000 cGy radiation or underwent reirradiation were excluded. A proactive SLP program for patients with HNSCC was initiated in 2011. Study cohorts were divided into 2 groups: 2004 through 2010 and 2011 through 2015. Primary outcome variables were SLP referral placement and timing of the referral. Secondary outcomes were feeding tube placement and ability to tolerate any oral intake. A total of 254 patients met inclusion criteria (135 before and 119 after implementation of SLP program; median age, 60 years [range, 14-94 years]; 77% male). With the initiation of a proactive SLP program, pretreatment evaluations increased from 29 (21.5%) to 70 (58.8%; risk ratio [RR], 2.74; 95% CI, 1.92-3.91), and rate of referral overall at any time increased from 60.0% to 79.8% (RR, 1.33; 95% CI, 1.13-1.57). Feeding tube placement rates decreased from 45.9% (n = 62) to 29.4% (n = 35; RR, 0.64; 95% CI, 0.46-0.89). Among patients receiving a swallow evaluation, feeding tube requirements were less frequent for those receiving a pretreatment evaluation (31 of 99 [31%]) than for those referred during (11 of 18 [61%]) or after (38 of 59 [64%]) treatment. The rate of tolerating any oral intake at the end of treatment improved from 71.1% (n = 96) in the preimplementation period to 82.4% (n = 98; RR, 1.16; 95% CI, 1.01-1.33). A proactive SLP program can be successfully established as part of the multidisciplinary care of patients with HNSCC and improve patient quality of life.

Accuracy of available methods for quantifying the heat power generation of nanoparticles for magnetic hyperthermia.

PubMed

Andreu, Irene; Natividad, Eva

2013-12-01

In magnetic hyperthermia, characterising the specific functionality of magnetic nanoparticle arrangements is essential to plan the therapies by simulating maximum achievable temperatures. This functionality, i.e. the heat power released upon application of an alternating magnetic field, is quantified by means of the specific absorption rate (SAR), also referred to as specific loss power (SLP). Many research groups are currently involved in the SAR/SLP determination of newly synthesised materials by several methods, either magnetic or calorimetric, some of which are affected by important and unquantifiable uncertainties that may turn measurements into rough estimates. This paper reviews all these methods, discussing in particular sources of uncertainties, as well as their possible minimisation. In general, magnetic methods, although accurate, do not operate in the conditions of magnetic hyperthermia. Calorimetric methods do, but the easiest to implement, the initial-slope method in isoperibol conditions, derives inaccuracies coming from the lack of matching between thermal models, experimental set-ups and measuring conditions, while the most accurate, the pulse-heating method in adiabatic conditions, requires more complex set-ups.

Vehicle Charging on the 29.036 and 29.037 Rockets of the EQUIS II Campaign.

NASA Astrophysics Data System (ADS)

Barjatya, A.; Swenson, C.; Fish, C.; Hummel, A.; Hysell, D.

2004-12-01

The rocket investigation "Scattering Layer in the Bottomside Equatorial F-region Ionosphere", was part of the NASA EQUIS II campaign. Two salvos of sounding rockets were launched from Roi Namur in Kwajalein on August 7th and 15th of 2004. The project's mission was to investigate the thin scattering layers in the post sunset equatorial F region ionosphere that act as precursors to a fully developed equatorial spread F. Each of the salvos consisted of one instrumented and two chemical release payloads. The instrumented rockets were launched westward into equatorial spread F precursor that was first observed from ground using the Altair radar. The instrumented rockets reached an apogee of ~450 km. The instruments consisted of a Sweeping Langmuir Probe (SLP), a fixed bias DC Probe (DCP), a Plasma Impedance Probe consisting of a Plasma Frequency Probe and a Plasma Sweeping Probe built at Utah State University. The instrument suite also included an Electric Field Probe built by Penn State University. This poster presents observations of vehicle charging and preliminary data from the SLP and DCP.

Wave Probe - New Instrument For Space Research

NASA Astrophysics Data System (ADS)

Korepanov, V.; Dudkin, F.

2007-12-01

The dispersion relations are very important for the wave activity study in space plasmas. One of the most efficient methods for their analysis is the simultaneous measurements of spatial current density and magnetic field fluctuations during such a wave process. Whereas the measurement of the magnetic field is a routine task realized onboard practically every spacecraft (SC), the direct measurement of spatial current density (SCD) still remains a complicated scientific and technological problem. First attempt to solve it was executed in late 60-ties by a group headed by F. Mozer. They proposed and launched in a rocket experiment the device named "Split Langmuir Probe" (SLP) - two conducting plates separated by a thin insulated split. Unfortunately this experiment failed what diverted the attention of experimenters in space branch from this instrument for many years, practically till now. But the importance to know the SCD stimulated the development of new principles and devices to measure it. A short review of known versions is discussed. The newly evoked interest to this problem caused next attempt to improve the SLP construction and methodology of its application for SCD measurements, which resulted in first successful attempt in 1985: the measured SCD onboard Prognos-10 SC in the bow shock region was in rather good agreement with the calculated value. This attempt was continued onboard Interball-Tail SC (1995-2000) where again a qualitatively good coincidence of measured and calculated values was observed. The obtained experience and further theoretical research allowed developing a new instrument - Wave Probe - which is a combination of induction magnetometer and SLP in one body. Both on-ground tests in plasma chamber and the spatial experiment executed onboard Ukrainian "Sich-1M" SC (2004) showed that the combined in-situ simultaneous measurements of SCD and magnetic field fluctuations allowed obtaining the wave number of the whistler wave. The same wave number was calculated theoretically from dispersion relations of whistler wave using known ionosphere model and the comparison of measured and calculated values of both wave number and SCD gave a good quantitative agreement. The details of theoretical and experimental study are discussed in the report. There is a pleasant duty of the authors to thank Prof. F. Mozer and Prof. S. Klimov for continuous attention and practical support of this work. It was also supported by NSAU contract No 1-02/03.

Science Literacy in School and Home Contexts: Kindergarteners' Science Achievement and Motivation

ERIC Educational Resources Information Center

Mantzicopoulos, Panayota; Patrick, Helen; Samarapungavan, Ala

2013-01-01

We examined science learning and motivation outcomes as a function of children's participation in the classroom and classroom-plus-home components of the Scientific Literacy Project (SLP). The sample was comprised of kindergarten children in 4 low income, neighboring schools. Children in Schools 1 and 2 (n = 120) participated in the SLP science…

Silkworm larvae plasma (SLP) assay for detection of bacteria: False positives secondary to inflammation in vivo.

PubMed

Ma, Michelle; Rice, Tyler A; Percopo, Caroline M; Rosenberg, Helene F

2017-01-01

The silkworm larvae plasma (SLP) assay has been developed as a means to detect bacterial peptidoglycan as a surrogate for live bacteria. Here, we present results that indicate that generation of melanin by this assay is not fully reliable as a surrogate marker for bacterial count. Published by Elsevier B.V.

"We Learn How to Predict and Be a Scientist": Early Science Experiences and Kindergarten Children's Social Meanings about Science

ERIC Educational Resources Information Center

Mantzicopoulos, Panayota; Samarapungavan, Ala; Patrick, Helen

2009-01-01

We examine kindergarten children's emerging social meanings about science as a function of their participation in integrated science inquiry and literacy activities associated with the Scientific Literacy Project (SLP). We describe changes in 123 SLP kindergarten children's narrative accounts of learning science in school during three different…

The Perceived Importance of Anatomy and Neuroanatomy in the Practice of Speech-Language Pathology

ERIC Educational Resources Information Center

Martin, Kate; Bessell, Nicola J.; Scholten, Ingrid

2013-01-01

The purpose of this study was to examine the application of anatomy and neuroanatomy knowledge to current practice of speech-language pathology (SLP), based on the perceptions of practicing SLPs, and to elicit information on participants' experiences of learning these subjects in their primary SLP degree with a view to inform potential…

K-5 Educators' Perceptions of the Role of Speech Language Pathologists

ERIC Educational Resources Information Center

Hatcher, Karmon D.

2017-01-01

Rarely is a school-based speech language pathologist (SLP) thought of as an active contributor to the achievement of students or to the learning community in general. Researchers have found benefits for students when members of the learning community collaborate, and the SLP should be a part of this community collaboration. This qualitative case…

Dysphagic Independent Feeders' Justifications for Noncompliance with Recommendations by a Speech-Language Pathologist

ERIC Educational Resources Information Center

Colodny, Nancy

2005-01-01

The purpose of this study was to examine the various ways in which independent-feeding patients with dysphagia justified their noncompliance with swallowing recommendations suggested by a speech-language pathologist (SLP). Sixty-three independent-feeding dysphagia patients between the ages of 65 and 100 years who had been identified by the SLP or…

78 FR 14074 - Foreign-Trade Zone 189-Kent/Ottawa/Muskegon Counties, MI, Notification of Proposed Production...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-04

... Printing Plates), Grand Rapids, Michigan Southern Lithoplate, Inc. (SLP) submitted a notification of... aluminum offset printing plates for the printing industry. Pursuant to 15 CFR 400.14(b), FTZ activity would... used in export production. On its domestic sales, SLP would be able to choose the duty rates during...

75 FR 2573 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-15

... matters concerning its previously assigned SLP securities upon termination of this 30-day period. Quoting... liquidity (e.g., reserve and dark orders), the 5% average quoting requirement can only be satisfied when an... determinations by the SLP Panel will constitute final action by the Exchange on the disputed matter. Regulatory...

System of Least Prompts. What Works Clearinghouse Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2018

2018-01-01

This intervention report presents findings from a systematic review of the System of Least Prompts (SLP) conducted using the WWC Procedures and Standards Handbook (version 3.0) and the Children and Students with Intellectual Disability review protocol (version 3.1). No studies of SLP that fall within the scope of the Children and Students with…

Arctic Sea Ice Export Through Fram Strait and Atmospheric Planetary Waves

NASA Technical Reports Server (NTRS)

Cavalieri, Donald J.; Koblinsky, Chester (Technical Monitor)

2001-01-01

A link is found between the variability of Arctic sea ice export through Ram Strait and the phase of the longest atmospheric planetary wave (zonal wave 1) in SLP for the period 1958-1997. Previous studies have identified a link between From Strait ice export and the North Atlantic Oscillation (NAO), but this link has been described as unstable because of a lack of consistency over time scales longer than the last two decades. Inconsistent and low correlations are also found between From Strait ice export and the Arctic Oscillation (AD) index. This paper shows that the phase of zonal wave 1 explains 60% - 70% of the simulated From Strait ice export variance over the Goodyear period 1958 - 1997. Unlike the NAB and AD links, these high variances are consistent for both the first and second halves of the Goodyear period. This consistency is attributed to the sensitivity of the wave I phase at high latitudes to the presence of secondary low pressure systems in the Barents Sea that serve to drive sea ice southward through From Strait. These results provide further evidence that the phase of zonal wave 1 in SLP at high latitudes drives regional as well as hemispheric low frequency Arctic Ocean and sea ice variability.

Studying the dynamics of SLP-76, Nck, and Vav1 multimolecular complex formation in live human cells with triple-color FRET.

PubMed

Pauker, Maor H; Hassan, Nirit; Noy, Elad; Reicher, Barak; Barda-Saad, Mira

2012-04-24

Protein-protein interactions regulate and control many cellular functions. A multimolecular complex consisting of the adaptor proteins SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kD), Nck, and the guanine nucleotide exchange factor Vav1 is recruited to the T cell side of the interface with an antigen-presenting cell during initial T cell activation. This complex is crucial for regulation of the actin machinery, antigen recognition, and signaling in T cells. We studied the interactions between these proteins as well as the dynamics of their recruitment into a complex that governs cytoskeletal reorganization. We developed a triple-color Förster resonance energy transfer (3FRET) system to observe the dynamics of the formation of this trimolecular signaling complex in live human T cells and to follow the three molecular interactions in parallel. Using the 3FRET system, we demonstrated that dimers of Nck and Vav1 were constitutively formed independently of both T cell activation and the association between SLP-76 and Nck. After T cell receptor stimulation, SLP-76 was phosphorylated, which enabled the binding of Nck. A point mutation in the proline-rich site of Vav1, which abolishes its binding to Nck, impaired actin rearrangement, suggesting that Nck-Vav1 dimers play a critical role in regulation of the actin machinery. We suggest that these findings revise the accepted model of the formation of a complex of SLP-76, Nck, and Vav1 and demonstrate the use of 3FRET as a tool to study signal transduction in live cells.

S-Layer Protein Mediates the Stimulatory Effect of Lactobacillus helveticus MIMLh5 on Innate Immunity

PubMed Central

Taverniti, Valentina; Stuknyte, Milda; Minuzzo, Mario; Arioli, Stefania; De Noni, Ivano; Scabiosi, Christian; Cordova, Zuzet Martinez; Junttila, Ilkka; Hämäläinen, Sanna; Turpeinen, Hannu; Mora, Diego; Karp, Matti; Pesu, Marko

2013-01-01

The ability to positively affect host health through the modulation of the immune response is a feature of increasing importance in measuring the probiotic potential of a bacterial strain. However, the identities of the bacterial cell components involved in cross talk with immune cells remain elusive. In this study, we characterized the dairy strain Lactobacillus helveticus MIMLh5 and its surface-layer protein (SlpA) using in vitro and ex vivo analyses. We found that MIMLh5 and SlpA exert anti-inflammatory effects by reducing the activation of NF-κB on the intestinal epithelial Caco-2 cell line. On the contrary, MIMLh5 and SlpA act as stimulators of the innate immune system by triggering the expression of proinflammatory factors tumor necrosis factor alpha and COX-2 in the human macrophage cell line U937 via recognition through Toll-like receptor 2. In the same experiments, SlpA protein did not affect the expression of the anti-inflammatory cytokine interleukin-10. A similar response was observed following stimulation of macrophages isolated from mouse bone marrow or the peritoneal cavity. These results suggest that SlpA plays a major role in mediating bacterial immune-stimulating activity, which could help to induce the host's defenses against and responses toward infections. This study supports the concept that the viability of bacterial cells is not always essential to exert immunomodulatory effects, thus permitting the development of safer therapies for the treatment of specific diseases according to a paraprobiotic intervention. PMID:23220964

Structure-Function Correlations using Scanning Laser Polarimetry in Primary Angle-Closure Glaucoma and Primary Open Angle Glaucoma

PubMed Central

Lee, Pei-Jung; Liu, Catherine Jui-Ling.; Wojciechowski, Robert; Bailey-Wilson, Joan E.; Cheng, Ching-Yu

2010-01-01

Purpose To assess the correlations between retinal nerve fiber layer (RNFL) thickness measured with scanning laser polarimetry (SLP) and visual field (VF) sensitivity in primary open angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Design Prospective, comparative, observational cases series Methods Fifty patients with POAG and 56 with PACG were examined using SLP with variable corneal compensation (GDx VCC) and Humphrey VF analyzer between August 2005 and July 2006 at Taipei Veterans General Hospital. Correlations between RNFL thickness and VF sensitivity, expressed as mean sensitivity (MS) in both decibel (dB) and 1/Lambert (L) scales, were estimated by Spearman's rank correlation coefficient (rs) and multivariate median regression models (pseudo R2). The correlations were determined globally and for six RNFL sectors and their corresponding VF regions. Results The correlation between RNFL thickness and MS (in dB) was weaker in the PACG group (rs = 0.38, P = 0.004, pseudo R2 = 0.17) than in the POAG group (rs = 0.51, P <0.001, pseudo R2 = 0.31), but the difference in the magnitude of correlation was not significant (P = 0.42).With Bonferroni correction, the structure-function correlation was significant in the superotemporal (rs = 0.62), superonasal (rs = 0.56), inferonasal (rs = 0.53), and inferotemporal (rs = 0.50) sectors in the POAG group (all P <0.001), while it was significant only in the superotemporal (rs = 0.53) and inferotemporal (rs = 0.48) sectors in the PACG group (both P <0.001). The results were similar when MS was expressed as 1/L scale. Conclusions Both POAG and PACG eyes had moderate structure-function correlations using SLP. Compared to eyes with POAG, fewer RNFL sectors have significant structure-function correlations in eyes with PACG. PMID:20202618

Development and implementation of the Saskatchewan Leadership Program: Leading for healthcare transformation.

PubMed

Mutwiri, Betty; Witt, Christine; Denysek, Christina; Halferdahl, Susan; McLeod, Katherine M

2016-01-01

The Saskatchewan Leadership Program (SLP) was developed based on the LEADS framework and aligned with Lean management to build leadership renewal and sustainability conducive to transformational change in the Saskatchewan health system. This article describes the development, implementation, and evaluation of the SLP, including experiences and lessons learned. © 2015 The Canadian College of Health Leaders.

Wave-Ice and Air-Ice-Ocean Interaction During the Chukchi Sea Ice Edge Advance

DTIC Science & Technology

2014-09-30

During cruise CU-B UAF UW Airborne expendable Ice Buoy (AXIB) Ahead, at and inside ice edge Surface meteorology T, SLP ~1 year CU-B UW...Balance (IMB) buoys Inside ice edge w/ >50cm thickness Ice mass balance T in snow-ice-ocean, T, SLP at surface ~1 year WHOI CRREL (SeaState DRI

Factors contributing to the brain drain in speech-language pathology: a New Zealand example.

PubMed

Tillard, Gina D A

2011-08-01

The aim of this research was to determine what attracts students to speech-language pathology (SLP), and the influence of intrinsic and extrinsic factors on two types of "brain drain" in SLP: emigration and career shift. Fifty undergraduate students and 13 recent graduates completed a questionnaire that tapped three main areas, level of student debt, intentions to emigrate, and career intentions. Ninety-seven per cent of respondents were female, with a median age of 25 years. Most SLP students and graduates had high levels of debt on graduation. Debt contributed to levels of worry and the ability to participate in education. However, debt alone did not influence career choice or long-term career planning. Over half of the respondents intended to leave New Zealand within 2 years of graduation, citing salary, travel, and training opportunities as factors. Incentives to remain in the profession included increased salary, more training opportunities, and student debt repayment. SLP students' career decisions were mainly influenced by interest in the profession. The conclusion was that three main factors need to be explored in an effort to increase the likelihood that SLPs remain in New Zealand: salary levels, increased training opportunities, and contributions to reduce student debt.

The impact of speech and language problems in kindergarten on academic learning and special education status in grade three.

PubMed

Janus, Magdalena; Labonté, Chantal; Kirkpatrick, Ryan; Davies, Scott; Duku, Eric

2017-11-24

This study addressed the implications of experiencing early speech-language pathologies (SLPs) in kindergarten on special education needs (SEN) and academic outcomes in grade three. Early Development Instrument (EDI) kindergarten data on development and the presence or absence of SLPs were matched with grade three school-system standardised tests of reading, writing and maths, and SEN classification in Ontario, Canada for 59 015 students. Children were classified as having a Persistent speech language pathology (SLP), Remittent SLP, Latent SEN or as a typically developing Control. Even though 72.3% of children's SLPs remitted by grade three, kindergarten SLPs conveyed higher likelihood of having an SEN, and of lower achievement levels in grade three. The degree of impact varied between Persistent and Remittent groups. Children in the Latent group had lower scores in kindergarten on all five EDI domains than Control children. These population level results provide strong evidence to indicate that all children who present with an SLP in kindergarten face further academic challenges, even if their SLP resolves over time. Findings have implications for early intervention and treatment for children with early SLPs.

Scaffold Protein SLP-76 Primes PLCγ1 for Activation by ITK-Mediated Phosphorylation.

PubMed

Devkota, Sujan; Joseph, Raji E; Min, Lie; Bruce Fulton, D; Andreotti, Amy H

2015-08-28

Activation of the phospholipase, PLCγ1, is critical for proper T cell signaling following antigen receptor engagement. In T cells, the Tec family kinase, interleukin-2-induced tyrosine kinase (ITK), phosphorylates PLCγ1 at tyrosine 783 (Y783) leading to activation of phospholipase function and subsequent production of the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. In this work, we demonstrate that PLCγ1 can be primed for ITK-mediated phosphorylation on Y783 by a specific region of the adaptor protein, SLP-76. The SLP-76 phosphotyrosine-containing sequence, pY(173)IDR, does not conform to the canonical recognition motif for an SH2 domain yet binds with significant affinity to the C-terminal SH2 domain of PLCγ1 (SH2C). The SLP-76 pY(173) motif competes with the autoinhibited conformation surrounding the SH2C domain of PLCγ1 leading to exposure of the ITK recognition element on the PLCγ1 SH2 domain and release of the target tyrosine, Y783. These data contribute to the evolving model for the molecular events occurring early in the T cell activation process. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mislocalization of SLP-76 leads to aberrant inflammatory cytokine and autoantibody production.

PubMed

Sonnenberg, Gregory F; Mangan, Paul R; Bezman, Natalie A; Sekiguchi, Debora R; Luning Prak, Eline T; Erikson, Jan; Maltzman, Jonathan S; Jordan, Martha S; Koretzky, Gary A

2010-03-18

Central and peripheral tolerance is required to prevent immune responses to self-antigens. We now present a mouse model in which wild-type (WT) SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) has been constitutively targeted to the membrane, where CD4+ T cells become spontaneously dysregulated and develop an inflammatory phenotype. Mice bearing membrane-targeted SLP-76 (MTS) have a partial T-cell lymphopenia and impaired signaling though the mature T-cell receptor. The CD4+ T cells that develop in these mice possess an activated-like phenotype and are skewed toward the inflammatory T(H)1 and T(H)17 lineages. MTS mice also spontaneously develop autoantibodies at an early age. To rule out abnormal thymic selection as the sole cause of the MTS phenotype, we expressed WT SLP-76 along with the MTS followed by deletion of the WT allele in peripheral T cells. The peripheral MTS-expressing T cells demonstrate skewed cytokine responses when transferred into lymphopenic hosts. Thus, the abnormal effector T-cell phenotype still occurs in the presence of preserved central and peripheral tolerance, suggesting that diminished T-cell receptor signaling can promote skewed T-cell responses.

The N terminus of SKAP55 enables T cell adhesion to TCR and integrin ligands via distinct mechanisms

PubMed Central

Ophir, Michael J.; Liu, Beiyun C.

2013-01-01

The T cell receptor (TCR) triggers the assembly of “SLP-76 microclusters,” which mediate signals required for T cell activation. In addition to regulating integrin activation, we show that Src kinase–associated phosphoprotein of 55 kD (SKAP55) is required for microcluster persistence and movement, junctional stabilization, and integrin-independent adhesion via the TCR. These functions require the dimerization of SKAP55 and its interaction with the adaptor adhesion and degranulation-promoting adaptor protein (ADAP). A “tandem dimer” containing two ADAP-binding SKAP55 Src homology 3 (SH3) domains stabilized SLP-76 microclusters and promoted T cell adhesion via the TCR, but could not support adhesion to integrin ligands. Finally, the SKAP55 dimerization motif (DM) enabled the coimmunoprecipitation of the Rap1-dependent integrin regulator Rap1-GTP–interacting adaptor molecule (RIAM), the recruitment of talin into TCR-induced adhesive junctions, and “inside-out” signaling to β1 integrins. Our data indicate that SKAP55 dimers stabilize SLP-76 microclusters, couple SLP-76 to the force-generating systems responsible for microcluster movement, and enable adhesion via the TCR by mechanisms independent of RIAM, talin, and β1 integrins. PMID:24368808

Vocal fold submucosal infusion technique in phonomicrosurgery.

PubMed

Kass, E S; Hillman, R E; Zeitels, S M

1996-05-01

Phonomicrosurgery is optimized by maximally preserving the vocal fold's layered microstructure (laminae propriae). The technique of submucosal infusion of saline and epinephrine into the superficial lamina propria (SLP) was examined to delineate how, when, and why it was helpful toward this surgical goal. A retrospective review revealed that the submucosal infusion technique was used to enhance the surgery in 75 of 152 vocal fold procedures that were performed over the last 2 years. The vocal fold epithelium was noted to be adherent to the vocal ligament in 29 of the 75 cases: 19 from previous surgical scarring, 4 from cancer, 3 from sulcus vocalis, 2 from chronic hemorrhage, and 1 from radiotherapy. The submucosal infusion technique was most helpful when the vocal fold epithelium required resection and/or when extensive dissection in the SLP was necessary. The infusion enhanced the surgery by vasoconstriction of the microvasculature in the SLP, which improved visualization during cold-instrument tangential dissection. Improved visualization facilitated maximal preservation of the SLP, which is necessary for optimal pliability of the overlying epithelium. The infusion also improved the placement of incisions at the perimeter of benign, premalignant, and malignant lesions, and thereby helped preserve epithelium uninvolved by the disorder.

Numerical Analysis of Storm Surge and Seiche at Tokyo Bay caused by the 2 Similar Typhoons, Typhoon Phanphon and Vongfong in 2014

NASA Astrophysics Data System (ADS)

Iwamoto, T.; Takagawa, T.

2017-12-01

A long period damped oscillation, or seiche, sometimes happens inside a harbor after passing typhoon. For some cases, a maximum sea level is observed due to the superposition of astronomical tide and seiche rather than a peak of storm surge. Hence to clarify seiche factors for reducing disaster potential is important, a long-period seiche with a fundamental period of 5.46 hours in Tokyo Bay (Konishi, 2008) was investigated through numerical simulations and analyses. We examined the case of Typhoon Phanphon and Vongfong in 2014 (Hereafter Case P and V). The intensity and moving velocity were similar and the best-tracks were an arc-shaped, typical one approaching to Tokyo Bay. The track of Case V was about 1.5 degree higher latitude than that of Case P, only Typhoon Phanphon caused significant seiche.Firstly, numerical simulations for the 2 storm surges at Tokyo Bay were conducted by Regional Ocean Modeling System (ROMS) and Meso-Scale Model Grid Point Values (MSM-GPV). MSM-GPV gave the 10m wind speed and Sea Level Pressure (SLP), especially the Mean Error (ME) and Root Mean Squire Error (RMSE) of SLP were low compared to the 12 JMA observation points data (Case P: ME -0.303hPa, RMSE 1.87hPa, Case V: ME -0.285hPa, RMSE 0.74hPa). The computational results showed that the maximum of storm surge was underestimated but the difference was less than 20cm at 5 observation points in Tokyo Bay(Fig.1, 2).Then, power spectrals, coherences and phase differences of storm surges at the 5 observation points were obtained by spectral analysis of observed and simulated waveforms. For Case P, the phase-difference between the bay mouth and innermost part of Tokyo Bay was little, and coherence was almost 1(Fig.3, 4). However, for Case V, coherence was small around the fundamental period of 5.46 hours. Furthermore, Empirical Orthogonal Function (EOF) analysis of storm surge, SLP and sea surface stress were conducted. The contributions of EOF1 were above 90% for the all variables, the gradient of storm surge EOF1 was parallel to the bay axis for Case P, but about 50-degree oblique from the axis for Case V(Fig.5, 6). In addition, the EOF1 of SLP for Case P showed a concentric circle structure above Tokyo Bay, besides the structure was not appeared for Case V.

Expression, Refolding and Crystallizations of the Grb2-like (GADS) C-Terminal SH3 Domain Complexed with a SLP-76 Motif Peptide

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

Faravelli,A.; Dimasi, N.

The Grb2-like adaptor protein GADS is composed of an N-terminal SH3 domain, an SH2 domain, a proline-rich region and a C-terminal SH3 domain. GADS interacts through its C-terminal SH3 domain with the adaptor protein SLP-76, thus recruiting this protein and other associated molecules to the linker for activation of T-cell (LAT) protein. The DNA encoding the C-terminal SH3 domain of GADS (GADS-cSH3) was assembled synthetically using a recursive PCR technique and the protein was overexpressed in Escherichia coli, refolded and purified. Several crystals of this domain in complex with the SLP-76 peptide were obtained and characterized.

The Perceptions of Students in the Allied Health Professions towards Stroke Rehabilitation Teams and the SLP's Role

ERIC Educational Resources Information Center

Insalaco, Deborah; Ozkurt, Elcin; Santiago, Dign

2007-01-01

The purpose of this study was to determine the perceptions and knowledge of final-year speech-language pathology (SLP), physical and occupational therapy (PT, OT) students toward stroke rehabilitation teams and the SLPs' roles on them. The investigators adapted a survey developed by (Felsher & Ross, 1994) and administered it to 35 PT, 35 OT, and…

Unique Transcriptional Profile of Sustained Ligand-Activated Preconditioning in Pre- and Post-Ischemic Myocardium

PubMed Central

Ashton, Kevin J.; Tupicoff, Amanda; Williams-Pritchard, Grant; Kiessling, Can J.; See Hoe, Louise E.; Headrick, John P.; Peart, Jason N.

2013-01-01

Background Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3–5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium. Methodology/Principal Findings Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated genes in normoxic hearts from SLP mice (≥1.3-fold change, FDR≤5%). Induced genes encoded sarcomeric/contractile proteins (Myh7, Mybpc3,Myom2,Des), natriuretic peptides (Nppa,Nppb) and stress-signaling elements (Csda,Ptgds). Highly repressed genes primarily encoded chemokines (Ccl2,Ccl4,Ccl7,Ccl9,Ccl13,Ccl3l3,Cxcl3), cytokines (Il1b,Il6,Tnf) and other proteins involved in inflammation/immunity (C3,Cd74,Cd83, Cd86,Hla-dbq1,Hla-drb1,Saa1,Selp,Serpina3), together with endoplasmic stress proteins (known: Dnajb1,Herpud1,Socs3; putative: Il6, Gadd45g,Rcan1) and transcriptional controllers (Egr2,Egr3, Fos,Hmox1,Nfkbid). Biological themes modified thus related to inflammation/immunity, together with cellular/cardiovascular movement and development. SLP also modified the transcriptional response to I-R (46 genes uniquely altered post-ischemia), which may influence later infarction/remodeling. This included up-regulated determinants of cellular resistance to oxidant (Mgst3,Gstm1,Gstm2) and other forms of stress (Xirp1,Ankrd1,Clu), and repression of stress-response genes (Hspa1a,Hspd1,Hsp90aa,Hsph1,Serpinh1) and Txnip. Conclusions Protection via SLP is associated with transcriptional repression of inflammation/immunity, up-regulation of sarcomeric elements and natriuretic peptides, and modulation of cell stress, growth and development, while conventional protective molecules are unaltered. PMID:23991079

Reliability, Validity, and Minimal Detectable Change of Four-Step Stair Climb Power Test in Community-Dwelling Older Adults.

PubMed

Ni, Meng; Brown, Lorna G; Lawler, Danielle; Bean, Jonathan F

2017-07-01

Stair climb power is an important clinical measure of lower-extremity power. The stair climb power test (SCPT) was validated by requiring individuals to climb a full flight of stairs. A 4-step SCPT (4SCPT) would be more clinically feasible and easier to perform, yet its reliability and validity are unknown. To evaluate reliability, validity, and minimal detectable change of 4SCPT among community-dwelling older adults. This study is a cross-sectional analysis of baseline data from a clinical trial. Fifty older adults ≥65 years of age, at risk for mobility decline, consented to participate in this ancillary study. Test-retest reliability was derived from 2 measurements within each participant measured by a single assessor. Pearson correlation analyses among leg power measures (4SCPT, SCPT, single leg press power at 40% and 70% of the 1-repetition maximum [SLP40, SLP70]) were performed. Separate multivariate linear regressions were conducted evaluating the associations between each leg power measure and 2 mobility outcomes, the Short Physical Performance Battery (SPPB) and habitual gait speed (HGS). Minimal detectable change was based on a 90% confidence interval (MDC 90 ). The 4SCPT had excellent test-retest reliability (ICC(2,1) = 0.951), and strong correlation with SCPT, SLP40, and SLP70 ( r = 0.85-0.96). The 4SCPT explained a greater amount of variance in the SPPB (R 2 = 0.31) than other leg power measurements (R 2 = 0.23-0.25). The 4SCPT (R 2 = 0.41) and SCPT (R 2 = 0.42) described equivalent amounts of variance in HGS, and greater than that with SLP40 (R 2 = 0.28) and SLP70 (R 2 = 0.30). The MDC 90 for 4SCPT was 44.0 watts. This was a cross-sectional analysis within a small, nonrepresentative sample. Interrater reliability was not evaluated. The 4SCPT shows scientific promise as a valid and reliable leg power measurement among community-dwelling older adults. © 2017 American Physical Therapy Association

The confidence of speech-language pathology students regarding communicating with people with aphasia

PubMed Central

2013-01-01

Background Aphasia is an acquired language disorder that can present a significant barrier to patient involvement in healthcare decisions. Speech-language pathologists (SLPs) are viewed as experts in the field of communication. However, many SLP students do not receive practical training in techniques to communicate with people with aphasia (PWA) until they encounter PWA during clinical education placements. Methods This study investigated the confidence and knowledge of SLP students in communicating with PWA prior to clinical placements using a customised questionnaire. Confidence in communicating with people with aphasia was assessed using a 100-point visual analogue scale. Linear, and logistic, regressions were used to examine the association between confidence and age, as well as confidence and course type (graduate-entry masters or undergraduate), respectively. Knowledge of strategies to assist communication with PWA was examined by asking respondents to list specific strategies that could assist communication with PWA. Results SLP students were not confident with the prospect of communicating with PWA; reporting a median 29-points (inter-quartile range 17–47) on the visual analogue confidence scale. Only, four (8.2%) of respondents rated their confidence greater than 55 (out of 100). Regression analyses indicated no relationship existed between confidence and students‘ age (p = 0.31, r-squared = 0.02), or confidence and course type (p = 0.22, pseudo r-squared = 0.03). Students displayed limited knowledge about communication strategies. Thematic analysis of strategies revealed four overarching themes; Physical, Verbal Communication, Visual Information and Environmental Changes. While most students identified potential use of resources (such as images and written information), fewer students identified strategies to alter their verbal communication (such as reduced speech rate). Conclusions SLP students who had received aphasia related theoretical coursework, but not commenced clinical placements with PWA, were not confident in their ability to communicate with PWA. Students may benefit from an educational intervention or curriculum modification to incorporate practical training in effective strategies to communicate with PWA, before they encounter PWA in clinical settings. Ensuring students have confidence and knowledge of potential communication strategies to assist communication with PWA may allow them to focus their learning experiences in more specific clinical domains, such as clinical reasoning, rather than building foundation interpersonal communication skills. PMID:23806028

The confidence of speech-language pathology students regarding communicating with people with aphasia.

PubMed

Finch, Emma; Fleming, Jennifer; Brown, Kyla; Lethlean, Jennifer; Cameron, Ashley; McPhail, Steven M

2013-06-27

Aphasia is an acquired language disorder that can present a significant barrier to patient involvement in healthcare decisions. Speech-language pathologists (SLPs) are viewed as experts in the field of communication. However, many SLP students do not receive practical training in techniques to communicate with people with aphasia (PWA) until they encounter PWA during clinical education placements. This study investigated the confidence and knowledge of SLP students in communicating with PWA prior to clinical placements using a customised questionnaire. Confidence in communicating with people with aphasia was assessed using a 100-point visual analogue scale. Linear, and logistic, regressions were used to examine the association between confidence and age, as well as confidence and course type (graduate-entry masters or undergraduate), respectively. Knowledge of strategies to assist communication with PWA was examined by asking respondents to list specific strategies that could assist communication with PWA. SLP students were not confident with the prospect of communicating with PWA; reporting a median 29-points (inter-quartile range 17-47) on the visual analogue confidence scale. Only, four (8.2%) of respondents rated their confidence greater than 55 (out of 100). Regression analyses indicated no relationship existed between confidence and students' age (p = 0.31, r-squared = 0.02), or confidence and course type (p = 0.22, pseudo r-squared = 0.03). Students displayed limited knowledge about communication strategies. Thematic analysis of strategies revealed four overarching themes; Physical, Verbal Communication, Visual Information and Environmental Changes. While most students identified potential use of resources (such as images and written information), fewer students identified strategies to alter their verbal communication (such as reduced speech rate). SLP students who had received aphasia related theoretical coursework, but not commenced clinical placements with PWA, were not confident in their ability to communicate with PWA. Students may benefit from an educational intervention or curriculum modification to incorporate practical training in effective strategies to communicate with PWA, before they encounter PWA in clinical settings. Ensuring students have confidence and knowledge of potential communication strategies to assist communication with PWA may allow them to focus their learning experiences in more specific clinical domains, such as clinical reasoning, rather than building foundation interpersonal communication skills.

Atypical birefringence pattern and the diagnostic ability of scanning laser polarimetry with enhanced corneal compensation in glaucoma.

PubMed

Rao, Harsha L; Yadav, Ravi K; Begum, Viquar U; Addepalli, Uday K; Senthil, Sirisha; Choudhari, Nikhil S; Garudadri, Chandra S

2015-03-01

To evaluate the effect of typical scan score (TSS), when within the acceptable limits, on the diagnostic performance of retinal nerve fibre layer (RNFL) parameters with the enhanced corneal compensation (ECC) protocol of scanning laser polarimetry (SLP) in glaucoma. In a cross-sectional study, 203 eyes of 160 glaucoma patients and 140 eyes of 104 control subjects underwent RNFL imaging with the ECC protocol of SLP. TSS was used to quantify atypical birefringence pattern (ABP) images. Influence of TSS on the diagnostic ability of SLP parameters was evaluated by receiver operating characteristic (ROC) regression models after adjusting for the effect of disease severity [based on mean deviation (MD)] on standard automated perimetry). Diagnostic abilities of all RNFL parameters of SLP increased when the TSS values were higher. This effect was statistically significant for TSNIT (coefficient: 0.08, p<0.001) and inferior average parameters (coefficient: 0.06, p=0.002) but not for nerve fibre indicator (NFI, coefficient: 0.03, p=0.21). In early glaucoma (MD of -5 dB), predicted area under ROC curve (AUC) for TSNIT average parameter improved from 0.642 at a TSS of 90 to 0.845 at a TSS of 100. In advanced glaucoma (MD of -15 dB), AUC for TSNIT average improved from 0.832 at a TSS of 90 to 0.947 at 100. Diagnostic performances of TSNIT and inferior average RNFL parameters with ECC protocol of SLP were significantly influenced by TSS even when the TSS values were within the acceptable limits. Diagnostic ability of NFI was unaffected by TSS values. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Signaling of the ITK (interleukin 2-inducible T cell kinase)-SYK (spleen tyrosine kinase) fusion kinase is dependent on adapter SLP-76 and on the adapter function of the kinases SYK and ZAP70.

PubMed

Hussain, Alamdar; Mohammad, Dara K; Gustafsson, Manuela O; Uslu, Merve; Hamasy, Abdulrahman; Nore, Beston F; Mohamed, Abdalla J; Smith, C I Edvard

2013-03-08

The inducible T cell kinase-spleen tyrosine kinase (ITK-SYK) oncogene consists of the Tec homology-pleckstrin homology domain of ITK and the kinase domain of SYK, and it is believed to be the cause of peripheral T cell lymphoma. We and others have recently demonstrated that this fusion protein is constitutively tyrosine-phosphorylated and is transforming both in vitro and in vivo. To gain a deeper insight into the molecular mechanism(s) underlying its activation and signaling, we mutated a total of eight tyrosines located in the SYK portion of the chimera into either phenylalanine or to the negatively charged glutamic acid. Although mutations in the interdomain-B region affected ITK-SYK kinase activity, they only modestly altered downstream signaling events. In contrast, mutations that were introduced in the kinase domain triggered severe impairment of downstream signaling. Moreover, we show here that SLP-76 is critical for ITK-SYK activation and is particularly required for the ITK-SYK-dependent phosphorylation of SYK activation loop tyrosines. In Jurkat cell lines, we demonstrate that expression of ITK-SYK fusion requires an intact SLP-76 function and significantly induces IL-2 secretion and CD69 expression. Furthermore, the SLP-76-mediated induction of IL-2 and CD69 could be further enhanced by SYK or ZAP-70, but it was independent of their kinase activity. Notably, ITK-SYK expression in SYF cells phosphorylates SLP-76 in the absence of SRC family kinases. Altogether, our data suggest that ITK-SYK exists in the active conformation state and is therefore capable of signaling without SRC family kinases or stimulation of the T cell receptor.

Signaling of the ITK (Interleukin 2-inducible T Cell Kinase)-SYK (Spleen Tyrosine Kinase) Fusion Kinase Is Dependent on Adapter SLP-76 and on the Adapter Function of the Kinases SYK and ZAP70*

PubMed Central

Hussain, Alamdar; Mohammad, Dara K.; Gustafsson, Manuela O.; Uslu, Merve; Hamasy, Abdulrahman; Nore, Beston F.; Mohamed, Abdalla J.; Smith, C. I. Edvard

2013-01-01

The inducible T cell kinase-spleen tyrosine kinase (ITK-SYK) oncogene consists of the Tec homology-pleckstrin homology domain of ITK and the kinase domain of SYK, and it is believed to be the cause of peripheral T cell lymphoma. We and others have recently demonstrated that this fusion protein is constitutively tyrosine-phosphorylated and is transforming both in vitro and in vivo. To gain a deeper insight into the molecular mechanism(s) underlying its activation and signaling, we mutated a total of eight tyrosines located in the SYK portion of the chimera into either phenylalanine or to the negatively charged glutamic acid. Although mutations in the interdomain-B region affected ITK-SYK kinase activity, they only modestly altered downstream signaling events. In contrast, mutations that were introduced in the kinase domain triggered severe impairment of downstream signaling. Moreover, we show here that SLP-76 is critical for ITK-SYK activation and is particularly required for the ITK-SYK-dependent phosphorylation of SYK activation loop tyrosines. In Jurkat cell lines, we demonstrate that expression of ITK-SYK fusion requires an intact SLP-76 function and significantly induces IL-2 secretion and CD69 expression. Furthermore, the SLP-76-mediated induction of IL-2 and CD69 could be further enhanced by SYK or ZAP-70, but it was independent of their kinase activity. Notably, ITK-SYK expression in SYF cells phosphorylates SLP-76 in the absence of SRC family kinases. Altogether, our data suggest that ITK-SYK exists in the active conformation state and is therefore capable of signaling without SRC family kinases or stimulation of the T cell receptor. PMID:23293025

Non-additive interactions involving two distinct elements mediate sloppy-paired regulation by pair-rule transcription factors

PubMed Central

Prazak, Lisa; Fujioka, Miki; Gergen, J. Peter

2010-01-01

The relatively simple combinatorial rules responsible for establishing the initial metameric expression of sloppy-paired-1 (slp1) in the Drosophila blastoderm embryo make this system an attractive model for investigating the mechanism of regulation by pair rule transcription factors. This investigation of slp1 cis-regulatory architecture identifies two distinct elements, a proximal early stripe element (PESE) and a distal early stripe element (DESE) located from −3.1 kb to −2.5 kb and from −8.1 kb to −7.1 kb upstream of the slp1 promoter, respectively, that mediate this early regulation. The proximal element expresses only even-numbered stripes and mediates repression by Even-skipped (Eve) as well as by the combination of Runt and Fushi-tarazu (Ftz). A 272 basepair sub-element of PESE retains Eve-dependent repression, but is expressed throughout the even-numbered parasegments due to the loss of repression by Runt and Ftz. In contrast, the distal element expresses both odd and even-numbered stripes and also drives inappropriate expression in the anterior half of the odd-numbered parasegments due to an inability to respond to repression by Eve. Importantly, a composite reporter gene containing both early stripe elements recapitulates pair-rule gene-dependent regulation in a manner beyond what is expected from combining their individual patterns. These results indicate interactions involving distinct cis-elements contribute to the proper integration of pair-rule regulatory information. A model fully accounting for these results proposes that metameric slp1 expression is achieved through the Runt-dependent regulation of interactions between these two pair-rule response elements and the slp1 promoter. PMID:20435028

Absence of SUN-domain protein Slp1 blocks karyogamy and switches meiotic recombination and synapsis from homologs to sister chromatids

PubMed Central

Vasnier, Christelle; de Muyt, Arnaud; Zhang, Liangran; Tessé, Sophie; Kleckner, Nancy E.; Zickler, Denise; Espagne, Eric

2014-01-01

Karyogamy, the process of nuclear fusion is required for two haploid gamete nuclei to form a zygote. Also, in haplobiontic organisms, karyogamy is required to produce the diploid nucleus/cell that then enters meiosis. We identify sun like protein 1 (Slp1), member of the mid–Sad1p, UNC-84–domain ubiquitous family, as essential for karyogamy in the filamentous fungus Sordaria macrospora, thus uncovering a new function for this protein family. Slp1 is required at the last step, nuclear fusion, not for earlier events including nuclear movements, recognition, and juxtaposition. Correspondingly, like other family members, Slp1 localizes to the endoplasmic reticulum and also to its extensions comprising the nuclear envelope. Remarkably, despite the absence of nuclear fusion in the slp1 null mutant, meiosis proceeds efficiently in the two haploid “twin” nuclei, by the same program and timing as in diploid nuclei with a single dramatic exception: the normal prophase program of recombination and synapsis between homologous chromosomes, including loading of recombination and synaptonemal complex proteins, occurs instead between sister chromatids. Moreover, the numbers of recombination-initiating double-strand breaks (DSBs) and ensuing recombinational interactions, including foci of the essential crossover factor Homo sapiens enhancer of invasion 10 (Hei10), occur at half the diploid level in each haploid nucleus, implying per-chromosome specification of DSB formation. Further, the distribution of Hei10 foci shows interference like in diploid meiosis. Centromere and spindle dynamics, however, still occur in the diploid mode during the two meiotic divisions. These observations imply that the prophase program senses absence of karyogamy and/or absence of a homolog partner and adjusts the interchromosomal interaction program accordingly. PMID:25210014

Characterization of adhesive molecule with affinity to Caco-2 cells in Lactobacillus acidophilus by proteome analysis.

PubMed

Ashida, Nobuhisa; Yanagihara, Sae; Shinoda, Tadashi; Yamamoto, Naoyuki

2011-10-01

The adhesive activities of eight Lactobacillus acidophilus strains toward intestinal epithelial Caco-2 cells were studied to understand the probiotic characteristics of the L. acidophilus L-92 strain. Most of the strains, including L-92, showed high adhesive activity; CP23 showed the lowest adhesive activity. CP23 was selected for comparative analysis of cell wall-associated proteins versus the L-92 strain. Cell wall-associated proteins extracted from L-92 and CP23 were subjected to two-dimensional electrophoresis, and major spots observed in the former were compared to the corresponding spots in the latter. To understand the effects of key components of L-92 on its adhesion to Caco-2 cells, 18 spots with stronger signals in L-92 than those in CP23 were identified by a MALDI-TOF/TOF of Ultraflex analysis. Among the identified proteins of L-92, surface-layer protein A (SlpA) was considered strongly involved in adhesion in the eight L. acidophilus strains. To study the importance of SlpA in the adhesion of L. acidophilus, the amounts of SlpA proteins in LiCl extracts of the eight strains were compared by SDSpolyacrylamide gel electrophoresis. As a result, the adhesive abilities of L. acidophilus strains to Caco-2 cells correlated closely to the amount of SlpA in the cells and the productivity of IL-12, an inflammatory cytokine, in all eight strains. These results strongly suggested that SlpA in L. acidophilus might play a key role in its attachment to Caco-2 cells and in the release of IL-12 from dendritic cells.

Influence of osmotic stress on the profile and gene expression of surface layer proteins in Lactobacillus acidophilus ATCC 4356.

PubMed

Palomino, María Mercedes; Waehner, Pablo M; Fina Martin, Joaquina; Ojeda, Paula; Malone, Lucía; Sánchez Rivas, Carmen; Prado Acosta, Mariano; Allievi, Mariana C; Ruzal, Sandra M

2016-10-01

In this work, we studied the role of surface layer (S-layer) proteins in the adaptation of Lactobacillus acidophilus ATCC 4356 to the osmotic stress generated by high salt. The amounts of the predominant and the auxiliary S-layer proteins SlpA and SlpX were strongly influenced by the growth phase and high-salt conditions (0.6 M NaCl). Changes in gene expression were also observed as the mRNAs of the slpA and slpX genes increased related to the growth phase and presence of high salt. A growth stage-dependent modification on the S-layer protein profile in response to NaCl was observed: while in control conditions, the auxiliary SlpX protein represented less than 10 % of the total S-layer protein, in high-salt conditions, it increased to almost 40 % in the stationary phase. The increase in S-layer protein synthesis in the stress condition could be a consequence of or a way to counteract the fragility of the cell wall, since a decrease in the cell wall thickness and envelope components (peptidoglycan layer and lipoteichoic acid content) was observed in L. acidophilus when compared to a non-S-layer-producing species such as Lactobacillus casei. Also, the stationary phase and growth in high-salt medium resulted in increased release of S-layer proteins to the supernatant medium. Overall, these findings suggest that pre-growth in high-salt conditions would result in an advantage for the probiotic nature of L. acidophilus ATCC 4356 as the increased amount and release of the S-layer might be appropriate for its antimicrobial capacity.

Rapid Prototyping: State of the Art

DTIC Science & Technology

2003-10-23

Rapid Prototyping SCS Solid Creation System SLM Selective Laser Melting SLP Solid Laser diode Plotter SLS Selective Laser Sintering SOAR State of the...121,000, respectively. SLP stands for Sold Laser Diode Plotter. The machines are relatively slow and parts are small, so, to date, the products have been...Gigerenzer, H., “Directed Laser Welding of Metal Matrix Composite Structures for Space Based Applications,“ Triton Systems Inc., Chelmsford, MA., 1

Immunoassay of paralytic shellfish toxins by moving magnetic particles in a stationary liquid-phase lab-on-a-chip.

PubMed

Kim, Myoung-Ho; Choi, Suk-Jung

2015-04-15

In this study, we devised a stationary liquid-phase lab-on-a-chip (SLP LOC), which was operated by moving solid-phase magnetic particles in the stationary liquid phase. The SLP LOC consisted of a sample chamber to which a sample and reactants were added, a detection chamber containing enzyme substrate solution, and a narrow channel connecting the two chambers and filled with buffer. As a model system, competitive immunoassays of saxitoxin (STX), a paralytic shellfish toxin, were conducted in the SLP LOC using protein G-coupled magnetic particles (G-MPs) as the solid phase. Anti-STX antibodies, STX-horseradish peroxidase conjugate, G-MPs, and a STX sample were added to the sample chamber and reacted by shaking. While liquids were in the stationary state, G-MPs were transported from the sample chamber to the detection chamber by moving a magnet below the LOC. After incubation to allow the enzymatic reaction to occur, the absorbance of the detection chamber solution was found to be reciprocally related to the STX concentration of the sample. Thus, the SLP LOC may represent a novel, simple format for point-of-care testing applications of enzyme-linked immunosorbent assays by eliminating complicated liquid handling steps. Copyright © 2014 Elsevier B.V. All rights reserved.

Keto acid-supplemented low-protein diet for treatment of adult patients with hepatitis B virus infection and chronic glomerulonephritis.

PubMed

Mou, Shan; Li, Jialin; Yu, Zanzhe; Wang, Qin; Ni, Zhaohui

2013-02-01

An open-label, randomized, controlled, single-centre clinical trial to evaluate the effects of low-protein intake, with or without keto acid supplementation, on nutritional status and proteinuria, in patients with hepatitis B virus (HBV) and early stage chronic glomerulonephritis. Patients with chronic glomerulonephritis and HBV infection were randomized to receive a low-protein diet (0.6-0.8 g/kg ideal body weight [IBW] per day) either without (LP group) or with (sLP group) keto acid supplementation (0.1 g/kg IBW per day), for 12 months. Nutritional, clinical and safety parameters were recorded. The study included 17 patients (LP group n = 9; sLP group n = 8). Proteinuria and microalbuminuria were significantly lower in the sLP group at 6 and 12 months compared with baseline, and at 12 months compared with the LP group. There were no significant differences in serum creatinine level or estimated glomerular filtration rate. Nutritional parameters (serum albumin and prealbumin) were significantly improved at 12 months, compared with baseline, in the sLP group. Restriction of dietary protein intake to 0.6-0.8 g/kg IBW per day appears to have an acceptable safety profile. Supplementation with keto acids is associated with decreased urine protein excretion.

Evidence-based practice in speech-language pathology curricula: a scoping study.

PubMed

Togher, Leanne; Yiannoukas, Corina; Lincoln, Michelle; Power, Emma; Munro, Natalie; Mccabe, Patricia; Ghosh, Pratiti; Worrall, Linda; Ward, Elizabeth; Ferguson, Alison; Harrison, Elisabeth; Douglas, Jacinta

2011-12-01

This scoping study investigated how evidence-based practice (EBP) principles are taught in Australian speech-language pathology (SLP) teaching and learning contexts. It explored how Australian SLP university programs: (1) facilitate student learning about the principles of EBP in academic and clinical settings, and (2) self-evaluate their curricula in relation to EBP. The research involved two surveys. Survey 1 respondents were 131 academic staff, program coordinators, and on-campus and off-campus clinical educators. This survey gathered information about EBP teaching and learning in SLP programs as well as future EBP curriculum plans. Survey 2 investigated how clinical educators incorporated EBP into the way they taught clinical decision-making to students. Surveys responses from 85 clinical educators were analysed using descriptive and non-parametric statistics and thematic grouping of open-ended qualitative responses. Both surveys revealed strengths and gaps in integrating EBP into Australian SLP curricula. Perceived strengths were that respondents were positive about EBP, most had EBP training and access to EBP resources. The perceived gaps included the academic staff's perceptions of students' understanding and application of EBP, respondents' understanding of research methodologies, communication and collaboration between academic staff and clinical educators, and a lack of explicit discussion by clinical educators and students of EBP in relation to clients.

The cumulative impact of physical activity, sleep duration, and television time on adolescent obesity: 2011 Youth Risk Behavior Survey.

PubMed

Laurson, Kelly R; Lee, Joey A; Eisenmann, Joey C

2015-03-01

Physical activity (PA), television time (TV), and sleep duration (SLP) are considered individual risk factors for adolescent obesity. Our aim was to investigate the concurrent influence of meeting PA, SLP, and TV recommendations on adolescent obesity utilizing 2011 Youth Risk Behavior Surveillance Survey (YRBSS) data. Subjects included 9589 (4874 females) high school students. PA, SLP, and TV were categorized utilizing established national recommendations and youth were cross-tabulated into 1 of 8 groups based on meeting or not meeting each recommendation. Logistic models were used to examine the odds of obesity for each group. Youth meeting the PA recommendation were not at increased odds of obesity, regardless of SLP or TV status. However, not meeting any single recommendation, in general, led to increased odds of not meeting the other two. In boys, 11.8% met all recommendations while 14.1% met 0 recommendations. In girls, only 5.0% met all recommendations while 17.8% met none. Boys and girls not meeting any of the recommendations were 4.0 and 3.8 times more likely to be obese compared with their respective referent groups. Further research considering the simultaneous influence these risk factors may have on obesity and on one another is warranted.

Distortion Representation of Forecast Errors for Model Skill Assessment and Objective Analysis

NASA Technical Reports Server (NTRS)

Hoffman, Ross N.; Nehrkorn, Thomas; Grassotti, Christopher

1998-01-01

We proposed a novel characterization of errors for numerical weather predictions. A general distortion representation allows for the displacement and amplification or bias correction of forecast anomalies. Characterizing and decomposing forecast error in this way has several important applications, including the model assessment application and the objective analysis application. In this project, we have focused on the assessment application, restricted to a realistic but univariate 2-dimensional situation. Specifically, we study the forecast errors of the sea level pressure (SLP), the 500 hPa geopotential height, and the 315 K potential vorticity fields for forecasts of the short and medium range. The forecasts are generated by the Goddard Earth Observing System (GEOS) data assimilation system with and without ERS-1 scatterometer data. A great deal of novel work has been accomplished under the current contract. In broad terms, we have developed and tested an efficient algorithm for determining distortions. The algorithm and constraints are now ready for application to larger data sets to be used to determine the statistics of the distortion as outlined above, and to be applied in data analysis by using GEOS water vapor imagery to correct short-term forecast errors.

Looking at the ICF and human communication through the lens of classification theory.

PubMed

Walsh, Regina

2011-08-01

This paper explores the insights that classification theory can provide about the application of the International Classification of Functioning, Disability and Health (ICF) to communication. It first considers the relationship between conceptual models and classification systems, highlighting that classification systems in speech-language pathology (SLP) have not historically been based on conceptual models of human communication. It then overviews the key concepts and criteria of classification theory. Applying classification theory to the ICF and communication raises a number of issues, some previously highlighted through clinical application. Six focus questions from classification theory are used to explore these issues, and to propose the creation of an ICF-related conceptual model of communicating for the field of communication disability, which would address some of the issues raised. Developing a conceptual model of communication for SLP purposes closely articulated with the ICF would foster productive intra-professional discourse, while at the same time allow the profession to continue to use the ICF for purposes in inter-disciplinary discourse. The paper concludes by suggesting the insights of classification theory can assist professionals to apply the ICF to communication with the necessary rigour, and to work further in developing a conceptual model of human communication.

Maximum imaging depth comparison in porcine vocal folds using 776-nm vs. 1552-nm excitation wavelengths

NASA Astrophysics Data System (ADS)

Yildirim, Murat; Ferhanoglu, Onur; Kobler, James B.; Zeitels, Steven M.; Ben-Yakar, Adela

2013-02-01

Vocal fold scarring is one of the major causes of voice disorders and may arise from overuse or post-surgical wound healing. One promising treatment utilizes the injection of soft biomaterials aimed at restoring viscoelasticity of the outermost vibratory layer of the vocal fold, superficial lamina propria (SLP). However, the density of the tissue and the required injection pressure impair proper localization of the injected biomaterial in SLP. To enhance treatment effectiveness, we are investigating a technique to image and ablate sub-epithelial planar voids in vocal folds using ultrafast laser pulses to better localize the injected biomaterial. It is challenging to optimize the excitation wavelength to perform imaging and ablation at depths suitable for clinical use. Here, we compare maximum imaging depth using two photon autofluorescence and second harmonic generation with third-harmonic generation imaging modalities for healthy porcine vocal folds. We used a home-built inverted nonlinear scanning microscope together with a high repetition rate (2 MHz) ultrafast fiber laser (Raydiance Inc.). We acquired both two-photon autofluorescence and second harmonic generation signals using 776 nm wavelength and third harmonic generation signals using 1552 nm excitation wavelength. We observed that maximum imaging depth with 776 nm wavelength is significantly improved from 114 μm to 205 μm when third harmonic generation is employed using 1552 nm wavelength, without any observable damage in the tissue.

North Atlantic sub-decadal variability in climate models

NASA Astrophysics Data System (ADS)

Reintges, Annika; Martin, Thomas; Latif, Mojib; Park, Wonsun

2017-04-01

The North Atlantic Oscillation (NAO) is the dominant variability mode for the winter climate of the North Atlantic sector. During a positive (negative) NAO phase, the sea level pressure (SLP) difference between the subtropical Azores high and the subpolar Icelandic low is anomalously strong (weak). This affects, for example, temperature, precipitation, wind, and surface heat flux over the North Atlantic, and over large parts of Europe. In observations we find enhanced sub-decadal variability of the NAO index that goes along with a dipolar sea surface temperature (SST) pattern. The corresponding SLP and SST patterns are reproduced in a control experiment of the Kiel Climate Model (KCM). Large-scale air-sea interaction is suggested to be essential for the North Atlantic sub-decadal variability in the KCM. The Atlantic Meridional Overturning Circulation (AMOC) plays a key role, setting the timescale of the variability by providing a delayed negative feedback to the NAO. The interplay of the NAO and the AMOC on the sub-decadal timescale is further investigated in the CMIP5 model ensemble. For example, the average CMIP5 model AMOC pattern associated with sub-decadal variability is characterized by a deep-reaching dipolar structure, similar to the KCM's sub-decadal AMOC variability pattern. The results suggest that dynamical air-sea interactions are crucial to generate enhanced sub-decadal variability in the North Atlantic climate.

How are warm and cool years in the California Current related to ENSO?

NASA Astrophysics Data System (ADS)

Fiedler, Paul C.; Mantua, Nathan J.

2017-07-01

The tropical El Niño-Southern Oscillation (ENSO) is a dominant mode of interannual variability that impacts climate throughout the Pacific. The California Current System (CCS) in the northeast Pacific warms and cools from year to year, with or without a corresponding tropical El Niño or La Niña event. We update the record of warm and cool events in the CCS for 1950-2016 and use composite sea level pressure (SLP) and surface wind anomalies to explore the atmospheric forcing mechanisms associated with tropical and CCS warm and cold events. CCS warm events are associated with negative SLP anomalies in the NE Pacific—a strong and southeastward displacement of the wintertime Aleutian Low, a weak North Pacific High, and a regional pattern of cyclonic wind anomalies that are poleward over the CCS. We use a first-order autoregressive model to show that regional North Pacific forcing is predominant in SST variations throughout most of the CCS, while remote tropical forcing is more important in the far southern portion of the CCS. In our analysis, cool events in the CCS tend to be more closely associated with tropical La Niña than are warm events in the CCS with tropical El Niño; the forcing of co-occurring cool events is analogous, but nearly opposite, to that of warm events.

Lost in Translation: Understanding Students' Use of Social Networking and Online Resources to Support Early Clinical Practices. A National Survey of Graduate Speech-Language Pathology Students

ERIC Educational Resources Information Center

Boster, Jamie B.; McCarthy, John W.

2018-01-01

The Internet is a source of many resources for graduate speech-language pathology (SLP) students. It is important to understand the resources students are aware of, which they use, and why they are being chosen as sources of information for therapy activities. A national online survey of graduate SLP students was conducted to assess their…

Treating voice disorders in the school-based setting: working within the framework of IDEA.

PubMed

Ruddy, Bari Hoffman; Sapienza, Christine M

2004-10-01

The role of the speech-language pathologist (SLP) has developed considerably over the last 10 years given the medical and technological advances in lifesustaining procedures. Over time, children born with congenital, surgical, or "medically fragile" conditions hav become mainstreamed into regular school-based settings, thus extending the traditional role of the SLP and multidisciplinary team. Understanding the impact of these voice disorders on the child's educational performance has been a struggle for many clinicians because the eligibility decisions for students in school-based settings must be made within the framework of federal legislation and regulations governing the provision of services for students with disabilities. This article discusses how to identify children with voice disorders under the Individuals With Disabilities Education Act (IDEA) definition, the role of the SLP in assigning priority in various voice management scenarios, and how models of therapy can be incorporated in the school-based setting.

Surface-layer (S-layer) of human and animal Clostridium difficile strains and their behaviour in adherence to epithelial cells and intestinal colonization.

PubMed

Spigaglia, Patrizia; Barketi-Klai, Amira; Collignon, Anne; Mastrantonio, Paola; Barbanti, Fabrizio; Rupnik, Maja; Janezic, Sandra; Kansau, Imad

2013-09-01

Clostridium difficile is a frequent cause of severe, recurrent post-antibiotic diarrhoea and pseudomembranous colitis. The surface layer (S-layer) is the predominant outer surface component of C. difficile which is involved in pathogen-host interactions critical to pathogenesis. In this study, we characterized the S-layer protein A (SlpA) of animal and human strains belonging to different PCR-ribotypes (PR) and compared the in vitro adherence and in vivo colonization properties of strains showing different SlpA variants. Since each SlpA variant has been recently associated with an S-layer cassette, we were able to deduce the cassette for each of our strains. In this study, an identity of 99-100 % was found among the SlpA of isolates belonging to PR 012, 014/020, 045 and 078. One exception was the SlpA of a poultry isolate, PR 014/020, which showed 99 % identity with that of strain 0160, another PR 014/020 which contains an S-layer cassette 6. Interestingly, this cassette has also been found in a PR 018 strain, an emerging virulent type currently predominant in Italy. Five other SlpA variants (v014/020a-e) were identified in strains PR 014/020. In vitro adherence assays and in vivo colonization experiments were performed on five PR 014/020 strains: human 1064 (v014/020e), human 4684/08 (v014/020b), human IT1106 (v078a), poultry P30 (v014/020d) and poultry PB90 (v014/020b) strains. Adhesion assays indicate that C. difficile strains vary in their capacity to adhere to cells in culture and that adhesion seems to be independent of the SlpA variant. Colonization properties were assessed in vivo using a dixenic mouse model of colonization. The kinetics of faecal shedding and caecal colonization were similar when human 4684/08 (v014/020b) strain was compared with human 1064 (v014/020e) and poultry PB90 (v014/020b) strain. In contrast, poultry P30 (v014/020d) strain outcompeted both human 4684/08 (v014/020b) and IT1106 (v078a) strains and its adherence to caeca at day 7 was significantly higher. The peculiar characteristics of C. difficile P30 seem to advantage it in colonizing the intestinal mice niche, increasing its ability to compete and adapt. The results obtained underline the need of an increased attention to the genetic evolution of C. difficile to prevent and limit the consequences of the emergence of increasingly virulent strains.

Lactobacillus buchneri S-layer as carrier for an Ara h 2-derived peptide for peanut allergen-specific immunotherapy.

PubMed

Anzengruber, Julia; Bublin, Merima; Bönisch, Eva; Janesch, Bettina; Tscheppe, Angelika; Braun, Matthias L; Varga, Eva-Maria; Hafner, Christine; Breiteneder, Heimo; Schäffer, Christina

2017-05-01

Peanut allergy is an IgE-mediated severe hypersensitivity disorder. The lack of a treatment of this potentially fatal allergy has led to intensive research on vaccine development. Here, we describe the design and initial characterization of a carrier-bound peptide derived from the most potent peanut allergen, Ara h 2, as a candidate vaccine. Based on the adjuvant capability of bacterial surface (S-) layers, a fusion protein of the S-layer protein SlpB from Lactobacillus buchneri CD034 and the Ara h 2-derived peptide AH3a42 was produced. This peptide comprised immunodominant B-cell epitopes as well as one T cell epitope. The fusion protein SlpB-AH3a42 was expressed in E. coli, purified, and tested for its IgE binding capacity as well as for its ability to activate sensitized rat basophil leukemia (RBL) cells. The capacity of Ara h 2-specific IgG rabbit-antibodies raised against SlpB-AH3a42 or Ara h 2 to inhibit IgE-binding was determined by ELISA inhibition assays using sera of peanut allergic patients sensitized to Ara h 2. IgE specific to the SlpB-AH3a42 fusion protein was detected in 69% (25 of 36) of the sera. Despite the recognition by IgE, the SlpB-AH3a42 fusion protein was unable to induce β-hexosaminidase release from sensitized RBL cells at concentrations up to 100ng per ml. The inhibition of IgE-binding to the natural allergen observed after pre-incubation of the 20 sera with rabbit anti-SlpB-AH3a42 IgG was more than 30% for four sera, more than 20% for eight sera, and below 10% for eight sera. In comparison, anti-Ara h 2 rabbit IgG antibodies inhibited binding to Ara h 2 by 48% ±13.5%. Our data provide evidence for the feasibility of this novel approach towards the development of a peanut allergen peptide-based carrier-bound vaccine. Our experiments further indicate that more than one allergen-peptide will be needed to induce a broader protection of patients allergic to Ara h 2. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

University of Akron: Training Speech-Language Pathology Specialists to Provide Quality Service to Children Who Are Deaf or Hard of Hearing--A Collaborative Preservice Program

ERIC Educational Resources Information Center

Wray, Denise; Flexer, Carol

2010-01-01

A collaborative team of faculty from The University of Akron (UA) in Akron, Ohio, and Kent State University (KSU) in Kent, Ohio, were awarded a federal grant from the U.S. Department of Education to develop a specialty area in the graduate speech-language pathology (SLP) programs of UA and KSU that would train a total of 32 SLP students (trainees)…

Repeatability and Reproducibility of Retinal Nerve Fiber Layer Parameters Measured by Scanning Laser Polarimetry with Enhanced Corneal Compensation in Normal and Glaucomatous Eyes.

PubMed

Ara, Mirian; Ferreras, Antonio; Pajarin, Ana B; Calvo, Pilar; Figus, Michele; Frezzotti, Paolo

2015-01-01

To assess the intrasession repeatability and intersession reproducibility of peripapillary retinal nerve fiber layer (RNFL) thickness parameters measured by scanning laser polarimetry (SLP) with enhanced corneal compensation (ECC) in healthy and glaucomatous eyes. One randomly selected eye of 82 healthy individuals and 60 glaucoma subjects was evaluated. Three scans were acquired during the first visit to evaluate intravisit repeatability. A different operator obtained two additional scans within 2 months after the first session to determine intervisit reproducibility. The intraclass correlation coefficient (ICC), coefficient of variation (COV), and test-retest variability (TRT) were calculated for all SLP parameters in both groups. ICCs ranged from 0.920 to 0.982 for intravisit measurements and from 0.910 to 0.978 for intervisit measurements. The temporal-superior-nasal-inferior-temporal (TSNIT) average was the highest (0.967 and 0.946) in normal eyes, while nerve fiber indicator (NFI; 0.982) and inferior average (0.978) yielded the best ICC in glaucomatous eyes for intravisit and intervisit measurements, respectively. All COVs were under 10% in both groups, except NFI. TSNIT average had the lowest COV (2.43%) in either type of measurement. Intervisit TRT ranged from 6.48 to 12.84. The reproducibility of peripapillary RNFL measurements obtained with SLP-ECC was excellent, indicating that SLP-ECC is sufficiently accurate for monitoring glaucoma progression.

[A rare parotid tumor].

PubMed

Doh, Kwame; Thiam, Ibou; Takin, Romulus Carmen Adechina; Sonhaye, Khaled; Woto-Gaye, Gisèle

2018-06-04

Sebaceous lymphadenoma of the parotid (SLP) is a rare, benign tumor with similar epidemiological and macroscopic characteristics with other sebaceous differentiated tumors of the parotid (SDTP). The authors report a case of SLP in an 80-year-old woman. They then recall the distinctive histological and immunohistochemical criteria of SDTP. Mrs P. D. was received during a surgical consultation for the management of a painless right parotid swelling that has evolved for 10years, increasing slightly in volume. At admission, the mass was movable, firm with a healthy skin without facial paralysis or satellite lymphadenopathy. The surgical intervention performed removed a nodular mass measuring 7cm, encapsulated, yellowish. It was made of regular epithelial cells without atypia or mitoses organized in nests, trabeculae and massifs. This tumor also included small canalicular cystic dilatations associated with several islands of sebaceous glands. The stroma was dense lymphoid with follicles and germinal centers. The tumor cells were CK7+, P63+, MSA+ and had a Ki67<5%. The diagnosis of an SLP was retained. No additional therapy was performed. One year after surgery, the patient had no local recurrence or metastatic foci. SLP is a rare tumor with a particular histological and immunohistochemical profile. It is an epithelial tumor with sebaceous islands, a dense reactional lymphoid stroma, expression of luminal and basal epithelial markers and a low proliferation index. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Omission of Dysphagia Therapies in Hospital Discharge Communications

PubMed Central

Kind, Amy; Anderson, Paul; Hind, Jacqueline; Robbins, JoAnne; Smith, Maureen

2009-01-01

Background Despite the wide implementation of dysphagia therapies, it is unclear whether these therapies are successfully communicated beyond the inpatient setting. Objective To examine the rate of dysphagia recommendation omissions in hospital discharge summaries for high-risk sub-acute care (i.e., skilled nursing facility, rehabilitation, long-term care) populations. Design Retrospective cohort study Subjects All stroke and hip fracture patients billed for inpatient dysphagia evaluations by speech-language pathologists (SLPs) and discharged to sub-acute care in 2003-2005 from a single large academic medical center (N=187). Measurements Dysphagia recommendations from final SLP hospital notes and from hospital (physician) discharge summaries were abstracted, coded, and compared for each patient. Recommendation categories included: dietary (food and liquid), postural/compensatory techniques (e.g., chin-tuck), rehabilitation (e.g., exercise), meal pacing (e.g., small bites), medication delivery (e.g., crush pills), and provider/supervision (e.g., 1-to-1 assist). Results 45% of discharge summaries omitted all SLP dysphagia recommendations. 47%(88/186) of patients with SLP dietary recommendations, 82%(93/114) with postural, 100%(16/16) with rehabilitation, 90%(69/77) with meal pacing, 95%(21/22) with medication, and 79%(96/122) with provider/supervision recommendations had these recommendations completely omitted from their discharge summaries. Conclusions Discharge summaries omitted all categories of SLP recommendations at notably high rates. Improved post-hospital communication strategies are needed for discharges to sub-acute care. PMID:20098999

The Influence of Drug Physical State on the Dissolution Enhancement of Solid Dispersions Prepared Via Hot-Melt Extrusion: A Case Study Using Olanzapine

PubMed Central

Pina, Maria Fátima; Zhao, Min; Pinto, João F; Sousa, João J; Craig, Duncan Q M

2014-01-01

In this study, we examine the relationship between the physical structure and dissolution behavior of olanzapine (OLZ) prepared via hot-melt extrusion in three polymers [polyvinylpyrrolidone (PVP) K30, polyvinylpyrrolidone-co-vinyl acetate (PVPVA) 6:4, and Soluplus® (SLP)]. In particular, we examine whether full amorphicity is necessary to achieve a favorable dissolution profile. Drug–polymer miscibility was estimated using melting point depression and Hansen solubility parameters. Solid dispersions were characterized using differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. All the polymers were found to be miscible with OLZ in a decreasing order of PVP>PVPVA>SLP. At a lower extrusion temperature (160°C), PVP generated fully amorphous dispersions with OLZ, whereas the formulations with PVPVA and SLP contained 14%–16% crystalline OLZ. Increasing the extrusion temperature to 180°C allowed the preparation of fully amorphous systems with PVPVA and SLP. Despite these differences, the dissolution rates of these preparations were comparable, with PVP showing a lower release rate despite being fully amorphous. These findings suggested that, at least in the particular case of OLZ, the absence of crystalline material may not be critical to the dissolution performance. We suggest alternative key factors determining dissolution, particularly the dissolution behavior of the polymers themselves. PMID:24765654

Effect of a multi-level intervention on nurse—patient communication in the intensive care unit: Results of the SPEACS trial

PubMed Central

Happ, Mary Beth; Garrett, Kathryn L.; Tate, Judith A.; DiVirgilio, Dana; Houze, Martin P.; Demirci, Jill R.; George, Elisabeth; Sereika, Susan M.

2014-01-01

Objective To test the impact of two levels of intervention on communication frequency, quality, success, and ease between nurses and intubated intensive care unit (ICU) patients. Design Quasi-experimental, 3-phase sequential cohort study: (1) usual care, (2) basic communication skills training (BCST) for nurses, (3) additional training in augmentative and alternative communication devices and speech language pathologist consultation (AAC + SLP). Trained observers rated four 3-min video-recordings for each nurseepatient dyad for communication frequency, quality and success. Patients self-rated communication ease. Setting Two ICUs in a university-affiliated medical center. Participants 89 intubated patients awake, responsive and unable to speak and 30 ICU nurses. Main results Communication frequency (mean number of communication acts within a communication exchange) and positive nurse communication behaviors increased significantly in one ICU only. Percentage of successful communication exchanges about pain were greater for the two intervention groups than the usual care/control group across both ICUs (p = .03) with more successful sessions about pain and other symptoms in the AAC + SLP group (p = .07). Patients in the AAC SLP intervention group used significantly more AAC methods (p = .002) and rated communication at high difficulty less often (p < .01). Conclusions This study provides support for the feasibility, utility and efficacy of a multi-level communication skills training, materials and SLP consultation intervention in the ICU. PMID:24495519

Climatic change projections for winter streamflow in Guadalquivir river

NASA Astrophysics Data System (ADS)

Jesús Esteban Parra, María; Hidalgo Muñoz, José Manuel; García-Valdecasas-Ojeda, Matilde; Raquel Gámiz Fortis, Sonia; Castro Díez, Yolanda

2015-04-01

In this work we have obtained climate change projections for winter streamflow of the Guadalquivir River in the period 2071-2100 using the Principal Component Regression (PCR) method. The streamflow data base used has been provided by the Center for Studies and Experimentation of Public Works, CEDEX. Series from gauging stations and reservoirs with less than 10% of missing data (filled by regression with well correlated neighboring stations) have been considered. The homogeneity of these series has been evaluated through the Pettit test and degree of human alteration by the Common Area Index. The application of these criteria led to the selection of 13 streamflow time series homogeneously distributed over the basin, covering the period 1952-2011. For this streamflow data, winter seasonal values were obtained by averaging the monthly values from January to March. The PCR method has been applied using the Principal Components of the mean anomalies of sea level pressure (SLP) in winter (December to February averaged) as predictors of streamflow for the development of a downscaled statistical model. The SLP database is the NCEP reanalysis covering the North Atlantic region, and the calibration and validation periods used for fitting and evaluating the ability of the model are 1952-1992 and 1993-2011, respectively. In general, using four Principal Components, regression models are able to explain up to 70% of the variance of the streamflow data. Finally, the statistical model obtained for the observational data was applied to the SLP data for the period 2071-2100, using the outputs of different GCMs of the CMIP5 under the RPC8.5 scenario. The results found for the end of the century show no significant changes or moderate decrease in the streamflow of this river for most GCMs in winter, but for some of them the decrease is very strong. Keywords: Statistical downscaling, streamflow, Guadalquivir River, climate change. ACKNOWLEDGEMENTS This work has been financed by the projects P11-RNM-7941 (Junta de Andalucía-Spain) and CGL2013-48539-R (MINECO-Spain, FEDER).

Synoptic climatological analyses on the seasonal transition from winter to spring in Europe also with attention to the day-to-day variability (Comparing with that in East Asia)

NASA Astrophysics Data System (ADS)

Kato, Kuranoshin; Hamaki, Tatsuya; Haga, Yuichi; Otani, Kazuo; Kato, Haruko

2016-04-01

There are many stages with rapid seasonal transitions in East Asia, greatly influenced by the considerable phase differences of seasonal cycle among the Asian monsoon subsystems, resulting in the variety of "seasonal feeling". The seasonal cycle has been an important background for generation of the many kinds of arts also in Europe around the western edge of the Eurasian Continent. Especially around Germany, there are so many music or literature works in which the "May" is treated as the special season. However, more detailed examination and its comparison with that in East Asia about the seasonal evolution from winter to spring including before May would be interesting. Deeper knowledge on the seasonal cycle would contribute greatly to the cultural understanding as mentioned above, as well as for considering the detailed response of the regional climate to the global-scale impacts such as the global warming. As such, the present study examined, based mainly on the NCEP/NCAR reanalysis data during 1971-2010, the synoptic climatological features on the seasonal transition from winter to spring in Europe also with attention to the day-to-day variability, by comparing with those in East Asia (detailed analyses were made mainly for 2000/01 - 2010/11 winters). Around the region from Germany to Turkey, the surface air temperature (TS) showed rather larger day-to-day variation (including the interannual or intraseasonal variation) throughout a year than in the Japan Islands area in East Asia. Especially from December to March (the minimum period of the climatological TS in the European side), the day-to-day variation was extremely great around Germany and its northern region (to the north of around 45N/10E). Thus, the extremely low temperature events sometimes appeared around Germany till the end of March, although the seasonal mean TS was not so considerably low. The day-to-day variation of sea level pressure (SLP) was also very large where such large amplitude of TS was found, although the extremely large day-to-day variation of SLP was found from the earlier season (October to March). It is interesting that the region where such large day-to-day amplitudes of TS and SLP were observed corresponded to the southeastern periphery zone of the Icelandic Low in the seasonal mean field. Besides, sub-monthly or about 30-day-period intraseasonal variation of the eastward intrusion of the Icelandic Low near the northwestern Europe was also clearly found in winter, as well as the short-period variation of the synoptic-scale disturbances to the southeast of the intraseasonal-scale Icelandic Low. In the seasonal mean field, relatively strong warm air advection in the lower layer was found to the southeast of the Icelandic Low due to combination of the strong westerly wind there and the cold air in the further eastern region. Such warm advection can be intermittently enhanced especially when the Icelandic Low intruded more closely to the northwestern Europe. These situations seem to result in the large day-to-day variation of TS around Germany and its northern region until the seasonal weakening of the Icelandic Low from March to April.

Scanning laser topography and scanning laser polarimetry: comparing both imaging methods at same distances from the optic nerve head.

PubMed

Kremmer, Stephan; Keienburg, Marcus; Anastassiou, Gerasimos; Schallenberg, Maurice; Steuhl, Klaus-Peter; Selbach, J Michael

2012-01-01

To compare the performance of scanning laser topography (SLT) and scanning laser polarimetry (SLP) on the rim of the optic nerve head and its surrounding area and thereby to evaluate whether these imaging technologies are influenced by other factors beyond the thickness of the retinal nerve fiber layer (RNFL). A total of 154 eyes from 5 different groups were examined: young healthy subjects (YNorm), old healthy subjects (ONorm), patients with normal tension glaucoma (NTG), patients with open-angle glaucoma and early glaucomatous damage (OAGE) and patients with open-angle glaucoma and advanced glaucomatous damage (OAGA). SLT and SLP measurements were taken. Four concentric circles were superimposed on each of the images: the first one measuring at the rim of the optic nerve head (1.0 ONHD), the next measuring at 1.25 optic nerve head diameters (ONHD), at 1.5 ONHD and at 1.75 ONHD. The aligned images were analyzed using GDx/NFA software. Both methods showed peaks of RNFL thickness in the superior and inferior segments of the ONH. The maximum thickness, registered by the SLT device was at the ONH rim where the SLP device tended to measure the lowest values. SLT measurements at the ONH were influenced by other tissues besides the RNFL like blood vessels and glial tissues. SLT and SLP were most strongly correlated at distances of 1.25 and 1.5 ONHD. While both imaging technologies are valuable tools in detecting glaucoma, measurements at the ONH rim should be interpreted critically since both methods might provide misleading results. For the assessment of the retinal nerve fiber layer we would like to recommend for both imaging technologies, SLT and SLP, measurements in 1.25 and 1.5 ONHD distance of the rim of the optic nerve head.

Rab27a negatively regulates CFTR chloride channel function in colonic epithelia: Involvement of the effector proteins in the regulatory mechanism

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

Saxena, Sunil K.; Kaur, Simarna

Cystic fibrosis, an autosomal recessive disorder, is caused by the disruption of biosynthesis or function of CFTR. CFTR regulatory mechanisms include channel transport to plasma membrane and protein-protein interactions. Rab proteins are small GTPases involved in vesicle transport, docking, and fusion. The colorectal epithelial HT-29 cells natively express CFTR and respond to cAMP with an increase in CFTR-mediated currents. DPC-inhibited currents could be completely eliminated with CFTR-specific SiRNA. Over-expression of Rab27a inhibited, while isoform specific SiRNA and Rab27a antibody stimulated CFTR-mediated currents in HT-29 cells. CFTR activity is inhibited both by Rab27a (Q78L) (constitutive active GTP-bound form of Rab27a) andmore » Rab27a (T23N) (constitutive negative form that mimics the GDP-bound form). Rab27a mediated effects could be reversed by Rab27a-binding proteins, the synaptotagmin-like protein (SLP-5) and Munc13-4 accessory protein (a putative priming factor for exocytosis). The SLP reversal of Rab27a effect was restricted to C2A/C2B domains while the SHD motif imparted little more inhibition. The CFTR-mediated currents remain unaffected by Rab3 though SLP-5 appears to weakly bind it. The immunoprecipitation experiments suggest protein-protein interactions between Rab27a and CFTR. Rab27a appears to impair CFTR appearance at the cell surface by trapping CFTR in the intracellular compartments. Munc13-4 and SLP-5, on the other hand, limit Rab27a availability to CFTR, thus minimizing its effect on channel function. These observations decisively prove that Rab27a is involved in CFTR channel regulation through protein-protein interactions involving Munc13-4 and SLP-5 effector proteins, and thus could be a potential target for cystic fibrosis therapy.« less

Potentiation of a p53-SLP vaccine by cyclophosphamide in ovarian cancer: a single-arm phase II study.

PubMed

Vermeij, Renee; Leffers, Ninke; Hoogeboom, Baukje-Nynke; Hamming, Ineke L E; Wolf, Rinze; Reyners, Anna K L; Molmans, Barbara H W; Hollema, Harry; Bart, Joost; Drijfhout, Jan W; Oostendorp, Jaap; van der Zee, Ate G J; Melief, Cornelis J; van der Burg, Sjoerd H; Daemen, Toos; Nijman, Hans W

2012-09-01

The purpose of the current phase II single-arm clinical trial was to evaluate whether pretreatment with low-dose cyclophosphamide improves immunogenicity of a p53-synthetic long peptide (SLP) vaccine in patients with recurrent ovarian cancer. Patients with ovarian cancer with elevated serum levels of CA-125 after primary treatment were immunized four times with the p53-SLP vaccine. Each immunization was preceded by administration of 300 mg/m2 intravenous cyclophosphamide as a means to affect regulatory T cells (Tregs). Vaccine-induced p53-specific interferon-gamma (IFN-γ)-producing T cells evaluated by IFN-γ ELISPOT were observed in 90% (9/10) and 87.5% (7/8) of evaluable patients after two and four immunizations, respectively. Proliferative p53-specific T cells, observed in 80.0% (8/10) and 62.5% (5/8) of patients, produced both T-helper 1 and T-helper-2 cytokines. Cyclophosphamide induced neither a quantitative reduction of Tregs determined by CD4+ FoxP3+ T cell levels nor a demonstrable qualitative difference in Treg function tested in vitro. Nonetheless, the number of vaccine-induced p53-specific IFN-γ-producing T cells was higher in our study compared to a study in which a similar patient group was treated with p53-SLP monotherapy (p≤0.012). Furthermore, the strong reduction in the number of circulating p53-specific T cells observed previously after four immunizations was currently absent. Stable disease was observed in 20.0% (2/10) of patients, and the remainder of patients (80.0%) showed clinical, biochemical and/or radiographic evidence of progressive disease. The outcome of this phase II trial warrants new studies on the use of low-dose cyclophosphamide to potentiate the immunogenicity of the p53-SLP vaccine or other antitumor vaccines. Copyright © 2011 UICC.

High level heterologous protein production in Lactococcus and Lactobacillus using a new secretion system based on the Lactobacillus brevis S-layer signals.

PubMed

Savijoki, K; Kahala, M; Palva, A

1997-02-28

A secretion cassette, based on the expression and secretion signals of a S-layer protein (SlpA) from Lactobacillus brevis, was constructed. E. coli beta-lactamase (Bla) was used as the reporter protein to determine the functionality of the S-layer signals for heterologous expression and secretion in Lactococcus lactis, Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus gasseri and Lactobacillus casei using a low-copy-number plasmid derived from pGK12. In all hosts tested, the bla gene was expressed under the slpA signals and all Bla activity was secreted to the culture medium. The Lb. brevis S-layer promoters were very efficiently recognized in L. lactis, Lb. brevis and Lb. plantarum, whereas in Lb. gasseri the slpA promoter region appeared to be recognized at a lower level and in Lb. casei the level of transcripts was below the detection limit. The production of Bla was mainly restricted to the exponential phase of growth. The highest yield of Bla was obtained with L. lactis and Lb. brevis. Without pH control, substantial degradation of Bla occurred during prolonged cultivations with all lactic acid bacteria (LAB) tested. When growing L. lactis and Lb. brevis under pH control, the Bla activity could be stabilized also at the stationary phase. L. lactis produced up to 80 mg/l of Bla which to our knowledge represents the highest amount of a heterologous protein secreted by LAB so far. The short production phase implied a very high rate of secretion with a calculated value of 5 x 10(5) Bla molecules/cell per h. Such a high rate was also observed with Lb. plantarum, whereas in Lb. brevis the competition between the wild type slpA gene and the secretion construct probably lowered the rate of Bla production. The results obtained indicate wide applicability of the Lb. brevis slpA signals for efficient protein production and secretion in LAB.

The effects of a spiritual learning program on improving spiritual health and clinical practice stress among nursing students.

PubMed

Hsiao, Ya-Chu; Chiang, Hui-Ying; Lee, Hsiang-Chun; Chen, Su-Hui

2012-12-01

Numerous studies have indicated an association between spirituality and health outcomes. However, little information is available about interventions that have been shown to enhance spiritual health and decrease stress. This study examined the effects of a spiritual learning program (SLP) on nursing student-perceived spiritual health and clinical practice stress. A convenience sample of nursing students currently enrolled at a nursing school in northern Taiwan were recruited to participate in this quasiexperimental study as participants to experimental and control groups via simple random sampling. Results from a spiritual health scale and a perceived clinical practice stress scale, together with the score for clinical nursing practice, were compared between the groups. Baseline data were collected from all participants. The experimental group participated in 8 weeks of 50-minute per week SLP, which included lectures, discussion, reflection, and spiritual practices. A second data set was collected from all participants after the intervention. A third data set was collected after all participants had performed 4 weeks of nursing clinical practice. Participants were all women. Average age was 19.4 years (SD = 1.3 years). Generalized estimating equation analysis showed SLP to have a significant short-term effect on improving the total score for spiritual health (p < .01). Significantly greater improvement in clinical practice stress scores was also seen in the experimental group as compared with the control group (all p < .05). The experimental group obtained a higher score of the final clinical practice than the control group (t = 3.771, p < .001). The SLP may encourage participants to see stressors as meaningful events that are connected to individual life purposes. The program developed in this study may be used to improve spiritual health and reduce stress in nursing students' clinical practice. This SLP may be referenced when designing similar spirituality-related courses and applied to nursing student counseling.

Long-term soil nutrient dynamics comparison under smallholding land and farmland policy in northeast of China.

PubMed

Ouyang, Wei; Wei, Xinfeng; Hao, Fanghua

2013-04-15

There are two kinds of land policies, the smallholding land policy (SLP) and the farmland policy (FLP) in China. The farmland nutrient dynamics under the two land policies were analysed with the soil system budget method. The averaged nitrogen (N) input of the SLP and the FLP over sixteen years increased about 23.9% and 33.3%, respectively and the phosphorus (P) input climbed about 39.1% and 42.3%, respectively. The statistical analysis showed that the land policies had significant impacts on N and P input from fertilizer and manure, but did not obviously affect the N input from seeds and biological N fixation. The efficiency percentage of N of the SLP and the FLP climbed about 54.5% and 59.4%, respectively, and the P efficiency improved by 52.7% and 82.6%, respectively. About the nutrient output, the F-test analysis indicated that the land polices had remarkable impacts on N output by crop uptake, ammonia volatilisation, denitrification, leaching and runoff, and P output by uptake, runoff, and leach. The balance showed that the absolute loss of N from land deceased about 43.6% and 46.0%, respectively, in the SLP and the FLP, and P discharge reduced about 34.2% and 75.2%, respectively. The F-test analysis of N and P efficiency and balance of between two polices both indicated that the FLP had significant impact on nutrient dynamic. With the Mitscherlich model, the correlations between nutrient input and crop uptake, usage efficiency and loss were analysed and showed that was a threshold value for the optimal nutrient input with the highest efficiency rate. For the optimal nutrient efficiency, the space for extra P addition was bigger than the N input. The FLP have more advantage than the SLP on the crop yield, nutrient efficiency and environmental discharge. Copyright © 2013 Elsevier B.V. All rights reserved.

Proteomic Analysis of ABCA1-Null Macrophages Reveals a Role for Stomatin-Like Protein-2 in Raft Composition and Toll-Like Receptor Signaling.

PubMed

Chowdhury, Saiful M; Zhu, Xuewei; Aloor, Jim J; Azzam, Kathleen M; Gabor, Kristin A; Ge, William; Addo, Kezia A; Tomer, Kenneth B; Parks, John S; Fessler, Michael B

2015-07-01

Lipid raft membrane microdomains organize signaling by many prototypical receptors, including the Toll-like receptors (TLRs) of the innate immune system. Raft-localization of proteins is widely thought to be regulated by raft cholesterol levels, but this is largely on the basis of studies that have manipulated cell cholesterol using crude and poorly specific chemical tools, such as β-cyclodextrins. To date, there has been no proteome-scale investigation of whether endogenous regulators of intracellular cholesterol trafficking, such as the ATP binding cassette (ABC)A1 lipid efflux transporter, regulate targeting of proteins to rafts. Abca1(-/-) macrophages have cholesterol-laden rafts that have been reported to contain increased levels of select proteins, including TLR4, the lipopolysaccharide receptor. Here, using quantitative proteomic profiling, we identified 383 proteins in raft isolates from Abca1(+/+) and Abca1(-/-) macrophages. ABCA1 deletion induced wide-ranging changes to the raft proteome. Remarkably, many of these changes were similar to those seen in Abca1(+/+) macrophages after lipopolysaccharide exposure. Stomatin-like protein (SLP)-2, a member of the stomatin-prohibitin-flotillin-HflK/C family of membrane scaffolding proteins, was robustly and specifically increased in Abca1(-/-) rafts. Pursuing SLP-2 function, we found that rafts of SLP-2-silenced macrophages had markedly abnormal composition. SLP-2 silencing did not compromise ABCA1-dependent cholesterol efflux but reduced macrophage responsiveness to multiple TLR ligands. This was associated with reduced raft levels of the TLR co-receptor, CD14, and defective lipopolysaccharide-induced recruitment of the common TLR adaptor, MyD88, to rafts. Taken together, we show that the lipid transporter ABCA1 regulates the protein repertoire of rafts and identify SLP-2 as an ABCA1-dependent regulator of raft composition and of the innate immune response. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Proteomic Analysis of ABCA1-Null Macrophages Reveals a Role for Stomatin-Like Protein-2 in Raft Composition and Toll-Like Receptor Signaling*

PubMed Central

Chowdhury, Saiful M.; Zhu, Xuewei; Aloor, Jim J.; Azzam, Kathleen M.; Gabor, Kristin A.; Ge, William; Addo, Kezia A.; Tomer, Kenneth B.; Parks, John S.; Fessler, Michael B.

2015-01-01

Lipid raft membrane microdomains organize signaling by many prototypical receptors, including the Toll-like receptors (TLRs) of the innate immune system. Raft-localization of proteins is widely thought to be regulated by raft cholesterol levels, but this is largely on the basis of studies that have manipulated cell cholesterol using crude and poorly specific chemical tools, such as β-cyclodextrins. To date, there has been no proteome-scale investigation of whether endogenous regulators of intracellular cholesterol trafficking, such as the ATP binding cassette (ABC)A1 lipid efflux transporter, regulate targeting of proteins to rafts. Abca1−/− macrophages have cholesterol-laden rafts that have been reported to contain increased levels of select proteins, including TLR4, the lipopolysaccharide receptor. Here, using quantitative proteomic profiling, we identified 383 proteins in raft isolates from Abca1+/+ and Abca1−/− macrophages. ABCA1 deletion induced wide-ranging changes to the raft proteome. Remarkably, many of these changes were similar to those seen in Abca1+/+ macrophages after lipopolysaccharide exposure. Stomatin-like protein (SLP)-2, a member of the stomatin-prohibitin-flotillin-HflK/C family of membrane scaffolding proteins, was robustly and specifically increased in Abca1−/− rafts. Pursuing SLP-2 function, we found that rafts of SLP-2-silenced macrophages had markedly abnormal composition. SLP-2 silencing did not compromise ABCA1-dependent cholesterol efflux but reduced macrophage responsiveness to multiple TLR ligands. This was associated with reduced raft levels of the TLR co-receptor, CD14, and defective lipopolysaccharide-induced recruitment of the common TLR adaptor, MyD88, to rafts. Taken together, we show that the lipid transporter ABCA1 regulates the protein repertoire of rafts and identify SLP-2 as an ABCA1-dependent regulator of raft composition and of the innate immune response. PMID:25910759

Genome-Wide Immune Modulation of TLR3-Mediated Inflammation in Intestinal Epithelial Cells Differs between Single and Multi-Strain Probiotic Combination.

PubMed

MacPherson, Chad W; Shastri, Padmaja; Mathieu, Olivier; Tompkins, Thomas A; Burguière, Pierre

2017-01-01

Genome-wide transcriptional analysis in intestinal epithelial cells (IEC) can aid in elucidating the impact of single versus multi-strain probiotic combinations on immunological and cellular mechanisms of action. In this study we used human expression microarray chips in an in vitro intestinal epithelial cell model to investigate the impact of three probiotic bacteria, Lactobacillus helveticus R0052 (Lh-R0052), Bifidobacterium longum subsp. infantis R0033 (Bl-R0033) and Bifidobacterium bifidum R0071 (Bb-R0071) individually and in combination, and of a surface-layer protein (SLP) purified from Lh-R0052, on HT-29 cells' transcriptional profile to poly(I:C)-induced inflammation. Hierarchical heat map clustering, Set Distiller and String analyses revealed that the effects of Lh-R0052 and Bb-R0071 diverged from those of Bl-R0033 and Lh-R0052-SLP. It was evident from the global analyses with respect to the immune, cellular and homeostasis related pathways that the co-challenge with probiotic combination (PC) vastly differed in its effect from the single strains and Lh-R0052-SLP treatments. The multi-strain PC resulted in a greater reduction of modulated genes, found through functional connections between immune and cellular pathways. Cytokine and chemokine analyses based on specific outcomes from the TNF-α and NF-κB signaling pathways revealed single, multi-strain and Lh-R0052-SLP specific attenuation of the majority of proteins measured (TNF-α, IL-8, CXCL1, CXCL2 and CXCL10), indicating potentially different mechanisms. These findings indicate a synergistic effect of the bacterial combinations relative to the single strain and Lh-R0052-SLP treatments in resolving toll-like receptor 3 (TLR3)-induced inflammation in IEC and maintaining cellular homeostasis, reinforcing the rationale for using multi-strain formulations as a probiotic.

Genome-Wide Immune Modulation of TLR3-Mediated Inflammation in Intestinal Epithelial Cells Differs between Single and Multi-Strain Probiotic Combination

PubMed Central

MacPherson, Chad W.; Shastri, Padmaja; Mathieu, Olivier; Tompkins, Thomas A.; Burguière, Pierre

2017-01-01

Genome-wide transcriptional analysis in intestinal epithelial cells (IEC) can aid in elucidating the impact of single versus multi-strain probiotic combinations on immunological and cellular mechanisms of action. In this study we used human expression microarray chips in an in vitro intestinal epithelial cell model to investigate the impact of three probiotic bacteria, Lactobacillus helveticus R0052 (Lh-R0052), Bifidobacterium longum subsp. infantis R0033 (Bl-R0033) and Bifidobacterium bifidum R0071 (Bb-R0071) individually and in combination, and of a surface-layer protein (SLP) purified from Lh-R0052, on HT-29 cells’ transcriptional profile to poly(I:C)-induced inflammation. Hierarchical heat map clustering, Set Distiller and String analyses revealed that the effects of Lh-R0052 and Bb-R0071 diverged from those of Bl-R0033 and Lh-R0052-SLP. It was evident from the global analyses with respect to the immune, cellular and homeostasis related pathways that the co-challenge with probiotic combination (PC) vastly differed in its effect from the single strains and Lh-R0052-SLP treatments. The multi-strain PC resulted in a greater reduction of modulated genes, found through functional connections between immune and cellular pathways. Cytokine and chemokine analyses based on specific outcomes from the TNF-α and NF-κB signaling pathways revealed single, multi-strain and Lh-R0052-SLP specific attenuation of the majority of proteins measured (TNF-α, IL-8, CXCL1, CXCL2 and CXCL10), indicating potentially different mechanisms. These findings indicate a synergistic effect of the bacterial combinations relative to the single strain and Lh-R0052-SLP treatments in resolving toll-like receptor 3 (TLR3)-induced inflammation in IEC and maintaining cellular homeostasis, reinforcing the rationale for using multi-strain formulations as a probiotic. PMID:28099447

Arctic sea ice variability in the context of recent atmospheric circulation trends

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

Deser, C.; Walsh, J.E.; Timlin, M.S.

Sea ice is a sensitive component of the climate system, influenced by conditions in both the atmosphere and ocean. Variations in sea ice may in turn modulate climate by altering the surface albedo; the exchange of heat, moisture, and momentum between the atmosphere and ocean; and the upper ocean stratification in areas of deep water formation. The surface albedo effect is considered to be one of the dominant factors in the poleward amplification of global warming due to increased greenhouse gas concentrations simulated in many climate models. Forty years (1958--97) of reanalysis products and corresponding sea ice concentration data aremore » used to document Arctic sea ice variability and its association with surface air temperature (SAT) and sea level pressure (SLP) throughout the Northern Hemisphere extratropics. The dominant mode of winter (January-March) sea ice variability exhibits out-of-phase fluctuations between the western and eastern North Atlantic, together with a weaker dipole in the North Pacific. The time series of this mode has a high winter-to-winter autocorrelation (0.69) and is dominated by decadal-scale variations and a longer-term trend of diminishing ice cover east of Greenland and increasing ice cover west of Greenland. Associated with the dominant pattern of winter sea ice variability are large-scale changes in SAT and SLP that closely resemble the North Atlantic oscillation. The associated SAT and surface sensible and latent heat flux anomalies are largest over the portions of the marginal sea ice zone in which the trends of ice coverage have been greatest, although the well-documented warming of the northern continental regions is also apparent. the temporal and spatial relationships between the SLP and ice anomaly fields are consistent with the notion that atmospheric circulation anomalies force the sea ice variations. However, there appears to be a local response of the atmospheric circulation to the changing sea ice variations. However, there appears to be a local response of the atmospheric circulation to the changing sea ice cover east of Greenland. Specifically, cyclone frequencies have increased and mean SLPs have decreased over the retracted ice margin in the Greenland Sea, and these changes differ from those associated directly with the North Atlantic oscillation. The dominant mode of sea ice variability in summer (July-September) is more spatially uniform than that in winter. Summer ice extent for the Arctic as a whole has exhibited a nearly monotonic decline (-4% decade{sup {minus}1}) during the past 40 yr. Summer sea ice variations appear to be initiated by atmospheric circulation anomalies over the high Arctic in late spring. Positive ice-albedo feedback may account for the relatively long delay (2--3 months) between the time of atmospheric forcing and the maximum ice response, and it may have served to amplify the summer ice retreat.« less

Applying ADLs to Assess Emerging Industry Specifications for Dynamic Discovery of Ad Hoc Network Services

DTIC Science & Technology

2001-01-31

function of Jini, UPnP, SLP, Bluetooth , and HAVi • Projected specific UML models for Jini, UPnP, and SLP • Developed a Rapide Model of Jini...is used by all JINI entities in directed -- discovery mode. It is part of the SCM_Discovery -- Module. Sends Unicast messages to SCMs on list of... SCMS to be discovered until all SCMS are found. -- Receives updates from SCM DB of discovered SCMs and -- removes SCMs accordingly -- NOTE

Method to characterize directional changes in Arctic sea ice drift and associated deformation due to synoptic atmospheric variations using Lagrangian dispersion statistics

NASA Astrophysics Data System (ADS)

Lukovich, Jennifer V.; Geiger, Cathleen A.; Barber, David G.

2017-07-01

A framework is developed to assess the directional changes in sea ice drift paths and associated deformation processes in response to atmospheric forcing. The framework is based on Lagrangian statistical analyses leveraging particle dispersion theory which tells us whether ice drift is in a subdiffusive, diffusive, ballistic, or superdiffusive dynamical regime using single-particle (absolute) dispersion statistics. In terms of sea ice deformation, the framework uses two- and three-particle dispersion to characterize along- and across-shear transport as well as differential kinematic parameters. The approach is tested with GPS beacons deployed in triplets on sea ice in the southern Beaufort Sea at varying distances from the coastline in fall of 2009 with eight individual events characterized. One transition in particular follows the sea level pressure (SLP) high on 8 October in 2009 while the sea ice drift was in a superdiffusive dynamic regime. In this case, the dispersion scaling exponent (which is a slope between single-particle absolute dispersion of sea ice drift and elapsed time) changed from superdiffusive (α ˜ 3) to ballistic (α ˜ 2) as the SLP was rounding its maximum pressure value. Following this shift between regimes, there was a loss in synchronicity between sea ice drift and atmospheric motion patterns. While this is only one case study, the outcomes suggest similar studies be conducted on more buoy arrays to test momentum transfer linkages between storms and sea ice responses as a function of dispersion regime states using scaling exponents. The tools and framework developed in this study provide a unique characterization technique to evaluate these states with respect to sea ice processes in general. Application of these techniques can aid ice hazard assessments and weather forecasting in support of marine transportation and indigenous use of near-shore Arctic areas.

T Cell Costimulation by CD6 Is Dependent on Bivalent Binding of a GADS/SLP-76 Complex.

PubMed

Breuning, Johannes; Brown, Marion H

2017-06-01

The cell surface receptor CD6 regulates T cell activation in both activating and inhibitory manners. The adaptor protein SLP-76 is recruited to the phosphorylated CD6 cytoplasmic Y662 residue during T cell activation, providing an activating signal to T cells. In this study, a biochemical approach identified the SH2 domain-containing adaptor protein GADS as the dominant interaction partner for the CD6 cytoplasmic Y629 residue. Functional experiments in human Jurkat and primary T cells showed that both mutations Y629F and Y662F abolished costimulation by CD6. In addition, a restraint on T cell activation by CD6 was revealed in primary T cells expressing CD6 mutated at Y629 and Y662. These data are consistent with a model in which bivalent recruitment of a GADS/SLP-76 complex is required for costimulation by CD6. Copyright © 2017 Breuning and Brown.

Development of nanoscale structure in LAT-based signaling complexes

PubMed Central

2016-01-01

ABSTRACT The adapter molecule linker for activation of T cells (LAT) plays a crucial role in forming signaling complexes induced by stimulation of the T cell receptor (TCR). These multi-molecular complexes are dynamic structures that activate highly regulated signaling pathways. Previously, we have demonstrated nanoscale structure in LAT-based complexes where the adapter SLP-76 (also known as LCP2) localizes to the periphery of LAT clusters. In this study, we show that initially LAT and SLP-76 are randomly dispersed throughout the clusters that form upon TCR engagement. The segregation of LAT and SLP-76 develops near the end of the spreading process. The local concentration of LAT also increases at the same time. Both changes require TCR activation and an intact actin cytoskeleton. These results demonstrate that the nanoscale organization of LAT-based signaling complexes is dynamic and indicates that different kinds of LAT-based complexes appear at different times during T cell activation. PMID:27875277

Sub-luminal pulses from cosmic ray air showers

NASA Technical Reports Server (NTRS)

Linsley, J.

1985-01-01

Some of the signals produced by air showers in scintillators possess a distinctive feature, a sub-luminal pulse (SLP) following the normal one with a time delay of approximately 1.5 r/c. The average amplitude of the SLP corresponds to an energy deposit of about 50 MeV, three times as much as is deposited in a typical scintillator by vertical minimum ionizing muons. The SLP account for approximately 5% of the energy deposited in the atmosphere by IR showers with energy 10 to the 10th power GeV at impact parameters 1 km. Assuming that these pulses are due to neutrons travelling with a speed slightly less than c, they provide a unique means of estimating E sub h, the energy deposited by slow hadrons, in showers of this very high energy. On the other hand, if not allowed for properly, these pulses are liable to cause errors in estimating the impact parameters of large showers from pulse width observations.

Amplicon Sequencing of the slpH Locus Permits Culture-Independent Strain Typing of Lactobacillus helveticus in Dairy Products

PubMed Central

Moser, Aline; Wüthrich, Daniel; Bruggmann, Rémy; Eugster-Meier, Elisabeth; Meile, Leo; Irmler, Stefan

2017-01-01

The advent of massive parallel sequencing technologies has opened up possibilities for the study of the bacterial diversity of ecosystems without the need for enrichment or single strain isolation. By exploiting 78 genome data-sets from Lactobacillus helveticus strains, we found that the slpH locus that encodes a putative surface layer protein displays sufficient genetic heterogeneity to be a suitable target for strain typing. Based on high-throughput slpH gene sequencing and the detection of single-base DNA sequence variations, we established a culture-independent method to assess the biodiversity of the L. helveticus strains present in fermented dairy food. When we applied the method to study the L. helveticus strain composition in 15 natural whey cultures (NWCs) that were collected at different Gruyère, a protected designation of origin (PDO) production facilities, we detected a total of 10 sequence types (STs). In addition, we monitored the development of a three-strain mix in raclette cheese for 17 weeks. PMID:28775722

Repeatability and Reproducibility of Retinal Nerve Fiber Layer Parameters Measured by Scanning Laser Polarimetry with Enhanced Corneal Compensation in Normal and Glaucomatous Eyes

PubMed Central

Ara, Mirian; Pajarin, Ana B.

2015-01-01

Objective. To assess the intrasession repeatability and intersession reproducibility of peripapillary retinal nerve fiber layer (RNFL) thickness parameters measured by scanning laser polarimetry (SLP) with enhanced corneal compensation (ECC) in healthy and glaucomatous eyes. Methods. One randomly selected eye of 82 healthy individuals and 60 glaucoma subjects was evaluated. Three scans were acquired during the first visit to evaluate intravisit repeatability. A different operator obtained two additional scans within 2 months after the first session to determine intervisit reproducibility. The intraclass correlation coefficient (ICC), coefficient of variation (COV), and test-retest variability (TRT) were calculated for all SLP parameters in both groups. Results. ICCs ranged from 0.920 to 0.982 for intravisit measurements and from 0.910 to 0.978 for intervisit measurements. The temporal-superior-nasal-inferior-temporal (TSNIT) average was the highest (0.967 and 0.946) in normal eyes, while nerve fiber indicator (NFI; 0.982) and inferior average (0.978) yielded the best ICC in glaucomatous eyes for intravisit and intervisit measurements, respectively. All COVs were under 10% in both groups, except NFI. TSNIT average had the lowest COV (2.43%) in either type of measurement. Intervisit TRT ranged from 6.48 to 12.84. Conclusions. The reproducibility of peripapillary RNFL measurements obtained with SLP-ECC was excellent, indicating that SLP-ECC is sufficiently accurate for monitoring glaucoma progression. PMID:26185762

The Breadth of Synthetic Long Peptide Vaccine-Induced CD8+ T Cell Responses Determines the Efficacy against Mouse Cytomegalovirus Infection

PubMed Central

Panagioti, Eleni; Redeker, Anke; van Duikeren, Suzanne; Franken, Kees LMC; Drijfhout, Jan Wouter; van der Burg, Sjoerd H.

2016-01-01

There is an ultimate need for efficacious vaccines against human cytomegalovirus (HCMV), which causes severe morbidity and mortality among neonates and immunocompromised individuals. In this study we explored synthetic long peptide (SLP) vaccination as a platform modality to protect against mouse CMV (MCMV) infection in preclinical mouse models. In both C57BL/6 and BALB/c mouse strains, prime-booster vaccination with SLPs containing MHC class I restricted epitopes of MCMV resulted in the induction of strong and polyfunctional (i.e., IFN-γ+, TNF+, IL-2+) CD8+ T cell responses, equivalent in magnitude to those induced by the virus itself. SLP vaccination initially led to the formation of effector CD8+ T cells (KLRG1hi, CD44hi, CD127lo, CD62Llo), which eventually converted to a mixed central and effector-memory T cell phenotype. Markedly, the magnitude of the SLP vaccine-induced CD8+ T cell response was unrelated to the T cell functional avidity but correlated to the naive CD8+ T cell precursor frequency of each epitope. Vaccination with single SLPs displayed various levels of long-term protection against acute MCMV infection, but superior protection occurred after vaccination with a combination of SLPs. This finding underlines the importance of the breadth of the vaccine-induced CD8+ T cell response. Thus, SLP-based vaccines could be a potential strategy to prevent CMV-associated disease. PMID:27637068

Identification of extracellular surface-layer associated proteins in Lactobacillus acidophilus NCFM

PubMed Central

Johnson, Brant; Selle, Kurt; O’Flaherty, Sarah; Goh, Yong Jun

2013-01-01

Bacterial surface (S-) layers are crystalline arrays of self-assembling, proteinaceous subunits called S-layer proteins (Slps), with molecular masses ranging from 40 to 200 kDa. The S-layer-forming bacterium Lactobacillus acidophilus NCFM expresses three major Slps: SlpA (46 kDa), SlpB (47 kDa) and SlpX (51 kDa). SlpA has a demonstrated role in adhesion to Caco-2 intestinal epithelial cells in vitro, and has been shown to modulate dendritic cell (DC) and T-cell functionalities with murine DCs. In this study, a modification of a standard lithium chloride S-layer extraction revealed 37 proteins were solubilized from the S-layer wash fraction. Of these, 30 have predicted cleavage sites for secretion, 24 are predicted to be extracellular, six are lipid-anchored, three have N-terminal hydrophobic membrane spanning regions and four are intracellular, potentially moonlighting proteins. Some of these proteins, designated S-layer associated proteins (SLAPs), may be loosely associated with or embedded within the bacterial S-layer complex. Lba-1029, a putative SLAP gene, was deleted from the chromosome of L. acidophilus. Phenotypic characterization of the deletion mutant demonstrated that the SLAP LBA1029 contributes to a pro-inflammatory TNF-α response from murine DCs. This study identified extracellular proteins and putative SLAPs of L. acidophilus NCFM using LC-MS/MS. SLAPs appear to impart important surface display features and immunological properties to microbes that are coated by S-layers. PMID:24002751

Polymorphism in and localization of the gene LCP2 (SLP-76) to chromosome 5q33.1-qter

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

Sunden, S.L.F.; Carr, L.L.; Clements, J.L.

This report describes the localization of the human LCP2 gene to human chromosome 5q33.1-qter using single-stranded conformation polymorphisms analysis. This gene encodes an SH2 domain containing leukocyte protein of 76 kDa (SLP-76), which plays a functional role in T-cell activation. It remains to be determined whether mutations in this gene or translocations at this chromosome location are the genetic basis for various diseases, including lymphoblastic leukemia. 12 refs., 1 fig.

Study on workshop layout of a motorcycle company based on systematic layout planning (SLP)

NASA Astrophysics Data System (ADS)

Zhou, Kang-Qu; Zhang, Rui-Juan; Wang, Ying-Dong; Wang, Bing-Jie

2010-08-01

The method of SLP has been applied in a motorcycle company's layout planning. In this layout design, the related graphics have been used to illuminate the logistics and non-logistics relationships of every workshop to get the integrated relationships of workshops and preliminary plans. Comparing the two preliminary plans including logistics efficiency, space utilization, management conveniences, etc, an improvement solution is proposed. Through the improvement solution, the productivity has been increased by 18% and the production capacity is able to make 1600 engines each day.

HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial.

PubMed

van Poelgeest, Mariette I E; Welters, Marij J P; van Esch, Edith M G; Stynenbosch, Linda F M; Kerpershoek, Gijs; van Persijn van Meerten, Els L; van den Hende, Muriel; Löwik, Margriet J G; Berends-van der Meer, Dorien M A; Fathers, Lorraine M; Valentijn, A Rob P M; Oostendorp, Jaap; Fleuren, Gert Jan; Melief, Cornelis J M; Kenter, Gemma G; van der Burg, Sjoerd H

2013-04-04

Human papilloma virus type 16 (HPV16)-induced gynecological cancers, in particular cervical cancers, are found in many women worldwide. The HPV16 encoded oncoproteins E6 and E7 are tumor-specific targets for the adaptive immune system permitting the development of an HPV16-synthetic long peptide (SLP) vaccine with an excellent treatment profile in animal models. Here, we determined the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in patients with advanced or recurrent HPV16-induced gynecological carcinoma. Patients with HPV16-positive advanced or recurrent gynecological carcinoma (n = 20) were subcutaneously vaccinated with an HPV16-SLP vaccine consisting of a mix of 13 HPV16 E6 and HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant. The primary endpoints were safety, toxicity and tumor regression as determined by RECIST. In addition, the vaccine-induced T-cell response was assessed by proliferation and associated cytokine production as well as IFNγ-ELISPOT. No systemic toxicity beyond CTCAE grade II was observed. In a few patients transient flu-like symptoms were observed. In 9 out of 16 tested patients vaccine-induced HPV16-specific proliferative responses were detected which were associated with the production of IFNγ, TNFα, IL-5 and/or IL-10. ELISPOT analysis revealed a vaccine-induced immune response in 11 of the 13 tested patients. The capacity to respond to the vaccine was positively correlated to the patient's immune status as reflected by their response to common recall antigens at the start of the trial. Median survival was 12.6 ± 9.1 months. No regression of tumors was observed among the 12 evaluable patients. Nineteen patients died of progressive disease. The HPV16-SLP vaccine was well tolerated and induced a broad IFNγ-associated T-cell response in patients with advanced or recurrent HPV16-induced gynecological carcinoma but neither induced tumor regression nor prevented progressive disease. We, therefore, plan to use this vaccine in combination with chemotherapy and immunomodulation.

Family-centered early intervention: an opportunity for creative practice in speech-language pathology.

PubMed

Gillette, Y

1992-01-01

Services for developmentally delayed children from birth to age three consider the family first. Eligibility for services is determined through a multidisciplinary assessment. Once a child qualifies for service, a multidisciplinary team that includes the family develops an IFSP. The SLP may serve as the service coordinator for the plan or as a team member. The plans must contain specific information that includes documentation of current status and major outcomes for the coming year. An SLP may find that contributing effectively to an IFSP requires new competencies. First, the SLP will need to learn to function in the family-centered, multidisciplinary process of early intervention. Second, the SLP may need to develop creative models to deliver effective service. SLPs can contribute valuable information to the IFSP by finding ways to activate daily life routines to promote a child's communication skills. SLPs can explore the child's life-space, including routines and partners, as a source of contexts for treatment. SLPs also can explore partner communication strategies, note their effects on the child's communication experiences, and recommend additional strategies for treatment. The case study illustrated an individual, home-based intervention program (Gillette, 1989; Lombardino and Magnan, 1983). Other service delivery models can include classroom-based approaches (Wilcox, Kouri, and Caswell, 1991); group parent training approaches (Weistuch, Lewis, and Sullivan, 1991; Cheseldine and McConkey, 1979); and video-assisted approaches (McConkey, 1988; Johnson and Harrison, 1990; Gillette, in press). Many SLPs may find that the process of early intervention with the birth-to-three population offers unique opportunities for practice in their profession. To function effectively in this process, the SLP needs communication-based information to promote the child's communication skills within his or her daily life and sensitivity with which to design a plan that considers the family first, yet meets the needs of the child. Although alternative models of delivering speech-language service have been explored, the process of early intervention will continue to require professionals who can creatively match family priorities with the child's intervention needs.

Acetyl group availability influences phosphocreatine degradation even during intense muscle contraction

PubMed Central

Timmons, James A; Constantin-Teodosiu, Dumitru; Poucher, Simon M; Greenhaff, Paul L

2004-01-01

We previously established that activation of the pyruvate dehydrogenase complex (PDC) using dichloroacetate (DCA) reduced the reliance on substrate-level phosphorylation (SLP) at the onset of exercise, with normal and reduced blood flow. PDC activation also reduced fatigue development during contraction with reduced blood flow. Since these observations, several studies have re-evaluated our observations. One study demonstrated a performance benefit without a reduction in SLP, raising a question mark over PDC's role in the regulation of ATP regeneration and our interpretation of fatigue mechanisms. Using a model of muscle contraction similar to the conflicting study (i.e. tetanic rather than twitch stimulation), we re-examined this question. Using canine skeletal muscle, one group was infused with saline while the other was pretreated with 300 mg (kg body mass)−1 DCA. Muscle biopsies were taken at rest, peak tension (1 min) and after 6 min of tetanic electrical stimulation (75 ms on−925 ms off per second) and blood flow was limited to 25% of normal values observed during contraction. DCA reduced phosphocreatine (PCr) degradation by 40% during the first minute of contraction, but did not prevent the almost complete depletion of PCr stores at 6 min, while muscle fatigue did not differ between the two groups. During intermittent tetanic stimulation PCr degradation was 75% greater than with our previous 3 Hz twitch contraction protocol, despite a similar rate of oxygen consumption at 6 min. Thus, in the present study enhanced acetyl group availability altered the time course of PCr utilization but did not prevent the decline towards depletion. Consistent with our earlier conclusions, DCA pretreatment reduces muscle fatigue only when SLP is attenuated. The present study and our met-analysis indicates that enhanced acetyl group availability results in a readily measurable reduction in SLP when the initial rate of PCr utilization is ∼1 mmol (kg dry mass)−1 s−1 or less (depending on intrinsic mitochondrial capacity). When measured early during an uninterrupted period of muscle contraction, acetyl group availability is likely to influence SLP under any condition where mitochondria are responsible for a significant proportion of ATP regeneration. PMID:15498812

Iron oxide nanoparticles modified with silanes for hyperthermia applications

NASA Astrophysics Data System (ADS)

Storozhuk, Liudmyla; Iukhymenko, Natalia

2018-04-01

Fe3O4-HDTMS nanocomposites were prepared and studied using Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy, X-ray analysis, thermal analysis (TGA), dynamic light scattering analysis, magnetic and specific loss power (SLP) measurements. FTIR results showed that during the modification, the formation of the silane coating occurs due to the appearance of the magnetite-O-Si-R bond. According to TGA results, the mass loss in the range of temperatures 410-650 °C is due to the destruction of covalent bonds Fe-O-Si. The Si-O-R coating leads to the decrease in the absolute value of the effective saturation magnetization due to the presence of a non-magnetic phase (coating) in the sample, but the coercivity increases with the coating thickness due to higher effective values of the magnetic anisotropy of the magnetostrictive nature. The thermal response of NP-based dispersions in silicone and oleic acid was shown that SLP value is higher for magnetic material dispersions in Lipiodol and oleic acid compared to silicone-based dispersions. This can be explained by the contribution of both Neel and Brownian relaxation processes. However, in the case of silicone-based dispersion, Brownian relaxation is negligible because of NP immobilization in viscous silicone matrix. As it is to the effect of coating on SLP, this is clearly evident in the case of silicone dispersions. The study of the heating ability of dispersions based on HDTMS-modified Fe3O4 NPs showed that the coating does not significantly decrease the SLP values.

Atypical retardation patterns in scanning laser polarimetry are associated with low peripapillary choroidal thickness.

PubMed

Tornow, Ralf P; Schrems, Wolfgang A; Bendschneider, Delia; Horn, Folkert K; Mayer, Markus; Mardin, Christian Y; Lämmer, Robert

2011-09-29

Scanning laser polarimetry (SLP) results can be affected by an atypical retardation pattern (ARP). One reason for an ARP is the birefringence of the sclera. The purpose of this study was to investigate the influence of the peripapillary choroidal thickness (pChTh) on the occurrence of ARP. One hundred ten healthy subjects were investigated with SLP and spectral domain OCT. pChTh was measured in B-scan images at 768 positions using semiautomatic software. Values were averaged to 32 sectors and the total peripapillary mean. Subjects were divided into four groups according to the typical scan score (TSS) provided by the GDxVCC: group 1 TSS, 100; group 2 TSS, 90-99; group 3 TSS, 80-89; group 4 TSS, <80. Mean pChTh (± SD) in 110 healthy subjects was 141 μm (±49 μm). There was a significant correlation between pChTh and TSS (r = 0.608; P < 0.001). In TSS groups 1 to 4, mean pChTh was 168 μm (±38 μm), 148 μm (± 48 μm), 119 μm (±35 μm), and 92 (±42 μm). Mean pChTh of TSS groups 3 and 4 was significantly lower than that of TSS group 1 (P < 0.001). Low values of TSS resulting from the appearance of ARP in SLP are associated with low peripapillary choroidal thickness. Reduced choroidal thickness may result in an increased amount of confounding light getting to the SLP light detectors.

Effect of short-term low-protein diet supplemented with keto acids on hyperphosphatemia in maintenance hemodialysis patients.

PubMed

Li, Haiming; Long, Quan; Shao, Chunhai; Fan, Hong; Yuan, Li; Huang, Bihong; Gu, Yong; Lin, Shanyan; Hao, Chuanming; Chen, Jing

2011-01-01

To evaluate the effects of short-term restriction of dietary protein intake (DPI) supplemented with keto acids on hyperphosphatemia in maintenance hemodialysis (MHD) patients. Forty MHD patients with uncontrolled hyperphosphatemia were randomized to either low DPI with keto acid-supplemented (sLP) or normal DPI (NP) group for 8 weeks. After 8 weeks, the sLP group was shifted to NP for another 8 weeks. Low-protein diet (LPD) was individualized with total caloric intake 30-35 kcal/kg/day, protein intake of 0.8 g/kg/day and phosphate intake of 500 mg/day. Keto acids were supplied in a dosage of 12 pills per day. Calcium phosphorous metabolism index and nutritional index (serum albumin, total protein, somatometric measurements, 3-day diaries and Mini-Nutritional Assessment score) were recorded. C-reactive protein, CO(2) combining power and Kt/V were measured to evaluate the inflammation, metabolic acidosis and dialysis adequacy, respectively. Serum phosphorus level and calcium-phosphate product were significantly decreased at the end of the first 8 weeks in the sLP group compared to the basal value and the NP group (p < 0.001). No difference was observed in C-reactive protein, Kt/V and nutritional index, while CO(2) combining power was significantly higher at week 8 in the sLP group (p < 0.001). Short-term restriction of DPI supplemented with keto acids could decrease hyperphosphatemia and calcium-phosphate product, while keeping stable nutritional status among MHD patients. Copyright © 2010 S. Karger AG, Basel.

The Surface Layer Homology Domain-Containing Proteins of Alkaliphilic Bacillus pseudofirmus OF4 Play an Important Role in Alkaline Adaptation via Peptidoglycan Synthesis.

PubMed

Fujinami, Shun; Ito, Masahiro

2018-01-01

It is well known that the Na + cycle and the cell wall are essential for alkaline adaptation of Na + -dependent alkaliphilic Bacillus species. In Bacillus pseudofirmus OF4, surface layer protein A (SlpA), the most abundant protein in the surface layer (S-layer) of the cell wall, is involved in alkaline adaptation, especially under low Na + concentrations. The presence of a large number of genes that encode S-layer homology (SLH) domain-containing proteins has been suggested from the genome sequence of B. pseudofirmus OF4. However, other than SlpA, the functions of SLH domain-containing proteins are not well known. Therefore, a deletion mutant of the csaB gene, required for the retention of SLH domain-containing proteins on the cell wall, was constructed to investigate its physiological properties. The csaB mutant strain of B. pseudofirmus OF4 had a chained morphology and alkaline sensitivity even under a 230 mM Na + concentration at which there is no growth difference between the parental strain and the slpA mutant strain. Ultra-thin section transmission electron microscopy showed that a csaB mutant strain lacked an S-layer part, and its peptidoglycan (PG) layer was disturbed. The slpA mutant strain also lacked an S-layer part, although its PG layer was not disturbed. These results suggested that the surface layer homology domain-containing proteins of B. pseudofirmus OF4 play an important role in alkaline adaptation via peptidoglycan synthesis.

Longitudinal Detection of Optic Nerve Head Changes by Spectral Domain Optical Coherence Tomography in Early Experimental Glaucoma

PubMed Central

He, Lin; Yang, Hongli; Gardiner, Stuart K.; Williams, Galen; Hardin, Christy; Strouthidis, Nicholas G.; Fortune, Brad; Burgoyne, Claude F.

2014-01-01

Purpose. We determined if the detection of spectral-domain optical coherence tomography (SDOCT) optic nerve head (ONH) change precedes the detection of confocal scanning laser tomography (CSLT) ONH surface, SDOCT retinal nerve fiber layer (RNFL), scanning laser perimetry (SLP), and multifocal electroretinography (mfERG) change in eight experimental glaucoma (EG) eyes. Methods. Both eyes from eight monkeys were tested at least three times at baseline, and then every 2 weeks following laser-induced chronic unilateral IOP elevation. Event and trend-based definitions of onset in the control and EG eyes for 11 SDOCT neural and connective tissue, CSLT surface, SDOCT RNFL, SLP, and mfERG parameters were explored. The frequency and timing of onset for each parameter were compared using a logrank test. Results. Maximum post-laser IOP was 18 to 42 mm Hg in the EG eyes and 12 to 20 mm Hg in the control eyes. For event- and trend-based analyses, onsets were achieved earliest and most frequently within the ONH neural and connective tissues using SDOCT, and at the ONH surface using CSLT. SDOCT ONH neural and connective tissue parameter change preceded or coincided with CSLT ONH surface change in most EG eyes. The SDOCT and SLP measures of RNFL thickness, and mfERG measures of visual function demonstrated similar onset rates, but occurred later than SDOCT ONH and CSLT surface change, and in fewer eyes. Conclusions. SDOCT ONH change detection commonly precedes or coincides with CSLT ONH surface change detection, and consistently precedes RNFLT, SLP, and mfERG change detection in monkey experimental glaucoma. PMID:24255047

A recyclable protein resource derived from cauliflower by-products: Potential biological activities of protein hydrolysates.

PubMed

Xu, Yang; Li, Yuting; Bao, Tao; Zheng, Xiaodong; Chen, Wei; Wang, Jianxu

2017-04-15

Cauliflower by-products (CBP) are rich in leaf protein. Every year tons of CBP will lead to environmental pollution. Therefore, this study was conducted to extract leaf protein from CBP and investigate its biological activities. Our results showed that the optimal extraction parameters were: a liquid to solid ratio of 4mL/g, a pH of 11, an ultrasonic extraction lasting 15min, and at an applied power of 175W. Under these optimized conditions, 12.066g of soluble leaf protein (SLP) was obtained from 1000g of CBP and its extraction yield was 53.07%. The obtained SLP was further hydrolysed by Alcalase and the SLP hydrolysate (SLPH) showed a potent angiotensin I-converting enzyme (ACE) inhibitory activity with an IC 50 value of 138.545μg/mL in vitro. In addition, SLPH promoted the glucose consumption and enhanced the glycogen content in HepG2 cells. Overall, our results suggested that CBP may be recycled for designing future functional foods. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Stoplight Program: A Proactive Physical Therapy Intervention for Children With Acute Lymphoblastic Leukemia.

PubMed

Tanner, Lynn; Sencer, Susan; Hooke, Mary C

Chemotherapy may cause neuromuscular impairments that can have life-long effects. The Stoplight Program (SLP) was developed as a proactive physical therapy (PT) intervention directed at impairments in children with acute lymphoblastic leukemia (ALL). In this program evaluation, we assessed the feasibility of the SLP delivered as part of standard care and identified body function and activity patterns in patients who received the intervention. Children ages 1 to 22 years, diagnosed with ALL, received an assessment by a physical therapist as part of usual care. The SLP intervention used 3 levels to categorize the impairment levels and intensity of PT. Of the children (n = 135) screened, 46% completed 5 intervention visits and 32% completed the program and met discharge criteria. At initial assessment, 46% of children ages 1 to 5 years and 67% of children ages 6 to 22 years had abnormal motor function. Those completing the program tested within the healthy norms. Research is needed on variables that influence adherence to a PT program and the range of functional impairment and activity limitations in this population.

An electrostatic selection mechanism controls sequential kinase signaling downstream of the T cell receptor

PubMed Central

Shah, Neel H; Wang, Qi; Yan, Qingrong; Karandur, Deepti; Kadlecek, Theresa A; Fallahee, Ian R; Russ, William P; Ranganathan, Rama; Weiss, Arthur; Kuriyan, John

2016-01-01

The sequence of events that initiates T cell signaling is dictated by the specificities and order of activation of the tyrosine kinases that signal downstream of the T cell receptor. Using a platform that combines exhaustive point-mutagenesis of peptide substrates, bacterial surface-display, cell sorting, and deep sequencing, we have defined the specificities of the first two kinases in this pathway, Lck and ZAP-70, for the T cell receptor ζ chain and the scaffold proteins LAT and SLP-76. We find that ZAP-70 selects its substrates by utilizing an electrostatic mechanism that excludes substrates with positively-charged residues and favors LAT and SLP-76 phosphosites that are surrounded by negatively-charged residues. This mechanism prevents ZAP-70 from phosphorylating its own activation loop, thereby enforcing its strict dependence on Lck for activation. The sequence features in ZAP-70, LAT, and SLP-76 that underlie electrostatic selectivity likely contribute to the specific response of T cells to foreign antigens. DOI: http://dx.doi.org/10.7554/eLife.20105.001 PMID:27700984

Evaluating a Speech-Language Pathology Technology

PubMed Central

Spinardi-Panes, Ana Carulina; Lopes-Herrera, Simone Aparecida; Maximino, Luciana Paula

2014-01-01

Abstract Background: The creation of new educational strategies based on technology is the essence of telehealth. This innovative learning is an alternative to promote integration and improve the professional practices in speech-language pathology (SLP). The objective of this study was to evaluate an SLP technology designed for distance learning. Materials and Methods: The survey selected fourth-year SLP students (n=60) from three public universities in the state of São Paulo, Brazil. The experimental group (EG) contained 10 students from each university (n=30), and the remaining students formed the control group (CG). Initially, both groups answered a preprotocol questionnaire, and the EG students received the technology, the recommendations, and the deadline to explore the material. In the second stage all students answered the postprotocol questionnaire in order to evaluate the validity and the learning of the technology contents. Results: The comparison between the CG students showed that their performance worsened in the majority in comparison with the EG students, who showed an improved performance. Conclusions: Therefore, this study concluded that the technology instrument actually responded to the population studied and is recommended to complement traditional teaching. PMID:24404815

Religion, Spirituality and Speech-Language Pathology: A Viewpoint for Ensuring Patient-Centred Holistic Care.

PubMed

Mathisen, Bernice; Carey, Lindsay B; Carey-Sargeant, Christa L; Webb, Gwendalyn; Millar, CaraJane; Krikheli, Lilli

2015-12-01

This paper presents a viewpoint concerning the largely neglected clinical relevance of spirituality and religious belief in speech-language pathology (SLP) assessments, interventions and outcomes across the lifespan. An overview of the refereed SLP literature is presented with regard to religion and spirituality. It was found that while there is increasing research with regard to spirituality, health and well-being, there is very little specific to SLP. What is available and clinically relevant, generally relates to holistic care and/or cultural and linguistic diversity. Amidst the health care literature, however, there is a growing number of recommended instruments (for religious/spiritual screening) sensitive to intercultural and interfaith issues that are currently available to medical, nursing, allied health and chaplaincy practitioners. These instruments can also be of value to SLPs to ensure holistic assessments and interventions. It would seem timely for SLPs (and other allied health practitioners) to consider including spiritual screenings/assessments as part of their clinical practice so as to ensure appropriate holistic care. This would also mean undertaking research and including relevant education within tertiary institutions and professional development programs.

Clients becoming teachers: Speech-language pathology students' understanding of rehabilitation following clinical practicum in a rehabilitation setting.

PubMed

Attrill, Stacie; Gunn, Simon

2010-04-01

There has been limited research investigating the conceptual development of rehabilitation in speech-language pathology (SLP) students. The aim of this study was to describe SLP students' understanding of rehabilitation following completion of a clinical practicum in a rehabilitation setting. This study was conducted using a qualitative approach according to grounded theory methodology. Semi-structured interviews were conducted with 10 SLP students who had completed a practicum in a rehabilitation setting. Interview data analysis revealed the emergence of five axial categories. Clients becoming teachers was identified as the core category, as the notion that clients were fundamental to students' understanding of rehabilitation occurred reliably throughout the data and related to all other categories. A theoretical model was proposed that demonstrated successive levels of support to students in the acquisition of their understanding of rehabilitation on practicum. Students' understanding of rehabilitation was derived from client-related interactions and factors experienced on practicum in rehabilitation settings. Rehabilitation practicum provided students with a rich and complex learning environment that may facilitate the development of the "core skills" identified for rehabilitation practice.

Effect of SLP properties of vanadium SO/sub 2/ oxidation on reaction mechanism

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

Xie, K.C.; Nobile, A. Jr.

The SLP properties of a K/sub 2/SO/sub 4/-V/sub 2/O/sub 5/ catalysts during SO/sub 2/ oxidation and the intrinsic kinetics of the reaction on the SLPC were investigated and measured. The reason for the sudden drop in activation energy in the temperature range 440-470/sup 0/C is explained from the results of an investigation of the thermal and electrical behavior of the catalyst, and the distribution of active melt components. A reaction mechanism and rate equation consistent with the results are proposed and developed.

Heating efficiency dependency on size and morphology of magnetite nanoparticles

NASA Astrophysics Data System (ADS)

Parekh, Kinnari; Parmar, Harshida; Sharma, Vinay; Ramanujan, R. V.

2018-04-01

Different size magnetite nanoparticles ranging from superparamagnetic (9 nm) to single domain (27 nm) and multi domain (53 nm) were synthesized using chemical route. Morphology of these particles as seen from TEM images indicates shape change from spherical to cubic with the growth of particles. The saturation magnetization (σs) and Specific Loss Power (SLP) showed maximum for single domain size, 72 emu/g and 102 W/g, respectively then those of multi domain size particles. These samples show higher SLP at relatively low concentration, low frequency and low amplitude compared to samples prepared by other routes.

Prediction of Summer Extreme Precipitation over the Middle and Lower Reaches of the Yangtze River Basin

NASA Astrophysics Data System (ADS)

Liu, L.; Ning, L.; Liu, J.; Yan, M.; Sun, W.

2017-12-01

Abstract: Summer extreme precipitation (SEP) often causes severe landslide, debris flow and floods over the middle and lower reaches of the Yangtze River Basin(MLYRB), so skillful prediction of the SEP is critical to the future climate adaptions and mitigations. In this work, the characteristic region over the MLYRB (27°N-32°N,108°1-118°E) is defined by the spatial mode of the rotated empirical orthogonal functions (REOF) of SEP over the China from 1961 to 2014. A physics-based empirical model (PEM) of SEP predictions is built with two preceding predictors with significant physical influences on the SEP over the MLYRB. The first predictor is the spring sea surface temperature (SST) over the Northern Indian Ocean (20°S-20°N,50°E-95°E), and the second predictor is the spring sea surface pressure (SLP) over the Aleutian Island (50°N-70°N,160°E-160°W). Analyses of physical mechanism show that when the spring SST over the Northern Indian Ocean is higher, the South Asian High (SAH) extends to the east and the western Pacific sub-tropical high (WPSH) extends to the west, therefore, the generated secondary circulation induces anomalous upward motions and more water vapor transportation to the MLYRB, resulting more SEP. Meanwhile, when the spring SLP over the Aleutian Island is lower, the also WPSH extends to the west, which leads to a negative omega anomaly centered the MLYRB and more water vapor transportation to the MLYRB, resulting in more SEP. The regression model is built using the data from a training period from 1961 to 1999 with correlation coefficient skill of 0.57 (p<0.01) for prediction of SEP in 1961-1999. The independent forecast of the PEM shows that it is skillful in SEP prediction with the correlation coefficient between observed SEP and model-simulated SEP over the validation period 2000-2014 is 0.51 (p<0.05). This finding shows that the preceding spring SST and SLP can provide useful information for prediction of SEP, and the methodology proposed here can be applied to a wide range of climate prediction studies. The future improvements are also discussed.

Simulation of the modern arctic climate by the NCAR CCM1

NASA Technical Reports Server (NTRS)

Bromwich, David H.; Tzeng, Ren-Yow; Parish, Thomas, R.

1994-01-01

The National Center of Atmospheric Research (NCAR) Community Climate Model Version 1 (CCM1's) simulation of the modern arctic climate is evaluated by comparing a five-year seasonal cycle simulation with the European Center for Medium-Range Weather Forecasts (ECMWF) global analyses. The sea level pressure (SLP), storm tracks, vertical cross section of height, 500-hPa height, total energy budget, and moisture budget are analyzed to investigate the biases in the simulated arctic climate. The results show that the model simulates anomalously low SLP, too much storm activity, and anomalously strong baroclinicity to the west of Greenland and vice versa to the east of Greenland. This bias is mainly attributed to the model's topographic representation of Greenland. First, the broadened Greenland topography in the model distorts the path of cyclone waves over the North Atlantic Ocean. Second, the model oversimulates the ridge over Greenland, which intensifies its blocking effect and steers the cyclone waves clockwise around it and hence produces an artificial circum-Greenland trough. These biases are significantly alleviated when the horizontal resolution increases to T42. Over the Arctic basin, the model simulates large amounts of low-level (stratus) clouds in winter and almost no stratus in summer, which is opposite to the observations. This bias is mainly due to the location of the simulated SLP features and the negative anomaly of storm activity, which prevent the transport of moisture into this region during summer but favor this transport in winter. The moisture budget analysis shows that the model's net annual precipitation (P-E) between 70 deg N and the North Pole is 6.6 times larger than the observations and the model transports six times more moisture into this region. The bias in the advection term is attributed to the positive moisture fixer scheme and the distorted flow pattern. However, the excessive moisture transport into the Arctic basin does not solely result from the advection term. The contribution by the moisture fixer is as large as from advection. By contrast, the semi-Lagrangian transport scheme used in the CCM2 significantly improves the moisture simulation for this region; however, globally the error is as serious as for the positive moisture fixer scheme. Finally, because the model has such serious problems in simulating the present arctic climate, its simulations of past and future climate change for this region are questionable.

Observed Changes at the Surface of the Arctic Ocean

NASA Astrophysics Data System (ADS)

Ortmeyer, M.; Rigor, I.

2004-12-01

The Arctic has long been considered a harbinger of global climate change since simulations with global climate models predict that if the concentration of CO2 in the atmosphere doubles, the Arctic would warm by more than 5°C, compared to a warming of 2°C for subpolar regions (Manabe et al., 1991). And indeed, studies of the observational records show polar amplification of the warming trends (e.g. Serreze and Francis, 2004). These temperature trends are accompanied by myriad concurrent changes in Arctic climate. One of the first indicators of Arctic climate change was found by Walsh et al. (1996) using sea level pressure (SLP) data from the International Arctic Buoy Programme (IABP, http://iabp.apl.washington.edu). In this study, they showed that SLP over the Arctic Ocean decreased by over 4 hPa from 1979 - 1994. The decreases in SLP (winds) over the Arctic Ocean, forced changes in the circulation of sea ice and the surface ocean currents such that the Beaufort Gyre is reduced in size and speed (e.g. Rigor et al., 2002). Data from the IABP has also been assimilated into the global surface air temperature (SAT) climatologies (e.g. Jones et al. 1999), and the IABP SAT analysis shows that the temperature trends noted over land extend out over the Arctic Ocean. Specifically, Rigor et al. (2000) found warming trends in SAT over the Arctic Ocean during win¬ter and spring, with values as high as 2°C/decade in the eastern Arctic during spring. It should be noted that many of the changes in Arctic climate were first observed or explained using data from the IABP. The observations from IABP have been one of the cornerstones for environmental forecasting and studies of climate and climate change. These changes have a profound impact on wildlife and people. Many species and cultures depend on the sea ice for habitat and subsistence. Thus, monitoring the Arctic Ocean is crucial not only for our ability to detect climate change, but also to improve our understanding of the Arctic and global climate system, and for forecasting weather and sea ice conditions. The IABP provides the longest continuing record of observations for the Arctic Ocean.

Fuzzy rule-based forecast of meteorological drought in western Niger

NASA Astrophysics Data System (ADS)

Abdourahamane, Zakari Seybou; Acar, Reşat

2018-01-01

Understanding the causes of rainfall anomalies in the West African Sahel to effectively predict drought events remains a challenge. The physical mechanisms that influence precipitation in this region are complex, uncertain, and imprecise in nature. Fuzzy logic techniques are renowned to be highly efficient in modeling such dynamics. This paper attempts to forecast meteorological drought in Western Niger using fuzzy rule-based modeling techniques. The 3-month scale standardized precipitation index (SPI-3) of four rainfall stations was used as predictand. Monthly data of southern oscillation index (SOI), South Atlantic sea surface temperature (SST), relative humidity (RH), and Atlantic sea level pressure (SLP), sourced from the National Oceanic and Atmosphere Administration (NOAA), were used as predictors. Fuzzy rules and membership functions were generated using fuzzy c-means clustering approach, expert decision, and literature review. For a minimum lead time of 1 month, the model has a coefficient of determination R 2 between 0.80 and 0.88, mean square error (MSE) below 0.17, and Nash-Sutcliffe efficiency (NSE) ranging between 0.79 and 0.87. The empirical frequency distributions of the predicted and the observed drought classes are equal at the 99% of confidence level based on two-sample t test. Results also revealed the discrepancy in the influence of SOI and SLP on drought occurrence at the four stations while the effect of SST and RH are space independent, being both significantly correlated (at α < 0.05 level) to the SPI-3. Moreover, the implemented fuzzy model compared to decision tree-based forecast model shows better forecast skills.

Quantifying the Hydrologic Effect of Climate Variability in the Lower Colorado Basin

NASA Astrophysics Data System (ADS)

Switanek, M.; Troch, P. A.

2007-12-01

Regional climate patterns are driven in large part by ocean states and associated atmospheric circulations, but modified through feedbacks from land surface conditions. The latter defines the climate elasticity of a river basin. Many regions that lie between semi-arid and semi-humid zones with seasonal rainfall, for instance, experience prolonged periods of wet and dry spells. Understanding the triggers that bring a river basin from one state (e.g. wet period of late 90s in the Colorado basin) abruptly to another state (multi-year drought initiated in 2001 to present) is what motivates the present study. Our research methodology investigates the causes of regional climate variability and its effect on hydrologic response. By correlating, using different monthly time lags, sea surface temperatures (SST) and sea level pressures (SLP) with basin averaged precipitation and surface temperature, we determine the most influential regions of the Pacific Ocean on lower Colorado climate variability. Using the most correlated data for each month, we derive precipitation and temperature distributions under similar conditions to that of the El Niño Southern Oscillation (ENSO). We compare the distributions of the climatic data, given ENSO constraints on SST and SLP, to the distributions considering non-ENSO years. Finally, we use observed stream flows and climatic data to determine the basin's climate elasticity. This allows us to quantitatively translate the predicted regional climate effects of ENSO on hydrologic response. Our presentation will use data for the Little Colorado as an example to demonstrate the procedure and produce preliminary results.

Evaluation of the EURO-CORDEX RCMs to accurately simulate the Etesian wind system

NASA Astrophysics Data System (ADS)

Dafka, Stella; Xoplaki, Elena; Toreti, Andrea; Zanis, Prodromos; Tyrlis, Evangelos; Luterbacher, Jürg

2016-04-01

The Etesians are among the most persistent regional scale wind systems in the lower troposphere that blow over the Aegean Sea during the extended summer season. ΑAn evaluation of the high spatial resolution, EURO-CORDEX Regional Climate Models (RCMs) is here presented. The study documents the performance of the individual models in representing the basic spatiotemporal pattern of the Etesian wind system for the period 1989-2004. The analysis is mainly focused on evaluating the abilities of the RCMs in simulating the surface wind over the Aegean Sea and the associated large scale atmospheric circulation. Mean Sea Level Pressure (SLP), wind speed and geopotential height at 500 hPa are used. The simulated results are validated against reanalysis datasets (20CR-v2c and ERA20-C) and daily observational measurements (12:00 UTC) from the mainland Greece and Aegean Sea. The analysis highlights the general ability of the RCMs to capture the basic features of the Etesians, but also indicates considerable deficiencies for selected metrics, regions and subperiods. Some of these deficiencies include the significant underestimation (overestimation) of the mean SLP in the northeastern part of the analysis domain in all subperiods (for May and June) when compared to 20CR-v2c (ERA20-C), the significant overestimation of the anomalous ridge over the Balkans and central Europe and the underestimation of the wind speed over the Aegean Sea. Future work will include an assessment of the Etesians for the next decades using EURO-CORDEX projections under different RCP scenarios and estimate the future potential for wind energy production.

Collaboration and conquest: MTD as viewed by voice teacher (singing voice specialist) and speech-language pathologist.

PubMed

Goffi-Fynn, Jeanne C; Carroll, Linda M

2013-05-01

This study was designed as a qualitative case study to demonstrate the process of diagnosis and treatment between a voice team to manage a singer diagnosed with muscular tension dysphonia (MTD). Traditionally, literature suggests that MTD is challenging to treat and little in the literature directly addresses singers with MTD. Data collected included initial medical screening with laryngologist, referral to speech-language pathologist (SLP) specializing in voice disorders among singers, and adjunctive voice training with voice teacher trained in vocology (singing voice specialist or SVS). Initial target goals with SLP included reducing extrinsic laryngeal tension, using a relaxed laryngeal posture, and effective abdominal-diaphragmatic support for all phonation events. Balance of respiratory forces, laryngeal coordination, and use of optimum filtering of the source signal through resonance and articulatory awareness was emphasized. Further work with SVS included three main goals including a lowered breathing pattern to aid in decreasing subglottic air pressure, vertical laryngeal position to lower to allow for a relaxed laryngeal position, and a top-down singing approach to encourage an easier, more balanced registration, and better resonance. Initial results also emphasize the retraining of subject toward a sensory rather than auditory mode of monitoring. Other areas of consideration include singers' training and vocal use, the psychological effects of MTD, the personalities potentially associated with it, and its relationship with stress. Finally, the results emphasize that a positive rapport with the subject and collaboration between all professionals involved in a singer's care are essential for recovery. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Hydrometeorological variability on a large french catchment and its relation to large-scale circulation across temporal scales

NASA Astrophysics Data System (ADS)

Massei, Nicolas; Dieppois, Bastien; Fritier, Nicolas; Laignel, Benoit; Debret, Maxime; Lavers, David; Hannah, David

2015-04-01

In the present context of global changes, considerable efforts have been deployed by the hydrological scientific community to improve our understanding of the impacts of climate fluctuations on water resources. Both observational and modeling studies have been extensively employed to characterize hydrological changes and trends, assess the impact of climate variability or provide future scenarios of water resources. In the aim of a better understanding of hydrological changes, it is of crucial importance to determine how and to what extent trends and long-term oscillations detectable in hydrological variables are linked to global climate oscillations. In this work, we develop an approach associating large-scale/local-scale correlation, enmpirical statistical downscaling and wavelet multiresolution decomposition of monthly precipitation and streamflow over the Seine river watershed, and the North Atlantic sea level pressure (SLP) in order to gain additional insights on the atmospheric patterns associated with the regional hydrology. We hypothesized that: i) atmospheric patterns may change according to the different temporal wavelengths defining the variability of the signals; and ii) definition of those hydrological/circulation relationships for each temporal wavelength may improve the determination of large-scale predictors of local variations. The results showed that the large-scale/local-scale links were not necessarily constant according to time-scale (i.e. for the different frequencies characterizing the signals), resulting in changing spatial patterns across scales. This was then taken into account by developing an empirical statistical downscaling (ESD) modeling approach which integrated discrete wavelet multiresolution analysis for reconstructing local hydrometeorological processes (predictand : precipitation and streamflow on the Seine river catchment) based on a large-scale predictor (SLP over the Euro-Atlantic sector) on a monthly time-step. This approach basically consisted in 1- decomposing both signals (SLP field and precipitation or streamflow) using discrete wavelet multiresolution analysis and synthesis, 2- generating one statistical downscaling model per time-scale, 3- summing up all scale-dependent models in order to obtain a final reconstruction of the predictand. The results obtained revealed a significant improvement of the reconstructions for both precipitation and streamflow when using the multiresolution ESD model instead of basic ESD ; in addition, the scale-dependent spatial patterns associated to the model matched quite well those obtained from scale-dependent composite analysis. In particular, the multiresolution ESD model handled very well the significant changes in variance through time observed in either prepciptation or streamflow. For instance, the post-1980 period, which had been characterized by particularly high amplitudes in interannual-to-interdecadal variability associated with flood and extremely low-flow/drought periods (e.g., winter 2001, summer 2003), could not be reconstructed without integrating wavelet multiresolution analysis into the model. Further investigations would be required to address the issue of the stationarity of the large-scale/local-scale relationships and to test the capability of the multiresolution ESD model for interannual-to-interdecadal forecasting. In terms of methodological approach, further investigations may concern a fully comprehensive sensitivity analysis of the modeling to the parameter of the multiresolution approach (different families of scaling and wavelet functions used, number of coefficients/degree of smoothness, etc.).

Statistical downscaling of summer precipitation over northwestern South America

NASA Astrophysics Data System (ADS)

Palomino Lemus, Reiner; Córdoba Machado, Samir; Raquel Gámiz Fortis, Sonia; Castro Díez, Yolanda; Jesús Esteban Parra, María

2015-04-01

In this study a statistical downscaling (SD) model using Principal Component Regression (PCR) for simulating summer precipitation in Colombia during the period 1950-2005, has been developed, and climate projections during the 2071-2100 period by applying the obtained SD model have been obtained. For these ends the Principal Components (PCs) of the SLP reanalysis data from NCEP were used as predictor variables, while the observed gridded summer precipitation was the predictand variable. Period 1950-1993 was utilized for calibration and 1994-2010 for validation. The Bootstrap with replacement was applied to provide estimations of the statistical errors. All models perform reasonably well at regional scales, and the spatial distribution of the correlation coefficients between predicted and observed gridded precipitation values show high values (between 0.5 and 0.93) along Andes range, north and north Pacific of Colombia. Additionally, the ability of the MIROC5 GCM to simulate the summer precipitation in Colombia, for present climate (1971-2005), has been analyzed by calculating the differences between the simulated and observed precipitation values. The simulation obtained by this GCM strongly overestimates the precipitation along a horizontal sector through the center of Colombia, especially important at the east and west of this country. However, the SD model applied to the SLP of the GCM shows its ability to faithfully reproduce the rainfall field. Finally, in order to get summer precipitation projections in Colombia for the period 1971-2100, the downscaled model, recalibrated for the total period 1950-2010, has been applied to the SLP output from MIROC5 model under the RCP2.6, RCP4.5 and RCP8.5 scenarios. The changes estimated by the SD models are not significant under the RCP2.6 scenario, while for the RCP4.5 and RCP8.5 scenarios a significant increase of precipitation appears regard to the present values in all the regions, reaching around the 27% in northern Colombia region under the RCP8.5 scenario. Keywords: Statistical downscaling, precipitation, Principal Component Regression, climate change, Colombia. ACKNOWLEDGEMENTS This work has been financed by the projects P11-RNM-7941 (Junta de Andalucía-Spain) and CGL2013-48539-R (MINECO-Spain, FEDER).

T cell specific adaptor protein (TSAd) promotes interaction of Nck with Lck and SLP-76 in T cells.

PubMed

Hem, Cecilie Dahl; Sundvold-Gjerstad, Vibeke; Granum, Stine; Koll, Lise; Abrahamsen, Greger; Buday, Laszlo; Spurkland, Anne

2015-07-11

The Lck and Src binding adaptor protein TSAd (T cell specific adaptor) regulates actin polymerization in T cells and endothelial cells. The molecular details as to how TSAd regulates this process remain to be elucidated. To identify novel interaction partners for TSAd, we used a scoring matrix-assisted ligand algorithm (SMALI), and found that the Src homology 2 (SH2) domain of the actin regulator Non-catalytic region of tyrosine kinase adaptor protein (Nck) potentially binds to TSAd phosphorylated on Tyr(280) (pTyr(280)) and pTyr(305). These predictions were confirmed by peptide array analysis, showing direct binding of recombinant Nck SH2 to both pTyr(280) and pTyr(305) on TSAd. In addition, the SH3 domains of Nck interacted with the proline rich region (PRR) of TSAd. Pull-down and immunoprecipitation experiments further confirmed the Nck-TSAd interactions through Nck SH2 and SH3 domains. In line with this Nck and TSAd co-localized in Jurkat cells as assessed by confocal microscopy and imaging flow cytometry. Co-immunoprecipitation experiments in Jurkat TAg cells lacking TSAd revealed that TSAd promotes interaction of Nck with Lck and SLP-76, but not Vav1. TSAd expressing Jurkat cells contained more polymerized actin, an effect dependent on TSAd exon 7, which includes interactions sites for both Nck and Lck. TSAd binds to and co-localizes with Nck. Expression of TSAd increases both Nck-Lck and Nck-SLP-76 interaction in T cells. Recruitment of Lck and SLP-76 to Nck by TSAd could be one mechanism by which TSAd promotes actin polymerization in activated T cells.

Structure–Activity Relationship Studies and in Vivo Activity of Guanidine-Based Sphingosine Kinase Inhibitors: Discovery of SphK1- and SphK2-Selective Inhibitors

PubMed Central

Kharel, Yugesh; Raje, Mithun R.; Gao, Ming; Tomsig, Jose L.; Lynch, Kevin R.; Santos, Webster L.

2015-01-01

Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that acts as a ligand for five G-protein coupled receptors (S1P1–5) whose downstream effects are implicated in a variety of important pathologies including sickle cell disease, cancer, inflammation, and fibrosis. The synthesis of S1P is catalyzed by sphingosine kinase (SphK) isoforms 1 and 2, and hence, inhibitors of this phosphorylation step are pivotal in understanding the physiological functions of SphKs. To date, SphK1 and 2 inhibitors with the potency, selectivity, and in vivo stability necessary to determine the potential of these kinases as therapeutic targets are lacking. Herein, we report the design, synthesis, and structure–activity relationship studies of guanidine-based SphK inhibitors bearing an oxadiazole ring in the scaffold. Our studies demonstrate that SLP120701, a SphK2-selective inhibitor (Ki = 1 μM), decreases S1P levels in histiocytic lymphoma (U937) cells. Surprisingly, homologation with a single methylene unit between the oxadiazole and heterocyclic ring afforded a SphK1-selective inhibitor in SLP7111228 (Ki = 48 nM), which also decreased S1P levels in cultured U937 cells. In vivo application of both compounds, however, resulted in contrasting effect in circulating levels of S1P. Administration of SLP7111228 depressed blood S1P levels while SLP120701 increased levels of S1P. Taken together, these compounds provide an in vivo chemical toolkit to interrogate the effect of increasing or decreasing S1P levels and whether such a maneuver can have implications in disease states. PMID:25643074

Improved plasma amino acids pattern following 12 months of supplemented low-protein diet in peritoneal dialysis patients.

PubMed

Jiang, Na; Qian, Jiaqi; Lin, Aiwu; Fang, Wei; Cao, Liou; Wang, Qin; Ni, Zhaohui; Lindholm, Bengt; Axelsson, Jonas; Yao, Qiang

2010-07-01

Decreased plasma essential amino acid (EAA) levels, increased nonessential amino acid (NEAA) levels, and low EAA to NEAA ratio (E/NEAA) are common in peritoneal dialysis (PD) patients and may impact uremic complications. In the present study, we investigate the impact of keto acids-supplemented low-protein (sLP) diet on plasma amino acids (AAs) patterns in stable PD patients. This is a supplemental analysis of a previously published prospective and randomized trial. Thirty-nine PD patients selected from the original population were divided to receive either low (LP: 0.6-0.8 g/kg ideal body weight [IBW]/d, n = 13), keto acids-supplemented low- (sLP: 0.6-0.8 g/kg IBW/d + 0.12 g/kg IBW/d of keto acids, n = 12), or high- (HP: 1.0-1.2 g/kg IBW/d, n = 14) protein diets and followed for 1 year. Plasma AA patterns were assessed at baseline and 12 months using high-performance liquid chromatography. Whereas there were no significant differences between the three groups at baseline, following 12 months, the E/NEAA had increased significantly in group sLP (0.58 +/- 0.16 to 0.83 +/- 0.20, p < 0.05), but was not different in either LP (0.62 +/- 0.20 to 0.72 +/- 0.13, p = ns) or HP (0.66 +/- 0.14 to 0.74 +/- 0.12, p = ns) group. This change in E/NEAA in group sLP was due to a significant decrease in NEAA concomitantly with maintained EAA levels, whereas in the other two groups, neither EAA nor NEAA changed significantly. A low-protein diet supplemented with keto acids significantly improved the pattern of plasma AA in prevalent PD patients.

On the use of Godhavn H-component as an indicator of the interplanetary sector polarity

NASA Technical Reports Server (NTRS)

Svalgaard, L.

1974-01-01

An objective method of inferring the polarity of the interplanetary magnetic field using the H-component at Godhavn is presented. The objectively inferred polarities are compared with a subjective index inferred earlier. It is concluded that no significant difference exists between the two methods. The inferred polarities derived from Godhavn H is biased by the (slp) sub q signature in the sense that during summer prolonged intervals of geomagnetic calm will result in inferred Away polarity regardless of the actual sector polarity. This bias does not significantly alter the large scale structure of the inferred sector structure.

Processing-in-Memory Technology for Knowledge Discovery Algorithms

DTIC Science & Technology

2006-07-01

e MP EG 2-d ist1 EP IC -u nq ua nti ze GS M- Ca lcu lat ion Sp ee du p ov er b as el in e MIT-SLP SLP SLPCF SLPCF+SLL 15 8 our infrastructure...to non-threat groups as well. Figure 15: Summary of ARDA/Eagle Data Sets. D at as et #o f N od es (P eo pl e ) #o f L in ks A vg . F an ou t Ph...on e C al ls Te le co ns Te le co n R es po nd en ts A vg . T el ec on Pa rt

Semilinear programming: applications and implementation

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

Mohan, S.

Semilinear programming is a method of solving optimization problems with linear constraints where the non-negativity restrictions on the variables are dropped and the objective function coefficients can take on different values depending on whether the variable is positive or negative. The simplex method for linear programming is modified in this thesis to solve general semilinear and piecewise linear programs efficiently without having to transform them into equivalent standard linear programs. Several models in widely different areas of optimization such as production smoothing, facility locations, goal programming and L/sub 1/ estimation are presented first to demonstrate the compact formulation that arisesmore » when such problems are formulated as semilinear programs. A code SLP is constructed using the semilinear programming techniques. Problems in aggregate planning and L/sub 1/ estimation are solved using SLP and equivalent linear programs using a linear programming simplex code. Comparisons of CPU times and number iterations indicate SLP to be far superior. The semilinear programming techniques are extended to piecewise linear programming in the implementation of the code PLP. Piecewise linear models in aggregate planning are solved using PLP and equivalent standard linear programs using a simple upper bounded linear programming code SUBLP.« less

Educating speech-language pathologists for the 21st century: course design considerations for a distance education Master of Speech Pathology program.

PubMed

McCormack, Jane; Easton, Catherine; Morkel-Kingsbury, Lenni

2014-01-01

The landscape of tertiary education is changing. Developments in information and communications technology have created new ways of engaging with subject material and supporting students on their learning journeys. Therefore, it is timely to reconsider and re-imagine the education of speech-language pathology (SLP) students within this new learning space. In this paper, we outline the design of a new Master of Speech Pathology course being offered by distance education at Charles Sturt University (CSU) in Australia. We discuss the catalyst for the course and the commitments of the SLP team at CSU, then describe the curriculum design process, focusing on the pedagogical approach and the learning and teaching strategies utilised in the course delivery. We explain how the learning and teaching strategies have been selected to support students' online learning experience and enable greater interaction between students and the subject material, with students and subject experts, and among student groups. Finally, we highlight some of the challenges in designing and delivering a distance education SLP program and identify future directions for educating students in an online world. © 2015 S. Karger AG, Basel.

Breeding goals for the Kenya dual purpose goat. I. Model development and application to smallholder production systems.

PubMed

Bett, R C; Kosgey, I S; Bebe, B O; Kahi, A K

2007-10-01

A deterministic model was developed and applied to evaluate biological and economic variables that characterize smallholder production systems utilizing the Kenya Dual Purpose goat (KDPG) in Kenya. The systems were defined as: smallholder low-potential (SLP), smallholder medium-potential (SMP) and smallholder high-potential (SHP). The model was able to predict revenues and costs to the system. Revenues were from sale of milk, surplus yearlings and cull-forage animals, while costs included those incurred for feeds, husbandry, marketing and fixed asset (fixed costs). Of the total outputs, revenue from meat and milk accounted for about 55% and 45%, respectively, in SMP and 39% and 61% in SHP. Total costs comprised mainly variable costs (98%), with husbandry costs being the highest in both SMP and SLP. The total profit per doe per year was KSh 315.48 in SMP, KSh -1352.75 in SLP and KSh -80.22 in SHP. Results suggest that the utilization of the KDPG goat in Kenya is more profitable in the smallholder medium-potential production system. The implication for the application of the model to smallholder production systems in Kenya is discussed.

Mechanism and function of Vav1 localisation in TCR signalling

PubMed Central

Ksionda, Olga; Saveliev, Alexander; Köchl, Robert; Rapley, Jonathan; Faroudi, Mustapha; Smith-Garvin, Jennifer E.; Wülfing, Christoph; Rittinger, Katrin; Carter, Tom; Tybulewicz, Victor L. J.

2012-01-01

Summary The antigen-specific binding of T cells to antigen presenting cells results in recruitment of signalling proteins to microclusters at the cell-cell interface known as the immunological synapse (IS). The Vav1 guanine nucleotide exchange factor plays a critical role in T cell antigen receptor (TCR) signalling, leading to the activation of multiple pathways. We now show that it is recruited to microclusters and to the IS in primary CD4+ and CD8+ T cells. Furthermore, we show that this recruitment depends on the SH2 and C-terminal SH3 (SH3B) domains of Vav1, and on phosphotyrosines 112 and 128 of the SLP76 adaptor protein. Biophysical measurements show that Vav1 binds directly to these residues on SLP76 and that efficient binding depends on the SH2 and SH3B domains of Vav1. Finally, we show that the same two domains are critical for the phosphorylation of Vav1 and its signalling function in TCR-induced calcium flux. We propose that Vav1 is recruited to the IS by binding to SLP76 and that this interaction is critical for the transduction of signals leading to calcium flux. PMID:22956543

Mechanism and function of Vav1 localisation in TCR signalling.

PubMed

Ksionda, Olga; Saveliev, Alexander; Köchl, Robert; Rapley, Jonathan; Faroudi, Mustapha; Smith-Garvin, Jennifer E; Wülfing, Christoph; Rittinger, Katrin; Carter, Tom; Tybulewicz, Victor L J

2012-11-15

The antigen-specific binding of T cells to antigen presenting cells results in recruitment of signalling proteins to microclusters at the cell-cell interface known as the immunological synapse (IS). The Vav1 guanine nucleotide exchange factor plays a critical role in T cell antigen receptor (TCR) signalling, leading to the activation of multiple pathways. We now show that it is recruited to microclusters and to the IS in primary CD4(+) and CD8(+) T cells. Furthermore, we show that this recruitment depends on the SH2 and C-terminal SH3 (SH3(B)) domains of Vav1, and on phosphotyrosines 112 and 128 of the SLP76 adaptor protein. Biophysical measurements show that Vav1 binds directly to these residues on SLP76 and that efficient binding depends on the SH2 and SH3(B) domains of Vav1. Finally, we show that the same two domains are critical for the phosphorylation of Vav1 and its signalling function in TCR-induced calcium flux. We propose that Vav1 is recruited to the IS by binding to SLP76 and that this interaction is critical for the transduction of signals leading to calcium flux.

Impact of the North Atlantic dipole on climate changes over Eurasia

NASA Astrophysics Data System (ADS)

Serykh, Ilya

2017-04-01

Hydrophysical and meteorological characteristics of negative (1948-1976, 1999-2015) and positive (1977-1998) phases of the Pacific Decadal Oscillation (PDO) / Interdecadal Pacific Oscillation (IPO) in the North Atlantic and Eurasia are constructed and investigated. Specifically, the near-surface temperature, sea-level atmospheric pressure, wind speed, heat content of the upper 700 m ocean layer, water temperature and salinity at various depths, the latent and sensible heat fluxes from the ocean to the atmosphere are analyzed. The fields obtained from different sources (20thC_ReanV2c, ERA-20C, JRA-55, NCEP/NCAR, HadCRUT4, HadSLP2, NODC, Ishii, SODA, OAFlux, HadSST3, COBE2, ERSSTv4) are in good agreement and complement each other. This gives important information about the hydrometeorological conditions in the region under study. Analysis of these data has shown that in the upper 1000 m North Atlantic layer there is a thermal dipole which can be interpreted as an oceanic analog of the atmospheric North Atlantic Oscillation (NAO). An index of the North Atlantic Dipole (NAD) as the difference between the mean heat contents in the upper 700 m oceanic layer between the regions (50°-70° N; 60°-10° W) and (20°-40° N; 80°-30° W) is proposed. A possible physical mechanism of the internal oscillations with a quasi-60-year period in the North Atlantics-Eurasia system of ocean-atmosphere interactions is discussed. Dipole spatial structure from observations datasets and re-analyses were compared with the results of the Historical Experiment from the climate models of the CMIP5 project. It is found that several climate models reproduce dipole spatial structure of the near-surface temperature and sea level pressure anomalies similarly to these fields in the re-analyses considered. However, the phase diagrams of the gradient of near-surface temperature and sea level pressure between the Azores High and Island Low from climate models do not separate on subsets as the observation diagrams. Keeping in mind the prognostic goals we supposed that this result could be essential for revealing the relationships between the climatic parameters of the Eurasian continent and the thermodynamic processes in the specific areas of the North Atlantic Ocean.

A teleconnection study of interannual sea surface temperature fluctuations in the northern North Atlantic and precipitation and runoff over Western Siberia

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

Peng, S.; Mysak, L.A.

The spatial distributions of northern North Atlantic sea surface temperature and the high-latitude Northern Hemisphere sea level pressure anomalies averaged over six consecutive warm SST winters (1951-1956) and six consecutive cold SST winters (1971-1976) are examined. Three SLP anomaly difference (i.e., warm - cold winters) centers, significant at the 5% level, are observed over the northern North Atlantic, Europe, and western Siberia. This anomaly pattern is consistent in principle with what was identified in a related analyses by Palmer and Sun, who used composite data from selected winter months. The SLP difference centers over the northern North Atlantic and westernmore » Siberia are in phase. The impact of the latter center upon the runoff from the underlying Ob and Yenisey rivers and especially the teleconnection between SST anomalies in the northern North Atlantic and runoff of those two rivers via the atmosphere are investigated. The temporal cross-correlation analyses of 50 years (1930-1979) of records of SST, precipitation, and runoff anomalies indicate that the winter SST anomalies in the northern North Atlantic are significantly correlated with the winter and following summer runoff fluctuations of the Ob and Yenisey rivers. Positive (negative) northern North Atlantic SST anomalies are related to less (more) precipitation, and hence, less (more) runoff, over western Siberia. Discussions of possible physical mechanisms and processes that lead to the above relationships are attempted. The analyses of spatial distributions of precipitation in the warm and cold SST winters suggest that precipitation fluctuations over Europe and western Siberia may be affected by shifts of cyclone tracks associated with the SST variations in the northern North Atlantic. 27 refs., 9 figs.« less

Reconstruction of Monsoon Driven South China Sea Surface Ocean Circulation using Coral Δ14C

NASA Astrophysics Data System (ADS)

Goodkin, N.; Bolton, A.; Karnauskas, K. B.; Hughen, K. A.; Griffin, S.; Druffel, E. R. M.

2016-12-01

The need to improve our understanding of annual and decadal climate behavior in the South China Sea is increasingly important, as this region includes the largest population density globally but encompasses few climate records. Here we present a record of annually resolved Δ14C from a coral collected off the coast of Nha Trang, Vietnam (12°12'49.90″N, 109°18'17.51″E), that reveals a significant correlation to regional winter sea level pressure (SLP) and sea surface temperature (SST), and extends back more than 400 years. Coral Δ14C during thermonuclear bomb testing indicates the presence of wet-season (summer) upwelling, demonstrated by low Δ14C values for both baseline and peak values relative to other records in the region (Bolton et al., 2016, Radiocarbon). However, annually resolved pre-bomb Δ14C correlates significantly to regional dry-season (winter) SLP and SST, indicating that annual variability is driven by changes to the East Asian Winter Monsoon (EAWM) and subsequent down-welling at this site. Spectral density is focused at 25, 11.8, 7, 4, and 3.2 years per cycle reflecting a range of influences on surface advection variability including the EAWM (D'Arrigo et al., 2005, GRL) and the El Nino Southern Oscillation (ENSO). Spectral power at all of these frequencies decreases following the Little Ice Age ( 1600-1850?) to today, indicating that wind driven surface advection was more variable when hemispheric temperatures were cooler. Decadal variance in the past 100 years is significantly correlated to variance records of the Arctic Oscillation (AO, Thompson and Wallace, 1989, GRL), suggesting that increasing variance in the EAWM may be tied to increasing variance of the AO during the Little Ice Age and vice versa.

The Characteristics of Cold Air Outbreaks in the Eastern United States and the Influence of Atmospheric Circulation Patterns

NASA Astrophysics Data System (ADS)

Smith, E. T.

2017-12-01

Periods of extreme cold impact the mid-latitudes every winter. Depending on the magnitude and duration of the occurrence, extremely cold periods may be deemed cold air outbreaks (CAOs). Atmospheric teleconnections impact the displacement of polar air, but the relationship between the primary teleconnections and the manifestation of CAOs is not fully understood. A systematic CAO index was developed from 20 surface weather stations based on a set of criteria concerning magnitude, duration, and spatial extent. Statistical analyses of the data were used to determine the overall trends in CAOs. Clusters of sea level pressure (SLP), 100mb, and 10mb geopotential height anomalies were mapped utilizing self-organizing maps (SOMs) to understand the surface, upper-tropospheric Polar Vortex (PV), and stratospheric PV patterns preceding CAOs. The Arctic Oscillation (AO), North Atlantic Oscillation (NAO), and Pacific-North American (PNA) teleconnections were used as variables to explain the magnitude and location of mid-latitude Arctic air displacement. Persistently negative SLP anomalies across the Arctic and North Atlantic were evident 1 - 2 weeks prior to the CAOs throughout the winter. The upper-tropospheric and stratospheric PV were found to be persistently weak/weakening prior to mid-winter CAOs and predominantly strong and off-centered prior to early and late season CAOs. Negative phases of the AO and NAO were favored prior to CAOs, while the PNA favored a near-neutral phase. This method of CAO and synoptic pattern characterization benefits from a continuous pattern representation and provides insight as to how specific teleconnections impact the atmospheric flow in a way that leads to CAOs in the eastern U.S.

Marine aerosol source regions to Prince of Wales Icefield, Ellesmere Island, and influence from the tropical Pacific, 1979-2001

NASA Astrophysics Data System (ADS)

Criscitiello, Alison S.; Marshall, Shawn J.; Evans, Matthew J.; Kinnard, Christophe; Norman, Ann-Lise; Sharp, Martin J.

2016-08-01

Using a coastal ice core collected from Prince of Wales (POW) Icefield on Ellesmere Island, we investigate source regions of sea ice-modulated chemical species (methanesulfonic acid (MSA) and chloride (Cl-)) to POW Icefield and the influence of large-scale atmospheric variability on the transport of these marine aerosols (1979-2001). Our key findings are (1) MSA in the POW Icefield core is derived primarily from productivity in the sea ice zone of Baffin Bay and the Labrador Sea, with influence from waters within the North Water (NOW) polynya, (2) sea ice formation processes within the NOW polynya may be a significant source of sea-salt aerosols to the POW core site, in addition to offshore open water source regions primarily in Hudson Bay, and (3) the tropical Pacific influences the source and transport of marine aerosols to POW Icefield through its remote control on regional winds and sea ice variability. Regression analyses during times of MSA deposition reveal sea level pressure (SLP) anomalies favorable for opening of the NOW polynya and subsequent oceanic dimethyl sulfide production. Regression analyses during times of Cl- deposition reveal SLP anomalies that indicate a broader oceanic region of sea-salt sources to the core site. These results are supported by Scanning Multichannel Microwave Radiometer- and Special Sensor Microwave/Imager-based sea ice reconstructions and air mass transport density analyses and suggest that the marine biogenic record may capture local polynya variability, while sea-salt transport to the site from larger offshore source regions in Baffin Bay is likely. Regression analyses show a link to tropical dynamics via an atmospheric Rossby wave.