Lung cancer in connective tissue disease-associated interstitial lung disease: clinical features and impact on outcomes.

PubMed

Watanabe, Satoshi; Saeki, Keigo; Waseda, Yuko; Murata, Akari; Takato, Hazuki; Ichikawa, Yukari; Yasui, Masahide; Kimura, Hideharu; Hamaguchi, Yasuhito; Matsushita, Takashi; Yamada, Kazunori; Kawano, Mitsuhiro; Furuichi, Kengo; Wada, Takashi; Kasahara, Kazuo

2018-02-01

Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.

Conductivity Cell Thermal Inertia Correction Revisited

NASA Astrophysics Data System (ADS)

Eriksen, C. C.

2012-12-01

Salinity measurements made with a CTD (conductivity-temperature-depth instrument) rely on accurate estimation of water temperature within their conductivity cell. Lueck (1990) developed a theoretical framework for heat transfer between the cell body and water passing through it. Based on this model, Lueck and Picklo (1990) introduced the practice of correcting for cell thermal inertia by filtering a temperature time series using two parameters, an amplitude α and a decay time constant τ, a practice now widely used. Typically these two parameters are chosen for a given cell configuration and internal flushing speed by a statistical method applied to a particular data set. Here, thermal inertia correction theory has been extended to apply to flow speeds spanning well over an order of magnitude, both within and outside a conductivity cell, to provide predictions of α and τ from cell geometry and composition. The extended model enables thermal inertia correction for the variable flows encountered by conductivity cells on autonomous gliders and floats, as well as tethered platforms. The length scale formed as the product of cell encounter speed of isotherms, α, and τ can be used to gauge the size of the temperature correction for a given thermal stratification. For cells flushed by dynamic pressure variation induced by platform motion, this length varies by less than a factor of 2 over more than a decade of speed variation. The magnitude of correction for free-flow flushed sensors is comparable to that of pumped cells, but at an order of magnitude in energy savings. Flow conditions around a cell's exterior are found to be of comparable importance to thermal inertia response as flushing speed. Simplification of cell thermal response to a single normal mode is most valid at slow speed. Error in thermal inertia estimation arises from both neglect of higher modes and numerical discretization of the correction scheme, both of which can be easily quantified. Consideration of thermal inertia correction enables assessment of various CTD sampling schemes. Spot sampling by pumping a cell intermittently provides particular challenges, and may lead to biases in inferred salinity that are comparable to climate signals reported from profiling float arrays.

Comprehensive nitrogen budgets for controlled tile drainage fields in eastern ontario, Canada.

PubMed

Sunohara, M D; Craiovan, E; Topp, E; Gottschall, N; Drury, C F; Lapen, D R

2014-03-01

Excessive N loading from subsurface tile drainage has been linked to water quality degradation. Controlled tile drainage (CTD) has the potential to reduce N losses via tile drainage and boost crop yields. While CTD can reduce N loss from tile drainage, it may increase losses through other pathways. A multiple-year field-scale accounting of major N inputs and outputs during the cropping season was conducted on freely drained and controlled tile drained agricultural fields under corn ( L.)-soybean [ (L.) Merr.] production systems in eastern Ontario, Canada. Greater predicted gaseous N emissions for corn and soybean and greater observed lateral seepage N losses were observed for corn and soybean fields under CTD relative to free-draining fields. However, observed N losses from tile were significantly lower for CTD fields, in relation to freely drained fields. Changes in residual soil N were essentially equivalent between drainage treatments, while mass balance residual terms were systematically negative (slightly more so for CTD). Increases in plant N uptake associated with CTD were observed, probably resulting in higher grain yields for corn and soybean. This study illustrates the benefits of CTD in decreasing subsurface tile drainage N losses and boosting crop yields, while demonstrating the potential for CTD to increase N losses via other pathways related to gaseous emissions and groundwater seepage. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Ambrisentan response in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) - A subgroup analysis of the ARIES-E clinical trial.

PubMed

Fischer, Aryeh; Denton, Christopher P; Matucci-Cerinic, Marco; Gillies, Hunter; Blair, Christiana; Tislow, James; Nathan, Steven D

2016-08-01

Pulmonary arterial hypertension (PAH) is a condition which may lead to right ventricular failure and early mortality and is an important complication in patients with connective tissue disease (CTD). Previously, the endothelin A selective receptor antagonist, ambrisentan, demonstrated efficacy and safety in treating patients with PAH due to WHO Group I etiologies. These analyses describe the 3-year efficacy and safety of ambrisentan in patients specifically with CTD associated PAH (CTD-PAH). Patients with CTD-PAH participating in the ARIES-1 and -2 clinical trials and their long-term extension were evaluated. Efficacy evaluations including 6-min walk distance (6MWD), clinical worsening, and survival were collected at routine study visits. Additional analyses of 6MWD categorical (30 m) breakpoints were conducted to determine any relationship between 6MWD and a prognostic threshold for survival. 124 patients with CTD-PAH were evaluated. 62.6%, 57.3%, and 58.2% of CTD-PAH patients treated with ambrisentan exhibited increases in 6MWD at 1-, 2-, and 3- years respectively. At 3 years, 64% of patients were free from clinical worsening and 76% of patients were still alive (Kaplan-Meier estimates). Identified factors holding prognostic relevance for survival include: baseline functional class, CTD-PAH subgroup, patient sex, improvement in 6MWD ≥30 m over the first 12 weeks of treatment, the most recent 6MWD, and a 6MWD absolute threshold of 222 m. These first analyses of the 3-year treatment of CTD-PAH patients with ambrisentan revealed fewer clinical worsening events and improved survival compared to historical controls. Key exercise parameters were also identified which appear important in guiding treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Uncertainties in Climatological Seawater Density Calculations

NASA Astrophysics Data System (ADS)

Dai, Hao; Zhang, Xining

2018-03-01

In most applications, with seawater conductivity, temperature, and pressure data measured in situ by various observation instruments e.g., Conductivity-Temperature-Depth instruments (CTD), the density which has strong ties to ocean dynamics and so on is computed according to equations of state for seawater. This paper, based on density computational formulae in the Thermodynamic Equation of Seawater 2010 (TEOS-10), follows the Guide of the expression of Uncertainty in Measurement (GUM) and assesses the main sources of uncertainties. By virtue of climatological decades-average temperature/Practical Salinity/pressure data sets in the global ocean provided by the National Oceanic and Atmospheric Administration (NOAA), correlation coefficients between uncertainty sources are determined and the combined standard uncertainties uc>(ρ>) in seawater density calculations are evaluated. For grid points in the world ocean with 0.25° resolution, the standard deviations of uc>(ρ>) in vertical profiles cover the magnitude order of 10-4 kg m-3. The uc>(ρ>) means in vertical profiles of the Baltic Sea are about 0.028kg m-3 due to the larger scatter of Absolute Salinity anomaly. The distribution of the uc>(ρ>) means in vertical profiles of the world ocean except for the Baltic Sea, which covers the range of >(0.004,0.01>) kg m-3, is related to the correlation coefficient r>(SA,p>) between Absolute Salinity SA and pressure p. The results in the paper are based on sensors' measuring uncertainties of high accuracy CTD. Larger uncertainties in density calculations may arise if connected with lower sensors' specifications. This work may provide valuable uncertainty information required for reliability considerations of ocean circulation and global climate models.

Hydrothermal venting on the flanks of Heard and McDonald islands, southern Indian Ocean

NASA Astrophysics Data System (ADS)

Lupton, J. E.; Arculus, R. J.; Coffin, M.; Bradney, A.; Baumberger, T.; Wilkinson, C.

2017-12-01

Heard Island and the nearby McDonald Islands are two sites of active volcanism associated with the so-called Kerguelen mantle plume or hot spot. In fact, it has been proposed that the Kerguelen hot spot is currently located beneath Heard Island. During its maiden maximum endurance voyage (IN2016_V01), the recently commissioned Australian R/V Investigator conducted a detailed bathymetric and water column survey of the waters around Heard Island and the McDonald Islands as well as other sites on the Kerguelen Plateau. Some 50 hydrographic profiles were completed using the CTD/rosette system equipped with trace metal sampling and a nephelometer for suspended particle concentrations. In addition to the hydrographic profiles, 244 bubble plumes were detected in the vicinity of the Heard and McDonald Islands using the ship's multibeam system. It is thought that the bubble plumes observed on sea knolls and other seafloor surrounding the McDonald Islands are likely hydrothermal in origin, while plumes northeast of Heard Island may be biogenic methane from cold seeps. At 29 of the hydrographic stations water samples for helium isotope measurements were drawn from the CTD rosette and hermetically sealed into copper tubing for subsequent shorebased mass spectrometer and gas chromatograph analysis. In this paper we report results for 3He/4He ratios and CO2 and CH4 concentrations in water samples collected with the CTD/rosette, and discuss how these results are correlated with suspended particle concentrations and temperature anomalies.

The effects of gender discrimination on refugee torture survivors: a cross-cultural traumatology perspective.

PubMed

Kira, Ibrahim A; Smith, Iris; Lewandowski, Linda; Templin, Thomas

2010-09-01

Trauma developmental theory identifies gender discrimination (GD) as a type of persistent, ongoing trauma that has the potential for serious, negative effects on mental health. This study was conducted to examine the potential role of GD in the development of cumulative trauma disorders (CTD) and symptoms of posttraumatic stress disorder (PTSD) as well as the role of GD in mediating the effects of other traumas on these disorders. The sample included 160 female torture survivors from more than 30 countries. Measures of PTSD, CTD, and types of trauma exposure were acquired as part of a larger study on refugee torture survivors. Structural equation modeling was used to test several plausible models for the direct and indirect effects of GD on PTSD and CTD, within the context of other trauma exposure. Results suggest that GD mediates the effects of identity traumas on CTD and PTSD. GD also had direct effects on CTD, including relationships with dissociation, suicidality, and deficits in executive function. GD did not appear to directly influence the development of PTSD. The implications of these results for assessment and treatment of women's trauma-related disorders as well as strategies for their prevention are discussed.

Carbon Dioxide, Hydrographic, and Chemical Data Obtained During the R/V Thomas G. Thompson Cruise in the Pacific Ocean

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

Sabine, C.L.; Key, R.M.; Hall, M.

1999-08-01

This data documentation discusses the procedures and methods used to measure total carbon dioxide (TCO2), total alkalinity (TALK), and radiocarbon (delta 14C), at hydrographic stations, as well as the underway partial pressure of CO2 (pCO2) during the R/V Thomas G. Thompson oceanographic cruise in the Pacific Ocean (Section P10). Conducted as part of the World Ocean Circulation Experiment (WOCE), the cruise began in Suva, Fiji, on October 5, 1993, and ended in Yokohama, Japan, on November 10, 1993. Measurements made along WOCE Section P10 included pressure, temperature, salinity [measured by conductivity temperature, and depth sensor (CTD)], bottle salinity, bottle oxygen,more » phosphate, nitrate, silicate, chlorofluorocarbons (CFC-11, CFC-12), TCO2, TALK, delta 14C, and underway pCO2.« less

Elephant Seals and Temperature Data: Calibrations and Limitations.

NASA Astrophysics Data System (ADS)

Simmons, S. E.; Tremblay, Y.; Costa, D. P.

2006-12-01

In recent years with technological advances, instruments deployed on diving marine animals have been used to sample the environment in addition to their behavior. Of all oceanographic variables one of the most valuable and easiest to record is temperature. Here we report on a series of lab calibration and field validation experiments that consider the accuracy of temperature measurements from animal borne ocean samplers. Additionally we consider whether sampling frequency or animal behavior affects the quality of the temperature data collected by marine animals. Rapid response, external temperature sensors on eight Wildlife Computers MK9 time-depth recorders (TDRs) were calibrated using water baths at the Naval Postgraduate School (Monterey, CA). These water baths are calibrated using a platinum thermistor to 0.001° C. Instruments from different production batches were calibrated before and after deployments on adult female northern elephant seals, to examine tag performance over time and under `normal' usage. Tag performance in the field was validated by comparisons with temperature data from a Seabird CTD. In April/May of 2004, casts to 200m were performed over the Monterey Canyon using a CTD array carrying MK9s. These casts were performed before and after the release of a juvenile elephant seal from the boat. The seal was also carrying an MK9 TDR, allowing the assessment of any animal effect on temperature profiles. Sampling frequency during these field validations was set at one second intervals and the data from TDRs on both the CTD and the seals was sub-sampled at four, eight, 30 and 300 (5 min) seconds. The sub-sampled data was used to determine thermocline depth, a thermocline depth zone and temperature gradients and assess whether sampling frequency or animal behavior affects the quality of temperature data. Preliminary analyses indicate that temperature sensors deployed on elephant seals can provide water column temperature data of high quality and precision.

Better care provided to patients with tuberculosis at county designated TB hospitals (CTD) compared to non-CTDs in rural China.

PubMed

Yuan, Li; Zhang, Hui; Zhou, Changming; Jiang, Weili; Zhao, Qi; Biao, Xu

2017-01-13

The primary unit of tuberculosis (TB) medical care in China is the county TB dispensary or county designated hospital (CTD), where patients can receive free diagnosis and treatment. However, a substantial number of patients seek their anti-TB treatment from general health facilities (Non-CTDs). This study aimed to investigate the first anti-TB treatment experience and choice of health facilities of retreated TB patients and their determinants. A cross-sectional study was conducted in Jiangsu, Shandong and Sichuan provinces. All registered re-treated TB patients were investigated using a structured questionnaire covering information on demographics, socio-economic characteristics, and previous anti-TB treatment experiences. Totally, 75.3% of 544 patients visited CTD directly for initial treatment. Patients who were female (OR:1.71, 95% CI: 1.01-2.87), over 40 years of age (OR:2.80, 95% CI: 1.24-6.33), from Jiangsu (OR:3.07, 95% CI: 1.57-6.01) and Sichuan (OR:4.47, 95% CI: 2.29-8.73) and those diagnosed before 2005 (OR:6.87, 95% CI: 4.24-11.13) had a significant higher risk receiving their initial treatment at a non-CTD. Patients were more likely to have standardized diagnosis and treatment regimens in CTD (89.8%) than in non-CTDs (65.9%). Patients treated in non-CTDs versus in CTD had a lower possibility to complete their treatment course during first TB episode (χ 2  = 3.926, P = 0.048), but there was no significant difference in the cure rate between different facilities (CTD 60.8%, Non-CTDs 59.1%). Patients in non-CTDs incurred higher costs (1,360 CNY) than those treated in CTD (920CNY). CTD play a key role in the National Tuberculosis Control Program. Patients should be guided to seek health care in county designated hospital, where they are more likely to receive appropriate examinations, treatment regimens and rigorous supervision, and to bear a lighter economic burden.

--No Title--

Science.gov Websites

Properties (CTD/profile data) Trawl Survey Data (including oceanographic profiles) Shiptrack Surface Properties (hull-mounted sensor data) Temperature & Salinity Anomalies (by region) Drifter Tracks eMOLT

Ocean Color Patterns Help to Predict Depth of Optical Layers in Coastal Marine Waters

DTIC Science & Technology

2012-02-09

Space Center, NASA, MS 39529, USA 3Institut des Sciences de la Mer, Universite du Quebec a Rimouski, Canada, *E-mail: martin_montes@uqar. qc. ca...depth was derived from CTD variables (i.e., temperature and conductivity without pressure correction) and using the standard UNESCO polynomial equation... la y *,es^ S Si es ti m at ed nt er re y B a n an d up ), th e up pe r te d in w h i 5112 ^ "a :*J ? tf?^ •a Mis a a •S M ^ « a fo

Interactive effects of dietary adaptation period length and titration diet type on apparent ileal phosphorus digestibility and phosphorus retention in growing broilers.

PubMed

Perryman, K R; Cattley, R C; Masey O'Neill, H V; Bedford, M R; Dozier, W A

2016-10-01

Two experiments were conducted to examine the effects of different corn titration diets and dietary adaptation period length (DAPL) on intestinal histology, apparent ileal P digestibility (AIPD), and apparent P retention (APR) in Ross × Ross 708 male broilers from 20 to 24 d of age. It was hypothesized that purified ingredients in nutrient-deficient titration diets may affect P availability with varying DAPL. In experiment 1, 1,152 broilers were utilized in a 3 × 3 factorial treatment structure with 3 diets (control, 25% corn titration diet [25CTD], or 75% corn titration diet [75CTD]) and 3 DAPL (0, 24, or 72 h). Experiment 2 was conducted with 576 broilers as a 4 × 3 factorial arrangement with 4 diets (control, 25CTD, 75CTD, or nitrogen-free diet [NFD]) and 3 DAPL (24, 48, or 72 h). All diets contained purified ingredients except for the control diet, which had the same formulation as the common starter and served as a control for DAPL. The NFD diet was fed as a highly purified protein-free diet. Broilers were fed a common diet until 19 d of age and then transferred to experimental diets at 20 d of age. In experiment 1, diet type did not affect (P > 0.05) intestinal histology. However, diet type and DAPL each influenced (P.≤.0.001) diet AIPD. Higher (P.≤.0.001) AIPD was measured for the control diet compared with the 75CDT, and the 25CTD had the lowest AIPD. Following a 24 h DAPL, AIPD was higher (P.≤.0.001) than after a DAPL of 0 or 72 h. In experiment 2, diet type × DAPL interactions (P.≤.0.001) were observed for APR of the control diet, 75CTD, and NFD, but not the 25CTD. Because APR of the control diet was affected by varying DAPL, factors other than differences in diet type may have been responsible for inconsistencies in the measure of P availability. Furthermore, no clear evidence was observed that broilers were able to adapt to P-deficient diets by increasing APR or AIPD. In conclusion, a standard DAPL should be established as a means to reduce variability associated with measuring of feedstuff P availability. © 2016 Poultry Science Association Inc.

Fine-scale thermohaline ocean structure retrieved with 2-D prestack full-waveform inversion of multichannel seismic data: Application to the Gulf of Cadiz (SW Iberia)

NASA Astrophysics Data System (ADS)

Dagnino, D.; Sallarès, V.; Biescas, B.; Ranero, C. R.

2016-08-01

This work demonstrates the feasibility of 2-D time-domain, adjoint-state acoustic full-waveform inversion (FWI) to retrieve high-resolution models of ocean physical parameters such as sound speed, temperature and salinity. The proposed method is first described and then applied to prestack multichannel seismic (MCS) data acquired in the Gulf of Cadiz (SW Iberia) in 2007 in the framework of the Geophysical Oceanography project. The inversion strategy flow includes specifically designed data preconditioning for acoustic noise reduction, followed by the inversion of sound speed in the shotgather domain. We show that the final sound speed model has a horizontal resolution of ˜ 70 m, which is two orders of magnitude better than that of the initial model constructed with coincident eXpendable Bathy Thermograph (XBT) data, and close to the theoretical resolution of O(λ). Temperature (T) and salinity (S) are retrieved with the same lateral resolution as sound speed by combining the inverted sound speed model with the thermodynamic equation of seawater and a local, depth-dependent T-S relation derived from regional conductivity-temperature-depth (CTD) measurements of the National Oceanic and Atmospheric Administration (NOAA) database. The comparison of the inverted T and S models with XBT and CTD casts deployed simultaneously to the MCS acquisition shows that the thermohaline contrasts are resolved with an accuracy of 0.18oC for temperature and 0.08 PSU for salinity. The combination of oceanographic and MCS data into a common, pseudo-automatic inversion scheme allows to quantitatively resolve submeso-scale features that ought to be incorporated into larger-scale ocean models of oceans structure and circulation.

Detecting deep sea hydrothermal vents with a split-beam echosounder

NASA Astrophysics Data System (ADS)

Gray, L. M.; Jerram, K.

2016-12-01

In May 2016, the NOAA Office of Exploration and Research exploration vessel, Okeanos Explorer, conducted a remotely operated vehicle (ROV) dive on a series of active `black smoker' hydrothermal vents at 3,300 m depth in the western Pacific Ocean near the Mariana Trench. The ROV system traversed 800 m along the seafloor and detected three distinct vent sites. The vent chimneys ranged in heights from 5 m to 30 m above the seafloor and vent fluid temperatures were measured as high as 337 °C. Immediately following the ROV dive, the Okeanos Explorer mapped the vent field with an 18 kHz split-beam echosounder traditionally used for fishery research and a 30 kHz multibeam echosounder with midwater capability. Six passes were made over the field, transiting at 4-5 knots on various headings. There was a clear and repeatable signal in the split-beam echogram from the venting but less obvious indication in the multibeam data. `Black smokers' have traditionally been detected using repeat conductivity-temperature-depth (CTD) `tow-yo' casts. Our field observations suggest an alternative, and potentially more efficient, method of detecting hydrothermal vent plumes within the beamwidth of the split-beam echosounder to inform ROV dive plans. Methods previously applied for locating marine gas seeps on the seafloor with split-beam echosounders can be applied to estimate the hydrothermal vent positions in this dataset and compared to the recorded ROV positions at each site. Additionally, assuming relatively stable venting and ambient conditions, the ROV position and CTD data recorded from the vehicles can be used to better understand the observed midwater acoustic backscatter signatures of the hydrothermal vent plumes.

Clinical Features of Idiopathic Interstitial Pneumonia with Systemic Sclerosis-Related Autoantibody in Comparison with Interstitial Pneumonia with Systemic Sclerosis

PubMed Central

Yamakawa, Hideaki; Hagiwara, Eri; Kitamura, Hideya; Yamanaka, Yumie; Ikeda, Satoshi; Sekine, Akimasa; Baba, Tomohisa; Iso, Shinichiro; Okudela, Koji; Iwasawa, Tae; Takemura, Tamiko; Kuwano, Kazuyoshi; Ogura, Takashi

2016-01-01

Background Patients with idiopathic interstitial pneumonias sometimes have a few features of connective tissue disease (CTD) and yet do not fulfil the diagnostic criteria for any specific CTD. Objective This study was conducted to elucidate the characteristics, prognosis, and disease behavior in patients with interstitial lung disease (ILD) associated with systemic sclerosis (SSc)-related autoantibodies. Methods We retrospectively analyzed medical records of 72 ILD patients: 40 patients with SSc (SSc-ILD) and 32 patients with SSc-related autoantibody-positive ILD but not with CTD (ScAb-ILD), indicating lung-dominant CTD with SSc-related autoantibody. Results Patients with SSc-ILD were predominantly females and non-smokers, and most had nonspecific interstitial pneumonia confirmed by high-resolution computed tomography (HRCT) and pathological analysis. However, about half of the patients with ScAb-ILD were male and current or ex-smokers. On HRCT analysis, honeycombing was more predominant in patients with ScAb-ILD than with SSc-ILD. Pathological analysis showed the severity of vascular intimal or medial thickening in the SSc-ILD patients to be significantly higher than that in the ScAb-ILD patients. Survival curves showed that the patients with ScAb-ILD had a significantly poorer outcome than those with SSc-ILD. Conclusion Data from this study suggest that lung-dominant CTD with SSc-related autoantibody is a different disease entity from SSc-ILD. PMID:27564852

Salinity Processes in the Upper Ocean Regional Study (SPURS)

NASA Image and Video Library

2012-09-04

CTD instruments used to measure Conductivity, Temperature, and Depth, are seen onboard the Woods Hole Oceanographic Institution's research vessel Knorr on Tuesday, Sept. 4, 2012, in Woods Hole, Mass. The CTDs will be deployed in the Atlantic Ocean as part of the Salinity Processes in the Upper Ocean Regional Study (SPURS) which is set to sail on Sept. 6. The NASA-sponsored expedition will sail to the North Atlantic's saltiest spot to get a detailed, 3-D picture of how salt content fluctuates in the ocean's upper layers and how these variations are related to shifts in rainfall patterns around the planet. Photo Credit: (NASA/Bill Ingalls)

An analysis of the clinical features of lung cancer in patients with connective tissue diseases.

PubMed

Saijo, Atsuro; Hanibuchi, Masaki; Goto, Hisatsugu; Toyoda, Yuko; Tezuka, Toshifumi; Nishioka, Yasuhiko

2017-03-01

Patients with connective tissue diseases (CTDs) are at increased risk for lung cancer (LC); interstitial lung disease (ILD) is a common form of organ dysfunction in cases of CTD. However, the influence of ILD on the treatment and prognosis in LC patients with CTD is unclear. Between January 2010 and December 2014, 27 patients among all patients with CTD at our institution were diagnosed with primary LC. We retrospectively analyzed the clinical features, treatment modalities, and outcomes of these patients, and evaluated the potential prognostic factors. Forty-four LC patients without CTD were also analyzed as a control cohort. LC patients with CTD had a significantly higher incidence of ILD as a complication compared with those without CTD (52% and 14%, respectively). CTD-associated ILD (CTD-ILD) at diagnosis was associated with significantly worse survival in LC patients with CTD. Multivariate analysis demonstrated that the complication of CTD-ILD was an independent poor prognostic factor in LC patients with CTD. The incidence of acute exacerbation (AE) of CTD-ILD was 21% among LC patients with CTD, and all of these patients died despite intensive treatment including high-dose corticosteroids. The restrictions in curative therapy for LC due to the presence of ILD and AE of CTD-ILD were thought to be the major reasons for the poor outcome. LC patients with CTD had a high prevalence of ILD, and the presence of CTD-ILD was significantly associated with poor prognosis. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Fission yeast RNA triphosphatase reads an Spt5 CTD code

DOE PAGES

Doamekpor, Selom K.; Schwer, Beate; Sanchez, Ana M.; ...

2014-11-20

mRNA capping enzymes are directed to nascent RNA polymerase II (Pol2) transcripts via interactions with the carboxy-terminal domains (CTDs) of Pol2 and transcription elongation factor Spt5. Fission yeast RNA triphosphatase binds to the Spt5 CTD, comprising a tandem repeat of nonapeptide motif TPAWNSGSK. Here we report the crystal structure of a Pct1·Spt5-CTD complex, which revealed two CTD docking sites on the Pct1 homodimer that engage TPAWN segments of the motif. Each Spt5 CTD interface, composed of elements from both subunits of the homodimer, is dominated by van der Waals contacts from Pct1 to the tryptophan of the CTD. The boundmore » CTD adopts a distinctive conformation in which the peptide backbone makes a tight U-turn so that the proline stacks over the tryptophan. We show that Pct1 binding to Spt5 CTD is antagonized by threonine phosphorylation. Our results fortify an emerging concept of an “Spt5 CTD code” in which (i) the Spt5 CTD is structurally plastic and can adopt different conformations that are templated by particular cellular Spt5 CTD receptor proteins; and (ii) threonine phosphorylation of the Spt5 CTD repeat inscribes a binary on–off switch that is read by diverse CTD receptors, each in its own distinctive manner.« less

Fission yeast RNA triphosphatase reads an Spt5 CTD code

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

Doamekpor, Selom K.; Schwer, Beate; Sanchez, Ana M.

mRNA capping enzymes are directed to nascent RNA polymerase II (Pol2) transcripts via interactions with the carboxy-terminal domains (CTDs) of Pol2 and transcription elongation factor Spt5. Fission yeast RNA triphosphatase binds to the Spt5 CTD, comprising a tandem repeat of nonapeptide motif TPAWNSGSK. Here we report the crystal structure of a Pct1·Spt5-CTD complex, which revealed two CTD docking sites on the Pct1 homodimer that engage TPAWN segments of the motif. Each Spt5 CTD interface, composed of elements from both subunits of the homodimer, is dominated by van der Waals contacts from Pct1 to the tryptophan of the CTD. The boundmore » CTD adopts a distinctive conformation in which the peptide backbone makes a tight U-turn so that the proline stacks over the tryptophan. We show that Pct1 binding to Spt5 CTD is antagonized by threonine phosphorylation. Our results fortify an emerging concept of an “Spt5 CTD code” in which (i) the Spt5 CTD is structurally plastic and can adopt different conformations that are templated by particular cellular Spt5 CTD receptor proteins; and (ii) threonine phosphorylation of the Spt5 CTD repeat inscribes a binary on–off switch that is read by diverse CTD receptors, each in its own distinctive manner.« less

Multi-Scale 4DVAR Assimilation of Glider Teams on the North Carolina Shelf

NASA Astrophysics Data System (ADS)

Osborne, J. J. V.; Carrier, M.; Book, J. W.; Barron, C. N.; Rice, A. E.; Rowley, C. D.; Smedstad, L.; Souopgui, I.; Teague, W. J.

2017-12-01

We demonstrate a method to assimilate glider profile data from multiple gliders in close proximity ( 10 km or less). Gliders were deployed in a field experiment from 17 May until 4 June 2017, north of Cape Hatteras and inshore of the Gulf Stream. Gliders were divided into two teams, generally two or three gliders per team. One team was tasked with station keeping and the other with moving and sampling regions of high variability in temperature and salinity. Glider data are assimilated into the Relocatable Navy Coastal Ocean Model (RELO NCOM) with four dimensional variational assimilation (NCOM-4DVAR). RELO NCOM is used by the US Navy to predict the ocean. RELO NCOM is a baroclinic, Boussinesq, free-surface, and hydrostatic ocean model with a flexible sigma-z vertical coordinate. Two domains are used, one focused north and one focused south of Cape Hatteras. The domains overlap near the gliders, thus providing two forecasts near the gliders. Both domains have 1 km horizontal resolution. Data are assimilated in a newly-developed multi-scale data-processing and assimilating approach using NCOM-4DVAR. This enables NCOM-4DVAR to use many more observations than standard NCOM-4DVAR, improving the analysis and forecast. Assimilation experiments use station-keeping glider data, moving glider data, or all glider data. Sea surface temperature (SST) data and satellite altimeter (SSH) data are also assimilated. An additional experiment omits glider data but still assimilates SST and SSH data. Conductivity, temperature, and depth (CTD) profiles from the R/V Savannah are used for validation, including data from an underway CTD (UCTD). Data from glider teams have the potential to significantly improve model forecasts. Missions using teams of gliders can be planned to maximize data assimilation for optimal impact on model predictions.

Controlling effects of mesoscale eddies on thermohaline structure and in situ chlorophyll distribution in the western North Pacific

NASA Astrophysics Data System (ADS)

Gao, Wei; Wang, Zhenyan; Zhang, Kainan

2017-11-01

Based on the conductivity, temperature and depth (CTD) data collected at 93 hydrographic stations during a marine cruise and on contemporary satellite altimeter observations, a series of eddies have been observed passing over the stratified upper water of the Parece Vela Basin. The results from hydrographic measurements and in situ chlorophyll fluorescence measurements have revealed that these eddies exerted significant controlling effects on the thermohaline structure and chlorophyll distribution, especially on the prevalent subsurface chlorophyll maximum layer (SCML). Based on these observations and particulate beam attenuation coefficient (cp) data, the in situ phytoplankton bloom around the pycnocline can be largely attributable to the formation of a well-developed SCML in the studied system. The uplift of the cold subsurface water within the cyclone, shoaling the pycnocline to a shallower layer, resulted in a low-temperature anomaly and different salinity anomalies at different depths. This uplift in the cyclone further caused the SCML to appear at a shallower depth with a higher in situ chlorophyll concentration than that in the normal domain. Conversely, the sinking of the warm surface water to the subsurface layer within the anticyclone depressed the pycnocline to a deeper layer and generated a high-temperature anomaly and opposite salinity anomalies compared with the cyclone. The sinking of the pycnocline within the anticyclone considerably influenced the characteristics of the SCML, which had a deeper depth and a lower in situ chlorophyll concentration than that of the normal sea. This study contributes rare quasi-synchronous CTD observations capturing mesoscale eddies and provides valuable descriptions of the variations in the SCML under the influence of mesoscale eddies based on in situ optical measurements from the seldom-discussed western North Pacific.

Characterization of double diffusive convection step and heat budget in the deep Arctic Ocean

NASA Astrophysics Data System (ADS)

Zhou, S.; Lu, Y.

2013-12-01

In this paper, we explore the hydrographic structure and heat budget in deep Canada Basin using data measured with McLane-Moored-Profilers (MMPs), bottom-pressure-recorders (BPRs), and conductivity-temperature-depth (CTD) profilers. From the bottom upward, a homogenous bottom layer and its overlaying double diffusive convection (DDC) steps are well identified at Mooring A (75oN, 150oW). We find that the deep water is in weak diapycnal mixing because the effective diffusivity of the bottom layer is ~1.8×10-5 m 2s-1 while that of the other steps is ~10-6 m 2s-1. The vertical heat flux through DDC steps is evaluated with different methods. We find that the heat flux (0.1-11 mWm-2) is much smaller than geothermal heating (~50 mWm-2), which suggests that the stack of DDC steps acts as a thermal barrier in the deep basin. Moreover, the temporal distributions of temperature and salinity differences across the interface are exponential, while those of heat flux and effective diffusivity are found to be approximately log-normal. Both are the result of strong intermittency. Between 2003 and 2011, temperature fluctuation close to the sea floor distributed asymmetrically and skewed towards positive values, which provides direct indication that geothermal heating is transferred into ocean. Both BPR and CTD data suggest that geothermal heating, not the warming of upper ocean, is the dominant mechanism responsible for the warming of deep water. As the DDC steps prevent the vertical heat transfer, geothermal heating will be unlikely to have significant effect on the middle and upper oceans.

Characterization of double diffusive convection steps and heat budget in the deep Arctic Ocean

NASA Astrophysics Data System (ADS)

Zhou, Sheng-Qi; Lu, Yuan-Zheng

2013-12-01

In this paper, we explore the hydrographic structure and heat budget in the deep Canada Basin by using data measured with McLane-Moored-Profilers (MMP), bottom pressure recorders (BPR), and conductivity-temperature-depth (CTD) profilers. Upward from the bottom, a homogeneous bottom layer and its overlaying double diffusive convection (DDC) steps are well identified at Mooring A (75°N,150°W). We find that the deep water is in weak diapycnal mixing because the effective diffusivity of the bottom layer is ˜1.8 × 10-5 m2s-1, while that of the other steps is ˜10-6 m2s-1. The vertical heat flux through the DDC steps is evaluated by using different methods. We find that the heat flux (0.1-11 mWm -2) is much smaller than geothermal heating (˜50 mWm -2). This suggests that the stack of DDC steps acts as a thermal barrier in the deep basin. Moreover, the temporal distributions of temperature and salinity differences across the interface are exponential, whereas those of heat flux and effective diffusivity are found to be approximately lognormal. Both are the result of strong intermittency. Between 2003 and 2011, temperature fluctuations close to the sea floor were distributed asymmetrically and skewed toward positive values, which provide a direct observation that geothermal heating was transferred into the ocean. Both BPR and CTD data suggest that geothermal heating and not the warming of the upper ocean is the dominant mechanism responsible for the warming of deep water. As the DDC steps prevent vertical heat transfer, geothermal heating is unlikely to have a significant effect on the middle and upper Arctic Ocean.

Path homogeneity along a horizontal line-of-sight path during the FESTER experiment: first results

NASA Astrophysics Data System (ADS)

Gunter, W. H.; Maritz, B.; Koago, M.; Wainman, C. K.; Gardener, M. E.; February, F.; van Eijk, A. M. J.

2016-10-01

The First European South African Experiment (FESTER) was conducted over about a 10 month period at the Institute of Maritime Technology (IMT) in False Bay, South Africa. One of the important goals was the establishment of the air-sea temperature difference (ASTD) homogeneity along the main propagation link atmospheric path since it is a basic assumption for most of the atmospheric turbulence models (caused by refractive index variations). The ASTD was measured from a small scientific work boat (called Sea Lab) moving along a straight in- and outbound track along the main propagation link path. The air temperature on-board was measured using standard weather sensors, while the sea surface temperature was measured using a long wavelength infrared radiometer, which was compared to the bulk sea temperature half a meter below the sea surface. This was obtained by an under water temperature sensor mounted on a `surfboard' that was towed alongside Sea Lab. Vertical water temperature profiles were also measured along the main propagation path in order to determine the depth of the surface mixed layer and thermocline using a Conductivity Temperature Depth profiler (CTD). First results investigated the ASTD variation along the horizontal line-of-sight path used by the principal electro-optic transmission link monitoring equipment (i.e. scintillometer and multi-spectral radiometer-transmissometer system).

Seasonal Ice Zone Reconnaissance Surveys Coordination

DTIC Science & Technology

2016-03-30

sea surface temperature (SST), sea level atmospheric pressure ( SLP ), and velocity (Steele), and dropsonde measurements of atmospheric properties...aircraft), cloud top/base heights UpTempO buoys for understanding and prediction…. Steele UpTempO buoy drops for SLP , SST, SSS, & surface velocity...reflectance, skin temperature, visible imagery AXCTD= Air Expendable CTD, AXCP= Air Expendable Current Profiler, SLP = Sea Level atmospheric

Salinity Processes in the Upper Ocean Regional Study (SPURS)

NASA Image and Video Library

2012-09-04

Sean Whelan, a Marine Technician for the Woods Hole Oceanographic Institution, prepares CTD instruments used to measure Conductivity, Temperature, and Depth, onboard the Institute's research vessel Knorr on Tuesday, Sept. 4, 2012, in Woods Hole, Mass. The CTDs will be deployed in the Atlantic Ocean as part of the Salinity Processes in the Upper Ocean Regional Study (SPURS) which is set to sail on Sept. 6. The NASA-sponsored expedition will sail to the North Atlantic's saltiest spot to get a detailed, 3-D picture of how salt content fluctuates in the ocean's upper layers and how these variations are related to shifts in rainfall patterns around the planet. Photo Credit: (NASA/Bill Ingalls)

Long Term Surface Salinity Measurements

NASA Technical Reports Server (NTRS)

Schmitt, Raymond W.; Brown, Neil L.

2005-01-01

Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

A Superhelical Spiral in the Escherichia coli DNA Gyrase A C-terminal Domain Imparts Unidirectional Supercoiling Bias

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

Ruthenburg,A.; Graybosch, D.; Huetsch, J.

DNA gyrase is unique among type II topoisomerases in that its DNA supercoiling activity is unidirectional. The C-terminal domain of the gyrase A subunit (GyrA-CTD) is required for this supercoiling bias. We report here the x-ray structure of the Escherichia coli GyrA-CTD (Protein Data Bank code 1ZI0). The E. coli GyrA-CTD adopts a circular-shaped {beta}-pinwheel fold first seen in the Borrelia burgdorferi GyrA-CTD. However, whereas the B. burgdorferi GyrA-CTD is flat, the E. coli GyrA-CTD is spiral. DNA relaxation assays reveal that the E. coli GyrA-CTD wraps DNA inducing substantial (+) superhelicity, while the B. burgdorferi GyrA-CTD introduces a moremore » modest (+) superhelicity. The observation of a superhelical spiral in the present structure and that of the Bacillus stearothermophilus ParC-CTD structure suggests unexpected similarities in substrate selectivity between gyrase and Topo IV enzymes. We propose a model wherein the right-handed ((+) solenoidal) wrapping of DNA around the E. coli GyrA-CTD enforces unidirectional (-) DNA supercoiling.« less

Structural dynamics of native and V260E mutant C-terminal domain of HIV-1 integrase

NASA Astrophysics Data System (ADS)

Sangeetha, Balasubramanian; Muthukumaran, Rajagopalan; Amutha, Ramaswamy

2015-04-01

The C-terminal domain (CTD) of HIV-1 integrase is a five stranded β-barrel resembling an SH3 fold. Mutational studies on isolated CTD and full-length IN have reported V260E mutant as either homo-dimerization defective or affecting the stability and folding of CTD. In this study, molecular dynamics simulation techniques were used to unveil the effect of V260E mutation on isolated CTD monomer and dimer. Both monomeric and dimeric forms of wild type and V260E mutant are highly stable during the simulated period. However, the stabilizing π-stacking interaction between Trp243 and Trp243' at the dimer interface is highly disturbed in CTD-V260E (>6 Å apart). The loss in entropy for dimerization is -30 and -25 kcal/mol for CTD-wt and CTD-V260E respectively signifying a weak hydrophobic interaction and its perturbation in CTD-V260E. The mutant Glu260 exhibits strong attraction/repulsion with all the basic/acidic residues of CTD. In addition to this, the dynamics of CTD-wild type and V260E monomers at 498 K was analyzed to elucidate the effect of V260E mutation on CTD folding. Increase in SASA and reduction in the number of contacts in CTD-V260E during simulation highlights the instability caused by the mutation. In general, V260E mutation affects both multimerization and protein folding with a pronounced effect on protein folding rather than multimerization. This study emphasizes the importance of the hydrophobic nature and SH3 fold of CTD in proper functioning of HIV integrase and perturbing this nature would be a rational approach toward designing more selective and potent allosteric anti-HIV inhibitors.

Gene-Environment Interplay in Twin Models

PubMed Central

Hatemi, Peter K.

2013-01-01

In this article, we respond to Shultziner’s critique that argues that identical twins are more alike not because of genetic similarity, but because they select into more similar environments and respond to stimuli in comparable ways, and that these effects bias twin model estimates to such an extent that they are invalid. The essay further argues that the theory and methods that undergird twin models, as well as the empirical studies which rely upon them, are unaware of these potential biases. We correct this and other misunderstandings in the essay and find that gene-environment (GE) interplay is a well-articulated concept in behavior genetics and political science, operationalized as gene-environment correlation and gene-environment interaction. Both are incorporated into interpretations of the classical twin design (CTD) and estimated in numerous empirical studies through extensions of the CTD. We then conduct simulations to quantify the influence of GE interplay on estimates from the CTD. Due to the criticism’s mischaracterization of the CTD and GE interplay, combined with the absence of any empirical evidence to counter what is presented in the extant literature and this article, we conclude that the critique does not enhance our understanding of the processes that drive political traits, genetic or otherwise. PMID:24808718

Hydrographic observations by instrumented marine mammals in the Sea of Okhotsk

NASA Astrophysics Data System (ADS)

Nakanowatari, Takuya; Ohshima, Kay I.; Mensah, Vigan; Mitani, Yoko; Hattori, Kaoru; Kobayashi, Mari; Roquet, Fabien; Sakurai, Yasunori; Mitsudera, Humio; Wakatsuchi, Masaaki

2017-09-01

The Sea of Okhotsk is a challenging environment for obtaining in situ data and satellite observation in winter due to sea ice cover. In this study, we evaluated the validity of hydrographic observations by marine mammals (e.g., seals and sea lions) equipped with oceanographic conductivity-temperature-depth (CTD) sensors. During 4-yr operations from 2011 to 2014, we obtained total of 997 temperature-salinity profiles in and around the Soya Strait, Iony Island, and Urup Strait. The hydrographic data were mainly obtained from May to August and the maximum profile depth in shelf regions almost reaches to the seafloor, while valuable hydrographic data under sea ice cover were also obtained. In strong thermoclines, the seal-derived data sometimes showed positive biases in salinity with spike-like signal. For these salinity biases, we applied a new thermal mass inertia correction scheme, effectively reducing spurious salinity biases in the seasonal thermocline. In the Soya Strait and the adjacent region, the detailed structure of the Soya Warm Current including the cold-water belt was well identified. Dense water up to 27.0σθ, which can be a potential source of Okhotsk Sea Intermediate Water, has flowed from the Soya Strait into the Sea of Okhotsk in mid-winter (February). In summer, around the Iony Island and Urup Strait, remarkable cold and saline waters are localized in the surface layers. These regions are also characterized by weak stratification, suggesting the occurrence of tidally induced vertical mixing. Thus, CTD-tag observations have a great potential in monitoring data-sparse regions in the Sea of Okhotsk.

Arctic Ocean outflow and glacier-ocean interactions modify water over the Wandel Sea shelf (northeastern Greenland)

NASA Astrophysics Data System (ADS)

Dmitrenko, Igor A.; Kirillov, Sergey A.; Rudels, Bert; Babb, David G.; Toudal Pedersen, Leif; Rysgaard, Søren; Kristoffersen, Yngve; Barber, David G.

2017-12-01

The first-ever conductivity-temperature-depth (CTD) observations on the Wandel Sea shelf in northeastern Greenland were collected in April-May 2015. They were complemented by CTDs taken along the continental slope during the Norwegian FRAM 2014-2015 drift. The CTD profiles are used to reveal the origin of water masses and interactions with ambient water from the continental slope and the tidewater glacier outlet. The subsurface water is associated with the Pacific water outflow from the Arctic Ocean. The underlying halocline separates the Pacific water from a deeper layer of polar water that has interacted with the warm Atlantic water outflow through the Fram Strait, recorded below 140 m. Over the outer shelf, the halocline shows numerous cold density-compensated intrusions indicating lateral interaction with an ambient polar water mass across the continental slope. At the front of the tidewater glacier outlet, colder and turbid water intrusions were observed at the base of the halocline. On the temperature-salinity plots these stations indicate a mixing line that is different from the ambient water and seems to be conditioned by the ocean-glacier interaction. Our observations of Pacific water are set within the context of upstream observations in the Beaufort Sea and downstream observations from the Northeast Water Polynya, and clearly show the modification of Pacific water during its advection across the Arctic Ocean. Moreover, ambient water over the Wandel Sea slope shows different thermohaline structures indicating the different origin and pathways of the on-shore and off-shore branches of the Arctic Ocean outflow through the western Fram Strait.

Connective Tissue Disease-associated Interstitial Lung Diseases (CTD-ILD) - Report from OMERACT CTD-ILD Working Group.

PubMed

Khanna, Dinesh; Mittoo, Shikha; Aggarwal, Rohit; Proudman, Susanna M; Dalbeth, Nicola; Matteson, Eric L; Brown, Kevin; Flaherty, Kevin; Wells, Athol U; Seibold, James R; Strand, Vibeke

2015-11-01

Interstitial lung disease (ILD) is common in connective tissue disease (CTD) and is the leading cause of mortality. Investigators have used certain outcome measures in randomized controlled trials (RCT) in CTD-ILD, but the lack of a systematically developed, CTD-specific index that captures all measures relevant and meaningful to patients with CTD-ILD has left a large and conspicuous gap in CTD-ILD research. The CTD-ILD working group, under the aegis of the Outcome Measures in Rheumatology (OMERACT) initiative, has completed a consensus group exercise to reach harmony on core domains and items for inclusion in RCT in CTD-ILD. During the OMERACT 12 meeting, consensus was sought on domains and core items for inclusion in RCT. In addition, consensus was pursued on a definition of response in RCT. Consensus was defined as ≥ 75% agreement among the participants. OMERACT 12 participants endorsed the domains with minimal modifications. Clinically meaningful progression for CTD-ILD was proposed as ≥ 10% relative decline in forced vital capacity (FVC) or ≥ 5% to < 10% relative decline in FVC and ≥ 15% relative decline in DLCO. There is consensus on domains for inclusion in RCT in CTD-ILD and on a definition of clinically meaningful progression. Data-driven approaches to validate these results in different cohorts and RCT are needed.

Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo.

PubMed

Li, Chi-Chuan; Yu, Fu-Shun; Fan, Ming-Jen; Chen, Ya-Yin; Lien, Jin-Cherng; Chou, Yu-Cheng; Lu, Hsu-Feng; Tang, Nou-Ying; Peng, Shu-Fen; Huang, Wen-Wen; Chung, Jing-Gung

2017-03-01

Cantharidin (CTD), a potential anticancer agent of Traditional Chinese Medicine has cytotxic effects in different human cancer cell lines. The cytotoxic effects of CTD on A431 human skin cancer (epidermoid carcinoma) cells in vitro and in A431 cell xenograft mouse model were examined. In vitro, A431 human skin cell were treated with CTD for 24 and 48 h. Cell phase distribution, ROS production, Ca 2+ release, Caspase activity and the level of apoptosis associated proteins were measured. In vivo, A431 cell xenograft mouse model were examined. CTD-induced cell morphological changes and decreased percentage of viable A431 cells via G0/G1 phase arrest and induced apoptosis. CTD-induced G0/G1 phase arrest through the reduction of protein levels of cyclin E, CDK6, and cyclin D in A431 cells. CTD-induced cell apoptosis of A431 cells also was confirm by DNA gel electrophoresis showed CTD-induced DNA fragmentation. CTD reduced the mitochondrial membrane potential and stimulated release of cytochrome c, AIF and Endo G in A431 cells. Flow cytometry demonstrated that CTD increased activity of caspase-8, -9 and -3. However, when cells were pretreated with specific caspase inhibitors activity was reduced and cell viability increased. CTD increased protein levels of death receptors such as DR4, DR5, TRAIL and levels of the active form of caspase-8, -9 and -3 in A431 cells. AIF and Endo G proteins levels were also enhanced by CTD. In vivo studies showed that CTD significantly inhibited A431 cell xenograft tumors in mice. Taken together, these in vitro and in vivo results provide insight into the mechanisms of CTD on cell growth and tumor production. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 723-738, 2017. © 2016 Wiley Periodicals, Inc.

A numerical analysis of the performance of unpumped SBE 41 sensors at low flushing rates

NASA Astrophysics Data System (ADS)

Alvarez, A.

2018-05-01

The thermal and hydrodynamic response of a Sea-Bird unpumped CTD SBE 41, is numerically modeled to assess the biases occurring at the slow flushing rates typical of glider operations. Based on symmetry considerations, the sensor response is approximated by coupling the incompressible Navier-Stokes and the thermal advection-diffusion equations in two dimensions. Numerical results illustrate three regimes in the thermal response of the SBE 41 sensor, when crossing water layers with different thermal signatures. A linear decay in time of the bulk temperature of the conductivity cell is initially found. This is induced by the transit of the inflow through the conductivity cell in the form of a relatively narrow jet. Water masses with new thermal signatures do not immediately fill the sensor chambers, where the cross-section widens. Thermal equilibrium of these water masses is then achieved, in a second regime, via a cross-flow thermal diffusion between the boundary of the jet and the walls. Consequently, the evolution of the bulk temperature scales with the square root of time. In a third regime, the evolution of the bulk temperature depends on the thermal gradient between the fluid and the coating material. This results on an exponential decay of the bulk temperature with time. A comprehensive analytical model of the time evolution of the bulk temperature inside a cell is proposed based on these results.

Seasonal Ice Zone Reconnaissance Surveys Coordination

DTIC Science & Technology

2014-09-30

profiler (AXCP) ocean velocity shear (Morison), UpTempO buoy measurements of sea surface temperature (SST), sea level atmospheric pressure ( SLP ), and...and prediction…. Steele UpTempO buoy drops for SLP , SST, SSS, & surface velocity Visible and Thermal Images of the SIZ from the Coast Guard...Expendable CTD, AXCP= Air Expendable Current Profiler, SLP = Sea Level atmospheric Pressure, SST= Seas Surface Temperature, A/C= aircraft, SIC=Sea Ice

Physical Chemical and in-situ CTD (Conductivity/Temperature/Depth) Data from the Ajax Expedition in the South Atlantic Ocean.

DTIC Science & Technology

1985-12-15

SALINITY SIGMA SIGMA S1; KA OVA DYN M T OXYGEN 000 I10 P04 Nn lA? 02 09 A EG C ’Er, C TAETA 2 4 MIL PCI UP/IL U MIL UIL 04/L . 15L 2,641 .641 03.923...epart ment i if the Nays t S TOI KA Priest fi 1ce N,,’.,l OLcin Sysrenis Center Prof C’ G 11 Rititf N) 0 ?% R /( %R San Iliego. C A 921 i2 I nisersity if...Dr. Adriana Huyer Cambridge, MA 02139 U.S. Dept. of Commerce, NOAA School of Oceanography Geophysical Fluid Dynamics Lab Oregon State University Dr

78 FR 9098 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

... executed contract for the MIAX Clearing Trade Drop (``CTD''), a messaging interface that will provide real... proposes to establish a new Port Fee for the MIAX CTD. CTD provides Exchange Members, their clearing firms... are routed to a CTD connection containing certain information. The information includes, among other...

77 FR 35691 - Update to Electronic Common Technical Document Module 1

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-14

... Electronic Common Technical Document (eCTD) Module 1, which is used for electronic submission of... they are received with a limit of 350. SUPPLEMENTARY INFORMATION: The eCTD is an International... Research (CBER) have been receiving submissions in the eCTD format since 2003, and the eCTD has been the...

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

PubMed Central

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

2017-01-01

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

Deletion of the COOH-Terminal Domain of CXC Chemokine Receptor 4 Leads to the Down-regulation of Cell-to-Cell Contact, Enhanced Motility and Proliferation in Breast Carcinoma Cells

PubMed Central

Ueda, Yukiko; Neel, Nicole F.; Schutyser, Evemie; Raman, Dayanidhi; Richmond, Ann

2009-01-01

The CXC chemokine receptor 4 (CXCR4) contributes to the metastasis of human breast cancer cells. The CXCR4 COOH-terminal domain (CTD) seems to play a major role in regulating receptor desensitization and down-regulation. We expressed either wild-type CXCR4 (CXCR4-WT) or CTD-truncated CXCR4 (CXCR4-ΔCTD) in MCF-7 human mammary carcinoma cells to determine whether the CTD is involved in CXCR4-modulated proliferation of mammary carcinoma cells. CXCR4-WT-transduced MCF-7 cells (MCF-7/CXCR4-WT cells) do not differ from vector-transduced MCF-7 control cells in morphology or growth rate. However, CXCR4-ΔCTD-transduced MCF-7 cells (MCF-7/CXCR4-ΔCTD cells) exhibit a higher growth rate and altered morphology, potentially indicating an epithelial-to-mesenchymal transition. Furthermore, extracellular signal-regulated kinase (ERK) activation and cell motility are increased in these cells. Ligand induces receptor association with β-arrestin for both CXCR4-WT and CXCR4-ΔCTD in these MCF-7 cells. Overexpressed CXCR4-WT localizes predominantly to the cell surface in unstimulated cells, whereas a significant portion of overexpressed CXCR4-ΔCTD resides intracellularly in recycling endosomes. Analysis with human oligomicroarray, Western blot, and immunohistochemistry showed that E-cadherin and Zonula occludens are down-regulated in MCF-7/CXCR4-ΔCTD cells. The array analysis also indicates that mesenchymal marker proteins and certain growth factor receptors are up-regulated in MCF-7/CXCR4-ΔCTD cells. These observations suggest that (a) the overexpression of CXCR4-ΔCTD leads to a gain-of-function of CXCR4-mediated signaling and (b) the CTD of CXCR4-WT may perform a feedback repressor function in this signaling pathway. These data will contribute to our understanding of how CXCR4-ΔCTD may promote progression of breast tumors to metastatic lesions. PMID:16740704

Long-Term Observations of Nitrogen and Phosphorus Export in Paired-Agricultural Watersheds under Controlled and Conventional Tile Drainage.

PubMed

Sunohara, M D; Gottschall, N; Wilkes, G; Craiovan, E; Topp, E; Que, Z; Seidou, O; Frey, S K; Lapen, D R

2015-09-01

Controlled tile drainage (CTD) regulates water and nutrient export from tile drainage systems. Observations of the effects of CTD imposed en masse at watershed scales are needed to determine the effect on downstream receptors. A paired-watershed approach was used to evaluate the effect of field-to-field CTD at the watershed scale on fluxes and flow-weighted mean concentrations (FWMCs) of N and P during multiple growing seasons. One watershed (467-ha catchment area) was under CTD management (treatment [CTD] watershed); the other (250-ha catchment area) had freely draining or uncontrolled tile drainage (UCTD) (reference [UCTD] watershed). The paired agricultural watersheds are located in eastern Ontario, Canada. Analysis of covariance and paired tests were used to assess daily fluxes and FWMCs during a calibration period when CTD intervention on the treatment watershed was minimal (2005-2006, when only 4-10% of the tile-drained area was under CTD) and a treatment period when the treatment (CTD) watershed had prolific CTD intervention (2007-2011 when 82% of tile drained fields were controlled, occupying >70% of catchment area). Significant linear regression slope changes assessed using ANCOVA ( ≤ 0.1) for daily fluxes from upstream and downstream monitoring sites pooled by calibration and treatment period were -0.06 and -0.20 (stream water) (negative values represent flux declines in CTD watershed), -0.59 and -0.77 (NH-N), -0.14 and -0.15 (NO-N), -1.77 and -2.10 (dissolved reactive P), and -0.28 and 0.45 (total P). Total P results for one site comparison contrasted with other findings likely due to unknown in-stream processes affecting total P loading, not efficacy of CTD. The FWMC results were mixed and inconclusive but suggest physical abatement by CTD is the means by which nutrient fluxes are predominantly reduced at these scales. Overall, our study results indicate that CTD is an effective practice for reducing watershed scale fluxes of stream water, N, and P during the growing season. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Bowhead whales feed on plankton concentrated by estuarine and tidal currents in Academy Bay, Sea of Okhotsk

NASA Astrophysics Data System (ADS)

Rogachev, Konstantin A.; Carmack, Eddy C.; Foreman, Michael G. G.

2008-08-01

Academy Bay in the Sea of Okhotsk is an important summertime feeding ground for pelagic-feeding Bowhead whales ( Balaena mysticetus) in the western subarctic North Pacific. The present work combines satellite observations with physical (CTD, currents, tides) and biological (zooplankton sampling) measurements. Data obtained aboard the RV Lugovoe in August-September 2003 and July-August 2004 show dense populations of zooplankton (such as copepods Calanus glacialis, Pseudocalanus sp., pteropods Limacina helicina, and chaetognaths Sagitta sp.) that are concentrated by physical mechanisms within this critically important ecosystem. We show that near-bottom, cold water intrusions from the northern Sea of Okhotsk associated with the estuarine circulation advect arctic herbivorous calanoids ( Calanus glacialis) and mollusks Limacina helicina into the region. Satellite and in situ observations that include conductivity-temperature-depth (CTD) data and measurements of tidal currents are used to study the nature of the estuarine circulation. Results show an anticyclonic circulation, associated with the effect of earth's rotation. An analytical model shows horizontally convergent flows in the lower layer toward the western coast of the bay that push water upward along the steep slope. This together with zooplankton vertical migration leads to aggregation. Thus the combination of the residual eddy formation and swimming behavior act to concentrate zooplankton near the cape and to provide the necessary densities of planktonic food supply for Bowhead whales.

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

Combination of ORP and pH sensors in tow-yo studies to map redox and acid-base anomalies in seawater due to hydrothermal activity in shallow areas

NASA Astrophysics Data System (ADS)

Santana-Casiano, J. M.; González-Dávila, M.; Fraile-Nuez, E.; Santana-González, C.; Baker, E. T.; Resing, J. A.; Walker, S. L.

2016-12-01

The detection of activity from low-temperature hydrothermal vents, where the increase in temperature is not evident, requires the utilization of alternative sensors that respond to emissions of certain chemical species. The character of both reduced and acid fluids in the volcanic emissions in the El Hierro submarine volcano allowed us to detect anomalies related with changes in the chemical potential and the proton concentration using ORP and pH sensors, respectively. Tow-yos with these sensors provided the approximate locations of the emissions plotting δ(ORP)/δt and ΔpH versus the latitude or longitude. The ORP sensor responds very quickly to the presence of reduced chemicals in the water column. The magnitude of this change is examined by the time derivative of ORP, δ(ORP)/δt. For pH changes, ΔpH, the mean pH for each depth at a reference station in an area not affected by the vent emission is subtracted from each point measured near the volcanic edifice. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to apply CTD-pH-ORP tow-yo methodology and to study the effect of CO2 emission on the seawater carbonate system, the global carbon flux, and local ocean acidification. Detailed surveys of the volcanic edifice were carried out during VULCANO 0314 and VULCANA0615 cruises using several CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. CTD-pH-ORP yo-yo studies were also conducted that included discrete sampling for carbonate system parameters and total dissolved Fe(II), TDFe(II). The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 105 ± 1.1 105 kg d-1and increases the acidity above the volcano by 20%. From the yo-yo studies important anomalies in both pHT and TDFe(II) were observed. The increased TDFe(II) concentrations and the low associated pHT values may be acting as an important fertilization event in the seawater around the volcano at the Island of El Hierro providing optimal conditions for the regeneration of the area.

The risk of cancer in patients with connective tissue diseases but without dermatomyositis or polymyositis: A multicenter cohort study conducted over 15 years in China.

PubMed

Xu, Wei; Guo, Huan; Liu, Zhi; Chen, Chen; Lei, Cong-Cong

2016-09-01

To investigate the relative risk of cancer in Chinese patients with connective tissue diseases (CTD) associated with and without dermatomyositis or polymyositis. A retrospective, multicenter cohort study investigated 32,380 CTD patients (2334 diagnosed with dermatomyositis or polymyositis) without a history of malignancies treated from January 1, 1997, to December 31, 2011. Standardized incidence ratios (SIR) of cancers determined the incidence of malignancies during follow-up. The data was compared with the cancer morbidity of the general population from the Chinese Cancer Registry Annual Report of National Central Cancer Registry. A total of 113 patients (348.98 per 100,000) developed cancer during follow-up, 75 (249.62 per 100,000) were patients with CTD without dermatomyositis or polymyositis. The risk of cancer among patients with CTD was increased (SIR=1.45, 95% confidence interval [CI] 1.22-1.71), and this risk increased with age (<40 years: SIR=1.00 [95%CI 0.45-2.21]; 41-60 years: SIR=1.53 [95%CI 1.17-2.00]; and >60 years SIR=2.34 (95%CI 0.93-2.77]) and the time of follow-up (<1year: SIR=1.22 [95%CI 0.88-1.70]; 1-5 years: SIR=1.14 [95%CI 0.79-1.65]; and 6-10 years SIR=1.70 [95%CI 1.34-2.85]), but was similar between genders (male SIR=1.60 [95%CI 1.10-2.31] and female SIR=1.25 [95%CI 1.01-1.55]). The cancer risk among CTD patients without dermatomyositis or polymyositis was not affected (SIR=0.93, 95%CI 0.75-1.16), regardless of gender, age, or follow-up. The cancer risk for patients with CTD without dermatomyositis or polymyositis was not increased or decreased, but it was increased when patients with dermatomyositis or polymyositis were included. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Crystal Structure of the Ternary Complex of a NaV C-Terminal Domain, a Fibroblast Growth Factor Homologous Factor, and Calmodulin

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

Wang, Chaojian; Chung, Ben C.; Yan, Haidun

2012-11-13

Voltage-gated Na{sup +} (Na{sub V}) channels initiate neuronal action potentials. Na{sub V} channels are composed of a transmembrane domain responsible for voltage-dependent Na{sup +} conduction and a cytosolic C-terminal domain (CTD) that regulates channel function through interactions with many auxiliary proteins, including fibroblast growth factor homologous factors (FHFs) and calmodulin (CaM). Most ion channel structural studies have focused on mechanisms of permeation and voltage-dependent gating but less is known about how intracellular domains modulate channel function. Here we report the crystal structure of the ternary complex of a human NaV CTD, an FHF, and Ca{sup 2+}-free CaM at 2.2 {angstrom}.more » Combined with functional experiments based on structural insights, we present a platform for understanding the roles of these auxiliary proteins in NaV channel regulation and the molecular basis of mutations that lead to neuronal and cardiac diseases. Furthermore, we identify a critical interaction that contributes to the specificity of individual NaV CTD isoforms for distinctive FHFs.« less

Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study.

PubMed

Oguz, Ekin Oktay; Kucuksahin, Orhan; Turgay, Murat; Yildizgoren, Mustafa Turgut; Ates, Askin; Demir, Nalan; Kumbasar, Ozlem Ozdemir; Kinikli, Gulay; Duzgun, Nursen

2016-03-01

It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p < 0.008 and p < 0.001, respectively). There was no statistically significant difference between the KL-6 levels in the healthy control group and the CTD without pulmonary involvement group (p = 0.289). The KL-6 levels did not differ significantly according to the connective tissue diseases in the diagnostic groups (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, scleroderma, polymyositis/ dermatomyositis). In the healthy control group, there was a statistically significant difference between KL-6 levels in smokers and non-smokers. Smokers had significantly higher serum KL-6 levels compared with non-smokers (p < 0.05). There was no statistically significant difference between smoking status (pack-year) and serum KL-6 levels. There was no statistically significant correlation between serum KL-6 levels and time since diagnosis of CTD and CTD-ILD. The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality. Further prospective clinical studies are needed to define whether levels of KL-6 might have prognostic value or might predict progressive ILD.

[Impaired endometrial receptivity in primary infertility in women with undifferentiated connective tissue dysplasia and hereditary thrombophilia].

PubMed

Zanozin, A S; Demura, T A; Kolosovsky, D Yu; Faizullina, N M; Kogan, E A

The concurrence of undifferentiated connective tissue dysplasia (uCTD) and hereditary thrombophilia (HT) often accompanies female infertility, in the pathogenesis of which impaired endometrial receptivity plays an important role. to investigate endometrial morphological and immunophenotypic features in patients with primary infertility in the presence of uCTD and HT. The pipelle endometrial biopsy specimens taken in the implantation window were examined in 81 patients, including 13 women with a clinical diagnosis of uCTD, 40 with HT, 19 with uCTD concurrent with HT, and in a control group of 9 heathy surrogate mothers. Morphological, immunohistochemical, and morphometric examinations were done to study the paraffin-embedded endometrial biopsy sections stained with hematoxylin and eosin, pikrofuksin by van Gieson, and with toluidine blue. Immunohistochemical tests were carried out using primary antibodies against ER, PgR, LIF, PAI-1, VEGF, Collagen I, Collagen III, fibronectin, laminin, MMP-2, and MMP-9. The uCTD, HT, and uCTD + HT groups were found to have signs of decreased endometrial receptivity as dramatically lower counts of mature pinopodes, slower endometrial maturation, reduced expression of the receptivity marker LIF, and deviations of the stromal progesterone-estrogen index from the normal value. Sclerotic foci with type III collagen accumulation were detected in the endometrial stroma. uCTD and HT and especially their concurrence are commonly a concomitant disease and risk factors for infertility in women due to impaired endometrial receptivity. In uCTD, connective tissue remodeling processes are substantially retarded, which ultimately leads to increased processes of endometrial stromal sclerosis, reduced endometrial receptivity, and infertility. The most pronounced morphological and immunophenotypical changes have been ascertained to develop in the uCTD + NT group. The findings may be used to predict and devise new infertility treatments in patients with uCTD + NT.

Suppression Analysis Reveals a Functional Difference between the Serines in Positions Two and Five in the Consensus Sequence of the C-Terminal Domain of Yeast RNA Polymerase II

PubMed Central

Yuryev, A.; Corden, J. L.

1996-01-01

The largest subunit of RNA polymerase II contains a repetitive C-terminal domain (CTD) consisting of tandem repeats of the consensus sequence Tyr(1)Ser(2)Pro(3)Thr(4) Ser(5)Pro(6) Ser(7). Substitution of nonphosphorylatable amino acids at positions two or five of the Saccharomyces cerevisiae CTD is lethal. We developed a selection ssytem for isolating suppressors of this lethal phenotype and cloned a gene, SCA1 (suppressor of CTD alanine), which complements recessive suppressors of lethal multiple-substitution mutations. A partial deletion of SCA1 (sca1Δ::hisG) suppresses alanine or glutamate substitutions at position two of the consensus CTD sequence, and a lethal CTD truncation mutation, but SCA1 deletion does not suppress alanine or glutamate substitutions at position five. SCA1 is identical to SRB9, a suppressor of a cold-sensitive CTD truncation mutation. Strains carrying dominant SRB mutations have the same suppression properties as a sca1Δ::hisG strain. These results reveal a functional difference between positions two and five of the consensus CTD heptapeptide repeat. The ability of SCA1 and SRB mutant alleles to suppress CTD truncation mutations suggest that substitutions at position two, but not at position five, cause a defect in RNA polymerase II function similar to that introduced by CTD truncation. PMID:8725217

Crystal structures of Lymnaea stagnalis AChBP in complex with neonicotinoid insecticides imidacloprid and clothianidin

PubMed Central

Ihara, Makoto; Okajima, Toshihide; Yamashita, Atsuko; Oda, Takuma; Hirata, Koichi; Nishiwaki, Hisashi; Morimoto, Takako; Akamatsu, Miki; Ashikawa, Yuji; Kuroda, Shun’ichi; Mega, Ryosuke; Kuramitsu, Seiki; Sattelle, David B.

2008-01-01

Neonicotinoid insecticides, which act on nicotinic acetylcholine receptors (nAChRs) in a variety of ways, have extremely low mammalian toxicity, yet the molecular basis of such actions is poorly understood. To elucidate the molecular basis for nAChR–neonicotinoid interactions, a surrogate protein, acetylcholine binding protein from Lymnaea stagnalis (Ls-AChBP) was crystallized in complex with neonicotinoid insecticides imidacloprid (IMI) or clothianidin (CTD). The crystal structures suggested that the guanidine moiety of IMI and CTD stacks with Tyr185, while the nitro group of IMI but not of CTD makes a hydrogen bond with Gln55. IMI showed higher binding affinity for Ls-AChBP than that of CTD, consistent with weaker CH–π interactions in the Ls-AChBP–CTD complex than in the Ls-AChBP–IMI complex and the lack of the nitro group-Gln55 hydrogen bond in CTD. Yet, the NH at position 1 of CTD makes a hydrogen bond with the backbone carbonyl of Trp143, offering an explanation for the diverse actions of neonicotinoids on nAChRs. PMID:18338186

The RNA polymerase II CTD coordinates transcription and RNA processing

PubMed Central

Hsin, Jing-Ping; Manley, James L.

2012-01-01

The C-terminal domain (CTD) of the RNA polymerase II largest subunit consists of multiple heptad repeats (consensus Tyr1–Ser2–Pro3–Thr4–Ser5–Pro6–Ser7), varying in number from 26 in yeast to 52 in vertebrates. The CTD functions to help couple transcription and processing of the nascent RNA and also plays roles in transcription elongation and termination. The CTD is subject to extensive post-translational modification, most notably phosphorylation, during the transcription cycle, which modulates its activities in the above processes. Therefore, understanding the nature of CTD modifications, including how they function and how they are regulated, is essential to understanding the mechanisms that control gene expression. While the significance of phosphorylation of Ser2 and Ser5 residues has been studied and appreciated for some time, several additional modifications have more recently been added to the CTD repertoire, and insight into their function has begun to emerge. Here, we review findings regarding modification and function of the CTD, highlighting the important role this unique domain plays in coordinating gene activity. PMID:23028141

The Cancer Target Discovery and Development Network Dashboard Allows Users to Search for Interesting Data and Results | Office of Cancer Genomics

Cancer.gov

The CTD2 Dashboard hosts analyzed data and other evidence generated by the CTD2 Network. It is a web interface for the research community to browse and search CTD2 Network data related to genes, proteins, and compounds from individual CTD2 Centers, or explore observations across multiple Centers.

Critical Thinking Disposition of Nurse Practitioners in Taiwan.

PubMed

Hsu, Hsiu-Ying; Chang, Shu-Chen; Chang, Ai-Ling; Chen, Shiah-Lian

2017-09-01

Critical thinking disposition (CTD) is crucial for nurse practitioners who face complex patient care scenarios. This study explored the CTD of nurse practitioners and related factors. The study was a cross-sectional descriptive design. A purposive sample was recruited from a medical center and its hospital branches in central Taiwan. A structured questionnaire was used to collect data from 210 nurse practitioners. The participants obtained the highest average score on systematicity and analyticity. CTD had a significant positive correlation with fundamental knowledge readiness, professional knowledge readiness, and confidence in making clinical decisions. Professional knowledge readiness, education level, and on-the-job training predicted the score of the participants on overall CTD. On-the-job training and education level may influence the CTD of nurse practitioners. Providing formal or on-the-job continuing education training to nurse practitioners may help enhance their CTD. J Contin Educ Nurs. 2017;48(9):425-430. Copyright 2017, SLACK Incorporated.

Role of the RNA polymerase α subunits in CII-dependent activation of the bacteriophage λ pE promoter: identification of important residues and positioning of the α C-terminal domains

PubMed Central

Kedzierska, Barbara; Lee, David J.; Węgrzyn, Grzegorz; Busby, Stephen J. W.; Thomas, Mark S.

2004-01-01

The bacteriophage λ CII protein stimulates the activity of three phage promoters, pE, pI and paQ, upon binding to a site overlapping the –35 element at each promoter. Here we used preparations of RNA polymerase carrying a DNA cleavage reagent attached to specific residues in the C-terminal domain of the RNA polymerase α subunit (αCTD) to demonstrate that one αCTD binds near position –41 at pE, whilst the other αCTD binds further upstream. The αCTD bound near position –41 is oriented such that its 261 determinant is in close proximity to σ70. The location of αCTD in CII-dependent complexes at the pE promoter is very similar to that found at many activator-independent promoters, and represents an alternative configuration for αCTD at promoters where activators bind sites overlapping the –35 region. We also used an in vivo alanine scan analysis to show that the DNA-binding determinant of αCTD is involved in stimulation of the pE promoter by CII, and this was confirmed by in vitro transcription assays. We also show that whereas the K271E substitution in αCTD results in a drastic decrease in CII-dependent activation of pE, the pI and paQ promoters are less sensitive to this substitution, suggesting that the role of αCTD at the three lysogenic promoters may be different. PMID:14762211

CTD2 Dashboard: a searchable web interface to connect validated results from the Cancer Target Discovery and Development Network

PubMed Central

Aksoy, Bülent Arman; Dančík, Vlado; Smith, Kenneth; Mazerik, Jessica N.; Ji, Zhou; Gross, Benjamin; Nikolova, Olga; Jaber, Nadia; Califano, Andrea; Schreiber, Stuart L.; Gerhard, Daniela S.; Hermida, Leandro C.; Jagu, Subhashini

2017-01-01

Abstract The Cancer Target Discovery and Development (CTD2) Network aims to use functional genomics to accelerate the translation of high-throughput and high-content genomic and small-molecule data towards use in precision oncology. As part of this goal, and to share its conclusions with the research community, the Network developed the ‘CTD2 Dashboard’ [https://ctd2-dashboard.nci.nih.gov/], which compiles CTD2 Network-generated conclusions, termed ‘observations’, associated with experimental entities, collected by its member groups (‘Centers’). Any researcher interested in learning about a given gene, protein, or compound (a ‘subject’) studied by the Network can come to the CTD2 Dashboard to quickly and easily find, review, and understand Network-generated experimental results. In particular, the Dashboard allows visitors to connect experiments about the same target, biomarker, etc., carried out by multiple Centers in the Network. The Dashboard’s unique knowledge representation allows information to be compiled around a subject, so as to become greater than the sum of the individual contributions. The CTD2 Network has broadly defined levels of validation for evidence (‘Tiers’) pertaining to a particular finding, and the CTD2 Dashboard uses these Tiers to indicate the extent to which results have been validated. Researchers can use the Network’s insights and tools to develop a new hypothesis or confirm existing hypotheses, in turn advancing the findings towards clinical applications. Database URL: https://ctd2-dashboard.nci.nih.gov/ PMID:29220450

Pneumocystis jirovecii pneumonia in mycophenolate mofetil-treated patients with connective tissue disease: analysis of 17 cases.

PubMed

Zhang, Yongfeng; Zheng, Yi

2014-12-01

The association of Pneumocystis jirovecii pneumonia (PJP) with connective tissue disease (CTD) and mycophenolate mofetil's (MMF) potent activity against PJP have been separately reported. Until now, there have been no papers describing the occurrence of PJP following MMF treatment in CTD patients. The objective of this study was to describe the clinical features, risk factors, outcomes of PJP in patients with CTD and investigates the effects of MMF on the occurrence of PJP in China. In this retrospective cohort study, we performed a chart review, analyzing clinical features, treatment, and outcomes of PJP in patients with CTD in a single hospital. A total of 17 cases met the inclusion criteria of having PJP and a CTD diagnosis: systemic lupus erythematosus; polymyositis; dermatomyositis; rheumatoid arthritis; Wegener's granulomatosis; and microscopic polyangiitis. Sixteen patients were treated with glucocorticoids (GCs) plus immunosuppressive drugs. Only one patient had GCs without immunosuppressive drugs. Ten subjects (62.5 %) received MMF (1-1.5 g/day), and all ten had lymphopenia. The mortality rates of MMF and non-MMF patients were 50 and 14 %, respectively. This study is the first report of PJP following MMF plus GC treatment in patients with CTD. CTD itself may be a risk factor for PJP. When CTD patients receiving MMF therapy have low lymphocyte counts and/or CD4 lymphocyte counts <250/µL, we should be care of occurrence of PJP.

Revisiting the co-existence of Attention-Deficit/Hyperactivity Disorder and Chronic Tic Disorder in childhood-The case of colour discrimination, sustained attention and interference control.

PubMed

Uebel-von Sandersleben, Henrik; Albrecht, Björn; Rothenberger, Aribert; Fillmer-Heise, Anke; Roessner, Veit; Sergeant, Joseph; Tannock, Rosemary; Banaschewski, Tobias

2017-01-01

Attention Deficit / Hyperactivity Disorder (ADHD) and Chronic Tic Disorder (CTD) are two common and frequently co-existing disorders, probably following an additive model. But this is not yet clear for the basic sensory function of colour processing sensitive to dopaminergic functioning in the retina and higher cognitive functions like attention and interference control. The latter two reflect important aspects for psychoeducation and behavioural treatment approaches. Colour discrimination using the Farnsworth-Munsell 100-hue Test, sustained attention during the Frankfurt Attention Inventory (FAIR), and interference liability during Colour- and Counting-Stroop-Tests were assessed to further clarify the cognitive profile of the co-existence of ADHD and CTD. Altogether 69 children were classified into four groups: ADHD (N = 14), CTD (N = 20), ADHD+CTD (N = 20) and healthy Controls (N = 15) and compared in cognitive functioning in a 2×2-factorial statistical model. Difficulties with colour discrimination were associated with both ADHD and CTD factors following an additive model, but in ADHD these difficulties tended to be more pronounced on the blue-yellow axis. Attention problems were characteristic for ADHD but not CTD. Interference load was significant in both Colour- and Counting-Stroop-Tests and unrelated to colour discrimination. Compared to Controls, interference load in the Colour-Stroop was higher in pure ADHD and in pure CTD, but not in ADHD+CTD, following a sub-additive model. In contrast, interference load in the Counting-Stroop did not reveal ADHD or CTD effects. The co-existence of ADHD and CTD is characterized by additive as well as sub-additive performance impairments, suggesting that their co-existence may show simple additive characteristics of both disorders or a more complex interaction, depending on demand. The equivocal findings on interference control may indicate limited validity of the Stroop-Paradigm for clinical assessments.

Quantum chemical calculations and molecular docking studies of 5-(4-chlorobenzylidene)thiazolidine-2,4-dione(CTD) and its mannich product 5-(4-chlorobenzylidene)-3-(morpholinomethyl)thiazolidine-2,4-dione (CMTD)

NASA Astrophysics Data System (ADS)

Fatma, Shaheen; Bishnoi, Abha; Verma, Anil Kumar; Singh, Vineeta; Srivastava, Krishna

2018-04-01

This work presents the synthesis of 5-(4-chlorobenzylidene)thiazolidine-2,4-dione (CTD) by Claisen condensation of thiazolidine-2,4-dione and mannich product of CTD, 5-(4-chlorobenzylidene)-3-(morpholinomethyl)thiazolidine-2,4-dione (CMTD). The static first hyperpolarizability values for thiazolidine-2,4-dione derivatives have been calculated as 10.28 × 10-30 esu for CTD and 19.42 × 10-30 esu for CMTD. The gradual increase in hyperpolarizability values of synthesized thiazolidine-2,4-dione derivatives from CTD to CMTD is due to the blockage of sbnd NH group on CTD by mannich reaction. The structures of these compounds have been derived by spectroscopic(IR, UV, Mass, 1H and 13C NMR) analysis as well as with the help of theoretical studies. The high values of first static hyperpolarizability indicate that the synthesized derivatives are suitable as non-linear optical (NLO) material. CTD with MIC value of 12.5 μg/mL can be developed as an alternative drug for the treatment of enteric fever. Calculated frontier orbital gap values suggest that the CMTD is a soft molecule with high chemical reactivity and is more polarizable as compared to the CTD. Molecular electrostatic potential is calculated for the optimized geometry of the molecules to estimate their chemical reactivity. The inhibitor CTD forms a stable complex with 3-dehydroquinase enzyme of Salmonella typhi. It is evident from the ligand receptor interactions and a binding affinity value of -5.88 kcal/mol and an inhibition constant of 49.22 μM. This is further confirmed by the experimental biological data. The molecular docking studies are supportive of the antibacterial activity of CTD exhibiting high inhibition constant and binding energy.

Revisiting the co-existence of Attention-Deficit/Hyperactivity Disorder and Chronic Tic Disorder in childhood—The case of colour discrimination, sustained attention and interference control

PubMed Central

Rothenberger, Aribert; Fillmer-Heise, Anke; Roessner, Veit; Sergeant, Joseph; Tannock, Rosemary; Banaschewski, Tobias

2017-01-01

Objective Attention Deficit / Hyperactivity Disorder (ADHD) and Chronic Tic Disorder (CTD) are two common and frequently co-existing disorders, probably following an additive model. But this is not yet clear for the basic sensory function of colour processing sensitive to dopaminergic functioning in the retina and higher cognitive functions like attention and interference control. The latter two reflect important aspects for psychoeducation and behavioural treatment approaches. Methods Colour discrimination using the Farnsworth-Munsell 100-hue Test, sustained attention during the Frankfurt Attention Inventory (FAIR), and interference liability during Colour- and Counting-Stroop-Tests were assessed to further clarify the cognitive profile of the co-existence of ADHD and CTD. Altogether 69 children were classified into four groups: ADHD (N = 14), CTD (N = 20), ADHD+CTD (N = 20) and healthy Controls (N = 15) and compared in cognitive functioning in a 2×2-factorial statistical model. Results Difficulties with colour discrimination were associated with both ADHD and CTD factors following an additive model, but in ADHD these difficulties tended to be more pronounced on the blue-yellow axis. Attention problems were characteristic for ADHD but not CTD. Interference load was significant in both Colour- and Counting-Stroop-Tests and unrelated to colour discrimination. Compared to Controls, interference load in the Colour-Stroop was higher in pure ADHD and in pure CTD, but not in ADHD+CTD, following a sub-additive model. In contrast, interference load in the Counting-Stroop did not reveal ADHD or CTD effects. Conclusion The co-existence of ADHD and CTD is characterized by additive as well as sub-additive performance impairments, suggesting that their co-existence may show simple additive characteristics of both disorders or a more complex interaction, depending on demand. The equivocal findings on interference control may indicate limited validity of the Stroop-Paradigm for clinical assessments. PMID:28594866

Ergonomics: CTD management evaluation tool.

PubMed

Ostendorf, J S; Rogers, B; Bertsche, P K

2000-01-01

Cumulative trauma disorder (CTD) occurrences peaked in number in 1994 and although decreasing in 1995, still accounted for 62% of all illness cases reported. A CTD Management Evaluation Tool was developed to assist Occupational Safety and Health Compliance Officers (CSHOs) in program evaluation and documentation of the occupational health management component and the need for an ergonomics program. Occupational and environmental health nurses may use the tool not only to reduce and prevent CTD occurrences, but also as a benchmark for program evaluation.

Chlorophyll-a thin layers in the Magellan fjord system: The role of the water column stratification

NASA Astrophysics Data System (ADS)

Ríos, Francisco; Kilian, Rolf; Mutschke, Erika

2016-08-01

Fjord systems represent hotspots of primary productivity and organic carbon burial. However, the factors which control the primary production in mid-latitude fjords are poorly understood. In this context, results from the first fine-scale measurements of bio-oceanographic features in the water column of fjords associated with the Strait of Magellan are presented. A submersible fluorescence probe (FP) was used to measure the Chlorophyll-a (Chl-a) concentration in situ, along with conductivity, temperature, hydrostatic pressure (depth) and dissolved oxygen (CTD-O2) of the water column. The Austral spring results of 14 FP-CTD-O2 profiles were used to define the vertical and horizontal patches of the fluorescent pigment distribution and their spatial relations with respect to the observed hydrographic features. Three zones with distinct water structures were defined. In all zones, the 'brown' spectral group (diatoms and dinoflagellates) predominated accounting for >80 wt% of the phytoplankton community. Thin layers with high Chl-a concentration were detected in 50% of the profiles. These layers harbored a substantial amount (30-65 wt%) of the phytoplankton biomass. Stratification was positively correlated to the occurrence of Chl-a thin layers. In stable and highly stratified water columns the integrated Chl-a concentration was higher and frequently located within thin layers whereas well mixed water columns displayed lower values and more homogeneous vertical distribution of Chl-a. These results indicate that mixing/stability processes are important factors accounting to the vertical distribution of Chl-a in Magellan fjords.

The distal C-terminal region of the KcsA potassium channel is a pH-dependent tetramerization domain.

PubMed

Kamnesky, Guy; Shaked, Hadassa; Chill, Jordan H

2012-05-04

The intracellular C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is a 40-residue-long segment that natively adopts a helical bundle conformation with 4-fold symmetry. A hallmark of KcsA behavior is pH-induced conformational change, which leads to the opening of the channel at acidic pH. Previous studies have reached conflicting conclusions as to the role of the CTD in this transition. Here, we investigate the involvement of this domain in pH-mediated channel opening by NMR using a soluble peptide corresponding to residues 128-160 of the CTD (CTD34). At neutral pH, CTD34 exhibits concentration-dependent spectral changes consistent with oligomer formation. We prove this slowly tumbling species to be a tetramer with a dissociation constant of (2.0±0.5)×10(-)(11) M(3) by NMR and sedimentation equilibrium experiments. Whereas monomeric CTD34 is only mildly helical, secondary chemical shifts prove that the tetrameric species adopts a tight native-like helical bundle conformation. The tetrameric species undergoes pH-dependent dissociation, and CTD34 is fully monomeric below pH 5.0. The structural basis for this phenomenon is the destabilization of the tetrameric CTD34 by protonation of residue H145 in the monomeric form of the peptide. We conclude that (i) the CTD34 peptide is independently capable of forming a tetrameric helical bundle, and (ii) this structurally significant conformational shift is modulated by the effects of solution pH on residue H145. Therefore, the involvement of this domain in the pH gating of the channel is strongly suggested. Copyright © 2012 Elsevier Ltd. All rights reserved.

Predictive value of nailfold capillaroscopy in patients with Raynaud's phenomenon.

PubMed

Meli, Madeleine; Gitzelmann, Gabriela; Koppensteiner, Renate; Amann-Vesti, Beatrice R

2006-03-01

The objective of this study was to evaluate the long-term follow-up of patients with Raynaud's phenomenon (RP) and pathological nailfold capillaroscopy (NC) in order to analyse the predictive value of specific features of capillaroscopy for the development of a connective tissue disease (CTD). From 1992 to 2002, NC alone or combined with fluorescence videomicroscopy with sodium fluorescein (NaF) was performed in 1024 consecutive patients because of RP. We analysed the follow-up and pathological features of NC in all patients who had neither clinical nor serological signs of a CTD at the time of NC. Of 308 patients with neither serological findings nor clinical signs of CTD but with RP and pathological features in NC suspicious for CTD, follow-up data were available for 133 patients. An additional NaF test had been performed in 51 (38.4%) patients. After a mean follow-up of 6.5 years (range: 1-15 years), 109 patients had developed a CTD and 24 patients did not show any clinical signs or serological markers for a CTD after a mean follow-up of 8.5 years (range: 2-15 years). There were no differences in age, duration of RP or of follow-up in patients who developed a CTD compared to patients who did not. Significantly more giant capillaries (p=0.0001), avascular fields (p=0.02) and irregular architecture (p=0.0001) had been observed in patients who had developed a CTD during the follow-up of 6.5 years. The presence of giant capillaries, avascular fields and irregular architecture of nailfold capillaries is predictive for the development of a CTD in patients with RP.

Interpreting & Biomechanics. PEPNet Tipsheet

ERIC Educational Resources Information Center

PEPNet-Northeast, 2001

2001-01-01

Cumulative trauma disorder (CTD) refers to a collection of disorders associated with nerves, muscles, tendons, bones, and the neurovascular (nerves and related blood vessels) system. CTD symptoms may involve the neck, back, shoulders, arms, wrists, or hands. Interpreters with CTD may experience a variety of symptoms including: pain, joint…

Korean Nursing Students' Acquisition of Evidence-Based Practice and Critical Thinking Skills.

PubMed

Kim, Sang Suk; Kim, Eun Joo; Lim, Ji Young; Kim, Geun Myun; Baek, Hee Chong

2018-01-01

Evidence-based practice (EBP) is essential for enhancing nurses' quality of care. We identified Korean nursing students' practices, attitudes, and knowledge concerning EBP, as well as their critical thinking disposition (CTD). The EBP Questionnaire (EBPQ) was administered to a convenience sample of 266 nursing students recruited from four nursing schools in Seoul and its metropolitan area. Average EBPQ and CTD total scores were 4.69 ± 0.64 and 3.56 ± 0.32, respectively. Students who were ages ⩾23 years, male, and satisfied with their major demonstrated higher EBPQ and CTD scores. EBPQ scores were significantly correlated with CTD scores (r = .459, p < .01), and CTD was an explanatory factor of EBP (adjusted R 2 = 0.200). It is necessary to develop comprehensive teaching strategies to help nursing students improve their CTD and information utilization skills, as well as integrate EBP in undergraduate programs to enhance nurses' EBP abilities. [J Nurs Educ. 2018;57(1):21-27.]. Copyright 2018, SLACK Incorporated.

Sustained-release microsphere formulation containing an agrochemical by polyurethane polymerization during an agitation granulation process.

PubMed

Terada, Takatoshi; Tagami, Manabu; Ohtsubo, Toshiro; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2016-07-25

In this report, a new solventless microencapsulation method by synthesizing polyurethane (PU) from polyol and isocyanate during an agglomeration process in a high-speed mixing apparatus was developed. Clothianidin (CTD), which is a neonicotinoid insecticide and highly effective against a wide variety of insect pests, was used as the model compound. The microencapsulated samples covered with PU (CTD microspheres) had a median diameter of <75μm and sustained-release properties. The CTD microspheres were analyzed by synchrotron X-ray computed tomography measurements. Multiple cores of CTD and other solid excipient were dispersed in PU. Although voids appeared in the CTD microspheres after CTD release, the spherical shape of the microspheres remained stable and no change in its framework was observed. The experimental release data were highly consistent with the Baker-Lonsdale model derived from drug release of spherical monolithic dispersions and consistent with the computed tomography measurements. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases

PubMed Central

Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong

2017-01-01

This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE. PMID:28273146

Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

PubMed

Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong

2017-01-01

This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

Catching the Dream Annual Report, 2002.

ERIC Educational Resources Information Center

Chavers, Dean, Ed.

2002-01-01

In 2002, Catching the Dream (CTD) provided college scholarships to 208 American Indian students as well as grants to improve education in schools that serve Native students. This annual report describes CTD's programs and activities in 2002. Contents include short descriptions of CTD's scholarship, fellowship, and internship programs; describe…

Measuring and modeling the effects of drainage water management on soil greenhouse gas fluxes from corn and soybean fields.

PubMed

Nangia, V; Sunohara, M D; Topp, E; Gregorich, E G; Drury, C F; Gottschall, N; Lapen, D R

2013-11-15

Controlled tile drainage can boost crop yields and improve water quality, but it also has the potential to increase GHG emissions. This study compared in-situ chamber-based measures of soil CH4, N2O, and CO2 fluxes for silt loam soil under corn and soybean cropping with conventional tile drainage (UTD) and controlled tile drainage (CTD). A semi-empirical model (NEMIS-NOE) was also used to predict soil N2O fluxes from soils using observed soil data. Observed N2O and CH4 fluxes between UTD and CTD fields during the farming season were not significantly different at 0.05 level. Soils were primarily a sink for CH4 but in some cases a source (sources were associated exclusively with CTD). The average N2O fluxes measured ranged between 0.003 and 0.028 kg N ha(-1) day(-1). There were some significantly higher (p ≤ 0.05) CO2 fluxes associated with CTD relative to UTD during some years of study. Correlation analyses indicated that the shallower the water table, the greater the CO2 fluxes. Higher corn plant C for CTD tended to offset estimated higher CTD CO2 C losses via soil respiration by ∼100-300 kg C ha(-1). There were good fits between observed and predicted (NEMIS-NOE) N2O fluxes for corn (R(2) = 0.70) and soybean (R(2) = 0.53). Predicted N2O fluxes were higher for CTD for approximately 70% of the paired-field study periods suggesting that soil physical factors, such as water-filled pore space, imposed by CTD have potentially strong impacts on net N fluxes. Model predictions of daily cumulative N2O fluxes for the agronomically-active study period for corn-CTD and corn-UTD, as a percentage of total N fertilizer applied, were 3.1% and 2.6%, respectively. For predicted N2O fluxes on basis of yield units, indices were 0.0005 and 0.0004 (kg N kg(-1) crop grain yield) for CTD and UTD corn fields, respectively, and 0.0011 and 0.0005 for CTD and UTD soybean fields, respectively. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Water Quality and Plankton in the United States Nearshore Waters of Lake Huron

EPA Science Inventory

We conducted an intensive survey for the US nearshore of Lake Huron along a continuous segment (523 km) from Port Huron Michigan to Detour Passage. A depth contour of 20 m was towed with a CTD, fluorometer, transmissometer, and laser optical plankton counter (LOPC). The continu...

Structural conversion of the transformer protein RfaH: new insights derived from protein structure prediction and molecular dynamics simulations.

PubMed

Balasco, Nicole; Barone, Daniela; Vitagliano, Luigi

2015-01-01

Recent structural investigations have shown that the C-terminal domain (CTD) of the transcription factor RfaH undergoes unique structural modifications that have a profound impact into its functional properties. These modifications cause a complete change in RfaH(CTD) topology that converts from an α-hairpin to a β-barrel fold. To gain insights into the determinants of this major structural conversion, we here performed computational studies (protein structure prediction and molecular dynamics simulations) on RfaH(CTD). Although these analyses, in line with literature data, suggest that the isolated RfaH(CTD) has a strong preference for the β-barrel fold, they also highlight that a specific region of the protein is endowed with a chameleon conformational behavior. In particular, the Leu-rich region (residues 141-145) has a good propensity to adopt both α-helical and β-structured states. Intriguingly, in the RfaH homolog NusG, whose CTD uniquely adopts the β-barrel fold, the corresponding region is rich in residues as Val or Ile that present a strong preference for the β-structure. On this basis, we suggest that the presence of this Leu-rich element in RfaH(CTD) may be responsible for the peculiar structural behavior of the domain. The analysis of the sequences of RfaH family (PfamA code PF02357) unraveled that other members potentially share the structural properties of RfaH(CTD). These observations suggest that the unusual conformational behavior of RfaH(CTD) may be rare but not unique.

Interpretacion y Biomecanica. Hoja de consejos de PEPNet (Interpreting and Biomechanics. PEPNet Tipsheet)

ERIC Educational Resources Information Center

DeGroote, Bill; Morrison, Carolyn

2010-01-01

This publication, written in Spanish, describes cumulative trauma disorder (CTD), which refers to a collection of disorders associated with nerves, muscles, tendons, bones, and the neurovascular (nerves and related blood vessels) system. CTD symptoms may involve the neck, back, shoulders, arms, wrists, or hands. Interpreters with CTD may…

78 FR 51192 - Secure Supply Chain Pilot Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-20

... (PDF) and using the Electronic Common Technical Document (eCTD) format and the Electronic Submissions.... The PDF file name should contain ``3676'' as part of the file name, and the eCTD leaf title should.... For further information regarding eCTD, please refer to the Web site at http://www.fda.gov/Drugs...

78 FR 34393 - Electronic Submission of Tobacco Product Applications and Other Information; Public Workshop...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-07

... manufacturers experienced with electronic Common Technical Document (eCTD); vendors of software used to support... electronic submission workshop will include discussion on eCTD, which is an International Conference on Harmonization (ICH) specification developed by ICH and its member parties. The eCTD provides an organizational...

Molecular dynamics study of the phosphorylation effect on the conformational states of the C-terminal domain of RNA polymerase II.

PubMed

Yonezawa, Yasushige

2014-05-01

The carboxyl-terminal domain (CTD) of RNA polymerase II in eukaryotes regulates mRNA processing processes by recruiting various regulation factors. A main function of the CTD relies on the heptad consensus sequence (YSPTSPS). The CTD dynamically changes its conformational state to recognize and bind different regulation factors. The dynamical conformation changes are caused by modifications, mainly phosphorylation and dephosphorylation, to the serine residues. In this study, we investigate the conformational states of the unit consensus CTD peptide with various phosphorylation patterns of the serine residues by extended ensemble simulations. The results show that the CTD without phosphorylation has a flexible disordered structure distributed between twisted and extended states, but phosphorylation tends to reduce the conformational space. It was found that phosphorylation induces a β-turn around the phosphorylated serine residue and the cis conformation of the proline residue significantly inhibits the β-turn formation. The β-turn should contribute to specific CTD binding of the different regulation factors by changing the conformation propensity combined with induced fit.

Cytoplasmic tail domain of glycoprotein B is essential for HHV-6 infection

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

Mahmoud, Nora F.; Faculty of Pharmacy, Suez Canal University, Ismailia; Jasirwan, Chyntia

2016-03-15

Human herpesvirus 6 (HHV-6) glycoprotein B (gB) is an abundantly expressed viral glycoprotein required for viral entry and cell fusion, and is highly conserved among herpesviruses. The present study examined the function of HHV-6 gB cytoplasmic tail domain (CTD). A gB CTD deletion mutant was constructed which, in contrast to its revertant, could not be reconstituted. Moreover, deletion of gB cytoplasmic tail impaired the intracellular transport of gB protein to the trans-Golgi network (TGN). Taken together, these results suggest that gB CTD is critical for HHV-6 propagation and important for intracellular transportation. - Highlights: • Glycoprotein B (gB) is highlymore » conserved among herpesviruses. • HHV-6 gB is also abundantly expressed in virions. • In the present study, we showed the function of HHV-6 gB cytoplasmic tail domain (CTD). • We found that deletion of gB CTD impairs the intracellular transport of gB protein to the trans-Golgi network (TGN), and CTD of gB is critical for HHV-6 propagation.« less

The clinical impact of Anti-DFS70 antibodies in undifferentiated connective tissue disease: case reports and a review of the literature.

PubMed

Infantino, M; Meacci, F; Grossi, V; Manfredi, M; Li Gobbi, F; Sarzi-Puttini, P; Atzeni, F; Benucci, M

2017-02-01

Anti-nuclear antibody (ANA) positivity suggests CTD but can also lead to a diagnosis of UCTD when a patient does not fulfill the CTD diagnostic criteria. An anti-dense fine speckled (DFS) immunofluorescence (IIF) pattern can be observed when using an ANA test on HEp-2 cells and is due to the presence of antibodies to the nuclear DFS70 antigen that has rarely found in CTD. Serological testing for anti-DFS70 antibodies could therefore play a very interesting negative predictive role in stratifying patients on the basis of the evolution of UCTD to CTD. We described two patients ANA and anti-DFS70 positive in which the use of new method allowing the immunoadsorption of anti-DFS70 antibodies has permitted to exclude the incorrect diagnosis of CTD.

Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II.

PubMed

Lu, Huasong; Yu, Dan; Hansen, Anders S; Ganguly, Sourav; Liu, Rongdiao; Heckert, Alec; Darzacq, Xavier; Zhou, Qiang

2018-06-01

Hyperphosphorylation of the C-terminal domain (CTD) of the RPB1 subunit of human RNA polymerase (Pol) II is essential for transcriptional elongation and mRNA processing 1-3 . The CTD contains 52 heptapeptide repeats of the consensus sequence YSPTSPS. The highly repetitive nature and abundant possible phosphorylation sites of the CTD exert special constraints on the kinases that catalyse its hyperphosphorylation. Positive transcription elongation factor b (P-TEFb)-which consists of CDK9 and cyclin T1-is known to hyperphosphorylate the CTD and negative elongation factors to stimulate Pol II elongation 1,4,5 . The sequence determinant on P-TEFb that facilitates this action is currently unknown. Here we identify a histidine-rich domain in cyclin T1 that promotes the hyperphosphorylation of the CTD and stimulation of transcription by CDK9. The histidine-rich domain markedly enhances the binding of P-TEFb to the CTD and functional engagement with target genes in cells. In addition to cyclin T1, at least one other kinase-DYRK1A 6 -also uses a histidine-rich domain to target and hyperphosphorylate the CTD. As a low-complexity domain, the histidine-rich domain also promotes the formation of phase-separated liquid droplets in vitro, and the localization of P-TEFb to nuclear speckles that display dynamic liquid properties and are sensitive to the disruption of weak hydrophobic interactions. The CTD-which in isolation does not phase separate, despite being a low-complexity domain-is trapped within the cyclin T1 droplets, and this process is enhanced upon pre-phosphorylation by CDK7 of transcription initiation factor TFIIH 1-3 . By using multivalent interactions to create a phase-separated functional compartment, the histidine-rich domain in kinases targets the CTD into this environment to ensure hyperphosphorylation and efficient elongation of Pol II.

CTD and Bottle Data from Leg 1: 20 December 1986 - 18 January 1987. Leg 2: 17 July - 15 August 1987

DTIC Science & Technology

1989-06-01

tabular data includes pressure, temperature, salinity, oxygen in ml/l and in micro -moles per kilogram, oxygen percent saturation, potential...I f T I T 7 1 1- - -1[ 1 1 1 1 I I IO- -r- Distribution List ARGENTINA FRANCE Alberto Piola Dr. Michele Fieux Armada Argentina, Servicio de

The key DNA-binding residues in the C-terminal domain of Mycobacterium tuberculosis DNA gyrase A subunit (GyrA)

PubMed Central

Huang, You-Yi; Deng, Jiao-Yu; Gu, Jing; Zhang, Zhi-Ping; Maxwell, Anthony; Bi, Li-Jun; Chen, Yuan-Yuan; Zhou, Ya-Feng; Yu, Zi-Niu; Zhang, Xian-En

2006-01-01

As only the type II topoisomerase is capable of introducing negative supercoiling, DNA gyrase is involved in crucial cellular processes. Although the other domains of DNA gyrase are better understood, the mechanism of DNA binding by the C-terminal domain of the DNA gyrase A subunit (GyrA-CTD) is less clear. Here, we investigated the DNA-binding sites in the GyrA-CTD of Mycobacterium tuberculosis gyrase through site-directed mutagenesis. The results show that Y577, R691 and R745 are among the key DNA-binding residues in M.tuberculosis GyrA-CTD, and that the third blade of the GyrA-CTD is the main DNA-binding region in M.tuberculosis DNA gyrase. The substitutions of Y577A, D669A, R691A, R745A and G729W led to the loss of supercoiling and relaxation activities, although they had a little effect on the drug-dependent DNA cleavage and decatenation activities, and had no effect on the ATPase activity. Taken together, these results showed that the GyrA-CTD is essential to DNA gyrase of M.tuberculosis, and promote the idea that the M.tuberculosis GyrA-CTD is a new potential target for drug design. It is the first time that the DNA-binding sites in GyrA-CTD have been identified. PMID:17038336

Overexpression of YB1 C-terminal domain inhibits proliferation, angiogenesis and tumorigenicity in a SK-BR-3 breast cancer xenograft mouse model.

PubMed

Shi, Jian-Hong; Cui, Nai-Peng; Wang, Shuo; Zhao, Ming-Zhi; Wang, Bing; Wang, Ya-Nan; Chen, Bao-Ping

2016-01-01

Y-box-binding protein 1 (YB1) is a multifunctional transcription factor with vital roles in proliferation, differentiation and apoptosis. In this study, we have examined the role of its C-terminal domain (YB1 CTD) in proliferation, angiogenesis and tumorigenicity in breast cancer. Breast cancer cell line SK-BR-3 was infected with GFP-tagged YB1 CTD adenovirus expression vector. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) proliferation assay showed that YB1 CTD decreased SK-BR-3 cell proliferation, and down-regulated cyclin B1 and up-regulated p21 levels in SK-BR-3 cells. YB1 CTD overexpression changed the cytoskeletal organization and slightly inhibited the migration of SK-BR-3 cells. YB1 CTD also inhibited secreted VEGF expression in SK-BR-3 cells, which decreased SK-BR-3-induced EA.hy926 endothelial cell angiogenesis in vitro. YB1 CTD overexpression attenuated the ability of SK-BR-3 cells to form tumours in nude mice, and decreased in vivo VEGF levels and angiogenesis in the xenografts in SK-BR-3 tumour-bearing mice. Taken together, our findings demonstrate the vital role of YB1 CTD overexpression in inhibiting proliferation, angiogenesis and tumorigenicity of breast cancer cell line SK-BR-3.

Intact Arabidopsis RPB1 functions in stem cell niches maintenance and cell cycling control.

PubMed

Zhang, Qian-Qian; Li, Ying; Fu, Zhao-Ying; Liu, Xun-Biao; Yuan, Kai; Fang, Ying; Liu, Yan; Li, Gang; Zhang, Xian-Sheng; Chong, Kang; Ge, Lei

2018-05-12

Plant meristem activity depends on accurate execution of transcriptional networks required for establishing optimum functioning of stem cell niches. An Arabidopsis mutant card1-1 (constitutive auxin response with DR5:GFP) that encodes a truncated RPB1 (RNA Polymerase II's largest subunit) with shortened C-terminal domain (CTD) was identified. Phosphorylation of the CTD repeats of RPB1 is coupled to transcription in eukaryotes. Here we uncover that the truncated CTD of RPB1 disturbed cell cycling and enlarged the size of shoot and root meristem. The defects in patterning of root stem cell niche in card1-1 indicates that intact CTD of RPB1 is necessary for fine-tuning the specific expression of genes responsible for cell-fate determination. The gene-edited plants with different CTD length of RPB1, created by CRISPR-CAS9 technology, confirmed that both the full length and the DK-rich tail of RPB1's CTD play roles in the accurate transcription of CYCB1;1 encoding a cell-cycle marker protein in root meristem and hence participate in maintaining root meristem size. Our experiment proves that the intact RPB1 CTD is necessary for stem cell niche maintenance, which is mediated by transcriptional regulation of cell cycling genes. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Heat-shock inactivation of the TFIIH-associated kinase and change in the phosphorylation sites on the C-terminal domain of RNA polymerase II.

PubMed

Dubois, M F; Vincent, M; Vigneron, M; Adamczewski, J; Egly, J M; Bensaude, O

1997-02-15

The C-terminal domain (CTD) of the RNA polymerase II largest subunit (RPB1) plays a central role in transcription. The CTD is unphosphorylated when the polymerase assembles into a preinitiation complex of transcription and becomes heavily phosphorylated during promoter clearance and entry into elongation of transcription. A kinase associated to the general transcription factor TFIIH, in the preinitiation complex, phosphorylates the CTD. The TFIIH-associated CTD kinase activity was found to decrease in extracts from heat-shocked HeLa cells compared to unstressed cells. This loss of activity correlated with a decreased solubility of the TFIIH factor. The TFIIH-kinase impairment during heat-shock was accompanied by the disappearance of a particular phosphoepitope (CC-3) on the RPB1 subunit. The CC-3 epitope was localized on the C-terminal end of the CTD and generated in vitro when the RPB1 subunit was phosphorylated by the TFIIH-associated kinase but not by another CTD kinase such as MAP kinase. In apparent discrepancy, the overall RPB1 subunit phosphorylation increased during heat-shock. The decreased activity in vivo of the TFIIH kinase might be compensated by a stress-activated CTD kinase such as MAP kinase. These results also suggest that heat-shock gene transcription may have a weak requirement for TFIIH kinase activity.

Heat-shock inactivation of the TFIIH-associated kinase and change in the phosphorylation sites on the C-terminal domain of RNA polymerase II.

PubMed Central

Dubois, M F; Vincent, M; Vigneron, M; Adamczewski, J; Egly, J M; Bensaude, O

1997-01-01

The C-terminal domain (CTD) of the RNA polymerase II largest subunit (RPB1) plays a central role in transcription. The CTD is unphosphorylated when the polymerase assembles into a preinitiation complex of transcription and becomes heavily phosphorylated during promoter clearance and entry into elongation of transcription. A kinase associated to the general transcription factor TFIIH, in the preinitiation complex, phosphorylates the CTD. The TFIIH-associated CTD kinase activity was found to decrease in extracts from heat-shocked HeLa cells compared to unstressed cells. This loss of activity correlated with a decreased solubility of the TFIIH factor. The TFIIH-kinase impairment during heat-shock was accompanied by the disappearance of a particular phosphoepitope (CC-3) on the RPB1 subunit. The CC-3 epitope was localized on the C-terminal end of the CTD and generated in vitro when the RPB1 subunit was phosphorylated by the TFIIH-associated kinase but not by another CTD kinase such as MAP kinase. In apparent discrepancy, the overall RPB1 subunit phosphorylation increased during heat-shock. The decreased activity in vivo of the TFIIH kinase might be compensated by a stress-activated CTD kinase such as MAP kinase. These results also suggest that heat-shock gene transcription may have a weak requirement for TFIIH kinase activity. PMID:9016617

Insights Into Ice-Ocean Interactions on Earth and Europa

NASA Astrophysics Data System (ADS)

Lawrence, J.; Schmidt, B. E.; Winslow, L.; Doran, P. T.; Kim, S.; Walker, C. C.; Buffo, J.; Skidmore, M. L.; Soderlund, K. M.; Blankenship, D. D.; Bramall, N. E.; Johnson, A.; Rack, F. R.; Stone, W.; Kimball, P.; Clark, E.

2016-12-01

Europa and Earth appear to be drastically different worlds, yet below their icy crusts the two likely share similar oceanic conditions including temperatures, pressures (relatively), and salinity. Earth's ice shelves provide an important analog for the physiochemical, and potentially microbial, characteristics of icy worlds. NASA's ASTEP program funded Sub-Ice Marine and PLanetary-analog Ecosystems (SIMPLE) to help address the fundamental processes occurring at ice ocean interfaces, the extent and limitations of life in sub-ice environments, and how environmental properties and biological communities interact. The relationships between currents, temperature, and salinity with physical processes such as melt, freeze, and marine ice accretion at the basal surfaces of ice shelves influence habitability yet are poorly understood even on Earth. Resultant processes such as the inclusion of ocean-derived material in ice shelves and the transport of biotics from the interface towards the surface via ablation, convection, and diapirism also have important astrobiological implications for Europa.Here, we present results from CTD and imaging data gathered at multiple locations beneath the McMurdo Ice Shelf (MIS) to highlight how the ice and ocean interact in a Europan analog environment. Over the course of three years, the SIMPLE team observed heterogeneity in the water column and basal ice beneath the MIS. During the recent 2015 field season we deployed ARTEMIS, an AUV capable of characterizing the interface over multiple kilometer missions, and conducted daily CTD casts to 480 m (bottom depth 529 m) in November adjacent to the terminus of the MIS to capture temporal variation in the water column. These casts show the presence of transient water masses related to the tidal period, each containing a single or double temperature minimum (down to -1.97 °C from -1.93 °C) between 60 to 150 m depth. Further comparisons between years and sampling locations demonstrate the homogeneity of the subshelf environment even on the scale of tens of kilometers. The technologies supported by SIMPLE are also supporting the ice penetrating radar on the upcoming Europa Flagship mission, and will hopefully inform future ocean world exploration.

Cleavage of a Gulf of Mexico Loop Current eddy by a deep water cyclone

NASA Astrophysics Data System (ADS)

Biggs, D. C.; Fargion, G. S.; Hamilton, P.; Leben, R. R.

1996-09-01

Eddy Triton, an anticyclonic eddy shed by the Loop Current in late June 1991, drifted SW across the central Gulf of Mexico in the first 6 months of 1992, along the ``southern'' of the three characteristic drift paths described by Vukovich and Crissman [1986] from their analyses of 13 years of advanced very high resolution radiometer sea surface temperature data. An expendable bathythermograph (XBT) and conductivity-temperature-depth (CTD) transect of opportunity through Triton at eddy age 7 months in January 1992 found that eddy interior stood 23 dyn. cm higher than periphery; this gradient drove an anticyclonic swirl transport of 9-10 Sv relative to 800 dbar. At eddy age 9-10 months and while this eddy was in deep water near 94°W, it interacted with a mesoscale cyclonic circulation and was cleaved into two parts. The major (greater dynamic centimeters) piece drifted NW to end up in the ``eddy graveyard'' in the NW corner of the gulf, while the minor piece drifted SW and reached the continental margin of the western gulf off Tuxpan. This southern piece of Eddy Triton then turned north to follow the 2000-m isobath to about 24°N and later coalesced with what remained of the major fragment. Because Eddy Triton's cleavage took place just before the start of marine mammals (GulfCet) and Louisiana-Texas physical oceanography (LATEX) field programs, the closely spaced CTD, XBT, and air dropped XBT (AXBT) data that were gathered on the continental margin north of 26°N in support of these programs allow a detailed look at the northern margin of the larger fragment of this eddy. Supporting data from the space-borne altimeters on ERS 1 and TOPEX/POSEIDON allow us to track both pieces of Eddy Triton in the western Gulf and follow their spin down in dynamic height, coalescence, and ultimate entrainment in January 1993 into another anticyclonic eddy (Eddy U).

C-MORE Science Kits: Putting Technology in the Hands of K-12 Teachers and Students

NASA Astrophysics Data System (ADS)

Achilles, K.; Weersing, K.; Daniels, C.; Puniwai, N.; Matsuzaki, J.; Bruno, B. C.

2008-12-01

The Center for Microbial Oceanography: Research and Education (C-MORE) is a NSF Science and Technology Center based at the University of Hawaii. The C-MORE education and outreach program offers a variety of resources and professional development opportunities for science educators, including online resources, participation in oceanography research cruises, teacher-training workshops, mini-grants to incorporate microbial oceanography-related content and activities into their classroom and, most recently, C- MORE science kits. C-MORE science kits provide hands-on classroom, field, and laboratory activities related to microbial oceanography for K-12 students. Each kit comes with complete materials and instructions, and is available free of charge to Hawaii's public school teachers. Several kits are available nationwide. C-MORE science kits cover a range of topics and technologies and are targeted at various grade levels. Here is a sampling of some available kits: 1) Marine Murder Mystery: The Case of the Missing Zooxanthellae. Students learn about the effect of climate change and other environmental threats on coral reef destruction through a murder-mystery experience. Participants also learn how to use DNA to identify a suspect. Grades levels: 3-8. 2) Statistical sampling. Students learn basic statistics through an exercise in random sampling, with applications to microbial oceanography. The laptops provided with this kit enable students to enter, analyze, and graph their data using EXCEL. Grades levels: 6-12. 3) Chlorophyll Lab. A research-quality fluorometer is used to measure the chlorophyll content in marine and freshwater systems. This enables students to compare biomass concentrations in samples collected from various locations. Grades levels: 9-12. 4) Conductivity-Temperature-Depth (CTD). Students predict how certain variables (e.g., temperature, pressure, chlorophyll, oxygen) vary with depth. A CTD, attached to a laptop computer, is deployed into deep water off a dock or a ship to collect real-time data and test their hypotheses. Grades levels: 9-12.

Seasonal, Oceanographic and Atmospheric Drivers of Diving Behaviour in a Temperate Seal Species Living in the High Arctic

PubMed Central

Blanchet, Marie-Anne; Lydersen, Christian; Ims, Rolf A.; Kovacs, Kit M.

2015-01-01

The harbour seal (Phoca vitulina) population in Svalbard marks the northernmost limit of the species’ range. This small population experiences environmental extremes in sea and air temperatures, sea ice cover and also in light regime for this normally temperate species. This study deployed Conductivity Temperature Depth Satellite Relay Data Loggers (CTD-SRDLs) on 30 adult and juvenile harbour seals in 2009 and 2010 to study their foraging behaviour across multiple seasons. A total of 189,104 dives and 16,640 CTD casts (mean depth 72 m ± 59) were recorded. Individuals dove to a mean depth of 41 m ± 24 with a maximum dive depth range of 24 – 403 m. Dives lasted on average 204 sec ± 120 with maximum durations ranging between 240 – 2,220 sec. Average daily depth and duration of dives, number of dives, time spent diving and dive time/surface time were influenced by date, while sex, age, sea-ice concentration and their interactions were not particularly influential. Dives were deeper (~150 m), longer (~480 sec), less numerous (~250 dives/day) and more pelagic during the winter/early spring compared to the fall and animals spent proportionally less time at the bottom of their dives during the winter. Influxes of warm saline water, corresponding to Atlantic Water characteristics, were observed intermittently at depths ~100 m during both winters in this study. The seasonal changes in diving behaviour were linked to average weekly wind stresses from the north or north-east, which induced upwelling events onto the shelf through offshore Ekman transport. During these events the shelf became flooded with AW from the West Spitsbergen Current, which presumably brought Atlantic fish species close to shore and within the seals’ foraging depth-range. Predicted increased in the influx of AW in this region are likely going to favour the growth and geographic expansion of this harbour seal population in the future. PMID:26196289

Rsp5 WW domains interact directly with the carboxyl-terminal domain of RNA polymerase II.

PubMed

Chang, A; Cheang, S; Espanel, X; Sudol, M

2000-07-07

RSP5 is an essential gene in Saccharomyces cerevisiae and was recently shown to form a physical and functional complex with RNA polymerase II (RNA pol II). The amino-terminal half of Rsp5 consists of four domains: a C2 domain, which binds membrane phospholipids; and three WW domains, which are protein interaction modules that bind proline-rich ligands. The carboxyl-terminal half of Rsp5 contains a HECT (homologous to E6-AP carboxyl terminus) domain that catalytically ligates ubiquitin to proteins and functionally classifies Rsp5 as an E3 ubiquitin-protein ligase. The C2 and WW domains are presumed to act as membrane localization and substrate recognition modules, respectively. We report that the second (and possibly third) Rsp5 WW domain mediates binding to the carboxyl-terminal domain (CTD) of the RNA pol II large subunit. The CTD comprises a heptamer (YSPTSPS) repeated 26 times and a PXY core that is critical for interaction with a specific group of WW domains. An analysis of synthetic peptides revealed a minimal CTD sequence that is sufficient to bind to the second Rsp5 WW domain (Rsp5 WW2) in vitro and in yeast two-hybrid assays. Furthermore, we found that specific "imperfect" CTD repeats can form a complex with Rsp5 WW2. In addition, we have shown that phosphorylation of this minimal CTD sequence on serine, threonine and tyrosine residues acts as a negative regulator of the Rsp5 WW2-CTD interaction. In view of the recent data pertaining to phosphorylation-driven interactions between the RNA pol II CTD and the WW domain of Ess1/Pin1, we suggest that CTD dephosphorylation may be a prerequisite for targeted RNA pol II degradation.

Using AnnAGNPS to Predict the Effects of Tile Drainage Control on Nutrient and Sediment Loads for a River Basin.

PubMed

Que, Z; Seidou, O; Droste, R L; Wilkes, G; Sunohara, M; Topp, E; Lapen, D R

2015-03-01

Controlled tile drainage (CTD) can reduce pollutant loading. The Annualized Agricultural Nonpoint Source model (AnnAGNPS version 5.2) was used to examine changes in growing season discharge, sediment, nitrogen, and phosphorus loads due to CTD for a ∼3900-km agriculturally dominated river basin in Ontario, Canada. Two tile drain depth scenarios were examined in detail to mimic tile drainage control for flat cropland: 600 mm depth (CTD) and 200 mm (CTD) depth below surface. Summed for five growing seasons (CTD), direct runoff, total N, and dissolved N were reduced by 6.6, 3.5, and 13.7%, respectively. However, five seasons of summed total P, dissolved P, and total suspended solid loads increased as a result of CTD by 0.96, 1.6, and 0.23%. The AnnAGNPS results were compared with mass fluxes observed from paired experimental watersheds (250, 470 ha) in the river basin. The "test" experimental watershed was dominated by CTD and the "reference" watershed by free drainage. Notwithstanding environmental/land use differences between the watersheds and basin, comparisons of seasonal observed and predicted discharge reductions were comparable in 100% of respective cases. Nutrient load comparisons were more consistent for dissolved, relative to particulate water quality endpoints. For one season under corn crop production, AnnAGNPS predicted a 55% decrease (CTD) in dissolved N from the basin. AnnAGNPS v. 5.2 treats P transport from a surface pool perspective, which is appropriate for many systems. However, for assessment of tile drainage management practices for relatively flat tile-dominated systems, AnnAGNPS may benefit from consideration of P and particulate transport in the subsurface. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

National Air Space (NAS) Data Exchange Environment Through 2060

NASA Technical Reports Server (NTRS)

Roy, Aloke

2015-01-01

NASA's NextGen Concepts and Technology Development (CTD) Project focuses on capabilities to improve safety, capacity and efficiency of the National Air Space (NAS). In order to achieve those objectives, NASA sought industry-Government partnerships to research and identify solutions for traffic flow management, dynamic airspace configuration, separation assurance, super density operations, airport surface operations and similar forward-looking air-traffic modernization (ATM) concepts. Data exchanges over NAS being the key enabler for most of these ATM concepts, the Sub-Topic area 3 of the CTD project sought to identify technology candidates that can satisfy air-to-air and air/ground communications needs of the NAS in the year 2060 timeframe. Honeywell, under a two-year contract with NASA, is working on this communications technology research initiative. This report summarizes Honeywell's research conducted during the second year of the study task.

Psychopathological Profile in Children with Chronic Tic Disorder and Co-Existing ADHD: Additive Effects

ERIC Educational Resources Information Center

Roessner, Veit; Becker, Andreas; Banaschewski, Tobias; Rothenberger, Aribert

2007-01-01

The nature of the co-occurrence of chronic tic disorders (CTD) and attention deficit hyperactivity disorder (ADHD) is unclear. Especially in the field of psychopathology, the relationship of CTD and ADHD remains to be clarified. Thus, the aim of the present chart review study was to specify the contribution of CTD and/or ADHD to the…

Evidence-based diuretics: focus on chlorthalidone and indapamide.

PubMed

DiNicolantonio, James J; Bhutani, Jaikrit; Lavie, Carl J; O'Keefe, James H

2015-03-01

Thiazide and thiazide-like diuretics are cornerstone treatments for hypertension. However, unlike chlorthalidone (CTD) and indapamide (IDP), hydrochlorothiazide (HCTZ) lacks evidence for reducing morbidity and mortality as monotherapy compared with placebo or control. Despite this fact, HCTZ is prescribed much more frequently than CTD or IDP. We believe that all hypertension guidelines should follow the National Institute for Health and Excellence (NICE) and make IDP and CTD first choice 'thiazide-like diuretics.' This article will focus on the available evidence pertaining to HCTZ versus CTD and IDP. We will review the pharmacological differences between these three diuretics, as well as the clinical trial data and important side effects.

Histopathology of lung disease in the connective tissue diseases.

PubMed

Vivero, Marina; Padera, Robert F

2015-05-01

The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. Copyright © 2015 Elsevier Inc. All rights reserved.

cis-Proline-mediated Ser(P)[superscript 5] Dephosphorylation by the RNA Polymerase II C-terminal Domain Phosphatase Ssu72

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

Werner-Allen, Jon W.; Lee, Chul-Jin; Liu, Pengda

2012-05-16

RNA polymerase II coordinates co-transcriptional events by recruiting distinct sets of nuclear factors to specific stages of transcription via changes of phosphorylation patterns along its C-terminal domain (CTD). Although it has become increasingly clear that proline isomerization also helps regulate CTD-associated processes, the molecular basis of its role is unknown. Here, we report the structure of the Ser(P){sup 5} CTD phosphatase Ssu72 in complex with substrate, revealing a remarkable CTD conformation with the Ser(P){sup 5}-Pro{sup 6} motif in the cis configuration. We show that the cis-Ser(P){sup 5}-Pro{sup 6} isomer is the minor population in solution and that Ess1-catalyzed cis-trans-proline isomerizationmore » facilitates rapid dephosphorylation by Ssu72, providing an explanation for recently discovered in vivo connections between these enzymes and a revised model for CTD-mediated small nuclear RNA termination. This work presents the first structural evidence of a cis-proline-specific enzyme and an unexpected mechanism of isomer-based regulation of phosphorylation, with broad implications for CTD biology« less

Laparoscopic Antireflux Surgery in Patients with Connective Tissue Diseases.

PubMed

Menezes, Mariano A; Herbella, Fernando A M; Patti, Marco G

2016-04-01

Different connective tissue diseases (CTDs), such as dermatomyositis, mixed CTD, rheumatoid arthritis, polymyositis, lupus, and Behçet's, may affect the esophagus, impairing its motor function. The muscular atrophy and fibrosis caused by the autoimmune vasculitis and neuronal dysfunction affect the esophageal body and the lower esophageal sphincter, leading to a clinical presentation of dysphagia and gastroesophageal reflux disease (GERD). The belief that the impaired esophageal motility may negatively affect surgical outcome has led to the common recommendation of avoiding laparoscopic antireflux surgery (LARS) for fear of creating or worsening dysphagia. This review focuses on the evaluation of the outcome of LARS in patients with CTD. Specifically, this review shows that the literature on LARS and CTDs is scarce and most studies have a small number of patients and a short follow-up. Furthermore, a subanalysis of the outcome based on the type of CTD or the manometric profile is still elusive. In the setting of these limitations, it appears that results are good and comparable to those of patients with GERD and without a CTD. Morbidity and mortality are insignificant even considering the systemic manifestations of the CTD. LARS should not be denied to patients with CTD and GERD.

Clinical Correlates and Mediators of Self-Concept in Youth with Chronic Tic Disorders.

PubMed

Hanks, Camille E; McGuire, Joseph F; Lewin, Adam B; Storch, Eric A; Murphy, Tanya K

2016-02-01

This study investigated the clinical correlates and mediators of self-concept in youth with Chronic Tic Disorders (CTD). Ninety-seven youth aged 6-17 (M = 11.1 ± 2.89; 79.4 % male) with CTD were administered the Yale Global Tic Severity Scale, the Piers-Harris Children's Self-Concept Scale-Second Edition, and self-report and clinician-administered measures assessing behavioral and psychological difficulties and comorbid conditions. Youth with CTD had a slightly below average level of self-concept, with 20 % (n = 19) exhibiting low self-concept. Youth with CTD-only had greater self-concept relative to youth with CTD and obsessive-compulsive disorder (OCD) (p = 0.04) or CTD, OCD, and attention deficit hyperactivity disorder (ADHD) combined (p = 0.009). Medium-to-large-sized associations were observed between youth's self-concept and clinical characteristics (e.g., severity of ADHD, OCD and depressive symptoms). Youth's self-concept partially mediated the relationship between tic severity and depressive symptom severity, and the interaction between tic impairment and youth's reliance on avoidant coping strategies moderated youth's self-concept. Implications, limitations, and recommendations for future interventions are discussed.

Clinical Correlates and Mediators of Self-Concept in Youth with Chronic Tic Disorders

PubMed Central

Hanks, Camille E.; McGuire, Joseph F.; Lewin, Adam B.; Storch, Eric A.

2015-01-01

This study investigated the clinical correlates and mediators of self-concept in youth with Chronic Tic Disorders (CTD). Ninety-seven youth aged 6–17 (M = 11.1 ± 2.89; 79.4 % male) with CTD were administered the Yale Global Tic Severity Scale, the Piers-Harris Children’s Self-Concept Scale—Second Edition, and self-report and clinician-administered measures assessing behavioral and psychological difficulties and comorbid conditions. Youth with CTD had a slightly below average level of self-concept, with 20 % (n = 19) exhibiting low self-concept. Youth with CTD-only had greater self-concept relative to youth with CTD and obsessive–compulsive disorder (OCD) (p = 0.04) or CTD, OCD, and attention deficit hyperactivity disorder (ADHD) combined (p = 0.009). Medium-to-large-sized associations were observed between youth’s self-concept and clinical characteristics (e.g., severity of ADHD, OCD and depressive symptoms). Youth’s self-concept partially mediated the relationship between tic severity and depressive symptom severity, and the interaction between tic impairment and youth’s reliance on avoidant coping strategies moderated youth’s self-concept. Implications, limitations, and recommendations for future interventions are discussed. PMID:25791488

Chromatin Condensing Functions of the Linker Histone C-terminal Domain are mediated by Specific Amino Acid Composition and Intrinsic Protein Disorder†

PubMed Central

Lu, Xu; Hamkalo, Barbara; Parseghian, Missag H.; Hansen, Jeffrey C.

2009-01-01

Linker histones bind to the nucleosomes and linker DNA of chromatin fibers, causing changes in linker DNA structure and stabilization of higher order folded and oligomeric chromatin structures. Linker histones affect chromatin structure acting primarily through their ~100 residue C-terminal domain (CTD). We have previously shown that the ability of the linker histone H1° to alter chromatin structure was localized to two discontinuous 24-/25-residue CTD regions (Lu, X., and Hansen, J. C. (2004) J Biol Chem 279, 8701–8707). To determine the biochemical basis for these results, we have characterized chromatin model systems assembled with endogenous mouse somatic H1 isoforms, or recombinant H1° CTD mutants in which the primary sequence has been scrambled, the amino acid composition mutated, or the location of various CTD regions swapped. Our results indicate that specific amino acid composition plays a fundamental role in molecular recognition and function by the H1 CTD. Additionally, these experiments support a new molecular model for CTD function, and provide a biochemical basis for the redundancy observed in H1 isoform knockout experiments in vivo. PMID:19072710

Operation and Hydrodynamic Evaluations of a Controlled-Depth Towed Depressor Designed to House a Conductivity, Temperature, Depth (CTD) Instrument System

DTIC Science & Technology

1981-03-01

ljIi 0 10 20 30 40 50 60 70 80 LENGTH (W) Figure 2 - Predicted Tension in Remote Sensor Cable at 10 Knots as a Function of Cable Length for Two Remote...10.0 -8.0 -10 4.11 0.68 40 5.0 -8.0 -15 0.66 0.44 41 8.0 -8.0 -15 1.57 0.41 42 10.0 -8.0 -15 2.63 0.44 43 5.0 -8.0 -20 0.48 0.32 44 8.0 -8.0 -20 0.89...HH fIH 1 IH r-4 H r- rIH rIH 4 i HHH.-4H H -4 rIH HHHHH r Cfr- 40 00 0 0q - zI - ri-4- oi 0 -A- \\.o. m M- r-. A- - rA- r-c r(0 P4 r

Coastal ocean forecasting with an unstructured grid model in the southern Adriatic and northern Ionian seas

NASA Astrophysics Data System (ADS)

Federico, Ivan; Pinardi, Nadia; Coppini, Giovanni; Oddo, Paolo; Lecci, Rita; Mossa, Michele

2017-01-01

SANIFS (Southern Adriatic Northern Ionian coastal Forecasting System) is a coastal-ocean operational system based on the unstructured grid finite-element three-dimensional hydrodynamic SHYFEM model, providing short-term forecasts. The operational chain is based on a downscaling approach starting from the large-scale system for the entire Mediterranean Basin (MFS, Mediterranean Forecasting System), which provides initial and boundary condition fields to the nested system. The model is configured to provide hydrodynamics and active tracer forecasts both in open ocean and coastal waters of southeastern Italy using a variable horizontal resolution from the open sea (3-4 km) to coastal areas (50-500 m). Given that the coastal fields are driven by a combination of both local (also known as coastal) and deep-ocean forcings propagating along the shelf, the performance of SANIFS was verified both in forecast and simulation mode, first (i) on the large and shelf-coastal scales by comparing with a large-scale survey CTD (conductivity-temperature-depth) in the Gulf of Taranto and then (ii) on the coastal-harbour scale (Mar Grande of Taranto) by comparison with CTD, ADCP (acoustic doppler current profiler) and tide gauge data. Sensitivity tests were performed on initialization conditions (mainly focused on spin-up procedures) and on surface boundary conditions by assessing the reliability of two alternative datasets at different horizontal resolution (12.5 and 6.5 km). The SANIFS forecasts at a lead time of 1 day were compared with the MFS forecasts, highlighting that SANIFS is able to retain the large-scale dynamics of MFS. The large-scale dynamics of MFS are correctly propagated to the shelf-coastal scale, improving the forecast accuracy (+17 % for temperature and +6 % for salinity compared to MFS). Moreover, the added value of SANIFS was assessed on the coastal-harbour scale, which is not covered by the coarse resolution of MFS, where the fields forecasted by SANIFS reproduced the observations well (temperature RMSE equal to 0.11 °C). Furthermore, SANIFS simulations were compared with hourly time series of temperature, sea level and velocity measured on the coastal-harbour scale, showing a good agreement. Simulations in the Gulf of Taranto described a circulation mainly characterized by an anticyclonic gyre with the presence of cyclonic vortexes in shelf-coastal areas. A surface water inflow from the open sea to Mar Grande characterizes the coastal-harbour scale.

Relationship between cognitive and non-cognitive symptoms of delirium.

PubMed

Rajlakshmi, Aarya Krishnan; Mattoo, Surendra Kumar; Grover, Sandeep

2013-04-01

To study relationship between the cognitive and the non-cognitive symptoms of delirium. Eighty-four patients referred to psychiatry liaison services and met DSM-IVTR criteria of delirium were assessed using the Delirium Rating Scale Revised-1998 (DRSR-98) and Cognitive Test for Delirium (CTD). The mean DRS-R-98 severity score was 17.19 and DRS-R-98 total score was 23.36. The mean total score on CTD was 11.75. The mean scores on CTD were highest for comprehension (3.47) and lowest for vigilance (1.71). Poor attention was associated with significantly higher motor retardation and higher DRS-R-98 severity scores minus the attention scores. There were no significant differences between those with and without poor attention. Higher attention deficits were associated with higher dysfunction on all other domains of cognition on CTD. There was significant correlation between cognitive functions as assessed on CTD and total DRS-R-98 score, DRS-R-98 severity score and DRS-R-98 severity score without the attention item score. However, few correlations emerged between CTD domains and CTD total scores with cognitive symptom total score of DRS-R-98 (items 9-13) and non-cognitive symptom total score of DRS-R-98 (items 1-8). Our study suggests that in delirium, cognitive deficits are quite prevalent and correlate with overall severity of delirium. Attention deficit is a core symptom of delirium. Copyright © 2012 Elsevier B.V. All rights reserved.

Top-Down Charge Transfer Dissociation (CTD) of Gas-Phase Insulin: Evidence of a One-Step, Two-Electron Oxidation Mechanism

NASA Astrophysics Data System (ADS)

Li, Pengfei; Kreft, Iris; Jackson, Glen P.

2018-02-01

Top-down analyses of protonated insulin cations of charge states of 4+, 5+, or 6+ were performed by exposing the isolated precursor ions to a beam of helium cations with kinetic energy of more than 6 keV, in a technique termed charge transfer dissociation (CTD). The 100 ms charge transfer reaction resulted in approximately 20% conversion efficiency to other intact charge exchange products (CTnoD), and a range of low abundance fragment ions. To increase backbone and sulfide cleavages, and to provide better structural information than straightforward MS2 CTD, the CTnoD oxidized products were isolated and subjected to collisional activation at the MS3 level. The MS3 CTD/CID reaction effectively broke the disulfide linkages, separated the two chains, and yielded more structurally informative fragment ions within the inter-chain cyclic region. CTD also provided doubly oxidized intact product ions at the MS2 level, and resonance ejection of the singly oxidized product ion revealed that the doubly oxidized product originates directly from the isolated precursor ion and not from consecutive CTD reactions of a singly oxidized intermediate. MS4 experiments were employed to help identify potential radical cations and diradical cations, but the results were negative or inconclusive. Nonetheless, the two-electron oxidation process is a demonstration of the very large potential energy (>20 eV) available through CTD, and is a notable capability for a 3D ion trap platform.

Regulation (EC) No 1901/2006 on medicinal products for paediatric use & clinical research in vulnerable populations.

PubMed

Lehmann, Birka

2008-12-08

Before any medicinal product is authorised for use in adults, it must undergo extensive pharmaceutical consistency and stability tests, toxicological tests and clinical trials to ensure that it is of high quality, safe and effective.The same approach may not always be applied to medicinal products used to treat children.Studies showed that over 50% of the medicinal products used in children may not have been tested for use in this age group. The absence of suitable authorised medicinal products to treat conditions in children results from the fact that pharmaceutical companies do not adapt medicinal products to the needs of the paediatric population. This leaves health care professionals with no alternative other than to use medicinal products "off-label" and to use unauthorised products with the associated risks of inefficacy and/or adverse reactions.The Regulation (EC) No 1901/2006 sets up a system of requirements, rewards and incentives, together with horizontal measures, to ensure that medicinal products are researched, developed and authorised to meet the therapeutic needs of children.The Regulation is addressed to: 1. The pharmaceutical industry by setting out the legal framework for receiving rewards and incentives by conducting clinical trials in the paediatric population. 2. The Member States to set out to support research into, and the development and availability of, medicinal products for paediatric use. 3. The Community as funds for research into medicinal products for the paediatric population shall be provided for in the Community budget in order to support studies relating to medicinal products or active substances not covered by a patent or a supplementary protection certificate. The legal framework for conducting clinical trials, including children/minors, is set up in Directive 2001/20/EC, the Clinical Trials Directive (CTD), for the European Union (EU). The CTD establishes specific provisions regarding conduct of clinical trials, including multi-centre trials, on human subjects involving medicinal products and in particular relating to the implementation of good clinical practice. Compliance with this good practice provides assurance that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible. The CTD is addressed to all investigators conducting clinical trials including clinical trials in the paediatric population and had to be applied accordingly.In the framework of the authorisation of medicinal products regulated by the Regulation (EC) No 726/2004 and Directive 2001/83/EC as amended and the CTD, and additional implementing Directives and guidelines, the new Regulation (EC) No 1901/2006 is an important new piece of legislation focusing on the requirements to improve the situation for the paediatric population. All Regulations/Directives to be found: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol1_en.htm.

Regulation (EC) No 1901/2006 on medicinal products for paediatric use & clinical research in vulnerable populations

PubMed Central

Lehmann, Birka

2008-01-01

Before any medicinal product is authorised for use in adults, it must undergo extensive pharmaceutical consistency and stability tests, toxicological tests and clinical trials to ensure that it is of high quality, safe and effective. The same approach may not always be applied to medicinal products used to treat children. Studies showed that over 50% of the medicinal products used in children may not have been tested for use in this age group. The absence of suitable authorised medicinal products to treat conditions in children results from the fact that pharmaceutical companies do not adapt medicinal products to the needs of the paediatric population. This leaves health care professionals with no alternative other than to use medicinal products "off-label" and to use unauthorised products with the associated risks of inefficacy and/or adverse reactions. The Regulation (EC) No 1901/2006 sets up a system of requirements, rewards and incentives, together with horizontal measures, to ensure that medicinal products are researched, developed and authorised to meet the therapeutic needs of children. The Regulation is addressed to: 1. The pharmaceutical industry by setting out the legal framework for receiving rewards and incentives by conducting clinical trials in the paediatric population. 2. The Member States to set out to support research into, and the development and availability of, medicinal products for paediatric use. 3. The Community as funds for research into medicinal products for the paediatric population shall be provided for in the Community budget in order to support studies relating to medicinal products or active substances not covered by a patent or a supplementary protection certificate. The legal framework for conducting clinical trials, including children/minors, is set up in Directive 2001/20/EC, the Clinical Trials Directive (CTD), for the European Union (EU). The CTD establishes specific provisions regarding conduct of clinical trials, including multi-centre trials, on human subjects involving medicinal products and in particular relating to the implementation of good clinical practice. Compliance with this good practice provides assurance that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible. The CTD is addressed to all investigators conducting clinical trials including clinical trials in the paediatric population and had to be applied accordingly. In the framework of the authorisation of medicinal products regulated by the Regulation (EC) No 726/2004 and Directive 2001/83/EC as amended and the CTD, and additional implementing Directives and guidelines, the new Regulation (EC) No 1901/2006 is an important new piece of legislation focusing on the requirements to improve the situation for the paediatric population. All Regulations/Directives to be found: PMID:19063722

Separate Intramolecular Targets for Protein Kinase A Control N-Methyl-d-aspartate Receptor Gating and Ca2+ Permeability*

PubMed Central

Aman, Teresa K.; Maki, Bruce A.; Ruffino, Thomas J.; Kasperek, Eileen M.; Popescu, Gabriela K.

2014-01-01

Protein kinase A (PKA) enhances synaptic plasticity in the central nervous system by increasing NMDA receptor current amplitude and Ca2+ flux in an isoform-dependent yet poorly understood manner. PKA phosphorylates multiple residues on GluN1, GluN2A, and GluN2B subunits in vivo, but the functional significance of this multiplicity is unknown. We examined gating and permeation properties of recombinant NMDA receptor isoforms and of receptors with altered C-terminal domain (CTDs) prior to and after pharmacological inhibition of PKA. We found that PKA inhibition decreased GluN1/GluN2B but not GluN1/GluN2A gating; this effect was due to slower rates for receptor activation and resensitization and was mediated exclusively by the GluN2B CTD. In contrast, PKA inhibition reduced NMDA receptor-relative Ca2+ permeability (PCa/PNa) regardless of the GluN2 isoform and required the GluN1 CTD; this effect was due primarily to decreased unitary Ca2+ conductance, because neither Na+ conductance nor Ca2+-dependent block was altered substantially. Finally, we show that both the gating and permeation effects can be reproduced by changing the phosphorylation state of a single residue: GluN2B Ser-1166 and GluN1 Ser-897, respectively. We conclude that PKA effects on NMDA receptor gating and Ca2+ permeability rely on distinct phosphorylation sites located on the CTD of GluN2B and GluN1 subunits. This separate control of NMDA receptor properties by PKA may account for the specific effects of PKA on plasticity during synaptic development and may lead to drugs targeted to alter NMDA receptor gating or Ca2+ permeability. PMID:24847051

4-D Current Experiment Using AUV and HF-Radar

DTIC Science & Technology

1998-01-01

the NICOP project at FAU. RESULTS Measurements of bathymetry, current and CTD measurements were acquired in shallow water on 5 and 11 Dec 97 in a lawn ... mower pattern (An et al., 1998). These surveys were conducted over about a 3 h period at a constant water depth of 7 m in the vicinity of an ADCP. On

[Morphological features of the myometrium in connective tissue dysplasia in women with uterine inertia].

PubMed

Konovalov, P V; Mitrofanova, L B; Gorshkov, A N; Ovsyannikov, F A

2015-01-01

to reveal the morphological features of the lower uterine segment myometrium in connective tissue dysplasia (CTD) in women with uterine inertia. Histological, immunohistochemical (with antibodies against collagen types I and III, matrix metalloproteinases 1 and 9 (MMR-1, MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), fibronectin; fibulin-5, connexin-43), electron microscopic, and electron immunocytochemical studies with morphometry of myometrial fragments from 15 parturient women with CTD and uterine inertia (a study group) and those from 10 women without CTD (a control group). The myometrium in CTD exhibited the decreased expression of connextin-43, fibulin-5, TIMP-1, collagens types I and III with collagen type III predominance and the unchanged levels of fibronectin and MMP-1 and MMP-9. Electron microscopy and immunocytochemistry showed fewer intercellular contacts and the dramatically lower expression of connexin-43 than in the control. A set of found myometrial changes in women with uterine inertia is a manifestation of CTD.

Workplace discrimination and cumulative trauma disorders: the national EEOC ADA research project.

PubMed

Armstrong, Amy J; McMahon, Brian T; West, Steven L; Lewis, Allen

2005-01-01

Employment discrimination of persons with cumulative trauma disorders (CTDs) was explored using the Integrated Mission System dataset of the US Equal Employment Opportunity Commission. Demographic characteristics and merit resolutions of the Charging Parties (persons with CTD) were compared to individuals experiencing other physical, sensory and neurological impairments. Factors compared also included industry designation, geographic region, and size of Respondents against which allegations were filed. Persons with CTD had proportionately greater allegations among large Respondents (greater than 500 workers) engaged in manufacturing, utilities, transportation, finance insurance and real estate. The types of discrimination Issues that were proportionately greater in the CTD group included layoff, failure to reinstate, and failure to provide reasonable accommodation. The CTD group was significantly less likely than the comparison group to be involved in discrimination Issues such as assignment to less desirable duty, shift or work location; demotion; termination, or failure to hire or provide training. Persons with CTD had higher proportions of merit Resolutions where allegations were voluntarily withdrawn by the Charging Party with benefits.

Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease-related interstitial lung diseases.

PubMed

Saketkoo, Lesley Ann; Mittoo, Shikha; Frankel, Sid; LeSage, Daphne; Sarver, Catherine; Phillips, Kristine; Strand, Vibeke; Matteson, Eric L

2014-04-01

Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.

Analysis of the MRPL3, DNAJC13 and OFCC1 variants in Chinese Han patients with TS-CTD.

PubMed

Guo, Yi; Deng, Xiong; Zhang, Jie; Su, Linyan; Xu, Hongbo; Luo, Ziqiang; Deng, Hao

2012-05-23

Tourette syndrome/chronic tic phenotype (TS-CTD) is a neurological disorder manifested particularly by motor and vocal tics and associated with a variety of behavioral abnormalities. Recently, the mitochondrial ribosomal protein L3 gene (MRPL3) S75N, the DnaJ (Hsp40) homolog subfamily C member 13 gene (DNAJC13) A2057S, the orofacial cleft 1 candidate 1 gene (OFCC1) R129G and c.-5A>G variants are reported to be associated with Tourette syndrome/chronic tic phenotype (TS-CTD) in patients of European ancestry. To evaluate whether these variants are associated with TS-CTD in Chinese Han patients, we screened 132 Chinese Han patients from Mainland China. None of the 132 samples from patients with TS-CTD showed the MRPL3 S75N, DNAJC13 A2057S, OFCC1 R129G and c.-5A>G variants, and these variants probably are a rare cause of TS-CTD in a Chinese Han ethnic group. Genetic heterogeneity of TS should be considered and tests designed to detect these variants in Chinese Han ethnic group probably will not have a diagnostic utility in clinical practice. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Self-esteem in adults with Tourette syndrome and chronic tic disorders: The roles of tic severity, treatment, and comorbidity.

PubMed

Weingarden, Hilary; Scahill, Lawrence; Hoeppner, Susanne; Peterson, Alan L; Woods, Douglas W; Walkup, John T; Piacentini, John; Wilhelm, Sabine

2018-07-01

Tourette syndrome (TS) and chronic tic disorders (CTD) are stigmatizing disorders that may significantly impact self-esteem. Alternatively, comorbid psychiatric illnesses may affect self-esteem more than tics themselves. Extant research on self-esteem in TS/CTD is limited, has inconsistently examined the effect of comorbidities on self-esteem, and yields mixed findings. This study aimed to clarify the roles of tics versus comorbid diagnoses on self-esteem in a large, carefully diagnosed sample of adults with TS/CTD (N = 122) receiving 10 weeks of Comprehensive Behavioral Intervention for Tics (CBIT) or Psychoeducation and Supportive Therapy (PST). Baseline self-esteem did not differ between adults with TS/CTD only and normative means, whereas self-esteem was significantly lower among adults with TS/CTD with a comorbid psychiatric illness. In a multiple regression testing the baseline association between tic severity, presence of comorbid psychiatric illness, and depression severity with self-esteem, comorbidity and depression severity were significantly associated with self-esteem, whereas tic severity was not. Finally, using a generalized linear model, we tested the effects of treatment assignment, comorbidity, and their interaction on changes in self-esteem across treatment, controlling for baseline depression severity. Results showed that for those with a comorbid illness, self-esteem improved significantly more with CBIT than with PST. Comorbid illnesses appear to affect self-esteem more so than tics among adults with TS/CTD. Therapeutic attention should be paid to treating comorbid diagnoses alongside tics when treating TS/CTD. Copyright © 2018 Elsevier Inc. All rights reserved.

Measurement of antinuclear antibodies and their fine specificities: time for a change in strategy?

PubMed

Otten, Henny G; Brummelhuis, Walter J; Fritsch-Stork, Ruth; Leavis, Helen L; Wisse, Bram W; van Laar, Jacob M; Derksen, Ronald H W M

2017-01-01

The current strategy for antinuclear antibody (ANA) analysis involves screening for presence with a subsequent detailed analysis of their specificity. The aim of this study is to compare the clinical and financial efficacy of this strategy between different commercial tests in a large cohort of unselected patients. In all consecutive 1030 patients associations were defined between results from different ANA test systems and the pre-test probability for connective tissue disease (CTDs). Test systems were used for screening (ANA-IIF vs. CTD screen) and definition of their fine specificity (profile 3 line blot vs. CTD single analytes). Positive ANA-IIF and/or CTD screen results were found in 304 sera. Further analysis for ANA-specificity by profile 3 line blot and CTD single analytes showed 86 discrepant results of which more than a third are clinically relevant, with the CTD single analyte assay performing better than the line blot in supporting or confirming the presence of a CTD. Autoantigens present in one test but absent in the other were of minor practical use. The ANA screening and identification strategies currently employed are not cost-effective as 83% of tests were performed in order to find specific autoantibodies in patients without the fitting clinical signs or symptoms. This causes many unexpected positive results and subsequent confusion with regard to interpretation. We advocate that some autoantigens should be excluded from the line blot and CTD assays and propose the use of a cost-effective and selective ANA specificity testing purely based on clinical guidance.

Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial

PubMed Central

Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

2017-01-01

Background Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. Objective To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. Methods This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). Results In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. Conclusions This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. Trial registration number NCT01178073, post results. PMID:28039187

Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial.

PubMed

Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

2017-07-01

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. NCT01178073, post results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Cumulative trauma disorders among apparel manufacturing employees in the southeastern United States.

PubMed

Dignan, M; Hayes, D; Main, H; Parker, K

1996-11-01

Factors associated with cumulative trauma disorders (CTDs) of the upper extremities were studied retrospectively, using data from three apparel manufacturing plants in the southeastern United States. Reported CTDs among the employees at risk during fiscal years 1991 and 1992 were analyzed focusing on individual and plant variables. Results showed that CTD rates increased from 1991 to 1992 and fluctuated in a cyclical pattern each year, peaking during January, March, and August. Employee age and duration of employment were associated with CTD rates. Employees aged 45 to 49 had higher CTD rates than those in any other age groups. Employees with 1 to 3 years' experience had higher CTD rates than employees with more years of service.

Transport of the Norwegian Atlantic current as determined from satellite altimetry

NASA Technical Reports Server (NTRS)

Pistek, Pavel; Johnson, Donald R.

1992-01-01

Relatively warm and salty North Atlantic surface waters flow through the Faeroe-Shetland Channel into the higher latitudes of the Nordic Seas, preserving an ice-free winter environment for much of the exterior coast of northern Europe. This flow was monitored along the Norwegian coast using Geosat altimetry on two ascending arcs during the Exact Repeat Mission in 1987-1989. Concurrent undertrack CTD surveys were used to fix a reference surface for the altimeter-derived SSH anomalies, in effect creating time series of alongtrack surface dynamic height topographies. Climatologic CTD casts were then used, with empirical orthogonal function (EOF) analysis, to derive relationships between historical surface dynamic heights and vertical temperature and salinity profiles. Applying these EOF relationships to the altimeter signals, mean transports of volume, heat, and salt were calculated at approximately 2.9 Sverdrups, 8.1 x 10 exp 11 KCal/s and 1.0 x 10 exp 8 Kg/s, respectively. Maximum transports occurred in February/March and minimum in July/August.

Helicopter- and ship-based measurements of mesoscale ocean color and thermal features in the marginal ice zone

NASA Astrophysics Data System (ADS)

Tanis, Fred J.; Manley, Thomas O.; Mitchell, Brian G.

1990-09-01

Eddies along the Polar Front/Marginal Ice Zone (MIZ) in Fram Strait are thought to make important contributions to nutrient flux and stimulation of primary productivity. During the Coordinated Eastern Arctic Regional Experiment (CEAREX) helicopter-based measurements of upwelling radiance were made in four visible spectral bands and in the thermal IR across mesoscale features associated with the MIZ. These structures were mapped by flying a grid pattern over the ocean surface to define eddy boundaries. Subsequently, the area was also sampled vertically with CTD and spectral radiometer profilers. Data obtained from a single structure were integrated to construct a three dimensional picture of physical and optical properties. Volume modeling of temperature, salinity, and density fields obtained from CTD survey define the subsurface eddy structure and are in good agreement with infrared derived characteristics. Maximum temperature in the core was found to be four degrees higher than the surrounding water. Volume modeling further indicates that a subsurface layer of Arctic Intermediate Water is intrinsically associated with the surface expression of the eddy. The ratio of upwelling radiances, L(44l)/L(565), was found to be correlated to surface chlorophyll, particulate absorption coefficient, and in water determinations of L using the optical profiling system. The remote sensing reflectance ratio along with the IR sea surface temperature were found to be useful to detect the surface expression of the eddy and to indicate near surface biological and physical processes.

Suicide in Tourette's and Chronic Tic Disorders.

PubMed

Fernández de la Cruz, Lorena; Rydell, Mina; Runeson, Bo; Brander, Gustaf; Rück, Christian; D'Onofrio, Brian M; Larsson, Henrik; Lichtenstein, Paul; Mataix-Cols, David

2017-07-15

Persons with neuropsychiatric disorders are at increased risk of suicide, but there is little data concerning Tourette's and chronic tic disorders (TD/CTD). We aimed to quantify the risk of suicidal behavior in a large nationwide cohort of patients with TD/CTD, establish the contribution of psychiatric comorbidity to this risk, and identify predictors of suicide. Using a validated algorithm, we identified 7736 TD/CTD cases in the Swedish National Patient Register during a 44-year period (1969-2013). Using a matched case-cohort design, patients were compared with general population control subjects (1:10 ratio). Risk of suicidal behavior was estimated using conditional logistic regressions. Predictors of suicidal behavior in the TD/CTD cohort were studied using Cox regression models. In unadjusted models, TD/CTD patients, compared with control subjects, had an increased risk of both dying by suicide (odds ratio: 4.39; 95% confidence interval [CI]: 2.89-6.67) and attempting suicide (odds ratio: 3.86; 95% CI: 3.50-4.26). After adjusting for psychiatric comorbidities, the risk was reduced but remained substantial. Persistence of tics beyond young adulthood and a previous suicide attempt were the strongest predictors of death by suicide in TD/CTD patients (hazard ratio: 11.39; 95% CI: 3.71-35.02, and hazard ratio: 5.65; 95% CI: 2.21-14.42, respectively). TD/CTD are associated with substantial risk of suicide. Suicidal behavior should be monitored in these patients, particularly in those with persistent tics, history of suicide attempts, and psychiatric comorbidities. Preventive and intervention strategies aimed to reduce the suicidal risk in this group are warranted. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Lysines in the RNA Polymerase II C-Terminal Domain Contribute to TAF15 Fibril Recruitment.

PubMed

Janke, Abigail M; Seo, Da Hee; Rahmanian, Vahid; Conicella, Alexander E; Mathews, Kaylee L; Burke, Kathleen A; Mittal, Jeetain; Fawzi, Nicolas L

2018-05-01

Many cancer-causing chromosomal translocations result in transactivating protein products encoding FET family (FUS, EWSR1, TAF15) low-complexity (LC) domains fused to a DNA binding domain from one of several transcription factors. Recent work demonstrates that higher-order assemblies of FET LC domains bind the carboxy-terminal domain of the large subunit of RNA polymerase II (RNA pol II CTD), suggesting FET oncoproteins may mediate aberrant transcriptional activation by recruiting RNA polymerase II to promoters of target genes. Here we use nuclear magnetic resonance (NMR) spectroscopy and hydrogel fluorescence microscopy localization and fluorescence recovery after photobleaching to visualize atomic details of a model of this process, interactions of RNA pol II CTD with high-molecular weight TAF15 LC assemblies. We report NMR resonance assignments of the intact degenerate repeat half of human RNA pol II CTD alone and verify its predominant intrinsic disorder by molecular simulation. By measuring NMR spin relaxation and dark-state exchange saturation transfer, we characterize the interaction of RNA pol II CTD with amyloid-like hydrogel fibrils of TAF15 and hnRNP A2 LC domains and observe that heptads far from the acidic C-terminal tail of RNA pol II CTD bind TAF15 fibrils most avidly. Mutation of CTD lysines in heptad position 7 to consensus serines reduced the overall level of TAF15 fibril binding, suggesting that electrostatic interactions contribute to complex formation. Conversely, mutations of position 7 asparagine residues and truncation of the acidic tail had little effect. Thus, weak, multivalent interactions between TAF15 fibrils and heptads throughout RNA pol II CTD collectively mediate complex formation.

LONG-TERM EFFECTS OF CHLORTHALIDONE VS HYDROCHLOROTHIAZIDE ON ELECTROCARDIOGRAPHIC LEFT VENTRICULAR HYPERTROPHY IN THE MULTIPLE RISK FACTOR INTERVENTION TRIAL

PubMed Central

Ernst, Michael E.; Neaton, James D.; Grimm, Richard H.; Collins, Gary; Thomas, William; Soliman, Elsayed Z.; Prineas, Ronald J.

2011-01-01

Chlorthalidone (CTD) reduces 24-hour blood pressure more effectively than hydrochlorothiazide (HCTZ), but whether this influences electrocardiographic left ventricular hypertrophy (LVH) is uncertain. One source of comparative data is the Multiple Risk Factor Intervention Trial (MRFIT), which randomly assigned 8,012 hypertensive men to special intervention (SI) or usual care (UC). SI participants could use CTD or HCTZ initially; previous analyses have grouped clinics by their main diuretic used (C-clinics: CTD; H-clinics: HCTZ). After 48 months, SI participants receiving HCTZ were recommended to switch to CTD, in part, because higher mortality was observed for SI compared to UC participants in H-clinics, while the opposite was found in C-clinics. In this analysis, we examined change in continuous measures of electrocardiographic LVH using both an ecologic analysis by previously-reported C- or H-clinic groupings, and an individual participant analysis where use of CTD or HCTZ by SI participants was considered and updated annually. Through 48 months, differences between SI and UC in LVH were larger for C-clinics compared to H-clinics (Sokolow-Lyon: −93.9 vs −54.9 μV, P=0.049; Cornell voltage: −68.1 vs −35.9 μV, P=0.019; Cornell voltage product: −4.6 vs −2.2 μV/ms, P=0.071; left ventricular mass: −4.4 vs −2.8 gm, P=0.002). At the individual participant level, Sokolow-Lyon and left ventricular mass were significantly lower for SI men receiving CTD compared to HCTZ through 48 months and 84 months of follow-up. Our findings on LVH support the idea that greater blood pressure reduction with CTD than HCTZ may have led to differences in mortality observed in MRFIT. PMID:22025372

Comparison of cyclophosphamide-thalidomide-dexamethasone to bortezomib-cyclophosphamide-dexamethasone as induction therapy for multiple myeloma patients in Brazil.

PubMed

Vigolo, Suelen; Zuckermann, Joice; Bittencourt, Rosane Isabel; Silla, Lúcia; Pilger, Diogo André

2017-09-01

Chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) remains the standard treatment for multiple myeloma (MM). Thalidomide or bortezomib may be combined with cyclophosphamide and dexamethasone, in what are known as the CTD and VCD protocols, respectively. The objective of this study was to evaluate the clinical characteristics and response rates obtained with CTD and VCD, observing whether the inclusion of bortezomib to treat MM patients in Brazil increases therapeutic efficiency. Forty-three MM patients treated with induction protocols CTD and VCD between January 2010 and March 2015 were included. The parameters analyzed were staging, frequency of comorbidities prior to treatment, response rates obtained at each induction cycle, progression-free survival, and overall survival of patients. Very good partial response and complete response obtained with the VCD protocol were superior, compared with the CTD treatment. The presence of comorbidities was similar in the two groups, except kidney failure, which prevailed in the VCD group. Also, 78.3% and 48.3% of patients treated with the VCD and CTD protocols underwent autologous HSCT, respectively. In patients given the VCD protocol, 45.5% had complete response before autologous HSCT. Among those given CTD, this number was only 7.1% (p=0.023). Disease progression after autologous HSCT did not differ between the two groups. VCD afforded better responses than the CTD protocol, and improved patient condition before autologous HSCT. However, more studies are necessary including more patients and addressing various clinical conditions, besides the analysis of cost-effectiveness of these treatments. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Cdc15 Phosphorylates the C-terminal Domain of RNA Polymerase II for Transcription during Mitosis.

PubMed

Singh, Amit Kumar; Rastogi, Shivangi; Shukla, Harish; Asalam, Mohd; Rath, Srikanta Kumar; Akhtar, Md Sohail

2017-03-31

In eukaryotes, the basal transcription in interphase is orchestrated through the regulation by kinases (Kin28, Bur1, and Ctk1) and phosphatases (Ssu72, Rtr1, and Fcp1), which act through the post-translational modification of the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. The CTD comprises the repeated Tyr-Ser-Pro-Thr-Ser-Pro-Ser motif with potential epigenetic modification sites. Despite the observation of transcription and periodic expression of genes during mitosis with entailing CTD phosphorylation and dephosphorylation, the associated CTD specific kinase(s) and its role in transcription remains unknown. Here we have identified Cdc15 as a potential kinase phosphorylating Ser-2 and Ser-5 of CTD for transcription during mitosis in the budding yeast. The phosphorylation of CTD by Cdc15 is independent of any prior Ser phosphorylation(s). The inactivation of Cdc15 causes reduction of global CTD phosphorylation during mitosis and affects the expression of genes whose transcript levels peak during mitosis. Cdc15 also influences the complete transcription of clb2 gene and phosphorylates Ser-5 at the promoter and Ser-2 toward the 3' end of the gene. The observation that Cdc15 could phosphorylate Ser-5, as well as Ser-2, during transcription in mitosis is in contrast to the phosphorylation marks put by the kinases in interphase (G 1 , S, and G 2 ), where Cdck7/Kin28 phosphorylates Ser-5 at promoter and Bur1/Ctk1 phosphorylates Ser-2 at the 3' end of the genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Tadalafil in idiopathic or heritable pulmonary arterial hypertension (PAH) compared to PAH associated with connective tissue disease.

PubMed

Galiè, Nazzareno; Denton, Christopher P; Dardi, Fabio; Manes, Alessandra; Mazzanti, Gaia; Li, Baohui; Varanese, Lucio; Esler, Anne; Harmon, Cathi; Palazzini, Massimiliano

2017-05-15

The primary objective of this post hoc analysis was to evaluate clinical outcomes of tadalafil in patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD-PAH) compared with patients with idiopathic/heritable PAH (I/H-PAH) for primary and key secondary efficacy endpoints, and safety. This analysis included adult patients with CTD-PAH or I/H-PAH who participated in the PHIRST and PHIRST-2 studies. Patients were randomized 1:1:1:1:1 to tadalafil (2.5, 10, 20, or 40mg) or placebo in the PHIRST study and the majority of these patients were subsequently assigned 40mg in PHIRST-2. Patients taking 20mg in PHIRST without demonstrating clinical worsening continued on 20mg in PHIRST-2. Outcomes analyzed included 6MWD, WHO-FC, and incidence and time to first occurrence of clinical worsening. Safety was assessed through evaluation of adverse events (AEs), clinical laboratory data, electrocardiograms, and physical examinations. Increased 6MWD in PHIRST was maintained in both CTD-PAH and I/H-PAH subgroups for 52weeks. Patients with CTD-PAH tended to be older, were more likely female, had lower exercise capacity, were more likely to have clinical worsening, and experienced AEs more frequently than patients with I/H-PAH. The effect of tadalafil treatment in patients enrolled in both PHIRST studies was detectable for both I/H-PAH and CTD-PAH subgroups. In general, subgroup differences were modest. Patients with CTD-PAH may perform less well than patients with I/H-PAH in safety and efficacy measures in all treatment groups, which is similar to other studies demonstrating a worse prognosis for patients with CTD-PAH. Copyright © 2017. Published by Elsevier B.V.

Long-Term Monitoring of Waterborne Pathogens and Microbial Source Tracking Markers in Paired Agricultural Watersheds under Controlled and Conventional Tile Drainage Management

PubMed Central

Wilkes, Graham; Brassard, Julie; Edge, Thomas A.; Gannon, Victor; Gottschall, Natalie; Jokinen, Cassandra C.; Jones, Tineke H.; Khan, Izhar U. H.; Marti, Romain; Sunohara, Mark D.; Topp, Edward

2014-01-01

Surface waters from paired agricultural watersheds under controlled tile drainage (CTD) and uncontrolled tile drainage (UCTD) were monitored over 7 years in order to determine if there was an effect of CTD (imposed during the growing season) on occurrences and loadings of bacterial and viral pathogens, coliphages, and microbial source tracking markers. There were significantly lower occurrences of human, ruminant, and livestock (ruminant plus pig) Bacteroidales markers in the CTD watershed in relation to the UCTD watershed. As for pathogens, there were significantly lower occurrences of Salmonella spp. and Arcobacter spp. in the CTD watershed. There were no instances where there were significantly higher quantitative loadings of any microbial target in the CTD watershed, except for F-specific DNA (F-DNA) and F-RNA coliphages, perhaps as a result of fecal inputs from a hobby farm independent of the drainage practice treatments. There was lower loading of the ruminant marker in the CTD watershed in relation to the UCTD system, and results were significant at the level P = 0.06. The odds of Salmonella spp. occurring increased when a ruminant marker was present relative to when the ruminant marker was absent, yet for Arcobacter spp., the odds of this pathogen occurring significantly decreased when a ruminant marker was present relative to when the ruminant marker was absent (but increased when a wildlife marker was present relative to when the wildlife marker was absent). Interestingly, the odds of norovirus GII (associated with human and swine) occurring in water increased significantly when a ruminant marker was present relative to when a ruminant marker was absent. Overall, this study suggests that fecal pollution from tile-drained fields to stream could be reduced by CTD utilization. PMID:24727274

Rainfall Effects on the Kuroshio Current East of Taiwan

NASA Astrophysics Data System (ADS)

Hsu, Po-Chun; Lin, Chen-Chih; Ho, Chung-Ru

2017-04-01

Changes of sea surface salinity (SSS) in the open oceans are related to precipitation and evaporation. SSS has been an indicator of water cycle. It may be related to the global change. The Kuroshio Current, a western boundary current originating from the North Equatorial Current, transfers warm and higher salinity to higher latitudes. It flows northward along the east coasts of Luzon Island and Taiwan Island to Japan. In this study, effects of heavy rainfall on the Kuroshio surface salinity east of Taiwan are investigated. Sea surface salinity (SSS) data taken by conductivity temperature depth (CTD) sensor on R/V Ocean Researcher I cruises, conductivity sensor on eight glider cruises, and Aquarius satellite data are used in this study. The rain rate data derived from the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) are also employed. A glider is a kind of autonomous underwater vehicle, which uses small changes in its buoyancy in conjunction with wings to convert vertical motion to horizontal in the underwater without requiring input from an operator. It can take sensors to measure salinity, temperature, and pressure. The TRMM/TMI data from remote sensing system are daily and are mapped to 0.25-degree grid. The results show a good correlation between the rain rate and SSS with a correlation coefficient of 0.86. The rainfall causes SSS of the Kuroshio surface water drops 0.176 PSU per 1 mm/hr rain rate.

Specific threonine-4 phosphorylation and function of RNA polymerase II CTD during M phase progression

PubMed Central

Hintermair, Corinna; Voß, Kirsten; Forné, Ignasi; Heidemann, Martin; Flatley, Andrew; Kremmer, Elisabeth; Imhof, Axel; Eick, Dirk

2016-01-01

Dynamic phosphorylation of Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 heptad-repeats in the C-terminal domain (CTD) of the large subunit coordinates progression of RNA polymerase (Pol) II through the transcription cycle. Here, we describe an M phase-specific form of Pol II phosphorylated at Thr4, but not at Tyr1, Ser2, Ser5, and Ser7 residues. Thr4 phosphorylated Pol II binds to centrosomes and midbody and interacts with the Thr4-specific Polo-like kinase 1. Binding of Pol II to centrosomes does not require the CTD but may involve subunits of the non-canonical R2TP-Prefoldin-like complex, which bind to and co-localize with Pol II at centrosomes. CTD Thr4 mutants, but not Ser2 and Ser5 mutants, display severe mitosis and cytokinesis defects characterized by multipolar spindles and polyploid cells. We conclude that proper M phase progression of cells requires binding of Pol II to centrosomes to facilitate regulation of mitosis and cytokinesis in a CTD Thr4-P dependent manner. PMID:27264542

Specific threonine-4 phosphorylation and function of RNA polymerase II CTD during M phase progression.

PubMed

Hintermair, Corinna; Voß, Kirsten; Forné, Ignasi; Heidemann, Martin; Flatley, Andrew; Kremmer, Elisabeth; Imhof, Axel; Eick, Dirk

2016-06-06

Dynamic phosphorylation of Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 heptad-repeats in the C-terminal domain (CTD) of the large subunit coordinates progression of RNA polymerase (Pol) II through the transcription cycle. Here, we describe an M phase-specific form of Pol II phosphorylated at Thr4, but not at Tyr1, Ser2, Ser5, and Ser7 residues. Thr4 phosphorylated Pol II binds to centrosomes and midbody and interacts with the Thr4-specific Polo-like kinase 1. Binding of Pol II to centrosomes does not require the CTD but may involve subunits of the non-canonical R2TP-Prefoldin-like complex, which bind to and co-localize with Pol II at centrosomes. CTD Thr4 mutants, but not Ser2 and Ser5 mutants, display severe mitosis and cytokinesis defects characterized by multipolar spindles and polyploid cells. We conclude that proper M phase progression of cells requires binding of Pol II to centrosomes to facilitate regulation of mitosis and cytokinesis in a CTD Thr4-P dependent manner.

Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization.

PubMed

Gong, Xin; Qian, Hongwu; Shao, Wei; Li, Jingxian; Wu, Jianping; Liu, Jun-Jie; Li, Wenqi; Wang, Hong-Wei; Espenshade, Peter; Yan, Nieng

2016-11-01

Sterol regulatory element-binding protein (SREBP) transcription factors are master regulators of cellular lipid homeostasis in mammals and oxygen-responsive regulators of hypoxic adaptation in fungi. SREBP C-terminus binds to the WD40 domain of SREBP cleavage-activating protein (SCAP), which confers sterol regulation by controlling the ER-to-Golgi transport of the SREBP-SCAP complex and access to the activating proteases in the Golgi. Here, we biochemically and structurally show that the carboxyl terminal domains (CTD) of Sre1 and Scp1, the fission yeast SREBP and SCAP, form a functional 4:4 oligomer and Sre1-CTD forms a dimer of dimers. The crystal structure of Sre1-CTD at 3.5 Å and cryo-EM structure of the complex at 5.4 Å together with in vitro biochemical evidence elucidate three distinct regions in Sre1-CTD required for Scp1 binding, Sre1-CTD dimerization and tetrameric formation. Finally, these structurally identified domains are validated in a cellular context, demonstrating that the proper 4:4 oligomeric complex formation is required for Sre1 activation.

The C-terminal domain of connexin43 modulates cartilage structure via chondrocyte phenotypic changes

PubMed Central

Gago-Fuentes, Raquel; Bechberger, John F.; Varela-Eirin, Marta; Varela-Vazquez, Adrian; Acea, Benigno; Fonseca, Eduardo

2016-01-01

Chondrocytes in cartilage and bone cells population express connexin43 (Cx43) and gap junction intercellular communication (GJIC) is essential to synchronize cells for coordinated electrical, mechanical, metabolic and chemical communication in both tissues. Reduced Cx43 connectivity decreases chondrocyte differentiation and defective Cx43 causes skeletal defects. The carboxy terminal domain (CTD) of Cx43 is located in the cytoplasmic side and is key for protein functions. Here we demonstrated that chondrocytes from the CTD-deficient mice, K258stop/Cx43KO and K258stop/K258stop, have reduced GJIC, increased rates of proliferation and reduced expression of collagen type II and proteoglycans. We observed that CTD-truncated mice were significantly smaller in size. Together these results demonstrated that the deletion of the CTD negatively impacts cartilage structure and normal chondrocyte phenotype. These findings suggest that the proteolytic cleavage of the CTD under pathological conditions, such as under the activation of metalloproteinases during tissue injury or inflammation, may account for the deleterious effects of Cx43 in cartilage and bone disorders such as osteoarthritis. PMID:27682878

Interoceptive Accuracy in Youth with Tic Disorders: Exploring Links with Premonitory Urge, Anxiety and Quality of Life.

PubMed

Pile, Victoria; Lau, Jennifer Y F; Topor, Marta; Hedderly, Tammy; Robinson, Sally

2018-05-18

Aberrant interoceptive accuracy could contribute to the co-occurrence of anxiety and premonitory urge in chronic tic disorders (CTD). If it can be manipulated through intervention, it would offer a transdiagnostic treatment target for tics and anxiety. Interoceptive accuracy was first assessed consistent with previous protocols and then re-assessed following an instruction attempting to experimentally enhance awareness. The CTD group demonstrated lower interoceptive accuracy than controls but, importantly, this group difference was no longer significant following instruction. In the CTD group, better interoceptive accuracy was associated with higher anxiety and lower quality of life, but not with premonitory urge. Aberrant interoceptive accuracy may represent an underlying trait in CTD that can be manipulated, and relates to anxiety and quality of life.

Glaucophane chloritoid-bearing assemblages from NE Oman: petrologic significance and a petrogenetic grid for high P metapelites

NASA Astrophysics Data System (ADS)

El-Shazly, A. K.; Liou, J. G.

1991-04-01

Pelitic layers and lenses interbedded with blueschists and eclogites in Saih Hatat, NE Oman contain chloritoid- and sodic amphibole-bearing mineral assemblages that are useful for reconstructing the P-T history of the area. Textural and mineral chemical relations suggest that coexisting glaucophane (Gln) and chloritoid (Ctd) formed at the expense of chlorite (Chl)+paragonite (Pg) and later broke down to garnet (Gt)+Pg during prograde metamorphism according to the reaction: Gln+Ctd+Qz=Gt+Pg+H2O. During retrogression, Gln and Chl first formed at the expense of Gt and Pg, followed by the breakdown of Ctd and Gt to Chl. The final stages of retrogression are marked by the breakdown of Gln to an aggregate of Chl+albite (Ab). A projection from quartz (Qz), H2O and phengite (Ph) on the (Al2O3+Fe2O3)-(FeO+MgO)-Na2O plane in the system NFMASH is best suited for the representation of the phase relations in high P metapelites. Petrogenetic grids for the model systems NMASH and NFASH were calculated using program GEO-CALC (Berman et al. 1987) and its database (Berman 1988) after the retrieval of S{i/o}and ΔH{f/o}for Gln and Ctd by mathematical programming and calculating all possible reactions among Gln, Ctd, Chl, jadeite (Jd), Ab, Gt, Pg, talc (Tc), pyrophyllite (Prl) and kyanite (Ky). The calculated petrogenetic grid for the system NFASH shows that Fe-Ctd and ferroglaucophane coexist at P>6.5 kbar and T<525°C, whereas the assemblage: Ct-Gln-Pg is stable between 435 and 630°C and P>6 kbar. This grid is consistent with the P-T estimates for high P metapelites from Oman, New Caledonia, Seward Peninsula, Ile de Groix, Sifnos and Peloponnese, where Gln+Ctd bearing units are interbedded with cofacial mafic blueschists and eclogites. The grid also explains the observed textural relations in the metapelites of Oman, and is consistent with the “clockwise” P-T path proposed for this area, but differs from the grids of Guiraud et al. (1990) in showing a larger stability field for Gln+Ctd that overlaps with the stability fields of Jd+Qz as well as Ab. The petrogenetic grid calculated for the system NMASH shows that Mg-Ctd+Gln-bearing assemblages require unusually low geothermal gradients to form in metapelites. It also shows that Mg-rich Ctd+Tc coexist at high pressures over a wider P-T range than predicted by Guiraud et al. (1990). This grid can therefore be applied to high P metamorphic assemblages from the eastern and western Alps.

Ocean mixing in deep-sea trenches: New insights from the Challenger Deep, Mariana Trench

NASA Astrophysics Data System (ADS)

van Haren, Hans; Berndt, Christian; Klaucke, Ingo

2017-11-01

Reliable very deep shipborne SBE 911plus Conductivity Temperature Depth (CTD) data to within 60 m from the bottom and Kongsberg EM122 0.5° × 1° multibeam echosounder data are collected in the Challenger Deep, Mariana Trench. A new position and depth are given for the deepest point in the world's ocean. The data provide insight into the interplay between topography and internal waves in the ocean that lead to mixing of the lowermost water masses on Earth. Below 5000 m, the vertical density stratification is weak, with a minimum buoyancy frequency N = 1.0 ± 0.6 cpd, cycles per day, between 6500 and 8500 m. In that depth range, the average turbulence is coarsely estimated from Thorpe-overturning scales, with limited statistics to be ten times higher than the mean values of dissipation rate εT = 3 ± 2 × 10-11 m2 s-3 and eddy diffusivity KzT = 2 ± 1.5 × 10-4 m2 s-1 estimated for the depth range between 10,300 and 10,850 m, where N = 2.5 ± 0.6 cpd. Inertial and meridionally directed tidal inertio-gravity waves can propagate between the differently stratified layers. These waves are suggested to be responsible for the observed turbulence. The turbulence values are similar to those recently estimated from CTD and moored observations in the Puerto Rico Trench. Yet, in contrast to the Puerto Rico Trench, seafloor morphology in the Mariana Trench shows up to 500 m-high fault scarps on the incoming tectonic plate and a very narrow trench, suggesting that seafloor topography does not play a crucial role for mixing.

Observations of transitional tidal boundary layers and their impact on sediment transport in the Great Bay, NH

NASA Astrophysics Data System (ADS)

Koetje, K. M.; Foster, D. L.; Lippmann, T. C.

2017-12-01

Observations of the vertical structure of tidal flows obtained in 2016 and 2017 in the Great Bay Estuary, NH show evidence of transitional tidal boundary layers at deployment locations on shallow mudflats. High-resolution bottom boundary layer currents, hydrography, turbidity, and bed characteristics were observed with an acoustic Doppler current profiler (ADCP), an acoustic Doppler velocimeter (ADV), conductivity-depth-temperature (CTD) sensors, optical backscatter sensors, multibeam bathymetric surveys, and sediment grab samples and cores. Over the 2.5 m tidal range and at water depths ranging from 0.3 m to 1.5 m at mean lower low water, peak flows ranged from 10 cm/s to 30 cm/s and were primarily driven by the tides. A downward-looking ADCP captured the velocity profile over the lowest 1 m of the water column. Results consistently show a dual-log layer system, with evidence of a lower layer within 15 cm of the bed, another layer above approximately 30 cm from the bed, and a transitional region where the flow field rotates between that the two layers that can be as much as 180 degrees out of phase. CTD casts collected over a complete tidal cycle suggest that the weak thermohaline stratification is not responsible for development of the two layers. On the other hand, acoustic and optical backscatter measurements show spatial and temporal variability in suspended sediments that are dependant on tidal phase. Current work includes an examination of the relationship between sediment concentrations in the water column and velocity profile characteristics, along with an effort to quantify the impact of rotation and dual-log layers on bed stress.

Tidal and residual circulation in a semi-arid bay: Coquimbo Bay, Chile

NASA Astrophysics Data System (ADS)

Valle-Levinson, Arnoldo; Moraga, Julio; Olivares, Jorge; Blanco, José Luis

2000-11-01

Velocity profiles and time-series data were combined with conductivity-temperature-depth (CTD) casts to describe the general circulation at tidal and subtidal scales in a bay of semi-arid climate, Coquimbo Bay (˜30°S), Chile. This was the first study that used a towed acoustic Doppler current profiler (ADCP) in coastal Chilean waters and is one of the very few in semi-arid bays. The ADCP was towed for two semi-diurnal tidal cycles in early austral autumn, between March 23 and 24, 1997 along a triangular trajectory that covered most of the bay. Additional data consisted of moored current meters and CTD casts. The observations indicated the presence of a surface layer, above the pycnocline, that showed predominantly diurnal variability forced by the breeze regime and by tides. The tidal circulation in the surface layer featured amplitudes of 10 cm/s within an anticyclonic gyre that occupied most of the bay. The subtidal circulation in the surface was characterized by a pair of counter-rotating gyres. The northernmost three-fourths of the bay showed an anticyclonic gyre, and the observations over the southern fourth implied a cyclonic gyre. The subtidal anticyclonic gyre had a counterpart rotating in opposite direction within a lower layer, underneath the pycnocline. The lower layer showed semidiurnal variability in addition to diurnal variability and was insulated by the pycnocline from heat and momentum fluxes through the air-water interface. Circulations that resemble estuarine and anti-estuarine patterns were found associated with the subtidal gyres. A horizontal divergence related to a 10 cm/s near-surface outflow around Point Tortuga, to the south of the bay entrance, allowed the development of upward motion off the Point, as evidenced by the tilt of the isopycnals at the entrance to the bay.

Relationship between Ocean Bottom Pressure Variations and Baroclinic Eddy off Kushiro-Tokachi

NASA Astrophysics Data System (ADS)

Hasegawa, T.; Nagano, A.; Matsumoto, H.; Ariyoshi, K.

2016-02-01

The scope of this study is to reveal relationships between ocean bottom pressure (BP) variations related to ocean plate changes, and oceanic climate changes. We analyzed BP data at stations PG1 (41.7040N-144.4375E) and PG2 (42.2365N-144.8454E) obtained from the Long-Term Deep Sea Floor Observatory off Kushiro-Tokachi in the Kuril Trench, gridded daily sea surface height (SSH) data provided by AVISO, and conductivity-temperature-depth (CTD) data at a repeated observation line off Akkeshi (A-line) from 2004 to 2013. In addition, we used Nino-3 index, which is the major index for El Nino/Southern Oscillation (ENSO) and is given by the CPC/NOAA. It is suggested that SSH at PG1 and PG2 similarly vary affected by the Oyashio, the western boundary current of the North Pacific subarctic gyre, and El Nino events in 2006 and 2007 via atmospheric telconnections. BP time series at PG1 and PG2 are almost in phase in most of the analysis period, but from the early 2006 to the end of 2007, are quit discrepant in amplitude; at that occasion, BP at PG1 is much higher than that at PG2. Expecting a peculiar hydrographic feature at the occasion, CTD data along the A-line in January 2007 are analyzed. A lenticular eddy was found to exist in a layer between 1500 and 3000 dbar and to deepen substantially isopycnals of approximately 27.7 sigma-theta around a depth of 2000 dbar. Probably due to the baroclinic eddy feature, BP is kept low at PG2, while high at PG1. The subthermocline water occupying the deep eddy are considered not to be originated in the North Pacific but to be derived from the Southern Ocean.

Correlation-based perfusion mapping using time-resolved MR angiography: A feasibility study for patients with suspicions of steno-occlusive craniocervical arteries.

PubMed

Nam, Yoonho; Jang, Jinhee; Park, Sonya Youngju; Choi, Hyun Seok; Jung, So-Lyung; Ahn, Kook-Jin; Kim, Bum-Soo

2018-05-22

To explore the feasibility of using correlation-based time-delay (CTD) maps produced from time-resolved MR angiography (TRMRA) to diagnose perfusion abnormalities in patients suspected to have steno-occlusive lesions in the craniocervical arteries. Twenty-seven patients who were suspected to have steno-occlusive lesions in the craniocervical arteries underwent both TRMRA and brain single-photon emission computed tomography (SPECT). TRMRA was performed on the supra-aortic area after intravenous injection of a 0.03 mmol/kg gadolinium-based contrast agent. Time-to-peak (TTP) maps and CTD maps of the brain were automatically generated from TRMRA data, and their quality was assessed. Detection of perfusion abnormalities was compared between CTD maps and the time-series maximal intensity projection (MIP) images from TRMRA and TTP maps. Correlation coefficients between quantitative changes in SPECT and parametric maps for the abnormal perfusion areas were calculated. The CTD maps were of significantly superior quality than TTP maps (p < 0.01). For perfusion abnormality detection, CTD maps (kappa 0.84, 95% confidence interval [CI] 0.67-1.00) showed better agreement with SPECT than TTP maps (0.66, 0.46-0.85). For perfusion deficit detection, CTD maps showed higher accuracy (85.2%, 95% CI 66.3-95.8) than MIP images (66.7%, 46-83.5), with marginal significance (p = 0.07). In abnormal perfusion areas, correlation coefficients between SPECT and CTD (r = 0.74, 95% CI 0.34-0.91) were higher than those between SPECT and TTP (r = 0.66, 0.20-0.88). CTD maps generated from TRMRA were of high quality and offered good diagnostic performance for detecting perfusion abnormalities associated with steno-occlusive arterial lesions in the craniocervical area. • Generation of perfusion parametric maps from time-resolved MR angiography is clinically useful. • Correlation-based delay maps can be used to detect perfusion abnormalities associated with steno-occlusive craniocervical arteries. • Estimation of correlation-based delay is robust for low signal-to-noise 4D MR data.

A randomized titrate-to-target study comparing fixed-dose combinations of azilsartan medoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension.

PubMed

Cushman, William C; Bakris, George L; White, William B; Weber, Michael A; Sica, Domenic; Roberts, Andrew; Lloyd, Eric; Kupfer, Stuart

2018-04-01

Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD). We compared FDCs of AZL-M/CTD 20/12.5 mg once daily titrated to 40/25 mg if needed or AZL-M/CTD 40/12.5 mg once daily titrated to 80/25 mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5 mg FDC once daily titrated to 40/25 mg if needed in a randomized, double-blind, 8-week study of 1085 participants with clinic SBP 160-190 mmHg and DBP 119 mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/90 mmHg (≥130/80 mmHg if diabetes or chronic kidney disease). The primary endpoint was change from baseline in clinic SBP; 24-h ambulatory BP monitoring was also measured. Greater reductions in clinic SBP from a baseline of 165 mmHg were observed (P < 0.001) in both AZL-M/CTD arms (-37.6 and -38.2 mmHg) versus OLM/HCTZ (-31.5 mmHg), despite greater dose titration in the OLM/HCTZ group. At 8 weeks, both AZL-M/CTD FDCs reduced 24-h SBP more than OLM/HCTZ (-26.4 and -27.9 versus -20.7 mmHg; both P < 0.001), and higher proportions in both AZL-M/CTD groups achieved target BP compared with the OLM/HCTZ group (69.4 and 68.9 versus 54.7%, both P < 0.001). Adverse events leading to drug discontinuation occurred in 6.2, 9.5, and 3.1% with the AZL-M/CTD lower and higher doses, and OLM/HCTZ, respectively. This large, titration-to-target BP study demonstrated AZL-M/CTD FDCs to have superior antihypertensive efficacy compared with the maximum approved dose of OLM/HCTZ.

A randomized titrate-to-target study comparing fixed-dose combinations of azilsartan medoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension

PubMed Central

Cushman, William C.; Bakris, George L.; White, William B.; Weber, Michael A.; Sica, Domenic; Roberts, Andrew; Lloyd, Eric; Kupfer, Stuart

2018-01-01

Background: Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD). Objective/methods: We compared FDCs of AZL-M/CTD 20/12.5 mg once daily titrated to 40/25 mg if needed or AZL-M/CTD 40/12.5 mg once daily titrated to 80/25 mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5 mg FDC once daily titrated to 40/25 mg if needed in a randomized, double-blind, 8-week study of 1085 participants with clinic SBP 160–190 mmHg and DBP 119 mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/90 mmHg (≥130/80 mmHg if diabetes or chronic kidney disease). The primary endpoint was change from baseline in clinic SBP; 24-h ambulatory BP monitoring was also measured. Results: Greater reductions in clinic SBP from a baseline of 165 mmHg were observed (P < 0.001) in both AZL-M/CTD arms (−37.6 and −38.2 mmHg) versus OLM/HCTZ (−31.5 mmHg), despite greater dose titration in the OLM/HCTZ group. At 8 weeks, both AZL-M/CTD FDCs reduced 24-h SBP more than OLM/HCTZ (−26.4 and −27.9 versus −20.7 mmHg; both P < 0.001), and higher proportions in both AZL-M/CTD groups achieved target BP compared with the OLM/HCTZ group (69.4 and 68.9 versus 54.7%, both P < 0.001). Adverse events leading to drug discontinuation occurred in 6.2, 9.5, and 3.1% with the AZL-M/CTD lower and higher doses, and OLM/HCTZ, respectively. Conclusion: This large, titration-to-target BP study demonstrated AZL-M/CTD FDCs to have superior antihypertensive efficacy compared with the maximum approved dose of OLM/HCTZ. PMID:29334491

Carbon dioxide, hydrographic, and chemical data obtained in the South Pacific Ocean (WOCE Sections P16A/P17A, P17E/P19S, and P19C, R/V Knorr, October 1992--April 1993)

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

Rubin, S.; Goddard, J.G.; Chipman, D.W.

1998-06-01

This data documentation discusses the procedures and methods used to measure total carbon dioxide concentration (TCO{sub 2}) and partial pressure of CO{sub 2} (pCO{sub 2}) in discrete water samples collected during three expeditions of the Research Vessel (R/V) Knorr in the South Pacific Ocean. Conducted as part of the World Ocean Circulation Experiment (WOCE), the first cruise (WOCE Section P16A/P17A) began in Papeete, Tahiti, French Polynesia, on October 6, 1992, and returned to Papeete on November 25, 1992. The second cruise (WOCE Section P17E/P19S) began in Papeete on December 4, 1992, and finished in Punta Arenas, Chile, on January 22,more » 1993. The third expedition (WOCE Section P19C) started in Punta Arenas, on February 22 and finished in Panama City, Panama, on April 13, 1993. During the three expeditions, 422 hydrographic stations were occupied. Hydrographic and chemical measurements made along WOCE Sections P16A/P17A, P17E/P19S, and P19C included pressure, temperature, salinity, and oxygen [measured by conductivity, temperature, and depth (CTD) sensor], as well as discrete measurements of salinity, oxygen, phosphate, nitrate, nitrite, silicate, chlorofluorocarbons (CFC-11, CFC-12), TCO{sub 2}, and pCO{sub 2} measured at 4 and 20 C. In addition, potential temperatures were calculated from the measured variables.« less

In Search for Diffuse Hydrothermal Venting at North Pond, Western Flank of the Mid-Atlantic-Ridge

NASA Astrophysics Data System (ADS)

Villinger, H. W.; Becker, K.; Hulme, S.; Kaul, N. E.; Müller, P.; Wheat, C. G.

2015-12-01

We present results from temperature measurements made with a ROV temperature lance in sediments deposited on the slopes of abyssal hills and small basins surrounding North Pond. North Pond is a ~8x15 km large sediment basin located on ~7 Ma year old crust west of the Mid-Atlantic Ridge at 23°N. Data were collected with the ROV Jason II during cruise MSM37 on the German RV Maria S. Merian in April 2014. The temperature lance consists of a 60 cm long stainless steel tube (o.d. 12 mm) housing 8 thermistors with a spacing of 80 mm, resulting in an active length of 56 cm. Data are logged with an 8-channel data logger (XR-420-T8, RBR, Ottawa) and transmitted online to the control van of the ROV. Data reduction and temperature gradient calculation is done according to the HFRED algorithm (Villinger & Davis, 1987). 90 sites in total were visited, 88 gave good data for temperature gradient calculation. Calculated gradients are usually of good to very good quality. The gradients vary between less than 20 to more than 1000 mK/m reflecting the very heterogeneous distribution of geothermal heat flow. The expected conductive lithospheric heat flow for North Pond is ~190 mW/m2 (geothermal gradient of ~190 mK/m with a thermal conductivity of 1 W/Km). The highest temperature gradients are measured in places where temperature ~50 cm below the sediment-water boundary exceeds bottom water temperature by ~0.5 K . These high temperature gradients may reflect local hydrothermal circulation within the pillow lavas, however no focused discharge was detected. The analysis of temperature measurements made with the ROV-mounted CTD shows clearly detectable bottom water temperature anomalies. We infer that they are either caused by hydrothermal discharge through the thin sediment cover or through unsedimented pillow basalts nearby. Hydrothermal circulation in a North-Pond-like environment appears to be diffuse in nature, hence very difficult if not impossible to detect and to quantify.

Structure of Atg7 Alone and its Atg8-Bound Forms

NASA Astrophysics Data System (ADS)

Noda, Nobuo

Atg7 is a noncanonical E1 enzyme that activates Atg8 and transfers it to Atg3 (E2 enzyme), thus playing an essential role in conjugating Atg8 with phosphatidylethanolamine and thus in autophagy. Atg7 protomer is comprised of two globular domains, the N-terminal domain (NTD) and the C-terminal domain (CTD), and forms a homodimer through CTD. Atg7-Atg8 complex structures and biochemical analyses revealed that Atg8 is initially recognized by the C-terminal tail of CTD and is then transferred to the adenylation domain in CTD, where Atg8 Gly116 is adenylated and thioester-linked to the catalytic cysteine of Atg7. Atg8 is then transferred to Atg3 bound to the NTD of the opposite protomer within an Atg7 dimer via a trans mechanism.

Creatine Transporter Deficiency: Screening of Males with Neurodevelopmental Disorders and Neurocognitive Characterization of a Case.

PubMed

Thurm, Audrey; Himelstein, Daniel; DʼSouza, Precilla; Rennert, Owen; Jiang, Susanqi; Olatunji, Damilola; Longo, Nicola; Pasquali, Marzia; Swedo, Susan; Salomons, Gajja S; Carrillo, Nuria

2016-05-01

Creatine transporter deficiency (CTD) is an X-linked, neurometabolic disorder associated with intellectual disability that is characterized by brain creatine (Cr) deficiency and caused by mutations in SLC6A8, the Cr transporter 1 protein gene. CTD is identified by elevated urine creatine/creatinine (Cr/Crn) ratio or reduced Cr peak on brain magnetic resonance spectroscopy; the diagnosis is confirmed by decreased Cr uptake in cultured fibroblasts, and/or identification of a mutation in the SLC6A8 gene. Prevalence studies suggest this disorder may be underdiagnosed. We sought to identify cases from a well-characterized cohort of children diagnosed with neurodevelopmental disorders. Urine screening for CTD was performed on a cohort of 46 males with autism spectrum disorder (ASD) and 9 males with a history of non-ASD developmental delay (DD) classified with intellectual disability. We identified 1 patient with CTD in the cohort based on abnormal urine Cr/Crn, and confirmed the diagnosis by the identification of a novel frameshift mutation in the SLC6A8 gene. This patient presented without ASD but with intellectual disability, and was characterized by a nonspecific phenotype of early language delay and DD that persisted into moderate-to-severe intellectual disability, consistent with previous descriptions of CTD. Identification of patients with CTD is possible by measuring urine Cr and Crn levels and the current case adds to the growing literature of neurocognitive deficits associated with the disorder that affect cognition, language and behavior in childhood.

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials.

PubMed

Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

2014-05-01

Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

PubMed Central

Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

2014-01-01

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field. PMID:24368713

Structure of the Z Ring-associated Protein, ZapD, Bound to the C-terminal Domain of the Tubulin-like Protein, FtsZ, Suggests Mechanism of Z Ring Stabilization through FtsZ Cross-linking.

PubMed

Schumacher, Maria A; Huang, Kuo-Hsiang; Zeng, Wenjie; Janakiraman, Anuradha

2017-03-03

Cell division in most bacteria is mediated by the tubulin-like FtsZ protein, which polymerizes in a GTP-dependent manner to form the cytokinetic Z ring. A diverse repertoire of FtsZ-binding proteins affects FtsZ localization and polymerization to ensure correct Z ring formation. Many of these proteins bind the C-terminal domain (CTD) of FtsZ, which serves as a hub for FtsZ regulation. FtsZ ring-associated proteins, ZapA-D (Zaps), are important FtsZ regulatory proteins that stabilize FtsZ assembly and enhance Z ring formation by increasing lateral assembly of FtsZ protofilaments, which then form the Z ring. There are no structures of a Zap protein bound to FtsZ; therefore, how these proteins affect FtsZ polymerization has been unclear. Recent data showed ZapD binds specifically to the FtsZ CTD. Thus, to obtain insight into the ZapD-CTD interaction and how it may mediate FtsZ protofilament assembly, we determined the Escherichia coli ZapD-FtsZ CTD structure to 2.67 Å resolution. The structure shows that the CTD docks within a hydrophobic cleft in the ZapD helical domain and adopts an unusual structure composed of two turns of helix separated by a proline kink. FtsZ CTD residue Phe-377 inserts into the ZapD pocket, anchoring the CTD in place and permitting hydrophobic contacts between FtsZ residues Ile-374, Pro-375, and Leu-378 with ZapD residues Leu-74, Trp-77, Leu-91, and Leu-174. The structural findings were supported by mutagenesis coupled with biochemical and in vivo studies. The combined data suggest that ZapD acts as a molecular cross-linking reagent between FtsZ protofilaments to enhance FtsZ assembly. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The HIP1 initiator element plays a role in determining the in vitro requirement of the dihydrofolate reductase gene promoter for the C-terminal domain of RNA polymerase II.

PubMed

Buermeyer, A B; Thompson, N E; Strasheim, L A; Burgess, R R; Farnham, P J

1992-05-01

We examined the ability of purified RNA polymerase (RNAP) II lacking the carboxy-terminal heptapeptide repeat domain (CTD), called RNAP IIB, to transcribe a variety of promoters in HeLa extracts in which endogenous RNAP II activity was inhibited with anti-CTD monoclonal antibodies. Not all promoters were efficiently transcribed by RNAP IIB, and transcription did not correlate with the in vitro strength of the promoter or with the presence of a consensus TATA box. This was best illustrated by the GC-rich, non-TATA box promoters of the bidirectional dihydrofolate reductase (DHFR)-REP-encoding locus. Whereas the REP promoter was transcribed by RNAP IIB, the DHFR promoter remained inactive after addition of RNAP IIB to the antibody-inhibited reactions. However, both promoters were efficiently transcribed when purified RNAP with an intact CTD was added. We analyzed a series of promoter deletions to identify which cis elements determine the requirement for the CTD of RNAP II. All of the promoter deletions of both DHFR and REP retained the characteristics of their respective full-length promoters, suggesting that the information necessary to specify the requirement for the CTD is contained within approximately 65 bp near the initiation site. Furthermore, a synthetic minimal promoter of DHFR, consisting of a single binding site for Sp1 and a binding site for the HIP1 initiator cloned into a bacterial vector sequence, required RNAP II with an intact CTD for activity in vitro. Since the synthetic minimal promoter of DHFR and the smallest REP promoter deletion are both activated by Sp1, the differential response in this assay does not result from upstream activators. However, the sequences around the start sites of DHFR and REP are not similar and our data suggest that they bind different proteins. Therefore, we propose that specific initiator elements are important for determination of the requirement of some promoters for the CTD.

Long-term monitoring of waterborne pathogens and microbial source tracking markers in paired agricultural watersheds under controlled and conventional tile drainage management.

PubMed

Wilkes, Graham; Brassard, Julie; Edge, Thomas A; Gannon, Victor; Gottschall, Natalie; Jokinen, Cassandra C; Jones, Tineke H; Khan, Izhar U H; Marti, Romain; Sunohara, Mark D; Topp, Edward; Lapen, David R

2014-06-01

Surface waters from paired agricultural watersheds under controlled tile drainage (CTD) and uncontrolled tile drainage (UCTD) were monitored over 7 years in order to determine if there was an effect of CTD (imposed during the growing season) on occurrences and loadings of bacterial and viral pathogens, coliphages, and microbial source tracking markers. There were significantly lower occurrences of human, ruminant, and livestock (ruminant plus pig) Bacteroidales markers in the CTD watershed in relation to the UCTD watershed. As for pathogens, there were significantly lower occurrences of Salmonella spp. and Arcobacter spp. in the CTD watershed. There were no instances where there were significantly higher quantitative loadings of any microbial target in the CTD watershed, except for F-specific DNA (F-DNA) and F-RNA coliphages, perhaps as a result of fecal inputs from a hobby farm independent of the drainage practice treatments. There was lower loading of the ruminant marker in the CTD watershed in relation to the UCTD system, and results were significant at the level P = 0.06. The odds of Salmonella spp. occurring increased when a ruminant marker was present relative to when the ruminant marker was absent, yet for Arcobacter spp., the odds of this pathogen occurring significantly decreased when a ruminant marker was present relative to when the ruminant marker was absent (but increased when a wildlife marker was present relative to when the wildlife marker was absent). Interestingly, the odds of norovirus GII (associated with human and swine) occurring in water increased significantly when a ruminant marker was present relative to when a ruminant marker was absent. Overall, this study suggests that fecal pollution from tile-drained fields to stream could be reduced by CTD utilization. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Hydraulic Control and Mixing in Chesapeake Bay

NASA Astrophysics Data System (ADS)

Ott, M. W.

2006-05-01

Properly modeling the exchange rate at the mouths of estuarine bays is critical to understanding the effects of freshwater and pollutants on the hydrographic and biological conditions within these bays. There is evidence that hydraulic control occurs at certain locations in the deeper channels of Chesapeake Bay and may be a mechanism in limiting the exchange rate. In addition, the vertical and horizontal mixing associated with the resulting hydraulic jumps has implications both for the hydrographic conditions and circulation, as well as for primary productivity within Chesapeake Bay. Shipboard acoustic Doppler current profiler (ADCP) data, as well as conductivity-temperature-depth (CTD) profiles were collected during the spring of 2005 at various locations within Chesapeake Bay to better understand the occurrence and strength of hydraulic controls in relation to the phases of the fortnightly and semi-diurnal tidal cycles as well as to topography. Mixing is shown to occur alternatively over both hollows and bumps, depending on the tidal phase, and the strength and effects if this mixing is compared.

A Simple Parameterization of Mixing of Passive Scalars in Turbulent Flows

NASA Astrophysics Data System (ADS)

Nithianantham, Ajithshanthar; Venayagamoorthy, Karan

2015-11-01

A practical model for quantifying the turbulent diascalar diffusivity is proposed as Ks = 1 . 1γ'LTk 1 / 2 , where LT is defined as the Thorpe length scale, k is the turbulent kinetic energy and γ' is one-half of the mechanical to scalar time scale ratio, which was shown by previous researchers to be approximately 0 . 7 . The novelty of the proposed model lies in the use of LT, which is a widely used length scale in stably stratified flows (almost exclusively used in oceanography), for quantifying turbulent mixing in unstratified flows. LT can be readily obtained in the field using a Conductivity, Temperature and Depth (CTD) profiler. The turbulent kinetic energy is mostly contained in the large scales of the flow field and hence can be measured in the field or modeled in numerical simulations. Comparisons using DNS data show remarkably good agreement between the predicted and exact diffusivities. Office of Naval Research and National Science Foundation.

The CTD Teacher Opinion Poll.

ERIC Educational Resources Information Center

Arato, Agnes

1985-01-01

Within the framework of Hungary's Curriculum Theory Department (CTD-80) national assessment, 2,391 teachers from 70 general schools were surveyed. The questionnaire included teachers' characteristics, reaction to the new curriculum, and teaching practices. The results are described. (GDC)

Mediating role of critical thinking disposition in the relationship between perceived barriers to research use and evidence-based practice.

PubMed

Kim, Sun-Ae; Song, Youngshin; Sim, Hee-Sook; Ahn, Eun-Kyong; Kim, Jung-Hee

2015-01-01

Despite the importance of critical thinking in clinical and educational settings, little is known about its role in evidence-based practice (EBP). This study examined whether critical thinking disposition (CTD) mediates the relationship between perceived barriers to research use and EBP in clinical nurses (N=409). A path diagram using structural equation modeling was used to estimate the direct and indirect effects of perceived barriers to research use on EBP, controlling for CTD as a mediator. CTD partially mediated the relationship between perceived barriers to research use and EBP. Furthermore, the hypothesized mediation model demonstrated an appropriate fit to the data. Individual and organizational efforts are needed to help nurses further improve their critical thinking skills. CTD is important as research barriers to engage effectively in EBP. Without the skills to evaluate evidence carefully, research utilization may be compromised.

A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction

PubMed Central

Tsai, Kuang-Lei; Sato, Shigeo; Tomomori-Sato, Chieri; Conaway, Ronald C.; Conaway, Joan W.; Asturias, Francisco J.

2013-01-01

The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) carboxy-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a preeminent complex in eukaryotic transcription regulation. We used macromolecular electron microscopy and biochemistry to investigate the subunit organization, structure, and Mediator interaction of the Saccharomyces cerevisiae CKM. We found that interaction of the CKM with Mediator’s Middle module interferes with CTD-dependent RNAPII binding to a previously unknown Middle module CTD-binding site targeted early on in a multi-step holoenzyme formation process. Taken together, our results reveal the basis for CKM repression, clarify the origin of the connection between CKM subunits and the CTD, and suggest that a combination of competitive interactions and conformational changes that facilitate holoenzyme formation underlie the Mediator mechanism. PMID:23563140

Phosphorylation-regulated Binding of RNA Polymerase II to Fibrous Polymers of Low Complexity Domains

PubMed Central

Xiang, Siheng; Wu, Leeju; Theodoropoulos, Pano; Mirzaei, Hamid; Han, Tina; Xie, Shanhai; Corden, Jeffry L.; McKnight, Steven L.

2014-01-01

SUMMARY The low complexity (LC) domains of the products of the fused in sarcoma (FUS), Ewings sarcoma (EWS) and TAF15 genes are translocated onto a variety of different DNA-binding domains and thereby assist in driving the formation of cancerous cells. In the context of the translocated fusion proteins, these LC sequences function as transcriptional activation domains. Here we show that polymeric fibers formed from these LC domains directly bind the C-terminal domain (CTD) of RNA polymerase II in a manner reversible by phosphorylation of the iterated, heptad repeats of the CTD. Mutational analysis indicates that the degree of binding between the CTD and the LC domain polymers correlates with the strength of transcriptional activation. These studies offer a simple means of conceptualizing how RNA polymerase II is recruited to active genes in its unphosphorylated state, and released for elongation following phosphorylation of the CTD. PMID:24267890

Separate intramolecular targets for protein kinase A control N-methyl-D-aspartate receptor gating and Ca2+ permeability.

PubMed

Aman, Teresa K; Maki, Bruce A; Ruffino, Thomas J; Kasperek, Eileen M; Popescu, Gabriela K

2014-07-04

Protein kinase A (PKA) enhances synaptic plasticity in the central nervous system by increasing NMDA receptor current amplitude and Ca(2+) flux in an isoform-dependent yet poorly understood manner. PKA phosphorylates multiple residues on GluN1, GluN2A, and GluN2B subunits in vivo, but the functional significance of this multiplicity is unknown. We examined gating and permeation properties of recombinant NMDA receptor isoforms and of receptors with altered C-terminal domain (CTDs) prior to and after pharmacological inhibition of PKA. We found that PKA inhibition decreased GluN1/GluN2B but not GluN1/GluN2A gating; this effect was due to slower rates for receptor activation and resensitization and was mediated exclusively by the GluN2B CTD. In contrast, PKA inhibition reduced NMDA receptor-relative Ca(2+) permeability (PCa/PNa) regardless of the GluN2 isoform and required the GluN1 CTD; this effect was due primarily to decreased unitary Ca(2+) conductance, because neither Na(+) conductance nor Ca(2+)-dependent block was altered substantially. Finally, we show that both the gating and permeation effects can be reproduced by changing the phosphorylation state of a single residue: GluN2B Ser-1166 and GluN1 Ser-897, respectively. We conclude that PKA effects on NMDA receptor gating and Ca(2+) permeability rely on distinct phosphorylation sites located on the CTD of GluN2B and GluN1 subunits. This separate control of NMDA receptor properties by PKA may account for the specific effects of PKA on plasticity during synaptic development and may lead to drugs targeted to alter NMDA receptor gating or Ca(2+) permeability. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice

PubMed Central

YANAI, Shogo; HIRANO, Tetsushi; OMOTEHARA, Takuya; TAKADA, Tadashi; YONEDA, Naoki; KUBOTA, Naoto; YAMAMOTO, Anzu; MANTANI, Youhei; YOKOYAMA, Toshifumi; KITAGAWA, Hiroshi; HOSHI, Nobuhiko

2017-01-01

Neonicotinoids are pesticides used worldwide. They bind to insect nicotinic acetylcholine receptors (nAChRs) with high affinity. We previously reported that clothianidin (CTD), one of the latest neonicotinoids, reduced antioxidant expression and induced germ cell death in the adult testis of vertebrates. Here, we investigated the male reproductive toxicity of prenatal and early postnatal exposure to CTD, because it is likely that developmental exposure more severely affects the testis compared to adults due to the absence of the blood-testis barrier. Pregnant C57BL/6 mice were given water gel blended with CTD (0, 10 or 50 mg/kg/day; no-observed-adverse-effect-level [NOAEL for mice]: 47.2 mg/kg/day) between gestational day 1 and 14 days post-partum. We then examined the testes of male offspring at postnatal day 14. The testis weights and the numbers of germ cells per seminiferous tubule were decreased in the CTD-50 group, and abnormal tubules containing no germ cells appeared. Nevertheless, the apoptotic cell number and proliferative activity were not significantly different between the control and CTD-exposed groups. There were no significant differences in the androgen-related parameters, such as the Leydig cell volume per testis, the Sertoli cell number and the tubule diameter. The present study is the first demonstration that in utero and lactational exposures to CTD at around the NOAEL for mice reduce the germ cell number, but our findings suggest that these exposures do not affect steroidogenesis in Leydig cells during prenatal or early postnatal life. PMID:28579575

A Thermodynamic Model for Genome Packaging in Hepatitis B Virus.

PubMed

Kim, Jehoon; Wu, Jianzhong

2015-10-20

Understanding the fundamentals of genome packaging in viral capsids is important for finding effective antiviral strategies and for utilizing benign viral particles for gene therapy. While the structure of encapsidated genomic materials has been routinely characterized with experimental techniques such as cryo-electron microscopy and x-ray diffraction, much less is known about the molecular driving forces underlying genome assembly in an intracellular environment and its in vivo interactions with the capsid proteins. Here we study the thermodynamic basis of the pregenomic RNA encapsidation in human Hepatitis B virus in vivo using a coarse-grained molecular model that captures the essential components of nonspecific intermolecular interactions. The thermodynamic model is used to examine how the electrostatic interaction between the packaged RNA and the highly charged C-terminal domains (CTD) of capsid proteins regulate the nucleocapsid formation. The theoretical model predicts optimal RNA content in Hepatitis B virus nucleocapsids with different CTD lengths in good agreement with mutagenesis measurements, confirming the predominant role of electrostatic interactions and molecular excluded-volume effects in genome packaging. We find that the amount of encapsidated RNA is not linearly correlated with the net charge of CTD tails as suggested by earlier theoretical studies. Our thermodynamic analysis of the nucleocapsid structure and stability indicates that ∼10% of the CTD residues are free from complexation with RNA, resulting in partially exposed CTD tails. The thermodynamic model also predicts the free energy of complex formation between macromolecules, which corroborates experimental results for the impact of CTD truncation on the nucleocapsid stability. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Pulmonary MR imaging with ultra-short TEs: utility for disease severity assessment of connective tissue disease patients.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Takenaka, Daisuke; Takahashi, Masaya; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Obara, Makoto; van Cauteren, Marc; Sugimura, Kazuro

2013-08-01

To evaluate the utility of pulmonary magnetic resonance (MR) imaging with ultra-short echo times (UTEs) at a 3.0 T MR system for pulmonary functional loss and disease severity assessments of connective tissue disease (CTD) patients with interstitial lung disease (ILD). This prospective study was approved by the institutional review board, and written informed consent was obtained from 18 CTD patients (eight men and ten women) and eight normal subjects with suspected chest disease (three men and five women). All subjects underwent thin-section MDCT, pulmonary MR imaging with UTEs, pulmonary function test and serum KL-6. Regional T2 maps were generated from each MR data set, and mean T2 values were determined from ROI measurements. From each thin-section MDCT data set, CT-based disease severity was evaluated with a visual scoring system. Mean T2 values for normal and CTD subjects were statistically compared by using Student's t-test. To assess capability for pulmonary functional loss and disease severity assessments, mean T2 values were statistically correlated with pulmonary functional parameters, serum KL-6 and CT-based disease severity. Mean T2 values for normal and CTD subjects were significantly different (p=0.0019) and showed significant correlations with %VC, %DLCO, serum KL-6 and CT-based disease severity of CTD patients (p<0.05). Pulmonary MR imaging with UTEs is useful for pulmonary functional loss and disease severity assessments of CTD patients with ILD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

77 FR 69634 - International Conference on Harmonisation; Guidance on Q11 Development and Manufacture of Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-20

... Document (CTD). The guidance is intended to harmonize the scientific and technical principles relating to... sections of the CTD. A summary of changes includes the following: (1) Revisions to the introduction and...

Creatine Transporter Deficiency in Two Brothers with Autism Spectrum Disorder.

PubMed

Aydin, Halil Ibrahim

2018-01-15

Creatine transporter deficiency (CTD) is a treatable, X-linked, inborn error of metabolism. Two brothers with autism spectrum disorder were diagnosed with CTD at the ages of 17 and 12 years. Both were found to have a previously reported hemizygous p.408delF (c.1216_1218delTTC) deletion mutation. Both patients were given creatine monohydrate, L-arginine, L-glycine and S-adenosylmethionine, which partially improved the behavioral problems. Serum creatinine levels, creatine peak at brain MR spectroscopy or creatine/creatinine ratio in urine should be evaluated to identify CTD in children with autistic behavior and language disorders.

Addison's disease secondary to connective tissue diseases: a report of six cases.

PubMed

Zhang, Zhuo-li; Wang, Yu; Zhou, Wei; Hao, Yan-jie

2009-04-01

Addison's disease is an autoimmune process. However, Addison's disease associated with connective tissue diseases (CTD) is only occasionally reported. Here, we report six cases of Addison's disease secondary to a variety of CTD, which include systemic lupus erythematosus, Takayasu arteritis, systemic sclerosis, ankylosing spondylitis (AS) and antiphospholipid antibody syndrome. The association of Addison's disease with Takayasu arteritis and AS is reported for the first time. We also found high prevalence of hypothyroidism as concomitant autoimmune disorder. Our case series highlight the autoimmune features of Addison's disease. Therefore, we suggest considering adrenal dysfunction in patients with CTD.

Cor triatriatum dexter, atrial septal defects, and pulmonary stenosis-a rare association.

PubMed

Simsek, Ziya; Koza, Yavuzer; Tas, Hakan

2014-04-01

Cor triatriatum dexter (CTD) is an extremely rare congenital anomaly in which the right atrium is divided into 2 chambers by a membrane. The estimated incidence of cor triatriatum has been reported as 0.1% of congenital cardiac malformations. The septation of the right atrium in the setting of CTD is the result of failed resorption of the right valve of the sinus venosus. This results in anterolateral and posteromedial portions of the divided right atrium. CTD can be diagnosed at any age, especially if it is incidentally discovered. © 2014, Wiley Periodicals, Inc.

Phenol degradation by TiO2 photocatalysts combined with different pulsed discharge systems.

PubMed

Zhang, Yi; Lu, Jiani; Wang, Xiaoping; Xin, Qing; Cong, Yanqing; Wang, Qi; Li, Chunjuan

2013-11-01

Films of TiO2 nanotubes distributed over the inner surface of a discharge reactor cylinder (CTD) or adhered to a stainless steel electrode surface (PTD) in a discharge reactor were compared with a single-discharge (SD) system to investigate their efficiencies in phenol degradation. Morphology studies indicated that the TiO2 film was destroyed in the PTD system, but that there was no change in the CTD system after discharge. X-ray diffraction results revealed that the anatase phase of the original sample was preserved in the CTD system, but that an anatase-to-rutile phase transformation occurred in the PTD system after discharge. The highest efficiencies of phenol degradation and total organic carbon (TOC) mineralization were observed in the CTD system, and there was no decrease in phenol degradation efficiency upon reuse of a TiO2 film, indicating high catalysis activity and stability of the TiO2 photocatalysts in the combined treatment. TiO2 photocatalysts favored the formation of hydrogen peroxide and disfavored the formation of ozone. A greater degree of oxidation of intermediates and higher energy efficiency in phenol oxidation were observed with the TiO2-plasma systems, especially in the CTD system, compared to those with the SD system. Copyright © 2013 Elsevier Inc. All rights reserved.

High resolution mapping of hydrothermal plumes in the Mariana back-arc relate seafloor sources to above-bottom plumes

NASA Astrophysics Data System (ADS)

Walker, S. L.; Baker, E. T.; Resing, J. A.; Chadwick, W. W., Jr.; Merle, S. G.; Kaiser, C. L.

2016-12-01

The Mariana backarc spreading center between 12.9°-18°N was systematically explored for hydrothermal activity in Nov-Dec 2015 (R/V Falkor cruise FK151121) by conducting long distance along-axis CTD tows (vertical range was 20-600 meters above bottom (mab)) followed by higher resolution, horizontal grid AUV Sentry surveys at 70 mab in some of the areas where plumes were found. In those areas, the combination of along-axis CTD tows and near-bottom AUV surveys provides a nearly 3-dimensional view of the above-bottom plume relative to the seafloor morphology and potential sources. In addition, photo surveys were run at 5 mab at two of the sites. At 15.4°N, strong ORP anomalies (ΔE=-39 mv) with weak to absent optical signals were aligned with a new (<3yr) lava flow, suggesting widespread diffuse venting was associated with still-cooling lava to create a broad, optically weak plume that extended to 500 mab. About 10 km north of the new lava flow (15.5°N) there were fewer, but more distinct instances where temperature, particle, and OPR anomalies were co-located at 70 mab, providing information for the likely locations where more focused, higher temperature venting generated an optically intense (dNTU=0.032) above-bottom plume (to 500 mab over the axial high). The plume over the backarc segment high at 17.0°N exhibited a significant optical anomaly (dNTU=0.023) with a very strong ORP anomaly (ΔE=-88 mv) that extended only 1.5 km along-axis. The near-bottom survey showed a broad area ( 3km2) with robust temperature, particle, and ORP signals. Directed by this information, and the high resolution bathymetry acquired from the AUV survey, several active chimneys (one being 30 m tall with temperatures up to 340°C) were found during NOAA Okeanos Explorer ROV dives in May 2016. At 18°N, anomalies seen in the 11 km2 AUV survey were generally located along the axis of the spreading center and, with one exception, were limited to areas of previously-known (1987) venting. The plume in the water column over the Burke vent site was defined by both particle (dNTU=0.010) and ORP (ΔE=-11 mv) anomalies from 400-800 mab, but only ORP signals 120-400 mab. ORP signals were seen over the other sites without any optical anomalies; the much lower rise heights (200-400 mab) suggest only lower temperature, diffuse venting persists at these sites.

A Small Diameter Rosette for Sampling Ice Covered Waters

NASA Astrophysics Data System (ADS)

Chayes, D. N.; Smethie, W. M.; Perry, R. S.; Schlosser, P.; Friedrich, R.

2011-12-01

A gas tight, small diameter, lightweight rosette, supporting equipment and an effective operational protocol has been developed for aircraft supported sampling of sea water across the Lincoln Sea. The system incorporates a commercial off the shelf CTD electronics (SBE19+ sensor package and SBE33 deck unit) to provide real-time measurement data at the surface. We designed and developed modular water sample units and custom electronics to decode the bottle firing commands and close the sample bottles. For a typical station, we land a ski-equipped deHaviland Twin Otter (DHC-6) aircraft on a suitable piece of sea-ice, drill a 12" diameter hole through the ice next to the cargo door and set up a tent to provide a reasonable working environment over the hole. A small winch with 0.1" diameter single conductor cable is mounted in the aircraft by the cargo door and a tripod supports a sheave above the hole. The CTD module is connected to the end of the wire and the water sampling modules are stacked on top as the system is lowered. For most stations, three sample modules are used to provide 12 four (4) liter sample bottles. Data collected during the down-cast is used to formulate the sampling plan which is executed on the up-cast. The system is powered by a 3,700 Watt, 120VAC gasoline generator. After collection, the sample modules are stored in passively temperature stabilized ice chests during the flight back to the logistics facility at Alert where a broad range of samples are drawn and stored for future analysis. The transport mechanism has a good track record of maintaining water samples within about two degrees of the original collection temperature which minimizes out-gassing. The system has been successfully deployed during a field program each spring starting in 2004 along a transect between the north end of Ellesmere Island (Alert, Nunavut) and the North Pole. During the eight field programs we have taken 48 stations with twelve bottles at most stations (eight at some shallow stations) and with a miss-fire rate within two percent of those achieved with traditional over-the-side CTD/rosette systems.

Physical Measurements of Water Properties Across the Mouth of the Gulf of California during April 2013 (PESCAR24 Cruise) (Mediciones Fisicas de las Propiedades del Agua a Traves de la Boca del Golfo de California Durante Abril de 2013 (Crucero PESCAR24)

DTIC Science & Technology

2013-11-26

Ciencias Marinas en Kiel, Alemania. El intervalo de profundidad entre súper-ensambles conjuntos se estableció en 8 m. Los perfiles de CTD...variation of the temperature and salinity at the entrance to the Gulf of California, Mexico. Ciencias Marinas 26(4): 561-583. Castro, R., R

Altimeter and Oceanographic in Situ Measurements in the Area of the Greenland-Iceland-Norwegian Sea, 1987-1988

DTIC Science & Technology

1992-06-01

of CTD data; J. Boyd for collecting AXBT data; Steve Piacsek from SACLANTCEN for GDEM data and help in arrangement of Planet Cruise; P. Minnett from...FCTE ft OCT -992 00 "Orgsnrdl oontot4ns color platgs: All DTIC reproduot- Ions Will be In blaok and white* Pavel Pistek Ocean Sensing and Prediction...temperature-depth and thermistor chain data collected by the West German ship WFS Planet , airborne expendable bathythermograph data deployed by P-3

The CTD-80 Survey Introduction.

ERIC Educational Resources Information Center

Kadar-Fulop, Judit; Bathory, Zoltan

1985-01-01

Hungary's national institute of education carried out the Curriculum Theory Department (CTD-80) national asessment in 1980. Reading, mathematics, and practical science achievement were measured, as well as teacher attitudes. Particular emphasis was placed on eighth-grade students; fourth graders were tested in reading. (GDC)

The CTD Science Practical Survey.

ERIC Educational Resources Information Center

Bathory, Zoltan

1985-01-01

As part of Hungary's Curriculum Theory Department (CTD-80) assessment, 1,543 14-year-olds were tested in the performance of science experiments in physics and chemistry. Skills included observing, measuring, hypothesizing, and drawing conclusions. Results are presented, and implications for curriculum are suggested. (GDC)

Pulmonary Function and Survival in Idiopathic vs Secondary Usual Interstitial Pneumonia

PubMed Central

Strand, Matthew J.; Sprunger, David; Cosgrove, Gregory P.; Fernandez-Perez, Evans R.; Frankel, Stephen K.; Huie, Tristan J.; Olson, Amy L.; Solomon, Joshua; Brown, Kevin K.

2014-01-01

BACKGROUND: The usual interstitial pneumonia (UIP) pattern of lung injury may occur in the setting of connective tissue disease (CTD), but it is most commonly found in the absence of a known cause, in the clinical context of idiopathic pulmonary fibrosis (IPF). Our objective was to observe and compare longitudinal changes in pulmonary function and survival between patients with biopsy-proven UIP found in the clinical context of either CTD or IPF. METHODS: We used longitudinal data analytic models to compare groups (IPF [n = 321] and CTD-UIP [n = 56]) on % predicted FVC (FVC %) or % predicted diffusing capacity of the lung for carbon monoxide (Dlco %), and we used both unadjusted and multivariable techniques to compare survival between these groups. RESULTS: There were no significant differences between groups in longitudinal changes in FVC % or Dlco % up to diagnosis, or from diagnosis to 10 years beyond (over which time, the mean decrease in FVC % per year [95% CI] was 4.1 [3.4, 4.9] for IPF and 3.5 [1.8, 5.1] for CTD-UIP, P = .49 for difference; and the mean decrease in Dlco % per year was 4.7 [4.0, 5.3] for IPF and 4.3 [3.0, 5.6] for CTD-UIP, P = .60 for difference). Despite the lack of differences in pulmonary function, subjects with IPF had worse survival in unadjusted (log-rank P = .003) and certain multivariable analyses. CONCLUSIONS: Despite no significant differences in changes in pulmonary function over time, patients with CTD-UIP (at least those with certain classifiable CTDs) live longer than patients with IPF—an observation that we suspect is due to an increased rate of mortal acute exacerbations in patients with IPF. PMID:24700149

Phosphatase Rtr1 Regulates Global Levels of Serine 5 RNA Polymerase II C-Terminal Domain Phosphorylation and Cotranscriptional Histone Methylation.

PubMed

Hunter, Gerald O; Fox, Melanie J; Smith-Kinnaman, Whitney R; Gogol, Madelaine; Fleharty, Brian; Mosley, Amber L

2016-09-01

In eukaryotes, the C-terminal domain (CTD) of Rpb1 contains a heptapeptide repeat sequence of (Y1S2P3T4S5P6S7)n that undergoes reversible phosphorylation through the opposing action of kinases and phosphatases. Rtr1 is a conserved protein that colocalizes with RNA polymerase II (RNAPII) and has been shown to be important for the transition from elongation to termination during transcription by removing RNAPII CTD serine 5 phosphorylation (Ser5-P) at a selection of target genes. In this study, we show that Rtr1 is a global regulator of the CTD code with deletion of RTR1 causing genome-wide changes in Ser5-P CTD phosphorylation and cotranscriptional histone H3 lysine 36 trimethylation (H3K36me3). Using chromatin immunoprecipitation and high-resolution microarrays, we show that RTR1 deletion results in global changes in RNAPII Ser5-P levels on genes with different lengths and transcription rates consistent with its role as a CTD phosphatase. Although Ser5-P levels increase, the overall occupancy of RNAPII either decreases or stays the same in the absence of RTR1 Additionally, the loss of Rtr1 in vivo leads to increases in H3K36me3 levels genome-wide, while total histone H3 levels remain relatively constant within coding regions. Overall, these findings suggest that Rtr1 regulates H3K36me3 levels through changes in the number of binding sites for the histone methyltransferase Set2, thereby influencing both the CTD and histone codes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Reduced specificity of autobiographical memories in young people with tic disorders.

PubMed

Pile, Victoria; Robinson, Sally; Roberts, Elystan; Topor, Marta; Hedderly, Tammy; Lau, Jennifer Y F

2018-05-01

Depression is common in Tourette syndrome and Chronic Tic Disorders (TS/CTD) and contributes to significant impairment. The specificity of autobiographical memories is implicated in an individual's sense of self and their daily functioning but also in the onset and development of depression in the general population. Here, we examined whether memory specificity is reduced in young people with TS/CTD, relative to control participants, and whether memory specificity is associated with depression. Thirty young people with TS/CTD (14 females; age: x̅ = 11.31; SD = 1.66; 87% White British) and twenty-six (12 females; age: x̅ = 11.23; SD = 2.43; 77% White British) control participants completed the study. Participants completed the Autobiographical Memory Task, which asks participants to respond with a specific memory to cue words, and a questionnaire measure of depressive symptoms. There was no significant difference between the two groups in terms of age, gender, ethnicity, IQ and depressive symptomatology. Young people with TS/CTD had less specific autobiographical memories than their peers (p < 0.001, r = 0.49). Across both groups, increased memory specificity for positive cue words was associated with reduced depressive symptomatology (p < 0.001, R 2  = 0.51). Our findings indicate that autobiographical memory in young people with TS is characterised by a lack of specificity and, as with neurotypical peers, reduced memory specificity for positive words is associated with depressive symptoms. Autobiographical memory specificity could be an important factor in understanding mood symptoms that characterise young people with TS/CTD and may be an important cognitive target to reduce the development of depression in young people with TS/CTD. Copyright © 2018 Elsevier Inc. All rights reserved.

The 13-kD FK506 Binding Protein, FKBP13, Interacts with a Novel Homologue of the Erythrocyte Membrane Cytoskeletal Protein 4.1

PubMed Central

Walensky, Loren D.; Gascard, Philippe; Field, Michael E.; Blackshaw, Seth; Conboy, John G.; Mohandas, Narla; Snyder, Solomon H.

1998-01-01

We have identified a novel generally expressed homologue of the erythrocyte membrane cytoskeletal protein 4.1, named 4.1G, based on the interaction of its COOH-terminal domain (CTD) with the immunophilin FKBP13. The 129-amino acid peptide, designated 4.1G–CTD, is the first known physiologic binding target of FKBP13. FKBP13 is a 13-kD protein originally identified by its high affinity binding to the immunosuppressant drugs FK506 and rapamycin (Jin, Y., M.W. Albers, W.S. Lane, B.E. Bierer, and S.J. Burakoff. 1991. Proc. Natl. Acad. Sci. USA. 88:6677– 6681); it is a membrane-associated protein thought to function as an ER chaperone (Bush, K.T., B.A. Henrickson, and S.K. Nigam. 1994. Biochem. J. [Tokyo]. 303:705–708). We report the specific association of FKBP13 with 4.1G–CTD based on yeast two-hybrid, in vitro binding and coimmunoprecipitation experiments. The histidyl-proline moiety of 4.1G–CTD is required for FKBP13 binding, as indicated by yeast experiments with truncated and mutated 4.1G–CTD constructs. In situ hybridization studies reveal cellular colocalizations for FKBP13 and 4.1G–CTD throughout the body during development, supporting a physiologic role for the interaction. Interestingly, FKBP13 cofractionates with the red blood cell homologue of 4.1 (4.1R) in ghosts, inside-out vesicles, and Triton shell preparations. The identification of FKBP13 in erythrocytes, which lack ER, suggests that FKBP13 may additionally function as a component of membrane cytoskeletal scaffolds. PMID:9531554

An Analysis of Effects of Background Variables on Student Achievement Based on the CTD Survey Data.

ERIC Educational Resources Information Center

Tolgyesi, Miklos

1985-01-01

Factors contributing to achievement were investigated as part of Hungary's Curriculum Theory Department (CTD-80) national assessment. Parent's education and occupation and student's sex predicted achievement results. School characteristics did not predict achievement or attitudes. (Author/GDC)

Idiopathic Interstitial Pneumonia Associated With Autoantibodies: A Large Case Series Followed Over 1 Year.

PubMed

Collins, Bridget F; Spiekerman, Charles F; Shaw, Megan A; Ho, Lawrence A; Hayes, Jennifer; Spada, Carolyn A; Stamato, Caroline M; Raghu, Ganesh

2017-07-01

Some patients with autoimmune characteristics and idiopathic interstitial pneumonia, particularly usual interstitial pneumonia (UIP), do not fit neatly into the category of connective tissue disease-associated interstitial lung disease (CTD-ILD), idiopathic pulmonary fibrosis (IPF), or recently proposed yet to be validated criteria for interstitial pneumonia with autoimmune features (IPAF). Outcomes of these patients are unknown. This was a retrospective single-center study. Analyses of variance compared differences in mean change in FVC and diffusion capacity (Dlco) over 1 year among 124 well-defined patients (20 patients with positive autoantibodies with or without symptoms of connective tissue disease [AI-ILD], 15 patients with IPAF, 36 patients with CTD-ILD, and 53 patients with IPF with negative CTD serologies [Lone-IPF]). Of the patients, 75% with AI-ILD, 33% with IPAF, and 33% with CTD-ILD had UIP. Initial FVC and Dlco were similarly moderately reduced across groups. Mean change in FVC over 12 months was as follows: -60 mL (IPAF), -110 mL (AI-ILD), -10 mL (CTD-ILD), and -90 mL (Lone-IPF) (P = .52). Mean change in Dlco was as follows: 2.39 mL/mm Hg/min (IPAF), -1.15 mL/mm Hg/min (AI-ILD), -0.27 mL/mm Hg/min (CTD-ILD), and -1.05 mL/mm Hg/min (Lone-IPF) (P < .001). By pattern of disease, the mean change in FVC was as follows: -140 mL (UIP), 10 mL (nonspecific interstitial pneumonia), and 12 mL (unclassifiable/other) (P = .001). No clinically significant differences in pulmonary function to distinguish between patients with AI-ILD, IPAF, CTD-ILD, and Lone-IPF were observed after 1 year. Longer periods of follow-up are needed to understand the outcomes of these patients. It is not yet clear whether AI-ILD is a distinct phenotype or a variant of the newly proposed entity IPAF. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Expression of human PQBP-1 in Drosophila impairs long-term memory and induces abnormal courtship.

PubMed

Yoshimura, Natsue; Horiuchi, Daisuke; Shibata, Masao; Saitoe, Minoru; Qi, Mei-Ling; Okazawa, Hitoshi

2006-04-17

Frame shift mutations of the polyglutamine binding protein-1 (PQBP1) gene lead to total or partial truncation of the C-terminal domain (CTD) and cause mental retardation in human patients. Interestingly, normal Drosophila homologue of PQBP-1 lacks CTD. As a model to analyze the molecular network of PQBP-1 affecting intelligence, we generated transgenic flies expressing human PQBP-1 with CTD. Pavlovian olfactory conditioning revealed that the transgenic flies showed disturbance of long-term memory. In addition, they showed abnormal courtship that male flies follow male flies. Abnormal functions of PQBP-1 or its binding partner might be linked to these symptoms.

The CTD Reading Study.

ERIC Educational Resources Information Center

Kadar-Fulop, Judit

1985-01-01

Reading ability of fourth- and eighth-grade Hungarians was assessed as part of the national CTD-80 (Curriculum Theory Department) survey. The texts used in the reading tests are analyzed, as are the reading tasks involved. Resulting achievement test results are presented and described in terms of the text characteristics. (GDC)

The outer-membrane export signal of Porphyromonas gingivalis type IX secretion system (T9SS) is a conserved C-terminal β-sandwich domain

PubMed Central

de Diego, Iñaki; Ksiazek, Miroslaw; Mizgalska, Danuta; Koneru, Lahari; Golik, Przemyslaw; Szmigielski, Borys; Nowak, Magdalena; Nowakowska, Zuzanna; Potempa, Barbara; Houston, John A.; Enghild, Jan J.; Thøgersen, Ida B.; Gao, Jinlong; Kwan, Ann H.; Trewhella, Jill; Dubin, Grzegorz; Gomis-Rüth, F. Xavier; Nguyen, Ky-Anh; Potempa, Jan

2016-01-01

In the recently characterized Type IX Secretion System (T9SS), the conserved C-terminal domain (CTD) in secreted proteins functions as an outer membrane translocation signal for export of virulence factors to the cell surface in the Gram-negative Bacteroidetes phylum. In the periodontal pathogen Porphyromonas gingivalis, the CTD is cleaved off by PorU sortase in a sequence-independent manner, and anionic lipopolysaccharide (A-LPS) is attached to many translocated proteins, thus anchoring them to the bacterial surface. Here, we solved the atomic structure of the CTD of gingipain B (RgpB) from P. gingivalis, alone and together with a preceding immunoglobulin-superfamily domain (IgSF). The CTD was found to possess a typical Ig-like fold encompassing seven antiparallel β-strands organized in two β-sheets, packed into a β-sandwich structure that can spontaneously dimerise through C-terminal strand swapping. Small angle X-ray scattering (SAXS) revealed no fixed orientation of the CTD with respect to the IgSF. By introducing insertion or substitution of residues within the inter-domain linker in the native protein, we were able to show that despite the region being unstructured, it nevertheless is resistant to general proteolysis. These data suggest structural motifs located in the two adjacent Ig-like domains dictate the processing of CTDs by the T9SS secretion pathway. PMID:27005013

The evolution of water property in the Mackenzie Bay polynya during Antarctic winter

NASA Astrophysics Data System (ADS)

Xu, Zhixin; Gao, Guoping; Xu, Jianping; Shi, Maochong

2017-10-01

Temperature and salinity profile data, collected by southern elephant seals equipped with autonomous CTD-Satellite Relay Data Loggers (CTD-SRDLs) during the Antarctic wintertime in 2011 and 2012, were used to study the evolution of water property and the resultant formation of the high density water in the Mackenzie Bay polynya (MBP) in front of the Amery Ice Shelf (AIS). In late March the upper 100-200 m layer is characterized by strong halocline and inversion thermocline. The mixed layer keeps deepening up to 250 m by mid-April with potential temperature remaining nearly the surface freezing point and sea surface salinity increasing from 34.00 to 34.21. From then on until mid-May, the whole water column stays isothermally at about -1.90℃ while the surface salinity increases by a further 0.23. Hereafter the temperature increases while salinity decreases along with the increasing depth both by 0.1 order of magnitude vertically. The upper ocean heat content ranging from 120.5 to 2.9 MJ m-2, heat flux with the values of 9.8-287.0 W m-2 loss and the sea ice growth rates of 4.3-11.7 cm d-1 were estimated by using simple 1-D heat and salt budget methods. The MBP exists throughout the whole Antarctic winter (March to October) due to the air-sea-ice interaction, with an average size of about 5.0×103 km2. It can be speculated that the decrease of the salinity of the upper ocean may occur after October each year. The recurring sea-ice production and the associated brine rejection process increase the salinity of the water column in the MBP progressively, resulting in, eventually, the formation of a large body of high density water.

Improved statistical method for temperature and salinity quality control

NASA Astrophysics Data System (ADS)

Gourrion, Jérôme; Szekely, Tanguy

2017-04-01

Climate research and Ocean monitoring benefit from the continuous development of global in-situ hydrographic networks in the last decades. Apart from the increasing volume of observations available on a large range of temporal and spatial scales, a critical aspect concerns the ability to constantly improve the quality of the datasets. In the context of the Coriolis Dataset for ReAnalysis (CORA) version 4.2, a new quality control method based on a local comparison to historical extreme values ever observed is developed, implemented and validated. Temperature, salinity and potential density validity intervals are directly estimated from minimum and maximum values from an historical reference dataset, rather than from traditional mean and standard deviation estimates. Such an approach avoids strong statistical assumptions on the data distributions such as unimodality, absence of skewness and spatially homogeneous kurtosis. As a new feature, it also allows addressing simultaneously the two main objectives of an automatic quality control strategy, i.e. maximizing the number of good detections while minimizing the number of false alarms. The reference dataset is presently built from the fusion of 1) all ARGO profiles up to late 2015, 2) 3 historical CTD datasets and 3) the Sea Mammals CTD profiles from the MEOP database. All datasets are extensively and manually quality controlled. In this communication, the latest method validation results are also presented. The method has already been implemented in the latest version of the delayed-time CMEMS in-situ dataset and will be deployed soon in the equivalent near-real time products.

Protein-Protein Interaction Reagents | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at Emory University has a library of genes used to study protein-protein interactions in mammalian cells. These genes are cloned in different mammalian expression vectors. A list of available cancer-associated genes can be accessed below. Emory_CTD^2_PPI_Reagents.xlsx Contact: Haian Fu

Use of Constant Time Delay and Attentional Responses with Adolescents.

ERIC Educational Resources Information Center

Wolery, Mark; And Others

1991-01-01

This study examined effectiveness of a constant time delay (CTD) procedure in teaching social studies and health facts to five adolescents with learning or behavioral disorders. Students were given praise with and without additional information. Results indicated CTD procedures were reliable and effective, and students acquired nontargeted as well…

The Development of an Instrument to Measure Creative Teaching Abilities.

ERIC Educational Resources Information Center

Riley, John F.

The development of an instrument to measure creative teaching abilities, the Creative Teaching Dilemma (CTD), involved three phases. The instrument was constructed and refined, and scoring procedures were outlined. The activities comprising the CTD included defining the teaching dilemma, gathering additional facts, identifying and stating the…

The Comparative Toxicogenomics Database (CTD): A Resource for Comparative Toxicological Studies

PubMed Central

CJ, Mattingly; MC, Rosenstein; GT, Colby; JN, Forrest; JL, Boyer

2006-01-01

The etiology of most chronic diseases involves interactions between environmental factors and genes that modulate important biological processes (Olden and Wilson, 2000). We are developing the publicly available Comparative Toxicogenomics Database (CTD) to promote understanding about the effects of environmental chemicals on human health. CTD identifies interactions between chemicals and genes and facilitates cross-species comparative studies of these genes. The use of diverse animal models and cross-species comparative sequence studies has been critical for understanding basic physiological mechanisms and gene and protein functions. Similarly, these approaches will be valuable for exploring the molecular mechanisms of action of environmental chemicals and the genetic basis of differential susceptibility. PMID:16902965

Mesoscale variability observed in the Northern Adriatic in autumn 2016

NASA Astrophysics Data System (ADS)

Pasaric, Zoran; Iva, Medjugorac; Nastjenka, Supic; Tamara, Djakovac; Mirko, Orlic

2017-04-01

Quasi-synoptic measurements of hydrographic properties were performed in the Northern Adriatic along the transect extending from Rovinj to the Po River mouth in an approximately east-west direction. The depth along the transect slowly varies between 30 and 40 m. Three one-day cruises were conducted, the first on 12 Nov, the second on 18 Nov, and the third on 25 Nov 2016. During the first and the third cruise the sampling was done with a CTD probe lowered from the surface to the bottom, at eleven stations placed nearly equidistantly along the transect. Average distance between the stations was 6 km. The second cruise was conducted with a towed yo-yo profiler equipped with the CTD probe and continuously undulating between the surface and some 4 m above the bottom. With roughly three undulations per kilometer, horizontal resolution along the transect was about 200 m. The data suggest that three processes occurred during the cruises: 1) surface cooling and related vertical mixing, 2) intrusion of high-salinity waters into the western part of the transect, and 3) propagation of a mesoscale formation in a westward direction. The existence and propagation of the mesoscale feature is supported by a simple analytical model of topographic Rossby waves. By assuming that the bottom varies linearly in the direction perpendicular to the transect, the propagation speed of O(1 km/day) is obtained - in agreement with the observations.

Hydrothermal exploration of the Mariana Back Arc Basin: Chemical Characterization

NASA Astrophysics Data System (ADS)

Resing, J. A.; Chadwick, B.; Baker, E. T.; Butterfield, D. A.; Baumberger, T.; Buck, N. J.; Walker, S. L.; Merle, S. G.; Michael, S.

2016-12-01

In November and December 2015, we visited the Southern Mariana back-arc on R/V Falkor (cruise FK151121) to explore for hydrothermal and volcanic activity. We conducted our study using the SENTRY AUV, a CTD rosette designed to do tows and vertical casts into the deep back-arc, and a trace metal CTD-package for the upper 1000m of the water column to examine transport form the nearby arc. We conducted 7 SENTRY dives, 12 tow-yos, 7 vertical casts, and 14 trace metal casts. We also mapped 24,050 km2 of the seafloor using the Falkor EM 302 multibeam. We discovered four new hydrothermal vent sites, and at one of them we found that some of the venting was coming from recently erupted lava flows. That lava flow is the deepest contemporary eruption yet discovered (at 4100-4450 m), and the first to be documented on a slow-spreading ridge. In addition, we were able to map the previously known Alice Springs hydrothermal site in unprecedented detail with AUV Sentry. The distribution of hydrothermal activity as well as chemistry of the plumes above them will be discussed. Plume chemistry data will include , Fe, Mn, CH4, H2, and 3He. The ship time for this project was provided by the Schmidt Ocean Institute with science funding provided by NOAA-Ocean Exploration.

A Multi-Pumping Flow System for In Situ Measurements of Dissolved Manganese in Aquatic Systems

PubMed Central

Meyer, David; Prien, Ralf D.; Dellwig, Olaf; Waniek, Joanna J.; Schuffenhauer, Ingo; Donath, Jan; Krüger, Siegfried; Pallentin, Malte; Schulz-Bull, Detlef E.

2016-01-01

A METals In Situ analyzer (METIS) has been used to determine dissolved manganese (II) concentrations in the subhalocline waters of the Gotland Deep (central Baltic Sea). High-resolution in situ measurements of total dissolved Mn were obtained in near real-time by spectrophotometry using 1-(2-pyridylazo)-2-naphthol (PAN). PAN is a complexing agent of dissolved Mn and forms a wine-red complex with a maximum absorbance at a wavelength of 562 nm. Results are presented together with ancillary temperature, salinity, and dissolved O2 data. Lab calibration of the analyzer was performed in a pressure testing tank. A detection limit of 77 nM was obtained. For validation purposes, discrete water samples were taken by using a pump-CTD system. Dissolved Mn in these samples was determined by an independent laboratory based method (inductively coupled plasma–optical emission spectrometry, ICP-OES). Mn measurements from both METIS and ICP-OES analysis were in good agreement. The results showed that the in situ analysis of dissolved Mn is a powerful technique reducing dependencies on heavy and expensive equipment (pump-CTD system, ICP-OES) and is also cost and time effective. PMID:27916898

Use of multiple sensor technologies for quality control of in situ biogeochemical measurements: A SeaCycler case study

NASA Astrophysics Data System (ADS)

Atamanchuk, Dariia; Koelling, Jannes; Lai, Jeremy; Send, Uwe; Wallace, Douglas

2017-04-01

Over the last two decades observing capacity for the global ocean has increased dramatically. Emerging sensor technologies for dissolved gases, nutrients and bio-optical properties in seawater are allowing extension of in situ observations beyond the traditionally measured salinity, temperature and pressure (CTD). However the effort to extend observations using autonomous instruments and platforms carries the risk of losing the level of data quality achievable through conventional water sampling techniques. We will present results from a case study with the SeaCycler profiling winch focusing on quality control of the in-situ measurements. A total of 13 sensors were deployed from May 2016 to early 2017 on SeaCycler's profiling sensor float, including CTD, dissolved oxygen (O2, 3 sensors), carbon dioxide (pCO2, 2 sensors), nutrients, velocity sensors, fluorometer, transmissometer, single channel PAR sensor, and others. We will highlight how multiple measurement technologies (e.g. for O2 and CO2) complement each other and result in a high quality data product. We will also present an initial assessment of the bio-optical data, their implications for seasonal phytoplankton dynamics and comparisons to climatologies and ocean-color data products obtained from the MODIS satellite.

Construct Validity Examination of Critical Thinking Dispositions for Undergraduate Students in University Putra Malaysia

ERIC Educational Resources Information Center

Ghadi, Ibrahim; Alwi, Nor Hayati; Bakar, Kamariah Abu; Talib, Othman

2012-01-01

This research aims to evaluate the psychology properties of the construct validity for the Critical Thinking Disposition (CTD) instrument. The CTD instrument consists of 39 Likert-type items measuring seven dispositions, namely analyticity, open-mind, truth-seeking, systematicity, self-confidence inquisitiveness and maturity. The study involves…

Scholarships and School Improvement: Annual Report of Catching the Dream.

ERIC Educational Resources Information Center

Chavers, Dean, Ed.

2001-01-01

This issue of "The Native Scholar" is comprised entirely of the annual report of Catching the Dream (CTD), an organization that awards scholarships to Native American students and grants for improving Native American schools. CTD scholarship programs are described, as are scholarships in general and how to find them. Fourteen scholarship websites…

Using the Constructivist Tridimensional Design Model for Online Continuing Education for Health Care Clinical Faculty

ERIC Educational Resources Information Center

Seo, Kay Kyeong-Ju; Engelhard, Chalee

2014-01-01

This article presents a new paradigm for continuing education of Clinical Instructors (CIs): the Constructivist Tridimensional (CTD) model for the design of an online curriculum. Based on problem-based learning, self-regulated learning, and adult learning theory, the CTD model was designed to facilitate interactive, collaborative, and authentic…

Observational and Incidental Learning by Children with Autism during Small Group Instruction

ERIC Educational Resources Information Center

Ledford, Jennifer R.; Gast, David L.; Luscre, Deanna; Ayres, Kevin M.

2008-01-01

This study evaluated the acquisition of incidental and observational information presented to 6 children with autism in a small group instructional arrangement using a constant time delay (CTD) procedure. A multiple probe design across behaviors, replicated across 6 participants, was used to evaluate the effectiveness of the CTD procedure and to…

[WMSDs in supermarket cashiers].

PubMed

Di Pede, Cinzia; Manuli, Gianluca; Dini, Fulvia; Pinelli, Marco; Turini, Lucia; Mariani, Maurizio; Taddeo, Domenico

2011-01-01

High prevalence of Cumulative Trauma Disorders (CTD) of shoulder and wristle among supermarket cashiers have been reported by several studies. To evaluate CTD prevalence in a group of supermarket cashiers in Pisa area is the aim of this study. Standardized Questionnaire and clinical examination have been performed in 128 female supermarket cashiers. In subjects having Symptoms and Signs, Elettroneurography and Echography have been performed. 54 subjects had Paresthesias and performed elettroneurography: 44 (34,4%) had Median nerve impairment at the wrist and among them 37 cases were bilateral; 15 had Ulnar nerve impairment (11,7%), among them 8 were bilateral. Moreover we have performed the echographies in all the 25 subjects with a positive medical examination of the shoulder and they all (19,5% del totale) showed a rotator cuff tendinosis. 25 subjects with CTD (44,6%) showed a comorbidity. An index called BiCo considering both bilaterality and comorbility has been calculated. The percentage of CTD is much more elevated than in general population and many workers present comorbility and bilaterality: a strategy for primary prevention improving ergonomy and information is needed.

Prioritizing PubMed articles for the Comparative Toxicogenomic Database utilizing semantic information

PubMed Central

Wilbur, W. John

2012-01-01

The Comparative Toxicogenomics Database (CTD) contains manually curated literature that describes chemical–gene interactions, chemical–disease relationships and gene–disease relationships. Finding articles containing this information is the first and an important step to assist manual curation efficiency. However, the complex nature of named entities and their relationships make it challenging to choose relevant articles. In this article, we introduce a machine learning framework for prioritizing CTD-relevant articles based on our prior system for the protein–protein interaction article classification task in BioCreative III. To address new challenges in the CTD task, we explore a new entity identification method for genes, chemicals and diseases. In addition, latent topics are analyzed and used as a feature type to overcome the small size of the training set. Applied to the BioCreative 2012 Triage dataset, our method achieved 0.8030 mean average precision (MAP) in the official runs, resulting in the top MAP system among participants. Integrated with PubTator, a Web interface for annotating biomedical literature, the proposed system also received a positive review from the CTD curation team. PMID:23160415

Prioritizing PubMed articles for the Comparative Toxicogenomic Database utilizing semantic information.

PubMed

Kim, Sun; Kim, Won; Wei, Chih-Hsuan; Lu, Zhiyong; Wilbur, W John

2012-01-01

The Comparative Toxicogenomics Database (CTD) contains manually curated literature that describes chemical-gene interactions, chemical-disease relationships and gene-disease relationships. Finding articles containing this information is the first and an important step to assist manual curation efficiency. However, the complex nature of named entities and their relationships make it challenging to choose relevant articles. In this article, we introduce a machine learning framework for prioritizing CTD-relevant articles based on our prior system for the protein-protein interaction article classification task in BioCreative III. To address new challenges in the CTD task, we explore a new entity identification method for genes, chemicals and diseases. In addition, latent topics are analyzed and used as a feature type to overcome the small size of the training set. Applied to the BioCreative 2012 Triage dataset, our method achieved 0.8030 mean average precision (MAP) in the official runs, resulting in the top MAP system among participants. Integrated with PubTator, a Web interface for annotating biomedical literature, the proposed system also received a positive review from the CTD curation team.

Using Sediment Profile Imagery (SPI) to Quantify ...

EPA Pesticide Factsheets

We present the results of monthly sediment and water quality surveys to evaluate the impact of intermittent, seasonal hypoxia on benthic habitat condition. This study was conducted in the Pensacola Bay (Florida) estuary across nine sites extending from the mouth of the Escambia River down-estuary to the outlet into the Gulf of Mexico. The sites span the full salinity gradient and cover a range of sediment types and dissolved oxygen statuses. Monthly sediment profile imagery (SPI) was captured from each site in conjunction with water column conductivity-temperature-depth (CTD) profiles and sediment grabs to evaluate sediment characteristics and macrobenthic community composition. The results of this study will be used to evaluate the use of SPI to determine effects of water quality on the health of benthic communities in Gulf Coast estuaries. Whereas recent water quality management efforts in Florida (e.g., numeric nutrient criteria, marine dissolved oxygen standard) assumed linkages between dissolved oxygen and aquatic life use attainment based on laboratory tests, SPI methods can potentially provide an assessment of these relationships in realistic field settings. The work presented here is in support of better indicators and endpoints and will help improve quantitative relationships between nutrient pollution and ecosystem condition. The audience that would be interested in this presentation includes scientists and managers from across the southeastern U

Structural and sequencing analysis of local target DNA recognition by MLV integrase.

PubMed

Aiyer, Sriram; Rossi, Paolo; Malani, Nirav; Schneider, William M; Chandar, Ashwin; Bushman, Frederic D; Montelione, Gaetano T; Roth, Monica J

2015-06-23

Target-site selection by retroviral integrase (IN) proteins profoundly affects viral pathogenesis. We describe the solution nuclear magnetic resonance structure of the Moloney murine leukemia virus IN (M-MLV) C-terminal domain (CTD) and a structural homology model of the catalytic core domain (CCD). In solution, the isolated MLV IN CTD adopts an SH3 domain fold flanked by a C-terminal unstructured tail. We generated a concordant MLV IN CCD structural model using SWISS-MODEL, MMM-tree and I-TASSER. Using the X-ray crystal structure of the prototype foamy virus IN target capture complex together with our MLV domain structures, residues within the CCD α2 helical region and the CTD β1-β2 loop were predicted to bind target DNA. The role of these residues was analyzed in vivo through point mutants and motif interchanges. Viable viruses with substitutions at the IN CCD α2 helical region and the CTD β1-β2 loop were tested for effects on integration target site selection. Next-generation sequencing and analysis of integration target sequences indicate that the CCD α2 helical region, in particular P187, interacts with the sequences distal to the scissile bonds whereas the CTD β1-β2 loop binds to residues proximal to it. These findings validate our structural model and disclose IN-DNA interactions relevant to target site selection. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Assessment of Cumulative Trauma Disorder (CTD) Risk for 3 Different Tasks Constructing and Repairing Multi-Layer Insulation (MLI) Blankets, Preparing the Dough for a Pizza, and Operating the Becton-Dickinson FACSAria Flow Cytometer

NASA Technical Reports Server (NTRS)

Gentzler, Marc; Kline, Martin; Palmer, Andrew; Terrone, Mark

2007-01-01

The Cumulative Trauma Disorder (CTD) risks for three different tasks using McCauley-Bell and Badiru's (1993) formula based on task, personal, and organizational factors were examined. For the Multi-Layer Insulation (MLI) blanket task, the results showed that the task, personal, and organizational risks were at about the same level. The personal risk factors for this task were evaluated using a hypothetical female employee age 52. For the pizza dough task, it was shown that the organizational risk was particularly high, with task related factors also at quite dangerous levels. On the other hand, there was a very low level of personal risk factors, based on a female age 17. The flow cytometer task was assessed with three different participants, a11 of whom had quite disparate levels of personal risk, which slightly affected the overall CTD risk. This reveals how individual difference variables certainly need to be considered. The task and organizational risks for this task were rated at about the same moderate level. The overall CTD risk averaged across the three participants was .335, indicating some risk. Compruing across the tasks revealed that the pizza dough task created the greatest overall CTD risk by far (.568), with the MLI (.325) and flow cytometer task (.335) having some risk associated with them. Future research should look into different tasks for more of a comparison

Bedside talc pleurodesis for malignant pleural effusion: factors affecting success.

PubMed

Aydogmus, Umit; Ozdemir, Servet; Cansever, Levent; Sonmezoglu, Yasar; Kocaturk, Celalettin Ibrahim; Bedirhan, Mehmet Ali

2009-03-01

To determine the factors affecting the success of bedside talc slurry (TS) used for symptomatic treatment of patients with malignant pleural effusion (MPE). Data of 113 effusions in 103 MPE patients treated between 1999 and 2007 were retrospectively evaluated for the study. The study group involved 73 patients whose follow-up information was available out of 81 patients treated by TS. Causes of MPE were lung cancer in 22 patients (30.1%) and breast carcinoma in 21 patients (28.8%). The success rate of TS was significantly higher if the time period between radiological diagnosis of effusion and administration of TS was less than 30 days (P= .02), or spontaneous expansion was attained after chest tube drainage (CTD) (P= .01). Success rate was higher for patients with daily drainage of less than 200 ml before TS than patients with more than 200 ml of daily drainage (P= .01). Dose of talc, either 4 g or above (P= .34), primary cause of MPE (P= .53), time to termination of CTD (P= .57), amount of drainage when CTD was terminated (P= .23), and time period between CTD and administration of TS (P= .20) did not show a statistically significant effect on the success of TS. In the treatment of malignant pleural effusion, patients with daily drainage of less than 200 ml before TS developed less recurrence than patients with daily drainage of more than 200 ml. Longer time period between the diagnosis of MPE and onset of CTD increased recurrence.

Generating Gene Ontology-Disease Inferences to Explore Mechanisms of Human Disease at the Comparative Toxicogenomics Database.

PubMed

Davis, Allan Peter; Wiegers, Thomas C; King, Benjamin L; Wiegers, Jolene; Grondin, Cynthia J; Sciaky, Daniela; Johnson, Robin J; Mattingly, Carolyn J

2016-01-01

Strategies for discovering common molecular events among disparate diseases hold promise for improving understanding of disease etiology and expanding treatment options. One technique is to leverage curated datasets found in the public domain. The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) manually curates chemical-gene, chemical-disease, and gene-disease interactions from the scientific literature. The use of official gene symbols in CTD interactions enables this information to be combined with the Gene Ontology (GO) file from NCBI Gene. By integrating these GO-gene annotations with CTD's gene-disease dataset, we produce 753,000 inferences between 15,700 GO terms and 4,200 diseases, providing opportunities to explore presumptive molecular underpinnings of diseases and identify biological similarities. Through a variety of applications, we demonstrate the utility of this novel resource. As a proof-of-concept, we first analyze known repositioned drugs (e.g., raloxifene and sildenafil) and see that their target diseases have a greater degree of similarity when comparing GO terms vs. genes. Next, a computational analysis predicts seemingly non-intuitive diseases (e.g., stomach ulcers and atherosclerosis) as being similar to bipolar disorder, and these are validated in the literature as reported co-diseases. Additionally, we leverage other CTD content to develop testable hypotheses about thalidomide-gene networks to treat seemingly disparate diseases. Finally, we illustrate how CTD tools can rank a series of drugs as potential candidates for repositioning against B-cell chronic lymphocytic leukemia and predict cisplatin and the small molecule inhibitor JQ1 as lead compounds. The CTD dataset is freely available for users to navigate pathologies within the context of extensive biological processes, molecular functions, and cellular components conferred by GO. This inference set should aid researchers, bioinformaticists, and pharmaceutical drug makers in finding commonalities in disease mechanisms, which in turn could help identify new therapeutics, new indications for existing pharmaceuticals, potential disease comorbidities, and alerts for side effects.

Evolution of RNA-Protein Interactions: Non-Specific Binding Led to RNA Splicing Activity of Fungal Mitochondrial Tyrosyl-tRNA Synthetases

PubMed Central

Lamech, Lilian T.; Mallam, Anna L.; Lambowitz, Alan M.

2014-01-01

The Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (mtTyrRS; CYT-18 protein) evolved a new function as a group I intron splicing factor by acquiring the ability to bind group I intron RNAs and stabilize their catalytically active RNA structure. Previous studies showed: (i) CYT-18 binds group I introns by using both its N-terminal catalytic domain and flexibly attached C-terminal anticodon-binding domain (CTD); and (ii) the catalytic domain binds group I introns specifically via multiple structural adaptations that occurred during or after the divergence of Peziomycotina and Saccharomycotina. However, the function of the CTD and how it contributed to the evolution of splicing activity have been unclear. Here, small angle X-ray scattering analysis of CYT-18 shows that both CTDs of the homodimeric protein extend outward from the catalytic domain, but move inward to bind opposite ends of a group I intron RNA. Biochemical assays show that the isolated CTD of CYT-18 binds RNAs non-specifically, possibly contributing to its interaction with the structurally different ends of the intron RNA. Finally, we find that the yeast mtTyrRS, which diverged from Pezizomycotina fungal mtTyrRSs prior to the evolution of splicing activity, binds group I intron and other RNAs non-specifically via its CTD, but lacks further adaptations needed for group I intron splicing. Our results suggest a scenario of constructive neutral (i.e., pre-adaptive) evolution in which an initial non-specific interaction between the CTD of an ancestral fungal mtTyrRS and a self-splicing group I intron was “fixed” by an intron RNA mutation that resulted in protein-dependent splicing. Once fixed, this interaction could be elaborated by further adaptive mutations in both the catalytic domain and CTD that enabled specific binding of group I introns. Our results highlight a role for non-specific RNA binding in the evolution of RNA-binding proteins. PMID:25536042

Evolution of RNA-protein interactions: non-specific binding led to RNA splicing activity of fungal mitochondrial tyrosyl-tRNA synthetases.

PubMed

Lamech, Lilian T; Mallam, Anna L; Lambowitz, Alan M

2014-12-01

The Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (mtTyrRS; CYT-18 protein) evolved a new function as a group I intron splicing factor by acquiring the ability to bind group I intron RNAs and stabilize their catalytically active RNA structure. Previous studies showed: (i) CYT-18 binds group I introns by using both its N-terminal catalytic domain and flexibly attached C-terminal anticodon-binding domain (CTD); and (ii) the catalytic domain binds group I introns specifically via multiple structural adaptations that occurred during or after the divergence of Peziomycotina and Saccharomycotina. However, the function of the CTD and how it contributed to the evolution of splicing activity have been unclear. Here, small angle X-ray scattering analysis of CYT-18 shows that both CTDs of the homodimeric protein extend outward from the catalytic domain, but move inward to bind opposite ends of a group I intron RNA. Biochemical assays show that the isolated CTD of CYT-18 binds RNAs non-specifically, possibly contributing to its interaction with the structurally different ends of the intron RNA. Finally, we find that the yeast mtTyrRS, which diverged from Pezizomycotina fungal mtTyrRSs prior to the evolution of splicing activity, binds group I intron and other RNAs non-specifically via its CTD, but lacks further adaptations needed for group I intron splicing. Our results suggest a scenario of constructive neutral (i.e., pre-adaptive) evolution in which an initial non-specific interaction between the CTD of an ancestral fungal mtTyrRS and a self-splicing group I intron was "fixed" by an intron RNA mutation that resulted in protein-dependent splicing. Once fixed, this interaction could be elaborated by further adaptive mutations in both the catalytic domain and CTD that enabled specific binding of group I introns. Our results highlight a role for non-specific RNA binding in the evolution of RNA-binding proteins.

Targeted journal curation as a method to improve data currency at the Comparative Toxicogenomics Database

PubMed Central

Davis, Allan Peter; Johnson, Robin J.; Lennon-Hopkins, Kelley; Sciaky, Daniela; Rosenstein, Michael C.; Wiegers, Thomas C.; Mattingly, Carolyn J.

2012-01-01

The Comparative Toxicogenomics Database (CTD) is a public resource that promotes understanding about the effects of environmental chemicals on human health. CTD biocurators read the scientific literature and manually curate a triad of chemical–gene, chemical–disease and gene–disease interactions. Typically, articles for CTD are selected using a chemical-centric approach by querying PubMed to retrieve a corpus containing the chemical of interest. Although this technique ensures adequate coverage of knowledge about the chemical (i.e. data completeness), it does not necessarily reflect the most current state of all toxicological research in the community at large (i.e. data currency). Keeping databases current with the most recent scientific results, as well as providing a rich historical background from legacy articles, is a challenging process. To address this issue of data currency, CTD designed and tested a journal-centric approach of curation to complement our chemical-centric method. We first identified priority journals based on defined criteria. Next, over 7 weeks, three biocurators reviewed 2425 articles from three consecutive years (2009–2011) of three targeted journals. From this corpus, 1252 articles contained relevant data for CTD and 52 752 interactions were manually curated. Here, we describe our journal selection process, two methods of document delivery for the biocurators and the analysis of the resulting curation metrics, including data currency, and both intra-journal and inter-journal comparisons of research topics. Based on our results, we expect that curation by select journals can (i) be easily incorporated into the curation pipeline to complement our chemical-centric approach; (ii) build content more evenly for chemicals, genes and diseases in CTD (rather than biasing data by chemicals-of-interest); (iii) reflect developing areas in environmental health and (iv) improve overall data currency for chemicals, genes and diseases. Database URL: http://ctdbase.org/ PMID:23221299

Heat-shock-specific phosphorylation and transcriptional activity of RNA polymerase II.

PubMed

Egyházi, E; Ossoinak, A; Lee, J M; Greenleaf, A L; Mäkelä, T P; Pigon, A

1998-07-10

The carboxyl-terminal domain (CTD) of the largest RNA polymerase II (pol II) subunit is a target for extensive phosphorylation in vivo. Using in vitro kinase assays it was found that several different protein kinases can phosphorylate the CTD including the transcription factor IIH-associated CDK-activating CDK7 kinase (R. Roy, J. P. Adamczewski, T. Seroz, W. Vermeulen, J. P. Tassan, L. Schaeffer, E. A. Nigg, J. H. Hoeijmakers, and J. M. Egly, 1994, Cell 79, 1093-1101). Here we report the colocalization of CDK7 and the phosphorylated form of CTD (phosphoCTD) to actively transcribing genes in intact salivary gland cells of Chironomus tentans. Following a heat-shock treatment, both CDK7 and pol II staining disappear from non-heat-shock genes concomitantly with the abolishment of transcriptional activity of these genes. In contrast, the actively transcribing heat-shock genes, manifested as chromosomal puff 5C on chromosome IV (IV-5C), stain intensely for phosphoCTD, but are devoid of CDK7. Furthermore, the staining of puff IV-5C with anti-PCTD antibodies was not detectably influenced by the TFIIH kinase and transcription inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). Following heat-shock treatment, the transcription of non-heat-shock genes was completely eliminated, while newly formed heat-shock gene transcripts emerged in a DRB-resistant manner. Thus, heat shock in these cells induces a rapid clearance of CDK7 from the non-heat-shock genes, indicating a lack of involvement of CDK7 in the induction and function of the heat-induced genes. The results taken together suggest the existence of heat-shock-specific CTD phosphorylation in living cells. This phosphorylation is resistant to DRB treatment, suggesting that not only phosphorylation but also transcription of heat-shock genes is DRB resistant and that CDK7 in heat shock cells is not associated with TFIIH.

Acquisition of Oceanographic Measurements from Baleen Whales and Acquisition of Oceanographic Measurements from Baleen Whales: Field Deployments of Tags Developed Under Grant ONR (N00014-13-1-0854)

DTIC Science & Technology

2015-09-30

Jonas Teilmann Department of Bioscience Aarhus University Fredriksborgvej 399 DK-4000 Roskilde Denmark phone: +45 21424291 fax: +45 87 16 87 51...Mammal Research Unit (SMRU, www.smru.st-andrews.ac.uk), University of St. Andrews, Scotland. WORK COMPLETED The project developed a prototype CTD...temperature and depth components from that work along with the tag controller/transmitter etc, are all still valid. • The risk for building a new tag fall

Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial.

PubMed

Saunders, Peter; Tsipouri, Vicky; Keir, Gregory J; Ashby, Deborah; Flather, Marcus D; Parfrey, Helen; Babalis, Daphne; Renzoni, Elisabetta A; Denton, Christopher P; Wells, Athol U; Maher, Toby M

2017-06-15

Interstitial lung disease (ILD) frequently complicates systemic autoimmune disorders resulting in considerable morbidity and mortality. The connective tissue diseases (CTDs) most frequently resulting in ILD include: systemic sclerosis, idiopathic inflammatory myositis (including dermatomyositis, polymyositis and anti-synthetase syndrome) and mixed connective tissue disease. Despite the development, over the last two decades, of a range of biological therapies which have resulted in significant improvements in the treatment of the systemic manifestations of CTD, the management of CTD-associated ILD has changed little. At present there are no approved therapies for CTD-ILD. Following trials in scleroderma-ILD, cyclophosphamide is the accepted standard of care for individuals with severe or progressive CTD-related ILD. Observational studies have suggested that the anti-CD20 monoclonal antibody, rituximab, is an effective rescue therapy in the treatment of refractory CTD-ILD. However, before now, there have been no randomised controlled trials assessing the efficacy of rituximab in this treatment population. RECITAL is a UK, multicentre, prospective, randomised, double-blind, double-dummy, controlled trial funded by the Efficacy and Mechanism Evaluation Programme of the Medical Research Council and National Institute for Health Research. The trial will compare rituximab 1 g given intravenously, twice at an interval of 2 weeks, with intravenously administered cyclophosphamide given monthly at a dose of 600 mg/m 2 body surface area in individuals with ILD due to systemic sclerosis, idiopathic inflammatory myositis (including anti-synthetase syndrome) or mixed connective tissue disease. A total of 116 individuals will be randomised 1:1 to each of the two treatment arms, with stratification based on underlying CTD, and will be followed for a total of 48 weeks from first dose. The primary endpoint for the study will be change in forced vital capacity (FVC) at 24 weeks. Key secondary endpoints include: safety, change in FVC at 48 weeks as well as survival, change in oxygen requirements, total 48-week corticosteroid exposure and utilisation of health care resources. This is the first randomised control trial to study the efficacy of rituximab as first-line treatment in CTD-associated ILD. The results generated should provide important information on the treatment of a life-threatening complication affecting a rare group of CTDs. ClinicalTrials.gov, NCT01862926. Registered on 22 May 2013.

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo.

PubMed

Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M; Melendy, Thomas; Archambault, Jacques

2016-01-06

The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural integrity of the helicase domain, followed by an acidic region (AR) and a C-terminal tail (C-tail) that have been shown to regulate the oligomerization of BPV1 E1 in vitro. Characterization of E1 chimeras revealed that, while the function of the AR could be transferred from BPV1 E1 to HPV11 E1, that of the C-tail could not. These results suggest that the E1 CTD performs multiple functions in DNA replication, some of them in a virus type-specific manner. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo

PubMed Central

Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M.

2016-01-01

ABSTRACT The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function in vivo is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1 in vivo, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1 in vitro and confirmed here in vivo. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1 in vivo and suggest that the function of the C-tail has evolved in a PV type-specific manner. IMPORTANCE While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1 in vivo and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural integrity of the helicase domain, followed by an acidic region (AR) and a C-terminal tail (C-tail) that have been shown to regulate the oligomerization of BPV1 E1 in vitro. Characterization of E1 chimeras revealed that, while the function of the AR could be transferred from BPV1 E1 to HPV11 E1, that of the C-tail could not. These results suggest that the E1 CTD performs multiple functions in DNA replication, some of them in a virus type-specific manner. PMID:26739052

Comprehensive evaluations of cone-beam CT dose in image-guided radiation therapy via GPU-based Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Montanari, Davide; Scolari, Enrica; Silvestri, Chiara; Jiang Graves, Yan; Yan, Hao; Cervino, Laura; Rice, Roger; Jiang, Steve B.; Jia, Xun

2014-03-01

Cone beam CT (CBCT) has been widely used for patient setup in image-guided radiation therapy (IGRT). Radiation dose from CBCT scans has become a clinical concern. The purposes of this study are (1) to commission a graphics processing unit (GPU)-based Monte Carlo (MC) dose calculation package gCTD for Varian On-Board Imaging (OBI) system and test the calculation accuracy, and (2) to quantitatively evaluate CBCT dose from the OBI system in typical IGRT scan protocols. We first conducted dose measurements in a water phantom. X-ray source model parameters used in gCTD are obtained through a commissioning process. gCTD accuracy is demonstrated by comparing calculations with measurements in water and in CTDI phantoms. Twenty-five brain cancer patients are used to study dose in a standard-dose head protocol, and 25 prostate cancer patients are used to study dose in pelvis protocol and pelvis spotlight protocol. Mean dose to each organ is calculated. Mean dose to 2% voxels that have the highest dose is also computed to quantify the maximum dose. It is found that the mean dose value to an organ varies largely among patients. Moreover, dose distribution is highly non-homogeneous inside an organ. The maximum dose is found to be 1-3 times higher than the mean dose depending on the organ, and is up to eight times higher for the entire body due to the very high dose region in bony structures. High computational efficiency has also been observed in our studies, such that MC dose calculation time is less than 5 min for a typical case.

Essential role of the flexible linker on the conformational equilibrium of bacterial peroxiredoxin reductase for effective regeneration of peroxiredoxin

PubMed Central

Kamariah, Neelagandan; Eisenhaber, Birgit; Eisenhaber, Frank; Grüber, Gerhard

2017-01-01

Reactive oxygen species (ROS) can damage DNA, proteins, and lipids, so cells have antioxidant systems that regulate ROS. In many bacteria, a dedicated peroxiredoxin reductase, alkyl hydroperoxide reductase subunit F (AhpF), catalyzes the rapid reduction of the redox-active disulfide center of the antioxidant protein peroxiredoxin (AhpC) to detoxify ROS such as hydrogen peroxide, organic hydroperoxide, and peroxynitrite. AhpF is a flexible multidomain protein that enables a series of electron transfers among the redox centers by accepting reducing equivalents from NADH. A flexible linker connecting the N-terminal domain (NTD) and C-terminal domain (CTD) of AhpF suggests that the enzyme adopts a large-scale domain motion that alternates between the closed and open states to shuttle electrons from the CTD via the NTD to AhpC. Here, we conducted comprehensive mutational, biochemical, and biophysical analyses to gain insights into the role of the flexible linker and the residues critical for the domain motions of Escherichia coli AhpF (EcAhpF) during electron transfer. Small-angle X-ray scattering studies of linker mutants revealed that a group of charged residues, 200EKR202, is crucial for the swiveling motion of the NTD. Moreover, NADH binding significantly affected EcAhpF flexibility and the movement of the NTD relative to the CTD. The mutants also exhibited a decrease in H2O2 reduction by the AhpF-AhpC ensemble. We propose that a concerted movement involving the NTD, C-terminal NADH, and FAD domains, and the flexible linker between them is essential for optimal intra-domain cross-talk and for efficient electron transfer to the redox partner AhpC required for peroxidation. PMID:28270505

Physical, Chemical and CTD (Conductivity/Temperature/Depth) Data from the Marathon II Expedition.

DTIC Science & Technology

1987-05-01

143i 1 493 4 fi ? 3 is 40 is 4 2 11 1 2 2 1: ;7, 1’ oil 41 󈧭 7 2 9 41 439?5 1 4 :4 34 6 : 7 3 3 9 4 3 2 Ill 2 2 1 7 4 ISO 27 9 74 411) 1 4 7 1 44 43...34 6 39 114 3 2 5 0 42 2 3 3 5 L1 9 25 1l )4 35 42 1 i)6S 1.3 42 33 6i1 6 3q 1)0 , 1 0 0 S3 14 9 3 2 L. ISO 5 a] 3: 4 66: 4, 09 L36 5 )95 13 42 5 796...231, s 3468 113 2 -74 33 4357 4 1 25 413 44 433 348 1 3 27 𔄁 4’ 94i: 45 5 3 332 9- 41 IS 1465 11352 2� 3’ 738 43 35D 45 C 339 4 4 73 34657 1 2753

Constant Time Delay: One Way to Provide Positive Behavioral Support for Students with Emotional and Behavioral Disorders

ERIC Educational Resources Information Center

Stevens, Kay B.; Lingo, Amy S.

2005-01-01

Teachers of students with emotional and behavioral disorders (EBD) understand conceptually, emotionally, and legally the importance of using research-based procedures as well as positive behavioral supports. One way to provide positive behavioral support for students with EBD is constant time delay (CTD). CTD is an instructional delivery procedure…

Beyond Critical Thinking Skills: Investigating the Relationship between Critical Thinking Skills and Dispositions through Different Online Instructional Strategies

ERIC Educational Resources Information Center

Yang, Ya-Ting C.; Chou, Heng-An

2008-01-01

The purpose of this study was to investigate (1) the relationship between critical thinking skills (CTS) and critical thinking dispositions (CTD), and (2) the effectiveness of different levels of instructional strategy (asynchronous online discussions (AODs), CTS instruction via AODs, and CTS instruction with CTD cultivation via AODs) in improving…

Caregivers as Teachers: Using Constant Time Delay To Teach Adults How To Use Constant Time Delay.

ERIC Educational Resources Information Center

Wall, Maureen E.; Gast, David L.

1997-01-01

A study involving four caregivers evaluated the effectiveness of a systematic instructional procedure known as constant time delay (CTD) in teaching caregivers how to use CTD to teach their adolescent or adult children, siblings, or clients with disabilities, response chain skills. Results found the procedure to be effective. (CR)

A new non-pharmacological vacuum therapy for female sexual dysfunction.

PubMed

Billups, K L; Berman, L; Berman, J; Metz, M E; Glennon, M E; Goldstein, I

2001-01-01

Although Female Sexual Dysfunction (FSD) affects 40% of American women, there is no FDA-approved pharmaceutical therapy. The EROS-CTD (Clitoral Therapy Device, UroMetrics, Inc., St. Paul, MN) treatment is the first FDA cleared-to-market therapy for FSD. Clitoral engorgement is believed to play an important role in female sexual arousal and overall sexual satisfaction. The EROS-CTD is a small, battery-powered device designed to enhance clitoral engorgement, increase blood flow to the clitoris, and ultimately improve arousal in women with FSD. The objective of this study was to assess the effectiveness of the EROS-CTD on sexual arousal (genital sensation, vaginal lubrication, ability to reach orgasm, and sexual satisfaction) in normal volunteers and women with FSD.

Variation of subsurface chlorophyll maximum layer from the vertical profiler and in-situ observation in the eastern coastal region of Korea (the East/Japan Sea)

NASA Astrophysics Data System (ADS)

Son, Y. T.; Chang, K. I.; Nam, S.; Kang, D. J.

2016-02-01

Coastal monitoring buoy (called it as ESROB) has been continually operated to monitor meteorological (wind, air temperature, air pressure, PAR) and oceanic properties (temperature, salinity, current, chlorophyll fluorescence, DO, turbidity) using equipment such as CTD, fluorometer and WQM (Water Quality Monitor) in the eastern coastal region of Korea (the East/Japan Sea) since April 2011. The ESROB produced temporal evolution of physical and biogeochemical parameters of the water column with high resolution of 10 min interval. In order to understand horizontal influence of physical and biogeochemical parameters on variation of subsurface chlorophyll maximum layer (SCM), interdisciplinary in-situ surveys with small R/V in the study area for about week were conducted in June/October 2014 and in May 2015. A wirewalker, a wave-driven vertically profiling platform (Rainville and Pinkel 2001), was also deployed at two points (about 30 m and 80 m water depth) along cross-shore direction with the ESROB for about one or two weeks with in-situ survey durations. The wirewalker was equipped with CTD, turbidity and chlorophyll a fluorometer profiler, which was completed approximately every 3 10 minute depending on sea surface state. The SCM was observed in almost every deployment nearest coast, except for June in 2014, with variation of semi- and diurnal time periods. Temporal evolution of the wirewalker showed that disappearance and reoccurrence of the SCM within the water column in October 2014, which was associated with vertical mixing induced by strong wind stress. Low salinity plume in the surface layer and shoaling of bottom cold water were concurrently observed after homogeneous water column, affecting another condition to the vertical distribution of chlorophyll a in this coastal region. Moreover in-situ observation with densely points and temporal interval for 1 day revealed that distribution with high concentration of chlorophyll a on isopycnal was association with the horizontal local circulation that has influence on stability (vertical stratification and shear) of the water column. Optical and biogeochemical parameter analyzed from the water samples, affecting on the variation of chlorophyll a concentration within the water column, will be also discussed in the presentation of Ocean Science Meeting.

The use of infrared thermal imaging as a non-destructive screening tool for identifying drought-tolerant lentil genotypes.

PubMed

Biju, Sajitha; Fuentes, Sigfredo; Gupta, Dorin

2018-06-01

Lentil (Lens culinaris, Medik.) is an important legume crop, which often experience drought stress especially at the flowering and grain filling phenological stages. The availability of efficient and robust screening tools based on relevant non-destructive quantifiable traits would facilitate research on crop improvement for drought tolerance. The objective of this study was to evaluate the drought tolerance of 37 lentil genotypes using infrared thermal imaging (IRTI), drought tolerance parameters and multivariate data analysis. Potted plants were kept in a completely randomized design in a growth chamber with five replicates. Plants were subjected to three different drought treatments: 100, 50 and 20% of field capacity at the onset of reproductive period. The relative drought stress tolerance was determined based on a set of morpho-physiological parameters including non-destructive measures based on IRTI, such as: canopy temperature (Tc), canopy temperature depression (CTD) and crop water stress index (CWSI) during the growing period and destructive measures at harvest, such as: dry root-shoot ratio (RS ratio), relative water content (RWC) and harvest index (HI). The drought tolerance indices used were drought susceptibility index (DSI) and drought tolerance efficiency (DTE). Results showed that drought stress treatments significantly reduced the RWC, HI, CTD and DSI, whereas, the values of Tc, CWSI, RS ratio and DTE significantly increased for all the genotypes. The cluster analysis from morpho-physiological parameters clustered genotypes in three distinctive groups as per the level of drought stress tolerance. The genotypes with higher values of RS ratio, RWC, HI, DTE and CTD and lower values of DSI, Tc and CWSI were identified as drought-tolerant genotypes. Based on this preliminary screening, the genotypes Digger, Cumra, Indianhead, ILL 5588, ILL 6002 and ILL 5582 were identified as promising drought-tolerant genotypes. It can be concluded that the IRTI analysis is a high-throughput constructive screening tool along with RS ratio, RWC, HI and other drought tolerance indices to define the drought stress tolerance variability within lentil plants. These results provide a foundation for future research directed at identifying powerful drought assessment traits using rapid and non-destructive techniques, such as IRTI along with the yield traits, and understanding the biochemical and molecular mechanisms underlying lentil tolerance to drought stress. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Structural characterization of molecular complexes formed by trimethoprim and cimitidine with 2,3,5,6-tetrachloro-1,4-benzoquinone

NASA Astrophysics Data System (ADS)

Balraj, C.; Ganesh, K.; Elango, K. P.

2011-07-01

Spectroscopic and spectrofluorimetric techniques have been employed to investigate the structure of the charge transfer (CT) complexes of Trimethoprim (TMP) and Cimitidine (CTD) drugs with 2,3,5,6-tetrachloro-1,4-benzoquinone ( p-chloranil, p-CHL). The stoichiometry of the complexes was found to be 1:2 for TMP- p-CHL system and 1:1 for CTD- p-CHL system. The thermodynamic results indicated that the formation of molecular complex between the donors and the acceptor is spontaneous and endothermic. The results of electronic spectral studies indicated that the formation constant for CTD- p-CHL system is found to be higher than that for TMP- p-CHL system. The observation is well supported by the results of fluorescence quenching studies and the association constants calculated for CTD- p-CHL system is 36.2 × 10 3 mol L -1 and that for TMP- p-CHL system is 2.6 × 10 3 mol L -1. The kinetic results, in both the cases, indicated that the interaction is first order each with respect to the concentration of the donor and the acceptor. The physico-chemical parameters viz. oscillator strength, dipole moment, ionization potential and dissociation energy of the complexes were also determined and discussed. Structural characterization of the complexes were done using FT-IR and 1H NMR spectral techniques and the results indicated that, in TMP, the free NH 2 group while in CTD the pyrazole N sbnd H moiety involves in complexation with the acceptor, p-CHL.

LRET Determination of Molecular Distances during pH Gating of the Mammalian Inward Rectifier Kir1.1b.

PubMed

Nanazashvili, Mikheil; Sánchez-Rodríguez, Jorge E; Fosque, Ben; Bezanilla, Francisco; Sackin, Henry

2018-01-09

Gating of the mammalian inward rectifier Kir1.1 at the helix bundle crossing (HBC) by intracellular pH is believed to be mediated by conformational changes in the C-terminal domain (CTD). However, the exact motion of the CTD during Kir gating remains controversial. Crystal structures and single-molecule fluorescence resonance energy transfer of KirBac channels have implied a rigid body rotation and/or a contraction of the CTD as possible triggers for opening of the HBC gate. In our study, we used lanthanide-based resonance energy transfer on single-Cys dimeric constructs of the mammalian renal inward rectifier, Kir1.1b, incorporated into anionic liposomes plus PIP 2 , to determine unambiguous, state-dependent distances between paired Cys residues on diagonally opposite subunits. Functionality and pH dependence of our proteoliposome channels were verified in separate electrophysiological experiments. The lanthanide-based resonance energy transfer distances measured in closed (pH 6) and open (pH 8) conditions indicated neither expansion nor contraction of the CTD during gating, whereas the HBC gate widened by 8.8 ± 4 Å, from 6.3 ± 2 to 15.1 ± 6 Å, during opening. These results are consistent with a Kir gating model in which rigid body rotation of the large CTD around the permeation axis is correlated with opening of the HBC hydrophobic gate, allowing permeation of a 7 Å hydrated K ion. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Optical Constituents at the Mouth of the Columbia River: Variability and Signature in Remotely Sensed Reflectance

DTIC Science & Technology

2013-09-30

constructed at BIO, carried the new Machine Vision Floc Camera (MVFC), a Sequoia Scientific LISST 100x Type B, an RBR CTD, and two pressure-actuated...WetStar CDOM fluorometer, a Sequoia Scientific flow control switch, and a SeaBird 37 CTD. The flow-control switch allows the ac- 9 to collect 0.2-um

Using the Technology of Critical Thinking Development (CTD) as a Means of Forming Competencies of Students Majoring in "Life Safety"

ERIC Educational Resources Information Center

Kayumova, Leysan R.; Morozova, Marina A.

2016-01-01

The relevance of the research problem is caused by the need to use various teaching methods and techniques in training students majoring in pedagogical specialties while implementing the competency approach in education. Information about the technology of critical thinking development (CTD) in future teachers training is limited, and the…

The Effectiveness of a Constant Time Delay Procedure on Teaching Lifetime Sport Skills to Adolescents with Severe to Profound Intellectual Disabilities.

ERIC Educational Resources Information Center

Zhang, Jiabei; And Others

1995-01-01

A constant time delay (CTD) procedure was used to teach four adolescents with severe/profound intellectual disabilities to perform bowling, throwing, and putting. Results indicated that the adolescents could be effectively taught gross motor lifetime sport skills with the CTD procedure and that verbal description plus physical assistance could be…

Review of Recent Research Using Constant Time Delay to Teach Chained Tasks to Persons with Developmental Disabilities

ERIC Educational Resources Information Center

Dogoe, Maud; Banda, Devender R.

2009-01-01

We reviewed twelve studies that used the constant time delay (CTD) procedure to teach chained tasks to individuals with developmental disabilities from years 1996-2006. Variables analyzed include types of tasks that have been taught with the procedure, how effective CTD has been in teaching participants, and whether researchers have investigated…

A Review of the Accomplishments of the CTD² Network | Office of Cancer Genomics

Cancer.gov

The Office of Cancer Genomics (OCG) Cancer Target Discovery and Development or CTD2 initiative was established by the National Cancer Institute (NCI) to accelerate the “translation” of high-throughput, high-content genomic data to the bedside through functional genomics. The CTD2 initiative is a collaborative network of 13 different research teams, or Centers.

Activation and modulation of human α4β2 nicotinic acetylcholine receptors by the neonicotinoids clothianidin and imidacloprid

PubMed Central

Li, Ping; Ann, Jason; Akk, Gustav

2013-01-01

Neonicotinoids are synthetic, nicotine-derived insecticides used for agricultural and household pest control. While highly effective at activating insect nicotinic receptors, many neonicotinoids are also capable of directly activating and/or modulating the activation of vertebrate nicotinic receptors. In this study, we have investigated the actions of the neonicotinoids clothianidin (CTD) and imidacloprid (IMI) on human neuronal α4β2 nicotinic acetylcholine receptors. The data demonstrate that the compounds are weak agonists of the human receptors with relative peak currents of 1–4 % of the response to 1 mM acetylcholine (ACh). Coapplication of IMI strongly inhibited currents elicited by ACh. From Schild plot analysis, we estimate that the affinity of IMI to the human α4β2 receptor is 18 µM. The application of low concentrations of CTD potentiated responses to low concentrations of ACh, suggesting that receptors occupied by one ACh and one CTD molecule have a higher gating efficacy than receptors with one ACh bound. Interestingly, subunit stoichiometry affected inhibition by CTD, with (α4)2(β2)3 receptors significantly more strongly inhibited than the (α4)3(β2)2 receptors. PMID:21538459

Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review.

PubMed

Atzeni, Fabiola; Gerardi, Maria Chiara; Barilaro, Giuseppe; Masala, Ignazio Francesco; Benucci, Maurizio; Sarzi-Puttini, Piercarlo

2018-01-01

Interstitial lung diseases (ILDs) are among the most serious complications associated with systemic rheumatic diseases, and lead to significant morbidity and mortality; they may also be the first manifestation of connective tissue diseases (CTDs). The aim of this narrative review is to summarise the data concerning the pathogenesis of CTD/ILD and its distinguishing features in different rheumatic diseseas. Areas covered: The pathogenesis, clinical aspects and treatment of ILD associated with rheumatic systemic diseases and CTDs were reviewed by searching the PubMed, Medline, and Cochrane Library databases for papers published between 1995 and February 2017 using combinations of words or terms. Articles not written in English were excluded. Expert commentary: The management of CTD-ILD is challenging because of the lack of robust data regarding the treatments used, the heterogeneity of the diseases themselves, and the scarcity of well-defined outcome measures. Treatment decisions are often made clinically on the basis of functional, radiographic progression, and exacerbating factors such as age and the burden of comorbidities. Given the complexities of diagnosis and the paucity of treatment trials, the management of CTD patients with ILD requires multidisciplinary collaboration between rheumatologists and pulmonologists in CTD-ILD clinics.

Analysis of costs to dispense prescriptions in independently owned, closed-door long-term care pharmacies.

PubMed

Carroll, Norman V; Rupp, Michael T; Holdford, David A

2014-03-01

The need for accurate calculation of long-term care (LTC) pharmacies' costs to dispense (CTD) has become more important as payers have moved toward reimbursement models based on pharmacies' actual acquisition cost for drug products and the Centers for Medicare Medicaid Services (CMS) has implemented requirements that LTC pharmacies must dispense prescriptions for certain branded drugs in 14-day-or-less quantities. To (a) calculate the average cost that the typical independently owned, closed-door LTC pharmacy currently incurs to dispense and deliver a prescription to the resident of a client LTC facility and (b) estimate how CMS-mandated changes to a 14-day-or-less dispensing cycle would affect the typical LTC pharmacy's average CTD. The data requirements and measurement model were developed by academic researchers in consultation with an industry advisory committee of independent LTC pharmacy owners. A survey instrument was constructed to collect financial and operating data required to calculate the CTD. Surveys were distributed via 3 dissemination channels to approximately 1,000 independently owned, closed-door LTC pharmacies. The National Community Pharmacists Association mailed surveys to their LTC members; 3 major national wholesalers distributed surveys to their LTC customers through their newsletters; and 3 LTC group purchasing organizations distributed the surveys to their members through emails, newsletters, mailings, and/or regional meetings. Each pharmacy's CTD was calculated by dividing total LTC dispensing-related 
costs by the total number of prescriptions dispensed. Dispensing-related costs included costs incurred to physically dispense and deliver prescriptions (e.g., dispensing pharmacists' and technicians' salaries and costs of medication containers) and costs incurred to support the dispensing function (e.g., salaries of delivery and medical records personnel). A model based on dispensing-related fixed, variable, and semivariable costs was developed to examine the impact of shorter dispensing cycles on LTC pharmacies' CTD. A prescription volume increase of 19% was assumed based on converting only solid oral branded drugs to short-cycle dispensing. A diverse sample of 64 closed-door LTC pharmacies returned usable surveys. Sales from dispensing to LTC facilities accounted for more than 98% of total sales. Respondents indicated that they currently dispensed 23% of total doses in 14-day-or-less cycles and 76% in 28-31 day cycles. Most pharmacies used automated medication packaging technology, heat and cold package sealers, bar code systems, sterile compounding hoods, LTC printers or labelers, and electronic prescribing. The median CTD was $13.54 with an interquartile range (25th to 75th percentiles) of $10.51 to $17.66. More than half of dispensing-related costs were from personnel expense, of which pharmacists and managers accounted for more than 40%. The results of the fixed and variable cost modeling suggested that converting solid oral brand-name drugs from 30-day to 14-day dispensing cycles would lower the median per prescription CTD to between $11.63 and $12.54, depending on the assumptions made about the effects of semivariable costs. However, this decrease in per prescription dispensing cost is dwarfed by an increase in total dispensing cost incurred by pharmacies that results from doubling the monthly volume of short-cycle prescriptions that must be dispensed. The result is that the typical LTC pharmacy in our sample incurred a CTD of $13.54 if the medication is dispensed in a 30-day cycle or $23.26 if the medication is dispensed in two 14-day cycles (at a cost of $11.63 for each cycle dispensed). Our results indicated a median CTD of $13.54 for the typical independently owned, closed-door LTC pharmacy. Moving to a shorter cycle would reduce pharmacies' average per-prescription CTD but would increase the number of prescriptions dispensed per month. Our results indicated that transitioning solid oral branded products to 14-day cycles would reduce the median CTD to a minimum of $11.63 but would increase total dispensing costs because each sold oral branded prescription would require twice the number of monthly dispensing events.

Long non-coding RNA-CTD-2108O9.1 represses breast cancer metastasis by influencing leukemia inhibitory factor receptor.

PubMed

Wang, Mozhi; Wang, Mengshen; Wang, Zhenning; Yu, Xueting; Song, Yongxi; Wang, Chong; Xu, Yujie; Wei, Fengheng; Zhao, Yi; Xu, Yingying

2018-06-01

Breast cancer (BC) is an aggressive malignant disease in women worldwide with a high tendency to metastasize. However, important biomarkers for BC metastasis remain largely undefined. In the present study, we identified that long non-coding RNA-CTD-2108O9.1 is downregulated in BC tissues and cells and acts as a metastatic inhibitor of BC. Mechanistic investigation determined that lncRNA-CTD-2108O9.1 represses metastasis by targeting leukemia inhibitory factor receptor (LIFR), which is designated as a metastasis suppressor in BC. Our study characterizes a significant tumor suppressor active in BC metastasis repression through the known metastasis inhibitor LIFR. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

The C-terminal domain of Nrf1 negatively regulates the full-length CNC-bZIP factor and its shorter isoform LCR-F1/Nrf1β; both are also inhibited by the small dominant-negative Nrf1γ/δ isoforms that down-regulate ARE-battery gene expression.

PubMed

Zhang, Yiguo; Qiu, Lu; Li, Shaojun; Xiang, Yuancai; Chen, Jiayu; Ren, Yonggang

2014-01-01

The C-terminal domain (CTD, aa 686-741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ.

Simultaneous application of multiple platforms (Glider, Scanfish, profiling mooring, CTD) to improve detection and quantification of temporal ocean dynamics

NASA Astrophysics Data System (ADS)

Meyer, D.; Prien, R. D.; Lips, U.; Naumann, M.; Liblik, T.; Schulz-Bull, D. E.

2016-02-01

Ocean dynamics are difficult to observe given the broad spectrum of temporal and spatial scales. Robotic technology can be used to address this issue, and help to investigate the variability of physical and biogeochemical processes. This work focuses on ocean robots and in particular on glider technology which seems to be one of the most promising oceanographic tools for future marine research. In this context, we present the results of an observational program conducted in the Baltic Sea combining a profiling mooring (GODESS - Gotland Deep Environmental Sampling Station) and glider technology (Slocum). The temporal variability is captured by the mooring, while the spatial variability is obtained from the glider sampling the surrounding area. Furthermore, classical CTD-measurements and an underwater vehicle (Scanfish) are used simultaneously by two different research vessels to validate and complement the observing network. The main aim of the study is to identify possible synergies between the different platforms and to get a better understanding of maximizing the information content of the data collected by this network. The value and the quality of the data of each individual platform is analyzed and their contribution to the performance of the network itself evaluated.

Initial Psychometric Properties of a Brief Parent-Report Instrument for Assessing Tic Severity in Children with Chronic Tic Disorders

ERIC Educational Resources Information Center

Chang, Susanna; Himle, Michael B.; Tucker, Benjamin T. P.; Woods, Douglas W.; Piacentini, John

2009-01-01

This article describes the development and initial psychometric properties of the Parent Tic Questionnaire (PTQ)--a new measure assessing the number, frequency, and intensity of motor and vocal tics in children and adolescents with Chronic Tic Disorder (CTD). Parents of 40 children with a CTD completed the PTQ as part of a larger assessment…

The Effects of Embedded Skill Instruction on the Acquisition of Target and Nontarget Skills in Preschoolers with Developmental Delays.

ERIC Educational Resources Information Center

Daugherty, Stefanie; Grisham-Brown, Jennifer; Hemmeter, Mary Louise

2001-01-01

In the current study, a constant time delay (CTD) procedure was embedded in classroom activities and routines to teach counting to three preschool children with speech and language delays. CTD was effective in teaching numbers to all three children. One child out of two also was able to acquire non-target information. (Contains references.) (CR)

Web services-based text-mining demonstrates broad impacts for interoperability and process simplification.

PubMed

Wiegers, Thomas C; Davis, Allan Peter; Mattingly, Carolyn J

2014-01-01

The Critical Assessment of Information Extraction systems in Biology (BioCreAtIvE) challenge evaluation tasks collectively represent a community-wide effort to evaluate a variety of text-mining and information extraction systems applied to the biological domain. The BioCreative IV Workshop included five independent subject areas, including Track 3, which focused on named-entity recognition (NER) for the Comparative Toxicogenomics Database (CTD; http://ctdbase.org). Previously, CTD had organized document ranking and NER-related tasks for the BioCreative Workshop 2012; a key finding of that effort was that interoperability and integration complexity were major impediments to the direct application of the systems to CTD's text-mining pipeline. This underscored a prevailing problem with software integration efforts. Major interoperability-related issues included lack of process modularity, operating system incompatibility, tool configuration complexity and lack of standardization of high-level inter-process communications. One approach to potentially mitigate interoperability and general integration issues is the use of Web services to abstract implementation details; rather than integrating NER tools directly, HTTP-based calls from CTD's asynchronous, batch-oriented text-mining pipeline could be made to remote NER Web services for recognition of specific biological terms using BioC (an emerging family of XML formats) for inter-process communications. To test this concept, participating groups developed Representational State Transfer /BioC-compliant Web services tailored to CTD's NER requirements. Participants were provided with a comprehensive set of training materials. CTD evaluated results obtained from the remote Web service-based URLs against a test data set of 510 manually curated scientific articles. Twelve groups participated in the challenge. Recall, precision, balanced F-scores and response times were calculated. Top balanced F-scores for gene, chemical and disease NER were 61, 74 and 51%, respectively. Response times ranged from fractions-of-a-second to over a minute per article. We present a description of the challenge and summary of results, demonstrating how curation groups can effectively use interoperable NER technologies to simplify text-mining pipeline implementation. Database URL: http://ctdbase.org/ © The Author(s) 2014. Published by Oxford University Press.

Web services-based text-mining demonstrates broad impacts for interoperability and process simplification

PubMed Central

Wiegers, Thomas C.; Davis, Allan Peter; Mattingly, Carolyn J.

2014-01-01

The Critical Assessment of Information Extraction systems in Biology (BioCreAtIvE) challenge evaluation tasks collectively represent a community-wide effort to evaluate a variety of text-mining and information extraction systems applied to the biological domain. The BioCreative IV Workshop included five independent subject areas, including Track 3, which focused on named-entity recognition (NER) for the Comparative Toxicogenomics Database (CTD; http://ctdbase.org). Previously, CTD had organized document ranking and NER-related tasks for the BioCreative Workshop 2012; a key finding of that effort was that interoperability and integration complexity were major impediments to the direct application of the systems to CTD's text-mining pipeline. This underscored a prevailing problem with software integration efforts. Major interoperability-related issues included lack of process modularity, operating system incompatibility, tool configuration complexity and lack of standardization of high-level inter-process communications. One approach to potentially mitigate interoperability and general integration issues is the use of Web services to abstract implementation details; rather than integrating NER tools directly, HTTP-based calls from CTD's asynchronous, batch-oriented text-mining pipeline could be made to remote NER Web services for recognition of specific biological terms using BioC (an emerging family of XML formats) for inter-process communications. To test this concept, participating groups developed Representational State Transfer /BioC-compliant Web services tailored to CTD's NER requirements. Participants were provided with a comprehensive set of training materials. CTD evaluated results obtained from the remote Web service-based URLs against a test data set of 510 manually curated scientific articles. Twelve groups participated in the challenge. Recall, precision, balanced F-scores and response times were calculated. Top balanced F-scores for gene, chemical and disease NER were 61, 74 and 51%, respectively. Response times ranged from fractions-of-a-second to over a minute per article. We present a description of the challenge and summary of results, demonstrating how curation groups can effectively use interoperable NER technologies to simplify text-mining pipeline implementation. Database URL: http://ctdbase.org/ PMID:24919658

Estimation of Geotropic Currents in the Bay of Bengal using In-situ Observations.

NASA Astrophysics Data System (ADS)

T, V. R.

2014-12-01

Geostraphic Currents (GCs) can be estimated from temperature and salinity observations. In this study an attempt has been made to compute GC using temperature and salinity observations from Expendable Bathy Thermograph (XBT) and CTD over Bay of Bengal (BoB). Although in recent time we have Argo observations but it is for a limited period and coarse temporal resolutions. In BoB Bengal, where not enough simultaneous hydrographic temperature and salinity data are available with reasonable spatial resolution (~one degree spatial resolution) and for a longer period. To overcome the limitations of GC computed from XBT profiles, temperature-salinity relationships were used from simultaneous temperature and salinity observations. We have demonstrated that GCs can be computed with an accuracy of less than 8.5 cm/s (root mean square error) at the surface with respect to temperature from XBT and salinity from climatological record. This error reduces with increasing depth. Finally, we demonstrated the application of this approach to study the temporal variation of the GCs during 1992 to 2012 along an XBT transect.

Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease.

PubMed

Oldham, Justin M; Lee, Cathryn; Valenzi, Eleanor; Witt, Leah J; Adegunsoye, Ayodeji; Hsu, Scully; Chen, Lena; Montner, Steven; Chung, Jonathan H; Noth, Imre; Vij, Rekha; Strek, Mary E

2016-12-01

Azathioprine is a commonly prescribed therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). Combination therapy that included azathioprine was recently shown to increase the risk of death and hospitalization in patients with idiopathic pulmonary fibrosis. Whether azathioprine increases the risk of adverse outcomes in patients with fibrotic CTD-ILD, including those with CTD-associated usual interstitial pneumonia (UIP), remains unknown. A retrospective cohort analysis was performed to determine the combined incidence rate of death, transplant and respiratory hospitalization associated with azathioprine exposure. A fibrotic CTD-ILD cohort treated with mycophenolate mofetil served as a comparator group. Incidence rates were compared with an incidence rate ratio (IRR) generated by negative binomial regression. Longitudinal pulmonary function response was then assessed using mixed effects linear regression models. Fifty-four patients were treated with azathioprine and forty-three with mycophenolate. Medication discontinuation due to non-respiratory side effects occurred in 27% and 5% of the azathioprine and mycophenolate cohorts, respectively. The combined incidence rate of adverse outcomes was 0.015 and 0.013 for azathioprine and mycophenolate, respectively (IRR 1.23; 95% CI 0.49-3.12; p = 0.66). Similar incidence rates were observed among those with CTD-UIP (IRR 0.83; 95% CI 0.21-3.31; p = 0.79). Both groups demonstrated pulmonary function stability over time, with the azathioprine group demonstrating a marginal improvement. A significant minority of patients could not tolerate azathioprine due to non-respiratory side effects. Of those who did tolerate azathioprine, a similar incidence of adverse outcomes was observed as those treated with mycophenolate. Both therapies were associated with stability in pulmonary function. Copyright © 2016 Elsevier Ltd. All rights reserved.

A CTD-Pfizer collaboration: manual curation of 88,000 scientific articles text mined for drug-disease and drug-phenotype interactions.

PubMed

Davis, Allan Peter; Wiegers, Thomas C; Roberts, Phoebe M; King, Benjamin L; Lay, Jean M; Lennon-Hopkins, Kelley; Sciaky, Daniela; Johnson, Robin; Keating, Heather; Greene, Nigel; Hernandez, Robert; McConnell, Kevin J; Enayetallah, Ahmed E; Mattingly, Carolyn J

2013-01-01

Improving the prediction of chemical toxicity is a goal common to both environmental health research and pharmaceutical drug development. To improve safety detection assays, it is critical to have a reference set of molecules with well-defined toxicity annotations for training and validation purposes. Here, we describe a collaboration between safety researchers at Pfizer and the research team at the Comparative Toxicogenomics Database (CTD) to text mine and manually review a collection of 88,629 articles relating over 1,200 pharmaceutical drugs to their potential involvement in cardiovascular, neurological, renal and hepatic toxicity. In 1 year, CTD biocurators curated 254,173 toxicogenomic interactions (152,173 chemical-disease, 58,572 chemical-gene, 5,345 gene-disease and 38,083 phenotype interactions). All chemical-gene-disease interactions are fully integrated with public CTD, and phenotype interactions can be downloaded. We describe Pfizer's text-mining process to collate the articles, and CTD's curation strategy, performance metrics, enhanced data content and new module to curate phenotype information. As well, we show how data integration can connect phenotypes to diseases. This curation can be leveraged for information about toxic endpoints important to drug safety and help develop testable hypotheses for drug-disease events. The availability of these detailed, contextualized, high-quality annotations curated from seven decades' worth of the scientific literature should help facilitate new mechanistic screening assays for pharmaceutical compound survival. This unique partnership demonstrates the importance of resource sharing and collaboration between public and private entities and underscores the complementary needs of the environmental health science and pharmaceutical communities. Database URL: http://ctdbase.org/

Text Mining Effectively Scores and Ranks the Literature for Improving Chemical-Gene-Disease Curation at the Comparative Toxicogenomics Database

PubMed Central

Johnson, Robin J.; Lay, Jean M.; Lennon-Hopkins, Kelley; Saraceni-Richards, Cynthia; Sciaky, Daniela; Murphy, Cynthia Grondin; Mattingly, Carolyn J.

2013-01-01

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) is a public resource that curates interactions between environmental chemicals and gene products, and their relationships to diseases, as a means of understanding the effects of environmental chemicals on human health. CTD provides a triad of core information in the form of chemical-gene, chemical-disease, and gene-disease interactions that are manually curated from scientific articles. To increase the efficiency, productivity, and data coverage of manual curation, we have leveraged text mining to help rank and prioritize the triaged literature. Here, we describe our text-mining process that computes and assigns each article a document relevancy score (DRS), wherein a high DRS suggests that an article is more likely to be relevant for curation at CTD. We evaluated our process by first text mining a corpus of 14,904 articles triaged for seven heavy metals (cadmium, cobalt, copper, lead, manganese, mercury, and nickel). Based upon initial analysis, a representative subset corpus of 3,583 articles was then selected from the 14,094 articles and sent to five CTD biocurators for review. The resulting curation of these 3,583 articles was analyzed for a variety of parameters, including article relevancy, novel data content, interaction yield rate, mean average precision, and biological and toxicological interpretability. We show that for all measured parameters, the DRS is an effective indicator for scoring and improving the ranking of literature for the curation of chemical-gene-disease information at CTD. Here, we demonstrate how fully incorporating text mining-based DRS scoring into our curation pipeline enhances manual curation by prioritizing more relevant articles, thereby increasing data content, productivity, and efficiency. PMID:23613709

Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding.

PubMed

Gui, Miao; Song, Wenfei; Zhou, Haixia; Xu, Jingwei; Chen, Silian; Xiang, Ye; Wang, Xinquan

2017-01-01

The global outbreak of SARS in 2002-2003 was caused by the infection of a new human coronavirus SARS-CoV. The infection of SARS-CoV is mediated mainly through the viral surface glycoproteins, which consist of S1 and S2 subunits and form trimer spikes on the envelope of the virions. Here we report the ectodomain structures of the SARS-CoV surface spike trimer in different conformational states determined by single-particle cryo-electron microscopy. The conformation 1 determined at 4.3 Å resolution is three-fold symmetric and has all the three receptor-binding C-terminal domain 1 (CTD1s) of the S1 subunits in "down" positions. The binding of the "down" CTD1s to the SARS-CoV receptor ACE2 is not possible due to steric clashes, suggesting that the conformation 1 represents a receptor-binding inactive state. Conformations 2-4 determined at 7.3, 5.7 and 6.8 Å resolutions are all asymmetric, in which one RBD rotates away from the "down" position by different angles to an "up" position. The "up" CTD1 exposes the receptor-binding site for ACE2 engagement, suggesting that the conformations 2-4 represent a receptor-binding active state. This conformational change is also required for the binding of SARS-CoV neutralizing antibodies targeting the CTD1. This phenomenon could be extended to other betacoronaviruses utilizing CTD1 of the S1 subunit for receptor binding, which provides new insights into the intermediate states of coronavirus pre-fusion spike trimer during infection.

Carboxyl-terminal Domain of Transient Receptor Potential Vanilloid 1 Contains Distinct Segments Differentially Involved in Capsaicin- and Heat-induced Desensitization*

PubMed Central

Joseph, John; Wang, Sen; Lee, Jongseok; Ro, Jin Y.; Chung, Man-Kyo

2013-01-01

Multiple Ca2+-dependent processes are involved in capsaicin-induced desensitization of transient receptor potential vanilloid 1 (TRPV1), but desensitization of TRPV1 by heat occurs even in the absence of extracellular Ca2+, although the mechanisms are unknown. In this study, we tested the hypothesis that capsaicin and heat desensitize TRPV1 through distinct mechanisms involving distinct structural segments of TRPV1. In HEK293 cells that heterologously express TRPV1, we found that heat-induced desensitization was not affected by the inclusion of intracellular ATP or alanine mutation of Lys155, both of which attenuate capsaicin-induced desensitization, suggesting that heat-induced desensitization occurs through mechanisms distinct from capsaicin-induced desensitization. To determine protein domains involved in heat-induced desensitization, we generated chimeric proteins between TRPV1 and TRPV3, a heat-gated channel lacking heat-induced desensitization. We found that TRPV1 with the carboxyl-terminal domain (CTD) of TRPV3 retained heat activation but was impaired in heat-induced desensitization. Further experiments using chimeric or deletion mutants within TRPV1 CTD indicated that the distal half of CTD regulates the activation and desensitization of TRPV1 in modality-specific manners. Within the distal CTD, we identified two segments that distinctly regulated capsaicin- and heat-induced desensitization. The results suggest that the activation and desensitization of TRPV1 by capsaicin and heat can be modulated differentially and disproportionally through different regions of TRPV1 CTD. Identifying the domains involved in thermal regulation of TRPV1 may facilitate the development of novel anti-hyperalgesic approaches aimed at attenuating activation and enhancing desensitization of TRPV1 by thermal stimuli. PMID:24174527

Forecast of drifter trajectories using a Rapid Environmental Assessment based on CTD observations

NASA Astrophysics Data System (ADS)

Sorgente, R.; Tedesco, C.; Pessini, F.; De Dominicis, M.; Gerin, R.; Olita, A.; Fazioli, L.; Di Maio, A.; Ribotti, A.

2016-11-01

A high resolution submesoscale resolving ocean model was implemented in a limited area north of Island of Elba where a maritime exercise, named Serious Game 1 (SG1), took place on May 2014 in the framework of the project MEDESS-4MS (Mediterranean Decision Support System for Marine Safety). During the exercise, CTD data have been collected responding to the necessity of a Rapid Environmental Assessment, i.e. to a rapid evaluation of the marine conditions able to provide sensible information for initialisation of modelling tools, in the scenario of possible maritime accidents. The aim of this paper is to evaluate the impact of such mesoscale-resolving CTD observations on short-term forecasts of the surface currents, within the framework of possible oil-spill related emergencies. For this reason, modelling outputs were compared with Lagrangian observations at sea: the high resolution modelled currents, together with the ones of the coarser sub-regional model WMED, are used to force the MEDSLIK-II oil-spill model to simulate drifter trajectories. Both ocean models have been assessed by comparing the prognostic scalar and vector fields as an independent CTD data set and with real drifter trajectories acquired during SG1. The diagnosed and prognosed circulation reveals that the area was characterised by water masses of Atlantic origin influenced by small mesoscale cyclonic and anti-cyclonic eddies, which govern the spatial and temporal evolution of the drifter trajectories and of the water masses distribution. The assimilation of CTD data into the initial conditions of the high resolution model highly improves the accuracy of the short-term forecast in terms of location and structure of the thermocline and positively influence the ability of the model in reproducing the observed paths of the surface drifters.

The role of nailfold capillaroscopy in interstitial lung diseases - can it differentiate idiopathic cases from collagen tissue disease associated interstitial lung diseases?

PubMed

Çakmakçı Karadoğan, Dilek; Balkarlı, Ayşe; Önal, Özgür; Altınışık, Göksel; Çobankara, Veli

2015-01-01

Nailfold capillaroscopy (NFC) is a non-invasive diagnostic test that is mostly used for early diagnosis of collagen tissue diseases (CTDs). We aimed to evaluate whether NFC findings could be a clue for discriminating idiopathic interstitial lung diseases (ILD) from CTD associated ILDs (CTD-ILD). Additionally it was aimed to determine whether NFC could be helpful in discriminating usual interstitial pneumonia (UIP) pattern from non-specific interstitial pneumonia (NSIP) pattern. We grouped patients into three main groups: 15 CTD-ILD, 18 idiopathic ILD, and 17 patients in the control group. The CTD-ILD group was split into two subgroups: 8 patients with Sjögren's syndrome (SJS)-associated ILD and 7 with rheumatoid arthritis (RA)-associated ILD. The idiopathic-ILD group consisted of 10 idiopathic NSIP and 8 IPF patients. The control group consisted of 10 SJS and 7 RA patients without lung disease. None of the patients were on acute exacerbation at the time of examination, and none had Reynaud's phenomenon. Mean capillary density was significantly reduced only in the CTD-ILD group as compared to the control group (p= 0.006). In subgroup analysis, it was determined that RA-ILD, IPF, and SJS-ILD subgroups had more severe capillaroscopic abnormalities. Mean capillary density in patients with the UIP pattern was reduced compared to patients with the NSIP pattern and those in the control group; p values were 0.008 and < 0.001, respectively. This study is to be the first describing and comparing the nailfold capillaroscopic findings of patients with NSIP and UIP patterns. NFC findings can be helpful in discriminating UIP patterns from NSIP patterns. But to show its role in differentiating idiopathic disease, more studies with more patients are needed.

Resolving Hot Spots in the C-Terminal Dimerization Domain that Determine the Stability of the Molecular Chaperone Hsp90

PubMed Central

Reimann, Sven; Smits, Sander H. J.; Schmitt, Lutz; Groth, Georg; Gohlke, Holger

2014-01-01

Human heat shock protein of 90 kDa (hHsp90) is a homodimer that has an essential role in facilitating malignant transformation at the molecular level. Inhibiting hHsp90 function is a validated approach for treating different types of tumors. Inhibiting the dimerization of hHsp90 via its C-terminal domain (CTD) should provide a novel way to therapeutically interfere with hHsp90 function. Here, we predicted hot spot residues that cluster in the CTD dimerization interface by a structural decomposition of the effective energy of binding computed by the MM-GBSA approach and confirmed these predictions using in silico alanine scanning with DrugScorePPI. Mutation of these residues to alanine caused a significant decrease in the melting temperature according to differential scanning fluorimetry experiments, indicating a reduced stability of the mutant hHsp90 complexes. Size exclusion chromatography and multi-angle light scattering studies demonstrate that the reduced stability of the mutant hHsp90 correlates with a lower complex stoichiometry due to the disruption of the dimerization interface. These results suggest that the identified hot spot residues can be used as a pharmacophoric template for identifying and designing small-molecule inhibitors of hHsp90 dimerization. PMID:24760083

Acquisition of an Underway CTD System for the Flow Encountering Abrupt Topography DRI

DTIC Science & Technology

2015-09-30

Acquisition of an Underway CTD System for the Flow Encountering Abrupt Topography DRI T. M. Shaun Johnston Scripps Institution of Oceanography...westward flow in the North Equatorial Current (NEC) encounters tall, steep, submarine topography and islands. During the Flow Encountering Abrupt... Topography (FLEAT) DRI, investigators will determine: • Whether appreciable energy/momentum is lost from the large-scale NEC flow to smaller scales and

The Effect of a Constant Time Delay Procedure on Teaching an Adult with Severe Mental Retardation a Recreation Bowling Skill

ERIC Educational Resources Information Center

Zhang, Jiabei; Cote, Bridget; Chen, Shihui; Liu, John

2004-01-01

The purpose of this study was to examine the effect of a constant time delay (CTD) procedure on teaching a recreational bowling skill to a 39-year-old male with severe mental retardation. The CTD procedure used 5 seconds as delay interval, task direction as target stimulus, physical assistance as controlling prompt, and oral praise as reinforcer.…

Comparison of Constant Time Delay and Simultaneous Prompting Procedures: Teaching Functional Sight Words to Students with Intellectual Disabilities and Autism Spectrum Disorder

ERIC Educational Resources Information Center

Swain, Rasheeda; Lane, Justin D.; Gast, David L.

2015-01-01

Constant time delay (CTD) and simultaneous prompting (SP) are effective response prompting procedures for teaching students with moderate to severe disabilities. The purpose of this study was to compare the efficiency of CTD and SP when teaching functional sight words to four students, 8-11 years of age, with moderate intellectual disability (ID)…

Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor agonist.

PubMed

Li, Xuefei; Azlina, Ahmad; Karabasil, Mileva Ratko; Purwanti, Nunuk; Hasegawa, Takahiro; Yao, Chenjuan; Akamatsu, Tetsuya; Hosoi, Kazuo

2008-07-01

By chorda tympani denervation (CTD, parasympathectomy), the aquaporin 5 (AQP5), but not AQP1, protein level in the rat submandibular gland (SMG) was significantly decreased, dropping to 37% of that of the contralateral gland at 4 wk. The protein levels of AQP5 and AQP1 were not significantly affected by denervation of the cervical sympathetic trunk (sympathectomy). Administration of cevimeline hydrochloride, an M3 muscarinic receptor agonist (10 mg/kg for 7 days po), but not pilocarpine (0.3 mg/kg for 7 days po), recovered the AQP5 protein level reduced by CTD and increased the AQP1 protein level above the control one. The mRNA level of AQP5 was scarcely affected by CTD and cevimeline hydrochloride administration. Administration of chloroquine (50 mg/kg for 7 days po), a denaturant of lysosomes, increased the AQP5 protein level reduced by CTD. An extract obtained from the submandibular lysosomal fraction degraded the AQP5 protein in the total membrane fraction in vitro. These results suggest the possible regulation of the AQP5 protein level in the SMG by the parasympathetic nerves/M3 muscarinic receptor agonist and imply the involvement of lysosomal enzymes, but not a transcriptional mechanism, in this regulation.

Tubular Crystals and Helical Arrays: Structural Determination of HIV-1 Capsid Assemblies Using Iterative Helical Real-Space Reconstruction

PubMed Central

Zhang, Peijun; Meng, Xin; Zhao, Gongpu

2013-01-01

Helical structures are important in many different life forms and are well-suited for structural studies by cryo-EM. A unique feature of helical objects is that a single projection image contains all the views needed to perform a three-dimensional (3D) crystallographic reconstruction. Here, we use HIV-1 capsid assemblies to illustrate the detailed approaches to obtain 3D density maps from helical objects. Mature HIV-1 particles contain a conical- or tubular-shaped capsid that encloses the viral RNA genome and performs essential functions in the virus life cycle. The capsid is composed of capsid protein (CA) oligomers which are helically arranged on the surface. The N-terminal domain (NTD) of CA is connected to its C-terminal domain (CTD) through a flexible hinge. Structural analysis of two- and three-dimensional crystals provided molecular models of the capsid protein (CA) and its oligomer forms. We determined the 3D density map of helically assembled HIV-1 CA hexamers at 16 Å resolution using an iterative helical real-space reconstruction method. Docking of atomic models of CA-NTD and CA-CTD dimer into the electron density map indicated that the CTD dimer interface is retained in the assembled CA. Furthermore, molecular docking revealed an additional, novel CTD trimer interface. PMID:23132072

Randomized interpolative decomposition of separated representations

NASA Astrophysics Data System (ADS)

Biagioni, David J.; Beylkin, Daniel; Beylkin, Gregory

2015-01-01

We introduce an algorithm to compute tensor interpolative decomposition (dubbed CTD-ID) for the reduction of the separation rank of Canonical Tensor Decompositions (CTDs). Tensor ID selects, for a user-defined accuracy ɛ, a near optimal subset of terms of a CTD to represent the remaining terms via a linear combination of the selected terms. CTD-ID can be used as an alternative to or in combination with the Alternating Least Squares (ALS) algorithm. We present examples of its use within a convergent iteration to compute inverse operators in high dimensions. We also briefly discuss the spectral norm as a computational alternative to the Frobenius norm in estimating approximation errors of tensor ID. We reduce the problem of finding tensor IDs to that of constructing interpolative decompositions of certain matrices. These matrices are generated via randomized projection of the terms of the given tensor. We provide cost estimates and several examples of the new approach to the reduction of separation rank.

Akt phosphorylation regulates the tumour-suppressor merlin through ubiquitination and degradation.

PubMed

Tang, Xiaoling; Jang, Sung-Wuk; Wang, Xuerong; Liu, Zhixue; Bahr, Scott M; Sun, Shi-Yong; Brat, Daniel; Gutmann, David H; Ye, Keqiang

2007-10-01

The neurofibromatosis-2 (NF2) tumour-suppressor gene encodes an intracellular membrane-associated protein, called merlin, whose growth-suppressive function is dependent on its ability to form interactions through its intramolecular amino-terminal domain (NTD) and carboxy-terminal domain (CTD). Merlin phosphorylation plays a critical part in dictating merlin NTD/CTD interactions as well as in controlling binding to its effector proteins. Merlin is partially regulated by phosphorylation of Ser 518, such that hyperphosphorylated merlin is inactive and fails to form productive intramolecular and intermolecular interactions. Here, we show that the protein kinase Akt directly binds to and phosphorylates merlin on residues Thr 230 and Ser 315, which abolishes merlin NTD/CTD interactions and binding to merlin's effector protein PIKE-L and other binding partners. Furthermore, Akt-mediated phosphorylation leads to merlin degradation by ubiquitination. These studies demonstrate that Akt-mediated merlin phosphorylation regulates the function of merlin in the absence of an inactivating mutation.

The C-Terminal Domain of Nrf1 Negatively Regulates the Full-Length CNC-bZIP Factor and Its Shorter Isoform LCR-F1/Nrf1β; Both Are Also Inhibited by the Small Dominant-Negative Nrf1γ/δ Isoforms that Down-Regulate ARE-Battery Gene Expression

PubMed Central

Zhang, Yiguo; Qiu, Lu; Li, Shaojun; Xiang, Yuancai; Chen, Jiayu; Ren, Yonggang

2014-01-01

The C-terminal domain (CTD, aa 686–741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ. PMID:25290918

Properties of Two Carbon Composite Materials Using LTM25 Epoxy Resin

NASA Technical Reports Server (NTRS)

Cruz, Juan R.; Shah, C. H.; Postyn, A. S.

1996-01-01

In this report, the properties of two carbon-epoxy prepreg materials are presented. The epoxy resin used in these two materials can yield lower manufacturing costs due to its low initial cure temperature, and the capability of being cured using vacuum pressure only. The two materials selected for this study are MR50/LTM25, and CFS003/LTM25 with Amoco T300 fiber; both prepregs are manufactured by The Advanced Composites Group. MR50/LTM25 is a unidirectional prepreg tape using Mitsubishi MR50 carbon fiber impregnated with LTM25 epoxy resin. CRS003/LTM25 is a 2 by 2 twill fabric using Amoco T300 fiber and impregnated with LTM25 epoxy resin. Among the properties presented in this report are strength, stiffness, bolt bearing, and damage tolerance. Many of these properties were obtained at three environmental conditions: cold temperature/dry (CTD), room temperature/dry (RTD), and elevated temperature/wet (ETW). A few properties were obtained at room temperature/wet (RTW), and elevated temperature/dry (ETD). The cold and elevated temperatures used for testing were -125 F and 180 F, respectively. In addition, several properties related to processing are presented.

Sustaining observations in the polar oceans.

PubMed

Abrahamsen, E P

2014-09-28

Polar oceans present a unique set of challenges to sustained observations. Sea ice cover restricts navigation for ships and autonomous measurement platforms alike, and icebergs present a hazard to instruments deployed in the upper ocean and in shelf seas. However, the important role of the poles in the global ocean circulation provides ample justification for sustained observations in these regions, both to monitor the rapid changes taking place, and to better understand climate processes in these traditionally poorly sampled areas. In the past, the vast majority of polar measurements took place in the summer. In recent years, novel techniques such as miniature CTD (conductivity-temperature-depth) tags carried by seals have provided an explosion in year-round measurements in areas largely inaccessible to ships, and, as ice avoidance is added to autonomous profiling floats and gliders, these promise to provide further enhancements to observing systems. In addition, remote sensing provides vital information about changes taking place in sea ice cover at both poles. To make these observations sustainable into the future, improved international coordination and collaboration is necessary to gain optimum utilization of observing networks. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Salt Plug Formation Caused by Decreased River Discharge in a Multi-channel Estuary

PubMed Central

Shaha, Dinesh Chandra; Cho, Yang-Ki

2016-01-01

Freshwater input to estuaries may be greatly altered by the river barrages required to meet human needs for drinking water and irrigation and prevent salt water intrusion. Prior studies have examined the salt plugs associated with evaporation and salt outwelling from tidal salt flats in single-channel estuaries. In this work, we discovered a new type of salt plug formation in the multi-channel Pasur River Estuary (PRE) caused by decreasing river discharges resulting from an upstream barrage. The formation of a salt plug in response to changes in river discharge was investigated using a conductivity-temperature-depth (CTD) recorder during spring and neap tides in the dry and wet seasons in 2014. An exportation of saline water from the Shibsa River Estuary (SRE) to the PRE through the Chunkhuri Channel occurred during the dry season, and a salt plug was created and persisted from December to June near Chalna in the PRE. A discharge-induced, relatively high water level in the PRE during the wet season exerted hydrostatic pressure towards the SRE from the PRE and thereby prevented the intrusion of salt water from the SRE to the PRE. PMID:27255892

Synoptic eddy-resolving Ocean Surveys over the Slope of the Chukchi Sea 2016 and 2017

NASA Astrophysics Data System (ADS)

Muenchow, A.; Elmer, C.; Badiey, M.; Eickmeier, J.; Ryan, P. A.

2017-12-01

Mild weather and warm waters kept the outer continental shelf of the Chukchi Sea ice-free in 2016 when we conducted ocean surveys as part of the Canada Basin Acoustic Propagation Experiment (CANAPE). We used standard CTD and ADCP profiling systems aboard R/V Sikuliaq to describe ocean density and velocity fields at 3 km scales across and 6 km scales along the slope. Our survey covers 800 km2between the 100-m and 400-m isobaths and resolves the internal Rossby radius of deformation which represents the dominant spatial (or eddy) scale for a density-stratified ocean. Our early November 2016 data revealed Bering Sea Summer Waters with temperatures exceeding 1.0 C at 80-m depth near the 200-m isobath. Three-dimensional distribution of this water and associated density gradients suggests a current to the east. The flow is likely unstable, we speculate, because it spawns eddy-like features that we will describe. We will test this hypothesis with ocean current shear estimated from vessel-mounted ADCP profiles. A similar survey is planned for October 2017, when USCGC Healy will re-visit the area to recover ocean moorings deployed prior to the 2016 surveys.

Molecular determinants of tetramerization in the KcsA cytoplasmic domain.

PubMed

Kamnesky, Guy; Hirschhorn, Orel; Shaked, Hadassa; Chen, Jingfei; Yao, Lishan; Chill, Jordan H

2014-10-01

The cytoplasmic C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is an amphiphilic domain that forms a helical bundle with four-fold symmetry mediated by hydrophobic and electrostatic interactions. Previously we have established that a CTD-derived 34-residue peptide associates into a tetramer in a pH-dependent manner (Kamnesky et al., JMB 2012;418:237-247). Here we further investigate the molecular determinants of tetramer formation in the CTD by characterizing the kinetics of monomer-tetramer equilibrium for 10 alanine mutants using NMR, sedimentation equilibrium (SE) and molecular dynamics simulation. NMR and SE concur in finding single-residue contributions to tetramer stability to be in the 0.5 to 3.5 kcal/mol range. Hydrophobic interactions between residues lining the tetramer core generally contributed more to formation of tetramer than electrostatic interactions between residues R147, D149 and E152. In particular, alanine replacement of residue R147, a key contributor to inter-subunit salt bridges, resulted in only a minor effect on tetramer dissociation. Mutations outside of the inter-subunit interface also influenced tetramer stability by affecting the tetramerization on-rate, possibly by changing the inherent helical propensity of the peptide. These findings are interpreted in the context of established paradigms of protein-protein interactions and protein folding, and lay the groundwork for further studies of the CTD in full-length KcsA channels. © 2014 The Protein Society.

Molecular determinants of tetramerization in the KcsA cytoplasmic domain

PubMed Central

Kamnesky, Guy; Hirschhorn, Orel; Shaked, Hadassa; Chen, Jingfei; Yao, Lishan; Chill, Jordan H

2014-01-01

The cytoplasmic C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is an amphiphilic domain that forms a helical bundle with four-fold symmetry mediated by hydrophobic and electrostatic interactions. Previously we have established that a CTD-derived 34-residue peptide associates into a tetramer in a pH-dependent manner (Kamnesky et al., JMB 2012;418:237-247). Here we further investigate the molecular determinants of tetramer formation in the CTD by characterizing the kinetics of monomer-tetramer equilibrium for 10 alanine mutants using NMR, sedimentation equilibrium (SE) and molecular dynamics simulation. NMR and SE concur in finding single-residue contributions to tetramer stability to be in the 0.5 to 3.5 kcal/mol range. Hydrophobic interactions between residues lining the tetramer core generally contributed more to formation of tetramer than electrostatic interactions between residues R147, D149 and E152. In particular, alanine replacement of residue R147, a key contributor to inter-subunit salt bridges, resulted in only a minor effect on tetramer dissociation. Mutations outside of the inter-subunit interface also influenced tetramer stability by affecting the tetramerization on-rate, possibly by changing the inherent helical propensity of the peptide. These findings are interpreted in the context of established paradigms of protein-protein interactions and protein folding, and lay the groundwork for further studies of the CTD in full-length KcsA channels. PMID:25042120

The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes.

PubMed

Fletcher, Katherine; Ulferts, Rachel; Jacquin, Elise; Veith, Talitha; Gammoh, Noor; Arasteh, Julia M; Mayer, Ulrike; Carding, Simon R; Wileman, Thomas; Beale, Rupert; Florey, Oliver

2018-02-15

A hallmark of macroautophagy is the covalent lipidation of LC3 and insertion into the double-membrane phagophore, which is driven by the ATG16L1/ATG5-ATG12 complex. In contrast, non-canonical autophagy is a pathway through which LC3 is lipidated and inserted into single membranes, particularly endolysosomal vacuoles during cell engulfment events such as LC3-associated phagocytosis. Factors controlling the targeting of ATG16L1 to phagophores are dispensable for non-canonical autophagy, for which the mechanism of ATG16L1 recruitment is unknown. Here we show that the WD repeat-containing C-terminal domain (WD40 CTD) of ATG16L1 is essential for LC3 recruitment to endolysosomal membranes during non-canonical autophagy, but dispensable for canonical autophagy. Using this strategy to inhibit non-canonical autophagy specifically, we show a reduction of MHC class II antigen presentation in dendritic cells from mice lacking the WD40 CTD Further, we demonstrate activation of non-canonical autophagy dependent on the WD40 CTD during influenza A virus infection. This suggests dependence on WD40 CTD distinguishes between macroautophagy and non-canonical use of autophagy machinery. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

NOAEL-dose of a neonicotinoid pesticide, clothianidin, acutely induce anxiety-related behavior with human-audible vocalizations in male mice in a novel environment.

PubMed

Hirano, Tetsushi; Yanai, Shogo; Takada, Tadashi; Yoneda, Naoki; Omotehara, Takuya; Kubota, Naoto; Minami, Kiichi; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

2018-01-05

Neonicotinoids are novel systemic pesticides acting as agonists on the nicotinic acetylcholine receptors (nAChRs) of insects. Experimental studies have revealed that neonicotinoids pose potential risks for the nervous systems of non-target species, but the brain regions responsible for their behavioral effects remain incompletely understood. This study aimed to assess the neurobehavioral effects of clothianidin (CTD), a later neonicotinoid developed in 2001 and widely used worldwide, and to explore the target regions of neonicotinoids in the mammalian brain. A single-administration of 5 or 50mg/kg CTD to male C57BL/6N mice at or below the no-observed-adverse-effect level (NOAEL) induced an acute increase in anxiety during the elevated plus-maze test. In addition, mice in the CTD-administered group spontaneously emitted human-audible vocalizations (4-16kHz), which are behavioral signs of aversive emotions, and showed increased numbers of c-fos immunoreactive cells in the paraventricular thalamic nucleus and dentate gyrus of the hippocampus. In conclusion, mice exposed to NOAEL-dose CTD would be rendered vulnerable to a novel environment via the activation of thalamic and hippocampal regions related to stress responses. These findings should provide critical insight into the neurobehavioral effects of neonicotinoids on mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

The curation paradigm and application tool used for manual curation of the scientific literature at the Comparative Toxicogenomics Database

PubMed Central

Davis, Allan Peter; Wiegers, Thomas C.; Murphy, Cynthia G.; Mattingly, Carolyn J.

2011-01-01

The Comparative Toxicogenomics Database (CTD) is a public resource that promotes understanding about the effects of environmental chemicals on human health. CTD biocurators read the scientific literature and convert free-text information into a structured format using official nomenclature, integrating third party controlled vocabularies for chemicals, genes, diseases and organisms, and a novel controlled vocabulary for molecular interactions. Manual curation produces a robust, richly annotated dataset of highly accurate and detailed information. Currently, CTD describes over 349 000 molecular interactions between 6800 chemicals, 20 900 genes (for 330 organisms) and 4300 diseases that have been manually curated from over 25 400 peer-reviewed articles. This manually curated data are further integrated with other third party data (e.g. Gene Ontology, KEGG and Reactome annotations) to generate a wealth of toxicogenomic relationships. Here, we describe our approach to manual curation that uses a powerful and efficient paradigm involving mnemonic codes. This strategy allows biocurators to quickly capture detailed information from articles by generating simple statements using codes to represent the relationships between data types. The paradigm is versatile, expandable, and able to accommodate new data challenges that arise. We have incorporated this strategy into a web-based curation tool to further increase efficiency and productivity, implement quality control in real-time and accommodate biocurators working remotely. Database URL: http://ctd.mdibl.org PMID:21933848

Spacing requirements for interactions between the C-terminal domain of the alpha subunit of Escherichia coli RNA polymerase and the cAMP receptor protein.

PubMed Central

Lloyd, G S; Busby, S J; Savery, N J

1998-01-01

During transcription initiation at bacterial promoters, the C-terminal domain of the RNA polymerase alpha subunit (alphaCTD) can interact with DNA-sequence elements (known as UP elements) and with activator proteins. We have constructed a series of semi-synthetic promoters carrying both an UP element and a consensus DNA-binding site for the Escherichia coli cAMP receptor protein (CRP; a factor that activates transcription by making direct contacts with alphaCTD). At these promoters, the UP element was located at a variety of distances upstream of the CRP-binding site, which was fixed at position -41.5 bp upstream of the transcript start. At some positions, the UP element caused enhanced promoter activity whereas, at other positions, it had very little effect. In no case was the CRP-dependence of the promoter relieved. DNase I and hydroxyl-radical footprinting were used to study ternary RNA polymerase-CRP-promoter complexes formed at two of the most active of these promoters, and co-operativity between the binding of CRP and purified alpha subunits was studied. The footprints show that alphaCTD binds to the UP element as it is displaced upstream but that this displacement does not prevent alphaCTD from being contacted by CRP. Models to account for this are discussed. PMID:9461538

Deep inflow into the Mozambique Basin

NASA Astrophysics Data System (ADS)

Read, J. F.; Pollard, R. T.

1999-02-01

More than 200 conductivity-temperature-depth (CTD) stations were worked around the Southwest Indian Ridge and Del Caño Rise as part of the World Ocean Circulation Experiment. A selection of these data provides information about the inflow of bottom water into the Mozambique Basin. The basin is closed below 3000 m, yet the inflow is significantly large, of order 1 Sv (1 Sv = 106 m3 s-1). Estimates of the basin-scale upwelling at 4000 m suggest that the vertical velocity is also large, 10 × 10-5 cm s-1 or more, an order of magnitude greater than global ocean estimates. Examination of the characteristics of the bottom water in the Mozambique and Agulhas Basins and the Prince Edward Fracture Zone shows that bottom water enters the Mozambique Basin from the Agulhas Basin and also directly from the Enderby Basin. Most of the transport enters the Mozambique Basin via the Agulhas Basin, where two regions of northward flow below 4000 m are found. The major flow, on the eastern flank of the Mozambique Ridge, is through and above the deep, extending (5900 m) trench that connects the Agulhas and Mozambique Basins. The second, weaker flow enters the Transkei Basin along the deep eastern flank of the Agulhas Plateau, then turning east into the Mozambique Basin. The only source of bottom water to the Agulhas Basin is the Enderby Basin, but a more direct route between the Enderby and Mozambique Basins exists via the Prince Edward fracture, which extends deeper than 4000 m throughout its length and links the two basins directly across the Southwest Indian Ridge. Full depth CTD stations trace the changing characteristics of the deep and bottom water in the fracture, and moored current meter data show the strength and persistence of the throughflow. Strong mixing with the overlying deep water elevates the salt content of the bottom water by comparison with the other water in the Mozambique Basin. Thus two distinct bottom waters of the Mozambique Basin originate in the same place (the Enderby Basin), and their different characteristics are solely a function of the routes they have taken and the processes encountered along the different pathways.

Significant discharge of CO2 from hydrothermalism associated with the submarine volcano of El Hierro Island

NASA Astrophysics Data System (ADS)

Santana-Casiano, J. M.; Fraile-Nuez, E.; González-Dávila, M.; Baker, E. T.; Resing, J. A.; Walker, S. L.

2016-05-01

The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 105 ± 1.1 105 kg d-1 which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%.

Significant discharge of CO2 from hydrothermalism associated with the submarine volcano of El Hierro Island.

PubMed

Santana-Casiano, J M; Fraile-Nuez, E; González-Dávila, M; Baker, E T; Resing, J A; Walker, S L

2016-05-09

The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 10(5) ± 1.1 10(5 )kg d(-1) which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%.

Significant discharge of CO2 from hydrothermalism associated with the submarine volcano of El Hierro Island

PubMed Central

Santana-Casiano, J. M.; Fraile-Nuez, E.; González-Dávila, M.; Baker, E. T.; Resing, J. A.; Walker, S. L.

2016-01-01

The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 105 ± 1.1 105 kg d−1 which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%. PMID:27157062

First oceanographic observations on the Wandel Sea shelf in Northeast Greenland: Tracing the Arctic Ocean outflow through the western Fram Strait

NASA Astrophysics Data System (ADS)

Dmitrenko, Igor A.; Kirillov, Sergei A.; Rudels, Bert; Babb, David G.; Pedersen, Leif T.; Rysgaard, Soeren; Kristoffersen, Yngve; Barber, David G.

2016-04-01

The first-ever conductivity-temperature-depth (CTD) observations on the Wandel Sea shelf in North Eastern Greenland were collected from the land-fast ice in April-May 2015 as a part of the Arctic Science Partnership collaboration during the first research campaign at the Villum Research Station. They were complemented by (i) the ice-tethered profiler (ITP) and Acoustic Dopler Current Profiler (ADCP) mooring observations in ~300 m of the tidewater glacier outlet from the Flade Isblink Ice Cap and (ii) CTDs taken in June-July 2015 along the Wandel Sea continental slope during the Norwegian FRAM 2014-15 sea ice drift. The CTD profiles deeper than 100 m are used to reveal the origin of water masses and determine the extent to which these water masses have interacted with ambient water from the continental slope. The subsurface water layer from ~20-70 m depth is comprised of freshened water (30-32 psu) that is likely associated with the Pacific Water outflow from the Arctic Ocean through the western Fram Strait. The underlying halocline layer centered at ~80 m (~33 psu) separates the Pacific Water layer from a deeper (<140 m) layer of modified Polar Water that has interacted with the warm Atlantic Water outflow through Fram Strait. The Atlantic Water layer with temperature above 0°C is recorded below 140 m. Over the outer shelf, the halocline layer shows numerous cold density-compensated intrusions indicating lateral interaction with an ambient Polar Water mass across the continental slope. Mooring data shows an enhanced shelf-slope interaction responding the storm event in 23-24 April 2015 with northerly winds exceeding 10 m/s. The on-shelf transport of a cold and turbid water from the upper continental slope results in enhanced interleaving within the depth range of the halocline layer (~70-100 m). Our observations of Pacific Water in the Wandel Sea subsurface layer are set in the context of upstream observations in the Beaufort Sea for 2002-2011 and downstream observations from the Northeast Water Polynya (1992-1993), and clearly show the modification of Pacific Water during its advection across the Arctic Ocean from the Bering Strait to Fram Strait. Moreover, the Wandel Sea shelf and continental slope water shows a different water mass structure indicating the different origin and pathways of the on-shore and off-shore branches of the Arctic Ocean outflow through the Western Fram Strait.

Upper ocean mixing processes and their impact on the mixed layer heat balance during the onset of the Atlantic Cold Tongue.

NASA Astrophysics Data System (ADS)

Dengler, M.; Brandt, P.; McPhaden, M. J.; Thomsen, S.; Krahmann, G.; Fischer, T.; Freitag, P.; Hummels, R.

2012-04-01

An extensive measurement program within the Atlantic Cold Tongue (ACT) region was carried out during the ACT onset in boreal summer 2011. During two consecutive cruises shipboard microstructure profiles, conductivity-temperature-depth-O2 (CTD-O2) profiles and shipboard velocity profiles were collected between mid-May and mid-July. The shipboard measurements were complemented by a Glider swarm experiment during which 5400 CTD-O2 profiles were collected along specified transects within the ACT region. One of those Gliders was equipped with a MicroRider turbulence package and collected a 5-week microstructure time series of about hourly-resolution in the center of the cold tongue on the equator at 10°W. The MicroRider/Glider package was circling a PIRATA mooring from which additionally high-resolution acoustic Doppler current profiles are available for this time period to allow analysis of the background conditions. In this contribution we use a subset from the above data to detail mixing processes in the upper stratified ocean and describe the background conditions favoring enhanced mixing. From end of May to mid-July, sea surface temperature decreased from 26°C to below 22°C at 10°W. During the whole period of autonomous microstructure observations, strong bursts of turbulence were observed extending from the mixed layer into the upper thermocline. These bursts lasted for 3-5 hours and were found to penetrate to about 30m below the base of the mixed layer. They were observed to occur predominately during night-time while during day-time they were less frequent. Dissipation rates of turbulent kinetic energy (ɛ) during these bursts were above 3x10-6Wkg-1 in the upper stratified water column and turbulent eddy diffusivities (Kρ) often reached 1x10-3m2s-1. The data set suggests that strength and frequency of occurrence of the turbulent bursts is modulated by the presents of Tropical Instability Waves which additionally enhance background shear at the equator. The presents of internal waves having frequencies close to the buoyancy frequency during enhanced mixing events will be discussed. From the first 6 days of microstructure data, a diapycnal heat flux divergence from the mixed layer into the upper stratified ocean of 80Wm-2 was inferred. Other contributions to the mixed layer heat balance will be examined to evaluate their relevance during ACT onset.

Generating Gene Ontology-Disease Inferences to Explore Mechanisms of Human Disease at the Comparative Toxicogenomics Database

PubMed Central

Davis, Allan Peter; Wiegers, Thomas C.; King, Benjamin L.; Wiegers, Jolene; Grondin, Cynthia J.; Sciaky, Daniela; Johnson, Robin J.; Mattingly, Carolyn J.

2016-01-01

Strategies for discovering common molecular events among disparate diseases hold promise for improving understanding of disease etiology and expanding treatment options. One technique is to leverage curated datasets found in the public domain. The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) manually curates chemical-gene, chemical-disease, and gene-disease interactions from the scientific literature. The use of official gene symbols in CTD interactions enables this information to be combined with the Gene Ontology (GO) file from NCBI Gene. By integrating these GO-gene annotations with CTD’s gene-disease dataset, we produce 753,000 inferences between 15,700 GO terms and 4,200 diseases, providing opportunities to explore presumptive molecular underpinnings of diseases and identify biological similarities. Through a variety of applications, we demonstrate the utility of this novel resource. As a proof-of-concept, we first analyze known repositioned drugs (e.g., raloxifene and sildenafil) and see that their target diseases have a greater degree of similarity when comparing GO terms vs. genes. Next, a computational analysis predicts seemingly non-intuitive diseases (e.g., stomach ulcers and atherosclerosis) as being similar to bipolar disorder, and these are validated in the literature as reported co-diseases. Additionally, we leverage other CTD content to develop testable hypotheses about thalidomide-gene networks to treat seemingly disparate diseases. Finally, we illustrate how CTD tools can rank a series of drugs as potential candidates for repositioning against B-cell chronic lymphocytic leukemia and predict cisplatin and the small molecule inhibitor JQ1 as lead compounds. The CTD dataset is freely available for users to navigate pathologies within the context of extensive biological processes, molecular functions, and cellular components conferred by GO. This inference set should aid researchers, bioinformaticists, and pharmaceutical drug makers in finding commonalities in disease mechanisms, which in turn could help identify new therapeutics, new indications for existing pharmaceuticals, potential disease comorbidities, and alerts for side effects. PMID:27171405

The Binding of Plasmodium falciparum Adhesins and Erythrocyte Invasion Proteins to Aldolase Is Enhanced by Phosphorylation.

PubMed

Diaz, Suraya A; Martin, Stephen R; Howell, Steven A; Grainger, Munira; Moon, Robert W; Green, Judith L; Holder, Anthony A

2016-01-01

Aldolase has been implicated as a protein coupling the actomyosin motor and cell surface adhesins involved in motility and host cell invasion in the human malaria parasite Plasmodium falciparum. It binds to the cytoplasmic domain (CTD) of type 1 membrane proteins of the thrombospondin-related anonymous protein (TRAP) family. Other type 1 membrane proteins located in the apical organelles of merozoites, the form of the parasite that invades red blood cells, including apical membrane antigen 1 (AMA1) and members of the erythrocyte binding ligand (EBL) and reticulocyte binding homologue (RH) protein families have been implicated in host cell binding and invasion. Using a direct binding method we confirm that TRAP and merozoite TRAP (MTRAP) bind aldolase and show that the interaction is mediated by more than just the C-terminal six amino acid residues identified previously. Single amino acid substitutions in the MTRAP CTD abolished binding to aldolase. The CTDs of AMA1 and members of the EBL and RH protein families also bound to aldolase. MTRAP competed with AMA1 and RH4 for binding to aldolase, indicating overlapping binding sites. MTRAP CTD was phosphorylated in vitro by both calcium dependent kinase 1 (CDPK1) and protein kinase A, and this modification increased the affinity of binding to aldolase by ten-fold. Phosphorylation of the CTD of members of the EBL and RH protein families also increased their affinity for aldolase in some cases. To examine whether or not MTRAP expressed in asexual blood stage parasites is phosphorylated, it was tagged with GFP, purified and analysed, however no phosphorylation was detected. We propose that CTD binding to aldolase may be dynamically modulated by phosphorylation, and there may be competition for aldolase binding between different CTDs. The use and efficiency of alternate invasion pathways may be determined by the affinity of adhesins and cell invasion proteins for aldolase, in addition to their host ligand specificity.

Attentional validity effect across the human menstrual cycle varies with basal temperature changes.

PubMed

Beaudoin, Jessica; Marrocco, Richard

2005-03-07

This study examined the correlation between covert attention and basal temperature change during menstrual cycle phase in 22 adult females. Previous work showing beneficial effects of estrogen on working memory led us to hypothesize that attentional function would be facilitated at the apparent time of ovulation. Menstrual phase was determined through questionnaires and objective measurements of basal body temperature (BBT) spikes over a 1 month period. The cued target detection (CTD) task was used to assess visuospatial attentional performance at three times during the menstrual cycle. The mean reaction times (RTs) to visual targets were measured as a function of menstrual cycle phase, cue type and target location. As predicted, the onset of ovulation showed decreased reaction times and a significant increase in the cue validity effect on the days immediately preceding and following ovulation. The magnitude of the attention validity effect was negatively correlated with the basal temperature rise. Women lacking basal temperature shifts failed to show these changes. Results support the conclusion that the natural fluctuations of body temperature, and possibly reproductive hormones, during the menstrual cycle may enhance the attentional component of cognitive performance.

Structure and variability of the Western Maine Coastal Current

USGS Publications Warehouse

Churchill, J.H.; Pettigrew, N.R.; Signell, R.P.

2005-01-01

Analyses of CTD and moored current meter data from 1998 and 2000 reveal a number of mechanisms influencing the flow along the western coast of Maine. On occasions, the Eastern Maine Coastal Current extends into the western Gulf of Maine where it takes the form of a deep (order 100 m deep) and broad (order 20 km wide) southwestward flow with geostrophic velocities exceeding 20 cm s -1. This is not a coastally trapped flow, however. In fields of geostrophic velocity, computed from shipboard-CTD data, the core of this current is roughly centered at the 100 m isobath and its onshore edge is no closer than 10 km from the coast. Geostrophic velocity fields also reveal a relatively shallow (order 10 m deep) baroclinic flow adjacent to the coast. This flow is also directed to the southwest and appears to be principally comprised of local river discharge. Analyses of moored current meter data reveal wind-driven modulations of the coastal flow that are consistent with expectations from simple theoretical models. However, a large fraction of the near-shore current variance does not appear to be directly related to wind forcing. Sea-surface temperature imagery, combined with analysis of the moored current meter data, suggests that eddies and meanders within the coastal flow may at times dominate the near-shore current variance. ?? 2005 Elsevier Ltd. All rights reserved.

Buoy observation for typhoon in southeast of Taiwan during summers of 2015 and 2016

NASA Astrophysics Data System (ADS)

Hsieh, C. Y.; Yang, Y. J.; Chang, M. H.; Chang, H. I.; Jan, S.; Wei, C. L.

2016-12-01

The western North Pacific is the most active area for the typhoon in the world, and typhoon caused disasters in this area. The marine observations are very important for the typhoon prediction. National Taiwan University (NTU) was developed a real-time data buoy system for typhoon observation. This buoy not only collected meteorological data, but also measured the temperature and salinity profiles of ocean's upper 500 m. The buoys, NTU1 and NTU2, were moored about 375 km and 175 km, respectively, from the southernmost tip of Taiwan. In summer of 2015, NTU1 buoy equipped with temperature and humidity probes, wind sensor, pyranometer, barometer, conductivity-temperature-depth (CTD) recorders, and temperature-pressure recorders. In summer of 2016, NTU1 and NTU2 buoys installed more instruments, such as rain gauge, net radiometer, and current meter, etc. During the observation period, there were three typhoons (Chan-hom, Soudler, and Goni) in 2015 and one typhoon (Nepartak) in 2016 approached buoy. Goni passed south and west side of NTU1 and the air pressure dropped around 25 hPa. Nepartak passed north side of NTU1 and south side of NTU2. The minimum distance between center of typhoon and NTU1 and NTU2 were about 11.48 km and 4.85 km, respectively. The NTU2 buoy recorded a maximum wind gust of 44 m/s, thickness of mixed layer increased to 120 m, and sea-surface temperature dropped 3 °C. In addition, the typhoon induced the near inertial internal motion for a couple of days. Applied the in-situ data to derive the net heat flux and its variations were from 600 W/m2 to -1000W/m2 during typhoon period. It indicate that the ocean provide energy to typhoon around this area. Moreover, the sum of sensible and latent heat flux calculated from observation data was 4.5 times than satellite-based products.

Solution structure and DNA-binding properties of the C-terminal domain of UvrC from E.coli

PubMed Central

Singh, S.; Folkers, G.E.; Bonvin, A.M.J.J.; Boelens, R.; Wechselberger, R.; Niztayev, A.; Kaptein, R.

2002-01-01

The C-terminal domain of the UvrC protein (UvrC CTD) is essential for 5′ incision in the prokaryotic nucleotide excision repair process. We have determined the three-dimensional structure of the UvrC CTD using heteronuclear NMR techniques. The structure shows two helix–hairpin–helix (HhH) motifs connected by a small connector helix. The UvrC CTD is shown to mediate structure-specific DNA binding. The domain binds to a single-stranded–double-stranded junction DNA, with a strong specificity towards looped duplex DNA that contains at least six unpaired bases per loop (‘bubble DNA’). Using chemical shift perturbation experiments, the DNA-binding surface is mapped to the first hairpin region encompassing the conserved glycine–valine–glycine residues followed by lysine–arginine–arginine, a positively charged surface patch and the second hairpin region consisting of glycine–isoleucine–serine. A model for the protein– DNA complex is proposed that accounts for this specificity. PMID:12426397

Structural analyses of Ca2+/CaM interaction with NaV channel C-termini reveal mechanisms of calcium-dependent regulation

PubMed Central

Wang, Chaojian; Chung, Ben C.; Yan, Haidun; Wang, Hong-Gang; Lee, Seok-Yong; Pitt, Geoffrey S.

2014-01-01

Ca2+ regulates voltage-gated Na+ (NaV) channels and perturbed Ca2+ regulation of NaV function is associated with epilepsy syndromes, autism, and cardiac arrhythmias. Understanding the disease mechanisms, however, has been hindered by a lack of structural information and competing models for how Ca2+ affects NaV channel function. Here, we report the crystal structures of two ternary complexes of a human NaV cytosolic C-terminal domain (CTD), a fibroblast growth factor homologous factor, and Ca2+/calmodulin (Ca2+/CaM). These structures rule out direct binding of Ca2+ to the NaV CTD, and uncover new contacts between CaM and the NaV CTD. Probing these new contacts with biochemical and functional experiments allows us to propose a mechanism by which Ca2+ could regulate NaV channels. Further, our model provides hints towards understanding the molecular basis of the neurologic disorders and cardiac arrhythmias caused by NaV channel mutations. PMID:25232683

Charge Transfer Dissociation of Complex Oligosaccharides: Comparison with Collision-Induced Dissociation and Extreme Ultraviolet Dissociative Photoionization

NASA Astrophysics Data System (ADS)

Ropartz, David; Li, Pengfei; Fanuel, Mathieu; Giuliani, Alexandre; Rogniaux, Hélène; Jackson, Glen P.

2016-10-01

The structural characterization of oligosaccharides still challenges the field of analytical chemistry. Tandem mass spectrometry offers many advantages toward this aim, although the generic fragmentation method (low-energy collision-induced dissociation) shows clear limitations and is often insufficient to retrieve some essential structural information on these molecules. In this work, we present the first application of helium charge transfer dissociation (He-CTD) to characterize the structure of complex oligosaccharides. We compare this method with low-energy collision-induced dissociation and extreme-ultraviolet dissociative photoionization (XUV-DPI), which was shown previously to ensure the successful characterization of complex glycans. Similarly to what could be obtained by XUV-DPI, He-CTD provides a complete description of the investigated structures by producing many informative cross-ring fragments and no ambiguous fragmentation. Unlike XUV-DPI, which is performed at a synchrotron source, He-CTD has the undeniable advantage of being implementable in a conventional benchtop ion trap in a conventional laboratory setting.

Crystal structure of an HIV assembly and maturation switch

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

Wagner, Jonathan M.; Zadrozny, Kaneil K.; Chrustowicz, Jakub

Virus assembly and maturation proceed through the programmed operation of molecular switches, which trigger both local and global structural rearrangements to produce infectious particles. HIV-1 contains an assembly and maturation switch that spans the C-terminal domain (CTD) of the capsid (CA) region and the first spacer peptide (SP1) of the precursor structural protein, Gag. The crystal structure of the CTD-SP1 Gag fragment is a goblet-shaped hexamer in which the cup comprises the CTD and an ensuing type II β-turn, and the stem comprises a 6-helix bundle. The β-turn is critical for immature virus assembly and the 6-helix bundle regulates proteolysismore » during maturation. This bipartite character explains why the SP1 spacer is a critical element of HIV-1 Gag but is not a universal property of retroviruses. Our results also indicate that HIV-1 maturation inhibitors suppress unfolding of the CA-SP1 junction and thereby delay access of the viral protease to its substrate.« less

Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins

PubMed Central

Kang, Hyeog; Oka, Shinichi; Lee, Duck-Yeon; Park, Junhong; Aponte, Angel M.; Jung, Young-Sang; Bitterman, Jacob; Zhai, Peiyong; He, Yi; Kooshapur, Hamed; Ghirlando, Rodolfo; Tjandra, Nico; Lee, Sean B.; Kim, Myung K.; Sadoshima, Junichi; Chung, Jay H.

2017-01-01

Sirt1 is an NAD+-dependent protein deacetylase that regulates many physiological functions, including stress resistance, adipogenesis, cell senescence and energy production. Sirt1 can be activated by energy deprivation, but the mechanism is poorly understood. Here, we report that Sirt1 is negatively regulated by ATP, which binds to the C-terminal domain (CTD) of Sirt1. ATP suppresses Sirt1 activity by impairing the CTD's ability to bind to the deacetylase domain as well as its ability to function as the substrate recruitment site. ATP, but not NAD+, causes a conformational shift to a less compact structure. Mutations that prevent ATP binding increase Sirt1's ability to promote stress resistance and inhibit adipogenesis under high-ATP conditions. Interestingly, the CTD can be attached to other proteins, thereby converting them into energy-regulated proteins. These discoveries provide insight into how extreme energy deprivation can impact Sirt1 activity and underscore the complex nature of Sirt1 structure and regulation. PMID:28504272

MDCT quantification is the dominant parameter in decision–making regarding chest tube drainage for stable patients with traumatic pneumothorax

PubMed Central

Cai, Wenli; Lee, June-Goo; Fikry, Karim; Yoshida, Hiroyuki; Novelline, Robert; de Moya, Marc

2013-01-01

It is commonly believed that the size of a pneumothorax is an important determinant of treatment decision, in particular regarding whether chest tube drainage (CTD) is required. However, the volumetric quantification of pneumothoraces has not routinely been performed in clinics. In this paper, we introduced an automated computer-aided volumetry (CAV) scheme for quantification of volume of pneumothoraces in chest multi-detect CT (MDCT) images. Moreover, we investigated the impact of accurate volume of pneumothoraces in the improvement of the performance in decision-making regarding CTD in the management of traumatic pneumothoraces. For this purpose, an occurrence frequency map was calculated for quantitative analysis of the importance of each clinical parameter in the decision-making regarding CTD by a computer simulation of decision-making using a genetic algorithm (GA) and a support vector machine (SVM). A total of 14 clinical parameters, including volume of pneumothorax calculated by our CAV scheme, was collected as parameters available for decision-making. The results showed that volume was the dominant parameter in decision-making regarding CTD, with an occurrence frequency value of 1.00. The results also indicated that the inclusion of volume provided the best performance that was statistically significant compared to the other tests in which volume was excluded from the clinical parameters. This study provides the scientific evidence for the application of CAV scheme in MDCT volumetric quantification of pneumothoraces in the management of clinically stable chest trauma patients with traumatic pneumothorax. PMID:22560899

Mindfulness-based stress reduction for Tourette Syndrome and Chronic Tic Disorder: a pilot study.

PubMed

Reese, Hannah E; Vallejo, Zayda; Rasmussen, Jessica; Crowe, Katherine; Rosenfield, Elizabeth; Wilhelm, Sabine

2015-03-01

In this pilot study we sought to develop and test a modified form of mindfulness-based stress reduction (MBSR-tics) for the treatment of Tourette Syndrome (TS) and Chronic Tic Disorder (CTD). Our specific aims were: 1) To determine the feasibility and acceptability of an 8-week trial of MBSR-tics in individuals 16 and older with TS or CTD and 2) To determine the efficacy of an 8-week trial of MBSR-tics in individuals 16 and older with TS or CTD. Eighteen individuals age 16-67 completed an uncontrolled open trial of MBSR-tics. The intervention consisted of 8 weekly 2-hour classes and one 4hour retreat in the fifth or sixth week of the program. Symptomatic assessments were performed at baseline, post-treatment, and one-month follow-up. MBSR-tics proved to be a feasible and acceptable intervention. It resulted in significant improvement in tic severity and tic-related impairment. 58.8% of subjects were deemed treatment responders. Therapeutic gains were maintained at 1-month follow-up. Improvements in tic severity were correlated with increases in self-reported levels of mindfulness. This small open pilot study provides preliminary support for the feasibility, acceptability, and efficacy of MBSR-tics for individuals 16 or older with TS or CTD. A larger randomized controlled trial with blind assessment is necessary to confirm these initial, promising findings. Trial Registration Partners Clinical Trials Registry Number 2011P000606 (clinicaltrials.partners.org). Copyright © 2014 Elsevier Inc. All rights reserved.

Caenorhabditis elegans fibroblast growth factor receptor signaling can occur independently of the multi-substrate adaptor FRS2.

PubMed

Lo, Te-Wen; Bennett, Daniel C; Goodman, S Jay; Stern, Michael J

2010-06-01

The components of receptor tyrosine kinase signaling complexes help to define the specificity of the effects of their activation. The Caenorhabditis elegans fibroblast growth factor receptor (FGFR), EGL-15, regulates a number of processes, including sex myoblast (SM) migration guidance and fluid homeostasis, both of which require a Grb2/Sos/Ras cassette of signaling components. Here we show that SEM-5/Grb2 can bind directly to EGL-15 to mediate SM chemoattraction. A yeast two-hybrid screen identified SEM-5 as able to interact with the carboxy-terminal domain (CTD) of EGL-15, a domain that is specifically required for SM chemoattraction. This interaction requires the SEM-5 SH2-binding motifs present in the CTD (Y(1009) and Y(1087)), and these sites are required for the CTD role of EGL-15 in SM chemoattraction. SEM-5, but not the SEM-5 binding sites located in the CTD, is required for the fluid homeostasis function of EGL-15, indicating that SEM-5 can link to EGL-15 through an alternative mechanism. The multi-substrate adaptor protein FRS2 serves to link vertebrate FGFRs to Grb2. In C. elegans, an FRS2-like gene, rog-1, functions upstream of a Ras/MAPK pathway for oocyte maturation but is not required for EGL-15 function. Thus, unlike the vertebrate FGFRs, which require the multi-substrate adaptor FRS2 to recruit Grb2, EGL-15 can recruit SEM-5/Grb2 directly.

The combined effect of clothianidin and environmental stress on the behavioral and reproductive function in male mice

PubMed Central

HIRANO, Tetsushi; YANAI, Shogo; OMOTEHARA, Takuya; HASHIMOTO, Rie; UMEMURA, Yuria; KUBOTA, Naoto; MINAMI, Kiichi; NAGAHARA, Daichi; MATSUO, Eiko; AIHARA, Yoshiko; SHINOHARA, Ryota; FURUYASHIKI, Tomoyuki; MANTANI, Youhei; YOKOYAMA, Toshifumi; KITAGAWA, Hiroshi; HOSHI, Nobuhiko

2015-01-01

Neonicotinoids, some of the most widely used pesticides in the world, act as agonists to the nicotinic acetylcholine receptors (nAChRs) of insects, resulting in death from abnormal excitability. Neonicotinoids unexpectedly became a major topic as a compelling cause of honeybee colony collapse disorder, which is damaging crop production that requires pollination worldwide. Mammal nAChRs appear to have a certain affinity for neonicotinoids with lower levels than those of insects; there is thus rising concern about unpredictable adverse effects of neonicotinoids on vertebrates. We hypothesized that the effects of neonicotinoids would be enhanced under a chronic stressed condition, which is known to alter the expression of targets of neonicotinoids, i.e., neuronal nAChRs. We performed immunohistochemical and behavioral analyses in male mice actively administered a neonicotinoid, clothianidin (CTD; 0, 10, 50 and 250 mg/kg/day), for 4 weeks under an unpredictable chronic stress procedure. Vacuolated seminiferous epithelia and a decrease in the immunoreactivity of the antioxidant enzyme glutathione peroxidase 4 were observed in the testes of the CTD+stress mice. In an open field test, although the locomotor activities were not affected, the anxiety-like behaviors of the mice were elevated by both CTD and stress. The present study demonstrates that the behavioral and reproductive effects of CTD become more serious in combination with environmental stress, which may reflect our actual situation of multiple exposure. PMID:25960033

Structural and functional probing of PorZ, an essential bacterial surface component of the type-IX secretion system of human oral-microbiomic Porphyromonas gingivalis.

PubMed Central

Lasica, Anna M.; Goulas, Theodoros; Mizgalska, Danuta; Zhou, Xiaoyan; de Diego, Iñaki; Ksiazek, Mirosław; Madej, Mariusz; Guo, Yonghua; Guevara, Tibisay; Nowak, Magdalena; Potempa, Barbara; Goel, Apoorv; Sztukowska, Maryta; Prabhakar, Apurva T.; Bzowska, Monika; Widziolek, Magdalena; Thøgersen, Ida B.; Enghild, Jan J.; Simonian, Mary; Kulczyk, Arkadiusz W.; Nguyen, Ky-Anh; Potempa, Jan; Gomis-Rüth, F. Xavier

2016-01-01

Porphyromonas gingivalis is a member of the human oral microbiome abundant in dysbiosis and implicated in the pathogenesis of periodontal (gum) disease. It employs a newly described type-IX secretion system (T9SS) for secretion of virulence factors. Cargo proteins destined for secretion through T9SS carry a recognition signal in the conserved C-terminal domain (CTD), which is removed by sortase PorU during translocation. Here, we identified a novel component of T9SS, PorZ, which is essential for surface exposure of PorU and posttranslational modification of T9SS cargo proteins. These include maturation of enzyme precursors, CTD removal and attachment of anionic lipopolysaccharide for anchorage in the outer membrane. The crystal structure of PorZ revealed two β-propeller domains and a C-terminal β-sandwich domain, which conforms to the canonical CTD architecture. We further documented that PorZ is itself transported to the cell surface via T9SS as a full-length protein with its CTD intact, independently of the presence or activity of PorU. Taken together, our results shed light on the architecture and possible function of a novel component of the T9SS. Knowledge of how T9SS operates will contribute to our understanding of protein secretion as part of host-microbiome interactions by dysbiotic members of the human oral cavity. PMID:27883039

Efficacy and toxicity of the combination chemotherapy of thalidomide, alkylating agent, and steroid for relapsed/refractory myeloma patients: a report from the Korean Multiple Myeloma Working Party (KMMWP) retrospective study.

PubMed

Kwon, Jihyun; Min, Chang-Ki; Kim, Kihyun; Han, Jae-Joon; Moon, Joon Ho; Kang, Hye Jin; Eom, Hyeon-Seok; Kim, Min Kyoung; Kim, Hyo Jung; Yoon, Dok Hyun; Lee, Jeong-Ok; Lee, Won Sik; Lee, Jae Hoon; Lee, Je-Jung; Choi, Yoon-Seok; Kim, Sung Hyun; Yoon, Sung-Soo

2017-01-01

We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression-free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Observations of Temperature Finestructure in the Gulf of California. XBT Data Report, November 1984 - March 1985,

DTIC Science & Technology

1985-03-01

99.9 Wapd : 8.8 CTD i: 3 CAPl-16 REREAD ON NH 7 MAR 85 BWW 22 JAN 86 ANC CH:LTMINLGMIN.CW. POS:CRAD PR TE SA SGTH PR TE SA SGTH 2.0 16.60 35.079...7.6 60 16.3 250 10.4 441 7.5 .70 15.9 264 10.3 450 7.4 89 15.5 271 10.2 460 7.4 " 99 15.1 280 9.7 469 7.3 10 14.7 28g 9.4 480 7.2- 110 14.2 366 9.3 4T A...38.5W 9 MAR 85 0828 MST Temperature 2.0 4.9 5.9 8.0 10.9 12.0 14.9 16.9 13.0 29.9 22.9 24.9 26.9 28.9 ISO. 3W0 459 % 1 XBT DROP 264 T-7 RADAR: SE 8.8nm

Mixed layer warming-deepening in the Mediterranean Sea and its effect on the marine environment

NASA Astrophysics Data System (ADS)

Rivetti, Irene; Boero, Ferdinando; Fraschetti, Simonetta; Zambianchi, Enrico; Lionello, Piero

2015-04-01

This work aims at investigating the evolution of the ocean mixed layer in the Mediterranean Sea and linking it to the occurrence of mass mortalities of benthic invertebrates. The temporal evolution of selected parameters describing the mixed layer and the seasonal thermocline is provided for the whole Mediterranean Sea for spring, summer and autumn and for the period 1945-2011. For this analysis all temperature profiles collected in the basin with bottles, Mechanical Bathy-Thermographs (MBT), eXpendable Bathy-Thermographs (XBT), and Conductivity-Temperature-Depth (CTD) have been used (166,990). These data have been extracted from three public sources: the MEDAR-MEDATLAS, the World Ocean Database 2013 and the MFS-VOS program. Five different methods for estimating the mixed layer depth are compared using temperature profiles collected at the DYFAMED station in the Ligurian Sea and one method, the so-called three-segment method, has been selected for a systematic analysis of the evolution of the uppermost part of the whole Mediterranean Sea. This method approximates the upper water column with three segments representing mixed layer, thermocline and deep layer and has shown to be the most suitable method for capturing the mixed layer depth for most shapes of temperature profiles. Mass mortalities events of benthic invertebrates have been identified by an extensive search of all data bases in ISI Web of Knowledge considering studies published from 1945 to 2011. Studies reporting the geographical coordinates, the timing of the events, the species involved and the depth at which signs of stress occurred have been considered. Results show a general increase of thickness and temperature of the mixed layer, deepening and cooling of the thermocline base in summer and autumn. Possible impacts of these changes are mass mortalities events of benthic invertebrates that have been documented since 1983 mainly in summer and autumn. It is also shown that most mass mortalities occurred in months with anomalously high mixed layer depth temperature leading to the conclusion that warming of upper Mediterranean Sea has allowed interannual temperature variability to reach environmental conditions beyond the thermal tolerance of some species.

Unique sail-like structure of cor triatriatum dexter in three-dimensional echocardiogram.

PubMed

Low, Ting Ting; Uy, Celia Catherine C; Wong, Raymond Ching Chiew

2014-08-01

Cor triatriatum dexter (CTD) is an extremely rare congenital condition arising from the persistence of the right valve of the sinus venosus. It divides the right atrium (RA) into 2 separate chambers. We report a case of a 50-year-old man who had an incidental finding of CTD on transesophageal echocardiogram. An incomplete membrane of the RA was seen, and three-dimensional echocardiogram delineated the structure clearly as a triangular sail-like structure with multiple orifices and a fenestration. © 2013, Wiley Periodicals, Inc.

Collaborative Research to Advance Precision Medicine in the Post-Genomic World | Office of Cancer Genomics

Cancer.gov

My name is Subhashini Jagu, and I am the Scientific Program Manager for the Cancer Target Discovery and Development (CTD2) Network at the Office of Cancer Genomics (OCG). In my new role, I help CTD2 work toward its mission, which is to develop new scientific approaches to accelerate the translation of genomic discoveries into new treatments. Collaborative efforts that bring together a variety of expertise and infrastructure are needed to understand and successfully treat cancer, a highly complex disease.

Entitymetrics: Measuring the Impact of Entities

PubMed Central

Ding, Ying; Song, Min; Han, Jia; Yu, Qi; Yan, Erjia; Lin, Lili; Chambers, Tamy

2013-01-01

This paper proposes entitymetrics to measure the impact of knowledge units. Entitymetrics highlight the importance of entities embedded in scientific literature for further knowledge discovery. In this paper, we use Metformin, a drug for diabetes, as an example to form an entity-entity citation network based on literature related to Metformin. We then calculate the network features and compare the centrality ranks of biological entities with results from Comparative Toxicogenomics Database (CTD). The comparison demonstrates the usefulness of entitymetrics to detect most of the outstanding interactions manually curated in CTD. PMID:24009660

Collaborating with the local community of Kullorsuaq, Greenland to obtain high-quality hydrographic measurements near Alison Glacier

NASA Astrophysics Data System (ADS)

Porter, D. F.; Turrin, M.; Tinto, K. J.; Giulivi, C. F.; Cochran, J. R.; Bell, R. E.

2014-12-01

Warming ocean waters around Greenland have been implicated, along with warmer air temperatures, in the rapid increase of melt of the tidewater glaciers that drain the ice sheet. Most available regional oceanographic measurements have been collected during the summer seasons and are concentrated near the largest and most accessible glaciers. In order to gain a more comprehensive picture of the changing environment around the entirety of Greenland, more fjords, especially in the north, must be sampled. In July 2014, we travelled to Kullorsuaq in Northwest Greenland in order to foster a partnership with the local community to obtain new hydrographic data from CTD casts near Alison Glacier (74.6N, 57W). The terminus of this glacier abruptly retreated 10 km between 2000 and 2006. Although adequate observations from that time period are unavailable, our recently collected temperature and salinity data suggests that the deep water near Alison is similar to the waters further south, where near-synchronous ocean warming and glacial acceleration has been documented. Over the course of two sampling days, a hand-operated winch from a small boat was used to make standard CTD casts in front of Alison Glacier. We find evidence of glacial and mélange melt and the signature of both Polar and Atlantic Water masses at depth. Along-fjord casts illustrate how the ocean waters are modified as they circulate in and out of the fjord and the interaction of this water with the melting glacial front. At 500m depths, ocean temperatures are about 3°C above the in-situ freezing point of seawater, suggesting a possible influence of warm ocean waters on the mass loss of Alison Glacier. Using NASA Operation IceBridge and satellite altimetry data, we relate our new hydrographic data to the observed recent changes in Alison Glacier. An additional important result is that this short field campaign uncovered the possibility of working with local Greenlandic communities to aid scientists in both environmental monitoring and scientific discovery. Plans are underway to collaborate with the same and other communities in Greenland to take additional oceanographic measurements throughout the year.

Domain Interaction Studies of Herpes Simplex Virus 1 Tegument Protein UL16 Reveal Its Interaction with Mitochondria

PubMed Central

Chadha, Pooja; Sarfo, Akua; Zhang, Dan; Abraham, Thomas; Carmichael, Jillian

2016-01-01

ABSTRACT The UL16 tegument protein of herpes simplex virus 1 (HSV-1) is conserved among all herpesviruses and plays many roles during replication. This protein has an N-terminal domain (NTD) that has been shown to bind to several viral proteins, including UL11, VP22, and glycoprotein E, and these interactions are negatively regulated by a C-terminal domain (CTD). Thus, in pairwise transfections, UL16 binding is enabled only when the CTD is absent or altered. Based on these results, we hypothesized that direct interactions occur between the NTD and the CTD. Here we report that the separated and coexpressed functional domains of UL16 are mutually responsive to each other in transfected cells and form complexes that are stable enough to be captured in coimmunoprecipitation assays. Moreover, we found that the CTD can associate with itself. To our surprise, the CTD was also found to contain a novel and intrinsic ability to localize to specific spots on mitochondria in transfected cells. Subsequent analyses of HSV-infected cells by immunogold electron microscopy and live-cell confocal imaging revealed a population of UL16 that does not merely accumulate on mitochondria but in fact makes dynamic contacts with these organelles in a time-dependent manner. These findings suggest that the domain interactions of UL16 serve to regulate not just the interaction of this tegument protein with its viral binding partners but also its interactions with mitochondria. The purpose of this novel interaction remains to be determined. IMPORTANCE The HSV-1-encoded tegument protein UL16 is involved in multiple events of the virus replication cycle, ranging from virus assembly to cell-cell spread of the virus, and hence it can serve as an important drug target. Unfortunately, a lack of both structural and functional information limits our understanding of this protein. The discovery of domain interactions within UL16 and the novel ability of UL16 to interact with mitochondria in HSV-infected cells lays a foundational framework for future investigations aimed at deciphering the structure and function of not just UL16 of HSV-1 but also its homologs in other herpesviruses. PMID:27847362

Evaluation of computer-based computer tomography stratification against outcome models in connective tissue disease-related interstitial lung disease: a patient outcome study.

PubMed

Jacob, Joseph; Bartholmai, Brian J; Rajagopalan, Srinivasan; Brun, Anne Laure; Egashira, Ryoko; Karwoski, Ronald; Kokosi, Maria; Wells, Athol U; Hansell, David M

2016-11-23

To evaluate computer-based computer tomography (CT) analysis (CALIPER) against visual CT scoring and pulmonary function tests (PFTs) when predicting mortality in patients with connective tissue disease-related interstitial lung disease (CTD-ILD). To identify outcome differences between distinct CTD-ILD groups derived following automated stratification of CALIPER variables. A total of 203 consecutive patients with assorted CTD-ILDs had CT parenchymal patterns evaluated by CALIPER and visual CT scoring: honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume, emphysema, and traction bronchiectasis. CT scores were evaluated against pulmonary function tests: forced vital capacity, diffusing capacity for carbon monoxide, carbon monoxide transfer coefficient, and composite physiologic index for mortality analysis. Automated stratification of CALIPER-CT variables was evaluated in place of and alongside forced vital capacity and diffusing capacity for carbon monoxide in the ILD gender, age physiology (ILD-GAP) model using receiver operating characteristic curve analysis. Cox regression analyses identified four independent predictors of mortality: patient age (P < 0.0001), smoking history (P = 0.0003), carbon monoxide transfer coefficient (P = 0.003), and pulmonary vessel volume (P < 0.0001). Automated stratification of CALIPER variables identified three morphologically distinct groups which were stronger predictors of mortality than all CT and functional indices. The Stratified-CT model substituted automated stratified groups for functional indices in the ILD-GAP model and maintained model strength (area under curve (AUC) = 0.74, P < 0.0001), ILD-GAP (AUC = 0.72, P < 0.0001). Combining automated stratified groups with the ILD-GAP model (stratified CT-GAP model) strengthened predictions of 1- and 2-year mortality: ILD-GAP (AUC = 0.87 and 0.86, respectively); stratified CT-GAP (AUC = 0.89 and 0.88, respectively). CALIPER-derived pulmonary vessel volume is an independent predictor of mortality across all CTD-ILD patients. Furthermore, automated stratification of CALIPER CT variables represents a novel method of prognostication at least as robust as PFTs in CTD-ILD patients.

Tempest in Vailulu'u Crater

NASA Astrophysics Data System (ADS)

Hart, S. R.; Staudigel, H.; Koppers, A.; Young, C.; Baker, E.

2005-12-01

The summit crater of the Samoan submarine volcano, Vailulu'u, has been actively erupting since 2001. Based on water chemistry, CTD and temperature logger data from 2000 and 2001, we formulated a model for the hydrothermal system in the crater involving a tidally-modulated "breathing" (Staudigel et al., 2004). During low stands of internal waves (exterior to the crater), the crater exhales warm buoyant hydrothermal water that forms a "halo" around the crater rich in Mn, 3He, and particulates. During "high tides", cold dense external water is inhaled into the crater through the three breaches, and cascades to the crater floor. In April 2005, we used the HURL PISCES V submersible to deploy various temperature and particulate loggers and current meters in and around the crater; these were retrieved by Pisces V in July 2005. In addition, continuous CTD profiling was carried out over 12 hour tidal cycles at one location inside, and one outside, the crater. The accumulated data set fully reinforces our "breathing" model. An ADCP, deployed for 93 days in the NW breach at 752m, showed dominant easterly inflow currents and westerly outflow currents, with maximum velocities of approximately 25 cm/s. The flows were coherent for distances up to 50-60m above the ADCP; the mean inflow velocity and azimuth (20-40 m interval above the ADCP) was 7 cm/s due east; the mean outflow velocity and azimuth was 5 cm/s at 260 degrees. Mean inflows were consistently colder than outflows (5.00 C vs 5.20 C); the maximum observed range in temperature was 1.1 C, correlated with peak flow velocities. The coldest inflows would require very large regional internal wave amplitudes, up to 50-100 meters. A 2-D acoustic current meter was deployed on top of the west crater rim summit (582m) for 90 days, and in the S breach (697m) for 4 days. The summit flows are presumed to represent the regional scale currents; these were largely from the SW quadrant, with typical velocities of 8-15 cm/s, and peaks to 25 cm/s. The S breach flows had a clear semi-diurnal tidal modulation, with strong NE quadrant inflows at high velocity (15-30 cm/s), separated by short outflow spikes of 1-2 hour duration at much lower velocity (greater than10 cm/s). The outflow water was typically warmer by 0.1-0.2 C; the maximum temperature range was 0.6 C, about half of that observed at the NW breach. A 12-hour continuous profiling CTD-LBSS station was serendipitously sited on top of a large diffuse-venting hydrothermal field, in the crater moat just north of the new volcanic cone. The water column here was incredibly dynamic, with a 5-10m bottom boundary layer, 1 C above ambient, forming by diffuse flow from the basalt substrate in a matter of minutes; this layer would destabilize, detach, and rise with velocities of ~ 1 cm/sec. This buoyant water was both warmer and less saline than either the ambient crater water, or the cold outside water which occasionally cascaded onto this site from the nearby NW breach; it was also laden with particulates, with LBSS readings up to 1.7 NTU. Water chemistry and He isotope analyses are in progress.

MDCT quantification is the dominant parameter in decision-making regarding chest tube drainage for stable patients with traumatic pneumothorax.

PubMed

Cai, Wenli; Lee, June-Goo; Fikry, Karim; Yoshida, Hiroyuki; Novelline, Robert; de Moya, Marc

2012-07-01

It is commonly believed that the size of a pneumothorax is an important determinant of treatment decision, in particular regarding whether chest tube drainage (CTD) is required. However, the volumetric quantification of pneumothoraces has not routinely been performed in clinics. In this paper, we introduced an automated computer-aided volumetry (CAV) scheme for quantification of volume of pneumothoraces in chest multi-detect CT (MDCT) images. Moreover, we investigated the impact of accurate volume of pneumothoraces in the improvement of the performance in decision-making regarding CTD in the management of traumatic pneumothoraces. For this purpose, an occurrence frequency map was calculated for quantitative analysis of the importance of each clinical parameter in the decision-making regarding CTD by a computer simulation of decision-making using a genetic algorithm (GA) and a support vector machine (SVM). A total of 14 clinical parameters, including volume of pneumothorax calculated by our CAV scheme, was collected as parameters available for decision-making. The results showed that volume was the dominant parameter in decision-making regarding CTD, with an occurrence frequency value of 1.00. The results also indicated that the inclusion of volume provided the best performance that was statistically significant compared to the other tests in which volume was excluded from the clinical parameters. This study provides the scientific evidence for the application of CAV scheme in MDCT volumetric quantification of pneumothoraces in the management of clinically stable chest trauma patients with traumatic pneumothorax. Copyright © 2012 Elsevier Ltd. All rights reserved.

The disordered C-terminal domain of human DNA glycosylase NEIL1 contributes to its stability via intramolecular interactions.

PubMed

Hegde, Muralidhar L; Tsutakawa, Susan E; Hegde, Pavana M; Holthauzen, Luis Marcelo F; Li, Jing; Oezguen, Numan; Hilser, Vincent J; Tainer, John A; Mitra, Sankar

2013-07-10

NEIL1 [Nei (endonuclease VIII)-like protein 1], one of the five mammalian DNA glycosylases that excise oxidized DNA base lesions in the human genome to initiate base excision repair, contains an intrinsically disordered C-terminal domain (CTD; ~100 residues), not conserved in its Escherichia coli prototype Nei. Although dispensable for NEIL1's lesion excision and AP lyase activities, this segment is required for efficient in vivo enzymatic activity and may provide an interaction interface for many of NEIL1's interactions with other base excision repair proteins. Here, we show that the CTD interacts with the folded domain in native NEIL1 containing 389 residues. The CTD is poised for local folding in an ordered structure that is induced in the purified fragment by osmolytes. Furthermore, deletion of the disordered tail lacking both Tyr and Trp residues causes a red shift in NEIL1's intrinsic Trp-specific fluorescence, indicating a more solvent-exposed environment for the Trp residues in the truncated protein, which also exhibits reduced stability compared to the native enzyme. These observations are consistent with stabilization of the native NEIL1 structure via intramolecular, mostly electrostatic, interactions that were disrupted by mutating a positively charged (Lys-rich) cluster of residues (amino acids 355-360) near the C-terminus. Small-angle X-ray scattering (SAXS) analysis confirms the flexibility and dynamic nature of NEIL1's CTD, a feature that may be critical to providing specificity for NEIL1's multiple, functional interactions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication.

PubMed

Thenin-Houssier, Suzie; de Vera, Ian Mitchelle S; Pedro-Rosa, Laura; Brady, Angela; Richard, Audrey; Konnick, Briana; Opp, Silvana; Buffone, Cindy; Fuhrmann, Jakob; Kota, Smitha; Billack, Blase; Pietka-Ottlik, Magdalena; Tellinghuisen, Timothy; Choe, Hyeryun; Spicer, Timothy; Scampavia, Louis; Diaz-Griffero, Felipe; Kojetin, Douglas J; Valente, Susana T

2016-04-01

The human immunodeficiency virus type 1 (HIV-1) capsid plays crucial roles in HIV-1 replication and thus represents an excellent drug target. We developed a high-throughput screening method based on a time-resolved fluorescence resonance energy transfer (HTS-TR-FRET) assay, using the C-terminal domain (CTD) of HIV-1 capsid to identify inhibitors of capsid dimerization. This assay was used to screen a library of pharmacologically active compounds, composed of 1,280in vivo-active drugs, and identified ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], an organoselenium compound, as an inhibitor of HIV-1 capsid CTD dimerization. Nuclear magnetic resonance (NMR) spectroscopic analysis confirmed the direct interaction of ebselen with the HIV-1 capsid CTD and dimer dissociation when ebselen is in 2-fold molar excess. Electrospray ionization mass spectrometry revealed that ebselen covalently binds the HIV-1 capsid CTD, likely via a selenylsulfide linkage with Cys198 and Cys218. This compound presents anti-HIV activity in single and multiple rounds of infection in permissive cell lines as well as in primary peripheral blood mononuclear cells. Ebselen inhibits early viral postentry events of the HIV-1 life cycle by impairing the incoming capsid uncoating process. This compound also blocks infection of other retroviruses, such as Moloney murine leukemia virus and simian immunodeficiency virus, but displays no inhibitory activity against hepatitis C and influenza viruses. This study reports the use of TR-FRET screening to successfully identify a novel capsid inhibitor, ebselen, validating HIV-1 capsid as a promising target for drug development. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Occlusion pressure analysis role in partitioning of pulmonary vascular resistance in CTEPH.

PubMed

Toshner, Mark; Suntharalingam, Jay; Fesler, Pierre; Soon, Elaine; Sheares, Karen K; Jenkins, David; White, Paul; Morrell, Nicholas W; Naeije, Robert; Pepke-Zaba, Joanna

2012-09-01

Flow-directed pulmonary artery occlusion is posited to enable partitioning of vascular resistance into small and large vessels. As such it may have a role in assessment for pulmonary endarterectomy. To test if the occlusion technique distinguished small from large vessel disease we studied 59 subjects with chronic thromboembolic pulmonary hypertension (CTEPH), idiopathic pulmonary arterial hypertension (IPAH), and connective tissue disease (CTD)-associated PAH. At right heart catheterisation, occlusion pressures were recorded. With fitting of the pressure decay curve, pulmonary vascular resistance was partitioned into downstream (small vessels) and upstream (large vessels, Rup). 47 patients completed the study; 14 operable CTEPH, 15 inoperable CTEPH, 13 idiopathic or CTD-PAH and five post-operative CTEPH. There was a significant difference in mean Rup in the proximal operable CTEPH group 87.3 (95% CI 84.1-90.5); inoperable CTEPH mean 75.8 (95% CI 66.76-84.73), p=0.048; and IPAH/CTD, mean 77.1 (95% CI 71.86-82.33), p=0.003. Receiver operating characteristic curves to distinguish operable from inoperable CTEPH demonstrated an area under the curve of 0.75, p=0.0001. A cut-off of 79.3 gave 100% sensitivity (95% CI 73.5-100%) but 57.1% specificity (95% CI 28.9-82.3%). In a subgroup analysis of multiple lobar sampling there was demonstrable heterogeneity. Rup is significantly increased in operable proximal CTEPH compared with non-operable distal CTEPH and IPAH/CTD-PAH. Rup variability in patients with CTEPH and PAH is suggestive of pathophysiological heterogeneity.

Interdomain Contacts Control Native State Switching of RfaH on a Dual-Funneled Landscape

PubMed Central

Ramírez-Sarmiento, César A.; Noel, Jeffrey K.; Valenzuela, Sandro L.; Artsimovitch, Irina

2015-01-01

RfaH is a virulence factor from Escherichia coli whose C-terminal domain (CTD) undergoes a dramatic α-to-β conformational transformation. The CTD in its α-helical fold is stabilized by interactions with the N-terminal domain (NTD), masking an RNA polymerase binding site until a specific recruitment site is encountered. Domain dissociation is triggered upon binding to DNA, allowing the NTD to interact with RNA polymerase to facilitate transcription while the CTD refolds into the β-barrel conformation that interacts with the ribosome to activate translation. However, structural details of this transformation process in the context of the full protein remain to be elucidated. Here, we explore the mechanism of the α-to-β conformational transition of RfaH in the full-length protein using a dual-basin structure-based model. Our simulations capture several features described experimentally, such as the requirement of disruption of interdomain contacts to trigger the α-to-β transformation, confirms the roles of previously indicated residues E48 and R138, and suggests a new important role for F130, in the stability of the interdomain interaction. These native basins are connected through an intermediate state that builds up upon binding to the NTD and shares features from both folds, in agreement with previous in silico studies of the isolated CTD. We also examine the effect of RNA polymerase binding on the stabilization of the β fold. Our study shows that native-biased models are appropriate for interrogating the detailed mechanisms of structural rearrangements during the dramatic transformation process of RfaH. PMID:26230837

Hydrography of the Gulf of Maine and Massachusetts Bay, data report for R/V OCEANUS cruise 181, 5-15 February 1987

USGS Publications Warehouse

Moody, John A.; Butman, Bradford; Shoukimas, Polly; Donoghue, Terence G.

1990-01-01

During Cruise 181, a total of 95 hydrographic profiles were obtained by means of a conductivity-temperature-depth (CTD) profiler. Stations are numbered sequentially and station information is tabulated in table 1. The stations were arranged in ten transects (figure 1). Section 1 was across the Great South Channel and section 7 was across the Northeast Channel--the two main oceanic entrances and exits of the Gulf of Maine. Section 2 was along a saddle (Rodgers Pass) separating Wilkinson Basin from Georges Basin. Sections 3,5, and 10 were across different regions of Wilkinson Basin and all intersected at the longterm mooring site W1 in the center of Wilkinson Basin; section 8 was a dog-leg section through the southern portion of Jordan Basin; and sections 6 (east-west) and 9 (north-south) were within Georges Basin. A severe winter storm (see table 2 and 3) occurred between February 9 and 10 and work was stopped while the OCEANUS rode out the storm in Cape Cod Bay and repaired storm damage. Section 4 across Massachusetts Bay and section 5 across Wilkinson Basin, were repeated twice, once before the storm (sections 4a and 5a) and once after the storm (sections 4b and 5b).

The hydrothermal exploration system on the 'Qianlong2' AUV

NASA Astrophysics Data System (ADS)

Tao, W.; Tao, C.; Jinhui, Z.; Cai, L.; Guoyin, Z.

2016-12-01

ABSTRACT: Qianlong2, is a fully Autonomous Underwater Vehicle (AUV) designed for submarine resources research, especially for polymetallic sulphides, and the survey depths of is up to 4500 m. Qianlong2 had successfully explored hydrothermal vent field on the Southwest Indian Ridge (SWIR), and collected conductance, temperature and depth (CTD), turbidity, and Oxidation-Reduction Potential (ORP) data. It also had mapped precise topography by high resolution side scan sonar (HRBSSS) during every dive; and obtained photographs of sulfide deposits during some dives. Here, we detailedly described the implementation of investigation, data administration, and fast mapping of hydrothermal exploration system by Qianlong2. Giving a description of how to remove the platform magnetic interference by using magnetic data during Qianlong2 spin. Based on comprehensive hydrochemical anomalies, we get a rapid method for finding the localization of hydrothermal vents. Taking one dive as an example, we systemically showed the process about how to analyse hydrothermal survey data and acquire the location results of hydrothermal vents. Considering that this method is effective and can be used in other deep-submergence assets such as human occupied vehicles (HOVs) and remotely operated vehicles (ROVs) during further studies. Finally, we discussed how to promote and optimize the installation and application of those sensors and how to improve Qianlong2's autonomy of investigation.

Seabird, fish, marine mammal, and oceanography coordinated investigations (SMMOCI) in Sitka Sound, Alaska, July 2000

USGS Publications Warehouse

Piatt, John F.; Dragoo, Donald E.

2005-01-01

Surveys for seabirds and marine mammals were conducted in and near Sitka Sound, Alaska (Fig. 1) from the M/V Tiĝlax̂ during 12-16 July 2000 (Table 1, Fig. 1). The objective was to characterize the marine environment in the vicinity of St. Lazaria Island, one of ten seabird colonies monitored annually by the Alaska Maritime National Wildlife Refuge (See Dragoo et al. 2003). In addition to censusing seabirds and mammals encountered on line transects, local oceanography was characterized by measuring water temperature and salinity continuously at the sea surface, and by taking profiles of the water column on a series of CTD transects. The relative abundance of zooplankton and fish biomass was measured using a dual -frequency echosounder. Significant acoustic targets were sampled with a m id-water trawl net. Long-lines were se t twice to catch and characterize diets of large demersal fish species.Rosenthal et al. (1981 and 1982) studied the bottomfish component of the nearshore habitats in southeastern Alaska including the Sitka Sound area during the summers of 1980 and 1981, allowing comparisons of our findings to those from the earlier works. There are no previous surveys for seabirds or marine mammals in this area with which we can compare our surveys.

Pinatubo Lake Chemistry and Degassing 1991-2010

NASA Astrophysics Data System (ADS)

Schwandner, F. M.; Newhall, C. G.; Christenson, B. W.; Apfelbeck, C. A.; Arpa, M. C. B.; Vaquilar, R.; Bariso, E.

2016-12-01

We review the history of degassing, bathymetry and water chemistry of the crater lake of Mt. Pinatubo (Philippines) using data obtained during 1991-2001, and 2010. In late 1992, the initial small lake had a significant acid-sulfate component from a volcanic degassing through a hydrothermal system and the lake, and anhydrite dissolution. Subsequently, this component was "drowned" by rainfall (2-4 m/y), meteoric groundwater draining from the crater walls into the lake, and a few neutral chloride crater wall springs. Conductivity-Temperature-Depth (CTD) measurements in August 2000 found a strong inverted thermal gradient below 20m depth, reaching over 70°C at 50-60 m depth. By January 2001 the lake had homogenized and was much cooler (27°C at all depths), and it was again well-mixed and still cool when re-surveyed in June 2001 and November 2010. By 2010, the lake was well mixed, at neutral pH, with no significant vertical or horizontal structure. Bubbling of a predominantly carbon dioxide (CO2) gas phase persists throughout the lake's history, some from 1991-92 magma and some from degassing of the long-standing (pre-1991) hydrothermal system fed from a deeper magmatic or mantle source. Crater wall fumaroles emit boiling-point hydrothermal gases dominated by water, air, and CO2.

TFIIH and P-TEFb Coordinate Transcription with Capping Enzyme Recruitment at Specific Genes in Fission Yeast

PubMed Central

Viladevall, Laia; St. Amour, Courtney V.; Rosebrock, Adam; Schneider, Susanne; Zhang, Chao; Allen, Jasmina J.; Shokat, Kevan M.; Schwer, Beate; Leatherwood, Janet K.; Fisher, Robert P.

2009-01-01

Summary Cyclin-dependent kinases (CDKs) are subunits of transcription factor (TF) IIH and positive transcription elongation factor b (P-TEFb). To define their functions, we mutated the TFIIH-associated kinase Mcs6 and P-TEFb homologs Cdk9 and Lsk1 of fission yeast, making them sensitive to bulky purine analogs. Selective inhibition of Mcs6 or Cdk9 blocks cell division, alters RNA polymerase (Pol) II carboxyl-terminal domain (CTD) phosphorylation and represses specific, overlapping subsets of transcripts. At a common target gene, both CDKs must be active for normal Pol II occupancy, and Spt5—a CDK substrate and regulator of elongation—accumulates disproportionately to Pol II when either kinase is inhibited. In contrast, Mcs6 activity is sufficient, and necessary, to recruit the Cdk9/Pcm1 (mRNA cap methyltransferase) complex. In vitro, phosphorylation of the CTD by Mcs6 stimulates subsequent phosphorylation by Cdk9. We propose that TFIIH primes the CTD and promotes recruitment of P-TEFb/Pcm1, serving to couple elongation and capping of select pre-mRNAs. PMID:19328067

Allosteric control of transcription in GntR family of transcription regulators: A structural overview.

PubMed

Jain, Deepti

2015-07-01

The GntR family of transcription regulators constitutes one of the most abundant family of transcription factors. These modulators are involved in a variety of mechanisms controlling various metabolic processes. GntR family members are typically two domain proteins with a smaller N-terminus domain (NTD) with conserved architecture of winged-helix-turn-helix (wHTH) for DNA binding and a larger C-terminus domain (CTD) or the effector binding domain which is also involved in oligomerization. Interestingly, the CTD shows structural heterogeneity depending upon the type of effector molecule that it binds and displays structural homology to various classes of proteins. Binding of the effector molecule to the CTD brings about a conformational change in the transcription factor such that its affinity for its cognate DNA sequence is altered. This review summarizes the structural information available on the members of GntR family and discusses the common features of the DNA binding and operator recognition within the family. The variation in the allosteric mechanism employed by the members of this family is also discussed. © 2015 International Union of Biochemistry and Molecular Biology.

The Comparative Toxicogenomics Database: update 2017.

PubMed

Davis, Allan Peter; Grondin, Cynthia J; Johnson, Robin J; Sciaky, Daniela; King, Benjamin L; McMorran, Roy; Wiegers, Jolene; Wiegers, Thomas C; Mattingly, Carolyn J

2017-01-04

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) provides information about interactions between chemicals and gene products, and their relationships to diseases. Core CTD content (chemical-gene, chemical-disease and gene-disease interactions manually curated from the literature) are integrated with each other as well as with select external datasets to generate expanded networks and predict novel associations. Today, core CTD includes more than 30.5 million toxicogenomic connections relating chemicals/drugs, genes/proteins, diseases, taxa, Gene Ontology (GO) annotations, pathways, and gene interaction modules. In this update, we report a 33% increase in our core data content since 2015, describe our new exposure module (that harmonizes exposure science information with core toxicogenomic data) and introduce a novel dataset of GO-disease inferences (that identify common molecular underpinnings for seemingly unrelated pathologies). These advancements centralize and contextualize real-world chemical exposures with molecular pathways to help scientists generate testable hypotheses in an effort to understand the etiology and mechanisms underlying environmentally influenced diseases. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I.

PubMed

Wang, Yanli; Ludwig, Janos; Schuberth, Christine; Goldeck, Marion; Schlee, Martin; Li, Haitao; Juranek, Stefan; Sheng, Gang; Micura, Ronald; Tuschl, Thomas; Hartmann, Gunther; Patel, Dinshaw J

2010-07-01

RIG-I is a cytosolic helicase that senses 5'-ppp RNA contained in negative-strand RNA viruses and triggers innate antiviral immune responses. Calorimetric binding studies established that the RIG-I C-terminal regulatory domain (CTD) binds to blunt-end double-stranded 5'-ppp RNA a factor of 17 more tightly than to its single-stranded counterpart. Here we report on the crystal structure of RIG-I CTD bound to both blunt ends of a self-complementary 5'-ppp dsRNA 12-mer, with interactions involving 5'-pp clearly visible in the complex. The structure, supported by mutation studies, defines how a lysine-rich basic cleft within the RIG-I CTD sequesters the observable 5'-pp of the bound RNA, with a stacked phenylalanine capping the terminal base pair. Key intermolecular interactions observed in the crystalline state are retained in the complex of 5'-ppp dsRNA 24-mer and full-length RIG-I under in vivo conditions, as evaluated from the impact of binding pocket RIG-I mutations and 2'-OCH(3) RNA modifications on the interferon response.

Improved Statistical Method For Hydrographic Climatic Records Quality Control

NASA Astrophysics Data System (ADS)

Gourrion, J.; Szekely, T.

2016-02-01

Climate research benefits from the continuous development of global in-situ hydrographic networks in the last decades. Apart from the increasing volume of observations available on a large range of temporal and spatial scales, a critical aspect concerns the ability to constantly improve the quality of the datasets. In the context of the Coriolis Dataset for ReAnalysis (CORA) version 4.2, a new quality control method based on a local comparison to historical extreme values ever observed is developed, implemented and validated. Temperature, salinity and potential density validity intervals are directly estimated from minimum and maximum values from an historical reference dataset, rather than from traditional mean and standard deviation estimates. Such an approach avoids strong statistical assumptions on the data distributions such as unimodality, absence of skewness and spatially homogeneous kurtosis. As a new feature, it also allows addressing simultaneously the two main objectives of a quality control strategy, i.e. maximizing the number of good detections while minimizing the number of false alarms. The reference dataset is presently built from the fusion of 1) all ARGO profiles up to early 2014, 2) 3 historical CTD datasets and 3) the Sea Mammals CTD profiles from the MEOP database. All datasets are extensively and manually quality controlled. In this communication, the latest method validation results are also presented. The method has been implemented in the latest version of the CORA dataset and will benefit to the next version of the Copernicus CMEMS dataset.

Observations of The Dense Storfjord Plume Using A Ctd-mounted Adp

NASA Astrophysics Data System (ADS)

Fer, I.; Skogseth, R.; Haugan, P. M.

Observations were made of the outflow of the dense bottom water plume from Stor- fjord (110 km long and 190 m deep at maximum depth) in the Svalbard Archipelago, using a CTD mounted ADP at densely spaced hydrographic stations during May 28 - June 2, 2001. Due to heavy ice inside the fjord, measurements were made from about 70 km downstream of a 115 m deep sill (7645 N) and onward. The dense bottom water generated by strong winter cooling, enhanced ice formation, and the consequent brine rejection drains into and fills the depressions of the fjord and cascades following the bathymetry. Data acquired by ADP allow for examination of the velocity structure associated with the plume as close as 1 m to the bottom with 1 m resolution in the vertical. The plume water was observed to have salinities within 34.9 - 35.1 psu with temperatures close to the freezing point temperature. The plume has a thickness of 51 +/- 20 m, and a density difference of 0.14 +/- 0.03 kg m-3 from the ambient wa- ters. The velocity profiles yield the most well-defined two-layered structure near the sloping sides with a mean plume speed of 0.15 +/- 0.04 m s-1, relative to the ambient waters. Mean overall Richardson number, estimated using these profiles, are within the range of 2 to 4. The plume is less distinct with respect to the velocity profile when it reaches the plane, Storfjordrenna, after cascading about 50 m in vertical. The width of the plume increases from about 8 km to 25 km along its path of 105 km leading to an entrainment rate of 5x10-4, when the plume thickness and speed are assumed constant. The values compare well with those obtained from moorings in the same region in the past, as well as those obtained from laboratory experiments of turbulent gravity currents flowing down a slope.

Complete A-V block: incidental or a part of cor triatriatum dexter.

PubMed

Guler, Y; Akgun, T; Toprak, C; Guler, A; Esen, A M

2014-05-01

Cor triatriatum dexter (CTD) is an extremely rare cardiac anomaly in which the right atrium is divided into two distinct chambers by a membrane. The persistence of the right valve of sinus venosus results in a complete septation of the right atrium. This anomaly is frequently associated with other right-sided cardiac abnormalities. Its clinical manifestation and the need for intervention are determined by the number and the size of the fenestrations on the membrane, associated cardiac anomalies and arrhythmias. We describe a case of CTD in a patient with complete atrioventricular (A-V) block.

Systematic heat flow measurements across the Wagner Basin, northern Gulf of California

NASA Astrophysics Data System (ADS)

Neumann, Florian; Negrete-Aranda, Raquel; Harris, Robert N.; Contreras, Juan; Sclater, John G.; González-Fernández, Antonio

2017-12-01

A primary control on the geodynamics of rifting is the thermal regime. To better understand the geodynamics of rifting in the northern Gulf of California we systematically measured heat-flow across the Wagner Basin, a tectonically active basin that lies near the southern terminus of the Cerro Prieto fault. The heat flow profile is 40 km long, has a nominal measurement spacing of ∼1 km, and is collocated with a seismic reflection profile. Heat flow measurements were made with a 6.5-m violin-bow probe. Although heat flow data were collected in shallow water, where there are significant temporal variations in bottom water temperature, we use CTD data collected over many years to correct our measurements to yield accurate values of heat flow. After correction for bottom water temperature, the mean and standard deviation of heat flow across the western, central, and eastern parts of the basin are 220 ± 60, 99 ± 14, 889 ± 419 mW m-2, respectively. Corrections for sedimentation would increase measured heat flow across the central part of basin by 40 to 60%. We interpret the relatively high heat flow and large variability on the western and eastern flanks in terms of upward fluid flow at depth below the seafloor, whereas the lower and more consistent values across the central part of the basin are suggestive of conductive heat transfer. Moreover, heat flow across the central basin is consistent with gabbroic underplating at a depth of 15 km and suggests that continental rupture here has not gone to completion.

Variational data assimilative modeling of the Gulf of Maine in spring and summer 2010

NASA Astrophysics Data System (ADS)

Li, Yizhen; He, Ruoying; Chen, Ke; McGillicuddy, Dennis J.

2015-05-01

A data assimilative ocean circulation model is used to hindcast the Gulf of Maine [GOM) circulation in spring and summer 2010. Using the recently developed incremental strong constraint 4D Variational data assimilation algorithm, the model assimilates satellite sea surface temperature and in situ temperature and salinity profiles measured by expendable bathythermograph, Argo floats, and shipboard CTD casts. Validation against independent observations shows that the model skill is significantly improved after data assimilation. The data-assimilative model hindcast reproduces the temporal and spatial evolution of the ocean state, showing that a sea level depression southwest of the Scotian Shelf played a critical role in shaping the gulf-wide circulation. Heat budget analysis further demonstrates that both advection and surface heat flux contribute to temperature variability. The estimated time scale for coastal water to travel from the Scotian Shelf to the Jordan Basin is around 60 days, which is consistent with previous estimates based on in situ observations. Our study highlights the importance of resolving upstream and offshore forcing conditions in predicting the coastal circulation in the GOM.

Collection of Arctic Ocean Data from US Navy Submarines on the New SCICEX Program

NASA Astrophysics Data System (ADS)

Smethie, W. M.; Sambrotto, R.; Boyd, T.; Richter-Menge, J.; Corbett, J.

2011-12-01

The SCICEX submarine Arctic science program originated in the 1990s when six dedicated science cruises were conducted in the Arctic Ocean aboard US Navy Sturgeon class submarines. After the cold war era Sturgeon class submarines were retired, several Science Accommodation cruises, for which a few days for scientific measurements were added to planned submarine transits through the Arctic Ocean, were carried out when opportunities arose. Renewed interest in conducting further Science Accommodation cruises on a regular basis to better document and understand how the Arctic Ocean responds to climate change resulted in publication of a scientific plan in 2010 (http://www.arctic.gov/publications/scicex_plan.pdf). In the spring of 2011 testing of data collection and water sampling methods aboard newer Virginia and Seawolf class submarines on transit from a Navy ice camp in the Beaufort Sea, was conducted in order to develop protocols and evaluate techniques. Ice draft measurements were also taken in the vicinity of the ice camp and near the North Pole to evaluate new data collection systems. This evaluation will include a comparison of the ice draft data with a comprehensive set of in situ ice thickness measurements taken near the ice camp. Under-ice submarine-launched eXpendable Condutivity Temperature Depth (XCTD) probes were deployed from the USS Connecticut (SSN-22), a Seawolf class submarine, and the resulting profiles compared to CTD casts from the APLIS ice station and historical profiles. Water samples were collected through the hull for measurements of tritium, helium isotopes, oxygen isotopes, chlorofluorocarbons, sulfur hexafluoride, nutrients, dissolved organic carbon, bacterioplankton, phytoplankton and particulates levels. These samples were returned to Lamont-Doherty Earth Observatory and were in the process of being measured at the time this abstract was written. Measurements completed at this time indicate good samples can be collected for CFC-12, nutrients and biological and inorganic particulates. Measurements of the other samples will be completed and reported on at the meeting. Early results indicate that both of the submarine types evaluated are capable of reliably collecting important information on water temperature, salinity, tracers, chemistry, and biology and ice draft.

Domain activities of PapC usher reveal the mechanism of action of an Escherichia coli molecular machine.

PubMed

Volkan, Ender; Ford, Bradley A; Pinkner, Jerome S; Dodson, Karen W; Henderson, Nadine S; Thanassi, David G; Waksman, Gabriel; Hultgren, Scott J

2012-06-12

P pili are prototypical chaperone-usher pathway-assembled pili used by Gram-negative bacteria to adhere to host tissues. The PapC usher contains five functional domains: a transmembrane β-barrel, a β-sandwich Plug, an N-terminal (periplasmic) domain (NTD), and two C-terminal (periplasmic) domains, CTD1 and CTD2. Here, we delineated usher domain interactions between themselves and with chaperone-subunit complexes and showed that overexpression of individual usher domains inhibits pilus assembly. Prior work revealed that the Plug domain occludes the pore of the transmembrane domain of a solitary usher, but the chaperone-adhesin-bound usher has its Plug displaced from the pore, adjacent to the NTD. We demonstrate an interaction between the NTD and Plug domains that suggests a biophysical basis for usher gating. Furthermore, we found that the NTD exhibits high-affinity binding to the chaperone-adhesin (PapDG) complex and low-affinity binding to the major tip subunit PapE (PapDE). We also demonstrate that CTD2 binds with lower affinity to all tested chaperone-subunit complexes except for the chaperone-terminator subunit (PapDH) and has a catalytic role in dissociating the NTD-PapDG complex, suggesting an interplay between recruitment to the NTD and transfer to CTD2 during pilus initiation. The Plug domain and the NTD-Plug complex bound all of the chaperone-subunit complexes tested including PapDH, suggesting that the Plug actively recruits chaperone-subunit complexes to the usher and is the sole recruiter of PapDH. Overall, our studies reveal the cooperative, active roles played by periplasmic domains of the usher to initiate, grow, and terminate a prototypical chaperone-usher pathway pilus.

A Study of Future Communications Concepts and Technologies for the National Airspace System-Part III

NASA Technical Reports Server (NTRS)

Ponchak, Denise S.; Apaza, Rafael D.; Wichgersm Joel M.; Haynes, Brian; Roy, Aloke

2014-01-01

The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) is investigating current and anticipated wireless communications concepts and technologies that the National Airspace System (NAS) may need in the next 50 years. NASA has awarded three NASA Research Announcements (NAR) studies with the objective to determine the most promising candidate technologies for air-to-air and air-to-ground data exchange and analyze their suitability in a post-NextGen NAS environment. This paper will present progress made in the studies and describe the communications challenges and opportunities that have been identified as part of the study. NASA's NextGen Concepts and Technology Development (CTD) Project integrates solutions for a safe, efficient and high-capacity airspace system through joint research efforts and partnerships with other government agencies. The CTD Project is one of two within NASA's Airspace Systems Program and is managed by the NASA Ames Research Center. Research within the CTD Project is in support the 2011 NASA Strategic Plan Sub-Goal 4.1: Develop innovative solutions and advanced technologies, through a balanced research portfolio, to improve current and future air transportation. The focus of CTD is on developing capabilities in traffic flow management, dynamic airspace configuration, separation assurance, super density operations and airport surface operations. Important to its research is the development of human/automation information requirements and decisionmaking guidelines for human-human and human-machine airportal decision-making. Airborne separation, oceanic intrail climb/descent and interval management applications depend on location and intent information of surrounding aircraft. ADS-B has been proposed to provide the information exchange, but other candidates such as satellite-based receivers, broadband or airborne internet, and cellular communications are possible candidate's.

Molecular Dissection of the Homotrimeric Sliding Clamp of T4 Phage: Two Domains of a Subunit Display Asymmetric Characteristics.

PubMed

Singh, Manika Indrajit; Jain, Vikas

2016-01-26

Sliding clamp proteins are circular dimers or trimers that encircle DNA and serve as processivity factors during DNA replication. Their presence in all the three domains of life and in bacteriophages clearly indicates their high level of significance. T4 gp45, besides functioning as the DNA polymerase processivity factor, also moonlights as the late promoter transcription determinant. Here we report a detailed biophysical analysis of gp45. The chemical denaturation of gp45 probed by circular dichroism spectroscopy, tryptophan fluorescence anisotropy, and blue-native polyacrylamide gel electrophoresis suggests that the protein follows a three-state denaturation profile and displays an intermediate molten globule-like state. The three-state transition was found to be the result of the sequential unfolding of the two domains, the N-terminal domain (NTD) and the C-terminal domain (CTD), of gp45. The experiments involving Trp fluorescence quenching by acrylamide demonstrate that the CTD undergoes substantial changes in conformation during formation of the intermediate state. Further biophysical dissection of the individual domain reveals contrasting properties of the two domains. The NTD unfolds at low urea concentrations and is also susceptible to protease cleavage, whereas the CTD resists urea-mediated denaturation and is not amenable to protease digestion even at higher urea concentrations. These experiments allow us to conclude that the two domains of gp45 differ in their dynamics. While the CTD shows stability and rigidity, we find that the NTD is unstable and flexible. We believe that the asymmetric characteristics of the two domains and the interface they form hold significance in gp45 structure and function.

Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns.

PubMed

Alberti, María Laura; Paulin, Francisco; Toledo, Heidegger Mateos; Fernández, Martín Eduardo; Caro, Fabián Matías; Rojas-Serrano, Jorge; Mejía, Mayra Edith

To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Structural basis of HIV-1 capsid recognition by PF74 and CPSF6

DOE PAGES

Bhattacharya, Akash; Alam, Steven L.; Fricke, Thomas; ...

2014-12-17

Upon infection of susceptible cells by HIV-1, the conical capsid formed by ~250 hexamers and 12 pentamers of the CA protein is delivered to the cytoplasm. In this study, the capsid shields the RNA genome and proteins required for reverse transcription. In addition, the surface of the capsid mediates numerous host–virus interactions, which either promote infection or enable viral restriction by innate immune responses. In the intact capsid, there is an intermolecular interface between the N-terminal domain (NTD) of one subunit and the C-terminal domain (CTD) of the adjacent subunit within the same hexameric ring. The NTD–CTD interface is criticalmore » for capsid assembly, both as an architectural element of the CA hexamer and pentamer and as a mechanistic element for generating lattice curvature. Here we report biochemical experiments showing that PF-3450074 (PF74), a drug that inhibits HIV-1 infection, as well as host proteins cleavage and polyadenylation specific factor 6 (CPSF6) and nucleoporin 153 kDa (NUP153), bind to the CA hexamer with at least 10-fold higher affinities compared with nonassembled CA or isolated CA domains. The crystal structure of PF74 in complex with the CA hexamer reveals that PF74 binds in a preformed pocket encompassing the NTD–CTD interface, suggesting that the principal inhibitory target of PF74 is the assembled capsid. Likewise, CPSF6 binds in the same pocket. Given that the NTD–CTD interface is a specific molecular signature of assembled hexamers in the capsid, binding of NUP153 at this site suggests that key features of capsid architecture remain intact upon delivery of the preintegration complex to the nucleus.« less

Long-term, High Frequency, High Precision pH Measurements on the MBARI deep-water FOCE Experiment at the MARS Cabled Observatory in Monterey Bay, CA

NASA Astrophysics Data System (ADS)

Peltzer, E. T.; Maughan, T.; Barry, J. P.; Brewer, P. G.; Headley, K. L.; Herlien, R.; Kirkwood, W. J.; Matsumoto, G. I.; O'Reilly, T. C.; Salamy, K. A.; Scholfield, J.; Shane, F. F.; Walz, P. M.

2012-12-01

The MBARI deep-water FOCE experiment was deployed on the MARS cabled observatory in Monterey Bay on May 4th, 2011. It has been in continuous operation (excluding a few minor shore based power outages) ever since. During the fifteen months of deployment, we have been able to observe both the daily variation in pH in response to water mass movements associated with the semi-diurnal tides, internal waves and longer-term trends as a function of the seasonal variations in the water masses within the Monterey Bay Canyon. Our experimental site is located at 890 meters, just below the oxygen minimum for Monterey Bay, and we clearly see the anticipated inverse correlation between seawater temperature and pH. Daily variation in pH is on the order of 0.020-0.030 pH units with longer term trends adding an additional variation of similar magnitude. Instrumentation on this experiment included two CTDs with oxygen sensors (Sea-Bird 52). One CTD is mounted on the external FOCE framework to measure the background conditions, and one CTD is installed within the FOCE pH control area to monitor the experimentally manipulated conditions. In addition, 6 MBARI modified Sea-Bird 18 pH sensors were mounted on the FOCE apparatus. Four of these pH sensors monitored pH inside the experimental chamber and two monitored the external background seawater conditions. Although we originally intended to conduct several in situ CO2 enrichment experiments to study the impact of ocean acidification on the benthic biology and then recover the apparatus after one year, unanticipated changes in the ship schedule have left the FOCE experiment in place for nearly fifteen months at the time of this writing. Throughout this time period, all sensor data has been logged by the MBARI Shore-Side Data System (SSDS) resulting in the longest continuous record of high precision pH measurements in the intermediate water column. We present an analysis of the data obtained from this unique data set, and discuss our in-situ calibration techniques used to compensate for long term sensor drift associated with the reference electrode.

Quality DOTS management and empowering tuberculosis patients.

PubMed

Chugh, Satish

2009-03-01

Central Tuberculosis Division (CTD) has covered whole of India under DOTS. IMA is a proud partner of RNTCP which is managed by CTD. International Standards for Tuberculosis Care is expected from all healthcare providers. The basic principles of care is same worldwide. IMA GFATM RNTCP PPM is completing 2 years of its inception. Sensitisation programme and district training programmes has yielded DOTS/DMC centres in the target states. IMA is having 100% commitment for containing tuberculosis in India. There are International Standards for quality management in tuberculosis control, some of the Standards are elaborated in this write-up. In the Indian context, DOTS needs some innovations that is discussed in this article.

Threonine-4 of mammalian RNA polymerase II CTD is targeted by Polo-like kinase 3 and required for transcriptional elongation

PubMed Central

Hintermair, Corinna; Heidemann, Martin; Koch, Frederic; Descostes, Nicolas; Gut, Marta; Gut, Ivo; Fenouil, Romain; Ferrier, Pierre; Flatley, Andrew; Kremmer, Elisabeth; Chapman, Rob D; Andrau, Jean-Christophe; Eick, Dirk

2012-01-01

Eukaryotic RNA polymerase II (Pol II) has evolved an array of heptad repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 at the carboxy-terminal domain (CTD) of the large subunit (Rpb1). Differential phosphorylation of Ser2, Ser5, and Ser7 in the 5′ and 3′ regions of genes coordinates the binding of transcription and RNA processing factors to the initiating and elongating polymerase complexes. Here, we report phosphorylation of Thr4 by Polo-like kinase 3 in mammalian cells. ChIPseq analyses indicate an increase of Thr4-P levels in the 3′ region of genes occurring subsequently to an increase of Ser2-P levels. A Thr4/Ala mutant of Pol II displays a lethal phenotype. This mutant reveals a global defect in RNA elongation, while initiation is largely unaffected. Since Thr4 replacement mutants are viable in yeast we conclude that this amino acid has evolved an essential function(s) in the CTD of Pol II for gene transcription in mammalian cells. PMID:22549466

COMPUTING THERAPY FOR PRECISION MEDICINE: COLLABORATIVE FILTERING INTEGRATES AND PREDICTS MULTI-ENTITY INTERACTIONS.

PubMed

Regenbogen, Sam; Wilkins, Angela D; Lichtarge, Olivier

2016-01-01

Biomedicine produces copious information it cannot fully exploit. Specifically, there is considerable need to integrate knowledge from disparate studies to discover connections across domains. Here, we used a Collaborative Filtering approach, inspired by online recommendation algorithms, in which non-negative matrix factorization (NMF) predicts interactions among chemicals, genes, and diseases only from pairwise information about their interactions. Our approach, applied to matrices derived from the Comparative Toxicogenomics Database, successfully recovered Chemical-Disease, Chemical-Gene, and Disease-Gene networks in 10-fold cross-validation experiments. Additionally, we could predict each of these interaction matrices from the other two. Integrating all three CTD interaction matrices with NMF led to good predictions of STRING, an independent, external network of protein-protein interactions. Finally, this approach could integrate the CTD and STRING interaction data to improve Chemical-Gene cross-validation performance significantly, and, in a time-stamped study, it predicted information added to CTD after a given date, using only data prior to that date. We conclude that collaborative filtering can integrate information across multiple types of biological entities, and that as a first step towards precision medicine it can compute drug repurposing hypotheses.

COMPUTING THERAPY FOR PRECISION MEDICINE: COLLABORATIVE FILTERING INTEGRATES AND PREDICTS MULTI-ENTITY INTERACTIONS

PubMed Central

REGENBOGEN, SAM; WILKINS, ANGELA D.; LICHTARGE, OLIVIER

2015-01-01

Biomedicine produces copious information it cannot fully exploit. Specifically, there is considerable need to integrate knowledge from disparate studies to discover connections across domains. Here, we used a Collaborative Filtering approach, inspired by online recommendation algorithms, in which non-negative matrix factorization (NMF) predicts interactions among chemicals, genes, and diseases only from pairwise information about their interactions. Our approach, applied to matrices derived from the Comparative Toxicogenomics Database, successfully recovered Chemical-Disease, Chemical-Gene, and Disease-Gene networks in 10-fold cross-validation experiments. Additionally, we could predict each of these interaction matrices from the other two. Integrating all three CTD interaction matrices with NMF led to good predictions of STRING, an independent, external network of protein-protein interactions. Finally, this approach could integrate the CTD and STRING interaction data to improve Chemical-Gene cross-validation performance significantly, and, in a time-stamped study, it predicted information added to CTD after a given date, using only data prior to that date. We conclude that collaborative filtering can integrate information across multiple types of biological entities, and that as a first step towards precision medicine it can compute drug repurposing hypotheses. PMID:26776170

Disease-Homologous Mutation in the Cation Diffusion Facilitator Protein MamM Causes Single-Domain Structural Loss and Signifies Its Importance

PubMed Central

Barber-Zucker, Shiran; Uebe, René; Davidov, Geula; Navon, Yotam; Sherf, Dror; Chill, Jordan H.; Kass, Itamar; Bitton, Ronit; Schüler, Dirk; Zarivach, Raz

2016-01-01

Cation diffusion facilitators (CDF) are highly conserved, metal ion efflux transporters that maintain divalent transition metal cation homeostasis. Most CDF proteins contain two domains, the cation transporting transmembrane domain and the regulatory cytoplasmic C-terminal domain (CTD). MamM is a magnetosome-associated CDF protein essential for the biomineralization of magnetic iron-oxide particles in magnetotactic bacteria. To investigate the structure-function relationship of CDF cytoplasmic domains, we characterized a MamM M250P mutation that is synonymous with the disease-related mutation L349P of the human CDF protein ZnT-10. Our results show that the M250P exchange in MamM causes severe structural changes in its CTD resulting in abnormal reduced function. Our in vivo, in vitro and in silico studies indicate that the CTD fold is critical for CDF proteins’ proper function and support the previously suggested role of the CDF cytoplasmic domain as a CDF regulatory element. Based on our results, we also suggest a mechanism for the effects of the ZnT-10 L349P mutation in human. PMID:27550551

A multi-sensor land mine detection system: hardware and architectural outline of the Australian RRAMNS CTD system

NASA Astrophysics Data System (ADS)

Abeynayake, Canicious; Chant, Ian; Kempinger, Siegfried; Rye, Alan

2005-06-01

The Rapid Route Area and Mine Neutralisation System (RRAMNS) Capability Technology Demonstrator (CTD) is a countermine detection project undertaken by DSTO and supported by the Australian Defence Force (ADF). The limited time and budget for this CTD resulted in some difficult strategic decisions with regard to hardware selection and system architecture. Although the delivered system has certain limitations arising from its experimental status, many lessons have been learned which illustrate a pragmatic path for future development. RRAMNS a similar sensor suite to other systems, in that three complementary sensors are included. These are Ground Probing Radar, Metal Detector Array, and multi-band electro-optic sensors. However, RRAMNS uses a unique imaging system and a network based real-time control and sensor fusion architecture. The relatively simple integration of each of these components could be the basis for a robust and cost-effective operational system. The RRAMNS imaging system consists of three cameras which cover the visible spectrum, the mid-wave and long-wave infrared region. This subsystem can be used separately as a scouting sensor. This paper describes the system at its mid-2004 status, when full integration of all detection components was achieved.

The C-terminal domain of Tetrahymena thermophila telomerase holoenzyme protein p65 induces multiple structural changes in telomerase RNA

PubMed Central

Akiyama, Benjamin M.; Loper, John; Najarro, Kevin; Stone, Michael D.

2012-01-01

The unique cellular activity of the telomerase reverse transcriptase ribonucleoprotein (RNP) requires proper assembly of protein and RNA components into a functional complex. In the ciliate model organism Tetrahymena thermophila, the La-domain protein p65 is required for in vivo assembly of telomerase. Single-molecule and biochemical studies have shown that p65 promotes efficient RNA assembly with the telomerase reverse transcriptase (TERT) protein, in part by inducing a bend in the conserved stem IV region of telomerase RNA (TER). The domain architecture of p65 consists of an N-terminal domain, a La-RRM motif, and a C-terminal domain (CTD). Using single-molecule Förster resonance energy transfer (smFRET), we demonstrate the p65CTD is necessary for the RNA remodeling activity of the protein and is sufficient to induce a substantial conformational change in stem IV of TER. Moreover, nuclease protection assays directly map the site of p65CTD interaction to stem IV and reveal that, in addition to bending stem IV, p65 binding reorganizes nucleotides that comprise the low-affinity TERT binding site within stem–loop IV. PMID:22315458

Hydrothermal Plume Activity at Teahitia Seamount: Re-Awakening of the Society Islands Hot-Spot?

NASA Astrophysics Data System (ADS)

German, C. R.; Xu, G.; Yeo, I. A.; Walker, S. L.; Moffett, J.; Cutter, G. A.; Devey, C. W.; Hyvernaud, O.; Reymond, D.; Resing, J. A.

2016-12-01

We report results from a combined mapping and CTD-rosette investigation of the summit of Teahitia Seamount, Society Islands hot-spot, that indicates that high temperature venting may have been present by late 2013 at a site that only hosted low-temperature vents ( 30°C) when previously visited by submersible, 25 years earlier. In 2013, a non-buoyant hydrothermal plume containing high concentrations (>100nmol/L) of both dissolved and total dissolvable Fe was observed at an apparent rise-height of 110-140m above a seafloor source at 1500-1530m water depth, implying a heat-flux for the underlying venting of 13-35MW. From a comparison to the past evolution of venting at Loihi seamount (Hawaii), coupled with an examination of recent seismicity detected by the Polynesian Seismic Network, we hypothesize that venting at Teahitia may have undergone perturbation only recently and that this, in turn, may be linked to a re-awakening of the Society Islands hotspot.

Analysis of the spatio-temporal variability of seawater quality in the southeastern Arabian Gulf.

PubMed

Mezhoud, Nahla; Temimi, Marouane; Zhao, Jun; Al Shehhi, Maryam Rashed; Ghedira, Hosni

2016-05-15

In this study, seawater quality measurements, including salinity, sea surface temperature (SST), chlorophyll-a (Chl-a), Secchi disk depth (SDD), pH, and dissolved oxygen (DO), were made from June 2013 to November 2014 at 52 stations in the southeastern Arabian Gulf. Significant variability was noticed for all collected parameters. Salinity showed a decreasing trend, and Chl-a, DO, pH, and SDD demonstrated increasing trends from shallow onshore stations to deep offshore ones, which could be attributed to variations of ocean circulation and meteorological conditions from onshore to offshore waters, and the likely effects of desalination plants along the coast. Salinity and temperature were high in summer and low in winter while Chl-a, SDD, pH, and DO indicated an opposite trend. The CTD profiles showed vertically well-mixed structures. Qualitative analysis of phytoplankton showed a high diversity of species without anomalous species found except in Ras Al Khaimah stations where diatoms were the dominating ones. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tide-related variability of TAG hydrothermal activity observed by deep-sea monitoring system and OBSH

NASA Astrophysics Data System (ADS)

Fujioka, Kantaro; Kobayashi, Kazuo; Kato, Kazuhiro; Aoki, Misumi; Mitsuzawa, Kyohiko; Kinoshita, Masataka; Nishizawa, Azusa

1997-12-01

Hydrothermal activities were monitored by an ocean bottom seismometer with hydrophone (OBSH) and a composite measuring system (Manatee) including CTD, current meter, transmission meter and cameras at a small depression on the TAG hydrothermal mound in the Mid-Atlantic Ridge. Low-frequency pressure pulses detected by the hydrophone with semi-diurnal periodicity seem to correspond to cycles of hydrothermal upflow from a small and short-lived smoker vent close to the observing site. The peaks of pressure pulses are synchronous with the maximum gradient of areal strain decrease due to tidal load release. Microearthquakes with very near epicenters occur sporadically and do not appear to be directly correlatable to hydrothermal venting. Temporal variations in bottom water temperature also have semi-diurnal periodicity but are more complicated than the pressure events. Temperatures may be affected both by upwelling of hot water and by lateral flow of the bottom current changing its directions with ocean tide.

Transient response of the Northwestern Iberian upwelling regime.

PubMed

Ferreira Cordeiro, Nuno Gonçalo; Dubert, Jesus; Nolasco, Rita; Desmond Barton, Eric

2018-01-01

The hydrography and dynamics of NW Iberian margin were explored for July 2009, based on a set of in situ and remote sensing observations. Zonal sections of standard CTD casts, towed CTD (SeaSoar), Acoustic Doppler Current Profilers (ADCP) and Lagrangian surveys were made to characterize cycles of upwelling and relaxation in this region. Two periods of northerly winds, bounded by relaxation periods, were responsible for the formation of an upwelling front extending to the shelf edge. An equatorward flow was quickly set up on the shelf responding to the northerly wind pulses. South of Cape Silleiro, the development and subsequent relaxation of an upwelling event was intensively surveyed in the shelf, following a Lagrangian drifter transported by the upwelling jet. This region is part of an upwelling center extending from Cape Silleiro to Porto, where the surface temperature was colder than the neighboring regions, under upwelling favorable winds. As these winds relaxed, persistent poleward flow developed, originating south of the upwelling center and consisting in an inner-shelf tongue of warm waters. During an event of strong southerly wind, the poleward flow was observed to extend to the whole continental shelf. Although the cruise was executed during summertime, the presence of river-plumes was observed over the shelf. The interaction of the plumes with the circulation on the shelf was also described in terms of coastal convergence and offshore advection. The sampling of the offshore and slope regions showed the presence of the Iberian poleward current offshore and a persistent equatorward flow over the upper slope.

Water column imaging on hydrothermal vent in Central Indian Ridge

NASA Astrophysics Data System (ADS)

Koh, J.; Park, Y.

2017-12-01

Water column imaging with Multibeam echosounder systems (MBES) is recently becoming of increasing interest for oceanographic studies. Especially gas bubbles and hot water exposed from hydrothermal vents make acoustic impedance anomalies in cold seawater, water column imaging is very useful for the researchers who want to detect some kinds of hydrothermal activity. We conducted a hydrothermal exploration program, called "INVENT17", using the MBES system, KONGBERG EM122 (12kHz, 1°×1°), mounted on R/V ISABU and we deployed other equipments including video guided hydraulic grab, tow-yo CTD and general CTD with MAPR (Miniature Autonomous Plume Recorder) in 2017. First, to evaluate its capabilities of detection of hydrothermal vent, the surveys using the MBES were conducted at the Solitaire Field, previously identified hydrothermal area of the Central Indian Ridge. The bathymetric data obtained from MBES provided information about detailed morphology of seafloor, but we were not able to achieve the information from the water column imaging data. But the clue of existence of active hydrothermal vent was detected through the values of ΔNTU, dEh/dt, and OPR gained from MAPR, the data means that the hydrothermal activity affects 100m from the seafloor. It could be the reason that we can't find the hydrothermal activity because the range resolution of water column imaging is pretty rough so that the size of 100m-scaled activity has low possibility to distinguish from seafloor. The other reason is there are no sufficient objects to cause strong scattering like as CO2 bubbles or droplets unlike in the mid-Okinawa Trough. And this suggests that can be a important standard to identify properties of hydrothermal vent sites depending on the presence of scattering objects in water mass. To justify this, we should perform more chemical analysis of hot water emanating from hydrothermal vent and collected several bottles of water sample to do that.

The C-terminal cytidine deaminase domain of APOBEC3G itself undergoes intersegmental transfer for a target search, as revealed by real-time NMR monitoring.

PubMed

Kamba, Keisuke; Nagata, Takashi; Katahira, Masato

2018-01-31

APOBEC3G (A3G), an anti-human immunodeficiency virus 1 factor, deaminates cytidines. We examined deamination of two cytidines located separately on substrate ssDNA by the C-terminal domain (CTD) of A3G using real-time NMR monitoring. The deamination preference between the two cytidines was lost when either the substrate or non-substrate ssDNA concentration increased. When the non-substrate ssDNA concentration increased, the deamination activity first increased, but then decreased. This indicates that even a single domain, A3G-CTD, undergoes intersegmental transfer for a target search.

RNA Seeds Higher Order Assembly of FUS Protein

PubMed Central

Schwartz, Jacob C.; Wang, Xueyin; Podell, Elaine R.; Cech, Thomas R.

2014-01-01

SUMMARY The abundant nuclear RNA-binding protein FUS binds the CTD of RNA polymerase II in an RNA-dependent manner, affecting Ser2 phosphorylation and transcription. Here we examine the mechanism of this process and find that RNA binding nucleates the formation of higher order FUS RNP assemblies that bind the CTD. Both the low-complexity domain and the RGG domain of FUS contribute to assembly. The assemblies appear fibrous by electron microscopy and have characteristics of beta-zipper structures. These results support the emerging view that the pathologic protein aggregation seen in neurodegenerative diseases such as ALS may occur by exaggeration of functionally important assemblies of RNA-binding proteins. PMID:24268778

A Structured and Unstructured grid Relocatable ocean platform for Forecasting (SURF)

NASA Astrophysics Data System (ADS)

Trotta, Francesco; Fenu, Elisa; Pinardi, Nadia; Bruciaferri, Diego; Giacomelli, Luca; Federico, Ivan; Coppini, Giovanni

2016-11-01

We present a numerical platform named Structured and Unstructured grid Relocatable ocean platform for Forecasting (SURF). The platform is developed for short-time forecasts and is designed to be embedded in any region of the large-scale Mediterranean Forecasting System (MFS) via downscaling. We employ CTD data collected during a campaign around the Elba island to calibrate and validate SURF. The model requires an initial spin up period of a few days in order to adapt the initial interpolated fields and the subsequent solutions to the higher-resolution nested grids adopted by SURF. Through a comparison with the CTD data, we quantify the improvement obtained by SURF model compared to the coarse-resolution MFS model.

The influence of tributary flow density differences on the hydrodynamic behavior of a confluent meander bend and implications for flow mixing

NASA Astrophysics Data System (ADS)

Herrero, Horacio S.; Díaz Lozada, José M.; García, Carlos M.; Szupiany, Ricardo N.; Best, Jim; Pagot, Mariana

2018-03-01

The goal of this study is to evaluate the influence of tributary flow density differences on hydrodynamics and mixing at a confluent meander bend. A detailed field characterization is performed using an Acoustic Doppler Current Profiler (ADCP) for quantification of the 3D flow field, flow discharge and bathymetry, as well as CTD measurements (conductivity, temperature, depth) to characterize the patterns of mixing. Satellite images of the confluence taken at complementary times to the field surveys were analyzed to evaluate the confluence hydrodynamics at different flow conditions. The results illustrate the differences in hydrodynamics and mixing length in relation to confluences with equal density tributaries. At low-density differences, and higher discharge ratio (Qr) between the two rivers, the flow is similar to equi-density confluent meander bends. In contrast, at high-density differences (low Qr), the tributary flow is confined to near the confluence but the density difference causes the flow to move across channel. In this case, the density difference causes the lateral spread of the tributary flow to be greater than at a greater Qr when the density difference is less. These results illustrate the potential importance of density differences between tributaries in determining the rate and spatial extent of mixing and sediment dispersal at confluent meander bends.

Variability of stratification according to operation of the tidal power plant in Lake Sihwa, South Korea.

NASA Astrophysics Data System (ADS)

Woo, S. B.; Song, J. I.; Jang, T. H.; Park, C. J.; Kwon, H. K.

2017-12-01

Artificial forcing according to operation of the tidal power plant (TPP) affects the physical environmental changes near the power plant. Strong turbulence by generation is expected to change the stratification structure of the Lake Sihwa inside. In order to examine the stratification changes by the power plant operation, ship bottom mounted observation were performed for 13 hours using an acoustic Doppler current profiler (ADCP) and Conductivity-Temperature-Depth (CTD) in Lake Sihwa at near TPP. The strong stratification in Sihwa Lake is maintained before TPP operation. The absence of external forces and freshwater inflow from the land forms the stratification in the Lake. Strong winds in a stratification statement lead to two-layer circulation. After wind event, multi-layer velocity structure is formed which lasted for approximately 4 h. After TPP operation, the jet flow was observed in entire water column at the beginning of the power generation. Vortex is formed by strong jet flow and maintained throughout during power generation period. Strong turbulence flow is generated by the turbine blades, enhancing vertical mixing. External forces, which dominantly affect Lake Sihwa, have changed from the wind to the turbulent flow. The stratification was extinguished by strong turbulent flow and becomes fully-mixed state. Changes in stratification structure are expected to affect material transport and ecological environment change continuously.

Marine benthic habitat mapping of Muir Inlet, Glacier Bay National Park and Preserve, Alaska, with an evaluation of the Coastal and Marine Ecological Classification Standard III

USGS Publications Warehouse

Trusel, Luke D.; Cochrane, Guy R.; Etherington, Lisa L.; Powell, Ross D.; Mayer, Larry A.

2010-01-01

Seafloor geology and potential benthic habitats were mapped in Muir Inlet, Glacier Bay National Park and Preserve, Alaska, using multibeam sonar, ground-truth information, and geological interpretations. Muir Inlet is a recently deglaciated fjord that is under the influence of glacial and paraglacial marine processes. High glacially derived sediment and meltwater fluxes, slope instabilities, and variable bathymetry result in a highly dynamic estuarine environment and benthic ecosystem. We characterize the fjord seafloor and potential benthic habitats using the Coastal and Marine Ecological Classification Standard (CMECS) recently developed by the National Oceanic and Atmospheric Administration (NOAA) and NatureServe. Substrates within Muir Inlet are dominated by mud, derived from the high glacial debris flux. Water-column characteristics are derived from a combination of conductivity temperature depth (CTD) measurements and circulation-model results. We also present modern glaciomarine sediment accumulation data from quantitative differential bathymetry. These data show Muir Inlet is divided into two contrasting environments: a dynamic upper fjord and a relatively static lower fjord. The accompanying maps represent the first publicly available high-resolution bathymetric surveys of Muir Inlet. The results of these analyses serve as a test of the CMECS and as a baseline for continued mapping and correlations among seafloor substrate, benthic habitats, and glaciomarine processes.

Pichicuco 6: Gulf of California CTD Data Report. R/V New Horizon,

DTIC Science & Technology

1984-11-01

cSient ists at Cent ro dj( Oceariografia Fisica eit re ivestilgadores, del Cell - . Inivestilgaciin CieriTica N Ldiucaciori Suiperior de’ t ro de...1 16 STAMIN PC6092 28 37.0 N 112 55.8 W 23/11/84 2054Z 896/1260mn Temperature a2.9 4.93 6.9 8.9 19.9 12.9 14.9 16.9 18.2 22.9 22.9 24.9 26.2 28.2 622...50.0 14.258 34.933 26.101 140.0 9.619 34.694 26.800 60.0 14.132 34.915 26.114 4 1 . . .. 1 󈧪 STAMIN PC6114 28 37.6 N 112 38.6 W 24/11/84 245Z 486/ 365m

Remote sensing observations of phytoplankton increases triggered by successive typhoons

NASA Astrophysics Data System (ADS)

Huang, Lei; Zhao, Hui; Pan, Jiayi; Devlin, Adam

2017-12-01

Phytoplankton blooms in the Western North Pacific, triggered by two successive typhoons with different intensities and translation speeds under different pre-existing oceanic conditions, were observed and analyzed using remotely sensed chlorophyll-a (Chl-a), sea surface temperature (SST), and sea surface height anomaly (SSHA) data, as well as typhoon parameters and CTD (conductivity, temperature, and depth) profiles. Typhoon Sinlaku, with relatively weaker intensity and slower translation speed, induced a stronger phytoplankton bloom than Jangmi with stronger intensity and faster translation speed (Chl-a>0.18 mg·m‒3 versus Chl-a<0.15 mg·m‒3) east of Taiwan Island. Translation speed may be one of the important mechanisms that affect phytoplankton blooms in the study area. Pre-existing cyclonic circulations provided a relatively unstable thermodynamic structure for Sinlaku, and therefore cold water with rich nutrients could be brought up easily. The mixed-layer deepening caused by Typhoon Sinlaku, which occurred first, could have triggered an unfavorable condition for the phytoplankton bloom induced by Typhoon Jangmi which followed afterwards. The sea surface temperature cooling by Jangmi was suppressed due to the presence of the thick upper-ocean mixed-layer, which prevented the deeper cold water from being entrained into the upper-ocean mixed layer, leading to a weaker phytoplankton augment. The present study suggests that both wind (including typhoon translation speed and intensity) and pre-existing conditions (e.g., mixed-layer depths, eddies, and nutrients) play important roles in the strong phytoplankton bloom, and are responsible for the stronger phytoplankton bloom after Sinlaku's passage than that after Jangmi's passage. A new typhoon-influencing parameter is introduced that combines the effects of the typhoon forcing (including the typhoon intensity and translation speed) and the oceanic pre-condition. This parameter shows that the forcing effect of Sinlaku was stronger than that of Jangmi.

4DVAR data Assimilation with the Regional Ocean Modeling System (ROMS): Impact on the Water Mass Distributions in the Yellow Sea

NASA Astrophysics Data System (ADS)

Lee, Joon-Ho; Kim, Taekyun; Pang, Ig-Chan; Moon, Jae-Hong

2018-04-01

In this study, we evaluate the performance of the recently developed incremental strong constraint 4-dimensional variational (4DVAR) data assimilation applied to the Yellow Sea (YS) using the Regional Ocean Modeling System (ROMS). Two assimilation experiments are compared: assimilating remote-sensed sea surface temperature (SST) and both the SST and in-situ profiles measured by shipboard CTD casts into a regional ocean modeling from January to December of 2011. By comparing the two assimilation experiments against a free-run without data assimilation, we investigate how the assimilation affects the hydrographic structures in the YS. Results indicate that the SST assimilation notably improves the model behavior at the surface when compared to the nonassimilative free-run. The SST assimilation also has an impact on the subsurface water structure in the eastern YS; however, the improvement is seasonally dependent, that is, the correction becomes more effective in winter than in summer. This is due to a strong stratification in summer that prevents the assimilation of SST from affecting the subsurface temperature. A significant improvement to the subsurface temperature is made when the in-situ profiles of temperature and salinity are assimilated, forming a tongue-shaped YS bottom cold water from the YS toward the southwestern seas of Jeju Island.

Hand cumulative trauma disorders in Nigerian custom tailors: the need for redesign of manual scissors.

PubMed

Adeleye, Adedoyin Abiodun; Akanbi, Olusegun Gabriel

2015-01-01

Cutting scissors are important working tools for Nigerian custom tailors (CTs) but its usage apparently does not meet the ergonomics need of these artisans. A survey was carried out amongst CTs using questionnaires to obtain their background social-occupational demographics and observation methods to study their work performance, use of scissors and any cumulative trauma disorder (CTD) in their hands. Thicknesses of various fabrics were measured and comparison between Western world's custom tailoring job and the Nigerian type was done. The results showed some CTD risk factors with finger contusions on the 71 CTs evaluated. The right-hand contusions were traced to the constant usage of unpadded manual scissors with ungloved hands. Disparity between Western and Nigerian tailoring practice may account for the high occurrence of disorders in Nigerian CTs. Since hand dimensions are crucial in the design of hand tools, it is therefore concluded that hand anthropometry of Nigerian CTs and soft padding of manual scissors may mitigate CTD burdens on CTs' hands. Cumulative trauma disorders on the hands of low-income Nigerian CTs needed investigation. This was done via self-assessment and observational methods of the artisans’ work system. Frequent usage of unpadded manual scissors with un-gloved hands cause and exacerbate the problem. Hand anthropometry of users is crucial in scissors manufacturing.

The premonitory urge to tic: measurement, characteristics, and correlates in older adolescents and adults.

PubMed

Reese, Hannah E; Scahill, Lawrence; Peterson, Alan L; Crowe, Katherine; Woods, Douglas W; Piacentini, John; Walkup, John T; Wilhelm, Sabine

2014-03-01

In addition to motor and/or vocal tics, many individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) report frequent, uncomfortable sensory phenomena that immediately precede the tics. To date, examination of these premonitory sensations or urges has been limited by inconsistent assessment tools. In this paper, we examine the psychometric properties of a nine-item self-report measure, the Premonitory Urge to Tic Scale (PUTS) and examine the characteristics and correlates of the premonitory urge to tic in a clinical sample of 122 older adolescents and adults with TS or CTD. The PUTS demonstrated adequate internal consistency, temporal stability, and concurrent validity. Premonitory urges were endorsed by the majority of individuals. Most individuals reported some relief from the urges after completing a tic and being able to stop their tics even if only temporarily. Degree of premonitory urges was not significantly correlated with age, and we did not observe any gender differences. Degree of premonitory urges was significantly correlated with estimated IQ and tic severity, but not severity of comorbid obsessive-compulsive disorder or attention-deficit hyperactivity disorder. Also, it was not related to concomitant medication status. These findings represent another step forward in our understanding of the premonitory sensations associated with TS and CTD. © 2013.

Reward enhances tic suppression in children within months of tic disorder onset.

PubMed

Greene, Deanna J; Koller, Jonathan M; Robichaux-Viehoever, Amy; Bihun, Emily C; Schlaggar, Bradley L; Black, Kevin J

2015-02-01

Tic disorders are childhood onset neuropsychiatric disorders characterized by motor and/or vocal tics. Research has demonstrated that children with chronic tics (including Tourette syndrome and Chronic Tic Disorder: TS/CTD) can suppress tics, particularly when an immediate, contingent reward is given for successful tic suppression. As a diagnosis of TS/CTD requires tics to be present for at least one year, children in these tic suppression studies had been living with tics for quite some time. Thus, it is unclear whether the ability to inhibit tics is learned over time or present at tic onset. Resolving that issue would inform theories of how tics develop and how behavior therapy for tics works. We investigated tic suppression in school-age children as close to the time of tic onset as possible, and no later than six months after onset. Children were asked to suppress their tics both in the presence and absence of a contingent reward. Results demonstrated that these children, like children with TS/CTD, have some capacity to suppress tics, and that immediate reward enhances that capacity. These findings demonstrate that the modulating effect of reward on inhibitory control of tics is present within months of tic onset, before tics have become chronic. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

REWARD ENHANCES TIC SUPPRESSION IN CHILDREN WITHIN MONTHS OF TIC DISORDER ONSET

PubMed Central

Greene, Deanna J.; Koller, Jonathan M.; Robichaux-Viehoever, Amy; Bihun, Emily C.; Schlaggar, Bradley L.; Black, Kevin J.

2014-01-01

Tic disorders are childhood onset neuropsychiatric disorders characterized by motor and/or vocal tics. Research has demonstrated that children with chronic tics (including Tourette syndrome and Chronic Tic Disorder: TS/CTD) can suppress tics, particularly when an immediate, contingent reward is given for successful tic suppression. As a diagnosis of TS/CTD requires tics to be present for at least one year, children in these tic suppression studies had been living with tics for quite some time. Thus, it is unclear whether the ability to inhibit tics is learned over time or present at tic onset. Resolving that issue would inform theories of how tics develop and how behavior therapy for tics works. We investigated tic suppression in school-age children as close to the time of tic onset as possible, and no later than six months after onset. Children were asked to suppress their tics both in the presence and absence of a contingent reward. Results demonstrated that these children, like children with TS/CTD, have some capacity to suppress tics, and that immediate reward enhances that capacity. These findings demonstrate that the modulating effect of reward on inhibitory control of tics is present within months of tic onset, before tics have become chronic. PMID:25220075

Context-dependent modulation of Pol II CTD phosphatase SSUP-72 regulates alternative polyadenylation in neuronal development

PubMed Central

Chen, Fei; Zhou, Yu; Qi, Yingchuan B.; Khivansara, Vishal; Li, Hairi; Chun, Sang Young; Kim, John K.; Fu, Xiang-Dong; Jin, Yishi

2015-01-01

Alternative polyadenylation (APA) is widespread in neuronal development and activity-mediated neural plasticity. However, the underlying molecular mechanisms are largely unknown. We used systematic genetic studies and genome-wide surveys of the transcriptional landscape to identify a context-dependent regulatory pathway controlling APA in the Caenorhabditis elegans nervous system. Loss of function in ssup-72, a Ser5 phosphatase for the RNA polymerase II (Pol II) C-terminal domain (CTD), dampens transcription termination at a strong intronic polyadenylation site (PAS) in unc-44/ankyrin yet promotes termination at the weak intronic PAS of the MAP kinase dlk-1. A nuclear protein, SYDN-1, which regulates neuronal development, antagonizes the function of SSUP-72 and several nuclear polyadenylation factors. This regulatory pathway allows the production of a neuron-specific isoform of unc-44 and an inhibitory isoform of dlk-1. Dysregulation of the unc-44 and dlk-1 mRNA isoforms in sydn-1 mutants impairs neuronal development. Deleting the intronic PAS of unc-44 results in increased pre-mRNA processing of neuronal ankyrin and suppresses sydn-1 mutants. These results reveal a mechanism by which regulation of CTD phosphorylation controls coding region APA in the nervous system. PMID:26588990

Development of Clinical Trial Assessments for the Study of Interstitial Lung Disease in Patients who have Connective Tissue Diseases-Methodological Considerations.

PubMed

Huscher, Dörte; Saketkoo, Lesley Ann; Pittrow, David; Khanna, Dinesh

2010-05-01

This review article discusses the proposed methodology that will be utilized to develop core set items for connective tissue disease-associated interstitial lung disease (CTD-ILD). CTD-ILD remain an important enigma in clinical medicine. No consensus exists on measurement of disease activity or what constitutes a significant response to therapeutic interventions. Lack of appropriate measures inhibit effective drug development and hamper regulatory evaluation of candidate therapies.An interdisciplinary and international Steering Committee (SC) will oversee the execution of a 3-tier Delphi exercise involving experts in CTD and ILD. In parallel to the Delphi, qualitative information will be gathered from patients with ILD using focus groups. These data will subsequently be used to construct surveys to collect quantitative response from patients with ILD. The final Delphi and Patient Perspective results are to be scrutinized by SC and specialty sub-groups (including patient advocates) for truth, discrimination and feasibility - the OMERACT filters. Through application of Nominal Group technique, a core set of outcome measures will be proposed. Subsequent exercises will evaluate the applicability of a proposed core set to the unique issues posed by individual CTDs in addition to guidelines on screening, prognostication and damage scoring.

Methylation of RNA polymerase II non-consensus Lysine residues marks early transcription in mammalian cells

PubMed Central

Dias, João D; Rito, Tiago; Torlai Triglia, Elena; Kukalev, Alexander; Ferrai, Carmelo; Chotalia, Mita; Brookes, Emily; Kimura, Hiroshi; Pombo, Ana

2015-01-01

Dynamic post-translational modification of RNA polymerase II (RNAPII) coordinates the co-transcriptional recruitment of enzymatic complexes that regulate chromatin states and processing of nascent RNA. Extensive phosphorylation of serine residues at the largest RNAPII subunit occurs at its structurally-disordered C-terminal domain (CTD), which is composed of multiple heptapeptide repeats with consensus sequence Y1-S2-P3-T4-S5-P6-S7. Serine-5 and Serine-7 phosphorylation mark transcription initiation, whereas Serine-2 phosphorylation coincides with productive elongation. In vertebrates, the CTD has eight non-canonical substitutions of Serine-7 into Lysine-7, which can be acetylated (K7ac). Here, we describe mono- and di-methylation of CTD Lysine-7 residues (K7me1 and K7me2). K7me1 and K7me2 are observed during the earliest transcription stages and precede or accompany Serine-5 and Serine-7 phosphorylation. In contrast, K7ac is associated with RNAPII elongation, Serine-2 phosphorylation and mRNA expression. We identify an unexpected balance between RNAPII K7 methylation and acetylation at gene promoters, which fine-tunes gene expression levels. DOI: http://dx.doi.org/10.7554/eLife.11215.001 PMID:26687004

Birth outcomes of cases with conotruncal defects of heart - a population-based case-control study.

PubMed

Vereczkey, Attila; Kósa, Zsolt; Csáky-Szunyogh, Melinda; Gerencsér, Balázs; Czeizel, Andrew E

2015-03-01

The aim of this study was to evaluate the birth outcomes of cases with four types of conotruncal defects (CTDs), i.e. common truncus, transposition of great arteries, tetralogy of Fallot and double-outlet right ventricle. Birth outcomes of 597 live-born cases with CTD and 38,151 population controls without any defects were compared in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities completed by socio-demographic variables of their mothers. There was a male excess in cases with CTD (56.8%) with the same mean gestational age (39.4 versus 39.4 weeks) and preterm birth rate (8.2 versus 9.2%), but their mean birth weight was smaller (3077 versus 3276 g) with a high rate of low birthweight (14.6 versus 5.7%) compared to the birth outcomes of population controls. These data indicate intrauterine growth restriction of fetuses affected with transposition of great arteries, tetralogy of Fallot and double-outlet right ventricle particularly in females, while there were a shorter mean gestational age and smaller mean birth weigh in cases with common truncus. In general CTD, except common truncus, had no effect for gestational age but associated with a high risk for intrauterine fetal growth restriction particularly in female cases.

Trafficking Dynamics of PCSK9-Induced LDLR Degradation: Focus on Human PCSK9 Mutations and C-Terminal Domain

PubMed Central

Villeneuve, Louis; Demers, Annie; Mayer, Gaétan

2016-01-01

PCSK9 is a secreted ligand and negative post-translational regulator of low-density lipoprotein receptor (LDLR) in hepatocytes. Gain-of-function (GOF) or loss-of-function (LOF) mutations in PCSK9 are directly correlated with high or low plasma LDL-cholesterol levels, respectively. Therefore, PCSK9 is a prevailing lipid-lowering target to prevent coronary heart diseases and stroke. Herein, we fused monomeric fluorescent proteins to PCSK9 and LDLR to visualize their intra- and extracellular trafficking dynamics by live confocal microscopy. Fluorescence recovery after photobleaching (FRAP) showed that PCSK9 LOF R46L mutant and GOF mutations S127R and D129G, but not the LDLR high-affinity mutant D374Y, significantly accelerate PCSK9 exit from the endoplasmic reticulum (ER). Quantitative analysis of inverse FRAP revealed that only R46L presented a much slower trafficking from the trans-Golgi network (TGN) to the plasma membrane and a lower mobile fraction likely suggesting accumulation or delayed exit at the TGN as an underlying mechanism. While not primarily involved in LDLR binding, PCSK9 C-terminal domain (CTD) was found to be essential to induce LDLR degradation both upon its overexpression in cells or via the extracellular pathway. Our data revealed that PCSK9 CTD is required for the localization of PCSK9 at the TGN and increases its LDLR-mediated endocytosis. Interestingly, intracellular lysosomal targeting of PCSK9-ΔCTD was able to rescue its capacity to induce LDLR degradation emphasizing a role of the CTD in the sorting of PCSK9-LDLR complex towards late endocytic compartments. Finally, we validated our dual fluorescence system as a cell based-assay by preventing PCSK9 internalization using a PCSK9-LDLR blocking antibody, which may be expended to identify protein, peptide or small molecule inhibitors of PCSK9. PMID:27280970

Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease

PubMed Central

Girgis, Reda E; Frost, Adaani E; Hill, Nicholas S; Horn, Evelyn M; Langleben, David; McLaughlin, Vallerie V; Oudiz, Ronald J; Robbins, Ivan M; Seibold, James R; Shapiro, Shelley; Tapson, Victor F; Barst, Robyn J

2007-01-01

Introduction Endothelin receptor antagonism has become an important component in the treatment of pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD). The purpose of this study was to analyse the safety and effectiveness of sitaxsentan, a selective antagonist of the ETA receptor, in a cohort of patients with PAH and CTD. Short‐term clinical and haemodynamic effects and longer‐term follow‐up data are presented. Methods A post hoc subgroup analysis was performed on 42 patients who had PAH associated with CTD, out of a group of 178 patients enrolled in a 12‐week, double‐blind, randomised clinical trial of sitaxsentan versus placebo. Data from 33 patients assigned to sitaxsentan 100 mg or 300 mg daily were pooled and compared with nine placebo‐treated patients. There were 41 patients entered into the blinded extension study, in which all patients received either 100 mg or 300 mg sitaxsentan once daily. Results Patients treated with sitaxsentan had a mean (SD) increase in 6 minute walk distance of 20 (5) m from baseline to week 12 (p = 0.037), whereas the placebo group had a decrease of 38 (84) m, resulting in a placebo‐subtracted treatment effect of 58 m (p = 0.027). Parallel improvements in quality of life and haemodynamics were also observed. No patient discontinued their drug during the 12‐week trial. In the blinded extension study (median treatment duration 26 weeks), more patients were in functional class I–II than in III–IV (p<0.001) at the end of the study compared with the start of active therapy. Elevation of hepatic transaminase levels occurred in two patients. Conclusions Sitaxsentan appears to be efficacious in patients with PAH associated with CTD. PMID:17472992

An integrative data mining approach to identifying adverse outcome pathway signatures.

PubMed

Oki, Noffisat O; Edwards, Stephen W

2016-03-28

The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or population. Computational approaches to explore and determine these connections can accelerate the assembly of AOPs. By leveraging the wealth of publicly available data covering chemical effects on biological systems, computationally-predicted AOPs (cpAOPs) were assembled via data mining of high-throughput screening (HTS) in vitro data, in vivo data and other disease phenotype information. Frequent Itemset Mining (FIM) was used to find associations between the gene targets of ToxCast HTS assays and disease data from Comparative Toxicogenomics Database (CTD) by using the chemicals as the common aggregators between datasets. The method was also used to map gene expression data to disease data from CTD. A cpAOP network was defined by considering genes and diseases as nodes and FIM associations as edges. This network contained 18,283 gene to disease associations for the ToxCast data and 110,253 for CTD gene expression. Two case studies show the value of the cpAOP network by extracting subnetworks focused either on fatty liver disease or the Aryl Hydrocarbon Receptor (AHR). The subnetwork surrounding fatty liver disease included many genes known to play a role in this disease. When querying the cpAOP network with the AHR gene, an interesting subnetwork including glaucoma was identified. While substantial literature exists to support the potential for AHR ligands to elicit glaucoma, it was not explicitly captured in the public annotation information in CTD. The subnetwork from this analysis suggests a cpAOP that includes changes in CYP1B1 expression, which has been previously established in the literature as a primary cause of glaucoma. These case studies highlight the value in integrating multiple data sources when defining cpAOPs for HTS data. Copyright © 2016. Published by Elsevier Ireland Ltd.

In situ fluorescence measurements of protein-, humic- and HAP-like materials in the Northwestern Mediterranean Sea

NASA Astrophysics Data System (ADS)

Tedetti, Marc; Bachet, Caroline; Germain, Chloé; Ferretto, Nicolas; Bhairy, Nagib; Guigue, Catherine; Besson, Florent; Beguery, Laurent; Goutx, Madeleine

2015-04-01

Understanding the biogeochemical functioning of the ocean requires high frequency measurements of dissolved organic matter (DOM) descriptors. For 10 years, the technological developments of fluorescence sensors try to cover this need. In this context, our laboratory developed the MiniFluo-UV sensor, a prototype of miniaturized submersible fluorometer for the detection of aromatic compounds that fluoresce in the UV spectral domain. The qualification of the sensor consisted in measurements of drift, linearity, repeatability, sensitivity to light, temperature and pressure, and detection limits of phenanthrene (HAP) and tryptophan (aromatic amino acid) in standard solutions. Measurements were also conducted in crude oil water soluble fractions (WSFs). The MiniFluo-UV sensor was then deployed in two distinct areas of the Northwestern Mediterranean Sea: 1) in the Gulf of Lion during the continuous monitoring of the surface water layer (DEWEX cruise, winter and spring 2013) and 2) in the Bay of Marseilles, heavily impacted by urban activities, where the sensor was mounted onto the SeaExplorer underwater glider and onto a CTD vertical profiler (July-December 2014). These platforms were also equipped with a humic-like fluorescence sensor and other sensors for hydrological and biogeochemical parameters (T, S, Chla, oxygen, turbidity). The patterns of fluorescence signatures enabled to distinguish interesting distributions of DOM in relation with hydrological features and spring biological production in the Gulf of Lion, and showed the accumulation of contaminants in marine areas under anthropogenic pressure. This work was conducted within the framework of the ANR-09-ECOT-009-01 "IBISCUS" in collaboration with ALSEAMAR-ALCEN (Aix-en-Provence) and MicroModule (Brest) companies. It is relevant to WP5 NEXOS objectives. The SACEUP team of the DEWEX-MERMEX experiment is warmly acknowledged.

Under-Ice Operations with AUVS in High Latitudes

NASA Astrophysics Data System (ADS)

Ferguson, J.; Kaminski, C. D.

2012-12-01

In 2010 and 2011, ISE Explorer Autonomous Underwater Vehicles (AUV), built for Natural Resources Canada (NRCan), were deployed to Canada's high Arctic. The mission was to undertake under-ice bathymetric surveys supporting Canada's submission under the United Nations Convention on the Law of the Sea (UNCLOS). During these deployments several under-ice records were broken and several new technologies were demonstrated. The NRCan AUV is a 5000 meter depth rated vehicle, with several innovative additions to make it suitable for arctic survey work. Most notable are a depth rated variable ballast system, a 1300 Hz long-range homing system, and under-ice charging and data transfer capabilities. The Explorer's range was extended to approximately 450 km by adding a hull section to accommodate extra batteries. The scientific payload onboard included a Seabird SBE49 Conductivity-Temperature-Depth (CTD) sensor, Knudsen singlebeam echosounder, and a Kongsberg Simrad EM2000 multibeam echosounder. In 2010, operations were conducted from an ice camp near Borden Island (78°14'N, 112°39'W) operating through an ice hole. Following several test missions, the AUV spent 10 days surveying under ice before being successfully recovered. In total, close to 1100 km of under-ice survey was undertaken at depths to 3160 meters. A further set of operations was carried out in August and September 2011 from the Canadian Icebreaker CCGS Louis St. Laurent operating with the American Icebreaker USCGS Healy. Here the operations were much further north to latitudes of 88°30' N and to depths of 3500 meters. In this paper, the 2010 ice camp and the 2011 icebreaker missions are described, with an outline of technology developments that were undertaken, the preparations that were necessary for the success of the missions and finally, the outcome of the missions themselves.

The IAOOS arctic network project, status and prospect

NASA Astrophysics Data System (ADS)

Pelon, J.; Provost, C.; Sennechael, N.; Calzas, M.; Blouzon, F.; Gascard, J. C.

2015-12-01

It is quite clear that for studying Arctic climate changes, and better understand interacting processes it is essential to follow an integrated approach for observing and modeling the whole Arctic system encompassing the atmosphere, the ocean and sea-ice at once. Due to the difficulties in retrieving key parameters, satellite observations alone are not the right answer. The project we are developing, is an attempt to tackle this challenge by providing and maintaining a new integrated observing network of instrumented buoys over the Arctic Ocean in order to collect simultaneously and in real time information related to the state of the upper Ocean, the lower Atmosphere and the Arctic sea-ice/snow. It is planned to operate several autonomous platforms in a network in the Arctic Ocean for a period of at least 5 years. Each platform is equipped to vertically sense and profile key variables in the ocean, sea-ice and atmosphere using - CTD (conductivity, temperature, depth) vertical profilers sensors collecting ocean temperature and salinity down to 800m depth, - Temperature and heat conductivity in snow and ice from ice-mass-balance systems - Cloud and aerosol lidar profiling of the lower atmosphere - Diffuse and direct solar flux using wide angle radiometer - Meteorological standard parameters at the surface Platforms allow measurements to be transmitted in near real time via Iridium satellites. As they will be drifting, it is planned to replace part of them every year. Major tests were performed deploying progressively fully equipped IAOOS platform at the North Pole in April 2012, 2013 and 2014. These platforms drifted from the North Pole in April to Fram Strait (September, October) providing spring summer and fall field data. Important fieldwork for IAOOS was also taking place within the Norwegian ice camp on board R/V Lance organized by the Norsk Polar Institute from January to June 2015, as part of the Norwegian young ICE (N-ICE 2015) cruise project. These intensive tests were very timely. The first IAOOS array deployment will start in August 2015 from R/V Araon during the Korean cruise organized by the KOPRI in the Canadian Basin and from R/V Polarstern during the German cruise TRANSARC II organized by the Alfred Wegener Institute in the Eurasian Basin. First results obtained in the frame of IAOOS will be presented and discussed.

A snapshot of internal waves and hydrodynamic instabilities in the southern Bay of Bengal

NASA Astrophysics Data System (ADS)

Lozovatsky, Iossif; Wijesekera, Hemantha; Jarosz, Ewa; Lilover, Madis-Jaak; Pirro, Annunziata; Silver, Zachariah; Centurioni, Luca; Fernando, H. J. S.

2016-08-01

Measurements conducted in the southern Bay of Bengal (BoB) as a part of the ASIRI-EBoB Program portray the characteristics of high-frequency internal waves in the upper pycnocline as well as the velocity structure with episodic events of shear instability. A 20 h time series of CTD, ADCP, and acoustic backscatter profiles down to 150 m as well as temporal CTD measurements in the pycnocline at z = 54 m were taken to the east of Sri Lanka. Internal waves of periods ˜10-40 min were recorded at all depths below a shallow (˜20-30 m) surface mixed layer in the background of an 8 m amplitude internal tide. The absolute values of vertical displacements associated with high-frequency waves followed the Nakagami distribution with a median value of 2.1 m and a 95% quintile 6.5 m. The internal wave amplitudes are normally distributed. The tails of the distribution deviate from normality due to episodic high-amplitude displacements. The sporadic appearance of internal waves with amplitudes exceeding ˜5 m usually coincided with patches of low Richardson numbers, pointing to local shear instability as a possible mechanism of internal-wave-induced turbulence. The probability of shear instability in the summer BoB pycnocline based on an exponential distribution of the inverse Richardson number, however, appears to be relatively low, not exceeding 4% for Ri < 0.25 and about 10% for Ri < 0.36 (K-H billows). The probability of the generation of asymmetric breaking internal waves and Holmboe instabilities is above ˜25%.

RIMPAC 08: Naval Oceanographic Office glider operations

NASA Astrophysics Data System (ADS)

Mahoney, Kevin L.; Grembowicz, Ken; Bricker, Bruce; Crossland, Steve; Bryant, Danielle; Torres, Marc; Giddings, Tom

2009-05-01

The Naval Oceanographic Office (NAVOCEANO) Glider Operations Center (GOC) supported its first joint-mission exercise during Rim of the Pacific (RIMPAC) 08, a multi-national naval exercise conducted during July 2008 near the Hawaiian Islands. NAVOCEANO personnel deployed four Seagliders from USNS SUMNER for Anti-submarine Warfare (ASW) operations and four Slocum gliders for Mine Warfare (MIW) operations. Each Seaglider was equipped with a Sea-Bird Electronics (SBE) 41cp CTD and Wet Labs, Inc. bb2fl ECO-puck optical sensor. The instrumentation suite on the Slocum gliders varied, but each Slocum glider had an SBE 41cp CTD combined with one of the following optical sensors: a Wet Labs, Inc. AUVb scattering sensor, a Wet Labs, Inc. bb3slo ECO-puck backscattering sensor, or a Satlantic, Inc. OCR radiometer. Using Iridium communications, the GOC had command and control of all eight gliders, with Department of Defense (DoD) personnel and DoD contractors serving as glider pilots. Raw glider data were transmitted each time a glider surfaced, and the subsequent data flow included processing, quality-control procedures, and the generation of operational and tactical products. The raw glider data were also sent to the Naval Research Laboratory at Stennis Space Center (NRLSSC) for fusion with satellite data and modeled data (currents, tides, etc.) to create optical forecasting, optical volume, and electro-optical identification (EOID) performance surface products. The glider-based products were delivered to the ASW and MIW Reach Back Cells for incorporation into METOC products and for dissemination to the Fleet. Based on the metrics presented in this paper, the inaugural joint-mission operation was a success.

Unstructured-grid coastal ocean modelling in Southern Adriatic and Northern Ionian Seas

NASA Astrophysics Data System (ADS)

Federico, Ivan; Pinardi, Nadia; Coppini, Giovanni; Oddo, Paolo

2016-04-01

The Southern Adriatic Northern Ionian coastal Forecasting System (SANIFS) is a short-term forecasting system based on unstructured grid approach. The model component is built on SHYFEM finite element three-dimensional hydrodynamic model. The operational chain exploits a downscaling approach starting from the Mediterranean oceanographic-scale model MFS (Mediterranean Forecasting System, operated by INGV). The implementation set-up has been designed to provide accurate hydrodynamics and active tracer processes in the coastal waters of Southern Eastern Italy (Apulia, Basilicata and Calabria regions), where the model is characterized by a variable resolution in range of 50-500 m. The horizontal resolution is also high in open-sea areas, where the elements size is approximately 3 km. The model is forced: (i) at the lateral open boundaries through a full nesting strategy directly with the MFS (temperature, salinity, non-tidal sea surface height and currents) and OTPS (tidal forcing) fields; (ii) at surface through two alternative atmospheric forcing datasets (ECMWF and COSMOME) via MFS-bulk-formulae. Given that the coastal fields are driven by a combination of both local/coastal and deep ocean forcings propagating along the shelf, the performance of SANIFS was verified first (i) at the large and shelf-coastal scales by comparing with a large scale CTD survey and then (ii) at the coastal-harbour scale by comparison with CTD, ADCP and tide gauge data. Sensitivity tests were performed on initialization conditions (mainly focused on spin-up procedures) and on surface boundary conditions by assessing the reliability of two alternative datasets at different horizontal resolution (12.5 and 7 km). The present work highlights how downscaling could improve the simulation of the flow field going from typical open-ocean scales of the order of several km to the coastal (and harbour) scales of tens to hundreds of meters.

Ocean mixing beneath Pine Island Glacier ice shelf, West Antarctica

NASA Astrophysics Data System (ADS)

Kimura, Satoshi; Jenkins, Adrian; Dutrieux, Pierre; Forryan, Alexander; Naveira Garabato, Alberto C.; Firing, Yvonne

2016-12-01

Ice shelves around Antarctica are vulnerable to an increase in ocean-driven melting, with the melt rate depending on ocean temperature and the strength of flow inside the ice-shelf cavities. We present measurements of velocity, temperature, salinity, turbulent kinetic energy dissipation rate, and thermal variance dissipation rate beneath Pine Island Glacier ice shelf, West Antarctica. These measurements were obtained by CTD, ADCP, and turbulence sensors mounted on an Autonomous Underwater Vehicle (AUV). The highest turbulent kinetic energy dissipation rate is found near the grounding line. The thermal variance dissipation rate increases closer to the ice-shelf base, with a maximum value found ˜0.5 m away from the ice. The measurements of turbulent kinetic energy dissipation rate near the ice are used to estimate basal melting of the ice shelf. The dissipation-rate-based melt rate estimates is sensitive to the stability correction parameter in the linear approximation of universal function of the Monin-Obukhov similarity theory for stratified boundary layers. We argue that our estimates of basal melting from dissipation rates are within a range of previous estimates of basal melting.

Carbon Dioxide, Hydrographic, and Chemical Data Obtained During the R/V John V. Vickers Cruise in the Pacific Ocean (WOCE Section P13, NOAA CGC92 Cruise, August 4 - October 21, 1992)

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

Kozyr, A.

This data documentation discusses the procedures and methods used to measure total carbon dioxide (TCO{sub 2}) and total alkalinity (TALK) at hydrographic stations during the R/V John V. Vickers oceanographic cruise in the Pacific Ocean (Section P13). Conducted as part of the World Ocean Circulation Experiment (WOCE) and the National Oceanic and Atmospheric Administration's Climate and Global Change Program, the cruise began in Los Angeles, California, on August 4, 1992, with a transit line (Leg 0) to Dutch Harbor, Alaska. On August 16, the ship departed Dutch Harbor on Leg 1 of WOCE section P13. On September 15, the R/Vmore » John V. Vickers arrived in Kwajalein, Marshall Islands, for emergency repairs, and after 11 days in port departed for Leg 2 of Section P13 on September 26. The cruise ended on October 21 in Noumea, New Caledonia. Measurements made along WOCE Section P13 included pressure, temperature, salinity [measured by a conductivity, temperature, and depth sensor (CTD)], bottle salinity, bottle oxygen, phosphate, nitrate, nitrite, silicate, chlorofluorocarbons (CFC-11, CFC-12), TCO{sub 2} , and TALK. The TCO{sub 2} was measured by coulometry using a Single-Operator Multiparameter Metabolic Analyzer (SOMMA). The overall precision and accuracy of the analyses was {+-}2 {micro}mol/kg. Samples collected for TALK were measured by potentiometric titration; precision was {+-}2 {micro}mol/kg. The CO{sub 2} -related measurements aboard the R/V John V. Vickers were supported by the U.S. Department of Energy. The WOCE Section P13 data set is available free of charge as a numeric data package (NDP) from the Carbon Dioxide Information Analysis Center. The NDP consists of two oceanographic data files, two FORTRAN 90 data-retrieval routine files, a documentation file, and this printed report, which describes the contents and format of all files as well as the procedures and methods used to obtain the data. Instructions on how to access the data are provided.« less

hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK RNA

DOE PAGES

Eichhorn, Catherine D.; Chug, Rahul; Feigon, Juli

2016-09-26

The 7SK small nuclear ribonucleoprotein (snRNP) sequesters and inactivates the positive transcription elongation factor b (P-TEFb), an essential eukaryotic mRNA transcription factor. The human La-related protein group 7 (hLARP7) is a constitutive component of the 7SK snRNP and localizes to the 3' terminus of the 7SK long noncoding RNA. hLARP7, and in particular its C-terminal domain (CTD), is essential for 7SK RNA stability and assembly with P-TEFb. The hLARP7 N-terminal Lamodule binds and protects the 3' end from degradation, but the structural and functional role of its CTD is unclear.We report the solution NMR structure of the hLARP7 CTD andmore » show that this domain contains an xRRM, a class of atypical RRM first identified in the Tetrahymena thermophila telomerase LARP7 protein p65. The xRRM binds the 3' end of 7SK RNA at the top of stem-loop 4 (SL4) and interacts with both unpaired and base-paired nucleotides. This study thus confirms that the xRRM is general to the LARP7 family of proteins and defines the binding site for hLARP7 on the 7SK RNA, providing insight into function.« less

High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders

PubMed Central

Abonia, J. Pablo; Wen, Ting; Stucke, Emily M.; Grotjan, Tommie; Griffith, Molly S.; Kemme, Katherine A.; Collins, Margaret H.; Putnam, Philip E.; Franciosi, James P.; von Tiehl, Karl F.; Tinkle, Brad T.; Marsolo, Keith A.; Martin, Lisa J.; Ware, Stephanie M.; Rothenberg, Marc E.

2013-01-01

Background Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease mediated by immune hypersensitization to multiple foods and strongly associated with atopy and esophageal remodeling. Objective We provide clinical and molecular evidence indicating a high prevalence of EoE in patients with inherited connective tissue disorders (CTDs). Methods We examined the rate of EoE among patients with CTDs and subsequently analyzed esophageal mRNA transcript profiles in patients with EoE with or without CTD features. Results We report a cohort of 42 patients with EoE with a CTD-like syndrome, representing 0.8% of patients with CTDs and 1.3% of patients with EoE within our hospital-wide electronic medical record database and our EoE research registry, respectively. An 8-fold risk of EoE in patients with CTDs (relative risk, 8.1; 95% confidence limit, 5.1-12.9; χ21 = 112.0; P < 10−3) was present compared with the general population. Esophageal transcript profiling identified a distinct subset of genes, including COL8A2, in patients with EoE and CTDs. Conclusion There is a remarkable association of EoE with CTDs and evidence for a differential expression of genes involved in connective tissue repair in this cohort. Thus, we propose stratification of patients with EoE and CTDs into a subset referred to as EoE-CTD. PMID:23608731

Characterizing turbulent overturns in CTD-data

NASA Astrophysics Data System (ADS)

van Haren, Hans; Gostiaux, Louis

2014-06-01

We are concerned with the shape of overturns due to irreversible effects of turbulent mixing through internal wave breaking in the ocean. Vertical (z) overturn displacements (d) are computed from ship-borne SeaBird-911 CTD-data using the well-established method of reordering unstable portions in vertical density profiles. When displayed as a function of z, the displacements d(z) reveal a characteristic zigzag shape. Here, we primarily investigate the particular slope (z/d) of this zigzag signature after assigning the displacements to the end-point depths. Using model-overturns we show that this slope equals ½ for a solid-body-rotation, while a more sophisticated Rankine-vortex overturn-model, here employed in the vertical, has slopes slightly >½ in the interior and >1 along the sides. In the case of a near-homogeneous layer, displacement-points fill a parallelogram with side-edges having a slope of 1. The models are used to interpret overturn shapes in NE-Atlantic-Ocean-data from moderately deep, turbulent waters above Rockall Bank (off Ireland) and from deep, weakly stratified waters above Mount Josephine (off Portugal). These are compared with salinity-compensated intrusion data in Mediterranean-outflow-waters in the Canary Basin. Dynamically, most overturns are found to resemble the half-turn Rankine-vortex model and very few a, small-only, solid-body-rotation. Additionally, the usefulness and uselessness of upcast-CTD-data are discussed for overturn characterization.

Cdk7 mediates RPB1-driven mRNA synthesis in Toxoplasma gondii

PubMed Central

Deshmukh, Abhijit S.; Mitra, Pallabi; Maruthi, Mulaka

2016-01-01

Cyclin-dependent kinase 7 in conjunction with CyclinH and Mat1 activates cell cycle CDKs and is a part of the general transcription factor TFIIH. Role of Cdk7 is well characterized in model eukaryotes however its relevance in protozoan parasites has not been investigated. This important regulator of key processes warrants closer examination particularly in this parasite given its unique cell cycle progression and flexible mode of replication. We report functional characterization of TgCdk7 and its partners TgCyclinH and TgMat1. Recombinant Cdk7 displays kinase activity upon binding its cyclin partner and this activity is further enhanced in presence of Mat1. The activated kinase phosphorylates C-terminal domain of TgRPB1 suggesting its role in parasite transcription. Therefore, the function of Cdk7 in CTD phosphorylation and RPB1 mediated transcription was investigated using Cdk7 inhibitor. Unphosphorylated CTD binds promoter DNA while phosphorylation by Cdk7 triggers its dissociation from DNA with implications for transcription initiation. Inhibition of Cdk7 in the parasite led to strong reduction in Serine 5 phosphorylation of TgRPB1-CTD at the promoters of constitutively expressed actin1 and sag1 genes with concomitant reduction of both nascent RNA synthesis and 5′-capped transcripts. Therefore, we provide compelling evidence for crucial role of TgCdk7 kinase activity in mRNA synthesis. PMID:27759017

An Integrative data mining approach to identifying Adverse ...

EPA Pesticide Factsheets

The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or population. Computational approaches to explore and determine these connections can accelerate the assembly of AOPs. By leveraging the wealth of publicly available data covering chemical effects on biological systems, computationally-predicted AOPs (cpAOPs) were assembled via data mining of high-throughput screening (HTS) in vitro data, in vivo data and other disease phenotype information. Frequent Itemset Mining (FIM) was used to find associations between the gene targets of ToxCast HTS assays and disease data from Comparative Toxicogenomics Database (CTD) by using the chemicals as the common aggregators between datasets. The method was also used to map gene expression data to disease data from CTD. A cpAOP network was defined by considering genes and diseases as nodes and FIM associations as edges. This network contained 18,283 gene to disease associations for the ToxCast data and 110,253 for CTD gene expression. Two case studies show the value of the cpAOP network by extracting subnetworks focused either on fatty liver disease or the Aryl Hydrocarbon Receptor (AHR). The subnetwork surrounding fatty liver disease included many genes known to play a role in this disease. When querying the cpAOP

hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK RNA

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

Eichhorn, Catherine D.; Chug, Rahul; Feigon, Juli

The 7SK small nuclear ribonucleoprotein (snRNP) sequesters and inactivates the positive transcription elongation factor b (P-TEFb), an essential eukaryotic mRNA transcription factor. The human La-related protein group 7 (hLARP7) is a constitutive component of the 7SK snRNP and localizes to the 3' terminus of the 7SK long noncoding RNA. hLARP7, and in particular its C-terminal domain (CTD), is essential for 7SK RNA stability and assembly with P-TEFb. The hLARP7 N-terminal Lamodule binds and protects the 3' end from degradation, but the structural and functional role of its CTD is unclear.We report the solution NMR structure of the hLARP7 CTD andmore » show that this domain contains an xRRM, a class of atypical RRM first identified in the Tetrahymena thermophila telomerase LARP7 protein p65. The xRRM binds the 3' end of 7SK RNA at the top of stem-loop 4 (SL4) and interacts with both unpaired and base-paired nucleotides. This study thus confirms that the xRRM is general to the LARP7 family of proteins and defines the binding site for hLARP7 on the 7SK RNA, providing insight into function.« less

Water masses in the Monterey Bay during the summer of 2000

NASA Astrophysics Data System (ADS)

Warn-Varnas, Alex; Gangopadhyay, Avijit; Hawkins, J. A.

2007-06-01

Water masses in Monterey Bay are determined from the CTD casts of the Monterey Ocean Observing System (MOOS) Upper-water-column Science Experiment (MUSE) August 2000 dataset. It is shown through cluster analysis that the MUSE 2000 CTD dataset contains 5 water masses. These five water masses are: bay surface water (BSW), bay warm water (BWW), bay intermediate water (BIW), sub arctic upper water (SUW) and North Pacific deep water (NPDW). The BWW is a new water mass that exists in one area and is attributed to the effects of solar heating. The volumes occupied by each of the water masses are obtained. The BIW water is the most dominant water mass and occupies 68.8% of the volume. The statistical means and standard deviations for each water parameter, including spiciness and oxygen concentration, are calculated during separate upwelling and relaxed periods. The water mass content and structure are analyzed and studied during upwelling and a relaxed period. During upwelling, along a CTD track off Pt. Ano Nuevo, the water mass T, S distribution tended to be organized along three branches. Off Pt. Ano Nuevo the innovative coastal observation network (ICON) model showed the formation of a cyclonic eddy during the analyzed upwelling period. In time the eddy moved southwest and became absorbed into the southerly flow during the initial phases of the following wind-relaxed period.

The role of parental perceptions of tic frequency and intensity in predicting tic-related functional impairment in youth with chronic tic disorders.

PubMed

Espil, Flint M; Capriotti, Matthew R; Conelea, Christine A; Woods, Douglas W

2014-12-01

Tic severity is composed of several dimensions. Tic frequency and intensity are two such dimensions, but little empirical data exist regarding their relative contributions to functional impairment in those with chronic tic disorders (CTD). The present study examined the relative contributions of these dimensions in predicting tic-related impairment across several psychosocial domains. Using data collected from parents of youth with CTD, multivariate regression analyses revealed that both tic frequency and intensity predicted tic-related impairment in several areas; including family and peer relationships, school interference, and social endeavors, even when controlling for the presence of comorbid anxiety symptoms and Attention Deficit Hyperactivity Disorder diagnostic status. Results showed that tic intensity predicted more variance across more domains than tic frequency.

Synthesis of IgM, IgG and IgA in rheumatoid arthritis.

PubMed Central

Poikonen, K; Oka, M; Möttönen, T; Jokinen, I; Arvilommi, H

1982-01-01

We studied the production of immunoglobulins by lymphocytes separated from the blood of 15 rheumatoid arthritis (RA) patients, of 12 patients suffering from other connective tissue diseases (CTD), and of 18 healthy controls. The production of IgM, IgG and IgA in pokeweed-mitogen-stimulated cultures was measured by counting the number of plaque-forming cells (PFC) and by determining the concentration of secreted immunoglobulins by means of an enzyme immunoassay. Synthesis of immunoglobulins, particularly IgM and IgG, was lower than in other CTD patients or controls. The IgM response of RA patients was 20% and 29% (PFC and Ig concentrations) that of the controls. The respective figures for IgG were 33% and 53% and for IgA 61% and 72%. PMID:6756322

Small Moves, NUI. Small Moves: Beginning to Investigate Biogeochemical Exchange From the Seafloor to the Exterior of an Ice-Covered Ocean

NASA Astrophysics Data System (ADS)

German, C. R.; Boetius, A.

2017-12-01

We present results from two recent cruises, using the new Nereid Under Ice (NUI) vehicle aboard the FS Polarstern, in which we investigated biogeochemical fluxes from the deep seafloor of the Gakkel Ridge, an ultraslow spreading ridge that spans the ice-covered Arctic Ocean, and the mechanisms by which biogeochemical signals might be transferred from within the underlying ocean to the overlying Arctic ice. The scientific advances for this work progress hand in hand with technological capability. During a first cruise in 2014, our NUI-based investigations focused on photosynthetically-driven biogeochemical cycling in the uppermost water column and how to study such processes using in situ sensing immediately at and beneath the rough topography of the overlying ice-cover. For that work we relied entirely upon human-in-the-loop control of the vehicle via a single optical fiber light tether than provided real-time monitoring and control of the vehicle as it ranged laterally out under the ice up to 1km distant from the ship, conducting physical, geochemical and biological surveys. Instrumentation used for that work included multibeam mapping and imaging (digital still photographs and HD video), in situ spectroscopy to study light transmission through the ice and biogeochemical mapping of the ocean water column using a combination of CTD sensing, fluorometry and an in situ nitrate analyzer. Returning to the Arctic in 2016 we extended our exploration modes with NUI further, investigating for seafloor fluid flow at a shallow setting on the flanks of the Gakkel Ridge where the seabed rises from >4000m to <600m depth. In AUV mode, NUI conducted water column sensing using CTD, optical backscatter and Eh sensors and seafloor surveys using high resolution multibeam bathymetry and stereoscopic seafloor imaging. In subsequent ROV operations, NUI was used to conduct detailed investigation of seabed biological communities. This included targeted sampling of individual organisms and ecosystems at precise locations at the seabed completely decoupled from the movement of the ship (horizontal displacements of 1km or more) at the ice-covered ocean surface. While the existing NUI vehicle does not map directly to model payloads for future SLS missions to Europa or Enceladus it does provide for important small moves in the right direction.

A Two-Dimensional Flow Sensor with Integrated Micro Thermal Sensing Elements and a Back Propagation Neural Network

PubMed Central

Que, Ruiyi; Zhu, Rong

2014-01-01

This paper demonstrates a novel flow sensor with two-dimensional 360° direction sensitivity achieved with a simple structure and a novel data fusion algorithm. Four sensing elements with roundabout wires distributed in four quadrants of a circle compose the sensor probe, and work in constant temperature difference (CTD) mode as both Joule heaters and temperature detectors. The magnitude and direction of a fluid flow are measured by detecting flow-induced temperature differences among the four elements. The probe is made of Ti/Au thin-film with a diameter of 2 mm, and is fabricated using micromachining techniques. When a flow goes through the sensor, the flow-induced temperature differences are detected by the sensing elements that also serve as the heaters of the sensor. By measuring the temperature differences among the four sensing elements symmetrically distributed in the sensing area, a full 360° direction sensitivity can be obtained. By using a BP neural network to model the relationship between the readouts of the four sensor elements and flow parameters and execute data fusion, the magnitude and direction of the flow can be deduced. Validity of the sensor design was proven through both simulations and experiments. Wind tunnel experimental results show that the measurement accuracy of the airflow speed reaches 0.72 m/s in the range of 3 m/s–30 m/s and the measurement accuracy of flow direction angle reaches 1.9° in the range of 360°. PMID:24385032

A two-dimensional flow sensor with integrated micro thermal sensing elements and a back propagation neural network.

PubMed

Que, Ruiyi; Zhu, Rong

2013-12-31

This paper demonstrates a novel flow sensor with two-dimensional 360° direction sensitivity achieved with a simple structure and a novel data fusion algorithm. Four sensing elements with roundabout wires distributed in four quadrants of a circle compose the sensor probe, and work in constant temperature difference (CTD) mode as both Joule heaters and temperature detectors. The magnitude and direction of a fluid flow are measured by detecting flow-induced temperature differences among the four elements. The probe is made of Ti/Au thin-film with a diameter of 2 mm, and is fabricated using micromachining techniques. When a flow goes through the sensor, the flow-induced temperature differences are detected by the sensing elements that also serve as the heaters of the sensor. By measuring the temperature differences among the four sensing elements symmetrically distributed in the sensing area, a full 360° direction sensitivity can be obtained. By using a BP neural network to model the relationship between the readouts of the four sensor elements and flow parameters and execute data fusion, the magnitude and direction of the flow can be deduced. Validity of the sensor design was proven through both simulations and experiments. Wind tunnel experimental results show that the measurement accuracy of the airflow speed reaches 0.72 m/s in the range of 3 m/s-30 m/s and the measurement accuracy of flow direction angle reaches 1.9° in the range of 360°.

Numerical modeling of thermal regime in inland water bodies with field measurement data

NASA Astrophysics Data System (ADS)

Gladskikh, D.; Sergeev, D.; Baydakov, G.; Soustova, I.; Troitskaya, Yu.

2018-01-01

Modification of the program complex LAKE, which is intended to compute the thermal regimes of inland water bodies, and the results of its validation in accordance with the parameters of lake part of Gorky water reservoir are reviewed in the research. The modification caused changing the procedure of input temperature profile assignment and parameterization of surface stress on air-water boundary in accordance with the consideration of wind influence on mixing process. Also the innovation consists in combined methods of gathering meteorological parameters from files of global meteorological reanalysis and data of hydrometeorological station. Temperature profiles carried out with CTD-probe during expeditions in the period 2014-2017 were used for validation of the model. The comparison between the real data and the numerical results and its assessment based on time and temperature dependences in control points, correspondence of the forms of the profiles and standard deviation for all performed realizations are provided. It is demonstrated that the model reproduces the results of field measurement data for all observed conditions and seasons. The numerical results for the regimes with strong mixing are in the best quantitative and qualitative agreement with the real profiles. The accuracy of the forecast for the ones with strong stratification near the surface is lower but all specificities of the forms are correctly reproduced.

Quantifying Methane Emissions from the Arctic Ocean Seabed to the Atmosphere

NASA Astrophysics Data System (ADS)

Platt, Stephen; Pisso, Ignacio; Schmidbauer, Norbert; Hermansen, Ove; Silyakova, Anna; Ferré, Benedicte; Vadakkepuliyambatta, Sunil; Myhre, Gunnar; Mienert, Jürgen; Stohl, Andreas; Myhre, Cathrine Lund

2016-04-01

Large quantities of methane are stored under the seafloor in the shallow waters of the Arctic Ocean. Some of this is in the form of hydrates which may be vulnerable to deomposition due to surface warming. The Methane Emissions from Arctic Ocean to Atmosphere MOCA, (http://moca.nilu.no/) project was established in collaboration with the Centre for Arctic Gas Hydrate, Environment and Climate (CAGE, https://cage.uit.no/). In summer 2014, and summer and autumn 2015 we deployed oceanographic CTD (Conductivity, Temperature, Depth) stations and performed state-of-the-art atmospheric measurements of CH4, CO2, CO, and other meteorological parameters aboard the research vessel Helmer Hanssen west of Prins Karl's Forland, Svalbard. Air samples were collected for isotopic analysis (13C, 2H) and quantification of other hydrocarbons (ethane, propane, etc.). Atmospheric measurements are also available from the nearby Zeppelin Observatory at a mountain close to Ny-Ålesund, Svalbard. We will present data from these measurements that show an upper constraint of the methane flux in measurement area in 2014 too low to influence the annual CH4 budget. This is further supported by top-down constraints (maximum release consistent with observations at the Helmer Hansen and Zeppelin Observatory) determined using FLEXPART foot print sensitivities and the OsloCTM3 model. The low flux estimates despite the presence of active seeps in the area (numerous gas flares were observed using echo sounding) were apparently due to the presence of a stable ocean pycnocline at ~50 m.

Lung cancer development in patients with connective tissue disease-related interstitial lung disease: A retrospective observational study.

PubMed

Enomoto, Yasunori; Inui, Naoki; Yoshimura, Katsuhiro; Nishimoto, Koji; Mori, Kazutaka; Kono, Masato; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Iwashita, Toshihide; Suda, Takafumi

2016-12-01

Previous studies have reported that patients with idiopathic pulmonary fibrosis occasionally develop lung cancer (LC). However, in connective tissue disease (CTD)-related interstitial lung disease (ILD), there are few data regarding the LC development. The aim of the present study was to evaluate the clinical significance of LC development in patients with CTD-ILD. A retrospective review of our database of 562 patients with ILD between 2000 and 2014 identified 127 patients diagnosed with CTD-ILD. The overall and cumulative incidences of LC were calculated. In addition, the risk factors and prognostic impact of LC development were evaluated. The median age at the ILD diagnosis was 63 years (range 37-84 years), and 73 patients (57.5%) were female. The median follow-up period from the ILD diagnosis was 67.4 months (range 10.4-322.1 months). During the period, 7 out of the 127 patients developed LC (overall incidence 5.5%). The cumulative incidences at 1, 3, and 5 years were 0.0%, 1.8%, and 2.9%, respectively. The risk of LC development was significantly higher in patients with higher smoking pack-year (odds ratio [OR] 1.028; 95% confidence interval [CI] 1.008-1.049; P = 0.007) and emphysema on chest high-resolution computed tomography (OR 14.667; 95% CI 2.871-74.926; P = 0.001). The median overall survival time after developing LC was 7.0 months (95% CI 4.9-9.1 months), and the most common cause of death was LC, not ILD. According to the Cox proportional hazard model analysis with time-dependent covariates, patients who developed LC showed significantly poorer prognosis than those who did not (hazard ratio 87.86; 95% CI 19.56-394.67; P < 0.001). In CTD-ILD, clinicians should be careful with the risk of LC development in patients with a heavy smoking history and subsequent emphysema. Although not so frequent, the complication could be a poor prognostic determinant.

Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions.

PubMed

Pannek, Kerstin; Boyd, Roslyn N; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E

2014-01-01

Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Data of 50 children with unilateral CP caused by periventricular white matter lesions (5-17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7-16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm(2)) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment-AHA) was assessed in connections that showed significant differences in FA compared to CTD. FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r(2) = 0.16-0.44; p < 0.05). This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.

Chemical Fluxes from a Recently Erupted Submarine Volcano on the Mariana Arc

NASA Astrophysics Data System (ADS)

Buck, N. J.; Resing, J. A.; Lupton, J. E.; Larson, B. I.; Walker, S. L.; Baker, E. T.

2016-12-01

While hydrothermal circulation is paramount to the geochemical budget for a wide array of elements, relatively few flux estimates exist in the literature. To date most studies have concentrated on constraining global and vent-field scale inputs originating from ocean spreading ridges. The goal of this study is to directly measure the chemical flux from an active submarine volcano injecting hydrothermal fluids into the surface ocean. Ahyi Seamount, a submarine intraoceanic arc volcano located in the Northern Mariana Islands, has a summit depth <100 m and erupted in May 2014. In November 2014 a hydrothermal plume originating from Ahyi was sampled aboard the R/V Roger Revelle during the Submarine Ring of Fire 2014 Ironman Expedition. Shipboard hull mounted Acoustic Doppler Current Profile data was collected to provide current vector measurements to be used in combination with continuous and discrete CTD data. Towed CTD sections were conducted perpendicular to the current direction - a sampling strategy that optimizes chemical flux estimate calculations by reducing complexities introduced by temporal variability in the speed and direction of plume dispersion. The Ahyi plume had a significant optical backscatter signal accompanied by evidence of reduced chemical species and a lowered pH. It was sampled for He isotopes, CH4, H2, H2S, total CO2, nutrients, TSM and total and dissolved Fe and Mn. Laboratory analyses found enriched concentrations of H2, 3He, CO2 and Fe, consistent with a recent eruption. Preliminary flux calculations estimate a Fe input of 16 mmol s-1. This indicates shallow submarine arc volcanoes are capable of supplying appreciable quantities of Fe into the surface ocean. Further laboratory analyses and calculations to characterize and constrain the fluxes of other chemical constituents are underway.

The Role of Parental Perceptions of Tic Frequency and Intensity in Predicting Tic-Related Functional Impairment in Youth with Chronic Tic Disorders

PubMed Central

Espil, Flint M.; Capriotti, Matthew R.; Conelea, Christine A.; Woods, Douglas W.

2014-01-01

Tic severity is composed of several dimensions. Tic frequency and intensity are two such dimensions, but little empirical data exist regarding their relative contributions to functional impairment in those with Chronic Tic Disorders (CTD). The present study examined the relative contributions of these dimensions in predicting tic-related impairment across several psychosocial domains. Using data collected from parents of youth with CTD, multivariate regression analyses revealed that both tic frequency and intensity predicted tic-related impairment in several areas; including family and peer relationships, school interference, and social endeavors, even when controlling for the presence of comorbid anxiety symptoms and Attention Deficit Hyperactivity Disorder diagnostic status. Results showed that tic intensity predicted more variance across more domains than tic frequency. PMID:24395287

International Conference on Harmonisation; guidance on the M4 Common Technical Document--Quality: Questions and Answers/Location Issues; availability. Notice.

PubMed

2004-06-09

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "M4: The CTD--Quality: Questions and Answers/Location Issues." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). This guidance provides further clarification for preparing the quality components of an application file in the common technical document (CTD) format. The guidance addresses the relationship between linked sections for certain parameters (such as polymorphism and particle size), and it addresses location issues (by indicating the section in which to place requested information). The guidance is intended to ease the preparation of paper and electronic submissions, facilitate regulatory reviews, and simplify the exchange of regulatory information among regulatory authorities.

Retrieving the CTD:Rosette

NASA Image and Video Library

2017-12-08

On June 28, 2011, Holley Kelly, a teacher from Farragut High School, helped retrieve the CTD/Rosette ensemble from the Bering Strait, east of the Diomede Islands. The ICESCAPE mission, or "Impacts of Climate on Ecosystems and Chemistry of the Arctic Pacific Environment," is a NASA shipborne investigation to study how changing conditions in the Arctic affect the ocean's chemistry and ecosystems. The bulk of the research took place in the Beaufort and Chukchi seas in summer 2010 and 2011. Credit: NASA/Kathryn Hansen NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Stability, folding dynamics, and long-range conformational transition of the synaptic t-SNARE complex

PubMed Central

Zhang, Xinming; Rebane, Aleksander A.; Ma, Lu; Li, Feng; Jiao, Junyi; Qu, Hong; Pincet, Frederic; Rothman, James E.

2016-01-01

Synaptic soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs) couple their stepwise folding to fusion of synaptic vesicles with plasma membranes. In this process, three SNAREs assemble into a stable four-helix bundle. Arguably, the first and rate-limiting step of SNARE assembly is the formation of an activated binary target (t)-SNARE complex on the target plasma membrane, which then zippers with the vesicle (v)-SNARE on the vesicle to drive membrane fusion. However, the t-SNARE complex readily misfolds, and its structure, stability, and dynamics are elusive. Using single-molecule force spectroscopy, we modeled the synaptic t-SNARE complex as a parallel three-helix bundle with a small frayed C terminus. The helical bundle sequentially folded in an N-terminal domain (NTD) and a C-terminal domain (CTD) separated by a central ionic layer, with total unfolding energy of ∼17 kBT, where kB is the Boltzmann constant and T is 300 K. Peptide binding to the CTD activated the t-SNARE complex to initiate NTD zippering with the v-SNARE, a mechanism likely shared by the mammalian uncoordinated-18-1 protein (Munc18-1). The NTD zippering then dramatically stabilized the CTD, facilitating further SNARE zippering. The subtle bidirectional t-SNARE conformational switch was mediated by the ionic layer. Thus, the t-SNARE complex acted as a switch to enable fast and controlled SNARE zippering required for synaptic vesicle fusion and neurotransmission. PMID:27911771

[Stomach cancer in patients with systemic non-differentiated connective tissue dysplasia].

PubMed

Zil'ber, V S

2014-01-01

The study was designed as a comparative analysis of clinical and anamnestic data and results of morphological studies of surgically obtained tissues from 61 patients with stomach cancer (SC) aged 29-78 yr with (group 1) and without (group 2) signs of connective tissue dysplasia (CTD). The groups had an identical structure of SC hystological types, but in group 1 the tumours were localized mainly in the stomach body (60.6%, p < 0.05) and in group 2 in the cardia (32.1%, p < 0.05). In group 1, SC was more frequently associated with chronic (sometimes multiple) ulcers outside the tumor (18.2 compared with 7.1% in group 2). Comparative analysis revealed the following features of SC in patients with CTD: predominance of stigmatization signs in the urogenital system (57.6%) and gastrointestinal tract (42.4%), cyst formation in different organs (75.8%) especially in kidneys (48.5%), high frequency of gastric problems in medical history (chronic gastritis, ulcer disease) (72.7 and 35.7% in groups 1 and 2 respectively, p < 0.05) and concomitant pathology of urogenital system (42.4%, p < 0.05). These peculiarities may be used as the marker for the inclusion of patients in the risk group for SC. Taking into account plastic, morphogenetic, and protective functions of connective tissue under physiological conditions, the above epithelial-stromal relationships and peculiarities of reparative processes in gastric mucosa one can not exclude effect of CTD on gastric cancerogenesis. This implies the necessity of further studies.

Stabilization of Nucleosomes by Histone Tails and by FACT Revealed by spFRET Microscopy

PubMed Central

Valieva, Maria E.; Gerasimova, Nadezhda S.; Kudryashova, Kseniya S.; Kozlova, Anastasia L.; Kirpichnikov, Mikhail P.; Hu, Qi; Botuyan, Maria Victoria; Mer, Georges; Feofanov, Alexey V.; Studitsky, Vasily M.

2017-01-01

A correct chromatin structure is important for cell viability and is tightly regulated by numerous factors. Human protein complex FACT (facilitates chromatin transcription) is an essential factor involved in chromatin transcription and cancer development. Here FACT-dependent changes in the structure of single nucleosomes were studied with single-particle Förster resonance energy transfer (spFRET) microscopy using nucleosomes labeled with a donor-acceptor pair of fluorophores, which were attached to the adjacent gyres of DNA near the contact between H2A-H2B dimers. Human FACT and its version without the C-terminal domain (CTD) and the high mobility group (HMG) domain of the structure-specific recognition protein 1 (SSRP1) subunit did not change the structure of the nucleosomes, while FACT without the acidic C-terminal domains of the suppressor of Ty 16 (Spt16) and the SSRP1 subunits caused nucleosome aggregation. Proteolytic removal of histone tails significantly disturbed the nucleosome structure, inducing partial unwrapping of nucleosomal DNA. Human FACT reduced DNA unwrapping and stabilized the structure of tailless nucleosomes. CTD and/or HMG domains of SSRP1 are required for this FACT activity. In contrast, previously it has been shown that yeast FACT unfolds (reorganizes) nucleosomes using the CTD domain of SSRP1-like Pol I-binding protein 3 subunit (Pob3). Thus, yeast and human FACT complexes likely utilize the same domains for nucleosome reorganization and stabilization, respectively, and these processes are mechanistically similar. PMID:28067802

Stabilization of Nucleosomes by Histone Tails and by FACT Revealed by spFRET Microscopy.

PubMed

Valieva, Maria E; Gerasimova, Nadezhda S; Kudryashova, Kseniya S; Kozlova, Anastasia L; Kirpichnikov, Mikhail P; Hu, Qi; Botuyan, Maria Victoria; Mer, Georges; Feofanov, Alexey V; Studitsky, Vasily M

2017-01-06

A correct chromatin structure is important for cell viability and is tightly regulated by numerous factors. Human protein complex FACT (facilitates chromatin transcription) is an essential factor involved in chromatin transcription and cancer development. Here FACT-dependent changes in the structure of single nucleosomes were studied with single-particle Förster resonance energy transfer (spFRET) microscopy using nucleosomes labeled with a donor-acceptor pair of fluorophores, which were attached to the adjacent gyres of DNA near the contact between H2A-H2B dimers. Human FACT and its version without the C-terminal domain (CTD) and the high mobility group (HMG) domain of the structure-specific recognition protein 1 (SSRP1) subunit did not change the structure of the nucleosomes, while FACT without the acidic C-terminal domains of the suppressor of Ty 16 (Spt16) and the SSRP1 subunits caused nucleosome aggregation. Proteolytic removal of histone tails significantly disturbed the nucleosome structure, inducing partial unwrapping of nucleosomal DNA. Human FACT reduced DNA unwrapping and stabilized the structure of tailless nucleosomes. CTD and/or HMG domains of SSRP1 are required for this FACT activity. In contrast, previously it has been shown that yeast FACT unfolds (reorganizes) nucleosomes using the CTD domain of SSRP1-like Pol I-binding protein 3 subunit (Pob3). Thus, yeast and human FACT complexes likely utilize the same domains for nucleosome reorganization and stabilization, respectively, and these processes are mechanistically similar.

Tetramerization and interdomain flexibility of the replication initiation controller YabA enables simultaneous binding to multiple partners

PubMed Central

Felicori, Liza; Jameson, Katie H.; Roblin, Pierre; Fogg, Mark J.; Garcia-Garcia, Transito; Ventroux, Magali; Cherrier, Mickaël V.; Bazin, Alexandre; Noirot, Philippe; Wilkinson, Anthony J.; Molina, Franck; Terradot, Laurent; Noirot-Gros, Marie-Françoise

2016-01-01

YabA negatively regulates initiation of DNA replication in low-GC Gram-positive bacteria. The protein exerts its control through interactions with the initiator protein DnaA and the sliding clamp DnaN. Here, we combined X-ray crystallography, X-ray scattering (SAXS), modeling and biophysical approaches, with in vivo experimental data to gain insight into YabA function. The crystal structure of the N-terminal domain (NTD) of YabA solved at 2.7 Å resolution reveals an extended α-helix that contributes to an intermolecular four-helix bundle. Homology modeling and biochemical analysis indicates that the C-terminal domain (CTD) of YabA is a small Zn-binding domain. Multi-angle light scattering and SAXS demonstrate that YabA is a tetramer in which the CTDs are independent and connected to the N-terminal four-helix bundle via flexible linkers. While YabA can simultaneously interact with both DnaA and DnaN, we found that an isolated CTD can bind to either DnaA or DnaN, individually. Site-directed mutagenesis and yeast-two hybrid assays identified DnaA and DnaN binding sites on the YabA CTD that partially overlap and point to a mutually exclusive mode of interaction. Our study defines YabA as a novel structural hub and explains how the protein tetramer uses independent CTDs to bind multiple partners to orchestrate replication initiation in the bacterial cell. PMID:26615189

Hydrographic Conditions in the Gulf of Carpentaria During Australian Monsoon Experiment

NASA Astrophysics Data System (ADS)

Inoue, M.; Steinberg, C.; Wolanski, E.; Ridd, P.

2002-12-01

Gulf of Carpentaria located in the northern Australia, is a shallow wide basin with the deepest bottom depths of approximately 60 m. It is connected to Arafura Sea to the north and west, and to the Torres Strait to the east. Hydrographic surveys of the Gulf of Carpentaria were carried out in January and March, 1987 as part of Australian Monsoon Experiment. During the January survey, Tropical Cyclone (TC) Irma was formed in the Gulf of Carpentaria. An east-west CTD section at 13o52'S was occupied twice, one prior to and during, and the other after the formation of TC Irma. In addition, two post-Irma east-west sections were occupied at 12o40'S and 11o30'S. The pre-cyclone section indicates a well-defined stratified two-layer system, while the post-cyclone sections show deepening of the surface warm layer due to significant mixing by TC Irma. Overall, significant cooling of near surface warm water on the order of more than 1oC was observed. Significant heat loss estimated for the water column has presumably contributed toward the development of TC Irma. In February 1987, TC Jason was formed in the gulf. During the March survey, two east-west CTD sections were occupied at 11o30'S and 13o52'S. The March survey reveals notable warming of the bottom water. Detailed discussion of the CTD data from the two cruises will be presented.

Biomechanical considerations in slipped capital femoral epiphysis and insights into prophylactic fixation.

PubMed

Leblanc, E; Bellemore, J M; Cheng, T; Little, D G; Birke, O

2017-04-01

Slipped capital femoral epiphysis (SCFE) is a deformity of the proximal femur secondary to widened and unstable physis. In stabilising the slip, gold standard treatments stop growth and involve premature physeal closure, which prevents the remodelling of the acquired deformity and creates a leg length discrepancy that may be significant in younger patients. We measured the impact of placing threaded screws across the proximal femoral physis by measuring the centre-trochanteric distance (CTD) and articulo-trochanteric distance (ATD) in participants with or without prophylactic fixation. We then compared the mechanical performance of static (stainless and titanium cannulated Synthes screws) and potentially growing implants (Synthes SCFE screw and Pega Medical Free Gliding screw) in a validated synthetic bone model. In the review of 30 non-fixed and 60 fixated hips over a mean follow-up of 1.9 years, we have noted a significant difference in pre/post CTD and ATD, as well as the change in CTD and ATD over time. In the biomechanical study, the newer implants allowing growth (Synthes SCFE screw and Pega Medical Free Gliding screw) were both shown to be at least non-inferior. The primary deformity of a SCFE in itself alters hip mechanics. Also, as confirmed in this study, there is a secondary deformity that is created by static fixation and relative trochanteric overgrowth. To help remodel mild deformities and prevent secondary trochanteric overgrowth, growing implants seem to be non-inferior to the more standard means of fixation in static testing.

Significance of myositis autoantibody in patients with idiopathic interstitial lung disease.

PubMed

Song, Ju Sun; Hwang, Jiwon; Cha, Hoon-Suk; Jeong, Byeong-Ho; Suh, Gee Young; Chung, Man Pyo; Kang, Eun-Suk

2015-05-01

Some patients with interstitial lung disease (ILD) related to connective tissue disease (CTD) have a delayed diagnosis of the underlying CTD when the ILD is categorized as idiopathic. In this study, we evaluated the frequency of myositis autoantibodies in patients diagnosed with idiopathic ILD and investigated the clinical significance stemming from the presence of the antibodies. A total 32 patients diagnosed with idiopathic ILD were enrolled in this study. We analyzed a panel of 11 myositis autoantibody specificities in the patients using a line blot immunoassay. Then, we divided them into myositis autoantibody-positive and -negative groups and compared the clinical features and laboratory data between the two groups. Of the 32 idiopathic ILD patients, 12 patients had myositis autoantibodies encompassing 9 specificities, except for anti-Mi-2 and anti-PM-Scl 100 (12/32, 38%). Anti-synthetase autoantibodies including Jo-1, EJ, OJ, PL-7, and PL-12 were present in 7 patients (7/32, 22%). The group with myositis autoantibodies presented more frequently with the symptom of mechanic's hand and showed abnormal pulmonary function test results with low forced vital capacity, diffusing capacity for carbon monoxide, total lung capacity, and high lactate dehydrogenase values in blood when compared with the group without myositis antibodies. We strongly suggest that patients undergo an evaluation of myositis autoantibodies, if they are diagnosed with idiopathic ILD in the presence of clinical characteristics including mechanic's hand, arthralgia, and autoantibodies which are insufficient to make a diagnosis of a specific CTD category.

[The diagnostic significance of nailfold video-capillaroscopy in systemic sclerosis].

PubMed

Li, Lin-Guang; Zhang, Jiang-Lin; Liu, Xiu-Hua; Huang, Feng

2012-05-01

To observe nailfold capillary changes in a cohort of connective tissue disease (CTD) with Raynaud's phenomenon (RP) and to explore the diagnostic value of nailfold video-capillaroscopy (NVC) in systemic sclerosis (SSc). Sixty CTD patients with RP divided into SSc group (n = 36) and non-SSc group (n = 24) were referred to an experienced operator for NVC. The patients had decreased capillary loops in SSc group with the capillary diameter more enlarged in SSc group than non-SSc group. The number of patients in SSc group with giant capillaries was 14, while 3 in non-SSc group. There were 23 patients with haemorrhages in SSc group and 9 in non-SSc group. The number of patients with severe effusion was 15 in SSc group, while 2 in non-SSc group. By using the ROC curves, indexes with AUC at least 0.7 of the input capillary diameter, the output capillary diameter, the middle capillary diameter, blood color and effusion for the diagnostic cutoff points were 18.5 µm, 24.5 µm, 19.5µm, deep red and severe effusion. With at least 2 out of the top 3 indexes, the diagnostic sensitivity and specificity of SSc were higher. CTD Patients with RP of SSc have less capillary loops, more enlarged capillaries, more giant capillaries, more severe effusion and more haemorrhages than non-SSc patients. The characteristics of nailfold capillary changes in SSc patients with RP can be helpful for the diagnosis and the differential diagnosis of SSc.

3.3 Å structure of Niemann–Pick C1 protein reveals insights into the function of the C-terminal luminal domain in cholesterol transport

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

Li, Xiaochun; Lu, Feiran; Trinh, Michael N.

Niemann–Pick C1 (NPC1) and NPC2 proteins are indispensable for the export of LDL-derived cholesterol from late endosomes. Mutations in these proteins result in Niemann–Pick type C disease, a lysosomal storage disease. Despite recent reports of the NPC1 structure depicting its overall architecture, the function of its C-terminal luminal domain (CTD) remains poorly understood even though 45% of NPC disease-causing mutations are in this domain. Here, we report a crystal structure at 3.3 Å resolution of NPC1* (residues 314–1,278), which—in contrast to previous lower resolution structures—features the entire CTD well resolved. Notably, all eight cysteines of the CTD form four disulfidemore » bonds, one of which (C909–C914) enforces a specific loop that in turn mediates an interaction with a loop of the N-terminal domain (NTD). Importantly, this loop and its interaction with the NTD were not observed in any previous structures due to the lower resolution. Our mutagenesis experiments highlight the physiological relevance of the CTD–NTD interaction, which might function to keep the NTD in the proper orientation for receiving cholesterol from NPC2. Additionally, this structure allows us to more precisely map all of the disease-causing mutations, allowing future molecular insights into the pathogenesis of NPC disease.« less

Identification of Lynch syndrome mutations in the MLH1-PMS2 interface that disturb dimerization and mismatch repair

PubMed Central

Kosinski, Jan; Hinrichsen, Inga; Bujnicki, Janusz M.; Friedhoff, Peter; Plotz, Guido

2010-01-01

Missense alterations of the mismatch repair gene MLH1 have been identified in a significant proportion of individuals suspected of having Lynch syndrome, a hereditary syndrome which predisposes for cancer of colon and endometrium. The pathogenicity of many of these alterations, however, is unclear. A number of MLH1 alterations are located in the C-terminal domain (CTD) of MLH1, which is responsible for constitutive dimerization with PMS2. We analyzed which alterations may result in pathogenic effects due to interference with dimerization. We used a structural model of CTD of MLH1-PMS2 heterodimer to select 19 MLH1 alterations located inside and outside two candidate dimerization interfaces in the MLH1-CTD. Three alterations (p.Gln542Leu, p.Leu749Pro, p.Tyr750X) caused decreased co-expression of PMS2, which is unstable in the absence of interaction with MLH1, suggesting that these alterations interfere with dimerization. All three alterations are located within the dimerization interface suggested by our model. They also compromised mismatch repair, suggesting that defects in dimerization abrogate repair and confirming that all three alterations are pathogenic. Additionally, we provided biochemical evidence that four alterations with uncertain pathogenicity (p.Ala586Pro, p.Leu636Pro, p.Thr662Pro, and p.Arg755Trp) are deleterious because of poor expression or poor repair efficiency, and confirm the deleterious effect of eight further alterations. PMID:20533529

Identification of Lynch syndrome mutations in the MLH1-PMS2 interface that disturb dimerization and mismatch repair.

PubMed

Kosinski, Jan; Hinrichsen, Inga; Bujnicki, Janusz M; Friedhoff, Peter; Plotz, Guido

2010-08-01

Missense alterations of the mismatch repair gene MLH1 have been identified in a significant proportion of individuals suspected of having Lynch syndrome, a hereditary syndrome that predisposes for cancer of colon and endometrium. The pathogenicity of many of these alterations, however, is unclear. A number of MLH1 alterations are located in the C-terminal domain (CTD) of MLH1, which is responsible for constitutive dimerization with PMS2. We analyzed which alterations may result in pathogenic effects due to interference with dimerization. We used a structural model of CTD of MLH1-PMS2 heterodimer to select 19 MLH1 alterations located inside and outside two candidate dimerization interfaces in the MLH1-CTD. Three alterations (p.Gln542Leu, p.Leu749Pro, p.Tyr750X) caused decreased coexpression of PMS2, which is unstable in the absence of interaction with MLH1, suggesting that these alterations interfere with dimerization. All three alterations are located within the dimerization interface suggested by our model. They also compromised mismatch repair, suggesting that defects in dimerization abrogate repair and confirming that all three alterations are pathogenic. Additionally, we provided biochemical evidence that four alterations with uncertain pathogenicity (p.Ala586Pro, p.Leu636Pro, p.Thr662Pro, and p.Arg755Trp) are deleterious because of poor expression or poor repair efficiency, and confirm the deleterious effect of eight further alterations.

Recent progress and tests of radiation resistant impregnation materials for Nb3Sn coils

NASA Astrophysics Data System (ADS)

Bossert, R.; Krave, S.; Ambrosio, G.; Andreev, N.; Chlachidze, G.; Nobrega, A.; Novitski, I.; Yu, M.; Zlobin, A. V.

2014-01-01

Fermilab is collaborating with Lawrence Berkeley National Laboratory (LBNL) and Brookhaven National Laboratory (BNL) (US-LARP collaboration) to develop a large-aperture Nb3Sn superconducting quadrupole for the Large Hadron Collider (LHC) luminosity upgrade. An important component of this work is the development of materials that are sufficiently radiation resistant for use in critical areas of the upgrade. This paper describes recent progress in characterization of materials, including the baseline CTD101K epoxy, cyanate ester blends, and Matrimid 5292, a bismaleimide-based system. Structural properties of "ten stacks" of cable impregnated with these materials are tested at room and cryogenic temperatures and compared to the baseline CT-101K. Experience with potting 1 and 2 meter long coils with Matrimid 5292 are described. Test results of a single 1-m coil impregnated with Matrimid 5292 are reported and compared to similar coils impregnated with the traditional epoxy.

Satellite Analysis of Ocean Biogeochemistry and Mesoscale Variability in the Sargasso Sea

NASA Technical Reports Server (NTRS)

Siegel, D. A.; Micheals, A. F.; Nelson, N. B.

1997-01-01

The objective of this study was to analyze the impact of spatial variability on the time-series of biogeochemical measurements made at the U.S. JGOFS Bermuda Atlantic Time-series Study (BATS) site. Originally the study was planned to use SeaWiFS as well as AVHRR high-resolution data. Despite the SeaWiFS delays we were able to make progress on the following fronts: (1) Operational acquisition, processing, and archive of HRPT data from a ground station located in Bermuda; (2) Validation of AVHRR SST data using BATS time-series and spatial validation cruise CTD data; (3) Use of AVHRR sea surface temperature imagery and ancillary data to assess the impact of mesoscale spatial variability on P(CO2) and carbon flux in the Sargasso Sea; (4) Spatial and temporal extent of tropical cyclone induced surface modifications; and (5) Assessment of eddy variability using TOPEX/Poseidon data.

Recent variability in the Atlantic water intrusion and water masses in Kongsfjorden, an Arctic fjord

NASA Astrophysics Data System (ADS)

Divya, David T.; Krishnan, K. P.

2017-03-01

The present study reports high inter-annual variability in the water masses and in the intrusion of Atlantic origin waters in Kongsfjorden from 2000 to 2013 using both the historical (2000-2010 summers) and recent CTD measurements (2011-2013 summer/fall). An earlier intrusion of Atlantic Water (AW) into Kongsfjorden was observed in the contemporary years. An overall summertime subsurface warming is evident from the maximum September AW temperature in 2011 (4.8 °C), 2012 (5.8 °C) and 2013 (7 °C). The combination of a compensating surface flow to the subsurface intrusion of AW and the strong southeasterly surface winds during the peak summer, resulted in a corresponding net outflow of the surface fresh water layer from Kongsfjorden. This led to the decreased freshwater volume inside the fjord during 2013 (1 km3) compared to 2011 (3.1 km3) and 2012 (2.3 km3).

Numerical analysis of internal solitary wave generation around a Island in Kuroshio Current using MITgcm.

NASA Astrophysics Data System (ADS)

Kodaira, Tsubasa; Waseda, Takuji

2013-04-01

We have conducted ADCP and CTD measurements from 31/8/2010 to 2/9/2010 at the Miyake Island, located approximately 180 km south of Tokyo. The Kuroshio Current approached the island in this period, and the PALSAR image showed parabolic bright line upstream of the island. This bright line may be a surface signature of large amplitude internal solitary wave. Although our measurements did not explicitly show evidence of the internal solitary wave, critical condition might have been satisfied because of the Kuroshio Current and strong seasonal thermocline. To discover the generation mechanism of the large amplitude internal solitary wave at the Miyake Island, we have conducted non-hydrostatic numerical simulation with the MITgcm. A simple box domain, with open boundaries at all sides, is used. The island is simplified to circular cylinder or Gaussian Bell whose radius is 3km at ocean surface level. The size of the domain is 40kmx40kmx500m for circular cylinder cases and 80kmx80kmx500m for Gaussian bell cases. By looking at our CTD data, we have chosen for initial and boundary conditions a tanh function for vertical temperature profile. Salinity was kept constant for simplicity. Vertical density profile is also described by tanh function because we adopt linear type of equation of state. Vertical velocity profile is constant or linearly changed with depth; the vertical mean speed corresponds to the linear phase speed of the first baroclinic mode obtained by solving the eigen-value problem. With these configurations, we have conducted two series of simulations: shear flow through cylinder and uniform flow going through Gaussian Bell topography. Internal solitary waves were generated in front of the cylinder for the first series of simulations with shear flow. The generated internal waves almost purely consisted of 1st baroclinic component. Their intensities were linearly related with upstream vertical shear strength. As the internal solitary wave became larger, its width became wider compared to the KdV solution described by Grimshaw (2002). This is predicted because higher order analytical solution for 2-layer fluids, i.e. the eKdV solution, gives broader solitary wave shape than that of the KdV solution because of the cubic nonlinear term. When we look at the surface velocity distribution, a parabolic shape corresponding to internal solitary wave is clearly seen. According to the fully nonlinear theoretical model for internal wave between two fluids having background linear shear flow profiles (Choi and Camassa1999), the shape of internal wave is influenced by the velocity shear as well. However, we could not clarify the effect of vertical shear because there is no fully nonlinear analytical solution for large amplitude internal wave in continuously stratified fluid. Second series of simulations with uniform flow going through Gaussian Bell topography show that internal solitary wave shows up from sides of the topography. This generation is similar to the one developed in lee side of sill topography by tidal flow. With broader bell topography, generated internal waves become larger. This makes sense because forcing region is wider. A horizontal shape of the internal solitary wave is not parabolic but the two bending line forms from the sides of the island. However, no solitary wave in front of the island develops. Our results imply that vertical shear profile is needed for the formation of the depression type internal solitary, and explains the parabolic bright line observed in the SAR image

Quantitative weight of evidence assessment of risk to honeybee colonies from use of imidacloprid, clothianidin, and thiamethoxam as seed treatments: a postscript.

PubMed

Solomon, Keith R; Stephenson, Gladys L

2017-01-01

This paper is a postscript to the four companion papers in this issue of the Journal (Solomon and Stephenson 2017a , 2017b ; Stephenson and Solomon 2017a , 2017b ). The first paper in the series described the conceptual model and the methods of the QWoE process. The other three papers described the application of the QWoE process to studies on imidacloprid (IMI), clothianidin (CTD), and thiamethoxam (TMX). This postscript was written to summarize the utility of the methods used in the quantitative weight of evidence (QWoE), the overall relevance of the results, and the environmental implications of the findings. Hopefully, this will be helpful to others who wish to conduct QWoEs and use these methods in assessment of risks.

Breadboard stellar tracker system test report

NASA Technical Reports Server (NTRS)

Kollodge, J. C.; Parrish, K. A.

1984-01-01

BASD has, in the past, developed several unique position tracking algorithms for charge transfer device (CTD) sensors. These algorithms provide an interpixel transfer function with the following characteristics: (1) high linearity; (2) simplified track logic; (3) high gain; and (4) high noise rejection. A previous test program using the GE charge injection device (CID) showed that accuracy for BASD's breadboard was limited to approximately 2% of a pixel (1 sigma) whereas analysis and simulation indicated the limit should be less than 0.5% of a pixel, assuming the limit to be detector response and dark current noise. The test program was conducted under NASA contract No. NAS8-34263. The test approach for that program did not provide sufficient data to identify the sources of error and left open the amount of contribution from parameters such as image distribution, geometric distortion and system alignment errors.

Testing of SIR (a transformable robotic submarine) in Lake Tahoe for future deployment at West Antarctic Ice Sheet grounding lines of Siple Coast

NASA Astrophysics Data System (ADS)

Powell, R. D.; Scherer, R. P.; Griffiths, I.; Taylor, L.; Winans, J.; Mankoff, K. D.

2011-12-01

A remotely operated vehicle (ROV) has been custom-designed and built by DOER Marine to meet scientific requirements for exploring subglacial water cavities. This sub-ice rover (SIR) will explore and quantitatively document the grounding zone areas of the Ross Ice Shelf cavity using a 3km-long umbilical tether by deployment through an 800m-long ice borehole in a torpedo shape, which is also its default mode if operational failure occurs. Once in the ocean cavity it transforms via a diamond-shaped geometry into a rectangular form when all of its instruments come alive in its flight mode. Instrumentation includes 4 cameras (one forward-looking HD), a vertical scanning sonar (long-range imaging for spatial orientation and navigation), Doppler current meter (determine water current velocities), multi-beam sonar (image and swath map bottom topography), sub-bottom profiler (profile sub-sea-floor sediment for geological history), CTD (determine salinity, temperature and depth), DO meter (determine dissolved oxygen content in water), transmissometer (determine suspended particulate concentrations in water), laser particle-size analyzer (determine sizes of particles in water), triple laser-beams (determine size and volume of objects), thermistor probe (measure in situ temperatures of ice and sediment), shear vane probe (determine in situ strength of sediment), manipulator arm (deploy instrumentation packages, collect samples), shallow ice corer (collect ice samples and glacial debris), water sampler (determine sea water/freshwater composition, calibrate real-time sensors, sample microbes), shallow sediment corer (sample sea floor, in-ice and subglacial sediment for stratigraphy, facies, particle size, composition, structure, fabric, microbes). A sophisticated array of data handling, storing and displaying will allow real-time observations and environmental assessments to be made. This robotic submarine and other instruments will be tested in Lake Tahoe in September, 2011 and results will be presented on its trials and geological and biological findings down to the deepest depths of the lake. Other instruments include a 5m-ling percussion corer for sampling deeper sediments, an ice-tethered profiler with CTD and ACDP, and in situ oceanographic mooring designed to fit down a narrow (30cm-diameter) ice borehole that include interchangeable packages of ACDPs, CTDs, transmissometers, laser particle-size analyzer, DO meter, automated multi-port water sampler, water column nutrient analyzer, sediment porewater chemistry analyzer, down-looking color camera (see figure), and altimeter.

Application of acoustic-Doppler current profiler and expendable bathythermograph measurements to the study of the velocity structure and transport of the Gulf Stream

NASA Technical Reports Server (NTRS)

Joyce, T. M.; Dunworth, J. A.; Schubert, D. M.; Stalcup, M. C.; Barbour, R. L.

1988-01-01

The degree to which Acoustic-Doppler Current Profiler (ADCP) and expendable bathythermograph (XBT) data can provide quantitative measurements of the velocity structure and transport of the Gulf Stream is addressed. An algorithm is used to generate salinity from temperature and depth using an historical Temperature/Salinity relation for the NW Atlantic. Results have been simulated using CTD data and comparing real and pseudo salinity files. Errors are typically less than 2 dynamic cm for the upper 800 m out of a total signal of 80 cm (across the Gulf Stream). When combined with ADCP data for a near-surface reference velocity, transport errors in isopycnal layers are less than about 1 Sv (10 to the 6th power cu m/s), as is the difference in total transport for the upper 800 m between real and pseudo data. The method is capable of measuring the real variability of the Gulf Stream, and when combined with altimeter data, can provide estimates of the geoid slope with oceanic errors of a few parts in 10 to the 8th power over horizontal scales of 500 km.

The design, status and performance of the ZEUS central tracking detector electronics

NASA Astrophysics Data System (ADS)

Cussans, D. G.; Fawcett, H. F.; Foster, B.; Gilmore, R. S.; Heath, G. P.; Llewellyn, T. J.; Malos, J.; Morgado, C. J. S.; Tapper, R. J.; Gingrich, D. M.; Harnew, N.; Hallam-Baker, P.; Nash, J.; Khatri, T.; Shield, P. D.; McArthur, I.; Topp-Jorgensen, S.; Wilson, F. F.; Allen, D.; Baird, S. A.; Carter, R.; Galagardera, S.; Gibson, M. D.; Hatley, R. S.; Jeffs, M.; Milborrow, R.; Morissey, M.; Quinton, S. P. H.; White, D. J.; Lane, J.; Nixon, G.; Postranecky, M.; Jamdagni, A. K.; Marcou, C.; Miller, D. B.; Toudup, L.

1992-05-01

The readout system developed for the ZEUS central trackign detector (CDT) is described. The CTD is required to provide an accurate measurement of the sagitta and energy loss of charged particles as well as provide fast trigger information. This must be carried out in the HERA environment in which beams cross every 96 ns. The first two aims are achieved by digitizing chamber pulses using a pipelined 104 MHz FADC system. The trigger uses a fast determination of the difference in the arrival times of a pulse at each end of the CTD. It processes this data and gives information to the ZEUS global first level trigger. The modules are housed in custom-built racks and crates and read out using a DAQ system based on Transputer readout controllers. These also monitor data quality and produce data for the ZEUS second level Trigger.

Using Performance Assessment Model in Physics Laboratory to Increase Students’ Critical Thinking Disposition

NASA Astrophysics Data System (ADS)

Emiliannur, E.; Hamidah, I.; Zainul, A.; Wulan, A. R.

2017-09-01

Performance Assessment Model (PAM) has been developed to represent the physics concepts which able to be devided into five experiments: 1) acceleration due to gravity; 2) Hooke’s law; 3) simple harmonic motion; 4) work-energy concepts; and 5) the law of momentum conservation. The aim of this study was to determine the contribution of PAM in physics laboratory to increase students’ Critical Thinking Disposition (CTD) at senior high school. Subject of the study were 11th grade consist 32 students of a senior high school in Lubuk Sikaping, West Sumatera. The research used one group pretest-postest design. Data was collected through essay test and questionnaire about CTD. Data was analyzed using quantitative way with N-gain value. This study concluded that performance assessmet model effectively increases the N-gain at medium category. It means students’ critical thinking disposition significant increase after implementation of performance assessment model in physics laboratory.

C-terminal domain of SMYD3 serves as a unique HSP90-regulated motif in oncogenesis

PubMed Central

Harriss, June; Das, Chhaya; Zhu, Li; Edwards, Melissa; Shaaban, Salam; Tucker, Haley

2015-01-01

The SMYD3 histone methyl transferase (HMTase) and the nuclear chaperone, HSP90, have been independently implicated as proto-oncogenes in several human malignancies. We show that a degenerate tetratricopeptide repeat (TPR)-like domain encoded in the SMYD3 C-terminal domain (CTD) mediates physical interaction with HSP90. We further demonstrate that the CTD of SMYD3 is essential for its basal HMTase activity and that the TPR-like structure is required for HSP90-enhanced enzyme activity. Loss of SMYD3-HSP90 interaction leads to SMYD3 mislocalization within the nucleus, thereby losing its chromatin association. This results in reduction of SMYD3-mediated cell proliferation and, potentially, impairment of SMYD3′s oncogenic activity. These results suggest a novel approach for blocking HSP90-driven malignancy in SMYD3-overexpressing cells with a reduced toxicity profile over current HSP90 inhibitors. PMID:25738358

An acoustic charge transport imager for high definition television applications

NASA Technical Reports Server (NTRS)

Hunt, William D.; Brennan, Kevin F.; Summers, Christopher J.

1993-01-01

This report covers: (1) invention of a new, ultra-low noise, low operating voltage APD which is expected to offer far better performance than the existing volume doped APD device; (2) performance of a comprehensive series of experiments on the acoustic and piezoelectric properties of ZnO films sputtered on GaAs which can possibly lead to a decrease in the required rf drive power for ACT devices by 15dB; (3) development of an advanced, hydrodynamic, macroscopic simulator used for evaluating the performance of ACT and CTD devices and aiding in the development of the next generation of devices; (4) experimental development of CTD devices which utilize a p-doped top barrier demonstrating charge storage capacity and low leakage currents; (5) refinements in materials growth techniques and in situ controls to lower surface defect densities to record levels as well as increase material uniformity and quality.

OSCAR - Oceanographic and Seismic Characterisation of heat dissipation and alteration by hydrothermal fluids at an Axial Ridge

NASA Astrophysics Data System (ADS)

Hobbs, Richard

2017-04-01

The interdisciplinary OSCAR project is examining the heat and mass fluxes in the solid Earth and overlying ocean at the Costa Rica mid-ocean Ridge (CRR) in the Panama Basin. The 3500 m deep Panama basin is isolated from the wider Pacific Ocean below 2000 m by the Cocos and Carnegie Ridges except for a deep water channel along the Ecuador trench. This channel supplies cold abyssal water into the Basin at a rate of 0.35 Sv (million cubic metres per second)) at a temperature of 1.75°C. Within the basin the water is heated to 2°C. The energy for this heating is dominated by geothermal effects with a smaller contribution from mainly tidal induced mixing over the ridges. The main geophysical transect for the OSCAR survey links the CRR with the ODP 504B borehole which is drilled 2111 m into 5.9 Ma oceanic crust. Changes in the solid Earth properties from the CRR to 504B are mapped using a combination of seismic 2D- and 3D-refraction and synthetic-aperture reflection, magnetics, gravity, magnetotelluric data, swath bathymetry and heat-flow. Results show that the properties of layer 2 are variable and are more likely a function of changes in magma supply at the ridge rather than the effects of ageing. Of particular note is the abrupt change at 5 Ma. Older crust has a higher velocity and lower topography when compared with younger crust. Also the heat-flow over the older crust is largely through conduction whereas in the younger crust it is largely by advection. The physical oceanography data include conductivity temperature depth (CTD) casts, micro-structure casts, helium and other isotope data, together with seabed and moored temperature, pressure and Doppler current measurements. The inflowing water along the Ecuador trench initially mix with with the warmer water as it enters the basin. Mixing and heating continues as the water circulates into the western part of the basin where it shows no vertical density gradient for over 1000 m and an overall temperature increase of 0.25°C combined with a decrease of 0.01 psu in salinity. Evidence of hydrothermally driven plumes were also detected along the CRR but exact locations of their sources were not found. Our best estimate from the OSCAR data show that the geothermal contribution is over 70% to the abyssal water upwelling. This is the largest contribution yet observed in abyssal basins and is in line with a growing number of studies arguing that geothermal heating plays a significant role in driving the abyssal and global circulation.

About the seasonal variability of the Alboran Sea circulation

NASA Astrophysics Data System (ADS)

Vargas-Yáñez, M.; Plaza, F.; García-Lafuente, J.; Sarhan, T.; Vargas, J. M.; Vélez-Belchi, P.

2002-07-01

Data from a mooring line deployed midway between the Alboran Island and Cape Tres Forcas are used to study the time variability of the Alboran Sea from May 1997 to May 1998. The upper layer salinity and zonal velocity present annual and semiannual cycles characterised by a minimum in spring and autumn and a maximum in summer and winter. Temperature has the opposite behaviour to that of salinity indicating changes in the presence of the Atlantic water within the Alboran Passage. A large set of SST images is used to study these cycles. The decrease of salinity and velocity in our mooring location in spring and autumn seems to be related to the eastward drifting of the Western Alboran Gyre (WAG). The increase of salinity and velocity is caused by the Atlantic current flowing south of the Alboran Island and its associated thermohaline front. Conductivity-temperature-depth (CTD) data from two cruises along the 3°W are coherent with current meters and SST interpretations. During the period analysed, summer months are characterised by the stability of the two-gyre system, while in winter, the circulation is characterised by a coastal jet flowing close to the African shore. We use sea level differences across the Strait of Gibraltar for studying the variability of the Atlantic inflow. We discuss the changes in the Alboran Sea circulation and its relation with the variability of the inertial radius of the Atlantic inflow. Though our results are speculative, we find a possible relation between the disappearance of the two-gyre system and a reversal of the circulation in Gibraltar. Longer time series are needed to conclude, but comparison with previous works makes us think that the seasonal cycle described from May 1997 to May 1998 could be the most likely one for the Alboran Sea upper layer.

Storm-induced water dynamics and thermohaline structure at the tidewater Flade Isblink Glacier outlet to the Wandel Sea (NE Greenland)

NASA Astrophysics Data System (ADS)

Kirillov, Sergei; Dmitrenko, Igor; Rysgaard, Søren; Babb, David; Toudal Pedersen, Leif; Ehn, Jens; Bendtsen, Jørgen; Barber, David

2017-11-01

In April 2015, an ice-tethered conductivity-temperature-depth (CTD) profiler and a down-looking acoustic Doppler current profiler (ADCP) were deployed from the landfast ice near the tidewater glacier terminus of the Flade Isblink Glacier in the Wandel Sea, NE Greenland. The 3-week time series showed that water dynamics and the thermohaline structure were modified considerably during a storm event on 22-24 April, when northerly winds exceeded 15 m s-1. The storm initiated downwelling-like water dynamics characterized by on-shore water transport in the surface (0-40 m) layer and compensating offshore flow at intermediate depths. After the storm, currents reversed in both layers, and the relaxation phase of downwelling lasted ˜ 4 days. Although current velocities did not exceed 5 cm s-1, the enhanced circulation during the storm caused cold turbid intrusions at 75-95 m depth, which are likely attributable to subglacial water from the Flade Isblink Ice Cap. It was also found that the semidiurnal periodicities in the temperature and salinity time series were associated with the lunar semidiurnal tidal flow. The vertical structure of tidal currents corresponded to the first baroclinic mode of the internal tide with a velocity minimum at ˜ 40 m. The tidal ellipses rotate in opposite directions above and below this depth and cause a divergence of tidal flow, which was observed to induce semidiurnal internal waves of about 3 m height at the front of the glacier terminus. Our findings provide evidence that shelf-basin interaction and tidal forcing can potentially modify coastal Wandel Sea waters even though they are isolated from the atmosphere by landfast sea ice almost year-round. The northerly storms over the continental slope cause an enhanced circulation facilitating a release of cold and turbid subglacial water to the shelf. The tidal flow may contribute to the removal of such water from the glacial terminus.

Exercise training in pulmonary arterial hypertension associated with connective tissue diseases

PubMed Central

2012-01-01

Introduction The objective of this prospective study was to assess short- and long-term efficacy of exercise training (ET) as add-on to medical therapy in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH). Methods Patients with invasively confirmed CTD-APAH received ET in-hospital for 3 weeks and continued at home for 12 weeks. Efficacy parameters have been evaluated at baseline and after 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of 2.9 ± 1.9 years. Results Twenty-one consecutive patients were included and assessed at baseline, and after 3 weeks, 14 after 15 weeks. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 67 ± 52 meters after 3 weeks (p < 0.001) and by 71 ± 35 meters after 15 weeks (p = 0.003), scores of quality of life (p < 0.05), heart rate at rest, peak oxygen consumption, oxygen saturation and maximal workload. Systolic pulmonary artery pressure and diastolic systemic blood pressure improved significantly after 3 weeks of ET. The 1- and 2-year overall-survival rates were 100%, the 3-year survival 73%. In one patient lung transplantation was performed 6 months after ET. Conclusion ET as add-on to medical therapy is highly effective in patients with CTD-APAH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further randomized controlled studies are needed to confirm these results. Trial registration ClinicalTrials.gov: NCT00491309. PMID:22709477

Analysis of the antibacterial activity and plaque control benefit of colgate total dentifrice via clinical evaluation and real-time polymerase chain reaction.

PubMed

Xu, Tao; Deshmukh, Meenal; Barnes, Virginia Monsul; Trivedi, Harsh M; Du-Thumm, Laurence; Richter, Rose; Cummins, Diane

2005-01-01

This study analyzed, from a combined clinical and molecular biologic perspective, the antibacterial and antiplaque efficacy of Colgate Total dentifrice (CTD). A single-blind crossover study design utilized 11 healthy human subjects. After a one-week washout period, subjects donated dental plaque, received a dental prophylaxis, and subsequently brushed with a test product. Twenty-four hours postbrushing, dental plaque was collected and a clinical plaque score determined. Dental plaque was submitted for Real-time Polymerase Chain Reaction (Real-time PCR) analysis. The same procedure was repeated in accordance with a crossover design for the use of the second test product. Following a one-week washout, a plaque donation, prophylaxis, and brushing with the test product ensued for each subject. Twenty-four hours post-brushing, the subjects returned for a plaque score and plaque donation. Twenty-four hours after brushing, dental plaque coverage increased 17.88% +/- 8.27% with CTD, compared to 30.42% +/- 9.97% with Colgate Cavity Protection (CCP; p = 0.005). Real-time PCR found plaque collected 24 hours after brushing with CTD exhibited, on average, fewer representative periodontal pathogens (Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, Tannerella forsythensis, and Porphyromonas gingivalis) and fewer early colonizers (Actinomyces naeslundii) than plaque collected before brushing, whereas CCP showed a moderate effect on oral bacteria. The study provides clinical and molecular biological evidence to substantiate the antibacterial and plaque control benefits of Colgate Total, and suggests the value of combining a molecular biological method with clinical research to corroborate clinical benefits.

Structural basis for ribosome protein S1 interaction with RNA in trans-translation of Mycobacterium tuberculosis.

PubMed

Fan, Yi; Dai, Yazhuang; Hou, Meijing; Wang, Huilin; Yao, Hongwei; Guo, Chenyun; Lin, Donghai; Liao, Xinli

2017-05-27

Ribosomal protein S1 (RpsA), the largest 30S protein in ribosome, plays a significant role in translation and trans-translation. In Mycobacterium tuberculosis, the C-terminus of RpsA is known as tuberculosis drug target of pyrazinoic acid, which inhibits the interaction between MtRpsA and tmRNA in trans-translation. However, the molecular mechanism underlying the interaction of MtRpsA with tmRNA remains unknown. We herein analyzed the interaction of the C-terminal domain of MtRpsA with three RNA fragments poly(A), sMLD and pre-sMLD. NMR titration analysis revealed that the RNA binding sites on MtRpsA CTD are mainly located in the β2, β3 and β5 strands and the adjacent L3 loop of the S1 domain. Fluorescence experiments determined the MtRpsA CTD binding to RNAs are in the micromolar affinity range. Sequence analysis also revealed conserved residues in the mapped RNA binding region. Residues L304, V305, G308, F310, H322, I323, R357 and I358 were verified to be the key residues influencing the interaction between MtRpsA CTD and pre-sMLD. Molecular docking further confirmed that the poly(A)-like sequence and sMLD of tmRNA are all involved in the protein-RNA interaction, through charged interaction and hydrogen bonds. The results will be beneficial for designing new anti-tuberculosis drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

Attention bias for social threat in youth with tic disorders: Links with tic severity and social anxiety.

PubMed

Pile, Victoria; Robinson, Sally; Topor, Marta; Hedderly, Tammy; Lau, Jennifer Y F

2018-06-07

Many individuals with Tourette syndrome and chronic tic disorders (TS/CTDs) report poor social functioning and comorbid social anxiety. Yet limited research has investigated the role of cognitive factors that highlight social threats in youth with TS/CTD, and whether these biases underlie tic severity and co-occurring social anxiety. This study examined whether selective attention to social threat is enhanced young people with TS/CTDs compared to healthy controls, and whether attention biases are associated with tic severity and social anxiety. Twenty seven young people with TS/CTDs and 25 matched control participants completed an experimental measure of attention bias toward/away from threat stimuli. A clinician-rated interview measuring tic severity/impairment (YGTSS Total Score) and questionnaire measures of social anxiety were completed by participants and their parents. Young people with TS/CTD showed an attention bias to social threat words (relative to benign words) compared to controls but no such bias for social threat faces. Attention bias for social threat words was associated with increasing YGTSS Total Score and parent-reported social anxiety in the TS/CTDs group. Mediation analysis revealed a significant indirect path between YGTSS Total Score and social anxiety, via attention to social threat. Tentatively, these associations appeared to be driven by impairment rather than tic severity scores. Preliminary data suggests that youth with TS/CTD have enhanced attention to threat, compared to controls, and this is associated with impairment and social anxiety. Attention to threat could offer a cognitive mechanism connecting impairment and social anxiety, and so be a valuable trans-diagnostic treatment target.

Funding oncology clinical trials: are cooperative group trials sustainable?

PubMed

Seow, Hsien-Yeang; Whelan, Patrick; Levine, Mark N; Cowan, Kathryn; Lysakowski, Barbara; Kowaleski, Brenda; Snider, Anne; Xu, Rebecca Y; Arnold, Andrew

2012-05-01

Many oncology clinical trials departments (CTDs) are in serious fiscal deficit and their sustainability is in jeopardy. This study investigates whether the payment models used to fund industry versus cooperative group trials contribute to the fiscal deficit of a CTD. We examined the lifetime costs of all cooperative group and industry trials activated in the CTD of a cancer center between 2007 and 2011. A trial's lifetime is defined as being from the date the first patient was accrued until the last patient's actual or projected final follow-up visit. For each trial, we calculated the lifetime monthly net income, which was defined as monthly revenue minus monthly costs. Data sources included study protocols, trial budgets, and accrual data. Of the 97 trials analyzed, 64 (66%) were cooperative group trials. The pattern of lifetime net income for cooperative group trials has a positive peak during patient accrual followed by a negative trough during follow-up. In contrast, the pattern for industry trials resembled an "l" shape. The patterns reflect the differing payment models: upfront lump-sum payments (cooperative group) versus milestone payments (industry). The negative trough in the lifetime net income of a cooperative group trial occurs because follow-up costs are typically not funded or are underfunded. CTDs accrue more patients in new trials to offset that deficit. The CTD uses revenue from accrual to existing trials to cross-subsidize past trials in follow-up. As the number of patients on follow-up increases, the fiscal deficit grows larger each year, perpetuating the cycle.

Significance of Myositis Autoantibody in Patients with Idiopathic Interstitial Lung Disease

PubMed Central

Song, Ju Sun; Hwang, Jiwon; Cha, Hoon-Suk; Jeong, Byeong-Ho; Suh, Gee Young; Chung, Man Pyo

2015-01-01

Purpose Some patients with interstitial lung disease (ILD) related to connective tissue disease (CTD) have a delayed diagnosis of the underlying CTD when the ILD is categorized as idiopathic. In this study, we evaluated the frequency of myositis autoantibodies in patients diagnosed with idiopathic ILD and investigated the clinical significance stemming from the presence of the antibodies. Materials and Methods A total 32 patients diagnosed with idiopathic ILD were enrolled in this study. We analyzed a panel of 11 myositis autoantibody specificities in the patients using a line blot immunoassay. Then, we divided them into myositis autoantibody-positive and -negative groups and compared the clinical features and laboratory data between the two groups. Results Of the 32 idiopathic ILD patients, 12 patients had myositis autoantibodies encompassing 9 specificities, except for anti-Mi-2 and anti-PM-Scl 100 (12/32, 38%). Anti-synthetase autoantibodies including Jo-1, EJ, OJ, PL-7, and PL-12 were present in 7 patients (7/32, 22%). The group with myositis autoantibodies presented more frequently with the symptom of mechanic's hand and showed abnormal pulmonary function test results with low forced vital capacity, diffusing capacity for carbon monoxide, total lung capacity, and high lactate dehydrogenase values in blood when compared with the group without myositis antibodies. Conclusion We strongly suggest that patients undergo an evaluation of myositis autoantibodies, if they are diagnosed with idiopathic ILD in the presence of clinical characteristics including mechanic's hand, arthralgia, and autoantibodies which are insufficient to make a diagnosis of a specific CTD category. PMID:25837172

The Clinical Features of Myositis-Associated Autoantibodies: a Review.

PubMed

Gunawardena, Harsha

2017-02-01

The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases traditionally defined by clinical manifestations including skeletal muscle weakness, skin rashes, elevated skeletal muscle enzymes, and neurophysiological and/or histological evidence of muscle inflammation. Patients with myositis overlap can develop other features including parenchymal lung disease, inflammatory arthritis, gastrointestinal manifestations and marked constitutional symptoms. Although patients may be diagnosed as having polymyositis (PM) or dermatomyositis (DM) under the IIM spectrum, it is quite clear that disease course between subgroups of patients is different. For example, interstitial lung disease may predominate in some, whereas cutaneous complications, cancer risk, or severe refractory myopathy may be a significant feature in others. Therefore, tools that facilitate diagnosis and indicate which patients require more detailed investigation for disease complications are invaluable in clinical practice. The expanding field of autoantibodies (autoAbs) associated with connective tissue disease (CTD)-myositis overlap has generated considerable interest over the last few years. Using an immunological diagnostic approach, this group of heterogeneous conditions can be separated into a number of distinct clinical phenotypes. Rather than diagnose a patient as simply having PM, DM or overlap CTD, we can define syndromes to differentiate disease subsets that emphasise clinical outcomes and guide management. There are now over 15 CTD-myositis overlap autoAbs found in patients with a range of clinical manifestations including interstitial pneumonia, cutaneous disease, cancer-associated myositis and autoimmune-mediated necrotising myopathy. This review describes their diagnostic utility, potential role in disease monitoring and response to treatment. In the future, routine use of these autoAb will allow a stratified approach to managing this complex set of conditions.

Researchers use Modified CRISPR Systems to Modulate Gene Expression on a Genomic Scale

Cancer.gov

Cancer Target Discovery and Development Network (CTD2) researchers at the University of California, San Francisco, developed a CRISPR system that can regulate both gene repression and activation with fewer off-target effects.

Structure of the Paramyxovirus Parainfluenza Virus 5 Nucleoprotein in Complex with an Amino-Terminal Peptide of the Phosphoprotein

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

Aggarwal, Megha; Leser, George P.; Kors, Christopher A.

Parainfluenza virus 5 (PIV5) belongs to the familyParamyxoviridae, which consists of enveloped viruses with a nonsegmented negative-strand RNA genome encapsidated by the nucleoprotein (N). Paramyxovirus replication is regulated by the phosphoprotein (P) through protein-protein interactions with N and the RNA polymerase (L). The chaperone activity of P is essential to maintain the unassembled RNA-free form of N in order to prevent nonspecific RNA binding and premature N oligomerization. Here, we determined the crystal structure of unassembled PIV5 N in complex with a P peptide (N 0P) derived from the N terminus of P (P50) at 2.65 Å. The PIV5 Nmore » 0P consists of two domains: an N-terminal domain (NTD) and a C-terminal domain (CTD) separated by a hinge region. The cleft at the hinge region of RNA-bound PIV5 N was previously shown to be an RNA binding site. The N 0P structure shows that the P peptide binds to the CTD of N and extends toward the RNA binding site to inhibit N oligomerization and, hence, RNA binding. Binding of P peptide also keeps the PIV5 N in the open form. A molecular dynamics (MD) analysis of both the open and closed forms of N shows the flexibility of the CTD and the preference of the N protein to be in an open conformation. The gradual opening of the hinge region, to release the RNA, was also observed. Together, these results advance our knowledge of the conformational swapping of N required for the highly regulated paramyxovirus replication. IMPORTANCEParamyxovirus replication is regulated by the interaction of P with N and L proteins. Here, we report the crystal structure of unassembled parainfluenza virus 5 (PIV5) N chaperoned with P peptide. Our results provide a detailed understanding of the binding of P to N. The conformational switching of N between closed and open forms during its initial interaction with P, as well as during RNA release, was analyzed. Our data also show the plasticity of the CTD and the importance of domain movement for conformational switching. The results improve our understanding of the mechanism of interchanging N conformations for RNA replication and release.« less

Structure of the Paramyxovirus Parainfluenza Virus 5 Nucleoprotein in Complex with an Amino-Terminal Peptide of the Phosphoprotein.

PubMed

Aggarwal, Megha; Leser, George P; Kors, Christopher A; Lamb, Robert A

2018-03-01

Parainfluenza virus 5 (PIV5) belongs to the family Paramyxoviridae , which consists of enveloped viruses with a nonsegmented negative-strand RNA genome encapsidated by the nucleoprotein (N). Paramyxovirus replication is regulated by the phosphoprotein (P) through protein-protein interactions with N and the RNA polymerase (L). The chaperone activity of P is essential to maintain the unassembled RNA-free form of N in order to prevent nonspecific RNA binding and premature N oligomerization. Here, we determined the crystal structure of unassembled PIV5 N in complex with a P peptide (N 0 P) derived from the N terminus of P (P50) at 2.65 Å. The PIV5 N 0 P consists of two domains: an N-terminal domain (NTD) and a C-terminal domain (CTD) separated by a hinge region. The cleft at the hinge region of RNA-bound PIV5 N was previously shown to be an RNA binding site. The N 0 P structure shows that the P peptide binds to the CTD of N and extends toward the RNA binding site to inhibit N oligomerization and, hence, RNA binding. Binding of P peptide also keeps the PIV5 N in the open form. A molecular dynamics (MD) analysis of both the open and closed forms of N shows the flexibility of the CTD and the preference of the N protein to be in an open conformation. The gradual opening of the hinge region, to release the RNA, was also observed. Together, these results advance our knowledge of the conformational swapping of N required for the highly regulated paramyxovirus replication. IMPORTANCE Paramyxovirus replication is regulated by the interaction of P with N and L proteins. Here, we report the crystal structure of unassembled parainfluenza virus 5 (PIV5) N chaperoned with P peptide. Our results provide a detailed understanding of the binding of P to N. The conformational switching of N between closed and open forms during its initial interaction with P, as well as during RNA release, was analyzed. Our data also show the plasticity of the CTD and the importance of domain movement for conformational switching. The results improve our understanding of the mechanism of interchanging N conformations for RNA replication and release. Copyright © 2018 American Society for Microbiology.

Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data.

PubMed

Hettne, Kristina M; Boorsma, André; van Dartel, Dorien A M; Goeman, Jelle J; de Jong, Esther; Piersma, Aldert H; Stierum, Rob H; Kleinjans, Jos C; Kors, Jan A

2013-01-29

Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with gene set analysis (GSA) methods for chemical treatment identification, for pharmacological mechanism elucidation, and for comparing compound toxicity profiles. We created 30,211 chemical response-specific gene sets for human and mouse by next-gen TM, and derived 1,189 (human) and 588 (mouse) gene sets from the Comparative Toxicogenomics Database (CTD). We tested for significant differential expression (SDE) (false discovery rate -corrected p-values < 0.05) of the next-gen TM-derived gene sets and the CTD-derived gene sets in gene expression (GE) data sets of five chemicals (from experimental models). We tested for SDE of gene sets for six fibrates in a peroxisome proliferator-activated receptor alpha (PPARA) knock-out GE dataset and compared to results from the Connectivity Map. We tested for SDE of 319 next-gen TM-derived gene sets for environmental toxicants in three GE data sets of triazoles, and tested for SDE of 442 gene sets associated with embryonic structures. We compared the gene sets to triazole effects seen in the Whole Embryo Culture (WEC), and used principal component analysis (PCA) to discriminate triazoles from other chemicals. Next-gen TM-derived gene sets matching the chemical treatment were significantly altered in three GE data sets, and the corresponding CTD-derived gene sets were significantly altered in five GE data sets. Six next-gen TM-derived and four CTD-derived fibrate gene sets were significantly altered in the PPARA knock-out GE dataset. None of the fibrate signatures in cMap scored significant against the PPARA GE signature. 33 environmental toxicant gene sets were significantly altered in the triazole GE data sets. 21 of these toxicants had a similar toxicity pattern as the triazoles. We confirmed embryotoxic effects, and discriminated triazoles from other chemicals. Gene set analysis with next-gen TM-derived chemical response-specific gene sets is a scalable method for identifying similarities in gene responses to other chemicals, from which one may infer potential mode of action and/or toxic effect.

Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions

PubMed Central

Pannek, Kerstin; Boyd, Roslyn N.; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E.

2014-01-01

Background Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. Aim The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Methods Data of 50 children with unilateral CP caused by periventricular white matter lesions (5–17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7–16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm2) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment—AHA) was assessed in connections that showed significant differences in FA compared to CTD. Results FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r2 = 0.16–0.44; p < 0.05). Conclusion This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention. PMID:25003031

Next-generation text-mining mediated generation of chemical response-specific gene sets for interpretation of gene expression data

PubMed Central

2013-01-01

Background Availability of chemical response-specific lists of genes (gene sets) for pharmacological and/or toxic effect prediction for compounds is limited. We hypothesize that more gene sets can be created by next-generation text mining (next-gen TM), and that these can be used with gene set analysis (GSA) methods for chemical treatment identification, for pharmacological mechanism elucidation, and for comparing compound toxicity profiles. Methods We created 30,211 chemical response-specific gene sets for human and mouse by next-gen TM, and derived 1,189 (human) and 588 (mouse) gene sets from the Comparative Toxicogenomics Database (CTD). We tested for significant differential expression (SDE) (false discovery rate -corrected p-values < 0.05) of the next-gen TM-derived gene sets and the CTD-derived gene sets in gene expression (GE) data sets of five chemicals (from experimental models). We tested for SDE of gene sets for six fibrates in a peroxisome proliferator-activated receptor alpha (PPARA) knock-out GE dataset and compared to results from the Connectivity Map. We tested for SDE of 319 next-gen TM-derived gene sets for environmental toxicants in three GE data sets of triazoles, and tested for SDE of 442 gene sets associated with embryonic structures. We compared the gene sets to triazole effects seen in the Whole Embryo Culture (WEC), and used principal component analysis (PCA) to discriminate triazoles from other chemicals. Results Next-gen TM-derived gene sets matching the chemical treatment were significantly altered in three GE data sets, and the corresponding CTD-derived gene sets were significantly altered in five GE data sets. Six next-gen TM-derived and four CTD-derived fibrate gene sets were significantly altered in the PPARA knock-out GE dataset. None of the fibrate signatures in cMap scored significant against the PPARA GE signature. 33 environmental toxicant gene sets were significantly altered in the triazole GE data sets. 21 of these toxicants had a similar toxicity pattern as the triazoles. We confirmed embryotoxic effects, and discriminated triazoles from other chemicals. Conclusions Gene set analysis with next-gen TM-derived chemical response-specific gene sets is a scalable method for identifying similarities in gene responses to other chemicals, from which one may infer potential mode of action and/or toxic effect. PMID:23356878

On the freshwater budget in the eastern tropical Atlantic during the development of the cold tongue

NASA Astrophysics Data System (ADS)

Schlundt, Michael; Krahmann, Gerd; Brandt, Peter; Karstensen, Johannes

2013-04-01

The most striking sea surface temperature (SST) phenomenon in the tropical Atlantic is the seasonal appearance of the Atlantic Cold Tongue (ACT). Onset, duration, spatial extent and strength of cooling are subject to significant interannual variability. The ACT onset is also associated with remarkable changes in upper ocean salinity. To examine the different contributions to these changes we here focus on and present a mixed layer freshwater budget in the eastern tropical Atlantic. Our investigation is based on an exceptionally large set of observations during the onset of the ACT in late boreal spring/ early boreal summer 2011: more than 5400 CTD-profiles acquired by seven gliders running simultaneously to two research cruises, 180 ship based CTD-profiles, time series data from the PIRATA buoy array as well as measurements from the Argo float program are used to derive mixed layer depth, lateral and vertical salinity gradients. To derive turbulent mixing and inferred diapycnal salt flux, microstructure observations are taken into account. Furthermore satellite measurements of sea surface salinity (SSS) by the SMOS mission and of SST by the TMI radiometer as well as atmospheric reanalysis data and the OSCAR project products are implemented. Freshwater budget terms were calculated for different sub-regions. These sub-regions are chosen using pre-defined thresholds in SSS, SST or mixed layer depth. Overall the freshwater budget is dominated by the net surface freshwater flux and horizontal advection by strong zonal currents. Other terms, like entrainment and diapycnal mixing are found to be regionally important. In particular, the observed increase in salinity in the near-equatorial region during ACT onset is found to be the result of the northward migration of the ITCZ associated with reduced net surface freshwater flux at the equator as well as mixing of salty subsurface waters into the surface mixed layer.

Near-surface Stratification and Submesoscale Fronts in the north Bay of Bengal during Summer Monsoon of 2014 and 2015.

NASA Astrophysics Data System (ADS)

Sengupta, D.; Jarugula, S. L.; D'Asaro, E. A.; Chaudhuri, D.; S, S.; Tandon, A.; M, R.; Lucas, A.; Simmons, H. L.

2016-02-01

The north bay of Bengal is characterised by a shallow layer of fresh water from monsoon rainfall and river discharge, with very strong stratification at its base, and a warm subsurface layer. The thermodynamic structure of the ocean has significant influence on air-sea interaction. We conducted two research cruises of ORV Sagar Nidhi in August-September 2014 and 2015, to study the physical processes that maintain the shallow fresh layer. We collected a total of about 4000 kilometers of underway Conductivity-Temperature-Depth (uCTD) and Acoustic Doppler Current Profiler (ADCP) data. The vertical resolution of the data is 1-2 m; at ship speeds of 4-5 knots, the horizontal resolution is 300-1500 m, sufficient to resolve submesoscale (1-20 km) features. It is known that dynamical instability of submesoscale fronts can lead to slumping of heavier water under lighter water, enhancing vertical stratification. We identified 35 major salinity-dominated near-surface density fronts along the ship track, with surface density gradient exceeding 0.03 kg/m3 per kilometer, and density difference exceeding 0.3 kg/m3. The largest gradients in the open ocean, between fresh water of riverine origin and ambient seawater, exceeded 10 psu in 40 km and 6 psu in 50 km; the spatial scales of the other fronts range from 1 to 25 km. At several submesoscale fronts, the surface mixed layer is shallower directly under the front than on either side, suggesting active restratification. ADCP observations reveal a region of confluence and narrow jets associated with some fronts, consistent with frontal slumping. In addition, wind-driven Ekman transport can enhance near-surface stratification by carrying lighter water over denser water. We discuss the relevance of these two mechanisms in observations and model simulations.

The new Seafloor Observatory (OBSEA) for remote and long-term coastal ecosystem monitoring.

PubMed

Aguzzi, Jacopo; Mànuel, Antoni; Condal, Fernando; Guillén, Jorge; Nogueras, Marc; del Rio, Joaquin; Costa, Corrado; Menesatti, Paolo; Puig, Pere; Sardà, Francesc; Toma, Daniel; Palanques, Albert

2011-01-01

A suitable sampling technology to identify species and to estimate population dynamics based on individual counts at different temporal levels in relation to habitat variations is increasingly important for fishery management and biodiversity studies. In the past two decades, as interest in exploring the oceans for valuable resources and in protecting these resources from overexploitation have grown, the number of cabled (permanent) submarine multiparametric platforms with video stations has increased. Prior to the development of seafloor observatories, the majority of autonomous stations were battery powered and stored data locally. The recently installed low-cost, multiparametric, expandable, cabled coastal Seafloor Observatory (OBSEA), located 4 km off of Vilanova i la Gertrú, Barcelona, at a depth of 20 m, is directly connected to a ground station by a telecommunication cable; thus, it is not affected by the limitations associated with previous observation technologies. OBSEA is part of the European Multidisciplinary Seafloor Observatory (EMSO) infrastructure, and its activities are included among the Network of Excellence of the European Seas Observatory NETwork (ESONET). OBSEA enables remote, long-term, and continuous surveys of the local ecosystem by acquiring synchronous multiparametric habitat data and bio-data with the following sensors: Conductivity-Temperature-Depth (CTD) sensors for salinity, temperature, and pressure; Acoustic Doppler Current Profilers (ADCP) for current speed and direction, including a turbidity meter and a fluorometer (for the determination of chlorophyll concentration); a hydrophone; a seismometer; and finally, a video camera for automated image analysis in relation to species classification and tracking. Images can be monitored in real time, and all data can be stored for future studies. In this article, the various components of OBSEA are described, including its hardware (the sensors and the network of marine and land nodes), software (data acquisition, transmission, processing, and storage), and multiparametric measurement (habitat and bio-data time series) capabilities. A one-month multiparametric survey of habitat parameters was conducted during 2009 and 2010 to demonstrate these functions. An automated video image analysis protocol was also developed for fish counting in the water column, a method that can be used with cabled coastal observatories working with still images. Finally, bio-data time series were coupled with data from other oceanographic sensors to demonstrate the utility of OBSEA in studies of ecosystem dynamics.

The New Seafloor Observatory (OBSEA) for Remote and Long-Term Coastal Ecosystem Monitoring

PubMed Central

Aguzzi, Jacopo; Mànuel, Antoni; Condal, Fernando; Guillén, Jorge; Nogueras, Marc; del Rio, Joaquin; Costa, Corrado; Menesatti, Paolo; Puig, Pere; Sardà, Francesc; Toma, Daniel; Palanques, Albert

2011-01-01

A suitable sampling technology to identify species and to estimate population dynamics based on individual counts at different temporal levels in relation to habitat variations is increasingly important for fishery management and biodiversity studies. In the past two decades, as interest in exploring the oceans for valuable resources and in protecting these resources from overexploitation have grown, the number of cabled (permanent) submarine multiparametric platforms with video stations has increased. Prior to the development of seafloor observatories, the majority of autonomous stations were battery powered and stored data locally. The recently installed low-cost, multiparametric, expandable, cabled coastal Seafloor Observatory (OBSEA), located 4 km off of Vilanova i la Gertrú, Barcelona, at a depth of 20 m, is directly connected to a ground station by a telecommunication cable; thus, it is not affected by the limitations associated with previous observation technologies. OBSEA is part of the European Multidisciplinary Seafloor Observatory (EMSO) infrastructure, and its activities are included among the Network of Excellence of the European Seas Observatory NETwork (ESONET). OBSEA enables remote, long-term, and continuous surveys of the local ecosystem by acquiring synchronous multiparametric habitat data and bio-data with the following sensors: Conductivity-Temperature-Depth (CTD) sensors for salinity, temperature, and pressure; Acoustic Doppler Current Profilers (ADCP) for current speed and direction, including a turbidity meter and a fluorometer (for the determination of chlorophyll concentration); a hydrophone; a seismometer; and finally, a video camera for automated image analysis in relation to species classification and tracking. Images can be monitored in real time, and all data can be stored for future studies. In this article, the various components of OBSEA are described, including its hardware (the sensors and the network of marine and land nodes), software (data acquisition, transmission, processing, and storage), and multiparametric measurement (habitat and bio-data time series) capabilities. A one-month multiparametric survey of habitat parameters was conducted during 2009 and 2010 to demonstrate these functions. An automated video image analysis protocol was also developed for fish counting in the water column, a method that can be used with cabled coastal observatories working with still images. Finally, bio-data time series were coupled with data from other oceanographic sensors to demonstrate the utility of OBSEA in studies of ecosystem dynamics. PMID:22163931

Synthesis, spectral characterization and catalytic activity of Co(II) complexes of drugs: crystal structure of Co(II)-trimethoprim complex.

PubMed

Madhupriya, Selvaraj; Elango, Kuppanagounder P

2014-01-24

New Co(II) complexes with drugs such as trimethoprim (TMP), cimetidine (CTD), niacinamide (NAM) and ofloxacin (OFL) as ligands were synthesized. The complexes were characterized by analytical analysis, various spectral techniques such as FT-IR, UV-Vis, magnetic measurements and molar conductivity. The magnetic susceptibility results coupled with the electronic spectra suggested a tetrahedral geometry for the complexes. The coordination mode of trimethoprim ligand and geometry of the complex were confirmed by single crystal X-ray studies. In this complex the metal ion possesses a tetrahedral geometry with two nitrogen atom from two TMP ligands and two chloride ions coordinated to it. The catalytic activity of the complexes in aryl-aryl coupling reaction was screened and the results indicated that among the four complexes [Co(OFL)Cl(H2O)] exhibited excellent catalytic activity. Copyright © 2013 Elsevier B.V. All rights reserved.

Critical Role of the HTLV-1 Capsid N-Terminal Domain for Gag-Gag Interactions and Virus Particle Assembly.

PubMed

Martin, Jessica L; Mendonça, Luiza; Marusinec, Rachel; Zuczek, Jennifer; Angert, Isaac; Blower, Ruth J; Mueller, Joachim D; Perilla, Juan R; Zhang, Wei; Mansky, Louis M

2018-04-25

The retroviral Gag protein is the main structural protein responsible for virus particle assembly and release. Like human immunodeficiency virus type 1 (HIV-1) Gag, human T-cell leukemia virus type 1 (HTLV-1) has a structurally conserved capsid (CA) domain, including a β-hairpin turn and a centralized coiled-coil-like structure of six α helices in the CA amino-terminal domain (NTD) as well as four α-helices in the CA carboxy-terminal domain (CTD). CA drives Gag oligomerization, which is critical for both immature Gag lattice formation and particle production. The HIV-1 CA CTD has previously been shown to be a primary determinant for CA-CA interactions, and while both the HTLV-1 CA NTD and CTD have been implicated in Gag-Gag interactions, our recent observations have implicated the HTLV-1 CA NTD as encoding key determinants that dictate particle morphology. Here, we have conducted alanine-scanning mutagenesis in the HTLV-1 CA NTD nucleotide-encoding sequences spanning the loop regions and amino acids at the beginning and ends of α-helices due to their structural dissimilarity from the HIV-1 CA NTD structure. We analyzed both Gag subcellular distribution and efficiency of particle production for these mutants. We discovered several important residues (i.e., M17, Q47/F48, and Y61). Modeling implicated that these residues reside at the dimer interface (i.e., M17 and Y61) or at the trimer interface (i.e., Q47/F48). Taken together, these observations highlight the critical role of the HTLV-1 CA NTD in Gag-Gag interactions and particle assembly, which is, to the best of our knowledge, in contrast to HIV-1 and other retroviruses. Importance Retrovirus particle assembly and release from infected cells is driven by the Gag structural protein. Gag-Gag interactions, which form an oligomeric lattice structure at a particle budding site, are essential to the biogenesis of an infectious virus particle. The capsid (CA) domain of Gag is generally thought to possess the key determinants for Gag-Gag interactions, and the present study has discovered several critical amino acid residues in the CA domain of human T-cell leukemia virus type 1 (HTLV-1) Gag, an important cancer-causing human retrovirus, which are distinct from that of human immunodeficiency virus type 1 (HIV-1) as well as other retroviruses studied to date. Altogether, our results provide important new insights into a poorly understood aspect of HTLV-1 replication, which significantly enhances our understanding of the molecular nature of Gag-Gag interaction determinants crucial for virus particle assembly. Copyright © 2018 American Society for Microbiology.

Exposure to silica and silicosis among tin miners in China: exposure-response analyses and risk assessment

PubMed Central

Chen, W; Zhuang, Z; Attfield, M; Chen, B; Gao, P.; Harrison, J; Fu, C; Chen, J; Wallace, W

2001-01-01

OBJECTIVES—To investigate the risk of silicosis among tin miners and to investigate the relation between silicosis and cumulative exposure to dust (Chinese total dust and respirable crystalline silica dust).
METHODS—A cohort study of 3010 miners exposed to silica dust and employed for at least 1 year during 1960-5 in any of four Chinese tin mines was conducted. Historical total dust data from China were used to create a job exposure matrix for facility, job title, and calendar year. The total dust exposure data from China were converted to estimates of exposure to respirable crystalline silica for comparison with findings from other epidemiological studies of silicosis. Each worker's work history was abstracted from the complete employment records in mine files. Diagnoses of silicosis were based on 1986 Chinese pneumoconiosis Roentgen diagnostic criteria, which classified silicosis as stages I-III—similar to an International Labour Organisation (ILO) classification of 1/1 or greater.
RESULTS—There were 1015 (33.7%) miners identified with silicosis, who had a mean age of 48.3 years, with a mean of 21.3 years after first exposure (equivalent to 11.0 net years in a dusty job). Among those who had silicosis, 684 miners (67.4%) developed silicosis after exposure ended (a mean of 3.7 years after). The risk of silicosis was strongly related to cumulative exposure to silica dust and was well fitted by the Weibull distribution, with the risk of silicosis less than 0.1% when the Chinese measure of cumulative exposure to total dust (CTD) was under 10 mg/m3-years (or 0.36 mg/m3-years of respirable crystalline silica), increasing to 68.7% when CTD exposure was 150 mg/m3-years (or 5.4 mg/m3-years of respirable crystalline silica). Latency period was not correlated to the risk of silicosis or cumulative dose of exposure. This study predicts about a 36% cumulative risk of silicosis for a 45 year lifetime exposure to these tin mine dusts at the CTD exposure standard of 2 mg/m3, and a 55% risk at 45 years exposure to the current United States Occupational Safety and Health Administration and Mine Safety and Health Administration standards of 0.1 mg/m3 100% respirable crystalline silica dust.
CONCLUSIONS—A clear exposure-response relation was detected for silicosis in Chinese tin miners. The study results were similar to most, but not all, findings from other large scale exposure-response studies.


Keywords: silicosis; exposure to silica; dose-response relation PMID:11119632

The Miniaturized Autonomous Moored Profiler

DTIC Science & Technology

2004-07-20

power sleep mode. All collected data is stored on a flashcard memory module for later retrieval or remote transmission. With the optical telemetry...board flashcard for later retrieval or remote transmission. Although the descent operation ultimately depends upon the cable-pay, the CTD remains on

EVALUATION OF SUPERCRITICAL CARBON DIOXIDE TECHNOLOGY TO REDUCE SOLVENT IN SPRAY COATING APPLICATIONS

EPA Science Inventory

This evaluation, part of the Pollution Prevention Clean Technology Demonstration (CTD) Program, addresses the product quality, waste reduction, and economic issues of spray paint application using supercritical carbon dioxide (CO2). Anion Carbide has developed this technology and...

Hemodynamic heterogeneity of connective tissue disease patients with borderline mean pulmonary artery pressure and its distinctive characters from those with normal pulmonary artery pressure: a retrospective study.

PubMed

Asari, Yusa; Yamasaki, Yoshioki; Tsuchida, Kosei; Suzuki, Kengo; Akashi, Yoshihiro J; Okazaki, Takahiro; Ozaki, Shoichi; Yamada, Hidehiro; Kawahata, Kimito

2018-05-18

To clarify whether patients with connective tissue disease (CTD)-associated borderline mean pulmonary artery pressure (mPAP) have distinctive hemodynamic characteristics from those with normal mPAP and whether pathogenesis is as heterogeneous as manifest pulmonary hypertension (PH). Seventy-five CTD patients who underwent right heart catheterization (RHC) from 2008 through 2016 were retrospectively analyzed. We compared between-group differences in clinical and hemodynamic findings: normal mPAP (n = 35), borderline mPAP (n = 15), and PH (n = 25). A therapeutic intervention trial based on RHC results was performed in nine patients. The values of tricuspid regurgitation pressure gradient (TRPG) in patients with borderline mPAP were comparable at rest but became higher after exercise compared to those with a normal mPAP (P = 0.01). Pulmonary artery wedge pressure in patients with borderline mPAP was higher than in those with normal mPAP (P < 0.0001) and comparable to those with PH. Each of the three patients was treated for pre-capillary and post-capillary disease and two for interstitial lung disease (ILD). During the mean follow-up period of 40 months, mPAP or TRPG normalized in all patients treated for pre-capillary and post-capillary disease. One patient with severe ILD developed to PH and died from it. CTD patients with borderline mPAP, the underlining pathogenesis of which is heterogeneous as PH, have distinctive hemodynamic characteristics from those with normal mPAP. Whether a specific treatment targeting the inflammatory process or local hemodynamics may alter the clinical course to PH is a topic for future research.

A portable digital microphotography unit for rapid documentation of periungual nailfold capillary changes in autoimmune connective tissue diseases.

PubMed

Sontheimer, Richard D

2004-03-01

While employing a DermLite dermoscopy unit to assess pigment pattern networks in melanocytic skin lesions, it was observed that this compact, portable dermoscopy unit can also be used to quickly detect nailfold capillary changes when entertaining a diagnosis of autoimmune connective tissue diseases (CTD) such as dermatomyositis (DM), scleroderma/systemic sclerosis (SSc), or systemic lupus erythematosus. Aware that the suppliers of the DermLite dermoscopy unit also market a portable digital microphotography unit based on the DermLite optical principles for efficiently documenting cutaneous pigment network patterns, we investigated whether this unit (DermLite Foto flash unit attached to a Nikon Coolpix digital camera) might be used to photographically document nailfold capillary changes in patients with autoimmune CTD. A DermLite Foto flash unit attached to a Nikon Coolpix digital camera was used in a controlled observational study to obtain digital photographs of nailfold capillaries in a small sequential sample of patients with autoimmune CTD attending a rheumatic skin disease subspecialty clinic in an academic department of dermatology. The digital microphotography system proved to be highly useful in documenting the nailfold vascular changes observed in a small sample of patients with DM. We observed that the nailfold capillary changes seen in patients with clinically amyopathic DM were qualitatively and quantitatively similar to those seen in patients with classical DM. Digital microphotography systems designed for examining pigmented skin lesions can be used easily to document nailfold capillary changes often observed in DM and SSc. Nailfold capillary changes documented in this manner appear to be indistinguishable in clinically amyopathic DM and classical DM.

Structure of the paramyxovirus parainfluenza virus 5 nucleoprotein–RNA complex

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

Alayyoubi, Maher; Leser, George P.; Kors, Christopher A.

Parainfluenza virus 5 (PIV5) is a member of the Paramyxoviridae family of membrane-enveloped viruses with a negative-sense RNA genome that is packaged and protected by long filamentous nucleocapsid-helix structures (RNPs). These RNPs, consisting of ~2,600 protomers of nucleocapsid (N) protein, form the template for viral transcription and replication. In this paper, we have determined the 3D X-ray crystal structure of the nucleoprotein (N)-RNA complex from PIV5 to 3.11-Å resolution. The structure reveals a 13-mer nucleocapsid ring whose diameter, cavity, and pitch/height dimensions agree with EM data from early studies on the Paramyxovirinae subfamily of native RNPs, indicating that it closelymore » represents one-turn in the building block of the RNP helices. The PIV5-N nucleocapsid ring encapsidates a nuclease resistant 78-nt RNA strand in its positively charged groove formed between the N-terminal (NTD) and C-terminal (CTD) domains of its successive N protomers. Six nucleotides precisely are associated with each N protomer, with alternating three-base-in three-base-out conformation. The binding of six nucleotides per protomer is consistent with the “rule of six” that governs the genome packaging of the Paramyxovirinae subfamily of viruses. PIV5-N protomer subdomains are very similar in structure to the previously solved Nipah-N structure, but with a difference in the angle between NTD/CTD at the RNA hinge region. Based on the Nipah-N structure we modeled a PIV5-N open conformation in which the CTD rotates away from the RNA strand into the inner spacious nucleocapsid-ring cavity. Finally, this rotation would expose the RNA for the viral polymerase activity without major disruption of the nucleocapsid structure.« less

Regulation of RIG-I Activation by K63-Linked Polyubiquitination.

PubMed

Okamoto, Masaaki; Kouwaki, Takahisa; Fukushima, Yoshimi; Oshiumi, Hiroyuki

2017-01-01

RIG-I is a pattern recognition receptor and recognizes cytoplasmic viral double-stranded RNA (dsRNA). Influenza A virus, hepatitis C virus, and several other pathogenic viruses are mainly recognized by RIG-I, resulting in the activation of the innate immune responses. The protein comprises N-terminal two caspase activation and recruitment domains (2CARDs), an RNA helicase domain, and the C-terminal domain (CTD). The CTD recognizes 5'-triphosphate viral dsRNA. After recognition of viral dsRNA, the protein harbors K63-linked polyubiquitination essential for RIG-I activation. First, it was reported that TRIM25 ubiquitin ligase delivered K63-linked polyubiquitin moiety to the 2CARDs. The polyubiquitin chain stabilizes a structure called the 2CARD tetramer, in which four 2CARDs assemble and make a core that promotes the aggregation of the mitochondrial antiviral-signaling (MAVS) protein on mitochondria. MAVS aggregation then triggers the signal to induce the innate immune responses. However, subsequent studies have reported that Riplet, MEX3C, and TRIM4 ubiquitin ligases are also involved in K63-linked polyubiquitination and the activation of RIG-I. MEX3C and TRIM4 mediate polyubiquitination of the 2CARDs. By contrast, Riplet ubiquitinates the CTD. The physiological significance of each ubiquitin ligases has been shown by knockout and knockdown studies, but there appears to be contradictory to evidence reported in the literature. In this review, we summarize recent findings related to K63-linked polyubiquitination and propose a model that could reconcile current contradictory theories. We also discuss the physiological significance of the ubiquitin ligases in the immune system against viral infection.

Regulation of RIG-I Activation by K63-Linked Polyubiquitination

PubMed Central

Okamoto, Masaaki; Kouwaki, Takahisa; Fukushima, Yoshimi; Oshiumi, Hiroyuki

2018-01-01

RIG-I is a pattern recognition receptor and recognizes cytoplasmic viral double-stranded RNA (dsRNA). Influenza A virus, hepatitis C virus, and several other pathogenic viruses are mainly recognized by RIG-I, resulting in the activation of the innate immune responses. The protein comprises N-terminal two caspase activation and recruitment domains (2CARDs), an RNA helicase domain, and the C-terminal domain (CTD). The CTD recognizes 5′-triphosphate viral dsRNA. After recognition of viral dsRNA, the protein harbors K63-linked polyubiquitination essential for RIG-I activation. First, it was reported that TRIM25 ubiquitin ligase delivered K63-linked polyubiquitin moiety to the 2CARDs. The polyubiquitin chain stabilizes a structure called the 2CARD tetramer, in which four 2CARDs assemble and make a core that promotes the aggregation of the mitochondrial antiviral-signaling (MAVS) protein on mitochondria. MAVS aggregation then triggers the signal to induce the innate immune responses. However, subsequent studies have reported that Riplet, MEX3C, and TRIM4 ubiquitin ligases are also involved in K63-linked polyubiquitination and the activation of RIG-I. MEX3C and TRIM4 mediate polyubiquitination of the 2CARDs. By contrast, Riplet ubiquitinates the CTD. The physiological significance of each ubiquitin ligases has been shown by knockout and knockdown studies, but there appears to be contradictory to evidence reported in the literature. In this review, we summarize recent findings related to K63-linked polyubiquitination and propose a model that could reconcile current contradictory theories. We also discuss the physiological significance of the ubiquitin ligases in the immune system against viral infection. PMID:29354136

A CTD–Pfizer collaboration: manual curation of 88 000 scientific articles text mined for drug–disease and drug–phenotype interactions

PubMed Central

Davis, Allan Peter; Wiegers, Thomas C.; Roberts, Phoebe M.; King, Benjamin L.; Lay, Jean M.; Lennon-Hopkins, Kelley; Sciaky, Daniela; Johnson, Robin; Keating, Heather; Greene, Nigel; Hernandez, Robert; McConnell, Kevin J.; Enayetallah, Ahmed E.; Mattingly, Carolyn J.

2013-01-01

Improving the prediction of chemical toxicity is a goal common to both environmental health research and pharmaceutical drug development. To improve safety detection assays, it is critical to have a reference set of molecules with well-defined toxicity annotations for training and validation purposes. Here, we describe a collaboration between safety researchers at Pfizer and the research team at the Comparative Toxicogenomics Database (CTD) to text mine and manually review a collection of 88 629 articles relating over 1 200 pharmaceutical drugs to their potential involvement in cardiovascular, neurological, renal and hepatic toxicity. In 1 year, CTD biocurators curated 2 54 173 toxicogenomic interactions (1 52 173 chemical–disease, 58 572 chemical–gene, 5 345 gene–disease and 38 083 phenotype interactions). All chemical–gene–disease interactions are fully integrated with public CTD, and phenotype interactions can be downloaded. We describe Pfizer’s text-mining process to collate the articles, and CTD’s curation strategy, performance metrics, enhanced data content and new module to curate phenotype information. As well, we show how data integration can connect phenotypes to diseases. This curation can be leveraged for information about toxic endpoints important to drug safety and help develop testable hypotheses for drug–disease events. The availability of these detailed, contextualized, high-quality annotations curated from seven decades’ worth of the scientific literature should help facilitate new mechanistic screening assays for pharmaceutical compound survival. This unique partnership demonstrates the importance of resource sharing and collaboration between public and private entities and underscores the complementary needs of the environmental health science and pharmaceutical communities. Database URL: http://ctdbase.org/ PMID:24288140

Baseline Characteristics of the Korean Registry of Pulmonary Arterial Hypertension.

PubMed

Chung, Wook-Jin; Park, Yong Bum; Jeon, Chan Hong; Jung, Jo Won; Ko, Kwang-Phil; Choi, Sung Jae; Seo, Hye Sun; Lee, Jae Seung; Jung, Hae Ok

2015-10-01

Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December 2011. A total of 625 patients were enrolled. The patients' mean age was 47.6 ± 15.7 yr, and 503 (80.5%) were women. The diagnostic methods included right heart catheterization (n = 249, 39.8%) and Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency, were connective tissue disease (CTD), congenital heart disease, and idiopathic PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%) patients received combination therapy. Incident cases during the registry represented 297 patients; therefore, the incidence rate of PAH was 1.9 patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients exhibited similar age, gender, and survival rate compared with western registries, they showed relatively more CTD-PAH in the etiology and also systemic lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and more specialized therapies should be needed to improve the survival of PAH patients.

Structure of the paramyxovirus parainfluenza virus 5 nucleoprotein–RNA complex

DOE PAGES

Alayyoubi, Maher; Leser, George P.; Kors, Christopher A.; ...

2015-03-23

Parainfluenza virus 5 (PIV5) is a member of the Paramyxoviridae family of membrane-enveloped viruses with a negative-sense RNA genome that is packaged and protected by long filamentous nucleocapsid-helix structures (RNPs). These RNPs, consisting of ~2,600 protomers of nucleocapsid (N) protein, form the template for viral transcription and replication. In this paper, we have determined the 3D X-ray crystal structure of the nucleoprotein (N)-RNA complex from PIV5 to 3.11-Å resolution. The structure reveals a 13-mer nucleocapsid ring whose diameter, cavity, and pitch/height dimensions agree with EM data from early studies on the Paramyxovirinae subfamily of native RNPs, indicating that it closelymore » represents one-turn in the building block of the RNP helices. The PIV5-N nucleocapsid ring encapsidates a nuclease resistant 78-nt RNA strand in its positively charged groove formed between the N-terminal (NTD) and C-terminal (CTD) domains of its successive N protomers. Six nucleotides precisely are associated with each N protomer, with alternating three-base-in three-base-out conformation. The binding of six nucleotides per protomer is consistent with the “rule of six” that governs the genome packaging of the Paramyxovirinae subfamily of viruses. PIV5-N protomer subdomains are very similar in structure to the previously solved Nipah-N structure, but with a difference in the angle between NTD/CTD at the RNA hinge region. Based on the Nipah-N structure we modeled a PIV5-N open conformation in which the CTD rotates away from the RNA strand into the inner spacious nucleocapsid-ring cavity. Finally, this rotation would expose the RNA for the viral polymerase activity without major disruption of the nucleocapsid structure.« less

Critical congenital heart disease--utility of routine screening for chromosomal and other extracardiac malformations.

PubMed

Baker, Kimberly; Sanchez-de-Toledo, Joan; Munoz, Ricardo; Orr, Richard; Kiray, Shareen; Shiderly, Dana; Clemens, Michele; Wearden, Peter; Morell, Victor O; Chrysostomou, Constantinos

2012-01-01

Objective.  Infants with critical congenital heart disease (CHD) can have genetic and other extracardiac malformations, which add to the short- and long-term risk of morbidity and perhaps mortality. We sought to examine our center's practice of screening for extracardiac anomalies and to determine the yield of these tests among specific cardiac diagnostic categories. Design.  Retrospective review of infants admitted to the cardiac intensive care unit with a new diagnosis of CHD. Subjects were categorized into six groups: septal defects (SD), conotruncal defects (CTD), single-ventricle physiology (SV), left-sided obstructive lesions (LSO), right-sided obstructive lesions (RSO), and "other" (anomalous pulmonary venous return, Ebstein's anomaly). Screening modalities included genetic testing (karyotype and fluorescent in situ hybridization for 22q11.2 deletion), renal ultrasound (RUS), and head ultrasound (HUS). Results.  One hundred forty-one patients were identified. The incidence of cardiac anomalies was: CTD (36%), SD (18%), SV (18%), LSO (14%), RSO (3%), and "other" (8%). Overall 14% had an abnormal karyotype, 5% had a deletion for 22q11.2, 28% had an abnormal RUS and 22% had abnormal HUS. Patients in SD and SV had the highest incidence of abnormal karyotype (36% and 17%); 22q11.2 deletion was present only in CTD and LSO groups (9% and 7%, respectively); abnormal RUS and HUS were seen relatively uniformly in all categories. Premature infants had significantly higher incidence of renal 43% vs. 24%, and intracranial abnormalities 46% vs. 16%. Conclusion.  Infants with critical CHD and particularly premature infants have high incidence of genetic and other extracardiac anomalies. Universal screening for these abnormalities with ultrasonographic and genetic testing maybe warranted because early detection could impact short and long-term outcomes. © 2011 Wiley Periodicals, Inc.

Solution structure of the c-terminal dimerization domain of SARS coronavirus nucleocapsid protein solved by the SAIL-NMR method.

PubMed

Takeda, Mitsuhiro; Chang, Chung-ke; Ikeya, Teppei; Güntert, Peter; Chang, Yuan-hsiang; Hsu, Yen-lan; Huang, Tai-huang; Kainosho, Masatsune

2008-07-18

The C-terminal domain (CTD) of the severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein (NP) contains a potential RNA-binding region in its N-terminal portion and also serves as a dimerization domain by forming a homodimer with a molecular mass of 28 kDa. So far, the structure determination of the SARS-CoV NP CTD in solution has been impeded by the poor quality of NMR spectra, especially for aromatic resonances. We have recently developed the stereo-array isotope labeling (SAIL) method to overcome the size problem of NMR structure determination by utilizing a protein exclusively composed of stereo- and regio-specifically isotope-labeled amino acids. Here, we employed the SAIL method to determine the high-quality solution structure of the SARS-CoV NP CTD by NMR. The SAIL protein yielded less crowded and better resolved spectra than uniform (13)C and (15)N labeling, and enabled the homodimeric solution structure of this protein to be determined. The NMR structure is almost identical with the previously solved crystal structure, except for a disordered putative RNA-binding domain at the N-terminus. Studies of the chemical shift perturbations caused by the binding of single-stranded DNA and mutational analyses have identified the disordered region at the N-termini as the prime site for nucleic acid binding. In addition, residues in the beta-sheet region also showed significant perturbations. Mapping of the locations of these residues onto the helical model observed in the crystal revealed that these two regions are parts of the interior lining of the positively charged helical groove, supporting the hypothesis that the helical oligomer may form in solution.

Architecture of the bacteriophage T4 activator MotA/promoter DNA interaction during sigma appropriation.

PubMed

Hsieh, Meng-Lun; James, Tamara D; Knipling, Leslie; Waddell, M Brett; White, Stephen; Hinton, Deborah M

2013-09-20

Gene expression can be regulated through factors that direct RNA polymerase to the correct promoter sequence at the correct time. Bacteriophage T4 controls its development in this way using phage proteins that interact with host RNA polymerase. Using a process called σ appropriation, the T4 co-activator AsiA structurally remodels the σ(70) subunit of host RNA polymerase, while a T4 activator, MotA, engages the C terminus of σ(70) and binds to a DNA promoter element, the MotA box. Structures for the N-terminal (NTD) and C-terminal (CTD) domains of MotA are available, but no structure exists for MotA with or without DNA. We report the first molecular map of the MotA/DNA interaction within the σ-appropriated complex, which we obtained by using the cleaving reagent, iron bromoacetamidobenzyl-EDTA (FeBABE). We conjugated surface-exposed, single cysteines in MotA with FeBABE and performed cleavage reactions in the context of stable transcription complexes. The DNA cleavage sites were analyzed using ICM Molsoft software and three-dimensional physical models of MotA(NTD), MotA(CTD), and the DNA to investigate shape complementarity between the protein and the DNA and to position MotA on the DNA. We found that the unusual "double wing" motif present within MotA(CTD) resides in the major groove of the MotA box. In addition, we have used surface plasmon resonance to show that MotA alone is in a very dynamic equilibrium with the MotA element. Our results demonstrate the utility of fine resolution FeBABE mapping to determine the architecture of protein-DNA complexes that have been recalcitrant to traditional structure analyses.

Interstitial Lung Disease in India. Results of a Prospective Registry.

PubMed

Singh, Sheetu; Collins, Bridget F; Sharma, Bharat B; Joshi, Jyotsna M; Talwar, Deepak; Katiyar, Sandeep; Singh, Nishtha; Ho, Lawrence; Samaria, Jai Kumar; Bhattacharya, Parthasarathi; Gupta, Rakesh; Chaudhari, Sudhir; Singh, Tejraj; Moond, Vijay; Pipavath, Sudhakar; Ahuja, Jitesh; Chetambath, Ravindran; Ghoshal, Aloke G; Jain, Nirmal K; Devi, H J Gayathri; Kant, Surya; Koul, Parvaiz; Dhar, Raja; Swarnakar, Rajesh; Sharma, Surendra K; Roy, Dhrubajyoti J; Sarmah, Kripesh R; Jankharia, Bhavin; Schmidt, Rodney; Katiyar, Santosh K; Jindal, Arpita; Mangal, Daya K; Singh, Virendra; Raghu, Ganesh

2017-03-15

Interstitial lung disease (ILD) is a heterogeneous group of acute and chronic inflammatory and fibrotic lung diseases. Existing ILD registries have had variable findings. Little is known about the clinical profile of ILDs in India. To characterize new-onset ILDs in India by creating a prospective ILD using multidisciplinary discussion (MDD) to validate diagnoses. Adult patients of Indian origin living in India with new-onset ILD (27 centers, 19 Indian cities, March 2012-June 2015) without malignancy or infection were included. All had connective tissue disease (CTD) serologies, spirometry, and high-resolution computed tomography chest. ILD pattern was defined by high-resolution computed tomography images. Three groups independently made diagnoses after review of clinical data including that from prompted case report forms: local site investigators, ILD experts at the National Data Coordinating Center (NDCC; Jaipur, India) with MDD, and experienced ILD experts at the Center for ILD (CILD; Seattle, WA) with MDD. Cohen's κ was used to assess reliability of interobserver agreement. A total of 1,084 patients were recruited. Final diagnosis: hypersensitivity pneumonitis in 47.3% (n = 513; exposure, 48.1% air coolers), CTD-ILD in 13.9%, and idiopathic pulmonary fibrosis in 13.7%. Cohen's κ: 0.351 site investigator/CILD, 0.519 site investigator/NDCC, and 0.618 NDCC/CILD. Hypersensitivity pneumonitis was the most common new-onset ILD in India, followed by CTD-ILD and idiopathic pulmonary fibrosis; diagnoses varied between site investigators and CILD experts, emphasizing the value of MDD in ILD diagnosis. Prompted case report forms including environmental exposures in prospective registries will likely provide further insight into the etiology and management of ILD worldwide.

Structure of the paramyxovirus parainfluenza virus 5 nucleoprotein-RNA complex.

PubMed

Alayyoubi, Maher; Leser, George P; Kors, Christopher A; Lamb, Robert A

2015-04-07

Parainfluenza virus 5 (PIV5) is a member of the Paramyxoviridae family of membrane-enveloped viruses with a negative-sense RNA genome that is packaged and protected by long filamentous nucleocapsid-helix structures (RNPs). These RNPs, consisting of ∼2,600 protomers of nucleocapsid (N) protein, form the template for viral transcription and replication. We have determined the 3D X-ray crystal structure of the nucleoprotein (N)-RNA complex from PIV5 to 3.11-Å resolution. The structure reveals a 13-mer nucleocapsid ring whose diameter, cavity, and pitch/height dimensions agree with EM data from early studies on the Paramyxovirinae subfamily of native RNPs, indicating that it closely represents one-turn in the building block of the RNP helices. The PIV5-N nucleocapsid ring encapsidates a nuclease resistant 78-nt RNA strand in its positively charged groove formed between the N-terminal (NTD) and C-terminal (CTD) domains of its successive N protomers. Six nucleotides precisely are associated with each N protomer, with alternating three-base-in three-base-out conformation. The binding of six nucleotides per protomer is consistent with the "rule of six" that governs the genome packaging of the Paramyxovirinae subfamily of viruses. PIV5-N protomer subdomains are very similar in structure to the previously solved Nipah-N structure, but with a difference in the angle between NTD/CTD at the RNA hinge region. Based on the Nipah-N structure we modeled a PIV5-N open conformation in which the CTD rotates away from the RNA strand into the inner spacious nucleocapsid-ring cavity. This rotation would expose the RNA for the viral polymerase activity without major disruption of the nucleocapsid structure.

Measurement of Antinuclear Antibodies: Assessment of Different Test Systems

PubMed Central

Kern, P.; Kron, M.; Hiesche, K.

2000-01-01

The performance of rat liver and HEp-2 in the detection of antinuclear antibodies (ANA) was studied by two independent sites and compared against an ANA enzyme immunoassay (EIA) screen and EIA systems for the measurement of antibodies to double-stranded DNA (dsDNA) and ENA. Sixty-two sera from patients with connective tissue disease (CTD) and 398 from controls suffering from other disorders were included. The level of agreement was, for HEp-2 and rat liver (within one site), 82.0% (ANA positive/ANA negative) and 51.0% (ANA pattern); and for HEp2- and HEp-2 (between sites), 71.8 and 86.5%. On sera with the ANA homogeneous pattern, the measurement of anti-ENA EIA added little to the detection rate with anti-dsDNA EIA alone. On ANA speckled sera, the EIA reactivity depended on the reaction of the mitotic cells: while sera with positive mitoses reacted similarly to ANA homogeneous sera, in those with negative mitoses the measurement of anti-ENA added about 10% to the detection rate achieved with anti-dsDNA alone. The measurement of anti-Scl-70 and anti-Jo-1 did not markedly improve the positive rate with classical ENA (anti-SSA, -SSB, -Sm, and -RNP) alone, raising doubts about the cost efficiency of including these measurements in unselected sera. The ANA EIA identified patients with CTD at a rate similar to that for rat liver and HEp-2. However, up to 98% of the sera found to be negative by ANA EIA but positive by use of rat liver and HEp-2 were from controls. Thus, the ANA EIA may possible be used as an alternative screen, particularly in laboratories with a high frequency of sera from patients not suffering from CTD. PMID:10618281

Longitudinal Changes in Segmental Aortic Stiffness Determined by Cardiac Magnetic Resonance in Children and Young Adults With Connective Tissue Disorders (the Marfan, Loeys-Dietz, and Ehlers-Danlos Syndromes, and Nonspecific Connective Tissue Disorders).

PubMed

Merlocco, Anthony; Lacro, Ronald V; Gauvreau, Kimberlee; Rabideau, Nicole; Singh, Michael N; Prakash, Ashwin

2017-10-01

Aortic stiffness measured by cardiac magnetic resonance (CMR) in connective tissue disorder (CTD) patients has been previously shown to be abnormal and to be associated with adverse aortic outcomes. The rate of increase in aortic stiffness with normal aging has been previously described. However, longitudinal changes in aortic stiffness have not been characterized in CTD patients. We examined longitudinal changes in CMR-derived aortic stiffness in children and young adults with CTDs. A retrospective analysis of 50 children and young adults (median age, 20 years; range, 0.2 to 49; 40% < 18 years old) with a CTD, and with at least 2 CMR examinations (total 152 examinations) over a median duration of 3.9 (1 to 13.2) years was performed. Aortic stiffness measures (strain, distensibility, and β stiffness index) were calculated on each examination at the aortic root (AoR), ascending aorta, and descending aorta. Longitudinal changes in parameters were analyzed using linear mixed-effects models. Aortic strain and distensibility decreased with age, whereas the β stiffness index increased at all aortic segments. The average rates of decline in distensibility (x10 -3  mm Hg -1 per 10-year increase in age) were 0.7, 1.3, and 1 at the AoR, ascending aorta, and descending aorta, respectively. The rates of decline in distensibility were not associated with the rates of AoR dilation or surgical AoR replacement. In conclusion, on serial CMR measurements in children and young adults with CTDs, aortic stiffness progressively increased with age, with rates of change only slightly higher than those previously reported in healthy adults. Copyright © 2017 Elsevier Inc. All rights reserved.

The NMR solution structure of Mycobacterium tuberculosis F-ATP synthase subunit ε provides new insight into energy coupling inside the rotary engine.

PubMed

Joon, Shin; Ragunathan, Priya; Sundararaman, Lavanya; Nartey, Wilson; Kundu, Subhashri; Manimekalai, Malathy S S; Bogdanović, Nebojša; Dick, Thomas; Grüber, Gerhard

2018-03-01

Mycobacterium tuberculosis (Mt) F 1 F 0 ATP synthase (α 3 :β 3 :γ:δ:ε:a:b:b':c 9 ) is essential for the viability of growing and nongrowing persister cells of the pathogen. Here, we present the first NMR solution structure of Mtε, revealing an N-terminal β-barrel domain (NTD) and a C-terminal domain (CTD) composed of a helix-loop-helix with helix 1 and -2 being shorter compared to their counterparts in other bacteria. The C-terminal amino acids are oriented toward the NTD, forming a domain-domain interface between the NTD and CTD. The Mtε structure provides a novel mechanistic model of coupling c-ring- and ε rotation via a patch of hydrophobic residues in the NTD and residues of the CTD to the bottom of the catalytic α 3 β 3 -headpiece. To test our model, genome site-directed mutagenesis was employed to introduce amino acid changes in these two parts of the epsilon subunit. Inverted vesicle assays show that these mutations caused an increase in ATP hydrolysis activity and a reduction in ATP synthesis. The structural and enzymatic data are discussed in light of the transition mechanism of a compact and extended state of Mtε, which provides the inhibitory effects of this coupling subunit inside the rotary engine. Finally, the employment of these data with molecular docking shed light into the second binding site of the drug Bedaquiline. Structural data are available in the PDB under the accession number 5YIO. © 2018 Federation of European Biochemical Societies.

Core Mediator structure at 3.4 Å extends model of transcription initiation complex.

PubMed

Nozawa, Kayo; Schneider, Thomas R; Cramer, Patrick

2017-05-11

Mediator is a multiprotein co-activator that binds the transcription pre-initiation complex (PIC) and regulates RNA polymerase (Pol) II. The Mediator head and middle modules form the essential core Mediator (cMed), whereas the tail and kinase modules play regulatory roles. The architecture of Mediator and its position on the PIC are known, but atomic details are limited to Mediator subcomplexes. Here we report the crystal structure of the 15-subunit cMed from Schizosaccharomyces pombe at 3.4 Å resolution. The structure shows an unaltered head module, and reveals the intricate middle module, which we show is globally required for transcription. Sites of known Mediator mutations cluster at the interface between the head and middle modules, and in terminal regions of the head subunits Med6 (ref. 16) and Med17 (ref. 17) that tether the middle module. The structure led to a model for Saccharomyces cerevisiae cMed that could be combined with the 3.6 Å cryo-electron microscopy structure of the core PIC (cPIC). The resulting atomic model of the cPIC-cMed complex informs on interactions of the submodules forming the middle module, called beam, knob, plank, connector, and hook. The hook is flexibly linked to Mediator by a conserved hinge and contacts the transcription initiation factor IIH (TFIIH) kinase that phosphorylates the carboxy (C)-terminal domain (CTD) of Pol II and was recently positioned on the PIC. The hook also contains residues that crosslink to the CTD and reside in a previously described cradle. These results provide a framework for understanding Mediator function, including its role in stimulating CTD phosphorylation by TFIIH.

Challenges for the registration of vaccines in emerging countries: Differences in dossier requirements, application and evaluation processes.

PubMed

Dellepiane, Nora; Pagliusi, Sonia

2018-06-07

The divergence of regulatory requirements and processes in developing and emerging countries contributes to hamper vaccines' registration, and therefore delay access to high-quality, safe and efficacious vaccines for their respective populations. This report focuses on providing insights on the heterogeneity of registration requirements in terms of numbering structure and overall content of dossiers for marketing authorisation applications for vaccines in different areas of the world. While it also illustrates the divergence of regulatory processes in general, as well as the need to avoid redundant reviews, it does not claim to provide a comprehensive view of all processes nor existing facilitating mechanisms, nor is it intended to touch upon the differences in assessments made by different regulatory authorities. This report describes the work analysed by regulatory experts from vaccine manufacturing companies during a meeting held in Geneva in May 2017, in identifying and quantifying differences in the requirements for vaccine registration in three aspects for comparison: the dossier numbering structure and contents, the application forms, and the evaluation procedures, in different countries and regions. The Module 1 of the Common Technical Document (CTD) of 10 countries were compared. Modules 2-5 of the CTDs of two regions and three countries were compared to the CTD of the US FDA. The application forms of eight countries were compared and the registration procedures of 134 importing countries were compared as well. The analysis indicates a high degree of divergence in numbering structure and content requirements. Possible interventions that would lead to significant improvements in registration efficiency include alignment in CTD numbering structure, a standardised model-application form, and better convergence of evaluation procedures. Copyright © 2018.

Identification and Molecular Characterization of the Chloroplast Targeting Domain of Turnip yellow mosaic virus Replication Proteins

PubMed Central

Moriceau, Lucille; Jomat, Lucile; Bressanelli, Stéphane; Alcaide-Loridan, Catherine; Jupin, Isabelle

2017-01-01

Turnip yellow mosaic virus (TYMV) is a positive-strand RNA virus infecting plants. The TYMV 140K replication protein is a key organizer of viral replication complex (VRC) assembly, being responsible for recruitment of the viral polymerase and for targeting the VRCs to the chloroplast envelope where viral replication takes place. However, the structural requirements determining the subcellular localization and membrane association of this essential viral protein have not yet been defined. In this study, we investigated determinants for the in vivo chloroplast targeting of the TYMV 140K replication protein. Subcellular localization studies of deletion mutants identified a 41-residue internal sequence as the chloroplast targeting domain (CTD) of TYMV 140K; this sequence is sufficient to target GFP to the chloroplast envelope. The CTD appears to be located in the C-terminal extension of the methyltransferase domain—a region shared by 140K and its mature cleavage product 98K, which behaves as an integral membrane protein during infection. We predicted the CTD to fold into two amphipathic α-helices—a folding that was confirmed in vitro by circular dichroism spectroscopy analyses of a synthetic peptide. The importance for subcellular localization of the integrity of these amphipathic helices, and the function of 140K/98K, was demonstrated by performing amino acid substitutions that affected chloroplast targeting, membrane association and viral replication. These results establish a short internal α-helical peptide as an unusual signal for targeting proteins to the chloroplast envelope membrane, and provide new insights into membrane targeting of viral replication proteins—a universal feature of positive-strand RNA viruses. PMID:29312393

Alterations in receptor expression or agonist concentration change the pathways gastrin-releasing peptide receptor uses to regulate extracellular signal-regulated kinase.

PubMed

Chen, Pei-Wen; Kroog, Glenn S

2004-12-01

G protein-coupled receptors activate extracellular signal-regulated kinases (ERKs) via different pathways in different cell types. In this study, we demonstrate that gastrin-releasing peptide receptor (GRPr) regulates ERK through multiple pathways in a single cell type depending upon receptor expression and agonist concentration. We examined stably transfected BALB/c 3T3 fibroblasts expressing GRPr constructs at different levels and treated the cells with several concentrations of bombesin (BN, a GRPr agonist) to activate a variable number of GRPr per cell. GRPr induced two waves of ERK activation and one wave of ERK inhibition. One wave of activation required an intact GRPr carboxyl-terminal domain (CTD). It peaked 6 min after addition of high BN concentration ([BN]) in cells with high GRPr expression. Another wave of activation was CTD-independent. It peaked 2 to 4 min after BN addition in cells when [BN] and/or GRPr expression were lower. The early wave of ERK activation was more sensitive than the later one to pretreatment with Bisindolylmaleimide I (GF 109203X) (a protein kinase C inhibitor) or hypertonic sucrose. Because these two waves of activation differ in time course, dose-response curve, requirement for GRPr CTD, and sensitivity to inhibitors, they result from different signaling pathways. A third pathway in these cells inhibited ERK phosphorylation 2 min after addition of high [BN] in cells with high GRPr expression. Furthermore, a GRPr-expressing human duodenal cancer cell line showed differential sensitivity to GF 109203X throughout BN-induced ERK activation, indicating that GRPr may activate ERK via multiple pathways in cells expressing endogenous GRPr.

Distribution and ecology of planktic foraminifera in the North Pacific: Implications for paleo-reconstructions

NASA Astrophysics Data System (ADS)

Taylor, Ben J.; Rae, James W. B.; Gray, William R.; Darling, Kate F.; Burke, Andrea; Gersonde, Rainer; Abelmann, Andrea; Maier, Edith; Esper, Oliver; Ziveri, Patrizia

2018-07-01

Planktic foraminifera census data have been used to reconstruct past temperatures through transfer functions, as well as changes in ocean ecosystems, chemistry and circulation. Here we present new multinet, plankton net and core-top census data from 20 sites in the Subpolar North Pacific. We combine these with previous data to provide an up to date compilation of North Pacific planktic foraminifera assemblage data. Our compilation is used to define 6 faunal zones: the subpolar zone; transitional zone; upwelling zone; subtropical zone; east equatorial zone; west equatorial zone; based on the distribution of 10 major species of planktic foraminifera. Two species of planktic foraminifera Neogloboquadrina pachyderma and Globigerina bulloides provide the basis for many subpolar paleo-reconstructions. Through the analysis of new multinet and CTD data we find that G. bulloides and N. pachyderma are predominantly found within 0-50 m of the water column and coincide with high food availability. N. pachyderma also shows a strong temperature control and can thrive in food poor waters where temperatures are low. Both species bloom seasonally, particularly during the spring bloom of March to June, with G. bulloides exhibiting greater seasonal variation. We suggest that percentage abundance of N. pachyderma in paleo-assemblages can be used to assess relative changes in past temperature, with G. bulloides abundance more likely to reflect changes in food availability. By comparing our core-top and multinet data, we also find a dissolution bias of G. bulloides over N. pachyderma in the North Pacific, which may enrich assemblages in the latter species.

Computed and observed turbulent heat fluxes during an extreme Bora event in the Adriatic using atmosphere-ocean coupling

NASA Astrophysics Data System (ADS)

Ličer, Matjaž; Smerkol, Peter; Fettich, Anja; Ravdas, Michalis; Papapostolou, Alexandros; Mantziafou, Anneta; Strajnar, Benedikt; Cedilnik, Jure; Jeromel, Maja; Jerman, Jure; Petan, Sašo; Benetazzo, Alvise; Carniel, Sandro; Malačič, Vlado; Sofianos, Sarantis

2016-04-01

We have studied the performances of (a) a two-way coupled atmosphere-ocean modeling system and (b) one-way coupled ocean model (forced by the atmosphere model), as compared to the available in situ measurements during and after a strong Adriatic Bora wind event in February 2012, which led to extreme air-sea interactions. The simulations span the period between January and March 2012. The models used were ALADIN (4.4 km resolution) on the atmosphere side and Adriatic setup of POM (1°/30 × 1°/30 angular resolution) on the ocean side. The atmosphere-ocean coupling was implemented using the OASIS3-MCT model coupling toolkit. Two-way coupling ocean feedback to the atmosphere is limited to sea surface temperature. We have compared modeled atmosphere-ocean fluxes (computed using modified Louis scheme) and sea temperatures from both setups to platform and CTD measurements of fluxes (computed using COARE scheme) and temperatures from three observational platforms (Vida, Paloma, Acqua Alta) in the Northern Adriatic. We show that turbulent fluxes from both setups differ up to 20% during the Bora but not significantly before and after the event. The impact of the coupling on the ocean is significant while the impact on the atmosphere is less pronounced. When compared to observations, two way coupling ocean temperatures exhibit a four times lower RMSE than those from one-way coupled system. Two-way coupling improves sensible heat fluxes at all stations but does not improve latent heat loss.

Fred Hutchinson Cancer Research Center (FHCRC1): Genetic Disruption of CTCF Destabilizes DNA Methylation | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at Fred Hutchinson Cancer Research Center identified the DNA binding protein CTCF as a tumor suppressor and regulator of DNA methylation. Read the abstract Experimental Approaches Read the detailed Experimental Approaches

Fred Hutchinson Cancer Research Center (FHCRC-1): Genetic Disruption of CTCF Destabilizes DNA Methylation | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at Fred Hutchinson Cancer Research Center identified the DNA binding protein CTCF as a tumor suppressor and regulator of DNA methylation. Read the abstract Experimental Approaches Read the detailed Experimental Approaches

Protein-Protein Interactions (PPI) reagents: | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at Emory University has a library of genes used to study protein-protein interactions in mammalian cells. These genes are cloned in different mammalian expression vectors. A list of available cancer-associated genes can be accessed below.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRi) plasmids | Office of Cancer Genomics

Cancer.gov

CTD2 researchers at the University of California in San Francisco developed a modified Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) CRISPR/dCas9 system. Catalytically inactive dCas9 enables modular and programmable RNA-guided genome regulation in eukaryotes.

University of California San Francisco (UCSF-2): Integrative Genomic Approaches in Neuroblastoma (NBL) | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at University of California San Francisco (UCSF-2) used an integrative genomics approach to reveal unidentified mRNA splicing patterns in neuroblastoma. Read the abstract Experimental Approaches Read the detailed Experimental Approaches

The yeast prefoldin-like URI-orthologue Bud27 associates with the RSC nucleosome remodeler and modulates transcription

PubMed Central

Mirón-García, María Carmen; Garrido-Godino, Ana Isabel; Martínez-Fernández, Verónica; Fernández-Pevida, Antonio; Cuevas-Bermúdez, Abel; Martín-Expósito, Manuel; Chávez, Sebastián; de la Cruz, Jesús; Navarro, Francisco

2014-01-01

Bud27, the yeast orthologue of human URI/RMP, is a member of the prefoldin-like family of ATP-independent molecular chaperones. It has recently been shown to mediate the assembly of the three RNA polymerases in an Rpb5-dependent manner. In this work, we present evidence of Bud27 modulating RNA pol II transcription elongation. We show that Bud27 associates with RNA pol II phosphorylated forms (CTD-Ser5P and CTD-Ser2P), and that its absence affects RNA pol II occupancy of transcribed genes. We also reveal that Bud27 associates in vivo with the Sth1 component of the chromatin remodeling complex RSC and mediates its association with RNA pol II. Our data suggest that Bud27, in addition of contributing to Rpb5 folding within the RNA polymerases, also participates in the correct assembly of other chromatin-associated protein complexes, such as RSC, thereby modulating their activity. PMID:25081216

Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures

DOE PAGES

Hubin, Elizabeth A.; Lilic, Mirjana; Darst, Seth A.; ...

2017-07-13

The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the a CTD may play a role in Mtb transcription regulation. Here, our results reveal the structure of an Actinobacteria-unique insert ofmore » the RNAP β' subunit. Finally, our analysis reveals the disposition of the N-terminal segment of Msm σ A, which may comprise an intrinsically disordered protein domain unique to mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues to the profound instability of mycobacteria RPo compared with E. coli.« less

Internationalization of regulatory requirements.

PubMed

Juillet, Y

2003-02-01

The aim of harmonisation of medicines regulatory requirements is to allow the patient quicker access to new drugs and to avoid animal and human duplications. Harmonisation in the European Union (EU) is now completed, and has led to the submission of one dossier in one language study leading to European marketing authorizations, thanks in particular to efficacy guidelines published at the European level. With the benefit of the European experience since 1989, more than 40 guidelines have been harmonised amongst the EU, Japan and the USA through the International Conference on Harmonisation (ICH). ICH is a unique process gathering regulators and industry experts from the three regions. Its activity is built on expertise and trust. The Common Technical Document (CTD), an agreed common format for application in the three regions, is a logical follow-up to the ICH first phase harmonising the content of the dossier. The CTD final implementation in July 2003 will have considerable influence on the review process and on the exchange of information in the three regions.

Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis.

PubMed

Ma, Lu; Rebane, Aleksander A; Yang, Guangcan; Xi, Zhiqun; Kang, Yuhao; Gao, Ying; Zhang, Yongli

2015-12-23

Synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins couple their stage-wise folding/assembly to rapid exocytosis of neurotransmitters in a Munc18-1-dependent manner. The functions of the different assembly stages in exocytosis and the role of Munc18-1 in SNARE assembly are not well understood. Using optical tweezers, we observed four distinct stages of assembly in SNARE N-terminal, middle, C-terminal, and linker domains (or NTD, MD, CTD, and LD, respectively). We found that SNARE layer mutations differentially affect SNARE assembly. Comparison of their effects on SNARE assembly and on exocytosis reveals that NTD and CTD are responsible for vesicle docking and fusion, respectively, whereas MD regulates SNARE assembly and fusion. Munc18-1 initiates SNARE assembly and structures t-SNARE C-terminus independent of syntaxin N-terminal regulatory domain (NRD) and stabilizes the half-zippered SNARE complex dependent upon the NRD. Our observations demonstrate distinct functions of SNARE domains whose assembly is intimately chaperoned by Munc18-1.

Urine screening for patients with developmental disabilities detected a patient with creatine transporter deficiency due to a novel missense mutation in SLC6A8.

PubMed

Kato, Hidekazu; Miyake, Fuyu; Shimbo, Hiroko; Ohya, Makoto; Sugawara, Hidenori; Aida, Noriko; Anzai, Rie; Takagi, Mariko; Okuda, Mitsuko; Takano, Kyoko; Wada, Takahito; Iai, Mizue; Yamashita, Sumimasa; Osaka, Hitoshi

2014-08-01

Creatine transporter deficiency (CTD) is an example of X-linked intellectual disability syndromes, caused by mutations in SLC6A8 on Xq28. Although this is the second most frequent genetic cause of intellectual disabilities in Europe or America after Fragile X syndrome, information on the morbidity of this disease is limited in Japan. Using the HPLC screening method we have established recently, we examined samples of urine of 105 patients (73 males and 32 females) with developmental disabilities at our medical center. And we have found a family with three ID boys with a novel missense mutation in SLC6A8. This is the second report of a Japanese family case of CTD. A systematic diagnostic system of this syndrome should be established in Japan to enable us to estimate its frequency and treatment. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Structure of the Siz/PIAS SUMO E3 ligase Siz1 and determinants required for SUMO modification of PCNA

PubMed Central

Yunus, Ali A.; Lima, Christopher D.

2009-01-01

Summary Siz1 is a founding member of the Siz/PIAS RING family of SUMO E3 ligases. The x-ray structure of an active Siz1 ligase revealed an elongated tripartite architecture comprised of an N-terminal PINIT domain, a central zinc-containing RING-like SP-RING domain, and a C-terminal domain we term the SP-CTD. Structure-based mutational analysis and biochemical studies show that the SP-RING and SP-CTD are required for activation of the E2~SUMO thioester while the PINIT domain is essential for redirecting SUMO conjugation to the proliferating cell nuclear antigen (PCNA) at lysine 164, a non-consensus lysine residue that is not modified by the SUMO E2 in the absence of Siz1. Mutational analysis of Siz1 and PCNA revealed surfaces on both proteins that are required for efficient SUMO modification of PCNA in vitro and in vivo. PMID:19748360

OmpA: A Flexible Clamp for Bacterial Cell Wall Attachment.

PubMed

Samsudin, Firdaus; Ortiz-Suarez, Maite L; Piggot, Thomas J; Bond, Peter J; Khalid, Syma

2016-12-06

The envelope of Gram-negative bacteria is highly complex, containing separate outer and inner membranes and an intervening periplasmic space encompassing a peptidoglycan (PGN) cell wall. The PGN scaffold is anchored non-covalently to the outer membrane via globular OmpA-like domains of various proteins. We report atomically detailed simulations of PGN bound to OmpA in three different states, including the isolated C-terminal domain (CTD), the full-length monomer, or the complete full-length dimeric form. Comparative analysis of dynamics of OmpA CTD from different bacteria helped to identify a conserved PGN-binding mode. The dynamics of full-length OmpA, embedded within a realistic representation of the outer membrane containing full-rough (Ra) lipopolysaccharide, phospholipids, and cardiolipin, suggested how the protein may provide flexible mechanical support to the cell wall. An accurate model of the heterogeneous bacterial cell envelope should facilitate future efforts to develop antibacterial agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Architecture of the RNA polymerase II-Mediator core initiation complex.

PubMed

Plaschka, C; Larivière, L; Wenzeck, L; Seizl, M; Hemann, M; Tegunov, D; Petrotchenko, E V; Borchers, C H; Baumeister, W; Herzog, F; Villa, E; Cramer, P

2015-02-19

The conserved co-activator complex Mediator enables regulated transcription initiation by RNA polymerase (Pol) II. Here we reconstitute an active 15-subunit core Mediator (cMed) comprising all essential Mediator subunits from Saccharomyces cerevisiae. The cryo-electron microscopic structure of cMed bound to a core initiation complex was determined at 9.7 Å resolution. cMed binds Pol II around the Rpb4-Rpb7 stalk near the carboxy-terminal domain (CTD). The Mediator head module binds the Pol II dock and the TFIIB ribbon and stabilizes the initiation complex. The Mediator middle module extends to the Pol II foot with a 'plank' that may influence polymerase conformation. The Mediator subunit Med14 forms a 'beam' between the head and middle modules and connects to the tail module that is predicted to bind transcription activators located on upstream DNA. The Mediator 'arm' and 'hook' domains contribute to a 'cradle' that may position the CTD and TFIIH kinase to stimulate Pol II phosphorylation.

Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures

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

Hubin, Elizabeth A.; Lilic, Mirjana; Darst, Seth A.

The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the αCTD may play a role in Mtb transcription regulation. Our results reveal the structure of an Actinobacteria-unique insert of the RNAPmore » β' subunit. Finally, our analysis reveals the disposition of the N-terminal segment of Msm σA, which may comprise an intrinsically disordered protein domain unique to mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues to the profound instability of mycobacteria RPo compared with E. coli.« less

Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures

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

Hubin, Elizabeth A.; Lilic, Mirjana; Darst, Seth A.

The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the a CTD may play a role in Mtb transcription regulation. Here, our results reveal the structure of an Actinobacteria-unique insert ofmore » the RNAP β' subunit. Finally, our analysis reveals the disposition of the N-terminal segment of Msm σ A, which may comprise an intrinsically disordered protein domain unique to mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues to the profound instability of mycobacteria RPo compared with E. coli.« less

Mean hydrography on the continental shelf from 26 repeat glider deployments along Southeastern Australia

NASA Astrophysics Data System (ADS)

Schaeffer, Amandine; Roughan, Moninya; Austin, Tim; Everett, Jason D.; Griffin, David; Hollings, Ben; King, Edward; Mantovanelli, Alessandra; Milburn, Stuart; Pasquer, Benedicte; Pattiaratchi, Charitha; Robertson, Robin; Stanley, Dennis; Suthers, Iain; White, Dana

2016-08-01

Since 2008, 26 glider missions have been undertaken along the continental shelf of southeastern Australia. Typically these missions have spanned the continental shelf on the inshore edge of the East Australian Current from 29.5-33.5°S. This comprehensive dataset of over 33,600 CTD profiles from the surface to within 10 m of the bottom in water depths ranging 25-200 m provides new and unprecedented high resolution observations of the properties of the continental shelf waters adjacent to a western boundary current, straddling the region where it separates from the coast. The region is both physically and biologically significant, and is also in a hotspot of ocean warming. We present gridded mean fields for temperature, salinity and density, but also dissolved oxygen and chlorophyll-a fluorescence indicative of phytoplankton biomass. This data will be invaluable for understanding shelf stratification, circulation, biophysical and bio-geochemical interactions, as well as for the validation of high-resolution ocean models or serving as teaching material.

Mean hydrography on the continental shelf from 26 repeat glider deployments along Southeastern Australia.

PubMed

Schaeffer, Amandine; Roughan, Moninya; Austin, Tim; Everett, Jason D; Griffin, David; Hollings, Ben; King, Edward; Mantovanelli, Alessandra; Milburn, Stuart; Pasquer, Benedicte; Pattiaratchi, Charitha; Robertson, Robin; Stanley, Dennis; Suthers, Iain; White, Dana

2016-08-30

Since 2008, 26 glider missions have been undertaken along the continental shelf of southeastern Australia. Typically these missions have spanned the continental shelf on the inshore edge of the East Australian Current from 29.5-33.5°S. This comprehensive dataset of over 33,600 CTD profiles from the surface to within 10 m of the bottom in water depths ranging 25-200 m provides new and unprecedented high resolution observations of the properties of the continental shelf waters adjacent to a western boundary current, straddling the region where it separates from the coast. The region is both physically and biologically significant, and is also in a hotspot of ocean warming. We present gridded mean fields for temperature, salinity and density, but also dissolved oxygen and chlorophyll-a fluorescence indicative of phytoplankton biomass. This data will be invaluable for understanding shelf stratification, circulation, biophysical and bio-geochemical interactions, as well as for the validation of high-resolution ocean models or serving as teaching material.

Hydrothermal plumes in the Gulf of Aden, as characterized by light transmission, Mn, Fe, CH4 and δ13C-CH4 anomalies

NASA Astrophysics Data System (ADS)

Gamo, Toshitaka; Okamura, Kei; Hatanaka, Hiroshi; Hasumoto, Hiroshi; Komatsu, Daisuke; Chinen, Masakazu; Mori, Mutsumi; Tanaka, Junya; Hirota, Akinari; Tsunogai, Urumu; Tamaki, Kensaku

2015-11-01

We conducted water column surveys to search for hydrothermal plumes over the spreading axes in the Gulf of Aden between 45°35‧E and 52°42‧E. We measured light transmission and chemical tracers Mn, Fe, CH4 and δ13C of CH4 in seawater taken using a CTD-Carrousel multi-sampling system at 12 locations including a control station in the Arabian Sea. We recognized three types of hydrothermal plumes at depths of 650 to 900 m (shallow plumes), 1000 to 1200 m (intermediate plumes), and >1500 m (deep plumes). The shallow plumes were apparently originated from newly discovered twin seamounts (12°03-06‧N and 45°35-41‧E) at the westernmost survey area, where two-dimensional distributions of light transmission and Mn were mapped by tow-yo observations of the CTD-sampling system with an in situ auto-analyzer GAMOS. The maximum concentrations of Mn, Fe, and CH4 of 46 nM, 251 nM, and 15 nM, respectively, were observed for collected seawater within the shallow plumes. The intermediate plumes were characterized by anomalies of light transmission, Mn, Fe, and δ13C of CH4, but by little CH4 anomalies, suggesting that CH4 had been consumed down to the background level during the aging of the plumes. Anomalies of δ3He already reported by the World Ocean Circulation Experiment (WOCE) program exhibited a hydrothermal plume-like peak at 2000 m depth in the Gulf of Aden, which seems to coincide with the deep plumes observed in this study. The endmember δ13C-CH4 values for the shallow and the deep plumes were estimated to be in a range between -10‰ and -15‰, demonstrating that the sources of CH4 are not biogenic but magmatic as similarly observed at sediment-starved mid-oceanic ridges.

Intense mesoscale variability in the Sardinia Sea

NASA Astrophysics Data System (ADS)

Russo, Aniello; Borrione, Ines; Falchetti, Silvia; Knoll, Michaela; Fiekas, Heinz-Volker; Heywood, Karen; Oddo, Paolo; Onken, Reiner

2015-04-01

From the 6 to 25 June 2014, the REP14-MED sea trial was conducted by CMRE, supported by 20 partners from six different nations. The at-sea activities were carried out onboard the research vessels Alliance (NATO) and Planet (German Ministry of Defense), comprising a marine area of about 110 x 110 km2 to the west of the Sardinian coast. More than 300 CTD casts typically spaced at 10 km were collected; both ships continuously recorded vertical profiles of currents by means of their ADCPs, and a ScanFish® and a CTD chain were towed for almost three days by Alliance and Planet, respectively, following parallel routes. Twelve gliders from different manufacturers (Slocum, SeaGliderTM and SeaExplorer) were continuously sampling the study area following zonal tracks spaced at 10 km. In addition, six moorings, 17 surface drifters and one ARVOR float were deployed. From a first analysis of the observations, several mesoscale features were identified in the survey area, in particular: (i) a warm-core anticyclonic eddy in the southern part of the domain, about 50 km in diameter and with the strongest signal at about 50-m depth (ii) another warm-core anticyclonic eddy of comparable dimensions in the central part of the domain, but extending to greater depth than the former one, and (iii) a small (less than 15 km in diameter) cold-core cyclonic eddy of Winter Intermediate Water in the depth range between 170 m and 370 m. All three eddies showed intensified currents, up to 50 cm s-1. The huge high-resolution observational data set and the variety of observation techniques enabled the mesoscale features and their variability to be tracked for almost three weeks. In order to obtain a deeper understanding of the mesoscale dynamic behaviour and their interactions, assimilation studies with an ocean circulation model are underway.

GALREX 2011: Initial Results of the 2011 NOAA Ocean Exploration Cruise to the Galápagos Rift Using Interactive Telepresence Technology

NASA Astrophysics Data System (ADS)

Holden, J. F.; Baker, E. T.; Embley, R. W.; Hammond, S. R.; Shank, T. M.; Walker, S. L.; White, S. M.; Galrex 2011 Team

2011-12-01

The Galápagos Rift is a classic example of ridge-hotspot interaction. In theory, the increased magma supply to the Rift should create an abundance of active hydrothermal vent sites, and yet previous surveys found that high-temperature vents were more scarce than predicted. The mission goals of GALREX 2011 were to explore the diverse habitats and geological settings of the deep Galápagos region primarily to search for hydrothermal venting, but also to explore other areas of interest. In June 2011, the first multibeam bathymetric map of the Galápagos Rift axis from 101° 18' W to 98° W was made with the EM302 sonar, and an along-axis 'tow-yo' CTD-LSS-ORP hydrocast was conducted for hydrothermal plume signals along with additional EM302 mapping from 89° 18' W to 85° 21' W. In July 2011, the ROV Lil' Hercules explored new sites of hydrothermal venting along the eastern arm of the Rift, the Rosebud hydrothermal vent field, hydrothermal mounds 20 km south of the Rift, one of the Paramount Seamounts for a macrofaunal survey, and a volcano on the Ecuador Rift. Data and ROV video feeds were transmitted by broad-band satellite in real time from the ship to a team of scientists in Seattle, WA; Newport, OR; and Woods Hole, MA. The team evaluated the transmitted data and helped direct seafloor ROV operations in real-time. In total, nearly 4,000 km of seafloor were mapped by EM302, 11 CTD tows covered the entire eastern arm of the Rift, and 12 ROV dives collected > 5 TB of high-definition digital video of the seafloor. The hydrocast survey along the eastern Rift identified two regions with abundant optical and ORP signals directly over the spreading axis. The largest of these was nearly 50 km long between 88° 5' W and 88° 33' W. Five ROV dives near 88° 18' W found recently erupted lobate lava flows and several regions of active diffuse hydrothermal venting. The site had the appearance of a relatively recent eruption as the diffuse venting at the site led to extensive white particles of putative sulfur, presumably of bacterial origin, on the rocks and suspended in the lower water column (hence the high optical signal) and there were only mobile rather than sessile fauna at these vents. Extinct hydrothermal sulfide chimneys over 30 m tall were found within 2 km of the active vents suggesting that the region had previously experienced a period of intense heat loss. Three ROV dives at another plume site near 86° W showed reinvigorated diffuse venting in a once massive clam bed now actively colonized by tubeworms, mussels, and microbial mats and ringed with abundant dandelions. The lack of biota and vitreous, unsedimented lobate flows at the Rosebud diffuse vent field (86° 12' W) suggests that it was paved over by an eruption since 2005. The eastern Galápagos Rift appears to have experienced a series of recent dike injections producing new lava flows and extensive diffuse venting, possibly within the past 5 years. Active, focused high-temperature hydrothermal flow has yet to be found on the eastern Rift, though extinct sulfide chimneys attest that it has occurred.

Deep Diving Cetacean Behavioral Response Study MED 09

DTIC Science & Technology

2009-09-30

distribution may be affected by anthropogenic noise. The role of the SPAWAR Systems Center (SSC) Pacific team was to intergrate the interdisiplinary...over 100 hours of data was collected on production sonobuoys for post test ambient noise data. CTD casts were taken at 56 sites, collecting

Basin-Wide Temperature Constraints On Gas Hydrate Stability In The Gulf Of Mexico

NASA Astrophysics Data System (ADS)

MacDonald, I. R.; Reagan, M. T.; Guinasso, N. L.; Garcia-Pineda, O. G.

2012-12-01

Gas hydrate deposits commonly occur at the seafloor-water interface on marine margins. They are especially prevalent in the Gulf of Mexico where they are associated with natural oil seeps. The stability of these deposits is potentially challenged by fluctuations in bottom water temperature, on an annual time-scale, and under the long-term influence of climate change. We mapped the locations of natural oil seeps where shallow gas hydrate deposits are known to occur across the entire Gulf of Mexico basin based on a comprehensive review of synthetic aperture radar (SAR) data (~200 images). We prepared a bottom water temperature map based on the archive of CTD casts from the Gulf (~6000 records). Comparing the distribution of gas hydrate deposits with predicted bottom water temperature, we find that a broad area of the upper slope lies above the theoretical stability horizon for structure 1 gas hydrate, while all sites where gas hydrate deposits occur are within the stability horizon for structure 2 gas hydrate. This is consistent with analytical results that structure 2 gas hydrates predominate on the upper slope (Klapp et al., 2010), where bottom water temperatures fluctuate over a 7 to 10 C range (approx. 600 m depth), while pure structure 1 hydrates are found at greater depths (approx. 3000 m). Where higher hydrocarbon gases are available, formation of structure 2 gas hydrate should significantly increase the resistance of shallow gas hydrate deposits to destabilizing effects variable or increasing bottom water temperature. Klapp, S.A., Bohrmann, G., Kuhs, W.F., Murshed, M.M., Pape, T., Klein, H., Techmer, K.S., Heeschen, K.U., and Abegg, F., 2010, Microstructures of structure I and II gas hydrates from the Gulf of Mexico: Marine and Petroleum Geology, v. 27, p. 116-125.Bottom temperature and pressure for Gulf of Mexico gas hydrate outcrops and stability horizons for sI and sII hydrate.

Calibration procedures and first data set of Southern Ocean chlorophyll a profiles collected by elephant seal equipped with a newly developed CTD-fluorescence tags

NASA Astrophysics Data System (ADS)

Guinet, C.; Xing, X.; Walker, E.; Monestiez, P.; Marchand, S.; Picard, B.; Jaud, T.; Authier, M.; `Cotté, C.; Dragon, A. C.; Diamond, E.; Antoine, D.; Lovell, P.; Blain, S.; D'Ortenzio, F.; Claustre, H.

2012-08-01

In-situ observation of the marine environment has traditionally relied on ship-based platforms. The obvious consequence is that physical and biogeochemical properties have been dramatically undersampled, especially in the remote Southern Ocean (SO). The difficulty in obtaining in situ data represents the major limitations to our understanding, and interpretation of the coupling between physical forcing and the biogeochemical response. Southern elephant seals (Mirounga leonina) equipped with a new generation of oceanographic sensors can measure ocean structure in regions and seasons rarely observed with traditional oceanographic platforms. Over the last few years, seals have allowed for a considerable increase in temperature and salinity profiles from the SO. However we were still lacking information on the spatio-temporal variation of phytoplankton concentration. This information is critical to assess how the biological productivity of the SO, with direct consequences on the amount of CO2 "fixed" by the biological pump, will respond to global warming. In this research program, we use an innovative sampling fluorescence approach to quantify phytoplankton concentration at sea. For the first time, a low energy consumption fluorometer was added to Argos CTD-SRDL tags, and these novel instruments were deployed on 27 southern elephant seals between 25 December 2007 and the 4 February 2011. As many as 3388 fluorescence profiles associated with temperature and salinity measurements were thereby collected from a vast sector of the Southern Indian Ocean. This paper address the calibration issue of the fluorometer before being deployed on elephant seals and present the first results obtained for the Indian Sector of the Southern Ocean. This in situ system is implemented in synergy with satellite ocean colour radiometry. Satellite-derived data is limited to the surface layer and is restricted over the SO by extensive cloud cover. However, with the addition of these new tags, we're able to assess the 3 dimension distribution of phytoplankton concentration by foraging southern elephant seals. This approach reveals that for the Indian sector of the SO, the surface chlorophyll a (chl a) concentrations provided by MODIS were underestimated by a factor of the order of 2-3 compared to in situ measurements. The scientific outcomes of this program include an improved understanding of both the present state and variability in ocean biology, and the accompanying biogeochemistry, as well as the delivery of real-time and open-access data to scientists (doi:10.7491/MEMO.1x).

Calibration procedures and first dataset of Southern Ocean chlorophyll a profiles collected by elephant seals equipped with a newly developed CTD-fluorescence tags

NASA Astrophysics Data System (ADS)

Guinet, C.; Xing, X.; Walker, E.; Monestiez, P.; Marchand, S.; Picard, B.; Jaud, T.; Authier, M.; Cotté, C.; Dragon, A. C.; Diamond, E.; Antoine, D.; Lovell, P.; Blain, S.; D'Ortenzio, F.; Claustre, H.

2013-02-01

In situ observation of the marine environment has traditionally relied on ship-based platforms. The obvious consequence is that physical and biogeochemical properties have been dramatically undersampled, especially in the remote Southern Ocean (SO). The difficulty in obtaining in situ data represents the major limitations to our understanding, and interpretation of the coupling between physical forcing and the biogeochemical response. Southern elephant seals (Mirounga leonina) equipped with a new generation of oceanographic sensors can measure ocean structure in regions and seasons rarely observed with traditional oceanographic platforms. Over the last few years, seals have allowed for a considerable increase in temperature and salinity profiles from the SO, but we were still lacking information on the spatiotemporal variation of phytoplankton concentration. This information is critical to assess how the biological productivity of the SO, with direct consequences on the amount of CO2 "fixed'' by the biological pump, will respond to global warming. In this research programme, we use an innovative sampling fluorescence approach to quantify phytoplankton concentration at sea. For the first time, a low energy consumption fluorometer was added to Argos CTD-SRDL tags, and these novel instruments were deployed on 27 southern elephant seals between 25 December 2007 and the 4 February 2011. As many as 3388 fluorescence profiles associated with temperature and salinity measurements were thereby collected from a vast sector of the Southern Indian Ocean. This paper addresses the calibration issue of the fluorometer before being deployed on elephant seals and presents the first results obtained for the Indian sector of the Southern Ocean. This in situ system is implemented in synergy with satellite ocean colour radiometry. Satellite-derived data is limited to the surface layer and is restricted over the SO by extensive cloud cover. However, with the addition of these new tags, we are able to assess the 3-dimension distribution of phytoplankton concentration by foraging southern elephant seals. This approach reveals that for the Indian sector of the SO, the surface chlorophyll a (chl a) concentrations provided by MODIS were underestimated by a factor 2 compared to chl a concentrations estimated from HPLC corrected in situ fluorescence measurements. The scientific outcomes of this programme include an improved understanding of both the present state and variability in ocean biology, and the accompanying biogeochemistry, as well as the delivery of real-time and open-access data to scientists (doi:10.7491/MEMO.1).

Emory University: High-Throughput Protein-Protein Interaction Analysis for Hippo Pathway Profiling | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at Emory University used high-throughput protein-protein interaction (PPI) mapping for Hippo signaling pathway profiling to rapidly unveil promising PPIs as potential therapeutic targets and advance functional understanding of signaling circuitry in cells. Read the abstract.

CTD² Dashboard: a searchable web interface to connect validated results from the Cancer Target Discovery and Development Network* | Office of Cancer Genomics

Cancer.gov

The Cancer Target Discovery and Development (CTD2) Network aims to use functional genomics to accelerate the translation of high-throughput and high-content genomic and small-molecule data towards use in precision oncology.

Dissolved Oxygen Sensor in Animal-Borne Instruments: An Innovation for Monitoring the Health of Oceans and Investigating the Functioning of Marine Ecosystems

PubMed Central

Bailleul, Frederic; Vacquie-Garcia, Jade; Guinet, Christophe

2015-01-01

The current decline in dissolved oxygen concentration within the oceans is a sensitive indicator of the effect of climate change on marine environment. However the impact of its declining on marine life and ecosystems’ health is still quite unclear because of the difficulty in obtaining in situ data, especially in remote areas, like the Southern Ocean (SO). Southern elephant seals (Mirounga leonina) proved to be a relevant alternative to the traditional oceanographic platforms to measure physical and biogeochemical structure of oceanic regions rarely observed. In this study, we use a new stage of development in biologging technology to draw a picture of dissolved oxygen concentration in the SO. We present the first results obtained from a dissolved oxygen sensor added to Argos CTD-SRDL tags and deployed on 5 female elephant seals at Kerguelen. From October 2010 and October 2011, 742 oxygen profiles associated with temperature and salinity measurements were recorded. Whether a part of the data must be considered cautiously, especially because of offsets and temporal drifts of the sensors, the range of values recorded was consistent with a concomitant survey conducted from a research vessel (Keops-2 project). Once again, elephant seals reinforced the relationship between marine ecology and oceanography, delivering essential information about the water masses properties and the biological status of the Southern Ocean. But more than the presentation of a new stage of development in animal-borne instrumentation, this pilot study opens a new field of investigation in marine ecology and could be enlarged in a near future to other key marine predators, especially large fish species like swordfish, tuna or sharks, for which dissolved oxygen is expected to play a crucial role in distribution and behaviour. PMID:26200780

Spatial and Temporal Patterns of Chlorophyll Concentration in the Southern California Bight

NASA Astrophysics Data System (ADS)

Nezlin, Nikolay P.; McLaughlin, Karen; Booth, J. Ashley T.; Cash, Curtis L.; Diehl, Dario W.; Davis, Kristen A.; Feit, Adriano; Goericke, Ralf; Gully, Joseph R.; Howard, Meredith D. A.; Johnson, Scott; Latker, Ami; Mengel, Michael J.; Robertson, George L.; Steele, Alex; Terriquez, Laura; Washburn, Libe; Weisberg, Stephen B.

2018-01-01

Distinguishing between local, anthropogenic nutrient inputs and large-scale climatic forcing as drivers of coastal phytoplankton biomass is critical to developing effective nutrient management strategies. Here we assess the relative importance of these two drivers by comparing trends in chlorophyll-a between shallow coastal (0.1-16.5 km) and deep offshore (17-700 km) areas, hypothesizing that coastal regions influenced by anthropogenic nutrient inputs may have different spatial and temporal patterns in chlorophyll-a concentration from offshore regions where coastal inputs are less influential. Quarterly conductivity-temperature-depth (CTD) fluorescence measurements collected from three southern California continental shelf regions since 1998 were compared to chlorophyll-a data from the more offshore California Cooperative Fisheries Investigations (CalCOFI) program. The trends in the coastal zone were similar to those offshore, with a gradual increase of chlorophyll-a biomass and shallowing of its maximum layer since the beginning of observations, followed by chlorophyll-a declining and deepening from 2010 to present. An exception was the northern coastal part of SCB, where chlorophyll-a continued increasing after 2010. The long-term increase in chlorophyll-a prior to 2010 was correlated with increased nitrate concentrations in deep waters, while the recent decline was associated with deepening of the upper mixed layer, both linked to the low-frequency climatic cycles of the Pacific Decadal Oscillation and North Pacific Gyre Oscillation. These large-scale factors affecting the physical structure of the water column may also influence the delivery of nutrients from deep ocean outfalls to the euphotic zone, making it difficult to distinguish the effects of anthropogenic inputs on chlorophyll along the coast.

Hydrological state of the Large Aral Sea in the fall season of 2013

NASA Astrophysics Data System (ADS)

Izhitskiy, Alexander; Zavialov, Peter

2014-05-01

We report here the results of the latest expedition of the Shirshov Institute to the Aral Sea. The survey encompassed 8 field days in October-November, 2013. Direct measurements of thermohaline characteristics and water currents were conducted in the western basin of the Large Aral Sea during the expedition. Vertical profiles of temperature and salinity were obtained using a CTD profiler at 9 stations, situated on two cross-sections of the western basin. Four mooring stations equipped with current meters, as well as pressure gauges, were deployed for 4-6 days on the slopes of the deepest portion of the western basin. A portable automatic meteorological station, continuously recording the variability of wind and principal meteorological parameters, was installed near the mooring sites. Analysis of the current measurements data along with the meteorological data records demonstrated the current velocity and level anomalies responded energetically to winds. Correlation analysis of the velocity series versus the wind stress allowed to quantify the response of the system to the wind forcing. Together with the similar results of more earlier surveys, recently collected data shows that the mean surface circulation of the western basin remains anti-cyclonic under the predominant winds. Character of the interannual variability of salinity values in the Aral Sea water manifested increase in the surface layer during last 5 years. On the other hand, salinity values in the bottom layer appear to be decreased due to ceasing of the influence of the interbasin water exchange since 2010. Water level of the Large Aral Sea is still falling. Assessment of the on-going changes holds promise to help predicting the subsequent state of the Aral Sea region.